ZOE Science & Nutrition - This is what the Keto Diet does to your body...

Episode Date: July 7, 2022

Keto has been promoted as a magic bullet for weight loss by its supporters and slammed as dangerous by its opponents. It's no surprise - completely removing almost all carbohydrates is not what most people consider ‘a balanced diet’. With carbs off the table, Keto diets involve a dramatically increased fat intake. At the same time, drastically reducing carbs means starving our gut microbes of the fiber that feeds them.  Nonetheless, doctors prescribe keto diets to treat people with severe diabetes and see dramatic improvements, and many healthy people swear by keto for weight loss. On top of this, removing carbohydrates prevents blood sugar spikes and crashes linked to inflammation and disease.  In today’s episode, Jonathan speaks to a leading nutritional researcher to understand whether or not keto diets are a crazy fad: Christopher Gardner is a professor at Stanford University and a member of ZOE’s scientific advisory board who’s produced a clinical trial of keto diets, published in the American Journal of Clinical Nutrition. Download our FREE guide — Top 10 Tips to Live Healthier: https://zoe.com/freeguide Timecodes: 00:00 - Intro 00:10 - Topic introduction 01:38 - Quick-fire questions 05:20 - What is a ketogenic diet? How does it work? 08:34 - Why have people become interested in keto? 10:16 - To promote ketosis, how low-carb should a diet be? 11:46 - Why are randomized trials so important? 14:37 - Christopher’s study 18:46 - What is a Mediterranean diet? 21:31 - Study results 25:33 - How sustainable is a keto diet? 31:22 - How strictly should you follow the keto diet? 32:47 - Diabetes and keto 35:36 - Keto’s impact on the microbiome 37:57 - Is there a long-term impact on the ability to process carbs? 39:51 - Summary 41:40 - Listener’s question 42:12 - Goodbyes 42:32 - Outro Episode transcripts are available here. Read Chris’ Study here. Follow Chris: https://twitter.com/GardnerPhD Follow ZOE on Instagram: https://www.instagram.com/zoe/ This podcast was produced by Fascinate Productions.

Welcome to ZOE Science and Nutrition, where world-leading scientists explain how their research can improve your health. Ketogenic diets ignite furious debate. Keto has been promoted as a magic bullet for weight loss by its supporters, and slammed as dangerous by its opponents. It's no surprise, completely removing almost all carbohydrates is not what most people consider a balanced diet. With carbs off the table on keto, we still need to find our energy somewhere. This means a dramatic increase in fat intake. At the same time,

drastically reducing carbs means starving our gut microbes of the fiber that feeds them. Nonetheless, doctors prescribe keto diets to treat people with severe diabetes and see dramatic improvements. And many healthy people swear by keto for weight loss. On top of this, removing carbohydrates prevents blood sugar spikes and crashes linked to inflammation and disease. On today's show, we want to ask what the latest science says. Are keto diets a crazy fad or could keto be right for me? To help answer this question, I'm joined by leading nutritional researcher, Christopher Gardner, a professor at Stanford University and a member of Zoe's Scientific Advisory Board.

Christopher is excited to share the results of his landmark clinical trial of keto diets published this week in the American Journal of Clinical Nutrition. You will find links to this paper in our show notes. Christopher it's always such a pleasure to spend time with you and I'd like to start with our regular quickfire round of questioners that our listeners are sort of used to now. So let's kick off. Can you improve your health on a ketogenic diet? That's complicated because there's good and bad ketogenic diets and there's good and bad normal diets. I can imagine a ketogenic diet that's healthier than some people's regular diet if you followed it a certain way. So we'll have to come back to that.

All right. So it's complicated. Can you lose weight on a keto diet? Absolutely. It's a very restrictive diet. And for the things that are still allowed, the palatability will run out quick and you'll say, I am hungry, but not for that. So nope, not going to eat, lowered my calories, lost weight. Is keto a good diet for most people? I'm personally opposed to it because of its absence of grains and fruits and beans, which don't seem justified to me. So I don't think in the long run that it is. It's great for getting rid of added sugar and refined grains. Is doing keto from time to time helpful? I'm opposed to anything that isn't a diet pattern that you'll

follow for life. I'm opposed to things that are just transient. I'm going to do this for a while and it's a diet that I'm going on and then I will go off the diet when I got where I wanted to be. Well, if you go off it, then the other stuff comes back and it was useless. What's the biggest misconception about the ketogenic diet? That it's high meat. People think it's low carb and what has low carbs? Oh, well, meats have low carbs, but really the ketogenic diet is a high fat diet. If you end up eating a lot of protein, then you've met your needs for the day and you convert your proteins into carbs and fats and whoop, you threw yourself out of ketosis by making carbs out of your protein. That's amazing. And I did not know that.

