Dr. Rhonda Patrick: Okay, we're running out of time. I do—there’s another topic I want to cover. I also want to ask you about personal routine, but the topic is something that you and I have probably butted heads with a little bit, at least on social media in the past, years ago. I don’t know that it’s been recent. And that has to do with time-restricted eating and, you know, a form of intermittent fasting. So my question to you is, well, first of all, I want to say this. Over the years, my view of certain benefits of what I think of time-restricted eating has changed as more data has come in.

And specifically referring to the fact that there are studies out there that have calculated if people are just in their free-living environment and they're naturally doing time-restricted eating and they actually are doing it, they do decrease their calorie intake.

Dr. Layne Norton: Correct.

Dr. Rhonda Patrick: Between 200 and 500 calories depending on how short of a time window they're eating their food. And so if you don't consider the calories that they are restricting, the weight loss benefits seem to go away when you then consider the calories. So in other words, if they aren’t restricting calories, the time-restricted effect on weight loss seems to go away.

Dr. Layne Norton: That's correct.

Dr. Rhonda Patrick: Now, I didn’t always believe that, but as more data came out, I now say, okay, well, this seems to be real for sure. There are a lot of types of time-restricted eating. There’s, like, a six-hour window you’re eating in, an eight-hour window. There's even 10 hours, which I don't think you're going to get a big difference if you're comparing ten to twelve. But what about other effects of time-restricted eating? Do you think there is a circadian component to time-restricted eating? Right. There is a circadian component. You’re eating—humans are diurnal creatures. We're eating within our time window when our circadian rhythm is more metabolically inclined to process glucose and fatty acids and everything. Right. Do you think there is a possibility of a benefit of time-restricted eating, like independent of calories?

Dr. Layne Norton: I think there's a possibility, but I think based on the research I've seen, if it does exist, it's probably pretty small. You do in some studies, I actually posted about this, I think yesterday. You do in some studies, see some of the more transient markers have an effect with like, especially like early time-restricted eating versus like continuous feeding. But you don't, at least to my knowledge, I haven't really seen one that shows a difference in HbA1c or HOMA-IR, those sorts of things. What you tend to see is, like, fasting blood glucose, fasting insulin, maybe a little bit lower in the early time-restricted eating, which I think it's possible. It's possible that is a real effect. I think it’s also possible that, okay, well, if they're early time-restricted eating and they finish eating at, like, 01:00 p.m. and they're not eating until, you know, 08:00 a.m. the next day when they're doing a blood draw, whereas the person who is just regular eating eats right before bed, gets a blood draw the next day, I think it's possible that that might explain that small difference. Now, I could be wrong, and so there could be. There could be a small extra benefit to it.

Dr. Rhonda Patrick: Have you seen the blood-pressure one?

Dr. Layne Norton: I haven’t seen the blood-pressure one.

Dr. Rhonda Patrick: That's the six-hour, I think it was Dr. Krista Varady from Chicago. The blood pressure was interesting. Again, calories were equated, so there was no weight loss. There was the fasting blood glucose, but blood pressure was the thing that was most interesting to me, because it was, like, effect sizes that you get with antihypertensive treatment drugs, which was very interesting. And so that's something. I mean, there's, again, you're getting into the potential cardiometabolic effects. There needs to be more research, but I just wanted to see what your stance is.

Dr. Layne Norton: And I think, again, that would be one where I'm like, I'd like to see how the timing of the measurement affects it. Right. So what I would like to see is somebody do a study just like that. But when they do their final blood draw and blood pressure, they do the same length fasted from the day before. Right. So that you're equating that fasting period before those things, because, again, I think, you know, blood pressure responds relatively acutely to a lot of different things. Stress. You know, if you just ate, you'll have a higher blood pressure due to solutes in your blood. So, you know, I think it's possible. And I hold open that possibility. I think what I tell people is, like, practically, it's probably very little difference.

And so I look at, practically, is this something that you can implement in your life and make a lifestyle? And if the answer is yes, by all means, it's a great tool, right? Like, it's a great tool. It's one of your only levers. The levers you have are dietary restriction, like low carb, low fat, plant-based, whatever, calorie tracking restriction. Right, where you’re tracking stuff or time restriction, those are your three levers you can really pull in terms if you want to put things into buckets, right?

Dr. Rhonda Patrick: Right, right.

