作者：  医学博士伊丽莎白·克洛达斯

  最后更新：2024 年 2 月 10 日

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上个月发表的一项研究表明，吃奥利奥饼干比他汀类药物可以更好地降低胆固醇，这一研究引起了很多关注，尤其是在社交媒体上。但在你扔掉立普妥并拿起一盒黑白光盘之前，请继续阅读。  

该实验涉及一名治疗溃疡性结肠炎的 27 岁男性，他尝试了两种不同的方法来降低 LDL 胆固醇水平。首先，他每天吃 12 块奥利奥饼干，持续 16 天，然后在 3 个月的饼干休息期后，他每天服用 20 毫克瑞舒伐他汀 (Crestor)，持续 6 周。令人惊讶的是，OREO 使他的 LDL 降低了 71%，而他汀类药物仅降低了 32.5%。到目前为止，太神奇了。

但这里有更多细节。该男子遵循严格的酮饮食。他的起始 LDL 胆固醇在 380 至 420 mg/dL 范围内 (!)。如果您还记得，导致高 LDL 的机制之一是饱和脂肪摄入影响LDL 受体功能。酮饮食富含饱和脂肪，可以关闭低密度脂蛋白受体，从而保持高低密度脂蛋白水平。第 1 课：一些遵循生酮饮食的人可能会发现他们的低密度脂蛋白 (LDL) 上升到极高的水平。

添加奥利奥可以降低他的低密度脂蛋白这一事实并不是重点。关键是添加碳水化合物降低了他的低密度脂蛋白。第 2 课：我们的身体对营养素的反应方式很复杂，为了整体健康，通常更喜欢混合使用营养素，而不是只选择一种营养素。也许，只是也许超高脂肪饮食并不是一个好主意。

事实上他对克雷斯托没有那么大的反应也不是重点。另一种可能导致高 LDL 的机制是肝脏中与HMGCo-A 还原酶活性相关的过量 LDL 产生。他汀类药物会抑制这种酶，但如果它不是导致特定个体高低密度脂蛋白水平的主要驱动因素，那么即使高剂量的他汀类药物也不会有太大作用。这是我们对服用他汀类药物的人进行后续实验室测试的原因之一。我们提前不知道他们的 LDL 升高是否是 HMGCo-A 还原酶驱动的。第三课：并不是每个人都能看到他汀类药物显着降低 LDL。

最后，除了低密度脂蛋白的影响之外，健康还有更多的因素——无论是通过药物还是食物来实现。事实上，在限制性生酮饮食中添加奥利奥饼干可以降低低密度脂蛋白，但这并不意味着奥利奥或生酮饮食就成为健康的最佳选择。我们有大量数据表明，全食植物性饮食不仅可以提高胆固醇水平，而且也是与健康长寿最相关的饮食模式。这就是为什么Step One Foods立足于全食植物性方法，以及为什么它可以降低大多数人的胆固醇，而不仅仅是那些遵循生酮饮食的人。同样，我们有大量数据表明，食用高度加工的碳水化合物（我说的是奥利奥）会导致胰岛素失调、慢性炎症和更高的慢性疾病负担。与此同时，没有任何例子表明遵循生酮饮食的人群寿命更长或健康寿命更长。

第四课：你总是知道这好得令人难以置信。

https://www.steponefoods.com/blogs/news/why-you-shouldn-t-lower-your-cholesterol-with-oreos

Edit:2025.05.05

肥胖是一种慢性疾病，已在全球范围内流行。肥胖被定义为过度或异常的脂肪堆积，这对健康构成风险。自 1975 年以来，全球肥胖率几乎增加了两倍。全球范围内，13% 的成年人肥胖，39% 的人超重并有肥胖风险。 肥胖或超重会增加患其他疾病或病症的风险，包括 2 型糖尿病、高血压、血脂异常、肝脂肪变性和睡眠呼吸暂停。这些情况都会增加患心血管疾病和某些癌症的风险。此外，肥胖和超重也会影响患者的身体和精神。正因为如此，包括限制碳水化合物在内的特殊饮食越来越受欢迎。 在本文中，我们探讨了 MDPI 作者的新研究，该研究调查了碳水化合物限制饮食以及与这些类型饮食相关的可能的负面影响。

低碳水化合物饮食没有官方定义。然而，根据美国国家科学、工程和医学院的说法：

• __<10%，即20-50克碳水化合物，被认为是非常低的碳水化合物摄入量。__

<26%或<130克被认为是低碳水化合物摄入量。

26-44%被认为是适度的碳水化合物摄入量。

≥45%被视为高碳水化合物摄入量。

低碳水化合物饮食有很多种。这包括生酮饮食、阿特金斯饮食和帕洛饮食。生酮饮食的特点是每天碳水化合物摄入量<50g，并且脂肪和蛋白质消耗量增加。它们可以根据碳水化合物、蛋白质和脂肪消耗的比例进一步细分。例如，标准生酮饮食需要摄入 10% 碳水化合物、20% 蛋白质和 70% 脂肪。其他类型的生酮饮食可能会根据碳水化合物、蛋白质和脂肪摄入量的变化而有所不同。以及增加日常锻炼。如果不负责任地遵循碳水化合物限制饮食，可能会导致一系列健康问题。因此，任何饮食改变都应得到医生或医疗保健专业人员的讨论和批准。

减肥和低碳水化合物饮食之间的关联可以通过减少碳水化合物摄入量降低胰岛素水平的假设来解释。胰岛素是一种产生合成代谢、脂肪储存状态的激素，有助于将能量以脂肪的形式储存。限制碳水化合物的摄入量会立即减少消耗的卡路里数量。这直接影响消化过程中产生的胰岛素量，导致脂肪和糖的能量储存减少，即脂肪生成。

由于储存的脂肪和糖减少，身体必须燃烧现有的脂肪来产生能量。这是一种称为酮症的代谢状态。因此，在遵循医生或医疗保健专业人士推荐的定制饮食时，低碳水化合物饮食被建议有助于治疗各种疾病，包括II 型糖尿病和癫痫症。然而，在改变饮食甚至考虑低碳水化合物饮食之前，咨询您的医生或医疗保健提供者始终很重要。

碳水化合物摄入量减少导致血糖水平下降，刺激肝脏通过糖原生成分解糖原储存，产生葡萄糖作为能量。持续的低血糖水平会导致脂肪分解，这被称为脂肪分解。此时身体很难产生能量，而能量又会产生乙酰辅酶 A (CoA)。 CoA 负责合成酮体，酮体是葡萄糖的替代形式，用于产生能量。因此，对于那些第一次适应生酮饮食的人来说，出现一些副作用是正常的，包括疲劳、脑雾、头痛和头晕。

人们对低碳水化合物饮食存在一些担忧，因为目前尚不清楚酮饮食如何长期影响身体。有人认为，生酮饮食可能会促进不健康脂肪的消耗，增加患心脏病和心血管疾病的风险。此外，它还会导致低血压，增加患肾结石、便秘和营养缺乏的风险。

最近，哈佛医学院和脂蛋白与代谢紊乱研究所的研究人员 Norwitz 和 Cromwell采用了一种创造性的方法来研究补充碳水化合物对生酮饮食个体胆固醇水平的影响。 这项研究是独一无二的，因为它是一项单受试者自学，并且碳水化合物补充剂以奥利奥饼干的形式出现。奥利奥饼干是一种垃圾食品，碳水化合物含量很高。单受试者自学在此类实验中很有价值。纵向研究不需要大样本量，并且可以通过对自己进行研究来规避在较长时间内只给一群人喂奥利奥的道德许可要求。 CKGE_TMP_i CKGE_TMP_i 该研究基于最近的数据，表明低碳水化合物饮食可能会增加低密度脂蛋白胆固醇（LDL-C），有时被称为“坏”胆固醇。低密度脂蛋白胆固醇水平升高是与动脉粥样硬化性心血管疾病 (ASCVD) 相关的危险因素。 特别是，这种现象已被证明发生在通常被认为健康且瘦、高密度脂蛋白胆固醇（HDL-C；80 mg/dL）和低甘油三酯（≤ 70 mg/dL）的个体中。那些符合这一特征并遵循低碳水化合物饮食的人被称为具有瘦体重高反应表型。 此外，研究人员发现，个体越瘦，LDL-C 升高的可能性就越大。

研究人员解释说，这种瘦体重高反应表型的主要原因是碳水化合物限制期间肝脏中糖原储存的耗尽。这被称为脂质能量模型（LEM）。此外，他们解释说，在苗条、健康的个体中，这会导致脂肪酸等脂肪燃料的运动增加。这种脂肪燃料用于生产其他能源，包括 COA。脂肪酸重新合成为甘油三酯 (TG)，并通过极低密度脂蛋白 (VLDL) 移出肝脏。VLDL 和其他脂蛋白的增加导致 LDL 颗粒和 LDL-C 增加、HDL-C 增加和 TG 水平降低。LDL-C 升高会阻塞血管，从而造成损害，从而增加心脏病发作或中风的风险。

研究人员决定对尼古拉斯·G·诺维茨博士进行自我实验，他一直遵循生酮饮食来改善个人健康状况的症状。与传统实验相比，自我实验具有更大的功效，特别是对于与健康有关的主题，例如减肥。这是因为与组织一群志愿者相比，他们更容易控制。此外，这可以让研究人员以比传统实验更快的速度产生结果。 Nicholas G. Norwitz 博士符合实验​​标准，因为他表现出 LMHR 表型，并且在研究开始前遵循生酮饮食 4 年多。这项研究是在医学专家的监督下进行的。

两位作者假设，通过重新引入碳水化合物，肝糖原储备将会得到补充，从而阻止替代脂肪燃料的移动以及 LDL、LDL-C、HDL-C 颗粒的增加和 TG 水平的降低。 他们还测试了高强度他汀类药物治疗对降低这些分子水平的效果。他汀类药物通常用于降低心血管疾病高风险患者的低密度脂蛋白胆固醇。 这两项独立的研究相隔 3 个月的清除期。在此期间，尼古拉斯·G·诺维茨博士恢复了生酮饮食。这使他能够恢复到基线体重和相似的胆固醇水平。然后，该研究继续比较两个不同的实验，并确定哪一个具有更大的效果。

任何碳水化合物都可以用于这个实验，比如香蕉、土豆、面食等。然而，研究人员尝试了一些令人惊讶的事情，并决定使用奥利奥饼干作为碳水化合物。研究人员强调，做出这一决定是为了他们的实验能够吸引更广泛的受众，并且他们不推荐奥利奥饼干作为健康食品。

研究人员惊讶地发现，每天食用 12 块奥利奥饼干 14 天后，Nicholas G. Norwitz 博士血液中的 LDL 水平显着下降。在高强度他汀类药物治疗后，结果显示奥利奥饼干显着降低了他的低密度脂蛋白，其速度比高强度他汀类药物治疗的速度更快。 奥利奥饼干在 16 天内将他的 LDL 降低了 71%，而高强度他汀类药物治疗在 6 周内将他的 LDL 降低了 32.5%。作者强调，这是一个代谢演示，本案例研究实验中提供的数据不应暗示任何形式的健康建议。此外，他们还表示，

“补充奥利奥不应被视为有益的健康干预措施，长期食用精制碳水化合物很可能会对健康产生负面影响。”

随着低碳水化合物饮食越来越受欢迎，这项研究很重要的一点是表明这些饮食可能会产生显着的副作用。 短期坚持低碳水化合物饮食确实对患有二型糖尿病和癫痫等疾病的成年人有有益的影响。它们可以帮助患者减轻体重，这些患者通常很难通过运动和适度的饮食改变来减肥。 然而，饮食的任何改变都应与医疗专业人员详细讨论，并且在没有此建议的情况下不应遵循。由于低碳水化合物饮食的好处，研究发现需要对 LMHR 表型进行更多研究。

如果您有兴趣了解有关这项有趣研究的更多信息，请参阅此处的论文。或者，如果您有兴趣提交有关该主题的研究，请参阅我们的期刊*《代谢物》//*以获取更多信息。

Edit:2025.05.05

00:00

The Oreo cookies lowered my LDL by 71% in just 16 days. I think the top 10 drugs only help like 1 to 4 to 1 in 10 people who take them. Nick Norwitz is a Harvard med student. An Oxford PhD who reversed his own chronic illness. And now he's redefining what science says about food and health.

