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you

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Hey everyone, it's Mikki here. You're listening to mikkipedia and this week on the podcast I speak to Michael Snyder, PhD. He's a professor of genetics at Stanford, an expert in understanding why people respond differently to various foods, supplements, behavioural and prescription interventions. And we dive into all of this. We discuss the links between metabolic and gut health, the use of wearables for the general population.

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how our genome can influence how food affects us and more. Such a great and interesting conversation. And I first heard of Professor Mike Snyder on Rhonda Patrick's Found My Fitness podcast. This was several years ago. And in fact, he just did a deep dive on the Huberman Lab as well. For those of you unfamiliar with Mike, Professor Michael Snyder is an American genomicist.

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Chair of Genetics and Director of Genomics and Personalised Medicine at Stanford University and the former Director of the Yale Centre for Genomics and Proteomics, was elected to the American Academy of Arts and Science in 2015. During his tenure as Chair of the Department at Stanford, the US News and World Report has ranked Stanford University first or tied for first in genetics, genomics and bioinformatics under his leadership.

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Snyder Lab was the first to perform a large-scale functional genomics project in any organism and has developed many technologies in genomics and proteomics. And these technologies have been used for characterizing genomes, proteomes, and regulatory networks. Snyder has co-founded companies in genetics, genomics, and personalized medicine, including Personalis, a company that develops software to interpret genomes after sequencing. January AI, a health startup.

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Proteometrics, Affomax and Q-Bio. Dr. Snyder received his PhD training at the California Institute of Technology and carried out postdoctoral training at Stanford University. He is a leader in the field of functional genomics and proteomics and one of the major participants of the ENCODE project and a principal investigator of that project since its inception in 2003. And we dive a little bit into that in today's interview. I have got m

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links as to where you can find Professor Mike Snyder over at Stanford, his book on X, LinkedIn, Facebook and YouTube and these are all in the show notes. I think you guys are really going to love this conversation. Before we crack on into it though I would like to remind you if you're listening to this on Wednesday when it is released I have my webinar taking place today at 1pm and 7pm NZT and it is free and it is going through some strategies that help you stay

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strong fit confident in the festive season where a lot of people can feel sort of anxious and unsure about food choices and exercise so sign up it is being recorded if you can't make it live and I'll send it to you after the fact. I'd also like to remind you that the best way to support this podcast is to hit the subscribe button on your favorite podcast listening platform that increases the visibility of micipedia and amongst literally thousands of other podcasts out there.

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So more people get to hear from the experts that I have on the show like Prof Mike Snyder. Alright team, enjoy this conversation.

03:37
Prof Mike Snyder. Mike, thank you so much for joining me this morning, New Zealand time. It's the future here. So you're looking at the future. All right. Love it. Love it. So really great to have this opportunity. I've been following your work and what you do for several years. I think I first heard you on Rhonda Patrick's podcast several years ago now. And ever since, it's it's fascinating stuff that you work on. Thanks. Yeah. Now we're having a lot of fun here.

04:06
Yeah, nice one. And I often wonder this, people in your position, Mike, you're a scientist, you have to think quite mechanistically about concepts and as a result, or as they relate, I'm sorry, to the human body. I'm really curious to know sort of if there was a moment when you had that light bulb, like this isn't just biology as a concept, but literally you can change your own health with the stuff that you're looking at.

04:36
Yeah, I guess our work has kind of evolved from mechanistic to becoming very translational. think it's kind of a natural progression just the way things work. I mean, putting things a little historical context, used to think that used to be the theme. People would study genes and proteins one at a time. And then our lab became known because we actually set up the first project to sort of study all the genes and proteins involved in a biological process. This idea of

05:05
systems biology, if you will. So we were doing that to study biological problems. And then it became kind of natural to apply that to medicine. And that's when things really kicked off into the space that you probably got to know me through, which is the idea of taking very, very big data, very global looks at people's health states. And I guess we started out trying to solve diseases like autism and things and realized we don't really know much about health.

05:31
Why aren't we studying health and following health and tracking health? And so that's kind of how the whole thing evolved. But probably the biggest aha moment was way back when was let's look at everything as a system, not just these individual compounds. And if you think about medicine today, it's very much that way. You have a cardiologist who, you know, make sure you don't die of a heart attack. You have a diabetes person who wants to make sure your glucose is under control. And then there's, you know, autoimmune people and things like that.

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Nobody's looking you as an integrated entity. And that's a big, big deal, we think, because you may know, like, and I'm a classic textbook case, if I go on statins to help better control my, you know, my bad cholesterol LDL, my glucose goes up. I, my cardiologist kept telling me, Mike, why don't you, um you should increase your, your statins. I said, no, because then my glucose goes up and

06:26
You know, you're just trying to keep me from getting a heart attack. You don't care if I die of something else. He's a friend of mine, so could talk to him kind of honestly that way. Yeah, it's interesting you say that because I often look at like big epidemiological papers and think, you know, they look at things in terms of like overall cardiovascular disease risk or overall sort of cancer risk with certain things in the diet. uh

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There's often some disparity between whether or not you'll die from cardiovascular disease or does it all cause mortality? you know, what people focus on or what tends to be more important seems to depend on who's asking the question. Yeah, I think that's true. But I think the world of the future is going to be looking at that in terms of you, what you're at risk for, what your trajectories. And that's the power of collecting a lot of data around a single person. You can see

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Like in my case, I now I'm a type 2 diabetic managed for the most part, like to improve it further, but I will track certain things because that puts me at risk for all kinds of things, cardiovascular disease, for example. So I think knowing, and then if you ever get your genome sequence, I don't know if you've had that, Mickey, but if yeah, then you want to know what that tells you about what your risk for us, so can keep an eye out for those things and maybe adjust your lifestyle to help avoid it.

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Well, this is interesting because I have had my genome sort of looked at through a company called FitGenes and they do tend to update their database every once in a while to give me more information on it. But how much do we know about the interventions that supposedly optimize for your health at this point in time? Like, do we know enough to be able to say, this is your genome, this is what you should do?

