The 3 Daily Supplements Everyone Should Be Taking For Longevity | Mark Hyman

90 plus percent of Americans are deficient in something. Nutrients are such a critical part of our biology. And if we don't have enough, our health degrades.

What are the top three supplements that we could consider taking when it comes to longevity? If you had three, that would be out there.

I mean, this is the worst possible question you could ever ask me, Drew. It's like saying, what are the three favorite foods you could want to eat?

That's it.

I'm like, what are the three favorite foods that you want to eat? Lamb chops, sweet potatoes and chunky monkey ice cream. I could live forever on that. So I always say, you know, the obvious question is, why do we need supplements? Right? We evolved for the last 200,000 years and, you know, you couldn't, there was no Whole Foods or GNC or supplement store. We couldn't buy vitamin D or vitamin C or any of this stuff. We didn't even know what it was. And yet somehow we managed to survive. So from an evolutionary point of view, supplements are kind of irrelevant. But right now we're living so out of sync with our evolutionary biology that we need to really look at the facts about what's happening with our food supply, with our nutrient levels, both in our food and in our bodies, and the consequences that for our health. So I always say, you know, I don't think anybody needs supplements, but only under certain kind of about it, Drew. Bruce Ames, one of the leading researchers in nutrition and science, they something a test called out after him, the Ames test to look for cancer inducing compounds. and he's like probably in his late 80s now, he's still around, and he wrote an article years ago which basically mapped out that one third of our whole DNA, our entire DNA codes for enzymes. Enzymes are basically catalysts that change one chemical to another chemical in your body to do what it's supposed to do. Well, if one third of your entire DNA codes for enzymes, that that's important. So what do enzymes need to work? They need coenzymes or cofactors, which are usually vitamins and minerals, but also phytonutrients. So how does, you know, enzymes work? Well, there's a little key that goes in the enzyme, it turns it on, and that key is usually a nutrient, vitamin C, B6, folate. For example, to make tryptophan into serotonin, which is your happy mood chemical, you take the amino acid you're eating from tryptophan, which comes from food like protein, turkey, everybody knows turkey and tryptophan, that has to get converted to serotonin. Well, that requires vitamin B6, there's an enzyme, or your thyroid, in order to make the thyroid that your thyroid gland makes into the active thyroid hormone T3, you have an enzyme there which actually requires selenium. So if you don't have selenium, it can't work. Or if you want to see the thyroid action on the nucleus where it actually does all its work to control your metabolism, you need vitamin D as a cofactor to help it function at the nuclear level to create the downstream effects, which is to turn on different genes and do different things. They regulate your metabolism and so many other things. So nutrients are such a critical part of our biology. And if we don't have enough of the required nutrients, our health degrades. And years ago, and I know this is a long answer to your question, but I'm on a roll here. It's all great knowledge. I love that. There's a, there's a, a scientist named Robert Heaney who recently died, who wrote an article called Long Latency Deficiency Diseases. So we all learned about vitamins. I mean, the vitamins we learned about only about 120 years ago, the term comes from vital amine. It's a thing that's needed for your health, for vitality basically. And they were first discovered because they started refining grains in the 1800s because the grain mill came up and it was a great discovery that you could refine grains. And what happened was they took out all the nutrients that are in the husk and the fiber and the and the ectosperm where all the vitamins and vitamin E and the everything is in there. And all they left was the starch. And so they started feeding this refined grains to chickens and the chickens all got really sick and they started feeding it to prisoners. and the prisoners all got really sick. They got like Beriberi and Pellagra and all these horrible vitamin deficiency diseases. And they're terrible. They're really terrible diseases. Scurvy, obviously, is something people don't know about. And these will kill you or make you demented or turn your skin into this whole raw mess just from little vitamin deficiency. And so that's what's the discovery of vitamins. And they realized that these were sort of things needed in very little amounts that had profound effects. I mean, imagine if there was a drug that cost pennies, that had no side effects, that literally worked in days to cure illness. I mean, that would be pretty amazing. But that's what vitamins do. If you take someone who's vitamin deficient and you give them a vitamin, like vitamin C to someone who's got scurvy, it's like, well, in a few days they're better and everything's gone. So, and even vitamin C, you think, oh, vitamin C, everybody's got vitamin C. But 10% of Americans are deficient in vitamin C at the level that would cause scurvy. This is no joke. Long story short, one, our food supply has been hybridized to breed out nutrition. It's bred for starch and maybe a little protein, but not for nutrients. It's also grown in soils that have very little organic matter that can't extract the nutrients from the soil for the plant. There are nutrients in the soil, but the plants need the microorganisms in the soil to actually as symbiotic helpers to extract the nutrients from the soil to go into the plant so then it's in the plant then you can eat it. But now maybe your broccoli today is 50% less nutritious than it was 50 years ago. So that's another problem. And then we have increased nutrient needs because we're under chronic stress because we're exposed to environmental toxins. I mean, there were 80,000 new chemicals introduced into the marketplace since the 1900s. I mean, our bodies have to deal with all that stuff. And there's chemical reactions and detoxification, and they all require nutrients. And we are also under a tremendous amount of psychological stress, even in the society. And, you know, magnesium, your body wastes magnesium when you're under psychological stress. So there's so many things that are happening in our omega-3 fats. We don't get those because we don't really eat wild food anymore. Maybe some fish, but that's got mercury. So there's all these problems that happen because of our nutritional environment. And so more than ever now, people need foundational nutritional support. I believe that. And I, and I, and I say this not from a, you know, sort of a, a sort of a general opinion, but actually from really hard scientific data. And they go, oh, well, all the vitamin studies, they show that it don't, that they don't prevent heart attacks, they don't prevent cancer, they don't do this, they don't do that, or they may have side effects. And, and the truth is, the studies are just all poorly designed. I mean, it's like think about Michael Jordan, arguably the best basketball player in history. If you put him on a court by himself, he could not win a single game.

Against another team that had a full team.

Yeah, right. So, nutrients work as a team. And if you don't have all of them, your biochemistry gets gummed up and it can actually cause worse problems. So, for example, they did this large study called the Carrot Study where they gave smokers who were at high risk for lung cancer beta-carotene, because it seemed like people who ate fruits and vegetables with lots of beta-carotene actually did better. But when they actually gave the beta-carotene as a supplement, what happened was there was more cancer. Now, the science was like, oh, this is terrible. Supplements don't work. I'm like, one, this is a perfect example of what Michael Pollan calls nutritionism, which is reductionism in nutrients, where you basically see, oh, it's maybe this single thing and we're going to replace that. It doesn't work like that. Which is how they think about drugs. Drugs, right? so basically the carrot study gave high dose of beta carotene. Now, if you actually understand basic biology and how antioxidants work in the system, they work as a team. So if you give one of them, the way they work is they donate an electron to some damaged tissue or free radical, like a, an oxidized compound in the body. So an antioxidant will actually help deal with oxidative stress or rusting in the body, but the way it does it is it donates one of its electrons. Then it becomes a radical. So for example, vitamin C is a great antioxidant, but it'll donate one of its electrons and then it becomes an ascorbyl radical, which is highly dangerous. But don't worry, then you got vitamin E to help take that electron from vitamin E and give it to the vitamin C and it becomes a tocopherol radical. And then that has to be dealt with by all these systems like poik acid. And that then has to be dealt with by glutathione. So you've got a whole system. if you don't have all the antioxidants and you don't have the final pathways of glutathione, you're gonna get in trouble. And so you actually create more oxidative stress and more damage if you just give a high dose of a single nutrient like that.

All to say that it's another reason why that even if we have a good idea about a cocktail that would be supplemental, this just is another reminder why the base foundation of your diet is so key because there could be co-factors and co-enzymes and other aspects that are all related to this that we can't even begin to understand. So having a really incredible diet, even if you do choose to dabble into supplements here and there to be a bonus, a supplemental to your diet, is such a key reminder.