Thank you, Chris. Final question. Will cutting out carbs stop your body's ability to process them? No. That was simple. All right. Well, look, I'm really looking forward to digging into those answers more. The whole topic of ketogenic diets ignites furious discussion and I think a lot of confusion. I personally have never tried it because the idea of giving up bread and croissant for good, I just know that's a step too far. But as someone with bad blood sugar control, I know there's some impressive evidence that keto can help people with diabetes, come off insulin. So there's some real clinical evidence to suggest there's something interesting there.

And so I think really fascinating, Christopher, for you to take us through this. And maybe we could just start with what is a ketogenic diet and how does it work? Sure, so the ketogenic diet actually goes back 50 years as a diet that was used to treat epileptic seizures. It's been around for a really, really long time, but it's really odd that people are now taking this and doing it for weight loss, and some athletes are trying it,

and it's certainly relevant in the world of overweight, obesity, diabetes, because a lot of that has to do with excessive carbohydrate intake and inability to process those carbs. So if you wipe carbs out of your diet, if you go to extremely low levels, other than some above ground vegetables and maybe some berries, you can resolve some insulin resistance issues. You will lose some weight. And so there is some basis of interest in this, especially given how many simple and unhealthy carbs people eat these days. But a central component of our discussion, Jonathan,

should be good carbs versus bad carbs. Brilliant. And before we go on to that, because you mentioned this word ketosis before, can you explain a little bit more beyond just this idea that I'm not eating carbs and I'm eating fat? What is this ketosis? What is going on inside my body as a result of following this diet? If you think about this, the normal person on an average day is going to burn a combination of carbohydrates and fats all day long. I think everybody, at least in the U.S., learns this phrase, the mitochondria is the powerhouse of the cell. That is like the basis of biology in the US. I think my son told me he learned that this month. So there you go. I think it's universal. I think it's universal. And it has to do with

the thing called the Krebs cycle or the TCA cycle is another name for it. And basically- Okay, so you've lost me now. So explain. It's a cycle where carbs feed in at one end and fats feed in at the other end. And carbohydrates are usually five or six carbon atoms bound together and fats are anywhere from four to 26. And you feed in as fats break down little two carb units and you feed in as glucose breaks down little three and four carb units and you spit out carbon dioxide. You breathe in oxygen and as you breathe in oxygen, you breathe out CO2. What happened? You added carbon to the oxygen. You just breathed in and in doing that, every time you

break carbon bonds, you make energy. So glucose and fat all day long is what people burn. If you stop eating carbohydrate to a very low low low level then this cycle stops running and these little two carb units of fats that are breaking down to provide you energy that usually get burned together with carbs start to pool up and they have an alternate path. They make ketones. They make four carbon units and these four carbon units can be broken down to single carbs and can generate energy, but it's in a slightly different pathway that excludes the use of carbohydrate. And a lot of people probably do this actually overnight. If you haven't eaten for 6, 8, 10, 12 hours, some of your carbohydrate stores are used up.

And so overnight, most people probably make some ketones. Over the course of teaching nutrition, we say, you know, really is healthiest to have carbs and fats burning together. There's a blood-brain barrier. The blood-brain barrier in the central nervous system don't like to burn fats. They really prefer and almost exclusively can only use glucose because that's what will get into the cells. But in the absence of glucose, if you had to, these four carbon units that are ketones could feed the brain and they could feed

the central nervous system. And so now there's this movement, oh my God, maybe it's even better. The keto folks are saying, oh God, maybe ketones are even better than glucose feeding the brain, feeding the central nervous system. And that was sort of a pivot point in trying to think, could you just burn fat instead of burning carbohydrate and fat together, which is the usual recommendation. Got it. So it's an unusual situation to be in for our sort of normal historical diets to be in this ketosis.