08:10
A little bit. think the things that are most informative for your genome are these single gene mutations that you've probably heard of BRCA. And there's another thing, there's about 70 or 80 genes like that, that if you have a mutation, puts you much, much higher risk. So if you're a woman who has a BRCA mutation, you you should be getting screen for breast and ovarian cancer at a much higher frequency than if you don't have that.

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Not only that, a lot of women, typically when they go past childbearing years, they may actually do prophylactic surgery, have their breasts and ovaries removed so that risk goes away. So there are things you can do. So those are the so-called, they're called highly penetrant changes in your DNA that you can watch out for. Other things are a little less prescriptive and there's a probability most diseases like diabetes, even arthritis, things like this

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They tend to be what are called complex diseases. Those are thought to be due to common changes, but a very small effect. And if you're unfortunate to get a lot of uh the bad, if you will, variants, well, then you're at higher risk. And if you're, you know, fortunate to not have those, you'll be at lower risk. But that's very hard to predict. We're a long ways from being.

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Good at that. And last year at the very, very severe end of what they call the risk or actually am I my diabetes was predict that way, but I'm one of the few people that that worked for. Yeah, it's interesting. As I understand it, your diabetes um not came about, was was in part related to a virus that you had, Mike. Is that it? was. Yeah. So it was kind of interesting because someone who is very expert at predicting these complex diseases.

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analyze my genome and said, Mike, you're at high, very high risk for type two diabetes. And, you know, and ah I wasn't aware of it running in my family. In hindsight, it might've been there. I grew up in rural America where people died of old age, which means they didn't really know what they died of. ah And so in hindsight, it might've been there, but I was, so that was news to me. And when we, I moved to Stanford about 16 years ago, and that's when we set up this idea.

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about doing very, very deep data collection on people while they're healthy to understand what their healthy profile looked like. So we started with me and then later with about 109 people we were tracking. And from my genome, it was predicted the high risk for diabetes. then once you know it about a year and a half in the study, did become diabetic, as you point out, right after a respiratory syncytial virus infection. That's a very common virus, by the way, especially in kids.

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When adults get it, they often get it more severe, which I did. I was bedridden for a few days, it hit me kind of hard and I became diabetic right after that actually. So we think it's a combination of genetic predisposition together with the viral infections what caused my diabetes. Yeah. And because you're like quite an active guy, aren't you? I am. Yeah. So I got it under control. I generally been doing a lot, but I started running. I used to be a runner a long time ago, then started running and

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that and I cut out all cakes and sugars, all that, you know, things people used to like to eat. I didn't know as a rest. That's why I was eating that stuff. So I cut all that out and then it all went away. Actually, I got my glucose comfortably under control and then it had been running fine for several years. Now I stopped looking at the data, in fact, ah and I interestingly enough, I stopped running.

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And at some point later, somebody looked at my data and said, Mike, you realize you're diabetic again. And I looked back at the data and it coincided with the second viral infection as well as when I had stopped running. So I did. And my glucose again shot up to be definitely diabetic. Right. So I started running. I got it back down, but I never got all the way down the baseline. I would be in this what would be called pre-diabetic phase. And then so running did help, but it kept creeping up.

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over time. So I've been doing this tracking on me for over 15 years now, and it just kept creeping up and up and up. And so finally I switched from running to weightlifting and you, I'm still a thin guy, but I did gain 10 pounds of muscle mass and, but it failed to control my glucose. And at the end of the day, it's because of the type of diabetic I am. So we're used to lumping diabetes into type one and type two.

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But we think there are many subtypes of diabetes and I imagine we can talk about that quite a bit. But we think there are multiple subtypes. The most common is something called insulin resistance, muscle insulin resistance in particular. And that's not my problem. It took me a while to figure this out. I actually have a beta cell defect, meaning I make insulin, my cells respond to insulin, but I don't release it from the pancreas. We figured this out through all the studying of me. And the net result was that um

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I could lift weights till the cows come home, but I will never fix my diabetes because of my problem. It's this insulin release from the pancreas, not increasing muscle mass. Now I keep muscle mass up anyway. I'm a big believer in strength training because I think that's important as you get older for avoiding sarcopenia. It's one of the biggest problems that can appear. By the way, it's a big deal for both men and women. Everybody should definitely keep their s***.

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you know, strength up, I would argue, and keep their muscle mass up because that's so important for, you know, a long healthy health span. Yeah, for sure. Well, it's interesting because I've heard like you will be familiar with Professor Tim Noakes and he speaks about his type 2 diabetes as being like an overproduction of glucose from the liver and you're speaking about it from a beta cell perspective. how that...

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both of you in a position to probably be able to do the tests required to understand that a little bit more, but is this something that anyone can figure out? We're getting there. we, I mean, this is all pretty recent in our lab. We started subtyping diabetes in the people of muscle insulin resistance, meaning their cells don't respond. The beta cell defect that I just mentioned, I have something called an inkretin. You may have heard of the GLPs that

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are very hot these days, ozempic and these things are mimics of those. That's another, there can be people who are defective in that. There's what's called hepatic insulin resistance, so your liver has issues, and also fat insulin resistance, adipose insulin. So there are these different subtypes. And by the way, your microbiome probably participates here as well. So we think people can have problems in any one or a combination of these areas. That's what we figured out first. We took people who are

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so-called normal or pre-diabetic. And sure enough, they will have glucose dysregulation, one or more of these sub-pathways. And then what we discovered is that those folks, first of all, they have different glucose curves. So these days we do a lot with something called continuous glucose monitors. I don't know if you've ever tried one, Mickey, yeah. Yeah, have, yeah, interesting. They're amazing because you see in real time what food does to you.

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And that's a bit of our claim to fame. started putting these on so-called, they're being used for insulin dependent type one and type two diabetics, but we started putting them on so-called normal and pre-diabetics and discovered a lot of people are actually spiking their glucose. They have glucose cis regulation, never had any idea. And you can catch it early with these things. But the other thing we discovered, and you may have seen this as well, but if people take a shot of glucose, their curves are very unique.