It's key. And so, I believe everybody needs a good multivitamin, fish oil, vitamin D. Yeah.

So let's divide this and let's go through this. Instead of the three, let's divide this into foundational items that are there. And then, let's get into really the topic of today's episode, which is kind of these bonus ones that are really being highlighted for their specific role in longevity. So, take us through the supplemental foundational ones.

I mean, so basically everybody should be on a good multivitamin with the right forms of nutrients in the right balance. And, when I say the right forms and bioavailable, because for example, you can go to the drugstore and buy magnesium oxide, but it's the cheapest form of magnesium, but it's poorly absorbed. Or you could buy folic acid, but maybe your genetics don't allow you to convert it to the effective form of folic acid called methylfolate, so you need to buy methylfolate. It's really important to know what your body needs. But a basic good multivitamin from a company that focuses on therapeutic products that are mostly doctor-related companies, but you can still get these products, that's a good place to start. Then fish oil, really important. and there's many different kinds of fish oil. There's, you know, you kind of worry about where it comes from. Was it distilled? Does all the are the toxins in mercury out of it? Is it oxidized? How was it preserved with? What kind of animal is it from? Like there's a whole bunch of questions, right? But, but like there's also also ways of processing it that preserve a lot of the benefits of fish oil. Like Big Bold Health has a product called Dutch Harbor Omega. Just transparently, we're involved with Big Bold Health. It's my mentor, Jeffrey Blaine's company. And, and it's very impressive. He's basically found a process by which they extract the fish oil in Alaska from wild salmon and other fish that preserves something that is really important in fish oil called pro-oxyl and mediators. So you can get EPA DHA, which is fish oil. But then also what's so amazing about eating fish and fish is that there's these compounds that have been recently discovered that are like the break on your immune system. So we have an accelerator on an immune system break on immune system. So our immune system is so overactive inflammation. so these pro-resolving mediators, which have been extensively studied at Harvard, are amazing. And they're contained in this particular fish oil, Dutch Harbor Omega, because it actually processes in a way that doesn't destroy it. The third key supplement is, and by the way, like I said, 90 plus percent of people are deficient omega-3 fats.

So it's just a no-brainer. And there was a big study that came out last year showing that individuals who are at the right omega index had an extra three to five years of their life. Yeah, no doubt. So, if you're talking about longevity, even though it's foundational, this is one of those things to really look at.

These are called essential fatty acids. That means they're essential for life. They're like a vitamin. If you don't have them, you're screwed. And, every cell membrane in your body is made out of them. Your brain is 60% made out of them. Your skin, your hair, your nails, all your body functions, it regulates inflammation, prostaglandins. I mean, it's just really, really important. So it regulates metabolism, blood sugar. So it's really critical to have the right one. The, the next one that I think in addition to multi and fish oil is vitamin D. 80% of us are deficient or insufficient vitamin D. It's, it's so important. And COVID has kind of highlighted the, the consequences of this, because when you look at the data around COVID, if you're low in vitamin D, you're 70% more likely to end up in the hospital on the ICU and die. If your vitamin D level is higher, your, it's actually you're 97% protected from ending up in the hospital or dying. And if you are vitamin D levels over 50, which is where I like to see it, nanograms per deciliter, there's a, there was zero deaths, zero deaths, which is better than any vaccine out there, you know, I think so. That's, and people are sort of ignoring that for the most part. But the data is very clear. So multifocal vitamin D. And then if I had to add a couple others around the margins, it would be magnesium or really magnesium-rich foods and then maybe a probiotic because our guts are also messed up. So that's sort of the stack that.

I like to sit on with everything else. And with the D, how important do you think it is the K2 and.

You always hear that conversation? Yeah, so you need vitamin D3, which is different than a lot of doctors prescribe. And vitamin K2 is also a fat soluble vitamin. It should be made by your gut bacteria. It's often not because our guts are messed up. But it works in conjunction with vitamin D and helps with the improvement in cardiovascular health, bone health, and it's actually also an important supplement. So I often prescribe them combined.

Okay, Mark, so that's the foundational area of supplementation. Let's get into the next one, which are these targeted supplements that are out there, again, built on top of incredible lifestyle, foundational diet, sleep, movement, all the things you shared community. Get into some of the really interesting ones that are showing up now in the longevity space. The bonus supplements.

Yeah. Before we do that, I just want to address a couple of things that we didn't touch on. We talked about the general research around supplements and I think it's confusing for people because you look at these big studies and they often don't show a result. And, it doesn't mean that it's not effective or important. I want people to understand that because we don't rely on just studies like that because often they're poorly designed or they don't take into account the biology of the nutrients or if I, for example, if I give vitamin E to a bunch of smoking, overweight, non-exercising, junk food eating people, it's not gonna do anything. Right.

And what's the timeline of the study?

Yeah, so why are they looking at this? It's complicated, yeah. It's not gonna replace a healthy diet and lifestyle. The second is, how does conventional medicine view supplements? And I think this is a really important note because many times doctors will say, oh, supplements, they just create expensive urine. It's a waste of time. You'll get everything you need from food. and I'm like, well, gee, if that philosophy were true, then you shouldn't drink any water because it just comes out as pee. So why bother drinking any water? Your body takes in what it needs and it lets go of the rest, which is exactly what it's supposed to do. The other thing is that in the closet, and this was shocking to me, Drew, at Cleveland Clinic, which is arguably one of the best health establishments in the world, Mayo and Cleveland Clinic or like one and two. The doctors are very smart, they're very well educated, they're up on the latest research, and I thought they'd be more conservative. And so we did a survey when I got there of, one, who was using supplements for themselves, who was recommending to their patients, and what was the percentage? And I was just shocked that 70% of the doctors at Cleveland Clinic were recommending supplements to their patient. whether it was an OB with a multivitamin for prenatal or whether it was a, you know, endocrine doctor for osteoporosis or whether it was a heart doctor for CoQ10 or folate or fish oil, you know, it was so prevalent and I was shocked. So I think if you go into a conference and you ask doctors, you know, who's actually, you know, supporting patients getting supplements and very few will raise their hands. You say, how many of you are actually taking supplements? Most of the doctors raise their hands.

It's also funny that sometimes I come across physicians again, well-intentioned everything who would be so strong to recommend a prenatal, but then are like, oh no, the patient doesn't need to take anything if they're not pregnant or trying to have a baby or whatever. It's like, well, let's just think about that. You want a woman to be taking a prenatal vitamin. And now there's actually companies that are out there that have prenatal vitamins that are also for men because their sperm is a big part of that. We have a former employee that started a company called WeNatal. So there's like supplements for the mom, supplements for the dad in their process of trying to conceive. But anyways, going back to the mom, So you want a mother to take a prenatal vitamin to help grow a healthy baby and a healthy baby brain and take this thing and that, but then you're not recommending anything for her afterwards. That seems kind of like a little crazy.

Yeah, it's a bit crazy. So going to your question about what's happening in the space of longevity, it's fascinating. I'm really deep in that science right now and I think the question is, what are you trying to achieve with supplements in the space of longevity? What pathways are you activating? What are the important longevity switches in the body and how do you regulate those? So I think aside from the foundational stuff, which has a lot to do with extending life, you mentioned the fish oil study, vitamin D, I mean there's just so much data on this, it's really impressive. But in terms of specific thinking about which product supplements are effective for longevity and aging, there's There's a number that really come to mind. And, you know, just to kind of back up a little bit, and then I'm going to get a little geeky here if it's okay, because this is a masterclass.

Please do.

