Dr. Nathan Bryan Links Nitric Oxide Loss to Chronic Disease

Nathan Bryan 博士指出一氧化氮流失与慢性病存在关联 使用漱口水和抗酸药等日常习惯会阻断一氧化氮的生成，从而导致高血压、勃起功能障碍并加速血管衰老。 Nathan Bryan 博士阐释了一氧化氮（NO）在人类长寿、血管健康及疾病预防中的关键作用，并指出伴随年龄增长的 NO 生成减少是导致高血压、勃起功能障碍和阿尔茨海默病等疾病的重要诱因。他强调，使用含氟牙膏、抗菌漱口水和质子泵抑制剂等常见日常习惯，会破坏内源性 NO 合成所需的口腔微生物群和胃酸通路。此外，Bryan 博士还提出了通过鼻呼吸、红光照射、饮食调整以及保持良好口腔卫生来优化一氧化氮水平的可行方法。 一氧化氮（NO）是一种关键的信号分子，具有舒张血管、改善血液循环、支持能量生成以及动员干细胞进行组织修复的作用。 (0:00) 一氧化氮的生成随年龄增长显著下降，大约从 30 岁开始每十年减少 10% 到 12%，这是引发与年龄相关的慢性疾病的主要诱因。 (4:22) 勃起功能障碍是潜在内皮功能障碍和心血管疾病的早期临床预警信号，堪称“煤矿里的金丝雀”。 (5:24) 接受传统处方降压药治疗的患者中约有 50% 未能达到正常血压，这是因为传统疗法并不能恢复一氧化氮的生成。 (6:39) 一氧化氮缺乏在诱发阿尔茨海默病、糖尿病、代谢功能障碍和心血管疾病中扮演着核心角色。 (17:36)

Physiologist Dr. Nathan Bryan argues that age-related depletion of nitric oxide is an overlooked root cause of cardiovascular disease and chronic illness. He contends that restoring endogenous nitric oxide pathways can mitigate major degenerative conditions, challenging conventional pharmaceutical models focused on lifelong symptom management. Endothelial Decline, Cardiovascular Disease, and Early Warnings (4:22) Nitric oxide (NO) is an endogenously synthesized signaling gas that prompts vascular smooth muscle to relax, widening vessels to regulate perfusion, oxygenation, and nutrient delivery. According to Dr. Bryan, endothelial function declines by 10% to 12% per decade after age 30, dropping production capacity by roughly 50% by age 40 and up to 75% in advanced age. As vessels lose the ability to dilate, arterial stiffness, inflammation, and plaque deposition accelerate. Dr. Bryan identifies erectile dysfunction as the earliest clinical warning sign of vascular deficiency across sexes, reflecting a failure of local blood flow engorgement. Unchecked endothelial loss progresses to hypertension, which affects two out of three American adults. Dr. Bryan notes that 50% of patients prescribed standard antihypertensives fail to control blood pressure because conventional drugs do not restore nitric oxide production. Furthermore, Dr. Bryan claims deficient nitric oxide impairs insulin signaling—fostering metabolic disease—and induces cerebral hypoperfusion, which he argues is the primary driver of Alzheimer's disease before amyloid plaques accumulate. The Oral Microbiome and Dietary Nitrate Conversion (45:53) Humans lack the enzymes required to reduce dietary nitrate from green vegetables into bioactive nitrite. Instead, this conversion relies on commensal nitrate-reducing bacteria living on the tongue. Swallowed nitrite encounters gastric acid to form nitric oxide, which enters systemic circulation to dilate resistance arteries and regulate blood pressure. Consequently, eradicating these oral bacteria abolishes the cardiovascular benefits of nitrate-rich plant foods. Dr. Bryan highlights that common hygiene practices actively disrupt this pathway. He cites clinical findings showing that normotensive young adults using antiseptic mouthwash twice daily experienced significant blood pressure increases—including an individual spike of 26 mmHg—and a loss of the vascular dilation normally triggered by exercise. Dr. Bryan advises tongue scraping to clear stagnant biofilm, but cautions against combining it with antiseptic rinses. He also warns against fluoridated toothpaste due to reported neurotoxic risks, and notes that modern commercial beet powders frequently lack detectable nitrate due to agricultural soil depletion. Biochemical Inhibitors: Sugar, Acid Blockers, and Respiration (63:40) Endothelial nitric oxide synthase (eNOS) is vulnerable to dietary and pharmaceutical interference. Elevated blood glucose causes glycation of eNOS and hemoglobin, structurally locking the enzyme and halting nitric oxide synthesis. Dr. Bryan links this mechanism to the elevated incidence of heart attacks, neuropathy, and non-healing ulcers among diabetics. Concurrently, acid-suppressing drugs such as proton pump inhibitors (PPIs) and H2 blockers disable stomach acid production, impairing gastric nitrite conversion and blocking the absorption of critical micronutrients like magnesium and iodine. Respiratory habits also dictate nitric oxide output. The eNOS enzyme lines the epithelial cells of the nasal sinuses; deep nasal inhalation and the acoustic resonance of humming stimulate this enzyme to release nitric oxide gas into the lungs, dilating bronchioles and pulmonary arteries. Conversely, chronic mouth breathing bypasses upper airway nitric oxide delivery, alters salivary pH, and degrades the oral bacterial communities required for nitrate metabolism. Medical System Incentives and Cellular Longevity (21:39) Dr. Bryan critiques modern healthcare for operating in specialized clinical silos that prioritize chronic symptom management over root-cause resolution. He observes that while the United States spends nearly 20% of GDP on healthcare, it ranks poorly in high-income health outcomes, leaving individuals an average of 13 to 15 years burdened by chronic disease. Under rapid insurance-based fee structures, physicians are constrained to manage symptoms via pharmaceutical polypharmacy rather than addressing foundational cellular signaling. At the cellular level, Dr. Bryan identifies nitric oxide as an essential regulator of three longevity mechanisms: activating telomerase to preserve chromosomal telomeres, stimulating mitochondrial biogenesis, and mobilizing stem cells from bone marrow and adipose tissue to replace senescent cells. While acknowledging that excessive exposure carries risks such as severe hypotension and methemoglobinemia, he argues that restoring functional nitric oxide production through sunlight, moderate exercise, and targeted therapies can reverse biological vascular age. Dr. Bryan concludes that targeted nitric oxide restoration represents a critical shift for preventive medicine, offering a mechanism to halt cardiovascular and metabolic decline. However, his claim that nitric oxide can eradicate conditions like Alzheimer's depends on intervention during early, reversible disease stages before permanent tissue loss occurs, leaving unresolved questions regarding clinical trial validation in diverse human populations.

生理学专家Dr. Nathan Bryan指出，一氧化氮（NO）作为调控血流、氧气输送与细胞修复的关键信号分子，其内源性生成随年龄增长显著衰退，是心血管疾病及阿尔茨海默病等退行性病变的核心推手。他认为现代医学在应对慢性病时忽视了这一底层机制，而过度清洁口腔、滥用抑酸药及高糖饮食等日常习惯正系统性切断人体的NO生成通路。 血管生理机制与随龄衰退的病理连锁 (4:22) 一氧化氮（NO）是一种由人体内源性生成的气体信号分子，与俗称笑气的一氧化二氮（N2O）截然不同。它主要作用于血管平滑肌使其松弛舒张，保障各器官的血流与氧供。人体血管内皮功能自30岁起以每十年约10%至12%的速度衰退；流行病学与人群数据显示，40岁人群的内皮NO生成能力平均较年轻时减半，至70至80岁时降幅可达75%。内皮生成NO能力的丧失会导致血管持续处于收缩与僵硬状态，诱发系统性炎症与动脉粥样硬化斑块沉积。 Dr. Bryan指出，勃起功能障碍（ED）是内皮损伤最早期的临床警示，充当着心血管健康的“金丝雀”。随着缺乏加剧，管壁弹性降低直接导致难治性高血压；他主张约半数服用传统降压药的患者无法达标，主因在于常规药物未能恢复内皮NO。此外，Bryan提出阿尔茨海默病本质上是脑局部缺血与胰岛素抵抗（“3型糖尿病”）引发的血管病变，主张在早期病程中通过恢复NO改善脑血流与糖代谢，有望遏制神经退行性病变进程。 口腔微生态对硝酸盐代谢的关键作用 (38:18) 人类自身缺乏将饮食中硝酸盐还原为亚硝酸盐的代谢酶，这一过程完全依赖舌背表面的共生还原菌群。绿色蔬菜中的硝酸盐被肠道吸收后浓缩于唾液，经口腔细菌还原为亚硝酸盐，随吞咽进入胃酸环境后进一步转化为活性NO，最终进入全身循环调节外周血管阻力。如果缺失这一菌群转化步骤，摄入的膳食硝酸盐将直接随排泄物排出，无法产生任何心血管保护与降压作用。 现代卫生习惯对该菌群构成了严重破坏。一项2019年的干预研究显示，健康受试者连续使用抑菌漱口水7天后，口腔细菌被清除导致血压明显上升，有受试者收缩压飙升26 mmHg达高血压标准，停用4天后菌群与血压才逐步恢复；漱口水同时也会抵消剧烈运动带来的降压效应。Bryan亦警告含氟牙膏可通过口腔黏膜直接吸收氟化物，抑制有益菌并产生神经与甲状腺潜在毒性；他建议日常改用无氟牙膏，采用铜质刮舌板物理清除老化生物膜以改善菌群环境，并严禁在刮舌后立即使用化学杀菌漱口水。 生活习惯干扰与非药物促生路径 (63:40) 不良生活习惯会从多个生化节点直接切断NO的生成。高糖饮食与高血糖会促发非酶糖基化反应，葡萄糖与内皮型一氧化氮合酶（eNOS）结合后将其分子结构刚性锁定，彻底终止其催化功能，这也是糖尿病患者易并发坏疽溃疡与视网膜病变的病理根源。此外，质子泵抑制剂（PPI）等抑酸药阻断胃酸生成，严重破坏胃内亚硝酸盐向NO的酸化转化，并导致镁、铁及维生素B群吸收障碍。Bryan实验室检测还发现，市售脱水甜菜根粉多因土壤贫瘠或过度加工而完全检测不到活性硝酸盐，形同“死甜菜”。 针对NO水平的日常维护，Bryan提出了明确的非药物调节路径：深长鼻呼吸能物理刺激鼻窦上皮细胞的eNOS生成NO气体并吸入下呼吸道，扩张支气管与肺动脉，而口呼吸则丧失该效应并恶化口腔酸碱度；以特定共振频率哼鸣（如冥想唱诵）可利用气流震动促进鼻窦内NO释放；适度接受阳光照射时，紫外线可将结合在蛋白质与金属载体上的NO解离释放，红光与近红外光则能直接促进线粒体生物发生，增强细胞能量合成效率。 医疗激励困境、检测手段与安全阈值 (21:39) 从学术界转向产业转化后，Dr. Bryan对现代商业化医疗体制提出了尖锐批评。他认为现代医学在学科间割裂严重，各专科倾向于按ICD编码开具处方管理局部症状，而非探究亚细胞层面的共有病因（如线粒体功能障碍与NO亏虚）；制药利益导向更偏向于获取长期终身用药的慢性病客户。在临床客观评估上，他推荐采用颈动脉内膜中层厚度超声（CIMT）、血流介导的血管舒张测试（FMD）以及表观遗传时钟来量化个体的血管真实生物学年龄。 关于NO疗法的边界，Bryan强调“剂量决定毒性”，盲目过量补充同样存在临床危险。过量NO会导致全身血管极度舒张引起严重低血压，丧失逆重力向大脑泵血的灌注压，诱发昏厥甚至缺血性脏器衰竭；过高浓度的特定氮化合物还可能将血红蛋白氧化为高铁血红蛋白，使其失去携氧能力导致发绀。任何针对阿尔茨海默病或血管退化的干预，都必须立足于早期可逆阶段并严格控制有效治疗窗口。 Dr. Nathan Bryan断言利用生物技术恢复人体一氧化氮通路将是根除老年慢性病与突破健康寿命瓶颈的核心方向。然而，受试群体生活方式的复杂性、市售补充剂成分的不稳定以及主流医疗系统对终身用药模式的依赖，依然构成了该类疗法全面临床转化的现实阻碍；其能否在早期阿尔茨海默病等重症中展现出稳定的逆转疗效，仍需依赖更多设计严密的大规模人体临床试验证据。

## Background 该视频由 YouTube 频道 The Diary Of A CEO（主持人 Steven Bartlett）于 2025 年 4 月 14 日发布。视频对话围绕知名生物化学家、企业家兼作家 Nathan Bryan 博士展开，深入探讨了他过去 18 年对一氧化氮（Nitric Oxide）的前沿科学研究，并揭示了为何疲劳与慢性退行性疾病并非不可避免的衰老宿命。 ## TL;DR Bryan 博士指出，一氧化氮是调控微循环、氧气输送、干细胞动员与线粒体能量的核心生命分子，其在 30 岁后的断崖式下跌是高血压、勃起功能障碍、糖尿病及阿尔茨海默病等退行性病变的最底层原点。访谈颠覆性地揭露了现代医学体系受利益驱使陷入“多重用药”陷阱，并警告滥用含氟牙膏、抑菌漱口水及抑酸药物正在毁灭合成一氧化氮必不可少的口腔微生物与胃酸环境。通过刮舌板物理清洁舌苔、彻底戒断精制糖、保证鼻呼吸与充足日照，甚至直接补充活性一氧化氮，人们完全有能力逆转血管生理年龄并重构健康寿命。 ## Atmosphere & style 整场对话在严谨硬核的生物化学推导与颠覆认知的震撼揭秘之间从容切换，既有科学家面对现代商业化医疗建制弊端时的直言不讳与愤慨，也饱含其因父亲瘫痪经历而立志救赎疾病的深厚人文温度。主持人 Steven 展现出极强的好奇心与代入感，从最初将一氧化氮误认为“笑气”的懵懂，到面对漱口水推高血压和根管治疗隐患时倒吸一口凉气的真实反应，让听众在层层递进的病理拆解中体验到认知被彻底刷新的警醒与顿悟。 ## Bulletin - [04:22](https://www.youtube.com/watch?v=zECoaEZRRFU&t=262s) 人体一氧化氮生成能力在30岁后每十年断崖式下跌10%至12%，其合成匮乏是心血管硬化、代谢紊乱及阿尔茨海默病等退行性慢性病的最早原发事件，且半数高血压患者对常规处方药无效皆因未对准此核心靶点。 - [43:03](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2583s) 临床试验证实，连续7天每日使用两次广谱抑菌漱口水会彻底摧毁口腔硝酸盐还原菌，导致健康受试者收缩压急剧攀升多达26 mmHg，并完全阻断摄入蔬菜与日常运动所带来的心血管降压获益。 - [51:38](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3098s) 经过根管治疗的牙齿因神经与供血被彻底切除而成为生物学上的死组织，其微管深处滋生的厌氧菌毒素会引发隐匿性颌骨坏死与骨髓炎，并在临床晚期实体瘤患者中呈现出高度的病灶共存关联。 - [01:11:15](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4275s) 全球滥用质子泵抑制剂（PPI）等抑酸药会从根源上破坏胃酸酸性环境，不仅切断了亚硝酸盐质子化转化为一氧化氮的必需通路，更导致镁、碘及B族维生素等微量元素的吸收全面停滞。 ## Key takeaways - [02:17](https://www.youtube.com/watch?v=zECoaEZRRFU&t=137s) 一氧化氮（NO）是血管内皮天然生成的关键气体信号分子，直接调控平滑肌舒张、血流供氧及线粒体代谢，绝非赛车增压或牙科麻醉使用的“笑气”（一氧化二氮，N₂O）。 - [04:22](https://www.youtube.com/watch?v=zECoaEZRRFU&t=262s) 人体血管内皮功能与一氧化氮生成自30岁起每十年衰退10%至12%，至70至80岁时老年人体内合成量相比20岁青年暴跌整整75%。 - [05:24](https://www.youtube.com/watch?v=zECoaEZRRFU&t=324s) 勃起功能障碍（ED）是全身性一氧化氮匮乏的最早临床警报（“矿井里的金丝雀”），本质是微血管内皮细胞失能与隐匿性全身血管病变的先兆。 - [17:35](https://www.youtube.com/watch?v=zECoaEZRRFU&t=1055s) 阿尔茨海默病底层本质是脑局部缺血与葡萄糖无法被摄取利用的血管性病变（3型糖尿病），通过恢复微循环一氧化氮灌注可消除氧化应激并阻断淀粉样蛋白错误折叠。 - [24:18](https://www.youtube.com/watch?v=zECoaEZRRFU&t=1458s) 现代西方医疗体系被高度分割为专科孤岛，受制于商业利润与多重用药陷阱，聚焦于终身药物维持而忽视了细胞线粒体能量衰竭与一氧化氮缺乏这一共同深层病根。 - [29:03](https://www.youtube.com/watch?v=zECoaEZRRFU&t=1743s) 一氧化氮被称为终极长寿分子，能同时支配三大衰老核心支柱：唤醒骨髓与脂肪干细胞靶向迁移分化、激活端粒酶保护端粒长度，以及维持线粒体呼吸链偶联与ATP产能效率。 - [34:23](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2063s) 过量摄入一氧化氮存在明确的毒性监测指标：全身血管过度舒张导致的急性危险性低血压休克，以及血红蛋白被氧化失活的高铁血红蛋白血症。 - [43:03](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2583s) 健康青年连续使用杀菌漱口水仅一周即可人为诱发高血压，心血管疾病风险暴增26%，推翻了百年来牙科学试图无差别扑灭所有口腔细菌的错误教条。 - [45:53](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2753s) 人体自身基因组缺乏硝酸盐还原酶，必须百分之百依赖舌背表面的共生还原菌将蔬菜中的无机硝酸盐转化为亚硝酸盐，经吞咽入胃酸后才可生成活性一氧化氮气体。 - [51:38](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3098s) 根管治疗抽空牙髓血液供给后使患牙沦为无免疫巡查的坏死结构，厌氧菌代谢酸性毒素暗中腐蚀下颌骨，常规抗生素无法送达且普通2D牙科X光片极易漏诊。 - [56:04](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3364s) 氟化物是强效神经毒素与甲状腺抑制剂，且极易通过口腔颊黏膜迅速渗透入血，重塑口腔微生态的首要步骤是停止使用含氟牙膏与含氟漱口水。 - [58:06](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3486s) 使用黄铜刮舌板深层剥离舌面厚重生物膜有助于翻松微生态、营造厌氧还原菌隐窝；但刮舌后若立即使用抑菌漱口水，化学药剂将长驱直入开放孔隙将有益菌赶尽杀绝。 - [01:04:15](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3855s) 高升糖饮食产生的游离葡萄糖具备极强物理黏性，能直接附着并机械锁死一氧化氮合成酶的构象变化，使其丧失电子传递活性并诱发糖尿病坏疽等微循环病变。 - [01:07:08](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4028s) 由于现代农业土壤严重贫瘠化及脱水加工损耗，市售商业甜菜粉绝大多数已成为缺乏活性硝酸盐的“死甜菜”，无法依靠单纯冲服此类补剂代偿体内一氧化氮。 - [01:11:15](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4275s) 滥用质子泵抑制剂（PPI）人为阻断胃酸分泌破坏了亚硝酸盐转化为NO的物理中枢，同时剥夺了人体吸收镁、硒、碘及B族维生素的关键微量元素解离能力。 - [01:15:00](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4500s) 经由鼻腔深呼吸可直接刺激副鼻窦上皮细胞合成释放一氧化氮以扩张肺小动脉并提升血氧，而长期口呼吸会导致口腔过度充氧并改变pH值，彻底毁掉产NO共生菌群。 - [01:17:16](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4636s) 特定频率的低音蜂鸣震颤（Humming）可借助物理共振使呼出气一氧化氮瞬间飙升，但这一物理激活手段的前提是体内的一氧化氮合成酶系统必须处于未损坏的偶联状态。 - [01:18:32](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4712s) 全光谱日光沐浴通过紫外线裂解半胱氨酸键、红外线共振剥离血红素金属中心而释放体内储备的一氧化氮，全面涂抹高倍数化学防晒霜反而切断了这一演化利好。 ## Detailed walkthrough ### [00:00](https://www.youtube.com/watch?v=zECoaEZRRFU&t=0s) 根除阿尔茨海默病与现代医学的盲区 内森·布莱恩博士（Dr. Nathan Bryan）以极其坚定的口吻开门见山地断言：“我完全确信这项研究将能够根除并治愈阿尔茨海默病（Alzheimer's）。”作为一个用数据说话的生物化学家，他深信全球医疗与健康体系的未来正依赖于对一类特定分子的探索——一氧化氮（Nitric Oxide, NO）。 一氧化氮是人体内至关重要的信号分子，负责调节全身的血流动力学与氧气输送。布莱恩博士明确指出，一氧化氮生成能力的减弱，是人类所有衰老相关慢性疾病发生与恶化的最早启动事件。从勃起功能障碍（ED）、糖尿病、阿尔茨海默病，再到作为心血管疾病头号推手的高血压，其根源无不与一氧化氮的匮乏紧密相连。令人震惊的是，在接受常规药物治疗的高血压患者中，有整整 50% 的人血压并未得到实质性改善，这正是因为现有的标准药物从未对准一氧化氮这一核心靶点。 绝大多数普通人甚至从未意识到这种缺失的存在。日常生活中，如果一个人爬不上一段楼梯，或者无法维持 15 至 20 分钟的中度运动，其本质就是一氧化氮严重缺乏。与此同时，市面上绝大多数牙膏和杀菌漱口水正在无情地摧毁口腔微生物菌群，而这些微生物正是人体合成一氧化氮不可或缺的生产线。然而，布莱恩博士直言不讳地指出，由于当今的医药体系本质上是一门商业生意，几乎没有人真正致力于“彻底治愈”疾病，而是不断销售维持性药物。 - 50% 接受处方药治疗的高血压患者对药物无应答，根本原因在于常规疗法未针对一氧化氮机制。 - 无法完成 15–20 分钟的中度运动或爬一段楼梯气喘吁吁，是一氧化氮缺乏的日常直观信号。 - 常见的市售牙膏与漱口水会破坏负责辅助生成一氧化氮的口腔微生物。 --- ### [02:17](https://www.youtube.com/watch?v=zECoaEZRRFU&t=137s) 一氧化氮究竟是什么？澄清与“笑气”的混淆 主持人史蒂芬·巴特利特（Steven Bartlett）坦言，尽管自己平日对各类健康主题有广泛涉猎，但在为本期节目录制做功课之前，他对一氧化氮几乎一无所知。布莱恩博士表示，这正反映了当下科普的断层与他肩负的使命之重。 许多人听到 Nitric Oxide 时，第一反应会联想到赛车游戏（如《极品飞车》）里按下氮气加速按钮瞬间飞驰的“氮气”，或是牙科诊所里用来让人镇静止痛的“笑气”。布莱恩博士特别澄清了这一极其常见的混淆： - **笑气 / 一氧化二氮（Nitrous Oxide, $N_2O$）**：化学式为两个氮原子结合一个氧原子，是一种常用于吸入麻醉与赛车增压的气体。 - **一氧化氮（Nitric Oxide, NO）**：由一个氮原子和一个氧原子结合而成，是人体内源性生成的气体信号分子，是人体基础健康与长寿的关键基石。 ```mermaid flowchart TD accTitle: 一氧化氮与一氧化二氮的本质区别 accDescr: 对比人体关键信号分子一氧化氮和麻醉气体一氧化二氮的化学式与功能 subgraph NO_Card["一氧化氮 (Nitric Oxide)"] NO_Chem["化学式: NO<br>(1 氮 + 1 氧)"] NO_Role["核心功能:<br>• 血管内皮天然生成信号分子<br>• 调控血流量与组织供氧<br>• 动员干细胞与细胞修复<br>• 驱动能量代谢与长寿机制"] end subgraph N2O_Card["一氧化二氮 (Nitrous Oxide)"] N2O_Chem["化学式: N₂O<br>(2 氮 + 1 氧)"] N2O_Role["常见用途:<br>• 牙科吸入式麻醉气体 (笑气)<br>• 赛车引擎短期氮气加速推进"] end ``` 在人体生理机能中，一氧化氮掌控着多条核心生命线：它直接指导血管舒张以调节氧气输送；它动员自体干细胞前往受损组织进行修复并替换衰亡细胞；它提升细胞内部线粒体的能量生成；无论是运动时的器官供血、大脑进行记忆提取时的神经血流，还是性唤起时生殖器官的充分充血，无一不需要一氧化氮的即时调动。布莱恩博士的核心使命就是让大众明白：一氧化氮是什么、身体如何合成它、衰老如何剥夺它的产量，以及最关键的——普通人该如何阻断这一断崖式衰退，主动掌握自身健康。 --- ### [04:22](https://www.youtube.com/watch?v=zECoaEZRRFU&t=262s) 30岁后的衰老断崖：血管内皮功能的退化 当主持人展示出一张人体一氧化氮合成水平随年龄急剧下滑的趋势图，并惊呼“这种断崖式下跌居然从 30 岁就已经开始了（自己恰好就是 30 岁）”时，布莱恩博士证实了这一事实。基于大量人群队列研究显示，人类在 30 岁之后，血管内皮功能（Endothelial Function）每过 10 年就会平均衰退 10% 到 12%。 血管内皮是铺衬在全身每一根血管内壁上的单层细胞。它的核心职责是感知血流剪切应力并释放一氧化氮气体，以此控制血管张力（即调节血管该收紧还是舒张），并监督营养物质、溶质与免疫细胞跨血管壁的渗出和转运。当内皮细胞老化或受损，丧失了制造一氧化氮气体的能力后，血管便无法再正常扩张。随之而来的是血管异常痉挛收缩、慢性血管炎症萌生、动脉硬化增厚以及脂质斑块沉积——这正是动脉粥样硬化与全套心血管疾病的病理原点。 --- ### [05:24](https://www.youtube.com/watch?v=zECoaEZRRFU&t=324s) 缺乏一氧化氮的先兆：从勃起功能障碍到高血压 针对“日常生活中一氧化氮缺乏会表现出哪些症状”的问题，布莱恩博士提出了一个清晰的“症状金字塔”结构。首当其冲的最早信号，往往是勃起功能障碍（ED）。 在生理学上，无论男性还是女性，性冲动与伴侣亲密时的生理唤起完全依赖于靶器官血管的迅速扩张与大量血流涌入——男性阴茎海绵体或女性阴蒂、阴唇的充血膨胀，本质上都是纯粹的一氧化氮介导事件。如果局部血管无法按指令合成释放一氧化氮，血管就无法扩张充血。布莱恩博士将 ED 比作“矿井里的金丝雀”，过去医学界常误将其归结为生活方式或心理障碍，但现代血管生物学早已证实，它是全身性一氧化氮系统衰竭的最早表征，实际上代表着一种极度加速的隐匿性心血管疾病。 如果身体发出的这一早期警报被忽视，病变就会向上级血管系统蔓延，接踵而至的便是不可逆的高血压： ```mermaid flowchart LR accTitle: 一氧化氮缺乏导致高血压与心血管病变的过程 accDescr: 描述从内皮功能受损到血管口径缩小、阻力升高引发耐药性高血压的链条 A["内皮损伤 / NO缺乏"] --> B["血管失去舒张功能<br>持续痉挛收缩"] B --> C["全身血管口径缩窄<br>外周阻力显著增加"] C --> D["相同血容量被硬挤压<br>血压剧烈升高 (高血压)"] D --> E["常规降压药无效<br>(难治性高血压)"] ``` 布莱恩博士解释，人体的血液总容积在一定时间内是相对恒定的，心脏每分每秒都在全力推动这批血液循环。在一氧化氮充沛时，血管口径舒展宽松，阻力极低；一旦失去一氧化氮，同样的血容量被迫流经口径骤缩的“狭窄管道”，依照最基础的流体力学与物理定律，管壁受到的压力（即血压）必然急剧攀升。 - 全美有三分之二的成年人处于不安全的升高血压状态，全球数据也大致类似。 - 传统的一线降压药物（如 ACE 抑制剂、血管紧张素受体拮抗剂 ARB、钙通道阻滞剂等）对半数患者完全不起效，临床上称之为“难治性高血压”（Resistant Hypertension）。 - 难治性高血压的根源在于：这些传统药物并未触及“缺乏一氧化氮”这一核心病理机制，无法从根源上恢复血管内皮的自身舒张功能。 --- ### [08:05](https://www.youtube.com/watch?v=zECoaEZRRFU&t=485s) 人生转折点：诺贝尔奖得主的预言与瘫痪父亲的褥疮 布莱恩博士回顾了自己是如何投身于这一冷门却极为关键的领域的。在 20 世纪 90 年代末至 21 世纪初，他还是路易斯安那州立大学（LSU）医学院的一名一年级年轻研究生。恰逢 1998 年，三位美国科学家因发现一氧化氮在心血管系统中的信号分子作用而荣获诺贝尔生理学或医学奖。 刚获奖不久的诺奖得主之一路易斯·伊格纳罗（Louis Ignarro）受邀来到布莱恩博士所在的医学院向全体师生发表演讲。布莱恩不仅有幸在演讲后与伊格纳罗当面交谈，更在当晚受邀与他共进晚餐。餐桌上，这位刚登上科学巅峰的长者对布莱恩说了一句震撼人心的话： > “如果科学界能够找出恢复人体一氧化氮生成的办法，那将彻底改变整个世界，重塑全球医学的格局。” 当时医学界就已经意识到，一氧化氮生成的枯竭是无数老年慢性疾病的始作俑者。这句来自诺奖得主极具前瞻性的断言，成了点燃布莱恩科研探索的第一个顿悟时刻（Eureka moment）。 而将这一学术追求转化为生死救赎的，则是他家庭内部的切肤之痛。布莱恩的父亲在 1984 年遭遇了一场惨烈的车祸，导致中背部以下高位截瘫，终身依赖轮椅。在布莱恩的整个童年及成长岁月中，他每天都在协助父亲处理下半身的压疮（褥疮，Decubitus Ulcers）与皮肤坏死溃烂。随着年岁渐长，父亲患上了糖尿病、截瘫引发的极度末梢循环障碍以及严重高血压，臀部和足部形成了久治不愈的慢性顽固性溃疡。布莱恩带着父亲跑遍了顶尖的创面修复与褥疮专科医生，面对标准疗法的全盘失效，他下定决心亲自研制外用局部一氧化氮配方，最终在绝境中实现了创面愈合。 ### [10:03](https://www.youtube.com/watch?v=zECoaEZRRFU&t=603s) 父亲的瘫痪与医学体系的无力感 Nathan Bryan 博士分享了一个极具震撼力的临床案例：一名六十多岁、长期久坐、患有糖尿病且下半身瘫痪的男性，腿部有一个长达四年都无法愈合的严重溃疡伤口。然而，通过提供一氧化氮疗法以恢复流向伤口的血流并清除感染，仅仅用了 6 个月时间就彻底治愈了该创面。主持人 Steven Bartlett 随即指出，Bryan 博士早年的成长经历——包括父母离异，以及后来父亲遭遇车祸导致瘫痪——似乎是他选择从医和科研道路的核心驱动力。 Bryan 博士坦承，正是亲眼目睹现代医疗体系在照料父亲时的无能为力，彻底改变了他的人生轨迹。当时他深感困惑与愤怒：人类拥有全世界最先进的医疗技术和最顶尖的医学院，却治不好一个伤口，无法真正逆转高血压，也控制不好糖尿病。这段经历让他坚信现有的“标准治疗”（Standard of Care）存在重大缺陷，必须寻找更好的出路。这也铸就了他如今的心态——每当觉得日子艰难时，只要想到父亲坐在轮椅上的样子，就会意识到自己四肢健全、拥有健康，便会怀揣感恩之心醒来，不再怨天尤人。 - 治愈案例：一名瘫痪且患糖尿病的六旬老人，其长达 4 年不愈的伤口通过一氧化氮改善血流与杀菌，在 6 个月内完全愈合。 - 个人心力源泉：父亲因车祸瘫痪后饱受病痛折磨，而主流医学的束手无策促使 Bryan 博士立志寻找从根本上解决慢性病的方法。 --- ### [11:52](https://www.youtube.com/watch?v=zECoaEZRRFU&t=712s) 从学术巅峰到产业转化 面对主持人关于其学术背景的询问，Bryan 博士梳理了自己深厚的专业履历。他获得了分子与细胞生理学博士学位，随后被诺贝尔生理学或医学奖得主 Ferid Murad 教授亲自招募，进入坐落于休斯敦的德克萨斯大学健康科学中心（UTHealth Houston）分子医学研究所担任教授。那里是全球规模最大的医疗中心枢纽。 在学术界深耕的岁月里，Bryan 博士在同行评审期刊上发表了 100 多篇高水平学术论文，编撰了多本关于一氧化氮的医学教科书，并长期在医学院执教。然而，在 COVID-19 疫情期间，他决定辞去教职离开学术界，迈入职业生涯的下一阶段。他意识到，光把知识留在象牙塔里还不够，必须将这 25 年的科学探索与重大发现转化为安全、有效的大众消费品、医疗技术及创新药物，从源头上根除当今困扰全人类却缺乏有效手段管理的慢性疾病。 --- ### [12:58](https://www.youtube.com/watch?v=zECoaEZRRFU&t=778s) 血管舒张机制与“衰老”的假象 主持人试图用直白的语言复述一氧化氮的作用机制：它是不是血液中的一种化学物质，能让血细胞像气球一样扩张，从而让血液顺利通过？Bryan 博士立即进行了精准纠偏：一氧化氮并不是直接作用于血细胞本身，而是由血管内皮细胞释放，作用于环绕在血管壁周围的“平滑肌”（smooth muscle）。当平滑肌接收到一氧化氮信号后会发生松弛，从而使整个血管管径舒张（dilation），血流量因此成倍增加；一旦一氧化氮不足，平滑肌紧缩，血管无法舒张，血压便随之升高，引发一系列下游疾病。 随后，主持人提出了一个许多人心中的核心疑虑：数据显示，人类在 20 岁左右一氧化氮水平处于巅峰，而在 30 岁至 70 岁期间会出现 80% 至 90% 的悬崖式暴跌，这难道不是人体自然衰老的“必然结果”吗？Bryan 博士指出，这种观点是倒果为因。衰老的本质，是人体修复和替换受损或失能细胞的能力衰退；而一氧化氮在 2007 年被其团队首次证实具备激素（hormone）的属性。科学证据确凿表明：“一氧化氮生成的丧失，是年龄相关慢性疾病发生与发展的最早事件。”换言之，这一生理衰退并非不可逆转的宿命，人们完全可以通过干预手段将衰老曲线向左推迟或向右拉平。 ```mermaid flowchart TD accTitle: 一氧化氮与血管调控及衰老病理机制 accDescr: 展示一氧化氮作用于血管平滑肌的正常舒张过程，以及生成不足时导致的病理级联反应。 subgraph NormalPathway["正常生理机制"] A["血管内皮生成一氧化氮 (NO)"] --> B["作用于环绕血管的平滑肌"] B --> C["平滑肌充分松弛与管径舒张"] C --> D["血流通畅、营养输送、组织代谢正常"] end subgraph DeficiencyPathway["缺乏与病理级联"] E["NO 随年龄/生活方式暴跌"] --> F["血管平滑肌持续紧缩狭窄"] F --> G["阻力增大导致高血压"] G --> H["不可逆组织缺血与细胞失能"] H --> I["慢性病全面爆发 (衰老加速)"] end ``` - 年轻人现状警示：如今在临床中频繁看到 18 至 20 岁的青少年患上高血压、糖尿病、勃起功能障碍（ED）甚至认知障碍，这些全是一氧化氮过早枯竭的典型指征。 - 逆龄案例：许多五六十甚至七十岁的人群在科学干预下，血管状态宛如三四十岁；Bryan 博士本人现年 51 岁，但其血管生理年龄仅相当于 36 岁。 --- ### [15:52](https://www.youtube.com/watch?v=zECoaEZRRFU&t=952s) 如何客观评估人体的“血管年龄” 当被问及如何测定自己拥有 36 岁的血管年龄时，Bryan 博士解释了评估生物学年龄（Biological Age）与实际日历年龄（Chronological Age）差异的几项成熟客观指标。现代医学已经建立了庞大的健康数据库，可以将个体的生理指标与同龄群体进行精准比对： 1. **颈动脉内膜中层厚度（CIMT, Carotid Intima-Media Thickness）**：通过超声波扫描颈动脉，检测内膜厚度及平滑肌增生情况，并与同龄人大数据库进行横向对标。 2. **血流介导的血管舒张功能（FMD, Flow-Mediated Dilatation）**：评估血管内皮在应激血流下的自主舒张反应能力，直接量化内皮功能健康状态。 3. **表观遗传与生化标记物**：如组蛋白修饰、DNA 甲基化图谱，以及类似 GlycanAge（利用聚糖标记物分析全身慢性炎症与生物学年龄的检测技术）。 根据 Bryan 博士书中的数据，人体在 40 岁时，血管生成一氧化氮的能力已经流失了约 50%；在此之后，每过十年还会继续损失 10% 到 12%。一项来自日本的临床对照研究表明，70 至 80 岁老年人的血管一氧化氮生成量，相较于 20 岁的年轻人减少了整整 75%。 --- ### [17:35](https://www.youtube.com/watch?v=zECoaEZRRFU&t=1055s) 一氧化氮枯竭引发的慢性疾病图谱与阿尔茨海默病 随后，Bryan 博士梳理了一氧化氮缺乏引发的系统性“慢性病清单”： - **勃起功能障碍（ED）**：在美国，40 岁以上男性中有 50% 自我报告患有 ED。Bryan 博士认为实际比例更高，因为绝大多数 40 岁的男性往往因为自尊心而隐瞒该病情。 - **难治性高血压**：临床上 50% 正在接受降压药处方治疗的患者，其血压并未得到有效控制。而高血压是引发心血管疾病（全球头号死因）的首要危险因素。 - **代谢综合征与糖尿病**：Bryan 博士团队于 2011 年发表里程碑论文证实，一氧化氮是胰岛素信号传导的“必需底物”；一旦细胞无法生成一氧化氮，就会直接形成胰岛素抵抗。目前全美有十分之九的人处于代谢不健康状态。 - **运动不耐受（Exercise Intolerance）**：如果一个人爬一层楼梯就气喘吁吁，或者无法维持 15 到 30 分钟的中度运动，本质上就是组织严重缺乏一氧化氮导致的灌注不足。 在谈到神经退行性疾病时，Bryan 博士强调**阿尔茨海默病本质上是一种血管性疾病**（曾被称为“3 型糖尿病”）。其病因链条极为清晰：首先是脑部局部缺血（Focal Ischemia）与血流骤减，导致葡萄糖无法被脑细胞摄取利用（缺乏主要能量基质）；紧接着出现严重的氧化应激与免疫功能失调，细胞能量衰竭后无法维持蛋白质的正常折叠，最终沉淀为临床上看到的淀粉样蛋白斑块（Amyloid Plaques）和神经原纤维缠结（Tangles）。 Bryan 博士斩钉截铁地表示，他坚信一氧化氮气体分子能够彻底根除并治愈阿尔茨海默病。因为一氧化氮能同时击中该病的所有生理底层病根：它能瞬间恢复脑部微循环血流，促进葡萄糖摄取，强效抗炎并阻断氧化应激，纠正免疫紊乱；只要脑血流重新畅通，废物被运走，营养源源不断进入，蛋白质就不会错误折叠，斑块和缠结根本无从产生。 针对这一激进观点，主持人追问这是否意味着必须在疾病极早期就介入。Bryan 博士确认了这一点，指出任何临床药物试验的成败，完全取决于试验方案设计中何时将患者纳入（即入组与排除标准）。任何疾病（无论心血管病、肾衰竭还是脑退行）都有一个“不可逆点”（Point of no return），一旦神经元大面积死亡坏死，任何疗法都无力回天。因此，他们的研发重心瞄准了处于“血管性痴呆”、“轻度认知障碍”（MCI）及极早期阿尔茨海默病的患者群，力求首先验证其能否彻底阻断疾病的病理恶化进程。 ### [21:11](https://www.youtube.com/watch?v=zECoaEZRRFU&t=1271s) 治愈疾病的初衷与学术界的顿悟 在临床研究中，最理想的目标永远是实现疾病的逆转（regression），而最底线也是阻止其继续恶化。Dr. Nathan Bryan 指出，现代医学疗法的终极意义本应建立在彻底厘清疾病发病机制的基础上，从而达到预防、治疗、逆转乃至彻底治愈。当主持人 Steven Bartlett 问及 Dr. Bryan 是否持有一些被传统医学界与主流媒体所忽视甚至抵触的观点时，Dr. Bryan 坦言自己始终站在客观科学数据与真理的一边。主持人提到，Dr. Bryan 在以往的许多采访中经常直言“他们根本不想让你知道这些”，这种反叛传统的姿态引起了极大共鸣。 Dr. Bryan 回忆起促使他思维发生根本性转变的“顿悟时刻”（Eureka moment）。当时他身处学术界，在德克萨斯大学医学院（UT Medical School）执教并从事科研。一个困扰整个生物医学界的核心矛盾摆在眼前：科学界几乎已经在小鼠和大鼠身上攻克并治愈了人类已知的所有疾病，但为什么这些惊人的突破在转化到患者临床治疗时却屡屡受挫？他解释道，动物实验中科研人员可以绝对掌控其生活环境、饮食结构、昼夜节律及生命周期；而在现实世界中，每个患者的饮食、用药史和卫生生活习惯都千差万别，这种高度复杂的异质性使得实验室成果极难直接落地。 - **临床试验的层次目标**：最低目标是遏制疾病进展（Stop progression），最高追求则是实现病变组织的逆转与复原（Regress disease）。 - **动物模型与人体的鸿沟**：科学界在啮齿类动物中治愈了绝大多数疾病模型，但受限于环境受控度、饮食多样性以及个体生活方式差异，临床转化率极其受限。 --- ### [23:06](https://www.youtube.com/watch?v=zECoaEZRRFU&t=1386s) 医学孤岛与 MD 安德森的残酷现实 在学术界工作期间，Dr. Bryan 曾满怀激情地试图建立一个跨学科的卓越中心（Center of Excellence）。他敏锐地观察到西方现代医学已被严重“割裂成孤岛”（siloed）：心脏不舒服去看心脏科医生，肠胃不适去挂消化内科，神经或精神症状则求助于神经科或精神科医生。然而，各专科之间互不沟通，同一位患者在不同科室面对的是截然不同、甚至相互冲突的治疗方案。Dr. Bryan 提出疑问：如果这些不同器官表现出的疾病，本质上源于完全相同的深层细胞根源呢？人体所有代谢与功能都始于亚细胞水平的线粒体能量生成，既然病源同源，就理应把遗传学、神经科、心血管科、肾脏科、呼吸科和胃肠科专家召集在同一间屋子里，共同攻克这台精密的生理轮轴。 然而，当他真正接触到诸如世界顶尖的 MD 安德森癌症中心（MD Anderson Cancer Center）等机构的运作模式后，现实给了他当头一棒。他震惊地发现，在这套庞大的医疗建制内部，“根本没有人对彻底治愈癌症或人类疾病感兴趣”。医学不仅是一项学术研究，它早已演变为全球规模最大的营利性商业体系。 ```mermaid flowchart TD accTitle: 现代西方医学的分裂模式与综合细胞根源对比 accDescr: 对比传统专科割裂孤岛与以线粒体能量和一氧化氮为核心的整合医学模式 subgraph Siloed["传统西方医学专科孤岛"] Cardio["心血管科 (Cardiology)"] Neuro["神经科 (Neurology)"] GI["消化科 (Gastroenterology)"] Nephro["肾脏科 (Nephrology)"] end subgraph RootCause["深层病理根源 (亚细胞机制)"] Mito["线粒体功能障碍与能量匮乏 (ATP Production)"] NO_Def["一氧化氮缺乏与微循环受阻"] end Mito --> Siloed NO_Def --> Mito ``` --- ### [24:18](https://www.youtube.com/watch?v=zECoaEZRRFU&t=1458s) 医疗商业帝国与多重用药陷阱 Dr. Bryan 直言不讳地揭露，医疗保健产业是一个年产值数万亿美元的超级庞然大物。作为商业社会的一员，人人都懂得企业运营的第一法则——“获取客户并尽可能长久地留存客户”，即最大化客户的终身价值（Lifetime Value, LTV）。而在现代医疗体系中，病人就是那个被捕获的“客户”。医生首先为你开具某种药物，该药物产生副作用后，再开第二种药物来对抗前一种药的不良反应；接着，这种多重用药（Polypharmacy）引发了更复杂的并发症，于是第三、第四种药物接踵而至。到了五六十岁，许多普通人每天不得不吞下 10 种、12 种甚至 18 种不同的处方药。 这种模式从商业回报来看是“世界上最完美的财务飞轮”，但其代价却是全人类健康的慢性透支。Dr. Bryan 指出，大型跨国药企不仅出资资助并深刻影响着《美国医学会杂志》（JAMA）、《新英格兰医学杂志》（NEJM）等顶级学术期刊的评审与发表风向，还通过政治献金深度介入国家卫生政策与监管机构的制定。更令人触目惊心的是美国食品药品监督管理局（FDA）与大药企之间公开的“旋转门”机制——在过去二三十年间，几乎每一位离任的 FDA 高级官员，最终都会入职大型药企担任董事或领取数百万美元的高额年薪。 - **多重用药恶性循环**：初始用药 $\rightarrow$ 引发药物副作用 $\rightarrow$ 开具对冲药物 $\rightarrow$ 产生复合毒副反应 $\rightarrow$ 演变为终身依赖数十种药物。 - **监管与资本的旋转门**：FDA 往往成为通往大药企高薪董事会职位的跳板，导致体制无法容忍“帮助患者停药”（Weaning off drugs）的声音，因为任何减少用药的行为都在侵蚀这些制药巨头的千亿市场份额。 - **资源错配与健康悖论**：美国将近 20% 的国内生产总值（GDP）投入到医疗卫生中，然而在所有高收入国家中，美国的整体健康结局却排名垫底，甚至面临最低的人均预期寿命与最高的婴儿死亡率。 --- ### [27:08](https://www.youtube.com/watch?v=zECoaEZRRFU&t=1628s) 戴着镣铐起舞的医生与被剥夺的健康寿命 Dr. Bryan 特别澄清，他不愿将矛头对准一线临床医生。他曾担任德克萨斯大学医学院招生委员会委员多年，深知绝大多数踏入医学大门的热血青年并非为了暴利，而是怀揣着改变世界、探寻科学奥秘和救死扶伤的崇高理想。然而，现行的医疗制度从入职第一天起就彻底给医生“戴上了手铐”。医院的计费与偿付机制完全受制于国际疾病分类（ICD-10）编码系统——医生必须先给出一个明确的疾病诊断代码，才能触发保险报销与工资支付。 在这样的流水线工厂模式下，医生必须严格按照既定指南开药，根本没有空间去探寻深层病因。为了覆盖昂贵的诊所管理成本，普通医生平均每天必须接诊 60 到 80 位患者，分配给每个人的面诊时间被压缩到仅剩几分钟。诊室里配有速记员，医生快速打勾、下诊断、开药，然后机械地交代一句：“吃两周药，不行再回来换更强的药。”数据是残酷而真实的：美国人平均有约 13 年的生命是在受慢性疾病折磨的状态下度过的，这一健康恶化跨度远高于其他发达国家。这正是为什么医学界亟需将目光从单纯追求寿命长短（Lifespan）转移到“健康寿命”（Healthspan）上——没人希望活到 100 岁，却有整整 25 年躺在床上穿着纸尿裤、完全丧失自理能力。 --- ### [29:03](https://www.youtube.com/watch?v=zECoaEZRRFU&t=1743s) 为什么说一氧化氮是“终极长寿分子”？ 面对健康寿命的挑战，Dr. Nathan Bryan 将一氧化氮（Nitric Oxide, NO）定性为维持人类活力的“长寿分子”（The Molecule of Longevity）。他阐述了界定衰老与长寿的三大核心客观生理支柱，并阐明了一氧化氮如何在最底层发挥决定性支配作用： ```mermaid flowchart TD accTitle: 一氧化氮调控长寿的三大生物学支柱 accDescr: 展示一氧化氮如何作为上游核心信号调控干细胞动员、端粒稳定性以及线粒体呼吸功能 NO["一氧化氮 (Nitric Oxide) 核心生物信号分子"] subgraph Pillars["长寿的三大生物学支柱"] direction TB P1["1. 干细胞动员与分化 修复衰老/受损组织 (对抗僵尸细胞/衰老细胞)"] P2["2. 端粒长度维护 防止染色体末端磨损 (调控细胞复制极限与寿命)"] P3["3. 线粒体功能与ATP合成 维持电子传递链偶联 (防止线粒体数量与活性衰退)"] end NO -->|"动员骨髓与脂肪干细胞"| P1 NO -->|"维持端粒酶及结构稳定性"| P2 NO -->|"维持内膜偶联与能量代谢"| P3 ``` 第一大支柱是**多能干细胞（Pluripotent Stem Cells）的动员与再生**。再生医学的核心在于调动体内自身的干细胞，让它们迁移到受损部位修复并替换坏死细胞。无论是来自骨髓的干细胞，还是来自脂肪组织的基质血管组分（Stromal Vascular Fraction, SVF），多能干细胞都可以按需分化为心肌细胞、神经元、巨噬细胞或各类白细胞。随着年龄增长，骨髓内的干细胞储备逐渐耗竭，尽管人体脂肪沉积增多使得脂肪干细胞数量尚存，但衰老的最大致命伤在于“机体失去了动员自身干细胞的能力”。失去修复信号后，体内充斥着无法工作却持续分泌炎症因子的“僵尸细胞”（即衰老细胞 Senescent Cells）。而**一氧化氮正是体内唤醒、动员干细胞并指导其定向分化的初始触发信号**。 第二大支柱是**染色体末端的端粒（Telomeres）长度**。Dr. Bryan 用鞋带末端的塑料封套（Aglet）作比喻：端粒就像保护鞋带不散架的保护套，染色体端粒越短，预期寿命越短；端粒越长，健康寿命越持久。一旦端粒耗尽，细胞分裂就会停滞并走向凋亡。 第三大支柱是**线粒体生物发生与功能状态（Mitochondrial Function）**。在一切与衰老相关的慢性病中，单个细胞内的线粒体绝对数量均显著下降，且残留的线粒体往往发生线粒体内膜电子传递链的“解偶联”（Uncoupling），导致三磷酸腺苷（ATP）的生成效率暴跌。一氧化氮是维持线粒体呼吸链偶联、微循环氧气输送与能量稳态的核心调控分子。没有充足的一氧化氮，干细胞无法响应呼唤，组织修复彻底停摆，机体只能在细胞能量枯竭中加速坠入衰老深渊。 ### [32:13](https://www.youtube.com/watch?v=zECoaEZRRFU&t=1933s) 一氧化氮与长寿：端粒酶、线粒体与干细胞 随着机体衰老，循环干细胞的数量会不断减少。一氧化氮（Nitric Oxide, NO）在细胞中扮演着至关重要的调控角色：它能够激活端粒酶（telomerase），从而防止染色体末端的端粒缩短；缺乏一氧化氮时，端粒酶无法被有效激活，端粒便会加速磨损。与此同时，一氧化氮也是细胞内启动线粒体生物合成的关键信号，它指令细胞生成更多线粒体，并提高线粒体能量转换效率，使其用更少的氧气产出更多的细胞能量（ATP）。 通过恢复体内的一氧化氮水平，机体能够同时改善干细胞活性、维持端粒长度并优化线粒体功能。正如 Nathan Bryan 博士所强调，人体内没有任何其他单一分子能够同时精准覆盖这三大长寿核心支柱。 ```mermaid flowchart TD accTitle: 一氧化氮对长寿机制的调控途径 accDescr: 展示一氧化氮如何通过激活端粒酶、线粒体合成和改善干细胞循环来延缓衰老 NO["恢复一氧化氮水平 (Nitric Oxide)"] --> Telo["激活端粒酶 (Telomerase)<br/>防止端粒缩短与基因损伤"] NO --> Mito["促进线粒体增生与优化<br/>以更少耗氧生成更多细胞能量"] NO --> Stem["维护血液循环干细胞<br/>保持组织再生修复活力"] Telo --> Long["实现机体长寿与延缓衰老"] Mito --> Long Stem --> Long ``` --- ### [32:45](https://www.youtube.com/watch?v=zECoaEZRRFU&t=1965s) 对 Bryan Johnson 及生物黑客圈的看法 主持人提到了硅谷著名的抗衰老探索者 Bryan Johnson，并询问 Bryan 博士如何看待他的做法。Bryan 博士直言自己绝不会效仿其方案，也不认为那是一种合理的方式。尽管他不想专门批评某个人，但如今整个“生物黑客”（Biohacking）领域存在普遍隐患：许多既无科学背景、又无医学或生物化学专业训练的博主，凭借网络影响力对数百万人发号施令，给出极为糟糕的建议。这通常不是出于恶意，而是源于“无知”。 Bryan 博士郑重提醒受众：在追随任何健康博主或生物黑客前，首先要审查他们的专业资历。如果对方是前科技从业人员或完全脱离生命科学背景，就必须对他们推崇的理论做深入的事实核查。尽管 Bryan Johnson 本人十分推崇一氧化氮对心血管健康和抗衰的益处，但生物黑客圈内仍有一些坐拥数百万粉丝的知名人物宣称“一氧化氮是一种会阻断线粒体呼吸的毒素，必须彻底避免”，这种谬论反映出对生物化学机制的极度脱节。 --- ### [34:23](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2063s) 一氧化氮会过量中毒吗？两项关键毒性指标 针对公众对“过度补充一氧化氮是否会导致中毒”的担忧，Bryan 博士给出了肯定的回答。正如“剂量决定毒性”（dose dictates poison），即使是维持生命不可或缺的水，若短时间内饮用过量也会引发低渗性裂解（低钠血症/水中毒）致命。因此，在开发与使用一氧化氮产品时，必须严格把控剂量边界以维护整个学术与临床领域的声誉。幸运的是，一氧化氮在生物体内的过量表现仅有两项非常明确的毒性指标： - **血压发生危险性暴跌**：作为强效血管舒张剂，过量的一氧化氮会导致全身血管系统剧烈扩张。相同的血容量在骤然扩张的“管道网络”中流动，会导致灌注压急剧下降。由于无法克服重力维持向大脑供血，患者首先会感到头晕目眩，随即昏厥休克；若低灌注状态持续，将直接导致末端器官缺血性损伤、多器官衰竭甚至死亡。 - **高铁血红蛋白血症（Methemoglobinemia）**：过量一氧化氮会将血红蛋白中的亚铁离子氧化为三价铁，剥夺其携带氧气的能力。患者会出现缺氧发绀（紫绀），如口唇呈蓝紫色、四肢末梢因缺血缺氧而惨白。 在实际临床与生活中，血压骤降的出现远远早于高铁血红蛋白的积累。因此，一旦出现明显的低血压反应，机体便已发出了最早期的过量预警。 --- ### [36:18](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2178s) 端粒缩短与一氧化氮在基因层面的调控 科学研究早已证实端粒长度与生存期密切相关：端粒偏短的个体其死亡率几乎是端粒较长者的两倍。Bryan 博士解释，一氧化氮对端粒的保护是在细胞核及 DNA 层面实现的。研究表明，一氧化氮会与雌激素受体产生共定位（colocalization），从而在转录与翻译层面开启端粒酶的合成表达，并同步调节该酶的催化活性。如果缺乏一氧化氮，细胞内端粒酶的合成量骤降，残存的酶也缺乏功能活性。 在每一次细胞分裂复制的过程中，端粒都会自然磨损。只要端粒酶处于活性状态，就能抵御染色体末端序列的丢失与损伤。不同组织器官的细胞更替速率截然不同：例如暴露于外部环境的肠道上皮组织具有极高的自我更新与再生频率；而脑神经元细胞虽然传统认为无法再生（现代科学证实仍具备微弱新生能力），更新却极为缓慢。但无论何种器官系统，数据铁证如山：“端粒越短，寿命越短”。 --- ### [38:18](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2298s) 一氧化氮与口腔微生物组的共生平衡 在深入探讨如何安全有效地提升一氧化氮之前，Bryan 博士重点指出了口腔微生物组与一氧化氮之间密不可分的共生关系。大约在二十年前，“人类微生物组计划”完成了对人体各部位微生物的宏基因组测序，从消化道、皮肤表面到女性阴道，各类微生物群落与宿主形成了高度互利的共生生态系统（Symbiosis）：宿主为细菌提供生存温床，细菌则行使人体自身无法完成的关键生理功能。 如果滥用抗生素或强力杀菌剂彻底剿灭这些共生菌群，人类必然疾病缠身： - **微生物是机体的“巡逻警察”**：人体内细菌细胞的绝对数量是人类自身细胞数量的 10 倍左右，这意味着在微观层面，我们有九成是“细菌形态”。这支庞大的微生态军团筑成了抵御外敌的第一道防线。 - **抗生素滥用的惨痛代价**：全世界没有任何合格的医生会建议患者终身每天服用广谱抗生素。因为抗生素在杀灭致病菌的同时，会毁灭全部有益菌群，引发肠漏综合征、自身免疫性疾病、白色念珠菌与寄生虫泛滥、阿尔茨海默病以及高血压等一系列系统性血管疾患。 --- ### [40:39](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2439s) 过度清洁的恶果：“卫生假说”与氟化物、杀菌漱口水隐患 Bryan 博士对当代社会病态的“无菌偏执”表达了强烈担忧，尤其是疫情后全社会对消毒洗手液和抗菌漱口水的盲目依赖。许多父母极力想让孩子一尘不染，但这其实剥夺了免疫系统的成熟机会。“卫生假说”（Hygiene Hypothesis）在流行病学调查中已得到充分证实：在乡村自然环境中成长、经常在泥土中翻滚、接触大量多样化微生物的孩子反而最健康，成年后心血管疾病、糖尿病以及自身免疫疾病的发病率显著偏低；“孩子需要接触泥土”。 现代牙科实践同样充斥着此类认知偏差。Bryan 博士质疑道：为什么牙科诊所广泛使用氟化物漱口水？为什么牙膏和美国高达 72% 的市政自来水中都添加氟化物？氟化物本质上是一种强效抑菌剂、环境毒素、甲状腺毒素和神经毒素。 这一错误逻辑可追溯至一百多年前的牙科学历史： - **致命斑块的起源发现**：一百多年前，病理学家在突发心脏病死亡患者的冠状动脉血栓活检中，首次提取到了口腔细菌。 - **口腔-系统性循环链条（Oral-Systemic Link）**：牙龈出血之所以危险，是因为破损的毛细血管为口腔致病菌敞开了直接进入全身血液循环的大门。细菌转移引发内皮炎症，促使斑块破裂形成血栓，最终酿成心肌梗死和中风。 - **矫枉过正的历史悲剧**：百年前的医学界得出这一结论后，出于良好初衷，制定了“用强力防腐杀菌剂清除口腔内所有细菌”的策略，却全然不知这种无差别清洗将维系血管健康的有益共生菌也一同抹杀。 ### [43:03](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2583s) 漱口水与高血压：短短七天让心血管风险暴增 26% 百年前的牙医学界曾普遍认为，口腔里的细菌是一大祸害——若牙龈出血，细菌就会渗入全身血液循环，引发心脏病或中风，因此必须把它们斩草除根。然而在过去这一百年里，科学认知发生了颠覆性的变化，医学界终于意识到人体内外栖息着极其庞大的微生物组。内森·布莱恩（Dr. Nathan Bryan）指出，当他询问牙医为何至今仍在推荐氟化物和广谱抗菌剂时，对方给出的理由往往是“因为我们过去一百年都是这么干的”。内森直言：“不管你的问题是什么，这都是你能给出的最糟糕的回答。难道过去一直这么做，现在就必须盲从吗？”如今真正的科学前沿，应当是如何在精准清除致病菌的同时，完好保留维持人体健康的共生菌群。 研究早在上世纪 90 年代就开始萌芽，并在 2000 年代后期逐步成型。内森团队在 2008 至 2009 年发表研究，确立了一项核心相关性：口腔中菌群越健康、物种多样性越丰富的人群，血压控制得越理想；而那些口腔菌群极其单一、无法培养出一氧化氮产菌的人，往往伴随着极高的血压。为了从“相关性”走向“因果性”，内森团队在 2019 年设计了一项严谨的干预临床试验。他们招募了一批血压完全正常、一氧化氮水平良好的年轻健康受试者，让他们每天使用两次广谱杀菌漱口水，连续使用七天以清除口腔菌群，期间通过舌苔刮取物检测细菌灭活情况并监测血压；七天后停用漱口水四天，再次采样复测。 实验结果令人震惊：只要把口腔菌群破坏殆尽，短短七天内所有人的血压都会显著飙升，甚至在七天之前就已经开始恶化。在其中一名年仅 21 岁的健康年轻人身上，使用漱口水仅一周，收缩压就暴涨了 26 毫米汞柱（mmHg），直接跨入临床高血压的范畴。内森严肃地解释了这个数字的分量：在流行病学上，血压每上升 1 毫米汞柱，罹患心血管疾病的风险就会增加 1%。换言之，仅仅是因为遵医嘱使用普通杀菌漱口水，研究人员就在短短七天内，把一个 21 岁健康青年的心血管疾病风险人为推高了 26%。 - 1990 年代起，多项学术研究便证实使用杀菌漱口水会破坏口腔微生物环境，进而诱发血压上升。 - 内森团队在 2008-2009 年证实，口腔菌群多样性缺失与原发性高血压之间存在高度吻合的临床关联。 - 2019 年针对年轻健康人群的临床干预显示，每日两次连续使用漱口水 7 天，可使正常人血压飙升至临床高血压水平。 - 血压每上升 1 mmHg，心血管疾病致死与发病风险即同步增加 1%。 --- ### [45:53](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2753s) 口腔菌群与一氧化氮循环：为什么吃蔬菜降血压全靠舌头上的细菌 面对主持人关于微观运作机制的追问，内森用通俗易懂的语言拆解了这一人体与微生物共生的生化奇迹。绿色蔬菜在土壤中生长时会吸收氮素并富集为硝酸盐（Nitrate，$NO_3^-$）。当我们吃下这些蔬菜后，硝酸盐被肠道吸收进入血液，并被主动浓缩在唾液腺中。当唾液分泌到口腔后，舌头表面附着的“硝酸盐还原菌”便开始大显身手，将完全没有生物活性的硝酸盐转化为亚硝酸盐（Nitrite，$NO_2^-$）以及一氧化氮（$NO$）。这一步至关重要，因为人体自身的基因组中根本不具备编码这种硝酸盐还原酶的能力，人类在这一代谢节点上百分之百依赖口腔细菌。 如果通过漱口水等手段消灭了这群细菌，被唾液浓缩排出的硝酸盐就成了彻头彻尾的惰性分子。它们在体内循环一圈后，无法被转化利用，只能通过肾脏经尿液过滤排出，或者伴随汗液与粪便白白流失。相反，只有在这些细菌存在的前提下，生成的亚硝酸盐随着吞咽进入胃酸环境，才能在强酸催化下大量生成一氧化氮气体并被机体利用，从而精准调控全身阻力动脉的舒张，维持系统性血压平稳。内森强调，如果口腔菌群遭到破坏，饮食疗法的效果将大打折扣：哪怕每天摄入海量绿叶蔬菜或坚持极度健康的纯素饮食，虽然依然能摄取到维生素、抗氧化物与膳食纤维，但“依靠蔬菜改善血管弹性、降低血压”这一最关键的一氧化氮生理获益，将彻底归零。 ```mermaid flowchart TD accTitle: 口腔-肠道一氧化氮循环通路 accDescr: 绿色蔬菜中的硝酸盐经肠道吸收、唾液浓缩，依赖舌部细菌还原为亚硝酸盐，进入胃酸转化为一氧化氮以扩张血管并降低血压。 subgraph INTAKE["摄入与吸收"] A["摄入富含硝酸盐的蔬菜<br/>(绿叶蔬菜/甜菜根)"] --> B["肠道吸收进入血循环"] B --> C["唾液腺主动浓缩并分泌"] end subgraph ORAL["口腔转化枢纽"] C --> D{"舌部菌群是否完整？"} D -- "存在硝酸盐还原菌" --> E["还原为亚硝酸盐与一氧化氮<br/>(人体自身缺乏该还原酶)"] D -- "使用杀菌漱口水破坏" --> F["硝酸盐无法还原<br/>随尿液/汗液完全排出"] end subgraph SYSTEMIC["全身循环调控"] E --> G["吞咽进入胃部强酸环境"] G --> H["释放活性一氧化氮 (NO)"] H --> I["扩张全身阻力动脉，正常调控血压"] end ``` --- ### [48:10](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2890s) 口腔感染与癌症的惊人关联：实体瘤患者的隐形病灶 当主持人转而探讨口腔健康与恶性肿瘤的联系时，内森给出了坚定的肯定回答，并披露了他在临床咨询中观察到的极具争议的现象。内森谈到，尽管自己并不是肿瘤专科医生，但经常有经历过所有常规治疗依然复发转移、最终被医院放弃并转入临终关怀（Hospice）的晚期癌症患者辗转联系到他寻求希望。内森接待这些患者时，给出的第一条建议永远是：“马上去看专业的生物牙医，彻底排查口腔内是否存在潜伏的活跃感染。” 内森指出，在临床分类中，癌症可分为血液肿瘤（如白血病、淋巴瘤、多发性骨髓瘤）与实体瘤（如乳腺癌、结肠癌、前列腺癌、肺癌、肝癌）。在接触这些原本被宣判死刑的晚期实体瘤患者时，内森观察到一个极度反常的模式：无一例外，100% 的实体瘤患者口内都存在严重的牙源性活跃感染病灶，例如慢性根尖周炎、根管治疗留下的死牙，或是拔牙后颌骨未完全愈合留下的空洞性病灶（Cavitation）。这种感染有时会伴随剧烈牙痛（有症状性），但更多时候处于完全无痛、不易察觉的静默状态（无症状性）。 当听到癌症患者需要看牙医时，很多走投无路的患者甚至医生第一反应都是难以置信，甚至嘲讽：“我得的是癌症，不是牙病，你到底在胡言乱语什么？”内森对此回应道，无论是在印度阿育吠陀医学、传统中医（TCM）还是针灸学体系中，早在数千年前就明确指出了每一颗牙齿都通过经络通道与特定的内脏器官紧密相连。现代科学虽然尚未完全建立起大规模双盲实验的因果证据链，但文献与临床事实已经无法忽视。内森用生动的电气系统打了个比方：“人体的本质是一个精密运作的电气回路，我们判断一个人是否死亡，靠的就是心电图（EKG）或脑电图（EEG）是否还有电信号。牙齿与其相连的经络就像家里的空气开关（Circuit Breaker），当牙齿发生严重感染并坏死时，就相当于跳了闸。一旦断路，通往对应脏器的生物电和能量供给就被彻底掐断，长期处于缺电状态的器官，自然更容易沦为癌细胞滋生与转移的温床。” - 晚期转移性实体瘤（乳腺、结直肠、前列腺、肺、肝等）患者在临床观察中，几乎百分之百伴随隐秘或活跃的口腔牙源性感染。 - 传统医学与现代生物物理学均认为牙齿是连接内脏的“能量经络节点”；牙齿病灶如同跳闸断路，会导致靶器官丧失正常生物电压。 --- ### [51:38](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3098s) 根管治疗的隐患：被保留在体内的“坏死组织”与骨坏死 内森随后将锋芒直指现代牙科中最常见的治疗手段之一——根管治疗（Root Canal），并提出了一个颠覆许多人认知的硬核生物学逻辑：“百分之百经过根管治疗的牙齿，在生物学层面上都是被细菌感染的死组织。”人们做根管治疗的原因，通常是牙髓感染导致了无法忍受的剧痛。牙医的操作流程是：将牙齿内部的神经末梢全部抽走，这样患者便不再感到疼痛；但与此同时，牙髓内部供给该牙齿的血管系统也被一并彻底切除。 内森强调，牙齿绝不是一块没有生命的石灰石，它本身是一个具有微细晶体管道结构的鲜活器官。一旦血供和神经全部被拔除，这颗牙齿在生物学上就已经彻底坏死。“试想一下，如果外科医生把你的胆囊神经和供血血管全部切断，却把这个失去血供的死胆囊原封不动地缝在你的肚子里，不出七到十天，你就会死于严重的全身性败血症。没有任何合格的外科医生会允许把一块坏死腐烂的器官留在人体内，唯独牙科每天都在这么做。”更荒谬的是，患者做完根管离开诊室时，牙医通常会开具口服抗生素，却完全忽视了这颗牙齿的血液循环早已被切断——没有血液作为载体，口服抗生素根本不可能抵达牙根深处的感染灶。 失去了氧气供给和血液免疫细胞的巡查，牙根微管便成了厌氧菌的绝佳温床。这些厌氧菌在低氧密闭环境中持续代谢繁殖，排出大量酸性毒素，不仅会彻底切断该牙齿经络的生物电压，还会日积月累地侵蚀颌骨，导致隐匿性极深的颌骨坏死与骨髓炎（Osteonecrosis / Osteomyelitis）。更危险的是，由于神经已被拔除，患者对颌骨的腐蚀毫无痛感；而普通牙科诊所广泛使用的平面 2D X 光光片根本无法穿透骨质识别这类早期病灶，必须依靠更高分辨率的 3D 锥形束 CT（CBCT）才能显形。 听到这里，主持人史蒂芬也分享了他为本期访谈准备时查阅到的一份极具分量的科研证据：纽约大学（New York University）科研团队历时 15 年、追踪分析了超过 160,000 名参与者的唾液微生物样本，该项研究不仅在学界引起轰动，也被《纽约邮报》等媒体广泛报道。该长期追踪研究明确筛选出了十几种特定口腔致病菌，证实其与头颈部恶性肿瘤的高发风险存在着直接且显著的生物学关联，进一步印证了口腔微生态一旦崩溃对远端组织恶变产生的致命助推作用。 - 根管治疗抽走牙神经和血管后，牙齿成为无血供坏死组织，常规口服抗生素完全无法到达病灶发挥效用。 - 根管深处的厌氧菌代谢毒素会暗中腐蚀下颌骨，引发慢性颌骨坏死与骨髓炎，而普通 2D 牙科 X 光片极易漏诊，需依赖高精度 3D 锥形束 CT 确诊。 - 纽约大学针对超 16 万人、长达 15 年的前瞻性大样本研究证实，口腔特定菌群异常与头颈癌等恶性肿瘤的发生有着极为密切的关联。 ### [53:43](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3223s) 赞助插播：足底健康与生活方式反思 听闻漱口水破坏口腔菌群可能导致患癌风险飙升 50% 的惊人事实后，Steven 忍不住自嘲，恨不得立刻发短信让助理预约牙医洁牙师，并立刻把家里的漱口水彻底换掉。随后节目进入赞助环节，Steven 分享了自己投资的抹茶品牌 Perfect Ted 的故事——该品牌采用来自日本的典礼级抹茶粉，口感顺滑且自带天然甘甜，彻底打破了传统抹茶苦涩如嚼草的刻板印象。接着，他聊到了哈佛大学演化生物学教授 Daniel Lieberman 博士曾在这档播客中提出的观点：现代跑鞋过度缓冲和支撑的设计反而弱化了足部天然肌群。Steven 透露自己曾饱受足底筋膜炎折磨，双脚一度剧痛难忍，后来通过坚持换穿 Vivobarefoot 赤足鞋来重建脚部力量。利物浦大学的实证研究也表明，坚持穿赤足鞋 6 个月能使足部肌肉力量提升高达 60%。 --- ### [56:04](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3364s) 改善口腔微生态的第一步：全面告别氟化物 回到正题，面对“普通人究竟该如何改善口腔微生态”的疑问，Dr. Nathan Bryan 给出了一个出人意料的原则：改善的第一步从来不是“该做什么”，而是“千万不能做什么”。当务之急就是彻底淘汰含氟产品。就在前不久，Nathan 刚参加了盐湖城的一场牙科医学峰会，现场有来自美国国家毒理学规划署（National Toxicology Program, NTP）的官方专家。该机构专门负责评估环境毒素对人类健康的暴露风险，他们的最新调研结论十分严酷：氟化物对人体没有任何确切益处，反而充斥着全身性风险——它不仅会导致儿童智商（IQ）下降多达 7 分，还会严重抑制甲状腺功能，是一种明确的神经毒素。 更荒谬的是日常牙膏的设计陷阱。Nathan 提醒大家仔细阅读牙膏管背面的警示标签：上面明确写着“若不慎吞咽，请立刻联系中毒控制中心”，说明它本质上就是一种毒药。包装指南规定每次只能使用“豌豆大小”（pea-sized）的剂量，大约含有 0.5 毫克氟化物。然而，绝大多数消费者在挤牙膏时都会习惯性挤满整个刷毛，用量达到标准剂量的 10 至 20 倍，一次性暴露在 5 到 10 毫克的氟化物中。氟的分子量极小（仅为 19），根本不需要吞进胃里，它能瞬间通过口腔颊黏膜（buccal mucosa）直接被毛细血管吸收并进入全身血液循环。Steven 听后当场表示自己再也不会碰含氟牙膏，而 Nathan 的唯一替代方案就是选择纯天然、无氟的牙膏。 - **氟化物神经毒性**：美国国家毒理学规划署最新指出，氟化物会损害儿童神经系统，使 IQ 下降最高达 7 分，并破坏甲状腺内分泌代谢。 - **超量摄入风险**：牙膏说明书推荐的单次用量仅为“豌豆大小”（含约 0.5 mg 氟），但大众挤满刷毛的习惯导致单次暴露量飙升至 5–10 mg。 - **颊黏膜快速吸收**：氟原子分子量仅 19，具有极强的黏膜穿透力，未被吞咽即可直接渗透进入全身血液循环系统。 --- ### [58:06](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3486s) 刮舌板的科学原理与致命误区 当 Steven 询问古代流传至今的“刮舌板”（tongue scrapers）是否真有用时，现场气氛变得十分微妙。Steven 坦白自己被女友念叨了整整两年要用刮舌板，他表面上敷衍答应，背地里却觉得那东西长相怪异，甚至质疑“刮舌头难道不会把口腔里的有益益生菌也全刮掉吗？”然而 Nathan 却明确证实了他女友的正确性：科学临床数据显示，长期坚持刮舌苔的人群不仅拥有更多样化的口腔微生态，整体口腔健康水平也显著更高。 为了让对园艺一窍不通的 Steven 听懂，Nathan 打了个生动的比方：“你想播种花草，难道会把种子直接撒在未开垦的硬土上吗？你必须先翻土，把土壤弄松散透气。”刮舌板的作用正是“给舌头翻土”，其核心是物理破坏厚重的舌苔生物膜（biofilm）。正确的做法是使用黄铜（copper）刮舌板，深入伸到舌背（dorsal tongue）深处甚至接近咽反射的敏感区域，用力将黏腻的污垢刮拭带出，从而为厌氧的有益还原菌营造理想的栖息微环境。 随后 Nathan 发出了极其严厉的警告：虽然刮舌板益处显著，但如果“刮完舌苔立刻使用抑菌漱口水”，就会酿成临床观察中最可怕的灾难。在他们的临床测试中，血压飙升最严重的恰恰是一名同时做这两件事的受试者。因为刮舌板刚把舌头深处的隐窝（crypts）和毛细孔道全部打开并破坏了保护性屏障，此时灌入广谱杀菌漱口水，化学药剂就能毫无阻碍地直插舌根深部，将刚刚露头的还原菌赶尽杀绝。因此，唯一的正解是：坚持刮舌苔，改用无氟牙膏，并绝对禁止使用抑菌漱口水。 ```mermaid flowchart TD accTitle: 口腔微生态与舌苔护理路径对比 accDescr: 展示正确刮舌与错误使用漱口水对口腔微生态及一氧化氮生成的截然相反后果 subgraph Correct["正向机制：翻土重构微生态"] A["使用黄铜刮舌板深探舌背"] --> B["物理剥离老旧生物膜 (翻土松菌)"] B --> C["舌隐窝充分暴露透气"] C --> D["硝酸盐还原菌群多样性提升"] D --> E["一氧化氮充足 / 血管弹性舒张"] end subgraph FatalError["致命组合：开放通道下的赶尽杀绝"] F["舌面隐窝破开暴露"] --> G["立刻倒入广谱抑菌漱口水"] G --> H["抗菌化学成分深层浸润渗透"] H --> I["关键产酶益生菌被全面灭活"] I --> J["一氧化氮归零 / 血压急剧暴增"] end ``` --- ### [01:00:00](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3600s) 牙医洗牙建议与漱口水如何抵消运动益处 针对定期看牙医洗牙的习惯，Steven 询问每季度找一次口腔卫生洁牙师是否妥当。Nathan 给予了充分肯定：专业洁牙能够监测牙龈组织的健康状态、清除牙结石与牙菌斑，并促使牙釉质实现健康的再矿化，是很好的主动预防手段，但关键防线依然是：**“绝不能接受牙医诊室推荐的涂氟或含氟漱口治疗。”** 随后 Nathan 揭露了另一个被大众严重忽视的医学事实——抑菌漱口水会彻底抹杀运动带来的心血管保护效应。现代医学普遍提倡通过运动和饮食来维持血管活力并延年益寿，许多人每天克服甜食诱惑、自律跑步流汗，以为这样就能强身健体；但假如他们晨起使用了抑菌漱口水，运动降压和扩张血管的生理机制就会彻底停摆。更致命的是，前文已证实漱口水会切断饮食中蔬菜硝酸盐的转化通路。现实数据触目惊心：全美有三分之二的成年人每天早晨都在使用漱口水，而全美恰好有整整三分之二的人口正承受着不健康的危险高血压。背后的生理机制一目了然：口腔杀菌药剂将产一氧化氮的关键微生物屠戮殆尽，内皮失去了一氧化氮这个最重要的舒张因子，全身血管便只能陷入持续的痉挛收缩，从而诱发顽固性高血压。 --- ### [01:01:36](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3696s) 性激素、维生素D与一氧化氮的双向调控机制 讨论随后延伸到内分泌与一氧化氮的深层纠缠。Nathan 指出，性激素与一氧化氮之间存在着紧密的“双向奔赴”关系：在男性体内，睾酮（testosterone）会直接激活一氧化氮的合成路径；而在女性体内，雌激素（estrogen）则扮演着唤醒一氧化氮合酶（eNOS）的催化角色。只要人体维持着最优的性激素水平，且血管内皮细胞上的酶系统保持健康的偶联（coupled）状态，细胞就能在感应到性激素信号后顺畅制造一氧化氮——这也正是医学界观察到“激素替代疗法（HRT）具有心血管保护益处”的生化底层真相。 同理，运动与一氧化氮也是互为因果的双向闭环。运动本身通过血流剪切力刺激内皮释放一氧化氮，但前提是身体最初得拥有一氧化氮来打开微循环；如果因微生态破坏导致内皮功能障碍，血管将保持狭窄僵硬，肌肉得不到充足的氧气和养分灌注，运动表现和耐力便会大幅跳水。Nathan 进一步扩展了这一逻辑：包括维生素 D（全美绝大多数人均处于缺乏状态）同样是一氧化氮生成的核心激活激动剂（agonist）。许多男性因睾酮低下而出现勃起功能障碍（ED），根源正是因为缺乏足够的一氧化氮来松弛平滑肌和充盈血流。无论是维生素 D 缺乏、性激素衰退、饮食结构崩塌还是久坐不动，绝大部分亚健康与心血管危机的生理终点，都能在一氧化氮的严重匮乏中找到终极解释。 - **男性睾酮通道**：睾酮直接结合受体激活内皮酶系，促进一氧化氮生成；睾酮匮乏直接导致血管平滑肌舒张受阻，成为勃起功能障碍（ED）的核心诱因。 - **女性雌激素通道**：雌激素是女性心血管保护伞，刺激一氧化氮合酶表达；这也是绝经期后女性心血管疾病发病率陡增的关键机制。 - **维生素 D 协同**：维生素 D 是维持内皮合酶活性必不可少的全身性激动剂，缺乏会导致内皮细胞一氧化氮产量断崖式下滑。 --- ### [01:03:15](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3795s) 饮食对一氧化氮的影响：首先必须戒断糖分 当 Steven 询问到底该吃什么来维系体内一氧化氮的充盈与健康时，Nathan 再次给出了极具个人风格的辩证回答：重点依旧不是“我们该吃什么”，而是“我们必须停止吃什么”。 在一切营养补充方案启动前，排在第一优先级的绝对禁忌是**彻底避开糖分与高升糖指数（high glycemic index）食物**。Nathan 斩钉截铁地定性：“糖就是一种毒素，一种纯粹的毒药。”无论摄入的是蔗糖、果糖，还是食品工业中泛滥的高果糖玉米糖浆，它们进入人体后的生化终局完全一致——造成血液中的葡萄糖浓度急剧飙升。如今动态血糖仪（CGM）越来越普及，人们可以实时监控餐后血糖的剧烈震荡；而这种高糖环境会直接造成内皮糖毒性浸润，将脆弱的一氧化氮合酶解偶联并破坏微血管微环境，最终将整个血管系统一步步拖入糖尿病和不可逆退行性病变的深渊。 ### [01:04:15](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3855s) 糖是绝对的毒药：糖化如何摧毁一氧化氮生成系统 高血糖对人体的毒害在生物化学层面有极其直观的物理机制。葡萄糖（Glucose）在英文语境中顾名思义就像“胶水”（Glue）一样具备强烈的黏性。如同将含糖苏打水泼在操作台面上隔天会变黏变硬一样，糖进入人体后也会黏附在所有接触到的组织上，包括蛋白质、关键酶类以及血红蛋白。当糖分子黏附在血红蛋白上时，便形成了临床上衡量长期血糖控制水平的指标——糖化血红蛋白（HbA1c）。一旦 HbA1c 指标超过 5.7%，个体就已经进入了糖尿病前期或糖尿病状态。然而，糖的破坏性远不止于黏附血红蛋白，它更会直接黏附并锁定负责合成一氧化氮的生物酶。 酶学与生物化学的核心在于酶必须能够自由进行构象变化（Conformational changes），从而完成电子在供体与受体之间的传递。但如果多余的糖分子死死黏附在合成酶上，就会将其彻底锁死在某种固定构象中，使其完全丧失制造一氧化氮的功能。因此，Dr. Nathan Bryan 严厉指出“糖是绝对的毒药”，它不仅杀死各类功能酶，还通过破坏口腔微生态环境摧毁细菌生态，从源头上切断一氧化氮的产生。这也直接解释了为何糖尿病患者面临比常人高出十倍的心脏病发作、中风以及全因死亡风险，同时伴随严重的周围神经病变、视网膜病变、黄斑变性、胰腺炎以及极难愈合的溃疡伤口——这一切灾难的共同底层病理都是一氧化氮的全面匮乏。 ```mermaid flowchart TD accTitle: 高糖破坏一氧化氮生成机理 accDescr: 展示高血糖如何通过酶构象锁定与微生态破坏导致组织缺血与糖尿病并发症 subgraph SugarIntake ["高血糖状态"] A["血液中过量葡萄糖 ('生理胶水')"] end subgraph DirectLock ["生物化学损伤"] B["强力黏附一氧化氮合成酶 (NOS)"] C["酶构象被机械性锁死<br/>无法进行电子转移"] D["一氧化氮 (NO) 生成彻底停滞"] end subgraph Complications ["临床恶果"] E["微循环缺血与内皮功能障碍"] F["糖尿病足溃疡 / 神经病变 / 视网膜损伤"] end A --> B B --> C C --> D D --> E E --> F ``` - **糖黏附作用（Glycation）**：多余的葡萄糖像胶水一样无差别附着在蛋白质与酶上，直接干扰生物体内电子传递的动态平衡。 - **HbA1c 阈值**：HbA1c 大于 5.7% 即标志着糖代谢受损与糖尿病风险。 - **并发症级联反应**：糖尿病患者高发的神经病变、伤口不愈合（如糖尿病溃疡）及器官功能退化，均与微血管内皮失去一氧化氮保护直接相关。 --- ### [01:06:04](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3964s) 一氧化氮促进伤口与疤痕愈合的现场演示 针对糖尿病足部溃疡久不愈合的病理机制，主持人 Steven Bartlett 随即联想到一氧化氮在组织再生中的作用，并分享了一则亲身经历：几天前他踢足球时后脑勺遭遇猛烈撞击，对方当场休克并被救护车紧急送医，而他自己后脑则留下了一道需要胶水缝合的巨大伤口与疤痕。Steven 现场向 Dr. Bryan 请教，是否可以直接涂抹双管一氧化氮精华液来改善这处创伤的血流供应、加快细胞更替并淡化疤痕。 Dr. Bryan 给予了十分坚决的肯定答复，并在现场指导 Steven 如何正确使用双管精华。该产品的核心机制在于两剂活性成分分开保存，使用时从左右两个泵头各取一泵乳液在掌心混合；一旦两者交融，就会瞬间发生化学反应释放出高浓度的一氧化氮气体。当气体渗透进受损皮肤组织时，能迅速促进微血管扩张与血流灌注，动员机体干细胞加速迁移，进而显著加快表皮和真皮组织的更新重塑与伤口修复；此外，如果创面存在致病菌或潜在感染，高活性的一氧化氮还能直接发挥强力的杀菌作用。 - **使用方法**：左右两侧泵头各按压一次，混合即刻生成游离一氧化氮气体。 - **组织修复三重机制**： 1. 扩张局部微血管，即刻增加创面血流供应； 2. 动员体内成体干细胞，加速上皮细胞重塑与胶原修整； 3. 杀灭局部创面浸润的细菌，预防继发性感染。 --- ### [01:07:08](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4028s) 饮食建议与《战胜概率》：为什么市面上的甜菜根产品是“骗局”？ 在回归饮食原则时，Dr. Bryan 强调无论采取生酮饮食还是纯素饮食，其最本质的健康益处其实都来源于“对精制糖和碳水化合物的剔除”。针对现代饮食问题，他给出的核心原则极为纯粹：适度摄入优质蛋白质和优质脂肪，尽量做到极低或零精制碳水，因为现代人普遍处于营养过剩而微量元素匮乏的严重肥胖危机中。当 Steven 问及他为何专门写了一本关于甜菜根的书《战胜概率》（*Beet the Odds*）时，Dr. Bryan 揭开了甜菜根风靡背后一段鲜为人知的科研与商业内幕。 甜菜根在全球范围内的爆红始于 2012 年伦敦奥运会，当时大量数据表明饮用甜菜根汁能显著增强耐力与竞技表现，其底层科学逻辑正是甜菜根中的无机硝酸盐在体内转化成了一氧化氮。然而当时的顶尖运动员为了提升成绩，每天被迫狂饮数升甜菜根汁，引发了严重的胃肠道绞痛和剧烈腹泻，甚至尿液与排泄物全被染成鲜红色，常被误诊为胃肠道大出血或血尿。更严重的是，商业市场上迅速涌现出铺天盖地的脱水甜菜根粉末产品。Dr. Bryan 的团队化验后发现，这些商业甜菜粉几乎完全不含活性硝酸盐或亚硝酸盐，人体摄入后根本无法生成一氧化氮，他戏称这些毫无生气的劣质补剂为“死甜菜产品”（Dead beets）。在他们多年前开展的随机安慰剂对照临床试验中，甚至直接拿药店和营养品店货架上买来的商业甜菜粉充当完美的安慰剂。 ```mermaid flowchart LR accTitle: 甜菜根中无机硝酸盐转化瓶颈 accDescr: 展示摄入甜菜根后依赖土壤质量和口腔健康生成一氧化氮的脆弱链条 A["摄入甜菜根/硝酸盐"] --> B{"土壤条件与加工方式"} B -- "现代贫瘠土壤/劣质脱水粉" --> C["'死甜菜' (无硝酸盐无效果)"] B -- "富含有机硝酸盐原料" --> D["口腔微生物还原为亚硝酸盐"] D --> E{"是否存在干扰因素？"} E -- "使用抑菌漱口水 / 含氟牙膏" --> F["口腔菌群死亡，转化归零"] E -- "健康口腔生态 + 正常胃酸" --> G["生成活性 NO，提升血流与耐力"] ``` 关于甜菜的历史渊源，古代埃及壁画和洞穴岩画曾记录战士在奔赴战场前饮用红色的神秘液体，后世一度误认为是红酒，但考古与历史研究证实他们喝的正是甜菜榨汁，以此在战斗前改善循环、提升体能与警觉度。然而 Dr. Bryan 明确表示，**目前绝不推荐普通人单纯靠吃现代甜菜根来补充一氧化氮**： 1. **现代农业土壤退化**：由于除草剂、杀虫剂滥用与土壤肥力枯竭，2015 年的权威普查显示现代甜菜根中的有效硝酸盐含量微乎其微，一个人物理上根本吃不下足够量的甜菜来达到生理有效剂量； 2. **口腔微生态破坏阻断通路**：若消费者平时使用杀菌漱口水、含氟牙膏或饮用含氟自来水冲泡甜菜粉，口腔中的还原共生菌被杀死，摄入的硝酸盐便毫无转化为一氧化氮的可能。 --- ### [01:11:15](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4275s) 抑酸药物全球激增与胃酸抑制的毁灭性健康危机 Steven 拿出一张过去二十年（2004 至 2024 年）的全球统计图表，显示全球抑酸药（Antacids）的使用量几乎暴增了四倍。作为一名生物化学家和生理学家，Dr. Bryan 严肃指出：“从生理学角度来看，没有什么比人为抑制胃酸生成更具毁灭性的了。”胃酸绝非身体的设计失误，它是分解动植物蛋白为氨基酸的绝对前提，更是微量营养素在胃腔内解离与吸收的物理枢纽。缺乏足够浓度的胃酸，人体将彻底丧失吸收 B 族维生素、硒、铬、碘、镁和铁等核心元素的能力。当前全美有 75% 的人群严重缺镁，95% 的人群缺碘，滥用抑酸药难辞其咎。 对话深入辨析了三类不同机制的抗酸与抑酸药物及其危害： - **质子泵抑制剂（PPIs）与 H2 受体拮抗剂**：如 Prilosec（奥美拉唑）、Prevacid（兰索拉唑）、Nexium（耐信/埃索美拉唑）以及处方药泮托拉唑（Pantoprazole）。这类药物会从根本上关闭胃壁细胞分泌胃酸的质子泵，如今在许多国家甚至无需处方即可随处购得，是导致营养吸收崩溃的元凶； - **局部酸缓冲剂（Buffers）**：如 Tums（碳酸钙）或小苏打（碳酸氢钠）。它们仅仅是在胃酸急性过度分泌时通过弱碱性进行化学中和，并不会阻断胃壁细胞天然制造酸的生理机能，二者具有本质区别； - **含铝抗酸剂的重金属毒性**：针对 Steven 提到的英联邦畅销品牌嘉胃斯康（Gaviscon），其主要活性成分为氢氧化铝和碳酸镁。Dr. Bryan 警告，虽然氢氧化铝是作为强碱缓冲剂中和胃酸，但任何含有金属“铝”（Aluminum）的产品都应该被绝对杜绝使用，长期摄入重金属铝具有不可逆的神经毒性。 --- ### [01:14:30](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4470s) 鼻呼吸与口呼吸：上皮细胞中潜藏的一氧化氮生成酶 讨论随后转向了呼吸模式对健康的深远影响。Steven 提到他的女友是一名专业呼吸疗愈导师（创办了 Bali Breathwork），她日常反复告诫口呼吸的危害并倡导通过鼻腔呼吸。Steven 由此发问：究竟一氧化氮与我们的呼吸途径（鼻呼吸 vs 口呼吸）之间存在怎样严密的生物学联系？ Dr. Bryan 由此将话题引回血管内皮与呼吸道内壁的生理同源性：人体不仅在全身血管内壁的内皮细胞中部署了一氧化氮合成酶，在鼻腔、副鼻窦以及上呼吸道黏膜的上皮细胞中，同样密集分布着相同的生物合成酶。当人类使用鼻腔进行气体交换时，气流会刺激鼻旁窦大量分泌高浓度的一氧化氮气体并随吸气进入肺泡，而长期依赖口呼吸则会彻底绕过这套天然的一氧化氮生成与富集机制。 ### [01:15:00](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4500s) 鼻呼吸与口呼吸：一氧化氮的天然激活与破坏机制 深呼吸与鼻呼吸对心血管和呼吸系统的调节有着立竿见影的生物学机制。就像体育运动能够刺激血管内皮生成一氧化氮一样，经由鼻腔的深长呼吸会直接激活鼻窦上皮细胞中的一氧化氮合酶（NOS）。随着吸气，高浓度的一氧化氮气体被顺流导入下呼吸道与细支气管，促使气道平滑肌舒张，并显著扩张肺动脉，从而成倍提升肺部对氧气的摄取与全身输送效率——这正是科学界证实深呼吸和鼻呼吸能够有效降低血压的核心机制。 ```mermaid flowchart TD accTitle: 鼻呼吸与口呼吸对一氧化氮生成的不同影响 accDescr: 流程图展示了鼻呼吸激活一氧化氮通路并改善血氧，而口呼吸破坏微生物群并阻断一氧化氮生成的过程。 subgraph Nasal["鼻呼吸路径"] A["鼻腔深呼吸"] --> B["激活鼻窦上皮细胞NOS酶"] B --> C["一氧化氮气体进入细支气管"] C --> D["扩张肺动脉 / 提升血氧摄取"] D --> E["全身血管舒张、降低血压"] end subgraph Mouth["口呼吸危害"] F["长期口呼吸"] --> G["完全绕过鼻窦一氧化氮通道"] F --> H["口腔过度充氧与唾液pH值改变"] H --> I["破坏口腔微生态菌群"] I --> J["口腔还原一氧化氮能力彻底停滞"] end ``` 谈及近年来的健康趋势，Steven 展示了一张 Google 搜索趋势图，显示过去二十年间大众对“口呼吸（Mouth Breathing）”的关注度呈爆发式增长，并提到了英国《龙门阵》（*Dragon's Den*，即英国版《创智赢家》）节目中致力于推广呼吸法的 Patrick McKeown。Dr. Nathan Bryan 指出，口呼吸的危害绝不仅是绕过了鼻腔中天然的一氧化氮生成路径，更致命的是它从物理与生化层面彻底摧毁了口腔微生态：口呼吸导致大量干燥空气直接充氧口腔，大幅改变唾液的酸碱度（pH值），使原本赖以生存的硝酸盐还原菌群凋亡殆尽，从而将口腔与鼻腔这两大一氧化氮生成通道全部切断。 尽管 Dr. Bryan 非常赞同通过“睡眠封口贴（Mouth Taping）”来强制纠正口呼吸，但他提出了极其严厉的安全警告：绝对不能在未排查气道结构的情况下盲目贴嘴。 - **气道结构排查优先级**：许多人存在先天性或后天性的气道结构狭窄、鼻中隔偏曲或阻塞性睡眠呼吸暂停。若在呼吸道受阻的情况下强行封嘴，极易导致夜间缺氧甚至窒息风险。 - **专业影像评估**：在尝试口唇贴胶带之前，务必前往牙科进行专业影像学检查（如 CBCT 气道评估），确保鼻咽气道畅通无阻，能够完成正常的通气与气体交换。必要时需先通过牙科矫治器或外科手术解除阻塞。 --- ### [01:17:16](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4636s) 蜂鸣振动激活合酶与内皮酶功能的前提条件 除了鼻呼吸，日常生活中一种极其简单却被长久忽视的物理刺激能够瞬间拉高一氧化氮浓度，那就是“蜂鸣呼吸（Humming）”或冥想中的“Om”发音。Dr. Bryan 解释道，特定频率的声波振动能够物理性地激活鼻窦组织中的一氧化氮合酶。由于每个人的鼻腔、鼻窦腔隙容积与口腔结构各不相同，并不存在一个放之四海皆准的绝对频率，但只要发出持续低沉的蜂鸣震颤，就能产生共振刺激。 为了证实这一点，科研团队曾在实验室中将高精度的臭氧/气相化学发光分析仪连接到受试者呼气端。只要受试者开始发声蜂鸣，检测仪器上的呼出气一氧化氮数值便会立刻飙升。然而，这种物理刺激法存在一个不可违背的生化前提：体内的一氧化氮合酶必须本身具备功能。 - **酶失活的局限性**：Dr. Bryan 指出，在他们多年前发表的研究以及其他独立实验室的反复验证中，针对内皮功能严重衰退、一氧化氮合酶发生“解偶联（Uncoupling）”或彻底受损的老年患者，无论如何进行深呼吸或发声蜂鸣，其呼出气体中都测不到额外的一氧化氮。 - **核心结论**：声波振动、鼻呼吸和体育锻炼都是优秀的“促发剂（Activator/Stimulator）”，但它们完全仰赖健全的酶促机制；若合成一氧化氮的底层酶系统已经坏死损坏，外部的物理刺激便无法无中生有。 --- ### [01:18:32](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4712s) 日光沐浴、红光疗法与现代防晒迷思 谈到日常生活中还能通过哪些方式维护一氧化氮水平，Dr. Bryan 归纳了一套化繁为简的干预清单：首要任务是“停止破坏”，即停用含氟牙膏、停用抑菌漱口水、停止滥用抑酸药，并戒断引起血糖骤升的高精制糖饮食；其次是保持适度运动与均衡饮食；而最被低估的强效手段，是每天保证 20 至 30 分钟的阳光照射。 阳光对一氧化氮的调控机制跨越了可见光光谱的两端：紫外线（UV）具备足够的能量，能将体内半胱氨酸及蛋白质上结合的一氧化氮共价键精准击断释放；而红外线（全光谱红外）则通过特定的分子共振频率，将结合在金属蛋白和血红素中心的一氧化氮剥离出来，使其迅速扩散进入微循环系统。 - **光照疗法的多重生理收益**：除了直接释放储存在皮肤中的一氧化氮库，全光谱光疗还能促进线粒体生物发生（Mitochondrial Biogenesis）、大幅提升细胞 ATP 能量代谢并舒张外周微血管降压。 - **个人日常实践**：Dr. Bryan 透露自己每天都会使用配有红光阵列的全光谱红外桑拿房（Infrared Sauna）与全身红光舱，以此保持高水平的一氧化氮循环。 - **批判现代防晒教条**：针对当下主流医学与护肤界推崇的防晒狂热，他直言不讳地表达了震惊与反对。现代人被恐吓着不敢踏入阳光，出门便涂抹含有致癌化学物质的高倍数防晒霜（如 SPF 60），将皮肤彻底与有益光波隔绝，这种违背生命演化规律的行为完全是在“自服毒素（Intoxicate ourselves）”。 --- ### [01:19:54](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4794s) 医学的未来：从对抗恶习到分子层面的救赎 当 Steven 询问今天还有什么最核心的话题尚未涉及、而公众必须知晓时，Dr. Bryan 给出了极为严肃的论断。他引用了认知的三个进阶层次：“人对一件事有三种确信阶段：你认为（Think）、你相信（Believe）、你确知（Know）。而我现在处于‘确知’的阶段——全球医学与公共卫生的未来，将彻底取决于一氧化氮产品与应用技术的突破。” 这种确定性来源于对人类行为学现实的深刻清醒。医学专家可以终日向公众宣教健康指南，告诫大家戒断含糖苏打水、每天坚持半小时有氧运动、改变高加工饮食，但改变人类根深蒂固的生活习惯和走出舒适区是世界上最艰难的事情，患者的临床依从性（Compliance）向来极其低下。现代人被规训得只想依靠“每天吞下一粒药丸”来抵消所有的健康透支。 > “一氧化氮极其重要，但它不是一劳永逸的银色子弹（Silver Bullet）。它不可能完全抵消你所有的不良生活恶习；但它的伟大之处在于，它能精准修复因你的恶习所导致的关键分子匮乏。” Steven 深有感触地总结道，自己在对话前对一氧化氮几乎一无所知，甚至一度将其与年轻人滥用的笑气（NOS / 氧化亚氮）混为一谈。正因为大众缺乏对其底层逻辑和病理链条的认知，医学才迟迟未能摆脱“下游被动治病”的困局。Dr. Bryan 致力于将这一基础生命科学推向公众视野，正是扭转慢性退行性疾病泛滥的关键所在。 --- ### [01:21:57](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4917s) 最后一问：家庭平衡的代价与终极使命 按照节目传统，Steven 翻开了上一位造访嘉宾 Kim 在日记本中留下的未知问题：“你目前处于幸福还是不幸的伴侣关系中（Are you happily or unhappily mated）？为什么？” 面对这个私密的情感问题，Dr. Bryan 坦率地剖析了自己作为顶尖科学家背后的内心拉扯。他承认，在人生中维持全面平衡是他遭遇过的最严酷挑战。多年来，他将全副精力孤注一掷地投入到科研突破、开拓未知领域、创造持久遗产，以及挑战医学界认为“不可能完成”的技术攻关中。 - **追求伟大的牺牲**：因为频繁的学术差旅、演讲与研发日程，他长期远离家庭与年幼的孩子。“可以说我是处于幸福的伴侣关系中，但这其中存在着亏欠与不足（Deficiencies）。” - **不可避免的权衡取舍**：Dr. Bryan 坦言，要在事业雄心、家庭陪伴，以及心智、肉体与精神健康之间取得绝对平衡几乎是乌托邦式的幻想。“世上凡事皆有代价（Sacrifice）。我们能做的只有清醒地挑选自己愿意承受的代价，并时刻警醒自己要在家庭中做得更好。” --- ### [01:23:22](https://www.youtube.com/watch?v=zECoaEZRRFU&t=5002s) 知识普及与权威资源渠道 访谈尾声，Steven 高度评价了 Dr. Bryan 新书的通俗性与震撼力，并向听众征询进一步获取一氧化氮知识与科技转化成果的官方渠道。Dr. Bryan 详细介绍了读者可以深入探索的路径： - **重磅专著**：《一氧化氮的秘密：让科学走进生活》（*The Secret of Nitric Oxide: Bringing The Science To Life*）。该书不仅翔实记录了他从早年立志投身生物医药到重大科学发现的心路历程，更系统性还原了一氧化氮斩获诺贝尔生理学或医学奖的历史脉络，并提供了防止人体分子流失的实操方案。读者可通过专属网站 `nathansbook.com`、Amazon 或 Barnes & Noble 购阅。 - **科普与教育平台**：Dr. Bryan 在 YouTube 建立了名为 “Dr. Nathan S. Bryan Nitric Oxide” 的专属频道，持续追踪并发布全球一氧化氮领域的最新科研成果与临床见解；其个人日常动态与医学见解亦可在 Instagram（@drnathansbryan）获取。 - **技术研发转化平台**：针对希望体验安全高效、能直接释放一氧化氮活性分子技术的受众，可通过创新科研转化平台 `n1o1.com`（即字母 N、数字 1、字母 O、数字 1）了解其科研团队落地转化的突破性产品。 ### [01:25:04](https://www.youtube.com/watch?v=zECoaEZRRFU&t=5104s) 总结致谢与主持人的订阅呼吁 在对话接近尾声时，主持人史蒂芬·巴特利特（Steven Bartlett）向内森·布赖恩博士（Dr. Nathan Bryan）表达了由衷的感谢。史蒂芬感慨道，这次对话彻底改变了他对日常决策和生活习惯的看法，无论是运动锻炼、接受日照，还是维护口腔微生物菌群的平衡，这些科学见解都如同一份珍贵的礼物，为日常生活带来了深远的启发。布赖恩博士也欣然回应，表示能来参加节目并分享这些研究成果是一件非常愉快的事。 随后，节目进入尾声呼吁环节。史蒂芬分享了一个令他颇感意外的数据：在长期收听该节目的听众群体中，竟然有高达 53% 的人尚未点击订阅。他真诚地向大家发出倡议，如果大家喜欢节目的内容并希望给予支持，最简单且完全免费的方式就是顺手点击“订阅”按钮。史蒂芬向观众郑重承诺，只要大家支持订阅，他和团队必将竭尽全力不断提升节目品质，认真倾听观众反馈，持续邀请听众最想见到的重量级嘉宾，为大家带来更有价值的深度对话。 - **生活习惯的全新认知**：关于运动、日光暴露以及口腔微生态的科学机制，直接重塑了人们对自身健康选择的理解。 - **听众互动数据**：统计显示，有 53% 的忠实听众尚未订阅播客；主持人以此呼吁大家通过免费订阅来支持团队持续创作与邀请优质嘉宾。 ## Notable quotes > [00:00](https://www.youtube.com/watch?v=zECoaEZRRFU&t=0s) 我完全确信这项研究将能够根除并治愈阿尔茨海默病。 — Dr. Nathan Bryan > [08:05](https://www.youtube.com/watch?v=zECoaEZRRFU&t=485s) 如果科学界能够找出恢复人体一氧化氮生成的办法，那将彻底改变整个世界，重塑全球医学的格局。 — Louis Ignarro > [12:58](https://www.youtube.com/watch?v=zECoaEZRRFU&t=778s) 一氧化氮生成的丧失，是年龄相关慢性疾病发生与发展的最早事件。 — Dr. Nathan Bryan > [43:03](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2583s) 不管你的问题是什么，这都是你能给出的最糟糕的回答。难道过去一直这么做，现在就必须盲从吗？ — Dr. Nathan Bryan > [48:10](https://www.youtube.com/watch?v=zECoaEZRRFU&t=2890s) 人体的本质是一个精密运作的电气回路，我们判断一个人是否死亡，靠的就是心电图或脑电图是否还有电信号。牙齿与其相连的经络就像家里的空气开关，当牙齿发生严重感染并坏死时，就相当于跳了闸。 — Dr. Nathan Bryan > [51:38](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3098s) 百分之百经过根管治疗的牙齿，在生物学层面上都是被细菌感染的死组织。 — Dr. Nathan Bryan > [01:03:15](https://www.youtube.com/watch?v=zECoaEZRRFU&t=3795s) 糖就是一种毒素，一种纯粹的毒药。 — Dr. Nathan Bryan > [01:11:15](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4275s) 从生理学角度来看，没有什么比人为抑制胃酸生成更具毁灭性的了。 — Dr. Nathan Bryan > [01:19:54](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4794s) 一氧化氮极其重要，但它不是一劳永逸的银色子弹。它不可能完全抵消你所有的不良生活恶习；但它的伟大之处在于，它能精准修复因你的恶习所导致的关键分子匮乏。 — Dr. Nathan Bryan > [01:21:57](https://www.youtube.com/watch?v=zECoaEZRRFU&t=4917s) 世上凡事皆有代价。我们能做的只有清醒地挑选自己愿意承受的代价，并时刻警醒自己要在家庭中做得更好。 — Dr. Nathan Bryan ## Mentioned Dr. Nathan Bryan, Steven Bartlett, Louis Ignarro, Ferid Murad, Bryan Johnson, Daniel Lieberman, Patrick McKeown, The Secret of Nitric Oxide-Bringing The Science To Life, Beet the Odds, The 33 Laws Of Business & Life, Diary Of A CEO, Perfect Ted, Vivobarefoot, Prilosec, Prevacid, Nexium, Gaviscon, Tums, GlycanAge, MD Anderson Cancer Center, UTHealth Houston, FDA, National Toxicology Program (NTP), New York University, Harvard University, University of Liverpool, Bali Breathwork ## Video description Dr Nathan Bryan is a renowned nitric oxide biochemist, entrepreneur and author, who has researched nitric oxide for the past 18 years and made many seminal discoveries in the field. He is also the author of books such as, ‘The Secret of Nitric Oxide-Bringing The Science To Life’. 00:00 Intro 02:17 Nathan's Mission 04:22 Decline in Nitric Oxide (NO) Production 05:24 Symptoms of Low NO Levels 06:39 Diseases Linked to NO 08:05 What Prompted Nathan's Interest in NO? 10:19 Your Experience With Your Dad Setting You on This Path 11:52 Who Are You & Your Experience 12:58 Nitric Oxide Breakdown 14:09 Is Everything You See Just Aging? 15:52 How to Measure Vascular Age 17:35 Chronic Diseases Associated With NO Deficiency 21:39 The Medical Industry Is Broken 27:25 Doctors Are Trapped in the Broken System 29:03 The Molecule of Longevity 32:45 What Do You Think of Bryan Johnson? 34:23 Can NO Be Overdosed? 36:18 NO’s Role in Increasing Telomere Length 38:18 Relationship Between NO and Oral Microbiome 40:39 Nathan's View on Antibacterial Products 43:49 Negative Impacts of Using Mouthwash 45:53 Oral Microbiome and Blood Pressure Connection 48:10 Link Between Oral Health and Cancer 53:55 Ads 56:04 How to Improve Our Oral Microbiome 58:06 Are Tongue Scrapers Beneficial for Oral Microbiome? 59:12 Relationship Between NO and Hormones 1:00:00 Should We Be Seeing Dental Hygienists? 1:00:31 Mouthwash Eliminates Benefits of Exercise 1:00:52 Foods to Boost Nitric Oxide Production 1:03:40 Wound-Healing Properties of NO 1:04:49 Foods for NO Production 1:05:22 *Beet the Odds*: Why Nathan Wrote a Book About Beetroots 1:08:52 Growth of Interest in Antacid Medication 1:12:08 Link Between NO Levels and Nasal Breathing 1:14:51 Humming Increases NO Levels 1:16:09 Things to Stimulate NO 1:17:31 The Future of Medicine Relies on This 1:19:48 Are You Happily or Unhappily Mated? You can purchase Dr Nathan’s book, ‘The Secret of Nitric Oxide-Bringing The Science To Life’, here: https://amzn.to/4jxM0Ke Follow Dr. Nathan: Instagram - https://g2ul0.app.link/bRZbIr6ZtSb YouTube - https://g2ul0.app.link/urFHgP9ZtSb Website - https://g2ul0.app.link/AJpc3jc0tSb Get your hands on the Diary Of A CEO Conversation Cards here: https://bit.ly/conversationcards-mp My new book! 'The 33 Laws Of Business & Life' is out now - https://g2ul0.app.link/DOACBook Sign up to receive email updates about Diary Of A CEO here: https://bit.ly/diary-of-a-ceo-yt Ready to think like a CEO? Gain access to the 100 CEOs newsletter here: https://bit.ly/100-ceos-newsletter Independent research - https://nathanbryan.tiiny.co Follow me: https://g2ul0.app.link/gnGqL4IsKKb Sponsors: Perfect Ted - https://www.perfectted.com with code STEVEN40 for 40% off Vivobarefoot - https://vivobarefoot.com/DOAC with code DOAC20 for 20% off [Source](https://www.youtube.com/watch?v=zECoaEZRRFU)

[0:00] Dr. Nathan Bryan: 我完全确信这项研究将能够根除并治愈阿尔茨海默病。 [8:05] Louis Ignarro: 如果科学界能够找出恢复人体一氧化氮生成的办法，那将彻底改变整个世界，重塑全球医学的格局。 [12:58] Dr. Nathan Bryan: 一氧化氮生成的丧失，是年龄相关慢性疾病发生与发展的最早事件。 [43:03] Dr. Nathan Bryan: 不管你的问题是什么，这都是你能给出的最糟糕的回答。难道过去一直这么做，现在就必须盲从吗？ [48:10] Dr. Nathan Bryan: 人体的本质是一个精密运作的电气回路，我们判断一个人是否死亡，靠的就是心电图或脑电图是否还有电信号。牙齿与其相连的经络就像家里的空气开关，当牙齿发生严重感染并坏死时，就相当于跳了闸。 [51:38] Dr. Nathan Bryan: 百分之百经过根管治疗的牙齿，在生物学层面上都是被细菌感染的死组织。 [63:15] Dr. Nathan Bryan: 糖就是一种毒素，一种纯粹的毒药。 [71:15] Dr. Nathan Bryan: 从生理学角度来看，没有什么比人为抑制胃酸生成更具毁灭性的了。 [79:54] Dr. Nathan Bryan: 一氧化氮极其重要，但它不是一劳永逸的银色子弹。它不可能完全抵消你所有的不良生活恶习；但它的伟大之处在于，它能精准修复因你的恶习所导致的关键分子匮乏。 [81:57] Dr. Nathan Bryan: 世上凡事皆有代价。我们能做的只有清醒地挑选自己愿意承受的代价，并时刻警醒自己要在家庭中做得更好。

[8:05] Dr. Louis Ignaro: If the scientific community can figure out how to restore the production of nitric oxide, it'll change the world and it'll change the landscape of medicine. [5:24] Dr. Nathan Bryan: Erection in both men and women is dependent upon dilation of the blood vessels to get engorgment... and without nitric oxide there's no increase in blood flow. [21:39] Dr. Nathan Bryan: No one is interested in curing cancer. No one is interested in curing human disease because... medicine is a business. It's a for-profit business—in fact, it's the largest business and economic model in the world. [21:39] Dr. Nathan Bryan: The number one rule of business... is acquire a customer and keep that customer as long as you can... They acquire you as a customer, they put you on a drug, that drug has side effects, they have to put you on another drug to mitigate the side effects of that drug... and now you look up and people who are 50 to 60 years old and older are on 10, 12, 18 different medications. [17:36] Dr. Nathan Bryan: This simple molecule, nitric oxide gas... will eradicate and cure Alzheimer's [40:39] Dr. Nathan Bryan: There's no physician in the world that would recommend you or I take an antibiotic every day for the rest of our lives... Because the antibiotics are killing the good bacteria... and when you disrupt the microbiome, you get systemic disease. [56:04] Dr. Nathan Bryan: If you swallowed this, call poison control. [57:58] Dr. Nathan Bryan: If you're going to plant a garden, do you plant a garden on untilled soil? [57:58] Dr. Nathan Bryan: If you tongue scrape and use antiseptic mouthwash, that's the absolute worst scenario. You're opening up the pores, and now the mouthwash can easily penetrate deep into the crypts of the tongue and more effectively kill the bacteria. [79:54] Dr. Nathan Bryan: I'm happily mated, but there's deficiencies, right? Because again, my challenge is always maintaining balance... work, home life, kind of maintaining, you know, my spiritual, mental, and physical health. I'm trying to do better at that now, but... there's always sacrifice, right? And we just have to pick our sacrifices.