00:18

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01:22

To try Omega-3 Rejuvenate, visit BigBoldHealth.com and use code DRMARK25 at checkout for a special discount. Prioritize your health today with this amazing supplement. Now, before we jump into today's episode, I'd like to note that while I wish I could help everyone by my personal practice, there's simply not enough time for me to do this at scale. And that's why I've been busy building several passion projects to help you better understand, well, you. If you're looking for data about your biology, check out FunctionHealth.com.

01:48

for real-time lab insights. And if you're in need of deepening your knowledge around your health journey, check out my membership community, the Hyman Hive. And if you're looking for curated and trusted supplements and health products for your health journey, visit my website at drhyman.com for my website store for a summary of my favorite and thoroughly tested products. Now, before we dive in, I want to make a quick note about this episode. This conversation with Nick Norris was released before

02:13

the release of a new keto diet study co-authored by today's guest, Dr. Nick Norwitz. Now, this study sparked a lot of interest and a lot of debate online. It was pretty interesting to see the amount of blowback it got. And now, while this new study isn't discussed in the episode, the study that I'm talking about now, the conversation gets into some of these topics and offers valuable context for

02:33

on what led Nick to explore this topic in the first place, including his own health struggles, and now a viral experiment where he lowered his LDL cholesterol by eating a whole sleeve of Oreos a day. It was very fascinating, he's a character. Welcome to the Dr. Hyman Show. This is Dr. Hyman, and this is a place for conversations that matter. And today, if you're confused about nutrition, I can't promise you you won't be confused in the end, but at least you'll be more educated, 'cause we're talking to a MD, almost MD,

03:02

from Harvard and Oxford PhD, who's made it his job to understand the science beneath nutrition and metabolic health. His name is Nick Norwitz. He's a graduate at Ballard-Dick-Turn from Dartmouth. He majored in cell biology and biochemistry. He went to Oxford to get his PhD in metabolism and studied ketones and Parkinson's.

03:22

He is an enthusiastic person, to say the least. He's very passionate about understanding the underlying mechanism behind our chronic disease epidemic and our metabolic health. He's personally suffered from severe inflammatory bowel disease and cured himself of it through food, which I think is important to take note of. He's making a name for himself online, and he is also making a name for himself through the academic community.

03:47

work on various diets and approaches through scientific literature, including ketogenic diets, cholesterol, lipids, LDL, and he's a great scientific communicator with all kinds of expertise across a array of things that I don't even think I understand. His mantras stay curious. He loves hard questions, and we went through a lot of hard questions today. We talked about all kinds of things from whether artificial sweeteners are good or bad for you to what does LDL

04:14

do in terms of your body's risk for heart disease. And it is at the Boogeyman we thought it was. We talked about carnivore diets, vegan diets, and lots more. So stay tuned for an amazing conversation with Nick. Well, Nick, welcome to the Dr. Hyman Show. It's great to have you. And I have been following your work, which is such a joy because you have a

04:34

brilliant way of breaking down really difficult scientific concepts into digestible bites that people can eat. It's like a digestible diet of science. You graduated from Oxford with a PhD in studying effective ketones on Parkinson's disease and ended up at Harvard Medical School where you become a little bit of a firebrand and having a side gig

05:01

as a sort of YouTube educator on metabolic health, which is, I think, pretty amazing given all the things you've got to deal with when you're in medical school. Maybe you can kind of take us down how you first sort of got interested in this and then what happened with your own personal health journey

05:15

and how you sort of experimented on yourself as a human guinea pig to figure out a lot of things that work and don't work when it comes to health. - First of all, thanks for having me. I'm very excited to be here and have this conversation. As for my backstory, I grew up in a household of both my parents are MD, PhDs, and I always wanted to do medicine and science. I was always fascinated by biological sciences. I always had highest esteem for the medical profession, so that's always what I wanted to do as long as I can remember. That said,

05:42

I had a very fluffy idea of what nutrition science really was. I think my understanding… Fluffy idea? A fluffy diminutive… It was kind of not real medicine. Yeah, it was one of those things where I think a lot of people still think, oh, I kind of know what healthy is. My plate, before that, the food pyramid, eat a balanced diet, eat your five a day. I would say a lot of platitudes.

06:04

but platitudes that people take as gospel. I generally felt that way as well. I kind of knew, or I thought I knew, what healthy was. You know, I eat my fruits and vegetables, not too much saturated fat, not too much salt, and then get enough energy to fuel my activities. And blessed or cursed, I don't know what you want to call it, I was a young person who never struggled with my weight. I was a pretty athletic young person, so throughout college,

06:26

in most of college, I really didn't think much about my diet. And then things took a little bit of a left turn for me at the end of college when I started to develop inflammatory bowel disease. Before that, I was known as like– - Like colitis. - Colitis, ulcerative colitis. So what that looks like for people who don't know, sorry if this is a bit graphic, but bloody diarrhea 12 to 20 times a day.

06:49

No fun. No fun whatsoever. And it was a really big shift for me because before that I had no dietary restrictions. I was known as the trash compactor of the family and my friend group. And I loved, you know, adventurous eating was one of my favorite parts of traveling. You can catch me eating basically anything. But I went from that to being able to eat basically nothing that didn't upset my stomach, just

07:11

But just to kind of give insight to the psychology of, or the psychological impact of something like ulcerative colitis, you become, well, I'll say the physical impact is only a tiny fraction, the tip of the iceberg of the whole impact, because it really causes you to withdraw from life socially, psychologically. At this point, I'm finishing up college, starting grad school. And as a young man, you can imagine I would, you know, be going out with my friends, dating, just to kind of give like a quick example.

07:38

dating's not really on the table when, you know, if you're going to have a girl over, you might have bloody diarrhea in an instance, not really a,

07:43

romantic mood setter. So you just let those things drift away. And for me, it continued to get worse and worse. After graduation, I went to Oxford to do my PhD. And that's when the shit hit the fan, pardon the pun, almost probably literally did. I started having these terrible flares and ending up in and out of the hospital. Yeah. I see you- Down to like 90 pounds, right? How care? At some points I was under a hundred pounds. I was-

08:08

So malnourished, my heart rate was hitting like, you know, getting to the 20s. I had gone in the period of a couple years from, apologies for patting myself on the back, but this was the reality. I was a top performing academic, valedictorian at my college, sub three marathoner, breaking like

08:22

state pushup records to being so frail that getting up and going to the bathroom costs more energy than running sub three marathons used to. And on top of that, you know, my sub three hour marathon. So that's a pretty good feat. Yeah. I mean, I'm a pretty intense person. Really? Yeah.

08:39

Well, if you Google, this is one of the funny things I did. Yeah, when I get my mind on something, I never stop. 2014 Boston Marathon, this was the year after the terrorist bombings, and I'd always wanted to do the Boston Marathon. So I qualified doing a sub three when I was 17, which actually made me the youngest time qualifier for the 2014 marathon. But if you look at my time for the 2014 marathon, it was just under seven hours. And that's because I ended up breaking my tibia right before the race. So I did the whole marathon on crutches. Wow.

09:01

which I had to get special permission to do anyway. Back to Oxford, yeah, no, I was, my quality of life had been completely destroyed. I was barely staying afloat with my studies, doing a lot of my work from the hospital. No social life, no romantic social life, really just had nothing beyond what was on paper for me. And you basically were studying a keto diet, in a sense, or the role of ketones. Exogenous ketones. Yeah, like taking them,

09:27

not by diet, but actually by supplementing with ketones, right? Well, that's the great irony is you think I'm in a ketone lab and then I start a ketogenic diet. Somebody might intuit like, Oh, he was informed by his studies. That's not at all what happened. So I had read a beautiful paper by Cox et al and sell in 2017 about exercise metabolism as an undergrad from this lab in Oxford using exogenous ketones, this ketone ester that had, uh,

09:54

been developed using a grant from DARPA, US military, some like super soldier project to enhance athletic performance and cognitive performance. So I was just drawn to actually the possible

10:06

physical performance boosting effects and just metabolism and physiology. So I went to this lab because I found the work just really fascinating. Using the tool as a supplement, completely separate from the diet. At that time, starting at Oxford using ketone esters, I still had a very negative view of the diet. My PI actually did as well. Her name was Kieran Clark. Keto diet was still in my shit list, I guess you could say. Or I had a very negative perception of it.

10:31

like I think a lot of people do based on what you see in the media around ketogenic diets and what I had internalized through growing up as a kid in the late 90s and early 2000s, really, about what healthy is. And I just could not conceive of a world where a high-fat, very low-carbohydrate diet was a healthy diet. Well, we're all trained that fat was bad and that made you fat and fat causes heart disease and it's terrible. Yeah, yeah. So I had a very negative perception of it. Now, how I ultimately found my way to it is after a

11:00

couple years of trying standard therapy for ulcerative colitis i just i wasn't getting better and it was even then like steroids and yeah and immune suppressants and yeah all the regular stuff all the regular stuff you know first line therapies and then steroids for flares and you know like i'd exit a flare and go into remission and then i just relapsed which is obviously incredible incredibly frustrating it was just uh tearing at me from the inside i just i

11:23

I couldn't be a reliable person. I couldn't say yes to offers that I wanted to say yes to because I just didn't know what would happen to me. I got very desperate and I started experimenting with things. I didn't think diet would help, but I had nothing to lose. So I started experimenting with diet because, you know, on a superficial level. There's a really key paper I read years ago about autoimmune paleo diet for ulcerative colitis and Crohn's disease. So it was very effective.

11:44

I tried paleo, I tried Mediterranean, I tried vegan, I tried pescatarian. Anything you can imagine, I've probably tried, along with the standard things like low FODMAP, specific carbohydrate.

11:55

And I'd try them pretty rigorously for like a month or so. And then eventually I came to a ketogenic diet and I just thought I'd try it because what the heck. And what happened for me was my inflammatory markers dropped to the lowest they'd been. My disease started. I started feeling so much better, getting my energy back, getting my mind back. And then the next time I got a colonoscopy, I was in biopsy proof remission.

12:17

which was stunning. And I was forced to reconcile with the fact that this was my lived experience. This has been my lived experience, despite the fact that it's not a quote, evidence-based approach. So a lot of what I've been thinking about with respect to metabolic health. The absence of evidence is not the evidence of absence. You beat me to the punchline. But, you know, I'd heard that saying before starting medical school, but it really didn't sink in until I

12:44

I started to think about, you know, our current biomedical infrastructure business models around health.

12:52

and why certain interventions would or would not be explored. And basically the realization I came to is that- Well, it's not a pill and you can't patent it and you can't sell it for enormous profit. And so no, diet is not something we study. Right, so it hasn't been properly explored and which makes it to me the low-hanging fruit for treating all these chronic metabolic diseases, which we have been poorly-

13:14

poorly equipped to address cardiovascular disease, inflammatory bowel disease, obesity, diabetes. - Mental health issues. - Mental health issues as well. - There's whole departments of metabolic psychiatry now. We've had the head of that from Stanford on the podcast. - Is it Shabani Sethi? - Yeah. - Yeah, she's great. I've done a little bit of work with her, Chris Palmer.

13:33

Suzuki Group Metabolic Mind. The universe of things that we could treat with rigorous metabolic therapies is truly impressive. But in order to make that standard of care, we need to grapple with the fact that they're not

13:45

by conventional metrics currently, quote, evidence-based because there isn't the research and funding infrastructure to do these trials with the same degree of, quote, rigor as pharmaceuticals. Because again, the business model isn't as clear. It's very clear if you produce a pill and it treats a disease, you can sell that drug and make a massive profit, even if the drug doesn't help most people. If you can get a statistically significant

14:09

in a trial that you publish in the New England Journal, and it can still help only a minority of people. - Well, most drugs don't work for most of the people who take them. They just work for a small section. - I think one to four, I think the top 10 drugs only help like one to four to one in 10 people who take them. - I mean, like statin, you have to treat

14:25

you know, eight or nine people for five years to prevent one heart attack on one diet. It's like not very good. So Nick, your story is very compelling. And I think you came to a sort of a personal choice about your own diet and health, but it led you down this sort of rabbit hole of metabolic health.