There are a number of things called the hallmarks of aging, which are these fundamental dysfunctions that happen as we age if we age abnormally. So aging should be considered a disease. It's not normal. The way we see aging in this culture is, is a sign of abnormal aging. And we think it's normal because it pretty much happens to everybody, which they get old disease and decrepit. You know, if you're 65 years old, it's like you're gonna have three or more chronic illnesses. Just how it goes. Right. But it's not inevitable. And, and so one of the Hallmarks of Aging is, is as a dysfunction of these nutrient sensing pathways. So we have Exquisite systems in our biology that sense either abundance or scarcity. Oh, there's too much of a. food, we just, we want to start to build and grow and make stuff in our body. But if there's scarcity, it activates all these repair and healing and general mess next. And we need both, we need, we need both a demolition team and we need a, a construction team to actually continue to renew and rebuild our bodies. And a lot of these supplements that are, we're talking about are working on some of these key pathways. So one, one of them is really important is called NAD. NAD, you've probably heard about it. It's, it's an important compound. That's part of your cellular metabolism helps produce energy. but it turns out it has a lot broader effects. And one of the key nutrient sensing pathways is something called sirtuins. These compounds, these pathways were discovered in 1991 by Lenny Guarente and his colleagues at MIT. And it was a real breakthrough because they were able to stimulate this certain sirtuins in yeast models and mice models and extend life dramatically, double it, sometimes even up to a thousand years equivalent in a worm. or 120 or 140 in a human, how they were doing it with some of the mice studies. So, what it turns out is NAD is a sirtuin activator. So, when NAD levels are good, which means you have energy, it turns on the sirtuins, which then creates a whole downstream series of effects that creates longevity. So, it sends out a massive DNA repair team. which is awesome because we get 100,000 hits to our DNA every minute, basically from various insults from food, from oxidation, from metabolizing food, from environmental toxins, from all sorts of things. Second, it actually inhibits one of the key hallmarks of aging, which is inflammation. And we talked a lot about inflammation on the podcast, but it does so through a particularly important mechanism that is one of the master inflammation switches in the body, which is called NF-Kappa B or nuclear factor kappa B. And essentially this is a transcription factor, a transcription factor are what tell your gene what to transcribe. So how does your DNA know what to do? Well, it's listening for messages all the time from signals from your body. And NF-kB is a signaling molecule that tells your DNA to make more cytokines, to make more inflammation. So when you activate sirtuins, it shuts that off. It also increases your metabolism, increases your insulin sensitivity, which we've talked about a lot on the podcast. If you want to be healthy, you have to be insulin sensitive. So it's through a whole series of different mechanisms, NAD is his multiple actions through sirtuins in addition to just powering up cellular energy. And some of the studies from David Sinclair are just mind boggling. He uses derivatives, so NR nicotinamide riboside is made into NMN, which is then made into NAD in the body. So this is a normal consequence of cellular reactions. So you can give NAD as a shot or as an IV, but if you want to take it as a pill, you have to take it as NR or NMN. And he, and David gave NMN to these mice. Now, these old mice. Now they had these mice treadmill, which I'm not a researcher, so I don't really know about it, but they had these mice treadmill that they have an upper limit because no mouse has ever run more than two kilometers. Like young, old, any mice, right? And so they had this mouse treadmill. It was like two kilometers and then it would just kind of turn off and it would like overheat and stop. And they gave this old mice NMN and the mouse ran three kilometers and broke the treadmill. So, it's pretty amazing. And even in some studies, it regulates all sorts of stuff like hormones and fertility. In some studies, they've literally been able to reverse mouseopause. So, take menopausal mice and give them NMN and they start menstruating and get fertile again. Wow. It's really trippy. So, that's just one example of one compound. Another one I think that's really important is is something that actually, and I think curcumin or this product I think are really important, which is regulating inflammation through, again, these variety of effects. But there's a compound called HTB, Himalayan Tardive Buckwheat derivative that has like 132 phytochemicals including quercetin and rutin, which quercetin also is a longevity supplement. So it contains a lot of these things, but it also contains a compound only found in this ancient grain, which isn't really grains of flour. called Himalayan tartary buckwheat, which has only been recently been recultivated after thousands of years of being sort of out. And because it's in the Himalayas, and it's called Tuhoba, and it actually is regulating some of the inflammatory systems that are involved in senescent cells and chipped cells. So as we age, some of our cells just get older and they don't really die. They're kind of like zombie cells, but they're not just inert, they're actually creating a whole inflammatory cascade. And then they're causing other cells to become senescent zombie cells. It's terrible. So you get this kind of wave of inflammation and so this can help to kill that. And there's something called chipped cells, which are cells that are from the bone marrow, from damaged stem cells that produce white blood cell. And you get these funky white blood cells in your body that are just generating tons of inflammation. So some of these compounds really help to regulate this inflammatory senescence thing. So one of the hallmarks of aging is cellular senescence, which means the aging of your cells. And how does that happen? The zombie cells is essentially what happens. And we can go into how they're created, but it's really fascinating how these natural plant compounds combat this. And what's also exciting Drew is there are so many other compounds, in addition to just three that are super powerful, like green tea, extracts, epigallocatechin gallates, resveratrol, you might have heard about resveratrol was the thing that was first sort of discovered, which is from red wine that helps to activate sirtuins to extend life by a third. So, if you actually take resveratrol from red wine, you give it to mice, they'll live a third longer, which is equivalent to humans being 120, right? Which is kind of cool. But then, how much resveratrol did they get?

They got a lot.

They got the equivalent of 1,500 bottles of red wine. well, I got the 1500 bottles of red wine, so don't try this at home. Okay. But what was interesting is that there was spirultral. And this was fascinating, and it's kind of wild. These Pathways, these conserved longevity Pathways that are really survival Pathways, when they're activated, they're so powerful that they have so many beneficial effects. So even though the mice kept eating junk food and not exercising, their. Metabolism got faster. Their exercise capacity increased, what we call VO2 max. They reversed their diabetes and insulin resistance and high blood pressure and even while eating crap. So I'm like, wow, what if you actually ate well and exercise and then use this as a booster? Amazing. So that's the thing. And there's also incredible compounds that are now looking at how we can actually help to extend life called fist fisting, which is F-I-S-T-I-N which from strawberries is a compound from strawberries, but turns out to be incredible longevity supplement. Sulforaphane, which comes from broccoli. Broccoli sprouts are the highest concentration of these. So this is a hugely detoxifying molecule, anti-cancer, it improves glutathione, it really helps with some of the key longevity pathways. So I think, you know, you've got these incredible compounds. And there's more, obviously, there's compounds from persimmon, there's compounds from lychees, there's berries, there's compounds in Chinese medicine. There's all these wonderful compounds that actually help to activate these longevity pathways. We were talking about AMPK and before, but quercetin, resveratrol, catechins, curcumin, all these things from the plant kingdom all regulate these pathways. So, do I think we should take three? Yeah. There's probably a lot more that are going to be coming around the pike. And, I think a basic longevity stack of supplements would be NAD, HTB rejuvenate, and I think vitamin D is up there for sure. But, and I would like to sort of see a polyphenol blend, like polyphenol blend. And if I could put it all in a pill, I would put in catechins, I put in resveratrol, I put in quercetin, I'd put in fisting, I put in curcumin. I put in a lot of these very important compounds that come from plants as a cocktail of various phytochemicals that all have very different effects. But that's what I would do.

It's great. I love it.

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There's a lot of ones that you covered there, Mark. Just a few questions on some of them individually. So in the case of NAD, because there's, you know, you mentioned NAD and then before that you have NMN and NR. So there's a few different supplements that are out on the market, you know, a lot of different people who are involved with different ones. I think you recently had like Tony Robbins on the podcast and I think he has a new company that you're an advisor to. So which form do you take and is there a difference between what you would recommend to most of your patients?