That is my strong opinion. Got it. So why have people become interested in this? You mentioned that 50 years ago, they looked at this for epilepsy. That's a long time. Why the discussion today? Sure. I would just speculate that it's part of this ongoing whiplash about low-fat diets not being the best thing for us. And so maybe it should be low-carb. Maybe it should be lower-carb. Oh my God, maybe it should be extremely low-carb. When you use the terms low-fat and low-carb, you need a qualifier to go with that. Is low lower than yesterday? Is low half as much as you had before? Is low 75 or 25% of what you had? But it's quite undefined what low carb and low fat mean. And so, Jonathan, when we go to the literature and I'm trying to

pool studies together and say, oh, let me summarize all the low fat, low carb studies. Oh my gosh, they are all over the place. And when a headline says low fat, yes, low carb, no. And the next day, the other thing you have to say, oh my God, those are not really similar levels of carbs and fats. They use completely different ones. They use different sources of foods to achieve them. So it's a gray area. And I think keto has been a result of, well, could we go lower? Could we go lower? Could we go lower? And there's some people who are fanatical about it and some people who are appalled. Many of them on the West Coast is, I think, definitely one of the hot spots of this, right? And so what you're saying is, you know, there was this whole thing about low fat being the way that we're all going to be healthier. The evidence turned out to be really bad for this.

And so there's always been this, just to make sure I understand, it's almost a swing back, which is, well, if that case, maybe carbs are the source of all evil. Could we go down to the point there's almost none? So if I want to be on a ketogenic diet, I want to be in ketosis. Like how low carb is that? What fraction of my diet is actually coming from carbs? So generally people start out at about 20 grams a day as a kickstarter point and then maybe go up to 50 grams a day. Now let me just tell you what that means with a little bit of math. I was going to say, how many pieces of toast am I allowed with that, Christopher? Yeah. So I mean, most people have about 400 grams of carbs a day.

So picture this. So it's not a lot of taste. Carbohydrates have four calories per gram. That if you're eating 400 grams of carbs times four calories is 1600 calories and you're eating 3000 calories a day, that would be 50% carb. So that wouldn't be 80 or 70 or 60. So let's say you're eating 300 grams of carbs. That would be 1,200 calories. And if you're eating 2,000 calories a day, that would be 60%. Most people's diet is more than half carbs.

So to go to 20 to 50 grams means cutting back from 3 or 400 grams a day to 20 or 50 grams a day. There's not many choices. So it's almost nothing. There's almost no carbohydrate whatsoever is what you're saying. This is extremely extreme. I'm not even allowed a single slice of bread, I guess, is what you're telling me. Not a chance. Nope. Okay. We've already established this is not the diet for me, but that is fine. That is not the purpose of this podcast. Let's talk about your new study. So it's just been published in the top journal, American Journal of Clinical Nutrition. We will provide links in the show notes for anybody who'd like to read that. Before we talk about the results of the study, I'd just like to take a minute to talk about the approach because you're really famous for doing

large-scale randomized control trials and have done many and it's part of how we first got to meet. Can you just explain why these sorts of studies are so important and why they are rare in nutrition? Sure. Yeah. So first of all, it's really hard to get people to change their diet. It's much easier to get rats to change their diet. Put them in a cage, you only put that food in there and you're pretty sure they ate that. And if they didn't, you can see it. The other thing we do is we say, oh, I've got 10,000 people, and I asked them what they ate, and I watched them over time to see what happened, and I can select the people who ate the lowest of this or the highest of that. And those are called observational epidemiological studies. And the challenge there is that the people who did eat

the most or the least of this or that tended to also do the most or least of other things like exercise or take supplements. And it's very hard to pinpoint a causal relationship between diet and health outcome if they also did lots of other things that were different. So the gold standard in theory, and I do want to provide some caveats to this, is you randomly assigned them to diet A or diet B. They had to agree to participate in one or the other willingly. And so you do have people who exercise more or less. You do have people who take more or less supplements. You do have people of different weight and physical capacity. But when you're randomized, an equal number of both of those ended up in both groups. And that's actually the way we control for those confounders is we say, ah, we balanced

it. It's in both groups. So it's not different. So that's the gold standard for us. The challenge here, Jonathan, is when you do a randomized control trial, you really only get to pick one approach. So in our randomized control trial, which as you said, is a great way to do a study from my perspective, good design, good to get it

published, good to find out information. Let's keep in mind that our one study is that. It's one study. Got it. So it doesn't answer all things. It answers this very specific ketogenic diet, this very specific alternative diet, and compares those two, gives you these really strong scientific results, but it doesn't tell you anything about a third diet. You're saying at this point, I have no information on that. Yeah. So I know some of the headlines are going to appear and say, keto and Mediterranean, do this and do that. And I'm just going to cringe. And I'm going to say, no, if you really wanted to

