The Diet that Changes Everything!

Gil and Michael discuss diets, nutrition, epidemiology, and strategies in health. They look at Mediterranian, paleo, fasting, and other diets; the latest research on TMAO (a molecule associated with heart disease that is made from precursor molecules found in high concentrations in meat and eggs); and how many cookies you should eat for best health (the answer may surprise you!).

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Michael: My guest today is Dr. Gil Carvalho, who became a medical doctor at the University of Lisbon and later earned his PhD in biology from Caltech. Gil is a physician, a research scientist, and a science communicator; and he has published peer-reviewed research in genetics, molecular biology, nutrition, behavior, aging, and neuroscience; and he has a very popular podcast called Nutrition Made Simple, which is a fantastic series that explains and simplifies research; and he also does a lot of great interviews with many of the top experts in the fields. So, Gil, thank you for taking the time to chat with me. I’ve watched a lot of your videos, and I really love your very honest and fair take on food science and diet. So, everyone wants to know what to eat — or not eat — to stay healthy, and we’re bombarded by research and reports on diets… but also on specific foods, when to eat or not eat, exercise, and so forth. And there’s also a lot of variability between people because of genetics, age, disease, risk factors, … not to mention environment, stress, socioeconomics, and other factors like these. And so, we see all these epidemiological studies from animal studies to cohort studies to randomized controlled trials to meta studies. For example: the Blueberry Consortium funds a study (which may be totally legit) showing how the anthocyanins in blueberries are powerful antioxidants and how they can help cure cancer or prevent other risk factors. And perhaps you see this graph that shows this huge effect because of the way the graph is presented. But there are lots of foods with pigments that are antioxidants, and probably eating a pound of blueberries a day isn’t the best diet. So, how do you advise people how to navigate all this noise and make practical decision that are best for them as individuals?

Gil: One answer to nutrition is these common patterns that have emerged from decades of research that we keep seeing over and over and over across populations, across ethnicities, across experimental approaches. And these are the type of recommendations that people will hear in guidelines. So, you know: avoid an excess of ultra-processed foods. Avoid an excess of alcohol in your diet. Eat an abundant of unprocessed fruits and vegetables. Avoid an excess of salt, especially if you have some risk factors. Avoid…. So, this type of thing — this type of general advice and where that’s coming from is precisely the type of experiments that we talked about and the fact that we keep seeing over and over and over… positive or negative effects of these foods respectively, depending on whether they’re recommended or discouraged. So, those broad strokes, let’s call them, are very consistent, and we’ve seen them for decades. I mean, and the consistency is, why you keep hearing them repeated now. The other side of this is that when the more specific a question gets… so, okay: how many blueberries exactly and at what time of the day should my aunt eat who has this age and these exact parameters? How many should she to not have cancer? I mean, right? So, when you get to the specifics, it becomes almost impossible. And the data just not just does not allow it. And the ultimate, specific question is the individual. For this guy. For this guy, what is the exact right diet? Tell him exactly what to eat to avoid disease. That doesn’t really work. Now, we can make an educated guess. It’s based on things like blood work, for example, right? So, that can give you an idea of risk factors the person has. So, obviously, if somebody has a propensity for high blood pressure, for example, it makes sense to watch out for the sodium in the diet and to increase the potassium and this type of thing. And if somebody… and vice-versa, if somebody has great blood pressure, chances are they are more resistant to the normal triggers of our Western diets. So, this aspect of the individual, which is often what people are looking for, not so much the broad strokes, but they want to know: okay… for me right now, tell me exactly. And that is where it’s hardest. So, that is where you make educated guesses based on A: the science that we have for populations, which sometimes gives us information with regards to specific contexts, because you have populations with specific characteristics. So, one population that has cardiovascular disease, another that doesn’t; one population that has diabetes, one that doesn’t; one population that is more overweight, another that isn’t. So, you can get, sometimes, this nuance in the answer, but there’s obviously a limit to that. And then you’re going to integrate this aspect of the biomarkers, as we said… the specific clinical details of the person. And then family history would be the other very important aspect, as well, that can give you clues as to which, like: where are the bullets most likely coming from that you’ve got to dodge, right? If everybody in your family has heart disease or a stroke, that’s probably something that is in your genes. Obviously, environment and diet and all these factors and smoking will also play a role, but if in your family everybody has that disease, chances are you have the susceptibility, and so chances are it makes sense for you to avoid those specific triggers; whereas somebody who has zero family history of heart or cardiovascular disease but has a lot of some cancer or kidney disease or something… it’s not that you’re going to ignore the risk factors for heart disease, but it makes sense to focus on the things that are in your… that run in your blood, right? So, those are, again, some very general pointers. Let me know if that makes sense and where you want to dive deeper.

Michael: That makes total sense, and I think, going back to these studies and how people interpret them… a big part of the problem is: if people try to look at individual studies, whether they’re scientists or not, but particularly if they’re not scientists it’s hard enough to make sense of them… but once they get up to the level where: Okay, it seems like eating a lot of red meat is bad. So, scientists are not all are going to ever agree on anything, but enough scientists agree: “Okay; this is probably something we should recommend.” So, it goes up to the government level, and then the government says, “Yeah; this makes sense. Okay, we’ll recommend people….” And then the lobbyists come in and it’s like: “No; you can’t do that.” So, it gets changed into, well, “eat less saturated fats” rather than “eat less meat.” And then, I think that the next part of the problem is: Okay; well, if I’m eating less meat or eating less saturated fat, that’s part of the answer, but the other part of the answer is what am I replacing it with, right? And I think in a lot of foods and a lot of diets, that’s a real problem. Because people may substitute something that maybe is a little bit bad for them with something that’s worse for them or causes a different kind of issue. So, at the end of the day because of all these… just understanding the science — and then how it gets communicated to the public from trusted sources — it makes it very difficult for people to really understand what it is they’re supposed to do. And then that just creates a lot of stress in people and then that stress is probably shortening their lives more than maybe some dietary change that maybe not have a big effect or isn’t maybe across the board, like you say.

Gil: One obvious thing right out of the gate is: show me evidence. So, a claim in science and someone on social media making a claim has zero value if there’s no evidence to back it up. And I realized that in this format we’re having a free-flowing conversation. I’m not showing you studies because it’s not how these conversations work, but when you’re looking at content on the Internet (nutrition content), a lot of nutrition content is — and even content that’s very popular — includes zero evidence. [It] is just somebody saying things. It’s just somebody saying, “This is bad for you; this is good for you.” Zero proof of anything. Zero scientific evidence. That’s not really helpful, because you can make the video… you can make the exact same — the opposite video, you know, in two minutes… sit down and say the opposite. And that has the same value when no evidence is shown. That’s kind-of an easy, first pass. Litmus test: If someone in their content consistently does not show you evidence, they could be right, but you just have no way of knowing. It’s just there’s no way of you to tell. And because we have this panoply of views on the internet…. You can’t go by charisma. You can’t go by confidence. You can’t even go by credentials. It doesn’t work nowadays, because you can always find someone with a medical doctor degree or PhD degree or whatever that will say the opposite. So, scientific evidence for the claim is Ground Zero. Another level slightly above would be what we were touching on a minute ago. These kind-of buckets of evidence, right? If you make a claim, okay: “Food X is bad for humans. Here’s a study.” And you look at the study and it’s a study in mice — this mechanistic realm that we touched on — okay, it’s not garbage. It’s not these exaggerations. It’s interesting data, but is there evidence in humans? Why is this person showing me a study in mice? Do we not have evidence in humans? — in which case, it’s a big question mark. Do we have evidence in humans? Then why is the person not showing me that? Ask these questions. It’s less about accepting things passively or rejecting things by knee-jerk reaction. But get used to asking these questions. Where’s the evidence for this claim? What type of evidence is this person showing me? Is it in human beings? If it is in human beings, how compelling is it? Is it an isolated study? Is it a gathering of studies? Is it a meta analysis where you put together a bunch of studies? All other things being equal, that has more weight because you’re looking at a broader data set. So, those are just some very general kind-of first pointers to start making sense of this diversity: all these different voices saying different things. The reality is, once you go a little bit below the surface, these things do fall into place, and they do make sense. And a lot of times, these messages that seem out of nowhere… and you look a little bit behind the curtain, and they make sense because it tends to be always the same things: claims without evidence, claims from studies in cell culture, or studies in mice that then have been tested in humans that didn’t pan out. And the person is just mentioning those. Those are two examples. I mean, obviously, there’s more; but those are two examples of things that we often see where a message can appear confusing to the public, but then when you dig a little bit beneath the surface, and you go, “Oh, okay; it’s this pattern. I’ve seen this before.” And I see this resonating with people because our viewers you… we see the gears turning. Like, people start to recognize these patterns, and when messages are shown that are not the most substantive scientifically, they can already — even with no scientific training — people can identify these things if they’re used to looking at this content, for example, and spotting: “Oh, this is a mechanistic argument”  when it’s “Oh, he’s just talking about a biochemical path” or, “he’s talking about an isolated nutrient, but he’s not showing me the result in a human being eating it. What happens to human beings? Do they have more or less heart attacks? Don’t just show me… don’t just tell me about the pathway in isolated cells, but show me what happens to human beings. So, hopefully that makes sense.