14:40

So people listening, I don't know if they actually understand, what does it mean when you say metabolic health? I mean, metabolism, I have a slow metabolism. What does that mean? I don't burn calories fast, but people don't really understand what metabolic health means. Can you define it? I think the first thing to acknowledge is there's not a good definition of metabolic health. When we're talking about scientific communication, there are some terms that have very strict definitions and criteria and other terms that are more like

15:07

porn where you know it when you see it. Another example, we ultra-process foods. Really defining that scientifically is difficult, but it's a useful term and heuristic in the public sphere. So I'll just say up front, I feel like metabolic health is similar where it encompasses a lot of things and there's a lot of definitions, but I just want to be up front. There is no consensus on what the definition is. With that said, there are different ways to slice it. The way I like to think about it is it's when you

15:32

your body's systems are running in a way to optimize performance and minimize risk of chronic disease. You can start to intuit that through certain biomarkers. So there's like canaries in the coal mine for poor metabolic health. Like if you have high, you know, fasting insulin or insulin resistance score, things like triglyceride to HDL ratio, or, you know, features of metabolic syndrome. You look at your waist or conference, your visceral fats. There's a lot of things you can look at. Essentially, you're talking about the spectrum of like

16:01

- From imbalanced blood sugar and insulin to prediabetes, type 2 diabetes. And you don't have to have actually the type 2 diabetes to experience many of the consequences of poor metabolic health, including heart attacks, strokes, cancer, Alzheimer's.

16:16

mental health issues such as bipolar disease, schizophrenia, depression, the list goes on and on, ADHD, autism. And it's sort of fascinating how these seemingly unrelated diseases, I mean, what does autism have to do with diabetes? Or what does Alzheimer's have to do with cancer?

16:31

but yet they're connected by this common thread of poor metabolic health and metabolic dysfunction. - I think a way to think about it is, I don't know if I came up with this analogy, I can't imagine I did, but that of the tree of metabolic illness, where if you look at a tree and you look at all the different branches, you can see each different branch of the disease, obesity, diabetes, cardiovascular disease. The way we go about modern medicine now is trying to prune the tree as the branches grow. But the fact of the matter is they're just gonna keep growing back. And I think the mind shift we need is to look at

16:59

the roots in the soil, which are these underlying pathologies, things you mentioned like insulin resistance and inflammation that are at the root of all chronic metabolic disease. And when we make that mind shift, we can gain insight into, I think, how we can more potently address disease and also why certain

17:20

fundamental interventions might hit a lot of different diseases. Like, yeah, depression and schizophrenia in addition to obesity. And it's not because it's snake oil. It's because they all have the same underlying dysfunctions that just manifest differently in different people with different susceptibilities. I mean, I think, you know, at a high level, metabolism is the sum total of all the biochemical reactions that happen in your body, which is 37 billion trillion chemical reactions every second.

17:44

From a top line medical definition is when we think of what is metabolism. - Right. - What you and I are talking about really is metabolic health as determined by mostly our diet. - Yeah. - And it's driven by the amount of sugar and starch in our diet that's driving our metabolisms to be broken in some way and to not function as they were designed and to do all the opposite things we wanted to do. You sort of came to a ketogenic diet for your own autoimmune disease, which makes sense.

18:11

But it's kind of an unusual application, right? And I think it's worked for you, which is great. And I'm glad you're well. And I'm glad you're doing what you're doing. But I think the deeper question is really, as a society, we're now facing…

18:24

a staggering number of people with broken metabolism, or severely to moderately to mildly, but somewhere in the spectrum that's driving them to poor health. And it's costing our society trillions of dollars. It's creating tremendous amounts of loss of productivity. It's threatening our national security. It's threatening our global competitiveness, making us all feel like shit. The question is, what is the biology underneath it? And let's just unpack it. And then let's talk about, you know, the different kind of approaches to it, because I think there's a lot of

18:51

views on this, you should be vegan, you should be carnivore, you should be low fat, you should be high fat, you should be keto, you should be paleo, you should be Mediterranean, you should be, I mean, it makes people crazy. I mean, I think that's why people just throw up their hands, I'm just gonna eat pizza because I don't really know what to do, you know? We now actually have an interesting test, which I had the first patient I've had who was able to do this test through Quest called the insulin resistance score, where they measure C-peptide and insulin

19:17

through a special technology called mass spectrometry that is a very predictive marker of insulin resistance, as good as you get in a sort of a science lab where you do very fancy invasive tests to measure your insulin resistance.

19:30

And it's something that I think every American should have measured. - I agree. - It's something that we actually now offer through Function Health, which is a company I co-founded that allows people access to their own biology and their own data and their own labs. And it's now available. And I think it probably should

19:46

should be like the most important biological test. And yet most doctors never measure insulin. They never test it. They never look at it. They don't have to interpret it. The reference ranges are completely screwed up on the Quest laboratory because they say it's normal up to 18. It should probably be less than five. And so we have this moment where we're in this metabolic crisis. We have this broken metabolism. We have it driven by our diet that's high in starch and sugar and processed food, which is really the vehicle for it.

20:11

And it's creating all these downstream problems. And as you referred to it as sort of like this, this sort of the trunk and the roots rather than the branches. And this is exactly the metaphor we use in functional medicine. I don't know if you're aware of that. Do you, are you aware of that? That metaphor? That exact metaphor. I figured I hadn't, I might've like heard, I don't know where I heard it, but I'm like, I

20:27

couldn't have created this. It's just so obvious. Yeah, we literally have this as a fundamental teaching tool where we show, you know, by getting to the root causes, you don't have to treat all the different diseases. You can just treat the root cause and then all the diseases go away. A few things I want to respond to there. One, with respect to why doctors don't order these sort of tests, I mean, first rule of medicine is don't order a test if you're not going to do anything with it or you don't know what to do with it. So I think a lot of people don't know, you know, if somebody comes back with a high insulin resistance score, there's not a pill for that.

20:54

So how are you going to manage it in the current, you know, medical system?

20:59

Whereas, you know, if you measure an LDL cholesterol, we very clearly have a pill that can target that biomarker and you can get an easy win on paper. I'm not saying that, you know, statins don't have their place, but in terms of like why someone would test for one thing and not another, it is the treating clinician. What are they equipped to handle in terms of data? How do they know how to manage the results and what tools do they have to prescribe? It's the joke I always tell. I was going to stop for a second. This joke I always tell about, you know, I'm giving a lecture about why doctors don't look for where the problem is.

21:28

They look for where they can find something, right? So there's this guy who's looking for his keys on the street and his friend comes and sees him. He's looking under this lamppost. He says, what are you doing? I'm looking for my keys. He said, where'd you drop them? He said, well, I dropped them over there. He said, why are you looking over here? He said, well, the light's better here. And that's what we do. You can measure LDL. You can give a statin. Ba-boom, you've done something useful. But insulin, well, one, nobody thought to measure it. Two,

21:53

And we've asked Quest, less than 1% of all the diagnostic tests that are sent to Quest have an insulin as a metric that they're looking at.

22:02

And number two, no one knows what to do with it once you find it high. Well, eat better, eat less, have less sugar. Like, what are you going to tell somebody? Because doctors have no training in nutrition. So the second thing I wanted to say, you just alluded to it when you're like, eat better, eat less, is circling back to what I used to see nutrition as, which I thought was a fluffy science.

22:23

And I think a lot of conventional medicine still sees it as a fluffy science. Take that as, you know, the internalized perspective of what nutrition is. And now I am juxtaposing that, contrasting that to what I'm studying. We were talking about a few things offline, but things that I read that come out like every day, every weekend in the metabolic health literature that are just jaw dropping. Like a couple of examples I was mentioning was how

22:49

the body produces cyanide to boost metabolism. Like that's weird, I didn't expect that. Or how there are cells in the brain, support cells called astrocytes, that can literally like reach out cytoplasmic arms and connect with neurons and suck out damaged proteins and then donate healthy mitochondria. - And in English that means if you have Alzheimer's, it could suck out, the immune cells can help suck out bad proteins and put in

23:12

- Healthy new mitochondria that help you– - Yeah, so like the pathological hallmarks of the, you know, leading neurodegenerative diseases, Alzheimer's, Parkinson's, they come down to misfolded proteins. Imagine if you had a cell in the brain that could stick its arm into a neuron, pull these out, oh, and by the way, these damaged proteins harmed mitochondria, the powerhouse of the cell, so let's replace those. You stick another arm in, and you give the healthy mitochondria. Like that's something that literally happens in the human brain.

23:36

A lot of this is in the area of preclinical. You can imagine this is a very hard thing to study in a living human, but just understanding the fundamentals of the physiology, the biology, the metabolism gives us insight into one, just how remarkable our bodies are, and two, gives us insight into how we can tweak these systems

23:59

in profound way to get astonishing results like lowering your cholesterol with Oreo cookies or like, you know, sucking damaged proteins out of brain cells. They can give a lot of examples. I'm going to come back to the Oreo cookie study. I know, I'm teasing the audience. But so the reason I want to frame these two things and I want to add in another element is what you said about people just

24:19

throwing their hands up in the air and being like, too complicated, I'm done, I'll just do whatever. - Yeah, this great scientist says I should be vegan, this other great scientist says I should be eating more keto, this other great scientist said I should be eating more Mediterranean or paleo, like what the hell? - So what I would say is– - If they can't figure it out, what am I supposed to do? - What I hate is the platitudes around nutrition. Things like eat a balanced diet, eat the rainbow. I think they're just like so,

24:42

useless because they're just platitudes. They have no deeper level of thought. And then on the other hand, you have this really cool physiology. But, you know, if I say to a person, isn't it cool that glycine can increase, you know, cyanide production in lysosomes, it's going to go completely over their head. So how do you, as a communicator,

25:00

take your love and awe for metabolism and health and transform it into nuanced functional takeaways for people so you can bring them along the journey of genuine learning and exciting them about this physiology while not just giving them platitudes, but give them takeaways that are actionable, which hopefully does not include chugging cyanide or misleading information around that. You can see how it becomes an ecosystem of confusion, I guess you could say. And like how do you give people

25:27

give people the respect of feeding them a nuanced message while also not confusing them is I think a really interesting challenge that I've had at the front of my mind for the last year. - And also the personalization, right? So I think one of the fundamental principles of medicine now is personalized medicine and it's been core to functional medicine for a long time. Not everybody responds the same way to the same diet. Different people need to eat different ways to thrive. And this is something that's just so ignored when it comes to literature.

25:55

Well, vegetarian and vegan diets are healthy, or you should eat Mediterranean diet, or whatever that means. Is that pizza and spaghetti, or is it fish and vegetables? And I think one of the things I want to double-click on is something you've kind of spent a bunch of time looking at that I've actually found in my own practice, which is this phenomena of how different people have a heterogeneous response to

26:19

their diets when it comes to keto diets, when it comes to saturated fat, when it comes to carbohydrates. And that some people really thrive even in the face of very high cholesterol levels. And we've been taught, not just taught, but basically,

26:37

under the penalty of death been told that if you don't treat someone with a high LDL, you're being a bad doctor. And if you don't give someone a statin with a high LDL, regardless of what everything else is going on in their biology, you are practicing bad medicine slash malpractice. And that just isn't true. I just had a kookook stories and then we'll sort of dive into this concept that I think you guys have been working a lot at Harvard.

27:03

And that you and my buddy, David Lidway, who's one of your mentors, has talked a lot about is sort of the role of low glycemic diets and their role of treating metabolic dysfunction.

27:14

And I had a patient who was really struggling with her weight, very inflamed, and terrible cholesterol, like 300 total cholesterol, 200 plus LDL, triglycerides, like 350, 400, HDL, like 30-something. It was a walking disaster. Insulin levels through the chart, and then we even did a glucose tolerance test in her postprandial, or after eating insulin, but super high as well as her glucose.

27:39

So she was on the pre-diabetic range. Another guy was a 55-year-old biker who just crushed it every day, 50 miles on his bike, lean, fit, healthy. Both of them had heard about a keto diet. And I said to this woman, I said, “I think this might be really helpful for you.”