define the way we did it, it would be too long a headline and no one would read it and it wouldn't be good clickbait, but that's really how it works. Well, so the good news is this is a podcast. We've got a bit longer, Christopher. So maybe just tell us about the study. What were you actually doing? And then tell us what the results were. Yeah, I took a very specific approach to this. I think it's really been fascinating, this whiplash from low fat to low carb back and forth. And I tend to see the two compared head to head. And ketogenic is definitely a low carb diet. So you would think maybe somebody would want to compare that to a low fat diet. But my interest is actually in grades of low carb. I mean, a really fascinating thing about the yummy, tasty Mediterranean diet is it exceeded what was for a long time in the US a cutoff of 30%

total fat. Don't have any more than that. If you do that, you end up with a lot of carbs. And so if the Mediterranean diet ends up being 35, 40, 45, or 50% fat, and you get 20% of calories from protein, you now have a low carb diet, but not 5 or 10% calories, 30, 35, or 40%. Got it. So in comparison to what you're talking about, to be ketogenic, you've got to have this incredibly low level of carbohydrates. You could still have what a normal person might think of as

a relatively high fat diet, maybe compared to what they were taught when they were younger. I always talk about my dad being told he had to go on this very low fat diet because he had high cholesterol 50 years ago. So for him, what still seems like a radically high fat diet, because it's got olive oil and nuts and whatever, but you're saying it's still radically different from the ketogenic diet that you were testing. Yeah. And so our idea here was that we would make a Mediterranean and a ketogenic diet that were designed in such a way that they agreed on three things, lots of above ground vegetables. And I'll just clarify, the reason I'm saying that is that avoids potatoes and tubers and carrots. So the ketogenic diet focuses on broccoli, and cauliflower,

and red bell peppers, and things like that that are above ground because the below ground vegetables tend to be starchier. And the absence of added sugar and refined grains. So those are three components that are similar. And then beyond that, the ketogenic diet says, oh my god, to get down to 20 or 50 grams of carb a day, you can't have any grains, even whole grains. You can't have any fruits other than occasional berries. That's the one allowance they give you. And you can't have any beans, no chickpeas, no lentils, no pinto beans, kidney beans, things like that, which is quite odd because if you go to the Dietary Guidelines for Americans or the World Health Organization or the American Heart, they will say, please try to increase your

whole grain intake, your fruit intake, and your legume intake, legume covering the whole thing of lentils, chickpeas, peanuts, beans, things like that. And your issue is that these high fiber foods also inevitably have carbohydrate in them. So you just can't eat them and stay within this very, very tight daily limit. And being the microbiome lover that you are, Jonathan, and I know you are a recent convert to the microbiome. If we're going to feed the microbiome with fiber, the main sources are going to be whole grains and beans and fruits. And yes, vegetables, but I don't think you can get all that much fiber from vegetables. So yes, all those fiber-rich

sources are also high in dietary carbohydrates. So if you wanted to get to 20 to 50 grams of carbs a day, you'd have to wipe out those entire food groups, which would run counter to pretty much every public health recommendation that's out there. And so Jonathan, I want to be very specific about how we frame this question. We want to design our specific diets. We're calling it the KetoMed study, but it's really a well-formulated ketogenic diet, according to Finney and Volick, reading that book. And it's also a Mediterranean plus diet. If you go to lots of different Mediterranean scores, they'll tell you the things to eat the

most of and the least of. And none of those scores have I ever seen avoid added sugar and refined grain. I don't think it's counter to the Mediterranean diet, but I don't see it in the scores where they try to see how Mediterranean you are. So we called it the Mediterranean plus diet. If you're in nutrition, people talk about Mediterranean diet all the time. But I think you're outside of nutrition, particularly maybe if you're living in Europe somewhere, then you're a bit confused because there's a lot of countries. And I've been to Spain and I've been to France and Italy and Greece,

and they seem to eat really different things. So there's a sort of concept of a Mediterranean diet, right, Christopher, which is more like a label to be applied to the view of what is healthy. What is a Mediterranean diet when you describe this? Because I think everybody, every nutritionist I ask would give me a different answer. So it's funny because I'm actually working on a write-up of this right now, and I've got a whole bunch of Mediterranean studies where it said, this is what we call Mediterranean. And it's basically more vegetables, more whole grains, more beans, more fruits, fatty fish, avocados, olive oil. It's actually less meat. I've seen them flip-flop on dairy, actually. Greek yogurt

seems very Mediterranean. Some of the scores want to do an absence of yogurt. Quite a few of them say less meat. Some of them say switch red meat for poultry and fish. Most of them say fish is Mediterranean. So those would be the major categories. Alcohol is a really odd one. Alcohol in all the Mediterranean diet scores, hopefully this will sound Mediterranean to your listeners, you get dinged for not drinking and you get dinged for excessive drinking and you get a point for drinking moderately. All right. That sounds like most of my Mediterranean experiences. So that seems real. So, and I guess one of the things out of that then that's in common is in all those cases, you're saying not sort of the highly processed foods that are such a big part of our diet. Even with all those variations, that sounds like that's