Lenny Guarente from MIT has really focused in on NR nicotinamide riboside, and he sells it through his company's involved with called Elysium, and the product is called Basis. And, I think, that's a legitimate, well-researched product. David Sinclair thinks that NMN is a better precursor molecule to give and is studying that extensively. not as widely available and there's sources in China, but harder to get for now. But I think his research is really coming along. And third, you can do it, those are oral. Third, you can do it as a sub-Q injection of pure NAD or an intravenous drip of NAD. Now, intravenous drip is hard, but the sub-Q injection is just like a diabetic needle. And I tend to use that one, but I also take the oral too.

Is that typically something like an IV drip? So it's administered by like a nurse? A doctor, yeah. But, does that be you going to like a wellness center or something? For sure. Where they regularly do those things.

Yeah, but you could do sub-Q every day, which is basically a diabetic syringe. You just do it yourself and you just buy the bottle and you dilute it. And, I use that on a regular basis. And, I'm sort of experimenting because I want to see what if I do all these things and I recheck my biological age, I'm going to get younger. So, I'm using myself as a guinea pig.

But, I'm doing things that are safe and I know are potentially effective and the side effect profile is low and the cost isn't exorbitant. Yeah, so I would probably say for most people an easier thing would be either to supplement with NAD as a pill form or NMN.

And, you know, if you Google it, NAD or NR. I think NAD is not really available.

You probably don't want to be recommending that everybody's out there go starts injecting.

No, no, but there's true niacin, there's bases, there's all these companies out there.

That are... Yeah, there's a lot of really good companies.

Thorne Research church has a whole bunch of.

So you believe in it strongly enough that you would say, like, if somebody was serious and had a good foundation. Yeah.

That this is an area that they could explore. Probably in the number one thing, I would say, to get your NAD levels up. And when my book comes out young forever in 2023 and February, you'll be able to understand more why I'm saying this. But it's, it's, it's, it's regulate some of the key Pathways for longevity that, that are so important. And as we age, our NAD levels drop. So restoring those NAD levels restores so many of our cellular processes to a youthful phase.

So, let's talk about resveratrol. And, still, there's a lot of people that think like, great, I'm gonna get it from wine. And, again, wine doesn't have as much resveratrol as we would need to hit comparatively for the clinical trials and studies that are out there on the research on resveratrol. So, would you put supplemental resveratrol in.

Your list of things? Yes, I did mention it. So, it's in part of the that I would do a polyphenol cocktail. And, it would include resveratrol, curcumin, epigallocatechin gallate from green tea, and quercetin and fustin and all these things that are now being studied. Because, the beautiful thing about these is they're, you know, if you don't OD on them, and I'm going to talk about that in a minute, and you get a reasonable dose, they are pretty safe and they're well researched and they're cost effective, and do we have enough data to say they're going to extend your life by a third? No. But do we know the mechanisms of action? Do we know how they work? Do we know the biological effects of them in real time? Yes. I mean, it's hard to say, I'm going to give you Drew these supplements at 40 years old, and I'm going to wait 80 years and see if you get to 120. It's like, sure, it's a hard study to do. So we have to go by intermediate things. And so the hierarchy is, you know, is there science? Is it safe? is it cost effective? Now, a lot of these molecules are not meant for us, right? They're plant molecules that the plant uses to defend themselves, their own immune system, their defenses, right? And they can be a little toxic in a way, right? Because they are trying to deter pests or they're trying to protect against UV radiation or they're trying to, you know, do something that is protecting them from some harsh environment. that's why this Himalayan buckwheat has so many of these compounds because it's grown in really harsh conditions in the Himalayas. And it turns out that there's this concept called xeno-hormesis. Xeno means foreign, hormesis means a stress that makes you stronger. So exercise is hormetic. In other words, exercise will cause you to tear muscles, to push yourself, but then you repair faster. Or hypoxia. short bursts of hypoxia of low oxygen states will actually cause your mitochondria to kick in even more and you'll get a souped up energy system by that. Or a cold plunge. I just came back from Antarctica, we did a polar plunge and now it's cold jumping in the South Pole with the icebergs floating around. But that activates brown fat, increases your metabolism, resets your autonomic nervous system. so many benefits. Saunas, and I just did a sauna cold plunge this morning. A sauna increases heat shock proteins, activates your, which helps refold proteins that are deformed that are a key part of the aging process. This whole phenomenon of proteostasis, which is keeping our proteins properly folded so they can do their right action. Well, there's a lot of insults that happen and that kind of gets screwed up. But when you take a sauna, it helps to fix that or it activates your innate immune system to help protect against infections or activate healing response in your body. So there's all these, these hormetic therapies. So the plant compounds are kind of a little bit of a poison almost. It's a little, a little dose is good, a little more, maybe not good. So it's kind of finding the Goldilocks level of all these things, but they basically are little stresses to your system that make your body go, oh, I better get my head together and figure out what to do to stay safe. And, and it activates various Pathways that are involved in repair and healing and reducing inflammation, increasing metabolism. So your body's really smart. And I think, you know, I always say disease is your body's best way of dealing with a bad set of circumstances. It's doing its best. So the beautiful thing that if, and this is really such a core principle of the foundational functional medicine is your body has an innate desire to be healthy. Its default state is healthy. It's not sick. You know, Andrew Weil talked about this in Spontaneous Healing. How do we activate our body's healing system? I mean, you cut your skin. you don't go, oh, I need you to close up and do this and recruit white blood cells and like get stem cells there and make new skin. Your body just knows what to do, right? And not just on your skin, but all the way through. So the question is how do you activate that? If you're nutritionally deficient, if you have no zinc, if you're low in protein, if you're low in vitamin C and deficient, your skin won't heal, right? Your skin won't heal because you don't have the raw materials, you don't have the right messages. And the same way with all these other mechanisms, we need the right ingredients. and so this is really what's fascinating in the longevity research is we're now learning about what are the ingredients that we need for longevity and what are the things that actually are really critical and essential. And a lot of them are these compounds from plants and a lot of them are these things that our body naturally makes that diminish over time with age but can be replenished and restored, restoring youthful levels of function and activity like the mouse that ran three kilometers and broke the treadmill.

So outside of people like piecemealing their own stack of all these things that you had mentioned. Are there any formulas or things that are out there on the market that are close or validated that are some of the things that you're talking about?

I'm still looking at it, to be honest with you, Drew. I'm very suspicious about what's what and I think a lot of products have window dressing or they're not the right forms or it's not thoughtfully designed. There are a lot of companies that are thinking about doing this. You can buy individual products of these, you can buy cocktails. Thorn has a lot of these. Designs for Health has a lot of these. There are companies that are looking at the longevity space and starting to design products that provide a lot of the things we need. Yeah. And as more of them come on.

The market, I'm sure we'll talk about them over here, but you gotta probably do a little bit of investigation, but at least some of the basics that you covered on the foundation piece, there's plenty of companies that make really good quality ones there. And there's plenty of companies that make really good quality NAD, NMR, sorry, NMN and NR. Thorne does have a really interesting product called Resveratrol that has a few of.

The ingredients that you mentioned, but the dosages are a little low. Yeah, it's resveratrol and phytostilbene and nicotinamide riboside NR. And it's fine, it's a great cocktail, I recommend it.

But I think there's more.

There's more, yeah, for sure. And the doses matter, you probably need more of stuff, like a thousand milligrams and they might give you 500 or 100 or 200, you need the right dose.

Yeah, and of course if you're working with a good practitioner, they can help you piece this together. And then who knows, maybe one day you'll come out with something so that.

You'Ll make my life easier and I'll just take that. Yeah, for very, very selfish reasons, Drew, I want to do it I don't want to be taking 15 bottles of pills. I want everything in one bottle.

So Mark, this is the part of the interview where we're going to go into some questions.

I feel like you put in a good- Are we done yet?

