## Background
This episode of The Diary Of A CEO, hosted by Steven Bartlett, was published on YouTube on February 06, 2025, and features metabolic scientist Dr. Benjamin Bikman. The video description highlights how 88% of adults suffer from metabolic disease and explores Dr. Bikman's insights into the hidden dangers of insulin, insulin resistance, and practical strategies to take control of personal health.
## TL;DR
Dr. Benjamin Bikman breaks down how insulin resistance serves as the common metabolic root for major modern health conditions, including Type 2 diabetes, cardiovascular disease, Alzheimer's, and PCOS. He explains the cellular mechanics of fat storage, fuel selection, and how modern high-carbohydrate diets and continuous eating keep insulin chronically elevated. To restore metabolic health and longevity, Dr. Bikman advocates for controlling carbohydrates, prioritizing protein, embracing natural fats, incorporating fasting or exercise, and critically evaluates popular trends like GLP-1 agonists (Ozempic), artificial sweeteners, and extreme low-calorie diets.
## Atmosphere & style
The conversation carries an urgent, highly authoritative, yet accessible tone that blends rigorous molecular science with pragmatic lifestyle advice. Host Steven Bartlett guides the discussion with intense curiosity and personal anecdotes, while Dr. Bikman speaks with intense passion, clinical clarity, and a plain-spoken candor that challenges conventional medical norms. The atmosphere feels like an empowering, deep-dive masterclass that moves seamlessly between granular biological mechanisms and vulnerable personal reflections.
## Key takeaways
- [00:00](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=0s) Conventional clinical care treats conditions like type 2 diabetes, high blood pressure, and heart disease as isolated disorders, but they share a common root in insulin resistance.
- [05:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=305s) Insulin resistance manifests through impaired cellular signaling and elevated insulin levels (hyperinsulinemia), often presenting early as erectile dysfunction or PCOS.
- [23:27](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1407s) Fat cell dynamics play a critical role in metabolic health: hypertrophic (expanding) fat cells promote systemic inflammation and insulin resistance, whereas hyperplastic (multiplying) fat cells remain metabolically protective.
- [01:05:34](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3934s) Differences in personal fat thresholds and fat distribution explain why certain ethnicities, particularly East Asian populations, develop metabolic dysfunction at lower body weights due to lower subcutaneous fat capacity.
- [51:29](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3089s) The amyloid plaque hypothesis for Alzheimer's disease is flawed, and cognitive decline is better understood as brain glucose hypometabolism ('type 3 diabetes') that can be bypassed using ketones.
- [01:13:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4385s) Chronically elevated insulin suppresses autophagy and locks the body in an anabolic state, whereas lower insulin levels promote longevity, cellular cleanup, and fat oxidation.
- [01:19:17](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4757s) High cholesterol levels correlate with longer lifespans in older adults, and statins can impair mitochondrial function and hormone production by suppressing cholesterol synthesis.
- [01:22:15](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4935s) Environmental factors such as cigarette smoke, vaping emissions, diesel exhaust, and endocrine disruptors (BPA, microplastics) directly induce systemic insulin resistance and fat cell growth.
- [01:40:23](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6023s) Ketones serve as an efficient alternative fuel for the brain and increase metabolic rate in adipose tissue while protecting muscle mass from breakdown.
- [01:41:42](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6102s) Restricting dietary carbohydrates, prioritizing protein, and embracing healthy fats lower insulin levels and allow sustainable fat loss without destroying resting metabolic rate.
- [02:11:04](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7864s) Salt restriction is largely ineffective for treating hypertension because insulin resistance—which forces the kidneys to retain sodium—is the primary driver of high blood pressure.
- [02:19:22](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8362s) Muscle-building resistance training improves insulin sensitivity faster than aerobic exercise by triggering insulin-independent glucose uptake into muscle cells.
- [02:25:51](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8751s) GLP-1 drugs like Ozempic cause significant muscle and bone mass loss alongside fat loss, and natural GLP-1 release can be achieved through low-carbohydrate and high-fat meals.
- [02:34:56](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9296s) Liposuction physically removes fat cells without altering metabolic health, forcing subsequent fat accumulation into visceral depots and remaining bloated cells.
## Detailed walkthrough
### [00:00](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=0s) Overview of Insulin Resistance and Chronic Disease
The hidden epidemic of insulin resistance lies at the core of most chronic diseases killing people today. While conventional clinical care treats conditions like type 2 diabetes, high blood pressure, and heart disease as isolated disorders with separate origins, they are actually branches extending from a single, shared metabolic root. Prescribing medications to target individual symptoms is akin to merely pruning a tree's branches; the underlying issue remains untouched and the branch simply grows back.
A vast majority of adults—including 88% of adults in the United States—have some degree of metabolic dysfunction. However, this is far from just an American problem. Broad lifestyle habits, dietary patterns, and ethnic differences in fat distribution influence metabolic health across the globe. By addressing insulin levels through fundamental, simple pillars, individuals can regain control of their health and mitigate risks across a wide spectrum of life-threatening conditions.
[02:19](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=139s) Dr. Benjamin Bikman's Mission and the Discovery of "Diabesity"
Dr. Benjamin Bikman's overarching mission as a metabolic scientist and educator is to shift public and medical understanding toward this unifying metabolic foundation. Early in his academic career in the early 2000s, Dr. Bikman stumbled upon a research paper detailing how expanding fat tissue dramatically increases the risk of developing type 2 diabetes. At the time, the concept of "diabesity"—the dual epidemic where rising obesity directly parallels rising type 2 diabetes—was not widely recognized or studied.
That seminal manuscript revealed a key mechanism: as fat tissue expands, it becomes stressed and begins secreting pro-inflammatory proteins into circulation. This systemic inflammation triggers insulin resistance in other tissues throughout the body, setting off a cascade of chronic ailments:
* **Hypertension (High Blood Pressure):** The most common cardiovascular issue and a primary driver of heart disease, caused directly by insulin resistance within the blood vessels.
* **Alzheimer's Disease:** Often referred to as "type 3 diabetes" or, more accurately, insulin resistance of the brain.
* **Infertility:**
* **Erectile Dysfunction (ED):** The most common form of male infertility, caused by insulin resistance in the vascular tissue preventing proper blood flow.
* **Polycystic Ovary Syndrome (PCOS):** The primary cause of female infertility, where insulin resistance affects ovarian function and disrupts sex hormone production.
[05:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=305s) What Is Insulin Resistance?
At its core, insulin resistance is a two-sided disorder: **impaired cellular signaling** on one side, and **chronically elevated blood insulin levels (hyperinsulinemia)** on the other.
Insulin is a master hormone produced by the beta cells of the pancreas, an organ tucked beneath the stomach that manufactures both digestive enzymes for the intestines and endocrine hormones for the bloodstream. In type 1 diabetes, the immune system destroys these beta cells, making external insulin a life-saving daily necessity. In healthy individuals, beta cells release insulin primarily in response to rising blood glucose levels following the consumption of carbohydrates—whether simple sugars or complex starches found in bread, rice, chips, or plant-based foods.
> "Insulin comes out like a taxi and transports all the glucose in my blood to various places around the body to store them."
Insulin acts as a key or a bouncer knocking on the door of muscle and fat cells, signaling them to take in glucose from the blood. While other organs like the liver can take up glucose without needing insulin to open the door, insulin still serves as the master conductor telling the liver—and every other cell—what to do with energy in all its forms, including lactate, ketones, fats, and amino acids.
When a person develops insulin resistance:
1. **Cells become deaf:** Muscle and other target tissues ignore insulin's signal, refusing to take in glucose efficiently.
2. **Insulin levels spike:** To compensate for this deafness, the pancreas works overtime, creating an "angry mob of bouncers" (higher blood insulin levels) to force the doors open and lower blood sugar.
This dynamic is clearly illustrated in erectile dysfunction, which researchers have questioned as being "the earliest manifestation of insulin resistance in otherwise young, healthy men." Normally, insulin signals blood vessels to dilate and expand to increase blood flow. When vascular tissue becomes deaf to insulin, the blood vessels remain constricted, directly resulting in dysfunction.
[13:53](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=833s) The Fast Lane to Insulin Resistance: Stress and Beyond
There are two primary pathways—or "roads"—that lead to insulin resistance: the **fast lane** and the **slow lane**. Fast insulin resistance can be induced in a laboratory setting in as little as 6 hours through three primary triggers, but it can be reversed just as rapidly once those triggers are removed:
1. **Stress:** Any state of acute or chronic elevated stress triggers the adrenal glands to release stress hormones.
2. **Inflammation:** Pro-inflammatory signals directly impair insulin signaling pathways within target tissues.
3. **Hyperinsulinemia (Too Much Insulin):** Paradoxically, exposed high levels of insulin itself cause cells to downregulate their receptors, driving further resistance.
From an endocrinological perspective, stress is defined by the elevation of two distinct hormones: **cortisol** and **epinephrine** (commonly known in the UK as adrenaline). While these two hormones have vastly different cellular mechanisms, both drive the body into a heightened state of alertness—increasing heart rate, causing jitteriness, and directly counteracting insulin's ability to manage energy storage.
- **Fast Lane Characteristics:** Takes as little as 6 hours to induce; resolves quickly upon removal of the stressor or inflammatory trigger.
- **Key Stress Hormones:** Cortisol and Epinephrine / Adrenaline.
[16:11](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=971s) The Drivers of "Fast" Insulin Resistance: Stress, Inflammation, and High Insulin
The stress hormones epinephrine (adrenaline) and cortisol directly counter insulin by driving up blood glucose levels. From an evolutionary perspective, this "fight or flight" response prepares the body to run away from danger by ensuring ample energy is circulating in the bloodstream. However, when stress is sustained through modern lifestyle factors—such as sleep deprivation (which raises cortisol) or excessive caffeine intake (which strongly elevates epinephrine)—the body's insulin must work exponentially harder to keep blood sugar under control, ultimately leading to acute insulin resistance.
A similar phenomenon occurs during immune challenges and systemic inflammation. Anyone wearing a continuous glucose monitor (CGM) during an infection or seasonal illness will notice significantly elevated blood glucose levels. This spike reflects temporary insulin resistance triggered by inflammation. The same link is observable in autoimmune conditions like rheumatoid arthritis: during painful flare-ups, a patient's measured insulin resistance tracks directly with the degree of immune system activation.
```
Stress / Inflammation / High Caffeine
│
▼
Elevated Blood Glucose & Hormones (Epinephrine/Cortisol)
│
▼
Insulin Must Work Overtime
│
▼
Insulin Resistance (Fast Lane Onset)
```
High insulin itself acts as a primary trigger for insulin resistance, creating a biological feedback loop:
* **The Bouncer Analogy:** Just as sending ten bouncers to a door when one fails is the body's response to resistance, high insulin is both a cause and a consequence of cellular insensitivity.
* **Selective Deafness:** Similar to a parent becoming desensitized to a child constantly calling "Mom," muscle cells exposed to persistent insulin cease responding effectively to its signal.
* **Rapid Reversibility:** In a laboratory setting, initiating a low-dose insulin drip induces measurable insulin resistance within just a few hours. Once the infusion stops, insulin sensitivity returns to baseline within hours.
---
[21:01](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1261s) The Daily Carbohydrate Rollercoaster and High-Frequency Eating
While "fast" insulin resistance resolves quickly when the underlying stimulus is removed, modern dietary habits prevent insulin levels from ever dropping. Approximately 70% of global calories come from carbohydrates, and conventional guidelines often advise eating six times per day. Consequently, people spend virtually all their waking hours in a postprandial state with elevated insulin.
> "The average individual is spending every waking moment in a state of elevated insulin. And thus, the signal never really goes away because they never give themselves a break."
This cycle typically unfolds over the course of a day:
1. **Morning:** Overnight fasting allows insulin levels to recover. However, breaking the fast with starchy or sugary items (e.g., toast with jam, cereal, bagels) spikes blood glucose and forces a sharp rise in insulin.
2. **Mid-Morning:** Because insulin stays elevated in the bloodstream longer than glucose to ensure full clearance (often taking 3 to 4 hours to return to baseline), a mid-morning snack or sugary coffee pushes insulin back up before it ever reaches resting levels.
3. **Afternoon & Evening:** Carbohydrate-dense lunches, afternoon snacks, dinners, and late-night treats ensure that the pancreas secretes insulin continuously until bedtime.
---
[23:27](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1407s) "Slow" Insulin Resistance: Fat Cell Hypertrophy and Ethnic Differences
Beyond immediate metabolic impacts, chronically high insulin initiates "slow" insulin resistance within adipose (fat) tissue. This process takes longer to develop but is similarly slower to reverse. Metabolic health is determined not by total fat mass, but by the physical size of individual fat cells (*hypertrophy* vs. *hyperplasia*).
* **Gender Differences:** Women typically carry more overall body fat than men, yet maintain better metabolic health and insulin sensitivity. Female sex hormones promote a higher quantity of smaller fat cells (*hyperplasia*), which are naturally anti-inflammatory and insulin-sensitive.
* **Fat Cell Lifespan:** Adult fat cell counts remain relatively static. Fat cell numbers increase during infancy, childhood, and puberty, locking in by late adolescence or early twenties. Afterward, fat cells survive for roughly 10 years, shrinking or expanding based on energy storage.
```
┌───────────────────────────────┐
│ Adipose Tissue Dynamics │
└───────────────┬───────────────┘
│
┌──────────────────────────┴──────────────────────────┐
▼ ▼
Hyperplasia (More cells, smaller) Hypertrophy (Fewer cells, larger)
• Protective & insulin-sensitive • Prone to inflammation & rupture
• Common in females & Caucasians • Common in East Asian populations
```
Significant ethnic variations dictate where fat is stored and how quickly metabolic dysfunction occurs:
* **East Asian vs. Caucasian Variations:** Genetic factors influence the total number of fat cells an individual can produce. Caucasian populations generally produce a higher number of fat cells, allowing fat to be distributed across more units. East Asian populations typically produce fewer total fat cells.
* **Metabolic Consequences:** If a Caucasian male and an East Asian male both gain 10 kilograms of fat, the Caucasian individual's fat cells expand modestly, maintaining relatively normal blood pressure and blood sugar. The East Asian individual's limited number of fat cells must expand dramatically to fit the same energy volume, rapidly triggering hypertension, type 2 diabetes, fatty liver disease, and metabolic dysfunction.
---
[28:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1685s) What Makes Fat Cells Grow: The Dual Requirement of Insulin and Energy
Fat cell expansion requires two mandatory conditions: an endocrine signal instructing the cell to grow (**insulin**) and the raw material to fill it (**calories**). Neither element can expand fat cells on its own.
> "It is literally impossible for the type 1 diabetic to get fat if they are skipping their insulin injections... The body goes into such a dramatic fat burning state in the absence of insulin that keeping fat becomes impossible."
This principle is demonstrated by several key phenomena:
* **Diabulimia:** Young individuals with Type 1 diabetes sometimes skip insulin injections to shed weight rapidly while consuming unconstrained calories. This dangerous behavior constitutes a formal eating disorder known as diabulimia.
* **Petri Dish Studies:** Cultured human fat cells bathed in glucose and lipids will not expand until insulin is introduced to the medium. Within 4 hours of adding insulin, the cells absorb the surrounding nutrients and swell in size.
* **Cellular Membrane Stress:** As a fat cell expands toward its physical limit, its cellular membrane stretches like an overfilled water balloon. To prevent membrane rupture and cell death, the fat cell deliberately downregulates its insulin receptors—becoming insulin-resistant to halt further growth.
| Requirement | Biological Role | Impact Without It |
|:--- |:--- |:--- |
| **Insulin** | The indispensable signaling hormone that commands fat storage and blocks fat breakdown. | Without insulin, calories cannot be stored as fat; the body enters an unconstrained fat-burning state. |
| **Calories (Glucose & Lipids)** | The physical substrate and energy volume that fills the expanding fat cell. | Without excess calories, insulin has no substrate to build fat mass, preventing cellular hypertrophy. |
---
<ElicitationsGroup message="To explore these metabolic mechanisms further:">
<Elicitation label="Examine the link between visceral fat, liver health, and insulin resistance" query="How does hypertrophic fat expansion lead to visceral fat storage, non-alcoholic fatty liver disease, and systemic metabolic collapse?"/>
<Elicitation label="Analyze why liposuction fails to improve metabolic health long-term" query="Why does removing fat via liposuction fail to improve long-term insulin sensitivity, and how does it affect remaining fat storage?"/>
</ElicitationsGroup>
[32:44](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1964s) The Thermodynamic Waste of Low-Insulin Diets
Dr. Benjamin Bikman breaks down a powerful comparison to illustrate how insulin regulates fat storage and energy expenditure. Imagine two distinct meals containing the exact same caloric value—for example, 1,000 calories. One meal follows the conventional high-carbohydrate, low-fat model, while the other is low-carbohydrate and high-fat. Despite the equal caloric load, the low-carb version produces a significantly lower insulin response, resulting in less stored fat.
When skeptics challenge this by invoking the laws of thermodynamics—asking where the "lost" calories go if energy cannot be destroyed—Bikman explains that low insulin levels actually elevate metabolic rate. Keeping insulin low throughout the day on a lower-carbohydrate diet can increase rest energy expenditure by nearly 300 calories per day. To put that in perspective, burning 300 calories through exercise would require roughly an hour of continuous effort on a stair stepper.
Furthermore, low insulin levels accelerate fat oxidation to the point where the liver begins producing ketones. Because every ketone molecule carries a caloric value roughly equivalent to glucose, the body starts actively dumping energy into the environment. When ketones elevate in the bloodstream, they are continuously expelled through breath and urine. In a low-insulin state, the body is so determined to expend energy that it simultaneously raises its baseline metabolic rate and physically excretes unused calories into the universe.
[35:03](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2103s) The Expensive Tissue Hypothesis and Brain Evolution
To understand how to manage insulin levels, Bikman suggests exploring the evolutionary mechanisms behind human metabolism and insulin resistance. He highlights the "Expensive Tissue Hypothesis," a leading theory explaining how early humans diverged so dramatically from other primates like chimpanzees and apes. According to the theory, human ancestors shifted toward eating meat—a highly nutrient-dense, calorie-packed food rich in bioavailable fats and proteins. This nutritional upgrade sparked two major evolutionary adaptations:
1. **A Shrunken Digestive Tract:** Because meat requires far less fermentation than plant matter, the human colon shrank dramatically compared to other primates, allowing the body to redirect energy away from maintaining a massive digestive system.
2. **Rapid Brain Expansion:** The surplus of high-density calories and fats supplied the fuel needed to grow a vastly superior brain.
Ketones played a pivotal role in this cognitive expansion. Bikman points out that human infants are born with a high percentage of body fat—a physiological design specifically meant to produce abundant ketones to support brain development. If a six-month-old infant fasts for just two hours, the baby reaches a deeper state of ketosis than an adult fasting for two full days. While misinformed educators often claim that the brain prefers glucose, scientific literature demonstrates that the moment ketones enter the bloodstream, the brain rapidly switches to prioritize them as its primary fuel source. Even at a modest blood ketone concentration of 1 millimolar (compared to a normal blood glucose level of 5 millimolar), the brain already obtains more than half of its energy from ketones.
Bikman notes a newly published, controversial book title: *Vegetarians Have Smaller Brains*. He explains that human brain structure relies heavily on the dense nutrition found in animal-sourced foods. Depriving the brain of these nutrients—such as essential omega-3 fatty acids, of which only two biologically active forms come from animal sources—can impair brain health and contribute to higher rates of depression. While strict vegans can supplement to bridge this gap, doing so requires significant nutritional education and financial means.
[40:36](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2436s) Physiological vs. Pathological Insulin Resistance
Addressing why humans developed the capacity for insulin resistance, Bikman explains that it evolved as an adaptive mechanism to hold onto energy during critical physiological phases. While modern discussions focus heavily on *pathological* (harmful) insulin resistance—which drives hypertension, heart disease, and Alzheimer's—there is also *physiological* (helpful) insulin resistance that serves a vital purpose.
Physiological insulin resistance occurs naturally during the "two Ps" of human development:
* **Puberty:** Elevated insulin acts like a body-wide fertilizer, signaling tissues, muscles, bones, and fat stores to expand rapidly during explosive growth spurts.
* **Pregnancy:** Insulin levels rise to support the massive tissue growth required to build the placenta and enlarge the uterus, while also directing extra energy toward breast tissue and fat reserves.
During pregnancy, a mother's body becomes temporarily insulin resistant to shunt additional glucose toward the developing fetus. Progesterone accelerates this energy storage, ensuring the mother builds up sufficient fat reserves to survive potential food scarcity and successfully lactate after childbirth.
[43:39](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2619s) Gestational Diabetes and Intergenerational Health
Gestational diabetes is essentially a short-term, pregnancy-induced form of type 2 diabetes. In a healthy pregnancy, a woman experiences normal physiological insulin resistance; her insulin levels rise to support fetal growth while her blood glucose remains stable. However, in women with an underlying genetic predisposition—compounded by high-sugar, refined-carbohydrate diets—the body's insulin resistance spirals out of control. Insulin remains elevated, but it can no longer keep blood glucose levels within a safe range.
This condition directly affects the developing child. Developing in a hyperglycemic and hyperinsulinemic womb "hardwires" the baby's metabolic pathways to expect high insulin and glucose levels after birth.
* Children born to mothers with gestational diabetes face a **40% higher risk of obesity** and subsequent metabolic complications throughout their teenage years and adult life.
* These infants carry a significantly higher probability of developing type 2 diabetes later in life.
[46:00](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2760s) Explaining the Surge in Female Cancer Rates
Steven Bartlett brings up a recent chart circulating on social media regarding cancer trends over the past two decades. The data shows a sharp upward trajectory in cancer diagnoses among women under the age of 49, whereas cancer incidence among men in the same age bracket has remained relatively flat.
Bikman offers several key factors driving this trend:
1. **Increased Screening Rates:** Part of the spike may be a diagnostic artifact caused by younger women undergoing more frequent health screenings, such as mammograms, MRIs, and ultrasounds, catching early-stage cancers that previously went undetected.
2. **Spike in Breast Cancer:** Breast cancer accounts for the vast majority of cancer cases in women under 50.
3. **Decreased and Delayed Childbearing:** Early pregnancy and lactation alter estrogen dynamics in ways that significantly protect against breast cancer. As modern birth rates fall and women delay having children, this natural protective factor decreases.
4. **Rising Obesity Rates:** Higher body fat directly elevates systemic insulin and estrogen levels, both of which serve as growth signals that promote tumor development.
<FollowUp label="Want to explore the next section on Alzheimer's and fat distribution?" query="Please continue with the next part of the transcript covering Alzheimer's, ethnic fat distribution, and strategies for longevity."/>
[48:53](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2933s) The Cellular Mechanism Behind Breast Cancer and High Insulin
Dr. Benjamin Bikman shifts to a cell-biological perspective to explain why breast cancer rates track so closely with rising obesity over the last two decades. While he acknowledges non-mechanistic theories—such as declining childbirth rates among women—he stresses that as a cell biologist, he is drawn to direct, verifiable mechanisms. When researchers compare a cancerous breast tumor directly to normal, healthy tissue right next to it (which shares the exact same cellular origin), they consistently observe that the cancer cells express **seven times more insulin receptors** than the normal tissue.
He explains that this is not necessarily caused by obesity in isolation, but by the underlying "metabolic milieu"—specifically, elevated circulating insulin. While high insulin instructs fat cells to expand, it simultaneously acts as an accelerator on tumor cells. Insulin is inherently an anabolic hormone that tells cells to grow; unregulated growth is the very definition of cancer. Thus, the correlation between rising obesity and breast cancer is most directly explained by the growing prevalence of hyperinsulinemia and insulin resistance.
Steven Bartlett takes a brief pause to discuss one of the show's key sponsors, Whoop. He highlights his personal investment in the company and answers the most frequent audience question regarding why he prefers Whoop over competing wearables. He attributes this choice primarily to its non-invasive, screen-less design. He recounts a conversation with Whoop CEO Will Ahmed, who emphasized that screens equal distraction; by omitting a display, the device gathers continuous physiological data without interrupting meetings or workouts.
---
[51:29](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3089s) Alzheimer's, Dementia, and the Collapse of the Amyloid Plaque Theory
Returning to the main conversation, Steven points out that dementia now accounts for a new diagnosis every **3.2 seconds** worldwide, questioning whether Alzheimer's disease is truly on the rise. Dr. Bikman confirms that Alzheimer's has rapidly escalated from relative obscurity to a top 10 killer in Western nations. He asserts that this surge is driven by its underlying metabolic origin, challenging the conventional amyloid plaque paradigm that has dominated medical research for decades despite billions of dollars in funding.
Dr. Bikman outlines two major flaws in the plaque-based theory:
* **Pharmaceutical Failure:** Multiple drugs capable of successfully clearing amyloid plaques from human brains completely failed to reverse cognitive decline or improve patient outcomes.
* **Autopsy Discrepancies:** Post-mortem brain evaluations regularly reveal identical distributions of amyloid plaques in both severe Alzheimer's patients and individuals who died with pristine cognitive function.
> "The plaque-based theory doesn't make sense... You would be just as likely to find plaques in both brains."
He adds that the foundational research papers originally establishing the amyloid plaque hypothesis were exposed two to three years prior as containing **fabricated, fraudulent data**. With the plaque hypothesis falling apart, researchers are increasingly acknowledging that Alzheimer's is fundamentally rooted in metabolic dysfunction.
---
[54:44](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3284s) Brain Glucose Hypometabolism and the "Type 3 Diabetes" Concept
While Dr. Bikman dislikes the popular media moniker "Type 3 Diabetes"—preferring the term **insulin resistance of the brain**—he validates the core concept. He categorizes the brain within a "trinity of high metabolic rate organs" alongside two other hyper-demanding tissues, noting that the brain consumes immense energy relative to its size. Under normal conditions, the brain relies almost exclusively on two fuels: **glucose** and **ketones**.
```
+-------------------------------------------------------------------+
| BRAIN METABOLIC ENERGY GAP IN ALZHEIMER'S |
| |
| Healthy Brain Energy: |
| [========================= GLUCOSE =========================] |
| |
| Insulin Resistant Brain: |
| [========== GLUCOSE ==========][??? ENERGY GAP???] |
| │ |
| Requires Ketones to Fill |
| (Blocked by High Insulin) |
+-------------------------------------------------------------------+
```
In regions of the brain affected by Alzheimer's, glucose cannot enter cells freely; it requires insulin to bind to receptors and unlock cellular doors, identical to the mechanism in skeletal muscle. When the brain becomes insulin resistant, glucose uptake plummets—a clinical condition known as **brain glucose hypometabolism**. If a person's diet keeps blood glucose and insulin constantly elevated, ketone production is fully suppressed, leaving the brain stranded with an energetic shortfall. Lacking sufficient fuel, brain cells downregulate function, manifesting as cognitive decline.
Dr. Bikman points out that this exact pattern of impaired glucose metabolism is not unique to Alzheimer's; it appears across a spectrum of neurological conditions:
Because all of these disorders share underlying cerebral energy starvation, flooding the brain with ketones can provide an alternative fuel source that bypasses impaired insulin signaling.
---
[59:06](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3546s) Clinical Diagnostics and Testing for Insulin Resistance
Steven cites conflicting literature regarding the prevalence of insulin resistance among Alzheimer's patients, noting that some studies place the figure at **40%** (such as a 2011 paper in the *Journal of Neurology*), while others—such as research by Dr. Suzanne de la Monte at Brown University—find rates as high as **70% to 80%**. Dr. Bikman attributes this disparity to poor diagnostic methodology, observing that clinicians who only measure blood glucose consistently miss early-stage insulin resistance.
```
+-------------------------------------------------------------------+
| FASTING INSULIN CUT-OFF THRESHOLDS |
| |
| US Standard Units: > 10 µIU/mL ──► Elevated (Warning Sign) |
| UK Standard Units: > 40 pmol/L ──► Elevated (Warning Sign) |
+-------------------------------------------------------------------+
```
Dr. Bikman laments the systemic barriers that prevent patients from obtaining fasting insulin tests. In centralized medical systems like the UK's NHS or Canada, general practitioners frequently decline to order fasting insulin, incorrectly dismissing it as clinically irrelevant. He emphasizes that fasting glucose remains normal for years while insulin quietly spikes. For those able to secure testing, he offers clear cut-off guidelines for elevated fasting insulin:
* **US Units:** Anything above **10 µIU/mL** indicates potential insulin resistance.
* **UK/Metric Units:** Anything above **40 pmol/L** serves as an early warning sign.
---
[01:01:50](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3710s) Lean Phenotypes, PCOS, and Ethnic Differences in Fat Distribution
Addressing common misconceptions, Dr. Bikman clarifies that a low body mass index does not guarantee insulin sensitivity. He points to research conducted in northern Canada on young, healthy-weight women with **Polycystic Ovary Syndrome (PCOS)**, who exhibited significant insulin resistance compared to age- and weight-matched controls. Responding to Steven's query about a female friend with PCOS who gains weight easily, Dr. Bikman confirms this experience is typical: chronically high baseline insulin actively prevents fat oxidation and accelerates storage. Encouragingly, clinical literature demonstrates complete reversal of PCOS symptoms through targeted dietary interventions.
```
+-------------------------------------------------------------------+
| ETHNIC FAT STORAGE DIFFERENCES |
| |
| Demographic Adipocyte Count Metabolic Risk Profile |
| ─────────── ─────────────── ────────────────────── |
| East Asian Fewer / Lower Cap High risk at lower BMI |
| Caucasian Intermediate Moderate expansion cap |
| Black/African Higher Capacity Higher BMI tolerance |
+-------------------------------------------------------------------+
```
The discussion shifts to ethnic variations in adipose tissue structure. Dr. Bikman corrects a mistranscription in Steven's research notes regarding East Asian populations: while East Asians have fewer total fat cells and are resistant to *obesity* (visual weight gain), they are exceptionally vulnerable to *metabolic dysfunction* and Type 2 diabetes at much lower body weights due to limited subcutaneous fat storage capacity. Conversely, individuals of African descent typically possess a higher capacity for subcutaneous fat expansion, allowing them to carry higher body mass before experiencing profound systemic insulin resistance.
<ElicitationsGroup message="Explore further details from this conversation:">
<Elicitation label="Examine how ketones bypass insulin resistance in the brain" query="How do ketones bypass insulin resistance in the brain to supply fuel?"/>
<Elicitation label="Review the connection between PCOS and high insulin levels" query="Explain the connection between Polycystic Ovary Syndrome (PCOS) and insulin resistance."/>
</ElicitationsGroup>
Here is a detailed, faithful walkthrough of this transcript section.
---
[01:04:24](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3864s) Ethnicities and the "Personal Fat Threshold"
The conversation opens with a discussion on how ethnicity and genetics dictate the way human bodies store fat and handle metabolic stress. Dr. Benjamin Bikman explains that different ethnic groups fall along a spectrum regarding their sensitivity to fat accumulation and their capacity to store it safely. African and Northern European ethnicities sit at one end of the spectrum, possessing a high tolerance for storing fat without immediately suffering metabolic harm. Moving along the spectrum, Latino and Hispanic populations fall somewhere in the middle, while East Asian and Southeast Asian groups land on the most sensitive end—meaning their bodies experience adverse metabolic consequences at significantly lower fat levels.
This phenomenon aligns with a concept known as the **"personal fat threshold,"** an idea originating from research teams in Australia. Every individual body—heavily influenced by both sex and ethnicity—has a maximum limit or rate at which it can expand its fat stores in a metabolically healthy way. Once an individual's body reaches that threshold, any additional demand to store fat forces the cells into a state of metabolic distress, triggering insulin resistance. The threshold is dictated by how many fat cells a person possesses and how much physical room those cells have to expand. In simple terms, having a higher number of fat cells grants a person a higher fat threshold, allowing them to gain more weight before it causes physiological harm.
```
+-----------------------------------------------------------------------------------+
| PERSONAL FAT THRESHOLD |
+-----------------------------------------------------------------------------------+
| [ Higher Threshold / Safer Storage ] [ Lower Threshold ] |
| |
| Northern European / African -----> Latino / Hispanic -----> East Asian / |
| Southeast Asian |
| |
| * High subcutaneous fat capacity * High visceral fat |
| * Ability to create new fat cells * Cell hypertrophy |
| * Lower relative risk at higher weight * Early metabolic |
| distress |
+-----------------------------------------------------------------------------------+
```
- The personal fat threshold defines the point where healthy fat storage ends and insulin resistance begins.
- Individuals with more fat cells can store more fat before experiencing metabolic dysfunction.
- Susceptibility to metabolic disease varies heavily by genetic background and population origin.
---
[01:05:34](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3934s) Fat Distribution: Subcutaneous vs. Visceral Adipose Tissue
Steven Bartlett brings up research demonstrating how fat distribution differs dramatically across racial backgrounds and asks how location changes risk profiles. Dr. Bikman clarifies the two distinct anatomical locations where the body stores fat:
1. **Subcutaneous adipose tissue:** The layer of fat sitting directly beneath the skin—the "loose belly fat" that can be pinched and jiggled.
2. **Visceral adipose tissue:** The deep fat packed tightly within the abdominal cavity, wrapped around vital organs such as the liver, kidneys, and intestines.
Northern European and African populations store a higher proportion of their body fat in subcutaneous depots. Subcutaneous fat possesses the ability to form new fat cells (hyperplasia) when overloaded. While fat cell numbers remain relatively static throughout adult life, subcutaneous tissue maintains a small degree of flexibility to recruit new cells. This allows the body to distribute incoming lipids across more cells, keeping individual cell size smaller and healthier.
Conversely, East Asian, Southeast Asian, and Hispanic populations store a much higher proportion of fat viscerally. The abdominal cavity is a strictly bounded, finite space. Because space is so constrained, visceral fat cannot safely multiply or recruit new cells without physically compressing surrounding organs like the kidneys and digestive tract. As a result, visceral fat cells cannot increase in number; they can only expand in size through **hypertrophy**. As established earlier in their discussion, large, bloated fat cells become inflamed, sicker, and severely insulin resistant. Therefore, populations prone to visceral fat accumulation suffer metabolic consequences at much lower body weights.
- Subcutaneous fat sits beneath the skin, can expand via new cell creation, and acts as a relatively inert storage buffer.
- Visceral fat surrounds core organs, expands purely through cell enlargement (hypertrophy), and rapidly causes tissue dysfunction.
- "The bigger the fat cell, the sicker the fat cell"—cell size rather than total weight dictates cellular health.
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[01:07:48](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4068s) Visceral Fat Transplants and Alzheimer's Disease
Steven highlights a striking statistic from Alzheimer's Disease International: the global population living with dementia is projected to rise from 55 million in 2020 to 139 million by 2050. While part of this increase stems from modern medical interventions keeping people alive longer with chronic illnesses, Dr. Bikman stresses that it is primarily driven by our deteriorating metabolic environment. Chronic elevated insulin levels render the brain insulin resistant, effectively starving brain cells of the energy they need to function.
To illustrate the inherent toxicity of visceral fat, Dr. Bikman details a landmark animal study. Researchers surgically removed subcutaneous fat from an obese animal and transplanted it into a lean animal; the receiving animal remained completely healthy because subcutaneous fat is biologically inert. However, when researchers transplanted **visceral fat** from an obese animal into a lean animal, the recipient immediately developed systemic insulin resistance and became diabetic. This demonstrates that visceral fat itself actively secretes harmful inflammatory signals and causes systemic metabolic harm.
> "Subcutaneous fat is inert. It really is just sort of hanging out there and minding its own business. But, in that same study, if you move the visceral adipose over, now all of a sudden that animal that got that extra dose of visceral fat is going to become sicker."
- Global dementia cases are projected to reach 139 million by 2050, driven heavily by brain insulin resistance.
- Transplanting subcutaneous fat between animals causes no metabolic harm.
- Transplanting visceral fat instantly induces systemic insulin resistance and diabetes in healthy recipient animals.
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[01:10:03](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4203s) Longevity Science vs. "Longevity Gurus"
Steven brings up biohacker Bryan Johnson—who has become a prominent public figure in the anti-aging space—and asks Dr. Bikman for his assessment of modern longevity protocols. Dr. Bikman carefully distinguishes between genuine, rigorous longevity research conducted by academic scientists and the sensationalized claims made by self-proclaimed "longevity gurus." He acknowledges that modern biohackers enjoy a commercial advantage: because their goal is extending human lifespan decades into the future, their claims cannot easily be proven wrong in the short term.
Dr. Bikman points out that many popular anti-aging protocols rely on weak, flawed evidence—specifically correlational human studies and basic animal or insect research. Correlational dietary studies rely on self-reported food surveys, which are notoriously inaccurate because people forget, lie, or fail to account for massive confounding variables. For example, people who belong to tight-knit social or religious groups live significantly longer, while severe loneliness is a far deadlier health risk than cigarette smoking. Epidemiological studies routinely misattribute longevity to specific dietary choices while ignoring these massive social factors.
- Academic longevity science must be distinguished from commercial "longevity guru" culture.
- Longevity claims often rely on observational survey data that cannot establish cause and effect.
- Confounding lifestyle factors—such as strong social connection versus chronic loneliness—exert a far larger impact on lifespan than minor dietary variances captured in surveys.
---
[01:13:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4385s) The Metabolic Foundation of Longevity and Autophagy
Dr. Bikman frames longevity through his perspective as a metabolic scientist, pointing back to the foundational work of researcher **Cynthia Kenyon**. Kenyon pioneered modern aging research using the roundworm model (*C. elegans*). Her laboratory discovered that restricting glucose intake extended the worms' lifespan by 50%. More importantly, when her team genetically knocked down or underexpressed the genes controlling **insulin signaling**, the worms lived significantly longer *without* any food restriction.
This discovery highlighted the cellular process of **autophagy**—the cell's internal recycling mechanism where it cleans out damaged proteins and organelles. Autophagy is widely accepted as a primary driver of longevity. While the anti-aging community heavily promotes prolonged fasting to trigger autophagy, Dr. Bikman explains that fasting works simply because it lowers circulating **insulin**. Insulin acts as a master biochemical switch that suppresses autophagy.
Metabolism consists of two opposing forces:
- **Anabolism (building up):** Driven by high insulin levels.
- **Catabolism (breaking down):** Enabled when insulin levels drop.
When insulin remains chronically elevated, the body is locked in a perpetual anabolic state and cannot engage in catabolic cleanup. Unchecked cellular growth without breakdown creates an ideal environment for diseases of proliferation, such as cancer. Conversely, lowering insulin through fasting or a **ketogenic diet** allows autophagy to occur. Dr. Bikman notes an animal study where mice fed a ketogenic diet lived significantly longer than littermates fed standard high-carbohydrate chow, even when eating equal calories without restriction.
> "The very word metabolism encompasses anabolism, which is anabolic or building up, and catabolism or catabolic, which is breaking down. The key to a healthy growing living cell is this nice ongoing balance of build and break."
- Cynthia Kenyon proved that reducing insulin gene expression extended lifespan in laboratory models without calorie restriction.
- Insulin is a powerful direct inhibitor of cellular autophagy.
- A ketogenic diet lowers insulin and permits autophagy even in the absence of calorie restriction.
- Chronically elevated insulin suppresses cellular breakdown, accelerating aging and creating fertile ground for cancer growth.
---
[01:18:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4685s) What Centenarians Have in Common: Glucose, Insulin, and Cholesterol
Steven shares that he is currently following a ketogenic diet and is eager to explore its specific physiological impacts. Dr. Bikman highlights a key finding from his book, *Why We Get Sick*: across human populations, the longest-lived individuals systematically display high insulin sensitivity and low resting insulin levels.
He points to a comprehensive epidemiological study from Sweden—a nation known for its meticulous public health record-keeping and relatively homogeneous population, which minimizes confounding variables. Researchers tracked long-term health metrics to identify common physiological traits among individuals who lived exceptionally long lives. The data revealed two primary traits common to centenarians:
1. **Excellent blood glucose and insulin control:** Maintaining stable, low blood sugar and minimal insulin requirements over time.
2. **Higher circulating cholesterol levels:** A finding that runs counter to conventional dietary guidelines, yet remains one of the most consistent themes in longevity literature.
Dr. Bikman concludes this segment by noting how ironic it is that modern medicine remains fixated on lowering cholesterol, even though higher cholesterol levels are consistently correlated with extreme human longevity.
- Studies tracking centenarians consistently show that superior insulin sensitivity and tight glucose control correlate with extreme longevity.
- Meticulous population data from Sweden confirms that long-lived individuals maintain high insulin sensitivity.
- Long-lived individuals frequently exhibit higher overall cholesterol levels, challenging traditional medical assumptions about cholesterol and lifespan.
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[01:19:17](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4757s) High Cholesterol, Longevity, and the "Molecule of Life"
The discussion opens with a counterintuitive perspective on cholesterol: prescribing cholesterol-lowering drugs the moment numbers tick up might be the complete wrong strategy for helping people live longer. A major Swedish study published around 2023–2024 evaluated the biomarkers of some of the longest-living humans on record and found two primary recurring themes: exceptional blood glucose control and **high cholesterol**. Dr. Benjamin Bikman proudly describes himself as a "great defender of cholesterol," declaring it to be an essential "molecule of life."
The necessity of cholesterol spans critical physiological functions across the entire human body:
* **Mitochondria:** The very powerhouses of our cells require cholesterol embedded within their membranes to function properly; aggressively lowering cholesterol via drug interventions compromises mitochondrial vitality.
* **Sex Hormones:** All sex hormones (including testosterone and estrogen) are chemically built on a cholesterol backbone. When patients take heavy doses of statins or other cholesterol-lowering medications, sex hormone levels drop, leading many men to suffer a devastating loss of libido due to low testosterone.
* **Immune Function:** The conventional binary narrative of "good" (HDL) versus "bad" (LDL) cholesterol is oversimplified. LDL is actually an unsung hero of the immune system that directly helps the body fight off infections.
Steven points out studies showing that in very old age, elevated cholesterol levels no longer correlate with higher mortality and often correlate with a longer lifespan. Bikman agrees, arguing that our modern anti-cholesterol hysteria is what is truly bizarre. He offers a candid, self-described "cynic's view" of biomedical research: modern medicine is obsessed with tracking glucose over insulin, and LDL cholesterol over triglycerides, simply because pharmaceutical companies have profitable, well-designed drugs to lower glucose and LDL. Because there are no patented drugs that directly lower insulin or effectively crush triglycerides—which can be easily controlled through diet—the medical industry ignores those far more predictive risk factors in favor of actionable drug targets.
[01:22:15](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4935s) Smoking, Vaping, and Pollution: Unseen Drivers of Insulin Resistance
Turning to surprising environmental triggers of metabolic disease, Steven highlights a Bulgarian study where seven healthy non-smokers smoked just four cigarettes a day for three days, instantly developing measurable insulin resistance. Bikman confirms that smoking triggers a severe influx of toxins and a powerful systemic inflammatory response, which rapidly disrupts insulin signaling. When asked about vaping, Bikman reveals that in collaboration with his colleague and lung specialist Dr. Paul Reynolds, their lab published findings showing that hyper-heated vape emissions produce results equal to—or chemical-for-chemical, potentially **worse** than—filtered traditional cigarettes regarding airway damage, inflammation, and insulin resistance.
When Steven asks if smoking makes people fat, Bikman explains that while the inflammatory damage would theoretically cause weight gain, smoking acts as an appetite suppressant that replaces food cravings. Interestingly, when smokers try to quit, they often switch addictions to physical comfort foods—specifically carbohydrates like hard candies carried in their pockets—leading to substantial weight gain. Bikman notes that across all human addiction literature, people only exhibit true addictive behaviors toward carbohydrates, with zero evidence for addictive responses to pure fats or proteins.
Bikman also details his 2024 study published in the *International Journal of Molecular Sciences* regarding diesel exhaust particulates:
* Animal models exposed to aerosolized diesel exhaust particulates for a controlled period developed significantly larger fat cells (hypertrophy), increased total fat mass, elevated systemic inflammation, and severe insulin resistance—even while eating the **exact same number of calories** as control animals breathing room air.
* Bikman deliberately conducted this study to dismantle the simplistic "calories in, calories out" (CICO) model of obesity, demonstrating that environmental toxins can force fat cells to expand regardless of energy intake.
* Epidemiological data mirrors these findings: geographic populations living in high-pollution areas consistently show higher rates of obesity and type 2 diabetes, though correlational confounding factors exist.
* Inhaled and ingested non-caloric toxins like microplastics enter fat tissue and directly trigger adipocyte expansion. Endocrine disruptors found in plastics and soaps, such as **BPA** and **DES** (diethylstilbestrol), act as estrogen mimetics that tell fat cells to store fat and grow, directly imitating insulin's signal.
[01:31:04](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=5464s) Ketosis and How Insulin Controls Fuel Selection
The conversation pivots to ketosis and the ketogenic diet, which Steven shares he is currently following. Bikman breaks down the metabolic biochemistry, describing the human body as a "metabolic hybrid" designed to run primarily on two fuel sources: glucose (blood sugar) and fat. While the brain can utilize either glucose or ketones, the rest of the body relies on switching between sugar and fat burning.
Insulin acts as the master fuel switch. High insulin levels lock the body into sugar-burning mode, which can be measured using an indirect calorimeter to track the Respiratory Exchange Ratio ($\text{RER}$)—the ratio of carbon dioxide ($\text{CO}_2$) produced to oxygen ($\text{O}_2$) consumed. A higher $\text{RER}$ indicates active glucose oxidation, whereas dropping insulin shifts the body into fat-burning mode, lowering the $\text{RER}$.
* When a person fasts or restricts carbohydrates so that insulin remains low for roughly **16 consecutive hours**, the liver experiences a metabolic transition.
* The liver burns significant amounts of fat—both its internal fat stores and free fatty acids leaking out from shrinking adipose tissue.
* Eventually, the liver satisfies all its internal energy needs. However, because insulin remains suppressed, the liver cannot stop processing incoming fats.
* To manage this excess fat energy, the liver begins converting fatty acids into **ketones**, releasing them into the bloodstream as a clean, highly efficient alternative energy source for the brain and body.
[01:33:43](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=5623s) Ketones as the Ultimate Brain Fuel and Fat-Cell Burner
Dr. Benjamin Bikman explains that when insulin stays low, the body's fat-burning process runs continuously. Because glucose levels drop, the liver burns fat at such an accelerated rate that it eventually exceeds its immediate energy needs. That excess fat breakdown produces ketones, functioning almost as a "metabolic release valve" for liver cells to feed an energy-hungry brain. Anyone who fasts for just 24 hours wakes up in some degree of ketosis, proving it is a natural, routine human state rather than an extreme anomaly.
Ketones serve as exceptional fuel for the brain, offering profound therapeutic potential for neurological conditions like Alzheimer's disease. In published case studies, early-stage Alzheimer's patients struggled with simple cognitive tasks—such as attempting to draw an analog clock face or tie their shoelaces—resulting in utter chaos. Yet, when placed in ketosis, those same individuals could draw recognisable clock faces, dress themselves, and tie their shoes. Beyond brain function, Dr. Bikman's lab published research showing that human belly fat tissue cultured in a state of ketosis experienced a threefold increase in its metabolic rate compared to non-ketotic states, transforming sluggish fat cells into active, energy-burning units similar to muscle cells.
Furthermore, studies demonstrate that when muscle cells are incubated with ketones, they become significantly more resistant to stress and injury. Ketones act as a "defender of muscle," signaling the brain to consume ketone bodies for fuel rather than stripping protein from muscle tissues. Because of this ergogenic benefit, top elite athletes—including the championship-winning cross-country teams at Brigham Young University (BYU) and teams competing in the Tour de France—utilize ketone supplements to protect muscle and sustain high-level energy without relying purely on glycogen.
* Ketosis elevates the metabolic rate of belly fat tissue by $3\times$ ($300\%$).
* Ketones protect muscle tissue from breakdown by preventing gluconeogenesis from muscle protein.
* BYU's men's and women's cross-country national championship teams and Tour de France cyclists use exogenous ketone drinks before training and races.
[01:39:16](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=5956s) Exogenous Ketone Supplements and Instant Ketosis
Dr. Bikman breaks down the spectrum of exogenous ketone supplements available on the market:
* **Ketone Salts:** The cheapest and most widely available option, which binds a ketone molecule to minerals like calcium or magnesium. However, they are less effective and high mineral loads can cause side effects like dental plaque or kidney stones.
* **Ketone Esters:** Typically sold as concentrated liquid shots, offering a stronger spike in circulating ketones.
* **Bioidentical BHB (e.g., Original Ketone):** Highly effective bioidentical formulations that reliably elevate blood ketone levels, with prices becoming increasingly competitive.
Drinking a shot of bioidentical ketones rapidly absorbs through the gut. Even after consuming a high-carb meal like two bagels and a sugary coffee—which spikes insulin and shuts down endogenous ketone production—taking an exogenous ketone shot can bump blood ketone levels up to $1\text{ mmol/L}$ within an hour. While human clinical trials on immediate cognitive enhancement from acute shots are still evolving, animal studies from Dr. Bikman's lab showed that animals given ketones navigated mazes faster, solved problems better, and retained memory far more effectively.
[01:41:12](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6072s) Why "Eat Less, Exercise More" Fails and How Low Insulin Unlocks Weight Loss
Steven shares his personal experience on a ketogenic diet, noting that checking his blood ketones showed readings reaching $2.5\text{ mmol/L}$, accompanying a dramatic loss of body fat. Dr. Bikman uses this breakthrough to contrast the low-carb approach with conventional calorie-restriction diets. Standard advice tells people to "eat less and exercise more," but Dr. Bikman illustrates why this fails using a thought experiment: if you were invited to a massive gourmet buffet and wanted to arrive as hungry as humanly possible, you would eat less beforehand and exercise heavily. Thus, standard weight loss advice is literally the perfect recipe to maximize hunger—and "hunger always wins."
Dr. Bikman highlights the US reality TV show *The Biggest Loser* as a prime example of severe caloric restriction. A study published by the National Institutes of Health (NIH) followed former contestants and revealed that their extreme regimen "broke" their metabolism. Normally, metabolic rate tracks body weight; as weight drops, metabolic rate decreases, and as weight is regained, metabolic rate rises back up. However, *The Biggest Loser* contestants suffered a permanently suppressed metabolic rate even after regaining their weight, leaving their metabolism functioning well below normal baseline levels.
When individuals cut calories without lowering insulin, high insulin keeps their body in energy-storage mode, triggering extreme hunger. Research by Harvard professor David Ludwig shows that low-calorie meals that spike insulin cause far more hunger than low-calorie meals that keep insulin stable. To sustainably shrink fat cells and unlock the body's massive internal energy stores (resembling a camel's hump), individuals must follow three simple diet principles:
1. **Control carbohydrates:** Cut out processed carbs from bags, boxes, and barcodes.
2. **Prioritize protein:** Focus on essential protein sources.
3. **Don't fear natural fat:** Pair healthy fats with protein for maximum satiety.
* Blood ketone levels around $2.5\text{ mmol/L}$ indicate robust nutritional ketosis and low insulin levels.
* NIH research on *The Biggest Loser* contestants proved that extreme caloric restriction suppresses long-term resting metabolic rate even after weight regain.
* Carbohydrates spike insulin and lock fat inside cells; lowering insulin allows the body to access hundreds of thousands of stored fat calories naturally, reducing appetite without forcing starvation.
[01:47:53](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6473s) Steven's Keto Experience: Brain Power, Hunger, and Fat Loss
Steven Bartlett shares his personal, striking observations from adopting a ketogenic diet, noting how dramatically it impacts his mental clarity. During podcasting or public speaking—where he used to feel a strange disconnect between his brain and mouth—being in ketosis gives him intense, effortless focus. He describes feeling as though his world opens up with heightened clarity, completely eliminating the brain fog that previously varied unpredictably.
Beyond mental sharpness, Steven highlights three significant physical changes: his appetite control shifted dramatically, causing him to get full quickly and stop binging; his energy levels remained steady throughout the day without afternoon slumps; and his body fat dropped rapidly. He describes a literal "cliff edge" drop in weight on his smart scale within a matter of weeks. However, this extreme loss led to a major concern: losing visible muscle mass. After his girlfriend pointed out that he looked leaner than ever but noticeably smaller, Steven sought ways to preserve muscle mass while maintaining a ketogenic lifestyle.
* **Cognitive Benefits:** Sudden elimination of brain fog and an ability to articulate thoughts effortlessly during long interviews and public speaking.
* **Appetite & Energy:** Reduced hunger, quick satiety without binge eating, and complete removal of afternoon energy crashes.
* **Fat Loss:** Rapid loss of abdominal fat within a few weeks, visible as a sharp downward drop on digital weight scales.
* **The Dilemma:** Significant loss of muscle volume alongside fat loss, prompting questions on how to stay lean without shrinking.
---
[01:51:04](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6664s) Preserving Muscle Mass and Hydration on Keto
Dr. Benjamin Bikman validates Steven's experience while clarifying that peer-reviewed literature proves humans can maintain total muscle mass and strength on a ketogenic diet. Addressing Steven's muscle loss, Dr. Bikman hypothesizes two main culprits: electrolyte imbalance and accidental calorie deficits. When insulin levels drop on keto, the hormone aldosterone decreases, causing the kidneys to rapidly excrete salt and water. This rapid drop in fluid is why blood pressure normalizes so quickly—often requiring patients to stop blood pressure medications within two days to avoid hypotension—but it can also lead to dehydration, weaker workouts, and less muscle fullness if fluid and salt intake aren't actively increased.
Secondly, Dr. Bikman notes that muscle is "metabolically expensive" for the body to maintain. As body fat drops significantly, the body reaches a threshold where it must decide between fasting and starvation. He references the world-record fast of Angus Barbieri in the UK, who went 384 days without eating a single calorie under medical supervision without starving because he had adequate body fat. Starvation begins when fat reserves run out; at that point, if the brain lacks sufficient fat-derived ketones for fuel, it forces the liver to convert muscle amino acids into glucose via gluconeogenesis.