27:55

Why don't we try it? And she did. And her cholesterol dropped 100 points. Her triglycerides dropped 200 points. Her LDL dropped like 150 points. Her HDL went up 30 points. It was remarkable without any drugs. Whereas the other guy, his lipid particles went like

28:11

Sky high, his LDL went sky high. And I was like, well, what should we do? Like, what do you do? And I think there's a movie that you were involved in called The Cholesterol Code. There's a guy named Dave Feldman who's done a lot of work. He was an engineer, basically decided he was going to take this on as a project, you know, basically to show the world

28:27

What happens when you have a whole group of people who are lean, fit, and healthy who go on a keto diet, but their LDLs go through the roof, whether it's 100, 200, 300, 400, 500, 600, 700, and it freaks doctors out. In this movie and in some of the literature, it's like you actually get better lipids. And Virta Health, and we've had Sammy on the podcast who started Virta Health, you know, you see with these types of diabetics, when you look at all the cardiovascular biomarkers,

28:51

when they go on keto and they're eating high diets, fat, and even saturated fat, their numbers all improve. And yet others don't. So how do you kind of make sense of all that? To frame up why this is so important, I would first say that

29:03

We've already mentioned that carbohydrate-restricted diets can help with a broad range of conditions, with ketogenic diets potentially helping with severe mental illnesses, depression, schizophrenia, bipolar. Stuff that's really untreatable and intractable most of the time. But however, there's an obstacle to clinical implementation of these diets broadly, and that is some people have these astronomical jumps

29:25

and cholesterol, in particular LDL cholesterol, and that scares physicians. Just reinforcing what you said, but the reason this is so important is it's a deterrent

29:33

from prescribing these diets to people who could genuinely benefit from them as a metabolic health therapy so it's a critical question to answer one who is susceptible to these increases in ldl because it's only a minority of people so it's a minority but it is a decent population why in some people and not others we need to identify that population what's the mechanism and then also what's the risk associated with the high ldl in different contexts and we need this information in order to you know

29:59

promote the adoption of ketogenic diets for a broad range of conditions and properly treat people on an individual basis. So with that framing, I would say one really interesting observation that explains why only a minority of people see increases in LDL on low-carb ketogenic diets is that there is an inverse association

30:21

between your BMI and LDL change, meaning the leaner you are, the higher your LDL goes. Now, if you're very overweight and you're obese and you're diabetic and you go on an extremely high-fat diet, your LDL goes down. It tends to. Whereas if you're fit, thin, healthy, and an athlete and you want a keto diet for various reasons, like mental health or gut health or whatever one of the issues, your LDL goes through the roof. Like yours, yours is like 500 or something, right? Yeah, mine's like 500, 550.

30:48

And we can get into the saturated fat or something later. Which would make most cardiologists have a heart attack. Right. Ironically, this is true. We can talk about my profile later, the contributions to that. But with respect to the literature, we did a meta-analysis of the 41 human randomized control trials with low-carb diets where we had

31:10

the information to like look at LDL changes and lipid changes. And what we found was if you broke it up by BMI category, the only group of studies where LDL went up was BMI under 25, the lean group.

31:23

Overweight, class one obesity, no increase. Class two obesity, LDL actually went down. And if you look at the individual participant level data, there was an inverse association across the BMI spectrum, where the leaner you were, the higher your LDL went. So this is encoded in the human randomized controlled trial literature. And I'll give a big hat tip to my friend Adrian Sotomoto, who was the guns behind that one, the first author, and then David Ludwig, who we worked with on that paper. - What happens when people who are

31:51

- Obese and diabetic become fit and fit and healthy and have more mass. - That's the fascinating thing, so. - Do they flip over to the other side? - I've seen this happen. I've seen, I'll give you one instance was a patient with a starting BMI of 43.2. - That's big, that's very big. - And actually had low LDL baseline, like in the 80s. Despite that, you know, I mean, they had high triglycerides, low HDL, and probably a pattern B LDL phenotype, but they had lowish LDL at 80.

32:17

they started losing weight. They went on a ketogenic diet. They were losing lots of weight. BMI went to 30, 27. And right around BMI 26, 25, their LDL took a hairpin turn where it was more or less stable sub 100 and then shot up to 250.

32:32

just shot up as they got, they didn't really change their diet at all. They just got into this lean area and their LDL went through the roof. So as a practical takeaway to people and things I'd highlight for the healthcare practitioners listening is like, if you have a patient with insulin resistance, type two diabetes, obesity, and you're interested in trying a ketogenic diet for them, they're very unlikely

32:51

to see the LDL change that might scare you. They're unlikely to have that response. There might be a transient bump that's small that comes back down. We do see that in the literature. But as for this like jump to 400, you're unlikely to see it. So I think a few things that really need to be reconciled that are points of confusion around this

33:09

are terms like, you know, LDL is causal and necessary for cardiovascular disease. And this idea of context dependency. So what I'm not saying is that LDL or Applebee don't matter. I'm also not saying they're not part of the causal cascade. They are.

33:24

But just because something is part of a causal cascade and necessary doesn't mean you need to treat it. Because context matters so much. What do you mean by context? The context of the rest of their metabolic health? Their metabolic health is one element of context. The context around what is actually driving up the biomarker. Because biomarkers can change for different reasons.

33:43

And you can start to gain insight into why a biomarker might be where it is when you start to know the whole patient story. Which is why, again, I teased it, but like I legitimately can lower my LDL with Oreos more than I can with a statin. That is not generalizable, but it comes down to the context because when you understand the physiology, you can get amazing results. Breathing clean air is one of the simplest ways to support your health.

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35:00

Just talk about this for a sec, because I think it's fascinating. You're on a keto diet, your LDL is 500 and change. Right. And you start to eat Oreo cookies. Yeah. Along with your keto diet. Yeah. And you notice something radical happen, and you also try to drug yourself.

35:16

to do the same thing and the Oreo cookies work better than the drug. Explain that. - So first why I did this, people are gonna say, well isn't this clickbait? Oh 100%, it was engineered to be clickbait. I was trying to engineer the most clickbaity experiment I possibly could to start a really important discussion about fascinating physiology. So it was clickbait backed by legitimate science.

35:36

Now, at the point I designed the experiment, we had already had about 10 papers on this topic. One, they weren't getting talked about, I think, enough. And two, there were what I perceived as efforts to not only suppress the dialogue, but circumvent it with misleading messaging, intellectually misleading messaging. I can support that. I realize that sounds like a strong claim. I'll give examples later. But with the resources available to me at the time I was 27, I was like, how can I force this discussion?

36:06

I am not a esteemed professor emeritus. I do not have millions of dollars. I don't even have that big a social media profile at the time. - But you can afford a pack of Oreo cookies. - But I can afford a pack of Oreos per day. And so I'm like, I want to engineer something that will catch attention and hopefully bring people towards a more nuanced discussion that needs to happen.

36:31

I designed this study, and to be clear, I designed it and announced it before I did it. I thought it was the appropriate scientific thing to do, saying like, this is my prediction based on my understanding of the physiology, then I'm gonna do it. - It's your hypothesis. - My hypothesis. I announced it on, you can even look, Chris McCaskill, he goes by Plant Chompers, is a prominent vegan. I announced it on his platform. And I said, what I'm gonna do is an experiment.

36:52

In this experiment, I'm gonna lock in my diet as a kind of strict baseline ketogenic diet, my normal one, for a couple weeks. And then I'm gonna do an intervention where I eat Oreo cookies.

37:02

a sleeve per day, so that's 12 cookies, about 100 grams of net carbs, in addition to my diet. So I'm not swapping out fat, I'm adding this. So I'm actually adding saturated fat along with sugar and carbs for about two weeks, and then I'm gonna do a washout period, kind of reset everything, and end up being a three-month washout period. And then I'm gonna try high-intensity statin therapy. So it was Crestor, 20 milligrams for six weeks. - That's a high dose, right. - Gorilla statin. - That's a very high dose. No one knows it's five.

37:29

10 is good and 20 is a lot. - I wanted to steel man the comparator, which in this case was frontline therapy, statin therapy. In addition to this, I know how to dot my I's and cross my T's, so I went to Harvard, their institutional review board, got the appropriate exemptions for this experiment, had my PCP ordering all my labs into my electronic medical record, and then I got a consultant lipidologist, I don't know if you know Professor William Cromwell,

37:55

but he trained thomas dayspring thomas daystring trained peter attia in lipidology so really in cuomo over 30 years of experience he's the senior author on this paper and was consulting so i did this as by the books as you could an oreo experiment yeah um and then i executed and published the results which were that the oreo cookies lowered my ldl by 71 in just 16 days

38:17

Now the reason it was 16 days and not 14, I had mentioned two weeks, was because at the two week mark, the drop was so astronomical, we wanted to make sure it wasn't a lab error, so we wanted to triplicate. So we said we're gonna measure the next two days. And it was still dropping. So that was the effect of the Oreo

38:32

And then the statins lowered my LDL by 32.5%. - So more than double the effect of the- - In one third of the time. - Statin by eating Oreos. Explain that, 'cause that doesn't make any sense to most people listening. - It comes down to- - Explain yourself, doctor. - Me understanding the physiology in myself. So we talked about different things can drive biomarkers up or down and the context matters. So our understanding of why lean people have high LDL and low carb has to do with the fact that the leaner and the more insulin sensitive you are,

39:01

When you go low carb, when you go keto and the carbohydrate stores in your liver starts to drop, it kicks off this cycle whereby you're burning a lot more fat as fuel. And you're actually releasing more free fatty acids from your fat cells into your bloodstream. And then those free fatty acids need to cycle throughout the liver and then back through the body. So they get taken up by the liver, packaged on these big ship-like particles containing cholesterol and stored fat.

39:29

um they're called vldl and then the vldl drop the stored fat the triglycerides back off at the muscle tissue in the fat tissue and what happens in this process is those that those big particles that are packed with the stored fat have the fat siphoned out of them they shrink down into ldl particles that contain ldl cholesterol and what you end up with as a result of this system is

39:52

Very high LDL. Because you need it to transport the energy around your body so you can use fat as fuel. It's like a decay product of the thing that was transporting the energy effectively. An epiphenomenon. So yes, there are these particles that are the precursors to LDL. They drop off their cargo, the fat, at fat tissue to replenish small fat cells and muscle tissue. And then the VLDL will shrink. VLDL is…

40:12

like a more like less triglyceride rich particle. - The VLDL has a lot of triglycerides in it. It drops off the triglycerides and becomes an LDL, which sticks around longer than the VLDL. So what you end up with is actually very low triglycerides because the triglycerides get sucked out so fast. Triglycerides are low, not high. Your LDL ends up being very high because the VLDL are being turned over really, really quickly into LDL. And then as an added nuance, when the VLDL shrink, remember they're big spheres, they lose surface components.

40:39

from their shell you could say and some of that is cholesterol that gets picked up by hdl so the result is this pattern of very high ldl high hdl and low triglycerides the high ldl the high hdl the low triglycerides with particular thresholds is what we call lean mass hyper responders and is this pattern we see on lean people who go low carb but we can get a little bit more into the model if you want but the point is the model starts with

41:05

your metabolism shifting towards lots of fat burning so if you put carbs back into the system it

41:12

puts the brake on the system, or at least takes the foot off the gas pedal, and your LDL should drop. That is the prediction of the model. So it should drop with any carb. The fact of the matter is, even before I did the Oreo experiment– - Could be a sweet potato or an Oreo. - We had used sweet potatoes in patients. There are case reports on this, or fruit, or starches. It just wasn't sexy enough to catch headlines. So I'm like, “What is?” And I'm like, “Oreo cookies, that should do it.”

41:36

So I did a rigorous controlled experiment with my locked in baseline diet, a pure addition. You can look at all the macro breakdowns in the paper. And the result was the Oreo cookies lowered my LDL by a dramatic 71%. And I'll just say as an aside. This is what we call an N of one study. And I think this is a fairly rigorous type of data that's been mostly dismissed, which basically means you're studying yourself against yourself. Right.

42:00

and different diets and different conditions with a break in between. That's called the washout period. And that is not something that we typically think of as valid data. We only think of these large, randomized,

42:10

controlled trials as being valid, but those are great for looking at pharmaceuticals, but not necessarily looking at other stuff. - Well, the fact of the matter is, I think you learn so much in science and medicine by studying the outliers. And when you do the randomized controlled trial, yes, it has certain benefits, but you're, by the nature of the study, looking at a large group of diverse humans. So when you get a quote, statistically significant result, that doesn't speak to any individual in the trial.

42:36

And if we want to shift medicine towards more focusing on targeting underlying metabolic dysfunctions in an individual manner, then we need to start taking the mindset of N equals one medicine. And we have more and more tools where we can do this. Things like multiomics, where we take an individual's genome and microbiome transcript and you integrate them into an incredibly high resolution picture of the individual. If you take that mindset, then you can get incredible results.

43:02

in a reproducible manner, like lowering your LDL with Oreo cookies. I'm not saying that's healthy. I'm just saying it's incredible. And it's explainable when you understand the physiology. And is it generalizable? I've actually had other doctors at Harvard replicate this who are lean mass hyper-responders. They're actually quite a

43:18

decent number of lean mass hyper responders and people at Keto at Harvard. And I get texts like- So you got a lot of subterranean Keto community at Harvard? Atheists and the clergy. Yeah. You'd be surprised. Keto, carnivore. Who are in the medical community. Yeah. I mean,

43:34

- Yeah, I mean they– - Not just sort of like studying history, but actually– - No, I know senior attendings who are like carnivore, lean mass hyper responders. And they're not out about it because it's stigmatized. They don't wanna have to deal with the headache that comes with putting that target on your back. So most of the time, a paper will come out and they're like, Nick, did you see this BS about red meat? Will you respond to it? I'm like, you wanna get up there with me? And they're like, nah, nah, you do it. It's true, it's a very stigmatized dietary pattern, keto into a greater extent.