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Meaning some people have a very sharp rise, slow fall, some it's a slow rise, some slow fall, some have double humps in there. Just from a simple straight shot of glucose after they've been fasting. And we've actually figured out that that is due to their subtype of diabetes. And normally that costs thousands of dollars, the subtype things. So what's special about what we did is now we can show with the simple continuous glucose monitor, which

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I don't know about New Zealand, but here in the US you can buy them in a drug store. Most places in the world you can now get them without a prescription. You put that on there, you take a shot of glucose, we can see what your curve looks like. And at least in two of these cases, muscle interresistant beta cell defects, we can tell what subtype you are from the shape of that curve. So suddenly what was, yeah, this is one of these areas where AI has been powerful. So suddenly where there was, you know,

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say $1,000 to do these tests, you can figure it out with a simple, you know, glucose shot from a glucose from one of these drugstore CGMs. So we think, and that'll come out, I hope pretty soon, and we hope to get that out to the world so you can subtype yourself. So then you might say, so what? What do I care? Well, it turns out depending on the food you eat, your subtype determines how you will spike. So meaning if your muscle is resistant,

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You will spike to potatoes and pasta, but not if you're insulin sensitive. If you have a beta cell defect, you'll spike to potatoes. So I should point out that most people spike to rice, white rice. And in fact, white rice for some people is worse than ice cream in terms of spiking their glucose. Yeah, you wouldn't think that, but it's true. that white rice can be quite spiky for your glucose. Anyway, so we can do the subtyping now and then.

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predict what foods people should and shouldn't eat. And also the drugs I mentioned earlier, meaning if your muscle is to resist, if you have a beta cell defect, then exercise will not necessarily help your glucose control. I still recommend it anyway for all kinds of reasons, but it may not help that particular subtyping of glucose there. But if your muscle is to resist, the exercise is really, really valuable for helping control your glucose.

18:15
So these subtypes, and they're also important for your drugs you take, meaning I respond well now. You know, obviously I tried doing it all through lifestyle with semi-effective, least initially. Now I do need drugs to get my glucose better under control. And initially, it turns out ironically, I'm a metformin non-responder. That's the most common drug out there that people take for diabetes. And for whatever reasons, I didn't respond. I kept upping the dose, still no effect. So then I basically,

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took something called Rapinilitum, I'm just pronouncing it, but basically it promotes insulin release from the pancreas. And given that's my problem, well, that turns out works like a charm. So that worked, whereas metformin went, this one did. Now these days I'm on some other things, they're called SGLT2 inhibitors. This gets into the weeds a little bit, but- I like weeds. Okay, oh, you do. Okay, so farcegia. And then I also went on these GLPs, initially trolicity.

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later Manjaro. So those have been extremely effective for uh controlling my glucose. Now I'm a little bit textbook there too, in the sense that with the Manjaro, the one before it, especially Trulicity, I actually got a little bit of nausea, which is the most common side effect. Manjaro is better, but it wasn't zero. So it's nice to be able to control these things as best you can by lifestyle and other means.

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But it was a big deal for me because at one point my glucose got all the way to, it's called my hemoglobin A1C, a measure of glucose, got up to 8,4, which is very, very high. And so it took that combination of the GLPs and the SGLT2 inhibitors to bring it down. I got it down to about 5,7. It's hovering around between 5,7 and 6 now. And I've come up with schemes to do microdosing and lifestyle.

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try to minimize my drugs and maximize my lifestyle, but still keep it reasonably not too bad. Yeah, that's awesome. I've, I know of many people who use sort of micro dosing of GLP ones for inflammatory based conditions and things like that as well. I guess

20:29
the Monjaro in its original form is a diabetes drug anyway, right? Correct. Yeah. then they discovered these that were incredible for weight loss. A lot of people do it for weight loss now and should probably know. And by the way, I take it for diabetes. I'm a thin guy. That's the last thing. In fact, the little story there was that

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uh I went on to, even the bottom dose of Manjaro did cause weight loss, which I'm trying not to do. And some of reasons for lifting weights, they cause muscle mass loss too, which I largely mitigated, but not entirely. I mean, it kept going down. My fat totally evaporated once I went on Manjaro. In fact, it evaporated so much everybody would look at me and say, oh, you've lost weight. And I kind of got to the point, I thought I looked a little bit gaunt, a little bit like I just got out of the grave or something.

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That's reason I backed off a little bit and started on the microdosing because, and I've been able to use lifestyle and other means to get it better under control. But, and, I still need some because it will come back up if I don't. But, and then I gained a little bit of weight, which I think makes me look and feel a little better. ah I feel like people, they seem to be

21:45
camps of people, like people who really hate monitoring for healthy people. particularly in the nutrition space, there are very loud vocal voices, like dieticians who are like, no one, if you do not have type 1 diabetes, you should not have a continuous glucose monitor. It is ridiculous that we need to monitor healthy people. Yet, if you look at population statistics, I think that the last survey that I saw, particularly from the States, like 94 % of people had some sort of metabolic challenge.

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i.e. essentially like not very few percentage of people would actually be considered healthy. Why do you think this is so contentious, Mike? Oh, yeah. So I know the numbers for glucose. So 11.6 % of people are diabetic, most are type 2s. And 33 % are pre-diabetic and most of those will become diabetic. 90 % don't even know it, but they will become diabetic. And so that means approximately half the people in the US are pre-diabetic or diabetic.

22:45
those numbers are going up and up and up. So what's causing it? it's pretty clear. It's our diet. we eat 40,000 times more sugar than we did at the end of World War II. So that's the number I've been told, which is just incredible. So there's sugar everywhere. If you were to evaporate everything out of the ketchup bottle, but the sugar, you'd see it's still mostly sugar. It fills the bottle pretty close. If you've ever seen that picture, it's amazing.

23:14
And so there's just sugar everywhere. It's in even things where it doesn't need to be. And so it's just everywhere. And we just eat so much ultra processed food, which is usually synonymous with sugar and not always. But yeah, so it's just our nutrition is terrible. Our exercise is terrible activities down. So it's a lifestyle thing. And so the consequences with the population.