* **Aldosterone Mechanism:** Dropping insulin lowers aldosterone, prompting the kidneys to flush out water and sodium rapidly.
* **Hypertension Reversal:** High blood pressure often normalizes within 48 hours on a ketogenic diet due to fluid and sodium excretion.
* **Fasting Record:** Angus Barbieri fasted for 384 days in the UK under medical supervision, surviving solely on fat reserves, vitamins, minerals, and water.
* **Gluconeogenesis:** When body fat drops too low to generate enough ketones for the brain, the body breaks down muscle protein into amino acids to synthesize glucose.
* **Dr. Bikman's Solution:** Increase dietary fat intake—such as adding butter to steak or morning coffee/tea—to supply adequate calories and protect lean muscle mass. Dr. Bikman shares that during his annual January carnivore reset, adding butter to his morning yerba mate helps him maintain muscle mass while dropping body fat.
---
[01:55:25](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6925s) Downsides, Metabolic Flexibility, and the Gut Microbiome
When asked about the potential downsides of a ketogenic diet, Dr. Bikman first reiterates its immense secondary benefits, including direct anti-inflammatory effects and reduced oxidative stress. However, he notes one temporary trade-off: a temporary reduction in metabolic flexibility. Metabolic flexibility refers to the body's seamless ability to switch between burning glucose when carbohydrates are consumed and burning fat when they are absent. After prolonged keto adaptation, the body becomes so efficiently locked into fat-burning mode that consuming a heavy carbohydrate meal (like two bagels and a sugary drink) causes blood glucose to remain elevated much longer than normal—taking up to 180 minutes to clear instead of 90 minutes.
The discussion pivots to the gut microbiome after Steven mentions a nutritionist warning him, "Oh, your poor gut," regarding his keto diet. Dr. Bikman forcefully refutes the idea that lowering carb or fiber intake harms the microbiome, calling such claims unscientific. He highlights a recent case study tracking an individual transitioning from a standard omnivorous diet to a zero-carb, purely carnivorous diet, which documented zero change in microbiome diversity or composition.
* **Metabolic Flexibility:** Prolonged keto adaptation locks the body into fat oxidation; a sudden heavy carb intake can take up to 180 minutes to clear from the bloodstream compared to 90 minutes in carb-adapted individuals.
* **Microbiome Volatility:** Microbiome compositions fluctuate constantly based on air quality, drinking water, and travel location (e.g., flying from Utah to California), making isolated gut readings difficult to interpret.
* **Alternative Microbial Fuel:** Gut bacteria do not strictly rely on fiber; they can metabolize amino acids, short-chain fatty acids, fats, and trace glycogen found in meat.
* **Questioning Diversity:** Dr. Bikman challenges the popular dogma that high plant diversity equals a healthier gut, noting that increased fiber fermentation often just increases gas production and flatulence without proven health improvements over clinical outcomes like reversed diabetes or lower insulin.
[02:02:42](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7362s) The Gut Microbiome vs. Overall Human Health
Steven Bartlett and Dr. Benjamin Bikman debate the true value of gut microbiome diversity when measured against concrete clinical outcomes. Dr. Bikman pushes back against the common assumption that high bacterial diversity automatically equates to superior human health. He argues that if an individual successfully reverses metabolic conditions like type 2 diabetes and hypertension, a slight reduction in bacterial diversity in their gut is largely irrelevant. He points out that much of the narrative around microbiome diversity is speculative, questioning whether promoting bacteria that exist solely to ferment fiber—which often just yields excess flatulence—actually improves the human host.
When Steven questions whether a less diverse gut microbiome might harbor hidden, long-term net negative impacts that take years to manifest, Dr. Bikman urges caution. He suggests that we shouldn't assume every strain of bacteria cultivated by a high-plant diet is inherently beneficial.
- **Clinical Markers over Microbial Diversity**: Dr. Bikman prioritizes systemic health markers (like blood pressure and insulin levels) over bacterial diversity scores.
- **The Fiber Dilemma**: Increased plant intake feeds fiber-fermenting gut bacteria, which Dr. Bikman notes may simply produce gas rather than confer tangible health benefits to the host.
---
[02:05:00](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7500s) Ketosis Nuances and Medical Applications
Steven shares his personal experience tracking his blood ketone levels, noting that he fluctuates in and out of ketosis throughout the day—spiking higher after runs and dipping lower at night. Dr. Bikman validates this, explaining that metabolic flexibility and periodic ketosis are ideal for most healthy individuals to supply the brain with clean energy, without requiring strict, perpetual keto adherence.
However, Dr. Bikman stresses that for individuals suffering from specific clinical conditions, deep and continuous ketosis can be transformational or even curative:
* **Type 2 Diabetes**: Adopting a ketogenic diet can enable patients to come off all diabetes medications within months.
* **Epilepsy & Migraines**: Grounded in clinical observations dating as far back as 1913, continuous ketosis can prevent epileptic seizures and eliminate migraine headaches entirely.
* **General Population Advice**: For those without severe metabolic or neurological conditions, Dr. Bikman advises simply controlling carbohydrates—focusing on whole fruits and vegetables while ditching processed carbs coming from "bags and boxes with barcodes."
> "Humans do not need, we have no requirement for carbohydrate. We do have requirement for fat and protein."
---
[02:07:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7625s) Decoding Artificial Sweeteners: Aspartame, Sucralose, and Sugar Alcohols
The conversation pivots to artificial and natural sweeteners, with Steven admitting that zero-calorie sodas are his primary indulgence when following a ketogenic protocol. Dr. Bikman categorizes sweeteners based on their impact on insulin levels and their physiological behavior in the body.
```
ARTIFICIAL & NATURAL SWEETENERS
│
┌───────────────────────┴───────────────────────┐
▼ ▼
INERT / SAFE PROBLEMATIC
(No Insulin Spike) (Insulin / GI Impact)
├─ Aspartame (Diet drinks; broken down) ├─ Sugar Alcohols (Maltitol, Mannitol)
├─ Monk Fruit & Stevia │ └─ Causes GI distress, draws water
├─ Allulose └─ Sucralose (Zero drinks)
└─ Erythritol & Xylitol └─ Crosses blood-brain barrier
```
Dr. Bikman personally prefers classic **diet drinks** over **zero drinks**:
* **Aspartame**: Safe from an insulin standpoint. It cleanly breaks down into regular amino acids during digestion without spiking insulin.
* **Sucralose**: Commonly found in "zero" products; while it doesn't spike insulin, it has been shown to cross the blood-brain barrier—a property that makes Dr. Bikman hesitant to consume it.
* **Plant Extracts**: Allulose, stevia, and monk fruit extract are completely inert regarding insulin secretion.
* **Sugar Alcohols**: Ending in *-itol*, these vary widely. While erythritol and xylitol are generally safe, **maltitol** and **mannitol** can spike insulin. Furthermore, because sugar alcohols remain unabsorbed in the intestinal tract, they draw water into the gut, frequently causing severe flatulence and diarrhea.
---
[02:11:04](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7864s) The Salt Myth and Its Connection to Insulin Resistance
Steven recalls a past medical checkup where a doctor warned him that his sodium levels were elevated due to food seasonings, prompting a broader conversation about society's misplaced fear of salt. Dr. Bikman explains that while consuming salt temporarily causes the body to retain water to preserve electrolyte balance—causing a momentary blip in blood pressure—restricting salt is completely ineffective at treating chronic hypertension.
Large population studies show that telling hypertensive patients to cut salt reduces blood pressure by a negligible one or two points at best. The real driver of high blood pressure is **insulin resistance**, which constricts blood vessels and forces the kidneys to retain salt and water.
* **The DASH Diet Flaw**: Decades ago, the landmark Dietary Approaches to Stop Hypertension (DASH) study credited salt reduction for lowering blood pressure. However, the diet simultaneously cut out refined starches and sugars. Dr. Bikman asserts that dropping refined carbohydrates was the actual therapeutic mechanism, while salt restriction was merely an "innocent bystander."
* **The Danger of Salt Restriction**: When healthy humans cut salt intake drastically, their bodies become **significantly more insulin resistant** within just one week. As salt intake drops, insulin spikes higher to force the kidneys to hold onto whatever scarce sodium remains, paradoxically worsening the metabolic state.
---
[02:15:19](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8119s) The Four Pillars of Human Nutrition
To wrap up his nutritional framework for controlling insulin and combating chronic disease, Dr. Bikman outlines the essential dietary principles featured in his book, *Why We Get Sick*. Managing macronutrients to keep baseline insulin low is the absolute foundation of metabolic health.
1. **Control Carbohydrates**: Prioritize whole fruits and vegetables (eat them, don't juice or drink them). Eliminate packaged, processed carbohydrates that come in bags, boxes, or bear barcodes.
2. **Prioritize Protein**: Emphasize animal-source protein, as it contains the full spectrum of essential amino acids required for human physiology.
3. **Don't Fear Fat**: Eat fat alongside protein as it naturally occurs in nature. Pure protein intake yields minimal muscle synthesis and can cause digestive upset, whereas combining protein with fat enhances digestion and significantly amplifies muscle protein synthesis.
4. **Frequently Fast**: Once the first three pillars are established, implement regular fasting periods to allow insulin levels to reset to baseline.
[02:17:42](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8262s) Fasting Strategies and Carbohydrate Addiction
Dr. Benjamin Bikman notes that once someone improves their base diet, they are well-positioned to adopt a structured strategy of fasting. He emphasizes that there is no single right or wrong way to fast—whether it is skipping one meal a day (intermittent fasting) or doing alternate-day fasting. However, he cautions that fasting should be the final principle implemented after adjusting food quality. For individuals who are already in ketosis, frequent fasting can make it extremely difficult to retain muscle mass, especially if they are lean, because ketosis itself already keeps insulin levels low.
While these core health concepts are simple in theory, Dr. Bikman stresses that they are not easy to execute. Humans demonstrate unique addictive tendencies toward carbohydrates, unlike fats or proteins. Neurobiological evidence of addiction in humans points overwhelmingly to carbohydrates. Because self-discipline around carbohydrate consumption is so difficult, many people ultimately turn to prescription drugs to manage their appetite and metabolic health.
* Neurobiological evidence shows human food addiction is almost exclusively tied to carbohydrates.
* Fasting while already in ketosis can endanger lean muscle retention depending on body fat levels.
---
[02:19:22](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8362s) Muscle, Exercise, and Insulin Sensitivity
Addressing physical activity, Dr. Bikman highlights that the single best exercise for improving insulin sensitivity is "the one you'll do"—whether that is an 80-year-old grandmother walking around the block with friends, cross-country skiing, or CrossFit. However, minute for minute, muscle-building resistance training is far more effective at improving insulin sensitivity than aerobic exercise. Muscle is the primary consumer of glucose in the human body.
During muscle contraction, an insulin-independent mechanism takes over. Normally, muscle cells wait for insulin to "knock on the door" to pull glucose from the blood. When a muscle actively contracts, it opens those glucose doors on its own without needing insulin. The more muscle mass a person has, the easier it becomes to clear blood glucose and control insulin. This direct connection explains why muscle mass and physical strength are far superior predictors of longevity compared to markers of cardiovascular aerobic fitness.
* Muscle contractions trigger an insulin-independent uptake of blood glucose.
* Muscle mass and strength measures are significantly better predictors of long-term human longevity than aerobic fitness metrics.
---
[02:22:04](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8524s) The Case for Carbohydrate Restriction
When asked about the debate surrounding calorie restriction across low-fat versus low-carb diets, Dr. Bikman expresses an unabashed preference for carbohydrate restriction. His rationale rests on two main points: globally, 70% of all human calories come from carbohydrates (which drive the highest insulin spikes), and carbohydrates are biologically non-essential.
Dr. Bikman references a classic U.S. Department of Agriculture report on human nutrition which concluded that the lower limit of dietary carbohydrate requirement in humans is zero. While essential fatty acids and essential amino acids exist—requiring humans to ingest fat and protein—there is no such thing as an essential dietary carbohydrate. He argues that nutritional focus should center on essential fats and proteins first, leaving non-essential carbohydrates and plants to fill whatever space remains.
* Carbohydrates represent roughly 70% of total calories consumed globally.
* Dietary carbohydrates are scientifically classified as non-essential for human survival.
---
[02:23:51](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8631s) GLP-1 Agonists and Satiety Mechanisms
Dr. Bikman addresses GLP-1 receptor agonist drugs like Ozempic, drawing on his early doctoral dissertation work on gut-derived hormones. GLP-1 (Glucagon-like peptide-1) is naturally secreted by the small intestine to signal satiety to the brain. Dietary choices directly impact natural GLP-1 release: research shows that low-carbohydrate meals induce a three-times higher GLP-1 response in the blood compared to equal-calorie high-carbohydrate meals.
Dr. Bikman cites a study examining GLP-1 responses in lean versus obese individuals:
1. **Pure Fat Consumption:** Both lean and obese individuals exhibited identical, robust GLP-1 releases, signaling full satiety in both groups.
2. **Pure Carbohydrate Consumption:** Lean individuals experienced a strong GLP-1 spike and felt full, whereas obese individuals showed an almost negligible GLP-1 response and remained hungry.
* Low-carbohydrate meals trigger a 3x greater natural GLP-1 spike than high-carbohydrate meals of equal calories.
* Obese individuals experience a blunted GLP-1 satiety signal when consuming pure carbohydrates compared to lean individuals.
---
[02:26:19](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8779s) Ozempic Side Effects: Muscle Loss and Mental Health
Dr. Bikman warns against the significant, underreported risks associated with high-dose GLP-1 weight loss drugs. Citing data from the STEP 5 clinical trials published in the *New England Journal of Medicine*, he notes that for every 6 pounds of fat lost on these medications, patients lose 4 pounds of fat-free lean mass (40% total loss in muscle and bone). In the UK, roughly 69% of patients stop taking the drug within two years. For an older individual—such as a 60-year-old woman—losing muscle and bone density can be catastrophic, as rebuilding lean tissue at that age is extremely difficult, whereas fat mass quickly returns after drug cessation.
The hosts watch a viral video from a singer named Avery, who detailed being diagnosed with severe osteoporosis and osteopenia after using Ozempic for a year. Dr. Bikman notes that lean individuals using these drugs to facilitate extreme weight loss experience severe malnutrition-induced lean mass loss. Furthermore, recent studies link starting GLP-1 drugs to a doubled risk of suicidal ideation and a tripling in the risk of major depression. He explains that by dampening brain reward signaling, these drugs suppress not just food cravings, but an individual's drive for exercise, hobbies, and social interactions.
> "I have to speak a little more boldly about the negative consequences because nobody talks about them... 40% of weight loss is coming from fat-free mass."
* **Lean Mass Loss:** Clinical trials indicate approximately 40% of weight lost on GLP-1 agonist drugs comes from lean tissue (muscle and bone).
* **Discontinuation Rate:** Around 69% to 70% of users stop taking GLP-1 weight loss medications within 2 years.
* **Mental Health Risks:** Research shows starting GLP-1 agonist drugs is associated with a 200% increase (doubling) in suicidal thoughts and a 300% increase (tripling) in major depression risk.
Here is a detailed, faithful walkthrough of the transcript excerpt:
[02:33:18](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9198s) Strategic Use of Weight-Loss Drugs and Bone Density Effects
Dr. Benjamin Bikman argues that while GLP-1 receptor agonists (like Ozempic or semaglutide) are often misused, there is a legitimate therapeutic use case for them: curbing carbohydrate addiction. The drug significantly reduces sweet cravings within six months of starting treatment. However, he emphasizes that the injection shouldn't replace self-discipline. Users should aim for the lowest effective dose to ease cravings while actively practicing dietary discipline, prioritizing protein and fat, controlling carbohydrates, and lifting weights to protect lean muscle and bone mass. Muscle and bone are made from protein and fat—not carbohydrates—so proper nutrition and resistance training are essential while gradually tapering off the drug.
Addressing concerns about GLP-1 drugs causing bone density loss, Steven notes that scientific literature shows semaglutide generally has no direct harmful effect on bone mineral density, though rapid weight loss itself can impact bone health. Dr. Bikman agrees, calling the observed bone loss an "artifact"—a side effect of behavioral changes rather than a direct cellular attack by GLP-1 on bone tissue. He explains that when people take these drugs, they often suffer from a combination of mild malnutrition and reduced physical activity, as they lose the desire to move or go to the gym, accelerating lean mass loss.
- GLP-1 drugs noticeably reduce sweet cravings within six months.
- Muscle and bone integrity depend on consuming protein and fat combined with weightlifting.
- Scientific reviews show semaglutide does not directly attack bone mineral density; bone loss during treatment is an artifact of rapid weight loss, reduced food intake, and sedentary behavior.
[02:34:50](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9290s) The Hidden Metabolic Dangers of Liposuction
Steven brings up his takeaway from previous podcast discussions that liposuction is inherently dangerous, asking Dr. Bikman for his perspective. Dr. Bikman agrees from a metabolic standpoint. While liposuction helps clothes fit better, it is deeply problematic for metabolic health because it targets the total mass of fat rather than the size of individual fat cells. Small fat cells are metabolically healthy, anti-inflammatory, and insulin-sensitive. When weight is lost naturally through lifestyle changes, fat cells shrink without dying, which improves overall systemic health.
When someone undergoes liposuction—for instance, a woman having fat surgically removed from her buttocks and hips where female sex hormones naturally dictate storage—the fat cells are physically sucked out rather than shrunken. If she does not change her eating habits, her elevated insulin levels and calorie surplus still signal her body to store fat. Since adults cannot easily generate new fat cells and the original fat cells in the hips and buttocks are gone, the body redirects fat storage to remaining intact cells, particularly in the abdomen. As a result, metabolic health markers fail to improve, remaining fat cells become hyper-expanded and inflamed, and long-term health outcomes worsen.
- natural weight loss shrinks fat cells; liposuction physically removes them.
- Small fat cells release anti-inflammatory hormones and promote insulin sensitivity.
- Liposuction patients who do not alter their diet often gain the lost fat back in their abdominal region because the body forces remaining fat cells to expand.
[02:39:25](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9565s) Personal Reflection: Who Believed in Dr. Bikman
Concluding the interview with the show's traditional closing question left by the previous guest—"Who in your life gave you a chance or believed in you when no one else did?"—Dr. Bikman attributes his success to his wife, Cheryl. He candidly reflects on their early marriage when they were both young (he was 23) and both wanted her to be a full-time stay-at-home mother. Having lost his own mother at a young age, Dr. Bikman deeply valued having a mother present in the home. However, becoming the sole provider was a terrifying prospect that made him feel inadequate at the time.
His wife's unwavering trust and faith empowered him to persevere through academia and build a career where he can both financially provide for his family and maintain a flexible schedule. Her support allows him to spend mornings having breakfast with his children and return home early to help homeschool his daughter. He humorously recounts her telling him, "You're not dumb. I didn't marry you for your looks. I think you've got something. I'm going to trust you," noting that her confidence in him was both humbling and life-changing. Steven thanks Dr. Bikman for answering long-standing questions regarding insulin, ketosis, PCOS, and women's health.
- Dr. Bikman married his wife, Cheryl, at age 23.
- His mother passed away when he was young, inspiring his desire to afford his wife the opportunity to be a stay-at-home mother.
- His wife's trust gave him the foundation to build a career that balances income generation with family time, including homeschooling his daughter and eating breakfast with his family daily.
[02:42:33](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9753s) Outro and Conversation Cards
Steven Bartlett closes the episode by highlighting the Diary of A CEO conversation cards, created from the closing questions left by every guest on the show. He explains that the updated Second Edition cards allow buyers to scan a QR code on the back of each card to watch the specific guest answer that question on video. He notes that previous editions sold out quickly and advises viewers to act fast if they wish to purchase the limited-edition deck.
- The Second Edition Conversation Cards feature QR codes linking directly to video responses from podcast guests.
- The cards are available at `theconversationcards.com`.
## Notable quotes
> [05:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=305s) Insulin comes out like a taxi and transports all the glucose in my blood to various places around the body to store them. — Dr. Benjamin Bikman
> [21:01](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1261s) The average individual is spending every waking moment in a state of elevated insulin. And thus, the signal never really goes away because they never give themeselves a break. — Dr. Benjamin Bikman
> [28:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1685s) It is literally impossible for the type 1 diabetic to get fat if they are skipping their insulin injections... The body goes into such a dramatic fat burning state in the absence of insulin that keeping fat becomes impossible. — Dr. Benjamin Bikman
> [51:29](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3089s) The plaque-based theory doesn't make sense... You would be just as likely to find plaques in both brains. — Dr. Benjamin Bikman
> [01:07:48](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4068s) Subcutaneous fat is inert. It really is just sort of hanging out there and minding its own business. But, in that same study, if you move the visceral adipose over, now all of a sudden that animal that got that extra dose of visceral fat is going to become sicker. — Dr. Benjamin Bikman
> [01:13:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4385s) The very word metabolism encompasses anabolism, which is anabolic or building up, and catabolism or catabolic, which is breaking down. The key to a healthy growing living cell is this nice ongoing balance of build and break. — Dr. Benjamin Bikman
> [02:05:00](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7500s) Humans do not need, we have no requirement for carbohydrate. We do have requirement for fat and protein. — Dr. Benjamin Bikman
> [02:26:19](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8779s) I have to speak a little more boldly about the negative consequences because nobody talks about them... 40% of weight loss is coming from fat-free mass. — Dr. Benjamin Bikman
## Mentioned
Dr. Benjamin Bikman, The Diary Of A CEO, Steven Bartlett, Whoop, Will Ahmed, Dr. Suzanne de la Monte, Brown University, NHS, Polycystic Ovary Syndrome (PCOS), Alzheimer's Disease International, Bryan Johnson, Cynthia Kenyon, Why We Get Sick, International Journal of Molecular Sciences, BPA, DES, Brigham Young University (BYU), Tour de France, The Biggest Loser, National Institutes of Health (NIH), David Ludwig, Angus Barbieri, Avery, Cheryl Bikman, Ozempic, Semaglutide, U.S. Department of Agriculture, STEP 5 clinical trials, New England Journal of Medicine, DASH Diet
Metabolic scientist Dr. Benjamin Bikman argues that chronically elevated insulin and insulin resistance constitute the primary root cause of widespread chronic diseases, including cardiovascular issues, type 2 diabetes, Alzheimer's, and certain cancers.
Insulin Resistance as a Root Cause (0:00)
Bikman contends that modern clinical medicine misdiagnoses chronic illness by treating isolated symptoms rather than their shared metabolic driver: hyperinsulinemia and cellular resistance to insulin signaling. In the United States, an estimated 88% of adults suffer from some degree of metabolic dysfunction. When cells become resistant to insulin, the pancreas secretes higher amounts to clear circulating glucose, creating a cycle of chronically elevated blood insulin. This systemic dysfunction damages vascular tissue, leading to hypertension and erectile dysfunction, and fosters Polycystic Ovary Syndrome (PCOS) by inhibiting normal metabolic function.
Drivers of Insulin Resistance and Storage (16:11)
Insulin resistance develops via rapid and slow mechanisms. Rapid resistance is triggered by systemic inflammation, sleep deprivation, and elevated stress hormones like cortisol and epinephrine, which prompt insulin to work harder to counter circulating glucose. Slow resistance stems from dietary patterns where carbohydrates supply approximately 70% of global caloric intake, combined with frequent eating that never allows insulin levels to drop. Bikman highlights that fat cell expansion requires both energy and insulin; in cell cultures, human fat cells do not expand from glucose and lipids alone until insulin is added.
Ethnic differences and anatomical storage patterns shape metabolic risk through an individual's "personal fat threshold." Subcutaneous fat can undergo hyperplasia—multiplying into smaller, more insulin-sensitive cells—whereas visceral fat within the abdominal cavity is constrained to hypertrophy, swelling until cells become inflamed and insulin-resistant. East Asian and Hispanic demographics tend to store higher ratios of visceral fat, precipitating metabolic distress at lower BMI levels than populations of Northern European or African descent.
Neurological and Cellular Growth Consequences (48:53)
Elevated insulin directly influences cellular proliferation and neurodegeneration. In breast cancer, Bikman observes that tumor cells express seven times more insulin receptors than adjacent normal breast tissue, utilizing insulin's anabolic signaling to accelerate unregulated growth. In the brain, insulin resistance induces glucose hypometabolism, starving brain regions of energy—a pathology underlying Alzheimer's disease. Bikman notes this metabolic deficit can be bypassed by ketones, as ketone uptake in the brain does not rely on the impaired insulin mechanism.
Dietary Interventions, Ketosis, and Longevity (32:44)
To reverse metabolic dysfunction, Bikman advocates for carbohydrate restriction over standard low-calorie diets. While dietary carbohydrates are biologically non-essential, restricting them lowers resting insulin, prompting the liver to burn fats and generate ketones once suppressed for roughly 16 consecutive hours. Low insulin can elevate resting energy expenditure by nearly 300 calories per day through thermogenesis and ketone exhalation. Bikman points to Swedish longevity research showing that centenarians systematically share exceptional blood glucose control alongside higher circulating cholesterol, challenging conventional assumptions about aggressive cholesterol reduction.
Risks of GLP-1 Agonists and Liposuction (143:51)
Bikman warns against relying on rapid medical interventions like GLP-1 receptor agonists and cosmetic surgeries. While natural meals low in carbohydrates induce a three-times higher natural GLP-1 satiety response than equal-calorie carbohydrate meals, pharmaceutical GLP-1 agonists carry significant lean mass risks. Citing the STEP 5 trials, Bikman notes that for every 6 pounds of fat lost on these medications, patients lose 4 pounds of fat-free lean tissue, creating high risks for osteoporosis and metabolic rebound upon cessation. Similarly, liposuction physically extracts protective subcutaneous fat cells rather than shrinking them, forcing subsequent excess caloric storage into dangerous visceral depots.
Bikman identifies carbohydrate restriction, preservation of skeletal muscle through resistance training, and maintenance of low resting insulin as primary pillars for metabolic health, though questions remain around long-term metabolic flexibility and individual dietary adherence.
## Background
本期节目由知名播客频道 The Diary Of A CEO 于 2025 年 2 月 6 日在 YouTube 上发布。节目邀请了代谢科学家、细胞生物学与生理学教授 Benjamin Bikman 博士，探讨约 88% 成年人面临的代谢疾病危机，揭示胰岛素的潜在健康危害，并分享如何通过科学代谢手段掌控自身健康。
## TL;DR
节目深入剖析了胰岛素抵抗作为心脏病、阿尔茨海默病、2 型糖尿病及早发性癌症等现代慢性病共同根源的病理机制，颠覆了传统的单纯“卡路里热量平衡”迷思。Dr. Bikman 阐述了脂肪细胞肥大、环境毒素、吸烟与高碳水饮食如何诱发高胰岛素血症，并揭示了生酮状态下机体利用脂肪与酮体为大脑和肌肉高效供能的生理优势。全篇给出了控制加工碳水、优先摄入优质蛋白与天然脂肪、结合规律断食与抗阻运动的代谢重塑方案，同时对 Ozempic 等 GLP-1 药物导致的骨骼与肌肉严重流失及吸脂手术的长期代谢危害提出了严厉警示。
## Atmosphere & style
对谈节奏紧凑而充满学术穿透力，Dr. Bikman 将深奥严谨的细胞生理学机制化为生动形象的隐喻，言辞犀利且极具警示感。主持人 Steven Bartlett 提问直击要害并穿插切身体验，使关于代谢危机、心理成瘾与医疗误区的讨论兼具科学权威度与人文关怀。整体氛围在揭露慢性病危机与药企局限时的沉重冷峻，与分享代谢逆转方案时的清晰务实之间平稳切换，结尾致敬伴侣信任的温情讲述更赋予了整场理性科普动人的情感余韵。
## Bulletin
- [00:00](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=0s) 约88%的成年人存在不同程度的胰岛素抵抗，它是心脏病、阿尔茨海默病、2型糖尿病及脂肪肝等多数慢性病的共同代谢病根。
- [23:27](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1407s) 决定代谢健康的核心是脂肪细胞的体积大小而非脂肪总质量；细胞过度肥大将濒临破裂并被迫产生胰岛素抵抗以自卫。
- [54:41](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3281s) 阿尔茨海默病本质是大脑局部胰岛素抵抗引起的葡萄糖低代谢危机，生酮产生的酮体可穿透血脑屏障弥补大脑能量缺口并改善认知功能。
- [02:23:51](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8631s) Ozempic 等 GLP-1 药物减掉的体重中约40%来自瘦体重（肌肉与骨骼），停药反弹率高且伴随显著的抑郁与快感缺失风险。
## Key takeaways
- [02:19](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=139s) 胰岛素抵抗是多数致命慢性病的共同根基，传统医学头痛医头的对症治疗只是在修剪疾病的枝桠。
- [05:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=305s) 高血糖会刺激胰岛素分泌，而胰岛素是统管葡萄糖、脂肪酸、酮体及氨基酸燃烧与储存的总开关阀门。
- [12:04](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=724s) 血管内皮细胞对胰岛素失聪无法正常舒张加大血流，使得勃起功能障碍（ED）常成为年轻男性代谢异常的最早警讯。
- [13:53](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=833s) 压力、系统性炎症与过量胰岛素构成了诱发胰岛素抵抗的快车道，实验室中可在6小时内诱发并逆转该状态。
- [21:01](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1261s) 一日多餐伴随高碳水饮食让身体处于不间断的高胰岛素暴露中，使细胞产生受体脱敏与选择性失聪。