44:00

carnivore, people generally, be they your person in the general public or a senior MD, PhD, are gonna do what makes them feel good. And so if that helps them function and feel good for whatever reason, they're probably gonna do it. They might not be out about it. - So let me sort of back up, 'cause you covered a lot. I wanna make sure everybody listening,

44:17

Harvard, Oxford, MD, PhD, and most of us, including me, are not that smart. So let me see if I got this. First of all, there's a big heterogeneity in the population. I mean, there's a lot of differences depending on your genetics, your metabolic type, and how you respond to different foods at different times. And that's really important, that there is no one size fits all. Number two, that our whole hypothesis that LDL is the boogeyman, V with a capital T-H-E,

44:47

maybe starting to see cracks in it, in its theory. That keto is something that can actually help reverse a lot of the broken metabolism that affects us as a population, including across the spectrum from autism to Alzheimer's to cancer, diabetes, and even mental health things like depression and schizophrenia and bipolar disease.

45:09

This is just kind of a radical idea that there'd be like one quote drug that could treat so many different problems because it hits a simple common root. I'm not sure that cardiologists have caught up to this idea that LDL isn't the whole story. In the subtext of also what you said was that a lot of other biomarkers may be more important than LDL, are more important.

45:30

- I would say are more important. - Okay, okay, I was just being, I'm trying to be more scientific and say may, because I think some people still are questioning this. The basic orthodoxy is the only thing it matters to measure is LDL. - But I am being scientific in so far as that we can quantify the risk associated with different biomarker changes, and LDL is not the most important biomarker. It doesn't mean it doesn't matter, I didn't say that,

45:58

That doesn't mean that it shouldn't be treated, you know, in certain patients. But in terms of, is it the most important biomarker? I feel like we can say no pretty confidently. Yeah, it's interesting. You know, when you look at insulin resistance, it's six times greater risk factor for having a heart attack than having a high LDL.

46:15

- I think it's even more. - Yeah. - I think the, this might've even been in a documentary you were in, but you're talking about the women's health study. And I think the hazards ratio for a high lip lipoprotein insulin resistance score was six plus. - Yeah. - And for LDL it was like 1.38. - Yeah. - And since one is nil, a lot more than six. - Yeah. - Whatever, you know,

46:35

500 divided by 38. It's a lot. It's a lot more. And then even more is like triglyceride to HDL ratio and ApoB and a lot of other biomarkers, insulin, inflammation, all may be more important than LDL. And yet the thing we focus on is LDL cholesterol because it's what's easy to measure in a lab test at your doctor's office, in your annual checkup. And it's easy to give a prescription. Everybody feels good and goes home and thinks everything's great.

47:00

But the truth is we're missing a lot, and actually statins don't really treat underlying metabolic dysfunction, and they actually, I don't think, even really help

47:08

with correcting the quality of your cholesterol. They don't affect the small particles, and they may reduce total particles, and that may be helpful, but they don't actually improve the size of your cholesterol particles, which happens when you eat a higher-fat diet, which is what's so remarkable. And as we come to sort of understand the nuances of cholesterol, and this is why at Function Health we measure your lipoprotein fractionation, we measure insulin, we measure A1C, we measure your

47:33

your ApoB, we measure LPA, we measure a lot of the things that are not being looked at to round out the picture of what your overall cardiovascular risk is. We even are measuring qualities of HDL, which most people don't think about that you can actually measure. - That's a complicated sphere. - It's literally a sphere. And so, I think we're in this exciting inflection point in cardiology and medicine and understanding the metabolism and biology.

47:57

And yet, people are still in the old paradigm. I was literally on the phone with the people from the Dietary Guidelines Committee for the US government, and we still don't have a good National Academy of Sciences review of carbohydrates that are up to date because nobody's funding it. We can give 185 billion to Ukraine for the war, but we can't give a million dollars to the National Academy of Sciences to look at the data on carbohydrates, for example, which a lot of people have been doing outside of the government, but

48:24

but that's not good enough for the government to kind of make changes. We're kind of in this exciting moment, to me, where we should be really thinking about cardiovascular risk and overall health in a much more broader context of metabolism and our broken metabolism and how we can actually address that in a coherent way that may not have to be so extreme as a keto diet. I think Benjamin Franklin said it well, an ounce of prevention is worth a pound of cure. So if you've got a healthy, robust metabolism,

48:52

you can tolerate a wider range of degree of freedom in your diet. Right? If you have a broken metabolism, you know, one, one, you know, blueberry might shoot your blood sugar up. Whereas if you're healthy, you can maybe drink a can of Coke and that might not actually impact you that much. But if you did it repeatedly, it probably would. So we have this, this kind of inflection point, I think in medicine that is, is,

49:12

I think is happening in the science, but hasn't reached popular culture. And I know that's what you're really passionate about, Nick, is getting this message out to popular culture so people can actually take advantage of the science and it's not sitting on a shelf and we can go from 17 years to 17 seconds to get adoption. - The fact of the matter is people don't need to wait

49:29

for authorities approval before trying something when it's a dietary therapy. They have access to it. Now I think people should do it in a nuanced and responsible manner, but in order to empower people today, what I love is exciting people about this metabolic health journey and getting them to engage in the process of what I call like N equals one science on themselves.

49:50

where you identify an outcome you want to change in yourself. What do you care about? It could be, you know, improving brain fog. It could be your weight. It could be depression. It could be your GI symptoms. It doesn't matter what it is. Choose your outcome.

50:03

Then hypothesize what might improve that outcome. Like a scientist, create a hypothesis, then execute on that and collect your data. Your data could be something objective, like a biomarker or a weight on the scale, or just subjective data, and evaluate the outcome without judgment on yourself, but curiosity with respect to the data, then iterate forever on yourself.

50:26

That is what is living the N equals one lifestyle. And that is, I think, how every individual, even today, even in the ecosystem with like the food booby traps we have everywhere, platitudes around health, misinformation. If you really adopt that mindset and engage on that learning journey, you will achieve

50:43

incredible health results that are beyond your wildest dreams. I truly believe that. I've seen it happen again and again, including in people who don't have any scientific or medical background. One of my favorite examples is, I don't know if you've come across Dave Dana on social media, but he was a guy that I met, must have been 2022, maybe it was 2023, I think it was 2022. But when I met him, he had poor mental health, depression, was over 400 pounds,

51:07

and he wanted to improve his lot in life. You can imagine like a lot of people, he'd tried a lot of different diets that hadn't worked and was just kind of in a place of learned helplessness, but also like a lot of people had this fire in his belly to get better. He just didn't know how to direct his energy. So we started working together a little bit. I did honestly very little for him other than give him just a little bit of support, encouragement, and information. But I saw this light flick in him at one point where he got that mindset where he's like, actually, my metabolic health journey is a

51:34

curiosity and a privilege, not a chore. And I'll fast forward to where he is now, which is he's lost more weight than I am as a fully grown adult male. I don't know how much weight at this point, but a lot, probably close to 200 pounds.

51:48

He got his you know financial books in order a curd his depression. He got married. He finished an MBA He is just announced that he's gonna be a father. Oh, and by the way, just as an aside He's partying with Arnold Schwarzenegger on Venice Beach and at Arnold's house become such a fitness icon among people that struggle with similar journeys the point here is I genuinely believe that the gas achievable for every single person if we construct a

52:14

supportive communities and encourage people to engage in metabolic health learning and try to meet them best where they are. That's right. And I think, you know, what I found is you don't necessarily have to go fully extreme keto to achieve a lot of the benefits that you could achieve by kind of being more low glycemic, low starch and sugar. And I think that's kind of the key message here is that starch and sugar is the boogeyman. It's not necessarily fat.

52:43

although there are some people who are, have real significant genetic issues around fat. The vegan community has an incredible PR machine. It's 2% of the population, and yet there's more documentaries, there's more scientific studies, there's more papers on this,

52:59

than most other diets. And I don't understand exactly why it's kind of almost a priori assumed that if you can be a vegan, you're going to be healthier, that it's better for you and it's better for the planet. And we're going to leave that aside because that's a much deeper conversation. But

53:16

That's a very interesting frame that I think has been sort of accepted as a truth in our society, which I don't think has been properly challenged. And I think your work and Dr. Ludwig's work and others has really kind of shown that, gee, maybe we need to look at this a little more carefully. And the other stream is the carnivore diet. So one is like only plants,

53:39

only animals. And I think they're both potentially problematic. But I'd love you to sort of unpack a little bit of your perspective on the pros and cons of sort of a vegan diet versus a sort of a healthy omnivore or even a keto/vegetarian.

53:53

even more extreme carnivore diet. - You said something interesting where you said environmental impacts, and we're gonna leave this aside for now. I don't wanna leave it aside. I actually want to bring it up because I think the reason that there's such a great PR machine around a vegan diet, or let's even just broaden it to say why a lot of people are very attached to certain ways of eating is because food is such an emotional thing that

54:21

topics bleed into each other under the surface. So it becomes very difficult

54:27

when we're talking say about a carnivore diet and i'm like you know this actually might be an incredible therapeutic for people with inflammatory bowel disease people don't hear that they hear it don't hear that kill the planet climate change yeah well or they create they they that undertone leads into the topic so they do mental gymnastics in order to negate or ignore or overlook what i'm actually trying to say which it might be a very precise statement might be

54:52

For people with treatment resistant inflammatory bowel disease, this might make sense as a therapeutic. And so I think it's important to acknowledge that diet touches on a lot of different things. Animal welfare, climate change,

55:03

And that while all these things are important, we do need to parse them in order to have precise conversations. - I agree. - Where we actually like evaluate the data as objectively as possible. - I agree, I agree. And the reason I say I'll put it aside, 'cause I've written a lot about it, I've talked about it, I wrote about it in my food, “Food, What Things Should I Eat?” and other books, “Food Fix.” And I basically came up with exactly what you said. There's like three basic issues. It's health impact, environmental impact,

55:28

and its moral implications. - Right. - And so those are all separate. Like if you're morally opposed, there's nothing I can do to really make an argument against you. If that's your core values and belief, God bless you. - Right. - As far as the environment and planetary issues, there's a lot of flaws in that argument, and it has to do with regenerative versus CAFO arguments, and again, that's why I wanted to leave that aside. I really want to get into the sort of biology of, from a health perspective, you know,

55:55

And up till I think 1940 something, there wasn't a word for a vegan diet. There's been no historically vegan populations on the planet, at least who wanted to be vegan. And everybody's looking for meat 'cause it's the most dense form of nutrients, it's the most, you know,

56:13

nutrient dense, nutrient rich form of nutrients that you can consume to grow and thrive. - Well, I would say by and large, I'm diet agnostic when it comes to metabolic health. And what I mean by that is the great thing about metabolic health is the proof is in the pudding, how you feel in your biomarkers. So if an individual achieves great health, biomarkers, disease remission on a vegan diet, I will applaud them and be happy for them. - Have you seen that? - I've seen people who profess to it.

56:39

I mean, I believe it's doable. I believe it's not necessarily easy. It might require supplementation. I believe it is possible. I don't have any reason to like fully doubt it. And I will give that the benefit of the doubt. I don't think it's a fair assumption, which is often a common assumption that eating the higher proportion plant-based you can eat, the healthier you are. I think that is a problematic reason.

57:00

reasoning. Again, it comes down to biomarkers. Well, not biomarkers, but like, what is the proof? How are you actually doing? And what does a particular dietary intervention actually do to you? So I'll give an example where I can actually construct a scenario where I go from a very saturated, fat-rich, animal-based carnivoresque diet to a vegan diet and spike my LDL.