Michael: No; it does. And I think part of the problem is, you know your viewers are probably you know A) because they’re sort of naturally this way and that’s probably why they watch your channel — because they’re looking for this deeper information to help make sense of this — but there’s you know there are a lot of influencers out there who can be very charismatic and they’re great at selling a story, but they’re either… and maybe the story is true, or maybe it’s true but not super significant… or misleading. There are people who use blogs of someone… someone’s analysis, which may or may not be right, of some study or is a study… and I’ve seen people where they have an agenda and they’re presenting a story…. And there might be some really good scientific research and data in there: randomized, control trials; cohort studies; other studies; human studies; mice studies; whatever…. And there might be some study that they…. Well, this is showing this, and it’s a real study, and it does show this. But what they’re not telling you is, well, this same food causes this cancer, but it also lowers another kind of cancer. But they don’t mention that, right? I mean, there’s a lot of that kind of stuff going on as well. And you know, in the studies themselves there’s a lot of p-hacking and fraud and bad design and problems just in the studies. And some of those problems… sometimes don’t surface for years, and they have a huge impact on society and what we think about vaccines, for example. Or there are studies that have been intentionally done… there’s one on chocolate that was done under scientific protocols just to show how easy it is to hack the system and to make these things look like they’re real when really it’s bad science. So, for people who aren’t watching your channel, or other people like you, who are honestly looking at these things and trying to help make sense of them…. You know, we see it all the time where people… you just get confused. And then if… and the big problem I have with it, too, is there might be researchers out there — and there are some that I’m not going to name, but that I have a lot of respect for, but then I see them do something where it’s like this is discrediting you as a scientist because you’re doing some of these tactics which make people not trust other stuff that you’re saying. Or a show that has a lot of great information in it, but then they… like, your viewers recognize something in it, and it’s like, well, how do you know, then, what to trust in there and what not to trust? Because: I know this isn’t true. I don’t… this 98% of the rest of the stuff I don’t know whether it’s true or not, but now I can’t trust it.

Gil: Right; yeah. I mean; one thing that I often say, and it is kind-of controversial, is don’t base these… don’t base this on trust. And I get a lot of flack for saying that, because people get upset that… people say, “Well, what am I supposed to do? Go read 5,000 studies to decide what’s for dinner?” And I understand their point. They have a point. And also, they’re saying, “Well, you’re telling me to mistrust my doctor?” I’m not saying to assume that he is lying or he doesn’t have your best interests in mind. The vast majority of doctors do. What I’m saying is to develop a curious… an optimistic, but a curious mindset and an inquisitive mindset of asking these questions and of digging a little deeper. Because I genuinely… I have spent a lot of time thinking about these issues, and over the last few years I have… if there was another way; if there was another simpler system that I could give the public to see through all of this immediately, I would. I would love to do that. But this is the most reliable. What I’m trying to break down here is the most reliable way to do it. Because simply trusting does not work. I mean, I try really hard for my videos to be as accurate as possible — as objective as possible. I don’t want to be wrong. But human beings make mistakes, and I sometimes look at videos from three years or four years ago, and I go, “I don’t like how that’s said anymore.” And I take them down. So, I wouldn’t even recommend trusting me. So, you know, what I’m saying it’s… the trust thing is tough. It’s complicated. Because — especially because we’re talking about people you’ve never met. You’re talking about somebody that you see on the Internet talking. You have no idea if this person is just a good actor or what’s going on. And I see so much information that is truly appalling by people who are very charismatic — and, I’m sure, very well intentioned and Incredibly popular — but the information in some cases is abhorrent. Like, the level things that you can literally fact check with a Google search. And that are life-and-death. And yet, there are videos with millions of views, and people following this religiously. And it’s just scientifically void: the opposite of the evidence, right? And in things that are truly crucial: things that are truly life-and-death. Some of the biggest killers in our society, disease-wise. So, I’m not sure how helpful all this is. I’m trying to give an honest and a realistic picture that: yes, I think that all of this is possible, and it doesn’t take… you don’t need a PhD to see through this stuff. You don’t need to understand every detail. But having a sense of, “Okay; is this person showing me evidence?” —having just a broad idea of types of scientific evidence like we talked about. I mean, we covered it in two minutes, so it’s not exactly something very sophisticated. So, is this person showing me something in a mechanistic study, or is it in a human study? This idea of reproducibility…. Another thing that… another note of caution is these headlines that people are exposed to in in mainstream media. These headlines that always pop out when you have a new study that is sensational. You have to understand the structure of incentives for journalists and for blogs is to come up with headlines and with articles that get clicks, and it’s not that people want you to be sick. It’s not that, but you’re sitting there trying to come up with popular content in terms of news or, you know… you want to get the clicks that the other newspaper isn’t getting. Or you going to you want to attract the viewers you have to come up with something that sounds sensational if your life depends on it. One thing that I’m very happy about is when I started this channel I didn’t need it. I don’t need the channel for money or for pats on the back. So, I have the luxury of making content that… sometimes the content is made in a way that we know is not going to be popular, because we’re debunking myths and we… that are myths that are very popular. And we are going into a bit more depth and a bit little bit more nuance. And that’s not viral. That’s not the stuff that spreads like wildfire, so we’re very aware of that. But I don’t need, you know…. I don’t have sponsors. I don’t have any of that stuff, so I’m very… I have the privilege of just relaxing and doing the content that I’m proud of. And I don’t care if it gets…. I mean, if it gets millions of views, great! Because more people have access to it, but it doesn’t change my life. If a video gets 10 views or a million views, my life is the same. So, understanding that these headlines… typically the structure is: “Everything you thought you knew about nutrition is wrong, new study shows.” It’s usually this idea of the of the inversion, right? Of the 180. This field just did a 180 thanks to this one study. That is almost never the case. With these headlines, it’s… you look into the study. We do a lot of this, because these headlines become popular and people are scared and are excited and now we’ve develop a little bit of a reputation, so people will immediately come to us and say, “Hey; this study is out there making the headlines. Can you guys go over it?” And so, often when a popular study is making the headlines, we’ll make a short video going over the study and going over what it’s actually showing. And it’s almost never the case that this new study flips a hundred years of research on its head. It’s almost never the case. Sometimes it’s something interesting that needs to be confirmed. Sometimes it’s something that we already know, and it’s just being pitched in a way that seems novel. Other times there’s methodological issues with the study that don’t really support the headline or the claim. So, I think one realization in terms…. we were talking about people being stressed out and people kind of calming down. One thing that I find very calming… it’s a bit frustrating at first but then when you accept it, it’s very calming and very soothing, is understanding that science progresses very slowly. Over a scale of years or even decades is when these discoveries really come about and then solidify because you can observe something, but really you want you want it to be confirmed, and then you want it to be solidified, and then you want to tease out the details. So, really, we’re talking about a long, a kind-of, a glacial time scale when compared to social media where you need something new every day to be the influencer that people are talking about. Science doesn’t move at that — at all — and a lot of the things that we know now… that are the pillars of nutrition… most of those were already the pillars of nutrition 40 years ago. If you look at the guidelines. On the fundamentals, it’s very similar. Yes, there are differences. Yes, we’ve learned more nuance. We understand more in terms of details, and some things that we believed were true, we don’t believe anymore. But, on the fundamentals, it’s probably 80 or 90% that overlaps, right? So, maybe realizing that gives people some calm. And also knowing that all of the research that is done — there’s a lot of stuff that’s being figured out. We talked about individual variability. Things like the microbiome. All these are exciting. I’m sure we’re going to learn a lot about this in the years and decades to come. But the truth is, right now the main things that you can do to optimize your health are these things that we pretty much already know: maintain a healthy body weight; stay physically active; eat a healthy diet, which can be any of these patterns. It can be more lower a bit lower carb, a bit lower fat, or a bit more plant-based or more omnivore or more Mediterranean. All of these could work, and you could put together a healthy diet that fits under any of those umbrellas. But really, the bottom line is, the points that we talked about: does your diet have a lot of ultra-processed, junk foods? If so, it’s probably not ideal. Does it have fruits and vegetables and unprocessed foods and whole foods in general? Is it mostly whole foods? It’s harder to go wrong in that direction. Does it have a ton of alcohol? — probably not ideal for most people, right? So, these are the pillars. If you’re maintaining healthy body weight, you have the main boxes checked, diet-wise. Your blood work: there’s nothing that’s crazy out of whack, like: your glucose levels, your cholesterol levels, your blood pressure… these things. There are others, but, you know, these things are in the healthy range. That’s your that’s your 80%. We talk about the 80/20 rule doing 20% that gives you the 80% of results? This is the 20% that gets you the 80% of results. All the other stuff that people obsess about on the internet… does it have to be exactly this percentage of carbohydrate and this percentage of fat? Is it exact… what about: is it olive oil or is it canola oil? Or, is it GMO or grass-fed or pastry-fed?