- [26:00](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1560s) 东亚人群脂肪细胞基数较少且增殖期更早停止，在更低 BMI 下即面临脂肪细胞过度肥大与严重代谢并发症。
- [28:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1685s) 打破纯卡路里假说：缺乏胰岛素信号调度时身体无法有效储存脂肪，1型糖尿病患者在极低胰岛素下即使高热量也会疯狂燃脂消瘦。
- [32:11](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1931s) 在完全等热量和等蛋白质条件下，低碳生酮饮食比高碳饮食的基础代谢率高出近300大卡，且部分未利用酮体会直接排出体外。
- [40:36](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2436s) 生理性胰岛素抵抗见于青春期与妊娠期促生长，但妊娠期糖尿病会给胎儿代谢编码长期印记，增加后代40%的肥胖风险。
- [45:59](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2759s) 年轻女性早发乳腺癌急剧上升与高胰岛素环境密切相关，乳腺恶性肿瘤表面的胰岛素受体数量可达正常组织的7倍。
- [51:29](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3089s) 阿尔茨海默病的淀粉样蛋白斑块假说存在重大争议与造假，其真正的病理核心是大脑记忆区域的胰岛素抵抗与葡萄糖能量缺口。
- [01:13:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4385s) 长寿的底层机制依赖低胰岛素水平激发的细胞自噬，回顾性研究发现最长寿者通常具有极高的胰岛素敏感度与偏高的胆固醇水平。
- [01:22:15](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4935s) 吸烟、电子烟裂解物及微塑料与内分泌干扰物均可独立于热量摄入直接诱发全身急性胰岛素抵抗并刺激脂肪细胞肥大。
- [02:11:04](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7864s) 严格限盐仅能微幅降压，却会代偿性推高胰岛素分泌以保钠保水，反而在短期内诱发显著的胰岛素抵抗。
- [02:15:10](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8110s) 控糖改善代谢的核心支柱为控制加工碳水、优先优质蛋白质、不惧天然脂肪并结合肌肉抗阻运动利用非胰岛素葡萄糖摄取通道。
- [02:35:50](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9350s) 吸脂手术粗暴消灭皮下脂肪细胞储备库，若不改变饮食习惯，多余热量会强制转入内脏与剩余脂肪细胞，长期来看极度损害代谢健康。
## Detailed walkthrough
### [00:00](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=0s) 致命的隐形流行病：胰岛素抵抗与慢病危机
本期节目在一组令人震惊的医学洞察中拉开帷幕。谈及吸烟与电子烟时，代谢科学家本杰明·比克曼博士（Dr. Benjamin Bikman）指出，从呼吸道损伤以及引发胰岛素抵抗的角度来看，电子烟的危害可能比传统香烟更甚。然而更严峻的现实在于，胰岛素抵抗不仅关乎不良生活习惯，更是现代社会绝大多数致命慢性疾病的核心温床。作为人体极其关键的荷尔蒙，胰岛素几乎影响体内的每一个细胞；一旦这些细胞产生抵抗，病变便会在全身蔓延——阿尔茨海默病甚至已被学术界称为“大脑的胰岛素抵抗”，而男性勃起功能障碍（ED）以及女性多囊卵巢综合征（PCOS）等最常见的不孕不育问题，背后都有胰岛素抵抗的推波助澜。
根据最新统计，全美有高达 88% 的成年人存在不同程度的胰岛素抵抗。大众常常因此认定“美国人就是肥胖且代谢不健康”，但比克曼博士强调，美国在这一指标上并非全球最差，不同族裔之间脂肪储存模式的生物学差异深刻影响了患病特征。走向胰岛素抵抗有两条截然不同的通道：一条是“快车道”，只需特定三项诱因中的任意一项，就能在短短 6 小时内诱发急性胰岛素抵抗，但只要撤除刺激，身体也能同样迅速地恢复；另一条则是因饮食结构和日常作息长期失衡所致的“慢车道”，这也是最棘手的慢性健康隐患。面对当前风靡全球的降糖减肥神药（如 Ozempic），比克曼博士直言大众往往忽视了其严重的副作用：使用此类药物减掉的体重中，有高达 40% 实际上流失的是宝贵的瘦体重（肌肉组织）。
- **全美代谢现状**：约 88% 的美国成年人存在不同程度的代谢障碍与胰岛素抵抗。
- **快慢两条通路**：快车道可在 6 小时内诱导或逆转胰岛素抵抗；慢车道则由长期不良生活与饮食习惯积聚而成。
- **GLP-1 药物隐患**：Ozempic 等药物减重过程中，约有 40% 的流失重量来自肌肉等非脂肪组织。
---
### [01:32](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=92s) 团队的千万订阅赌局插曲
在严肃的医学探讨前，主持人史蒂文·巴特利特（Steven Bartlett）插播了一则幽默的幕后花絮：频道即将迎来突破 1000 万 YouTube 订阅的历史性里程碑。为了犒劳多年来在幕后默默付出的制作团队，团队成员与他打了一个赌——在接下来的 30 天内，每增加一名新订阅者，史蒂文就必须自掏腰包向团队的庆祝基金注入 1 美元。史蒂文笑着调侃道，虽然他非常感激大家的支持，但出于对自己钱包的担忧，这可能是他有史以来“第一次不得不劝观众千万别点订阅按钮”，因为这场赌局可能会让他破费巨大。
---
### [02:19](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=139s) 治病不应只“修剪枝桠”：慢性病的共同代谢根源
正式进入访谈后，史蒂文询问比克曼博士究竟怀揣着怎样的终极使命。比克曼博士动情地表示，传统临床医疗长期将各类慢性病视为彼此割裂、起源完全独立的孤岛，医生们习惯于开出各类对症药物，这就像是一棵树上的枝桠生了病，常规手段只是“把枝条剪短一点点”（"prune the branch back a little bit"），却从未触碰病根，枝条很快又会卷土重来。他的使命，正是唤醒公众认识到全球顶尖致死性疾病——从阿尔茨海默病、心脏病、2 型糖尿病到脂肪肝与肝功能衰竭——其实全都是从同一根代谢树干上滋生出来的枝桠。
这一学术顿悟始于 2000 年代初期。当时比克曼博士偶然读到一篇具有里程碑意义的论文，探讨脂肪组织在扩张过程中如何显著推高 2 型糖尿病的风险，揭示了如今广为人知的“糖胖症”（Diabesity）现象。研究表明，脂肪组织过度增生时会释放大量促炎蛋白（Pro-inflammatory proteins），这种系统性慢性炎症正是诱发胰岛素抵抗的导火索。随着全身其他器官逐渐出现胰岛素抵抗，各种慢性病便如多米诺骨牌般倒下：高血压这一心血管疾病的最大元凶，其本质驱动力就是血管内皮的胰岛素抵抗；阿尔茨海默病本质上是“3 型糖尿病”或脑部代谢障碍；而在生殖领域，男性的勃起功能障碍源于血管对胰岛素丧失敏感度，女性最普遍的不孕症 PCOS 则是卵巢胰岛素抵抗破坏了正常性激素的合成平衡。
```mermaid
flowchart TD
accTitle: 慢性疾病的共同代谢根源树状图
accDescr: 胰岛素抵抗作为核心根源，向上滋生出高血压、阿尔茨海默病、多囊卵巢综合征、勃起功能障碍等各类致命慢性疾病的分支。
subgraph CoreRoot["核心根基 (Core Problem)"]
IR["胰岛素抵抗<br/>(Insulin Resistance)"]
INF["脂肪组织增生释放炎性因子<br/>(Pro-inflammatory Signaling)"]
INF --> IR
end
subgraph ClinicalBranches["临床疾病表征 (Siloed Diseases)"]
HTN["心血管疾病 / 高血压<br/>(Hypertension)"]
ALZ["阿尔茨海默病<br/>(大脑胰岛素抵抗 / 3型糖尿病)"]
T2D["2型糖尿病 / 糖胖症<br/>(Diabesity)"]
FERT_M["男性不育 / 勃起功能障碍<br/>(血管内皮受损)"]
FERT_W["女性不育 / 多囊卵巢综合征<br/>(PCOS / 卵巢激素紊乱)"]
LIVER["非酒精性脂肪肝 / 肝衰竭"]
end
IR --> HTN
IR --> ALZ
IR --> T2D
IR --> FERT_M
IR --> FERT_W
IR --> LIVER
```
---
### [05:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=305s) 像对待10岁孩子一样解释：胰岛素与人体能量调度
面对错综复杂的代谢机制，史蒂文请比克曼博士“像对一个 10 岁小孩解释一样”，讲清胰岛素抵抗的本质。比克曼博士将胰岛素抵抗比作一枚硬币的两面，在剖析其病理前，必须先厘清胰岛素的生理角色。胰岛素是由胃下方狭长的胰腺所分泌的关键激素。胰腺是一个极其忙碌的器官，既分泌流入肠道协助消化食物的消化酶，也分泌流入血液调节全身的内分泌激素。在 1 型糖尿病患者体内，自身免疫系统摧毁了胰岛 β 细胞，导致其彻底无法产生胰岛素，因此外源胰岛素对其而言是不可或缺的救命药；而对于绝大多数普通人，β 细胞会根据血液中的信号随时待命。
触发 β 细胞释放胰岛素的最强生理刺激，就是血糖水平的上升。日常摄入的植物性碳水化合物——无论是显而易见的高糖零食，还是米饭、面包、饼干、薯片等淀粉类主食——在消化后都会分解为糖分涌入血液。血液中过高浓度的葡萄糖具有细胞毒性，此时胰岛素便会迅速出动将血糖降回安全线，随后自身浓度回落。史蒂文随即形象地比喻道：这就像是胰岛素化身出租车，把血液里的葡萄糖运载到全身各处仓库储存起来。
比克曼博士高度赞同这一类比，并作出了关键的机制补充：
1. **肌肉与脂肪组织（需凭票进门）**：骨骼肌和脂肪细胞的表面通道紧闭，它们必须等待胰岛素这名“保镖”前来敲门，或者像出租车专程开道，葡萄糖才能被顺利运送进门；
2. **肝脏与部分脑组织（自由出入但缺乏指挥）**：肝脏并不需要胰岛素来开门，只要血液中有糖分路过，肝脏就会自动敞开大门让其进入。然而，进门之后肝脏“根本不知道拿这些糖怎么办”——这便牵出了胰岛素更宏大的本质功能：它是统管全身所有能量底物（包括乳酸、酮体、脂肪酸、葡萄糖及氨基酸）的“总指挥官”，决定每一份摄入的热量是被即时燃烧还是转化存储。
由此，比克曼博士引出了胰岛素抵抗这枚硬币的第一面：**受体细胞的麻木与失效**。当肌肉组织发生胰岛素抵抗时，即便胰岛素载着满车的葡萄糖拼命敲门呼喊“嘿，我这有一批糖要送进来”，骨骼肌也充耳不闻，彻底拒之门外，使得过剩的糖分与不断飙升的胰岛素双双滞留积聚在血液之中。
### [09:37](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=577s) 肌肉的“失聪”与胰岛素抵抗的双重特征
在健康的生理状态下，肌肉细胞非常配合。当胰岛素带着降血糖的任务到来时，肌肉会爽快地开门，将葡萄糖迎入细胞内部。然而，一旦发生胰岛素抵抗，情况就彻底变了。Benjamin Bikman 博士打了一个生动的比方：胰岛素就像是站在门外的保镖（bouncer），正用力敲打着肌肉细胞的大门，但肌肉细胞却像彻底“失聪”了一样充耳不闻。肌肉之所以是一个关键的观察窗口，是因为对绝大多数人而言，肌肉是体内质量最大的组织；即便在体重超标的人群中，肌肉依然占据着身体的很大一部分比重。当肌肉细胞对胰岛素的呼唤充耳不闻时，胰岛素促进细胞摄取葡萄糖、降低血糖的核心能力便大幅受挫。
```mermaid
flowchart TD
accTitle: 胰岛素抵抗的双重恶性循环
accDescr: 展示胰岛素信号减弱与代偿性高胰岛素血症之间形成的相互加剧机制
subgraph SignalDrop ["效应减退"]
A["正常敲门（单分子胰岛素）"] --> B["细胞反应迟钝 / 产生抵抗"]
B --> C["血糖无法有效降低"]
end
subgraph CompRise ["代偿升高"]
C --> D["身体代偿机制启动"]
D --> E["派出'暴怒的保镖群'（大量胰岛素）"]
E --> F["外周血胰岛素水平激增"]
end
F -.->|"进一步诱发细胞脱敏"| B
```
这引出了理解胰岛素抵抗时必须同时考量的两个并存维度：一方面，胰岛素在身体各个器官和组织中的工作效率下降，即细胞对胰岛素指令的敏感性降低，这是“抵抗”这一名称的由头；但另一方面同样关键的是，血液中的胰岛素水平实际上显著升高了。过去只需要一位礼貌敲门的“保镖”（单个胰岛素分子），肌肉就会乖乖开门；现在既然这扇门纹丝不动，身体做出的适应性反应就是派出“一整群暴怒的保镖”（angry mob of bouncers）去猛砸大门。通过大幅拉高血中胰岛素浓度，身体试图迫使肌肉开门迎糖。因此，胰岛素抵抗本质上是“胰岛素信号在部分靶组织效应受损”与“血循环中胰岛素水平过高（高胰岛素血症）”这两种状态的合流。
### [12:04](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=724s) 勃起功能障碍：年轻男性胰岛素抵抗的早期警报
胰岛素抵抗的影响绝不仅限于血糖控制，它还深刻牵扯到生育健康。Benjamin Bikman 博士以男性的勃起功能障碍（ED）为例，指出 ED 实际上是男性不育症中最普遍的一种表现，而它与胰岛素抵抗之间存在极其紧密的直接联系。几年前一篇医学论文的标题曾让 Bikman 博士印象极其深刻，该论文直接提出疑问：“在表面年轻健康的男性群体中，勃起功能障碍是否就是胰岛素抵抗最早期的外在表现？”
这种深层机制揭示了大众对胰岛素认知的普遍盲区——人们总以为胰岛素只管血糖，但它实际上对心血管系统也发挥着深远作用：
- **血管舒张信号**：在维持正常勃起功能时，男性体内的局部血管必须发生剧烈的扩张，从而迅速增加血流量以维持功能。在健康生理状态下，向血管内皮发出“扩张并增加血流”指令的信号分子之一，恰恰就是胰岛素。
- **血管内皮的抵抗**：一旦男性的血管内皮细胞对胰岛素产生了抵抗，当胰岛素前来敲门示意“该扩张血管、加大供血了”时，血管壁根本不予理会。
- **功能障碍的成因**：由于血管持续处于收缩和僵直状态，局部血流灌注始终不足，最终直接引发了勃起功能障碍。
### [13:53](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=833s) 胰岛素抵抗的发生路径：快车道与慢车道
面对主持人 Steven Bartlett 表达的担忧，Bikman 博士解释道，理解胰岛素抵抗的成因至关重要，它能解释为何这种病理状态已演变成全球范围内最普遍的代谢顽疾。走向胰岛素抵抗的途径主要有两条：一条是反应极为迅速的“快车道”（fast insulin resistance），另一条则是需要更长时间累积、但也更难摆脱的“慢车道”（slow insulin resistance）。
在快车道中，有三个诱因可以在短短 6 个小时的临床实验室内让一个原本健康的人迅速出现胰岛素抵抗；然而，只要将这些诱因从环境中撤除，这种抵抗状态又会同样快速地消退。这三大急性诱发因素分别是：
1. **压力（Stress）**
2. **炎症（Inflammation）**
3. **过量胰岛素（Too much insulin / 自身诱导）**
### [15:22](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=922s) 快车道第一诱因：两大压力激素与胰岛素的交锋
作为内分泌学教授，Benjamin Bikman 博士从激素的角度严格定义了“压力”。人体内有两大致命的压力激素：皮质醇（cortisol）和肾上腺素（美式英语称 epinephrine，英式英语称 adrenaline）。这两者在分子结构和机制上大不相同，但在触发“战斗或逃跑”（fight or flight）的应激反应时，它们会共同发力——让人感到坐立难安、心跳加速、感官警觉度瞬间拉满。
更重要的是，这两种压力激素在代谢上有一个绝对统一的目标：推动血糖水平升高。身体并不清楚当事人到底遭遇了什么险境，但进化的程序设定必须确保血液中有足够充沛的葡萄糖随时准备“逃跑或迎战”。这种强行拉高血糖的举动，恰恰将它们置于胰岛素的绝对对立面：
- 肾上腺素与皮质醇拼命把血糖往上推，而胰岛素则全力试图压低血糖。
- **剥夺睡眠**是极具杀伤力的皮质醇刺激源；而**摄入过多咖啡因**则能强力刺激肾上腺素激增。
- 当这些应激源持续不断、两种压力激素居高不下时，体内的胰岛素就必须超负荷工作，被迫不断提高分泌量来抵抗升糖压力，进而迅速导致机体陷入胰岛素抵抗。
### [17:11](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1031s) 快车道第二诱因：急慢性炎症对代谢的绑架
炎症是通往急性胰岛素抵抗的第二条路。日常生活中当感冒或流感季来袭、人体遭受病原体感染时，如果当事人手臂上佩戴着连续血糖监测仪（CGM），就会观察到即使饮食没有改变，其基础血糖水平也会显著飙升。这是机体处于胰岛素抵抗状态的直接体征，说明在免疫系统全力抗击感染时，胰岛素维持血糖稳态的效率被严重削弱。
在自身免疫性疾病患者身上，这一现象表现得更加淋漓尽致：
- 以类风湿性关节炎（rheumatoid arthritis）为例，患者的关节会因为自身免疫系统的攻击而反复出现疼痛与肿胀。
- 这类疾病呈现明显的波动周期，有发作的“坏日子”，也有缓解的“好日子”。
- 人体临床数据明确证实，患者在炎症发作期的胰岛素抵抗程度，与免疫系统激活的强弱程度严密锁死。免疫系统反应越剧烈、体内炎症水平越高，机体的胰岛素抵抗程度就越严重。
### [18:24](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1104s) 快车道第三诱因：过量胰岛素导致的受体自我保护
第三个促发因素听起来颇具循环论证的荒谬感：过量胰岛素本身就是导致胰岛素抵抗的罪魁祸首。敏锐的听众很快会察觉到逻辑上的循环——前面刚刚论述过“高胰岛素是胰岛素抵抗的代偿结果”，因为一个胰岛素保镖敲不开门，身体就会调集十个胰岛素保镖过来猛轰大门；但此时 Bikman 博士却指出，**高胰岛素水平既是胰岛素抵抗的结果，同时也是其直接成因**。
这种机制背后依托着一条所有生物学领域共同遵循的基础铁律：**当任何外部刺激过量且持续存在时，具备适应能力的细胞就会本能地降低对该刺激的敏感性，以此进行自我防卫**。为了更通俗地解释过度暴露导致的这种脱敏现象，Bikman 博士聊起了自己家里的趣事：他的太太是一位全职妈妈，全心全意在家照顾孩子；而当自己尽可能抽空回家陪伴家人时，他发现孩子们对父母声音与呼唤的反应模式，生动展现了这种对高频刺激产生抵抗的心理与生理机制。
### [19:36](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1176s) “叫妈妈”的比喻与高胰岛素引发的细胞钝化
为了解释身体对胰岛素的反应机制，本杰明·比克曼（Dr. Benjamin Bikman）博士用了一个生动的家庭日常比喻：家里的孩子们总是不停地喊着“妈妈、妈妈、妈妈”，但妻子常常毫无反应，因为她整天听这些呼喊，已经产生了一种“选择性失聪”，对孩子索求关注的声音彻底麻木了；而比克曼白天在实验室工作，回到家时，孩子呼喊的声音对他而言是一个非常新鲜的信号，哪怕人还在另一个房间，他也会立刻敏锐地作出回应。肌肉细胞对待胰岛素也是一模一样的逻辑——如果血液中时刻充斥着胰岛素，而且水平不断攀升，肌肉细胞就会产生厌烦心理，抱怨“胰岛素，你一天到晚都在敲我的门，这套把戏已经过时了，我不想再理你了，也不会再像以前那样听话”。
这种机制证明：过量的胰岛素本身就是导致胰岛素抵抗的直接元凶。比克曼指出，如果把一个人带进实验室，仅通过静脉持续微量滴注胰岛素，只要短短几个小时，受试者对胰岛素的敏感度就会显著下降；然而，只要撤掉输液管，再给身体几个小时的代谢缓冲，敏感度又会迅速恢复正常。这属于“快速通道”下的胰岛素抵抗：诱发快，若能及时切断刺激源，逆转恢复也同样迅速。
```mermaid
flowchart LR
accTitle: 高胰岛素引发受体脱敏机制
accDescr: 展示胰岛素持续刺激如何导致细胞产生选择性耐受并最终引发抵抗
subgraph SignalLoop["持续刺激机制"]
A["高频胰岛素分泌"] --> B["持续敲击细胞受体"]
B --> C["细胞信号通路疲劳"]
C --> D["下调受体敏感度<br/>(选择性失聪)"]
D --> E["胰岛素抵抗形成"]
end
```
### [21:01](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1261s) 一日六餐与高碳饮食：让身体全天陷入高胰岛素状态
当史蒂文·巴特利特（Steven Bartlett）追问如果刺激无法撤除、胰岛素抵抗是否会变成慢性病时，比克曼给出了肯定的回答。他指出，目前全球有 70% 的总热量摄入来自碳水化合物。更糟糕的是，很多专家出于良好初衷，却给大众灌输“每天应该少食多餐、吃上六顿”的饮食建议，彻底堵死了胰岛素回落的通道。
正常情况下，人体在夜间睡眠禁食期间，胰岛素好不容易降下来，得以稍作喘息。然而第二天一早，英美两国的典型早餐基本都是高淀粉、高糖分的食物——烤吐司配果酱、麦片或是贝果，这些食物进入体内几乎会立刻转化为纯葡萄糖。血糖被骤然推高后，胰岛素随即大量分泌。胰岛素在血液中驻留的时间往往比血糖更长，因为它要确保所有糖分都被平复。这导致一顿高碳水早餐下肚后，胰岛素可能需要三到四个小时才能重回基线。但绝大多数人根本等不到它恢复，两小时后的上午茶时间又开始喝加糖咖啡、吃点心；接着是高淀粉的午餐、下午茶加餐、高碳水晚餐，甚至睡前还要再吃一份夜宵。现代普通人清醒时的每一分每一秒，都浸泡在高胰岛素的血泊之中，身体从未获得过喘息之机，直接将暂时的适应性耐受拖入了慢性的全身抵抗。
- **全球热量构成**：全球约 70% 的卡路里消耗依赖碳水化合物。
- **胰岛素回落周期**：摄入高升糖早餐后，胰岛素水平完全恢复基线需要 3 至 4 个小时。
- **全天候高胰岛素血症**：一日六餐加上零食习惯，导致胰岛素信号在患者清醒时段从未间断。
### [23:27](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1407s) 脂肪细胞的真正秘密：细胞大小决定代谢健康，而非脂肪总量
持续的高胰岛素不仅直接抑制肌肉受体，还会对脂肪细胞持续施加囤积信号，由此将机体推入“慢性胰岛素抵抗”的漫长阶段。比克曼强调，在脂肪组织与代谢健康的关系上，公众存在极大的误区：真正决定胰岛素抵抗风险的，从来不是身体上的脂肪总质量（Mass），而是“单个脂肪细胞的体积大小”（Size）。为了便于英国观众理解，比克曼打趣道：“假定史蒂文你全身上下有 10 公斤脂肪，而我有 20 公斤，但我在代谢层面完全可能比你更健康。”
女性的生理构造是这一规律的最佳证明。从普遍意义上讲，女性由于生理需要，体脂率天然高于同龄男性，但在胰岛素抵抗和绝大多数代谢疾病的患病率上，女性在绝经前往往显著优于男性。原因在于女性体内的性激素促使机体生成了“数量更多、但体积更小”的脂肪细胞。小尺寸的脂肪细胞处于健康、高胰岛素敏感且抗炎的状态；反之，一旦单个脂肪细胞被过度撑大，就会触发恶性级联反应，向全身释放炎症因子并驱动胰岛素抵抗。
史蒂文询问成年人一生的脂肪细胞数量是否固定，比克曼证实了这一点：脂肪细胞并非永生不死，但其寿命长达约 10 年。从婴儿期、童年期到青春期，人体内的脂肪细胞数量一直在不断增殖；但一旦结束青春期（年轻女性在十几岁中后期，男性在十几岁末或二十岁出头），成年人体内的脂肪细胞数量便基本固定。成年后的胖瘦，纯粹是现有脂肪细胞在“膨胀变大”或“缩水缩小”，这并非细胞数量的加减。
- **脂肪细胞寿命**：单个脂肪细胞平均寿命约为 10 年，并非不可替换，但成年后总数相对恒定。
- **增殖窗口期**：脂肪细胞数量的增加主要发生于婴儿期、儿童期和青春期，成年后极难通过自然途径增加新的脂肪细胞。
- **两性代谢差异**：女性拥有更多数量的小体积脂肪细胞，小脂肪细胞具备天然的抗炎与高胰岛素敏感特性。
- **抽脂手术的隐患**：抽脂手术强行移除皮下脂肪细胞库，反而破坏了日后储存脂肪的健康缓冲容量，从长远来看严重损害未来的代谢健康。
### [26:00](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1560s) 种族差异的脂肪门槛：为什么东亚人更容易得代谢疾病？
比克曼指出，脂肪细胞的生成上限在不同种族之间存在显著的遗传差异。在光谱的一端是北欧白人群体（高细胞数量上限），而在另一端则是东亚人群（包括中国人、日本人和韩国人）。东亚人在生长发育过程中，脂肪细胞数量的增殖很早就早早停止，导致成年后拥有的脂肪细胞总数在全人类各种族中处于偏低水平；而高加索白人则拥有庞大得多的脂肪细胞基数储备。
```mermaid
flowchart TD
accTitle: 种族脂肪储备与代谢疾病阈值差异
accDescr: 对比白种人与东亚人在相同脂肪净增重下的不同代谢结局
subgraph Caucasian["高加索白人特征"]
C1["脂肪细胞基数多"] --> C2["摄入超量能量"]
C2 --> C3["众多小细胞分摊储存"]
C3 --> C4["单细胞膨胀程度轻<br/>(仅影响体型外观)"]
end
subgraph EastAsian["东亚人群特征"]
E1["脂肪细胞基数少"] --> E2["摄入超量能量"]
E2 --> E3["有限细胞被迫极度肥大"]
E3 --> E4["迅速突破脂肪储存门槛<br/>(高血压/脂肪肝/2型糖尿病)"]
end
```
这种差异在现实体重增加时会造成截然相反的健康结局。比克曼虚构了“美国版比克曼”与“中国版比克曼”两个对照个体：如果两人在未来十年内都纯粹增加了 10 公斤纯脂肪，美国白人比克曼可能只是“穿泳裤变得难看了”（比克曼自嘲苍白的白人穿泳裤本来也不好看），但他内部的血压、血糖和所有代谢指标依然非常健康，因为这 10 公斤脂肪被成千上万个细胞分摊，单个细胞并没有被撑到极限。
然而，同样的 10 公斤脂肪若是加在东亚人身上，其后果将是灾难性的。由于东亚人先天的脂肪细胞储备库容量有限，为了容纳这 10 公斤脂肪，现存的脂肪细胞被迫在极短时间内急剧肥大、被撑到濒临破裂的极限。极度肿胀的脂肪细胞会向全身倾倒大量游离脂肪酸与炎症因子，导致其在极低的体重指数（BMI）下就迅速并发高血压、2型糖尿病、非酒精性脂肪肝以及生育障碍。
### [28:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1685s) 卡路里神话的破灭：1型糖尿病与“胰岛素限制进食障碍”
既然变胖的本质是脂肪细胞被撑大，那么究竟是什么力量促使脂肪细胞不断变大？主流观点几乎完全归咎于“卡路里超标”，但比克曼强调，这忽视了最为关键的生化驱动力——激素。卡路里仅仅是能量底物，而激素才是指挥人体各种组织“如何处置能量”的调度令。脂肪细胞即使被无尽的能量包围，只要没有胰岛素下达指令，它也根本无法将能量吸收储存。
比克曼举了一个极为极端的临床实例：如果让一名 1 型糖尿病患者每天吃下 10,000 卡路里的暴饮暴食，但只要严格剥夺其外源性胰岛素注射，该患者不仅无法增加一丁点脂肪，体重还会急剧下坠——没有胰岛素，人体在生理机制上是“绝对不可能”合成并储存脂肪的。
这种生化铁律甚至催生了一种致命的进食障碍。在临床上，许多十三四岁刚确诊 1 型糖尿病的少女正处于对自身外貌和体型极度敏感焦虑的青春期。这些年轻女孩很快发现了一个黑暗的生理漏洞：“只要我不给自己注射胰岛素，我就能随意吃任何想吃的食物，而且想多瘦就能多瘦。”这种病态利用生化漏洞的控重行为在医学上有专门的临床诊断名称——“胰岛素限制进食障碍”（Diabulimia）。比克曼指出，这种疾病的存在，以极其残酷且不容辩驳的事实彻底粉碎了“体重增减只取决于卡路里摄入”的简单神话，直接证明了胰岛素才是控制脂肪细胞膨胀或缩小的终极主控开关。
### [29:31](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1771s) 培养皿里的肥胖真相：过度膨胀的“水球”与胰岛素抵抗的防御机制
Dr. Benjamin Bikman 用自己在实验室中亲手指导学生做的一个实验，生动拆解了肥胖与胰岛素抵抗的底层关系。在他的实验室里，学生们在培养皿中培养脂肪细胞。起初，这些细胞浸泡在充满能量的“热量之海”里——周围有极其丰富的葡萄糖和脂肪分子，但令人惊讶的是，只要缺少胰岛素，脂肪细胞就会一直保持极为弱小、扁平的状态，根本不知道如何利用身边的能量。然而，一旦往培养皿中注入胰岛素，仅仅过了4个小时，细胞就肉眼可见地变肥大了；再过4小时，它们变得更加庞大。胰岛素就像一道明确的指令，突然教会了脂肪细胞如何摄取并囤积周围的养分。
这种病理性的过度膨胀正是慢性胰岛素抵抗的起源。当脂肪细胞被塞得极其巨大时，它会面临物理极限——细胞膜被撑到薄如蝉翼，随时面临破裂与坏死的威胁。Bikman 将其比作一个被淘气小男孩注水过量、濒临爆炸边缘的“水球”。脂肪细胞为了自保，不得不对胰岛素发出呼喊：“你一直在逼我继续变大，但我已经大到要撑爆了，我不能再听你的指令了！”于是，脂肪细胞主动下调对胰岛素的反应，关闭大门形成“胰岛素抵抗”，以此作为阻止自己继续膨胀致死的最后防御手段。
- **培养皿实验现象**：脂肪细胞周围即使有极高浓度的葡萄糖与脂肪，没有胰岛素时依然微小；加入胰岛素后4小时立即增大，8小时后进一步急剧肥大。
- **水球破裂隐喻**：肥大的脂肪细胞达到物理容积上限时，细胞膜退化濒临破裂，产生胰岛素抵抗本质上是细胞避免自我毁灭的生存自卫机制。
---
### [30:40](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1840s) 信号与原料：为什么没有胰岛素你就绝不可能发胖？
面对主持人 Steven Bartlett 关于“胰岛素是否直接导致肥胖”的追问，Bikman 斩钉截铁地回答：“绝对如此。”他进一步阐述，脂肪细胞要变大必须同时满足两个不可或缺的变量：第一是**信号**，即命令脂肪细胞生长的胰岛素；第二是**原料**，即血液中的热量与营养底物。在人体内，没有任何其他激素可以替代胰岛素发出储存脂肪的指令。以未注射外源胰岛素的 1 型糖尿病患者为例，无论体内其他激素如何波动，哪怕他们每天狂吞 10,000 大卡的巧克力蛋糕，也绝对不可能变胖。
在完全缺乏胰岛素的状态下，不仅无法增加脂肪，身体甚至根本无法留住现有的脂肪。脂肪细胞因为失去了“锁闭”和“生长”的命令，只能疯狂分解已有的脂肪，迫使整个机体进入极端剧烈的燃脂状态，导致体重急剧流失。因此，脂肪存储是一场双向协作：脂肪细胞必须先接收到胰岛素发出的“变大”信号，随后才会伸手向血液中抓取葡萄糖和脂肪分子来“填充体积”。信号与原料两者缺一不可，失去平衡就会演变成病态乃至危及生命的代谢崩溃。
```mermaid
flowchart TD
accTitle: 脂肪细胞变大的双变量机制
accDescr: 展示胰岛素信号与热量原料共同作用导致脂肪细胞膨胀并最终触发胰岛素抵抗的闭环路径。
subgraph Signals ["控制指令"]
Insulin["胰岛素水平升高<br/>（唯一的储存开关）"]
end
subgraph Substrates ["物质基础"]
Calories["血液中的热量原料<br/>（葡萄糖与游离脂肪酸）"]
end
subgraph Adipocyte ["脂肪细胞反应"]
Uptake["细胞吸收营养底物<br/>体积急剧膨胀"]
Limit{"达到膨胀极限<br/>（像过充的水球）"}
IR["产生胰岛素抵抗<br/>拒绝进一步变大自卫"]
end
Insulin --> Uptake
Calories --> Uptake
Uptake --> Limit
Limit -->|"细胞膜濒临破裂"| IR
```
- **绝对因果链**：没有胰岛素信号，无论摄入多少热量（如 1 型糖尿病患者摄入万卡热量），身体也只能剧烈燃脂而无法储存分毫脂肪。
- **存储前提**：高胰岛素负责提供“囤积命令”，血液中的糖和脂肪提供“填充体积”，二者共同促成肥胖。
---
### [32:11](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=1931s) 呼吸中排出的卡路里：等热量饮食下的代谢率差异与酮体浪费
当讨论延伸到“如果两人吃相同的 2,000 大卡，但胰岛素水平不同，会发生什么”时，Bikman 解释道：胰岛素抵抗或高胰岛素血症患者会将更多热量转化为脂肪储存起来，而当脂肪细胞达到极限无法再存时，机体便会陷入更深层的胰岛素抵抗。然而，人类临床等热量（Isocaloric）研究揭示了一个更惊人的现象：如果控制两组受试者摄入完全相同的热量和蛋白质（例如每餐严格控制在 1,000 大卡），仅仅改变碳水化合物与脂肪的比例——一组采用传统的高碳低脂饮食，另一组采用低碳高脂饮食，两者的代谢命运将天差地别。
低碳高脂饮食带来的胰岛素峰值更低，机体储存的脂肪显著减少。面对热力学第一定律“能量既不能被创造也不能被消灭”的质疑，Bikman 指出，这些热量并没有凭空消失，而是通过两种机制被身体主动“挥霍”掉了：
1. **基础代谢率的飙升**：在全天热量完全一致的前提下，低碳低胰岛素状态下的人体基础代谢率整整高出近 300 大卡。这意味着即使静止不动，身体每天维持生命本身所消耗的能量也大幅增加——相当于在踏步机上拼命锻炼一小时所燃烧的热量。
2. **酮体形式的热量排泄**：在超低胰岛素水平下，机体大量分解脂肪并在肝脏合成酮体。每个酮体分子所携带的热量负荷与葡萄糖大致相当。当血酮升高时，身体会通过呼气将丙酮排出体外，通过尿液将乙酰乙酸排出体外。“每一次你向外呼气或排尿，你其实都在把实打实的热量直接倾倒进宇宙中”，这种热量的无形浪费，彻底打破了单纯“卡路里进出”的机械计算。
- **300 大卡的代谢红利**：在等热量对照研究中，低碳水低胰岛素饮食组的每日代谢能耗高出约 300 kcal，等同于一小时高强度踏步机运动。
- **热量排出途径**：低胰岛素迫使肝脏高速燃脂产生酮体，多余的酮体分子通过呼吸和排尿被直接代谢浪费掉。
---
### [34:53](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2093s) 昂贵组织假说：肉食、脂肪与大脑进化的远古秘密
在探讨如何降低胰岛素之前，Dr. Bikman 引导听众回溯人类在进化史上的独特轨迹：人类究竟因何在生理构造上与最近的灵长类近亲（如黑猩猩和大猩猩）分道扬镳？目前人类学与演化生物学中最具说服力的假说之一是“昂贵组织假说”（Expensive Tissue Hypothesis），而这一假说与酮体代谢有着千丝万缕的联系。
根据该理论，人类远古祖先从灵长类谱系中分离的核心拐点在于饮食中肉类和动物脂肪比例的大幅增加。肉类是一种极度高营养密度、富含优质脂肪与蛋白质的食物。这种饮食结构带来了两个互为表里的演化飞跃：
- **肠道的大幅缩短**：植物性食物需要庞大的消化系统来进行漫长的微生物发酵，因此食草或高纤维饮食的灵长类拥有巨大而繁复的结肠。而肉类极其易于消化吸收，人类无需在笨重活跃的结肠上耗费大量生理能量，大肠与结肠显著缩小。
- **大脑体积的爆炸式增长**：肠道缩小省下的庞大代谢能量，被分配给了最“昂贵”的组织——大脑。高脂肪肉食不仅提供了丰沛的热量，更解放了祖先为了觅食而整日咀嚼植物的时间，使他们拥有了好奇探索世界的余力，驱动大脑容积不断膨胀。
- **昂贵组织假说核心**：高密度肉食使人类摆脱了大体积发酵结肠的生理负担，缩减的消化道能量被转移用于扩增高耗能的大脑。
- **演化分水岭**：与近亲黑猩猩相比，人类极短的消化道和不成比例的庞大大脑，是数百万年肉食与脂肪摄入直接塑造的结果。
---
### [37:07](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2227s) 婴儿生酮与大脑的燃料真相：击碎“大脑只爱葡萄糖”的神话
大脑能够支撑如此巨大的体积，关键的能量底物正是酮体。Bikman 指出，新生儿的发育规律完美印证了脂肪与大脑的演化共生关系：早产儿之所以在成长过程中更容易面临认知与学习障碍，一个关键原因在于早产儿未能来得及在母体内储备足够的体脂。在人类生理学中，“胖嘟嘟的婴儿才是健康的婴儿”，因为这些厚实的脂肪层是婴儿迅速进入生酮状态的燃料库。
为了展现婴儿惊人的生酮能力，Bikman 举例道：如果两个成年人连续断食 48 小时，其进入的生酮深度，可能还不如一个 6 个月大、仅禁食 2 小时的婴儿。婴儿全身丰满的脂肪在极低胰岛素信号下持续分解释放酮体，而全身对酮体获益最大、最贪婪吸收的器官正是大脑——一旦血液中出现酮体，大脑便会毫不犹豫地将其作为主要燃料吞噬。
Bikman 借此严厉批驳了许多大学教授常年灌输给医学生的陈旧认知——即“大脑的首选燃料是葡萄糖”。他指出，只需看一组简单的临床代谢数据即可戳破这个谎言：在正常人体中，空腹血糖浓度通常为 5 mmol/L（约 80 mg/dL），而轻度断食 24 小时后，血酮浓度通常仅上升至约 1 mmol/L。在这种情况下，血液中的葡萄糖浓度是酮体的整整 5 倍；然而，神经影像学与代谢测定显示，此时大脑超过一半的能量消耗已经切换为由酮体提供。“别再告诉我大脑偏爱葡萄糖了——在一个底物浓度高出 5 倍的环境里，大脑却主动抓取浓度低得多的酮体来满足自身大部分能量需求，这恰恰证明大脑对酮体具有极高的亲和力与偏好。”
- **婴儿极速生酮**：6 个月大的婴儿禁食 2 小时的生酮深度超过成年人完全禁食 2 天，体脂是婴儿大脑发育的天然酮体保障。
- **底物偏好反差**：即便血糖浓度（5 mmol/L）是血酮（1 mmol/L）的 5 倍，大脑依然会优先摄取酮体来供应其一半以上的能量消耗。
### [39:31](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2371s) 动物性食物、脑容量与必需营养素的争议
本杰明·比克曼博士（Dr. Benjamin Bikman）抛出了一个颇具争议的研究发现：在人类演化和现代人群观察中，肉类摄入越少的人群，往往伴随着更小的脑容量。人类大脑极度依赖动物源性食物所提供的高营养密度，一旦缺乏，大脑结构和功能就会受到损害。史蒂文·巴特利特（Steven Bartlett）直言这是一个极具争议的观点，比克曼博士则幽默地回应：“确实如此，你可以把它剪掉，但这是事实。”他进一步指出，当人们彻底停止摄入动物性食物时，抑郁症的发病率往往会显著上升，其根源正在于剥夺了大脑运转所必需的关键养分。
面对史蒂文关于“大脑究竟被剥夺了什么”的追问，比克曼解释道，最核心的缺口之一是必需的 Omega-3 脂肪酸。自然界存在三种主要的 Omega-3，植物只能提供其中一种（ALA），但人体对它的利用率极低，真正维系大脑结构与认知功能的是另外两种（EPA 和 DHA），而它们几乎只存在于动物性食物中。虽然纯素食主义者可以通过膳食补充剂来弥补，但这设立了极高的门槛——当事人不仅需要具备足够的营养学知识以识别自身的营养短板，还得拥有足够的财力去持续购买昂贵的针对性补剂。
- **脑部营养关键**：人类大脑需要动物源性食物中现成的长链 Omega-3 脂肪酸；植物性来源在人体内的转化效率极低。
- **纯素饮食补剂门槛**：严格的植物性饮食若要避免大脑营养缺乏，高度依赖个体的营养认知水平以及购买高品质营养补充剂的经济能力。
---
### [40:36](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2436s) 胰岛素抵抗的进化之谜：病理性与生理性
史蒂文将话题拉回核心演化问题：如果胰岛素抵抗会导致高血压、阿尔茨海默病和心脏病等致命疾病，人类身体为何会在演化中保留这一机制？比克曼指出，胰岛素抵抗的演化初衷是帮助机体在特定环境下“更牢固地锁住能量”。然而，大众常谈论的其实是“病理性胰岛素抵抗”（Pathological Insulin Resistance），它毫无生理益处，只会致病；但人体内同样存在有益且必需的“生理性胰岛素抵抗”（Physiological Insulin Resistance），其典型代表就是发育过程中的“两个 P”——青春期（Puberty）与妊娠期（Pregnancy）。
在青春期和妊娠期，机体处于生理性胰岛素抵抗状态，伴随着较高的胰岛素水平。比克曼将体内的胰岛素比作“肥料”（fertilizer），它的核心驱动力就是促进生长。对于青春期骨骼、肌肉和体脂都需要爆发式生长的儿童而言，胰岛素发出信号让机体储存能量、扩增组织，这是至关重要的生长引擎。对成年女性来说，在结束青春期之后，人生中唯一还会经历组织快速扩增的阶段就是怀孕。
```mermaid
flowchart TD
accTitle: 胰岛素抵抗的两大分类及其功能分支
accDescr: 展示生理性胰岛素抵抗与病理性胰岛素抵抗在机体中的不同作用机制与结局
A["胰岛素抵抗 (Insulin Resistance)"] --> B["生理性胰岛素抵抗<br/>(Physiological / 有益且必需)"]
A --> C["病理性胰岛素抵抗<br/>(Pathological / 慢性有害)"]
subgraph 生理性机制 ["'两个 P' 生长发育阶段"]
B --> D["青春期 (Puberty)<br/>促进骨骼、肌肉与脂肪爆发式增长"]
B --> E["妊娠期 (Pregnancy)<br/>增大子宫、形成胎盘、储备能量与乳腺发育"]
end
subgraph 疾病进展 ["失衡导致代谢紊乱"]
C --> F["慢性疾病风险上升<br/>(肥胖、高血压、阿尔茨海默病、心脏病)"]
E -.->|"叠加高糖饮食与遗传倾向"| G["妊娠期糖尿病 (Gestational Diabetes)"]
end
```
在怀孕期间，女性的身体不仅要扩增子宫、构建全新的胎盘组织，还需要通过产生轻度的胰岛素抵抗，将更多的葡萄糖分配给腹中胎儿，以加速胎儿的发育。与此同时，在孕酮等激素的协同刺激下，母体会大量储存脂肪。这是身体在发出明确指令：“我正在全力孕育另一个生命，这一过程在代谢上极其耗能；我必须尽可能多地储备额外能量，以防孕期遭遇食物匮乏，甚至为产后的哺乳期提前准备好能量底物。”
---
### [43:39](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2619s) 妊娠期糖尿病及其对下一代的长期影响
当谈到妊娠期糖尿病（Gestational Diabetes）时，比克曼将其定义为“妊娠期的 2 型糖尿病微缩版”。正常健康的孕妇在怀孕前胰岛素敏感度极高，怀孕后虽然进入生理性胰岛素抵抗，胰岛素水平显著上升以支持生长，但胰岛仍能分泌足够的量将血糖维持在安全范围内。然而，如果孕妇本身带有 2 型糖尿病的家族遗传倾向，且在孕期肆无忌惮地摄入大量糖分与精制碳水化合物，胰岛素抵抗就会被严重放大，导致胰岛素分泌再高也无法控制血糖，从而正式演变成妊娠期糖尿病。
这种宫内高糖高胰岛素环境对胎儿会造成深远且残酷的“代谢印记”。比克曼形容，胎儿在子宫内相当于直接浸泡在高血糖和高胰岛素的环境中生长，导致其神经和代谢系统在发育早期就被“硬编码”（hardwired），习惯并渴望出生后继续维持高胰岛素、高血糖的状态。因此，患有妊娠期糖尿病母亲所生的孩子，体重超标或肥胖的概率大幅上升，且未来罹患 2 型糖尿病的风险极高。
- **代际传递风险**：史蒂文引用比克曼书中的数据指出，这类胎儿在青少年期及成年后，面临高出 **40%** 的肥胖和代谢综合征风险。
- **临床意义**：比克曼强调，虽然面对面临代谢挣扎的母亲需要抱以极大同情，但这也是促使女性在孕期极度注重健康饮食的关键动力。
---
### [45:59](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2759s) 年轻女性癌症发病率上升之谜
史蒂文分享了一张社交媒体上引发广泛讨论的数据图表：在过去 20 年间，49 岁以下人群的癌症发病率走势出现巨大分化——年轻女性的癌症发病率急剧飙升，而年轻男性的发病率曲线却基本持平。
比克曼首先从流行病学和诊断机制的角度提出了一种“乏味但客观”的推测：检测技术的普及与筛查习惯。女性通常更早、更主动地接受乳腺钼靶、超声或磁共振（MRI）筛查，很多早发性肿瘤在早期就被捕获，而男性往往极少主动接受任何体检筛查（比克曼打趣说“这也是为什么男性死于各种疾病的概率通常更高”）。但在病理层面，比克曼认为这一激增曲线几乎完全是由**乳腺癌**驱动的，因为乳腺癌长期以来都是女性最主要的恶性肿瘤。
比克曼进一步分析了乳腺癌发病率上升的潜在推手：
1. **育龄推迟与生育率下降**：医学界早已证实，生育和母乳喂养是女性降低乳腺癌风险的最有效生理手段之一（可能与哺乳期雌激素水平的生理性改变有关）。随着现代女性生育年龄推迟或不育比例增加，乳腺癌的发生率随之抬升。
2. **肥胖流行趋势**：伴随超重和肥胖率的升高，体内过剩的脂肪组织和持续升高的胰岛素水平，为肿瘤细胞的增殖提供了源源不断的“促生长燃料”。
在对谈中，史蒂文现场通过人工智能对图表进行了检索核对，英国癌症研究中心（Cancer Research UK）的相关数据恰好验证了比克曼的论点：排名前列的原因正是早发性乳腺癌的激增、育龄推迟以及肥胖趋势的蔓延。
### [48:55](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=2935s) 胰岛素受体与乳腺癌：高胰岛素环境如何成为肿瘤的“催化剂”
作为一名细胞生物学家，本杰明·比克曼（Benjamin Bikman）博士强调自己习惯于深究直接的生理机制。在探讨过去二十年间肥胖率上升与女性癌症激增的关系时，他指出真正的元凶并非肥胖本身，而是与其密不可分的代谢内环境——即胰岛素抵抗与高胰岛素血症。如果将患者体内的乳腺肿瘤组织与其紧邻的正常乳腺组织进行比对，会发现一个惊人的生理突变：乳腺癌细胞表面的胰岛素受体数量是正常乳腺组织的整整 7 倍。
比克曼博士形象地解释道，胰岛素在人体内的基本职责之一就是“下达生长指令”。在几乎所有被检测过的肿瘤中，胰岛素受体的表达量都异常丰富。癌细胞仿佛在对周围的正常细胞叫嚣：“胰岛素马上就要过来了，它会命令我们所有人疯长，但我比你们拥有更多的受体，我要长得比你们更快！”癌症的本质正是失控的异常增殖，而持续处于高水平的胰岛素，一方面催生了更加庞大的脂肪细胞，另一方面则在不断为恶性肿瘤细胞的疯狂分裂“推波助澜”。因此，乳腺癌发病率的持续走高，极大概率是全社会胰岛素抵抗普遍蔓延的恶果。
- **7 倍受体突变**：乳腺肿瘤组织的胰岛素受体数量是同源正常乳腺组织的 7 倍，极度放大了胰岛素带来的促生长信号。
- **代谢环境诱因**：推动肿瘤加速恶化的关键并非单纯的脂肪堆积，而是高胰岛素血症营造的促增殖生化微环境。
---
### [50:32](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3032s) 中场插播：无屏幕健康追踪设备 Whoop
节目主持人史蒂文·巴特利特（Steven Bartlett）插播了赞助商 Whoop 的广告。作为该品牌的早期投资人与忠实用户，史蒂文常被问及为何弃用其他智能穿戴设备而独宠 Whoop。他解释称，核心优势在于其极具克制且“非侵入性”的极简设计。Whoop 创始人威尔·艾哈迈德（Will Ahmed）曾做客该节目并直言：“有屏幕就意味着有干扰（screens equal distraction）。”在日常会议或健身训练中，没有屏幕的 Whoop 从不主动抢夺注意力，只在后台默默采集生理体征数据，随时供用户调取分析。
---
### [51:29](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3089s) 阿尔茨海默病的真实死因与被推翻的“淀粉样蛋白斑块”假说
话题转入全球肆虐的认知障碍症与阿尔茨海默病。史蒂文指出，全球每 3.2 秒就会新增一例痴呆症患者，民间常将其称为“3型糖尿病”（Type 3 Diabetes）。比克曼博士确认，阿尔茨海默病已从昔日鲜为人知的小众病症跃升为西方社会的十大死因之一，其致死过程漫长而模糊。长期以来，全球医学界投入了数十亿美元开展淀粉样蛋白斑块（amyloid plaques）的研究，传统观点认定这些黏稠的蛋白质斑块阻断了神经元之间的信号传导，从而导致认知崩溃。
然而，比克曼博士坦言自己长期以来都坚决反对这种“斑块假说”。临床事实早已给出重重一击：多款获批上市的药物能够极为有效地清除脑内积聚的斑块，但患者的认知衰退却没有丝毫好转；而在病理尸检中，生前思维极其敏锐、毫无认知障碍的逝者，其脑内存在斑块的概率竟然与重度阿尔茨海默病死者完全相同。更具戏剧性的是，大约两三年前，学术界踢爆了最初确立“斑块致病论”的开山之作竟然通篇充斥着伪造的数据。这场席卷全球科研界数十载、耗资数十亿美元的“斑块追逐战”，最终被证实是一场被学术欺诈带偏的弯路，斑块充其量只是某些大脑自带的无害“斑纹”，根本不是疾病的始作俑者。
- **发病增速**：全球每 3.2 秒即涌现一例新的痴呆症病例，现已位列西方社会前十大致死疾病。
- **临床矛盾**：靶向清除脑内斑块的药物对改善患者认知功能毫无疗效，且健康高龄老人死后脑中同样广泛存在斑块。
- **学术丑闻**：奠定斑块假说核心基础的早期关键学术论文，因数据造假被正式撤稿与曝光。
---
### [54:41](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3281s) 大脑的胰岛素抵抗：被饥饿困死的“能量危机”
剥离了斑块假说的迷雾，在阿尔茨海默病患者体内普遍被检测到的核心异常，其实是明确的胰岛素抵抗，甚至就是确诊的 2 型糖尿病。比克曼博士直言自己并不青睐“3型糖尿病”这一新造词汇，因为这并非某种全新的糖尿病变种，其本质就是“大脑局部的胰岛素抵抗”。大脑是人体代谢率极高的三大核心器官之一（比克曼教学中称之为代谢率的“三位一体”），是个时刻都在疯狂索取能量的暴食器官，但它极度挑食，主要且仅能消耗两种能源燃料：葡萄糖与酮体。
在大脑中负责记忆与认知的核心区域，葡萄糖分子并不能自由出入，它必须依赖胰岛素充当“敲门者”来下达开门指令。当大脑发生胰岛素抵抗时，神经细胞对胰岛素的敲门声充耳不闻，紧闭大门。尽管患者外周血液中的血糖可能高得吓人，但脑细胞却因进不去葡萄糖而陷入“相对饥饿”。与此同时，由于高碳水摄入使得全身胰岛素水平常年居高不下，肝脏完全无法生成能够替代葡萄糖的酮体。这就导致大脑陷入了可怕的“能量缺口”（energy gap）。在既没有葡萄糖又缺乏酮体的窘境下，大脑只能被迫削减能耗、降低机能，临床上便直接表现为思考、处理信息与认知记忆能力的急剧滑坡。
```mermaid
flowchart TD
accTitle: 大脑胰岛素抵抗引发能量危机的病理生理机制
accDescr: 展示高碳水高胰岛素环境下，大脑葡萄糖利用受阻且酮体供应被阻断，最终导致认知能力下降的恶性循环链路
subgraph MetabolicDefect["代谢障碍根源"]
A["高碳水饮食与高胰岛素血症"] --> B["外周血糖持续高企"]
A --> C["肝脏产酮机制被完全抑制"]
end
subgraph BrainMetabolism["脑部摄能阻断"]
B --> D["脑细胞受体脱敏\n(大脑胰岛素抵抗)"]
D --> E["葡萄糖转运受阻\n门扉紧闭"]
C --> F["血液中严重缺乏酮体"]
end
subgraph EnergyCrisis["功能崩溃"]
E --> G["大脑葡萄糖低代谢\n(Glucose Hypometabolism)"]
F --> G
G --> H["大脑陷入无法弥合的\n'能量缺口' (Energy Gap)"]
H --> I["脑功能被迫降级:\n认知衰退 / 阿尔茨海默病"]
end
```
---
### [57:38](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3458s) 大脑葡萄糖低代谢：神经退行性疾病与精神疾患的共性
这种脑部营养不良的状态在医学科研界被称为“大脑葡萄糖低代谢”（brain glucose hypometabolism）。科学家借助放射性标记葡萄糖的成像技术（如 PET 扫描）可以清晰直观地观察到：阿尔茨海默病患者的大脑对葡萄糖的摄取与代谢活跃度出现了断崖式下跌。
更发人深省的是，比克曼博士指出，这一能量代谢崩溃机制绝非阿尔茨海默病所独有。翻开现代神经病学与精神病学的病谱，诸如抑郁症（depression）、偏头痛（migraines）、癫痫（epilepsy）以及帕金森病（Parkinson's disease）等神经系统疾患的底层病理生理改变中，全都可以检测到极为一致的大脑葡萄糖低代谢现象。大脑神经元的能源告急与代谢衰竭，正在成为贯穿多种大脑功能障碍的核心交汇点。
### [58:34](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3514s) 神经系统疾病与阿尔茨海默病：大脑的“3型糖尿病”
中枢神经系统的多种退行性与功能性疾病，在病理本质上都存在一个惊人的共同点：大脑无法从葡萄糖中获取足够的能量。换句话说，这些看似毫无关联的脑部疾病，其底层几乎都伴随不同程度的胰岛素抵抗。当葡萄糖代谢途径受阻时，如果能够产生酮体，酮体就能作为替代燃料“及时赶来救场（swoop in to save the day）”。然而，这种代谢拯救机制生效的前提，是人体必须从持续高企的胰岛素状态中解脱出来，给身体留出足够的时间去启动生酮机制。
斯蒂芬·巴特利特（Steven Bartlett）指出，公众和学界对胰岛素抵抗与阿尔茨海默病之间的深刻关联讨论得还远远不够。他引用相关临床数据提出疑问：在阿尔茨海默病患者中，符合胰岛素抵抗诊断标准的比例究竟有多高？不同的文献给出的跨度极大，2011年《神经病学杂志》（*Journal of Neurology*）发表的一项研究显示约为40%，而布朗大学（Brown University）苏珊·德拉蒙特博士（Dr. Suzanne de la Monte）等学者的研究甚至指出该比例高达70%至80%，德拉蒙特博士也正是将阿尔茨海默病定义为“3型糖尿病（Type 3 Diabetes）”的先驱倡导者。
本杰明·比克曼（Benjamin Bikman）博士对这一命名逻辑表示赞赏，尽管他个人对“3型糖尿病”这个字眼有所保留，但它明确指出了阿尔茨海默病的代谢根源。至于40%与80%之间的巨大统计差异，比克曼认为这完全取决于研究人员在定义胰岛素抵抗时采用了什么筛查指标：如果临床上仅仅检测血糖，那么在血糖尚未飙升之前，绝大部分早期胰岛素抵抗患者都会被彻底漏诊。
### [01:00:17](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3617s) 隐性胰岛素抵抗与常规检测盲区：瘦人与多囊卵巢综合征（PCOS）
比克曼博士指出，医学界对胰岛素检测的培训与制度支持严重缺失。在技术层面，测定空腹胰岛素十分简便，但英国的国民医疗服务体系（NHS）或加拿大的公共医疗系统中，全科医生（GP）通常不会也不会被授权开具胰岛素检测单。医疗系统往往带着一种“善意却无知”的偏见，认为胰岛素并非关键指标。但真相在于，许多处于胰岛素抵抗初期的患者，其空腹血糖完全处于健康范围，唯独胰岛素水平早已居高不下。比克曼给出了具体的预警阈值：
- 美制单位（US units）：空腹胰岛素高于 **10 μIU/mL** 即为危险警告；
- 英制单位（UK units）：空腹胰岛素高于 **40 pmol/L** 即提示存在严重胰岛素抵抗风险。
身材苗条并不等于代谢健康。斯蒂芬惊讶地提问外表消瘦的人是否也会出现胰岛素抵抗，比克曼斩钉截铁地确认了这一点，并指出这与种族以及特定内分泌状态高度相关。例如，加拿大北部开展的一项针对年轻、正常体重女性的研究发现，即便在体脂完全一致的情况下，患有多囊卵巢综合征（PCOS）的偏瘦女性，其胰岛素抵抗程度依然显著高于对照组。
斯蒂芬谈及自己一位患有PCOS且极易发胖的女性朋友。比克曼证实，PCOS患者极大概率伴随高胰岛素血症，这导致她们体内的胰岛素随时都处于偏高状态，脂肪合成被强力锁定、脂肪分解受到抑制。但比克曼强调“认知即力量（knowledge is power）”，只要通过科学检测明确指标，即便面对PCOS，许多文献也已证实仅仅依靠纯粹的饮食干预，就能实现疾病的完全逆转。
```mermaid
flowchart TD
accTitle: 胰岛素抵抗向代谢疾病发展的检测盲区
accDescr: 展示胰岛素升高如何早于血糖异常被常规检查忽视并诱发多种疾病
subgraph EarlyStage["早期隐匿阶段（常规体检易漏诊）"]
A["高碳水/不良生活方式"] --> B["高胰岛素代偿状态<br/>(胰岛素 > 10 μIU/mL)"]
B --> C["空腹血糖依然正常"]
end
subgraph LateStage["失代偿阶段"]
B --> D["个人脂肪阈值被突破"]
D --> E["血糖失控上升<br/>(确诊2型糖尿病)"]
end
subgraph Manifestations["代谢与神经系统并发症"]
B --> F["脑组织葡萄糖供能障碍<br/>(阿尔茨海默病 / 3型糖尿病)"]
B --> G["内分泌紊乱 / 易胖体质<br/>(多囊卵巢综合征 PCOS)"]
end
```
### [01:03:36](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=3816s) 种族差异、皮下与内脏脂肪以及“个人脂肪阈值”
针对种族与体脂代谢的研究，斯蒂芬提出一份数据称东亚人群脂肪细胞较少、不易患肥胖相关代谢病。比克曼当即纠正了后半句的致命误解：东亚人群确实具有极强的“抗肥胖体质”，但他们在代谢层面对肥胖极其脆弱。“你在日本街头要想找一个像美国平均体型那么胖的男性，简直像大海捞针；然而要找一个罹患2型糖尿病的日本男性，却轻而易举。”这背后的科学核心在于澳大利亚学者提出的“个人脂肪阈值（Personal Fat Threshold）”假说：每个人的身体能以安全、健康方式储存脂肪的容量上限由遗传、性别和种族严格决定，一旦突破这个临界点，多余的脂肪压力就会迅速引发胰岛素抵抗。
脂肪在体内的解剖分布决定了代谢风险的严重程度：
- **皮下脂肪（Subcutaneous Fat）**：位于皮肤正下方，即肉眼可见、用手“能捏起来且会晃动（pinch and jiggle）”的松弛脂肪。欧裔白人与非洲裔人群往往能将较多脂肪储存在皮下。这种脂肪细胞具有一定的增殖与扩张空间，因此皮下脂肪容量大的人具有更高的“脂肪安全阈值”，在出现严重时代谢损伤前可以承受更高的体脂率。
- **内脏脂肪（Visceral Fat）**：深藏在腹腔内部、紧密包裹在肝脏、肾脏与肠道周围。内脏所在的核心腹腔空间极其狭窄有限，无法容忍脂肪细胞肆意增殖压迫器官组织。东亚人群以及部分拉丁美裔（Hispanic）在储存脂肪时，倾向于将极高比例的脂肪直接塞入内脏区域，因此即便外表保持纤瘦，内脏脂肪也极易超载并触发代谢崩溃。
- **种族脂肪耐受度光谱**：以欧裔白人和非裔人群为一端（皮下脂肪储备能力最强、安全阈值相对较高），拉丁裔/西班牙裔处于中间阶段，东南亚与东亚人群则处于另一端（皮下脂肪存储能力最弱，对脂肪积聚最为敏感、极易转为内脏脂肪）。
- **空间解剖限制**：腹腔空间的不可扩展性是内脏脂肪危害极大的关键原因，它迫使溢出的脂质进入异位器官并释放炎症信号，从而在轻微增重时即摧毁全身的胰岛素敏感性。
### [01:07:17](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4037s) 内脏脂肪的毒性与阿尔茨海默病的代谢根源
脂肪细胞的膨胀方式决定了人体的代谢健康。皮下脂肪细胞数量较多但体积较小，主要通过增生（hyperplasia）来存储脂肪；而内脏脂肪细胞数量较少，只能通过肥大（hypertrophy）来扩容。本杰明·比克曼（Dr. Benjamin Bikman）指出，无论是拉美裔还是亚裔等族裔，只要遗传特征倾向于在腹部内脏区域优先积聚脂肪，就会更早面临内脏肥大带来的代谢后果——“脂肪细胞越大，脂肪细胞就越病态”。内脏空间极为有限，脂肪细胞一旦过度膨胀，不仅会从物理上挤压和压迫肠道、肾脏等维持生存所必需的器官，还会持续释放促炎因子。
为了实证不同脂肪库的本质差异，比克曼提到了一项极具启发性的动物移植实验：如果将一只动物的皮下脂肪移植到另一只瘦动物体内，受体动物依然非常健康，因为皮下脂肪呈代谢惰性，“只是待在那里自顾自地待着”；但如果将肥胖动物体内的内脏脂肪移植到瘦动物体内，接受移植的动物会瞬间出现胰岛素抵抗并迅速迈向糖尿病。这项研究直接证实，内脏脂肪本身具有强烈的全身病理毒性。
与此同时，这种系统性代谢恶化直接波及大脑。根据国际阿尔茨海默病协会（Alzheimer's Disease International）的数据，全球痴呆症患者预计将从2020年的约5500万飙升至2050年的1.39亿。尽管主持人史蒂芬·巴特利特（Steven Bartlett）推测这是否部分源于人类预期寿命的延长，但比克曼澄清道，近年来现代社会的预期寿命在历史上首次出现拐点下降。现代医学往往只是让人们“带着疾病活得更久”。大脑认知衰退的实质是我们人为制造的代谢内环境恶化：由于全身及脑部长期处于高胰岛素抵抗状态，脑细胞无法正常摄取葡萄糖，大脑实际上正陷入越来越严重的“代谢饥饿”。
- **内脏脂肪与皮下脂肪的移植差异**：移植皮下脂肪无害且具有惰性；移植内脏脂肪会立刻在原本健康的动物身上诱发全身胰岛素抵抗与糖尿病。
- **全球痴呆症危机**：预计到2050年全球患者人数将突破1.39亿，其核心推手是脑部胰岛素抵抗导致的神经能量匮乏（即“脑饥饿”）。
---
### [01:10:02](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4202s) 审视“长寿导师”与 Bryan Johnson：相关性研究的致命缺陷
当谈话转向科技富豪布莱恩·约翰逊（Bryan Johnson）及其轰动全网的长寿抗衰实验时，史蒂芬好奇比克曼如何看待这位长寿领域的“招牌人物”。比克曼极为审慎而礼貌地区分了真正的“长寿科学研究”与市面上的“长寿导师/网红（Longevity Gurus）”。他坦言自己对严谨的长寿科学家怀有崇高敬意，但对长寿导师们的运作方式持有明确的保留意见——这些导师最大的优势在于“他们永远无法在当下被证伪”。
长寿导师们宣扬的长寿策略，大多建立在极其薄弱的科学证据之上，主要依赖两类研究：昆虫或低等动物的基础实验，以及流行病学中的“相关性研究”（correlational studies）。比克曼尖锐地指出，饮食相关的观察性问卷调查是科学界最脆弱的证据类型之一：研究人员登门让受试者填写一份回忆性的饮食清单，受试者不仅极易遗忘、甚至可能撒谎，问卷更无法捕捉那些决定寿命的核心变量。
比克曼举例说明，一个人如果身处紧密的社交圈或宗教社团，其预期寿命往往显著高于孤立无援者；而现代医学已充分证明，**孤独对死亡率的助推效应甚至远远超过吸烟**。然而，流行病学问卷往往把“少吃红肉”与“寿命延长”生硬地挂钩，忽略了那些不吃肉的人可能同时拥有更好的健康习惯或更优越的社会支持。长寿导师们却乐于把这些充满漏洞的相关性数据直接包装成不容置疑的“终极饮食法则”。
```mermaid
flowchart TD
accTitle: 流行病学相关性与真实寿命影响因子的偏差
accDescr: 对比长寿导师依据的膳食调查问卷局限与真正影响寿命的生理社交变量
subgraph GurusMethod ["长寿导师依赖的弱证据"]
A["回忆性饮食调查问卷"] --> B["混杂变量：漏报、瞒报与记忆偏差"]
B --> C["粗暴归因：如'吃肉导致短命'"]
end
subgraph RealLifeFactors ["真正决定生存期的未控变量"]
D["紧密社交圈 / 社群归属感"] --> E["显著延长真实寿命"]
F["长期社交孤独"] --> G["致命危害：死亡风险远超吸烟"]
end
C -.->|"忽视真实决定因素"| RealLifeFactors
```
---
### [01:13:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4385s) 代谢视角的长寿真相：胰岛素、自噬与生酮
面对追求长寿的根本解法，比克曼坦言自己作为代谢科学家，必然坚信长寿的基石在于代谢控制。现代长寿科学的奠基人之一辛西娅·肯扬（Cynthia Kenyon）早年在研究线虫（C. elegans）时发现了一个颠覆性现象：限制线虫摄入的葡萄糖，能使其寿命惊人地延长约50%；更具突破性的是，当她的实验室通过基因敲除技术下调线虫体内与胰岛素信号传导相关的基因时，**完全不需要限制食物供应，线虫就能大幅延长寿命**。这一开创性发现奠定了胰岛素信号通路在衰老调控中的核心地位。
长寿界近年来高度推崇“自噬”（autophagy）概念，即细胞自我清理破损蛋白与废旧细胞器的清道夫机制。多数人认为只有长时间断食才能激发自噬，但比克曼揭示了其背后的生理真相：断食之所以能诱导自噬，根本机制在于其压低了胰岛素。来自胰腺的胰岛素是一种极为强效的“自噬抑制剂”。当血液中充斥着高浓度胰岛素时，细胞会始终停留在合成与扩张状态，清道夫功能被全面关闭。
发表在高水平期刊上的一项严谨动物实验进一步证明，研究人员完全不限制热量，让小鼠随意进食（ad libitum），只要将饲料换成低碳水、促成酮体生成的生酮饮食，使小鼠体内的胰岛素保持在低水平，这些小鼠的寿命显著长于那些食用常规高碳水饲料的同窝对照组。比克曼由此感叹，当今的长寿导师们热衷于每天吞服价值数千美元的花哨补剂，却忽视了细胞内部最根本的“生长与自噬”阴阳平衡机制：想要清理垃圾、延缓衰老，最有效且最具成本效益的途径，就是牢牢管住体内的胰岛素。
- **辛西娅·肯扬的线虫里程碑**：通过下调胰岛素相关基因表达，无需饥饿限食即可实现寿命成倍跃升。
- **生酮与自由进食的寿命增益**：实验证明在不剥夺热量、自由进食的前提下，仅靠生酮饮食维持低胰岛素水平，便足以激活自噬并显著延长哺乳动物寿命。
- **胰岛素的自噬刹车效应**：高胰岛素是阻止细胞自我修复与垃圾清理的最大生理阻碍；抗衰老不必寄托于昂贵补剂，压低基础胰岛素才是启动机体自噬的核心钥匙。
### [01:16:25](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4585s) 代谢的双向平衡与胰岛素的促生长特性
代谢（Metabolism）的本质就是构建与破坏的动态平衡。更准确地说，代谢涵盖了合成代谢（Anabolism，即物质的构建与合成）和分解代谢（Catabolism，即物质的降解与破坏）。细胞维持健康生长的核心机制，在于这种“构建与破坏”之间精妙而持续的节奏：先合成部分结构，再适度降解旧结构，随后重新合成新物质。自噬（Autophagy）正是细胞内分解周期中至关重要的一环，它负责清理老化残损的部件，为后续重建腾出空间。
胰岛素在这一过程中起着决定性的调控作用。如果体内的胰岛素水平长期偏高，细胞就永远无法进入分解代谢状态。这种机制也直接解释了为什么高胰岛素状态极其有利于癌症的发生发展：癌症本质上是一种异常生长的疾病，而胰岛素不断发出“促生长”的信号，使得肿瘤细胞永远不会启动分解过程，从而持续扩增。
```mermaid
flowchart LR
accTitle: 代谢的双向平衡与胰岛素的调节机制
accDescr: 展示合成代谢与分解代谢的动态平衡，以及高胰岛素对分解代谢的阻断作用。
subgraph Balance["代谢的双向节律"]
direction TB
A["合成代谢 (Anabolism)<br/>构建新物质与细胞"] <--> B["分解代谢 (Catabolism)<br/>自噬与清除老化构件"]
end
C["高胰岛素水平"] -->|持续刺激| A
C -.->|完全阻断| B
A --> D["肿瘤细胞无节制生长"]
```
### [01:17:26](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4646s) 酮体、生酮饮食与长寿的真正密码
酮体（Ketones）在传统观念中长期被妖魔化和误解，但如今它们正在重获科学界的正确认识。主持人 Steven 谈到自己目前也正在践行生酮饮食，因此迫切希望深入探究生酮在人体内引发的真实变化，以及这一饮食方式的利与弊。
Benjamin Bikman 博士在其著作《Why We Get Sick》中明确指出：人类群体中最长寿的个体，往往也是胰岛素敏感度最高的人。多项回顾性长寿研究试图找出那些与极高寿命高度吻合的生理指标，结果表明，出色的胰岛素敏感度与稳定的血糖控制是核心共性。
例如瑞典约一年前发表的一项大型高质量研究，正是依托瑞典详尽严谨的医疗档案和相对均质的人群结构，排除了多种混杂变量后得出的结论。该研究发现，长寿人群最普遍的生理特征之一是良好的血糖控制能力；但与此同时，长寿者身上还出现了另一个极为反直觉的现象——他们普遍拥有较高的胆固醇水平。
### [01:19:31](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4771s) 胆固醇：被现代医学误解的生命分子
长寿研究中最一致的发现之一便是长寿者往往具有偏高的胆固醇，然而现代社会却谈胆固醇色变，只要指标稍微偏高，医生便立刻开具降脂药。Bikman 博士直言，这种做法很可能适得其反。他将胆固醇称为“生命之分子”（The Molecule of Life），众多核心生命机能对其高度依赖：
- **线粒体功能**：线粒体作为细胞的“能量工厂”，其膜结构中必须含有胆固醇分子才能维持正常运转；药物强行压低胆固醇，首当其冲受损的便是线粒体活性。
- **性激素合成**：体内所有性激素（如睾酮、雌激素）均以胆固醇为原料合成。降脂药导致性激素断崖式下跌，也是许多男性服药后遭遇严重性欲减退甚至勃起功能障碍的直接根源。
- **免疫防线**：被普遍打上“坏胆固醇”标签的低密度脂蛋白（LDL），实际上是免疫系统的关键组分。LDL 能够协助机体识别并抵御细菌与感染，堪称免疫界未被歌颂的无名英雄。
针对“为什么极高龄老人高胆固醇反而与更长寿命相关”，Bikman 博士从生物医学研究的现实利益角度提出了犀利的批判：现代临床医学过度执着于血糖而非胰岛素，过度执着于 LDL 胆固醇而非甘油三酯（Triglycerides），很大程度上是因为药企拥有成熟且利润丰厚的“降糖药”和“降 LDL 药”，却缺乏针对胰岛素或单靠药物降甘油三酯的特效药。临床指标的筛选，在客观上沦为了药品销售的导向工具。
### [01:22:15](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4935s) 吸烟、电子烟与剧烈的胰岛素抵抗
保加利亚曾开展过一项震撼的临床试验：研究人员招募了 7 名从未吸烟的健康受试者，让他们在 1 小时内抽完 4 支香烟，并连续吸烟 3 天。检测结果显示，这些此前完全健康的非吸烟者迅速表现出了明显的胰岛素抵抗。烟草燃烧产生的海量有害颗粒和杂质吸入体内后，会瞬间诱发机体剧烈的全身性炎症反应，而炎症正是驱动胰岛素抵抗的强力推手。
对于当下广为流行的电子烟（Vaping），Bikman 博士与所在大学的肺病专家 Paul Reynolds 教授开展了深入合作，并联合发表了多篇学术论文。他们对比了普通卷烟滤嘴过滤后的烟雾成分与电子烟高温雾化后的分子毒性：
- 电子烟液体经超高温加热裂解后释放出的化学物质破坏力极大；
- 在等量化学物质对比下，电子烟在损伤呼吸道、诱发炎症以及引发胰岛素抵抗方面的毒性表现，甚至比传统香烟更加恶劣。
### [01:23:52](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=5032s) 吸烟会让人发胖吗？成瘾置换与环境毒素
吸烟本身并未让大多数烟民变胖，这是因为吸烟满足了机体强烈的渴求中枢，直接抑制了食欲；烟民对饼干、甜点等食物的兴趣显著减退。然而，这带来了一个典型现象：当烟民尝试戒烟时，体重往往会出现剧烈反弹。戒烟者为了克制烟瘾，往往会在口袋里随身携带硬糖，烟瘾一发作便拿出一颗含在嘴里，本质上是用糖瘾替代了烟瘾。在人类关于食物成瘾的研究中，人们唯一会表现出病理成瘾性的营养素只有碳水化合物，从未有人对纯脂肪或蛋白质产生过成瘾行为。
除了吸入性烟草，环境中的有害废气同样具备破坏代谢的毒性。Bikman 博士在 2024 年发表于《国际分子科学杂志》（*International Journal of Molecular Sciences*）的一项研究中证实：长期暴露于柴油机尾气（Diesel exhaust gas）环境，会直接诱导体内脂肪质量增加、脂肪细胞代偿性肥大、机体炎症水平飙升，并最终引发显著的全身性胰岛素抵抗。
### [01:25:10](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=5110s) 颠覆“卡路里进出”模型：吸入性颗粒物与胰岛素抵抗
Benjamin Bikman 博士提到他与同事 Paul Reynolds 共同发表的关于吸入性颗粒物的研究。Bikman 坦言，自己之所以涉足这一领域，初衷就是为了彻底打破单纯依赖“热量守恒”（卡路里模型）来解释肥胖的陈旧观念。大众普遍持有非常天真的观点：长胖是因为摄入卡路里大于消耗，变瘦是因为摄入小于消耗。能量固然重要，但脂肪细胞必须接收到激素信号，才会知道该如何处理手头的能量——而胰岛素正是最核心的指挥官。
在 Reynolds 的实验室中，他们对动物进行了严格对照实验，通过仪器将柴油尾气颗粒物气溶胶化，精准控制动物的吸入量。令人震惊的是，在摄入完全相同热量与食物的前提下，暴露于柴油废气颗粒物中的动物，其脂肪细胞体积明显膨胀变大，并产生了显著的胰岛素抵抗，而呼吸正常空气的对照组则全然没有这种现象。这表明呼吸环境对身体如何储存脂肪具有决定性作用。
```mermaid
flowchart TD
accTitle: Inhaled Particulates and Adipocyte Expansion Flow
accDescr: Diagram illustrating how inhaling environmental particulates triggers insulin resistance and fat expansion regardless of calorie intake.
