Transcription
Intermittent fasting and autophagy debunked. Next! Oh boy, do we have a hot one today! Oh man, this is a study published in Science Translational Medicine back in 2021, and I am shocked that I did not see it. Shout out to M. Henselman; I saw it on his Instagram and I DM'd him. I was like, "Bro, let me see this study."
So this study was looking at alternate-day fasting compared to normal calorie restriction, compared to alternate-day fasting with no calorie restriction, looking at fat loss, lean mass, a bunch of metabolic stuff, and markers of autophagy. But first, make sure you like the video, subscribe to the channel, and leave a comment for the algorithm.
This was a pretty short-term study; it was only three weeks, and I know that's going to be when everybody picks out blah blah blah. When researchers do what's called a power analysis, they look for what number of subjects do we need and what duration of time of a study do we need to feel confident that we can detect differences. For example, they have shown that you can detect differences in the gut microbiome within a few days of changing the diet. Within a week, they've shown that you can see differences in fasting glucose within a couple of weeks. They've shown you can see differences in fat mass within a few weeks if you have a certain number of subjects. If you know what you're looking for, what you're trying to detect, you can calculate how many people, subjects you need in each group and what period of time you need it in, in order to actually find differences.
The uneducated folks out there may scream about the duration of the study, but it doesn't matter because the research has shown this was a sufficient amount of time to detect differences in the things they measured. Let's talk about subjects. This was lean people, so anywhere from like a 20.5 to a 24.9 BMI, and I'm sure people will hit on that, but again, this data is very much in alignment with data from other studies in obese and type 2 diabetic people.
What was cool about this study was they measured a lot of stuff. They measured all kinds of blood lipids, blood glucose, insulin, leptin, ghrelin. They looked at mRNA expression of a bunch of different genes, including genes involved in autophagy, and they looked at energy balance. So they measured energy intake; they had weighted food records for all the subjects. They looked at energy expenditure; they looked at BMR; they looked at physical activity. They measured a lot of stuff. This was a very involved study, which again is why it was also short because the more things you're measuring, the more you're poking and prodding these individuals, the shorter duration it's going to have to be because people won't sign up to be going into a lab every single day for the rest of time.
I think people don't realize there's not like a pool of people that just sit around like twiddling their thumbs going, "Man, I just can't wait to be selected for a human randomized control trial, and I'm just going to put my entire life on hold and go do whatever they tell me to do." Yeah, those people don't exist. The people in the studies are people like you and me, people who have jobs, families, lives. That's why you don't see 10-year randomized control trials because nobody is going to let themselves be poked and prodded for 10 years. It just doesn't work that way. They're taking a lot of measurements; they also did DEXA for body composition. So this is a lot of measurements; these lab visits were probably several hours at a time.
Now, one of the things I really like about this and why I think it was a really good study was they also picked the right thing to randomize these people on because you have to randomize based on a variable so that between the two groups there's no differences at baseline. So they randomized them based on their body fat index, okay, based on how much fat mass they had for their height. It's basically body fat mass index, like BMI except with fat, with body fat instead of weight. So they randomized them based on fat mass index and physical activity, which I think is very, very smart because they didn't want differences in baseline in fat mass and they didn't want differences in baseline in physical activity because it could skew the results.
They put them into three groups, and those three groups were alternate-day fasting where they weren't in a calorie deficit across the course of a week, okay. So on one day they consumed 200% of their maintenance calories, what they maintain their body weight on; the next day they consumed nothing; then 200%; then nothing; 200%; then nothing, and so on and so forth. Then there was a group that was doing normal calorie restriction; they ate 75% of their maintenance calories every single day for the duration of the study. Then there was a third group that was doing alternate-day fasting with calorie restriction, so they were doing 150% of their maintenance calories one day, then 0%, then 150%, then zero. So over the course of the study, the calories were equated between the two energy-restricted groups, and then they had a separate alternate-day fasting group that was not in a calorie deficit and not losing weight. And so the purpose of this was to isolate out: are there unique effects of fasting on any of these markers?
And I have said this for a long time that, okay, let's take this example because I've said this before; you can go look up my old videos. I said, "Okay, I have no doubt that fasting increases autophagy, but if we're equating calories between groups, groups, if you're fasting one day and your autophagy is way up, then you're eating more the next day, then autophagy is going to go down relative to somebody who's just eating the same amount every single day." Yes, on a fasting day, autophagy may be higher than just normal calorie restriction because you're not eating anything, but then on a fed day, it's going to be lower, and the net is going to be nothing. I think math is hard for some of these fasting zealots because they'd say, "Well, no, that's not the purpose of fasting. The purpose of fasting is not to lose weight. If you get autophagy even without losing weight, well, fantastic, boyos!" Because guess what? This study did: we had a group not losing weight, not in a calorie deficit, and doing alternate-day fasting. If there was going to be some unique effects on autophagy or metabolic health from fasting independent of calorie restriction, we're going to see them. And what did they find? I'm so glad you asked.