[0:00] i'm absolutely convinced this will eradicate  and cure Alzheimer's really the data don't [0:04] lie and I'm a data guy and that the future of  medicine and healthcare around the globe is [0:08] going to be dependent upon this dr nathan  Bryan is the biochemist whose cuttingedge [0:13] research suggests how one crucial molecule  can impact our health brain function and [0:17] longevity that molecule is nitric oxide nitric  oxide is a ziggling molecule in the human body [0:22] which regulates things like blood flow and oxygen  delivery and the loss of nitric oxide production [0:27] is the earliest event in the onset progression  of age- related chronic disease so things like [0:31] erectile dysfunction diabetes Alzheimer's high  blood pressure which is the number one driver [0:35] of cardiovascular disease which is the number one  killer of men and women worldwide and 50% of the [0:39] patients that are treated with prescription  medication don't respond with better blood [0:43] pressure because they aren't targeted toward  nitric oxide but most people have never heard [0:47] of this they don't know that if you can't walk  up a flight of steps or exercise moderately for [0:50] 15 20 minutes then you're nitric oxide deficient  they don't know that most toothpaste and mouthwash [0:55] is killing the oral microbiome that's partly  responsible for production of nitric oxide [0:59] but no one is interested in curing human disease  because medicine is a business and the epiphany [1:05] for me came because my dad had a car accident and  he developed these non-healing wounds and I saw [1:10] the failure of the standard of care to treat dad's  wounds and so I just thought that there had to be [1:15] a better way and simply by giving nitric oxide  I've healed this wound within 6 months that's [1:20] crazy so how do I improve my nitric oxide levels  it's what you shouldn't be doing and we'll cover [1:25] those step by step number one you have to avoid  this has always blown my mind a little bit 53% [1:32] of you that listen to the show regularly haven't  yet subscribed to the show so could I ask you for [1:36] a favor before we start if you like the show  and you like what we do here and you want to [1:39] support us the free simple way that you can do  just that is by hitting the subscribe button [1:43] and my commitment to you is if you do that then  I'll do everything in my power me and my team [1:48] to make sure that this show is better for you  every single week we'll listen to your feedback [1:52] we'll find the guests that you want me to speak to  and we'll continue to do what we do thank you so [1:56] much dr nathan Brian you have committed much of  your life to writing about and educating people [2:06] on a subject that I know absolutely nothing about  but from doing the research for today I'm pretty [2:12] shocked that I don't know more about this subject  so for those people who have just clicked to [2:16] listen to this conversation can you tell them the  mission you're on and why it's so important yeah [2:23] well thanks so much for having this conversation  with me i think that illustrates the problem right [2:27] someone as informed as you don't know anything or  never heard of nitric oxide so it's important for [2:31] us to just make a distinction between um like  nitric gas that people you know inhale and that [2:39] used if you played like uh some of those racing  car games you press a button and the car goes [2:43] really fast if you That's nitrous nitrous nitrous  these are two separate things no very Yeah very [2:48] good point so this is not nitrous oxide nitrous  oxide is I mean a medicine is a dental anesthetic [2:55] right it's a gas it's called laughing gas that's  N2O that's the chemical formula what we're talking [3:00] about is nitric oxide or NO one nitrogen one  oxygen but yeah they sound very similar but [3:07] they're completely different this molecule is  is foundational for human health and longevity [3:12] so nitric oxide is a gas it's a naturally  produced molecule it's a signaling molecule [3:16] in the human body and so it's it regulates  things like blood flow and oxygen delivery [3:21] and it mobilizes our own stem cells to help us  recover and repair and replace dysfunctional cells [3:27] that uh improves energy production inside the  cell and it regulates blood flow you know when [3:32] we begin to exercise if we want to recall memory  that's dependent upon adequate blood flow to the [3:36] organs if we're you know it's intimately involved  in sexual activity and dilation of the sex organs [3:41] for sexual function so what we're finding is  that the older we get the less nitric oxide we [3:47] naturally produced and now today that's recognized  as the earliest event in the onset and progression [3:52] of age- related chronic disease so my mission  is to inform and educate the global population [4:00] on how important number one what nitric oxide  is how it's produced in the human body what [4:06] goes wrong in people that can't make it and then  perhaps most importantly how do we prevent that [4:10] age related decline in nitric oxide production  so everybody can be empowered to take control of [4:17] their own health and prevent age related disease  and that's what the science tells us but as you [4:22] illustrated most people have never heard of this  i mean this graph which I'll put on the screen for [4:26] anyone watching kind of illustrates what you're  talking about and quite notably this decline seems [4:30] to start when you're 30 years old which is how  old I am right now so well you know that's if you [4:37] look at population based studies at different age  groups we see about a 10 to 12% decline in what we [4:43] call endothelial function per decade so that means  so nitric oxide is a gas it's produced in the [4:49] endothelium so the endothelium is the single layer  of cells that line every blood vessel throughout [4:53] the body so the function of these endothelial  cells is to regulate vascular tone and to regulate [5:01] you know solute exchange and extravisation or  transport of molecules across that endothelial [5:07] layer and so when your endothelial cells can no  longer make nitric oxide gas they no longer dilate [5:13] so the blood vessels become constricted you start  to get inflammation you get stiff arteries plaque [5:19] deposition and that's what starts cardiovascular  disease or atlascerosis which So someone that's [5:25] struggling with their nitric oxide levels at the  moment what kind of symptoms would they experience [5:33] well we know there's a hierarchy right so the  first sign and symptom of nitric oxide deficiency [5:38] is usually erectile dysfunction and when you think  about this when we're stimulated or we're about to [5:44] have intimacy with our partner we have to dilate  the blood vessels so in erections in both men and [5:50] women are dependent upon dilation of the blood  vessels to get engorgment to get increase in [5:55] blood flow and that's what an erection is but if  those blood vessels can't make nitric oxide the [6:00] blood vessels don't dilate so there's no increase  in blood flow there's no engorgment and that's by [6:05] definition what we call in erectile dysfunction  and it's the same in men and women right whether [6:10] it's the penis or the clitoris or the labia you  have to have an increase in blood flow and without [6:15] nitric oxide there's no increase in blood flow so  that's number one and we call that the canary in [6:19] the coal mine because for years people thought  it was a lifestyle disorder right well erectile [6:25] dysfunction yeah but now it's recognized that it's  a symptom of loss of nitric oxide and really an [6:31] accelerated form of cardiovascular disease so  we have to focus on the vascular component of [6:37] erectile dysfunction what other diseases are  linked to nitric oxide deficiency so if if you [6:45] don't correct the ED then what you start to  see is an increase in blood pressure and when [6:49] you think about this mechanistically so we have  you know a finite volume of blood that's pumping [6:53] throughout our body every day every second and  if you can make nitric oxide the blood vessels [6:58] are more dilated so now we're pumping that volume  through you know more dilated blood vessels but if [7:04] we lose the ability to produce nitric oxide now  you don't get the dilation now you have smaller [7:08] blood vessels you're pumping that same volume of  blood through smaller pipes and simple physics [7:14] tells us that blood pressure goes up okay so  you're going to have cardiovascular challenges [7:18] well you're going to have high blood pressure or  hypertension and at least in the US and I think [7:23] these these statistics probably are worldwide  but two out of three Americans have an unsafe [7:27] elevation in blood pressure and 50% of the people  that are given prescription medications to treat [7:34] their blood pressure do not respond with better  blood pressure it's because most of the drugs out [7:40] there whether they're ACE inhibitors what's  called angotensin receptor blockers calcium [7:44] channel antagonists the main classes of drugs  that treat high blood pressure aren't targeted [7:50] toward restoration of nitric oxide so that's  why we call that resistant hypertension they're [7:55] resistant to traditional therapies and the reason  they're resistant is because it's a nitric oxide [8:00] problem and those drugs aren't designed to affect  nitric oxide production or improve it was there [8:05] a an aha moment in your career where you became  particularly interested in this subject because [8:11] you could have committed your life to studying any  facet of health or or science but for some reason [8:17] you chose nitric oxide as the thing that you chose  to focus on what was that eureka moment you know [8:24] for me it was I was a student at LSU School of  Medicine um this was the late 90s maybe early [8:30] 2000s but a Nobel Prize had just been awarded for  the discovery of nitric oxide there were three US [8:35] scientists that were awarded the Nobel Prize  in physiology and medicine in 1998 and I was [8:40] very fortunate at the time i was a young student  probably a first year student and Lou Ignaro who [8:45] had just won the Nobel Prize for the discovery  of nitric oxide came and spoke and gave a lecture [8:49] before the student body and I had a chance to  have a conversation with him afterwards and I was [8:54] fortunate to be invited to have dinner with him  that night and he made a very poignant statement [8:59] to me he goes "If we if the scientific community  can figure out how to restore the production of [9:04] nitric oxide it'll change the world and it'll  change the landscape of medicine." because even [9:09] then what is that 25 26 years ago that it was  recognized that a loss of nitric oxide production [9:16] is leading to the onset and development of many  poorly managed age- related chronic diseases so I [9:22] go that's a very profound statement from a guy  who just won the Nobel Prize but that was the [9:26] first kind of eureka moment for me that stimulated  the interest but then my dad and I talk about it [9:32] in the book is a dad is 76 years old in 1984 he  had a car accident it left him paralyzed from the [9:39] midback down so the majority of my life even as a  kid I was treating dad's wounds decubitous ulcers [9:46] pressure ulcers on his feet on his butt and he  developed these non-healing wounds he was diabetic [9:51] he was parapolgic poor blood flow hypertension and  he developed a non-healing wound and no wound care [9:57] doc that I took him to could heal this wound  so I started making a topical nitric oxide and [10:03] I've healed this wound within a per four years of  non-healing i healed it within 6 months simply by [10:09] giving nitric oxide and getting blood flow to that  wound killing the infection in the wound and this [10:14] was in a 60something year old paraplegic diabetic  sedentary old man what you went through as a young [10:21] man to me appears to be such an important sort of  throughine with all the work that you do and chose [10:27] to do there is this overarching question which is  even like why did you go into medicine why did you [10:32] want to help people where did that come from in  you and I feel like there's clues in that to some [10:37] degree based on what I I read about your family  your early upbringing the divorce of your parents [10:43] and then ultimately your dad getting in a car car  accident and being paralyzed is that an accurate [10:48] suspicion you know I certainly it directed kind  of my my life because I witnessed the failure of [10:55] the standard of care to treat dad with what I  thought should be pretty simple i mean we have [11:02] again the most advanced technology medical  technology best medical schools in the world [11:08] and yet we can't treat a wound we can't address  the hypertension we can't address the diabetes [11:15] medically and so I just thought that there had to  be a better way it's still with you now isn't it [11:25] yeah but I you know I see um you know dad when  think I'm having a bad day i just think look I'm [11:34] not in a wheelchair i got my health so no matter  how bad I think I got it it could always be worse [11:40] so I just wake up every day with a grateful  heart and you know some days are good some days [11:45] are bad but I always realize it could always be  better but it could be a hell of a lot worse so [11:49] I don't complain and who are you what are all the  reference points what's the experience you've had [11:57] in your career that have filled up your sort of  buckets of knowledge that you bring forth today [12:02] like what what have you studied where have you  been i was in molecular and cellular physiology [12:07] got a PhD in molecular and cellular physiology and  that was I was recruited by Fred Murad one of the [12:12] other guys who shared the Nobel Prize to join the  faculty at the University of Texas Health Science [12:17] Center in Houston which is the world's largest  medical center but it's part of the University of [12:21] Texas system so I was recruited as a professor of  molecular medicine published probably well over a [12:28] hundred peer-reviewed scientific publications i've  edited several medical textbooks on the subject [12:34] i taught in medical school and then I resigned  from academia I guess several years ago uh [12:39] during COVID to focus on the next phase of my  career is taking this 25 years of science and [12:46] research and discovery and now bringing that  to the four for safe and effective product [12:51] technology drug therapies to eradicate a lot of  these poorly managed chronic diseases that you [12:57] know we're faced with today so let me get this  straight i'll repeat back to you what I think I [13:01] understand about nitric oxide and you tell me if  it's accurate so this nitric oxide is a chemical [13:08] that is in all the blood cells of my body and  it allows my blood cells to basically expand [13:15] open up so blood can flow through there so if I  it dilates it dilates the smooth muscle so it's [13:20] not affecting the cells per se but it's dilating  the smooth muscle that surrounds the blood vessels [13:26] that leads to relaxation and dilation fine so my  blood cells would then expand your blood vessels [13:31] and more blood would go through there but if  I'm deficient that mechanism doesn't work and [13:35] my blood cells wouldn't expand ultimately expand  through the relaxation of the muscles that's right [13:41] and therefore I would have higher blood pressure  which can lead to a series of downstream diseases [13:48] and consequences and so when we look at the graph  that I showed a second ago where we're seeing for [13:53] anyone that can't see this graph because you're  listening on audio we're seeing nitric oxide [13:59] levels in young people up to the age of roughly  around 20 are optimal and then from about 30 to [14:06] 70 there's this tremendous sort of 80 90% drop  when I look at that graph though my question [14:11] becomes is that not just aging is that not just  normal is that not just inevitable well yeah [14:18] there are a lot of things that occur with aging  right we lose growth hormone with age we lose [14:22] u you know many hormones uh nitric oxide is a  is a hormone that we we first discovered nitric [14:28] oxide as a hormone back in 2007 but to understand  aging you have to understand what leads to aging [14:35] so aging from my perspective is the inability to  repair and replace dysfunctional cells right every [14:41] day we wear ourselves out and we just got to and  if we can repair and replace dysfunctional cells [14:45] then we combat or at least prolong the aging  process so what the science tells us in nitric [14:53] oxide is this that loss of nitric oxide production  is the earliest event in the onset progression of [14:59] age- related chronic disease so as that graph  implies it is part of the aging process but it [15:06] doesn't have to be right because today we know we  can shift that curve to the left or to the right [15:10] so we can accelerate it and you see this today  with 18 20 year old kids that are have high blood [15:17] pressure they have diabetes they have erectile  dysfunction they have learning and and cognitive [15:23] uh impairment and those are all symptoms of nitric  oxide deficiency and to the contrary we if we see [15:29] 50 60 70 year old patients that would fit on a  30 or 40 year old scale on that graph so this [15:37] this doesn't have to be the case we know how to  prevent this age- related decline in nitric oxide [15:41] production you know I'm I'm the best example i'm  51 years old but I've got the vascular age of a [15:45] 36 year old because I employ these principles  to prevent this age- related decline in nitric [15:51] oxide production and when you say you've got  the vascular age of a 36-y old how how does [15:56] one measure that you look at the sort of vascular  health of your You can So there's there's several [16:00] objective measures of of biological age obviously  we can affect our chronological age right but [16:06] we can certainly affect our biological age so  what you can do there's databases now of what [16:10] we call croted inima media thickness so they  take an ultrasound and look at your corroted [16:15] arteries and they can look at what's called smooth  muscle hyperlasia or the thickness of the inima [16:20] and compare it to a database of age matched  kind of really it's you're comparing against [16:27] your colleagues so that's one way another way is  looking at what's called flow mediated dilitation [16:33] or endothelial function and again through  database of hundreds of thousands or millions of [16:38] patients you can figure out where you fall on that  spectrum on endothelial function and then there's [16:44] um you know other mark markers looking at histone  modification of the DNA methylation profiles [16:50] there's a company or technology called glyen age  that looks at certain markers uh that can then [16:57] define a biological age for each individual so  by age 40 we have lost about 50% of our ability [17:04] to produce nitric oxide in our blood vessels and  we lose 10 to 12% of nitric oxide production per [17:12] decade this is all according to your book and  by age 70 to 80 nitric oxide levels in blood [17:17] vessels can be 75% lower than in young adults a  Japanese study found a 75% reduction in nitric [17:25] oxide production in people aged 70 to 80 compared  to 20 year olds interesting so in terms of chronic [17:36] disease that is downstream from me losing nitric  oxide level can you give me a bit of a menu [17:41] of chronic disease that is associated with this  nitric oxide deficiency yep we've touched on them [17:49] so erectile dysfunction um 50% of the men over the  age of 40 self-report erectile dysfunction that's [17:57] in the US so think about that 50% self-report  i think the numbers are higher because most 40 [18:04] year olds that I know are never going to admit  that they have erectile dysfunction so I think [18:08] the numbers are even worse so that's one high  blood pressure again 50% of the patients that [18:13] are treated with prescription medication don't  respond with better blood pressure that's a huge [18:17] problem because high blood pressure is the number  one driver of cardiovascular disease which is the [18:21] number one killer of men and women worldwide  number three metabolic disease and diabetes [18:27] we published in 2011 that nitric oxide production  is necessary for insulin signaling if the cell [18:33] can't make nitric oxide you develop insulin  resistance so diabetes a global pandemic nine out [18:39] of 10 Americans are metabolically unfit the other  thing is exercise intolerance if you if you try to [18:44] start an exercise regimen and you can't walk up  a flight of steps or exercise moderately for 15 [18:49] 20 30 minutes then you're nitric oxide deficient  and then the other one is uh obviously Alzheimer's [18:55] because Alzheimer's is a vascular disease it's  reduced blood flow to the uh to the brain we call [19:01] focal eskemia there's insulin resistance you know  Alzheimer's has been called diabetes type three so [19:07] you can't get it glucose into the cell that's the  primary energy source or substrate of the brain [19:12] oxidative stress and immune dysfunction and then  you get um misfolded proteins and that shows up [19:18] as the tangles and the amaloid plaque that we see  in Alzheimer's patients so if we can restore and [19:23] nitric oxide corrects every single thing we know  about Alzheimer's it improves blood flow to the [19:28] brain it improves glucose uptake so it overcomes  the metabolic aspect of Alzheimer's it reduces [19:35] inflammation in fact a number of my patents are  on a method of reducing inflammation it inhibits [19:40] the oxidative stress we see in in Alzheimer's and  neurological disease and it prevents the immune [19:44] dysfunction and when you do that when you restore  blood flow and you get nutrients and oxygen in and [19:49] you take out the metabolic waste products there's  no misfolding of protein so you don't get the [19:54] amaloid plaque you don't get the tangles so this  simple molecule nitric oxide gas I'm absolutely [20:01] convinced will eradicate and cure Alzheimer's  really because it it addresses every physiological [20:06] root cause of Alzheimer's if you can get it  administered therapeutically to patients early [20:13] enough or no I think that's a very key because the  success or failure of any clinical trial any drug [20:20] in any clinical trial is dependent upon the design  of the clinical trial and what patients at what [20:25] stage of disease that you enroll these patients  so what are the inclusion criteria and what are [20:30] the exclusion criteria and there's a stage in  every disease whether it's heart disease kidney [20:37] disease Alzheimer's where you've reached a point  of no return there's really no medical therapy [20:42] that's going to reverse that disease because  it's progressed to a state that's irreversible [20:46] so I think what we try to do is take take  patients early in the process what we call [20:52] vascular dementia mild cognitive impairment early  Alzheimer's because what I want to be able to [20:57] demonstrate is two things number one can we stop  the progression of disease once it's started can [21:04] we stop the progression and then number two is we  want to enroll patients far enough along to where [21:11] we can show regression so can you move can you  move the needle back and so That's a very kind of [21:17] a specific and finite patient population when you  design a clinical study number one at the at the [21:24] absolute worst we want to stop progression at the  absolute best we want to show that we can regress [21:28] disease and that's the goal of therapy is that you  understand the mechanism of disease to the extent [21:35] that you can treat it you can prevent it you can  reverse it and you can cure it is there something [21:41] you believe that the traditional world of medicine  and maybe the traditional media don't believe [21:49] yeah I believe in the truth and I come from a very  objective scientific background so everything that [21:55] we do is based on objective uh data i say this  because I was listening to your interview before [22:01] and there were several moments in the interview  where you'd reference that you'd say things like [22:06] they don't they don't want you to know this or  they don't they won't tell you this no absolutely [22:11] because you know the we talk about epiphies and  eureka moments in science but for me one of the [22:19] kind of complete change in paradigm in the way  that I think was changed in when I was in academia [22:26] and teaching in medical school and doing research  in in an academic institution and you start to [22:31] think what we in the scientific community we un  we've cured every disease every disease known [22:38] to man we've cured it in rats and mice so then the  question is why isn't this translated into patient [22:45] care why can't we do this in humans number one in  in animal experiments we control their environment [22:50] we control their food we control their life  cycle we control everything about them you [22:53] can't do that in everybody has a different diet  everybody has different drug therapy that they're [22:58] on or hygienic practices but then what I realized  was because when I was in academia we wanted to [23:06] create this consortium a center of excellence for  diseases because my thought process was you know [23:14] western medicine is siloed right if you have a  heart problem you go to a cardiologist you've [23:19] got a GI problem you go to gastronurologist if you  got a neurological problem you go to a neurologist [23:23] or psychiatrist but none of these disciplines talk  to one another so if you go to that neurologist is [23:30] going to treat that condition much different than  the cardiologist would much different than the GI [23:35] doc would but what if we're looking at the exact  same root cause and so my philosophy well let's [23:42] create a center of excellence and let's bring  everybody in the room let's bring the GI docs the [23:46] the neurologists the cardiologists the geneticists  the pulmonary docs the kidney docs the renal docs [23:52] and let's let's understand this kind of wheel and  cog because everything occurs at the mitochondria [23:58] subcellular level and energy production and then  basically everything can can manifest from that [24:05] but what I quickly realized when you when you go  to for instance MD Anderson and trying to treat [24:09] cancer no one is interested in curing cancer  no one is interested in curing human disease [24:18] because the epiphany for me came because medicine  is a business it's a for-profit business in fact [24:25] it's the largest business and economic model in  the world trillion dollar annualized market and [24:32] most of these drug companies who influence and pay  and support scientific journals JAMAMA New England [24:40] Journal of Medicine the major publications the  major journals and they're influencing regulation [24:46] and policy and FDA and so when you figure out  that there's undue influence by these for-profit [24:52] companies because the number one rule of business  as you know as an entrepreneur and a business guy [24:57] is acquire a customer and keep that customer as  long as you can call it lifetime value of that [25:03] customer and that's what medicine is they get you  they you acquire you as a customer they put you on [25:08] a drug that drug has side effects they have to put  you on another drug to mitigate the side effects [25:13] of that drug now you got side effects from that  polyarm pharmacy they have to put you on another [25:17] drug to mitigate those side effects and now you  look up and people who are 50 to 60 years old and [25:24] older are on 10 12 18 different medications  that's the best financial model in the world [25:31] so it's a great financial model but it's at the  expense of our health and the health of everybody [25:36] living on in the world and in the US you know we  have the sickest population in the world now for [25:41] the first time in the history of western medicine  have discussions between physician and patient how [25:46] do we wean you off this drug that conversation  has never had before because it's always if this [25:52] doesn't work come back and I'll prescribe you  more drugs let's do the opposite you come back [25:56] and let's understand the root of cause of disease  let's say okay well if we are addressing this you [26:01] don't need this medication and if you don't need  this medication you don't need this medication and [26:06] now for the first time you start weaning patients  off of drugs and what happens you're now impeding [26:11] upon the market share of these multi-billion  dollar drug companies who make their living [26:19] buying influence regulating policy influencing  policy and the FDA is a stepping stone to a board [26:26] seat of big pharma every former FDA official in  the US for the past 20 or 30 years goes on to [26:33] become multi-million dollar salaried employee from  big pharma it has to stop despite spending nearly [26:39] 20% of the United States GDP on healthcare the  US ranks last overall on health outcomes among [26:47] high income countries including having the highest  infant mortality rates and lowest life expectancy [26:55] it's like unbelievable no I mean that's that's  depressing i mean but those are the facts and [27:01] the you have to understand those those are  indisputable data right and so when people hear [27:08] that they go they this but when you look at kind  of the system and I don't blame doctors because [27:14] doctors are get into this field you know I was on  the admissions committee to UT medical school for [27:18] a number of years so we interviewed a lot of these  young kids figure out what their motivation was [27:23] will they have a successful career in medicine  and almost everyone I mean there's always the [27:27] exception but everyone gets into medicine  because they want to make make a difference [27:32] they're driven by curiosity and most of them want  to leave a lasting legacy and help people that's [27:36] what drives uh entry into healthcare but when you  look at the system in which they're trained in it [27:44] prevents them it basically handcuffs them because  when you figure out the pay the economic model of [27:50] medicine once you make a diagnosis now you've  got a diagnosible disease to which you have a [27:56] finite number of responses right if you make this  diagnosis that's called an ICD10 code which is [28:02] reimburseable and that's how you get paid so once  you make a diagnosis you only have a finite list [28:08] of things you can do you can't ask that question  and go well what's really causing this and spend [28:13] you know 90 minutes with that patient because most  physicians have to see 60 70 80 patients a day to [28:20] pay the bills to cover their overhead so it's a  factory you come in you look at you've got a a [28:27] transcriber you make a diagnosis okay I can I'm  going to prescribe this medication come back in [28:32] two weeks or six months and we'll see where you  are and then it's just it's a term it's a meal [28:36] but as you me the data don't lie right sickest  population highest infant mortality in the most [28:43] industrialized