subgraph EnvironmentalExposure["环境暴露"]
A["吸入柴油废气 / 香烟烟雾"]
end
subgraph PhysiologicalImpact["生理与细胞反应"]
B["引发系统性炎症与代谢失调"]
C["诱导胰岛素抵抗"]
D["脂肪细胞肥大 (Fat Cell Expansion)"]
end
subgraph CaloricParadox["能量摄入状态"]
E["恒定热量摄入 (无过量进食)"]
end
A --> B
B --> C
E -. 摄入受控.-> D
C --> D
```
- **动物对照实验设计**：实验在动物身上进行，以此完全排除混杂变量并精确掌控颗粒物吸入浓度。
- **能量与信号的分离**：两组动物摄入完全相同的热量，但仅仅因为吸入空气成分不同，废气暴露组就出现了肥大脂肪细胞与胰岛素抵抗。
- **人群流行病学印证**：空气污染指数高、大气悬浮颗粒较多的地理区域，其人口肥胖率和 2 型糖尿病发病率普遍更高。尽管这属于相关性研究，但也揭示了环境毒素对代谢健康的潜在威胁。
---
### [01:27:36](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=5256s) 日常生活中的环境毒素与内分泌干扰物
谈及其他环境毒素对胰岛素抵抗的影响，Bikman 博士指出有两大主要途径：吸入物与非热量摄入物。在吸入物方面，实验室已经证实柴油废气与香烟烟雾具有直接破坏性，目前他们还获得了一笔专门的研究基金，正在深入探讨电子烟（Vaping）对人体代谢与胰岛素抵抗的影响。
另一大隐患来自进入体内的非热量物质，最典型的就是微塑料（Microplastics）。微塑料颗粒极其细小，被人体饮用或摄入后能穿透肠道屏障直接进入血液循环。出于尚未完全明了的生理机制，这些微小塑料颗粒会靶向沉积在脂肪细胞中，直接刺激并促使脂肪细胞体积变大。此外，塑料制品、肥皂和洗涤剂中析出的双酚 A（BPA）或己烯雌酚（DES）等内分泌干扰物（雌激素模拟物），也会模仿或强化胰岛素的促合成信号，直接对脂肪细胞下达持续扩张生长的指令。
- **主要环境毒物分类**：
- 吸入物：柴油废气颗粒、香烟烟雾、电子烟气溶胶。
- 摄入性物理微粒：可通过肠壁进入血液并在脂肪细胞聚集的微塑料。
- 化学性内分泌干扰物：BPA、DES 等模拟雌激素与代谢信号的化学添加剂。
- **促肥机制**：这些毒素绕过传统的能量摄入途径，直接向脂肪组织下达类似胰岛素的“储存与生长”指令。
---
### [01:31:04](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=5464s) 酮症生理学：胰岛素掌控下的双燃料引擎
Steven Bartlett 提到生酮饮食（Keto Diet）在当下越来越流行，自己目前也正在践行这种饮食模式，并询问生酮机制究竟如何与胰岛素抵抗相互关联。Bikman 博士借此展开了一段关于机体代谢与生化反应的科普。他指出，人体本质上是一台“双燃料混合动力发动机”，主要依赖两种能量来源：血糖（葡萄糖）或脂肪。大脑虽然特殊，在葡萄糖之外依靠酮体（Ketones）供能，但身体其他大部分器官主要就是在葡萄糖和脂肪之间切换。
而决定打开哪个燃料阀门、关闭哪个燃料阀门的调度总管，正是胰岛素：
- **胰岛素高企**：身体处于“燃糖模式”（Sugar Burning），脂肪燃烧途径被完全锁死。
- **胰岛素走低**：身体自动切换至“燃脂模式”（Fat Burning）。
在临床与实验室中，可以通过间接测热仪（Indirect Calorimeter）测量人体的呼吸交换率（RER，即排出的二氧化碳与消耗的氧气之比）。当注入胰岛素使体内胰岛素升高时，呼吸交换率上升，表明正在大量燃烧葡萄糖并产生更多二氧化碳；当胰岛素水平下降时，RER 随之降低，表明机体已全面转入以脂肪为主要能量的代谢状态。
当人体胰岛素水平持续维持在低位约 16 小时左右，肝脏便会发生一种极其特殊的代谢转变。此时脂肪细胞不断向血液释放游离脂肪酸，肝脏自身也在持续摄入并剧烈分解燃烧脂肪。肝脏燃烧脂肪的速度非常迅猛，甚至远远超出了自身运作所需的能量额度，但由于低胰岛素信号的持续存在，肝脏并不能踩刹车停止氧化脂肪，从而为酮体的产生创造了前提条件。
```mermaid
flowchart LR
accTitle: Insulin Fuel Selector Switch
accDescr: Chart showing how insulin level determines whether the body burns sugar or enters fat oxidation and ketosis.
subgraph FuelState["代谢调控枢纽"]
Insulin{"胰岛素水平"}
end
subgraph HighInsulin["高胰岛素状态"]
SugarBurn["燃糖模式 (Sugar Burning)"]
HighRER["RER 升高 / 抑制脂肪分解"]
end
subgraph LowInsulin["低胰岛素状态 (~16小时)"]
FatBurn["燃脂模式 (Fat Burning)"]
LowRER["RER 降低 / 游离脂肪酸释放"]
LiverKetones["肝脏超负荷脂解 -> 生成酮体"]
end
Insulin -- "水平升高" --> SugarBurn --> HighRER
Insulin -- "水平降低" --> FatBurn --> LowRER --> LiverKetones
```
### [01:33:43](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=5623s) 酮体：肝脏的代谢安全阀与大脑的超级燃料
当人体内的胰岛素维持在低水平时，脂肪分解与燃烧就会持续不断地运转。此时，由于外界摄入的葡萄糖不足，身体必须寻找替代能源来弥补这一缺口。在肝脏持续燃烧脂肪的过程中，它最终会达到一个峰值——肝脏燃烧的脂肪远远超过了其自身的能量需求。这种过剩的脂肪代谢产物便转化为了“酮体”（Ketones）。Dr. Benjamin Bikman 将酮体形象地比喻为肝细胞的“代谢泄压阀”（metabolic release valve）：肝脏面对汹涌澎湃的脂肪氧化无处安放，同时意识到没有外界葡萄糖涌入、大脑即将挨饿，于是迅速开启酮体生成机制，将这些能量打包送出。因此，酮体本质上就是高强度脂肪燃烧的直接副产物。即便只是普通人轻断食 24 小时，次日清晨醒来体内也会处于某种程度的生酮状态（Ketosis）。频繁进出温和的生酮状态不仅毫不极端，反而是人类理想的生理常态。
大脑尤其渴望并高度适应酮体供能。在临床实践与已发表的研究报告中，研究人员观察到轻度阿尔茨海默病（Alzheimer's disease）患者在未生酮状态下进行认知测试时表现极差。例如，让患者在一张纸上画出带有 1 到 12 数字及指针的传统模拟时钟表盘，患者画出的完全是一团混乱与失序的线条；他们甚至无法集中注意力去理清系鞋带的步骤，也无法独立穿好衣服。然而，一旦引导他们进入生酮状态，大脑重新获得酮体作为高效燃料，奇迹便开始显现：虽然画出的表盘依然略显潦草，但那已经毫无疑问是一只结构清晰的钟表；不仅如此，他们忽然能够解开系鞋带的思维谜题，重新穿衣自理。这些真实的病例报告充分印证了一点：“大脑在拥有酮体作为燃料来源时，表现会极为出色。”
```mermaid
flowchart TD
accTitle: 肝脏脂肪燃烧与酮体生成机制
accDescr: 展示当胰岛素降低时，肝脏如何燃烧脂肪、释放过剩能量转化为酮体并供给大脑和肌肉使用。
subgraph S1["胰岛素受限环境"]
A["低胰岛素水平 / 葡萄糖摄入极低"] --> B["体脂分解，游离脂肪酸源源不断进入肝脏"]
end
subgraph S2["肝脏代谢泄压阀"]
B --> C["肝脏过度氧化脂肪<br/>（燃烧量超过自身能量需求）"]
C --> D["过剩能量转化为酮体<br/>（如乙酰乙酸、β-羟基丁酸）"]
end
subgraph S3["机体各组织收益"]
D --> E["跨越血脑屏障<br/>为大脑提供高效能量"]
D --> F["保护肌肉蛋白免遭分解"]
D --> G["提高外周组织与脂肪代谢率"]
end
```
### [01:35:47](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=5747s) 腹部脂肪代谢率翻三倍与肌肉的终极护卫
酮体带来的生理益处远不止于营养大脑。Dr. Benjamin Bikman 的实验室发表了一项令人瞩目的临床研究：科研人员在受试者处于生酮状态时，从其腹部提取少量脂肪组织，测量其局部代谢率。实验结果显示，在生酮状态下，人体腹部脂肪细胞的代谢率竟然比非生酮状态时“整整高出三倍”。脂肪组织原本被视作代谢极度迟钝、消耗极低的储能器官，但在酮体的刺激下，脂肪细胞忽然变得极其活跃，开始以数倍于常态的速度消耗能量，其代谢活跃程度几乎开始向肌肉细胞靠拢。这意味着在严格控制热量摄入的前提下，一旦人体进入生酮状态，全身体内的新陈代谢炉火就像被添足了优质燃料，全身整体能量消耗显著提升，这为追求减脂的人群带来了无与伦比的生理加速效应。
与此同时，Bikman 团队还探究了酮体对肌肉细胞的保护机制。在实验中，研究人员对培养皿中的肌肉细胞施加代谢压力和损伤性打击。结果发现，经过酮体培育的肌肉细胞表现出极强的损伤抗性。酮体实际上是“肌肉的坚定捍卫者”：当大脑误以为自身缺乏足够葡萄糖时，身体原本的应激策略是剥离肌肉组织中的蛋白质分解转化为葡萄糖；而酮体的出现向大脑宣告——“你可以直接燃烧我，请离肌肉远一点”。这种保护机制解释了为何当今顶尖耐力运动员纷纷将酮体视作强效的体能补剂（ergogenic aid）。例如 Bikman 所在的杨百翰大学（BYU），其男女越野跑队双双斩获全美越野锦标赛冠军，全队在训练与比赛前就会常规饮用生酮饮品；环法自行车赛（Tour de France）的多支顶级车队也已全面采用外源性酮体。在长时间高强度竞速中，常规运动员耗尽糖原后便会经历残酷的“撞墙”（bonk），而深度适应生酮代谢的人体能以远超常人极限的速度直接燃烧脂肪与酮体，从而将体内原本稀缺的肌糖原完好地保留到终点冲刺阶段。
- **腹部脂肪代谢飙升**：活检证实处于生酮状态的人类腹部脂肪细胞代谢率提升至平时的 3 倍。
- **防止肌肉分解**：酮体直接替代葡萄糖作为大脑的抗饥饿能源，免除机体分解肌肉蛋白进行糖异生的代价。
- **打破耐力运动壁垒**：适应酮体代谢的运动员能在高负荷运动中直接以脂肪与酮体为主要能量来源，避免耗尽糖原导致的“撞墙期”。
### [01:39:16](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=5956s) 外源性生酮饮品：从酮盐到生物同质性 BHB
面对市面上琳琅满目的生酮补充剂，Bikman 梳理了当前外源性酮体产品的层级梯队。位于入门端、价格最为亲民但效能相对打折的是“酮盐”（Ketone salts）。这类产品将酮体分子结合在钙、镁等矿物质离子上。由于摄入有效剂量的酮体需要伴随摄入大量矿物质，使用者往往会面临牙菌斑快速沉积、牙结石增多甚至肾结石风险上升等副作用。更进一步的则是目前高水平耐力赛道上常见的“酮酯”（Ketone esters），这类产品多以浓缩一口饮（shots）的形式呈现。而处于最顶端的高阶形态则是“生物同质性 β-羟基丁酸”（Bioidentical BHB），市面上由 Original Ketone 等专业机构研发。虽然生物同质性酮体生产工艺复杂、售价昂贵，但随着市场竞争加剧，其门槛正在逐步下探。
```mermaid
flowchart LR
accTitle: 外源性生酮补剂对比梯度
accDescr: 从低到高展示酮盐、酮酯和生物同质性BHB的特性、价格及吸收效率。
A["酮盐 (Ketone Salts)<br/>结合钙/镁矿物质"] -->|纯度与吸收率递增| B["酮酯 (Ketone Esters)<br/>浓缩Shot，效能强劲"]
B -->|结构一致性递增| C["生物同质性 BHB<br/>(Bioidentical BHB)<br/>人体高度匹配，利用率最高"]
subgraph CostEfficiency["性能与成本特征"]
direction TB
D["酮盐：便宜、含过量矿物质、有牙菌斑/肾结石风险"]
E["酮酯：吸收快、价格高、广泛用于顶尖赛事"]
F["生物同质性BHB：直接升酮、对胃肠友好、正逐步普及"]
end
```
针对 Steven Bartlett 提出的疑问——“如果我刚吃完两个百吉饼加一杯加糖咖啡，再喝下一杯生物同质性酮体，体内会发生什么？”Bikman 解释道，如果刚刚摄入了高碳水化合物食物，体内胰岛素会瞬间飙升，内源性产酮机制会被彻底掐断，血液中原本检测不到酮体。但外源性生物同质性酮体进入消化道后能被肠道近乎即时地吸收。短短一小时之内，血液中的酮体水平就能直接拉升至约 1.0 mmol/L 的显著水准。至于这是否能让人变得思维更敏捷，Bikman 坦言人类双盲临床试验还在深入探索中，但他实验室发表的动物行为学实验已给出了极为积极的佐证：摄入生酮饮食的大鼠在走迷宫导航与识别特定物体时表现出极高的智力清晰度，它们解决空间谜题的速度更快，且能清晰牢记之前测试中的通关路径。
### [01:41:12](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6072s) Steven 的生酮实测体验：打破卡路里迷思
听到这里，Steven 忍不住分享了自己最近两周的亲身体验。为了验证生酮的效果，他近来严格遵循生酮饮食，并在团队面前天天拿着刺指采血针检测血酮读数。Steven 透露自己的血酮浓度最高一度测得 2.5 mmol/L，并急切地向 Bikman 确认这个数字是否偏高。Bikman 立即打消了他的顾虑，指出 2.5 mmol/L 处于完全健康的营养性生酮范围内，绝非病理性酸中毒。这一数字是三大生理事实的确凿铁证：第一，机体正在进行极其高强度的脂肪氧化；第二，全身胰岛素已降至极低基线；第三，机体完美运转于生酮代谢之下。Steven 兴奋地感叹道：“我身上的脂肪开始以这辈子从未见过的速度疯狂往下掉，这简直太不可思议了！”
借由 Steven 的减脂奇迹，Dr. Bikman 顺势剖析了普通大众在减脂认知上的致命盲区。绝大多数想要缩小脂肪细胞的人，往往将全部注意力聚焦于“卡路里摄入与消耗”（CICO）这一单一维度。他们完全不知道决定脂肪细胞生长的方程式中存在着两个截然不同的变量，甚至对胰岛素在这套代谢公式中的主宰地位一无所知。只要体内的胰岛素居高不下，脂肪细胞的闸门就被锁死，即使忍饥挨饿削减热量，身体也只会陷入代谢率下滑与肌肉流失的恶性循环，而无法像在低胰岛素、高生酮状态下那样，促使脂肪作为主要燃料被彻底引爆。
- **安全血酮区间**：指尖采血测得 2.5 mmol/L 属于典型的健康生理性深度生酮，是低胰岛素水平与极速燃脂的直接标志。
- **减脂的双重变量**：决定脂肪细胞体积大小的不仅是卡路里差额，胰岛素这一控制脂肪储存与分解的内分泌开关具有不可替代的决定性作用。
### [01:42:08](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6128s) 传统减肥建议的致命陷阱：“少吃多动”与饥饿的必胜定律
本杰明·比克曼（Benjamin Bikman）博士指出，许多人在开启缩小脂肪细胞的减脂之旅时，往往立刻陷入“只要少吃热量就行”的思维盲区，并采取了完全错误的做法。为了生动揭示这一陷阱，比克曼设想了一个场景：假设史蒂文和他邀请所有观众参加一场汇聚全球顶级名厨的美食自助盛宴，邀请函上特别叮嘱“一定要空着肚子来，因为每样佳肴你都会想尝一点”。人们为了让自己在赴宴或感恩节大餐前尽可能饥肠辘辘，通常只会做两件事——提前一段时间少吃，同时增加运动量。这种做法立竿见影，确实会让人饥饿难耐。
比克曼随即指出，这正是现代主流减重建议“少吃多动”（Eat less, exercise more）注定失败的原因。这种方法或许能在极短期内让体重下降一点，但它本质上是在为身体调配一份“催生极致饥饿的完美药方”。而在人体的生理本能面前，意志力永远无法与饥饿抗衡，“饥饿感永远是最终的赢家”。
```mermaid
flowchart TD
accTitle: 热量限制与胰岛素控制对减重的机制对比
accDescr: 对比传统少吃多动的热量限制模式与通过低碳饮食控制胰岛素模式的不同生理生理路径及结果。
subgraph 传统热量限制模式["传统模式：纯热量限制"]
A1["少吃多动 (高碳低脂)"] --> B1["胰岛素居高不下"]
B1 --> C1["脂肪被锁死，无法供能"]
C1 --> D1["极度饥饿 + 代谢率永久损伤"]
D1 --> E1["体重报复性反弹"]
end
subgraph 激素代谢调控模式["科学模式：优先调控胰岛素"]
A2["严格控制精制碳水"] --> B2["胰岛素水平下降"]
B2 --> C2["开启脂肪氧化通道 (燃烧体脂)"]
C2 --> D2["体内数十万大卡储备供能"]
D2 --> E2["自然产生饱腹感，热量自发降低"]
end
```
### [01:43:47](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6227s) 《超级减肥王》的警示：被节食破坏的代谢率与胰岛素的关键作用
为了展示纯粹热量限制带来的毁灭性后果，比克曼以美国著名真人秀节目《超级减肥王》（The Biggest Loser）为例。该节目参赛者在极其严苛的卡路里赤字和疯狂高强度的魔鬼训练下，短期内减掉了惊人的体重。然而，公众几乎从未见过他们举办五周年或十周年的重聚活动，因为绝大多数人最终全都反弹了回去。
美国国家卫生研究院（NIH）发表的一项重量级追踪研究证实，这种极端的减重手段几乎“从字面意义上摧毁了选手的代谢系统”。在正常生理状态下，人体静息代谢率与体重紧密挂钩：体型大则代谢高，体型缩小则代谢相应下降；当体重反弹增加时，代谢率通常也会随之回升。但在《超级减肥王》的选手身上，即便他们日后重新长回所有体重，代谢率却永久性地滞留在低谷，未能同步恢复。比克曼指出，这种基于纯热量理论的极端节食不仅诱发了无法遏制的饥饿感，更锁死了脂肪：哈佛大学教授大卫·路德维格（David Ludwig）的研究表明，在摄入相同热量的前提下，引发胰岛素飙升的餐食会让人比摄入不刺激胰岛素的餐食感到强烈得多的饥饿。如果减重第一步只顾削减热量而不解决高胰岛素问题，高浓度的胰岛素会持续强迫身体储存能量，导致减重注定功亏一篑。
- **生理代谢断崖**：正常人体重增加时代谢率同步上升，而极低热量节食选手的代谢率在体重反弹后依然持续低迷。
- **大卫·路德维格教授的发现**：热量并非唯一变量；刺激胰岛素急剧上升的低卡食物，诱发的饥饿感远胜于不刺激胰岛素的同等热量食物。
- **恶性循环**：在高胰岛素状态下削减热量，细胞无法调用体内脂肪储备，身体只能发出强烈的饥饿警报逼迫进食。
### [01:45:37](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6337s) 缩小脂肪细胞的正确法则：控碳水、重蛋白与释放体内储备能量
比克曼强调，任何希望缩小脂肪细胞、健康减重的人，旅程的第一步必须是“降低胰岛素”。具体行动准则是：
1. **严格控制碳水化合物**：彻底摒弃来自塑料袋、包装盒及印有条形码的深加工碳水化合物；
2. **优先保证优质蛋白质**；
3. **不要害怕蛋白质天然自带的脂肪**。
蛋白质与健康脂肪的天然结合是带来持久饱腹感、提供人体必需营养素（人体存在必需氨基酸与必需脂肪酸，却不存在必需碳水化合物）的奇迹组合。当胰岛素降下来后，进食原则变得极其纯粹：饥饿时进食，不饿时无需强求。
在胰岛素维持低水平的状态下，人体的代谢率得以维持甚至提升，并重新激活了燃烧自体脂肪的“代谢混合动力”通道。比克曼用骆驼的驼峰打了一个生动的比方：骆驼背上的驼峰是储存丰富脂肪作为远行能量的器官，而人类自身也有这样的天然储备。一个微胖的普通人体内，脂肪细胞中往往储存着数十万卡路里的能量，随时等待被燃烧供能；然而由于长期居高不下的慢性胰岛素水平，这扇能量大门被彻底锁死。一旦通过饮食改变降低了胰岛素，身体终于能够自由调用自身脂肪作为燃料，饥饿感便会自然消退。比克曼告诫道：“控制热量应该是你因为彻底不饿而自发产生的结果，而不是靠强忍饥饿、克制饮食去强求的目标。”
### [01:47:40](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6460s) 史蒂文的生酮实战体验：惊人的脑力聚焦、极速减脂与肌肉流失的困惑
史蒂文分享了自己切身的生酮饮食（Keto Diet）经历。他过去每年都会进行大约8周的生酮周期，而这一次他打算维持更长时间。作为一名每天需要花费长达9小时构思采访问题、回忆海量研究资料，或是站在上千名观众舞台上演说的播客主持人，他敏锐地察觉到了认知能力的巨大差异：在以往某些日子里，他常常觉得大脑思维与嘴巴表达完全脱节，但在进入生酮状态后，思维如行云流水般顺畅，视野呈现出极其强烈的聚焦感。
不仅如此，史蒂文观察到自己的食欲发生了根本转变：虽然仍会感到饥饿，但那种过去难以自控的暴食倾向消失了，进食后很快就会自发停下，白天再也没有出现过午后的疲惫崩溃与精力骤降。更让他震撼的是腹部脂肪的消退速度。史蒂文坦言，没有任何方法比生酮饮食剥离腹部脂肪更快，数周之内，智能体重秤上的数据曲线就像遭遇了断崖一般垂直坠落。
然而，这也带来了史蒂文目前最大的困惑——“到底该如何在生酮饮食中保住肌肉？”他提到，第一次生酮后脱掉上衣时，他的女朋友惊叹从未见过他如此精瘦，但同时也显而易见地发现他的肌肉体积明显变小了。这促使他带着谨慎的态度再次尝试，并迫切想知道两全其美的方法。对此，比克曼报以由衷的认同（"A hearty amen"），表示自己是生酮饮食的坚定支持者，并准备深入探讨肌肉保护与生酮的具体机制。
- **认知表现提升**：生酮状态消除了脑雾，让长达数小时的高强度访谈和舞台演讲思维敏捷、表达流畅。
- **进食节律平稳**：彻底摆脱暴食冲动，饱腹信号反馈迅速，白天精力充沛且无能量断崖。
- **极速减脂的代价**：腹部脂肪呈断崖式快速剥离，但伴随肌肉围度缩小的负面影响，如何防止瘦体重（肌肉）流失成为核心痛点。
### [01:50:33](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6633s) 生酮饮食中肌肉流失的生理机制：脱水与“饥饿陷阱”
在探讨生酮饮食期间如何维持肌肉量时，本杰明·比克曼（Benjamin Bikman）博士指出，已有大量的同行评审文献证明人类在严格生酮状态下完全可以保持全部的肌肉量与力量。针对史蒂芬·巴特利特（Steven Bartlett）此前在生酮饮食中遭遇的力量下降和肌肉萎缩，比克曼化身“专属教练”进行排查，指出了两个隐蔽但致命的生理诱因：轻度脱水与热量严重不足。
当人体胰岛素水平骤降时，肾上腺皮质分泌的醛固酮（aldosterone）水平也会随之回落。醛固酮的主要功能是促使肾脏保钠排钾；一旦该激素下降，肾脏便会高速排出钠盐与水分。这也是为什么许多高血压患者在改用生酮饮食后，短短两天内血压就会迅速恢复正常，甚至必须停用降压药以防低血压。然而，对于经常运动的人而言，这种快速排水利尿会导致身体处于轻微脱水状态，直接削弱高强度训练时的爆发力与做功能力。
更为严峻的隐患在于极度精瘦状态下的热量供需矛盾。比克曼指出，“空腹断食”（fasting）与真正的“饥饿枯竭”（starvation）有着本质区别。英国曾有医学记录记载一名过度肥胖男子在严密医学监控下断食了整整384天，仅补充水分、维生素和矿物质，最终不仅成功减重且长期健康生活。断食与饥饿的分水岭在于体内是否耗尽了脂肪储备。肌肉是极度消耗代谢能量的“昂贵器官”；当体脂降到极致时，身体缺乏足够的脂肪来生成足量酮体以供大脑消耗。此时大脑无法仅凭酮体运转，只能强行索取葡萄糖，迫使身体分解肌肉组织中的蛋白质，将游离氨基酸运往肝脏进行糖异生（gluconeogenesis），最终“把自己的肌肉转化为葡萄糖来喂饱大脑”。
```mermaid
flowchart TD
accTitle: 生酮期间肌肉流失与能量供需机制
accDescr: 展示生酮饮食下低胰岛素导致的利尿效应，以及体脂不足时肌肉分解糖异生的完整生理通路。
subgraph HydrationPath["水盐平衡通道"]
A["低碳水 / 生酮饮食"] --> B["胰岛素水平下降"]
B --> C["醛固酮分泌减少"]
C --> D["肾脏加速排出水与钠盐"]
D --> E["轻度脱水 / 训练强度与爆发力下降"]
end
subgraph MuscleLossPath["极度精瘦状态下的能量危机"]
F["体脂过低 / 膳食热量严重不足"] --> G["脂肪酸不足以产生足量酮体"]
G --> H["大脑葡萄糖需求未被酮体满足"]
H --> I["骨骼肌分解并释放游离氨基酸"]
I --> J["肝脏糖异生: 将氨基酸转化为葡萄糖"]
J --> K["肌肉量减少与肌肉萎缩"]
end
```
- **极端断食案例**：文献中记录最长的人类断食案例持续了384天（英国男子），期间未摄入一卡路里能量，仅补充电解质、微量元素与水分，并未引发肌肉衰竭。
- **生酮低血压警示**：服用降压药的高血压患者转向生酮饮食后，通常需在48小时内就医调整或停药，否则因醛固酮下降引发的排水可能导致血压过低。
---
### [01:54:10](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6850s) 增肌保脂的实践法则：黄油、马黛茶与纯肉挑战
史蒂芬坦言自己在初次尝试生酮时并未进行常规血液检测，因此甚至无法确定自身当时是否处于深度生酮状态，抑或仅仅是因为热量严重亏空。比克曼强调，对于体型精干、基础代谢率高且运动频繁的人群，生酮的关键绝不是节食，而是要摄入足量、甚至过量的健康脂肪来充当能量缓冲池。
比克曼分享了他个人的日常饮食策略与抗衰经验。作为一名年近50岁的学者，他每年一月都会进行为期一个月的纯肉饮食（Carnivore Diet）。这既是为了在新年伊始刷掉多余体脂，更是一种心理层面的自律训练——打破对各类加工食物的嗜好与成瘾。比克曼笑着提到，每到这个时期他的腹肌就会清晰显现，连妻子都会赞叹连连；但他深知人到中年维持肌肉付出的心血极其艰辛，因此他会严格确保充足的蛋白质与大量脂肪输入。
在实践技巧上，比克曼建议每次煎牛排时都要慷慨地叠上一大块黄油；而在每天清晨世界尚在沉睡、孩子们还未醒来时，他习惯喝一杯南美马黛茶（Yerba Mate），并在热茶中融进一大坨醇厚的黄油，以此在静谧中提供充沛的脑力与脂质热量支持。
---
### [01:55:25](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=6925s) 生酮的潜在副作用：暂时性“代谢灵活性”钝化
在正面评价酮体具有强效抗炎活性（直接抑制机体炎症信号通路）并能增强内源性抗氧化酶防御、缓解氧化应激之后，史蒂芬追问生酮饮食是否存在任何不容忽视的负面影响。比克曼坦率地指出了一个真实的生理现象：短期内“代谢灵活性”（Metabolic Flexibility）的下调。
代谢灵活性是指健康机体在摄入碳水时迅速切换至燃糖模式、在禁食或低碳时切换至燃脂模式的双轨代谢能力。长期严格遵循生酮饮食的人，由于代谢酶系全面向脂肪氧化倾斜，身体会进入一种深度适应的“燃脂闭锁”状态。如果一个生酮多年的人突然和摄入普通高碳水饮食的朋友一起吃下两个百吉饼（bagel）并饮用高糖饮料，他的身体几乎会“忘记”如何高效清理和利用大剂量葡萄糖。
在这种情况下，正常杂食人群可能在90分钟内就能将血糖恢复至基线水平，而深度生酮适应者可能需要耗费180分钟甚至更久才能使血糖回落。在外行人看来，这甚至像是短暂的糖耐量受损，但实质上是机体对长期低碳水环境做出的自适应反应，并非不可逆的器质性病变。
---
### [01:57:18](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7038s) 肠道微生态迷思：零膳食纤维会摧毁肠道菌群吗？
谈及外界对生酮饮食的指责，史蒂芬提到有营养师警告他说生酮饮食缺乏植物膳食纤维，“会彻底毁掉肠道菌群”。比克曼直截了当地斥责这种观点是极其幼稚的无稽之谈（"what a naive thing to say"），并指出主流文献中没有任何证据表明生酮饮食会对肠道微生物造成有害破坏。
比克曼引用了一项新发表的人体个案追踪研究：研究者对一名受试者进行了长期监测，该受试者从包含丰富植物性膳食纤维的典型人类杂食饮食（omnivorous diet），彻底切换为零碳水化合物、零蔬菜纤维的纯肉食饮食（Carnivore Diet）。在长达数月的干预后，研究人员精确记录到其肠道微生物菌群结构完全没有发生本质性的不利变化。
比克曼从科学家的视角直言，许多所谓的“肠道微生态研究”目前仍停留在黑匣子阶段。人体微生物组极易受到微小环境波动的干扰：例如史蒂芬从英国伦敦搭乘航班来到美国洛杉矶加州，或者比克曼刚从犹他州飞抵加州，仅仅因为空气中的微粒变化、当地自来水矿物质差异及差旅环境，受试者的肠道菌群就会在24至48小时内产生明显的组成变化。比克曼总结道，没有植物纤维并不等于细菌会饿死。肠道细菌具有极高的底物代偿能力，能够通过分解利用食物中的短链脂肪酸（SCFA）、肉类和蛋类中的特定氨基酸及其他微量营养素正常存活繁衍，“肠道菌群绝没有因为不吃纤维而死掉，它们依然完好无损”。
### [01:59:34](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7174s) 肠道微生物多样性的迷思：植物饮食与生酮饮食的碰撞
Steven Bartlett 提出了许多人对低碳或生酮饮食的常见担忧：如果不吃植物，肠道菌群的多样性难道不会急剧下降吗？植物不是喂养肠道益生菌的核心来源吗？Dr. Benjamin Bikman 对这种根深蒂固的前提提出了质疑。他指出，认为不吃植物就必然毁掉肠道菌群不仅缺乏直接证据，而且在很多案例中，菌群结构甚至毫无变化。比如近期的一项个案研究表明，一位完全停止摄入植物的受试者，其肠道微生物群落种类和比例与此前完全一致。
针对“肠道细菌只能靠植物纤维喂养”的误区，Dr. Bikman 澄清道，细菌的食物来源远比想象中广泛。它们同样可以代谢脂肪、氨基酸（如谷氨酰胺，Glutamine），甚至肉类肌肉中储存的糖原（Glycogen）所释放的微量葡萄糖。Dr. Bikman 强调，声称生酮或纯肉饮食会“摧毁微生物组”根本没有科学事实支撑：
> “你可能确实改变了微生物群，但谁又能断定那是变坏了呢？也许那是一个更好的改变。你感觉更棒了、思维更敏捷、身体更紧致、胰岛素敏感度改善、认知能力也提升了。如果你的肠道菌群发生了改变，我认为这大概率是向好的方向转变。”
```mermaid
flowchart TD
accTitle: 肠道微生物代谢底物与健康指标对比
accDescr: 对比传统观念中肠道细菌仅以植物纤维为食，与实际细菌可代谢多种营养素并改善临床指标的现实情况。
subgraph Substrates["肠道细菌可利用的营养来源"]
A["植物纤维 (Fiber)"]
B["脂肪 (Fats)"]
C["氨基酸 (如 Glutamine)"]
D["肌糖原微量葡萄糖 (Glycogen)"]
end
subgraph Outcomes["生酮饮食带来的机体客观表现"]
E["逆转糖尿病与高血压"]
F["胰岛素敏感度显著提升"]
G["体脂下降与大脑认知改善"]
end
Substrates -->|维持菌群存活| H["肠道微生物生态重构"]
H -.->|假设的多样性变化?| Outcomes
```
- **细菌的替代能量来源**：肠道微生物不仅依赖碳水纤维，还能高效利用脂肪、谷氨酰胺等氨基酸，以及肉类中残存的微量肌糖原（葡萄糖）。
- **基础科学家的证据标准**：对于营养学界“菌群越多样就越好”的流行观点，Dr. Bikman 呼吁拿出确凿的人体临床证据，而不是把相关性假设当作真理。
---
### [02:01:07](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7267s) “关注人类，而非细菌”：菌群多样性与临床健康的辩证
面对 Steven 进一步追问“连续吃 6 个月丰富种类的植物，菌群多样性是否肯定会更高”，Dr. Bikman 承认，大量摄入植物确实很可能会增加肠道菌群的多样性，但核心问题在于：**这种多样性增加究竟是好是坏？**
Dr. Bikman 幽默而犀利地分析道，多吃植物所促进繁殖的细菌，可能仅仅是因为需要发酵处理更多难以消化的纤维；而这一过程的直接生理后果，往往只是让人产生更多的肠胃胀气（Flatulence）。如果这些细菌的存在只是为了解决宿主摄入的多余纤维，却没有带来全身代谢的实质改善，那么片面追求“菌群多样性”便毫无意义。面对肥胖、二型糖尿病和高血压患者，改用简单纯粹的生酮饮食后，所有客观生理临床指标全线好转：
> “如果有人说：‘没错，你逆转了糖尿病，治好了高血压，但可怜你的肠道微生物啊。’我会回答：‘我不关心我的微生物组，我关心的是人类本身。’如果多样性降低了，但每一项临床指标都变得更好，那或许过高的多样性本来就不是我们想要的。”
随后，Steven 联想到胰岛素抵抗对大脑的长期损害——长期 10 年的胰岛素抵抗会让大脑额外衰老约 2 岁——并提出，如果狭窄单一的饮食真的损害了菌群，会不会在几年后才显现负面代价？Dr. Bikman 承认这种长期滞后性理论上存在，但重申切勿预设立场，那些长期坚持生酮饮食多年的人身体状态依然极佳，不能盲目将植物引发的菌群增殖一概等同于健康增益。
- **纤维发酵与副产物**：摄入过量植物纤维促生的菌群，很多时候仅是增加了肠内发酵气体，引起胀气和不适，并不等于提升了宿主整体健康。
- **临床硬指标优先**：血糖、胰岛素敏感性、血压、体成分及脑功能等全身代谢指标，优先级远高于单一的粪便菌群多样性测序得分。
---
### [02:05:00](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7500s) 深度生酮的个体化需求与碳水摄入法则
对话转向生酮状态的实践体验。Steven 分享了自己测血酮的经历：剧烈跑步后酮体浓度会急剧飙升，而到了深夜有时又徘徊在生酮临界点，酮体数值总是在剧烈波动。他询问人类是否真的需要一天 24 小时保持极高浓度的深度生酮。
Dr. Bikman 表示，普通人完全不需要时刻处于严苛的深度生酮状态，人体本就具备灵活波动的代谢弹性；经常进入轻度生酮状态，让大脑定期接受纯净高效的酮体供能，就已经能收获绝大部分代谢与认知益处。然而，生酮的严格程度应严格取决于个体的健康目标与疾病负担：
1. **二型糖尿病患者**：采取生酮饮食可在短短数月内停掉所有的糖尿病处方药物。
2. **偏头痛（Migraine）与癫痫（Epilepsy）患者**：医学文献早在 1913 年就首次记录了生酮对偏头痛的显著疗效。只要患者维持在生酮状态，许多人就能彻底告别偏头痛的发作，实现完全预防乃至临床治愈。
3. **健康普通人群**：追求精干身材与清晰大脑的人无需极端自虐。核心策略是“控制碳水化合物，选择非加工碳水”——远离带有塑料包装袋、纸盒和条形码的精加工精炼碳水。
Dr. Bikman 强调，自己对待天然完整的水果和蔬菜态度非常宽容，鼓励大家放开享用，但底线是要保证足够的优质蛋白质和健康脂肪。他重申了一个在主流观念中看似激进的生物学事实：“人类不存在所谓的‘必需碳水化合物’（Essential Carbohydrate），机体没有摄入外源碳水化合物的硬性生理需求，但人类必须摄入必需脂肪酸和必需氨基酸。”
---
### [02:07:05](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7625s) 代糖大解密：健怡（Diet）与零度（Zero）的胰岛素反应差异
面对生酮饮食期间不可避免的甜味渴望，Steven 坦言自己经常想喝零度汽水（Soda Zero）或无糖健怡汽水（Diet Soda），并询问这些代糖究竟会不会刺激机体分泌胰岛素。
Dr. Bikman 解释道，代糖的世界极其庞大，从人工合成甜味剂、天然植物提取物到罕见糖类，各种分子在体内的生理机制截然不同。如果单从**是否刺激胰岛素分泌**这一核心标准来看：
- **阿斯巴甜（Aspartame）**：处于安全健康的优质端，人体研究表明它完全不会刺激胰岛素分泌。
- **“健怡（Diet）”与“零度（Zero）”配方的差异**：在许多经典饮料产品中，通常标有“Diet”的版本往往主要依靠阿斯巴甜作为单一甜味剂；而标有“Zero”的产品往往会复配其他新型甜味剂或成分（如三氯蔗糖等）。正因如此，Dr. Bikman 透露自己在两者之间通常会更倾向于选择含有阿斯巴甜的经典 Diet 版本，以确保对胰岛素水平实现真正的零扰动。
- **赤藓糖醇（Erythritol）**：作为一种天然糖醇，同样对胰岛素分泌几乎没有任何不良影响，属于低碳人群较为安全的甜味选择。
- **必需营养素原则**：生命代谢存在必需脂肪酸与必需氨基酸，缺乏会导致死亡；生物学上不存在“必需碳水化合物”。
- **代糖评估核心指标**：评价低碳饮料中的代糖安全性时，最直接的标准是其摄入后是否会激发胰腺分泌胰岛素，从而打断体内的燃脂与生酮通路。
### [02:08:35](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7715s) 甜味剂的生理机制：糖醇消化与血脑屏障
Dr. Benjamin Bikman 对生酮或低碳饮食中常用的各种甜味剂进行了详细剖析。在对胰岛素完全惰性（无影响）的甜味剂中，阿洛酮糖（allulose）、甜菊糖（stevia）、罗汉果提取物（monk fruit extract）以及阿斯巴甜（aspartame）表现优异。赤藓糖醇（erythritol）同样不会刺激胰岛素，但它名字中的后缀“-ol”揭示了它属于“糖醇”（sugar alcohol）类分子。Bikman 强调，“糖醇”并不意味着具有酒精麻醉性，而是指其化学结构带有羟基官能团。一旦涉足糖醇家族，情况就会变得复杂：赤藓糖醇和木糖醇（xylitol）通常算好的选择，但麦芽糖醇（maltitol）与甘露醇（mannitol）却会产生明显的胰岛素反应。这些糖醇常出现在无糖巧克力等加工食品中，具体添加逻辑连 Bikman 也觉得令人费解。
糖醇更直接的尴尬来自于人体的消化道反应。糖醇在口腔中呈现甜味，但人体无法吸收其热量，它们会滞留在肠道中。这种渗透压效应会从身体组织中反向把大量水分吸入肠腔，随之而来的便是严重的腹胀、胀气与腹泻。Bikman 笑着调侃，只要某个人吃了过量的糖醇，“他们的肠道很快就会亲自发出严正抗议”。
此外，针对市面上“零度”（Zero）与“无糖/健怡”（Diet）饮料的配方差异，Bikman 给出了独特的健康考量。零度饮料普遍采用三氯蔗糖（sucralose），尽管三氯蔗糖对胰岛素影响不大，但科学研究表明它能够穿透血脑屏障（blood-brain barrier）。Bikman 直言：“我不知道三氯蔗糖穿过血脑屏障在脑子里干些什么，但我绝不希望它出现在那里。”相反，传统健怡饮料中使用的阿斯巴甜进入体内后会被分解成普通的氨基酸直接吸收利用，不会穿透血脑屏障。正因如此，当 Bikman 在严格执行生酮饮食又想满足甜食口欲时，无糖汽水（Diet soda）是他唯一的自我放纵之选。
- **对胰岛素无刺激的甜味剂**：阿洛酮糖（allulose）、罗汉果提取物（monk fruit extract）、甜菊糖（stevia）、阿斯巴甜（aspartame）、赤藓糖醇（erythritol）。
- **具胰岛素效应且易引发腹泻的糖醇**：甘露醇（mannitol）、麦芽糖醇（maltitol）。
- **零度 vs 健怡成分区别**：三氯蔗糖（sucralose，常见于 Zero 饮品）可穿透血脑屏障；阿斯巴甜（aspartame，常见于 Diet 饮品）代谢为基本氨基酸。
---
### [02:11:04](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7864s) 盐分的污名化：限制摄入反而诱发胰岛素抵抗与高血压
Steven Bartlett 分享了自己多年前的经历：由于饮食中经常添加美极（Maggi）鲜味调味汁，家庭医生曾警告他体内盐分/钠含量过高。然而近年来他又频繁听闻大众实际上普遍摄盐不足的说法。Bikman 指出，常规体检中直接测出钠异常其实并不多见。盐之所以背负数十年的恶名，根源在于一系列声称“摄入食盐会导致高血压”的流行病学研究。从短期生理机制看，进食高盐后几小时内，人体为了防止体液过咸失衡，确实会滞留水分以稀释盐浓度，导致短暂的血压微升。
然而大规模人群干预试验却彻底颠覆了这个直觉常识：当医生要求患有高血压的人群严格削减食盐时，患者的血压往往仅仅下降可怜的 1 到 2 个点，在临床上几乎毫无意义。真正的主导元凶其实是胰岛素抵抗，而非食盐本身。胰岛素抵抗会促使肾脏锁住钠和水分，同时导致血管强烈收缩，两者叠加才会形成顽固性高血压。大众对盐的恐惧很大程度源于著名的降高血压饮食试验（DASH diet）。DASH 饮食在要求受试者少吃盐的同时，还严格限制了精制淀粉和添加糖的摄入。Bikman 明确指出，真正让受试者血压大幅下降的英雄是“低糖低精制碳水”，而减少食盐不过是恰好同行的“无辜旁观者”。
更具讽刺意味的是，严苛限盐甚至会反向损害代谢健康。多项人体临床试验证明，如果让健康人大幅度削减盐分摄入，仅仅一周后，这些受试者就会表现出显著加剧的胰岛素抵抗。其背后的生理补偿机制极为致命：胰岛素的一大核心机能就是促进机体保留钠和水分。当外界食盐摄入骤减时，身体为了防止珍贵的钠流失，会代偿性地分泌更高水平的胰岛素来紧紧锁住体内残存的盐与水。持续飙升的胰岛素最终将机体拖入更严重的胰岛素抵抗恶性循环。当医生要求高血压患者少吃盐时，往往不仅治不好高血压，反而因诱发胰岛素抵抗使血管进一步收缩。
```mermaid
flowchart TD
accTitle: 限盐与高血压的代偿性恶性循环
accDescr: 展示限制食盐摄入如何通过激活胰岛素升高机制，最终诱发胰岛素抵抗并加重高血压的生理链条。
subgraph S1["错误干预措施"]
A["严格限制食盐摄入"]
end
subgraph S2["机体生理代偿"]
B["体内钠离子水平偏低"]
C["胰岛素代偿性大幅分泌<br/>(启动保钠保水机制)"]
end
subgraph S3["病理后果"]
D["诱发/加剧胰岛素抵抗"]
E["血管长期紧缩 + 血压反弹恶化"]
end
A --> B
B --> C
C --> D
D --> E
```
---
### [02:15:19](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8119s) 控糖防病的四根饮食支柱
针对自己在著作《为什么我们会生病》（*Why We Get Sick*）中阐述的代谢干预框架，Bikman 深入剖析了对抗胰岛素抵抗的“四大饮食支柱”（Four Pillars）。调整宏量营养素（Macronutrients）的核心目标是尽最大可能降低胰岛素分泌水平，进而全面解决无论是长期缓慢累积还是急性激增的胰岛素抵抗：
1. **控制碳水化合物（Control Carbohydrates）**：首要原则是远离所有“装在印有条形码的袋子和盒子里”的加工食品。薯片、饼干、即食谷物和精制面包会引发剧烈的血糖与胰岛素峰值。碳水摄入必须回归完整的全果蔬形态，并且必须遵循“吃水果，不要喝果汁”的原则。
2. **蛋白质优先（Prioritize Protein）**：当压低碳水化合物时，身体需要充足的营养填充空间。Bikman 强烈主张优先摄入动物性蛋白，因为其能够提供人体必需的全部完整氨基酸谱。
3. **不要害怕脂肪（Don't Fear Fat）**：天然来源的优质脂肪与蛋白质常常天生共存。在自然界中，蛋白质从不孤立存在，天然食物中的蛋白质必然伴随脂肪。单喝一勺孤立的乳清蛋白粉往往会引发严重的胃肠不适，正是因为消化系统不习惯剥离脂肪的纯蛋白质。脂肪不仅赋予长效饱腹感、助益消化吸收，而且人体试验证明，伴随脂肪一同摄入蛋白质所激发的肌肉合成反应，要远远大于单独摄入纯蛋白。
4. **规律间歇性断食（Frequently Fast）**：在切实落实好前三个宏量营养素原则的基础上，配合规律断食来拉长机体维持超低胰岛素水平的时间窗口。
- **加工碳水辨识法则**：凡是来自带条形码的包装盒/袋中的精制谷物产品（如苏打饼、麦片、精制白面包），均属于需在货架上摒弃的强升糖食物。
- **蛋白质同化效应**：摄入伴随天然脂肪的肉蛋蛋白质，其促进肌肉蛋白合成与修复的效率显著优于纯分离蛋白（如纯乳清）。
### [02:17:40](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8260s) 断食策略与碳水化合物的成瘾性
在调整好饮食中的三大宏量营养素之后，第四个健康支柱便是采取有计划的断食策略。本杰明·比克曼（Benjamin Bikman）博士指出，断食的方式因人而异，“世界上有多少想要断食的人，就有多少种断食方法”，无论是每天少吃一餐的间歇性断食，还是隔日断食，都没有绝对的对错。但他强调，断食这一步必须放在最后，前提是身体已经学会摄入优质食物并适应了燃烧自身脂肪作为能量。斯蒂芬·巴特利特（Steven Bartlett）追问：“如果我已经处于生酮状态（Ketosis），还需要断食吗？”比克曼解释道，此时已经不需要频繁断食，因为生酮状态本身已经将胰岛素维持在极低水平；如果一个人已经处于深度生酮状态，尤其是体型本就偏瘦的人，频繁断食反而会导致极难维持肌肉量。
尽管这些控糖与抗胰岛素抵抗的原则在概念上非常简单，但在现实中却极难践行。比克曼指出，问题的症结在于人类的神经生物学特性：
> “所有关于人类成瘾神经生物学的证据都指向了同一种宏量营养素——碳水化合物，而不是脂肪，也不是蛋白质。”
正因为碳水化合物具有极强的神经成瘾性，单凭自律去抗拒高度精炼的糖与淀粉对绝大多数人来说堪称酷刑，这也正是许多人最终不得不退缩并依赖药物来控制体重与代谢的根本原因。
---
### [02:19:22](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8362s) 运动与肌肉：不依赖胰岛素的血糖摄取机制
当话题转向体育活动时，比克曼热情地肯定了运动的价值。他认为，改善胰岛素敏感性的“最佳运动就是你愿意去做的运动”——无论是一位 80 岁的老奶奶和闺蜜在街区散步，还是身体强健的人去越野滑雪或练 CrossFit，动起来就比不动强。然而，如果从代谢效率的角度考量，能够增加和保留肌肉的阻力训练在每一分钟的产出上都要显著优于单纯的有氧运动，因为肌肉是人体内最大的葡萄糖消耗器官。
```mermaid
flowchart TD
accTitle: 肌肉摄取葡萄糖的双通道机制
accDescr: 对比静息状态下依赖胰岛素介导与运动状态下肌肉收缩独立摄取葡萄糖的两种途径
subgraph 静息状态["静息状态（依赖胰岛素）"]
A["进食导致血糖上升"] --> B["胰腺分泌胰岛素"]
B --> C["胰岛素向肌肉细胞受体'敲门'"]
C --> D["细胞开启通道，吸收葡萄糖"]
end
subgraph 运动状态["运动状态（非胰岛素依赖型）"]
E["骨骼肌主动收缩与舒张"] --> F["肌肉发出高能耗饥饿信号"]
F --> G["绕过胰岛素，直接自主打开葡萄糖大门"]
G --> H["快速抽吸血液中葡萄糖"]
end
```
肌肉在运动时拥有一种神奇的生理特权：非胰岛素依赖型葡萄糖摄取。在静止状态下，肌肉细胞需要等待胰岛素敲门，才会打开通道吸收血糖；而在肌肉反复收缩和舒张时，肌肉细胞会直接越过胰岛素，仿佛在大喊：“我知道平时得等你来开门，但我现在太饿了，我等不及了！”随后自主开启所有葡萄糖通道。这不仅能极快地平抑血糖峰值，还能极大地减轻胰腺分泌胰岛素的负担。比克曼补充道，这也解释了为什么在评估长寿指标时，有氧心肺耐力并不能完美预测寿命，而肌肉量与力量才是最强大的长寿预测指标——肌肉越多，血糖与胰岛素控制力就越强，健康寿命也就越长。
- **肌肉的代谢地位**：骨骼肌是人体摄取清除循环葡萄糖的核心载体。
- **长寿预测指标**：肌肉力量和肌肉质量对寿命的预测效果远超单纯的有氧运动体能。
- **双重降糖路径**：规律运动不仅通过肌纤维收缩直接清空血糖，长期而言还通过增加肌肉总量放大了人体的整体葡萄糖代谢池。
---
### [02:22:04](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8524s) 限制卡路里还是限制碳水？非必需营养素的真相
面对营养学界关于“低脂限制热量”、“适度脂肪限制热量”还是“低碳水限制热量”的无休止争论，比克曼毫不掩饰地表明了立场：他坚定支持限制碳水化合物。他给出了两大不可辩驳的理由：
1. **摄入占比最高且对胰岛素刺激最大**：目前全球人类消耗的热量中有整整 70% 来自碳水化合物，而碳水化合物正是所有营养素中引发胰岛素激增最剧烈的元凶。
2. **碳水化合物在生物学上完全属于“非必需”**：人类存在必需脂肪酸（人体无法合成，必须从饮食中获取的脂肪），也存在必需氨基酸（必须从饮食中获取的蛋白质成分），但生物学上根本不存在“必需碳水化合物”。
比克曼援引了数十年前美国农业部（USDA）在一份官方人类营养需求报告中的经典论述：“人类摄入碳水化合物的下限是零。”虽然这并不意味着我们一片蔬菜或一口碳水都不能吃，但荒谬之处在于，现代社会 70% 的饮食热量竟然全建立在身体根本不需要的非必需物质之上。他建议，人们应该优先保障必需蛋白质和必需脂肪的摄入，把剩余的餐盘空间留给少量的植物性碳水即可。
---
### [02:23:51](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8631s) 为什么不直接打 Ozempic？GLP-1 激素与饱腹感机制
斯蒂芬抛出了一个许多现代人都抱有的投机疑问：如果自律戒除碳水这么难，“为什么我们不干脆吃药，比如直接打 Ozempic（司美格鲁肽）呢？”
比克曼指出，自己其实从读博士期间就在研究肠道来源激素，所在实验室是首批获得资助研究这类药物的先驱实验室之一。Ozempic 这类药物属于 GLP-1（胰高血糖素样肽-1）受体激动剂。GLP-1 是人体小肠细胞天然分泌的一种激素，主要作用是向大脑发出强烈的饱腹信号（“我饱了，不要再吃了”）。然而，完全无需依赖人工注射药物，日常饮食结构本身就能极大调控天然 GLP-1 的分泌水平：
- **等热量饮食对比**：最新研究显示，在卡路里完全相同的情况下，摄入低碳水化合物餐食的人群，其血液中的天然 GLP-1 浓度是摄入高碳水化合物餐食人群的 3 倍。
- **纯脂肪摄入实验**：不论是体型消瘦者还是肥胖者，在摄入纯脂肪后，体内产生的 GLP-1 峰值几乎完全一致，大脑均能获得相同的饱腹感反馈。
- **纯碳水摄入实验**：瘦人摄入纯碳水后会有明显的 GLP-1 释放，感知到饱腹；然而肥胖者摄入等量的纯碳水后，GLP-1 的上升微乎其微。这就导致肥胖者在吃完大量碳水后仍然感到饥饿，本能地问“接下来吃什么”。
---
### [02:26:19](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8779s) 减重药物的隐忧：瘦体重与肌肉流失
尽管 GLP-1 类药物在临床和降脂上展示出惊人效力，但比克曼感到自己必须站出来扮演那个“泼冷水”的角色。社交媒体上的网红们铺天盖地地宣扬这些药物的奇迹，炫耀自己轻松减掉了 50 磅体重，却对严重的副作用三缄其口。
比克曼指出，这些减重药物最令人担忧的隐患之一是瘦体重（Lean Mass）与骨骼肌的大幅流失。《新英格兰医学杂志》（NEJM）公布的 STEP 5 等关键临床试验数据明确揭示了这种代价：在药物带来的体重骤降中，相当高比例流失的并不是脂肪，而是对长期代谢、运动机能和长寿至关重要的肌肉组织。这一代价如果缺乏严谨的干预，将会对患者未来的代谢率产生不可逆的长期损害。
### [02:26:53](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8813s) GLP-1 药物背后的瘦体重隐患：肌肉流失与停药反弹陷阱
本杰明·比克曼（Dr. Benjamin Bikman）教授指出了当前风靡全球的 GLP-1 受体激动剂（如 Ozempic、司美格鲁肽）背后鲜为人知的巨大隐患：在这类药物的高剂量临床使用中，人们每减掉 6 磅脂肪，就会伴随丢失 4 磅的去脂体重（瘦体重，Lean mass）。换言之，**减掉的总体重中约有整整 40% 来自包括骨骼和肌肉在内的瘦组织**。临床上甚至已经开始出现年轻健康但略微超重的女性，在用药一段时间后竟被确诊患上骨质疏松症（Osteoporosis）的极端病例。
比克曼教授强调，真正令人不寒而栗的是停药后的代谢绝境。英国的数据显示，约有 **69%（近 70%）的人在用药 2 年后会选择停药**，因为他们无法或不愿终生注射。他举了一个典型的假设案例：一位 60 岁的女性使用该药物一年减掉了 20 公斤，其中 12 公斤是脂肪，而 8 公斤是宝贵的肌肉与骨量。一旦停药，失去的肌肉和骨骼在 60 岁以后的年龄段几乎永远无法再生；然而，反弹的脂肪却会以极快速度席卷而来。最终，患者不仅失去了代谢保护伞，还陷入了体脂率更高、骨骼更脆弱的衰老恶相之中。
```mermaid
flowchart TD
accTitle: GLP-1 药物减重与停药反弹机制
accDescr: 展示使用 GLP-1 药物减重期间的体成分损失比例，以及停药后不可逆的组织差异变化。
subgraph Phase1["阶段一：用药减重期"]
A["使用 GLP-1 药物 (如 Ozempic)"] --> B["体重总减轻"]
B --> C["60% 脂肪组织流失"]
B --> D["40% 瘦体重流失<br/>(骨量衰退 + 骨骼肌萎缩)"]
end
subgraph Phase2["阶段二：停药反弹期 (约 70% 患者在 2 年内停药)"]
D --> E["骨量与肌肉永久损失<br/>(中老年几乎无法再生)"]
C --> F["脂肪迅速卷土重来<br/>(脂肪细胞快速膨胀)"]
E & F --> G["恶果：体脂率攀升、骨质疏松与代谢崩溃"]
end
```
### [02:28:53](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8933s) 流行歌手的悲剧自白：骨脆如威化与被放大的进食障碍
史蒂文·巴特利特（Steven Bartlett）在访谈中分享了他在社交平台 Twitter（X）上看到的一段引发全网轰动的病毒式视频。歌手艾弗里（Avery）含泪记录了自己停用 Ozempic 两个月后去医院体检的经历。年仅轻龄且身材原本就非常苗条的她，在短短一年的用药后被医生诊断出患有严重的骨质疏松症与骨质减少症（Osteopenia）。随后她更在社交媒体发帖揭露了残酷真相：“唱片公司指责我太胖并解雇了我。我因此对 Ozempic 上瘾。现在的后果是，我得了骨质疏松，我的骨头变得脆得像威化饼干（wafer cookies）一样脆弱。”
比克曼对此感到极其痛心。他指出，这类减肥针剂在现实中正沦为促成和加剧“瘦人群体进食障碍”的工具。原本身材非常苗条健康的女性为了追求极致的干瘪，通过各种渠道拿到处方，导致真正需要药物的重度肥胖和糖尿病患者面临药物短缺。比克曼身边的熟人中也有原本健康的女性，用药后整个人变得面黄肌瘦、病态萎靡。药物作用于中枢神经彻底抹杀饥饿感，极端的热量饥饿和营养不良直接吞噬了骨骼矿物质与肌肉。
- **进食障碍的温床**：追求病态苗条的群体借助中枢食欲抑制剂彻底绝食，加剧非适应症滥用。
- **严重骨量流失**：年轻女性在一年内发展为严重骨质疏松，骨微结构遭到不可逆侵蚀。
- **药物资源挤兑**：正常体重或极瘦群体的滥用，导致真正需要救命的二型糖尿病患者面临断药危机。
### [02:31:08](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9068s) 精神神经副作用：抑郁倍增与全方位生活激情的钝化
除了骨骼和肌肉损耗，比克曼进一步引用了最新发表的研究论文，揭示了这类药物令人担忧的心理健康代价：
- 患者在开始用药后，**产生自杀念头的风险增加超过 100%（翻倍）**；
- 罹患**重度抑郁症（Major depression）的风险飙升至原先的 3 倍**。
比克曼深入解析了这一现象背后的神经生物学逻辑。大众常常将药物宣传为“帮助控制对食物的渴望（cravings）”，但药物在中枢神经系统并非精准靶向炸弹，它降低的是对**生活万事万物的欲望与快感**（引发快感缺失）。患者不仅不想吃东西，也彻底丧失了运动健身的内驱力，这进一步加速了肌肉和骨骼的萎缩；同时，患者也不再愿意去打匹克球（pickleball）、不再想和朋友聚会小酌，对所有的兴趣爱好和社交活动都丧失了热情，整个人陷入一种淡漠低沉的灰暗状态。
### [02:32:27](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9147s) 正确使用 GLP-1 的底层逻辑：拐杖而非轮椅
面对这些骇人听闻的负面效应，比克曼教授特别澄清了自己的立场：“我不希望听众觉得我在说这东西绝对邪恶、碰都不能碰。我之所以说得这么严厉，是因为现在几乎没人愿意讨论它的副作用，大家都想把问题扫到地毯下面。”他认为，GLP-1 药物确实存在合理的临床价值，但绝不是目前这种“无脑打针当轮椅”的模式。
比克曼指出，该药物真正的最佳用途是作为克服“碳水化合物成瘾”的过渡性辅助工具（拐杖）。在用药前 6 个月内，患者对甜食的狂热渴望会大幅削弱。在此窗口期内，正确的健康策略必须包括：
1. **寻找最低有效剂量（Lowest effective dose）**：不要完全把自律推给注射器。适度保留一点对欲望的抵抗，能够锻炼人的意志力。
2. **践行三大代谢营养支柱**：严格控制碳水化合物，**重点优先补充蛋白质并摄入健康脂肪**。因为骨骼和肌肉不是由碳水构成的，而是由蛋白质与脂肪构成；充足的营养素是留住瘦体重的底线。
3. **结合抗阻力量训练**：用抗阻负重给骨骼和肌肉施加机械压力，最大程度维持骨密度与瘦组织完整性。
4. **制定逐步减量与停药计划**：在药物辅助下建立起正确的低碳高蛋白饮食模式和健身习惯后，逐步阶梯式减少药量，直至最终彻底停药独立生活。
针对史蒂文提出的“部分科学研究认为司美格鲁肽本身并不直接破坏骨矿物质密度”的疑问，比克曼解释道，骨质疏松在科学上属于一种**副效应（Artifact）**：GLP-1 并非直接在骨细胞上发动生化攻击，而是药物引发的极度营养不良（完全不摄入优质蛋白与必需矿物质）与身体活动彻底停滞（缺乏机械应力刺激骨骼生成）两者叠加带来的灾难性后果。
### [02:35:50](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9350s) 危险的形体幻象：为什么吸脂手术在代谢上是致命的？
访谈尾声，史蒂文提到自己做播客以来学到的一个深刻观念：“吸脂手术（Liposuction）在本质上是非常危险的。”他向比克曼求证这一观点是否准确。
比克曼毫无保留地赞同这一结论：“**从代谢的角度来看，吸脂手术绝对是危险且深具破坏性的**。”尽管吸脂手术可以在短时间内让人穿上下围更小的衣服、在视觉上改变轮廓，但在生理代谢机制上，粗暴抽离皮下安全储脂细胞的操作，实际上打破了人体的脂肪缓冲屏障，为后续更深层次的内脏脂肪堆积与代谢崩溃埋下了巨大隐患。
### [02:36:10](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9370s) 为什么吸脂手术无法改善长期代谢健康
在代谢健康领域，最关键的并不是体内脂肪的总重量，而是每个脂肪细胞的实际体积。当人们通过健康的方式减轻体重时，体内的脂肪细胞并没有被杀死或消除，而是体积缩小了。体积较小的脂肪细胞具有极佳的代谢活性，它们不仅具有天然的抗炎作用、能释放对抗全身炎症的激素，而且对胰岛素高度敏感，进而带动全身维持良好的胰岛素敏感性。因此，缩小脂肪细胞是改善代谢的核心，而吸脂手术的本质却恰恰相反——它并非让细胞变小，而是直接利用负压将脂肪细胞粗暴地吸出体外。
一项针对美国女性的研究清晰地揭示了吸脂手术的长期弊端。女性体内的性激素通常会引导多余脂肪优先储存在臀部和大腿周围。许多女性因对这些部位的脂肪不满而选择局部抽脂，例如吸出约 6 公斤脂肪。然而，如果术后生活与饮食习惯完全没有改变，体内的胰岛素水平依然居高不下，过量的卡路里依然需要被转化储存。由于成年人体内很难凭空产生新的脂肪细胞，被抽脂的臀部和臀周失去了原有的储存容器，身体便只能将这笔“脂肪负担”转移到尚未被抽吸的区域——尤其是腹部。
```mermaid
flowchart TD
accTitle: 吸脂手术导致脂肪异位堆积机制
accDescr: 展示抽脂后饮食不改导致脂肪向腹部转移并使代谢恶化的生理流程
subgraph Normal["健康减重途径"]
A["改善生活与饮食习惯"] --> B["胰岛素水平下降"]
B --> C["全身脂肪细胞体积缩小"]
C --> D["释放抗炎因子 / 胰岛素敏感度提升"]
end
subgraph Lipo["吸脂手术途径"]
E["局部吸脂（如臀部/大腿）"] --> F["饮食与生活方式未变"]
F --> G["高胰岛素驱动相同热量储存"]
G --> H["成年人难生新细胞，原部位无处容纳"]
H --> I["脂肪转而堆积至腹部/内脏"]
I --> J["剩余细胞过度肥大，代谢指标恶化"]
end
```
这种脂肪的重新分布带来了灾难性的代谢后果。受试者在随后的数年随访中，即使体重秤上的数字因为切除了 6 公斤脂肪而减轻，包括胰岛素抵抗在内的任何健康指标都没有丝毫改善。更严重的是，随着原本由众多细胞分担的储存任务全压在仅存的脂肪细胞上，这些剩余细胞会被迫撑得更大、更肥大，反而导致长期的代谢健康指标进一步恶化。
- **减重与灭存的本质区别**：自然减重是缩小组胞体积（Hypertrophy 逆转），小脂肪细胞具备极强的抗炎能力和胰岛素敏感性；吸脂则是物理消除脂肪细胞数量。
- **临床追踪结果**：抽吸臀部脂肪后若饮食模式未变，身体会将热量强制分流至腹部和内脏区域，数年内健康指标毫无提升，甚至因单细胞负荷过重而加剧代谢损伤。
---
### [02:39:25](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9565s) 传统闭幕提问：谁在无人相信时给予了信任
在播客尾声，主持人 Steven Bartlett 提出了《CEO日记》的标志性传统问题——由上一位匿名嘉宾为下一位嘉宾留下的人生提问：“在你的人生中，当没有任何人相信你时，是谁给了你机会，或者毫无保留地信任了你？”
听到这个问题，Ben 博士露出了由衷的笑容，并深情地回答：“很有可能是我的妻子。”他分享了一段极为私密而真挚的个人过往：两人在 23 岁时便早早结为夫妻。当时他们都无比渴望建立一个完整的家庭，妻子 Cheryl 明确希望成为一名全职母亲。Ben 对此全力支持，因为他自己的母亲在他很小的时候就因病去世了，他童年最温馨、最珍贵的记忆，全都是母亲全职在家时给予的陪伴——无论是中午回家喝到热汤，还是肚子疼时母亲赶来学校接他回家。失去母亲的经历让他无比渴望让自己的孩子也能拥有母亲全程陪伴的童年。
然而，这也意味着年仅 23 岁的 Ben 必须承担起全家唯一经济支柱的重担。在当时的前途未卜面前，他感到巨大的恐慌和自我怀疑，甚至觉得自己配不上妻子毫无保留的托付。正是妻子 Cheryl 始终如一的坚定支持改变了一切。Ben 感慨道，如果当时妻子在任何一个艰难关头对他说：“算了，我受够了，你现在立刻去找份普通工作糊口。”他出于对妻子的深爱与尊重，绝对会照做并放弃学术道路。
> “本，你可不笨。我嫁给你可不是图你的长相，我知道你肚子里有真本事，我相信你。”
妻子的这番信任既让他感到敬畏，又给予了他无穷的底气与赋能。正是这份孤注一掷的信任，让他一路走到了细胞生物学教授和代谢专家的位置，不仅创造了优渥的收入来庇护家庭，更让他拥有了自由支配的时间——每天早晨为孩子们做完早餐、享受家庭时光后才去工作，下午能早早回家辅导女儿进行家庭教育（Homeschooling）。
访谈在双方诚挚的感谢中落下帷幕。Steven 感慨这次对话彻底解答了他多年来关于生酮状态、胰岛素抵抗以及其对女性生育能力、多囊卵巢综合征（PCOS）和妊娠期深远影响的诸多困惑。
---
### [02:42:33](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9753s) 节目结语与《CEO日记》对话卡片
对话结束后，Steven Bartlett 介绍了《CEO日记》由这一传统演化而来的文创产品——《CEO日记》深度对话卡牌第二版（Conversation Cards: Second Edition）。
该卡牌整理了播客历期嘉宾在离开录音室前，手写在《CEO日记》本中留给下一位客人的深度思考题。每张卡片正面印有往期嘉宾留下的问题，背面附有专属二维码，扫描后即可解锁当时对应嘉宾在不知提问者身份时做出的现场视频回答。Steven 表示，这套卡牌此前曾两度瞬间售罄，此次升级版本在 official 网站限量发售，旨在让观众能将这种直击心灵的深度交流带入朋友与家庭聚会的日常互动中。
## Notable quotes
> [02:19](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=139s) prune the branch back a little bit — Benjamin Bikman
> [01:19:31](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=4771s) The Molecule of Life — Benjamin Bikman
> [01:33:43](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=5623s) 大脑在拥有酮体作为燃料来源时，表现会极为出色。 — Dr. Benjamin Bikman
> [01:59:34](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7174s) 你可能确实改变了微生物群，但谁又能断定那是变坏了呢？也许那是一个更好的改变。你感觉更棒了、思维更敏捷、身体更紧致、胰岛素敏感度改善、认知能力也提升了。如果你的肠道菌群发生了改变，我认为这大概率是向好的方向转变。 — Dr. Benjamin Bikman
> [02:01:07](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=7267s) 如果有人说：‘没错，你逆转了糖尿病，治好了高血压，但可怜你的肠道微生物啊。’我会回答：‘我不关心我的微生物组，我关心的是人类本身。’如果多样性降低了，但每一项临床指标都变得更好，那或许过高的多样性本来就不是我们想要的。 — Dr. Benjamin Bikman
> [02:14:20](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8060s) 所有关于人类成瘾神经生物学的证据都指向了同一种宏量营养素——碳水化合物，而不是脂肪，也不是蛋白质。 — Dr. Benjamin Bikman
> [02:22:04](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8524s) 人类摄入碳水化合物的下限是零。 — USDA
> [02:28:53](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=8933s) 唱片公司指责我太胖并解雇了我。我因此对 Ozempic 上瘾。现在的后果是，我得了骨质疏松，我的骨头变得脆得像威化饼干（wafer cookies）一样脆弱。 — Avery
> [02:35:50](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9350s) 从代谢的角度来看，吸脂手术绝对是危险且深具破坏性的。 — Dr. Benjamin Bikman
> [02:39:25](https://www.youtube.com/watch?v=NyFSkGMWP5Q&t=9565s) 本，你可不笨。我嫁给你可不是图你的长相，我知道你肚子里有真本事，我相信你。 — Cheryl Bikman
## Mentioned
Benjamin Bikman, Steven Bartlett, Ozempic, The Diary Of A CEO, Why We Get Sick, Whoop, Will Ahmed, Cynthia Kenyon, David Ludwig, Avery, Cheryl Bikman, Suzanne de la Monte, Brown University, Brigham Young University (BYU), National Health Service (NHS), National Institutes of Health (NIH), USDA, Cancer Research UK, Alzheimer's Disease International, Bryan Johnson, Paul Reynolds, The Biggest Loser, Original Ketone, Tour de France
## Video description
88% of adults have metabolic disease, but what’s really making us sick? Dr Benjamin Bikman reveals the hidden dangers of insulin and how to take control of your health
Dr Benjamin Bikman is a metabolic scientist and Professor of Cell Biology and Physiology. He is the host of ‘The Metabolic Classroom’ podcast and author of books such as, ‘Why We Get Sick: The Hidden Epidemic at the Root of Most Chronic Disease―and How to Fight It’.
00:00 Intro
02:19 My Mission to Help with Chronic Diseases
05:05 What Is Insulin Resistance?
13:53 What Causes Insulin Resistance?
21:01 Can Insulin Resistance Become Chronic?
25:22 The Importance of Fat Cells Shrinking or Expanding
34:53 What's the Evolutionary Basis of Insulin Resistance?
42:17 The Role of Insulin During Pregnancy
43:39 What Is Gestational Diabetes?
45:05 Does It Impact the Future Baby?
45:59 Women's Cancer Is Increasing While Men's Remains the Same
50:33 Ads
51:29 Alzheimer's and Dementia Are on the Rise
01:05:34 Ethnicities and Their Different Fat Distributions
01:10:03 What to Do to Extend Our Lives
01:19:31 Cholesterol: The Molecule of Life
01:22:15 Smoking Causes Insulin Resistance
01:23:52 Does Smoking Make Us Fat?
01:29:04 Ads
01:31:04 Ketosis and Insulin Sensitivity
01:39:16 Ketone Shots
01:41:12 Steven's Keto Journey
01:47:40 How to Keep Your Muscles on a Keto Diet
01:55:25 Are There Downsides to the Ketogenic Diet?
01:57:17 Is Keto Bad for Your Gut Microbiome?
02:07:05 Are Sweeteners Okay in a Keto Diet?
02:11:04 Is Salt Bad for Us?
02:19:22 The Importance of Exercise to Maintain Healthy Insulin Levels
02:22:03 Calorie Restriction
02:23:51 Why Don't We Just Take Ozempic?
02:26:19 The Side Effects of Ozempic
02:34:56 Why Liposuction Doesn't Work Long-Term
02:39:30 Who Believed In You When No One Else Did?
Follow Dr Benjamin:
Website - https://benbikman.com?
Research doc: https://stevenbartlett.com/wp-content/uploads/2025/02/DOAC-Benjamin-Bikman-independent-research.pdf
My new book! 'The 33 Laws Of Business & Life' is out now - https://g2ul0.app.link/DOACBook
You can purchase the The Diary Of A CEO Conversation Cards: Second Edition, here: https://g2ul0.app.link/f31dsUttKKb
Follow me:
https://g2ul0.app.link/gnGqL4IsKKb
Sponsors:
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WHOOP - https://JOIN.WHOOP.COM/CEO
[Source](https://www.youtube.com/watch?v=NyFSkGMWP5Q)
Source quotes
[2:19] Benjamin Bikman: prune the branch back a little bit
[79:31] Benjamin Bikman: The Molecule of Life
[93:43] Dr. Benjamin Bikman: 大脑在拥有酮体作为燃料来源时，表现会极为出色。
[119:34] Dr. Benjamin Bikman: 你可能确实改变了微生物群，但谁又能断定那是变坏了呢？也许那是一个更好的改变。你感觉更棒了、思维更敏捷、身体更紧致、胰岛素敏感度改善、认知能力也提升了。如果你的肠道菌群发生了改变，我认为这大概率是向好的方向转变。
[121:07] Dr. Benjamin Bikman: 如果有人说：‘没错，你逆转了糖尿病，治好了高血压，但可怜你的肠道微生物啊。’我会回答：‘我不关心我的微生物组，我关心的是人类本身。’如果多样性降低了，但每一项临床指标都变得更好，那或许过高的多样性本来就不是我们想要的。
[134:20] Dr. Benjamin Bikman: 所有关于人类成瘾神经生物学的证据都指向了同一种宏量营养素——碳水化合物，而不是脂肪，也不是蛋白质。
[142:04] USDA: 人类摄入碳水化合物的下限是零。
[148:53] Avery: 唱片公司指责我太胖并解雇了我。我因此对 Ozempic 上瘾。现在的后果是，我得了骨质疏松，我的骨头变得脆得像威化饼干（wafer cookies）一样脆弱。