23:39
Western populations are exploding. Now even Eastern ones in terms of diabetes and poor glucose. So that's, I'm sure the number one cause, it's nutrition plus exercise. Yeah, I tend to agree. I was recently in the States and we went to the best breakfast in the particular town we were at. And in the breakfast buffet, there was like sweetened condensed milk, chopped up Oreo cookies, M &M cookies. I'm like,

24:09
What is this doing in the breakfast bar? Like that is crazy stuff. pancakes are giant probably too. And you have people flopping all the syrup on them there. You boy, that's like instant diabetes, right? It is. And then to your point, like the bread tasted sweet. it's like, it was quite different to what we have here in New Oh, is that right? Yeah. We're just, yeah, super interesting. But, and so I'm absolutely with you. Like the more that people

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understand how food affects them, the more they can be proactive with their health. But I think some people tend to think that you get a bit obsessive or, I don't know, it's an unhealthy obsession with health if you want to monitor. To your point about the monitoring, see, I think this stuff is really, really important for people. What's powerful about the continuous glucose monitors, they're very visual. You see exactly what's spiking you. And I remember eating a pulled pork sandwich once.

25:05
and watching my glucose go like over 360 or whatever. And it was ridiculous. And I showed it to a friend of mine. says, Mike, everybody knows bulgur has sugar in it. Well, I didn't know that, but now I did. So and there's a lot of stories like that. In fact, they talked to a reporter once who said, you know, I was eating salmon on salad every day for lunch. I thought I was being super healthy. So then he puts his glucose monitor on, sees it spike through the roof.

25:30
And once you know it, it's the sauce that he put on a salmon. So all you had to do is leave that off and he had the healthy lunch he wanted. And that's what you learn from these things. And so they teach you things that you wouldn't otherwise know. Some of it is obvious in hindsight, but it's so visual when you see this stuff and you just wear a monitor. You don't even have to food log whatever. I guarantee you'll improve your it's called time and range or glucose control.

25:56
just by wearing these monitors, they're very, very visual and that's why we need them. And the analogy I also use is that, you know, we have dashboards on cars and we do that because it helps us, you know, we don't speed, we fill the gas tank, all the things, your engine light goes off, something's off. Yeah, we don't do that for our health. And that's what these monitors are doing. They're tracking your health and sure, you'll learn, you know, your habits pretty quickly, but that's.

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valuable, right? Like the reporter doesn't need to put his sauce on a salmon and he's got that healthy lunch. And I've learned that for a ton of things. It trains you to have very, very healthy habits. yeah, we have, you know, I spin off companies as part of this, in part to try and get it out to the world. And one of them, January AI, uh uses glucose monitors to actually help people.

26:47
better manage your glucose control. And you just do this stuff for a few weeks or ideally 90 days. And I guarantee you're going to come out with healthier lifestyles just as a consequence of that. And what's kind of interesting, especially around the metabolic health is that we're all different. I probably forgot to emphasize that, but some people spike to potatoes, others to pasta, some to white breads and the brown bread. We're all very, very different. And so when you learn what spikes your glucose and what doesn't,

27:15
It's very easy to eat the things that don't spike you and avoid the ones that do. You still eat the things you like, but you'll put a greater emphasis on those that are healthy for you. So that's why anyone who wears these things will wind up, you know, improving their lifestyle habits. And we like to think, I'm not saying it's going to stop them from getting diabetes, but if it pushes off five or 10 years, that's a really good thing, I would argue. So, yeah, I agree. And then for people who do have type

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diabetes or diabetes, it allows them to see what the choices they're making in the moment are. Because some of the messages that are provided to people who already have disease, they don't seem appropriate to me, if I'm honest. To have a quarter of your plate still as carbohydrate. mean, this is just me speaking. I just think that's insane. And to sort of say a 20-minute walk is enough exercise or whatever. think that

28:14
There could be other recommendations made. And if someone had seen in real time what's happening to them, they're able to make those better decisions. Yeah. A good example along those lines is you mentioned the 20 minute walk. Well, if you are going to eat something spikes you, and this is one of the things that this January AI company does, again, you don't have to do them, but there many other just habits like this that are important. If you're going to eat something spikes you, say rice or ice cream, well, do your 20 minute walk, right?

28:42
after you do that and you'll see you suppress that spike. It's very, very obvious. And likewise, we've discovered, I mean, we do a lot of this research and lab, there's a lot of research, but, you know, people who do a walk after dinner at night, well, first of all, you should have your biggest meal in the morning, not at the end of the day. Don't eat for three hours before you go to bed. But, you know, even we've we discovered just eating and some level of this is known already, but you would eat.

29:06
If you're, you know, after dinner do a walk and those people do will have lower glucose the next day. It's as simple as that. And it probably makes you feel a little better too after eating a big meal. Again, it shouldn't be your biggest meal, but if it's going to take a longer walk even. Yeah, no, no, absolutely. And then Mike, you mentioned time and range. Like if someone does have a continuous glucose monitor, what is it that they should be looking to optimize? Because there is, you know, we spike, I mean, people know this.

29:35
I'll just say it anyway, when you exercise, you're going to spike your glucose. If you go in a sauna, you might spike your glucose. So what is it that we should be looking for and trying to optimize if we've got a CGM? Yeah, great question. I think it's the sort of height and length, it's called the time, we call it area under the curve. It's sort of the maximum glucose peak, if you will, that's there. That we think correlates the most with sort of bad glucose.

30:04
ah And so you're right, if you eat grapes, you will have a quick spike, but it goes down pretty fast. So grapes are like sugar, by the way. But they also they go down. Luckily, they have some fiber. Mixed berries are better than grapes. They'll have more fiber, turns out. So watch out for that. But exercise, I know this shouldn't frighten you, but especially if lift weights, you break down glycogen into glucose. So that's what happens when you do that. So you will get a glucose spike.

30:33
if you lift weights. I get one every morning. But it's fairly transient and I think it helps other benefits, like you say, in terms of building muscle mass and it's better for controlling your overall inflammation. All kinds of benefits come from exercise. And again, I'm going to argue, I will argue for strength training. I know a lot of people do cardiovascular, I still think that's important, but I think keeping your muscle mass up is a big, big deal if you want to live a long, healthy life.

31:03
Yeah, absolutely. so with you, so if you're time and range, then you're given like a in New Zealand units, it's sort of four to 10 actually, millimoles. ah And then if the more you spend of your, the more of your glucose is spent sort of within that range, the healthier you're going to be. Correct. So there's two comments on that. One is the more you're out of that range.

