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00:00 Coming up on today's show. If I put food into my mouth and it goes into my stomach and my GI tract, no matter what the food is, it's going to drive inflammation because inflammation is the body's natural protection against foreign material. Fructose, when it's metabolized, detoxified by the liver, it's handled naturally.

00:18 the same way or in a very similar fashion to alcohol. It produces fat and it damages the liver eventually and drives this fatty liver disease. Stress is not what happens in the world. Stress is how we respond to what happens in the world. And stress is affecting our inflammation, you know, directly drives inflammation, drives insulin resistance, all these things. I was blown away by the fact that both physical exercise, but also mental exercise,

00:46 could show within a short amount of time actually changes in the brain, presumably related to its effects on BDNF, brain-derived neurotropic factor, which, you know, certain parts of the brain, like you'd expect the hippocampus, can actually increase in size with these various activities. So it's really amazing. Rob, as a conventionally trained doctor who later went on to teach other doctors, I'm curious where along that journey did

01:15 Did cracks start seeping in that what you had learned might not be totally right? Thanks, Jesse. It actually came all of a sudden. Just my background, I've spent my whole career as a professor in a couple of different medical schools here in Southern California. So I got to practice medicine, teach, do research. The point is,

01:39 I represent the establishment, the medical establishment. I'm not a fringe doctor. I'm not a conspiracy theorist. I drank the Kool-Aid. I'm mainstream. But what happened to me…

01:53 Which is what happens to many people in this path. I came down with four chronic diseases sort of suddenly, hit me like a train. And I went to my doctors and they prescribed me medicines for them, prescription meds. And they assured me I needed to be on those for the rest of my life. And I knew that wasn't going to end well. So that was really what prompted me to begin investing.

02:20 an inquiry and re-examine my beliefs about the way things worked in medicine. And it was really a revelation. How far back does that go when you started to get sick and accumulate these medications? Yeah, it was about…

02:38 About 10 years ago when it happens. And it happens to a lot of people when they reach a certain age. I mean, most adult Americans are obese. Many half, half hypertension. Most are diabetic or pre-diabetic. So these chronic diseases are coming on to all of us.

03:00 but they all happened right about the same time. And unfortunately, a lot of people who go down your path end up on medications like you talked about for life and don't know of another way. So I'm just curious where, as a doctor, obviously you have a little bit of a different world than a lay person, but what was it for you specifically? You're taking these meds, it's controlling the symptoms. What was that crack for you where you saw, you know, maybe there's a different path here?

03:30 Yeah, part of it was the diseases I knew that I had, which were gout, hypertension, dyslipidemia, and prediabetes, which are common diseases that everyone had. I thought they were very separate diseases. I thought they were being controlled by the prescriptions. But knowing what I know about those diseases…

03:57 The future, at least as far as longevity, didn't look great for me. And I still have kids that aren't even in high school yet. So I wanted to be able to, out of self-interest really, it forced me to look for other options just to see if there was any other possibility to an alternative to what I was doing.

04:21 So what were the first steps for you? What part of the alternative health realm did you stumble into and start to make changes in to work your way back?

04:30 Well, as it turns out, a friend of mine is Gary Taubes, who is a science writer, and he was writing a lot of books about Nobel laureates and all, but he had just transitioned into writing about nutrition science, and he was writing a book called Good Calories, Bad Calories, but what he did was he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Calories, and he wrote a book called Good Calories, Bad Cal

04:51 We really didn't talk about that. I really wasn't paying attention to his work. But when this happened, I sort of went back to his book. I looked at Nina Teicholz's book, a great book on saturated fat, and just…

05:08 I began looking at the more current research that I wasn't necessarily on top of. And many of my colleagues at the medical schools and certainly the doctors I went to weren't on top of either. And I began to see that there was a lot of new understanding and new approaches to these diseases that I wasn't told about.

05:35 You touched on something there when you're telling your story about the different chronic diseases, the fact that you felt like these were all from different areas and they were separate silos. One of the positive messages through what we're going to get into today is that there's a common route to disease, chronic disease,

05:54 And when we apply some pressure on these different levers we're going to talk about, we can begin to correct for everything at once. So it's not very siloed, like I said before, where we need to look at symptoms and then how do we whack that separate symptom. We're going to get to the root of things by what we're going to get into today.

06:13 Exactly. And that was one of the revelations to me, certainly, that these diseases were certainly integrated, not only the four diseases that I came down with, but as we'll see later.

06:26 The the many, many diseases, the diseases that statistically you and I and most of your listeners will die of is a very short list. And it's, you know, things like cardiovascular disease, Alzheimer's disease, cancer. But it.

06:45 It blew my mind to think that all of these diseases, there were common root causes that when you begin to improve one, you improve your chances with all of them. And it's something that I don't think

07:00 mainstream medicine is is still on top of it and and this message is it is not getting out there as it should well let's talk about this common root which is metabolic dysfunction what that is and then we'll get into different ways to improve that yeah absolutely the um i guess the the model that the that i one model that i've heard that i like to repeat is um

07:30 The diseases I had were, were seemingly unrelated. You know, I had arthritis, uh, and then I had high blood pressure and most people don't think of arthritis and blood pressure as being related. You know, they're clearly different. And then diabetes, that's a whole nother, that's a whole nother disease. And that's the way our mainstream medicine is. But the, the fascinating thing is that, uh, well, the metaphor, I guess, is that, um,

07:56 it, that, uh, let's say I have a problem and my problem is my floor is wet in my house. So I get a mop and I mop it up. And then another problem is the, the door is wet. There's water on the door. So I get something and I wipe the door off, but I'm treating the symptoms for, for these various conditions when they actually, the problem is not with the floor and the problem is not with the door. The problem is with the roof and there's a leak in the roof. And, and,

08:26 The roof is sort of the metaphor for the root cause. And rather than taking prescription medicines for my blood pressure, my diabetes, my gout, these other things, which…

08:40 I was told and I thought not only control the symptoms, but actually manage the disease. I thought, you know, the disease was quote under control, but actually what, what I learned is that they manage the symptoms, but frequently with many diseases, they, they block, they block the symptoms, which is not necessarily a good thing because you forget you have the disease, but the disease goes on and continues to progress and,

09:09 And that's a fundamental problem. For example,

09:13 With a heart attack. You know, if you or I happen to go into the hospital, God forbid, to have a heart attack these days, where the blood flow is limited to our heart muscle through an obstruction in the coronary artery, which is the number one cause of death statistically for all of us, we will get what's called a stent, which is a mechanical opening of the blood vessel. And

09:41 For many people, it's like, wow, I got to thank God. I got my heart attack taken care of. Done with that. I got a stent. All is good. When in actual fact, the stent only prevents me from dying on the table, perhaps. And studies have shown that stenting the blood vessel doesn't do anything to the long-term outcome of the disease. In fact…

10:06 The cardiovascular disease, what's called atherosclerosis, continues to progress in all the blood vessels and even in the stent unless I do other things. But the stent itself is just sort of a band-aid. And that's true for insulin with type 2 diabetes. It'll keep me from dying of an acute high-glucose problem, but it doesn't control the long-term complications of diabetes.

10:34 or high blood pressure. I take blood pressure medicines, my blood pressure goes down, I think I'm done, but actually the damage to the blood vessels is continuing on in the background, but

10:47 I'm just not aware of it anymore. My doctor doesn't care because my blood, not that he doesn't care, she doesn't care. It's that it's managed and the blood pressure's down. So the fundamental problem was that the approach that I was given was managing the symptoms, but to your point, didn't address the basic underlying metabolic conditions that were the root cause.

11:11 And as you explain these different areas and approaching it through symptoms, it gets me thinking about a microcosm of that, what the body does with insulin as our metabolic health degrades and it tries to manage that blood glucose by making more and more insulin and we become insulin resistant. So there's the overt taking insulin like you were talking about, but then the body also is compensating in its own way as our metabolic health degrades and

11:42 which can take, you know, 10, 20 years before full-on type 2 diabetes occurs and all kinds of damage can be done in the meantime. Yeah, absolutely. The

11:53 the whole metaphor or the whole disease of type 2 diabetes, my thinking really changed on that. I used to think that type 2 diabetes was like many diseases. As a doctor, I thought, well, you either have it or you don't. It's an on-off switch. And that's where our healthcare system is set up for billing when

12:14 your audience has probably heard about hemoglobin A1C as a marker for diabetes. And once it gets over 6.5% in the United States, you're a diabetic. And if it's below that, you're not, you know, you're, you may be pre-diabetic, but it's sort of an on off switch. But, you know, to your point,

12:32 Diseases like diabetes and Alzheimer's disease and cardiovascular disease and all these diseases are present for years, if not decades, before the doctor will actually diagnose them in us. And it's really in our best interest to begin to address them now.

12:51 in the prevention stage and not wait until the doctor says, yep, you've got Alzheimer's disease. You've got diabetes because you really had it for, for years or decades beforehand. And the other thing about type two diabetes that my thinking has changed is, um,

13:09 There's a fascinating study that just came out with adult Americans without diabetes. These are healthy adult Americans. And if you plot their hemoglobin A1C, basically this blood test for diabetes, if you plot it over time, it goes like this. The older they get, the higher the HA1C goes. And what does that mean? Well,

13:34 The way I think of it is it's like gray hair. In other words, hemoglobin A1C is going to get higher and higher, and diabetes is something that many, if not all of us, certainly many of us will get if we live long enough and don't die of something else first. So what does that mean? So

13:55 When I make choices about my lifestyle, when I make choices about my metabolic health, I want to do those choices as if I were a diabetic, a type 2 diabetic now, because I'm already on the path to it. Even if I haven't crossed the threshold where my doctor will diagnose it, I'm en route to it. Well, what I really like about your book is you get to the root root of all this with TOR or mTOR.

14:21 So let's talk about what that is. And then when it's gone awry, it's not a bad thing in and of itself. It's something that we all need. But with the current diet that Westerners are taking in, high in carbohydrates, it's

14:36 we're causing it to be triggered more often than we'd like. So let's take it all the way back to Tor, talk about what that is, and then we'll work down to metabolic dysfunction, which then leads to all these chronic diseases. So it's all connected. I love Tor. That's one of my favorite molecules. And actually, arguably, it's probably one of the most important biological switches in

15:00 that there are, yet the amazing thing is mTOR or TOR wasn't discovered until the end of the 20th century. So, but it,

15:13 We now know that it's conserved evolutionarily over billions of years. What does that mean? It's present all the way from yeast to human beings. So any molecule that's present in all those organisms has to be important at a very, very fundamental level. And TOR is a simple thing. It's a switch. It's a biological switch that detects the presence of nutrients.

15:38 and by nutrients, primarily glucose and oxygen to some extent and insulin a little bit also. And when nutrients are present, it just instructs the cell to grow. So it's like a gas pedal. You turn TOR on when it detects nutrients and the cell grows. And that's an absolutely essential thing for every cell to recognize because if you grow and there are no nutrients, you'll die.