[155:50] Dr. Benjamin Bikman: 从代谢的角度来看，吸脂手术绝对是危险且深具破坏性的。
[159:25] Cheryl Bikman: 本，你可不笨。我嫁给你可不是图你的长相，我知道你肚子里有真本事，我相信你。
Source quotes
[5:05] Dr. Benjamin Bikman: Insulin comes out like a taxi and transports all the glucose in my blood to various places around the body to store them.
[21:01] Dr. Benjamin Bikman: The average individual is spending every waking moment in a state of elevated insulin. And thus, the signal never really goes away because they never give themeselves a break.
[28:05] Dr. Benjamin Bikman: It is literally impossible for the type 1 diabetic to get fat if they are skipping their insulin injections... The body goes into such a dramatic fat burning state in the absence of insulin that keeping fat becomes impossible.
[51:29] Dr. Benjamin Bikman: The plaque-based theory doesn't make sense... You would be just as likely to find plaques in both brains.
[67:48] Dr. Benjamin Bikman: Subcutaneous fat is inert. It really is just sort of hanging out there and minding its own business. But, in that same study, if you move the visceral adipose over, now all of a sudden that animal that got that extra dose of visceral fat is going to become sicker.
[73:05] Dr. Benjamin Bikman: The very word metabolism encompasses anabolism, which is anabolic or building up, and catabolism or catabolic, which is breaking down. The key to a healthy growing living cell is this nice ongoing balance of build and break.
[125:00] Dr. Benjamin Bikman: Humans do not need, we have no requirement for carbohydrate. We do have requirement for fat and protein.
[146:19] Dr. Benjamin Bikman: I have to speak a little more boldly about the negative consequences because nobody talks about them... 40% of weight loss is coming from fat-free mass.
Original transcript
[0:00] When we're looking at smoking versus
[0:01] vaping, vaping is probably worse in
[0:03] terms of the damage to the airway and
[0:05] the insulin resistance that comes from
[0:07] it. But this gets worse because we know
[0:09] that insulin resistance is the core for
[0:10] most chronic diseases that are killing
[0:12] us. And there's a handful of other
[0:13] lifestyle habits that's contributing to
[0:14] it.
[0:15] That's horrifying. So tell me
[0:17] everything.
[0:18] Dr. Benjamin Bikman is a leading
[0:19] metabolic scientist. His research
[0:21] focuses on the hidden epidemic of
[0:22] insulin resistance and its devastating
[0:24] consequences.
[0:25] And by regaining control of your insulin
[0:26] levels, he says you can regain control
[0:28] of your life.
[0:28] Insulin is a hormone that affects
[0:30] literally every single cell of the body.
[0:32] But if those cells become insulin
[0:33] resistant, you start to spread the
[0:35] disease. For example, they call
[0:36] Alzheimer's insulin resistance of the
[0:38] brain. And even the most common forms of
[0:39] infertility, erectile dysfunction, and
[0:41] PCOS, insulin resistance is a heavy
[0:43] contributor. Now, 88% of adults in the
[0:45] US have some degree of insulin
[0:47] resistance. And people hear this and
[0:49] think America is just fat and
[0:50] metabolically sick. But we're not
[0:52] actually the worst country when it comes
[0:53] to this. And part of it is because of
[0:55] how different ethnicities store fat. And
[0:57] I'll come back to that. But there's two
[0:58] roads to insulin resistance. So there's
[1:00] the fast lane, and I could make you
[1:01] insulin resistant in 6 hours with either
[1:03] of these common three things. But if I
[1:05] removed them, your resistance would go
[1:06] away just as quickly. Now, the slow
[1:08] lane, that's a problem. And there's
[1:10] certain lifestyle habits and problems
[1:11] with our diet that are massively
[1:13] contributing to slow insulin resistance.
[1:15] Now, thankfully, this can be resolved
[1:16] through four pillars, which are very
[1:18] simple.
[1:18] We'll get into that. But why don't we
[1:20] just cycle this off and just take his
[1:21] Ozempic?
[1:22] Well, because people may not know about
[1:23] the negative side effects. For example,
[1:25] 40% of the weight that people are losing
[1:27] on these drugs is coming from
[1:29] Highly
[1:32] I have been forced into a bet with my
[1:34] team. We're about to hit 10 million
[1:36] subscribers on YouTube, which is our
[1:37] biggest milestone ever, thanks to all of
[1:39] you. And we want to have a massive party
[1:41] for the people that have worked on this
[1:42] show for years behind the scenes. So,
[1:44] they said to me, "Steve, for every new
[1:46] subscriber we get in the next 30 days,
[1:48] can $1 be given to our celebration fund
[1:52] for the entire team?" And I've agreed to
[1:54] the bet. So, if you want to say thank
[1:56] you to the team behind the scenes at
[1:57] Diabetes Canada, all you've got to do is
[1:59] hit the subscribe button. So, actually,
[2:01] this is the first time I'm going to tell
[2:02] you not to subscribe because it might
[2:05] end up costing me AN AWFUL
[2:19] BENJAMIN,
[2:22] WHAT IS THE MISSION THAT YOU'RE ON?
[2:24] My mission is to help people appreciate
[2:28] that much of chronic disease
[2:30] we look at them as these siloed
[2:32] individual distinct disorders with
[2:34] totally distinct origins, and yet much
[2:37] of them
[2:38] uh share a common core. It's as if
[2:41] they're branches growing from the same
[2:42] tree. And the conventional clinical care
[2:46] will look at these branches and give
[2:48] someone a prescription for a medication,
[2:50] which is only going to prune the branch
[2:52] back a little bit, never actually
[2:54] solving the problem.
[2:56] It can just grow right back. And so, we
[2:59] can look at most of these chronic
[3:01] diseases that are killing us globally
[3:04] and and then say, "Okay, there are in
[3:06] fact some simple lifestyle changes that
[3:09] can be implemented that will help reduce
[3:11] the risk of not only one or two, but all
[3:13] of the top killers from things like
[3:15] Alzheimer's disease to
[3:17] uh heart disease to type 2 diabetes to
[3:20] uh liver failure or fatty liver disease.
[3:22] All of them share a common metabolic
[3:25] core. That's my mission.
[3:27] And what is that common metabolic core?
[3:30] Yeah, it's a little-known problem called
[3:31] insulin resistance.
[3:33] In fact, when I first started
[3:37] this topic, I stumbled on one paper
[3:40] that documented how when fat tissue is
[3:43] growing, it increases the risk of type 2
[3:47] diabetes. That wasn't a concept in the
[3:48] early 2000s that was is getting a lot of
[3:50] attention.
[3:51] Diabesity, this kind of dual epidemic of
[3:54] wherever we see obesity, we see more
[3:56] type 2 diabetes. And this manuscript
[3:58] outlined
[4:00] something that was to me a revelation at
[4:01] the time. It was so fascinating where
[4:04] when fat tissue is growing, it starts
[4:06] releasing pro-inflammatory proteins.
[4:09] That inflammation caused a problem
[4:11] called insulin resistance.
[4:14] And then that got me into this realm of
[4:16] understanding that other tissues of the
[4:19] body as they become insulin resistant,
[4:21] then you start to spread the chronic
[4:23] disease.
[4:24] And and essentially
[4:26] coming to the conclusion that something
[4:29] like hypertension, high blood pressure,
[4:31] which is the most common cardiovascular
[4:33] problem and the main contributor to
[4:35] heart disease.
[4:36] Well, insulin resistance is the main
[4:38] cause of hypertension. Um they call
[4:41] Alzheimer's disease type 3 diabetes or
[4:43] more accurately um insulin resistance of
[4:46] the brain. Even the most common forms of
[4:48] infertility in men, it's erectile
[4:50] dysfunction. Well, that's because of
[4:52] insulin resistance of the blood vessels.
[4:54] In women, the most common form of
[4:56] infertility is polycystic ovary syndrome
[4:58] or PCOS. That's because of the insulin
[5:01] resistance affecting her ovaries and the
[5:03] ability to produce the proper sex
[5:04] hormones.
[5:05] I guess the really important question
[5:07] here is what is insulin resistance? And
[5:10] can you explain this to me like I'm a
[5:12] 10-year-old because
[5:13] for sure. Insulin resistance is it's
[5:15] kind of a it's a disorder that has two
[5:18] parts. It's like a coin with two sides
[5:20] that as much as we think of we we think
[5:22] of one side just because we hear the
[5:24] word insulin resistance, but there's
[5:26] another part to it that I need to that
[5:28] is very important. So,
[5:30] insulin first of all is a hormone that
[5:32] we make from the pancreas, a long kind
[5:35] of gland tucked underneath the stomach.
[5:37] And the pancreas is a very busy organ.
[5:39] It makes a lot of different hormones. It
[5:42] makes hormones that come into the blood.
[5:43] It also makes enzymes that go into the
[5:45] the into the intestines to help digest
[5:47] food. But among the hormones that are
[5:50] being released into the blood is
[5:52] insulin. Now, in the person with type 1
[5:55] diabetes, their immune system has
[5:57] destroyed their beta cells. So, they
[5:59] don't make insulin anymore. That's why
[6:02] for a person with type 1 diabetes,
[6:03] insulin is a life-saving therapy. You're
[6:06] giving them what they're not making
[6:07] anymore. But for everybody else,
[6:10] we have beta cells and they're releasing
[6:12] insulin when they need to.
[6:14] Now, usually the main stimulus
[6:17] the main reason the beta cell is
[6:19] releasing the insulin is because blood
[6:21] glucose levels go up.
[6:22] So, I eat sugar.
[6:23] You eat sugar or not even something as
[6:25] obvious as sugar, but bread or or
[6:28] crackers.
[6:29] White rice.
[6:29] Chips. Oh, yes. Yes. So, basically
[6:32] anything that falls into the family of a
[6:34] carbohydrate. So, if the earth grows it,
[6:36] that's a carbohydrate. Um if it's a
[6:39] plant, it's a carbohydrate. Maybe that's
[6:40] a better way of describing it. And so,
[6:42] it's going to have starches and sugars,
[6:44] which all this kind of falls into this
[6:46] family of carbohydrate. Depending on how
[6:49] much starch or sugars that it has, then
[6:52] that will result in a bigger or a
[6:54] smaller blood glucose or blood sugar
[6:56] response.
[6:58] But then, if blood sugar is too high for
[7:00] too long, that becomes very harmful to
[7:02] the body. So, insulin comes in
[7:04] um and helps lower the blood glucose.
[7:06] And then, having done its job, insulin
[7:08] comes back down.
[7:09] So, insulin comes out like a taxi and
[7:11] transports all the glucose in my blood
[7:15] to various places around the body to
[7:17] store them.
[7:17] Perfect. Perfect. Yeah,
[7:19] Yeah, that's right. It's that's you can
[7:20] say look at it's a shuttle. It's a taxi
[7:22] saying, "Hey, glucose, come on in. I'm
[7:24] dropping you off at the muscle." So,
[7:26] mostly, just as an interesting tangent
[7:28] of insulin before I finish answering
[7:30] insulin resistance,
[7:32] insulin will open the doors for blood
[7:35] sugar to come in and drive the taxi in,
[7:38] mostly at the muscle and the fat.
[7:41] Muscle and fat tissue need insulin to
[7:43] come and bring the sugar in via taxi.
[7:47] However, other tissues and and the brain
[7:50] a little bit as well. Other tissues will
[7:52] still respond to insulin, but they don't
[7:55] need insulin to tell it what to do with
[7:57] the sugar. It just takes it in. But even
[7:59] on those like the liver for example,
[8:02] if the liver sees sugar driving by in a
[8:04] taxi, it just opens the doors and lets
[8:06] it in. It doesn't need insulin to come
[8:08] and tell it to let the sugar in.
[8:10] However, even at the liver and other
[8:13] every other cell has a similar degree of
[8:15] this.
[8:16] The liver doesn't know what to do with
[8:18] it.
[8:19] So, this is back to something I'd
[8:20] mentioned earlier where insulin's
[8:22] thematic effect of the entire body is to
[8:25] tell the body what to do with energy in
[8:27] all of its forms as as these kind of
[8:30] caloric rich molecules. What to do with
[8:32] lactate, what to do with ketones, what
[8:34] to do with fats or glucose, what to do
[8:36] with pro- amino acids. So, insulin will
[8:39] tell the body what to do with all of
[8:40] those things. But again, it's most
[8:42] famous effect is to control blood sugar.
[8:46] And that's not wrong because it's most
[8:49] powerful activator is blood sugar. So,
[8:52] with all of that in mind,
[8:54] insulin resistance is two problems
[8:56] wrapped into one. The one problem is the
[8:58] most obvious one, which is that insulin
[9:01] isn't working as well as it used to. So,
[9:02] back to the analogy of the taxis
[9:05] dropping off sugar,
[9:06] if the muscle tissue has become insulin
[9:09] resistant, insulin is coming and trying
[9:12] to pull the sugar-loaded taxi into the
[9:14] muscle, but the muscle's not listening.
[9:16] So, say that again. So, the
[9:17] Yeah.
[9:18] Insulin's coming past with the glucose
[9:21] inside it.
[9:22] Well, not not technically. Yeah, but
[9:24] just to sort of go with your metaphor.
[9:26] But maybe to use another one, insulin
[9:28] comes and knocks on the doors. It's like
[9:30] the bouncer
[9:31] Yeah.
[9:31] at the door. It's coming and knocking on
[9:33] the door of the muscle saying, "Hey
[9:35] muscle, I've got some sugar that wants
[9:36] to come in.
[9:37] Mhm.
[9:38] And normally the muscle will say, oh
[9:39] yeah, sure, okay, open up the doors and
[9:41] let the sugar come in.
[9:42] When the muscle is insulin resistant,
[9:44] the bouncer is knocking. Maybe there's
[9:46] even I'm almost getting ahead of myself,
[9:48] but
[9:49] one bouncer maybe two or three bouncers
[9:51] pounding on the doors of the muscle
[9:53] cell, but the muscle cell's not
[9:55] listening. It's become deaf.
[9:57] That's the insulin resistance of what we
[9:59] call insulin resistance, where some of
[10:01] insulin's effects, like helping lower
[10:04] blood sugar, it's not working very well
[10:06] anymore. And the muscle is just an
[10:08] obvious example because there's so much
[10:10] of it. You know, it is the biggest
[10:12] tissue on the average individual.
[10:14] Someone who's very obese perhaps now has
[10:15] more fat tissue, but even people who are
[10:18] overweight, most of us is muscle. So,
[10:20] that's a good it's a good tissue to look
[10:22] at. So, part of insulin resistance is
[10:26] that of all the things insulin's trying
[10:27] to do,
[10:29] including lower blood sugar, it doesn't
[10:31] do it quite as well as it used to. Some
[10:33] of the cells or tissues of the body have
[10:35] become deaf to insulin's demands.
[10:39] Now, however, at the same time that's
[10:41] happening,
[10:42] insulin levels are higher. And that is
[10:45] really important. Um and I'll I'll
[10:47] mention an example in just a moment that
[10:49] highlights the difference between the
[10:51] two, but we have to consider anytime we
[10:54] talk about insulin resistance, we think
[10:56] of two things happening
[10:57] um in concert. One, insulin isn't
[11:00] working quite as well as it used to in
[11:02] various places of the body.
[11:04] At the same time, insulin levels are
[11:07] higher. And that kind of takes us back
[11:09] to the um the muscle cell, where I'd
[11:12] mentioned getting a little ahead of
[11:13] myself, that a bouncer is knocking on
[11:16] the door,
[11:17] and once upon a time the muscle cell
[11:18] would hear that one polite knock from
[11:20] that one bouncer or one molecule of
[11:23] insulin, if you will, and it would open
[11:25] the door and let the glucose or the
[11:26] blood sugar come in. But now the muscle
[11:28] cell
[11:29] um the the the bouncer insulin's
[11:31] knocking on the door, but the muscle
[11:33] doesn't listen. It's resistant.
[11:35] And so, the body has adapted, and it
[11:38] learns, "Okay, well, if one bouncer
[11:40] wasn't enough, let's send an angry mob
[11:43] of bouncers." And then the glucose the
[11:46] muscle will start to open the door. And
[11:48] and and indeed it can. So, those two
[11:50] problems go together. On one hand,
[11:52] insulin isn't working as well as it used
[11:54] to. That's what gives it the name
[11:55] insulin resistance.
[11:57] But there's another part that is equally
[11:59] present, which is that blood insulin
[12:01] levels are higher. Now, there's
[12:04] um earlier at the outset of the
[12:05] conversation, I mentioned that even
[12:07] infertility has an origin has has some
[12:11] degree of um
[12:13] development because of insulin
[12:14] resistance.
[12:15] And it's a perfect example of both of
[12:18] these parts of insulin resistance, where
[12:20] in some instances insulin isn't working
[12:22] very well, always with insulin
[12:24] resistance blood insulin levels are
[12:26] higher. So, for example,
[12:28] erectile dysfunction is the most common
[12:31] form of male infertility. In fact,
[12:34] its connection to insulin resistance is
[12:36] so strong that just a few years ago I I
[12:39] was so struck by a title of a paper that
[12:40] had just been published, which stated
[12:43] something like, "Is erectile dysfunction
[12:45] the earliest manifestation of insulin
[12:49] resistance in otherwise young healthy
[12:51] men?" Now, what is the connection? It's
[12:53] because in a normal erectile function,
[12:56] in order for the man to have normal
[12:58] erectile function, he has to experience
[13:00] a pretty dramatic increase in the size
[13:03] of the blood vessels in his body. The
[13:05] blood vessels expand, that increases
[13:07] blood flow, and then he has normal
[13:08] function.
[13:10] Part of that signal that tells the blood
[13:12] vessels that it's time to expand is
[13:14] actually insulin. And so, this is what I
[13:17] said earlier, where insulin does so many
[13:19] things in the body, and we only think of
[13:21] it as being relevant to glucose, and
[13:23] that's not fair. Insulin does a a of
[13:25] stuff. Again, including telling blood
[13:28] vessels to expand. Now, unfortunately,
[13:30] in the case of this
[13:32] this unfortunate man,
[13:34] his blood vessels become insulin
[13:36] resistant. So, now it's insulin coming
[13:38] and knocking on the doors of the blood
[13:40] vessels saying, "Hey, it's time to
[13:41] expand and increase blood flow."
[13:44] But, the blood vessels don't respond.
[13:45] They don't listen. So, they stay
[13:47] constricted, blood flow stays
[13:49] insufficient, and thus he has erectile
[13:52] dysfunction.
[13:53] Now, I don't want to be insulin
[13:54] resistant.
[13:55] No. No one does. No one does.
[13:57] So, so tell me how it happens.
[13:59] Yeah, right. Yeah, so the origins are so
[14:01] important because it helps us understand
[14:02] why we've gotten into the situation we
[14:04] are, where it's the most common problem
[14:06] worldwide. There are two pathways to
[14:09] insulin resistance. So,
[14:11] two two roads to get to the same
[14:13] destination. Again, the destination
[14:15] being insulin resistance. There's the
[14:17] fast lane, which I call fast insulin
[14:20] resistance, and it actually has three
[14:21] lanes, which I'll describe in a moment.
[14:24] Then, there's the slow insulin
[14:25] resistance, which is a more it takes a
[14:28] little longer to get there, but at the
[14:30] same time it takes a little longer to
[14:31] get away from it. So, I'll start with
[14:33] fast insulin resistance because the slow
[14:36] one ends up getting a little excitingly
[14:38] complicated, but in a cool way.
[14:41] So, with fast insulin resistance, there
[14:43] are three things that I could take you
[14:45] to a clinical lab, and I could make you
[14:47] insulin resistant in 6 hours with either
[14:50] of these three things. But, as quickly
[14:53] as it settles in, if I remove those
[14:55] things, your insulin resistance would go
[14:58] away. So, these are fast causes, and
[15:00] they're fast resolution.
[15:02] They are stress
[15:05] is a is a primary cause of fast insulin
[15:07] resistance.
[15:09] So, too is inflammation.
[15:12] And then lastly, and this is going to
[15:14] sound somewhat paradoxical, too much
[15:16] insulin is also a cause, and I'll end
[15:19] with that one because I think it's the
[15:20] most important. Then transition to slow
[15:22] insulin resistance. So, anytime the body
[15:25] is experiencing too much stress, it will
[15:27] very quickly become insulin resistant.
[15:29] Now, as a professor who teaches
[15:31] endocrinology, no surprise, I define
[15:35] stress in the context of hormones. And
[15:38] there are two primary stress hormones,
[15:39] cortisol and what we call in the US
[15:42] epinephrine or in the UK adrenaline.
[15:45] Those are the two stress hormones. Now,
[15:47] those hormones are very distinct. They
[15:50] have almost nothing in common. But like
[15:52] when you are feeling a little stressed,
[15:55] it's both of those, especially
[15:56] adrenaline {slash} epinephrine, that are
[15:58] making you feel a little jittery. It's
[16:00] making your heart beat a little faster.
[16:02] You're a little more alert. Um that all
[16:05] starts to play into a stress response.
[16:08] But what those two hormones have in
[16:10] common
[16:11] is that they both want blood glucose
[16:13] levels to climb.
[16:14] It's kind of their way of saying, "Hey,
[16:16] we don't really know what's going on
[16:18] right now, but we want to be ready to
[16:19] run away." Or that's the fight or flight
[16:21] kind of aspect to stress. And so they
[16:24] want to push blood glucose levels up,
[16:26] and they do very well.
[16:27] That, of course, puts them at odds with
[16:29] the hormone insulin.
[16:31] Cuz these two, epinephrine or adrenaline
[16:33] and cortisol, the two stress hormones,
[16:35] they're pushing glucose up, insulin
[16:38] wants to push it down. So, the more of
[16:40] the body is has those stress hormones
[16:43] elevated because of, say, sleep
[16:45] deprivation, that's a very effective way
[16:47] to increase cortisol, or they are taking
[16:50] too much drinking too much caffeine,
[16:53] that is a way to increase epinephrine
[16:55] quite strongly. If both of those signals
[16:57] are too incessant, or the you know, they
[17:00] they continue to be present and climb,
[17:02] then insulin has to work harder and
[17:04] harder. And then we have insulin
[17:06] resistance. So, stress is a cause of
[17:09] insulin resistance. But then next is
[17:11] inflammation.
[17:13] You you know, you you and I were
[17:14] commenting about earlier about how,
[17:17] "Boy, there's a cold going around.
[17:18] People it's flu season. Even then, if a
[17:21] person were wearing a continuous glucose
[17:23] monitor on the back of their arm,
[17:25] measuring their glucose levels, they
[17:27] would see their glucose levels are much
[17:29] much higher like significantly higher
[17:32] during the time that they're struggling
[17:34] with this infection. That is a
[17:36] reflection of insulin resistance.
[17:38] Insulin's having a harder time keeping
[17:40] the blood glucose levels in check.
[17:43] Anytime inflammation is up, insulin
[17:45] resistance will be up as well. Even in
[17:48] things like autoimmune diseases, there
[17:50] are reports in humans that document the
[17:52] degree to which someone has say active
[17:55] rheumatoid arthritis. Their their joints
[17:57] are achy and because of of an autoimmune
[18:00] attacking of the joints,
[18:02] they will note on some days, like every
[18:05] autoimmune disease, there is an ebb and
[18:07] a flow. Some days it's good, some days
[18:10] it's bad. And on the bad days, if you
[18:13] measure their insulin resistance, it is
[18:15] absolutely locked with the degree to
[18:18] which their immune system is turned on
[18:20] or off or higher or lower. So,
[18:22] inflammation is another cause. And then
[18:24] the last one of the fast lane of insulin
[18:26] resistance is too much insulin itself.
[18:29] Now, the astute listener will realize
[18:32] the kind of circular thing I've just
[18:34] presented by invoking high insulin as a
[18:36] cause of insulin resistance because they
[18:38] will also think, "But wait a minute,
[18:40] Ben. You just said that high insulin is
[18:42] also a consequence of insulin
[18:44] resistance." That, you know, back to the
[18:46] bouncer knocking on the the the door of
[18:48] the muscle cell, if one bouncer wasn't
[18:51] enough or one molecule of insulin wasn't
[18:53] enough, the body will say, "Okay, well,
[18:55] let's send 10 molecules of insulin."
[18:58] So, high insulin is both a consequence
[19:01] of insulin resistance, but it's also a
[19:03] cause. And this is reflective of a
[19:07] fundamental principle in all of biology
[19:11] that if there is too much of a stimulus,
[19:14] a cell, if it's capable, will try to
[19:17] become resistant to that stimulus. This
[19:20] would be like a funny analogy of in in
[19:23] in my in the Bickman home, my darling
[19:25] wife is home with the children. That is
[19:28] what she wants to do. She She is
[19:30] full-time mom. When I'm home, and I try
[19:33] to be home as much as I can, it's funny
[19:35] for me to note the difference in how
[19:36] quickly we each respond to our children.
[19:38] I will hear my child saying, "Mom. Mom.
[19:42] Mom."
[19:43] And she's not responding. Mom has heard
[19:46] this for so much that she's become kind
[19:48] of selectively deaf to when my children
[19:51] are demanding her attention. I'm not as
[19:53] around my children quite as much cuz I'm
[19:55] working during the day. And so when I
[19:57] hear that, it's a very fresh signal to
[20:00] me. I've not heard it so much that I've
[20:01] become deaf to it. And so I will respond
[20:05] even though I'm in the other room
[20:06] because I'm so much more sensitive to
[20:09] the clamoring for attention.
[20:11] This is like the body in response to
[20:13] insulin. If there is always insulin,
[20:16] it's always going up, always going up,
[20:19] the body will start to say the muscle
[20:20] cell will start to say, "Boy, insulin,
[20:22] you are knocking on my door all the
[20:24] time. This is getting old. I'm not
[20:26] responding anymore. I'm not going to
[20:28] listen as much as I was before." So in
[20:30] that sense,
[20:32] insulin, too much insulin becomes a
[20:34] cause of insulin resistance. And back to
[20:36] what I said earlier, I could take you
[20:37] into the lab, start infusing you with
[20:40] just a little drip of insulin to
[20:41] increase your insulin, and over just a
[20:43] few hours, you would become demonstrably
[20:46] less sensitive to it than you were
[20:49] before we started. But again, as I would
[20:51] take that away, give your body a few
[20:53] hours, and it's back to normal. In every
[20:55] one of those instances, it's a fast
[20:57] onset, and it's also a fast solution if
[21:00] we can take it away.
[21:01] If we can take it away, but if we can't
[21:02] take it away, does it become sort of
[21:04] chronic?
[21:05] Yes, so that especially all of these can
[21:07] contribute to a more lingering insulin
[21:10] resistance, but especially insulin.
[21:12] Where I focus on that one the most
[21:14] because of not only its relevance to the
[21:16] slow lane, but also just how present it
[21:20] is where 70% of all calories globally
[21:24] are carbohydrates. And now, perhaps with
[21:27] the best of intentions, our experts are
[21:29] telling us that we should be eating six
[21:31] times a day.
[21:32] And so, we
[21:34] eat we wake up in the morning, insulin
[21:37] has finally been coming down while we've
[21:38] been fasting overnight. Insulin gets to
[21:41] take a little bit of a break. We're
[21:42] fasting. Then we break that fast by
[21:44] eating breakfast. And in the UK as it is
[21:47] in the US, by and large, this is going
[21:49] to be a very starchy sugary breakfast.
[21:52] It's toast with some jam or a cereal or
[21:55] it's bagels.
[21:57] That is going to be that is almost pure
[21:58] glucose. And so, what do we do? We wake
[22:01] up, we eat breakfast, we spike our blood
[22:03] sugar levels, and insulin has to come
[22:05] up.
[22:06] Insulin will take longer to come down
[22:08] than the blood sugar will.
[22:10] It will wait in the blood to make sure
[22:11] that all the blood sugar has gone back
[22:13] to normal. So, depending on how much
[22:15] carbohydrate we ate for breakfast, it
[22:17] could take our insulin levels three or
[22:19] even four hours to come back down to
[22:21] normal. Long before it's had a chance to
[22:23] come back down to normal, we've had a
[22:25] mid-morning snack, of course. We need to
[22:27] go get a sugary coffee and another bagel
[22:30] or something. And so, after just a
[22:32] couple hours, we do it again. And once
[22:35] again, before insulin has had a chance
[22:37] to come back down, we have a starchy
[22:39] carbohydrate-heavy lunch, then an
[22:41] afternoon snack, and then a
[22:43] carbohydrate-heavy dinner, and then of
[22:44] course we have to have an evening snack
[22:46] before we go to bed. So, the average
[22:48] individual is spending every waking
[22:50] moment in a state of elevated insulin.
[22:53] And thus, the signal never really goes
[22:55] away because they they never give
[22:57] themselves a break. But one of the
[22:59] consequences of that I mentioned, which
[23:01] is that it directly causes insulin
[23:03] resistance.
[23:04] But, when insulin is high,
[23:07] it starts to have a signal on the fat
[23:09] cell. And that then brings us to the
[23:11] slow insulin resistance, where you have
[23:14] something happening in the fat tissue
[23:16] that begins to set the stage for insulin
[23:18] resistance in the entire body. And it
[23:20] takes longer to settle in, but it takes
[23:22] also longer to go away. That's why I
[23:24] call this one slow insulin resistance.
[23:27] Now, in the case of insulin,
[23:29] most people So, the the the the key with
[23:32] the
[23:33] Yeah, I'll explain it this way first.
[23:34] So, the most relevant feature with fat
[23:36] tissue contributing to insulin
[23:38] resistance is the size of each fat cell.
[23:41] When we typically think of fat, we would
[23:43] maybe say, "Okay, Steve has um I'll do
[23:47] this in kilos for the UK audience. Steve
[23:49] has 10 kilos of fat on your entire body.
[23:51] That's probably too much for you. Ben
[23:53] has 20 kilos.
[23:56] And yet, it's possible that I'm
[23:59] healthier metabolically than you.
[24:01] Um and that's because it's not the mass
[24:04] of fat that matters most. It's the size
[24:06] of the fat cell that matters. This is
[24:08] why women, despite universally being
[24:11] fatter than her male counterparts, are
[24:13] healthier with regards to insulin
[24:15] resistance and every single metabolic
[24:17] problem. It's because women, as a result
[24:19] of her particular sex hormones, have
[24:22] more fat cells, but they're smaller. So,
[24:24] she has more fat, but smaller fat cells.
[24:27] And small fat cells are healthy, insulin
[24:31] sensitive, anti-inflammatory
[24:33] fat cells.
[24:35] The but the bigger the fat cell gets,
[24:37] the more it initiates a cascade of
[24:39] events or a series of events that
[24:41] creates insulin resistance.
[24:43] Am I right in thinking we have the same
[24:44] amount of fat cells for our whole life,
[24:46] pretty much?
[24:47] That's really, really safe assumption
[24:49] for most people. Yeah, for most people
[24:51] the a fat cell um sometimes students
[24:53] will hear that fat cells are immortal.
[24:55] That is not true.
[24:57] But, they're long-lived. Fat cells will
[24:59] live about 10 years. And so, typically,
[25:02] by the time you if you think of if you
[25:03] look at a newborn, during infancy,
[25:06] childhood, and puberty, the number of
[25:08] fat cells is going up up up up up. Once
[25:11] they finish puberty, so mid to late
[25:14] teens for a young woman, late teens or
[25:16] even early 20s for a young man, usually
[25:19] at that point the number of fat cells
[25:20] they have is going to be very static.
[25:22] This is something people don't really
[25:23] understand, and I actually need to
[25:24] discover it from doing this podcast and
[25:26] speaking to so many experts about this,
[25:28] that
[25:29] we pretty much, especially as an adult,
[25:30] have the same amount of fat cells,
[25:32] really regardless of what we eat.
[25:34] Yes.
[25:34] And it's actually just the fat cells we
[25:36] have shrinking
[25:38] Or growing.
[25:38] or expanding.
[25:39] Exactly. That's exactly right. Now,
[25:42] there are differences across
[25:43] makes liposuction a pretty bad
[25:46] idea.
[25:47] it in fact, it makes things worse.
[25:49] Please, let's make sure we come back to
[25:50] that.
[25:50] Okay, I'll write that on my list.
[25:51] Because it really becomes the person
[25:54] ends up their vanity ends up really
[25:56] ruining their their their future
[25:59] metabolic outcomes.