This is so much fun. I was just getting started. Okay, fine. And go off on any tangent that you want to. This is a really good opportunity for us to go into questions and they're right in alignment with some things you've been chatting about. So one of our Dr. Hyman Plus community members, which is your online membership community, people can go to your website to learn more about that. They ask, what is the best vitamin for brain health that you would add into your longevity stack? So, all these things that you've been mentioning, is there anything that people are really worried? I mean, the scariest disease on the planet are things like dementia and Alzheimer's and other stuff. Do you need anything about separate supplements just for that or does all this stuff work for those things too?

I mean, there's three things that are come to mind that are the most important, which is a B complex that regulates methylation, which is B6, folate, B12, and they're critically essential for healthy brain function. The second is fish oil we talked about, 60% of your brain is fish oil and vitamin D. So if you get a good multivitamin and a vitamin D and fish oil, you're covering those bases. That's really important. And then if you really want to get fancy, you can start with more mitochondrial support because your brain has more mitochondria than any other organ. I think your heart and brain are more or less the same. the brain actually has more. Every cell is filled with these energy producing factories and they need a lot of help. And so mitochondrial nutrients are a key part of longevity including lipoic acid, carnitine, glutathione.

I heard recently that melatonin is actually one of the most potent mitochondrial nutrients.

Yeah, it turns out melatonin is very helpful for for aging as well and can regulate inflammation. And it's pretty interesting. I think, you know, the, the, you know, we sort of think of melatonin for sleep, but actually it may be regulated regulating a lot of other really important functions that have to do with longevity. I would love to, you know, we're.

Not affiliated with them, but there's a product that I've been taking and I just love to give a shout out cuz I've tried so many different things. It's called herb tone. So it's plant based melatonin. and they have two different versions. They have a 0.3 milligrams, which is great for longevity. And a lot of people, a lot of practitioners were talking about including melatonin in people's stack when it came to helping support their immune system, especially for sure. For sure. And then there is another one that they make that's three milligrams of plant-based melatonin instead of the synthetic melatonin. And that was for people who struggle with jet lag or sleeplessness or other stuff. And it's a really great company that's out there. You can Google it and probably find.

It on Amazon and other places. Again, no affiliation with them. Amazing. I mean, it basically just helps with inflammation. Like you said, it can put a break on inflammation. It can do a lot of really important things with cancer and maybe reduce risk of cancer and other things.

So this next question again from our Dr. Hyman Plus community is around the topic of biomarkers and how do you measure your progress? So the audience member asks, Are there easily measurable biomarkers that can be assessed for whether these longevity supplements are doing anything and if you're heading in the right direction in the first place? So what are some of the things that you're using to look at all aspects of your life when it comes to knowing are you heading in the right direction?

I mean, I think it's complex, Drew. I think there's both the more traditional testing we do and there's some innovative testing around biological age that's happening. It's really kind of merging from the science. So the typical things that are really important to look at are the things that look at what is your nutritional state? We were talking to Inside Tracker, which usually your regular lab tests, but actually interprets them in a different way. So, look at your 43 different biomarkers that are pretty available on regular blood tests like your vitamin D or your homocysteine or C-reactive protein or your lipid levels, cholesterol, blood sugar, stuff that's pretty commonly done. I mean, some of them, not all of them. And then they analyze that and they say, okay, where are you off from the ideal? Like, where are you off from optimum? Because homocysteine, which is a measure of your B12 B6, the lab says 14 is good. but ideally it should be 6 to 8. If your level is 14 or over, your risk of dementia goes up by 50%. So you don't want to go on the regular lab values. So there's a lot of those conventional tests which are great. Then there's, you know, if I had like two tests probably to actually look at, one would be a glucose tolerance test with insulin. It's an old test. Doctors don't measure it properly. They use glucose tolerance test for seeing if you're diabetic or for women who are pregnant. They don't do it with the average patient and they certainly don't measure insulin fasting or one and two hours after, which is probably the most important medical test you could do to figure out how you're aging.

Fasting insulin.

Fasting with also a glucose tolerance test. So you basically drink the equivalent of two Coca-Colas of glucose. Yeah. First you take your blood sugar and you take your insulin. Then you drink two Coca-Colas glucose, and then you measure your blood sugar and insulin an hour later and two hours later. And if your insulin is high, that is driving the longevity pathways in the wrong direction.

Unnecessary aging, inflammation, all these things.

Diabetes, weight gain, heart disease, cancer, dementia, all the downstream consequences, and accelerating all the hallmarks of aging. So it's really bad. So, that's a really important test. The other one.

Just one clarification on that. Fasting insulin, very cheap test. I think it costs anywhere from $13. You can go to your regular doctor and ask them for that and be included in your medical work. If you're gonna go to your doctor and ask them for a glucose tolerance test, you probably wanna find somebody that's.

Familiar and has maybe- They don't know how to interpret it. I've had some people, I said, go.

Do this with your doctor.

I don't wanna do it. I don't know how to interpret it.

I'm like, and do you have to.

Look for an insulin? That's like saying I'm not gonna listen to your heart because I don't know how to listen to your heart sounds.

So it's irrelevant. Well, at least I found out. Figure it out. You're a doctor. So then how do you navigate? If you're talking about like literally this is one of fasting insulin, that's pretty straightforward. And again, we've written a bunch of newsletters on this topic. So we have the updated recommendation for what the optimal ranges are.

But again, you want people to be under five for their fasting insulin, right? And then ideally even maybe somewhere between.

Three and three and a half grams of protein.

Yeah, I mean my level when I test is often less than two fasting. I mean, you just don't want to have high insulin because it's just in your resting state, it prevents all the longevity pathways from being on. If your insulin's high, your longevity pathways are shut off.

Totally. So then how would somebody navigate if they want to go and get this glucose challenge test? Is it that, okay, you just have to get lucky and- well, here's the.

Thing, or do you go to an integrative doctor? I mean, you go to a functional medicine doctor, an integrative medicine doctor, There are now companies that you can order stuff on your own. I'm involved with a medical director of a company that's launching soon called Function Health, which is a company that you can get $15,000 for the test for $1,000. All the things that are- Will they.

Do this glucose test?

Yes. Yes. So, all the tests that and the advisor and medical director, so I've determined what the tests are, what the interpretations are, not just what the tests are. Because if you go, oh, your interpretation of homocysteine is 14, that's okay. Not okay, right? If your insulin's 15, which it says on a lab test, that's not okay. It should be less than 10, ideally less than five. So all that is possible. And I think we're gonna be democratizing lab tests and patients' own ability to self-assess and treat themselves and ways that are safe and also when to know to go to the doctor, because not everybody can do everything on their own.

Can I ask one more question about the glucose challenge test? Because I know people are gonna be curious about this. And I'm actually curious because I've never done that test before. So, when you're going and you're doing this glucose challenge test, you have to be at the clinic because you have.

To take a before and after.

Yeah, two hours. So, you're hanging out there for a little bit. Yeah. So, ask around, talk to an integrative doctor, talk to a functional medicine doctor, you know, look for somebody open-minded. And typically speaking, because a lot of, would it OB-GYN be more likely to be knowing how to navigate because they're working with gestational...

I mean they might, but they don't measure insulin and they don't know how to interpret insulin.

Okay, got it. So this is really looking for somebody.

Who'S in the know. Yeah. And I've talked about this before, but I had a patient that, you know, 25 years ago, they just kind of turned the lights on for me about this because she was an apple. And we've talked about her before, and she really big, you know, round tummy, skinny arms and legs. And I got this woman is diabetic or pre-diabetic or she's in trouble. Right. And I measured her blood sugar perfect. And then I gave her a glucose tolerance test. blood sugar absolutely perfect, like not even a little bit high, even after having two Coca-Colas. Her insulin on the other hand was off the chart because her insulin was trying to keep her blood sugar down. And what happens is your insulin keeps going up and up and up to try to control your blood sugar until your pancreas gets so tired that you can't manage that anymore and then you become more insulin resistant at the cell level. and then your blood sugar starts to go up. But rising blood sugar is a very late stage phenomena. Like by the time your blood sugar goes up, you're way down the road of pre-diabetic and metabolic bad health. The first step is your two hour insulin goes up, then your fasting insulin goes up, then your two hour sugar goes up, then your fasting sugar goes up. So it's a fourth thing that happens in the whole process. And we're, that's the only, we're looking so far down the stream, we're not, we need to go upstream. So that's one test. The other is a body composition, which is a little hard to get, but look at your where the fat and muscle isn't distributed in your body. If you have a lot of visceral belly fat, that is the number one driver of aging.