Michael: Pastry fed?

Gil: What’s it called? Pastry raised?

Michael: “Pasture-raised.”

Gil: Pasture-raised; right.

Michael: Bring some Danishes to your cows! And I think one telling thing, too, is that there’s lots of populations around the world. And if you look at their diets, there are a lot of very healthy people with very different types of diets. And some of those maybe… as you said, individuals — we all have different genetics, and so, even within a country or within a lineage, there might be a diet that’s… this one thing for this person may be different for someone else, which is part of the hard thing. But also, I think there’s a lot of different ways that you can approach it that are just fine. But, yeah; the recommendations: highly process foods… it’s kind of obvious that that’s… we need to limit those as much as possible. I saw a really interesting chart: you know the recommendation of less than 10% saturated fats is a general recommendation, but I saw a chart that it was sort-of an S-curve that showed: up to close to 10% there’s very little difference in health effect for saturated fat. And then it sort-of jumps up really fast and then you get above about 11 or 12% (or whatever it is) and then after that it’s it doesn’t really make that much of a difference. I don’t know if I’m interpreting that the right way, but that was super interesting.

Gil: You described it perfectly. That is the shape of the curve in… there’s a meta analysis: the last version is from 2020, I believe, that shows this. Now, I’ve lost confidence in that curve. The last time I talked about that was maybe two years ago, and I talked about that curve and since then I’ve had conversations with other scientists and other people that are interested in nutrition, and I’ve kind of lost confidence in that curve. So, I’m not sure anymore if that S curve is real. It could be. Some people argue that it’s a straight line; I don’t think we know exactly what the shape of the curve is in detail, but this is an example of something that I think: sometimes people get lost in this in this minutia of the exact percentage of saturated fat. I don’t think we know with precision. The 10% is a ballpark, and I think it it’s possible that it there’s some variation from Individual to individual. We had a cardiologist on a while back: Ethan Weiss. And he put this in terms that I completely agree [with]. Because for cardiovascular disease we have biomarkers that are very well validated… a lot of evidence behind them… this thing called ApoB [apolipoprotein], right? Most people don’t have a ApoB reading, but if you have your non-HDL cholesterol, that’s almost as good. So basically, your total cholesterol minus your HDL cholesterol is kind of a an estimate of the number of these lipoproteins that are in your blood that can get into the artery wall and cause plaque.

Michael: And there are specific test you can do for ApoB, right?

Gil: Yeah. You can measure your ApoB. It’s a lab test like any other, and it’s actually pretty cheap. But most people don’t have that, and the non-HDL cholesterol is a pretty decent, pretty good approximation. Where were we going with this? Oh, the saturated fat, right. So, this is a pretty good proxy for where you are in terms of: do you need to optimize your diet or not? If your ApoB or your non-HDL cholesterol are great, I would worry less. I mean, if somebody is eating a bit more saturated fat than the next guy but ApoB is phenomenal, I’m less worried about that guy than… because the evidence does indicate that saturated fat raises cardiovascular risk through elevation of these lipoproteins. In all likelihood that’s what’s going on. There might be other mechanisms too, but this seems to be the main one. So, and because we have easy ways to measure, this is similar to the salt and blood pressure conversation when people say, “Exactly how much salt should I eat?” Some people are more salt-sensitive than others, but if you look at your blood pressure… if your blood pressure is great and you’re eating a bit more salt than your neighbor, hey, you just won the genetic lottery, maybe. But the guy who says, “Well, I’m already not eating that much salt. I’m careful with my salt; my blood pressure is still a nightmare.” Well, maybe you need to be stricter, Brother. It’s not completely fair. You know, the genetics game is not that fair. It’s truly a spin of the wheel. So that’s one consideration that I think is very worthwhile to bear in mind: our circumstances.

Michael: And speaking of ApoB and genetics, you had someone on some time ago, I remember, who talked about cholesterol. And, you know, back in the 80s, I guess, it was when we thought that your blood cholesterol was directly related to your dietary cholesterol, right? So, eggs… and I if I remember right, you don’t eat a lot of eggs, I think…

Gil: I don’t, yeah. I don’t, but I don’t think that eggs are necessarily a problem. I think what you’re going to go into is this genetic variation, right?

Michael: I was… that there are some people in the normal range where maybe 20% of our blood cholesterol is based on our diet, but then there are people who have a genetic trait that will cause more of their blood cholesterol to be influenced by diet and people on the other side of the curve that have a genetic trait where less of it is. So, I think for most people it’s going to be: “Don’t go crazy, but you don’t have to really worry about it too much.”  You know in your body…. as you know, all your cells use cholesterol. And it’s… sterols are the basis of all kinds of hormones and things in your body, and your cell membranes need cholesterol and so forth. So, your body produces a lot of cholesterol to make things work. And so, I think the relationship of cholesterol and disease in your body is complicated to begin with, and then, depending on your genetics, maybe you’ve won the lottery — like the salt lottery as you said — and you can eat a lot more and it’s not going to affect you so much. But people still think that cholesterol is this horrible, evil thing. And at some point today, I hope we can also get into this trimethylamine-N-oxide thing with phospholipids and choline and carnitine, and so forth — and what that means. But I don’t want to get too far off this subject right now. Just in terms of all of these factors and how we do them. And then going back to this these diets and are there, I mean… I think that a lot of people agree that a Mediterranean type of diet is probably good for most people… that sort of philosophy. But, again, you have to look at you know really what you’re eating and what you’re substituting when you make substitutions.

Gil: Yeah; I mean, I couldn’t agree with that more. Just to give a quick concept that helps with this idea — the cholesterol idea — so, if we think about glucose…. Glucose is absolutely essential in the body. Without glucose, none of us is alive, right? You need glucose and you use… every cell uses glucose and everything, but you don’t want your blood levels of… your serum levels of glucose to be too high, right? That’s pre-diabetes or diabetes. So, there’s a very big difference between levels in the blood and the existence of the molecule throughout your body. A huge difference. Similar for cholesterol.

Michael: Similar for salt; similar for all kinds of stuff.