sort of one of the big thing that seems like that's in common and very different from what most of us are eating. Yeah. And I think if we stepped back and took it at that level, the Greeks and the Turks and the French and the Moroccans would say, well, yeah, yeah, yeah, you're right. So the question was centered around the keto diet having this complete absence as much as possible of whole grains and fruits and beans. So three things similar and three things different. And so the way the question is framed, Jonathan, is if we take people with type 2 diabetes or pre-diabetes and we ask them to go on these two diets for 12 weeks each in a crossover manner, so everybody gets to try both of them, we are assuming, since they both eliminate carbs in terms of added sugars and refined grains, that they will experience blood glucose benefits. But

would there be an additional benefit by getting rid of the whole grains and the fruits and the beans? That would seem counter to health professionals advice. So we were looking to see if there was an additional benefit. So what happened? You've been teasing us. And now we want to know, I hear quite a lot of skepticism about the ketogenic diet. So I'm assuming that it was terrible. What were the results? No. So people lost weight on both diets. We can get into some of the pros and cons, and there's some fun nuances to get into here. So the main outcome in terms of all of glucose, Jonathan, was glycosylated hemoglobin. I don't know how much your listeners will know what that

term is. If you are a person with diabetes or prediabetes, you would know this is something to do with the red blood cells in your body are sort of 90-day marker of how well you've been managing your glucose. So when you say glycosylated hemoglobin, the hemoglobin's from your red blood cell, and it means some glucose molecules randomly stuck on the red blood cells, and it's kind of a good hint. Then we looked at, okay, so what about other things that happen? Let's look at blood pressure. Let's look at blood lipids. Let's look at liver enzymes. And pretty much across the

board, everybody did better in everything on both diets. The things that stuck out as being statistically significant were two. One is that for the keto group, their LDL cholesterol went up, while in the Mediterranean group, it went down. And that was statistically significant. So that was a point for Mediterranean. In both groups, their blood triglycerides went down, but they went down even more drastically in the keto diet. And so that was actually a point for keto. And I think just to make sure we explain that for listeners, right? That's really surprising because triglycerides is just like all the fats in your blood, aren't they, Christopher?

So basically you're saying you ate nothing but fat pretty much is what you're saying. And yet the fats in your blood went down is rather remarkable, right? It is. And that's a really funny part of metabolism. If you want me to go on a quick riff for that, the idea there is that if you're eating fat, it gets processed and stored as fat. If you're eating a whole lot of carb, the idea here is that you quickly absorb

and use your carbohydrate for brain energy and muscles, immediate needs. The next thing you use it for is to replete these storage depots for glucose. So some is in your liver, some is in your skeletal muscle, and it's pretty easy to fill up your stores. And after that, you turn all your carbs into fats. So this is a bizarre concept, Jonathan, but you got it right. When you eat a high carbohydrate,

low fat diet, your blood triglycerides go up, but it's not because of the fat that you were eating. That was being metabolized and put away in a more controlled fashion than the excessive simple carbohydrates that you're eating. It's a very counterintuitive finding. You're correct. And so the summary of your results, if I understand rightly, is that if you go on to this sort of healthy ketogenic diet, sort of the best one that you've designed here, actually the health results are really good. You say all these markers have improved, I've lost weight. This sounds like a win, Christopher. So it's a wash. I would say it's a wash between the two. They both worked for weight loss. You get a point for one and a point against for the other. But we looked beyond that. So a couple of the key issues here are

adherence and being able to maintain the diet. And another factor, given that our study periods were only 12 weeks long, is what happens to other nutrient intake? What might happen over years and years of doing this? And what might happen to your microbiome? Because a ketogenic diet is pretty much by definition a lower fiber diet. And I actually won't have these results to share with the listeners today, but my colleagues Justin and Erica Sonnenberg right now have a freezer full of poop from our folks, and they are looking at what happened to the microbiome, and we're looking at a whole panel of inflammatory markers. So tell me if we're ready to look into the nutrient intake and even

more interesting actually to start with would be the adherence, if that's okay. Yeah. Let's talk about exactly that. So adherence is like science word for sort of like how sustainable this is, right? Like, is this something that I can keep doing? Like, adhere is when you tell me to do it, but for myself, it's like, can I stick with this for the long term? So for me, that's always been the biggest concern about the ketogenic diet, as I think about, you know, friends and family members who've done this, that they've tried it for a bit. And then it becomes very hard to maintain because you know, you go to your kid's birthday party, and they're having a cake, and there's a lot of societal pressure to eat a cake. And I think you just explained that's already blown my day.