nation in the world and according  to the data Americans are spending about 13 years [28:48] of their life living with disease and that is  significantly higher than many other highincome [28:55] western countries so although life expectancy  you know might be 70 80 years old you're going [29:00] to spend almost 15 years of that time living with  disease so your health span is um really probably [29:05] the more important thing to be focusing on not  your lifespan and so when we talk about nitric [29:09] oxide I've heard you describe it as the molecule  of longevity for sure why why' you say that why do [29:16] you say that well again longevity is this emerging  field that's driven by how do we live longer how [29:23] do we increase our health span and longevity right  because I think we can all agree that nobody wants [29:28] to live to be 100 years old if we spend the last  25 of that years incapacitated in a diaper unable [29:34] to get out of bed right that's not living so when  I look at longevity I look at kind of what are the [29:41] hallmarks of longevity what defines longevity  right how do we live longer healthier life free [29:46] of disease and really there's three objective  measures there is a stem cells you know this [29:52] whole field of regenerative medicine is based  on mobilizing our own stem cells or deploying [29:58] u stem cells throughout the body to repair and  replace dysfunctional cells so these stem cells [30:02] are cells that can basically act as like band-aids  repairs for any part of our body well we call them [30:07] pur potent stem cells so mean that and some of  these are bone marrow derived some of these are [30:11] what we call stromal vascular fraction that you  get from the atapost tissue or the fat pur potent [30:16] would mean pur potent means they can that stem  cell can go and become a neuron that stem cell [30:21] can go to the heart and become a functional meioy  it can go and become a macrofase or an immune cell [30:28] white blood cell so pur potent means it can become  many things whatever it needs to be in some cases [30:34] the amount of stem cells present in our bone  marrow get smaller with age the number of cells [30:40] decrease with age but fortunately or unfortunately  the older we get the more fat we deposit and so [30:47] we have a number of stem cells in our fat so we  increase the number of stem cells in our fat so [30:52] the problem with aging and longevity is when we  lose the ability to mobilize our own stem cells [30:58] we can't we can't repair and replace dysfunctional  cells so we have these what we call zombie cells [31:03] or scinsesscent cells they're there but they  can't do their job they're dysfunctional and [31:08] that's what leads to age number two it's telomeirs  and telomeirs are the ends of the chromosomes of [31:15] our DNA and so the they're the very end so it's  like the um the the tips of the sho strings [31:23] right that prevent the sho string from fraying  and those are like the telomeir so as long as [31:27] you have a functional telomeir and it prevents  it from getting shorter then shorter telomeir [31:32] shorter lifespan longer telomeres longer lifespan  so when telomeirs get shorter it decreases our [31:38] lifespan and longevity and then the third one is  mitochondrial function every age- related chronic [31:44] disease you have a lower number of mitochondria  per cell and the mitochondria that are present [31:50] aren't functional so you get a what's called an  uncoupling of the electron transport chain inside [31:55] the inner mitochondrial membrane and you can no  longer effectively produce cellular energy or ATP [32:02] so nitric oxide is the foundational longevity  longevity molecule because nitric oxide is the [32:07] signal in the body that tells our stem cells to  mobilize and differentiate without nitric oxide [32:13] you have less number of circulating stem cells  nitric oxide activates the enzyme toase which [32:19] prevents telomeir shortening without nitric oxide  you don't get activation of tomeorase telomeir [32:24] shorten and then nitric oxide is the signal in the  cell that tells the cell I need more mitochondria [32:32] and I need these mitochondria to be more efficient  generate more cellular energy with less oxygen so [32:39] when you when you restore nitric oxide you address  all three aspects of longevity and there's no [32:45] other molecule on the body that does that you know  Brian Johnson don't you yes what do you think of [32:50] Brian Johnson you know I would never replicate  or try to um do what he does i don't think it's [32:57] the proper approach you know and I I don't I don't  mean to criticize people because this whole field [33:02] of biohacking you know you get people who have  no science background no medical background no [33:08] biochemical background and yet they're out there  influencing millions of people that follow them [33:15] and many times they're giving really bad advice  not intentionally it's because of ignorance they [33:21] just don't know they don't know the science they  don't know the medicine behind it so before you [33:25] go and follow any influencer or biohacker number  one look at their credentials and if they don't [33:31] have any science background if they're you know  formal technologist or you know come from anything [33:37] besides science and medicine you really need to  do a little bit of deep dive and make sure that [33:42] what they're giving you is scientifically valid  or recommending he seems to be a fan of um the [33:47] role of nitric oxide as it relates to longevity  though he seems to have said positive things about [33:52] um nitric oxide and its impact on improving  your cardiovascular health yeah i think as [33:58] we advance the science and we we do more to  communicate the complex science into you know [34:03] layman's terms where the the non-scientists  non-medical professionals can understand it [34:07] and appreciate it i think more people are going to  pick up to that but there's also some well-known [34:12] biohackers with influences of you know millions  of people that still say that nitric oxide is a [34:18] toxin that inhibits mitochondrial respiration and  it should be avoided is there such thing as having [34:23] too much nitric oxide though because if people  hear this conversation today and they rush out [34:27] and they I don't know overdo their nitric oxide by  doing a bunch of uh therapies yeah is that a risk [34:36] absolutely you know we know water is essential  right but we can drink too much water and kill [34:41] ourselves you see it on the news you know a couple  times a year called hypotonic lis so yeah dose [34:46] dictates poison and so what we have to do is make  sure maintain the integrity of the field to make [34:52] sure that if there are nitric oxide products out  there that number one you don't overdo it and and [34:59] lead to you know health issues or kill a consumer  kill a patient that could kill the entire field [35:05] but we also understand that there's only two signs  of toxicity for nitric oxide so it's really pretty [35:11] straightforward number one if you take too much  nitric oxide you're going to get an unsafe drop [35:15] in blood pressure because think about this if  you if you take nitric oxide or you're enhancing [35:20] nitric oxide production through whatever means  it's going to lead to systemic vasoddilation now [35:26] you've got that same volume of blood pumping  through much larger pipes and you're going [35:30] to have a drop in blood pressure and if you lose  profusion pressure you're not going to be able to [35:35] peruse the brain because you got to pump against  gravity and you're going to get lightheaded and [35:38] you'll pass out and if that's prolonged it leads  to es schemic end organ damage and organ failure [35:44] and it can be deadly so that's number one  and then number two is a condition called [35:48] met hemoglobinia and that's a big word meaning  that your it oxidizes the iron of hemoglobin and [35:54] reduces your oxygen carrying capacity so you'll  become cyanotic you'll get blue around the lips [35:59] your extremities will turn will turn um you  know white from lack of profusion or lack of [36:05] oxygen but you never see that I mean you really  never see clinical met hemoglobinia fortunately [36:11] your your blood pressure will drop to an unsafe  level long before you get any accumulation of met [36:16] hemoglobinia so on this point of longevity then  one of the points you mentioned there was telmir [36:21] length and I've heard about telmir length because  I've heard about studies they've done in rats and [36:24] I think other rodents around telmir length so  it was discovered that indiv individuals with [36:29] shorter telomeres had a death rate nearly twice  of those with longer telomeres and you're telling [36:37] me that there has been research done that  shows how nitric oxide can increase telmir [36:42] length absolutely so we we understand at the DNA  level at the nuclear level that nitric oxide is [36:51] is what's called a collocicalizes with estrogen  recep receptor to allow for the turning the the [36:58] cell to turn on transcription and translation of  the tomeorase enzyme so it's not only affecting [37:04] the genetic transcription of that protein but  it's also regulating the function of the enzyme [37:10] so without nitric oxide you have less telomeir  tomeorase enzyme and that tomeorase enzyme isn't [37:16] functional okay so nitric oxide has an impact on  the tomease tomeorase enzyme that's right tomeres [37:23] enzyme so what happens with each cellular division  those telomeirs can get shorter right but as long [37:28] as that tomeorase enzyme is active it prevents the  shortening of the very ends of the chromosome okay [37:34] and just for people that don't understand the um  with every replication as we age we're continually [37:40] replicating ourselves to restore and repair them  but in that replication process harm is occurred [37:46] sometimes yeah and different cell types have  different replication rates right so the the [37:50] epithelium of the gut is highly regenerative right  it's it's a replicatable uh you replacing these [37:57] cells all the time because it's the outside  environment that you're having to continue [38:00] to replace those cells neurons to the exact  opposite aren't regenerative by nature so we don't [38:07] typically make I mean we can it was once thought  that you can't regenerate neurons but today we [38:10] know we can but yeah so it affects different organ  systems differently but the data are clear shorter [38:17] telomeres shorter lifespan the other thing that  um I wanted to talk to you about before we really [38:20] get into the heart of how do I improve my nitric  oxide levels keep them at a healthy range while I [38:26] age is nitric oxide's relationship with the oral  microbiome i had a conversation on this podcast [38:33] not too long ago about the oral microbiome again  another subject I hadn't thought much about but [38:37] is there a relationship there no doubt i mean  this is this is probably 20 year old science [38:43] um where we find that you know probably 20 years  ago the microbiome project was complete and what [38:51] that means is that the bacteria that live in and  on our body were completely mapped out and these [38:57] communities were identified in the gut started in  the gut the gastrointestinal tract and then you [39:02] know you can you can culture the the this the skin  flora there's bacteria that live on our skin there [39:08] are bacteria that live in our colon there are  bacteria in women that that that reside in the in [39:13] the vagina and so all of these different ecologies  of bacteria that live in and on the body are there [39:19] to do things to help the human host right we  call this symbiosis we're providing benefit to [39:25] the bacteria and the bacteria providing benefit  to the human host and so if you use antibiotics [39:33] or antiseptics to kill the bacteria that live  in and on our body you get human disease i mean [39:41] that's clear and the the best example is that  there's no physician in the world that would [39:45] recommend you or I take an antibiotic every day  for the rest of our lives right do you agree with [39:50] that and why is that because the antibiotics are  killing the good bacteria they kill the infectious [39:56] pathogen bacteria but they also destroy  the entire microbiome and when you disrupt [40:01] the microbiome you get systemic disease you get  vascular disease you get Alzheimer's you get uh [40:07] leaky gut syndrome you get autoimmune disease you  get high blood pressure you get yeast infections [40:13] uh you get overgrowth of candida you get parasites  so the bacteria are really the police of the human [40:22] kind of surveillance right so the n we have 10  times more bacteria cells that make up the human [40:28] than we have human cells so we're 10 times more  bacteria than we are human and so if you destroy [40:35] that microbiome then it leads to systemic disease  we live in a culture where we're constantly trying [40:40] to kill bacteria right like especially post  pandemic we're using all kinds of hand washes [40:45] and antiseptics and obviously the the big I  guess chemicals that we all typically use are [40:52] things like mouthwashes with uh which are again  trying to just clean out all the bacteria from [40:57] our mouths what how would you caution someone  on using these things and even the like the [41:03] antibacterial Yeah it's bad news really we give  it to our children because we want our kids to [41:08] be clean and not to have kids need to be dirty  you find and again you look at epidemological [41:13] data peop kids who grow up in the in a rural area  they're out in the environment they're rolling in [41:19] dirt they're they're got dirt on them and they  have um you know they're inoculated with a lot [41:24] of bacterium those kids are the healthiest people  and and you look later in life they have lower [41:29] incidence of cardiovascular disease diabetes they  have better immune dysfunction less autoimmune [41:33] disease so there's this whole hy hygienic  principle or hygienic hypothesis of disease [41:39] and I don't think it's a hypothesis anymore i  think it's proven out so for me I go back and I [41:45] go "What why are we doing this why are we using  fluoride rinses in dental offices why is there [41:51] fluoride in our toothpaste why is there fluoride  in the municipal water of 72% of municipalities in [41:57] the US when fluoride is a known antiseptic it's a  chemical toxicant it's a a thyroid toxic it kills [42:05] your thyroid and it's a neurological toxin." And  so when you go back and look at the history of [42:11] dentistry over a hundred years ago it was first  identified that oral bacteria can be found in [42:19] the plaque that killed someone from an acute  heart attack right people who died from sudden [42:24] cardiac death they'll take the thrombus or the  embleis that oluded that coronary artery and they [42:29] basically biops it and they find oral bacteria in  that plaque that caused the heart attack or stroke [42:37] so that told us there's an oral systemic  link there's bacterial transllocation of the [42:41] pathogens that's why bleeding gums are a problem  because you've got bacteria in the mouth if you [42:46] got bleeding gums there's open blood vessels for  those bacteria to get into our blood supply now [42:50] they become systemic cause inflammation plaque  rupture and heart attack and stroke so 100 years [42:57] ago with reason with good reason they go well  let's treat with an aneseptic we have to kill all [43:03] the bacteria in the mouth so if you have bleeding  gums there's no translloca transllocation of that [43:08] in the systemic circulation and we can prevent  heart attack or stroke that was a hundred years [43:14] ago and we've learned a lot in those hundred  years number one it wasn't recognized that we [43:19] have a microbiome on our body in our body so now  when I ask dentists all the time why do you use [43:26] floor and they go well it's been used for hundred  years and I go I don't care what the question is [43:30] that's the worst answer you could provide just  because we're doing it because that's the way [43:33] we've always done it right so now we have  to understand how do we selectively kill the [43:38] pathogens while maintaining a healthy microbiome  and so this this field started probably in the [43:46] I mean some of the first papers were published  probably in the 90s showing that there were if [43:51] you use mouthwash it destroyed the microbiome  and we saw an increase in blood pressure these [43:57] papers were published in the late 2000s we we  published on this probably in like 2008 2009 [44:03] we created what's called an association so people  who had the healthiest and most diverse bacteria [44:08] in their mouth had the best blood pressure people  who had the least diverse oral microbiome and we [44:15] we could not culture any of these nitric oxide  producing bacteria appeared to have the highest [44:20] blood pressure so that's what we call association  it's not causation but it's a nice association [44:27] so in 2019 we published a paper showing okay  let's now let's see if we do if we take normal [44:32] intensive patients young healthy people with good  nitric oxide good blood pressure and we just give [44:40] them mouthwash twice a day for seven days to kill  the entire oral microbiome and then we do tongue [44:46] scrapings to see if we're killing the bacteria  and we do blood pressure measurements and so we [44:51] do that twice a day for seven days seven days  we bring them back in we measure their blood [44:55] pressure and then we stop for four days we say  okay don't talk don't take mouthwash for four [45:00] days then come back let's rememeasure your blood  pressure and let's do tongue scrapings and figure [45:05] out what's happening to this these bacterial  communities and what we found was that if you [45:11] eradicate the bacteria within 7 days your blood  pressure goes up so if you use mouthwash within [45:18] seven days your blood pressure goes up i think it  occurs earlier but what we we looked at seven days [45:24] we only looked at day one at baseline seven days  and then four days after stopping the mouthwash [45:30] but in one 21-year-old kid his blood pressure went  up 26 millimeters of mercury which is put that in [45:36] context for me that's clinically hypertensive so  for every 1 millimeter increase in blood pressure [45:41] that increases your risk of cardiovascular  disease by 1% so within 7 days we increased [45:47] this kid's risk of cardiovascular disease by 26%  simply by giving him mouthwash and explain to me [45:53] in layman's terms the mechanism there what's  going on well we're still trying to understand [46:01] mechanism again we're at the observational level  that's really indisputable because these bacteria [46:06] there's what we call nitrate reducing bacteria  and humans do not have this enzyme so nitrate [46:11] is what's found in green leafy vegetables right  these these plants assimilate nitrogen in the [46:16] soil in the form of nitrate we consume these  vegetables the nitrate is taken up in the gut [46:21] it's concentrated in our salivary glands and the  bacteria perform this metabolism of nitrate into [46:28] nitrite and nitric oxide and humans do not have  the the functional enzyme to do this so we're [46:34] 100% dependent upon the bacteria so then now  because nitrate is inert in humans we we rely [46:41] on the bacteria to metabolize this molecule into a  usable form where we can make nitric oxide so when [46:48] you're killing the bacterium now the nitrate is  just being recirculated but you're you're you're [46:54] urinating because it's it's it's filtered across  the kidneys you poop it out and you sweat it out [47:00] so it's completely unchanged unless you have the  right bacteria and what we're finding is that that [47:07] oral production of nitride and nitric oxide  being produced in the acid environment of the [47:11] stomach is somehow regulating resistance arteries  in dilation to normalize systemic blood pressure [47:20] so if I don't have a healthy oral microbiome then  you have an elevation in blood pressure and much [47:26] of the things you you're talking to me about  today in terms of dietary um changes won't have [47:32] any effect anyway because I need the bacteria  to convert it into nitric oxide as it relates [47:38] there are many benefits of of many nutrients  in foods particular plants that confer some [47:43] health benefits but when we focus specifically  on the benefits of nitric oxide from your diet [47:49] if you don't have the right oral bacteria you  get zero nitric oxide benefits from your diet [47:56] now you're going to get you know obviously  hopefully vitamin A vitamin C vitamin D from [48:00] foods fiber other phytonutrients but in terms  of the blood pressure lowering effects of a for [48:06] instance a plant-based diet if you don't have the  right bacteria you get zero benefits of that have [48:11] you seen a link between oral health and cancer  yes absolutely what have you seen people that [48:19] have dental infections root canals cavitations  from previous extraction sites have typically [48:26] cancer it sets the stage for cancer cell growth  and proliferation so and and I've you know I made [48:33] a controversial statement on a on a previous  podcast where I say number one I'm not an [48:37] oncologist but people who have terminal metastatic  disease who aren't ready to die who are sent home [48:43] to die on hospice somehow find me and go can you  help me with this cancer and so the first thing [48:48] I always send them to is a dentist to see do you  have any active oral infections that may have led [48:55] to the development of the primary tumor in the  first place but obviously it's it's metastatic [48:59] meaning that it's now everywhere it's it's it's  migrated outside that primary tumor but almost [49:05] always without fail they have an active oral  infection and it may be a symptomatic infection [49:10] to where they know it and they have a toothache  or it may be an asymptomatic infection where they [49:14] don't even know they got a dental infection what  percentage of cancer patients that you see that [49:18] you then refer to a dentist have an oral infection  people with primary tumors solid tumors so we [49:24] categorize these in bloodborne cancers something  like lymphoma leukemia multiple myoma which is [49:29] a bloodborne cancer and those that have a solid  tumor a primary tumor that starts in the breast [49:35] the colon the prostate the lungs or the liver  without fail 100% of them have dental infections [49:43] but cause and effect is not possible to establish  here right because cause and effect no I don't [49:46] think we're there yet i think probably as the  science advances and people start to look at [49:52] this because you may imagine if you have cancer  and you've been to the best cancer doctors in the [50:00] world and you've done surgery you've done chemo  you've done radiation you've gone through the [50:05] standard of care and the cancer comes back  it's terminal it's metastatic and you tell [50:11] when I tell people well you need to go see a  dentist i mean many people laugh and they go [50:16] "Have you what what in the hell did you just say  i've got cancer i don't have a dental problem." [50:21] And I go "Well perhaps you do." Because again  if you go back and always look at back what's [50:27] what's held true throughout ages and if you look  at ayurveetic medicine if you look at traditional [50:32] Chinese medicine if you look at acupuncture you  know if you go back and you look if you don't [50:37] know what to look for you're never going to find  it if you know what to look for it's out there [50:41] it's in the published literature but every tooth  in the body is connected to an organ system right [50:47] and so these are these are the meridians the  acupuncture meridians you know the analogy is [50:51] they're circuit breakers so if you if you trip a  breaker in your home there's no electricity going [50:57] through that circuit so your oven doesn't work  your refrigerator doesn't work or your lights go [51:01] out well the body is electric right and how do we  diagnose death no electrical activity right either [51:09] through an EKG or an EEG so the body is electric  and we're we're batteries and so if we get if that [51:16] red light comes on on our phone it says we have  a low battery everybody panics and goes and plugs [51:20] it in and charges right and the human body is  the exact same we lose voltage over time and if [51:26] you've got a trip breaker from an infected tooth  there's no voltage there's no circuitry going to [51:32] that meridian that feeds individual organs so the  the best example is if you've got a root canal [51:38] and a 100% of root canal teeth are infected and  when you think and people go well that's not true [51:43] well think about what a root canal is you had a  toothache at some point because of an infection [51:50] so you go to the dentist and they pull the nerve  root out of that tooth so you don't feel the pain [51:56] anymore because there's no nerve root there and  they pull the blood supply out of that tooth now [52:01] you have no blood supply to that tooth and a tooth  is a crystallin structure it's a living organ with [52:06] no blood supply and no nerve root that's a dead  tissue so if you were to go in and we'd disconnect [52:12] your gallbladder for example and just cut the  blood supply to it the nerve supply to it within [52:16] seven or 10 days you'd be dead from sepsis nobody  leaves dead tissue in the body and so then what [52:23] happens is when you leave the dentist what do they  do they put you on an oral antibiotic but they [52:28] must have forgotten they took out the blood supply  to that infected site so an oral antibiotic isn't [52:34] going to reach the sight of infection i mean to me  when you think when you sit back and think about [52:38] this and go who the hell does this and why do they  do it well it's because what we've always done [52:44] so then what happens is these anorobic bacteria  they don't need oxygen they're sitting there in [52:48] an anorobic low oxygen environment and they're  just eating away at your jawline they're just [52:53] like us do they they they metabolize they take  stuff in they poop waste out those waste products [52:58] uh accumulate it shuts down voltage and they eat  away at your jawline so then you've got osteom [53:04] necrosis osteomiitis and you don't even know it  and an x-ray will not show it and most dentists [53:09] unfortunately still use x-rays instead of a higher  resolution CT it's really interesting i was doing [53:15] some research in preparation for this conversation  around this subject of oral microbiome and cancer [53:19] and the link there and one particular study that  was done um published in the New York Post but [53:23] done by a team of researchers found that this  was done at New York University as well so it [53:28] was published by the New York Post and done at  New York University they analyzed saliva samples [53:32] of over 160,000 participants over 15 years are you  familiar with this study and they identified over [53:38] a dozen bacteria species linked to a high risk  of head and neck cancers with certain bacteria [53:43] increasing the risk by 50% of getting a cancer  which is pretty shocking um literally I feel [53:48] like texting my assistant and asking us to book  a oral hygieneist and to change my mouthwash no [53:55] matter where I am in the world it seems like  everyone is drinking matcha and there's a good [54:00] chance that that matcha you're drinking is made  by a company that I've invested more than seven [54:03] figures in who are a sponsor of this podcast  called Perfect Ted because they're the brand [54:08] used globally by cafes like Blank Street Coffee  and Joe in the Juice and many many more not only [54:14] can you get Perfect Ted Match in cafes but you  can now also make it at home much cheaper in [54:20] seconds using our flavored matcha powders that  I have here in front of me perfect Ted matcher [54:24] is ceremonial grade and sourced from Japan it  is smooth it is naturally sweet not like those [54:30] bitter grassy matches that I tried before perfect  Ted and if you are one of those people that have [54:34] told yourself you don't like matcha it's probably  because you haven't tried our Perfect Ted Matcher [54:39] and you can find Perfect Ted Matcher in the  UK in Tesco Sainsbury's Holland and Barrett [54:44] and in Waitro or Albertine if you're in the  Netherlands and on Amazon in the USA or get [54:49] the full range online at perfectted.com where  you can get 40% off your first order with code [54:56] Steven40 this one change has transformed how my  team and I move train and think about our bodies [55:04] when Dr daniel Lieberman came on the diio he  explained how modern shoes with their cushioning [55:10] and support are making our feet weaker and less  capable of doing what nature intended them to do [55:14] we've lost the natural strength and mobility in  our feet and this is leading to issues like back [55:20] pain and knee pain i'd already purchased a pair  of Viva barefoot shoes so I showed them to Daniel [55:25] Lieberman and he told me that they were exactly  the type of shoe that would help me restore [55:30] natural foot movement and rebuild my strength  but I think it was planttoicitis that I had where [55:33] suddenly my feet started hurting all the time  and after that I decided to start strengthening [55:37] my own foot by using the Vivo barefoots and  research from Liverpool University has backed [55:41] this up they've shown that wearing Vivo barefoot  shoes for 6 months can increase foot strength [55:46] by up to 60% visit vivarefoot.com/doac  and use code DOAC20 for 20% off that's a [55:55] vivobarefoot.com/dac use code DOAC20 a strong body  starts with strong feet if I've just listened to [56:05] everything you've just said there and I want  to improve my oral microbiome what should I [56:09] be doing well I think the most important thing  we've learned is what you shouldn't be doing [56:14] right so it's not what should we do it's what  we shouldn't be doing number one we have to get [56:18] rid of fluoride you know just this past weekend I  was speaking at a dental conference in Salt Lake [56:22] City and there were there people there from  the National Toxicology Program which in the [56:27] US is the organization tasked with if there's any  kind of risk of exposure of environmental toxicant [56:35] they're charged with doing the toxicology studies  to see if there's an increased risk what is the [56:40] risk and is there a safe level that is without  risk and what they report is that fluoride there's [56:47] no benefit of fluoride and it's all risk it lowers  IQ in kids by as much as seven points and it shuts [56:54] down your thyroid function and it's a neurotoxin  and as I mentioned before most toothpaste has [57:02] fluoride in it and if you read the back of your  toothpaste it will tell you at least in the US [57:07] I don't know about in other countries but it  says if you swallow this call poison control [57:12] because it's a poison they're putting poison in  toothpaste and then if you also pay attention [57:17] it says only put a P-siz amount of toothpaste on  your toothbrush a P size but