Gil: Similar for all kinds of parameters; right. So, cells throughout your body produce their own cholesterol. You need cholesterol throughout your body. There’s no life without… there’s no human life, certainly, without cholesterol. That doesn’t mean that we want our blood levels of cholesterol to be through the roof. Similar to the glucose. [It’s] absolutely essential… talking about more or less saturated fat or more or less anything, really, does not make sense unless we talk about the replacement. And this is and this is one reason why more and more in nutrition, we talk about dietary patterns and not isolated foods, is because what matters is the overall picture of what you’re eating. If you cut back on saturated fat and you go eat a lot of refined carbohydrates, that’s not a step forward. You know, there’s a million swaps that you can envisage that aren’t helpful. And it this is relevant because, unfortunately, the default swaps that we see in our population — especially Western populations — tend to be the unhealthy ones people will often ping-pong between one unhealthy option and another unhealthy option. So, when they hear that sugar is bad, they go for more saturated, fat rich foods; and when they hear that saturated fat is bad, they go for refined carbohydrates. And unfortunately we have this sort of zig-zag.

Michael: Yeah; and it’s not just people: it’s manufacturers. They’re making low-fat foods, and so they’re substituting, maybe, maltodextrin or other starches and sugars and so forth, which, maybe, is making the food worse depending on what those substitutions are. But people think, “Oh, well, this is low fat so it must be better for me, right?”

Gil: Right; yeah. This, the focus on isolated nutrients, has this unintended effect — sometimes intended — which is to confuse people. And they’re looking at these: the same package of these concoctions — these artificial concoctions — but now it says, “fiber added” or it says, “no sugar added” or it says… you know these different things that basically are attempts to game the system. But really, the health benefits that we see are largely moving to whole foods. There are exceptions. There are some more-processed foods that we do see differences. I’m not suggesting that it’s all the same. For example, diet soda: we have substantiation that it is better than regular, sugar-sweetened soda. There are other examples, but in general, the recommendations are to move towards whole foods, and that is the hard thing to do. And I don’t know how to do it. I don’t know how to how to help people implement that. That is the true barrier, the true difficulty. Summating the research is not that hard. Looking at research and making sense of it is not that hard either. The hard part is to help people do what we already know helps.

Michael: Yeah; and I think I think one strategy with that is people about … I think about half of people’s diets are highly processed foods, right? So, if you can convince people to have a quarter of their diet instead of half, you know? Substitute half of the junk food that you eat basically (or we’ll say, rather than junk food, “highly processed food”) with whole foods, you can still eat that same Danish that you’re feeding to your cows, or a little bit of ice cream, or whatever. But if you’re just reducing, that that’s going to make a big difference in your health. And I think also if people do that, and it’s easy for them… and the problem, going back to what I was saying at the beginning, that I have with this “diet” term is it’s very restrictive. I mean, the term typically means it’s a restrictive thing. It’s hard to do. Compliance is a huge issue, so people try this diet and it’s too hard for them and then they just abandon it completely. Whereas, if it’s more of a… giving them information and saying, “Hey; you don’t have to let go crazy; but make these changes.” And they’re easier to do, and they start feeling better, then that’s more motivation to continue on that trend.

Gil: Yeah. I think talking about these swaps maybe helps. I’m not sure exactly how much, but I think it’s probably a better strategy. So telling people, “Okay; instead of the frozen pizza, try having a piece of salmon with some broccoli. Instead of the Cocoa Puffs or the Fruit Loops, have some oatmeal. Or, and we don’t have to be perfect… we’re not trying to impress anyone. There’s no jury holding up scorecards. But just trying to do some of these swaps from these highly processed foods to more whole foods; yeah, it’s very hard to go wrong with that.

Michael: So, Mediterranean diet aside, are there diets… and also diets like the keto diet… I think was designed in the 1920s for epilepsy in kids, but lots of people use that, and for some people it’s probably a good diet for them, for certain reasons or conditions. But aside from those, just as a broad… for the broad public, are there diets that you like or think make sense, among the really popular diets.  Or variations of the Mediterranean or the MIND diet or the fast diet or various [other] ones.

Gil: Yeah. The Mediterranean is the diet that has… and we should clarify, this refers to the classical Mediterranean diet. There a lot of… say, “Mediterranean” and people are going to ask, “Well, my cousin lives in Italy and he eats junk all day long, so what are you telling me?” Right? So, it’s not necessarily what people are eating there now, but it’s this concept of the classical Mediterranean diet which we already touched on: fruits and vegetables, legumes, whole grains, fatty fish (or fish and seafood predominantly), unsaturated fats, olive oil, not a ton of ultra-processed foods, not a ton of…. Yeah; this this kind of picture. That is the dietary pattern that has the most evidence behind it just because there’s a lot of trials that were conducted with that diet, and it has consistently shown benefits. It doesn’t mean that it’s the best diet for humans. It’s just where the evidence has accumulated so far, and there’s plenty of room for personalizing. So, people who prefer to eat a little bit lower carb, who don’t want to eat so much whole grains or breads or whatever or pasta… okay; go a little easy on that. Go higher on the high-quality fats; vice-versa for people who prefer to eat lower fat. So, I think there’s plenty of room to tweak. I eat a modified Mediterranean diet adapted for my goals, where I incorporate other things as well: my concern for the environment, all these other things I incorporate, and I tweak… The fundamentals of health are there. So, that’s an easy kind of starting point. Yeah; these other diets like, for example, ketogenic diets or extreme fat diets… they are popular in certain communities. There are people who do very well on them, who like them a lot, and who are able to sustain them. From the research that we have, from randomized trials that we have, most people… if you put them on those diets they struggle to keep them, to sustain them long term. Most people don’t stick to them, don’t find them very sustainable… mainly because they’re big deviations from what most people are used to eating in our society. So, if you tell somebody to eliminate most of the sources of fat or most of the sources of carbohydrate, that’s going to be a lot of foods that people normally eat, so it’s going to be a big shift. So, for those reasons, I think it’s very tricky to issue a broad recommendation for the public to go very low carb or very low fat, because I think many people will struggle to maintain it. But for people who did it, and it works for them, and they like it for whatever reason, and they they’re able to sustain it, they’re able to maintain healthy body weight… the very low carb diets… you mentioned epilepsy… weight loss is the other reason that people sometimes do it, managing of diabetes is another context where carbon moderation has evidence as well… so there are contexts where it’s evidence-based to utilize it. Yeah; I think I think these are all… fasting is another tool that seems to be popular. There’s a lot of research on fasting, and overall it’s pointing to calories being the main factor. There doesn’t seem to be anything magical about fasting, but who cares? if you like to fast and if it helps you achieve healthy body weight with fasting, I think that’s great. Fasting… I often say that as fads, or as these trends go, fasting is my favorite because it doesn’t involve anything that’s crazy. It doesn’t involve foods that are super unhealthy. It’s basically telling… it’s a fancy word where people tell Westerners, who in general tend to overeat,… and you’re telling people to eat a little bit less. And if you tell them eat less and move more, people think you’re a quack and you should be lynched. But if you tell them, “fast and do high-intensity interval training,” people think you’re a genius, because you change the… hey whatever works. If that name excites you and if hearing about autophagy excites you and gets you to fast and control your calories a bit more and achieve healthy body weight, phenomenal! I don’t care which mechanism is getting you there.  If you’re getting the health benefits, great. Yeah; so these are all valid tools.

Michael: I did see some research, which maybe can comment on, that when your body is in a state of fasting it’s basically going into a repair mode, essentially, and so there’s studies on your telomeres and it’s supposed to help preserve them more (if you do this periodic interval fasting than not), so maybe you can talk about that.