But you've now done this real study. What have you seen in terms of sustainability? Yeah. And let's talk about, there's an element of the design that I didn't explain for the 12 weeks, Jonathan. And that is we decided that we wanted to kickstart everybody and get them to be as adherent or compliant, following the directions as much as they could, use whatever term you want. And for four of the 12 weeks on each phase, they had food delivered to them.

Which sounds great. I haven't said all of this. If you deliver the food to me, I'd eat almost anything. There you go. And then by design, we left the last eight weeks for them to prepare food on their own so that we could see how well they were, you know, what did it look like when they were very adherent and what did they look like in real life? And we have one additional time point, Jonathan, which is after doing the crossover and doing

both diets in random order, 12 weeks later, we went back and asked them what they were eating. Because my big question was, okay, you definitely mastered this thing. You had 12 weeks of help from a dietician. You had group classes. You had individual meetings. You had more help than most people will ever get when they try this on their own. 12 weeks after the study, what did you do? So here's the fascinating thing is that on average, we had made an adherence score from zero to 10 and 10 was perfect and zero was lousy. We kind of assumed that when we delivered the food, everybody would be at a nine or a 10. Both groups on average, when we were feeding them food got a seven and a half out of 10. So they didn't do a very good job, but they went from, you know, a couple points before the study to seven and a half out of 10.

So that kind of looked pretty good. Okay. Interestingly, more so on the keto diet than the Mediterranean diet, we had people scoring at the two, 3, 4 level when we were delivering food. Some of them just outright rejecting the food that we delivered. Okay, now, first of all, I'm irate. But on the other hand, thank you for being honest. Really? We enrolled you in a study and you didn't do what we told you to do? So does that undermine the finding

or is that an important part of the finding that it was difficult to do? Fast forward now to when they do eight weeks on their own. And when they did eight weeks on their own, we again assessed how closely they were following the diet. And interestingly, on their own of the 40 or so people in the study, five of them on their own kicked butt on keto. They were all in the nine to 10 range, but about five of them were from zero to two. And so it was very polarizing in my mind. Some people got it and some people just could not do it. Interestingly, the Mediterranean diet group had the same average level of adherence as the ketogenic group. When they were on their own,

they were about a five and a half each. When they had been provided all their food, they were seven and a half each. Mediterranean group was, yeah, kind of from three to eight. But interestingly, no one, when they were feeding themselves in Mediterranean, was a nine or a 10. And I think that's partly because, Jonathan, our Mediterranean had a lot of rules. You had to eat beans and whole grains and fruit and cut out added sugar and cut out refined grain. And there were a couple other things like, God, I can't every day. I got to keep track of all these rules.

The keto diet was more like, don't eat carbs, eat lots of fat. It was a much shorter list of rules. And so pretty funny to me that on average, they look the same. But if you look at the distribution across people, some people did quite well at it and some people did not on keto. That was different between the two groups. And remember I said that we asked them 12 weeks when the study was over, what were they eating? Yeah, so what happened? You had these people who got both,

and then 12 weeks later, they had a real experience of both of these. What were they doing? Yeah, so the thing they all remembered the most was getting rid of added sugar and refined grain. They all did better than that. This is at week 36, 12 weeks of one diet, 12 weeks of the other diet, 12 weeks of nobody watching you anymore. The study's all over. They both did well at that. They both maintained pretty much all the weight loss that they got in the first 24 weeks,

which is really fun to see. But they pretty much went back to their old habits after that. And when you scored that, it ended up being a more Mediterranean diet than a ketogenic diet. So we saw that the keto diet was not sustainable. Even among those people who, when they were getting their own food, were scoring nines and tens for those eight weeks, yeah, they were gone. They couldn't do it 12 weeks after the study was over. So to me, this is a hugely important part. If the benefit that you get from the keto diet is being really low on carbs and seeing your triglycerides go down, if you can't maintain that, then I'm not a fan. And I think that's a really important question. And I think this study that you've done, like really takes us some way forward on this, which is how strictly do you have to follow the ketogenic diet in order to be worth it? And we had lots of listeners questions

really on this because many, many of our listeners have tried this and many of them are therefore not fully on it. In your view, how strictly keto do you need to be in order to get the sort of health benefits that you saw in the ketogenic part of this study? Well, in theory, you have to be in ketosis. And so another thing we did, Jonathan, that I haven't mentioned is we looked at blood levels of ketones, and most of them were not in ketosis. They couldn't do it. More of them did it during the feeding phase of this study. They were most successful there. Almost no one was able to do it when they were providing food for themselves. And by the time they got to 12 weeks after the study, no one was in ketosis at all.