57:20

and Applebee. I've done this. I have the video breaking down how I did it. Yes, it's a party trick. Nevertheless, it's again legitimate and resulting in a change in a biomarker that I would say the vegan community thinks is particularly important. Probably LDL. So it's just like throwing the wrench in there of saying, look, there's so much context around this that

57:42

do whatever you want with your diet, but don't be deluded to think that just eating more plants is gonna make you healthier. - Yeah, test, don't guess is my motto. - I like it. - Test, don't guess. I mean, look, I can say, God bless you, whatever you wanna do with your diet, do it, but track how you feel, track how your body systems are working, and track your biomarker. Get data on yourself. Because if you start to get real data,

58:05

you begin to see, and I've seen this, people who even want to profess to be healthy vegans, I'm not talking about the chips and Oreo cookies and Coca-Cola vegans. I'm talking about people who are trying. They're often more insulin resistant. They often have more lipid particles, smaller lipid particles. They have higher triglycerides. They have lower HDL. They often have lower levels of many nutrients, including zinc, iron, vitamin D, omega-3 fats, iodine, and the kind of list goes on.

58:35

And I measure these things. So I'm not doing it based on some belief or theory. I'm doing it based on just being a keen observer of data in the population that I've treated for 40 years. And even one patient who was so morally committed to being a vegan,

58:56

you know, we did her, her anti-malarian hormone, which is measured fertility. She's 30 years old. And she was like, had the fertility levels of something that was like in her late forties. And she wanted to have a baby. I'm like, this isn't good for you. And here's all the nutrient divisions you have. And, you know, also you look pale and sallow. I mean, you might want to consider changing your diet. And she did. And immediately she was able to get healthy and get pregnant. All right. I'm going to tease you before I talk about carnivore. Brian,

59:21

Brian Johnson. Is he healthy? That is a great question. I think he says he feels healthy and his biomarkers are good. I think he does what I think most vegans who

59:33

want to be as fit as he is and have as much muscle as he does, he supplements with processed plant protein powders that are most likely spiked with amino acids. Because the concern I have around people who are saying they're healthy, athletic vegans is they can't do it on

59:55

a pure vegan diet that you have to supplement in some way. For example, if you want to get 30 grams of protein, you can eat 400 cc of steak with 250 calories.

01:00:05

If you want to get that from brown rice, you got to eat six cups and it's a thousand plus calories. And that comes with all sorts of other implications of who's going to eat six cups of rice and what are those thousand calories doing to your blood sugar and insulin and so on and so forth. So, I mean, and they go, “Well, but look at them in China, they eat a lot of rice.” And it's true. I mean, I traveled around in China in the '80s and I was in medical school at the time.

01:00:28

And there were these super fit, thin, athletic-looking, lean Chinese who were working in the rice fields 12 hours a day who would come in and eat like a giant bowl of rice and put the vegetable on top. And they were able to do it because they burned through it. I mean, if you're a marathon runner, you'll burn through it. But that's not most people. It's an interesting kind of framework where we have to start to look at

01:00:48

more at what happens to individuals when they try these things and look at, honestly, at their own biology. And that's part of why we co-founded Function Health, which is to give people access to their data, not just having to go to the doctor, please beg, can I please measure my insulin? Can I please measure my ApoB? Can I please measure whatever? You can do it. It's your body. You should pick and choose what you get to do with it. One thing you said there stood out to me, which is not for most people. And I think something we both agree on is that like, it doesn't really matter what works for most people if it works for you at the end of the day.

01:01:15

With that, it's probably a good transition to talk about benefits of carnivore. - And what are the benefits and also the challenges you see on terms of the vegan side? 'Cause I think historically as populations, from an evolutionary biology perspective, we've been more carnivore than vegan, right? - We got most of our protein sources from animal-based foods, I think.

01:01:35

for most of our evolutionary history. - And there are certain populations that have more plants and if you're at 40th latitude and you're kind of in the equator zone, you're gonna probably have more plants to eat than if you're in the tundra of Alaska or somewhere and you gotta live on whale meat and stuff. - But one would also argue that when we were evolving, there wasn't a selection pressure for longevity that our priorities as individuals and organisms have shifted. So how far can the evolution

01:01:59

evolution perspective really take us in assessing what's best for our health. Okay, well, so let's talk about carnivore. I mentioned earlier in the pod that I had a very negative view of keto before I started it. But over time, I've developed an interest in probing areas of taboo. Carnivore is definitely one of them. When it came up on my radar, my first response was like, this is absurd. I can

01:02:19

I can only meet diet, this can't be healthy for you. Despite how I'd changed my mind on things before, but I like playing devil's advocate. So it started, I started to dig into it a little bit more. And what I found was that there was actually a lot of basic physiology and biological plausibility

01:02:37

to align with some of the things that people report clinically on a carnivore diet, like remission of inflammatory bowel disease, which is obviously of interest to me. So since that point in time, I've been delving into it as a topic a little bit with respect to writing case series. We had one on a carnivore diet for anorexia, because that's obviously a very controversial one for a carnivore diet for inflammatory bowel disease, where we did full medical histories, we had lab reports, colonoscopy reports.

01:03:05

and we interviewed, I interviewed like 10 patients and to hear their stories, people saying like, you know, that they had had Crohn's or colitis for a couple of decades, been through a litany of immunosuppressants, been through surgeries, and this was the first thing that really like brought them back to life and gave them a new life. Like you can't ignore that. Especially when, you know, it's dozens of people.

01:03:27

10 were reported, but there are many more. And then you square that up with physiology that actually makes a lot of sense. Like carnivore is usually keto, ketones in the gut reduce inflammation, higher ketone levels in the gut associated with lower IBD activity. There's even literature showing how thyroid elimination can have a therapeutic effect via changing called mucosporilium, I think.

01:03:48

a pathobiont on the gut that can put pediatric Crohn's disease into remission. I didn't know before studying it, but actually fiber-free liquid diets are quite commonly prescribed for refractory pediatric. - Elemental diets, yeah. - Yeah, it's like 60 to 85% of cases respond. They don't teach you that in medical school because it's like, I guess heresy against the beneficial effects of fiber. But say for that particular use case,

01:04:10

I was seeing so many stories. And when I say stories, I do mean like with medical histories, lab reports, colonoscopy reports that are just overwhelming along with interesting physiology. And it comes back to this question of, or the topic of absence of evidence isn't evidence of absence. Like nobody's done the three to $5 million randomized control trial of a strict carnivore diet versus a vegan diet for IBD.

01:04:32

I have my hypotheses about how it might turn out. I'd like to see it done. But that's the reason this isn't, or a reason it's not prescribed is because the studies haven't been done. It doesn't mean it can't really benefit people. Coming to that realization and feeling it's the intellectually honest thing, then abuts against some of the, what I would call intellectual dishonesty I see in the media and the scientific literature.

01:04:57

around carnivore diets. I'll give you a case in point. Did you see that JAMA Cardiology case report that came out about the blacks on the hands? The yellow nodules, it was over all the– - You mean the anthomas? - Yeah. So there was a report that came out a few weeks ago as we record this. It was in JAMA Cardiology, it was a case report.

01:05:14

of an individual who went on a carnivore diet and had, they say, cholesterol oozing from his skin, if people want to Google it. And there's these pictures of, you know, these yellow plaques on his hands from eating presumably a carnivore diet. Now, you look at the report, and it was word limited, but you look at the report, and the entire description of the patient was a man in his 40s.

01:05:35

That was the description. Didn't even give us the exact age, no medical history, no family history, no genetic history. And they described his diet as him eating six to nine pounds of cheese, butter and beef daily. - Wow. - Which is actually implausible. So this didn't read like a case report. This read like a skit from Monty Python. You know, the fat man. I'm like, this is not plausible. How did this get published?

01:05:56

I'm all for cautionary tales, but this is intellectual dishonesty. And if people actually do read the report, it was worded a little bit vaguely around his diet. The first author did get on the news, I think it was Fox News, and doubled down on the fact that he was reporting six to nine pounds of cheese, beef,

01:06:12

and butter intake per day again. For eight months, implausible. This isn't a legitimate report. And nevertheless, it just doesn't… This is what you don't understand. Like, four ounces is like, six ounces is a normal portion of meat. That's like four times that is a pound. You're talking about…

01:06:27

- Nine times four, you're talking about like– - Oh yeah, no. I mean, when you go to like get a 16 ounce ribeye, no bone, that's a pound. So the least he could eat was six of those per day, every day, the least, for eight months. Not, you know, even mentioning the density of cheese and butter. - Wow. - A human being can't eat this. Like not even like, I don't know, Eddie Hall or like the Mountain from Game of Thrones probably eats this much. Maybe them, but you can see his hands, it wasn't that person.

01:06:55

This was just one example of what I would call intellectual dishonesty. In order to, if I were to make the steel man, what they're probably trying to do is project a conservative and cautionary tale in order to dissuade people from doing something that

01:07:10

people presume is harmful. But the fact of the matter is when you have a pattern of reports like these, and there are a pattern, I can go through other examples, what ends up happening is the community of people who have benefited, that is their narrative. You're not gonna dissuade them otherwise. If an individual's benefited, they feel they've benefited. See this for what it is, intellectual dishonesty, double standards, and then process loss.

01:07:34

And that is what's dangerous. For us, it's lost in science and medicine. So now, why are they going to believe anything else that comes out of GMO cardiology? Because this nonsense came out, and it evidently was nonsense. So… And that's one of the top medical journals. So it's not like it's some… Happened with circulation too, with a report where they just

01:07:51

basically lied through their teeth. And in both these instances, there is no actual like good recourse. So they don't accept letter to the editors. I tried to do one for a circulation report. They said, you know, it's a case report. You can't actually do an e-letter. I emailed the journal. I emailed the first author. No responses. I even told the first author in an email on this general cardiology report. I said, like, this report seems deficient. If you have more details, I'm willing to help support you writing in the full case report as a cautionary tale. We want a detailed dietary record. If you want to get genetic testing, we can do it at my expense.

01:08:20

I'm not against N equals one. I'm not against cautionary tales. I'm not against case reports. I'm against intellectual dishonesty. And there is so much when it comes to meat and carnivore diets, and it just pervades the literature. I was reading a study in neurology about red meat and dementia, and they cited a study where they said saturated fat is bad because it lowers BDNF. And the study was a mouse study where the mice were fed an HFS diet, which stands for high-fat sucrose diet. So they were throwing saturated fat under the bus, citing…

01:08:48

Mice eating sugar. - Yeah, I mean, that's the whole 'nother conversation, which is eating saturated fat in the context of a high sugar carb diet. That's what makes it deadly. And I read a lot about that in my book, “Food, What the Heck Shall I Eat?” I think people even eat fat, get thin. It's like, it's not the,

01:09:02

saturated fat per se, it's when you combine it with the starch and sugar, which is mostly how it's found in our diet. - Milkshake is not a steak. Again, relatively diet agnostic, but I do think there's a systemic bias in the media and the scientific literature against red meat and certainly carnivore diets, and I like to call that out. - So let's just say for some people with severe illnesses that a carnivore diet can be a therapeutic diet. I think

01:09:25

The question I have is, is it the meat or is it what they're cutting out? And I, as a functional medicine practitioner, I'm leaning more towards it's what they're cutting out. They're not eating gluten, they're not eating dairy, they're not eating grains, they're not eating beans, they're not eating a lot of things that can irritate the gut. Is it the meat or is it just what they're not eating? - I don't think there's anything magical about meat. So I wouldn't say it's the meat per se. I would say that it's an elimination diet. But if the universe of foods that is an irritant to you is basically everything but meat,

01:09:52

Does it make a difference? It may not be like that. You could add back things systematically. Yes. What I would also want to sort of double click on here is the narrative in the culture that meat is unhealthy, inherently bad. It's going to cause heart attacks. It's going to cause cancer. It's bad for you. We all know that it's bad for you. We're all told to eat less meat. We're told to eat less red meat. Where do we stand in 2025 on this data? I think it's weak to non-existent.

01:10:18

I think most of it comes from large-scale population studies that are skewed by profound health user bias, and then mental gymnastics that people do and statistical manipulation to reinforce the narrative that red meat is bad. - So just to unpack that in English, people who, when they do these large population studies,

01:10:35

The people who were eating meat at the time, and a lot of these studies were done in the 70s, 80s when meat was the boogeyman. The people who ate the meat were less healthy. They ate more, they drank more, they weighed more, they smoked more, they didn't take their vitamins, they didn't eat the fruits and vegetables. There was a million reasons why they had more disease than the people who didn't. Conversely, those who did need meat

01:10:56

we actually saw, you know, were healthier, but was it 'cause they didn't eat meat or 'cause they were just healthier? They exercised, they didn't smoke and so forth. We saw that with these large population studies like the Nurses' Health Study where it was assumed that women who took hormones were healthier across the board for brain health, heart attacks, et cetera. It turns out that wasn't true when we did a randomized controlled trial that was a billion dollars from the NIH called the Women's Health Initiative where in fact it showed many of the opposite findings.