16:07 Conversely, if there are no nutrients present, TOR turns off into the off side. And what happens then? Well, it tells the cell not to grow, but it also tells the cell to turn on something called autophagy, which is kind of repair where it gets rid of…

16:26 older damaged, uh, parts of the cell. And it's actually a good thing. It's a healthy thing. So healthy organisms have mTOR turned both on and off, both growth and repair are good. And your, what you, your point you made is that, uh, modern humans, uh,

16:48 have mTOR turned on all the time or too much being turned on. And the reason is, arguably starting 12,000 years ago in the agricultural revolution, when we first began to domesticate plants, before that, if you imagine hunter-gatherers, you know, TOR would be turned on when you, when you

17:08 you know, capture a buffalo and eat a buffalo. And then maybe it's turned off for a couple of weeks while you're hunting and then it gets turned back on. It goes off and on. But beginning 12,000 years ago with agriculture, food became more and more available. And then it just rapidly accelerated in the last 20 to 40 years with, well, before that with refrigeration and then

17:32 most recently with junk food, which makes up the majority of our food supply now is to the point where people are eating all the time. And, uh, mTOR is turned on for most of us, uh,

17:46 on the on side, which contributes to cell growth. Now, cell growth is important when we're young and our bones are growing, our brains are maturing. But there's a theory of longevity, which is gaining a lot of acceptance, is that turning mTOR on in this on state drives hyperfunction. And the hyperfunction

18:12 actually drives the chronic diseases all the ones that kill us you know cardiovascular disease is hyperfunction the the blood vessel wall proliferates and it's overgrowth cancer of course is a poster child for hyperfunction cells grow beyond control and they spread they metastasize

18:34 Alzheimer's disease. Alzheimer's disease represents the ultimate failure of our medical research establishment. I mean, if you think about it, we've had decades of time to do the research. We've had essentially unlimited financial resources. And what have we come up with? There's no single, there's no pharmacological intervention for Alzheimer's that has any effect whatsoever.

18:56 And even our understanding of what causes Alzheimer's is flawed. You know, the beta amyloid hypothesis is really falling apart now. And there's reason to believe that Alzheimer's is driven by a type of inflammation and hyperfunction, among other causes, if you follow Dale Bredesen's work and all. And certainly metabolic disease, as we'll talk about,

19:22 if we correct metabolic abnormalities with things like ketosis and all, we can actually reverse Alzheimer's disease like no drug can and cause the brain fog to go away in some patients, not all patients, but it actually improved their function. So mTOR is fascinating. And the great thing about mTOR is we can influence it by…

19:49 by our lifestyle choices. Certainly with nutrition, we can avoid foods that turn mTOR on, but also with sleep, with exercise, with stress, other things that turn mTOR on. And there's actually a drug that specifically targets mTOR, which many people are taking for off-label use for longevity.

20:13 I wouldn't recommend replacing lifestyle changes and just say, hey, here's a pill. I don't need to do anything. This is a pill that's going to turn mTOR down. That's probably not the right approach for now. Stay salty with Element's tasty electrolyte drink mix that replaces vital electrolytes without sugar and other dodgy ingredients found in conventional sports drinks.

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21:42 As a listener of the show, you get a free Element sample pack with any drink mix purchase. And to take advantage of this deal, go to ultimatehealthpodcast.com slash element. That's ultimatehealthpodcast.com slash element. Element is spelled L-M-N-T. Pick up some Element electrolytes today and stay salty. Was I correct in saying that mTOR would be the root of chronic disease though? And then

22:09 it being triggered too much would lead to metabolic dysfunction and then chronic diseases like Alzheimer's and cancer. Do I have that right? Yeah. I mean, mTOR is a major metabolic switch in a network of switches like AMP kinase and other things. But mTOR arguably is one of the most important ones.

22:30 When we turn mTOR on and nutrients are possible, I mean, if you think about it, when nutrients are possible, food is coming into the cell, foreign matter is coming into the cell. So what else does mTOR do when nutrients are present and it tells the cell to grow?

22:49 it protects itself so it turns on inflammation. So when mTORs turn on, it's also an inflammation switch. And inflammation, as we'll see, is at a root cause one of the drivers that metabolic disease drives and vice versa that causes all these chronic diseases. So to your point,

23:13 We can do some interesting experiments with mTOR because there's this drug that's a very specific drug that targets mTOR that will turn mTOR off into this healthier repair state, this autophagy state. And so you might think, well, if mTOR is so fundamental in aging and longevity, what evidence do you have for it working in anything at all? So…

23:42 there's some interesting experiments. If you, if you look at, let's say aging, the phenotypes of aging, right. Um, I'm a poster for it, right. Wrinkles, gray hair, receding hair, you know, uh,

23:55 periodontal disease, hearing loss, all these things are phenotypes of aging. We all recognize them. So the drug that is available is called rapamycin. It was discovered on Rapa Nui in the soil from a bacteria in the 1960s. And because of its discovery,

24:17 they needed to understand what rapamycin worked on. And they, they found out this molecule, they named it TOR, which is sort of lack of a better name, target of rapamycin. So, so, so let, let's do, we can do some simple experiments. Well,

24:36 In mice that, in the mouse model for hair loss and gray hair with aging, you give rapamycin to these mice and the hair starts to grow back and the coloration returns. It's less gray than before. What about wrinkles? In humans, in a prospective trial, rubbing rapamycin on a double-blinded prospective rapamycin cream on the skin is

24:59 Once a day for six months, these humans then underwent punch biopsies of both hands. And the rapamycin-treated hand showed return of the collagen basal layers. And they were visibly younger-looking skin with the rapamycin being applied to that. And interestingly, the FDA has just approved rapamycin cream about 12 months ago, not for aging or wrinkles, but for other conditions.

25:28 cancer type diseases, but it's now being used off-label for that. But the list goes on and on. You apply rapamycin to animals with hearing loss, with age-related hearing loss, and the hair cells regrow in the cochlea and some of the hearing improves. You add rapamycin to…

25:51 There's one disease of aging that most people don't think of as a disease of aging, but it affects 50% of our population 100% of the time if they live long enough. And that, of course, is ovarian failure or menopause. So if this miracle mTOR affects something fundamental about aging and longevity, it should affect menopause too.

26:14 So when they give rapamycin to the rats or mice to the mouse model, they actually, it increases their litter size. They become more fertile and say, well,

26:25 they have a longer fertile window in other words it delays menopause so for all these all these uh applications that are now human trials in place for you know i quoted a lot of animal studies but they're beginning to look at humans things so this is this is fascinating i mean these things all have different mechanisms if you think about it for aging but rapamycin somehow gets to a basic root cause but you may say well wait a minute

26:54 Nobody dies of baldness. Nobody dies of menopause. Nobody dies of gray hair. This doesn't really affect longevity. It sure may make us look younger, may make our skin better, but

27:06 What happens if mTOR is so fundamental to our longevity? What happens when we apply mTOR to these diseases of aging that actually kill us? Like I said, it's a short list. Number one is cardiovascular disease, heart attacks and strokes. Number two is cancer. Number three is Alzheimer's. Okay. What happens with mTOR when we turn it down in those? Well, actually…

27:34 We talked about stents before, the mechanical things that are put in blood vessels when most people get heart attacks. Now they get these stents. The problem with the stents, as we alluded to, is the disease continues and the other blood vessels continue to clot down. And the stents actually re-clot off with atheromas over time.

27:57 So, um, what does turning down mTOR do? Well, actually there's now an FDA approved indication. If you coat the stents with rapamycin, she was dramatically slow or even stop the atherosclerosis from occurring. So it's FDA approved to stop atherosclerosis and there are studies underway. We're now taking oral rapamycin may slow down, uh,

28:24 uh atherosclerotic disease in in all of us okay that's that's okay great it works for that what about cancer cancer is a completely different disease completely different organ you know different organization different mechanism actually if you if you let's look at a human model for cancer um

28:47 The is transplants, you know, with the most common cause of death. I didn't know this, but when I first started looking at this, the most common cause of death in a transplant patient, let's say heart transplants within the first five years of getting a new transplant is now.

29:04 No, I don't know. I thought it was organ rejection or something, because that's what you're worried about when you transplant something in. You think, yeah. Yeah, you give immunosuppressive drugs. It's actually cancer, because the immunosuppressive drugs lower the immune system, and people get more higher rates of cancer. Makes sense now that you say it. Yeah. As it turns out, rapamycin, in fact, its first FDA-approved indication, is for…

29:33 helping with organ rejection. So there's a large population of patients who routinely get rapamycin for organ rejection. And then there's another group also who have transplants who may get something else that also works, but just isn't rapamycin. But what they found in this study was that

29:54 in this population whose human population is predisposed to getting huge amounts of cancer when they're given rapamycin, the cancer rates drop by 50%. And, uh,

30:06 And now to the point where there are at least eight FDA-approved indications for rapamycin for treatment for cancer, things like metastatic renal cell cancer, which is the most common type of kidney cancer, and other types as well. So it's like, so, whoa, something's going on here at a fundamental level. The last one is Alzheimer's disease, right? What evidence do we have that mTOR is involved in Alzheimer's disease? Well,

30:35 There's an animal model for Alzheimer's disease that in the mouse, it's called the mouse hammer mouse hammer model where they actually get cognitive impairment. They they forget their keys, whatever the mouse equivalent is, and they they have progression dementia and everything.

30:53 So when these mice are given rapamycin versus placebo, it actually reverses their mental fog and their mental acuity returns back towards normal. To the point now, the University of Texas is having a trial go under.

31:12 underway with rapamycin as a treatment for Alzheimer's disease. It's a multimillion-dollar study that's underway. But if you think about it, we talked about ketogenic therapies and all. Ketosis is really a way of turning that mTOR switch back to the repair mode because the nutrients it senses is glucose. And when you're in ketosis or on a ketogenic diet, your body is burning, you know,

31:40 and ketones-type substances rather than glucose. So your glucose levels are very low, and your mTOR tends to turn back like that. But it's amazing. mTOR seems to play a role in these chronic diseases. And then the last question is,

32:00 Well, is there any evidence that, fine, you can reverse the appearances of aging, you know, you could reverse or slow the chronic diseases that determine my and your longevity. Is there any evidence to show giving rapamycin improves longevity itself, you know, in humans? Yeah.

32:22 And the answer is there's no direct evidence because it's very hard to do longevity studies in humans. Humans live 70 years, very soon 100 years. But the point is it's hard to do longevity studies. But there is a gold standard longevity study that you may have talked about with your audience before that's run by the federal government. They use mice. It's called the Interventions Testing Program or the ITP.

32:49 And mice are great because they only live three years. So you can do a longevity study and know the results in three years. And the great thing about this longevity study, the ITP, is you and I as citizens can write in and suggest drugs to test it.