I want to point out where there was differences. Pretty much across the board, there were no differences between the groups doing energy restriction. So both normal, old, boring calorie restriction and alternate-day fasting, when equated for weekly calories, basically had no difference on most of the things that they measured. Weight loss was similar between the groups; however, the energy-restricted group lost significantly more fat mass compared to the alternate-day fasting group. They had a greater reduction in their fat mass index from normal calorie restriction than alternate-day fasting, a greater percentage of body fat loss, and when you look at the percentage of weight lost as fat versus lean in the daily calorie-restricted group, so 75% of their maintenance calories, normal boring calorie restriction, over 90% of the weight they lost was from body fat. In the group that was doing alternate-day fasting, half of the weight they lost was from fat mass and half was from lean; half of the weight was from fat, half was from lean. And by the way, they made sure to standardize them for body water, so this was not a difference in body water; this was likely a difference in actual lean tissue.
Now, all the other stuff they looked at—things like visceral fat, bone mineral content, bone mineral density—none of those things were different. Now comparing the non-energy-restricted alternate-day fasting group, that group did not have a reduction in fat mass; they did not have a reduction in fat mass index; they did not have a reduction in body weight that was significant; they did not have a reduction in body fat percentage. Basically, most of their stuff stayed the same. The only difference was they had a small but significant decrease in bone mineral density, but it wasn't different than any of the other groups, and I don't really think it means much, at least with the anthropometrics. No unique benefits to fasting without calorie restriction, and with calorie restriction, it actually performed significantly worse for alternate-day fasting.
Let's go to some of the metabolic stuff. We're looking at blood glucose, non-esterified fatty acids in the bloodstream; we're looking at HOMA-IR, a marker of insulin sensitivity; triglycerides, HDL, LDL, leptin. Out of Pekon, basically there was no difference in any of these measurements between pretty much any of the groups, okay. There was some, there was a couple of differences, but none of them were worth noting; they were very small, and they were expected. Like, for example, leptin decreased in the normal calorie restriction group more than the group that wasn't calorie restricted, which is to be expected because they reduce their fat mass more; leptin basically follows fat mass. But everything else was the same, so no unique effects of fasting on blood glucose or any markers here of metabolic health or insulin sensitivity. They also looked at like meal responses for things like plasma glucose, plasma triglycerides, plasma insulin, plasma ghrelin, and basically found no differences between either of the two energy-restricted groups.
The one other thing they found, too, was there was actually a significant decrease in energy expenditure in the alternate-day fasting group under energy-restricted conditions relative to the normal boring, old calorie-restricted group, and they found that this was due to decreased spontaneous physical activity. So neat. For example, they found that they just were less active without even realizing it in this alternate-day fasting group. And finally, markers of autophagy: no differences between the normal boring calorie-restricted group and the alternate-day fasting group. Where is your God now, fasting zealots?
I am not against fasting, right? I am not anti-fasting. It is a useful tool to control calorie intake, but in the studies where calories are equated between groups, we see virtually no differences between fasting and non-fasting protocols. And the one thing they have always fallen back on is, "But you just don't understand autophagy mode." Well, autophagy mode doesn't exist. Autophagy mode is not an on/off switch. Autophagy just refers to the rate of lysosomal protein degradation, which is never on or off; it increases or decreases the relative rate based on the metabolic milieu of whatever is going on in the body. And things like calorie deficit, exercise increase autophagy; fasting can increase autophagy, but not because fasting is magic, but because fasting induces a calorie deficit.
Now what I will tell people is I don't think fasting is necessarily worse than regular calorie restriction if you're doing one of the more moderate forms of fasting, like your normal 16/8, 18/6, maybe even 24. But once you get outside of those, you do see quite a few studies that show decreases in lean mass and physical activity. This is not the first study to show this; there's a couple of others as well. And so I would say that the more extreme forms of fasting, probably not the best for maintaining lean mass and energy expenditure. Again, I don't hate fasting; I think it's a useful tool for many people, but what I do dislike are people who say really dumb stuff about fasting and try to imbue it with magical properties when it quite obviously does not have any. This is a calorie effect. I'm sorry that the answer is boring, but guess what happens so often in science? Something that we like to call Occam's razor, which states that when all things are equal, the hypothesis that requires the least amount of assumptions is usually true. Stated more plainly, the simplest answer is usually true, all of the things being equal. But again, fasting is a useful tool, which is why our app, Carbon Diet Coach, does not pigeonhole you into any one way of dieting, and you can do regular intermittent fasting using the Carbon Diet Coach app because we do not force you into any specific meal frequency either. We have low-carb, low-fat, plant-based, balanced; we have all different kinds of options for you on Carbon Diet Coach and give nutrition coaching for less than 10 bucks a month. You can't beat it! Algorithm written by yours truly, put my coaching into a coach that fits in your pocket, in your smartphone. Go check it out; click the link in the description, and I'm out.