31:28
you will have a higher correlation with this hemoglobin A1C, which is kind of the gold standard people use for your glucose levels, which by the way, is not as good as a glucose monitor, in my opinion, uh because things can turn over your hemoglobin A1C as a measure of your red blood cell hemoglobin. And that can actually vary depending on your health conditions and people with anemia and things like that, they'll have different turnovers. So these glucose measurements are probably a more accurate way.

31:57
The other thing is there's been correlations independent of the glucose that, you know, these posts, they call them post perennial glucose spikes, so spikes after meals. That's correlated with cardiovascular events and things like that. So you, there's a variety of reasons to try to keep those more minimal. Yeah, no, that makes perfect sense. And, know, to your point, you know, people may spike to different things. I've seen people have a glucose spike to things like chicken.

32:26
Like, do we think is it coming from an immune immune response? I somebody put I think somebody put sugar on that chicken. OK, good point. I'm pretty sure because otherwise the chicken is mostly protein and fat. It won't have very much. I yeah, it should not have much sugar. I'm pretty sure somebody again, very common to sauces or the marinade, whatever will have something sweet in there. So leave that out.

32:53
By the way, once you leave that out, I'm sure you may have done this, don't know. When I first became diabetic, I went cold turkey, as I mentioned, cut out all these exogenous sugars, cakes, muffins, that kind of stuff. And then suddenly you don't miss it. I remember a dietician saying, well, just have one scoop of ice cream a week, this kind of thing. And I just thought this is crazy because that's just going to lead you back into a path of eating all this stuff.

33:20
So cut it out entirely and then suddenly you don't miss it at all. And now if I have something that's sugary, I taste it right away and it does not taste good to me. So you actually, I'm super sensitive. So you actually can train yourself pretty easily to avoid this stuff. And again, I think in the end, it's probably leading to a healthier you to do that. Now I completely agree. And to your point about what your dietitian said and not

33:48
trying to throw her under the bus because actually just as a profession over the years we've become quite dilute in the messaging around, like you're not allowed to say that there are good and bad foods. I think there are good and bad foods. It doesn't mean that someone's a good or bad person because they're eating the foods. But I mean, really, there is some pretty shit things out there. Oh man, yeah. Come on muffins, all this stuff. By the way, they'll sometimes serve those at diabetes meetings if you can believe it. know.

34:15
No, I do believe it. It's crazy. I'll be at these meetings and you'll see like these high carb things. It's like, hey guys, this is diabetes speed. So if I give a talk first thing in the morning, it helps. think the muffins tend to stay around at the break. But if I talk later in the day, the muffins will disappear. I see people make decisions around what they eat. in my head, I'm like, I just don't think you understand the ramifications of that. Like really what is going on. So if everyone slept on a CGM, they'd be

34:43
quickly realize what was actually happening. Because I think you said on Huberman that you noticed you felt super sleepy after having like a piece of pizza, for example. Whereas that's actually not a normal, like you shouldn't really feel like that after you eat, but a lot of people do. Yeah. No, as I probably said there and I said it several times, yeah, I can put myself to sleep with a piece of pizza. Usually two, but one will do it too. One will make me very sleepy.

35:13
So anyway, yeah, so I've learned to eat, especially at lunchtime, things that like, again, probably similar to the journalists, I'll have these chicken on salad kinds of things that that they just don't make me nearly sleepy. I wind up having more energy, a more productive day as a consequence. So it's just good all around, right? When you're

35:34
Feel like you're nodding off after lunch. That's just not productive for me or anyone I'm interacting with. good, good example is here we are in my time zone. We're right after lunch and the old me would be pretty sleepy right now. You might see my eyes. Anyway, I'm happy to say I had my chicken on salad today. So I think I'm in pretty good shape. Hey Mike, have you tried ketones or any like any similar?

36:04
supplement just to see if they affect anything for you? Yeah, not as systematically as I would like. Mostly I've just emphasized low carbs. Okay. And if I do eat carbs, it'll be in like the salad-y sort of things. It's in the form of fiber, which is good for you. feeds your microbiome and keeps you healthier in those ways. But I haven't

36:28
done, I do like to keep my protein levels up. I know it's a little controversial. Is too much protein bad for you or not? Most people, there's a lot of people who say, yeah, there's no such thing as too much protein. I'm not so sure that's true. I need to dig in more on the studies. anyway, I do want to keep my protein up because I do lift weights, as I say, I do light days. I alternate light days, heavy days, and a specialty day that actually builds my core.

36:56
So that's what I do and I want to keep my protein up to keep my muscle mass up because there's so many good things you get from from exercise and strength. They call them exokines, these molecules that promote health in a lot of different ways. By the way, you know, for certain psychiatric disease, a little sidebar here, I suppose, but like for bipolar ketogenic diets basically cures those people. You may have heard of this. It's pretty amazing. And I do know of someone personally who he

37:25
he's on it, he's fine. And when he goes off it, is, you know, he's struggling. so, ah you know, for certain mental illness, and so there's this whole, you know, neuropsychiatric with nutrition interface that's now starting to get recognized is pretty important. So nutrition is probably going to be a big deal for anxiety, depression, and I mentioned bipolar. So yeah, I've certainly seen it with clients, they report this there.

37:55
a level of calmness they've never experienced once they drop the carbs up the protein and just have just everything's a lot calmer in their mind and which yeah, which is pretty fantastic. Yeah, I'll say. No, I think I am a big believer food is medicine. 100%. Yeah. Mike, can we chat about resistant starch? Because you mentioned white rice and potatoes. And we know that well, we think we know that some of the studies show that that there's a shift in the

38:25
starch structure when these foods are cooked and if they cool completely, then those carbs are less available and they have less of a blood sugar spike. Have you seen that in work that you've done? We're doing systematic studies on this now. So I would say it's early days, but we have seen evidence of this. And I mentioned before, we're talking about now, guess that, so you can, we're working hard to figure out what takes to mitigate the spikes. So nearly everybody spikes the white rice I mentioned.

38:54
So we then started giving people either fat, protein, or fiber 10 minutes before they had the white rice. And what was kind of interesting is that for these insulin resistant folks, muscle insulin resistant in particular, would not have, unfortunately they kept spiking. But if you're insulin sensitive, two of the mitigators worked. was uh fiber and protein, not the fat.