33:06 And what they do is they just take these mice that are, they're not lab mice, they're actually wild-type mice with genetically diverse appearance. They're in three different labs around the country, so it's not even one lab. And then they give them

33:19 half the mice just get raised normally. They live their lives and die. The other half get whatever the intervention is, typically the drug or substance. And then at the end, they look at the lifespan of the mice. And is there a difference between the intervention and the regular mice? And is there an improvement? Is there a longevity effect? And because we get to suggest everything,

33:43 This has been around for 20 years. There have been some amazing thing tests that green tea, curcumin, NAD supplements, CoQ10, statins, all kinds of stuff that people wonder about for longevity. And the interesting thing is most of these had no effect at

34:06 And, um, they're only, they're only a handful of things that have an effect. And by far the most powerful, most significant fact that knocks it out of the park is rapamycin. And one last nuance to it, the, when they did the rapamycin study, typically they give the drugs for the whole life of the mouse, which is not really realistic for you and I, because, um,

34:32 you know, we're, we're older and we're not, we don't get a chance to start it from birth anymore. And we may not want to, you know, we don't know that that's a good idea, but for this, the last, uh, for the rapamycin trial, they messed up on making the food and they, um,

34:50 They wound up, they couldn't get the supplements right. So the mouse, the mice didn't start the rapamycin until they were the equivalent of 60 to 70 years old in human years. And even starting at that late age, they saw this dramatic longevity benefit. Wow. So we've talked about a ton of positives. Any negatives?

35:16 Yeah, well, rapamycin, it's one thing, just to be clear, the very first use of rapamycin and the groundbreaking use for which it got FDA approval in 1999 was for immune suppression for renal cell transplants and other organ transplants. So immune suppression is a good thing if you have a transplanted organ from a foreign donor in your body.

35:44 It's kind of a bad thing for you and I to suppress your immune system because immune system is important for all sorts of things. And most doctors, if you go to your private doctor and say, hey, I'm thinking about taking rapamycin for longevity, they'll go, whoa, whoa, whoa, no, no, no. You don't want to take that. That's an immunosuppressant. And so there's a lot of misunderstanding about rapamycin. To be clear,

36:11 When humans take rapamycin, and it's FDA approved for a number of indications, but it's not approved for longevity just because longevity is not an FDA indication or it's not considered a disease or aging. When people take rapamycin for longevity, they typically do it instead of the daily dose, which is the renal transplant immune suppression dose, they do it once a week.

36:34 And that once a week, the half-life of rapamycin is short enough, 48 hours, that it's gone in a couple days or at least significantly decreased. So there's that misunderstanding about rapamycin. So there's a lot of uncertainty with physicians. But what about safety, safety profile? That's a key point, right?

36:58 rapamycin is actually very safe drug it um there aren't a lot of contraindications for it someone there's a report in the literature someone tried to commit suicide with rapamycin with over 10 times the recommended dose in one in one shot they went into the er and basically nothing happened you know um so the the

37:23 The toxicity profile is very good. The side effects of rapamycin are…

37:30 people, the one thing some people note are mouth ulcers, little like cold sores or aphthous ulcer. A small percentage of patients get these. They're reversible. They go away and they usually stop. But other than that, the biggest thing about rapamycin is we really don't understand it. We're just at the beginning of all these things. And

37:55 It's a little bit of the Wild West. Even the dosage that people take, it's almost arbitrary. The dosage that we take, there's not a lot of data. It's still coming in. So it's kind of a leap of faith.

38:12 to take these drugs. I think the message that I try and communicate, and I certainly practice it myself, is that rapamycin is powerful. It does work on mTOR, but something even more powerful is our lifestyle. And I would never take rapamycin before I did all the lifestyle stuff first, because why is that? Rapamycin works, right? The ITP

38:42 Done. Deal. Why not just take it? Well, some interesting results came out in the last literally 24 months. The ITP took another drug called a carbose, which has a small lifespan benefit. Uh,

38:57 And when they combined, well, actually, there's another drug called metformin, which people also take for longevity. Metformin had no effect on the ITP. That doesn't mean it doesn't work at all for longevity. Nobody knows. But at the dose it was given, if something fails the ITP, it just means that that dose, it didn't work.

39:17 It's like if you take an antibiotic, if you take too low a dose, it won't work, but that doesn't mean it doesn't work theoretically. So metformin failed the ITP, but when they combined metformin with rapamycin, they got an even greater effect than rapamycin alone. So there's some synergy with AMP kinase that metformin affects with rapamycin, but it's

39:42 My point was about 12 months ago, they published a paper where they combined A-carbose with rapamycin. A-carbose has a small benefit in the ITP. Rapamycin has a huge benefit. When they combined the two of them, they got a greater benefit than either one of them separately. So there's some kind of synergy that we just don't understand. So rapamycin may be a great idea for longevity, but…

40:10 If you want to cover your bets, I would do longevity. I fix my diet, my sleep, my exercise, stress, all those other things as well, because otherwise you're leaving a lot on the table and you can miss out. And rapamycin or whatever longevity stack you use will…

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41:42 We know mTOR, again, isn't bad or good. It's just regulating how often it's activated. So what kind of effect does the drug have on mTOR specifically? Yeah, that's a great question. Unfortunately, nobody knows. You know, we don't have good, they're not good molecular markers in a clinical sense for mTOR, you know, M2A1.

42:04 If I, if I, you know, do NAD supplementation, for example, I can, I could check, you know, with, if I do NMN or, you know, NMR, I can, um,

42:16 I can, I can check my NAD levels with mTOR. You really, there aren't easy clinically accessible indicators of that. We know from, we know from the science that it's, you know, that it's affecting mTOR and these downstream effects, but there aren't easy indicators. So,

42:33 when I take my daily dose of mTOR or my daily dose of my weekly dose of rapamycin, people say, well, how do you feel? I say, I feel great, but I'm also fasting. I've exercised, I'm doing all sorts of other things. So it's hard to tell what the actual effect is. And

42:52 And it's not like I stop it and I feel bad or I take too much and I get side effects. It's really a black box. And that's the challenge with this particular longevity drug. It's both good and bad, but it's something that we'd like to, you know, hopefully in the future we'll know much more about it and get better indicators that we can follow that it's working and figure out even what the right dose is, you know. Yeah.

43:21 So you're taking it on a weekly basis. How long have you been doing that for? I think I'm going on three years now. Well, let's get into diet specifics. Talk about what we can eat specifically to downregulate the mTOR and when we're eating. And you've mentioned ketosis, but let's get into how all that works in physiology. Sure. Yeah. I mean, before we get into diets with nutrition, I mean,

43:52 There's one thing people can do that I talk about in the book. Even if you don't want to change what you eat, you say, forget it, I'm not into diets. Is there anything else I can do with my eating? And actually, the answer is yes. Just by changing when you eat, you can improve your metabolic state and turn down mTOR and do different things like that. And that is to…

44:19 eliminate snacking. I mean, I, my mom was a dietician, so I was raised on the misguided idea that, you know, you eat many small meals throughout the day and all that. So, um, instead what I recommend is, you know, start off when you get done with dinner, what I did, I brushed my teeth immediately because I'm basically lazy and I knew if I snacked again, I'd have to brush my teeth again. So I just do it that way.

44:45 And then eliminate snacks between meals. And if you're feeling really… If you really want to do something, you can eliminate breakfast. Skip breakfast if that works for you or even skip lunch. That's what I do. And I have one meal a day with my kids when they get home. And I'm basically fasting most of the other time. I drink… I have coffee or

45:08 or water, but no calories during those times. So that's the first thing you can do. Eat, you know, just eat a certain, narrow your eating window because when you're not eating, nutrients are not coming in, inflammation is going to be turned down just because, I mean, if you think about it, a lot of things affect inflammation. We talked about mTOR, but even eating itself, you know, if I put food into my mouth and it goes into my stomach and my GI tract,

45:36 No matter what the food is, it's going to drive inflammation because inflammation is the body's natural protection against foreign material. And food is foreign material going in. So every time I eat, I'm turning on inflammation. You know, if I eat all the time or all the time I'm awake,

45:52 inflammation will be turned on all the time. So even narrowing the eating window is a way of turning down inflammation. And depending on how long that window is, you may even get into ketosis and a favorable metabolic state there. So that's the first thing. Second thing you could do without changing what you eat that's going to help your nutrition that helped me was to think about macronutrients. You know,

46:17 Your audience, I'm sure, knows that proteins and fats are the two essential macronutrients. We need to have those. We'll die if we don't have them. The third macronutrient, of course, carbohydrates, we don't need. It's non-essential. And there are several human civilizations that exist without significant amounts of carbohydrates at all in their diet. And as it turns out, carbohydrates are the things that

46:42 drive insulin more than the others. They turn on mTOR more than the others. And even if you want evidence of how potentially problematic carbohydrates can be in our diet, that drug, that I mentioned that potentiates the effect of rapamycin in the longevity ITP program

47:07 The way a carbose works, it's really interesting. It's an FDA approved drug, but it's for diabetes. It's for type two diabetics and type one diabetics as well, I think. But it's not absorbed really significantly in the body. And the only way a carbose works is in our guts and it blocks the absorption of carbohydrates. So it slows carbohydrate absorption. And

47:32 at least in the animal model, taking a carbose, slowing carbohydrate absorption produces a longevity benefit. So you can do the same thing or get a similar effect. In other words, slow carbohydrate absorption. If you, if you think of carbs as, as the enemy or, you know, what you want to avoid, but I have a meal here in front of me with a bunch of pasta and maybe some cheese and something else I can, I,

48:00 I know that rather than eating the carbohydrates first, which will, on an empty stomach, spike my glucose and have rapid absorption, I can get a similar acarbose effect by eating fat first. Maybe having the cheese beforehand or the olive oil with a salad, and that will coat the lining of my gut.

48:21 maybe some protein as well, and save the carbs for the end. And that will delay the absorption of the carbs and the harmful effect of the glucose spikes will be mediated. So those are two things you can do nutrition-wise before you even touch what you eat. All right. So cutting down on snacking, narrowing the eating window, and then eating fats before carbohydrates. Yeah, fats and proteins. Either one will block it.

48:51 So then becomes the what to eat. And that's an interesting thing. Well, let me say first that I have no dog in the diet game. I love my vegan friends. I love my carnivore friends. In fact, I was a vegan for like 10 years at one point. I've been a carnivore for a while. I think…

49:17 I personally, I think we can all be healthy or unhealthy on a vegan diet or all the way to a carnivore diet. It's just the choices we make in between. And there are pitfalls with each of those diets. I think there are a lot more pitfalls with a vegan diet. There's a lot more vegan junk food than there is carnivore junk food, but it's present in each one. But so, yeah.