01:11:24

because they actually did a proper study, not just look for correlation, which didn't prove causation. And that's what a lot of these nutritional studies are that people quote about meat being bad. They're population studies that don't take into account all these confounding factors that can make it seem like the meat's the problem, but it's really not. I would, just to be fair to my own standards, point out that…

01:11:45

for some of the outcomes that you'd be interested in, say like a heart attack, it'd be really hard to do a randomized controlled trial in humans looking for that outcome where you just have like a very controlled meat intervention. Despite that, I still think the balance of literature is very weak. And you can even see that, and you were mentioning, you were talking to somebody on or related to the dietary guidelines. Like, I don't know if you read a draft of the

01:12:07

the guidelines or the data behind the guidelines for 2025. But I look through it and they even say they're like how weak and limited the evidence is. Nevertheless, red meat is bad for you just perpetuates as a meme because

01:12:23

it's already taken on a life of its own. To go back to the study that I mentioned before, or was mentioning before about the mice fed the high-fat sugar diet and then having saturated fat thrown under the bus, the broader point of that study was about the media was running with it saying red meat was bad for the brain, when as a matter of fact, there was tremendous health user bias. Unprocessed red meat was not associated with dementia in any way, shape, or form. It was only the processed red meat. And then when you looked at the physiologic explanations, there was nothing.

01:12:52

there that was specific to the unprocessed red meat, which is where the only place they found the effect. In effect, this study said nothing negative, really, about like, say a steak. Nevertheless, it got presented to the public as don't eat red meat 'cause it's bad for your brain. Instead have a cauliflower because we can take this nice sagittal section and make it look like a brain and feed into your base human emotions. - Right, that's amazing.

01:13:18

So your take is meat as a whole isn't the problem when it comes to our health. No. And metabolic health isn't.

01:13:26

broken by eating more meat, it's broken by eating more sugar and starch. - By and large, yes. - That's kind of the bottom line here. And then what we're finding is that across a whole array of human diseases, we've been listing, again, from autism to Alzheimer's, from diabetes to depression, from cancer to colitis, there may be some common link here that we have missed. And this common link that you talked about is the root. And I think that's, when you talk about metabolic health, and when I talk about it, that's really what we're referring to is

01:13:55

We have a society where we have a massive metabolic health crisis. And it's not going to get fixed by limiting red meat or by eating more vegetables. I mean, it's going to be fixed by addressing the massive amounts of sugar and starch in our diet. And that's kind of a…

01:14:11

Forest for the trees. We don't want to lose the forest for the trees. I agree. And to that extent, speaking about forests and plants, I just want to be very clear. Me saying a carnivore diet can be beneficial for certain people and red meat's not bad is not saying all fruit is terrible for you in all circumstances, fiber is bad for you. These are consistent ideas. And I think people get so captured in one camp that there are presumptions based on

01:14:35

unrelated statements. So red meat, not bad for you. Red meat can be a health food. Does it mean Brussels sprouts are poisoning you or broccoli's a conspiracy? No, it does not. If you tolerate those foods, I think they're perfectly fine. In fact, I'm quite jealous. I love Brussels sprouts. They just don't agree with me. So Nick, what is next on the frontier for you? Like you're about to graduate Harvard Medical School. You've got your PhD. What is the frontier for

01:14:58

in terms of your intellectual pursuits that's next and what's exciting for you? - This will be the first time I probably announced this on a platform of this size, but I took the very big step and decision of deciding I'm not going to apply to medical residency.

01:15:14

Now, you know the weight of that, but just to clarify it for other people, if you don't do a residency, you're not a practicing clinician. So I have spent my entire life imagining being a practicing clinician and doing everything by the book, which means getting into the best college I can, best grad school I can, best medical school I can, and I've basically done all that. And then you, you know, go to residency, you go to fellowship, you run a lab, you, you know,

01:15:43

do everything in a nice professional academic jade tower manner to give that up at this late stage is a big deal because on the one hand people could say like well what was the point of medical school for you what i've been thinking a lot about as i observe from my interesting vantage point as a patient medical student

01:16:07

trying to provide healthcare, a scientist and a young person in social media, what I've observed is that I think the biggest impact can be had from empowering individuals with knowledge about metabolic health and finding innovative ways to fund groundbreaking research that is not gonna come from normal channels. I'm not gonna get a million dollars from the NIH to do the study I wanna do. And I've seen people try to change the system from the inside

01:16:34

without major success. So what I've decided I want to do is try to, after graduation, scale up the early efforts that I've been making with respect to the social media education, metabolic health education, that a brand or scale. The last year for me, starting around New Year's 2024, was experimenting with how people responded to

01:16:58

to some of my communications kind of in my free time on the side of medical school. And I think the response has been tremendous publicly, but also on the back end, it has been really incredible to hear from certain parties who are interested in say giving $5 million for a particular trial because metabolic health is touching so many people's lives. Some people have resources and they'll support you. So for me, it's about finding a way going forward to stimulate

01:17:26

conversations, get research funded, and put people's data in their own hands, knowledge in their own hands, so they can start their health journey today while the system as a whole hopefully slowly changes. - Yeah. - Yeah, no residency for me. - Well, you know, you're right. I literally just read to what you're talking about, a woman, a wealthy woman in her family who had a son who was bipolar,

01:17:51

He cured himself through keto diet. They became very interested in this. Created something called Metabolic Minds, which you mentioned. And they just funded over $3 million with Mayo Clinic to study keto diets for mental health, which is, I think, revolutionary. The Buzuki family, they've been very nice to me. And yeah, they're a great example of someone who

01:18:10

You know, I would never wish bipolar disorder on Matt Pazuki. However, it's just like I'd never wish ulcerative colitis on me. But sometimes misfortune strikes the right group of people in order to build a highly motivated army to make change. And I think that's what's happening with metabolic health. And that's why I'm so…

01:18:29

optimistic is because on the one hand it's a david and goliath scenario where big pharma the current medical infrastructure biomedical infrastructure like the incentive structure business models are set up to favor pills and procedures yeah and an unhealthy food environment however there is a growing group of people who are just finding incredible success with metabolic health approaches and then

01:18:52

unionizing and coming together with, albeit, you know, individually maybe fewer resources, a purpose that is so powerful, I can't imagine things don't change dramatically. But they're only going to do so if we really lean into it. And so that's what I'm committing myself to. It's not because I don't think Western medicine has this place that I don't think it's important. It's that because over the past year or so, when I'm sitting in that intern room doing my intern level tasks, it's not that I don't care about the patient, but

01:19:21

But my mind is not there. My mind is how can I communicate this incredible scientific story about nanotubes in the brain or cyanide being produced by our lysosomes or whatever to the general public to excite them. Metabolic health, this incredible thing

01:19:34

my mind just wasn't in the clinical medicine. And so I thought that wasn't fair for me, the patients who, or whatever, you know, a member of my cohort, my peers would otherwise have that position in residency, that I'm going to try doing something different because it's where my story, my skillset, my passion, and my skills are most geared, where I genuinely think I can have the biggest impact. And maybe I'll fall on my face, but I have to try. Well, your life has been the perfect alchemy to get you to where you are now. I like that.

01:20:02

I think I'm very excited to see what you're up to next because I've been shouting from the rooftops about metabolic health for 30 years and to have someone with your credentials, with your mind and with your passion focus on this now, as David and I start to sort of round out the end of our careers, you're coming up strong and it makes me very excited. Because I think people don't understand this and they don't understand how

01:20:27

how easy it is to actually fix broken metabolism if you know what to do. - Thank you. I feel like I'm definitely standing on the shoulder of giants, just so excited for the future to come. One thing I will say that will hopefully bring listeners and you some more positive vibes, let's say, is like, I've been feeling out, just kind of naturally, the interest in metabolic health among my generation of future healthcare leaders. And it's incredible.

01:20:53

It's like people see, my peers see, our system is screwed up. Medicine has changed for the worse, that patients are suffering, and we are not stepping up as a system to help them enough, and they're looking for innovative solutions. Yeah.

01:21:06

And so I have found my peers to be so receptive to the metabolic health message. Actually, I was so concerned about this that before I started at Harvard, I wrote a piece for Stat News that was, will a ketogenic diet make me a pariah in medical school? And what I found to be the case is behind closed doors, like people are so open to these

01:21:24

fascinating innovations in metabolic health. - Well, doctors can see. I mean, they can see their patients are not getting better. They see they need more and more drugs. They see their diseases are progressing. They see it's getting worse as a society. I mean, since I graduated medical school, it's been a disaster in terms of our metabolic health.

01:21:39

and you can't not see it anymore. - So I guess the challenge set forth before me, and I present this not as a, I'm not trying to toot my own horn for what's coming up. For me, I'm actually asking for help from everybody listening, which is that we've gone through a lot in this podcast. I'm sure all of you listening caught moments

01:22:00

when Mark pulled me back and was like, “Let's simplify this because you're going off the deep end a little bit.” Clearly I have a lot of enthusiasm for this and I want to find a way to engage people in the discussion in the way that is practical,

01:22:19

functional, nuanced, and I want to scale the discussion. And one of the big challenges there that I think everybody who's a public communicator grapples with, I'm sure you've grappled with it over the years, is like how do you compete in this ecosystem of engagement bait in a way that is practical and intellectually honest?

01:22:44

I've really struggled with this because- You've done a great job, honestly, better than most. Well, it's difficult because it's like, I know exactly what I'm doing when I eat Oreo cookies to lower my cholesterol. I know the media is going to run with it and say, Harvard doctor, Harvard scientist lowers his cholesterol with Oreo cookies. And I know that's going to create confusion.

01:23:01

I also know that, you know, a similar thing's gonna happen when I do 720 eggs, or that it's kinda click-baity for me to do debunked with my picture next to a giant ribeye steak when I'm debunking eight carnivore myths. That said, I don't really see another way

01:23:14

to access people unless you provide them engagement bait that then draws them to the table to have nuanced discussions. Using Oreo cookie as a case in point. - Okay, you're just dangling a little bait on the hook. - Yeah, but I'm very transparent about, in fact, in some of my videos I say this is clickbait, let's see how it does. Here's how I engineered this clickbait.

01:23:32

But here's why I'm doing it. And so to use Oreo cookies as a case in point, because I was very nervous about doing that. I didn't just do it on a whim. I'm like, well, this had a net positive or net negative effect. I genuinely didn't know. - On your health or on your career? - Oh, definitely, talking about my health. I wasn't even worried about my career. I was talking about public impact. I'm like, I really can't see a scenario where

01:23:54

someone genuinely believes Oreo cookies are a health food, I don't think an adult could be persuaded by a thumbnail. And if they can, then, you know, natural selection can thank me, but that's another question. But what resulted was really exactly what I'd hoped and more, which was

01:24:09

It drew forth conversations that were incredibly productive. It drew into the fold researchers who were prior, previously not aware of the work, who then started digging down the rabbit hole and finding there's legitimate research here and then investing funds potentially in big studies and doing so. We have one $2 million project I want to get up and running either later this year or next year to like rigorously assess some of our work in multiomics. But, and it acts as clinicians.

01:24:37

To the point that in the months following the Oreo experiment,

01:24:41

I was literally getting emails from cardiologists left and right saying, I saw your Oreo study. It put me on a path to learning about lean mass type responders and lipid energy model. I realized I had a bunch of these in my practice. Some of them are statin intolerant and I've dropped their LDL by 400 points with sweet potatoes because I understand the physiology. So if anything, it had a quote positive clinical impact. If anything, I bring this up because it's hard. I'm sure you know it's hard to like

01:25:07

Put something out there that you know is, actually I'm gonna say a little bit, is clickbaity for the purposes of drawing people into discussion and also knowing that there's gonna be collateral damage. There's always collateral damage. Someone's gonna be confused, somebody's gonna be angry, and you just accept that. - Of course. - And I feel like at a point you just need to. - Of course. - At a point you'd be like, look– - There's gonna be haters and there's gonna be lovers and it doesn't matter who you are or what you say, it's always that way. - Yeah. - It's always been that way. And you could, you could,

01:25:33

You just kind of have to let it roll off your back. You kind of have to start enjoying it a little bit. Start playing with it a little bit. I don't know. I had a couple pieces recently about Diet Coke, aspartame, and both cardiovascular health and reproductive health, and you'd be surprised at how vitriolic people get about their diet. Oh, you mean you were coming out against it? Oh, yeah. Saying that there's harm? I think there is. I will probably never drink a Diet Coke again. Well, good.