[26:00] But, there are differences across
[26:02] ethnicity. Like um this is a little
[26:04] oversimplified, but not much. On one
[26:06] end, you'd have Caucasians, kind of
[26:08] northern European Caucasians. On the
[26:10] other wind end, you'd have East Asians,
[26:12] like uh Chinese, Japanese, uh Korean
[26:15] East Asians.
[26:16] And And then, if you look at that same
[26:18] spectrum of people making fat cells
[26:20] through their life,
[26:22] an East Asian will be making fat cells
[26:24] and then stop right about here.
[26:26] About sort of
[26:27] So, very few fat cells, relatively
[26:29] speaking, across all the ethnicities.
[26:31] They have very few fat cells. A
[26:33] Caucasian on the other end of the
[26:34] spectrum,
[26:36] they went way higher.
[26:38] And so, this guy, let's say American Ben
[26:41] versus Chinese Ben, overly simplified,
[26:43] but but here we are. Um
[26:45] so much of fat mass isn't the number of
[26:49] fat cells, even though American Ben has
[26:50] more, it's the size of the fat cell. So,
[26:53] I could be the same percent body fat
[26:57] really as Chinese Ben,
[26:59] um but that would just be because my fat
[27:01] cells were just that much smaller. But
[27:03] this is the problem then.
[27:05] If you have
[27:07] let's say American Ben and Chinese Ben
[27:09] both gained 10 kilos of pure fat over
[27:12] the next 10 years. Very easily done.
[27:14] Most people do that quite often.
[27:16] Caucasian Ben just doesn't look as good
[27:19] in his speedo.
[27:20] Um which is a pasty Caucasian, he's not
[27:22] going to look particularly good in that
[27:23] speedo anyway. But I'm just indulging a
[27:25] little more than I was before, but
[27:27] otherwise I'm healthy. My blood pressure
[27:28] is fine, my blood sugar is fine,
[27:30] everything is normal.
[27:32] Put that same 10 kilos of fat on Chinese
[27:34] Ben,
[27:36] hypertension, type 2 diabetes, fatty
[27:38] liver disease, infertility.
[27:41] Um and that is because Chinese Ben had
[27:44] fewer fat cells to start with. And so
[27:46] those fat cells, as the body was told to
[27:49] store fat, those fat cells were getting
[27:51] much, much bigger, much sooner.
[27:53] And the fat fat cell
[27:56] promotes insulin resistance very, very
[27:59] readily. And so that logically moves
[28:01] into this the question of what makes fat
[28:03] cells grow?
[28:05] And it is
[28:06] two essential variables that we only
[28:09] ever look at calories.
[28:10] And yet, if you take a person with type
[28:12] 1 diabetes
[28:14] and say, "I want you to eat 10,000
[28:16] calories, but don't give yourself your
[28:19] insulin injection." They cannot gain
[28:22] weight. It is It is literally impossible
[28:25] for the type 1 diabetic to get fat if
[28:28] they are skipping their insulin
[28:29] injections. In fact, this is so known
[28:32] that if you take Let's imagine a young
[28:33] woman who would maybe have more pressure
[28:35] to be thin than her male counterpart,
[28:38] although it's happening more in males,
[28:39] too.
[28:40] Imagine a young girl who gets diagnosed
[28:42] with type 1 diabetes at the age of 13 or
[28:44] 14. Very impressionable time. She's very
[28:47] worried about how how she looks and how
[28:49] thin she is.
[28:51] She learns that wait a minute, I can eat
[28:55] whatever I want and all I have to do is
[28:57] not inject my insulin and I'll be as
[28:59] skinny as I want and it works. It works
[29:01] so well that it's actually a formal
[29:03] eating disorder called diabulimia.
[29:06] So this the fact that this exists is
[29:08] absolute proof
[29:10] that the growing and the shrinking of
[29:11] the fat cell is more complicated than
[29:13] just calories being high or low.
[29:15] Because like I had said earlier when I
[29:17] talked about hormones, hormones are a
[29:19] way for the bot for the very tissues of
[29:21] the body to know what it ought to do
[29:23] with energy.
[29:24] And so a fat cell will have energy all
[29:27] around it and if it doesn't have insulin
[29:29] to tell it what to do, it won't do
[29:31] anything with it. And or maybe to make
[29:33] this more direct back home in my lab
[29:37] my students my students are growing fat
[29:39] cells in Petri dishes. These fat cells
[29:41] are swimming in a little sea of
[29:43] calories, lots of glucose, lots of fats
[29:46] and yet they stay really small
[29:49] until we add insulin. The moment we add
[29:52] insulin into that little Petri dish, if
[29:54] we check those cells 4 hours later,
[29:56] they're immediately fatter. If we check
[29:58] them 4 hours later, they're fatter
[30:00] still.
[30:01] Now they know what to do with the energy
[30:03] they have. So with slow insulin
[30:06] resistance
[30:07] it develops when fat cells get really
[30:09] really big. It's like a because they
[30:12] have to tell insulin, insulin you
[30:13] continue you you are telling me to keep
[30:15] growing, I can't keep growing. I'm so
[30:18] big that I'm going to pop. I mean
[30:20] literally the fat cell can get so big
[30:21] that it degrades its membrane. It's like
[30:23] a water balloon that a naughty little
[30:25] boy has overfilled and it's about to
[30:27] burst.
[30:28] The fat cell doesn't want to burst and
[30:30] so it tells insulin, insulin you are
[30:32] trying to make me grow. You're telling
[30:34] me to grow. I can't listen anymore. I'm
[30:37] becoming insulin resistant to stop
[30:39] growing.
[30:40] So insulin makes you fat?
[30:41] Oh very much. Now, if you So, so I A
[30:44] moment ago I said that the big fat cell
[30:46] has two variables. You must have both.
[30:48] You must have both a signal to tell the
[30:51] fat cell to get big, which is insulin.
[30:53] It is the There's no other signal that
[30:54] can do it. You can in a human just
[30:57] simply take away the insulin, like type
[30:59] 1 diabetes. It doesn't matter any other
[31:01] hormone in the body, it does not matter.
[31:03] They cannot get fat. They could Again,
[31:06] they can eat thousand They could eat
[31:09] 10,000 calories of chocolate cake. They
[31:11] cannot get fat. Not only can they not
[31:13] get fat, they can't hold on to their
[31:14] fat. Cuz if there's no insulin to tell
[31:17] the fat cell to hold on to it or get
[31:18] big, it has to shrink. It's breaking
[31:21] down its fat. So, the body goes into
[31:23] such a dramatic fat burning state in the
[31:26] absence of insulin that keeping fat
[31:28] becomes impossible. So, the insulin
[31:30] signal's necessary to tell the fat cell
[31:32] what to do.
[31:34] But, the fat cell will say, "Okay,
[31:35] insulin, you're high. You're telling me
[31:37] to grow, but what am I going to grow
[31:39] with?" That's where the calories come
[31:41] in. Now, the fat cell will say, "Hey,
[31:44] fats and glucose in the blood, insulin
[31:47] has told me to get big, and so I need to
[31:48] pull you in to help me grow. You're
[31:51] going to give me the bulk."
[31:53] And if you have one without the other,
[31:55] it is death.
[31:56] So, if I'm eating 2,000 calories and I
[31:59] have a different insulin sensitivity to
[32:02] you. Say we both eat 2,000 calories
[32:04] and I'm insulin resistant, doesn't that
[32:07] mean that I will
[32:09] You'll store more as fat.
[32:11] Oh, okay.
[32:11] Yeah. Yeah, so so your body now it would
[32:14] partly depend on There are people where
[32:17] you you if your if all of your fat cells
[32:19] had reached its maximum point, then
[32:20] you're done. You're not going to gain
[32:22] more fat. You're just going to become
[32:23] more and more and more insulin
[32:24] resistant.
[32:25] Okay, fine.
[32:26] So, you kind of start limiting yourself.
[32:27] But, there are studies in humans to show
[32:30] that if you give humans isocaloric diet
[32:33] meals, so the exact same number of
[32:35] calories,
[32:37] but they in the same amount of protein,
[32:39] but you differ those meals based on the
[32:41] amount of carbs to the amount of fat.
[32:44] So, let's say two meals, exact same
[32:46] calories, 2,000 calories, or that's in
[32:48] one meal, that's too high. 1,000
[32:49] calories in one meal.
[32:51] One version of this is the conventional
[32:54] way of eating, which is lower fat,
[32:56] higher carb.
[32:58] The other meal, same number of calories,
[33:01] but it's lower carb, higher fat.
[33:04] This lower carb, higher fat version will
[33:07] have a lower insulin response,
[33:11] and they they will store less fat from
[33:13] that meal. And their meta- And someone
[33:15] would say, "Well, where do the calories
[33:16] go?"
[33:17] You can't this it's the laws of
[33:19] thermodynamics. You can't destroy
[33:21] energy. The metabolic rate will go up.
[33:24] So, when insulin is low, if you have
[33:26] someone going a full day eating the same
[33:28] number of calories, but lower carb
[33:31] calories, their metabolic rate will be
[33:33] almost 300 calories higher in that day.
[33:35] And metabolic rate is the
[33:37] the total amount of energy that it just
[33:39] costs you and I to just live.
[33:40] Okay. So,
[33:41] It was going through the day. But that's
[33:42] But that's a significant amount. Like,
[33:44] if you and I were to go exercise and
[33:45] say, "Let's go burn 300 calories." We
[33:47] got to be on the stair stepper for an
[33:49] hour or something. So, it's 300
[33:51] calories, but at the same time,
[33:53] if your insulin is low,
[33:56] you're burning so much fat that you
[33:57] start making ketones. And I I don't
[33:59] intend to get onto that topic quite yet,
[34:01] but suffice it to say,
[34:03] every molecule of a ketone has a has a
[34:05] caloric load roughly similar to glucose.
[34:08] And one of the And And what the body
[34:11] when it starts making a lot of ketones,
[34:12] it starts eliminating the ketones. So,
[34:15] every time someone is breathing out
[34:17] ketones, they're literally breathing out
[34:19] calories.
[34:20] Or they're urinating, and they're
[34:21] urinating out ketones if they have
[34:23] higher ketones in their blood. They're
[34:25] urinating out calories, because ketones
[34:27] have energy.
[34:29] And so, this is the way that if insulin
[34:31] is low, it becomes impossible for the
[34:33] body to hold on to its energy. It is so
[34:36] determined to spend energy that it will
[34:38] both increase metabolic rate, and it
[34:40] will make the energy, the calories be
[34:42] wasted in the breath and in the urine,
[34:46] and and in the form of ketones because
[34:48] ketones have calories. Ketones are
[34:50] energy. Now we're just dumping them out
[34:52] into the universe.
[34:53] It's worth, before we talk about how to
[34:56] keep my
[34:57] insulin levels low so that I can benefit
[35:00] from all the health benefits we've
[35:01] talked about, it's probably also worth
[35:02] just spending a little bit of time
[35:03] trying to understand the evolutionary
[35:05] basis of insulin resistance.
[35:07] There are some theories that are very
[35:09] interesting that attempt to explain why
[35:12] is it that we became so fantastically
[35:14] different from let's say our closest
[35:16] animal relatives, other primates like
[35:18] chimpanzees or or apes.
[35:20] What was the difference that had us
[35:22] become so different than them? One of
[35:25] the leading theories is a is a theory
[35:27] called the expensive tissue hypothesis.
[35:31] And it actually does have something to
[35:32] do with ketones.
[35:34] In the expensive tissue hypothesis, as
[35:37] the theory goes,
[35:38] our earlier ancestors deviated in this
[35:42] kind of animal family line because we
[35:44] started eating more meat. We started
[35:47] eating food that was so nutritious, so
[35:50] nutrient dense, so loaded with good
[35:52] calories and all of the fats and
[35:54] proteins that we need, that it allowed
[35:57] two very distinct changes to occur in us
[36:00] compared to other primates. One, our
[36:03] intestines became significantly shorter.
[36:06] So if you compare the human digestive
[36:07] tract to any other
[36:09] primate animal, if if we are a primate,
[36:12] um then if you look at the intestines,
[36:14] they're fantastically different,
[36:16] particularly the large intestine or the
[36:18] colon. Because
[36:21] our ancestors, as the theory goes, began
[36:23] eating meat, we didn't need the the as
[36:25] much. Um and
[36:27] the colon is a place for food to
[36:29] ferment.
[36:30] And so, if you're eating a lot of plant
[36:32] matter, like other primates do, you need
[36:34] a much, much larger colon.
[36:37] So, we started eating food that was so
[36:38] nutrient-dense, our colon shrunk
[36:41] considerably. We didn't need to waste
[36:42] energy on a big, busy colon. At the same
[36:46] time, as we were eating food that was so
[36:48] nutrient-dense and so loaded with good
[36:50] fat,
[36:52] it allowed us to have more time to be
[36:54] curious and explore. And so, at the same
[36:56] time our intestines were shrinking,
[36:58] because we didn't need them to be so
[36:59] big, our brain was growing.
[37:02] And and it's because it had so much
[37:03] nutrition,
[37:05] including ketones. So, ketones are
[37:08] an extraordinary fuel for the brain. In
[37:10] fact, one of the reasons why a baby that
[37:13] is born premature
[37:15] will be more likely to have learning
[37:17] disorders later in life, is because
[37:19] premature baby didn't have time to get
[37:21] very fat.
[37:23] And fat baby is healthy baby. And fat
[37:27] baby gets into ketosis.
[37:29] Let's say you and I were to to fast
[37:31] straight for 2 days.
[37:33] If you took a 6-month-old baby, that
[37:35] baby would be in a deeper state of
[37:37] ketosis in 2 hours than you and I would
[37:40] be in 2 days.
[37:41] Because the baby is burning so much of
[37:43] its beautiful chubby fat, and the more
[37:45] the body burns fat, the more it makes
[37:47] ketones. And the tissue of the body that
[37:50] appears to benefit the most
[37:53] in response to ketones is the brain. The
[37:55] brain, the moment ketones hit the blood
[37:58] stream, the brain immediately starts
[37:59] taking in ketones for a fuel. Very
[38:02] often, I have students who have had a
[38:04] professor, perhaps with the best of
[38:06] intentions, but ignorant nonetheless,
[38:08] tell the student that the brain the main
[38:11] fuel for the brain is glucose, that the
[38:13] brain prefers glucose. And I show them
[38:15] just one or two papers to prove that
[38:17] wrong immediately.
[38:19] And it is reflected in in in this idea
[38:22] which
[38:23] if if to use some convenient UK units,
[38:26] if blood glucose is 5 millimolar, that's
[38:28] a concentration, a way of measuring an
[38:30] amount of of something.
[38:32] Blood glucose may be 5 millimolar or 80
[38:34] mg per deciliter for the American
[38:37] audience. Um that would be a normal
[38:39] glucose. And if you and I were to fast
[38:41] for 24 or so hours, we may get up to
[38:43] about 1 millimolar of of ketones. And
[38:47] yet even then, the brain has already
[38:49] switched to get the majority of its
[38:51] energy from the ketone.
[38:54] And so don't tell me that in this
[38:56] dynamic the brain prefers this one
[38:57] because this one's five times higher
[38:59] than this one. And even in that
[39:01] scenario, the brain is already getting
[39:03] more than half of its energy from the
[39:05] ketone. So all of this is my long-winded
[39:08] way of saying, when we look at the
[39:09] principles of evolution, one of the
[39:11] leading theories is this idea that we
[39:13] began eating essentially a meat-heavy
[39:15] diet that again is so nutritious that it
[39:18] allowed our brains to grow. Maybe one
[39:20] final point on this, although it is a
[39:22] bit of a barbed comment,
[39:24] people may find this somewhat amusing or
[39:26] disappointing or frustrating, the title
[39:29] of a book just published which is that
[39:31] vegetarians have smaller brains.
[39:33] This is seen in humans that the less a
[39:36] human eats meat,
[39:39] then the smaller the brain becomes. The
[39:41] brain is so dependent on the nutrient
[39:43] density that comes from animal-sourced
[39:45] foods that it will suffer
[39:47] um when it doesn't get them.
[39:50] Interesting. I mean, that's a
[39:51] controversial thing to say.
[39:52] It is, and you can cut it out.
[39:54] But it really is it's a real thing. And
[39:56] why does depression go up so much when
[39:58] people stop eating animal-sourced foods?
[40:00] It's because you are depriving the brain
[40:02] of what it needs.
[40:03] What is it exactly you're depriving the
[40:05] brain of in that situation?
[40:06] Yeah. Yeah. So at least among other
[40:08] things, at least it would be the the
[40:09] essential omega-3 fats.
[40:12] So there are three omega-3s, and you
[40:13] humans can only we can only get one from
[40:15] plants, but it's one that the humans
[40:17] don't use. We need the other two, and
[40:19] they only come from animal source foods.
[40:21] And you could supplement.
[40:22] Absolutely.
[40:23] Right. I mean, that's what I was
[40:24] Yeah, you can, but but that that So, the
[40:27] the solution in that regard is the vegan
[40:29] must be educated enough to know what
[40:30] they're deficient in, and then wealthy
[40:33] enough to afford the supplements to make
[40:34] up for it.
[40:36] So, is that the the only evolutionary
[40:39] sort of hypothesis towards why we
[40:41] develop this insulin resistance?
[40:43] Mm. Oh, yeah. In fact, it's funny that
[40:45] you bring the question up again because
[40:46] I realized I didn't quite answer it that
[40:48] way. So, insulin resistance, why would
[40:50] it exist at all? It would probably be a
[40:53] way for the body to know when it was
[40:55] needed to hold on to energy a little
[40:57] better.
[40:58] So, now Now, I say that now, and and
[41:01] someone would think, well, but you just
[41:03] why would I want to hold on to energy in
[41:05] a way where it's causing hypertension
[41:07] and Alzheimer's disease and increasing
[41:08] the risk of heart disease?
[41:10] Not all versions of insulin resistance
[41:13] are negative. So, there is um there is
[41:17] what all the insulin resistance that you
[41:19] and I have been talking about is
[41:20] pathological insulin resistance, or
[41:22] harmful insulin resistance. Insulin
[41:25] resistance that serves no good purpose,
[41:27] and it's making us sick.
[41:29] However, there is insulin resistance in
[41:32] human development, which is
[41:34] physiological, or helpful. It's supposed
[41:36] to happen. And that is the two P's of
[41:40] physiological insulin resistance,
[41:41] puberty
[41:43] and pregnancy. Because in both of those
[41:45] instances, as we outlined earlier, when
[41:47] the body's insulin resistant, insulin is
[41:49] high.
[41:50] That's not always bad, because insulin
[41:53] wants things to grow.
[41:55] It is like a fertilizer in the body.
[41:57] Now, sometimes it's misplaced, and
[41:59] results in problems, like increasing the
[42:01] risk of cancer, for example.
[42:03] But in other instances, if you have a
[42:04] young child who needs some explosive
[42:06] growth during puberty,
[42:08] well, then that's really helpful.
[42:10] Insulin's telling the body to store more
[42:12] energy, to build up tissues, including
[42:14] muscle and bone, but also including fat.
[42:17] So, in pregnancy, insulin's playing a
[42:19] role in growing the placenta.
[42:21] is.
[42:21] The breasts.
[42:22] Yes, so in the woman, after she's
[42:24] finished puberty, the only other time of
[42:26] growth she'll ever have will be
[42:27] pregnancy. And and so, those are the two
[42:30] instances where the body has become
[42:31] insulin resistant to take advantage of
[42:34] the heightened scenario where it can
[42:35] grow.
[42:36] Because the woman's body needs to more
[42:38] fat.
[42:38] goodness, yes. Yes, so her body not only
[42:40] needs to grow tissue mass, like the
[42:42] uterus has to get much bigger. She has
[42:44] to grow a placenta. She also needs to
[42:46] become a little insulin resistant to
[42:48] give a little more glucose to her baby,
[42:50] because she is after all now living for
[42:52] two people. And so, as she as her body
[42:55] becomes insulin resistant, it actually
[42:57] facilitates the growth of the baby a
[42:59] little more rapidly. But as you noted,
[43:01] it helps her store more fat, and
[43:03] progesterone is another hormone that
[43:05] even accelerates that process.
[43:08] But basically, it's the her way of her
[43:11] body's way of saying,
[43:12] "Hey, I am committing to growing another
[43:15] human, and it's going to be
[43:17] metabolically very demanding, and so I'm
[43:19] going to have as much extra fat or much
[43:22] as much extra energy as I can in order
[43:24] to ensure that if there's any sort of
[43:27] scarcity in food that happens during the
[43:29] course of the pregnancy, I'll have
[43:31] enough energy to get through it all. And
[43:33] then maybe I'll even have enough to
[43:35] continue to feed the baby with lactation
[43:38] after the baby's born."
[43:39] What is gestational diabetes?
[43:41] Yeah, it's a great question. Gestational
[43:43] diabetes is essentially type 2 diabetes
[43:46] of pregnancy. So, it's perfectly timed
[43:49] question because
[43:51] if you look at the average woman um who
[43:53] is very healthy, very insulin sensitive
[43:55] at the beginning of her pregnancy. So,
[43:57] glucose is normal and insulin is normal.
[44:01] Over the course of her pregnancy,
[44:03] she stays normal healthy pregnant woman,
[44:06] which is to say she has physiological
[44:08] insulin resistance. She doesn't get
[44:10] diagnosed with gestational diabetes
[44:12] though, which means her glucose is
[44:13] normal. But to keep her glucose normal
[44:16] because she is insulin resistant, but
[44:18] for a purpose to help her body grow, her
[44:20] insulin levels are high. And then the
[44:22] glucose is still in a normal range. And
[44:25] then in some women, especially if she
[44:28] has a family history of type 2 diabetes,
[44:30] the insulin resistance goes too far.
[44:33] Now, she has high insulin, like all
[44:35] pregnant women do, but she's not able to
[44:37] keep her glucose levels in check.
[44:40] So, if I'm eating loads and loads of
[44:42] sugar throughout pregnancy,
[44:43] That will compound the problem.
[44:45] Absolutely. So, then she will go from
[44:47] the normal insulin resistance of
[44:48] pregnancy into the insulin resistance of
[44:51] diabetes. So, it really is like type 2
[44:53] diabetes, but a microcosm of it, a mini
[44:56] version that was really instigated or
[44:59] initiated because of the pregnancy
[45:00] combined with a bit of a genetic
[45:02] predisposition combined with her eating
[45:04] the worst possible way.
[45:06] Does that then impact the future baby?
[45:08] Oh, for sure it does. Yeah. So, think
[45:10] about it's almost like the baby is
[45:12] develop literally developing in a
[45:14] hyperglycemic hyperinsulinemic
[45:17] environment. So, the baby's get the baby
[45:19] gets hardwired
[45:21] to want to continue to exist in a state
[45:23] of high insulin and high glucose after
[45:25] the baby is born. And so, yes, the
[45:27] offspring of mothers who have
[45:29] gestational diabetes are significantly
[45:32] more likely to gain weight and be
[45:34] chubbier or fatter than their
[45:36] counterparts and to later develop type 2
[45:38] diabetes. Yeah, a resounding yes.
[45:40] I read in your book that these infants
[45:41] have a 40%
[45:43] higher chance to be obese and have
[45:44] metabolic complications in their teenage
[45:46] years and beyond.
[45:47] Yes, I mean a significant thing and I I
[45:49] say that with all of the sympathy I can
[45:51] for the mother who may be struggling
[45:52] with this, but it is certainly a
[45:54] motivation for mom to just be mindful of
[45:58] what you're eating.
[46:00] One of the things that that I saw the
[46:01] other day on social media, which I
[46:03] wanted to ask you about, was this. I've
[46:05] got a picture of it here.
[46:07] Um
[46:08] it was someone online that posted this
[46:10] photo, and they said, well, this graph,
[46:14] and they said, we need to figure out
[46:15] what's going on here. Um this is the
[46:17] graph. I'll put it on screen for anybody
[46:19] that's watching, but also it'll be
[46:20] linked in the comments section below.
[46:22] Um it essentially shows that over the
[46:25] last, let's say, 20 years, there's been
[46:28] a really significant rise in cancer
[46:31] amongst women, but when we look at
[46:33] cancer amongst men, it's pretty flat.
[46:35] Mhm.
[46:35] Um and this is cancer incidence by age
[46:39] and gender up to 49 years old.
[46:42] Mhm.
[46:42] And I was wondering if you had any
[46:43] thoughts on why this is happening.
[46:45] Yeah. Yeah. Yeah, a few thoughts come to
[46:48] mind. Um whenever I see these kinds of
[46:50] reports, I always make sure I look
[46:52] firstly at the What are they actually
[46:53] measuring? So, just to set the stage,
[46:56] this is the number of women who are
[46:57] being diagnosed with cancer, so not
[46:59] dying from cancer, but it's going up.
[47:01] So, one one simple explanation, although
[47:04] perhaps the most disappointing, could be
[47:06] that more women are going in for testing
[47:09] younger, and so we're just seeing kind
[47:11] of an artifact of more women are just
[47:13] going in sooner, and they're detecting a
[47:15] problem that they wouldn't have
[47:16] otherwise detected, you know, for 10 or
[47:18] 20 years. And which is a good thing. You
[47:21] want to detect cancer as soon as
[47:22] possible. So, that's the boring answer,
[47:24] that it could be a reflection of just
[47:25] more women going in for ultrasounds or
[47:28] MRIs or mammary scans, whereas men don't
[47:32] ever get tested for anything,
[47:34] which is why we die more from
[47:35] everything, possibly. But to give a more
[47:38] exciting answer, this is very, very
[47:41] likely almost entirely driven by breast
[47:43] cancer. Um breast cancer is the main
[47:45] cancer for women um by far. And so, if I
[47:49] had to guess, I bet almost all of this
[47:51] increase in cancer incidence is because
[47:53] of breast cancer. Why might that be
[47:55] going up? I would suggest there's
[47:57] probably a couple instances. One, um
[48:00] although people might not appreciate
[48:02] this, is that one of the best ways for a
[48:04] woman to reduce her risk of breast
[48:05] cancer is actually having babies. It's
[48:07] very well known,
[48:09] um very well documented, that if a woman
[48:11] um has a fam- it has babies and
[48:13] breastfeeds, her risk of um breast
[48:15] cancer goes down.
[48:17] So, yeah, in fact, it's very meaningful.
[48:19] I actually don't know um the reasons for
[48:21] it. It could be the changes in estrogens
[48:23] during lactation phase.
[48:25] I've just I've just actually done a
[48:26] quick search here to I put a picture of
[48:29] that graph into AI and asked it the same
[48:31] question, and it said pretty much what
[48:32] you said. It said, "There's a rising
[48:34] breast cancer incidence according to
[48:35] Cancer Research UK." The other one that
[48:37] it came up with is obesity trends.
[48:39] Oh, yeah. I promise I was going to talk
[48:41] about that. I wouldn't leave that. Yeah.
[48:43] Sorry for interrupting there.
[48:44] No, no, no problem.
[48:45] Uh and then the other one was delayed
[48:46] childbearing.
[48:47] That's what I'm saying.
[48:48] Which is what you were saying.
[48:49] Yeah, so as child rates as childbirth
[48:51] rates are going down, it does increase
[48:53] the risk of breast cancer. Now, as I I'm
[48:55] a cell biologist, right? I like to
[48:57] understand the direct mechanism. And so,
[48:59] as much as I invoke the perhaps lower
[49:01] rates of childbirth among women, I don't
[49:03] know the mechanism, so I'm sort of loath
[49:05] to describe it. The mechanisms I'm very
[49:07] familiar with are the metabolic,
[49:09] um which is if you take a breast tissue
[49:13] that is tumor tissue and compare it to
[49:16] like if you take a breast tumor and
[49:18] compare it to the normal tissue right
[49:19] next to it, like that it would have
[49:21] shared its origins with, the cancer from
[49:24] the breast will have seven times more
[49:26] insulin receptors than the normal breast
[49:29] tissue. So, the idea of this tracking
[49:32] quite nicely with obesity rates going up
[49:34] over the past 20 years, I wouldn't say
[49:36] that it's the obesity per se, but I
[49:38] would say it's the entire metabolic
[49:40] milieu, which is the insulin resistance,
[49:43] that as much as the high insulin is
[49:44] promoting fat cells getting bigger, that
[49:47] high insulin is also accelerating the
[49:49] growth of the tumor cells. Because
[49:51] again, the main one of the main
[49:53] mutations in breast cancer is a
[49:55] sevenfold so a seven times increase in
[49:58] the number of insulin receptors. And
[50:00] insulin wants to tell things to grow. So
[50:02] it's no surprise that almost every tumor
[50:04] that's ever been measured for having
[50:06] insulin receptors will have a lot more.
[50:09] It's basically telling its neighboring
[50:11] cells, "Insulin's going to come by and
[50:13] it's going to tell us all to grow. I
[50:15] want to grow more than you." And that's
[50:17] what cancer is. Cancer is growth,
[50:18] unregulated growth. Insulin tells things
[50:21] to grow. So the connection between
[50:23] obesity with the rising incidence of
[50:25] breast cancer is very, very likely a
[50:29] consequence of the rising incidence of
[50:31] insulin resistance.
[50:32] As you guys know, Whoop is one of my
[50:34] show sponsors. It's also a company that
[50:36] I have invested in and it's one that you
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[50:44] And there is a bunch of reasons, but I
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[51:29] You know, one of the big subjects you
[51:30] touched on at the start was the was
[51:32] Alzheimer's and dementia.
[51:34] Yes.
[51:35] And I have heard several people on this
[51:36] podcast tell me that they think of
[51:38] Alzheimer's as type three diabetes.
[51:44] Worldwide, there is a new case of
[51:46] dementia every 3.2 seconds.
[51:49] Um it seems like I don't know if this is
[51:51] true, but is Alzheimer's and dementia on
[51:52] the rise?
[51:53] Oh, yes. Yeah, it is. In fact, it went
[51:55] from not being even on the radar to
[51:57] being a top 10 killer.
[51:59] Um now, it's interesting how people even
[52:01] die from Alzheimer's disease. It's a
[52:02] very kind of vague death.
[52:05] But yeah, Alzheimer's disease is one of
[52:06] the top 10 diseases now. Um certainly in
[52:08] the West.
[52:10] Um and and I would argue it's because it
[52:11] has a metabolic origin. Now, one of the
[52:13] interesting things about Alzheimer's
[52:15] disease is we have spent
[52:18] billions of dollars on Alzheimer's
[52:20] research trying to identify the the
[52:23] plaque. So so just to set the stage here
[52:26] so that people listening can appreciate
[52:28] this this paradigm shift that's occurred
[52:31] in Alzheimer's research. Originally, and
[52:34] even in many people still, people
[52:36] thought that Alzheimer's disease is the
[52:38] result of these plaques accumulating in
[52:40] the brain. These kind of little
[52:41] proteinaceous little
[52:44] thick things that are preventing neurons
[52:45] from sending the signals throughout the
[52:47] brain for the brain to think and and and
[52:49] have normal cognition.
[52:51] And and yet, there are those of us and I
[52:53] am proud to say I have long been one of
[52:55] them
[52:56] who has said that the plaque-based
[52:57] theory doesn't make sense. We have had
[53:00] drugs that have been available for human
[53:02] use for years that have effectively
[53:05] reduced plaques in the brain and yet did
[53:08] nothing to improve cognition. So that is
[53:10] an immediate challenge of the
[53:12] plaque-based theory of Alzheimer's. Even
[53:14] further,
[53:15] even beyond older than that evidence,
[53:18] when you would look
[53:20] postmortem or look at tissue donor,
[53:22] people who passed away, you would look
[53:24] at the brains of people who died with
[53:26] confirmed Alzheimer's disease at the
[53:28] time of death
[53:29] and look at the brain of someone who
[53:31] died without any evidence of any
[53:33] cognitive decline or any compromised
[53:35] thinking whatsoever. And you would be
[53:37] just as likely to find plaques in both
[53:39] brains.
[53:40] So the So whether the brain had
[53:42] Alzheimer's disease not, you would still
[53:43] see plaques in the brain. So the whole
[53:45] idea that plaques mattered has long been
[53:48] controversial. And just to put a fine
[53:50] point on it before transitioning to the
[53:51] metabolic origins,
[53:53] about two or three years ago,
[53:56] they found out that the very first
[53:59] published papers that implicated plaque
[54:02] as a cause of Alzheimer's disease were
[54:04] based on fabricated data.
[54:06] So the scientists who published those
[54:08] first reports that led to the entire
[54:10] theory that Alzheimer's disease is
[54:12] plaque-based
[54:13] were called out as fraudulent. And and
[54:15] indeed, all of it was fabricated. So the
[54:18] entire idea that Alzheimer And and we
[54:20] have spent billions of dollars on
[54:22] studies to try to
[54:23] how determine how do plaques cause cause
[54:26] Alzheimer's disease? Why when we reduce
[54:29] plaques, it doesn't appear to help the
[54:30] disease.
[54:32] Because the plaques had nothing to do
[54:33] with it. That's just something that some
[54:35] brains have. Some brains have more of
[54:37] these little specs than other brains,
[54:38] and they don't contribute to Alzheimer's
[54:40] disease at all.
[54:41] Now, what did
[54:44] can what kept rising to the top, and I
[54:46] would hope now is the dominant theory,
[54:48] is that people with Alzheimer's disease
[54:50] almost always have some detectable
[54:53] instance of insulin resistance, if not
[54:55] full-on diabetic type 2 diabetes. Now, I
[54:58] will say personally, I don't like the
[55:01] term type 3 diabetes because it makes it
[55:03] sound
[55:04] like it's a whole new version of
[55:06] diabetes.
[55:08] To say it more succinctly and
[55:09] accurately, it is simply insulin
[55:11] resistance of the brain. And the brain
[55:14] is a very hungry organ.
[55:16] It is in what I teach as as a tri a
[55:19] trinity of high metabolic rate organs.
[55:22] That there are three organs in the body
[55:24] whose metabolic rate is so high that it
[55:26] just really sets it apart from
[55:27] everything else. And the brain is one of
[55:29] them. The brain has a very high
[55:31] metabolic rate. So this is a very hungry
[55:34] organ that that a lot of energy all the
[55:36] time.
[55:37] But the brain is unique in that it
[55:39] primarily will only use two fuel
[55:41] sources, and I've mentioned them, namely
[55:42] glucose and ketones.
[55:45] But glucose in that section of the brain
[55:48] that gets compromised with Alzheimer's
[55:50] disease, the glucose can't just come
[55:52] straight in. It needs someone to open
[55:54] the door for it, and that is insulin, of
[55:57] course, just like we described with the
[55:59] muscle cell.
[56:00] Where in order for the glucose to go
[56:02] into the muscle, insulin had to come and
[56:04] knock on the door, if you will. And then
[56:06] the muscle, being a polite, responsive
[56:08] host, would open and allow the glucose
[56:09] to come in. The brain is similar.
[56:12] That in that section of the brain, it
[56:14] has doors that need insulin. It's locked
[56:17] until insulin comes and opens them. So,
[56:19] even though glucose levels may be high
[56:21] in the blood,
[56:22] like in type 2 diabetes, you would
[56:24] think, "Well, the brain can just get all
[56:26] the glucose it wants." And yet it cannot
[56:28] because it has insulin regulating the
[56:31] entrance of the glucose. And if the
[56:33] brain is insulin resistant, there's not
[56:35] enough glucose coming in. And thus the
[56:37] brain is forced to rely on the only
[56:39] other fuel that it can rely on, namely
[56:42] ketones.
[56:43] But the same person who's eating all the
[56:45] time to keep their blood glucose high
[56:47] all the time has so much insulin in
[56:49] their blood that they're never making
[56:51] enough ketones to fill the gap. You
[56:53] know,
[56:54] mind the gap, and the brain has an
[56:56] energy gap now. And where where the
[56:59] brain needs, you know, an amount of
[57:01] energy, I'm kind of acting it out for
[57:03] those that are watching, but the brain
[57:04] has a certain energy demand that it
[57:05] needs. And if there's a lot of glucose
[57:08] in a healthy insulin-sensitive person,
[57:10] glucose will fill all of that need. But
[57:12] as the brain becomes progressively
[57:14] insulin-resistant, it cannot get all of
[57:17] its energy from glucose. And thus
[57:19] there's an energetic gap.
[57:21] And in the absence of ketones, there's
[57:23] nothing to fill that gap, and the brain
[57:25] says, "Well, I don't have enough energy
[57:27] to keep functioning as well as I did
[57:28] before, so I have to reduce my function,
[57:31] which manifests as a reduction in the
[57:33] ability to think and process. In other
[57:35] words, cognition goes down. But, what's
[57:38] so interesting
[57:39] is I just got finished describing a
[57:41] scenario that scientists refer to as
[57:43] brain glucose hypometabolism,
[57:47] or a reduction in the amount of glucose
[57:50] the brain is using. There are scientists
[57:52] that measured this. We don't in my lab
[57:54] because we don't do these kinds of
[57:55] techniques, but you can actually infuse
[57:58] people with a glucose that you can take
[57:59] pictures of and see how much the brain
[58:02] is taking it in and metabolizing it. In
[58:04] Alzheimer's disease, the brain is not
[58:06] getting as much glucose, so they call
[58:08] that a hypo, or a reduction in
[58:10] metabolism of glucose.
[58:12] And as much as you and I are describing
[58:14] that scenario as relevant for
[58:15] Alzheimer's disease, you can essentially
[58:17] open up the book of neurological
[58:19] disorders and see the same thing.
[58:21] Depression
[58:22] has a brain glucose hypometabolism to
[58:25] it. Migraines have a brain glucose
[58:27] hypometabolism.
[58:29] Epilepsy um and Parkinson's so all of
[58:32] these disorders of the brain, of the
[58:34] central nervous system, the one thing
[58:36] they all have in common is the brain
[58:38] isn't getting enough energy from
[58:40] glucose.
[58:42] And another way of saying that is the
[58:43] one thing all of those seemingly
[58:45] unrelated brain problems have in common
[58:47] is that they all have some degree of
[58:48] insulin resistance. But, then it's no
[58:50] surprise that they all benefit
[58:53] when ketones can swoop in to save the
[58:55] day.
[58:56] Um but that only can happen if the
[58:59] person is giving their body a break from
[59:01] the insulin long enough to actually
[59:03] start making ketones.
[59:06] Really, really interesting on this point
[59:07] about Alzheimer's because I don't think
[59:09] people have spent enough time talking
[59:10] about the link between insulin
[59:12] resistance and Alzheimer's. Um
[59:15] and
[59:16] one of the things I was I was looking at
[59:18] there was how many people with
[59:20] Alzheimer's have meet the criteria for
[59:22] insulin resistance.
[59:24] And some studies have it at 40%. There's
[59:26] a study I found here that has it at 70
[59:28] to 80%.
[59:30] Um which I wanted to cite. Um
[59:33] Exact percentages vary, but one example
[59:35] is a study in the Journal of Neurology
[59:38] in 2011 that found insulin resistance at
[59:40] approximately 40% of individuals with
[59:42] Alzheimer's.
[59:43] Um but another study
[59:44] uh in Alzheimer's patients sometimes
[59:46] found it to be as high as 70 or 80%. For
[59:48] instance, research by Dr. Suzanne de la
[59:51] Monte
[59:52] Mhm.
[59:53] at Brown University has drawn attention
[59:54] to the concept of type 3 diabetes.
[59:58] Yeah, again, I don't love the term, but
[59:59] I appreciate the use of it, which is it
[60:02] does suggest a metabolic origin. But
[60:04] even you look at those ranges, Stephen,
[60:05] you'd say, "Well, one was 40, one was
[60:07] 80. Boy, what a difference." I suspect a
[60:09] lot of that is just how did they measure
[60:11] insulin resistance? If they were looking
[60:13] at the glucose like so many do, you're
[60:15] just going to miss a lot of people.
[60:17] Yeah, it's quite hard to
[60:19] I think there's different criteria,
[60:20] right, for how one defines someone as
[60:22] insulin resistant.
[60:23] Well, there Yeah, and that's just that's
[60:24] right. That's because there's not enough
[60:26] training, which is at the beginning of
[60:27] the conversation you asked my mission.
[60:29] One of my missions is to help people
[60:31] learn what to look for.
[60:32] What do they need to be looking for?
[60:34] Yeah, they need to be looking at
[60:35] insulin. So
[60:36] Is that easy to measure?
[60:38] Well, it is technically easy to measure.
[60:40] It's just that we have we don't have
[60:41] enough systems in place to allow to
[60:43] enable it. Like again,
[60:45] if if someone listening in the UK were
[60:48] to go to their GP and say, "Can you
[60:50] measure my insulin?"
[60:51] In many instances, they literally can't
[60:53] get it done. The system just isn't in
[60:55] place to take it to the lab and and
[60:57] measure it. Now, some do. I know some
[60:59] physicians in the UK who do so, and they
[61:01] have developed their own way of getting
[61:03] it done, and they're incredible
[61:05] advocates of this whole idea. But it is
[61:07] harder in the UK and Canada um where the
[61:11] system is such that they have said, out
[61:13] of ignorance, but perhaps well-placed or
[61:15] or well-intentioned, they will say,
[61:17] "Well, insulin isn't a marker that
[61:19] matters."
[61:20] It is. And if you're measuring insulin
[61:22] resistance, just to put things back to
[61:23] where we had talked about it earlier,
[61:26] many people with insulin resistance have
[61:27] normal blood glucose levels. It's the
[61:30] insulin that's high. And so, I would say
[61:32] if a person can get their insulin
[61:34] measured, get it measured. In US units,
[61:37] if it is anything above about 10 micro
[61:39] units per mil, that's a warning. In UK
[61:42] units, if it's anything above about 40
[61:44] picomoles, that's a warning. Insulin is
[61:47] high, you could have insulin resistance.
[61:50] And you could be skinny
[61:52] Oh, yes.
[61:52] and have insulin resistance.
[61:53] Yes, that's especially depending on the
[61:55] ethnicity. Like if someone listening to
[61:57] this is East Asian and they say, "Well,
[61:59] I'm quite thin. I don't have insulin
[62:01] resistance." You very well could. Um it
[62:04] it depends. Even in in young women, a a
[62:06] group out of northern Canada,
[62:09] which is of course pretty far north,
[62:11] they found that even in young healthy
[62:13] weight women with PCOS,
[62:15] they if they compared them to their
[62:17] identically matched other women without
[62:19] PCOS, they were more insulin resistant
[62:22] in the other group. So so anyway, that's
[62:24] my
[62:25] way of saying even if you look at
[62:27] yourself and think, "Well, I'm kind of
[62:28] lean. I'm not insulin resistant." You
[62:30] very well could be.
[62:31] Okay, so I've got a friend who's a a
[62:33] woman
[62:34] Mhm.
[62:34] who has PCOS.
[62:36] Yeah.
[62:36] And one of the things that she often
[62:38] says to me is that
[62:39] she gains weight easily. Is this true?
[62:42] Oh, for sure. And in fact, I wouldn't be
[62:44] surprised if she does because the fact
[62:46] that she has PCOS is not absolute
[62:49] evidence, but very likely evidence that
[62:52] she has insulin resistance, which would
[62:54] mean at any given moment her insulin is
[62:57] at the risk of being a little higher
[62:58] than her non-insulin resistant
[63:00] counterparts.
[63:01] So if she goes and gets the test done,
[63:03] I bet her insulin would be high.
[63:05] Um and so, all that would mean is which
[63:08] is good. I mean, knowledge is power. And
[63:10] my hope would be that as someone goes
[63:12] and gets their insulin measured, and
[63:13] there are a handful of other tests they
[63:15] could also look at, but that's the most
[63:17] succinct. Then it would be all the more
[63:19] impetus or encouragement to say, "Okay,
[63:22] I heard I listened to Steven and Ben. I
[63:24] really do need to start making some
[63:25] changes." And even in PCOS,
[63:28] there are reports that document the
[63:31] absolute reversal of the disease with
[63:33] nothing more than just dietary changes.
[63:36] I was looking also at second here cuz we
[63:37] mentioned ethnicity a few times and it
[63:39] says the research I was looking at says
[63:40] that East Asians have East Asians have
[63:43] fewer fat cells and they're more
[63:44] resistant to obesity-related metabolic
[63:47] issues.
[63:48] Well, that's second part of that
[63:50] statement is not true. They're more
[63:52] resistant to obesity,
[63:54] but they are like if it's an interesting
[63:56] dichotomy cuz
[63:57] Right. Okay, I got you.
[63:58] Yeah, so they're more you you like to
[63:59] find a Japanese man who's as fat as the
[64:02] average American, boy, you're going to
[64:03] have to look. It's hard. It's hard, but
[64:05] to find a Japanese man who has is just
[64:08] as much likely to get diabetes, type 2
[64:10] diabetes, very easy.
[64:12] Africans have
[64:14] more fat cells typically?
[64:15] Yeah, so so on that ethnicity, if now
[64:18] there's a lot of kind of wiggle room
[64:20] here, but on one end we'd have
[64:21] Caucasians, blacks would be right
[64:24] nearby. African ethnicities would be
[64:25] quite close
[64:27] um to the to the kind of northern
[64:29] European ethnicity. And then we would
[64:30] move through and and I don't mean to
[64:32] miss anyone here, but on the other end
[64:34] it would be East Asian and then
[64:36] sprinkled through that would be um
[64:39] uh
[64:40] Latino.
[64:41] Latino would be somewhere in the middle
[64:43] and Hispanic. And then other Southeast
[64:45] Asian and then East Asian kind of on the
[64:47] worst end or the least sensitive or the
[64:50] most sensitive to their fat. The most
[64:52] sensitive to their fat. This actually is
[64:54] a concept that has been presented called
[64:56] the personal fat threshold, which is
[64:59] this really interesting idea born from a
[65:01] group in Australia suggesting that
[65:03] across every individual body, which of
[65:06] course is heavily influenced by both
[65:07] ethnicity and sex, like we mentioned
[65:10] earlier, a body is going to have a rate
[65:12] at which it can store fat in a healthy
[65:15] way. And then once that threshold is
[65:17] met, any further pressure to store fat
[65:20] will start creating insulin resistance.
[65:22] And that threshold is essentially
[65:24] how big, how many fat cells do you have,
[65:26] and how much room do they have. So if
[65:28] you have more fat cells, you have a
[65:30] higher fat threshold. You can get fatter
[65:32] before it starts to hurt you.
[65:34] Does your fat distribution also matter
[65:36] here? Because
[65:37] does.
[65:37] different races, this research is
[65:40] telling me
[65:41] have different fat distribution. It's
[65:43] saying that Africans have better fat
[65:45] distribution, lower visceral fat, and
[65:48] less metabolic risk because of that.
[65:50] Yeah, yeah, yeah.
[65:51] Caucasians moderate fat cell quantity,
[65:53] more prone to subcutaneous fat
[65:55] accumulation, which
[65:55] Subcutaneous.
[65:56] Which is that's the fat around the
[65:57] organs.
[65:58] Yeah, so Caucasians and so so let's say
[65:59] northern European African, both store
[66:02] more of their fat subcutaneously, which
[66:04] is the fat just beneath the skin, or the
[66:06] fat that you can pinch and jiggle.
[66:08] That has an ability to expand more
[66:10] because there's nothing really to limit
[66:11] it. Um however, the other place for
[66:14] people to store fat is their visceral
[66:16] adipose, which is the fat that is tucked
[66:18] within the abdominal cavity, so tucked
[66:21] around the organs. It's sort of
[66:22] surrounding the kidneys and the
[66:24] intestines and the liver. That is an
[66:26] unhealthy place to gain fat, but an East
[66:28] Asian, all things equal, is putting much
[66:31] more fat there than they are
[66:33] subcutaneously. The advantage of
[66:35] subcutaneous fat is
[66:37] Which is the fat on the outside.
[66:38] Yeah, yeah, so the the fat beneath the
[66:40] skin. Yeah, the yeah, the loose belly
[66:42] fat, the fat that can pinch and jiggle.
[66:44] That fat has a greater ability to make
[66:46] new fat cells. So as much as earlier you
[66:48] and I said fat cells remain static, for
[66:50] the most part they do, there's a little
[66:52] bit of wiggle room, where it can go up.
[66:54] And that's purely subcutaneous.
[66:57] And Hispanics have higher fat cell
[66:58] quantity, more visceral fat,
[67:00] Yes.
[67:01] and increased risk of obesity related
[67:03] conditions.
[67:03] Yes, and so the problem with visceral
[67:04] fat is this is such a finite space.
[67:07] There's so little room within the core
[67:09] of your body that if we allowed those
[67:11] fats to multiply, it could theoretically
[67:14] start physically compressing on tissues.
[67:16] Right.
[67:17] And so those fat cells only grow through
[67:20] hypertrophy, which is the thing we
[67:22] talked about earlier with slow insulin
[67:24] resistance. Subcutaneous fat cells are
[67:26] more abundant but smaller. Visceral fat
[67:29] cells are fewer but much larger. And so
[67:32] any ethnicity including Hispanic or
[67:35] Asian that promotes relatively more fat
[67:37] storage in the visceral space is going
[67:40] to suffer from the consequences of that
[67:41] fat much sooner. And again, it still
[67:43] comes back to size. The bigger the fat
[67:46] cell, the sicker the fat cell.
[67:48] According to Alzheimer's Disease
[67:49] International, the total number of
[67:50] people living with dementia globally is
[67:52] expected to reach 139 million by 2050,
[67:55] which is up from around 55 million in
[67:57] 2020. Which I imagine is in part
[68:01] related to people living a bit longer
[68:03] than they once did as well.
[68:05] Although although over the past few
[68:06] years, life expectancy actually turned
[68:07] down for the first time in the history
[68:09] of modern
[68:11] world. So who knows if it will continue
[68:13] to go up, but yeah. It could be people
[68:15] are living longer. I mean one of the
[68:17] effects of modern medicine is that
[68:19] people live longer with disease.
[68:22] Um Alzheimer's included, but it's
[68:23] absolutely a consequence further of our
[68:26] overall metabolic milieu that we put
[68:28] ourselves in a position where we are
[68:30] making our brains insulin resistant and
[68:33] thus they're going hungrier and
[68:34] hungrier.
[68:35] There's a study you talk about
[68:38] which you've cited before that shows
[68:39] that if you move visceral fat from an
[68:43] obese animal to a lean animal, this
[68:45] immediately caused insulin resistance.
[68:48] Yeah. In the animal that received it.
[68:50] Okay.
[68:51] Yeah, so just to be clear, if if we took
[68:54] what they did in the study just to
[68:55] reflect why or that different depots of
[68:58] fat are harmful. And so the the human
[69:00] body has two distinct fat depots, and
[69:01] you and I described them subcutaneous,
[69:04] which is the fat beneath the skin, or
[69:05] visceral, which is the fat tucked within
[69:07] the organs of the abdominal space.
[69:10] And if you move subcutaneous fat,
[69:14] Which is like the belly fat?
[69:15] The belly fat, and and from one animal
[69:17] to another, you couldn't do this in
[69:18] humans, if you move belly fat, if you
[69:20] will, or subcutaneous fat from one
[69:22] animal to the other, the animal's very
[69:24] healthy. It's no problem. Subcutaneous
[69:26] fat is inert. It really is just sort of
[69:29] hanging out there and minding its own
[69:30] business. But, in that same study, if
[69:32] you move the visceral adipose over, now
[69:35] all of a sudden that animal that got
[69:37] that extra dose of visceral fat is going
[69:39] to become sicker. It's going to become
[69:41] more insulin resistant and diabetic
[69:43] because you've increased its visceral
[69:45] fat the amount of fat that it has in
[69:47] that space.
[69:48] The body wants to limit the amount of
[69:50] fat that it has there because if the
[69:52] fat, again, if the fat grows too much,
[69:55] you can physically start compressing and
[69:57] squishing organs that you need to be
[70:00] functioning, like the kidneys and the
[70:01] intestines.
[70:02] Have you seen Bryan Johnson?
[70:04] I have. I don't know him personally, but
[70:06] You've seen the documentaries and stuff
[70:07] made about him and the the work that
[70:09] he's doing. What do you make of what
[70:10] he's doing to extend his age? Cuz, you
[70:12] know, one of the subjects that I think's
[70:13] linked to this is the idea of longevity
[70:16] and aging, and he's become a bit of a
[70:18] poster child for the subject of
[70:19] longevity.
[70:20] Right, right. Well, I want to address
[70:22] this cuz this is a real person, so I
[70:23] want to address it very politely and
[70:25] diplomatically. I think that I want to
[70:28] distinguish the difference between
[70:30] longevity research and science, which is
[70:32] a very real, living, breathing field,
[70:34] and I'm proud to know individuals who
[70:36] are longevity scientists, and
[70:38] distinguish them from
[70:40] um longevity
[70:42] you said poster child, so the the gurus
[70:44] of longevity, and that's not the same
[70:46] thing. So, what I say, I don't mean to
[70:48] it to be an indictment of longevity
[70:50] research, but I don't mind if people
[70:52] hear a bit of an indictment in my voice
[70:55] of the modern longevity guru approach.
[70:59] So, these individuals, and he is
[71:00] certainly the most well-known, they do
[71:03] have the advantage of never really
[71:06] being able to be proven wrong. You know,
[71:08] so there's an inherent problem here.
[71:10] But, I will say that the the application
[71:13] of
[71:14] being a longevity
[71:16] expert or not a scientist, but a guru,
[71:19] and I don't mean for that to be
[71:20] negative, but it does have a bit of a
[71:22] negative sound to it, is that you have
[71:24] to rely on
[71:26] what I would call weak evidence. Now,
[71:28] what do I mean by that?
[71:30] Uh so, all of the approaches to
[71:32] longevity nowadays rely on either
[71:34] correlational studies
[71:36] or
[71:37] basic research or animals and insect
[71:39] studies.
[71:40] And then extrapolating that results or
[71:42] assuming those same results will apply
[71:44] to the human. So, let me briefly just
[71:45] mention my concerns with correlational
[71:47] research.