everybody that I know [57:25] fills the entire bristle of the toothpaste with  toothbrush with toothpaste so that's about 10 or [57:31] 15 sometimes 20 P-size amounts of toothpaste and  a P-siz amount of toothpaste contains about half [57:38] a milligram of fluoride now if you're using 10  20 times more than that P size now you're exposed [57:45] to 5 milligrams 10 milligrams of fluoride and you  don't even have to swallow it this is a very small [57:50] molecule a molecular weight of 19 so it's absorbed  directly across the bugal mucosa the oral cavity [57:57] and it becomes systemic i'm not going to use it  anymore no you shouldn't what should I use instead [58:03] you have to use a non florinated toothpaste  and what about things like tongue scrapers [58:08] now tongue scrapers the data again that's time-  tested that's an ancient practice and even in [58:13] our study we found that people who do tongue  scraping have a more diverse oral microbiome and [58:19] they seem to have better oral health why is this  my girlfriend's been banging on to me she's always [58:24] bloody right my girlfriend's been banging on to me  about tongue scraping for the last two years and [58:29] I've kind of just ignored her i've just kind of  Yeah babe sure and but when she's not in the bath [58:33] bathroom I'm not using her tongue scraper because  it just looks strange i for me based on what I [58:39] knew about the oral microbiome and the microbiome  generally I'm like should I be scraping off all my [58:43] bacteria well if you're going to plant a garden  do you plant a garden on untilled soil listen [58:50] I know nothing about gardening you're asking the  wrong guy so maybe yes I grow my own food okay so [58:55] you have to till the soil right you got to break  up the soil so the seeds actually can be irrated [59:00] and you just break up that um that bofilm yeah you  take the back of the dorsal tongue i mean almost [59:06] to the point of the gag reflex and you just pull  that ideally copper tongue scraper forward and [59:12] you're going to see this goop coming in there but  it's it's like kind of like tilling the soil and [59:18] it's it's increasing the diversity of the the  dorsal part of the tongue the microbiome so my [59:22] girlfriend was right in that regard yes but what  we found was in that one kid we saw the greatest [59:29] increase in blood pressure if you tongue scrape  and use antiseptic mouthwash that's the absolute [59:34] worst scenario interesting so if you just think  about this you're tongue scraping you're opening [59:41] up the pores and now you're using mouthwash  it's better to can easily penetrate deep in [59:46] the crypts of the tongue and more effectively kill  the bacteria so you want to tongue scrape and then [59:51] use a toothbrush without fluoride toothpaste  absolutely and no mouth no no antiseptic mouth [59:56] rinse okay and what about going to dental  hygienists and things like that do you think [60:02] that's a advisable idea because once every quarter  or so um I'll go and see a dental hygienist just [60:08] to get everything sort of cleaned out no I think  that's a good proactive uh practice but you know [60:13] because you need to look at the um the health of  the gum tissue and the the gingal tissue and a [60:20] routine clean and scraping the the plaque off  the teeth and allow making sure you have good [60:25] mineralization of the enamel of the tooth is  good but never let them do a fluoride rinse on [60:30] you okay is there anything else on this subject  of your microbiome and its relationship with [60:34] nitric oxide that I need to be aware of before we  move on yeah we there's also data showing that if [60:39] you use mouthwash you lose the cardioprotective  benefits of exercise so think about this we know [60:46] that diet and exercise is the best medicine  and many people aspire to do that they they [60:53] go and they they try to eat good they avoid the  temptations of sugars and sweets they exercise [60:58] every day to try to increase their longevity and  cardiovascular health if you do that and you're [61:05] using mouthwash you no longer get the benefits  from exercise and we've already established you [61:09] don't get the nitric oxide benefits from diet so  two out of three Americans wake up every morning [61:14] and use mouthwash and two out of three Americans  have an unsafe elevation in blood pressure what's [61:19] the mechanism there well because you're you're  killing the the the oral microbiome that's partly [61:24] responsible for production of nitric oxide without  nitric oxide you get constriction of blood vessels [61:29] and it leads to high blood pressure that's crazy  and is there a link between our hormone levels [61:36] things like my testosterone levels and the nitric  oxide yes so this is a two-way street so nitro So [61:42] in men testosterone activates nitric oxide  production okay in women estrogen activates [61:48] and stimulates nitric oxide production okay so  as long as we have optimal sex hormones and as [61:54] long as the enzyme in the lining of the blood  vessel can functionally produce nitric oxide [61:58] that explains the cardio protective benefits of  hormone replacement therapy got you so taking [62:03] testosterone or um estrogen therapies helps to  increase my nitro oxide levels as long as the [62:10] enzyme is functional and coupled which means that  we have to we have to understand the enzyology [62:15] and the biochemistry of that reaction to where  when it's exposed to testosterone it the cell [62:21] can actually make nitric oxide in response  and there's a two-way relationship as well [62:25] with exercise then because I've read in your book  that um exercise activates and stimulates nitric [62:31] oxide production but you also just told me that  if you want to get the great benefits of exercise [62:36] you need nitric oxide in the first place because  else your blood cells are going to be very narrow [62:41] less oxygen traveling through you're going to do a  worse workout as well presumably well think about [62:46] I mean there's other agonist too like vitamin D  i mean most Americans are deficient in vitamin D [62:51] uh people with low testosterone have erectile  dysfunction and why is that because they're not [62:55] stimulating nitric oxide production and they're  not dilating the blood vessels so they develop [62:59] ED so all of this no matter what it is whether  it's related to vitamin D deficiency which is [63:03] activating and stimulating of nitric oxide if it's  low hormones if it's poor diet sedentary lifestyle [63:10] all of that can be explained by insufficient  nitric oxide production when I think about the [63:15] role that food plays in my nitric oxide production  what should I be eating to increase um my nitric [63:24] oxide levels or to keep them at a healthy level i  think it the same answer is for that too it's it's [63:31] not so much what we should be eating it's what  we should not be eating okay so we we'll we'll [63:36] cover those step by step number one you have  to avoid sugar and high glycemic index foods [63:43] because sugar is a toxin it's a poison and let's  think about what sugar is so when we eat sugar or [63:50] drink sugar beverages right whether it's sucrose  whether it's fructose whether it's high fructose [63:55] corn syrup the end result inside the human is we  see an increase in glucose so elevation in blood [64:02] sugar or blood glucose is diabetes right and now  there's continuous glucose monitors that you can [64:10] get anywhere and everybody does this so if you eat  something and it causes an increase in your blood [64:15] sugar blood glucose then you should avoid that  because glucose as the name implies is glue right [64:21] it's sticky and if we if you have a soda and you  spill it on your countertop you come back the next [64:26] day it's sticky right well that's what happens  inside the body that sugar sticks to everything it [64:32] sticks to proteins it sticks to enzymes it binds  to hemoglobin and sugar stuck to hemoglobin is [64:38] what we call hemoglobin A1C and what is that it's  a it's a marker of long-term glucose control if [64:46] you have hemoglobin A1C of greater than 5.7 you're  diabetic so it's not just hemoglobin it sticks to [64:52] it sticks to the enzyme that makes nitric oxide  in in biochemistry and enzyology enzymes have to [65:00] be able to undergo confirmational changes right  so it transfers electrons from one donor to an [65:06] acceptor and that's how biochemistry is is done  but if sugar is stuck to that enzyme it locks it [65:12] in some confirmation and it can't do its job for  it can't make nitric oxide so sugar is an absolute [65:18] poison and it kills many enzymes and binds to  everything and it lowers nitric oxide production [65:24] absolutely that's why diabetics have a 10 times  higher incidence of heart attack stroke all cause [65:30] mortality mortality that's why they develop neur  neurological or peripheral neuropathy that's why [65:36] they have non-healing wounds there's no nitric  oxide that's why they're developing diabetic [65:40] retinopathy macular degeneration pancreatitis  i mean all of that can be traced back to a lack [65:47] of nitric oxide production because the sugar  stuck to the enzyme the sugar destroys the oral [65:53] microbiome and completely changes the the ecology  of the bacteria and completely shuts down nitric [65:58] oxide production just a bit of a tangent there  you mentioned that's why they have open wounds [66:04] that don't Yeah diabetic ulcers okay so nitric  oxide's playing a a role a healing role in wounds [66:11] and scars absolutely so I've got this scar on my  head i was playing football the other day someone [66:14] ran into the back of my head and uh they they like  they they passed out and um got taken away by an [66:20] ambulance but I was just left with this big like  scar on the back of my head which I've had like [66:25] glue stitched so I'm wondering I'm like if I apply  the nitric oxide serum it'll stimulate blood flow [66:31] to that it'll improve cellular turnover and and  heal that wound and basically remediate the scar [66:36] and how do I do that is it Yeah so you take one  pump from each side so one pump from this side [66:41] and turn it around one pump from the other yeah  and now if you apply that and mix it together as [66:46] soon as you mix it together it starts to generate  nitric oxide gas so then that gas will diffuse [66:50] into that tissue it's going to increase blood  flow and it's going to mobilize stem cells and [66:57] it's going to improve cellular turnover and  completely remodel that and heal that and if [67:01] it were an infection in there it would kill the  the the infectious bacteria okay well we shall we [67:08] shall see if that worked so back on this point of  food then so sugar's bad sugar's bad yeah you got [67:14] to eliminate sugar and I think the benefits of it  like a straight ketogenic diet or a straight you [67:19] know vegan vegetarian diet is just the elimination  of sugar and carbs right but I think to answer [67:25] your question what should we be eating i think  you've got to eat a balanced diet in moderation [67:30] you know Americans are overfed all you got to do  is walk around and see the the epidemic of obesity [67:36] good high quality protein good quality fats and  little or no carbs and it's really that simple and [67:44] why did you write a book about beetroots beets  yeah the beets hit the uh really the airwaves [67:51] back in 2012 in the London Olympic Games mhm uh  there was a lot of data coming out at the time [67:56] of the benefits of beetroot juice on enhancing  athletic performance and there was a a benefit [68:02] of the nitric oxide being produced that could  explain the improvement in athletic performance [68:08] the problem is these athletes were drinking liters  and liters of beetroot juice and causing a lot of [68:13] gastric discomfort causing diarrhea their urine  and their feces would turn red and a lot of people [68:18] interpreted misinterpreted that as gastric bleeds  or urinary bleeds and then when I started looking [68:24] at the products on the market most of the bead  products the desiccated bead powders provided [68:29] zero nitric oxide benefit they didn't contain any  nitrate no nitrite they were just we called them [68:36] dead beats they're they're a dead beat product  and so I thought if people if consumers are out [68:42] there looking for beets because they've been  shown to enhance their performance but that [68:49] enhancement in performance was dependent upon the  beets ability to improve nitric oxide production [68:53] in the body then the non-scientist out there  wouldn't know what to look for right they're [68:59] buying products that aren't providing any benefit  to them and so years ago we would do randomized [69:04] placeboc controlled clinical trials and we would  take some of these commercial bead products that [69:09] you can go to your local nutrition store or  pharmacy buy off the shelf and we would use [69:14] those as placeos in our clinical trials because  it's the perfect placebo so what I tried to do in [69:20] that book is educate okay what is it about beets  that are so important what's the mechanism and [69:25] what is necessary in those beets that can improve  nitric oxide production so again everything I do [69:32] is intended to educate and inform the consumer  so that they know how to make informed educated [69:39] choices on the products they're taking or the  foods they're eating or their oral hygienic [69:43] practices trying to find the page in your book  but there was a page in your book where you [69:51] describe beetroot as the most un as the most  underappreciated food in the history of eating [70:00] yeah that may be in the beat the odds um I  thought it was in this book but if you if you [70:04] go back to historical times and you look at the  the hieroglyphics on caves of the ancient cavemen [70:11] you know people thought they were drinking wine  because they would have these red stuff in this [70:15] before battle but what these ancient Egyptians  were doing was they were drinking beet juice [70:22] to improve their performance before they went  into battle so that they were ready they were [70:26] energized they improved their circulation  so that's the historical study on beets and [70:32] obviously these were beets grown at a time when  there were no herbicides pesticides and the soil [70:37] was probably fertile so these beets were full of  nutrients probably full of nitrate that provided [70:42] the the benefits of that but unfortunately today  the beets that are grown at least in America um [70:48] really are nutrient depleted just like most of the  food so would you recommend people eat beetroots [70:55] no because as would again through our survey  that we published in 2015 we realized that [70:59] you really can't eat enough beets to get enough  nitrate to improve your performance and the other [71:04] caveat is that if you're using mouthwash you've  got fluoride in your toothpaste or fluoride in [71:08] your drinking water that you're mixing the beet  powder in you're not going to get a nitric oxide [71:11] benefit from it there's a graph in front of me  here which I printed off which shows the rise [71:15] in antacid medications oh yeah from 2004 to so a  20-year period we're seeing um what is that almost [71:25] a quadrupling of the use of ant acids and this is  globally or is this in the US that's worldwide I [71:32] believe yeah worldwide now this is the problem I  mean these these ant acids what is an antacid so [71:39] it's a medication that's given orally to suppress  stomach acid production and as a biochemist [71:47] and physiologist I can't think of nothing more  damaging than to inhibit stomach acid production [71:53] because stomach acid is required to break down  proteins into amino acids whether it's you're [71:59] eating animal protein or or plant-based protein  it's required for nutrient absorption you need [72:04] stomach acid to absorb B vitamins you need stomach  acid to absorb selenium chromium iodine magnesium [72:12] iron i mean most nutrients micronutrients  are absorbed in the lumen of the stomach [72:18] and if the stomach cannot is not making stomach  acid then these nutrients are not absorbed and [72:23] most Americans 75% of Americans are deficient in  magnesium 95% of Americans are deficient in iodine [72:33] i mean it's a huge problem these are the brands  like Gavascon no these are like the the prylok the [72:39] previsids the nexium the prescription medications  are omerazol pentopresol these you today in in the [72:46] US I think it's probably worldwide you don't even  need a prescription for these from your physician [72:51] you can go to your local drugstore and you can buy  these what we call proton pump inhibitors or PPIs [72:57] what about Tums over the killer Tums so there's  a difference in so Tums and things like baking [73:04] soda are a buffer right sodium bicarb or calcium  carbonate and it's a buffer right so if you if you [73:12] have an acute bout of hyper secretion of acid you  can take a Tums or some buffer some base alkaline [73:20] substance to neutralize the acid neutralizing  acid is completely different than inhibiting its [73:26] natural production in the polyoric cells of the  stomach so what is the difference between some [73:30] have you heard of gavascon before yes yeah what's  the difference between like a gavon well there's [73:35] there's certain classes of ant acids there's what  we call H2 blockers there's proton pump inhibitors [73:41] and then there's the natural buffers that are  just kind of neutralizing the acid environment in [73:45] the stomach gavascon I'm trying to think um what  class that falls under i don't think it's widely [73:51] used here in the US i mean the main drugs used  here are Prolysk Nexium Previsid those are the [73:56] overthec counter and then the main prescription  medications are the omeraol and the pentoresol [74:01] gabaskcon is a commonly used antacid brand and  the active ingredients are aluminium hydroxide and [74:09] magnesium carbonate oh so Gavascon so number one  it's got aluminum in it which you should should [74:14] absolutely be avoided uh but yeah that just  it looks like a buffer it's got an hydroxide [74:19] aluminum hydroxide which is a strong base so it's  neutralizing the stomach acid production but it's [74:25] it's a neutralizing agent but anything that  contains aluminum you should absolutely avoid [74:30] um my as I mentioned her a few times today but  my girlfriend's a breath practitioner she runs [74:34] a business called barley breathwork.com hashtag  ad um and one of the things she's talked to me a [74:40] lot about is mouth breathing and I know there's  a a relationship between nitric oxide and how we [74:46] choose to breathe whether it's through our nose  or through our mouths can you explain to me that [74:50] that link you know when we talk about the enzyme  that's found in the lining of the blood vessels [74:56] we started this segment that same enzyme is  found in our epithelial cells in our upper [75:00] airways in our sinuses so just like exercise can  activate nitric oxide production in the lining of [75:07] the blood vessels deep breathing nasal breathing  activates that enzyme in the epithelial cells of [75:13] our sinuses and so when we do nasal breathing it's  activating the enzyme to make nitric oxide and now [75:19] we're delivering that nitric oxide gas into the  the bronchules the lower airway it's dilating [75:25] those bronchioles moreover it's dilating the  pulmonary arteries so now we're improving oxygen [75:31] uptake oxygen delivery and that's why nasal  breathing and deep breathing has been shown [75:35] to lower blood pressure this is a pretty crazy  graph I took from Google as well which shows [75:39] just how interested people are now getting in the  subject of mouth breathing oh yeah again going [75:44] over the past uh 20 years yeah i know I think  there's a lot of people I mean obviously your [75:50] girlfriend there's a Patrick Mchuan Mchuan in um  Oh yeah the UK came into Dragon's Den I and I uh [75:56] did a made a minoffer in Dragon's Den no I think  that the the the benefits of that are pretty well [76:02] and mechanistically we understand the benefits  of it so the the mouth breathers are not only [76:07] bypassing this natural nitric oxide production  pathway but when you mouth breathe it completely [76:13] changes the microbiome and you so you're not  only bypassing the nitric oxide producing in [76:19] the upper airway but you're inhibiting nitric  oxide production in the mouth from the microbiome [76:24] because you're fully oxygenating the mouth it's  changing the pH of the saliva and completely [76:29] changes the microbiome and completely shuts down  nitric oxide production interesting interesting [76:37] so so you have to I mean I'm a big fan of of  mouth taping but for me I know and I watch my [76:44] kids but sometimes there's anatomical issues where  there's obstructive airways and airway obstruction [76:50] that has to be corrected by dental appliances  or some sometimes surgery but the worst thing [76:56] you can do is tape your mouth and your airway be  constricted and you know suffocate so before you [77:02] do mouth taping you need to get um you know some  some imaging done from your dentist to make sure [77:07] that your airway is is open to where if you forced  to breathe through your nose you can actually have [77:11] oxygen exchange and is there anything else that I  could and should be doing to increase and improve [77:16] my nitric oxide levels that we haven't talked  about yet humming you know there are certain [77:20] frequencies um we've done this and looking at  nitric oxide coming out of the exhaled breath [77:25] when you're humming so certain frequencies can  activate this enzyme and it's dependent upon the [77:32] volume of the nasal sinuses so there's not one  frequency that would work in every single person [77:37] because the volume of your airways and and oral  cavity and sinuses was probably much different [77:41] than mine give me an example show me well if you  just you know like ohms like you do in meditation [77:47] or just simple humming you could actually so if  I had my ozone or gasphase analyzer here I could [77:53] hum and I could detect nitric oxide coming out  of my exhaled breath because of the frequency [78:00] of the because of the frequency and activating  the the nitric oxide synthes enzyme but if you [78:06] take older patients and we've demonstrated this  it's published years ago and other other groups [78:11] have demonstrated this older patients that their  enzyme isn't making nitric oxide whether they do [78:17] nasal breathing or whether they do humming there's  no nitric oxide coming out so again this is an [78:22] activator and a stimulator but it's dependent upon  the function of the enzyme that makes nitric oxide [78:27] if your enzyme is broken humming nasal breathing  exercise isn't going to produce any nitric oxide [78:32] is there anything else that I should be aware of  if I'm trying to improve my nitric oxide levels i [78:37] think it's it's it's doing the things that disrupt  it get rid of fluoride get rid of mouthwash stop [78:41] using ant acids stop eating sugar anything that  leads to an elevation in blood sugar a balanced [78:47] diet in moderation moderate physical exercise 20  to 30 minutes of sunlight a day sunlight sunlight [78:53] there are certain at both both ends of the  visible spectrum both or the UV spectrum and the [79:00] um full spectrum infrared so those frequencies and  vibrations again stimulate nitric oxide release [79:08] so the UV has enough energy to where it'll it'll  knock nitric oxide bound to a cysteine and protein [79:14] and then the UV spectrum will release nitric oxide  bound to metals so you mean go out in the sunshine [79:20] but also those red light beds and stuff yeah the  red light I have an inf I have a red light bed i [79:25] have an infrared sauna that uses red lights in  it and it's I use it every day for nitric oxide [79:30] production yeah and there's there's other benefits  of light you know it can stimulate mitochondrial [79:36] biogenesis it improves energy production it can  lower blood pressure but yeah lots of benefits [79:41] of light therapy and yet we're programmed to  not go outside if we go outside put on SPF 60 [79:47] and intoxicate oursel with these cancer-causing  chemicals and sunscreen I mean makes no sense what [79:54] is the most important thing we haven't talked  about that we should have talked about today [79:57] Dr nathan you know I think the future of Well I I  don't think I'm I'm I know you know there's three [80:04] levels of conviction you think you believe and  you know i'm at the point of knowing now that [80:09] the future of medicine and health care around the  globe is going to be dependent upon nitric oxide [80:14] product technology because I think we can inform  and instruct people to stop doing things or start [80:20] doing things but the most difficult thing to do  is to change people's habits and to get people [80:27] out of their comfort zone and stop drinking  sugar soda waters eliminate sugar to the best [80:34] extent possible get 20 30 minutes of exercise a  day and completely change your diet compliance is [80:40] an issue people don't do that they we're we're  programmed to want to take a pill to overcome [80:44] everything and there's that pill nitric oxide is  very important but it's not a silver bullet it's [80:49] not going to overcome all your bad habits but what  it is going to do it's going to correct a lot of [80:54] the things that your bad habits are leading to a  deficiency of well it's a good thing we have um [80:59] a lot of people that are devoted to finding new  solutions to old problems and you're certainly [81:05] one of those people and it's super fascinating  because as you say as I said at the start of [81:08] this conversation I had no idea about any of this  stuff beforehand i had no idea I'd not really even [81:13] heard that the word nitric oxide and maybe I'd  heard it in passing but um maybe I was confusing [81:18] it with that NOS gas that people talk about and  that some people inhale and maybe because I hadn't [81:24] added context and story and understanding to it  maybe I'd heard it in passing but didn't know [81:29] what it was or meant so it's really wonderful that  you're leading the charge in educating the world [81:33] on nitric oxide because it's clearly a a really  really important molecule in the the broader [81:37] picture of our health and the more we understand  it the more we ask questions about it and have [81:42] curiosity about it the higher the probability  that we're going to be able to build some of [81:45] these therapies that prevent us from ending up  in a state as we've seen in some of these graphs [81:49] where we're deficient in nitric oxide and then  have to deal with the downstream consequences [81:53] of that so thank you for all the work that you're  doing it's really really important i'm going to [81:57] ask you one final question which is the question  left by our previous guest Kim they don't know who [82:03] they're leaving it for and they write it into this  diary so the question that's been left for you [82:07] is are you happily or unhappily mated and why  happily or unhappily mated you know one of my [82:20] biggest challenges in life is maintaining  balance right because I've been so focused [82:25] on you know discovery and research and leaving a  lasting legacy and and making innovations and and [82:33] doing doing things in the scientific and medical  community that many people said couldn't be done [82:39] and so my the problem is is there's always  a deficiency you know I've got young kids i [82:45] spend a lot of a lot of time away and you know  that's you know I'm happily mated but there's [82:51] deficiencies right because again my challenge is  always maintaining balance work home life kind [82:59] of maintaining you know my spiritual my you  know it's it's it's it's mental it's physical [83:04] and it's spiritual health I'm trying to do better  at that now but you know you can't there's always [83:10] sacrifice right and we just have to pick pick  our sacrifices and you know so I've got to I've [83:16] got to choose to do better yeah everything has  a trade-off as many of my guests have told me [83:22] thank you so much for the work that you do  where do people if people want to find out [83:25] more about you if they want to read more they  should certainly get this book which you've [83:28] just released called The Secret of Nitric Oxide  um I'll link it below for anyone that wants to [83:34] have a read of this book i highly recommend you  do because it gives an even more comprehensive [83:37] understanding of everything we've talked about  today and it's incredibly accessible which is [83:41] always critically important to me um but if they  want to find out more if they want to understand [83:45] the products that you you sell and anything else  where do they go well I I mean obviously I'm I'm [83:50] here to educate and informal nitric oxide you  know this latest book The Secret of Nitric [83:54] oxide bringing the science to life really  chronicles both my kind of journey through [84:00] science and medicine as you revealed kind of my  early years and kind of what motivated me to go [84:04] into space but I think more importantly it tells  the story of nitric oxide what it is what led to [84:10] a Nobel Prize for its discovery what you can do  to prevent the loss of this molecule so you can [84:17] go to nathan'sbook.com or you can get it anywhere  books are sold Amazon Barnes & Noble i've got a [84:22] YouTube channel Dr nathan S brian nitric oxide  where we provide education information latest [84:29] scientific information on nitric oxide you can  find me on social media Instagram Dr nathan S [84:35] brian and then for those who want to follow our  product journey and you know bringing forth safe [84:40] and effective product technology that's none.com  so it's the letter N the number one letter number [84:46] one.com but you know we make products that release  nitric oxide dr nathan Brian thank you so much for [84:52] your time today being so incredibly generous  but thank you so much for educating the world [84:55] in such an articulate and accessible way on a  subject that few of us knew very little about [85:01] it's incredibly important work and it's gonna  it's inspired me to think again about my diet [85:04] and about the decisions I make the habits I have  about exercise about sunlight exposure about my [85:09] oral microbiome all of these things so thank you  so much for that it's a real gift and I appreciate [85:13] you taking the time today well thank you so much  it's pleasure being with you this has always blown [85:18] my mind a little bit 53% of you that listen to  the show regularly haven't yet subscribe to the [85:23] show if you like the show and you like what we do  here and you want to support us the free simple [85:27] way that you can do just that is by hitting the  subscribe button and my commitment to you is if [85:31] you do that then I'll do everything in my power  me and my team to make sure that this show is [85:35] better for you every single week we'll listen  to your feedback we'll find the guests that [85:39] you want me to speak to and we'll continue  to do what we do thank you so much [Music] [85:56] [Music]