49:42 I, I, you know, welcome. You can, you don't have to switch your type of diet. It's just the, the food you eat within that diet. So, um, the main thing I avoid is junk food. And I have to say, um,

49:59 full disclosure, I'm a recovering junk food addict. I love junk food. I can't keep it in the house. I've got a teenager and a younger daughter and they are continually trying me. But I find just like an alcoholic, I don't keep liquor at my desk. I don't keep it in the house. Same thing with junk food. So everybody agrees junk food's bad. The question is,

50:24 How do you define junk food? And that's a problem because you have organizations like the American Heart Association saying that vegetable oil is heart healthy. I don't agree with that. I think it's not heart healthy. So the key thing is defining how you define junk food. So for me, there are three things that I look out for. In general, just in generalities, junk food…

50:54 Some things that we'll let you know that something's junk food, it typically comes in a box. It's frequently brightly colored to attract children. It has a long ingredient list. But specifically, the things that I do are, first of all, carbohydrates. Because of the things we talked about with insulin stimulation,

51:23 I try to keep carbohydrates to a minimum, especially refined carbohydrates and sugars. So I have to watch out with fruits. You know, modern fruits are very rich in sugars, unlike the fruits that our ancestors ate, you know, 10,000 years ago. Also things like starches.

51:43 My wife's Chinese, so she grew up on rice. That's part of her cultural legacy. So rice is out. Any of the starches that break down into glucose. So first thing is just to eliminate carbohydrates as much as possible in my diet. Once I've done that, the second thing I also watch out for is something called industrial oils or products.

52:10 ultra-processed oils or seed oils. They have a healthy sounding name called vegetable oils, but they don't contain vegetables. And in my opinion, they're not healthy at all because they drive inflammation and make all the diseases we're talking about worse.

52:26 Um, so these are, I'm sure you've talked about them on your program, but these, these oils, the problem is more, I began looking at it. These oils are in nearly every single, uh, solid dressing that's available there in, um,

52:43 they're in mayonnaise, they're in hummus, they're in, they're in all the junk foods. Why are they in the junk foods? Because they're relatively stable and they, um, they don't degrade over time. They're very cheap. So you can replace more expensive butter that, that, that turns rancid with these seed oils and, um, and, and the food lasts longer. So seed oils is the second thing. And, um,

53:09 Yeah, so it's basically carbohydrates and seed oils. And the last thing is sort of counterintuitive, and I certainly wasn't expecting it at all, was grains, even whole grains. And why is that? I don't have celiac disease, which is a disease that some people have that's gluten intolerant. But I believe, like many experts do, that…

53:40 Much of the adult population are allergic to proteins in grains, if not gluten itself, but other proteins. And this allergy drives a low-grade inflammation that we may not even be aware of. It may manifest as irritable bowel disease. It may manifest as anger or depression. It may manifest as brain fog. It may manifest as anxiety.

54:04 exacerbating any of the diseases. So for that reason, I don't eat grains. Also in the United States, grains are soaked, most of them in a weed killer called glyphosate, which, you know, at least 34 countries around the world have banned for health reasons, but we still, our grains are soaked in it. And then the last thing is grains are

54:28 uh most grains have a large amount of carbohydrates so that they're ruled out for that reason so when i avoid those three things i'm pretty much on the path to uh to healthy eating and and it turns down

54:43 It helps me with my fasting because people say, how can you go and only eat one meal a day? You know, what kind of iron willpower do you have? Well, I don't have iron willpower, but when people go into ketosis, their, you know, their appetite decreases and it controls your appetite and allows you to go longer periods without craving food.

55:07 And do you test for ketosis? Because the way you eat one meal a day, controlling carbs, I'm curious if you're going in and out of it or just staying in ketosis. Yeah, the urinary tests are not that great. You can test your blood pressure.

55:25 blood urine for markers. Uh, but that's not good. That's not, not that useful for ketosis that I found. You can do a blood test, you know, stick your finger, but I hate sticking my finger. So, um, I had a breath meter, uh, from one company that you blow into and it, um, detects that. And I check it for a while and, you know, I'm reliably in ketosis and, um,

55:49 So the short answer is no, I don't check it. I don't check it routinely every day because I'm pretty much doing everything I could to be in ketosis. And there's not, you know, there's not much more I could do. I can't push the accelerator down much more. But that is the goal though, to be in ketosis 24 seven. For me, for me, it is. And, um, you know, it's not for everybody. Everybody has different things, but

56:15 The amazing thing is we're finding that this metabolic state, which an indicator is being in some form of ketosis, is it basically reverses seizures. We know that. That's the oldest application for a ketogenic diet is stopping seizures, and it's still being used today. Yeah.

56:42 Putting people in ketosis will reverse mental illness. Not everyone, not all mental illness, but as Chris Palmer and Georgia Ede have shown, some patients with psychiatric psychosis, manic repression, to the point where they're hospitalized on medications and they no longer have a job and they can't be with their family. When Chris Palmer put these patients on, some of the patients on a ketogenic diet, they…

57:11 Many of them are now going home and some of them off all medications. Uh,

57:17 uh i and and there are now independent studies one just came out at stanford doing doing just that so something about ketosis helping in all i mean helping in in mental health and and i asked chris a chris palmer he's a psychiatrist at harvard medical school mclean hospital who's written a book about about ketogenic diets for psychiatric conditions i said chris it

57:43 It's great, but how do you know it really works? Give me an anecdote. And he says, well, one of my patients, Bill, he was in the hospital with psychosis, schizophrenia. And the hallmark of schizophrenia, your patients may know, is we hear voices. Voices talk to us. A schizophrenic patient will frequently have those. So when Bill went on this diet, Chris was able to stop all his medications and

58:11 and literally send him home. And he's back with his family. He now has a job. And it doesn't work that way with all patients, but even any patients. And there's a significant portion where it does. So Chris said, he goes, yeah, Bill knows that he says he knows that when he slips, it has a piece of junk food and he starts going out of ketosis and

58:37 he knows he's out of ketosis because suddenly the voices will start talking to him again. And as soon as he goes back into ketosis, the voices stop. So it's something about this metabolic health, which ketosis is one path to it. But for Alzheimer's disease, you know, people drink exogenous ketones like MCT oils, um,

59:00 or even going into ketosis can, for some patients, again, not all patients, have dramatic effects on Alzheimer's disease, which is really untreatable. There's Heather Sandison, who you may have had on your program. She's a physician, runs a group of nursing homes around the country that specialize in Alzheimer's disease. She's a protege of Dale Bredesen, who's written expensively on it. But

59:28 Her nursing homes are unlike any other nursing homes that I'm aware of for Alzheimer's disease because the patients actually go there and they get better and then they go home. Most patients, sadly, I mean, my mom just died of Alzheimer's disease. Most patients with Alzheimer's disease, it's a one-way street. You go in and you get worse and worse and worse and you eventually die.

59:49 Well, I talked to Heather about, you know, what's her secret in these nursing homes, you know, and she does a number of different things, a big program. But one foundation is…

01:00:01 The only type of food they serve in the nursing home is a ketogenic diet. So it's high in fats, healthy fats and meat and eggs and things like that. And they avoid the foods that I just mentioned that I avoid there. So I said the same question to Heather. I go, oh, that's great. You do the ketogenic diet, but how do you know it works? Do you have any evidence for it? And she said, well, yeah.

01:00:27 There's Mr. Jones. I know that the ketogenic diet is working for him because when he's in ketosis and his grandchildren come in to see him, he smiles and hugs them and remembers all their names. But when he goes out of ketosis, the same thing happens. They come in the room and he doesn't recognize them and there's no… Nothing happens there. So…

01:00:52 The point is there's something about this ketogenic diet that affects not only mental health and Alzheimer's disease, blood pressure we've talked about. There's evidence that ketogenic diet is now being used in certain types of cancer for adjunctive treatments for cancer. There's evidence that the ketogenic diet…

01:01:15 also affects cardiovascular disease. And as we talked about with mTOR, mTOR and rapamycin is one method to being metabolically healthy. And

01:01:26 And ketosis, you know, if a ketogenic diet is for you, it's another path to get there or even something to do in addition to your rapamycin or whatever you're doing. So these all are working at some basic, primitive, primal mechanisms that help our health and longevity. It's just fascinating, I think. You talked about MCT oil there.

01:01:51 Do you personally use MCT oil or exogenous ketones to bring you… I guess you're always in ketosis, but do you use them as an adjunct or do you recommend them to people? Yeah, it's a great question. There's a lot of good work being done on MCT oils. Dom D'Agostino, our friend, is working on those and all. And…

01:02:16 They famously have some dramatic results with Alzheimer's disease. Literally, this woman, she was a physician. Her husband had Alzheimer's disease, severe mental problems. She started feeding him MCT oils and other exogenous ketones and was able to reverse this disease and bring him back healthy.

01:02:37 essentially, significantly. And the only reason she thought of it, because she was a neonatologist, essentially, where they were familiar with MCT oils and certain applications there. So yeah, it works there. I was just with Chris Palmer at a conference a few weeks ago, and someone from the audience asked Chris, so what about exogenous ketones for psychiatric conditions? And Chris said that

01:03:07 at least in his experience, and he's not aware of any case reports, that while they do work in Alzheimer's disease and other things for these mental health conditions, he's not aware of exogenous ketones doing that. So it may be something, some benefit you get from nutritional ketosis versus exogenous ketones. It just shows…

01:03:30 uh, show my shows, how much we, we have to learn by this whole thing, but it's, it's just fascinating. All the, all the possibilities out there. And I mean, the one thing from, from Chris's work and, and, uh, is that all of us, um,

01:03:47 You know, it's great for mental health, right? But most of us, most of your audience, me and you, are probably not going to be diagnosed with a clinical mental illness in our lifetime, statistically. But on the other hand, we're all human, right? We all go through ups and downs with our wives, our spouses, our children, our co-workers, our friends, our employees, our bosses, etc.

01:04:14 We all get angry. We all get anxiety. We all get stress. And you can't help but wondering,

01:04:22 What possible benefit improving our metabolism through, you know, one of these approaches with mTOR or ketogenic diets could have just on society in general, the way, you know, we get together. I mean, famously political organizations now, you know, the Republicans don't talk to the Democrats and vice versa, you know, when 30 years ago,

01:04:45 It wasn't that way at all. The world is changing in subtle ways about the way people get together. And junk food has amplified in the last 30 years and driving all these things. I wonder if it's driving the way people get along with each other. You can't help but wonder that question.

01:05:04 So when it comes to your diet, there's three different pieces, the seed oils, the no grains and lowering of carbs for you, ketosis. You take that down to that level for somebody that wants to use these guide rails. Two of them are black and white, but the low carb piece is a bit gray, depending on if they want to go all the way down to ketosis or not.

01:05:27 For the average person, would you say that's the goal to get to ketosis or just to lower the carbs and then expand upon that things like fruit and vegetables?

01:05:39 It sounds like you're not having any fruit, but for people that are more metabolically healthy, is that okay? How do you look at that whole gray area within the carb realm? Yeah, I do have fruit once in a while, but I'm aware that it has high fructose and there are downsides to that. There's a whole discussion around that. But I think

01:06:02 The goal necessarily isn't ketosis for everybody. It's not for everybody. But to be clear, there are people who are in ketosis their entire lives. I was just talking to a patient of mine whose daughter has had epilepsy since birth, and none of the medications worked. None of the surgical options were possible.