39:21
interestingly enough. And that was true for the beta cell folks as well. So if you're in good shape for, I guess, beta cell and for insulin resistant, you can mitigate these effects. So in fact, maybe a general lesson for everyone is, eat your salad before your French fries. Do eat those things that are not spiky and protein probably. Eat your chicken will probably be better than before your potatoes and your rice and things like that.

39:50
So anyway, we are mitigating that, but we think actually a common element there to your point is the resistant starch that's in potato and pasta. that's, we think it actually is contributing to the spiking. And this stuff turns out to be very, very personal. And so we're still, this is why we're trying to figure out. And a good example is we're now running people through very specific fibers. m

40:14
one called Arabidazol, which you find in physium husks and metamucil and things like that. It's very common fiber that's out there. And then another common fiber, it's called inulin. You'll see they're the most common fibers there. That one is in chicory pea roots and things. And if you read the literature, it's all over the map. And this is why it's complicated as to whether they help for glucose control or for cholesterol. So we just decided to put people on, you know, 10 grams a day, 20 grams a day, 30 grams a day. We ramped them up.

40:43
I should say a week each. So first one week, 10 grams, second week, 20 grams, 30 grams a day and tracked their cholesterol. And we actually collect big, big data around people. So we follow all these other things too, meaning we'll measure, you may remember, know hundreds of thousands of molecules, how their blood and their microbiome and all that stuff. So we can see what's going on in credible detail. And we did discover that Arabidazite land does drop people's cholesterol, which was kind of cool to see.

41:12
That wasn't a little, say, but a bit controversial, but very clear from us. Inulin had no effect on either cholesterol or glucose as a general rule. But then when you dug down to the individual person, what we discovered is that, yes, although most people do have their cholesterol quite substantially dropped by this Arabidazite land, this Metamucil thing, there are a few people that didn't, that didn't respond. And some of them then responded to Inulin.

41:40
So even though in general, there's a party line for specific individuals and it comes down to this personalization, think you, probably in part, but not entirely dependent on your microbiome. We're still trying to figure all this out. It's probably your immune system, other things as well. We think that's all very, very important to contributing to your metabolic health. Probably it's a very specific, you want to dig in, know, hydrolysis and things like that in your microbiome and elsewhere that are

42:09
that are digesting these sugars and these fibers. So I think what we want to do is understand this in the detail where if I profile you, Mickey, I'd be able to say, all right, here's your microbiome and other profile. These are the foods you can eat. These are the foods you shouldn't eat. And these are the foods that'll help you. should eat these fibers because they're gonna promote your microbiome in ways that help your glucose control, that sort of thing, and cholesterol and that. So I think that's the world we're headed towards.

42:38
It's complicated right now because there's a lot of variables involved, but I think it's totally solvable with data. Wow. Yeah. It's super interesting thinking about the microbiome, like so much of the nutrition, like a section of the nutrition space has been devoted to microbiome and its relationship to a whole host of the chronic diseases that we're seeing. so to that point, like how does, like, can you simply explain for people how the microbiome

43:08
could influence metabolic health because I just, you we only ever really think about glucose and food and exercise, but what is the full relationship? Yeah, well, it's an area that's pretty active and there's something called the gut brain axis and the gut being, you know, your microbiome. So your microbiome, backing up a little bit, your microbiome has anywhere from two to 10 times as many cells.

43:35
as your human cells. So meaning we're more microbes than we are human in terms of cell number. And it's very, very important. Most of it sits in your colon, a little bit in your small intestine, and it breaks down your food, your fibers, things like that, and makes important things. Some of your fibers have these things called polyphenols, or very, very valuable antioxidants, anti-inflammatory. So your microbiome breaks down food and makes important nutrients that way. But it also synthesizes

44:04
pretty important vitamins. Vitamin B12, if you ever looked at the structure of this thing, it's very complicated. To have your microbe manufacturing this is pretty cool. Anyway, that's what it does. You have 70 % of your immune cells are in your gut. They're there to make this balance with your microbiome.

44:27
So, and then when things get out of sync, if you will, that's how you get irritable bowel syndrome and inflammatory bowel disease and things like that. That's the more extreme forms. And so that balance is very, very important. Now, your microbiome also makes some interesting neurotransmitters. And this part's not fully understood, a little controversial, serotonin. And some of these other neurotransmitters are made for your microbiome. and they do enter your bloodstream. To what extent that...

44:55
serotonin in your blood reflects, you know, your brain serotonin levels is not as clear. So that's an area being studied. But there are a lot of very, very interesting connections. And there's a molecule discovered by one of my colleagues here, Jonathan Long, called lac-fee. It's a combination of lactose and phenylalanine that gets made uh after exercise. And that has all kinds of important effects like appetite suppression, things like this.

45:24
So again, your food is very tied into your metabolome. Your microbiomes are very tied in. They're all interconnected. The relationship has not fully worked out, but there's no question they're all, you we are an important integrative system. So keeping these things all in balance, I think is super, super important. Yeah. And of course, what effect does taking antibiotics have in this whole story? Because so many people have

45:54
just taking rounds and rounds of antibiotics over the course of their lifetime. So that surely will impact their metabolic health long-term. Yeah, it's very well established that uh from studies that people taking uh antibiotics prescribed by their parents in the first two years of life actually wind up more obese than those who don't. so I'm sure, and your microbiome gets set up in the first three years of life, by the way.

46:22
Not that you can't modify it, you can, but just think about building a ship. You build a lot of it in the first three years of life and then you can modify it through your life, but a lot of it's that early. So I think that's an important relationship and we're screwing it up if you take antibiotics and like now, having said that, you don't want kids becoming ultra sick and dying, obviously. you need the right, what you don't want to do is overprescribe.

46:48
You don't want to take antibiotics for a viral infection. That makes no sense. ah You can do it just for bacterial infections. So later in life, it's true. And I've measured this through me. If I take an antibiotic, it will reduce my microbes in my gut, but they bounce back pretty quickly within two weeks uh afterwards. So I think you're a little more resilient later in life to handle this. Now, having said that, I do think we may be a bit of a pro endemic problem. uh

47:18
Again, one of my colleagues, Justin Sunderberg, another colleague, he basically showed that native populations, Aboriginal populations have three times as much microbes as say Western, you know, those like me who have a less diverse microbiome. And it's thought that that will probably impact your health, not so well shown, but seems likely that you want a diverse microbiome for making all kinds of valuable nutrients to keep us healthy.