[71:48] So, the longevity guru will say,
[71:51] "Correlational evidence suggests that
[71:53] people who eat meat
[71:55] um die more."
[71:57] Well, a correlational study is, by my
[72:00] estimation, some of the weakest evidence
[72:03] that you can ever generate. A
[72:04] correlational study would just have
[72:06] someone come to your home and say,
[72:07] "Steven, can you please answer this
[72:08] survey about what you eat?"
[72:11] You answer the survey. You may lie. You
[72:13] may not remember.
[72:14] You may have things that you don't even
[72:16] think about including, like, for
[72:18] example, that you're part of a very
[72:20] um well-put-together religious
[72:23] organization. And I actually used that
[72:24] example very deliberately because people
[72:27] who are known to be
[72:28] part of good tight social circles, like
[72:30] a formal religious group, always live
[72:32] longer than people who don't. Maybe
[72:34] you're really lonely. Loneliness is a
[72:37] greater contributor to death than
[72:39] cigarette smoking, and it's not even
[72:40] close. So, there could be things on that
[72:42] survey that you just cannot capture. And
[72:45] yet, we end up making a conclusion. And
[72:48] so, all of that correlational evidence
[72:50] is deeply flawed research. And yet that
[72:53] becomes the basis for the longevity guru
[72:55] to determine diet.
[72:57] So, if I'm trying to extend my
[72:59] longevity,
[73:00] Yeah.
[73:01] trying to live longer,
[73:02] then exactly what should I be thinking
[73:04] about?
[73:05] So, my view on longevity is a metabolic
[73:07] view, no surprise. I'm a metabolic
[73:09] scientist and I don't mind someone sort
[73:11] of smirking at me declaring that or
[73:13] admitting it. But, I'm somewhat
[73:15] justified.
[73:17] Just by way of setting the stage, the
[73:19] earliest the birth of the modern
[73:22] longevity research
[73:24] uh at least if it didn't start, it was
[73:26] heavily influenced by the work of a
[73:27] woman named Cynthia Cynthia Kenyon.
[73:30] K E N Y O N
[73:32] Cynthia Kenyon was one of the kind of
[73:35] she really did, in my mind, kind of give
[73:37] give birth to the modern longevity
[73:39] focus.
[73:40] What her lab found using an insect
[73:43] model,
[73:44] and this is again a problem with the
[73:45] longevity gurus is that they rely on
[73:47] insect data and for example, but it was
[73:50] compelling what she found. I think it
[73:51] was worms. She found in worms
[73:55] that if they restricted the glucose that
[73:57] the worms were eating,
[73:59] they would live 50% longer or some some
[74:01] fantastic increase in the how long the
[74:04] animals lived. That kind of gave birth
[74:06] to the idea of fasting being beneficial,
[74:09] but it also allowed her lab to start
[74:11] playing around with some of the genes of
[74:13] these little insects. And when they
[74:15] started knocking down or under
[74:17] expressing some of the genes involved in
[74:20] insulin,
[74:22] they didn't have to restrict the food,
[74:24] the animals just lived longer.
[74:26] And so, that touches on this metabolic
[74:29] aspect and everyone nowadays is really
[74:31] interested in autophagy.
[74:33] Autophagy is a term for a cell
[74:36] essentially cleaning itself out.
[74:38] Which is typically associated with long
[74:39] fasting.
[74:40] Yeah, that's Yeah, yeah. In fact, yes.
[74:42] So, that is partly why fasting has been
[74:44] so embraced within the uh longevity
[74:46] community. it's because if you can
[74:49] promote longevity or autophagy rather,
[74:51] if you can promote autophagy, the cell
[74:54] keeping itself cleaned out, that is
[74:56] thought to be a key contributor to
[74:58] longevity. So, autophagy equating to
[75:01] longevity. I don't disagree with that. I
[75:03] think that probably is a very valid
[75:05] view.
[75:06] Then, the question comes, well, how can
[75:09] I control autophagy?
[75:11] Well, there is a humble hormone that
[75:13] comes from the pancreas that has a very
[75:15] powerful effect on autophagy called
[75:17] insulin. So, as much as people are
[75:20] fasting, what's the value of fasting in
[75:22] reducing autophagy? It's because insulin
[75:24] comes down. Now, what becomes
[75:26] interesting is what happens if you were
[75:28] to put someone allow them to eat
[75:30] calories, but the calories are such that
[75:32] their insulin is staying low
[75:35] and they're making ketones. In other
[75:36] words, a ketogenic diet.
[75:38] You also enable autophagy. There was a
[75:41] very well-done animal study finding that
[75:44] they didn't have to restrict calories
[75:46] and fast the animals. They could let the
[75:48] animals eat as much as they wanted, but
[75:50] it was a ketogenic diet. They lived
[75:53] significantly longer than their other
[75:55] littermates that were eating the normal
[75:57] high-carb chow, similar to what humans
[75:59] eat nowadays.
[76:01] And so, autophagy probably does matter
[76:03] for longevity.
[76:05] All the more reason to keep your insulin
[76:07] in check because insulin is a powerful
[76:09] inhibitor of autophagy. So, as much as
[76:12] we have longevity gurus who are taking
[76:14] thousands of dollars worth of
[76:16] supplements,
[76:17] I can't help but look at that and think,
[76:19] just control your insulin.
[76:21] That within every cell, there's this
[76:23] battle. There's a yin-yang of growth and
[76:25] death or building and breaking to say it
[76:27] a little more politely. In fact, that is
[76:30] metabolism. The very word metabolism
[76:33] encompasses anabolism,
[76:36] which is anabolic or building up, and
[76:38] catabolism or catabolic, which is
[76:40] breaking down.
[76:41] The key to a healthy growing living cell
[76:45] is this nice ongoing balance of build
[76:47] and break, build and break. You have to
[76:50] build something up and then modestly
[76:51] break it down. And then you build
[76:53] somethings up again. And autophagy is a
[76:55] very important part of that breaking
[76:57] cycle within the cell that hey, it's
[76:59] time to get rid of some old parts and
[77:01] now we'll rebuild some of that again.
[77:03] Now we're going to break down these
[77:04] parts and rebuild it. Insulin is the key
[77:07] to that process. If insulin stays high
[77:10] for too long, you never allow the
[77:12] catabolic or the breakdown. This is one
[77:15] reason why insulin is so facilitative to
[77:17] cancer. Insulin wants things to grow.
[77:19] Cancer is a disease of growth. We don't
[77:22] ever let the cancer start to break down.
[77:24] Insulin won't let it in part.
[77:26] You even repeatedly talked about
[77:28] ketosis.
[77:29] I have.
[77:30] Ketones. We'll eventually get there.
[77:31] We're kind of teasing the audience a
[77:32] little bit.
[77:33] Yeah, we are. Yeah. But rightly so. I
[77:34] mean, ketones are a very vilified
[77:37] misunderstood part of the body. And and
[77:38] to my great delight, um it's getting
[77:41] it's getting a sort of new appreciation.
[77:43] Well, I'm currently on the keto diet as
[77:45] well. So, I am incredibly interested to
[77:47] understand A, like what's going on in my
[77:49] body, but B, I I'm quite compelled by
[77:52] both the pros and cons of doing it. And
[77:54] I want to talk about the cons and the
[77:55] pros.
[77:55] Mhm.
[77:56] Um because they both exist. One thing
[77:58] you say in your book, Why We Get Sick,
[78:00] is that the longest living humans are
[78:03] also the most insulin sensitive.
[78:05] Yeah.
[78:05] So, you're telling me that the longest
[78:07] living humans are the ones that are able
[78:09] to stave off that
[78:10] insulin resistance.
[78:11] Yes. Yes, so there are
[78:12] keep their insulin levels low.
[78:14] That's right. Yeah, in fact, most of the
[78:16] longevity research
[78:17] a sort of a final point on this, um is
[78:19] that when you look at these studies that
[78:21] look back in time and say, "Okay, what
[78:24] is it about these people? What variables
[78:27] tend to go along with the longest lived
[78:29] humans?" One of them is that their
[78:31] insulin sensitive and their blood
[78:32] glucose levels are In fact, a very well
[78:34] done study just last year out of Sweden.
[78:37] I think it was just 1 year ago.
[78:39] They looked at all and Sweden is
[78:41] meticulous in its in its record keeping,
[78:43] which is an advantage. And and a
[78:46] fairly homogeneous society, so it kind
[78:48] of eliminates some confounding
[78:49] variables.
[78:51] But they attempted to document what were
[78:53] the what were the variables that were
[78:54] just the most consistent theme of people
[78:57] who lived very long. One of them was
[78:59] good glucose control.
[79:01] And this next one is very controversial
[79:02] because they found that they also the
[79:04] longest lived people had high
[79:05] cholesterol levels.
[79:07] And isn't that funny? It is one of the
[79:09] most consistent themes of longevity
[79:11] research that the longest lived people
[79:13] have higher cholesterol.
[79:15] And yet we live in a world that hates
[79:17] cholesterol and the moment cholesterol
[79:19] goes up we put them on a cholesterol
[79:20] lowering medication.
[79:22] We could be doing the perfectly wrong
[79:24] thing to help these people live longer.
[79:26] So, that was and and then low uric acid
[79:28] and there's a handful of other little
[79:30] variables that fit into this.
[79:31] So, they they found that some of the
[79:32] longest living humans had high
[79:34] cholesterol levels.
[79:35] That's right. That's what the Sweden
[79:36] study found for example. The paper just
[79:38] published a year or so ago. What were
[79:40] some of the most consistent themes? They
[79:41] had good glucose control and high
[79:44] cholesterol.
[79:45] I'm a great defender of of cholesterol.
[79:48] It is a molecule of life.
[79:53] And and so many so much depends on it.
[79:55] Mitochondria for example. Mitochondria
[79:57] have to have a cholesterol molecule in
[79:59] them in order to work. Like the very
[80:01] powerhouse of the cell. And the more you
[80:03] lower cholesterol through say drug
[80:05] interventions, the more you compromise
[80:07] the mitochondria.
[80:09] Um the sex hormones. All sex hormones
[80:12] are built on cholesterol. It's no
[80:14] surprise if someone takes a cholesterol
[80:16] lowering medication their sex hormones
[80:18] go down. This is why some men experience
[80:20] such terrible loss of libido because
[80:22] he's becoming low testosterone because
[80:24] of the war on cholesterol.
[80:26] But there's good and bad cholesterol,
[80:27] right?
[80:27] Well, that's as the story goes, yes. And
[80:30] yet I think that's overly simplified.
[80:32] Where people will say LDL cholesterol is
[80:34] the bad cholesterol.
[80:37] And yet, that gets included in these
[80:39] studies of longevity. So, I think the
[80:41] good and bad aspect of it is not
[80:43] entirely fair or accurate. We need LDL.
[80:46] And LDL is just as much a component of
[80:48] the immune system.
[80:49] LDL actually helps the body fight
[80:51] infections. So, it's also an unsung hero
[80:53] of immunity.
[80:55] There was research suggesting that in
[80:56] very old age, high cholesterol levels do
[80:58] not always correlate with higher
[81:00] mortality. And in some studies may even
[81:02] be linked to longer life.
[81:05] Exactly.
[81:06] Which is bizarre.
[81:07] Yeah, well, you say that and yet maybe
[81:10] our anti-cholesterol view is the bizarre
[81:12] one.
[81:12] Yeah.
[81:12] And so, as a cynic who's very familiar
[81:15] with biomedical research, I sometimes
[81:16] will look at clinical markers and say,
[81:18] "Why are we so obsessed with glucose?
[81:21] Why not insulin? Why are we so obsessed
[81:23] with cholesterol? Why not triglycerides,
[81:26] which is another lipid that can be
[81:27] measured that is far more predictive of
[81:29] who's going to have a heart attack or
[81:31] not?"
[81:32] And I think it's because we have chosen
[81:35] markers in modern medicine that we have
[81:37] well-designed drugs.
[81:40] So, it's a really, really good way to
[81:41] sell a lot of drugs. So, there's no drug
[81:44] that's going to address insulin. So,
[81:45] let's not measure it. But, there are
[81:47] lots of drugs that will lower glucose.
[81:49] So, let's measure glucose because then
[81:51] we can diagnose the problem and then we
[81:53] can give them a drug and make a lot of
[81:55] money. That's a cynical view, but I
[81:56] don't think it's unjustified. Similarly
[81:58] with cholesterol.
[82:00] Why look at LDL when triglycerides,
[82:02] another lipid marker, are a much better
[82:05] indicator? It's because we don't have a
[82:07] drug that effectively lowers
[82:08] triglycerides. You can with diet, but we
[82:11] do have drugs that very effectively
[82:12] lower LDL.
[82:15] One thing that really surprised me when
[82:16] I was reading your work is
[82:18] there was a study done
[82:21] in Bulgaria which proved that smoking
[82:23] causes insulin resistance in humans by
[82:26] having seven healthy non-smokers smoke
[82:29] four cigarettes over an hour for 3 days.
[82:32] What did they find in that study?
[82:34] Yeah, so they found that if you took
[82:35] healthy non-smoking people and had them
[82:36] start smoking, they became insulin
[82:38] resistant. I believe I invoked that
[82:40] study in the section where I was talking
[82:42] about inflammation.
[82:44] Um where when you cigarette smoke that
[82:46] elicits there's a lot of junk coming in
[82:49] and there's a powerful inflammatory
[82:50] response and that contributes to insulin
[82:52] resistance.
[82:53] Is this vaping as well?
[82:54] Oh, so that is a very good question. I
[82:57] have in fact published now multiple
[82:59] papers with a very good friend and
[83:00] colleague who is a lung expert at my
[83:03] university, a guy named by the name of
[83:05] Paul Reynolds. Paul and I, we have
[83:06] published reports together looking at
[83:08] cigarette smoking and the inflammatory
[83:10] and insulin resistance effects that come
[83:13] from that. And now we've even started
[83:15] looking at the molecules, the
[83:16] hyper-heated
[83:18] molecules from vaping and they're
[83:21] they're terrible. In fact,
[83:23] yes, very similar results. If you were
[83:25] to take a comparable amount of the
[83:27] chemicals from normal cigarette smoke
[83:29] with its filter
[83:31] versus vaping, the vaping ones are
[83:33] probably worse chemical for chemical.
[83:36] In terms of their insulin
[83:38] in terms of their inflammatory effect,
[83:40] of the damage to the airway and the
[83:42] insulin resistance that comes from it.
[83:44] That's horrifying.
[83:45] It is in part because of just how common
[83:48] it's become.
[83:52] Does smoking make us fat?
[83:53] Uh that's a great question. It doesn't
[83:56] because it replaces other interests. So
[83:58] if the cigarette smoker ate
[84:01] the way everyone else was eating, it
[84:03] would.
[84:04] But because the cigarette smoke
[84:06] satisfies a craving, they have less of
[84:09] an interest in food. What's so
[84:10] interesting about cigarette smoking is
[84:12] again, as I said, you begin to smoke
[84:14] other things don't tempt you as much
[84:16] like the cookies and the cakes. But one
[84:18] of the ways the smoker helps kick the
[84:20] habit of cigarette smoking is actually
[84:22] eating candy. Like they will literally
[84:24] start carrying around little candies in
[84:26] their pocket. So that they feel a
[84:28] craving for cigarette smoking, they will
[84:29] take out a little candy, open it up, and
[84:31] pop it in their mouth. And so it's no
[84:33] surprise that very commonly when a
[84:35] person quits smoking, they gain
[84:37] significant weight.
[84:39] They end up trading out their
[84:41] addictions, if you will. Um and
[84:43] unfortunately, in humans, all of the
[84:45] study of addictions with food, people
[84:48] only manifest an addiction to one type
[84:50] of food, and that is carbohydrate.
[84:51] There's no evidence of addiction to fats
[84:53] or proteins.
[84:54] You published a study in 2024, which
[84:56] found that exposure to diesel exhaust
[84:59] gas was associated with increased fat
[85:02] mass, enlarged fat cells, insulin
[85:04] resistance, and increased levels of
[85:06] inflammation. And that was published in
[85:08] the International Journal of Molecular
[85:09] Sciences.
[85:10] Yeah, that was one of the studies I just
[85:11] was referring to with regards to my
[85:13] colleague Paul Reynolds. Paul and I, we
[85:15] That was one of the papers we published
[85:17] looking at these inhaled particulates.
[85:19] The reason I was interested in this
[85:21] field of study in the first place
[85:23] was just to continue to kill the caloric
[85:26] model of obesity. So our And this
[85:29] touches on an earlier part of the
[85:30] conversation. Overwhelmingly, if you ask
[85:33] someone, "Why do we get fat?" Well,
[85:35] because you eat more calories than you
[85:36] burn. "Why do you lose fat?" Because you
[85:39] eat fewer calories. And I have long just
[85:42] been frustrated by how naive that view
[85:44] is. Yes, energy matters, but again, the
[85:46] fat cell must be told what to do with
[85:48] the energy that it has. That, of course,
[85:50] points an obvious finger at insulin,
[85:52] which is the strongest of all signals.
[85:54] But what we found in that study is that
[85:56] even something as seemingly unrelated as
[85:58] diesel exhaust particles,
[86:00] mind you, we did not do this study in
[86:01] humans.
[86:03] Full disclosure, we did the study in
[86:04] animals where we could perfectly control
[86:06] how much diesel exhaust they're getting.
[86:09] Um so we have this mechanism through in
[86:11] Paul's lab where you can aerosolize
[86:13] these particulates and know exactly how
[86:15] how the animals breathing. And then at
[86:16] the end of the study, after even though
[86:18] they ate the exact same amount of food,
[86:21] the animals that were exposed to the
[86:22] diesel exhaust particulates had fatter
[86:25] fat cells and more insulin resistance
[86:27] than the animals that had just been
[86:28] breathing normal room air.
[86:30] So, what we're breathing in
[86:31] theoretically could then be determining
[86:33] how fat we're getting.
[86:34] Yeah, yeah, in fact yeah yeah this
[86:35] evidence would suggest that it goes
[86:37] beyond theory. So, our evidence would
[86:39] state conclusively that yes, what you
[86:41] breathe does matter. Then theoretically
[86:43] we would say, well, how much does that
[86:45] apply to humans? That is where it would
[86:47] get into the realm of theoretical, but
[86:48] the evidence certainly suggests yes, the
[86:51] very air we breathe matters. And you see
[86:53] this at a population level. Look in
[86:55] areas where there are Now, there are
[86:57] confounding variables here. Here I am
[86:59] invoking correlational research and I
[87:00] was just criticizing it a moment ago
[87:02] with regards to longevity. But you look
[87:04] in areas where they have higher
[87:05] pollution levels, where the particulates
[87:07] are higher in the atmosphere, and those
[87:09] same areas are always fatter and more
[87:13] diabetic.
[87:14] Interesting.
[87:16] But of But of course that's
[87:17] correlational, so it's hard to say.
[87:19] Exactly. Yes, thank you for pointing it
[87:20] out. And but again, as much as you and I
[87:23] are citing the problem with the
[87:24] correlational study there, we need to
[87:26] always cite the problem with
[87:27] correlational studies when it comes to
[87:28] informing nutrition policy. Like, don't
[87:31] eat eggs because they cause diabetes,
[87:33] but when you actually look at the
[87:34] studies, you find nothing of the sort.
[87:36] What about other sort of environmental
[87:37] toxins and their impact on insulin
[87:40] resistance?
[87:40] Mhm. Yeah. So, there are the ones that
[87:42] you inhale. A handful of inhaled
[87:45] particulates will matter. We have shown
[87:47] in my lab alone with my with my
[87:49] collaborators, diesel exhaust will do
[87:51] it, cigarette smoke will do it, and more
[87:53] We have a funded grant right now to look
[87:56] at the effects of vaping. So, apparently
[87:58] stuff we breathe will matter.
[88:01] To some unknown degree, things that we
[88:04] drink will that are non-caloric. So,
[88:07] there can be like people have heard of
[88:09] the microplastics.
[88:11] Microplastics are things that you can't
[88:13] They're so small that you drink them
[88:16] and they will absorb through the
[88:17] intestine and get into the bloodstream.
[88:19] For reasons that are unknown to me at
[88:22] the moment, one of the sites where those
[88:24] microparticles will go is the fat cells.
[88:27] And once there, they will directly
[88:29] promote the growth of the fat cells. So,
[88:30] that's actual microscopic segments of
[88:33] plastic. But separate from that are
[88:35] molecules that can come from plastics
[88:37] and soaps and detergents like BPA
[88:40] or diethylstilbestrol DES. That's
[88:43] actually an estrogen mimetic, kind of
[88:46] what we referred to earlier with regards
[88:47] to other endocrine disruptors. But there
[88:49] are other chemicals that a person can
[88:51] drink
[88:52] um or inhale like I mentioned earlier,
[88:55] but that will directly impact the growth
[88:57] of fat cells or promote to tell that
[88:59] mimic what insulin wanted to do, which
[89:01] is tell the fat cell to grow.
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[90:07] As you guys know, Whoop is one of my
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[91:01] Let me know how you get on.
[91:04] So, let's talk about ketosis and
[91:06] ketones.
[91:07] Um the diet the keto diet is becoming
[91:10] increasingly popular from what I've
[91:12] seen. It's actually the diet that I'm on
[91:13] at the moment.
[91:16] How does that play into everything we've
[91:17] talked about?
[91:18] Yeah. Yeah, so it it this is an
[91:20] opportunity for me to do a little bit of
[91:22] um bio nutrient biochemistry or a little
[91:25] discussion of metabolism so that people
[91:27] appreciate what ketones even are and
[91:29] where they come from.
[91:31] So, the the entirety of the human body
[91:33] is a metabolic hybrid in that the body
[91:36] is largely burning fuel from two
[91:38] sources. It is burning blood glucose or
[91:41] sugar blood sugar or it's burning fat.
[91:45] Those are the two main fuels for the
[91:46] body my extension. Now, the brain was an
[91:48] exception. The brain is glucose or
[91:50] ketones and but I'll get to where the
[91:52] ketones come from. The rest of the body
[91:55] isn't really relying on ketones as much.
[91:57] It's fats or glucose
[91:59] or blood sugar. Insulin is what decides
[92:02] which fuel is used. So, as much as the
[92:04] metabolic engine has two fuel sources,
[92:07] insulin will decide which one is opened
[92:09] and which one is closed. If insulin is
[92:11] high, the body is sugar burning. And you
[92:13] can measure this in the whole body level
[92:15] by measuring the amount of
[92:16] oxygen and CO2 that the body is
[92:18] producing. Because different
[92:19] biochemistry or the burning of the fuels
[92:21] will produce a different amount of CO2.
[92:23] So, if I'm burning glucose, I might be
[92:25] producing more CO2.
[92:27] Yes. Yes, so we could hook you up to
[92:29] something called an indirect calorimeter
[92:31] and measure that your RER, the
[92:33] respiratory exchange ratio, the balance
[92:35] between CO2 and oxygen, would go higher.
[92:38] So, we we increase your insulin, like if
[92:40] I infused you with insulin in the next
[92:42] few minutes, we would see that your RER
[92:45] would go up and we'd say, "Boy, you're
[92:46] sugar burning."
[92:47] Or we allow insulin to come down and
[92:50] then the RER goes down, which is
[92:52] reflective of fat burning. So, it's
[92:54] insulin that determines whether the body
[92:56] is sugar burning or fat burning. Now,
[92:58] when insulin has been low for about 16
[93:00] or so hours,
[93:03] something interesting starts happening
[93:04] at the liver.
[93:05] So, the liver,
[93:07] with insulin being low, is burning a lot
[93:09] of fat.
[93:10] Including its own fat that the liver can
[93:12] store. The liver can store fat, but also
[93:14] fat coming from fat cells. Because if
[93:16] insulin is low, the fat cells are just
[93:19] leaking out fat to be burned by the
[93:21] body.
[93:22] And because insulin is low, the liver
[93:24] keeps burning it.
[93:25] And the liver essentially
[93:28] burns continues to burn so much fat that
[93:30] it it fills its own needs. It meets its
[93:33] own needs and says to itself, "Hey, I
[93:35] don't need to keep burning fat. I have
[93:37] all the energy I need. I'm I'm doing
[93:40] great." But it can't stop burning fat
[93:43] because insulin is low. And if insulin
[93:45] stays low, fat burning keeps going. And
[93:47] so,
[93:48] Because the body doesn't have enough
[93:49] glucose.
[93:50] Well, it's acting Yes, so in this sense,
[93:52] it's doing it to help replace the
[93:54] glucose that isn't coming in. That's
[93:55] what value of the ketone. So, as the
[93:57] liver is continuing to burn fat, it
[93:59] essentially gets to a point of fat
[94:01] burning where it's burning more fat than
[94:03] it needs.
[94:04] And that excess, if you will, is what
[94:06] becomes ketones. So, ketones are kind of
[94:09] a metabolic release valve for the liver
[94:12] cell to say, "I I can't I don't know
[94:14] what to do with all this fat burning.
[94:15] Okay, I know what I'm going to do.
[94:17] There's not a lot of glucose coming in.
[94:19] And so, the brain may start to get
[94:21] hungry. So, I'm going to start making
[94:23] ketones."
[94:24] And so, ketones are nothing more than a
[94:27] product of a lot of fat burning. And
[94:30] anyone who even fasts for 24 hours, you
[94:32] wake up that next morning, you're in
[94:34] some degree of ketosis. Lest anyone
[94:37] think it's an extreme thing. People are
[94:39] going in and out of ketosis ideally
[94:42] often. Now, why do I say ideally? It's
[94:44] because ketones are, as we've already
[94:46] outlined, perhaps the best fuel for the
[94:48] brain. The brain thrives on ketones. You
[94:51] can take a person
[94:53] with early stage Alzheimer's disease and
[94:56] have them go through a series of
[94:57] cognitive tests and they do horribly on
[94:59] them. Like one example is you ask the
[95:02] patient with Alzheimer's to draw the
[95:04] face of an analog clock,
[95:06] a circle with 1 2 through 12 and then
[95:08] some hands on it. And it is utter chaos.
[95:12] This is published reports. You then put
[95:14] them into ketosis,
[95:16] ask them, "Can you please draw the face
[95:18] of a clock?" It's still sloppy, but it
[95:20] is absolutely the face of a clock. You
[95:23] ask them, when they're not in ketosis,
[95:25] to try to tie their shoelaces, they
[95:26] can't think through the puzzle of tying
[95:29] the shoelaces. Ask them to do it again
[95:31] when they're in ketosis, all of a sudden
[95:33] they can tie their shoelaces. More than
[95:35] that, they can get themselves dressed.
[95:37] All of these are published case reports.
[95:39] It's just my long-winded way of saying
[95:41] the brain thrives when it has ketones as
[95:45] a fuel source. But, the benefits don't
[95:47] stop there. My lab published a report
[95:50] finding that when humans were in
[95:52] ketosis, which is just a term for
[95:53] ketones being elevated,
[95:55] we pulled out small pieces of belly fat
[95:58] and measured the metabolic rate of that
[96:00] belly fat. And we found that in ketosis,
[96:03] the metabolic rate of that belly fat was
[96:05] three times higher than when the people
[96:08] were not in ketosis.
[96:09] What does that mean?
[96:10] Yeah, so that means that the fat was
[96:12] suddenly behaving in a much more
[96:14] energetic way. That fat tissue has a
[96:16] very low metabolic rate. And then all of
[96:18] a sudden when the ketones came into
[96:20] them, they started getting much more
[96:22] active and they started burning more
[96:24] energy. Which is going to be very
[96:25] helpful for someone who wants to lose
[96:28] fat. If your fat cells now have a three
[96:30] times higher metabolic rate, that means
[96:33] that the fat cells are starting to act a
[96:34] little bit more like your muscle cells.
[96:37] And they're just burning more energy.
[96:38] So does that mean that I'm going to lose
[96:40] fat faster? What does that mean?
[96:41] absolutely. And that is what happens.
[96:43] There are very well-done controlled
[96:45] studies to show that if you control for
[96:47] all calories, when a human is in
[96:49] ketosis, the metabolic rate goes up.
[96:52] Your body Your whole body is just
[96:53] burning more.
[96:54] Um it it it's just everything's kind of
[96:56] been turned on a little more. The the
[96:57] the the furnace of the metabolism has
[96:59] just been it's you have a little more
[97:01] fuel kind of stoking the fire.
[97:04] So ketones will increase metabolic rate
[97:05] of fat tissue. We found a paper that we
[97:08] published documenting how we took muscle
[97:11] cells and kind of insulted the muscle
[97:13] cells to determine how tough the muscle
[97:15] cells were.
[97:17] When we incubated the muscle cells with
[97:19] ketones, they were much more resistant
[97:21] to injury.
[97:23] So the ketones act to protect muscle
[97:25] tissue.
[97:27] And in a way that is reflective of a
[97:28] function of ketones. Ketones are a
[97:31] defender of muscle.
[97:33] Ketones are basically the way to tell
[97:34] the brain, saying, "Brain, you think you
[97:37] need a lot of glucose.
[97:38] And if you don't get enough glucose, you
[97:40] would start stripping the protein from
[97:42] muscle to turn it into glucose. But I'm
[97:45] here as a ketone, so you can eat me
[97:47] instead and not and leave the muscle
[97:50] alone. So we published again a direct
[97:52] report finding that ketones actually
[97:54] make muscle more resistant to injury.
[97:56] And this could be why you're seeing more
[97:58] and more elite athletes using ketones as
[98:01] an actual
[98:02] ergogenic aid or like a supplement to
[98:04] help them better be better. So my
[98:06] university at BYU, just this year, our
[98:09] men's and women's cross country team
[98:11] took the national championships, the
[98:13] best college runners in the nation,
[98:15] pretty impressive. One of the things
[98:17] they do is they take these ketone drinks
[98:20] before they train and before they they
[98:22] race. Some more and more of the Tour de
[98:24] France teams
[98:26] take ketone supplements because it is
[98:28] just another fuel.
[98:30] It is something that the body can burn.
[98:32] The that we always say, well, if once
[98:34] you start running out of glucose, you're
[98:36] going to bonk or you're going to hit the
[98:37] wall. Well, what if you don't really use
[98:39] glucose because you're burning a lot of
[98:41] fat and a lot of ketones instead and
[98:43] that keeps your glucose kind of
[98:44] untouched. You're not You're not relying
[98:47] on the glu- And we see this in humans.
[98:49] If there's an a human that has adapted
[98:51] to a ketogenic diet, they burn fat at a
[98:55] higher rate than was ever thought
[98:56] humanly possible. That that fat is
[98:59] basically fueling all of their muscle
[99:01] movement during the exercise session
[99:04] rather than relying predominantly on
[99:05] glucose. The body has adapted. It's
[99:08] burning fat for fuel and when available,
[99:10] it's burning ketones for fuel and it's
[99:12] leaving the muscle as sort of a last
[99:14] resort when it really needs a big kick.
[99:16] I've seen these keto drinks. They're
[99:18] little They're almost like little shots.
[99:20] Well, there's a bunch of different
[99:21] types. If you look at the spectrum of
[99:23] ketones, you on one end you have the
[99:25] cheapest, most readily available,
[99:27] although less effective, called ketone
[99:29] salts, where it takes a molecule of
[99:31] ketone and binds it to a mineral like
[99:32] calcium or magnesium.
[99:34] Um not as effective and it's a lot of
[99:37] minerals, so people will find that they
[99:38] might get a lot of plaque on their
[99:39] teeth, maybe increased risk of kidney
[99:42] stones, so comes with some consequences.
[99:44] Then you have the ketone ester, which
[99:46] often comes in shots.
[99:47] Yeah.
[99:48] Then you have the bioidentical
[99:50] BHB or the bioidentical ketone. One
[99:52] company, which is original ketone, um
[99:55] they make it. Now, these ones are more
[99:57] effective. You take a little bit of
[99:58] these and you will get an increase in
[100:00] ketones. They're a little more
[100:01] expensive, too.
[100:02] But as the space is becoming more
[100:03] competitive, the price is coming down.
[100:05] And what exactly does it do? So if I
[100:07] took a shot of bioidentical ketone
[100:10] drink,
[100:10] Mhm.
[100:11] what would go on in my body and how
[100:12] would I
[100:13] how would that impact my cognitive
[100:15] performance or
[100:16] athletic performance?
[100:17] Yeah. Yeah. So it would result So you're
[100:20] drinking it in, you're immediately
[100:21] absorbing it from your gut.
[100:23] Yeah.
[100:23] So if you were not in ketosis, let's say
[100:25] you had and I'm not encouraging people
[100:27] to do this. You would just have eaten
[100:29] two bagels and a cup of sugary coffee.
[100:31] You're no ketones, undetectable cuz
[100:34] insulin has come up, it's inhibited
[100:35] ketone production. And then you drink a
[100:38] shot of the ketone, within an hour we
[100:40] would detect your ketones. They would
[100:41] have gone up maybe to 1 millimolar,
[100:42] which is a pretty significant bump.
[100:44] Yeah.
[100:44] And they're capable of that kind of
[100:45] movement. And maybe you do so because
[100:47] you're thinking I really need to be
[100:48] sharp right now.
[100:49] Would that make me sharper?
[100:51] Well, that's where we have to speculate.
[100:53] There's no
[100:54] I My lab published animal evidence
[100:56] suggesting that yes, indeed, it makes
[100:58] you sharper. That we had these animals
[101:00] navigate mazes and recognize objects.
[101:02] And when the animals were on a ketogenic
[101:04] diet, they were much sharper. They were
[101:06] much quickly, much better at solving
[101:08] problems and remembering solutions to
[101:11] previous problems.
[101:12] It's one of the I asked this in
[101:14] particular because
[101:16] as my team know cuz I've said it to them
[101:17] a lot over the last couple of weeks
[101:18] since I've been on the keto diet and
[101:20] I've been literally
[101:21] pricking my finger to check
[101:23] Yeah.
[101:24] Yeah.
[101:24] my keto levels and the highest I've
[101:26] gotten to is like 2.5.
[101:27] Which is high.
[101:28] Is it high?
[101:29] That's not problematic.
[101:30] Right.
[101:31] that is just proof positive that you're
[101:33] in ketosis, which itself is proof
[101:34] positive that you're burning a lot of
[101:36] fat
[101:36] Yeah.
[101:37] and three that your insulin levels are
[101:38] low.
[101:39] Fat dropped off my body like I've never
[101:40] seen in my life.
[101:41] Exactly.
[101:42] Yeah, it's crazy.
[101:43] So the power there is
[101:44] like if you'll allow me to kind of
[101:46] springboard off of that comment
[101:49] the power of So So if someone is
[101:51] listening to this and they're thinking,
[101:52] "Okay, I need to shrink my fat cells."
[101:54] Yeah.
[101:54] Unfortunately, they don't realize that
[101:56] there's two variables to what caused
[101:58] their fat cells to grow in the first
[101:59] place. They have no awareness of the
[102:01] value of insulin in this in this um um
[102:04] formula. All they do is pay attention to
[102:06] the calories. And so the average
[102:08] individual is looking down the road of
[102:10] this fat cell shrinking journey and
[102:12] they're thinking, "Okay, what I have to
[102:14] do is just cut my calories." And what do
[102:17] they do to cut their calories? They do
[102:18] the exact wrong thing.
[102:20] And before I even answer that, let me
[102:22] just present the scenario. Let's imagine
[102:24] that Steven and I everyone listening is
[102:26] invited. Steven and I are hosting a
[102:27] buffet. We have the world's best chefs.
[102:30] It is going to be a table filled with
[102:32] the most delicious food you can imagine.
[102:34] You're In our invitation, we say, "Come
[102:36] hungry cuz you're going to want to try a
[102:38] little bit of everything." Everyone
[102:40] listening, ask yourselves what would you
[102:42] do to come as hungry as possible. You'd
[102:44] probably do two things. Or think, "How
[102:47] did you go to your Thanksgiving or
[102:49] your your Christmas dinner as hungry as
[102:51] possible?" You would eat a little less
[102:54] in some period of time before the event
[102:56] and you would exercise a little more.
[102:58] And it would work. You would be very
[103:00] hungry.
[103:01] That's why the traditional advice given
[103:03] for weight loss doesn't work because we
[103:05] tell people, "Eat less, exercise more."
[103:08] Sure, you may be lose a little bit of
[103:09] weight in the short term, but all that
[103:11] does, you've given them the perfect
[103:13] recipe to promote hunger. And hunger
[103:15] always wins.
[103:16] As a good example uh in the US, we have
[103:19] a game show. Maybe there was some
[103:20] version of this in the UK called The
[103:21] Biggest Loser.
[103:23] It was essentially who can lose the most
[103:24] weight. And it was through a punishing
[103:27] regiment of caloric restriction. Eat
[103:29] less, exercise more. That is like the
[103:31] perfect embodiment of that approach.
[103:33] They were starving and they were
[103:35] exercising to insane degrees. And oh my
[103:38] goodness, did they lose a lot of weight?
[103:40] And yet you never see them again.
[103:41] They don't do a reunion tour 5 years or
[103:44] 10 years later because they gained it
[103:45] all back.
[103:47] Do Do you know they gain it all back?
[103:49] In fact, a paper published in the US
[103:50] from the National Institutes of Health
[103:52] documented not only the degree to which
[103:54] they gain weight back, but also how it
[103:56] almost literally breaks their
[103:58] metabolism. That normally a person's
[104:00] metabolic rate is connected to their
[104:02] body mass. A bigger body has a higher
[104:04] metabolic rate. A smaller body has a
[104:07] lower metabolic rate. This is just human
[104:09] physiology. And no surprise when someone
[104:11] loses weight, there's less of body and
[104:13] so metabolic rate goes down. As they
[104:15] gain weight back, metabolic rate will
[104:17] typically go back up as well.
[104:20] Except for the contestants in The
[104:21] Biggest Loser. They started with a high
[104:23] metabolic rate because of a high body
[104:25] fat level. They lost a substantial
[104:28] amount of weight. No surprise, metabolic
[104:31] rate went down substantially. But if
[104:33] this is such a dramatic change that as
[104:36] they started gaining weight back,
[104:38] metabolic rate did not come back with
[104:40] it. It stayed lower than it should have.
[104:43] Normally it's connected sort of
[104:45] one-to-one. Wherever body weight is
[104:47] going, metabolic rate is going. Except
[104:49] in these people. That method of dramatic
[104:51] weight loss through such severe
[104:54] restriction, which is based purely on
[104:56] the caloric theory of obesity,
[104:58] leads to such It leads to significant
[105:00] hunger. So no surprise, if a person's
[105:02] attempting to shrink their fat cells or
[105:04] lose weight,
[105:05] if the first step is I'm going to cut my
[105:08] calories and they don't address their
[105:09] high insulin,
[105:11] they're never going to lose weight in
[105:12] the long run. They're going to step
[105:14] right back to where they were. Because
[105:15] if they start cutting calories, but
[105:17] insulin is still high,
[105:19] that's going to make them very hungry
[105:20] because insulin wants to be storing
[105:22] energy.
[105:23] A A professor from Harvard named David
[105:25] Ludwig found this. If you have people
[105:28] eating a lower calorie meal that spikes
[105:30] their insulin, it makes them much
[105:32] hungrier
[105:33] than a lower calorie meal that doesn't
[105:35] spike insulin. So, that's the key.
[105:37] Anyone listening, if you're thinking I
[105:39] need to be on a fat cell shrinking
[105:40] journey, let the first step of that
[105:43] journey be
[105:45] I'm going to lower my insulin.
[105:46] Which means
[105:47] Which means I'm going to control my
[105:48] carbohydrates. I'm going to stop eating
[105:51] carbohydrates that come from bags and
[105:52] boxes with barcodes. And while I am
[105:55] restricting those carbohydrates, I'm
[105:57] going to focus more on protein and fat.
[106:00] So, control carbs, prioritize protein,
[106:04] and don't fear the fat that comes with
[106:06] those proteins. Fat and protein together
[106:09] is a
[106:11] a miraculous combination of helping you
[106:13] feel full, and it is literally giving
[106:15] everything you need.
[106:17] There are such things as essential
[106:18] proteins. There are such things as
[106:20] essential fats. So, focus on those.
[106:23] And that will be the key to helping
[106:24] insulin come down. Then, as you have
[106:27] found, you have and when you're hungry,
[106:29] eat. If you're not hungry, don't eat.
[106:31] But, what the person will find as
[106:32] they're lowering their insulin,
[106:34] all while their metabolic rate is going
[106:36] up. They're learning how to burn their
[106:38] own fat for fuel, because remember the
[106:40] metabolic hybrid, that metaphor, that if
[106:43] you want to lose fat, you need to burn
[106:44] fat. You're not going to lose fat if
[106:46] you're always burning glucose. It's fat
[106:48] that you need to burn. And as you start
[106:50] burning more fat, you realize that it's
[106:53] like the hump on a camel. That hump
[106:55] exists because it is a big source of fat
[106:58] for that animal to be using its own fat
[107:00] for energy. We have our own version of
[107:02] that. So, where the you think about the
[107:05] average individual who's chubby, they
[107:06] have hundreds of thousands of calories
[107:09] waiting to be burned in those fat cells.
[107:12] It's just that their chronically
[107:13] elevated insulin is never letting them
[107:15] burn it.
[107:16] And so, as the person starts making
[107:18] these changes in their diet to lower
[107:20] insulin, they now can finally start
[107:22] relying on their own fat for fuel. So,
[107:24] it's no surprise that their hunger
[107:26] starts to come down. Let that be the
[107:28] natural way in which you're controlling
[107:30] your calories. Don't control your
[107:33] calories because you're forcing yourself
[107:34] to be hungry and eat less.
[107:36] Control your calories because you simply
[107:39] aren't hungry.
[107:40] So, I have to I'll leave it at this with
[107:42] my own sort of anecdotal experience. So,
[107:43] I every year do a keto diet for usually
[107:46] for about 8 weeks.
[107:47] Mhm.
[107:48] This time it's going to go on for a
[107:50] little bit longer. Um the reason in part
[107:52] why it's going to go on a little bit
[107:53] longer is I just learned more about
[107:54] what's going on in my body, and also
[107:57] because I podcast now and do a lot of
[107:58] speaking on stage and those kinds of
[108:00] things, I see tremendous variance in my
[108:02] ability for my brain to articulate what
[108:04] I want to say.
[108:05] way.
[108:06] It's like it's absurd. Yes. I I was
[108:08] saying this the other night to the the
[108:10] team that were with me here in Los
[108:11] Angeles, and I tried to say it to so
[108:13] many people.
[108:14] As someone that can spend 9 hours a day
[108:17] trying to think of the next question to
[108:19] ask or trying to remember the research
[108:20] or on stage in front of a thousand
[108:22] people trying to deliver a story or a
[108:25] point, I get to see variance which I've
[108:29] never been able to explain.
[108:30] Yeah.
[108:31] Um where some days I'll go up on stage,
[108:33] I'll be in a podcast, and it's like my
[108:35] brain and my mouth aren't connected. And
[108:36] then on other days, specifically when I
[108:38] started doing ketosis or having a
[108:41] ketogenic diet,
[108:42] Mhm.
[108:43] it just flows. Yeah. It just flows so
[108:45] well. And I was saying to my team, it
[108:46] feels like I'm looking at the world like
[108:48] this these days. Like I've got this
[108:50] intense I probably anyone that can't see
[108:51] me, I just stretched my eyes, but like
[108:53] I've got this intense focus on the
[108:54] world. Um the other thing I've noticed
[108:56] with my diet is
[108:58] I
[108:59] I get hungry, but not like I used to get
[109:01] hungry.
[109:02] And then very quickly after I start
[109:04] eating,
[109:06] I stop.
[109:07] Mhm.
[109:08] I don't seem to be like doing like these
[109:09] I used to kind of binge a little bit.
[109:11] Yeah.
[109:12] I used to have like a longer eating
[109:13] sessions. And my hunger goes very
[109:14] quickly.
[109:15] Um I also found that I didn't have these
[109:18] like fluctuating energy levels
[109:19] throughout the day. I didn't crash
[109:21] anymore. I used to get like slumps.
[109:23] Yeah, for sure.
[109:24] I don't slump anymore. And then the
[109:26] other thing which a lot of people will
[109:27] care mostly about is the the fat, so
[109:29] like belly fat. I have never seen
[109:31] anything that has stripped belly fat off
[109:33] me faster. And I'm talking in a matter
[109:36] of weeks that I could
[109:37] Yeah.
[109:38] you know, count on one hand
[109:40] Yeah.
[109:40] than
[109:42] doing the ketogenic diet. And if I I
[109:43] could literally show a picture of my
[109:45] scales cuz I have these digital scales
[109:47] on the screen and it's just trundling
[109:49] along and then there's this cliff edge
[109:52] where it goes directly down. And it and
[109:55] so much so actually that one of my
[109:56] concerns with the ketogenic diet is how
[109:58] the hell do I keep my muscle?
[110:00] Oh, that's a great question.
[110:01] Because my girlfriend, to her credit,
[110:03] when I did ketosis the first time, she
[110:05] was like, "I've never ever seen you look
[110:07] like this." When I took my top off.
[110:10] But also, it was quite clear that my
[110:13] my muscles had got smaller.
[110:14] Mhm.
[110:14] I was as lean as but my muscles
[110:16] were small.
[110:16] Yeah.
[110:17] So, with I with with caution this time I
[110:19] did ketosis again and I've been
[110:21] thinking, "How the do I keep my
[110:22] muscles?"
[110:22] Yeah. Yeah. Okay, so first of all, let
[110:24] me just add a hearty amen. I'm an
[110:26] advocate of a ketogenic diet, although
[110:28] it can be applied differently across
[110:30] different people. But I would say anyone
[110:31] would benefit from having some modest
[110:33] period of time of elevated ketones, at
[110:36] least in some portion of the day. Now,
[110:38] how do you maintain muscle mass
[110:41] in the midst of such obvious weight
[110:42] loss?
[110:44] I can only speculate. Now, there are
[110:46] peer-reviewed studies that I can cite
[110:49] which do support the idea that a human
[110:51] can be on a ketogenic diet and have a
[110:53] total maintenance of muscle and
[110:55] strength. That is published. So, we know
[110:57] it's possible, although that isn't that
[110:59] doesn't seem to be what happened with
[111:01] you.
[111:02] I would suspect
[111:04] that there were two things
[111:07] two things happening, possibly. Now, I'm
[111:09] speculating here and I'm pretending to
[111:10] be your coach or your expert here.
[111:13] One
[111:14] could have been that you had relatively
[111:16] lower energy during your workouts
[111:18] because of a slight degree of
[111:19] dehydration.
[111:21] And then the other one would be
[111:21] calories, which I'll come back to in a
[111:23] moment. I just wanted to put it out
[111:24] there. So, when insulin comes down, one
[111:26] of the other one of the many effects in
[111:28] the body is that another hormone comes
[111:31] down called aldosterone, which is one
[111:34] we've never invoked yet. But low insulin
[111:36] leads to lower aldosterone. When
[111:38] aldosterone comes down, the kidneys
[111:40] become much
[111:42] uh begin to eliminate salt and water
[111:45] much more rapidly. Now, that's not
[111:47] problematic,
[111:48] but it does mean that a person does have
[111:51] to focus more on hydration and salts.
[111:53] So, if someone's going on this strategy
[111:56] and they exercise fairly often,
[111:58] you need to be much more focused on your
[112:00] hydration,
[112:02] literally drinking more because you will
[112:04] be urinating more,
[112:05] which is partly why people's blood
[112:07] pressure gets so good so quickly.
[112:10] And just to
[112:11] pause on that point, there if if someone
[112:13] is on one or two blood pressure
[112:15] medications and they adopt a ketogenic
[112:16] diet, they usually have to stop their
[112:18] medications within 2 days cuz their
[112:21] blood pressure goes to normal so quickly
[112:23] that if they stay on the medication,
[112:24] they're going too low. So, one could be
[112:27] that you were actually working out a
[112:28] little less intensely because of the
[112:30] dehydration.
[112:32] But then two,
[112:33] it's possible that you were eating too
[112:36] few calories to actually maintain
[112:38] muscle. Muscle is a hungry organ. It is
[112:41] metabolically expensive for the body to
[112:43] keep that muscle on. And as you start to
[112:46] get leaner and leaner,
[112:48] it gets harder and harder for the body
[112:50] to defend that muscle.
[112:51] In fact, that's the difference between
[112:53] fasting and starvation. The longest
[112:56] known evidence of a fast was a man in
[112:58] the UK who fasted for 384 days,
[113:02] literally not eating or drinking a
[113:03] single calorie. He was under medical
[113:05] supervision, getting vitamins and
[113:07] minerals and water, and he was went to
[113:09] live on went on to live a perfectly
[113:11] healthy life. Um so, but what was the
[113:14] difference? Why was that not starvation?
[113:16] Starvation is when you run out of fat.
[113:19] So, you might have gotten to the point
[113:21] of so lean that you didn't have enough
[113:23] fat to burn to make enough ketones to
[113:26] fuel the brain. If you don't have enough
[113:28] fat to burn to make enough ketones, and
[113:29] the brain is saying,
[113:31] "All right, well, I wanted to switch to
[113:33] ketones so that I could spare the
[113:34] glucose,
[113:36] but I can't. There's not enough ketones
[113:38] here, so I have to rely 100% on
[113:40] glucose."
[113:41] But, if you're not eating glucose, now
[113:43] the body has to start stripping the
[113:44] protein from muscle. And then it sends
[113:47] those amino acids to the liver, then the
[113:49] liver
[113:50] is so capable, it will turn those amino
[113:52] acids into glucose.
[113:53] So, it turns my muscle
[113:54] into glucose to feed the brain. So, my
[113:56] comment then, getting finally getting to
[113:58] my answer is
[114:00] in your version of a ketogenic diet,
[114:02] with your level of muscle mass, and your
[114:05] inherent metabolic rate based on your
[114:06] body size and your activity, you
[114:08] probably ought to eat more fat.
[114:10] I wasn't actually doing the blood test
[114:12] at that point.
[114:13] Mhm.
[114:14] I'm doing it this time around, but I
[114:15] wasn't doing the blood test, so I can
[114:16] actually see my keto levels.
[114:17] Yeah.
[114:18] So, maybe I wasn't even in ketosis cuz I
[114:20] was coming off
[114:20] and you might have been, but it could
[114:22] have been that you were simply not
[114:23] eating enough calories. That I have to
[114:25] So, this is an instance where
[114:27] That's what I'm trying to do this time.
[114:28] I'm trying to
[114:28] more fat. Like every time you're making
[114:30] a steak, put butter on there. And when
[114:32] you're drinking a cup of coffee, as
[114:33] crazy as it sounds, I I drink yerba mate
[114:35] every morning, I will put a big dab of
[114:38] butter
[114:39] In your coffee?
[114:39] dab of butter in my tea, and I'm sipping
[114:42] on it while the world's still asleep and
[114:44] the kids haven't woken up yet. And so, I
[114:45] know because I want to keep my muscle,
[114:48] as a guy who's almost 50,
[114:50] um I I find that when during my strict
[114:53] ketogenic phase, and I'm currently in it
[114:55] as well, every January I go to kind of a
[114:57] carnivore diet, to and I mostly do it to
[115:00] one lean down, but also to check any
[115:02] addictions and habits. I don't like
[115:04] feeling addicted to things.
[115:06] And and my wife will comment and even as
[115:08] an almost 50-year-old it's fun to see my
[115:10] six-pack coming. I don't want to lose my
[115:12] mass, my muscle mass because you have to
[115:14] work so hard to get it.
[115:16] Yeah.
[115:16] And what I find is if I increase my fat,
[115:19] I always get plenty of protein.
[115:21] But if I increase my fat content, I have
[115:23] an easier time maintaining my bulk.
[115:26] Are there any downsides of following a
[115:27] ketogenic diet that we need to be aware
[115:29] of?
[115:30] The only downside I can articulate, so
[115:32] in fact, I didn't even finish because I
[115:34] distracted myself mentioning some of the
[115:36] benefits of ketones, but ketones are
[115:38] further anti-inflammatory.
[115:40] Like they directly reduce inflammation
[115:42] in the body by inhibiting inflammatory
[115:44] processes and they also improve
[115:46] antioxidant defenses, so it helps reduce
[115:49] oxidative stress. So ketones do have
[115:51] benefits that go beyond even what we've
[115:53] taken the time to articulate. If there's
[115:55] any negative to a ketogenic diet,
[115:59] it could be that you start
[116:02] you acutely or you temporarily become
[116:05] less metabolically flexible. Now that's
[116:08] me invoking a term we haven't brought up
[116:10] yet, but metabolic flexibility is is a
[116:12] term to refer to the body's ability to
[116:15] when it eats glucose, to burn glucose.
[116:18] When it's not eating glucose,
[116:20] it burns fat. So you're shifting between
[116:22] the two metabolic fuels that we outlined
[116:24] earlier. When someone has been adhering
[116:26] to a ketogenic diet for some time,
[116:29] it's almost as if their body is stuck in
[116:31] fat-burning mode. And that if you and I,
[116:34] being in such adapted ketogenic state as
[116:36] we are, if we were to go to lunch and
[116:38] eat two bagels and a sugary drink,
[116:42] it would take us a very long time to
[116:44] clear that glucose from our blood.
[116:46] Um much longer than otherwise. Like
[116:48] let's say we go out with the production
[116:49] team, they're eating a normal higher
[116:51] carb diet, all things equal, same body
[116:54] size, same activity, their glucose
[116:56] levels would come up and down in 90
[116:57] minutes for
[116:58] perhaps. Yours and mine may take 180
[117:01] minutes to come back down. So the person
[117:03] may say, well gosh Steven and Ben are no
[117:06] longer burning glucose very well.
[117:09] And that's true in that one moment
[117:11] our bodies had almost forgotten what it
[117:14] was like to burn a bunch of glucose
[117:15] because we had adapted to fat burning.