Gil: Yeah; I haven’t seen the telomere research specifically, but in general this idea of the regeneration and the autophagy is a very common question and a very common talking point when people talk about fasting. The problem is, we have no human research showing that the autophagy induced by fasting has any benefit. We just don’t know. It’s possible, but it might not be providing any benefit per se, through autophagy, specifically. The other thing to say is when you when you match for calories, so you have one group of people fasting [while] the other group is not fasting but is eating a little bit less overall so that the calories are equated, you can get autophagy in both contexts. So it doesn’t seem to be… this autophagy idea doesn’t seem to be specific to fasting. So, in mice mostly, you do get these impressive results where… you can knock out the autophagy mechanisms of the autophagy genes, and the mice lose the benefits of fasting, even without messing with the calories. So there does seem to be something specific to and independent from calories in mice. The problem is the research that we have in humans doesn’t support that — not the autophagy specifically, but when you match for calories, you see very similar health outcomes, whether the person is fasting or just cutting calories continuously. So, in humans, the bulk the results that we have point to calories being the explanation. Now, like I said, this matters less for the average person who just wants to get the results. They don’t care which biochemical path it’s going through. And, I mean, if it excites them to hear a new name and to hear “autophagy” and to think that they’re activating some ancestral pathway, “Hey, man… whatever gets you the results,” you know? Is that is that scientifically accurate? Probably not. Certainly not . It’s not supported by any evidence that we have. Is this hyped to high heaven by influencers? Absolutely… by some people who have scientific training and should know better than to hype this. So, scientifically, I don’t like how this is portrayed, but in terms of in terms of HR and in terms of motivating people… can’t argue with that. I mean, if someone is motivated by the idea of fasting and the idea of autophagy and that helps them achieve a better optimized body weight, I I don’t want to get in their way.

Michael: Well, let me ask you two questions about the autophagy. So one is, when they’re measuring that in the mice, are they looking at the cumulative effect versus not fasting or are they looking at specific points in time. You know what I’m saying?

Gil: Yeah; you just… in mice that are fasting, you see that elevated. I don’t think it’s… I think if they’ve looked at multiple time points and you see a continuous elevation for as long as the animal is fasting…

Michael: Right? But when they’re not fasting. I mean, if you look at it over period of time

Gil: Area under the curve right because then you…

Michael: Exactly.

Gil: When you go back and eat maybe you’re under… you’re inhibiting, so overall it’s a wash. So, in the mice because you have this interesting result where you knock out autophagy and the benefits of fasting go away even if the ingestion of calories is the same there does seem to be something really interesting going on there. In humans we don’t have that, so what you’re saying in humans could be completely true: that when you go back to eating, which you have to do sooner or later, there could be an inhibition of autophagy and then… and overall, the level of autophagy could be similar because you have ups and downs, right? You have Peaks and valleys; and the total area under the curve could be similar to whether to if you if you hadn’t fasted it at all. If you match for calories between the two groups is the big… is always the factor there. So, I don’t think we know that. I think I asked I asked that question to Nick, and he… I don’t think we’ve seen that that measurement because the measurements in humans are much more limited in terms of autophagy. There’s autophagy in the context of fasting; there is research out there, but I don’t think it’s very… there’s a lot of time points or the… I don’t remember any studies where they measured autophagy again after refeeding, which is kind of what you’re asking, right? So, I think it’s all a big question mark. And in humans, because of all these factors of the calories, and the fact that not fasting gives you an increase in autophagy as well if you reduce calories, I’m skeptical that autophagy mediates the benefit. But in any case, there’s these all these ways to get there — whatever works for you. What matters at the end of the day are the outcomes… are the observable benefits in body weight, in risk of metabolic disease, and risk of cardiovascular disease and mortality. That’s the bottom line. Whether it works through pathway A or pathway B for practical application matters less. That’s basically as far as we know right now, yeah.

Michael: And you mentioned matching calories, and I have to assume that people who are on a fast whether it’s you know eight 16 or whatever that they’re going to end up if they’re doing that they’re going to end up eating fewer calories just because they’re restricting the amount of time that they’re eating and so forth, so you know you obviously have to account for that in your study but that might be a reason for all kinds of benefits of fasting just because it’s a method of calorie reduction that may be easier for some people than just eating your meals, and having snacks, and having something before you go to bed, and you end up having more calories than you would otherwise.

Gil: I think that in all likelihood, that’s exactly what’s going on. That it’s basically a way of cutting calories. So, it’s very similar if you tell somebody, “Okay; you’re going to eat low fat now.” You’re going to remove so many foods from what the person is normally used to eating, that overall they’re going to, in general, they’re going to tend to eat less calories. So that’s why low-fat diets lose weight; that’s why people on low carb diets lose weight; and that’s why people who fast lose weight. Because it’s just an easier way instead of saying, “Count your calories and eat under 1,800 calories a day,” which is a drag, you’re telling them, “Okay; after 600 p.m. you stop eating.” Simple. Anybody can follow that, and often people will eat less calories over the course of the day. There are studies that try to adjust for that and have the fasting and then on the “on” days people ate more, so that overall they’re eating the same amount of calories; and generally you don’t see a benefit there. So, again, it doesn’t seem to be about the fasting itself. It seems to be that the fasting is exactly as you said: an easy way to control calories… which I don’t think takes anything away from it in terms of a practical tool, because it’s simple; it’s doable…. Often the meals that people are going to skip by fasting are going to be, kind-of, snacks and, you know, foods outside of meals, mostly. They’re still going to have a couple meals earlier or later in the day and then they’re going to just have a bunch of snacks. So, yeah; I think it’s a very valid tool to cut back a little bit on calories and to reach towards a healthier body weight. I think that’s essentially what it is.

Michael: Okay; so I would like to get your thoughts on this idea about phosphatidylcholine, carnitine, and trimethylamine-N-oxide and… because there’s been a lot of research lately in this area and whether this is just a marker of heart disease or if it’s really because…. I think one thing that people surprises people about food is that with the exceptions of, like, apple juice or sugar, whatever, most of the whole foods that we eat have protein in them and they also have saturated fats in them, right? And so they [also] have these phospholipids and other things in them. It’s just a question of how much. So, if you’re eating egg yolks or you’re eating red meat, you’re getting a lot more density of these; and is that really directly related the way the choline breaks down and turns into the TMAO, right? Or is it just a marker, like I said.

Gil: Yeah, so we actually just shot a video on this topic a few weeks ago. It hasn’t been released yet, but it’s a video all on this exact question of TMAO and is it the marker is it a causal factor. And basically, it’s an interview with a registered dietitian who has a PHD… where he, among other things, worked on choline metabolism. So, it’s an interesting video. Basically… long story short, the evidence that we had over the course of the 2010s, give or take, kept pointing to concerns of TMAO because TMAO levels in the blood are associated to higher risks of cardiovascular disease and cancer, diabetes… all these things, right? So, people with higher levels tend to have higher risk of these diseases, and we know that certain foods will raise serum levels of TMAO. So, famously, the eggs and the meat will raise TMAO levels, and so the hypothesis was: okay; maybe this is one mechanism that these foods are raising risk of disease they’re creating. They’re introducing these metabolites: the carnitine and the betaine, and the microbiome is converting those, and you’re absorbing TMAO that gets converted in the liver into TMAO, and TMAO has all these mechanistic roles in the body. The wrench in the mechanism is… in the engine… is that starting in 2019, a couple of genetic studies started coming out looking at whether people who have higher levels of TMAO — genetically determined, so not necessarily through their behavior —whether they have higher risk of these diseases or not. And several of those have pointed to no causal role there… no cause and effect. So, that kind of shook the whole TMAO story. Now, what we went over in the video is that these studies also have their caveats. It’s not black and white, as always. There’s some nuance there. There’s ranges that… maybe in the range where they’re looking at the range of TMAO it doesn’t have a role but maybe at higher ranges it does; so there’s some uncertainty. Another factor that’s very interesting is that some foods that are less famous for raising TMAO are linked to good health outcomes, so…

Michael: Fish.

Gil: Fish for example. Fish. Fish has more TMAO and raises TMAO levels more than any of these. More than red meat and eggs. It’s one of the richest foods in TMAO. It actually contains already TMAO pre-formed. And yet, you look at the outcome data, and fish is consistently tied to good health outcomes. So, it really makes it tough to say that TMAO is a major player in causing disease when a food that has more of it causes…  is linked to good outcomes. And then these other foods that, sure they raise the level of TMAO, but, if anything, less than fish, and they are connected to bad outcomes. It just makes it very hard to….