So, you got to get rid of that. And, that's sugar and starch.

That's basically what I-- A lot of gyms have these scanners. I think they're called like-- They're a DEXA scanner. They have body composition scanners that look at your total body composition, which is looking at just your total body, which aren't as accurate. You want to know what the compartments are. So, for example, if you have strong.

Arms and legs, but all the fats.

In your belly, you might get an average that looks okay, but it's not okay. Right?

So, somebody want to do that test, where would they go?

You'd have to go to, it's like the same test that doctors use to check for osteoporosis. It's a different software program and it's called Dual Energy X-ray Absorptiometry or DEXA. And essentially, it's a way for very, very low radiation, less than flying across the country, seeing what your bone density is and your body composition is. And, and where that is, is important. And then there's a few other things. And obviously you want to check your lipids and your vitamin D and all the homocysteine and all that stuff, inflammation markers. But there's a whole new tranche of testing that's emerging that's helping us really look at the aging process itself. And the two that are really important is, well, maybe two, three, four. It turns out there's something called your biological clock. and Stephen Horvath discovered that the patterns of little tags on your DNA in the epigenome, when the epigenome is basically the control mechanism that controls which genes get read. So your genes are like the piano keys. Your epigenome is like the piano player. They can play Jazz, Rock, Blues, whatever. Right. Classical, just with 88 keys. So in the same way, the epigenome determines which genes are silenced, which genes are turned on. And so it turns out that this pattern of DNA methylation, we call it, these epigenetic tags, like bookmarks in your book of life, determined when you look at them in the ways he looked at them, actually determine your biological age. So I just did a test to look at my DNA methylation. I'm 62, but biologically I'm 43. So my biological age is- so you.

And I are almost the same age.

Almost the same age. I'm gonna get younger than you soon, so watch out. So, I'm working to get to 25.

I'm still 39, so.

And, and then I did my telomeres years ago when I was 58 and they were 39. So I'm about 20 years younger biologically than I am chronologically. Uh, and then there's, you know, telomere testing, which, you know, there's controversy about, but your telomeres are a good indicator of your long, your biological age. I know there's other testers are not directly measuring your biological age, but are measuring things that are so important that indicate you're aging fast. around inflammation. And there's a guy at Stanford, David Furman, who's looked at, you know, thousands and thousands of blood analytes, compounds that, you know, when you go to the doctor, they do like 20 tests, 30 tests, 50 tests, 100 tests. You look at thousands. You've got, you've got tens of thousands of molecules floating around your blood that most of we, which we just ignore, we don't check for. And he's been agnostically just looking for what was the correlations between these abnormal inflammatory markers and chronic disease and death. and it was this huge AI machine learning, very sophisticated science technology. But at the end of the day, it's like there's these four inflammation tests that are extremely predictive of your rate of aging and disease. And so you can actually check it and then intervene and then check it again and see what's happening. So it's called I age, and it's going to be out probably in the next few months. And there's, these are all emerging. And then there's, there's tests that look for cancer, which is kind of interesting thing because you can have latent cancers that are out there that you might not notice. And before you kind of had to wait till you had a subtle tumor or had a symptom. I mean, there's screening tests for colonoscopy, pap tests, breast mammograms, but it's pretty bad in terms of rest of cancers for screening. I mean, my father died of lung cancer. My sister died of she had non-Hodgkin's lymphoma and she died of bile duct cancer. So it's really hard to get those early. Turns out that now there's something called a liquid biopsy. what does that mean? I don't have to take a tissue sample with a knife, right? You literally just get a blood sample and you can find the proteins from over 50 different cancers in your blood if they're there. So if you have some really small cancer, I mean, a solid tumor is typically been going for 20 or 30 years before you can see it on an MRI. Like, that's right. But with this test, you can actually. pick up early signs of cancer and then 90 to 95% of cancers that picked up early are cured. So it's a way of doing sort of a, it's not really a longevity test, but it's a way of actually hacking a little bit of longevity so you don't end up getting something that you wouldn't be able to find otherwise.

And I know we covered a lot of different things, but just a couple takeaways from that, from what you shared is, you know, for those that are not getting their fasting insulin on their normal metabolic health labs that come back, that's like one test. That's like a no-brainer. No-brainer. That's a no-brainer. The glucose tolerance test at the two-hour level with the insulin response, that might be a little bit more tricky. It might be harder to navigate. But if there's doctors that are out there that are doing this test regularly, reach out to us and we'll maybe put up a little website to make.

A listing of people that can follow that area. Yeah. And, there's a surrogate test for insulin resistance that I really like, which is a special kind of cholesterol test which you can get at LabCorp. you can get a quest, it's not very expensive, it's really the 21st century cholesterol test and most doctors still don't do it. The one from LabCorp is called NMR, which essentially puts your cholesterol in an MRI machine and sees the particle number and the size and looks at all your triglycerides and your HDL and the sizes and that gives you an indirect indication of insulin resistance. Because if your particles are small, you have a lot of particles, if your triglycerides are small, if your HDLs, if your triglycerides are large, But your HDL and LDL is small, you know there's a problem. And it gives you an insulin resistance score out of zero to 100. That can be really helpful. And the one from Quest is called.

Cardio IQ, which is very similar. Yeah, especially important for those people. We have a news letter coming out on the topic of LDL. If you think that you eat a really clean diet and your HDL is going to be a little higher and people have natural variation with sometimes their LDL and your doctor sometimes gets worried and they're wanting to put you on a statin, But in that instance, that'd be a good opportunity for somebody, if they want to go deeper, to find somebody who will run one of these tests on you so that you can know, is that higher LDL really a problem?

Exactly. Or is it okay for you? I mean, honestly, Drew, this should just be standard of care at this point. It's been around forever. The data's so clear on this. There's no ambiguity. I mean, it's just doctors have habits. Their lab test requisitions have the same thing on it's had for 20 years.

They don't change it. And partially it's an interpretation thing. if you're not as familiar with that test.

Yes. But that's like the worst rationale I ever hear from doctors. Like, well, I don't know how to interpret it. Well, learn. You've got to keep learning as a doctor. It's not just what you learn in residency. Things change. I'm constantly learning. I mean, I spent six, eight hours yesterday just studying scientific papers and learning all kinds of new stuff that is certainly new, not stuff that I ever heard about in medical school. And it's really new discoveries since I graduated. you know, it's like science and medicine are not static. And, and unfortunately, you know, doctors, it takes up 17 years to get what's discovered in science into practice on average. And, and often people get in their little ruts and habits and totally so much compassion for them, especially after a.

Crazy year of COVID and trying to help all these patients and everything that's there. But shout out to all the doctors that listen. And, yeah.

And, you know, the thing is, work with your doctor. in a way that you can find a colleague who's going to collaborate with you and be a partner as opposed to the guy in the white coat who tells you what to do and.

Doesn'T give you a lab test results. Totally. One more thing about that and testing and again how this came up is that somebody from the Dr. Hyman Plus community was asking, How can you measure the progress? Would you also throw in how important do you think it is for people to get a nutritional screening? And, are there a couple labs that you want to shout out that people could look at as possible?

I mean, honestly, I do most of my nutritional testing through LabCorp or Quest.