And so that's the major point of the proponents as I understand them is that you have to maintain ketosis to get this improvement in insulin secretion and insulin resistance. And so they weren't experiencing that because they were back up to 100 grams of carbs a day, which was way less than they were eating before. But it wasn't as low as you'd need to be to be in ketosis. Got it. So they were no longer in this situation where they were just running on this fat, they were back into this sort of middle ground. So Christopher, one of the original arguments for these sorts of ketogenic diets, which I think you sort of touched on is people who have diabetes,

for whom really their ability to deal with blood sugar is really bad, and that there have been these studies showing that if you follow a ketogenic diet for a long time, that looks like the results are very good. Is that because actually they managed to be compliant and so that's different from this situation or is that, you know, most of our listeners are probably not injecting insulin with diabetes so they're in a more broader range. Are you saying ketogenic doesn't work for anybody? Are you saying how should we interpret this if you're listening right now and sort of trying to decide whether to give this a go? So I'll give a practical note here.

The folks on keto toward the end, I think we're better having anchored them so low in added sugar and refined grain. I mean, for them, cheating wasn't a cupcake. For them, cheating was a piece of whole grain bread, right? And said, whole grain bread? That's not cheating. That's following the Mediterranean diet. So God forbid you have a teaspoon of sugar or you have white bread. I really think that that

anchored them quite well in seeing, oh my God, I actually had these sugar cravings before. I clearly had to go completely off sugar. Wow. It's been a couple of weeks and I don't crave sugar as much as I thought. So there's some really interesting physiology there. So I think there's some potential benefits of seeing how well you could do, eliminating all those and keeping that up long term. We're actually doing another mini analysis from our old diet fit study that sort of supports that. So anchoring someone psychologically really low. So in that regard, for the people who are doing ketogenic transiently or temporarily, I could see learning some new things that could be helpful. But just from a taste and a longevity perspective, I think a high fat Mediterranean diet gives you more options, easier for social

events. And so people were really sticking with this more as I think just on that other side, the Mediterranean diet, although you said it was a very complex thing, it was easier to stick with as a permanent part of your life rather than a temporary diet, right? And I think, you know, we all know that diets are basically a bad idea, right? There's no one who's ever done a diet who believes it's a good idea, right? That you're saying that the problem with the ketogenic is it's sort of like a diet and this Mediterranean is potentially a lifestyle that you can sustain permanently. Is that right? Yep. And then we saw multiple nutrients that were lower on the ketogenic diet

than the Mediterranean diet. We didn't see any nutrient deficiency symptoms because these are only 12-week diets. But long-term, if you really did follow this long term, it's such a restrictive diet that there are quite a few nutrients that will be lower on ketogenic. And in particular, the one that you and I are very interested in is fiber and the microbiome. I was gonna say, can we talk about that for a few minutes? Because I think, you know, I know your study, you know, there's nothing published yet, but I know there've been some other things. What is the likely impact on the microbiome of a ketogenic diet? Part of this is a funny story, Jonathan, that we will have to pursue. So one of the things that

the microbiome produces from digesting fiber is short-chain fatty acids. And some of those short-chain fatty acids are ketones. So you could actually get some of the products of what the microbiome would generate from digesting fiber by eating a ketogenic diet. On the other hand, I have a colleague, Michael Fischbach at Stanford, who just got a massive grant award to study the molecules that are produced by the microbiome. And he has a little graphic of 100 different molecules. We haven't named them all. We don't understand what they all do. But that's part of the likely effect of the microbiome

is digesting the fiber, creating small molecules that we absorb that looks like they lower inflammation and improve immune profiles and immune function. And those are results that will take a longer study to look at. We actually are looking at some of that right now,

but we're also writing a grant to try to do a longer six or 12 month ketogenic Mediterranean type study where we could see longer effects on the microbiome. Fiber is sure to go down if you exclude all whole grains, all fruits, and all beans. So in your ketogenic group, the fiber intake is lower than in the Mediterranean group? Has to be. Yes, it is. Yes. That is the most significant difference of all the nutrient differences. And there were a half dozen, fiber was the one that stuck out the most.