Michael: Yeah; and that’s primarily cold water and deep sea fish that that generate that for their own protection; and I think people theorize that, well: it’s still bad in fish or at least I’ve read this, but there are so many benefits from fish in the fatty acids and so forth that it compensates for any negative effect of the TMAO.

Gil: Yeah; we touched on that in the video. So, that’s a formal possibility that the TMAO is causing some detriment but then everything else in the fish… the Omega-3s or whatever clumping the effect of TMAO…. It’s a formal possibility. The bottom line is there is no certainty whether TMAO is causal or not. There’s enough evidence there that isn’t supporting the causality to make this argument of causality pretty hard to make. Currently with the evidence we have, the bottom line… how we concluded the video… I’m really spilling the beans here, but that’s okay. How we concluded the video was kind of similar to our conversation about fasting, which was: whatever the mechanism is for the the effect of foods on health matters less than the effects that we have plenty of evidence for. So, you know; okay maybe TMAO has does have a bit of a negative effect, but we already know [for] fish, the bulk of the evidence is telling us that fish is health-promoting at certain doses. There’s concerns also with contamination and going over-board, especially [in that] certain types of fish can cause problems, but in general we’re talking about fatty fish like sardines or salmon a couple times a week… that’s consistently shown to associate with benefits. Whether the TMAO is reducing that benefit by 10% or not is less relevant than getting those results, right? And whether the concern of a large amount of saturated… a large amount of fatty red meat, let’s say, that’s enough to raise ApoB. Whether the harm is coming through TMAO or not is less important than knowing what dietary patterns give us the results. The mechanisms are interesting information, and things that scientists will continue to figure out will increase our confidence, but we don’t need to understand mechanisms in detail to have a lot of information in terms of how to put together dietary patterns that are going in the right direction. So, that was kind-of the conclusion of the video; and I think that’s a worthwhile message to emphasize.

Michael: I think it’s a good message for lots of things, as you say. But; yeah. I’ll look forward to seeing that, because that’s definitely been an interest of mine in trying to understand and figure out, and I know it’s an active area of research, so I look forward to that.

Gil: Yeah; that was one of the most technical videos that we’ve ever released, because he went into excruciating detail on these studies. But I think it’s an interesting study. It’s an interesting video for people to see discussion of these technical details. You know, sometimes on social media content is presented with an appearance of confidence — an appearance of: everything is black and white. That just doesn’t reflect scientific reality, and I think it’s valuable for people to see the considerations and the qualifiers that go into all this. And when somebody who has deep knowledge of that field, as he does, is talking about it, it’s not, “Oh; this is poison, and this is a super food.” That type of language goes out the window, and he’s talking about the details of the studies, the ranges of exposure; he’s talking about the caveats. “Maybe this; but then we have this other data set over here.” It’s a completely different universe, so hopefully people find it interesting.

Michael: And that’s a… you know, whenever I see a scientist talking about research that they’ve done or meta research or just analysis. When I see that kind of language and that positive posturing about, you know, “This is what it seems to say, but this is why it’s complicated.” Or, “There’s this other study, and we’re not really sure. We need to do more research in that area.” That, for me, builds trust in this person. And looking at that, rather than this, like you said, either these 180 degrees or “this is going to kill you and this is a miracle cure.” And particularly when I know people already have an agenda, which, you know, maybe it’s even an agenda I agree with, but when they present information and don’t present information or make it seem like it’s more than it is, or it’s extreme, and so forth, then that that makes it hard to really know what I can trust of what I don’t know and why I’m looking to them for this information.

Gil: Yeah; I think that’s a good point: nuance and presenting kind-of contrary viewpoints, I think, is a feature. I don’t think it’s going to work 100% of the time to distinguish quality content from lower-quality content, but it’s a, I would say… it’s a feature of higher-quality content than people who have good scientific background in making content on nutrition will typically… you’ll see more nuance, more of these considerations, more reference to uncertainty…. I think that’s another feature. They will acknowledge uncertainty. They will say, “We don’t know this yet; it’s being worked out.” The reason that that’s not more common is: that’s unpopular. When I make videos and talk about the uncertainty, I get a lots of complaints, and I get… and I know that people don’t like to hear that. People want black and white answers, and they say I’m wishy-washy. They say I just don’t want to tell the truth. But it’d be a lot easier to make a video saying “This food is perfect! Everybody should go eat it. If you’re not eating it, you’re killing yourself.” That’s an easy video to make. Much easier than going over 30 trials and explaining, “Okay; but there’s a nuance and an uncertainty over here.” That’s harder to do, and you get less applause in the end. But you know, I’m prouder of that content when I make it. I prefer that when I look in the mirror, even though you get less applause on social media. Ultimately, I’d rather make higher quality material and be less popular, but I think it’s a worthwhile trade-off.

Michael: Yeah; well… you get applause for me, and that’s one reason that I like your content so much, is because you’re not just out there trying to sell something or get clicks or clickbait or whatever. You’re trying to explain what we know and how complicated this is. And I think that also is important for people to know. Again, that you’re not going to start eating this one food… or doing this one thing is going to totally change your life, right? I think that there are sensible dietary recommendations, which is why I wanted to talk to you broadly about these diets and if there are things that that we should take from them or not take from them. You did a video a while ago talking about the…

Gil: ancestral diets…

Michael: …where the person you were interviewing was saying these…. I mean, first of all, we have no idea how much they ate of this or what they ate. There’s very… he was looking at the teeth and the pits and the teeth and the scrapes to try to determine… and I think that the fundamental really important thing of what he was expressing, also, is that part of our success as a species is because we eat such a broad range of foods. And basically, we eat what’s available. You know they’re not, like, “Oh…. Well; I think I’ll have this today and then I’m going to go over you know to this place and have this.” It’s just like: “This is food, and I need it, and I need the energy.” And so, we survived as a species by doing that. And also, there weren’t apples and pears and oranges and avocados and foods that we eat today. And the fruits that that they did eat were not very sweet and [were] filled with fiber. And they’re very different from the kinds of things we have today, right? So, this this whole notion of eating… that we evolved on these foods and therefore we should go back to eating them…. First of all, we don’t really have that understanding, and even if we did, it doesn’t really make sense, you know? Even if we could go back in time and know exactly what they were eating, that doesn’t mean it’s the right diet for us today.

Gil: No; because the problem is we don’t have outcomes. We don’t have… we have no idea what percentage of our ancestors had of a specific age right of a specific species…. Okay; what was the rate of heart disease at a certain age what was the rate of cancer, of Alzheimer’s. How long do they live? We don’t know the answer to these questions, so it’s like running an experiment and giving several groups different diets, but then not looking at what happens to them in the end. Basically, the main thing that you want to know is not there. Now, what people assume with these arguments when they say we should eat an ancestor diet… they’re assuming that whatever we ate, our body adapted to that, so that that diet can becomes the optimal diet for us. But that’s not at all the only option. There’s plenty of possibilities for our body to not have evolved to that diet in the in the in the way that we now aim for. So, what we care about now is longevity and avoiding heart disease at 60 and Alzheimer’s at 80 and cancer at 70, because those are the main killers in our society. We also want to be clean, and we also want to be healthy in general, but we also want to have longevity. There’s no way to know what effect different diets have on those outcomes without measuring. There’s no reason that evolution would select for… to protect us from Alzheimer’s at 80 if we weren’t even making it to that age. And if we weren’t reproducing at that age like there’s no… it’s a complete Black Box. So that that interview was one of my favorite interviews that I’ve made. Basically, it’s a good example of this. That guy, Professor Ungar, is a world-renowned paleoanthropologist who studies ancestor diets. And so, the contrast between the rhetoric that you see on social media where people say, “We know exactly what our ancestors ate. It’s exactly this diet, and it’s the diet that everybody should be eating, and you’re an idiot if you don’t eat it this exact diet I like.” And you talk to this guy who studies ancestor diets for a living and has done so for 30 years… completely different tone, this tone of uncertainty. He also went over things that they know. Things that they figured out. He explained that very well, and then he said, “Look; there’s lots of uncertainty. There’s lots of things we don’t know, and there’s lots of variability. They ate different diets depending on the place they were at, the time that we look at, the species, the environment….” So, this recognition of the variability and the uncertainty — great example of: we talk to somebody who knows his stuff, and he’s not oversimplifying to sell this idea… the simplistic idea.