You know, you do. So, these advanced ones that are looking.

At all the deeper panels and advanced nutrient testing. Yeah, I mean, my favorite is from Genova called the Ion Panel, an individual optimized nutritional panel. And, for me, and they were crazy, some learning curve to learn how to interpret this, right? I look at all the amino acids, I look at all the fatty acids, so I can tell someone's Omega-3 deficient. So, I'm not guessing. I look at all the antioxidant levels. I look at oxidative stress levels. I look at vitamin D levels in this test. I look at magnesium and all the mineral levels. I look at heavy metals. I look at something called organic acids, which is basically urine test that looks at all these metabolites of different pathways that relate to nutrients. So, you can tell if you're deficient in carnitine or B2 or CoQ10 or if you have B vitamin issues or you're low in biotin or you're low in magnesium or you're low in glutathione. and I can tell a lot from looking at these different tests. So that's my go-to. But I think for the average person, do an Omega check from your Omega, this is all through regular labs and your regular doctor. Omega check test, which is Omega-3s and all the fatty acids, get your 25-hydroxy vitamin D3, that's vitamin D test, check your homocysteine level, which relates to folate and B12, check your methylmalonic acid, a more sensitive indicator of B12. And doctors just check B12, they don't check this. check your red cell magnesium if you want to see if you're low in magnesium, because typical serum magnesium is really a very poor indicator and even red cell is not as good, but you can get a good idea of what's going on there. So those are just foundational things that you can easily, you can do plasma zinc levels, you can do iron levels in your blood, and you can do ferritin levels. So you can do a lot of the common nutritional factors you can test.

Easily through regular lab tests. It's not expensive. Yeah. Just gotta ask your doctor to run those. This is a really great question. What should I take if I'm on a budget? Tell me what I should absolutely not sacrifice. And I think that one of the things that that just brings up is that, look, if you're really on a budget, sticking to the foundations of the things that are the normal things that you do, that's going to be the one of the people. There's so many people that don't even get that right. There's so many people that don't work out on the basis that they need to work out to support muscle health and avoid muscle loss as they get older. There's some people that don't get the sleep that they need. So, if you're truly on a budget, which supplements often are a splurge that.

Are there, focus on the basics. What else do you wanna talk about? Exercise is the poor man's NAD. Why? Because exercise works through activating sirtuins, which are these master regulators of longevity and metabolism and insulin resistance and DNA repair and inflammation control. So, just by exercising, you're activating this whole cascade of longevity effects without taking an AD. So, there's a lot of ways to do it. Dietary restriction, basically time-restricted eating. Eating within an eight to 10 hour window, 14 hour, 16 hour fast every day, activates the same pathways and more.

Hot and cold exposure.

Hot and cold exposure.

You've done a bunch of classes.

You can take a hot bath and a cold shower. Or go in a cold bath. these don't have to be expensive. And these are things that are available to all of us. Just focusing on your diet and the quality of your diet is hugely important. And yes, it can be expensive if you want to eat only regenerative organic, grass-fed, blah, blah, blah. But if you focus on just eating real whole foods alone and increasing your plant intake, even if it's not the greatest soil, even if it's still good, and focusing on a phytochemically rich diet is super important. focusing on a diet that's rich in the right amino acids and the right types of carbohydrate and the right types of fat. So diet is hugely important. I've written about that with the Pegan diet. And then if you're, you know, you want the extra, extra, you know, I think there's a lot of data on this. I mean, first of all, a cost benefit of what you're going to save in terms of your good health and lack of having to deal with pay for disease later is important to consider. Right. So you're not just, it's like, why do you change the oil in your car? so your engine doesn't blow up, right? You don't want to pay for a whole new engine, so you put the oil in your car every whatever, 10 or 50,000 or 30,000 miles. So in the same way, there are some basic supplements that don't cost a lot that are on the 8020 rule, way more, maybe like the 95-5. So multi-fish oil vitamin D, that really can be had for pennies a day. Pennies a day. And when you think about what you spend money on, it's one cup of coffee at Starbucks is probably a week worth of supplements. So mature. I think it's just look at your priorities, look at what you spend your money. There's a really wonderful book I read when I was younger that really influenced my thinking called youd Money or youe Life. And it's really about really quantifying the work and the energy it takes to make money. and the hours you spend with the value you get when you spend it. How are you spending your money and doesn't equate to your values? If you care about health, if you care about, but if you're spending tons of money on, I don't know, drinking tons of alcohol or wine, maybe that's not your best strategy. Or maybe you're spending tons of money on video games or whatever. Where do you put your time and your money and your value? We always can look at, even if we don't make that much money, we can look at how do we spend our money, where is the value creation in our lives, and how do we be more strategic about it?

Here's another great question that we have, which is somebody asking, I take a lot of supplements and I'm a little bit worried about, you know, can one impact the other, the timing of these? And I know it's a big picture question, but any resources or places that you would guide people to who are concerned about that, if they're taking a lot of supplements, and does one counteract another? Does this?

Yeah, I love this question.

How much is that worth?

I love this question. I mean, first of all, do you have any idea the amount of compounds, medicinal compounds and nutrients in an average meal that's healthy, not your processed food, but like I ate last night, I had mushrooms, garlic, bok choy, grass-fed steak and a Japanese sweet potato, which was a cornucopia of compounds that are extremely active biologically in my body. And, I could bore everybody and go through it, but essentially you're eating like tons and tons and tons of stuff. So, your body is so smart, it knows what to do. Now, certain things you shouldn't do together, right? If you're taking charcoal capsules because you have gas or because you're taking it for some mold treatment that can absorb all the nutrients. So you don't want to take them together. And there's certain things you need to take an empty stomach to do better. Certain things you can take with food to do better. Like, for example, the fat soluble vitamins, vitamin K, D, E, the vitamin E, they require fat to be absorbed. So you need to have it with a meal. But, you know, my view is, when is, when is the right time to take supplements? When you remember, you know, and, and, you know, what do I do personally? I just take mine. I take probably a handful of stuff every morning and I might take some stuff later in the day too. But I try, I don't know. I'm always worried about when and what, no, I don't. I just like, my body knows what to do. It's gonna handle it all. They don't counteract each other for the most part.

Right, and if you're on prescription medications, obviously there might be some considerations that you have to think about.

That's important, true, because there's two things. Doctors often talk about, oh, don't take this supplement, don't take fish oil if you're on Coumadin, don't take vitamin E if you're on blood thinner, right? Because they're talking about nutrient drug interactions. But what about drug nutrient interactions? And a lot of drugs deplete nutrients, right? So you take a diuretic for blood pressure, it causes you to lose magnesium. Well, what's the cause of low blood pressure, high blood pressure, low magnesium? Or they say, you know, take this acid blocking pill because you got heartburn. Well, that blocks the absorption of B12 and zinc and magnesium and calcium, leads to osteoporosis and all kinds of problems. So, it leads to depression and B12 deficiency and cognitive impairment and neuropathy. So, yes, the drugs often interfere with your nutrition. So, it's not just the one way around, it's both ways.

Yeah, there was a really innovative company, I forgot their name that was working on trying to address this for some of the most common drugs they reached over to you on email. I forgot their name, but we'll put.

Them in the show notes. Yeah, yeah, yeah. Basically, there's a company that's actually focused on the science of how to mitigate the effects of drugs. So, for example, you take a statin for cholesterol, it blocks the enzyme that makes CoQ10. CoQ10 is necessary for your mitochondrial function for energy. All the things we've been talking about around longevity switches all have to do with the mitochondria. So, you're kind of gumming up your mitochondria and you can't produce energy. which is why your muscles hurt. It's like after running up a mountain, your muscles hurt. Why? Because you just depleted all the energy in your muscles. But when your muscles hurt without exercising because of a drug, it's because you're depleting the energy in the cell with a drug that blocks a key compound, CoQ10, that is necessary to make energy. And I could just go on all day about examples, but you get the idea.