So you know you're sort of taking a hit on how you're supporting the microbiome in the hope of trying to improve what's going on with your blood sugar, which maybe if you have bad diabetes is a good trade-off. That's a pretty big cost, I think, from other studies that we know about the importance of the microbiome, even if this study, which is sort of short-term in nature, is not going to be able to see that impact. Is that fair? Am I putting words in your mouth? Yeah, no, that's perfect. Getting started on it. And you know, as well as I, it's a complicated issue, but we really are pinging away at it. We're making some progress. We're going to know more soon. Fantastic. And so very final question, which you touched on right at the beginning. There are a lot of people who are concerned that if you follow a ketogenic for a

while, it's going to have some sort of permanent damage to your ability to deal with carbs. And I think this is because there's been a lot of things talked about, maybe transient effect on how you eat carbs when you just switch off a ketogenic diet. I mean, you would have gone through the ethics, I'm sure, of doing this study of putting people on the ketogenic diet for 12 weeks. Do you have any concerns? No, no, no. Yeah. I mean, all the molecular metabolic pathways there, the enzymes that you're making for digesting, they won't go away. Sorry, this reminds me of people who go vegan thinking, oh, now that I've gone vegan, I no longer make the enzymes that digest meat. God forbid I eat meat, then I won't be able to digest it.

Protein's made of 20 amino acids. Plants have 20 amino acids. Animal foods have 20 amino acids. You have the same enzymes. When it comes to carbs, glucose, fructose, galactose, that's all that's there. Starch, long chains of glucose. You've got these carbohydrates, A-S-E stands for enzyme. They digest carbohydrates. You wouldn't possibly be able to eliminate your ability to digest carbs. You would bounce right back. So no real concern, if I think about this as practical advice, maybe you can't stick with a ketogenic diet, but you're not causing yourself any long-term sort of permanent harm by having tried this.

Not for carbohydrate metabolism. If, as my partner, my division chief in preventive cardiology saw these folks on keto with LDL sky high, if that's adding to atherosclerosis and the plaque, that might not be something that you can recover from. Some of the long-term nutrient deficiencies could be something that you don't recover from, but carbohydrate metabolism, not a problem. Bounce right back. Amazing. Christopher, I'm going to try and summarize what was a wide-ranging conversation, so correct me if I get this wrong. So to start with, a ketogenic diet is a diet where you go very low in carbs. The diet's actually been around for a long time, but only

recently have people thought about it as a way that if you wipe out carbs, then you can resolve insulin resistance and fix diabetes. And from that, we started to say, well, maybe it's a good diet for everybody. In this study where you got people to do both, you saw a lot of people lose weight on this ketogenic diet, the same as they did on this sort of Mediterranean diet, that on many of the health measures, you saw improvements as well. So in that sense, can be some positive impact from following it. However, you saw that sustainability of this diet is significantly harder than the sort of broader Mediterranean diet that you tried. and that by the time you are 12 weeks off the study, actually, even the people who are most keen were no longer in this state

of ketosis, which is where they're just firing off fat. It just wasn't possible to sustain it at the level to give the results that are really required. It doesn't seem any better than a high quality, high carb diet. And you have some real concerns, particularly I think about certain nutrients and maybe most of all about what it might be doing to your microbiome because you're taking away all of this fibers. So, confusion with me is like, I get to stick with my current Zoe diet that lets me indulge in bread and the occasional cake and I don't need to move

for the ketogenic diet, which is good, but that it's very personal. And maybe I think that's the final thing that there are individuals you were saying who actually really found it possible to follow this. And so that if there is someone who just this really works great for them, then they might be able to do that. For most of us, we're probably not going to be able to do it. So before we wrap up, I've got one final listener question from Jane on Instagram. I just love to wrap up with this one because it made me laugh. And her question is, why is keto popular? It's horrendous. I think it's clickbait. I think a lot of people are having fun thinking, I think incorrectly, this is my invitation to eat meat. And so my takeaway from this is they don't actually

understand how keto works. Keto is high fat. It is not high meat. Christopher, thank you so much. As always, it's so much fun. There are so many other things that we could have touched on, so many of your other studies. So I'm hoping that you will come back again and we can talk about some of those as well as some of the following analysis that comes from this. More to come, Jonathan. Happy to come back sometime soon. Wonderful. Thank you, Christopher. Thank you to Christopher Gardner for joining me on Zoe's Science and Nutrition today. We hope you enjoyed today's episode. If you did, please be sure to subscribe and leave us a review as we love reading your feedback. If this episode left you with questions, please send them in on Instagram or Facebook and we'll try to answer them in a future episode. At Zoe, we want to improve the health of millions

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