Michael: I agree it was a great interview ,and you know it also reminds me… I interviewed a couple of researchers: Drs. Simpson and Raubenheimer, and they’ve done studies for 40 years on, mostly around protein leverage; but one of the studies that they did a long time ago on Drosophila were studies of diet and how basically they ate diets that optimize for fecundity over longevity, right? So, there are all kinds of factors that… we might have different goals, and maybe our evolution is geared towards that. And they’re not living… our ancestors are not living to be 80, 90…. Their bodies are trying to reproduce and they’re going to live from 0 to 30, or whatever. And, so, maybe the diets optimized for things that are different from our goals today as a species.

Gil: Yeah. And like you, said virtually none of the foods that our ancestors ate are available to us now anyway. Because you go to the supermarket and even when you look at whole foods, the vegetables and the fruits and the grains and the animals that we eat with almost no exception — maybe if you’re hunting a wild deer in the forest somewhere maybe it’s closer to what they were eating… maybe wild caught fish, maybe… — but the vast majority of animals and plants that we eat are very different because they’ve been bred for commercial purposes extensively by us. They’ve been artificially selected. And so, I think there’s such a massive gap between what our ancestors were doing and what we’re doing. It’s almost possible to replicate their diet, even if we knew what they were eating, which we don’t know with precision. But the good news is, all the research that we have of actual health effects of foods in human beings eating those foods is with modern foods. It’s not with paleo foods because they’re not around. So, we have abundant bodies of evidence of what the health effects are populationally with the foods that we have in the supermarket. And I think that the most reliable clues that we have come from that those bodies of evidence. But the thing we can agree on also across all these different views and all these different preferences… that our ancestors were not eating ultra-processed foods made in a in a factory. So that we know for sure. So it would still… at least on that we can all agree that it’s probably best to gravitate towards whole foods and to minimize these ultra-processed, highly artificial foods that don’t even look like anything you find in nature.

Michael: And even whole foods that we’re eating today… as you know, if you look at tomatoes and how they’ve been bred for yield and change the nutrients of it, if we look at farmed fish versus wild-caught fish and the fatty acid and nutrients in them, and even if we look at plants that are… because of global warming, the starch content is different in the plants, right? So, we’re basically, because of all these factors… even our whole foods are more processed in a way. I mean, they’re not going to be as good for us as the foods maybe a hundred years ago… the exact same foods would have been. And look at how chickens… Gil: I don’t know if they’re better or worse than the foods from 100 years ago. They probably have differences, I agree. But if we don’t have results in terms of health outcomes, I don’t know what the difference would be health-wise. Maybe they’re worse, maybe they’re better, maybe it’s equivalent to 100 years ago. I don’t know.

Michael: Well, I know over the last 100 years… I mean just some things in specific that I’ve looked at and, again, research that I’ve read or heard: things I’ve heard from other scientists… is there are a number of specific cases that we can look at where this exact same food is not as good for us. And maybe it’s a small amount. Maybe it’s a few percent or whatever, but we’re basically moving in this direction, and there are a lot of foods from monoculture and so forth that are definitely… because they’re bred for yield or they’re bred for disease or these other things… that the nutrition in them is changed from what it used to be.

Gil: Yeah; it’s definitely… and I’m open to the possibility that some of these changes have not been for the better in terms of the health effects. It’s certainly possible. But also, if the food is not around anymore… if the food from 100 years ago is not is not around, what choice do we have? I mean, we have the choice between the foods that exist now. Among those, which is a lot, plenty of choice, and among those I think we make educated choices based on… for me based on the scientific evidence of health outcomes that we have. I think that’s, by far, the best heuristic… the best source of information. But not everybody agrees. Some people don’t care. Some people just want to eat what they like and just enjoy the taste, and if it has a health outcome that is not the best, then that’s a price they’re willing to pay. And I think that’s valid too. That’s a personal choice that I completely respect.

Michael: No; I fully agree with that. I mean, food is one of the really important joys in life. So, if you’re eating a diet 100% for health and not for enjoyment… I mean for some people maybe that’s fine; but for me, it wouldn’t be. I do try to eat well and I, like you… I make decisions based on… not just on health, but on what’s good for the planet and for humane reasons and other things. So, you know, it’s complicated. But I wouldn’t want to live my life not eating foods that I really love, just in moderation, right? So, you try to balance those things so that…. To me, that makes me happy, and I think that’s going to make me live longer than having all the stress of worrying about diet, which is why… one of the things, again, I wanted to kind of go over with you is… how do people ignore all this hype and all this constant barrage of food information and this flip-flop of: coffee is good for you; it’s bad for you; it’s good for you bad for you… or alcohol, you know? You know, what’s the latest is on: is it a little bit of alcohol is better than no alcohol or a lot of alcohol or is that not really true? And that doesn’t really matter that much. I mean, obviously, a lot of alcohol is not going to be good for you, right? But if it’s zero or a little bit, probably it’s not going to really make that much of a difference, so if you enjoy a little bit of alcohol, I think that’s just fine.

Gil: Yeah. I think on alcohol, the idea that used to be around that eating a little bit is beneficial… that eating a little bit… not eating, so… this wine paradox that’s been largely well, if not completely debunked, very weakened substantially. The strongest evidence that we have argues against this idea of this benefit of eating a little bit, so it doesn’t seem to have any benefit. It seems to be pretty much a straight line. But, yeah. Once you get to a glass a week or something like that, is that going to be even measurable are you going to have a significant increase in risk? Probably not at that at that very sporadic level of intake. It’s hard to pick that up in in studies anyway, something so sporadic. It just becomes kind of this this educated guess. [For] somebody who really enjoys it and the risk is very small and the person is willing to… this educated gamble. For someone… for example, I don’t enjoy alcohol, so it’s easy for me to not drink. I wouldn’t drink it even if it had no detriment. I personally don’t like it, but yeah; there are other things that I do… I’m not a monk. I feel like eating a cookie once in a while… Once in a while, I’ll eat a cookie or I’ll eat something that is not ideal. I just won’t make that a staple of my diet. And I doubt that having a cookie once every other week is going to significantly affect health in the long run. If 99% of the things I have… the boxes I have checked. So, I agree with that. Trying to trying to do the best we can without being without becoming OCD that that is in itself becomes a factor.

Michael: Right; exactly. Do you have interest in or studying of some of the latest stuff that’s going on with the microbiome and like the gut-brain axis and you know I know there’s been a lot of research has gone on in recent years and it’s some really fascinating stuff.

Gil: Yeah; we’ve done a couple of videos touching on that. I think I mean I think it’s a fascinating field in development. I think that the microbiome is still very much at its early stages of understanding. I think mostly a black box, but we don’t know that much about microbiome because there’s all these gazillions of different species, and it varies dynamically. It’s so complicated, so difficult to study… and I think like with any one of these fields there’s…. the hype train runs 50 miles ahead of things that we actually know for sure, scientifically. But yes; I think it’s a fascinating field. I think it probably will have an impact on lots of different aspects of health. One thing that people who study the microbiome seem to agree on is that eating fermented foods is a good idea… try to include some of those in your diet. So, I try to I try to do that without again becoming OCD about, “Oh my God; I didn’t have anything fermented today.” Myself, I’m not that worried, but I try to integrate it. I try to rotate some of that with the rest of the stuff. But, yeah, I think mostly it’s an exciting new frontier to come. It’s one of the fields that I think is going to be really exciting: the microbiome, this thing of the individualization, the precision nutrition, figuring out how to individualize diets for each person I think is really exciting, and a lot of hype; but a lot of things are not necessarily panning out and a lot of stuff that’s being sold that’s not been demonstrated in any meaningful way. But I think probably a lot of interesting and empowering stuff is going to come from that from that field. Yeah; figuring out more about the genetic factors also, if we can have… because we have such limited understanding in terms of this individual susceptibility. Why do some people smoke like chimneys, and they don’t get that lung cancer ever, and then other people don’t even smoke and they get lung cancer, right? So, the susceptibility is such a huge factor, and we don’t have good ways of predicting that. But presumably that would be doable if we had a better understanding of the genetics and we could run some kind of chip and go, “Okay; so you have these polymorphisms. You have a pretty high susceptibility, so you definitely want to avoid tobacco and asbestos and all these exposures.” “Okay; you have very low susceptibility; it’s less of a concern for you.” This type of personalization I think we are still very poor at, and I think in the future is something that I see a lot of potential for.