01:06:27 And she's now, she's been on a ketogenic diet her entire life. And that's the way she stops her seizures. So it is, you know, it's possible to be on this, but, but anyway, I think the goal is to be metabolically healthy. How we get there are different ways. And if you want to be in ketosis, I like, I like fasting. I, I have a clear, my brain fog goes away. I feel better. I,

01:06:53 Now that I did when I was snacking all day long and, you know, having a big lunch and then falling asleep in meetings and stuff like that. So it's just, you know, you have to you have to look at yourself. But I think the goal is in ketosis and ketosis isn't for everybody, but you can.

01:07:10 use the ideas from it by cutting back your different things. And of the three things I do, it's interesting. I think it's important to note that they all have a different time scale as far as the effects. And so if you cut out sugars and cut out carbohydrates, you can see the effect in 24 to 48 hours. There will be an effect on your body. You'll begin noticing things.

01:07:35 Cutting out grains, though, you have to wait longer because the effect on the immune system and all typically you kind of wait about three months. So, you know, I have people who go, hey, I cut out all grains for a month and nothing happened. So, you know, doesn't work for me. But you need to wait longer for that.

01:07:57 And the bad news is with seed oils, it can be the half-life of seed oils because they're stored in our fat could be even years. So it could be a long time before you see the results of those. But in my opinion, seed oils are really the only reason people put seed oils in food is

01:08:19 is for convenience and cost in some cases, but there's no taste advantage of sea dulse. Nobody says, I like canola, I want some Crisco, I want some vegetable oil. So that should be an easy substitute. If you're willing to make the effort to exclude those from your diet, you can do that.

01:08:40 Things like carbohydrates, though, are different. There's a, you know, there's tastes that are activated, you know, sugar that's activated, grains the same way, baked goods. I love baked goods. You know, there's nothing I'd rather have than, you know, bagels and baked goods. The only thing, there's only one thing I love more than baked goods, and

01:09:01 And that's my children. And I want to live to see them. And I want to live to see my grandchildren. So you could make those, you know, we all get to make those choices ourselves. So, but, but it's all a matter of degree. And I'm just, I'm trying to illustrate maybe an extreme case with me. Everybody doesn't have to be as extreme as I am, you know, but you can, you could take

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01:10:36 fatty liver. So let's talk about that connection there and the physiology that happens in the body when we're consuming too much of that. Yeah, our understanding of fructose has dramatically changed in the last few years. It's

01:10:54 Fructose, as your audience may know, it's one of the primary sugar molecules. Glucose and fructose, when you combine them together, make sugar, table sugar, sucrose.

01:11:08 um for many years fructose was was felt to be the good sugar in other words unlike unlike glucose if i eat glucose and uh you know have my rice or my carbs my my insulin will spike and um my glucose will spike in my bloodstream if i eat pure fructose

01:11:33 which happens to be a sweeter molecule than glucose, so it actually tastes sweet. If I eat pure fructose, my insulin doesn't spike and my glucose doesn't spike, to the point that the American Diabetic Association, which is not an organization to be trusted for all sorts of reasons…

01:11:52 We can get into later if we want. But they used to recommend that diabetics substitute fructose for glucose and just eat fructose because, hey, it doesn't affect your insulin. It doesn't affect your glucose. It's a safe alternative, and it tastes sweet. The problem is fructose is exactly the same thing.

01:12:21 chemicals in fructose, carbon, hydrogen, and oxygen, but they're just, as in glucose, but they're just rearranged slightly. So they're very similar that way, but they're handled completely differently by the body. Every single cell practically in the body can utilize glucose for energy. Fructose, no cells in the body use it except in the liver where it's essentially detoxified for most of the fructose in our body. So

01:12:50 The liver is the detoxification organ. That's where alcohol goes. When we drink alcohol, it goes to the liver and it gets detoxified there. And it used to be up until 1980 that when people damage their liver, they get what's called fatty liver disease. And the number one cause, if you had fatty liver disease, you were most likely to have

01:13:16 be an alcoholic or have alcoholic liver disease. That's what it was called, alcoholic fatty liver disease. And something strange happened. A new disease appeared in 1980 that had never occurred before. And to the point, it's now the number one liver disease, the number one cause of liver transplants, but it didn't exist before 1980, largely.

01:13:38 And it looks just like alcoholic fatty liver disease to the point that patients would come in, they'd be diagnosed with these damage to their liver and the doctor would go, Oh, you've got alcoholic fatty liver disease. You need to quit drinking. And the patient would go, I don't drink. I've never drank. And the doctor would say, sure, but just stop it. And, um,

01:14:02 That created some tension there in the doctor-patient relationship until children started coming in with this fatty liver disease. And they were said, well, you've got alcoholic fatty liver disease. This is a six-year-old child. They've never had alcohol. How can they have fatty liver disease? And anyway, what they discovered was that fructose,

01:14:24 When it's metabolized, detoxified by the liver, which is the main place it goes, it's handled the same way or in a very similar fashion to ethanol, alcohol, and it produces fat and it damages the liver eventually and drives this fatty liver disease. So…

01:14:44 What happened in 1980 so that heavy liver disease is now caused by fructose and not alcohol? Because if you look at the drinking rates for alcohol, it hasn't changed that much. It's pretty much the same. But something happened with the discovery of a compound called high fructose corn syrup.

01:15:04 which is a, it's just a way of extracting something from corn that's made of fructose and glucose. It's similar to table sugar, but it doesn't have that

01:15:15 chemical bond there, but it doesn't really matter. But the thing was high fructose corn syrup became widely available and it was placed in all junk foods and it replaced the alternative, which was cane sugar. Cane sugar is sort of crunchy and it crystallizes and doesn't, you know, doesn't have a good taste.

01:15:35 High fructose corn syrup stays fluid. You can put it on the shelf for 12 years like all good junk food. It'll last forever. And the other thing about it is it's subsidized by the government. Corn is one of the crops that is artificially lower in cost. So high fructose corn syrup is low in cost. So what happened?

01:15:55 Everybody switched out cane sugar for high fructose corn syrup and Coca-Cola, Pepsi, all the soda companies switched out high fructose corn syrup and junk food just exploded. And this non-alcoholic fatty liver disease exploded to the point that now when someone comes in with a fatty liver, you don't ask them if they drank alcohol. But the problem is

01:16:22 Most of the medical establishment still considers it to be of unknown cause. It's vaguely related to metabolism. Even today, you hear that. Although experts like Robert Lustig at the University of San Francisco did a prospective controlled study of

01:16:41 with children and he basically substituted he removed fructose from their diet and substituted glucose and in a matter of weeks he was able to reverse the fatty liver disease in these children just by removing the fructose so there's there's tremendous evidence in my opinion it's caused by fructose and if you want to

01:17:04 This is shown throughout history because fatty liver didn't start out as a disease. It started out as a culinary item with foie gras, you know.

01:17:18 which has been around at least since the Egyptian times where an Egyptians learned to give geese fatty liver. And if they wanted to do that, they didn't give them alcohol. They didn't give them sugar or glucose, but they gave them things that had a large amount of fructose, um,

01:17:36 figs in particular and and the same thing that's true today too you uh you don't you don't feed them protein you don't feed them fat you feed them high carbs especially fructose

01:17:49 So anyway, that's a rambling conversation about fatty liver disease. And I think the lie is that we don't know what causes fatty liver disease. And I think the evidence is overwhelming. And I've cited it in my book. These aren't my ideas. All I'm doing is reading the literature as I interpret it.

01:18:10 But it's due in the vast majority of cases to fructose toxicity. And I think we all need to be concerned about fructose, even if we don't have fatty liver disease, that it's something to at least be cautious of. And one last point about fatty liver disease. It was usually only diagnosed when the liver enzymes, the liver blood markers got very high.

01:18:36 With CT scanning, it's possible to make the diagnosis on an X-ray image. And one interesting study where they scanned adult patients coming in for colonoscopy, which is unrelated to fatty liver disease, they just looked at all their livers and they found upwards of 50% of them had fatty liver disease, but they weren't diagnosed.

01:19:01 And then they looked at the radiology reports that the radiologists, uh, dictated. And, um,

01:19:08 Only 10% were dictated of those as fatty liver disease. And then they looked at the follow-up of the radiology reports, and less than half of those had any follow-up from the referring physician. So it's not on people's radar, yet it's a marker for insulin resistance. It's a marker for inflammatory disease. It's a marker for metabolic health. All these things get tied together.

01:19:34 And the good news is, like you talked about Dr. Lustig's research, if it's caught early enough, it's reversible. That's right. And in all of us, hopefully, yeah, we can do that. And I mentioned it doesn't spike glucose, right? And it doesn't directly spike insulin. So you think, well, what's bad about it? Well, it drives insulin resistance in the liver. So even though

01:19:59 The acute changes are not spiked. Fructose in itself will drive insulin resistance. Fructose also converts to uric acid, which is a driver for gout. And it also drives…

01:20:16 The endothelial glycocalyx, which is the lining of our blood vessels, which drives hypertension and cardiovascular disease, it affects nitric oxide production, which controls those. So the sugar we eat can actually drive hypertension and cardiovascular disease through these mechanisms. One of the things that typically happens when somebody adopts a lower carb diet, ketogenic diet, is

01:20:46 is they're going to have less plants in the diet, less fiber. And that would be one of the common arguments against going low carb because we need to eat a lot of plants and get our fiber in, get our diversity of different plants. How do you look at fiber? Is that something you're concerned about with the way you eat? And how do you feel about in general?

01:21:10 Yeah, I think fiber is good, especially non-soluble fiber that slows the absorption of the bad things in our gut. I don't think it's good enough that I should eat carbohydrates in order to get it. So I can eat low-carb things that have fiber, like celery and relatively unsweet vegetables, I think, are a good source of that. But…

01:21:39 Personally, I think that the carbohydrates are a bigger danger to me than low fiber, but I do get fiber in my diet for sure. If you weren't though, would you be concerned? Because there's a group of people these days in the health space saying fiber is overrated, we don't need fiber.

01:21:58 Would you take it that far? Yeah, I mean, I don't exclude it just because I don't think the evidence is that strong that it's actually harming me. But I do agree that the value of fiber has been exaggerated, like, you know,

01:22:14 Many people were taught that a low-fiber diet causes diverticulitis and certain bowel diseases like that when it's probably related to other things like inflammation and metabolic factors that we've been talking about rather than the fiber in the diet. And how do you feel about supplements? You've stated the perimeters of your diet. Following those, do you feel like they're essential? Is there any you're taking?