01:25:58

Give us this, we're about to close, but I want to hear the snapshot. Because, you know, for example, Lane Norton, who's, you know, a well-respected nutrition scientist and who sort of certainly has a following, he basically says all the data about

01:26:11

artificial sweeteners is garbage. Now when I looked at some of the papers that he was citing, it was like funded by the American Beverage Association, otherwise known as the American Soda Pop Association before it changed its name. - Yeah. - I'm like, hmm, I'm not sure about this. So what's your thumbnail perspective on artificial sweeteners? Give us the down and dirty. - I think it's first important to acknowledge getting rid of artificial sweeteners, in particular like say like aspirin and sucralose, costs you nothing. Like you like the taste.

01:26:40

But it's not like saying cut out red meat or something that might have a health benefit. There is no clear health benefit. - Well, you could say you're eating less calories, it's a way to lose weight. - You're not eating less calories though unless you have the binary of it's a Coke or a Diet Coke. And I hate that binary. People are like, is it worse than a Coke? I'm like, why are you choosing between these two things? - Right. - Like if that is actually your binary. - Like arsenic or strychnine, what do you think? - Then you can choose the lesser of two evils. That is a legitimate choice.

01:27:03

And my thing is not to say people shouldn't have Diet Coke. It is here are the data, make an informed decision like a freaking adult.

01:27:10

If you wanna slam Oreo cookies and eat milkshakes for the rest of your life. - So what is the data? What is the data? - So, what I would say is there are really interesting data showing potential high impact harms, like transgenerationally inheritable anxiety. There's a paper in PNAS, ironic 'cause it sounds like penis, but it was an animal model paper, mice, and I'll explain why that is totally legitimate in a moment, but where they fed mice the equivalent of two to four Diet Cokes for humans in aspartame.

01:27:40

not only did it generate anxiety on behaviorally validated tests, but it was a transgenerational effect. So the offspring of the mice, and even the grand offspring. - To epigenetic effects. - Yeah, presumably. So past, in this case, we're looking at the male lineage, but there was anxiety in the offspring and the grand offspring, even though they'd never been exposed to low dose aspartame because their fathers and grandfathers had been exposed. So, you know, and, and,

01:28:08

there's you know physiologic explanations for how this might work how aspartame also might affect brain health how it's breaking down how it changes amino acid transport to the brain we can get all that and also human data on quote say irritability including randomized controlled trials so there's some signal in the human literature for sure

01:28:25

It's not the most rigorous of all time study, but then very concerning things in the preclinical literature. And the thing that people tend to do, the Diet Coke defenders, like perverse Avengers or something, they tend to do is they put up a very implausible bar of evidence. So let's take the example of this study, this PNAS study. What it's saying is in medicine,

01:28:49

low dose aspartame, the equivalent to what the FDA says is totally fine, it's like seven to 15% what the FDA says is okay, two to four eight ounce Diet Cokes can cause anxiety that is trans-generationally inheritable. You can ask, well, oh, prove this in humans. I'm like, you're really gonna try to do a 50 to 60 year randomized controlled trial where you give human adults Diet Coke and then track, it's never gonna be done. - Never gonna be done. - And so you're asking for evidence that

01:29:13

can't be collected. And I'm not saying the evidence is entirely watertight. So another paper just came out, and I think it was Cell Metabolism, on aspartame and cardiovascular disease. And what they showed in mice, and also they had some monkey data, was that it can spike glucose and insulin. And what this did

01:29:32

was increased plaque progression in susceptible mice, admittedly susceptible mice. However, the mechanism had to do with increasing certain molecules on the endothelial lining. Basically, there were like baseball gloves for rolling around immune cells, the baseball that sucked them into the arterial lining.

01:29:48

and cause plaque to grow. So there is a very clear physiological model with data in mice and primates showing how this could negatively impact heart health in conjunction with associational data saying artificial sweetener intake is associated with cardiovascular disease.

01:30:02

Does this prove beyond a shadow of a doubt that Diet Coke starts with these? No. But you shouldn't need those data to incorporate the existing literature, which is of concern, into your individual algorithm of whether or not you want to make the decision. And artificial sweeteners, to be clear, in humans, have been shown to cause

01:30:21

insulin resistance, sometimes it takes longer than a day or so. There was one study out of the Weizmann Institute, I think it was Nature, where they showed that it was saccharin in this case caused insulin resistance by changing the microbiome. In this case, it was a majority, but not all people had a response. There might be individualistic elements. It may take time to result. The data are not

01:30:41

absolutely proven without a shadow of a doubt, but there's enough there to say, this is concerning. And then the question is, where do you put the burden of proof? Is the burden of proof defined the implausible study that proves it without a shadow of a doubt? Or can you just say, you know, these literature are concerning enough

01:31:00

for me to be like, I might be okay with freaking water. - Well, do you think, to speak to that, I mean, with this sort of new administration and the desire to sort of take chemicals out, do you think that should be a target? 'Cause right now it's kind of considered a grass substance. It's generally recognized as safe, but the FDA doesn't really regulate it other than saying food companies, well, do you think it's safe? They go, yeah, we think it's safe. And they're okay with safe. Well, we can have it and there it goes in the marketplace. That's kind of how we do it with chemicals in our food supply until we find out they're a problem. - It's funny.

01:31:28

because you actually hit on a broader point about this burden of proof. Because if you don't have evidence to say this is very harmful, and sometimes the harm is manifest over a long period of time, then…

01:31:41

should you be allowed to introduce a substance into the food supply? And the fact of the matter is right now, the way it is, the answer is you are allowed. You are. And then after the fact, we might do some assessment. Should first ask questions later. Right. And so let's say, just playing with random numbers here, there's only a one in 100 chance that any given chemical actually that is not proven to be safe over a long period of time

01:32:02

is harmful. Well, if you introduce 10,000 chemicals– - And they're all synergistic, and they're extractive. - Right, and so we see that with a lot of things. My position is we do live in a society of free choice. So I'm not for

01:32:19

restriction of most things and more about better education. So I think we can talk about these things. I don't think Diet Coke should be outlawed. - Well listen, when I was in South America, I was so shocked to see on the diet soda can a warning label for kids. Say this is harmful to kids, it can affect their behavior and da da da da. I was like wow, this is really interesting. They think there's enough data to kind of put a warning label on food. And I think that's what we should do in America is we should at least

01:32:43

meet the standards of other countries like those in South America and Europe that put warning labels on where there is some caution if there's a concern and not put the burden of proof on

01:32:54

the person who's eating it or the government, but put the burden of proof on the companies making these products and introducing them into the country and into our food supply. That's what I'm concerned about. So we don't follow the precautionary principle. We basically say, well, trans fat, you know, we came out in 1911, it's Crisco, great food, substitutes for butter, blah, blah, blah, better than butter, Fleischmann's marshmallow. And I remember growing up on all that shit. It turns out it's deadly. It's killed millions of people and took billions

01:33:20

50 years from the time we knew it was a problem to get it out of the food supply. I think the artificial sweetness story is yet to be fully told, but I think there's more and more signal that it's a concern. And I personally agree with you. It's not like it's a necessary thing in our diet. And I would say, if you want something sweet, put a teaspoon of sugar or a teaspoon of honey in it because no one's going to put 15 teaspoons of sugar in their

01:33:41

- Have you seen some of the coffees at Starbucks? - Well, no, no, no. Personally, you're not gonna sit at home and put 15 teaspoons of sugar, but you will get it when you have processed foods like a 20 ounce soda or a Starbucks coffee, you'll easily get that. - Again, informed choice. If you want sweet and say you're like, you know, you want sweet without calories, there are better options than aspartame or sucralose. I think you're gonna have say monk fruit, stevia, I think are like totally fine. Allulose, I think totally fine. So it's a matter of,

01:34:09

Making an informed choice in this particular case, I think the sacrifice is basically negligible. That said, if you want to have a Diet Coke, just understand and appreciate the data. Don't stick your head in the sand because the impact is potentially large. Genuinely, and this is going to sound hyperbolic, but I mean this sincerely, like say you're trying to conceive with your partner. You're a guy, you're producing more sperm every day. Is it worth it to you? Read this PNS paper if you want. It's linked on a YouTube video that I'll put up.

01:34:36

- And make anxious sperm, so don't do it. - I know, yeah, anxious sperm. Is it worth it to you to risk a potential impact on the mental health of your future children, which you'll never know for sure. Say they develop anxiety, you'll never know if it was your fault or not. You will never know. But is it worth it to you to have those two Diet Cokes per day? Is it? - Yeah.

01:34:56

And I would say it's just like, for me, no. If it really matters to you that much, okay, you're an individual. You can make adult decisions. Your kid's not mine. I mean, unless it's some evolutionary food that we've been eating for millions of years, I think the precautionary principle is a good idea. Whether it's red dye number three or butylated hydroxyethyl-A-B-N-O-T-R-A-N-S-F-A-T-S,

01:35:13

or aspartame, or any of these things that we've introduced that are new to nature that our bodies don't, might yet have adapted to or don't know what to do with and might be harmful. So I'm really excited to kind of how you think. I'm excited with your curious mind. I love your little tagline, stay curious. I think that's one of the most,

01:35:30

valuable qualities in human being. You even got a tattoo, Stay Curious. It's my first tattoo I got. I love that. My karate sensei and I got matching Stay Curious tattoos. I love that. My first and only. So I think staying curious is key and not having preformed ideas, being open, challenging your assumptions, challenging your hypotheses, asking questions, not being ideologically driven, but being scientifically driven. These are all important.

01:35:54

really important things as we start to think about how do we take care of ourselves. And there are things that are mostly missing, even from the nutrition landscape. It's all ideology. I'm a carnivore, I'm a vegan, I'm a keto. It's like…

01:36:03

you know like i know it's not cartoon was like how do you how do you know someone's a vegan they tell you all right so i think i think i think it's really important that we really have a moment to kind of pause reflect and go the science isn't completely settled anybody who says it's settled is is a doesn't understand science whether it's about vaccines or it's about nutrition or it's about anything that we kind of debate and we should stay curious and we should start to keep

01:36:28

kind of engaging in this dialogue where we're kind of investigating the data, keep questioning it, keep challenging it, try different weird experiments on yourself like Nick did. Naughty Dorios is not my health recommendation. So anyway, great, great, really great, great to talk to you about all this stuff. I feel like I literally, I could talk to you for another 10 hours and we wouldn't even get to the bottom of it. So perhaps once you graduate medical school and figure out what's next on your horizon, we'll have you back. And Nick,

01:36:54

Keep up the good work and stay curious. Thank you so much, Mark. Stay curious. When it comes to supplements, you only want the best for your body, the kind with the highest quality, cleanest, and most potent ingredients you can get. That's exactly what you'll find at my supplement store, where I've hand-selected each and every product to meet the most rigorous standards for safety, purity, and effectiveness. These are the only supplements I recommend to my patients, and they're also what I use myself.

01:37:17

Whether you want to optimize longevity or reduce your disease risk, or you're looking to improve your sleep, blood sugar, metabolism, gut health, you name it, drhyman.com has the world's best selection of top quality premium supplements, all backed by science and expertly vetted by me, Dr. Mark Hyman. So check out drhyman.com because when it comes to your health, nothing less than the very best will do. That's drhyman.com, D-R-H-Y-M-A-N.com.

01:37:41

If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at DrMarkHyman. Please reach out. I'd love to hear your comments and questions. Don't forget to rate, review, and subscribe to The Dr. Hyman Show wherever you get your podcasts. And don't forget to check out my YouTube channel at DrMarkHyman for video versions of this podcast and more. Thank you so much again for tuning in. We'll see you next time on The Dr. Hyman Show.

01:38:05

This podcast is separate from my clinical practice at the Ultra Wellness Center, my work at Cleveland Clinic and Function Health, where I am chief medical officer. This podcast represents my opinions and my guests' opinions. Neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided with the understanding that it does not constitute medical or other professional advice or services.

01:38:32

If you're looking for help in your journey, please seek out a qualified medical practitioner. And if you're looking for a functional medicine practitioner, visit my clinic, the Ultra Wellness Center at ultrawellnesscenter.com and request to become a patient. It's important to have someone in your corner who is a trained, licensed healthcare practitioner and can help you make changes, especially when it comes to your health.

01:38:53

This podcast is free as part of my mission to bring practical ways of improving health to the public. So I'd like to express gratitude to sponsors that made today's podcast possible. Thanks so much again for listening.

Edit:2025.05.05

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