47:47
Presumably we grew up in many millennia ago in these very rich environments and ah had a much more diverse microbiome that's largely been lost. So how to get that back, don't know. uh Might be harder as an adult because we've already set up this relationship. The microbiome is very, very interesting. I'm sure you noticed that. Everybody knows it's super important for your health, but...

48:13
actually trying to come up with the right formula has been very, very difficult. ah And the reason is we have personalized, once again, microbiomes, they're guilds, they're communities that have built in each of us. It probably has the right balance to make the right nutrients for us for metabolic health. That means you can't just go out and grab one, know, micro probiotic, it and fix the whole thing. You have to balance the whole community. And I think that's ultimately where we'll go as we understand this better.

48:42
But having said that, know, there's one, I have no conflict here. I conflicts a lot of what I said already, by the way, but on pendulum where I have no conflict, they market a antibiotic called acumencia. You may know this and that actually seems effective, drops your hemoglobin A1C by 1%, which is not too bad, right, for a natural product. So. Yeah, super interesting. And of course,

49:08
There are people that I work with who cannot tolerate any fiber at all without a lot of gut related issues. And there are the likes of people who are on an animal only diet who swear they feel great, they look great, and they do look, you know, objectively good and they perform well. And they have that sort of, know, fiber, is the thing which is helps uh sort of like promote, I guess, gut bacteria, albeit

49:37
I have seen there have been studies looking at people on animal only diets and they don't just have a different gut microbiome makeup. That's isn't necessarily worse. What what are your thoughts on that, Mike? I wish I understood this better myself. I like you. I'm a little confused because, yeah, I know someone who only ate eggs for a month, 720 of them. And he had a certain metabolic profile. And it's true. He runs very, very high cholesterol.

50:04
the other team worried about it, worries me a little bit. And it's pretty clear that for most people, again, maybe there are these people exceptions, and I'm sure there are, but for most people protein only diet can be pro-inflammatory, right? And you don't really want that. And so I think you want the right balance. I think we'd all agree that straight up sugar fructose in particular, not good.

50:33
And then, ah yeah, but I think, you know, I would hope that, you know, even your person out of fiber problem, they'd be able to find the right fibers. So the thing about fibers is it's often lumped into one fiber. But if you think about it, you know, they're fibers like they're very different. They're long chain, short chain, hydrophobic, hydrophilic. That means, know, greasier, watery.

51:01
positive, negative. They're all very, very different. There's, you know, it depends how you want to classify it. There's at least 30 major fiber types, but you could actually break it down and say there's 100 fiber types. And so they're all very different. It's like calling people, animals, I should say, all the same. You cockroaches are the same as humans. We don't think they are. And I think that's the way fibers are. They're very, very different. So we'd hope that you're a friend.

51:24
who couldn't have certain fibers would find other fibers they would tolerate because I'm sure that's an immune fiber reaction going on in the gut. And hopefully they can find the right combination that works for them and then feed their microbiome appropriately. Now, again, maybe it got misaligned way back when, you know, in age zero to three where this whole thing got set for them. Hopefully they would be able to, you know, find some combination that works and can still feed

51:54
you know, they're microbes in a way because you don't really, you do have your microbiome in your gut. And as I say, it's pretty important and it can eat away at your intestine. And that's how you get the so-called leaky gut. And then the thing spirals, right? If you're got a leaky gut, then more bad things happen. The whole thing spirals in a bad direction. So you really got, you know, I think metabolic health is so critical for us to really achieve the right balance. Yeah.

52:23
I completely agree. like, we, particularly post COVID era, there's a lot of germ phobia everywhere. know, the hand sanitizer, antibacterial soaps, all of these things to try and keep us clean and germ free. Like, are these having an impact on our microbiome, we think? ah I'm sure it does. And I'm sure it's unhealthy, especially allergies and asthma. So a good example.

52:51
There's some studies that, and there's now plenty of them, but there were one of my favorite ones, one in France where they had same zip code, but some people lived on farms and somewhere in the city. And it's very, very clear that the ones, kids in farms had lower allergies and asthma than the ones in cities. So the idea is we do need these early exposures, you know, for the farms, they would take the babies out in the basket and put them next to the cow they're milking, right? And you're getting it.

53:18
And if you've ever been to a farm, I'm sure you have, right? You can smell it. There's all kinds of stuff there. And so I do think having two clean, so the HEPA filters on one hand, we think is good for watching out for those COVID and those kind of microbes. But there's no question we need the beneficial exposures as well.

53:41
So I personally, once I learned all this a little bit later in life than I would have liked, but I eat my carrots with the skin on, right? And I don't peel the potatoes because, well, potatoes you tend to cook, so you probably killed your microbes. Like carrots, I eat raw carrots. And so I think there's some beneficial exposures that are important, especially in life, rolling around in grass, eating that sand at the beach may not be 100 % bad, and I'll say in the...

54:09
I'm not recommending it. What? Sorry. I better watch. You know what I'm Yeah. I mean, I grew up in farm areas. I got exposed, all that stuff. And I had pretty much no allergies and asthma until I moved away much, much later. then they were pretty mild. But so I think we need and think about just how we evolved as a human race. We grew up in the forest. We grew up in these natural environments where we were getting. I'm sure those are synergistic exposures. We have studies like that running now, by the way.