All right, Mark, we have a few more minutes here. Let's try to do a rapid fire. I don't know if that's possible, but Metformin was in the news recently and somebody here has asked asking about that because they're saying, what about metformin for longevity? And, have you seen some of the new stuff that was there?

Yes, absolutely. In fact, yesterday I was literally working on this part of my book around the effects of metformin. And again, earlier I talked about these nutrient sensing pathways that regulate our ability to actually build and grow new tissue or to clean up and recycle and get old parts out. So, you need both of those. So, you need the demolition crew and the construction crew. Metformin acts on one of these nutrient sensing pathways called AMPK and it turns it on, which helps improve blood sugar control, but has all these other effects of AMPK. AMPK inhibits mTOR, which is good because it increases autophagy, so cellular cleanup. It activates sirtuins, which then improves DNA repair and inflammation. There's all these wonderful benefits of activating AMPK. and metformin does that. But is that the best way? The only way? Well, it's again looking for the silver bullet. I think there's a lot of ways to activate AMPK just by time-restricted eating, for example. Simple. And we should really pay attention to the science of actually how we can regulate these pathways without necessarily medication. Now, that's not to say that there might not be a use for metformin. that it might be okay, but it actually has side effects. It's not completely side effect free. It's generally well tolerated. It's very cheap. There's all these new class of drugs also being developed called cinelytics that help with the senescent cells, the zombie cells. There's drugs called rapalogs, which are imitating rapamycin, an ancient compound found in Rapa Nui on Easter Island that actually inhibits this pathway or silences mTOR, which allows your body to clean up all the garbage through this recycling process called autophagy. So, there's all these ways to do this. And, I think there's going to be drugs that are going to be part of the longevity suite of treatments. But, I think the basic foundational stuff of lifestyle and the right supplements can get you probably 90% of the way there. Yeah.

And, when I was saying Metformin was in the news, I haven't had a chance to drill down into this study, but, you know, headlines from CNN, Men's use of diabetic drug just before conception is linked to a 40% increase in birth birth defects was on metformin specifically.

More birth defects taking the drug.

What's that? Taking the drug. Taking the drug, yeah, exactly. More birth defects taking the drug.

Yeah, exactly.

More birth defects taking the drug. So there's a lot that we don't know. Every prescription medication has to be sort of drilled into and is going to have other aspects. So we just need to look at that. And we have to look at also naturally when we are doing a lot of these studies that are there, the biggest actually wrote a newsletter on this. We'll link it to the show notes. But the biggest study showing compliance and results for diabetes, like the largest trial that was done, publicly funded trial, not funded by the drug companies. It looked at metformin versus placebo versus people who just had really strong coaching and were given lifestyle recommendations and exercise and taught how to cook. And the group that did the best was the group that wasn't on anything at all. So you never really think about drug companies don't necessarily do trials against compared to what?

Compared to what?

There's always great research around metformin and it's a big reason why it's a a darling drug in the longevity industry, if you're including a lot of other lifestyle basics, you may not necessarily need it and you can hedge against the risk by not taking it.

And here's the thing, Drew, that people need to understand is that these pathways that these drugs act on are not drug receptor pathways. There are bodies listening, basically like a satellite dish, listening to the communications from our lifestyle and our environment. and so you can activate all these pathways through things that have activated them for hundreds of thousands of years. The phytochemicals in food, exercise, restricting calories for periods of time, all these things that our bodies naturally did as part of evolution were so adapted to. And it's beautiful. It's like, so that's what I'm really interested in. How do we teach people these fundamental pathways so they can learn how regulate them through the most natural and often cheapest pathways.

Two more questions here and we'll wrap up. Any overrated supplements? Just something that you want to get a chance to talk, that's maybe getting a lot of attention or people put a lot of interest in it, but it's like, maybe we should hold back a little bit in our exploration. Is there anything that you feel like people are either overusing or putting too much weight Great question.

I've never really thought of that.

Naturally, anytime marketing gets involved, you know, there's always somebody that's out there that.

Wants to make money. Yeah, if everybody is promising this is a fountain of youth, there is no, there is no fountain. There's dozens, not only dozens, there's hundreds of different pathways, mechanisms, and systems that all have to be functioning and they require a broad array of interventions. It's not going to be like a longevity pill. That's it. So, there's a lot of this stuff. And, the same with supplements, there's no perfect pil or thing that's going to work. I think if there's anything that in my mind, and I'm still agnostic, but based on everything I know, I think metformin probably works, but I think other things will work better that we can do that are non-pharmacological.

On the topic of LDL, this is one from our live audience right now from the Dr. Hyman Plus community. Are there any supplements that can help with lowering cholesterol, specifically the small particle LDL? and I guess this also just comes back to, do you need a supplement for that or is lifestyle gonna make a difference?

I mean, listen, if you have really small particles, you could take anything in the world, if you're not gonna change your diet and get rid of starch and sugar, it's not gonna get fixed, right? I mean, you can take tons of niacin as a drug, you can take statins, you can take the Repatha drugs, the PCSK9 inhibitors, that's gonna help. But, you know, the reason your particles are small is because you have pre-diabetes so fix the pre-diabetes and reverse it with lifestyle and exercise. It's gonna work way better. Minimize sugar, refined grains.

Those are gonna be the biggest contributors.

To 10-day detox diet and exercise. And you'll be amazed what happens.

Yeah. As somebody who had, even though I thought I was really looking at, like, the sugar in my diet and the included sugar, the amount of prior to wearing like a continuous glucose monitor, the amount of, you know, oat milk or almond milk, right? Liquid calories and also the quantity of I used to have like, I love sweet potatoes, but like I used to literally base like an entire meal on a bowl of sweet potatoes on its own. And again, nothing wrong with having sweet potatoes and those other things, but there are certain vegetables in high quantities that essentially it's like eating a lot of sugar, right? Exactly. And I was doing a lot of, because this was the trend of a lot of like the flowers that are made out of tapioca, cassava, cereal. I was eating a clean diet, but it was a clean diet of packaged foods. And my LDL, small particle size, shot up. As soon as I cut those things out, it started to radically come down.

Exactly. A friend of mine found this healthy vegetable snacks and she was showing me this thing and I was like, Is this healthy? And, I'm like, let me look at it. And, it's like, oh, it's tapioca and cassava flour. Oh my God, these are fine, but.

They'Re super starchy and it's gonna high glycemic. It's gonna drive up your sugar. One other thing on the topic of LDL, you recently had Max on your podcast, a mutual friend of ours, Max Lugavere. Love Max. He has a little hack that he put out there. Now, I don't know if it affects small particle size LDL, but he reduced his LDL by 33% by Switching from a French press to using now a paper filter, like an unbleached paper filter, because the paper filter removes out cafe stall. And cafe stall is one of the compounds inside of coffee. Specifically, you get it from French press if you're making it that way. And if you're not using like a filter that has a dramatic effect on your LDL levels. And there's tons of scientific research around this. Like I went through all the papers of the day with our writer Taylor, and it's pretty mind blowing.

So you can't use the gold filters they have now. You got to use paper.

It seems to be that paper filter in particular is the thing that ended up working. I don't know about the mesh filters if they're too porous.

Yeah, it's unfortunate because paper is cutting down.

Right, but you can find unbleached paper, unbleached bamboo paper filters. And if you go on Amazon, you go to your natural health food store, you can find unbleached, right? Because a lot of those paper filters have toxins inside them, other stuff. So there's a lot of eco-friendly and cleaner paper filters.

If you love that last video, you're gonna love the next one. Check it out here. We have muffins, bagels, bread, pastas, right? I mean, it's just we have so much flour and that drives your body to think that there's high levels of sugar because this flour is actually worse than sugar for your blood sugar.