Dr. Layne Norton: And you can combine them if you want to, but whatever gets you consistent. That is the, that is the biggest thing. And so for some people, they love time-restricted eating. You know, I've had people say, like, hey, I eat in this eight-hour window, six-hour window. I don't feel hungry.

I'm good. And so I think where people, the messaging can get confusing, again, is like people say, well, there's some evidence that early time-restricted eating is better, okay? But what happens if somebody is, like, not being adherent to that because they get hungry at night and then they end up binging at night because they're, well, I already screwed up my feeding window. Might as well just have whatever I want, right? And so I think the messaging, it's important to understand why these things work, right? And so we would both agree, okay, if there's a benefit, it's probably small. And the biggest lever is making sure you're just being consistently controlling that calorie intake.

And so the benefit of time-restricted eating is for many people, they don't have to track and they'll limit their calories that way. But I have met people who use time-restricted eating as basically an excuse to binge eat during their feeding window. And for them, that's not going to work very well. Right. And so the other thing that gets brought up a lot is kind of, you know, autophagy and then longevity. And so what I'll say is, yes, time-restricted eating raises autophagy, but so does calorie restriction and so does exercise.

Dr. Rhonda Patrick: Yeah, all true.

Dr. Layne Norton: And also with autophagy, I think, again, this is where it's like, using terms as blanket good, bad. I mean, autophagy is elevated in some cancers. It's elevated in some wasting diseases. I mean, we're talking about lysosomal protein degradation, essentially. And so I just try to remind people, like, thinking about stuff in black and white is probably not the way you want to do it right? Now, I think the issue with trying to understand something like autophagy is really you'd have to almost do studies looking at autophagy where you're equating, like, weekly calories, like, if you want to get more extreme versions of fasting and then looking, okay, what is the overall net effect? Because, all right, let's say you're doing alternate-day fasting, right?

Like a more extreme version of fasting. Absolutely. I have no doubt that on your day of fasting, your autophagy is going up. But then if we are equating calories, right, you're going to be eating much more on your feeding day than a person who's just eating the same amount of calories every single day if we're equating apples to apples. Right. And so when you're eating more, that tends to reduce autophagy. And so what's the overall net effect? Right. I don't know. I don't know the answer. But I would suspect based on other things I've seen, that it's probably going to be really no difference, that it is a tool to control calories. And that is what affects autophagy. On longevity, I mean, really, there's some animal studies, there's some in vitro stuff as well, I think.

And even the calorie restriction stuff, I think I have a kind of a unique take on this because I’ve done animal research. So there’s nothing I’m aware of. I mean, there are a couple of rodent studies looking at time-restricted eating where they suggested a longevity benefit. I think the rodent model is probably a poor model for longevity because rodents grow throughout the course of their life. Humans kind of peak at like around 20 and then they kind of stay level, I mean, obesity notwithstanding. And then they start to decline later in life. Very different growth curve from rodents. Now rodents are good models for other things like protein metabolism, decent model for glucose metabolism, but for longevity, I'm not convinced.

Now if we look at the monkey study, the primate studies, we see the calorie restriction effects on primates, right. And so I think—but I'm not even convinced it's calorie restriction. And here's why. Because I know how these studies are done. Because when you're looking at lab animals, you just look at what they normally eat and then you cut 20% to 30% out and you go, that's calorie restriction. But I pulled up these studies and looked at the charts of these animals’ weights. They don't keep dropping. There's maybe a little drop and then it just kind of plateaus, right? Like they don't really lose much weight if at all. Animals tend to overeat in captivity.

And when you look at the odds ratios of what obesity does for longevity, what I think is happening and what I think you're seeing is these animals just don't become obese and they don't gain excess amounts of body fat. And so calorie restriction, it's probably more, probably better put as it's just like preventing excess body fat, right. Because, I mean, if you take that at face value, I mean, if you're truly in a calorie deficit entirely, you'll die eventually. You'll die, right. So I think a lot of this literally can be boiled down to just don't become obese, don't have excess body fat, and you don't have to be super lean either. Like, actually, the mortality data suggests if you're super lean, that's probably not good either.

There are some aspects of that that I tend to think that people who are very lean are probably extreme in other ways, and those aspects of their life probably contribute to the mortality rate. But, like 15% to 20% body fat if you're male appears to be a very protective effect for mortality compared to being 30% to 40% body fat. And so again, I am very convinced that excess body fat is really bad for metabolic health, cardiovascular disease, cancer and mortality. But how you get to a normal body weight or lean body weight, I think is way less important than actually just getting there.