54:39
So to study, uh we tend to think of exposures as bad, carcinogens, pesticides, all these things that are evil and they're there, plastics, right? But there's got to be good exposures. We're trying to actually work that out now. Yeah. No, that makes that hormetic response, right? That makes us more resilient and more effective. Yeah. Professor Mike, like just finally, if we think about

55:06
glucose tolerance, which is a lot of what we've discussed today. And of course, the microbiome, like obviously avoiding foods that are really high in processed refined carbohydrate is really important. All of the things like in terms of... Do you want to hear an interesting study there? Yeah. It's been shown not by us, but other groups that if you eat these ultra processed foods, you not only eat

55:30
more, you eat faster, you eat more. And so you gain weight. That's been very clear. But you also stimulate the production of dopamine, which in turn is a positive, it's a, it's an addiction, if you will, part of your, nervous system that, you know, trains you to eat more. So it's, it's basically an addiction. Eating ultra processed food, addicts you to eating ultra processed foods. Yeah. A hundred percent. And

55:59
And to your point, like a shift in behavior might initially be hard, but actually over time, your tastes change as well. And what you can and can't, and what you choose to eat can be quite different once you sort of get through that initial period. Yeah, yeah. But then suddenly, like I say, it's a very easy thing to overcome. Yeah, yeah, 100%. And Mike, finally, what about probiotics, probiotic foods?

56:27
prebiotic fibers, we've already talked about some of them obviously, but are these recommendations that we can sort of solidly make based on research? I think so. A good one is the prebiotics, where it's pretty clear women should get at least 25 grams a day of fiber, men 35. And the number at least in the US is something like 12. It's half of what we should if you're a woman and even less if you're a male.

56:57
Pretty clear, upping your fiber is a good thing. What the right probiotics eat, that still needs to be worked out. A lot of the probiotics you'll buy in a store, they're all dead anyway. knowing which one's reliable, which ones aren't. There's a lot of controversy around supplements. We know antioxidants in genuine food, antioxidant foods, anti-inflammatories are good. A lot of people say, well, nobody's shown any supplements. Now I myself take...

57:23
antioxidants, coenzyme Q, a bunch of other stuff like that. Anti-inflammatories like turmeric and cucurbin and what else. uh Yeah. But there are now getting to be really good studies for this one. The ultra processed food, I said, very solid studies show that's bad, but vitamin D3 has now been shown with

57:46
many, many thousands of people to be a great supplement. So I think some of these things are very, very well now worked out scientifically. Some have more to go, but they're kind of no brainers, if you know what I mean, to take your antioxidants and that sort of thing. I mean, there are just certain things that we know are happening as you get older. Your mitochondria do get damaged. They're not as good. And so things that help reduce that damage, keep it up, have got to be good for you intuitively.

58:13
And so we do need better scientific studies around it to prove that. Yeah, the probiotics, I'm not as sure, but I forgot what else is on your. Yeah, no, no, that's sort of covered it. to your point, just as a final comment, like actually understanding how food affects you so you can make better decisions. So if it is getting a CGM or even a glucometer or something like that to help assess that for yourself, like I don't think that's obsessive. I think that's proactive. Oh, for sure. Yeah. And it can...

58:43
Help, you know, I'm a super measurement guy. We do whole body MRIs or believe it, not so much in the lab, more with another one of my companies. And any physician today will say, you should not do whole body MRIs because they're worried you're going to find all these, they call them incidental findings, these nodules. And I guarantee you have nodules. Everybody has them, men and their prostate, women and their ovaries, if you go high enough resolution. And if you ask me, should you whole body MRI? say, absolutely. And the issue is uh

59:11
whether you have nodules or not, the issue is do you have any growing nodules? And you know that from the longitudinal profile. So we need to integrate that more in medicine. And so that's what you're looking for. I have nine nodules. I've done whole body, 20 whole body MRIs last nine years. And it's very clear none are growing. But imagine I ever get cancer someday. They take it out and then they scan me. If I didn't have my baseline measurements,

59:36
And then they see these nine nodules, they won't know if it metastasized or if they were there to begin with. we'll know, and I did not plan on getting cancer, but if I ever do, at least I'm prepared. So that's what this tracking is all about. Know what your healthy baseline is, and then detect shifts from that. And we're all so different, as you point out, that we have to know our personal profiles so that we can see those shifts. And you may know, we can out tell, here are all my smartwatches, by the way.

01:00:03
You can tell when we can tell when somebody's getting COVID a median of three days in advance of symptoms because their heart rate jumps up. And so this tracking can be very, very valuable, we think. Yeah, super interesting. Mike, you mentioned that you've got a paper coming out that talks about those shifts in the glucose response based on your sort of genetic profile or how you respond to glucose. When should we expect that paper out?

01:00:30
Well, the paper came out. I can send it to you. can figure out how to to your listeners. I'm going to make a little plug if I'm allowed to do. We're about to run an AI and Longevity uh certificate program here at Stanford. It's going to be super cool where you'll, you don't have to know any AI or programming, whatever. We're going to teach you and you may know you can make these little, your own coding. So the idea is we're going to do these fun projects where you design things yourself as part of the class. It's hands on. It's kind of fun.

01:00:59
And at the end, you'll be making little programs like what I take these, you what supplements should I take and what time of day and do they interact with one another? And you can do all this through this. They call it vibe coding for those. And it's going to be fun. So if you guys want to do sign up for the class, it starts October 14th. I you can do it. Yeah. So anyway, it's going to be fun if you're interested in the health span and longevity. It's this is like super cool.

01:01:28
That sounds awesome. And so I'll definitely put a link to that in the paper, in the show notes. Mike, for people who want to know more about your research lab and what you do, where's the best place to sort of find you? Yeah, I'll give you my link. But you can email me. It's msmichaelp, P as in Paul Snyder, S-M-Y-D-R, at stanford.edu. But I don't know if you have links. Somehow you can put there Mickey on your podcast. So I'll send you relevant links. That's probably the easiest way. We have a series of studies.

01:01:58
A few of them can be done remotely. Unfortunately, some of have to be in the Bay Area for the super deep profiling. No, that sounds cool. Awesome, Mike. Thank you so much for your time. I really appreciate it. Thanks for having me.

01:02:22
guys hopefully you enjoyed that conversation was super fun he's so enthusiastic and what a wealth of information really looking forward to seeing more of the work that is coming out from his lab next week on the podcast I catch up with professor Grant Schofield really looking forward to that until then though you can catch me over on Facebook @mikkiwillidennutrition Instagram threads and X @mikkiwilliden

01:02:49
head to my website mikkiwilliden.com and that's where can sign up for that webinar that is taking place today or connect in with me for one of my plans. All right team, you have the best week. See you later.