Michael: Yeah; that that’s a really good point about our body’s ability to repair itself. And whether it’s from the muons from the Sun or from reactive oxygen species or oxidative stress, stuff like that. And so, that’s why antioxidants are such a big thing. But, yeah; there’s a way that people could know. Especially if there’s if they’re susceptible to lung cancer or some specific type of disease and there’s a marker for that and we could say, “Okay; well, for you do these things.” And I know…. I haven’t really looked into this very much but like Zoe, you know, they’re trying to sell this this whole package. And maybe it’s good and maybe it’s not, I don’t really know. But it’s definitely a field that I think is going to have a lot of interest for people — especially when it becomes… it’s like with 23 and Me… it becomes so inexpensive to get your genome mapped, where the first time we did it was however many billions of dollars it a cost to do, right? …with scientists all over the world participating. So, as these things become easier and you can just spit on a stick and send it in and they… “And here’s your diet.” Right?

Gil: …do it on your phone probably in 50 years. Yeah, you plug it into some device, and it automatically gives you all this…. But yeah, I don’t think that the science is there yet to for all this personalization. And these programs, I haven’t seen any evidence that the science is there to be able to design diets for each individual with some exceptions. I mean, some things are obvious: if you have celiac disease which, yeah, you can test for that, obviously avoid gluten. If you have an allergy, avoid the allergen. Yeah; some exceptions to that, but this idea that we test every individual and you know what diet is right for you… I don’t think the science is there yet. I’d love to be proven wrong, because that would be phenomenal, but I haven’t seen evidence that we have the knowledge to do that yet.

Michael: Right; but, you and I both know that statistically that will work just because of the placebo effect and this doctor care… (I don’t know what it’s called) but when you… when you feel like you’re under the care of someone who cares about you, it’s going to have a positive impact on your health, right?

Gil: So, you can design the trial… they didn’t they didn’t do it that way, and I… there’s debate, you know, but I’ve talked to some of the people behind it, and they say that their goal was not to do. That their goal was just to just to see if there was a benefit, period. And not necessarily to test if this aspect of the personalization was working, so it’s kind of a first pass. But if you want to test if the personalization is working which is the highest bar and arguably the more interesting question, yeah you match for the level of attention. So, you have the your control group also receiving attention and also receiving a program that they are told is individualized for app. But you design the diet randomly, so you give them a diet that is not designed for them, but you say it is. So, you lie to them… which, you know, it’s okay to do in the setting of a of a study because you’re told beforehand that that might happen. You might get the placebo. So, then, you match for those aspects, and if you still see a benefit of the diet that is designed for the individual, that’s a very interesting, compelling argument that… it’s the personalization; it’s not just the use of the app or the interaction with the dietitians or any of this stuff. I mean, I think that that’s an incredibly high bar, and that would be a stunning result. That would be a huge, deserved headline of like: wow… they found something that’s truly groundbreaking. But that’s tough; that’s very tough to achieve. But yeah. I think it’s theoretically possible. I think it’s a matter of time. If you get to a point where you understand the genetics well enough that you can predict the reaction to different foods, it should be doable. But it’s, yeah… it’s going to require a lot of knowledge that I don’t think we have right now.

Michael: Yeah. And I think there’s a lot of things too that come down to cost/benefit. You know, there’s… I know someone who’s trying to sell me these vitamin pills that are super expensive, and I looked into what they’re made of, and it looks like good, natural stuff that you can probably just as easily get from eating whole foods, and you have a lot of other benefits from getting it from whole foods, but it’s not that it’s a bad thing other than that it costs so much money and it’s sort of a multi-level marketing, as a lot of them are. I don’t know. That kind of stuff makes me crazy, but so there’s a lot of things like that, that… no it’s not bad for you, and it may be even good for you. But is it really worth whatever the cost is? Whether it’s monetary cost or other costs, in in terms of doing that.

Gil: Only one way to find out… test it!

Michael: Yeah, well that’s true. But you know companies aren’t motivated to run trials unless you know if it’s going to maybe show… if it’s a really honest trial and they’re going to publish it either way, right?

Gil: For supplements, you don’t need to show evidence because people will buy it even with outside scientific evidence. Even without the supplement… have having been… first of all, you can get it approved. You can sell it without evidence that it works. You can sell it without evidence that it’s safe. And the public will buy it. So, there’s very little incentive for a company to run a trial, which is one reason that I respected Zoe for running the trial, even though a lot of people disagreed with the experimental design. But the fact that they ran a trial, I think, is already more than what most of these companies and these apps are willing to do. And I’m sure it wasn’t cheap, so I think that’s a respectable step. I think as we as we empower the public with more understanding and more knowledge and people start demanding more, the bar is raised for people to test their stuff better. That’s the direction it has to it has to go.

Michael: All right so do you have any final… This has gone… I super appreciate all time that you’ve spent. Do you have any final comments or advice for people or things or studies that you have found really interesting.

Gil: There’s so many studies, it depends on the field that people are interested in, but we have some videos… one or two videos. If people are interested in researching things at their level of looking at studies, we have one or two videos that explain the basics of how you go about researching a topic… how you find the databases and how you search to find information. So, Google Scholar is a great resource… works just like Google, looks just like Google, but instead of getting random web pages, you get peer-reviewed scientific material  — great resource. The Cochran is another great resource. It’s a web page where you find these meta analyses of trials for different conditions. So, that’s a more medical thing. Google Scholar, you can find a lot of biology and chemistry and nutrition as well. Yeah, so those are would be two kind of first tools for people to play around with.

Michael: Well, Gil; thank you so much again for your time. This has been fascinating. I love this stuff. And, I mean… I could talk for hours and hours and hours and ask you all kinds of questions, so I really appreciate all the time and advice, and I think people find this super interesting.

Gil: My pleasure.

Michael: Well, I am looking forward to seeing your TMAO video when it comes out. I will definitely be on the lookout for that, and I’ll put some links to some of the other videos we talked about and your site in general.

Gil: Sounds good thanks a lot.

Michael: all right thank you.

Gil: Take care!




Gil Carvalho

University of Southern California Hospital

Gil Carvalho, MD PhD is a physician, research scientist, and science communicator. Dr. Carvalho became a medical doctor in the University of Lisbon, in his native Portugal, and later obtained a PhD in Biology from Caltech (California Institute of Technology). He has published peer-reviewed medical research spanning the fields of genetics, molecular biology, nutrition, behavior, aging and neuroscience.

In parallel with his research career, Dr. Carvalho also has a passion for science communication. He directs and hosts Nutrition Made Simple, which aims to convey fundamental nutrition concepts to a general audience via educational videos. His content is watched by over half a million people monthly.

Dr. Carvalho’s research contributions at Caltech, where he trained with pioneer geneticist Seymour Benzer, included the identification of genetic and nutritional mechanisms of longevity.

Dr. Carvalho also pursued research, with neuroscientist Antonio Damasio, on mechanisms of neural signal transmission in the sensory system and the neural basis of interoception and feeling.

He has been a member of the Genetics Society of America and the American Society for Neuroscience. His accolades include a Delill Nasser Award for Professional Development in Genetics and a Mathers Foundation award. Both his research contributions and his expert commentary are regularly featured in the media, including The Proceedings of the National Academy of Sciences, Nature Methods, the San Diego Union-Tribune, Quanta magazine and ScienceDaily. He is also a contributor to the Institute of Limbic Health and the T. Colin Campbell Center for Nutrition Studies.