01:22:43 Yeah, I think supplements are, well, first of all, we want to correct any deficiencies that we have. So, you know, you can eat the best diet that you want, but if you have a, you know, genetic issue with…

01:23:00 you know, meth, methionine metabolism or folate metabolism or vitamin D, you may need to take vitamin D supplements or you may need to take other supplements. So I think supplements are good to correct, uh, basic levels and,

01:23:16 And then going beyond that, correct deficiencies, basically. So going beyond it, it really depends on the supplement and what you believe in it. There's been a whole explosion about resveratrol and debunking that, which is a

01:23:35 which was a sirtulin activator that's very controversial. It's found in grapes that was popular, you know, 20 years ago. We've touched on the longevity supplements like metformin or, you know, the non-prescription berberine has some of the similar effects. We've, you know, talked about rapamycin and some of these other things. So I think…

01:23:57 I would do those on a case-by-case basis, depending on your individual viewpoint, what you've seen to be valuable. And the short answer is nobody really knows. And if anybody tells you they do, probably I wouldn't trust them. How do you feel about organ meats, either through supplements or whole food form to

01:24:21 add additional nutrients to the diet. Yeah. I mean, when I was growing up, my mom used to feed us liver and that was probably a good thing. You know, one of the good things she did. Um, but I, I get it in, in theory, you know, in, in theory, I haven't gotten to the point where I'm taking the organ meat capsules and I don't order organ meats a lot in the, um,

01:24:45 you know, when I do it, but I, in theory, I, I agree with it. I haven't done a deep dive in it. You know, I might, I might draw the line at, uh, at brains, certainly because of prions and, uh, you know, that kind of thing. But, uh, in, in principle, I could see the value of, of, of those in, in getting, getting nutrients because, um,

01:25:08 hey, you know, eating red meat, it's not as simple as that or eating meat. It's, it's about, well, you know, what did the meat eat? And if they were fed corn, which most meat is fed these days, you know, it's the same corn that subsidizes cheap and it's, you know, unhealthy. Uh, so you want to, you know, grass fed, grass finished, uh, all those things. Um, it,

01:25:31 It gets really complex really fast. And if you just eat the muscles, then like you say, you're missing the organs and different things there. So a lot of nuance and complexity. And when you're buying meat, how much of a concern is it for you to get grass-fed, grass-finished, organic meat?

01:25:50 Is quality a big concern? Yeah. I mean, given the choice, I think organic is valuable in meats and many of the produce, it's valuable as well. And I'll pay attention to those things for sure. So we've went deep into diet, what you eat, when you eat. What are some of the other big levers we want to look at when it comes to metabolic health?

01:26:19 Wow. Well, one, one that completely caught me by surprise, I was unexpected. I mean, I knew, I knew it played a role, but I didn't, I sort of underestimated the role and that was mindset and sort of mental approach to things. And it's, it's almost like,

01:26:42 The future we imagine, how we look at the world, how we envision the future, how we envision our future affects the future we will have.

01:26:55 In other words, it's not just about not being depressed, not having anxiety, which is certainly a big factor. We want to be healthy, but I think it goes above just the baseline being mentally healthy. We want to go beyond that and have a mindset of abundance and a mindset of having a purpose in our lives. I mean, it's no surprise that

01:27:17 But, you know, many people retire or many people die at age 66 in this country. Why is that? Well, that's because they retire at age 65 and they lose their purpose. I mean, what is it? Firefighters, most of them die within five years after retiring. You know, I mean, there's there's some interesting statistics there about about purpose. So I think I think the the future we imagine for ourselves is different.

01:27:44 can be the future we create. In other words, if I look at older age as a time of infirmity, a time of decline, a time of impairment,

01:28:03 It's nothing I look forward to. And it, there's a good chance it will likely become that for me. If I look at my life as a time age of abundance, a possibility of, of goals I want to accomplish down the road, there's a good chance that will happen. I mean, I used to make a,

01:28:24 Not a joke, but a comment about talking about the phenotypes of aging, all the stuff like wrinkles and gray hair that we talked about before. And I used to say, well…

01:28:36 We could take Botox for wrinkles, right? I'm in Southern California. I'm very popular here. I'm obviously not taking it, but I sort of made the comment, well, the sad part is that people who… You could take Botox for wrinkles, but people will eventually find out that taking Botox for wrinkles doesn't make you live longer. It doesn't affect your longevity at a core level.

01:29:04 And then I began to have conversations with people and they said, you know, are you sure of that? In other words…

01:29:12 And what they were pointing out is that people who embrace youthful vitality, they look at their life as, you know, something happening long term and they make the effort to get the Botox or they they they look at life as, you know, powerful rather than someone look looking at it like I'm dying, I'm going to die forever.

01:29:37 And guess what? One of these days I'll be right. You know, that's true. They will. People who look at it as a chance of empowerment actually may live longer. So people, you know, getting the Botox and it's about the mindset. You know, I, I have a friend, uh,

01:29:54 You know, I was talking to him and I said, yeah, what are you doing this summer? He goes, I'm going to Burning Man. It's probably the last one I'm going to go to, though, you know, because he's in his 70s. And I think, well, why? What's going on? You know, it's…

01:30:09 is it you playing on dying or something and and that was sort of the unspoken thing well i'm going to be i'm old but with that attitude you are old you will be old you know but if uh if if it's like no i'm i'm gonna go i'm waiting i'm gonna go on my hundredths uh to the burn and you know do this or whatever whatever festival or you know event you look forward to uh

01:30:33 that, that mindset plays a role. And, and then I began to ask myself like, oh, well, sure. That makes sense. Uh, how could it possibly tie in mechanistically? You know, what, you know, we're, we're all evidence-based, right? We, we want scientific papers. How can we make a mechanism that, that ties in mindset to, um, to aging better? Well, one thing is stress, right? If we look

01:31:01 towards our future life as a life of joy, abundance, accomplishment, and purpose. You know, I'm going to do great things and maybe great things with my kids or my grandkids, or maybe, you know, great things for my charity or my job or whatever I'm doing, but looking towards the future as a place of abundance, um,

01:31:19 it changes the way we experience stress. And stress is affecting our inflammation, you know, directly drives inflammation, drives insulin resistance, all these things. So how do we affect stress by our mindset? Well,

01:31:38 Stress is really interesting. This is another wake-up call for me that I hadn't thought of before. Stress is one of the biggest drivers in aging and all these things through inflammation and these other factors. But stress, you ask people what causes stress, it's, well, what happens to me in the world. It's the environment, right? I don't get to pick the political candidates or pick there's an earthquake or, you know,

01:32:07 stuff happens, you know, and, and, you know, it's stressful. Well, that's true, sort of, but it's not completely true. Actually, stuff happens in the world, and we don't get to control what happens in the world, right? But stress is not what happens in the world. Stress is how we respond to what happens in the world, how we, you, me, everyone else individually responds to what happens in the

01:32:37 A similar thing can have a different response. When it starts raining, I can get really stressed out because my nice new clothes are ruined and da-da-da. It's a stressful experience. On the other hand, it's raining. It's warm. It's beautiful. It's glorious. I love it. I love the feel of rain. It's a beautiful moment. Or an extreme example, I have surgery. It's extremely painful. I'm extremely stressed out.

01:33:02 the same amount of pain, a similar surgery could be a joyous experience to someone else who's having a baby, you know, and it, a lot stress, we get to filter through our expectations and through our view of the world, through the reality that we create and we get to create it through our mindset. And I think this is really underestimated and it's a,

01:33:29 It's really an overlooked opportunity in healthcare and longevity for all of us. You mentioned inflammation there, tying the stress to health as a whole. Any other ties, physiology-wise? Yeah, I mean, the…

01:33:45 The stress, I mean, inflammation is the ground truth on that, but also driving metabolic conditions like insulin resistance. Inflammation, insulin resistance, metabolic disease are all interrelated. So I think it drives all of those as well. And just the stress…

01:34:11 the stress really frames our reality. In other words, if I look at the future and it's very stressful, that's a very dark future. And I'm not, I'm not, you know, happy about it. And I'm, I maybe I don't want to live that long, you know, on the other hand is if the future is joyous with opportunities, not that everything is happy. Um, but, but if I look at it with a, with a

01:34:39 attitude, a mindset of growth, a mindset of abundance. It changes the way the reality appears, I think. And pivoting off of stress into exercise, these two are tied together, exercise being a modality we can use to drive down our stress. And also exercise is tied to metabolic health through even walking after meals, putting on muscle mass.

01:35:06 So I'll have you bring exercise in and talk about how you use that personally and how people can use that as a tool for metabolic health. Yeah, exercise is huge. And I want to divide it into two parts. The first is exercise.

01:35:22 The obvious one, physical exercise. And then if we can, we can come to mental exercise. But physical exercise is really important for all sorts of reasons. Exercise in itself is stressful, but it's a good kind of stress. We react to it positively and all. One thing I wasn't aware of that was sort of a wake-up call, but maybe it shouldn't have been, is that

01:35:48 Exercise, like almost everything else we do, there's a good amount and a bad amount. In other words, low amounts of exercise, which most of us fall into, is bad. But there's actually…

01:36:02 There's actually some growing evidence that large amounts of exercise beyond a certain point could be harmful. So it's kind of a U-shaped curve. And the data came in with ultra marathoners, ultra athletes, where they actually have increased calcium scores and they have increased coronary artery calcium scores.

01:36:19 out of proportion to their age group or anything that they felt is tied to this stress of this exercise. But then you may say, well, maybe it's spurious. It's related to calcification, but it's not really heart disease. It's just calcification of the vessel, maybe due to flow or something. But then a darker part became revealed and they actually have myocardial fibrosis and

01:36:44 abnormalities of heart wall function, which is really concerning. So I guess the point is that the

01:36:53 that there's a sweet spot for exercise. Most of us are not doing enough, but, but on the far extreme, we need to be at least aware that, you know, we don't want to do too much, certainly to injure our bodies with our joints and everything else, but also there's a basic cardio metabolic factor going on there. So I think, you know, that's important. Um, uh, resistance training, you know, for osteoporosis, um,

01:37:20 muscle mass for glucose metabolism, just handling insulin, handling all these things. There's so many, so many advantages of exercise and

01:37:32 the physical exercise. I think that that's huge. The mental exercise is sometimes overlooked with people, but I think it's equally important. What blew me away was that my training is in radiology. So, you know, looking at x-rays and stuff like that. I was blown away by the fact that

01:37:51 that things like both physical exercise but also mental exercise could show within a short amount of time, in a matter of months, actually changes in the brain, actual brain growths,

01:38:04 Presumably related to its effects on BDNF, brain-derived neurotropic factor, which certain parts of the brain, like you'd expect, the hippocampus, can actually increase in size with these various activities. So it's really amazing. But so for mental activity, it's not…

01:38:26 It's not like watching TV or watching a movie, something passive, but ideally it's something active that's engaging your, your brain. I mean, if ideally you could do something that engages both physical and mental activity, like playing a musical instrument or, uh, something where you're, you know, doing both is good. If you're, if you're not doing that, um, I just started doing, uh,

01:38:52 a language, a Duolingo. I can do it on my phone. It's a free app. It doesn't cost anything. I do it five minutes a day. I'm now at 1400 days, a continuous streak. And slowly but surely, five minutes a day, I'm learning Mandarin Chinese. And, um,

01:39:14 Uh, what I, what I'm doing, if I, the next level up after, if you're learning a language and you want to up your game, there's so many resources on the internet today. So what I did is I took Siri or my, uh, my app on my phone, whatever your Alexa, Siri, whatever you use, but I just had it changed into Mandarin only. So now if I say, Hey Siri, set a timer for 15 minutes.