[117:18] So what about the gut microbiome?
[117:20] Oh yeah.
[117:21] Cuz cuz I told someone who is a
[117:23] nutritionist that I was doing a keto
[117:25] diet at the moment and they said oh your
[117:27] poor gut.
[117:28] Ah yes, well what a naive
[117:31] thing to say if I may gently reprimand
[117:34] your friend. There's no evidence to
[117:36] support that there's any harmful change
[117:37] in the microbiome. In fact, a paper was
[117:40] just published that looked at a man who
[117:42] went from a normal omnivorous human diet
[117:44] with abundant plant matter to a purely
[117:47] carnivorous diet.
[117:48] Literally zero carb.
[117:50] And they documented precisely no change
[117:53] in his microbiome. None whatsoever.
[117:55] But is he eating plants?
[117:57] No. Well he had been eating plants. So
[118:00] the case study was a person eating a
[118:01] normal
[118:02] diet of of plants and meat. A normal
[118:05] omnivore diet. And and then looked at
[118:07] the microbiome and then adapted to a
[118:09] purely carnivorous diet. Purely meat.
[118:12] And the microbiome didn't change at all.
[118:14] What's the time period?
[118:15] Months I think. The problem with the
[118:17] microbiome, the reason I don't take
[118:19] microbiome research too seriously as a
[118:22] scientist is that it is a big black box.
[118:26] You You came from the UK to London to to
[118:30] to LA to California. If we took a
[118:32] microbiome sample analysis of your time
[118:34] in the UK
[118:36] now it would be different now. Even
[118:38] though you're eating the same but you're
[118:39] drinking different water, you're
[118:40] breathing different air.
[118:42] Things I was just on a plane from Utah
[118:45] to California. Give me a day or so I
[118:47] would have some sort of shift in my
[118:49] microbiome. So the microbiome can change
[118:51] in response to all kinds of things.
[118:54] The idea that you somehow have decimated
[118:56] your microbiome because you aren't
[118:58] eating fiber is absolutely false. That
[119:00] is That is completely false. Now, there
[119:03] might be a change in some of the
[119:05] population of your microbiome, more of
[119:07] one, less of another, but there's no
[119:09] evidence to suggest that's problematic.
[119:11] Your microbiome is intact. Those
[119:13] bacteria do not die. They're just simply
[119:15] metabolizing other things. Maybe they're
[119:17] relying more on short-chain fatty acids.
[119:19] Maybe they're relying more on amino
[119:20] acids. They're not eating as They're not
[119:22] eating fiber, but there's still stuff in
[119:25] the meat or the eggs that the microbiome
[119:28] will eat.
[119:29] But if eating lots of plants does give
[119:32] me a more diverse gut microbiome, then
[119:34] if I stop eating plants, I'm going to
[119:37] have a less diverse gut microbiome.
[119:38] but Steven,
[119:40] but even then there's a bit of an
[119:41] assumption built into the question
[119:42] because it's Do we know that the
[119:45] microbiome will be less diverse? The
[119:46] case study I just mentioned found that
[119:48] in this one single man, it didn't change
[119:50] his microbiome at all. It was the exact
[119:53] same populations in all the same
[119:55] proportions.
[119:56] Because isn't the Aren't the plants like
[119:58] feeding the bacteria?
[120:00] Yeah, yeah, so the the fiber is. So,
[120:02] fiber will, but again,
[120:05] it's not That's not the only thing
[120:07] bacteria can eat. Bacteria can eat fats.
[120:10] Bacteria can eat amino acids. They can
[120:12] eat glutamine, for example. They
[120:15] They can even meat will have a little
[120:16] bit of glucose in it. Where the muscle
[120:19] has something called glycogen. And so,
[120:21] there's you know, trace amounts of
[120:23] glucose in even the meat that you're
[120:24] eating. So,
[120:26] I do not look at the argument that, you
[120:29] know, you're destroying your microbiome.
[120:31] That has no That has no scientific
[120:34] support. You may be changing your
[120:36] microbiome, but who's to say that's a
[120:38] bad change? Maybe it's a better change.
[120:40] You certainly are feeling better. You're
[120:42] thinking better. You're getting leaner.
[120:43] Your insulin sensitivity's improved.
[120:45] Cognition's improved. I would argue if
[120:47] there is a change in your microbiome,
[120:49] it's probably one that's for the best.
[120:53] And no one can prove that wrong. As much
[120:55] as I just stated that comment in a
[120:57] speculative fashion, it's speculative
[120:59] because there's no evidence. This is why
[121:01] I look at the microbiome and just say,
[121:03] "Yeah, it appears to matter, but in ways
[121:05] that we don't know."
[121:07] But the the You agree with the argument
[121:09] that if I sat here now and I ate
[121:13] a wide range of plants for the next,
[121:16] let's say, 6 months, when you analyzed
[121:19] my gut microbiome, it would be much more
[121:21] diverse.
[121:21] I'm not agreeing to that, really. I
[121:23] don't know if that's true.
[121:25] Um And again, I would cite that one case
[121:28] report I just mentioned now, which is
[121:30] the a man who did this, they reported
[121:33] that the microbiome was identical. That
[121:35] there was no significant change.
[121:37] But that's just one man, though.
[121:38] It was one man. It was a case report.
[121:40] Which is not a randomized clinical
[121:42] study.
[121:43] So, um but even still,
[121:46] I I with my speculation uh um
[121:49] heavy-handed here, I would say probably
[121:52] more plants would result in a more
[121:55] diverse
[121:56] microbiome.
[121:58] But I would say
[122:00] But then the next step is a harder one,
[122:02] which is is that good or bad? I don't
[122:04] know. Maybe all you're doing is
[122:06] promoting the growth of bacteria that
[122:08] make more gas.
[122:10] Because they're fermenting the fiber and
[122:11] you just have more flatulence as a
[122:13] result of it. People dieticians will
[122:15] say, "Well, a diverse microbiome is a
[122:17] good microbiome." Well, prove it.
[122:20] How do we know that? Like, how can you
[122:22] prove that to me as a basic scientist? I
[122:25] want to see the hard evidence.
[122:27] Because what I can prove is that we can
[122:29] take humans who are overweight and
[122:31] diabetic and hypertensive eating a
[122:33] standard American or global diet and put
[122:36] them under a ketogenic diet, which is
[122:38] going to be much simpler
[122:40] diet, and yet every clinical marker gets
[122:42] better. And so, if someone were to say,
[122:44] "Yeah, but sure, you reversed your
[122:46] diabetes and your hypertension, but your
[122:47] poor microbiome." I would say, "Well, I
[122:49] don't care about my microbiome. I care
[122:51] about the human." And so, if there's
[122:53] less diversity, but every single
[122:54] clinical marker has gotten better,
[122:56] perhaps more diversity is not what we
[122:58] want in our bacteria. I'm And I'm
[123:00] speculating, but so are the is the
[123:02] person who states that.
[123:04] Yes, I'm I'm not aware of um research
[123:07] that links the two. Um
[123:10] But I mean, I could always have a look,
[123:11] but um I would
[123:13] I I I was always under the assumption
[123:15] that a more diverse microbiome is a
[123:17] healthier person.
[123:18] I don't know. Yeah, but but do you do
[123:20] you feel healthier now?
[123:22] Um
[123:23] feel healthier. I certainly feel And And
[123:26] it's only been a short amount of time,
[123:27] so I don't know what what my health
[123:29] might look like if I'd done this for
[123:30] like 2 years.
[123:32] Right, cuz then that could be a really
[123:33] sort of deeper change to um
[123:36] my whole composition.
[123:38] for more than 2 years, and they're
[123:39] they're great.
[123:40] Because some of the some of the changes
[123:42] that occur in our health take time. Now,
[123:45] you you show this a lot in your work
[123:46] with insulin resistance, that if you're
[123:48] insulin resistance for 10 years, your
[123:51] brain, I think I read in your work, is
[123:52] like
[123:53] It ages.
[123:54] It ages by an an additional 2 years, is
[123:56] that correct?
[123:57] accelerates the aging.
[123:58] I wonder the same thing with like my gut
[124:00] microbiome. If I'm
[124:02] if my gut microbiome is not diverse, so
[124:05] I have a very sort of narrow diet or,
[124:08] you know, I'm not getting I'm not eating
[124:09] my plants,
[124:11] could it take me a couple of years to
[124:12] really understand the the net negative
[124:14] impact that has on my overall health?
[124:16] It It's entirely possible. Yeah, yeah, I
[124:19] would just I would just ask that we be
[124:21] careful with the assumptions that if
[124:23] there is an an increase in diversity
[124:26] with more plant matter,
[124:28] that's an if. Um is that change
[124:32] beneficial?
[124:33] Are the bacteria that we're now
[124:34] promoting the growth of, are they better
[124:36] for us, or are they just bacteria that
[124:38] exist in order to handle more fiber? And
[124:40] again, the outcome being that it perhaps
[124:43] is just making more gas.
[124:45] Um you know, the more plants you eat,
[124:46] the more gas you have to produce by
[124:48] fermenting more fiber. What if those
[124:49] bacteria are only existing to just eat
[124:52] the fiber and not actually improve the
[124:54] human host at all?
[124:57] Psychotosis.
[125:00] Possible to live in a It's I think one
[125:02] of the important points on ketosis is
[125:04] when I do my blood keto test, I
[125:06] fluctuate wildly. After I've gone for a
[125:08] run, my ketone levels are super high.
[125:10] Sometimes later at night, I'm just on
[125:12] the verge of ketosis sometimes. Um
[125:15] and I think that's interesting because
[125:17] we don't have to live in this
[125:18] necessarily deep state of ketosis the
[125:21] whole time. We can fluctuate uh
[125:23] a little bit in
[125:24] Yeah.
[125:25] Maybe even sometimes drop
[125:26] thought on it is that
[125:28] a person would benefit from some state
[125:30] of ketosis on on a frequent basis. If
[125:33] for no other reason than to really give
[125:35] the brain a heavy dose of just straight
[125:37] energy.
[125:39] Um not that everyone needs to be as
[125:40] strict as perhaps you and I are being at
[125:42] the moment. Um but I would say the more
[125:44] a person has a disorder or a disease
[125:46] that benefits from ketosis, the more
[125:48] than they ought to focus on it. Like if
[125:50] someone has type 2 diabetes, if they
[125:52] adopt a ketogenic diet, they will be off
[125:54] all of their diabetes medications in
[125:55] months. All of them.
[125:58] Um if someone has epilepsy,
[126:01] if they're or migraine headaches, if
[126:02] some of the if from 19
[126:04] uh 13, I think, was the first published
[126:06] report on this. If there's someone who
[126:08] suffers from migraines, as long as
[126:10] they're in ketosis, they may never have
[126:12] another migraine again.
[126:14] I mean, it is completely curative or
[126:15] preventative for the disorder. Same with
[126:17] epilepsy. There many forms of epilepsy.
[126:19] So, depending on the person,
[126:21] they would benefit from being ketosis
[126:23] forever. For everyone else who's just
[126:26] sort of a normal individual who wants to
[126:27] be lean and keep their brain healthy and
[126:30] happy, etc., I would say it's generally
[126:32] prudent to just control your carbs, be
[126:35] mindful of the type of carbohydrate
[126:36] you're eating, and as I said earlier,
[126:38] just try to focus on the carbs that
[126:40] don't come from bags and boxes with
[126:42] barcodes. I'm actually quite liberal in
[126:45] my view when it comes to whole fruits
[126:47] and vegetables.
[126:48] I would say eat them, enjoy them
[126:50] liberally, but then also make sure
[126:52] you're getting some good protein and fat
[126:54] because there's no such thing as an
[126:55] essential carbohydrate. That sounds
[126:57] controversial, but humans do not need,
[127:00] we have no requirement for carbohydrate.
[127:02] We do have requirement for fat and
[127:04] protein.
[127:05] What about artificial sweeteners? It's
[127:07] one of the things that I I'm tempted by
[127:11] when I'm on a ketosis diet is like the
[127:14] soda zeros of the world or the diet
[127:17] sodas of the world. What impact does
[127:19] that have on my insulin levels, etc.?
[127:20] Yeah, yeah, great question. There is
[127:22] such a breadth of of diversity when it
[127:25] comes to sweeteners, from artificial to
[127:27] natural to another rare sugar more and
[127:31] more, you know, there's all these random
[127:32] I'm not random, but a very broad
[127:35] spectrum of molecules that we have
[127:37] developed or found that taste like sugar
[127:40] but don't have the effect of sugar. So,
[127:42] on on the good end are things like that
[127:45] have been shown to have no insulin
[127:47] effect.
[127:48] And so, you know, I appreciate everyone
[127:50] listening letting me kind of stay with
[127:51] that as my framework
[127:53] because people are going to go on and
[127:55] criticize all kinds of other things
[127:56] about other sweeteners, and that's just
[127:58] too broad. That's a topic for a a whole
[128:00] book. With regards to just insulin, on
[128:03] the good end where they have no effect,
[128:05] it would be one as common as aspartame.
[128:07] So, like diet drinks, not the zero
[128:10] drinks,
[128:11] but the diet drinks will have aspartame
[128:13] as the sweetener.
[128:14] Is there a difference?
[128:15] There is a difference, and I'll get to
[128:16] that other one in a moment.
[128:18] So, I should be having diet instead of
[128:19] zero?
[128:19] Well, I personally go to diet rather
[128:22] than zero, um but that's because
[128:24] aspartame is the sole sweetener in the
[128:27] zero in the diet rather and it has no
[128:30] effect on insulin. So too erythritol
[128:33] sorry erythritol is a little right
[128:35] around aspartame is generally a good one
[128:37] but monk fruit extract stevia and
[128:40] especially allulose those are inert when
[128:42] it comes to insulin.
[128:44] You know allulose stevia monk fruit
[128:46] extract
[128:48] aspartame no effect erythritol no effect
[128:51] but erythritol that ending OL
[128:55] is reflective of a class of sweetener
[128:57] called a sugar alcohol and that does not
[128:59] mean it's alcoholic that just refers to
[129:00] the actual chemical structure that puts
[129:02] it in the alcohol family. Once you get
[129:05] into the sugar alcohols you start to get
[129:07] a little problematic.
[129:09] Where erythritol is a good one and
[129:11] xylitol is generally a good one but then
[129:14] you get to things like maltitol and
[129:15] mannitol and they do have an insulin
[129:18] effect.
[129:18] And what what's what kind of foods have
[129:20] they some?
[129:20] Yeah so often like you can get mannitol
[129:24] in like artificially sweetened chocolate
[129:26] sometimes for reasons that I don't know.
[129:28] I don't know why the food formula that
[129:29] puts them in some things and not other
[129:30] things. The
[129:32] the problem I chuckle because it becomes
[129:34] so apparent with some of those
[129:36] artificial sweeteners like the sugar
[129:38] alcohols is that as you eat them you
[129:41] taste it sweet in your mouth
[129:43] and it doesn't have any caloric value in
[129:45] the body because it stays in the
[129:47] intestines.
[129:49] And this is something that is largely
[129:51] unique to the sugar alcohols where as it
[129:53] stays in the intestines it starts
[129:55] pulling in water
[129:57] from the body which starts to create a
[130:00] fairly inconvenient degree of flatulence
[130:02] and diarrhea.
[130:04] And so a person will know if they've
[130:05] eaten too many of those types of
[130:07] sweeteners because their intestines will
[130:09] tell them so.
[130:11] So but also on that spectrum kind of in
[130:13] the middle is the one that's in the zero
[130:15] drinks which is one called sucralose.
[130:19] And while sucralose is generally not a
[130:21] problem with insulin It is a sweetener
[130:24] that has been shown to cross the
[130:25] blood-brain barrier.
[130:27] And so the reason I avoid the zero
[130:29] drinks and refer or go to the diet
[130:32] drinks is that aspartame does no such
[130:34] thing. Aspartame just gets divided into
[130:36] amino acids. We just digest it and
[130:38] absorb amino acids. Sucralose will go
[130:42] can cross the blood-brain barrier and I
[130:44] don't know what it's doing there, but I
[130:45] don't want it there.
[130:47] And so I avoid the zero drinks because I
[130:49] don't want that sweetener.
[130:52] But but personally, um when I'm adhering
[130:55] to this diet, a diet soda is my actual
[130:58] indulgence where I want something sweet
[131:00] um and yet I don't want the metabolic
[131:02] effect of it.
[131:04] One thing you mentioned earlier which
[131:05] I've been thinking a lot about is salt.
[131:07] And I think a lot about salt because I
[131:09] went to the doctor many years ago and I
[131:10] think I was using this like Maggie
[131:11] seasoning that I put on my food. And the
[131:14] doctor said to me that my salt levels
[131:16] were too high.
[131:18] And I And then I've heard since then
[131:20] from other people that we're actually
[131:21] probably not getting enough salt in our
[131:22] diet.
[131:23] Yeah. So I'm interested to hear that
[131:25] your physician would have said your salt
[131:26] is too high. That is very rare that that
[131:29] gets measured. Not salt sodium I think
[131:31] he said. Yep, yep. He could have
[131:32] measured sodium and that could have been
[131:33] higher. They absolutely could have. It's
[131:34] just not common. So salt has
[131:37] has earned a terrible reputation because
[131:40] of a series of studies that implicated
[131:42] salt consumption as a cause of high
[131:44] blood pressure.
[131:46] And and really briefly, as a as a
[131:49] momentary physiology
[131:51] that is a real effect. If you and I were
[131:54] to go eat salt, our body for the next
[131:56] several hours afterwards
[131:58] would retain its water in order to
[132:00] balance out the salt so that we didn't
[132:02] get too salty. So we would retain water
[132:04] in order to keep our salt at a normal
[132:06] level.
[132:08] And so that could be reflected by an
[132:10] elevated blood pressure.
[132:12] Um however, multiple huge studies have
[132:16] found that if you go to a population of
[132:18] humans that have high blood pressure and
[132:21] you tell them you need to cut your salt
[132:23] in order to correct your blood pressure,
[132:25] they may at most move their blood
[132:27] pressure by one or two points. It has an
[132:29] absolutely negligible, irrelevant
[132:32] effect.
[132:34] Um and it's because salt is not a key
[132:36] contributor to blood pressure. It's
[132:37] actually insulin resistance. Insulin
[132:39] resistance will force the body to hold
[132:41] on to salt. Insulin resistance will
[132:43] force the blood vessels to be very
[132:44] constricted. All of which play together
[132:46] to make for a very high blood pressure.
[132:48] So, as much as we have been telling the
[132:50] world that we should be cutting back
[132:52] salt, no, we should have been telling
[132:54] them to cut back on what spikes your
[132:55] insulin, refined starches and sugars.
[132:58] But with regards to salt, it's
[132:59] interesting for me to note where did
[133:02] that whole view come from?
[133:04] Within the United States decades ago,
[133:06] there was a study that was published and
[133:09] they called it the DASH diet. Dietary
[133:12] Approaches to Stop Hypertension, D A S
[133:15] H, the DASH diet. And in the DASH diet,
[133:18] one of the critical changes was to tell
[133:21] people to eat less salt.
[133:25] And when they found that when people
[133:26] adopt a DASH diet, it's amazing, their
[133:28] blood pressure goes down. However,
[133:31] unfortunately, they also tell people to
[133:33] do lots of other things with the DASH
[133:34] diet. Like when they tell someone to go
[133:36] on the DASH diet, they also tell them to
[133:38] eat less sugar and less refined starches
[133:41] and sugars.
[133:42] Well, it's possible, indeed, I would say
[133:46] it's absolutely the case, that what's
[133:47] actually lowering their blood pressure
[133:49] isn't that they cut their salt back,
[133:52] it's that they were cutting their
[133:52] refined starches and sugars back. And
[133:55] it's that that had the main effect. And
[133:57] the cutting the salt was just some
[133:58] innocent bystander. But to put a fine
[134:01] point on it, in human studies,
[134:04] if you have humans cut back their salt
[134:07] considerably, they become insulin
[134:09] resistant.
[134:11] So, you take a healthy group of humans,
[134:12] say you need to eat less salt, and they
[134:15] do so. If you measure them a week later,
[134:17] while they're adhering to this, they
[134:18] will be significantly more insulin
[134:20] resistant than before they ever cut back
[134:23] their salt. It's one of the ironies of
[134:25] the whole scenario where a physician may
[134:28] be telling a patient with high blood
[134:29] pressure, you need to cut back your
[134:31] salt.
[134:32] And they end up eating less salt, and
[134:35] yet their their blood pressure their
[134:36] blood pressure gets worse.
[134:38] It's because the main contributor to
[134:40] high blood pressure is insulin
[134:41] resistance. And by telling them to cut
[134:42] back on their salt, you made them more
[134:44] insulin resistant. And that whole
[134:46] mechanism is because one of insulin's
[134:49] many, many effects is to want the body
[134:51] to hold on to salt and water.
[134:53] And so, if you start cutting your salt,
[134:56] all of a sudden insulin says, well,
[134:58] there's little salt coming in. I need to
[134:59] do what I can to retain whatever salt we
[135:01] do have.
[135:02] And so, it starts retaining salt and
[135:04] water more in order to try to offset the
[135:07] lack of salt coming in. And while
[135:09] insulin's going higher and higher, the
[135:11] body's becoming more and more insulin
[135:13] resistant.
[135:14] So, salt restriction can cause insulin
[135:17] resistance in humans.
[135:19] You talk about four pillars to
[135:22] eating
[135:23] Mhm.
[135:24] in your book Why We Get Sick. You
[135:25] outline these four essential pillars to
[135:27] develop a strategy for maintaining low
[135:29] insulin levels and combating insulin
[135:31] resistance. What are the four pillars?
[135:34] Yes, so when it comes to controlling
[135:36] insulin resistance, the key is to manage
[135:38] macronutrients.
[135:39] And the best way to manage
[135:41] macronutrients is going to be a strategy
[135:42] that helps lower insulin. Lowering
[135:45] insulin is the key to both slow insulin
[135:47] resistance and fast insulin resistance.
[135:49] So, the more the strategy lowers
[135:51] insulin, the more effective it's going
[135:52] to be. And there are poor There are four
[135:55] pillars. So, the first one, control
[135:57] carbohydrates. Second, prioritize
[136:00] protein. Third, don't fear fat.
[136:04] And then fourth, after the first three
[136:06] have been taken care of, four,
[136:08] frequently fast.
[136:10] So, with the first one, very briefly, by
[136:13] control carbohydrates, I mean that it is
[136:15] time to focus more on whole fruits and
[136:17] vegetables. Eat them, don't drink them.
[136:20] And then don't get your carbohydrates
[136:21] from bags and boxes with barcodes. That
[136:23] the more you're opening up a package and
[136:25] getting your chips or your crackers or
[136:27] your cereal or your bread, the more
[136:29] you're going to be spiking your glucose
[136:30] and your insulin.
[136:32] Keep that on the shelves at the grocery
[136:34] store. Focus on whole fruits and
[136:36] vegetables. That's going to be the key
[136:37] for number one, control carbs. Now,
[136:40] while you're eating fewer carbohydrates,
[136:44] you need to eat something. And so,
[136:45] prioritize protein. I would say
[136:47] particularly animal source protein,
[136:50] which is the best source of all of the
[136:52] amino acids that humans need. And then
[136:55] with those proteins will come fat.
[136:57] Don't fear that fat. That's number
[136:59] three. Fat is very satiating when
[137:01] combined with protein. When fat and
[137:03] protein come together, we digest it
[137:05] better.
[137:07] Sometimes people will find that if they
[137:08] just have a scoop of whey protein, it
[137:10] can be very upsetting on their stomach.
[137:13] It's because we're not supposed to eat
[137:14] protein alone. In nature, that never
[137:16] happens. In nature, protein always comes
[137:19] with fat. That's how we should eat it.
[137:21] We digest it better. And human studies
[137:23] have shown that when a human eats pure
[137:25] protein, there is some degree of muscle
[137:27] growth, albeit microscopically
[137:29] minuscule. But when we eat protein with
[137:32] fat, we have significantly greater
[137:34] muscle growth than we do with the
[137:36] protein alone. So, that is the three
[137:38] pillars that encompass the
[137:40] macronutrients or the big parts of our
[137:42] diet. But once a person has done that,
[137:45] then they are well positioned
[137:48] to adopt a strategy, a structured
[137:50] strategy of fasting. And that can be
[137:53] There are as many ways to fast as there
[137:55] are people who want to do it. There's no
[137:57] right way or wrong way. My goal by
[138:00] invoking that fourth principle, and and
[138:02] I do think it should come last once
[138:04] you've learned how to eat better food.
[138:06] Your your your body has adapted to
[138:08] burning its own fat for fuel.
[138:10] But it can take it can take intermittent
[138:13] fasting where it's one meal of the day.
[138:15] You're fasting through it can do where
[138:17] people do alternate day fasting. There
[138:19] are countless different ways to do it.
[138:21] Even if I'm in ketosis?
[138:22] Then you don't need to do it as much cuz
[138:24] you're already lowering your insulin. So
[138:26] if a person's already in ketosis in
[138:28] fact, if a person were in ketosis and
[138:30] frequently fasting
[138:32] depending on how lean they are, it's
[138:33] going to become extremely difficult to
[138:35] retain muscle.
[138:36] Yeah.
[138:37] So those are the four pillars. It will
[138:38] be an extraordinarily effective way to
[138:41] address insulin resistance. But the
[138:42] problem as I started when I
[138:45] that I mentioned
[138:47] is that while these concepts are simple,
[138:49] that does not mean they're easy. Because
[138:52] humans show addiction addictive
[138:55] tendencies to only one macronutrient.
[138:58] Not fats, not proteins.
[139:01] All of the evidence of the neurobiology
[139:02] of addiction in humans points to
[139:04] carbohydrates. It And so as much as I
[139:07] lay out this simple plan, it can be
[139:09] difficult. And this is why
[139:11] this self-discipline required is
[139:13] difficult enough that it's why people
[139:16] find that they have to result in you
[139:18] know relying on drugs for these kinds of
[139:20] things.
[139:22] Physical activity?
[139:24] Mhm.
[139:24] Exercise?
[139:25] Useful for keeping my
[139:28] insulin levels in check?
[139:29] Yeah. Yeah, I'm really glad you brought
[139:31] up exercise. I'm an enormous advocate of
[139:33] exercise.
[139:35] The best exercise to improve insulin
[139:37] sensitivity is the one you'll do. And so
[139:39] if someone listening to this is an
[139:40] 80-year-old grandma
[139:42] if she if her form of exercise is
[139:44] walking around the street down around
[139:46] the block with her girlfriends. But then
[139:48] if someone else has the ability to go
[139:50] cross-country skiing or CrossFit, do it.
[139:53] So the best exercise is the one you'll
[139:54] do.
[139:55] Now having said that
[139:57] the better exercise is the one that
[139:59] you'll do that keeps muscle.
[140:01] Um muscle-building work is going to be
[140:04] minute for minute a more effective way
[140:06] of improving insulin sensitivity than
[140:08] than any kind of aerobic activity. And
[140:10] that's because muscle is the great
[140:12] consumer of glucose.
[140:14] Um and back to the In fact, not only
[140:17] does muscle eat the most glucose from
[140:19] the blood, but it's also how it eats the
[140:22] glucose when it's exercising. So,
[140:24] earlier we talked about how insulin kind
[140:27] of comes and knocks on the door of the
[140:28] muscle cell. And then the muscle cell
[140:30] will open the door and allow the glucose
[140:31] to come in, thereby lowering blood
[140:33] glucose. Unless the muscle is
[140:35] exercising. When a muscle is exercising,
[140:38] and I'm kind of mimicking the
[140:40] contraction and relaxion relaxation of a
[140:42] muscle,
[140:44] when the muscle is exercising, it has
[140:46] its own way of opening those doors. So,
[140:49] there's an insulin-independent
[140:52] method where the muscle cell essentially
[140:55] tells insulin,
[140:56] "Insulin, I know normally I have to wait
[140:58] for you to come and open these doors,
[141:00] but I'm so hungry during this exercise
[141:02] that I'm not going to wait." And so, the
[141:04] doors just open. So, the contracting
[141:06] muscle has its own way to rush to pull
[141:09] the glucose in, which means, of course,
[141:12] that a person's going to have an easier
[141:14] time controlling their blood glucose,
[141:16] which in turn would mean a better time
[141:18] controlling insulin. But,
[141:20] the more muscle a person has, the easier
[141:23] it is.
[141:24] And this could be one of the reasons
[141:26] why, if you look at longevity
[141:29] and look at the markers of muscle
[141:30] strength versus the markers of
[141:33] cardiovascular aerobic fitness,
[141:36] the aerobic fitness markers are terrible
[141:38] predictors of longevity. It's muscle and
[141:40] strength that predicts longevity for
[141:43] multiple reasons, including just the
[141:44] very active living and moving, but also
[141:47] because if you have more muscle, you're
[141:49] going to control your glucose better,
[141:51] which means you're going to control your
[141:52] insulin better. Then you're back to
[141:54] these variables that people use to
[141:55] predict or what are the most accurate
[141:58] indicators of longevity? It's who has
[142:00] the best glucose control. More muscle
[142:02] helps that happen.
[142:04] There's a big debate around whether we
[142:06] should be calorie restricting and
[142:08] low-fat diet, whether we should be
[142:10] calorie restricting in a moderate fat
[142:12] diet, or calorie restricting in a
[142:14] low-carb diet.
[142:16] What's What's your take on that?
[142:18] Yeah, I am unabashedly in favor of
[142:20] carbohydrate restriction. Um I I would
[142:22] say for two reasons.
[142:24] Um that one reason I think that
[142:26] carbohydrates should be the
[142:27] macronutrient that is most scrutinized
[142:29] is because it's the one we eat the most
[142:30] of. 70% of all calories consumed
[142:33] globally come from carbohydrates.
[142:35] That is the one that has the biggest
[142:37] insulin effect. For And that's a problem
[142:39] for all the reasons we've discussed. But
[142:41] two,
[142:43] carbohydrates are not essential. Um this
[142:45] is controversial. People don't like to
[142:47] acknowledge it, but there is literally
[142:49] no biological need that humans have for
[142:52] carbohydrate. Um the In the United
[142:55] States, a report decades ago from the
[142:57] Department of Agriculture looking at the
[143:00] needs of human nutrition,
[143:03] there's a quote there, and I'm not going
[143:04] to get it exactly right, but I'll get it
[143:06] pretty close.
[143:08] It stated in this document that the
[143:09] lower limit of carbohydrate consumption
[143:11] in humans is zero.
[143:14] In other words, there is no such thing
[143:16] as an essential carbohydrate. Now, I'm
[143:17] not saying, "Well, then let's not eat
[143:19] any of them." No. But I am saying, "Why
[143:22] is that the one we focus the most on as
[143:25] 70% of all calories globally are coming
[143:28] from that one?" You're telling me that
[143:29] we Most of what we eat comes from what
[143:31] we don't need. Why not put the focus on
[143:34] the things we do need? There are such
[143:36] things as essential fatty acids. Let's
[143:38] eat fat. There are such things as
[143:40] essential amino acids. So, let's eat
[143:42] protein and make sure we get what we
[143:44] need. And then, on any remainder of the
[143:47] plate, we can get some other things that
[143:49] we want to nibble on, like plants.
[143:51] Why don't we just cycle this off and
[143:53] just take a Zempic then?
[143:54] Ah, yeah, great question. So, the the I
[143:57] have a I have kept my finger on the
[143:59] pulse of the whole field of gut-derived
[144:02] hormones, which is what we talk about
[144:03] with these weight-loss drugs, almost
[144:05] since their beginning. My dissertation
[144:07] work was in a lab, one of the first
[144:09] funded labs to look at these drugs,
[144:11] although in the context of diabetes, and
[144:14] then it's blossomed into the context in
[144:16] the use of obesity. This This is the
[144:19] class of drug, GLP-1 receptor agonist.
[144:21] First of all, what is GLP-1? GLP-1 is a
[144:24] hormone that we all make from our guts.
[144:27] Our small intestine will make GLP-1.
[144:30] We're making it all the time to varying
[144:31] degrees. Some things we eat will result
[144:34] in a higher GLP-1, sometimes it'll be a
[144:37] lower GLP-1. Like, for example, a paper
[144:39] just published a few months ago found
[144:41] that if you have people eat the exact
[144:43] same meal of calories, but lower carb or
[144:46] higher carb, the lower carb version of
[144:48] the meal will increase GLP-1 three times
[144:51] higher in the blood than the high carb
[144:53] version of the meal.
[144:54] Which means that they'll feel
[144:56] Yeah, so then the What So, what's the
[144:57] point? Who cares about GLP-1? One of
[144:59] GLP-1's main effects is to tell the
[145:01] brain that we're full.
[145:03] Okay, so more GLP-1 means
[145:05] More satiety. Yeah, yeah, more GLP-1,
[145:06] less hunger, which is very impactful.
[145:09] In fact, I would be remiss if I didn't
[145:11] mention a study that was published in
[145:13] humans a while ago. They took obese
[145:16] humans and lean humans
[145:18] and had them eat fat
[145:20] and found that like pure fat, and they
[145:22] found that the GLP-1 response was the
[145:23] same. Whether you were lean or obese,
[145:26] you had the same amount of GLP-1. That
[145:28] would suggest that whether you're lean
[145:30] or obese,
[145:31] both of your brains in both of these
[145:33] populations will have the fat and have
[145:35] the same sense of I'm full.
[145:38] It would cuz it was matched with GLP-1.
[145:40] However, when they had these same groups
[145:43] eat pure carbohydrate,
[145:45] the lean group had a robust GLP-1
[145:48] response. Big GLP-1. In other words,
[145:50] they would eat the carbohydrate and say,
[145:53] "I'm full."
[145:54] Cuz GLP-1 would tell them so. However,
[145:56] in the obese group, they ate that exact
[145:58] same amount of carbohydrate and they had
[146:00] an almost negligible GLP-1 effect.
[146:03] They were still hungry.
[146:03] In other words, they would eat the same
[146:05] amount of carbohydrate as their lean
[146:06] counterpart and then just say, "Okay,
[146:08] what's next? I'm still hungry." And so,
[146:11] it is prudent to focus on GLP-1. GLP-1
[146:14] is a powerful hormone that does have an
[146:17] effect on human health.
[146:19] What I feel inclined to comment on is
[146:22] the negative side effects because the
[146:24] only thing we hear about is social media
[146:26] influencers extolling the benefits.
[146:28] And hey, I'm on this weight loss drug
[146:30] and I've lost 50 lb.
[146:32] Someone has to be the voice that says,
[146:34] "Yeah, but what about this?" And there
[146:36] are some significant
[146:38] but what abouts when it comes to these
[146:41] um weight loss drugs. One of them
[146:44] is the loss of muscle mass or lean mass.
[146:46] You've mentioned a couple papers from
[146:48] the New England Journal of Medicine. A
[146:49] paper a couple years ago from what was
[146:52] called the Step 5 trials looking at
[146:53] these drugs.
[146:55] They found that for every 6 lb of fat a
[146:58] person was losing on these drugs,
[147:01] they were losing 4 lb of fat-free mass
[147:04] or lean mass.
[147:05] So, 40% of the weight they were losing
[147:08] uh on these drugs is coming from lean
[147:11] mass, like including muscle and bone.
[147:14] So, there are now case reports of young
[147:16] healthy women who are overweight who go
[147:18] on the drug for some period of time and
[147:20] after they get diagnosed with
[147:21] osteoporosis
[147:23] where they have eroded their bone
[147:25] health. They're losing lean mass. So
[147:27] again,
[147:27] They've eroded that bone health.
[147:29] Yeah, so 40% of the weight that people
[147:32] are losing on these drugs
[147:34] appears to at these high doses is coming
[147:35] from lean mass. So, fat-free mass
[147:38] including muscle and bone. The reason I
[147:40] find that so troubling
[147:42] is that in the UK at 2 years on the drug
[147:46] 69% of people get off the drug.
[147:50] They don't want to be on it anymore. And
[147:52] now imagine this individual. Imagine if
[147:54] you will a 60-year-old woman
[147:56] who's been on the drug. I take that age
[147:58] and that sex on on purpose because it's
[148:00] so hard for her to to grow new muscle
[148:03] and bone. Let's say she's been on this
[148:05] drug for a year and she's lost 20 kilos.
[148:09] Well, 40% of that will have come from
[148:12] her lean mass and 60% of it came from
[148:15] her fat. And then when she gets off the
[148:17] drug
[148:18] now all of a sudden her lean mass, her
[148:21] muscle and bone, that's never coming
[148:22] back. The muscle and bone that she has
[148:24] lost is gone forever probably at that
[148:27] age
[148:27] because we can't at after the age of 60,
[148:30] good luck developing new muscle and
[148:31] bone. But what can come back rapidly is
[148:35] the fat mass.
[148:36] And so at 2 years
[148:38] she decides to get off the drug, which
[148:40] again about 70% of people do, they're
[148:42] going to gain that fat back. But they're
[148:44] not going to gain their muscle and bone
[148:47] back. That is a significant loss that
[148:49] may be depending on their age gone
[148:52] forever.
[148:53] I was scrolling on Twitter the other day
[148:55] and I saw a video go viral, which is now
[148:59] being reported in a bunch of news
[149:01] publications. It was yesterday that I
[149:03] saw um this video go viral. And I'm
[149:05] going to play this video to you. It's
[149:07] from a singer called Avery.
[149:10] And she talks about her experience with
[149:12] Ozempic.
[149:13] I just left the doctor's office. I went
[149:16] to get a checkup
[149:17] because I've been off of the Ozempic for
[149:19] 2 months now and I just wanted to see
[149:22] my body was in better condition, if
[149:23] there were any permanent damages. Kind
[149:26] of in shock right now because I wasn't
[149:28] expecting this.
[149:30] But um I guess Ozempic
[149:33] can cause bone density loss. And I
[149:36] didn't think that that would happen to
[149:38] me because
[149:40] I was only on it for a year.
[149:42] Um but I have significant bone loss. I
[149:45] have osteoporosis
[149:47] and um
[149:48] osteopenia. So, there are There's like
[149:51] several of them that I have.
[149:53] I wasn't expecting that.
[149:55] But, that's what happens if you um
[149:59] if you use Ozempic
[150:01] uh for weight loss and you lose too much
[150:03] weight.
[150:03] Yeah, I wonder.
[150:04] She's so lean.
[150:06] I wouldn't be surprised if she had it
[150:08] even worse than normal because we see it
[150:11] has become I don't mean to suggest this
[150:13] is the case for her.
[150:15] But, you do see people using these
[150:17] weight loss drugs who are already very
[150:19] lean.
[150:20] I mean, I've got a picture of her here.
[150:22] And she does look incredibly lean
[150:24] already.
[150:24] But, see this is what people are doing.
[150:26] They're basically using it to facilitate
[150:28] an eating disorder in the people who are
[150:30] lean. Um this has become so common that
[150:32] there are complaints saying that you
[150:34] know, lean healthy people are getting
[150:35] the prescription and people who are
[150:37] obese and diabetic aren't because of
[150:39] shortages.
[150:40] The more the the leaner I've seen this.
[150:43] I know someone personally who is already
[150:46] a perfectly lean healthy woman
[150:48] and then she now looks sickly.
[150:50] Um and
[150:51] what caused it? Well, she wasn't lean
[150:54] enough.
[150:55] And when you take enough of that drug
[150:57] that you just have no more hunger
[151:00] because of how it's acting at your
[151:01] brain, you do just stop eating. And the
[151:03] malnutrition at least in part is going
[151:05] to cause a loss of lean mass.
[151:08] Um but that also
[151:10] play it it it is even further
[151:13] exacerbated by the mental health
[151:15] problems. Where There was a paper
[151:16] recently published with the use of these
[151:18] drugs finding that people when they
[151:20] begin the drug, their risk of suicidal
[151:23] thoughts doubles. It It up by over 100%.
[151:26] and their risk of major depression
[151:28] triples.
[151:30] And this so as much as we talk about
[151:32] these drugs and we say
[151:34] the drug helps you control your
[151:36] cravings.
[151:38] What it's hap- what it's doing is
[151:40] perhaps reducing your craving for
[151:43] everything. That while you are eating
[151:44] less food, which is resulting in the
[151:46] weight loss, you also are not interested
[151:49] as much in exercise as you used to be,
[151:50] which is going to make it even easier
[151:52] for you to lose your muscle and bone.
[151:54] You're also less interested in hobbies
[151:56] like going to play pickleball with your
[151:58] friends or going out and drinking with
[152:00] the boys. Um so there is this kind of
[152:03] what's reflected across all of their
[152:05] interests is that their cravings for
[152:08] everything starts to
[152:09] decline.
[152:10] In the case of that girl who mentioned
[152:12] that Avery, I've just seen she's
[152:13] uploaded a post that says, "Thanks, my
[152:15] record label told me I was fat. They
[152:17] dropped me. I got addicted to Ozempic."
[152:20] I got addicted to Ozempic and now as a
[152:21] result I have osteoporosis and my bones
[152:24] are as as fragile as wafer cookies.
[152:27] Yeah, it's heartbreaking. Um so now that
[152:30] Obviously, you know, these are claims
[152:32] that she's alleging. Now we don't know
[152:33] the full picture of her health and there
[152:35] might be something more.
[152:36] But we do know
[152:38] based on that one report that 40% of
[152:40] weight loss is coming from fat-free mass
[152:41] and so it isn't people's best interest
[152:43] to be mindful of that tendency and that
[152:45] if they're going to explore the use of
[152:47] the drug to do so responsibly. And and I
[152:49] want to mention that um kind of caveat
[152:53] or angle to everything because I don't
[152:55] want someone listening to me thinking
[152:57] "All right, Ben says I should never
[152:58] touch this and it is uniformly evil and
[153:01] bad." I'm not saying that. I find that I
[153:03] have to speak a little more boldly about
[153:06] the negative consequences because nobody
[153:08] talks about them. What would she have
[153:09] done if she knew about them, for
[153:11] example? No one knows about these kinds
[153:13] of negatives because people want to
[153:14] sweep them under the rug. Now, I believe
[153:18] there is a use case for these drugs,
[153:21] although different from how it's being
[153:22] used currently, in my mind, the best use
[153:25] of these drugs is to help someone learn
[153:27] how to control their carbohydrate
[153:29] addiction because it will help you
[153:31] control your addiction. Sweet cravings
[153:34] goes down significantly within 6 months
[153:37] of the person taking the drug.
[153:39] So, I think in addition to getting
[153:41] proper education, and if I may be so
[153:44] bold, I would say it's those pillars I
[153:45] mentioned earlier. Control
[153:47] carbohydrates, prioritize protein, and
[153:49] don't fear fat. All the more reason
[153:52] prioritize protein and fat to help
[153:53] preserve your muscle and bone.
[153:56] Muscle and bone are not made of
[153:57] carbohydrate. They're made of mus- of
[153:59] protein and fat. Eat protein and fat.
[154:02] Lift weights to keep any of that lean
[154:04] mass you can. Keep the integrity of your
[154:06] bones intact. But, take advantage of the
[154:09] drug helping reduce your cravings for
[154:11] sweet things especially.
[154:13] I would say find the lowest effective
[154:16] dose you can where you are able with a
[154:18] little bit of self- discipline where
[154:20] you're not assigning all of the
[154:22] self-discipline to the syringe that
[154:23] you're going to inject into your tummy.
[154:25] There is value in learning to deny
[154:28] yourself something you know you
[154:29] shouldn't be doing. There's life lessons
[154:31] to learn there. And so, enough of the
[154:34] drug that makes it a little easier for
[154:36] you
[154:37] to overcome your carbohydrate addiction.
[154:40] At the same time,
[154:41] you're learning how to eat well. You're
[154:43] learning how to eat properly by managing
[154:45] your macronutrients and lifting weights.
[154:48] And then over time, ideally I would say,
[154:51] you find that you are able to reduce the
[154:53] dose of the drug and then eventually get
[154:55] off of it entirely.
[154:56] It's worth saying that I I did also
[154:58] search to see if there was a link
[154:59] between Ozempic and bone density, and
[155:01] there was no
[155:03] clear link in the studies that have been
[155:05] done. I I don't know whether there's
[155:06] been a lot of studies done. It says in
[155:08] the studies and reviews semaglutide
[155:09] generally shows no harmful effect on
[155:10] bone mineral density, although rapid
[155:12] weight loss itself can sometimes affect
[155:14] bone health.
[155:15] Yeah, so I actually think it's an
[155:16] artifact. That's a term that we would
[155:18] use as a scientist to say that it's it's
[155:20] an it's an effect that's happening
[155:22] without being a main effect. So, I don't
[155:24] believe the GLP-1 drug is attacking the
[155:26] bone.
[155:27] Yeah.
[155:27] I think it's because the person has just
[155:29] stopped eating and stopped moving.
[155:31] Remember what I said earlier, people
[155:33] find that they're just less interested
[155:35] in doing stuff like going to the gym,
[155:38] for example. Um and so that is probably
[155:41] combining where a little bit of
[155:42] malnutrition
[155:44] combined with a little less physical
[155:46] activity means you're accelerating some
[155:48] lean mass loss.
[155:50] One of the things that this podcast has
[155:52] taught me is that liposuction
[155:54] is
[155:56] dangerous.
[155:57] Do you agree with that statement?
[155:59] I do. From a metabolic perspective, I
[156:01] absolutely do. Um liposuction is not
[156:04] dangerous to fit into the clothes you
[156:06] want to wear, but it's deeply
[156:08] problematic for metabolic health. And
[156:10] that's because, as a reminder, it's not
[156:12] the mass of fat we have that matters
[156:14] most when it comes to metabolic health.
[156:16] It's the size of our fat cells. So,
[156:18] let's imagine an individual who has more
[156:21] fat than they want in some particular
[156:22] part of the body.
[156:24] The best way to help reduce that fat is
[156:28] to shrink your fat cells. So, that's
[156:29] very important for people to realize.
[156:31] When you lose weight, you're not killing
[156:33] fat cells. You're not You're not getting
[156:35] rid of them. You're shrinking them.
[156:37] And small fat cells are very healthy fat
[156:40] cells. They are literally
[156:41] anti-inflammatory. They're releasing
[156:43] hormones that fight inflammation in the
[156:45] body, and they're very
[156:47] insulin-sensitive, which helps the body,
[156:48] by extension, be very insulin-sensitive.
[156:51] So, very healthy. Small fat cells are
[156:53] healthy fat cells. The problem with
[156:55] liposuction is that you are going in,
[156:57] and rather than shrinking the fat cells,
[156:59] you are sucking them out.
[157:01] Now, let's say, like a study that was
[157:03] done in the US in women,
[157:06] they found that when women had
[157:08] liposuction from their buttocks and hips
[157:10] area,
[157:11] um which is where most women gain their
[157:13] weight, which is because of sex hormones
[157:15] telling her body to store that weight
[157:16] there,
[157:17] they may look at that fat on their
[157:19] buttocks and hips and say, "There's more
[157:20] than I want. I'm going to suck it out."
[157:23] So, they do. But, they don't change
[157:25] their habits. So, they're still eating
[157:27] the same way they were before.
[157:29] Essentially, now they have fewer fat
[157:31] cells, but the body wants to store that
[157:34] same amount of fat based on how they're
[157:37] eating. In other words, there's enough
[157:38] insulin telling the body to store a
[157:40] certain amount of fat and there's enough
[157:42] calories to fuel that fat storage.
[157:45] But, the the fat would be saying, "Hey,
[157:48] we don't have all these fat cells in the
[157:49] buttocks and hips like we used to. Let's
[157:51] go somewhere else." And so, it's no
[157:53] surprise that over the ensuing years
[157:55] after she's had liposuction, not only
[157:57] does she not experience any improvement
[157:59] in any health marker. Nothing gets
[158:02] better with regards to her health.
[158:04] And that is again reflective of the fact
[158:06] that it's the size of the fat cell that
[158:07] matters. Maybe she has lost 10 kilos of
[158:10] fat. That might be a little much for
[158:11] liposuction. 6 kilos.
[158:14] And you would say, "Well, you have 6
[158:16] kilos of less fat. Clearly, you're
[158:18] healthier." And yet, they're not at all.
[158:20] Nothing has gotten better. And then, if
[158:22] you follow them over the years, they
[158:24] cannot gain that fat back on their
[158:27] buttocks and hips because it was
[158:28] literally sucked out and adults have a
[158:30] hard time making new fat cells. So, it's
[158:33] no surprise that they start storing more
[158:35] fat in an area that wasn't sucked out,
[158:38] namely their belly. And so, a woman
[158:40] who's gone through liposuction, yes, she
[158:42] will have lost fat by liposuction at her
[158:45] buttocks and hips. But, if she doesn't
[158:47] change her lifestyle habits, the body
[158:49] will take those 6 kilos and say, "Well,
[158:51] I need to store those now somewhere else
[158:53] because you're eating in a way that
[158:55] makes me want to store that much fat."
[158:57] And so, her remaining fat cells that are
[158:59] intact get bigger and store a bigger
[159:01] burden. And so, over time, it's no
[159:04] surprise that health outcomes can start
[159:06] to get worse.
[159:07] By having fewer fat cells, she's
[159:09] increasing the burden that the remaining
[159:12] fat cells have to carry. Not only does
[159:14] that result in a a change in where she's
[159:16] storing fat, namely storing more on her
[159:18] abdomen,
[159:19] but all the fat cells will get bigger.
[159:22] And thus, metabolic health can get
[159:24] worse.
[159:25] We have a closing tradition on this
[159:27] podcast where the last guest leaves the
[159:29] last question for the next guest, not
[159:30] knowing who they're leaving it for. And
[159:32] the question that's been left for you,
[159:33] Ben, is who in your life gave you a
[159:35] chance or believed in you when no one
[159:37] else did?
[159:40] What a fun question.
[159:42] Um thank you.
[159:43] Um
[159:45] probably my wife.
[159:47] Uh frankly, I just adore her. I think
[159:50] about So, when we were newlyweds, uh we
[159:53] got married quite young, if you'll allow
[159:54] me to be a little personal for a moment.
[159:56] We both really wanted a family. We knew
[160:00] that we wanted to be m- uh mom and dad.
[160:04] And she really wanted to be uh a at-home
[160:06] mom, just full-time mom.
[160:08] Which I loved. I benefited. My mother,
[160:11] um who died when I was quite young, she
[160:13] was a full-time mom. And most of my
[160:15] memories come from her being home. When
[160:19] I would come home from lunch or I had a
[160:20] tummy ache and she would come pick me
[160:22] up. And I I mean, I think I thank God
[160:24] for my for my mother, of course, but
[160:26] also for the time I had with her because
[160:29] I had so little.
[160:30] Um and we both really wanted
[160:33] Cheryl to be able to be full-time mom.
[160:35] Mom is just that special.
[160:37] That meant, as a young newly married
[160:40] husband, I was anticipating a future
[160:43] where I would be the sole provider for
[160:45] the family.
[160:46] And it was very daunting, uh very um
[160:51] scary for me as a 23-year-old. That's
[160:53] how old I was when we got married. And I
[160:55] worried, how am I going to provide for
[160:58] my family? And And would look at the
[161:00] trust that my beautiful wife had in me
[161:03] and I felt inadequate. And I I have
[161:06] moments where I remember young Ben in
[161:09] his early 20s as a newlywed and how
[161:12] scared I was and how my wife's ongoing
[161:16] devotion
[161:17] put us in a position where I both make a
[161:20] wonderful amount of money to provide for
[161:22] the family and help secure our future
[161:24] and then at the same time still have a
[161:26] schedule that lets me be really home, to
[161:28] go home early and help one of our
[161:30] daughters with her homeschooling, which
[161:31] I do, to always not go into work until
[161:34] I've made breakfast for the kids and
[161:36] we've had some family time.
[161:38] So, um much of all of it is just this
[161:42] the support of my wife because at any
[161:44] moment if she would have said, "No, I'm
[161:46] done. You got to go get a job right
[161:47] now."
[161:49] I would have.
[161:50] I I love her and respect her enough and
[161:52] even rely on her insight that I would
[161:53] have done it.
[161:55] But she just really believed that,
[161:57] "Okay, Ben, you're not dumb.
[161:59] I didn't marry you for your looks. I
[162:01] think you've got something. I'm going to
[162:02] trust you." And that trust was it was
[162:05] both humbling and scary but also very
[162:07] empowering. And it's given us a
[162:09] beautiful life.
[162:11] Ben, thank you. It's been truly
[162:12] eye-opening and you've answered so many
[162:14] of the questions that I've had for so so
[162:15] long, especially as it relates to
[162:16] ketosis and the broader link between
[162:19] insulin, infertility, pregnancy, PCOS,
[162:23] all of these kinds of things which are
[162:24] topics of conversation amongst my
[162:26] friends and people that I love. Ben,
[162:27] thank you.
[162:28] My pleasure. Thank you.
[162:33] Isn't this cool? Every single
[162:35] conversation I have here on the Diary of
[162:36] a CEO, at the very end of it you'll know
[162:38] I ask the guest to leave a question in
[162:42] the Diary of a CEO. And what we've done
[162:45] is we turned every single question
[162:47] written in the Diary of a CEO into these
[162:49] conversation cards that you can play at
[162:52] home. So, you've got every guest we've
[162:54] ever had, their question, and on the
[162:57] back of it, if you scan that QR code,
[163:00] you get to watch the person who answered
[163:03] that question. We're finally revealing
[163:06] all of the questions and the people that
[163:09] answered the question. The brand new
[163:11] version two updated conversation cards
[163:14] are out right now at the
[163:16] conversationcards.com.
[163:18] They've sold out twice instantaneously,
[163:20] so if you are interested in getting hold
[163:21] of some limited edition conversation
[163:23] cards, I really, really recommend acting
[163:25] quickly.