01:39:40 It will basically, it responds in Chinese. It says, I don't know what you just said. So now it forces me every time I interact with Siri, I have to do something that I have to one, get my pronunciation right so that I, so that it works. So I, now I say, uh, Hey Siri, and now sure enough, 20 minutes. Yeah.

01:40:10 So there are all sorts of things you can do like that. If you're not into foreign language, you know, obviously crossword puzzles, you know, so the coup, those kinds of things like that. But mental stimulation, even just going for a walk and talking to your neighbor, you know, engaging in community, engaging in life.

01:40:31 The Blue Zones were very popular for longevity a few years ago. And with certain parts of the country, certain parts of the world where people had very long life expectancies. And Dan Buettner popularized it with a TV series. And there were a lot of wonderful things about it. Community, certain types of food, getting together, working in the fields, etc.

01:41:01 And, and they were, but that the sense of community, a lot of the other stuff has been criticized recently, like the record keeping probably, uh, confused the ages. And that was probably a thing. And then sadly, the, the whole blue zone brand has recently been sold to a, um, a group with strong religious, uh, affiliation, which has a strong nutritional agenda, which, um,

01:41:26 may influence the messaging with that. But I think there's a lot of good things to be said about community and family and social interactions with the blue zone theory, but that applies to the brain exercise anyway. All right. Tying in another piece that fits with the brain and with stress, sleep. Let's talk about its impact on metabolic health when we're getting enough and then when we're not.

01:41:52 Yeah. And I think this is a place where the medical profession is so messed up with this, uh, because, um, you know, I like many people in my profession or, or many other professions. I used to carry a beeper around a pager and I would be on call 24 hours a day, seven days a week. And I'd get called at all weird hours. My sleep would get disrupted, but you know, somehow I thought I was being tough and, you know, uh,

01:42:19 I was helping my patients when actually I was probably hurting them. And, and one wake up call to me in this book was, uh, did researching this book was that, um,

01:42:31 You hear some people like Elon Musk saying, oh, I only need four hours of sleep a night. There's growing evidence that just like for exercise, just like for so many things, the cost-benefit curve for sleep, for quantity of sleep, is fairly narrow. In other words…

01:42:52 It appears that risk of cardiovascular disease and other diseases, all these metabolic diseases that I've been talking about, is a fairly narrow window, around eight hours. And so maybe some people can get by at seven hours. Maybe some people need nine. But if you need much more than that,

01:43:10 Or if you think you can get by much less than that, you may be kidding yourself. And sleep, we know directly. With sleep deprivation, you take college kids, and there have been controlled studies with this. They sleep deprive them, and immediately their insulin resistance goes up. Their metabolism is messed up. Their glucose is screwed up. There's inflammation. So it directly affects these metabolic, these

01:43:36 primal metabolic markers that, that we're taking. So the wake up call for me was sleep quantity, which really, which really helped. And then the other thing was, uh, sleep quality. So, you know, you've got to get the right amount, but it's gotta be good sleep. And there are a number of trackers on your phone or different things that you can do, um,

01:43:58 to look at that. I mean, an interesting thing happened to me once I began on this path and changed my lifestyle and everything. I noticed that I was sleeping a lot better. I don't know what it was. I wasn't paying attention to it, but I was sleeping a lot better to the point that I didn't need an alarm clock anymore. So I just sort of woke up naturally. And now

01:44:21 Now I figure if I need an alarm clock to wake up, I'm probably not getting enough sleep, you know, so it's fascinating. But yeah, sleep, I think, is another area that's overlooked in our toolkit for metabolic health.

01:44:37 You mentioned trackers there. For somebody who's tuned into this point and they've taken in a lot of different information, different areas where they're wondering where they're at on this continuum of metabolic health, how does testing fit into this? For somebody early on to see where they're at and then ongoing to continue to

01:45:01 keep track of their progress. Yeah, I think testing is key to know where we are on that course. And like we talked about, the earlier the better. I mean,

01:45:16 These changes start happening in people's 30s, although these chronic diseases usually don't hit until people are 40 or so, although they're getting earlier and earlier. We're seeing now cancer, colon cancer, hitting in younger and younger populations and obesity. Type 2 diabetes used to be called adult-onset diabetes. Now it's occurring in children. Similarly, hypertension and everything. But so…

01:45:44 Tracking early is good. Some of the markers I would look at is…

01:45:50 hemoglobin A1C, which is a marker for glucose damage. It's a metabolic marker for insulin resistance. You can do, uh, and you can absolutely measure fasting insulin. I mean, I use a panel that I, that I do from, um, uh, I do a finger stick at home. I get about 20 markers. I, you know, I do it like once a month or two and it gives me hemoglobin A1C, insulin, uh, LDL, uh,

01:46:17 cortisol, testosterone, FSH, homocysteine. It's just a whole thing. And now these tests are getting so inexpensive and so easy, you can even do them from your home and begin to track where you are in this. And it's never too early to start thinking about metabolic health and to live a healthy lifestyle because…

01:46:41 you know, we don't know how early these things really start. And the sooner we engage in prevention, I think the better the outcome. And what's the name of that test you were just talking about, the finger prick? Yeah, I have it on my website. You can get it from a company called Sifox, S-I-F-O-X. But I have a discount on my website. It's about, I think…

01:47:06 It comes out to be about $15 a test or so, but it's significantly less than the Cyfox site, but that's who we use and it's a great one. So either on my website or at Cyfox, either one, you can try it out.

01:47:21 All right, Rob, we'll link that up in the show notes. We'll link up your new book, your website, your social media, everything, and really enjoyed this conversation. The new book is fantastic. I was telling you before we connected. And I just want to thank you for coming on and sharing all this about metabolic health. It's going to help a lot of people. Thank you.

01:47:39 Yeah, this has been fun, Jesse. I just got my first copy of it. It's full of pictures inside. So it's… Nice. I had the PDF. Hopefully people enjoy it. Yeah, no, that looks good. Congrats. And thanks again. Thanks so much for having me on your program. It was a real honor. Now that you're finished with the episode, head on over to ultimatehealthpodcast.com for detailed show notes, including links to everything we discussed. Thanks for listening and have a great day.

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节目开篇讨论了多个与健康相关的话题，包括糖食、乏食、酮食等饮食方式对身体的影响，例如果糖在肝脏的代谢与酒精类似，最终可能导致脂肪肝；压力并非外界事件本身，而是人体对事件的反应，且压力会直接引发炎症、胰岛素抵抗等问题；还有研究表明，体育锻炼和脑力锻炼能在短时间内改变大脑状态，可能与脑源性神经营养因子（BDNF）有关，像海马体这样的大脑区域甚至会因此增大。

随后，话题转向罗伯。作为一名传统培养的医生，后来还负责教导其他医生，罗伯的观念转变始于大约10年前。当时，他像很多人到了一定年纪一样，突然患上了痛风、高血压、血脂异常和糖尿病前期这四种慢性疾病，就像被火车撞到一样。他去看医生，医生给他开了处方药，并告知他可能余生都要服用这些药。但罗伯知道这并非长久之计，出于对自己和还未上高中的孩子的考虑，他开始重新审视自己对医学的认知，这一过程对他来说是一次启示。

罗伯提到，如今很多美国人都受慢性疾病困扰，大多数成年美国人肥胖，约一半人有高血压，多数人是糖尿病患者或糖尿病前期。这些疾病往往同时出现，但很多人只能终身服药，不知道还有其他办法。

罗伯指出，他曾经认为自己患的这些疾病是相互独立的，药物只是控制了症状，但从长寿的角度来看，前景并不乐观。这让他意识到，主流医学在治疗这些疾病时，更多的是针对症状进行管理，而没有解决根本的代谢问题。比如心脏病发作时使用的支架，只是机械地打开血管，防止患者在手术台上死亡，但并没有改变动脉粥样硬化在其他血管甚至支架内继续发展的趋势；胰岛素能解决2型糖尿病患者急性高血糖的问题，却无法控制糖尿病的长期并发症；降压药能降低血压，但血管的损伤仍在继续。

罗伯和访谈者都认为，慢性疾病存在共同的根源——代谢功能障碍。当对这些根源施加影响时，有可能同时改善多种疾病，而不是像以前那样针对不同症状分别处理。

罗伯用一个比喻来说明：家里地板湿了、门上有水，人们可能只是去拖地、擦门，却没意识到问题出在屋顶漏水。慢性疾病就像这些表面的水渍，而代谢功能障碍等就是屋顶的漏洞。很多人在治疗慢性疾病时，只是控制了症状，却忽略了根本原因。

以2型糖尿病为例，罗伯以前认为它像一个开关，要么患病要么健康，医生也是通过血红蛋白A1C是否超过6.5%来诊断。但实际上，像糖尿病、阿尔茨海默病、心血管疾病等，在被诊断出来之前，可能已经存在数年甚至数十年了。有研究显示，健康的美国成年人的血红蛋白A1C会随着年龄增长而升高，就像白发一样，很多人如果活得足够久，都可能走向糖尿病。所以，在生活方式和代谢健康方面做选择时，应该像已经是2型糖尿病患者一样去行动。

mTOR是一种重要的分子，是一个生物开关，能检测营养物质（主要是葡萄糖，在一定程度上还有氧气和胰岛素）的存在。当有营养时，它会指示细胞生长，就像油门踏板；没有营养时，它会关闭，细胞不再生长，同时启动自噬，即细胞清除受损部分的修复过程。

健康的生物体中，mTOR的开启（生长）和关闭（修复）都是必要的。但现代人类由于农业革命后食物越来越容易获取，尤其是近20-40年，垃圾食品充斥，人们几乎随时都在进食，导致mTOR大部分时间都处于开启状态，这会导致细胞过度生长（过度功能），进而引发多种慢性疾病。比如心血管疾病中血管壁的过度增生，癌症中细胞的不受控制生长和扩散。

阿尔茨海默病的研究也存在局限性，β淀粉样蛋白假说逐渐站不住脚，有观点认为它与炎症和过度功能有关。通过酮食等改善代谢异常的方法，能在一些患者身上改善甚至逆转阿尔茨海默病的症状，这是药物无法做到的。

人们可以通过生活方式影响mTOR，比如饮食上避免会激活它的食物，还有睡眠、运动、压力等因素。此外，有一种专门针对mTOR的药物，很多人出于长寿目的超说明书使用，但罗伯不建议仅依靠药物而忽略生活方式的改变。

雷帕霉素是一种能靶向作用于mTOR的药物，最初是在拉帕努伊岛的土壤细菌中发现的。在一些实验中，它对与衰老相关的现象有影响，比如让有脱发和白发问题的小鼠毛发重新生长且颜色恢复，在人类身上使用雷帕霉素乳膏，经活检显示胶原蛋白基底层恢复，皮肤看起来更年轻，美国食品药品监督管理局（FDA）已批准其乳膏用于某些癌症相关疾病，也有用于改善年龄相关听力损失等方面的研究，甚至能延长小鼠的生育期。

在影响寿命的疾病方面，雷帕霉素也有一定作用。在心血管疾病中，涂有雷帕霉素的支架能显著减缓甚至阻止动脉粥样硬化，口服雷帕霉素也可能减缓动脉粥样硬化疾病的进展。在癌症治疗中，雷帕霉素是FDA批准的用于肾细胞移植等器官移植的免疫抑制剂，而移植患者在术后五年内最常见的死亡原因是癌症，使用雷帕霉素后，癌症发病率下降了50%，目前至少有八项FDA批准的雷帕霉素用于癌症治疗的适应症。在阿尔茨海默病方面，给患有认知障碍的小鼠使用雷帕霉素，其精神状态能得到改善，得克萨斯大学正在进行雷帕霉素治疗阿尔茨海默病的试验。

关于雷帕霉素与长寿的关系，虽然很难在人类身上进行长寿研究，但美国联邦政府的干预测试计划（ITP）在小鼠身上的研究显示，雷帕霉素是目前效果显著的物质，即使小鼠在相当于人类60-70岁时才开始使用，仍有显著的长寿益处。

不过，雷帕霉素作为免疫抑制剂，在用于长寿时，人们通常每周服用一次，而不是肾移植时的每日剂量，因为其半衰期较短（48小时），几天内就会大幅减少。它的安全性较好，有报道称有人服用超过推荐剂量10倍试图自杀，也未出现严重问题，少数人可能会出现口腔溃疡等副作用，但目前对于其用于长寿的剂量等方面还缺乏足够数据。

研究还发现，雷帕霉素与二甲双胍、阿卡波糖联合使用时，效果比单独使用雷帕霉素更好，存在协同作用。所以，罗伯认为，雷帕霉素可能对长寿有益，但同时也应注重饮食、睡眠、运动、压力等生活方式的调整，这样能取得更好的效果。

在饮食方面，即使不想改变饮食内容，也可以通过改变进食时间来改善代谢状态、降低mTOR活性，比如停止吃零食，罗伯自己就是这样做的，吃完晚饭就刷牙，避免再次进食，还可以尝试不吃早餐或午餐，他每天只和孩子一起吃一顿饭，其他时间只喝咖啡或水，不摄入热量。因为不进食时，营养物质不进入体内，炎症也会相应降低，而且根据进食窗口的长短，可能还会进入酮症状态，这是一种有利的代谢状态。

从宏量营养素来看，蛋白质和脂肪是必需的，而碳水是非必需的，有一些人类文明在饮食中几乎不含碳水也能生存。碳水会比其他营养素更能刺激胰岛素分泌，激活mTOR。阿卡波糖是一种用于糖尿病的药物，它在肠道中阻断碳水的吸收，减缓碳水吸收，在动物模型中，服用阿卡波糖有延长寿命的益处。人们也可以通过先吃脂肪或蛋白质，再吃碳水的方式，延缓碳水吸收，减少葡萄糖峰值带来的不良影响。

罗伯认为，在饮食选择上，不同的饮食方式都可能健康或不健康，关键在于选择。他自己会避免垃圾食品，对于他而言，垃圾食品通常有包装、颜色鲜艳、成分表长。具体来说，他会尽量减少碳水的摄入，尤其是精制碳水和糖，现代水果含糖量高，淀粉类食物也会分解为葡萄糖；他还会避免工业用油或超加工油（如植物油），这些油存在于很多食品中，因为它们稳定、便宜；此外，他也不吃谷物，即使是全谷物，因为他认为很多成年人可能对谷物中的蛋白质过敏，会引发低度炎症，而且美国的很多谷物会用草甘膦处理。

罗伯提到，这三种饮食调整的效果显现时间不同，减少糖和碳水，24-48小时就能看到效果；停止吃谷物，可能需要等待三个月左右才能看到对免疫系统等的影响；而停止摄入种子油，由于其在脂肪中的半衰期可能长达数年，所以见效时间更长。

罗伯通常处于酮症状态，他以前用过呼吸检测仪检测，现在因为饮食方式稳定，就不再常规检测了。酮症对一些疾病有改善作用，比如能逆转癫痫，这是生酮饮食最古老的应用；在精神疾病方面，克里斯·帕尔默等人的研究显示，生酮饮食能让一些有精神问题的患者好转，甚至可以离开医院、停用药物；对于阿尔茨海默病，一些患者通过摄入MCT油等外源性酮体，病情得到显著改善。

不过，克里斯·帕尔默表示，在他的经验中，外源性酮体在精神健康方面的作用，目前还没有相关案例报道，可能营养性酮症和外源性酮体的效果有所不同，这也表明人们对这一领域还有很多需要学习的地方。

果糖和葡萄糖化学组成相似，但在体内的处理方式完全不同。几乎身体的每个细胞都能利用葡萄糖供能，而果糖只有在肝脏中才能被解毒代谢。

在1980年以前，脂肪肝主要是酒精性脂肪肝，由饮酒引起。但1980年后，一种新的疾病——非酒精性脂肪肝出现，现在已成为最主要的肝病和肝移植的主要原因。研究发现，果糖在肝脏中的代谢方式与乙醇（酒精）非常相似，会产生脂肪，损害肝脏，导致脂肪肝。

高果糖玉米糖浆的出现和广泛使用是导致非酒精性脂肪肝增多的重要原因。它由玉米提取，成分与蔗糖相似，但更稳定、成本低，被广泛用于各种垃圾食品中，替代了蔗糖，导致垃圾食品消费量激增，非酒精性脂肪肝也随之增多。

罗伯特·勒斯蒂格在对儿童的前瞻性对照研究中，通过移除饮食中的果糖，替换为葡萄糖，几周内就逆转了儿童的脂肪肝。历史上，人们通过给鹅喂高果糖的食物（如无花果）来制作肥鹅肝，也证明了果糖与脂肪肝的关系。

很多脂肪肝患者没有被诊断出来，即使被诊断，也很少有后续跟进。但好消息是，早期发现的脂肪肝是可以逆转的。果糖虽然不会像葡萄糖那样使胰岛素和血糖急剧升高，但它会导致肝脏胰岛素抵抗，还会转化为尿酸，引发痛风，影响血管内皮细胞，导致高血压和心血管疾病。

罗伯认为纤维是有益的，尤其是非可溶性纤维能减缓肠道对有害物质的吸收，但他不会为了获取纤维而摄入碳水，他会从芹菜等低碳水蔬菜中获取纤维。他觉得纤维的价值被夸大了，比如低纤维饮食导致憩室炎等肠道疾病的说法，可能与炎症和代谢因素有关，而非纤维本身。

对于补充剂，罗伯认为首先要纠正身体的营养缺乏，比如因遗传问题导致的叶酸、维生素D等缺乏，就需要补充相应的补充剂。对于那些用于长寿的补充剂，如二甲双胍、小檗碱、雷帕霉素等，人们可以根据自己的观点和观察来选择，但目前还没有明确的结论。

罗伯认同食用器官肉可能有一定价值，能获取更多营养，但他还没有深入研究，也会避免食用脑类，因为担心朊病毒等问题。在购买肉类时，在条件允许的情况下，他会选择有机、草饲、草育的肉类和一些农产品。

心态和思维方式对代谢健康的影响超出了罗伯的预期。人们对未来的想象、对世界的看法，会影响自己的未来。如果把老年看作是虚弱、衰退的时期，可能真的会如此；如果认为老年是富足、有目标的时期，情况可能会不同。有统计显示，很多人在65岁退休后，因为失去目标，可能在几年内去世，这也说明了目标感的重要性。

压力与心态密切相关，压力会直接引发炎症，导致胰岛素抵抗和代谢疾病。但压力并非由外界事件本身决定，而是由人们对事件的反应决定。同样的事情，不同的人可能有不同的反应，积极的心态能改变对压力的体验。

运动对代谢健康很重要，分为身体锻炼和脑力锻炼。身体锻炼虽有压力，但这种压力是有益的。不过，运动也有适量和过量之分，有证据显示，过量运动可能有害，比如超级马拉松运动员的冠状动脉钙化分数和心肌纤维化程度较高，所以运动存在一个最佳范围。阻力训练对预防骨质疏松、改善葡萄糖代谢等有很多好处。

脑力锻炼同样重要，身体锻炼和脑力锻炼能在几个月内改变大脑，使大脑某些区域（如海马体）增大，这可能与脑源性神经营养因子（BDNF）有关。脑力锻炼最好是积极参与的活动，比如学习语言、玩乐器等，与他人交流、参与社区活动等也有助于脑力锻炼。“蓝色地带”的研究虽然存在一些争议，但其中关于社区、家庭和社会互动对健康的积极影响是有一定道理的。

睡眠对代谢健康影响很大，但医学界在这方面存在问题。罗伯以前因工作原因睡眠被打乱，却认为自己很坚强，后来才意识到这可能对患者有害。有研究表明，睡眠时长的成本效益曲线较窄，心血管疾病和其他代谢疾病的风险在睡眠时长约8小时时较低，有些人可能需要7小时或9小时，但过少或过多的睡眠都可能有风险。

睡眠剥夺会直接影响代谢指标，在对大学生的对照研究中，睡眠剥夺会导致胰岛素抵抗、代谢紊乱、葡萄糖异常和炎症。除了睡眠时长，睡眠质量也很重要，有很多工具可以监测睡眠质量。罗伯改变生活方式后，睡眠质量提高，不需要闹钟就能自然醒来，他认为如果需要闹钟叫醒，可能就是睡眠不足。

罗伯认为检测对于了解自己的代谢健康状况很重要，而且越早越好。这些慢性疾病的变化在30多岁就可能开始，虽然通常在40岁左右才会显现，但现在有年轻化的趋势。

可以检测的指标包括血红蛋白A1C（反映葡萄糖损伤和胰岛素抵抗的代谢指标）、空腹胰岛素等。现在有一些居家检测工具，通过指尖采血就能获得多种指标，价格也比较便宜，人们可以定期检测，追踪自己的代谢健康状况。罗伯提到了Sifox（S-I-F-O-X）公司的检测，在他的网站上可以获得折扣，价格约为每次15美元。

访谈最后，访谈者感谢罗伯分享关于代谢健康的内容，并表示会在节目笔记中链接相关信息，罗伯也感谢参与节目。

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D:2025.07.09

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