Updated 11th August 2022

This is what the keto diet does to your body

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 chronic health conditions. 

In this podcast, 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. He has produced a clinical trial of keto diets, published in the American Journal of Clinical Nutrition.

If you want to uncover the right foods for your body, head to joinzoe.com/podcast and get 10% off your personalized nutrition program.

Transcript

[00:00:00] Jonathan Wolf: 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, that completely removing almost all carbohydrates is not what most people consider a balanced diet. With carbs off the table, and 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 am joined by a 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'll 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 quick-fire round of questionnaires that our listeners are sort of used to now. So let's kick off. Can you improve your health on a ketogenic diet? 

[00:01:52] Christopher Gardner: That's complicated because there are good and bad ketogenic diets and there are 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.

[00:02:06] Jonathan Wolf: All right, so it's complicated. Can you lose weight on a keto diet? 

[00:02:11] Christopher Gardner: Absolutely. It's a very restrictive diet. For the things that are still allowed, the palatability will run out quickly and you'll say, I am hungry, but not for that. So nope. Not gonna eat. Lowered my calories. Lost weight.

[00:02:23] Jonathan Wolf: Is keto a good diet for most people?

[00:02:26] Christopher Gardner: 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. 

[00:02:40] Jonathan Wolf: Is doing keto from time to time helpful?

[00:02:44] Christopher Gardner: 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 gonna 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. 

[00:03:02] Jonathan Wolf: What's the biggest misconception about the ketogenic diet? 

[00:03:06] Christopher Gardner: 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 outta ketosis by making carbs outta your protein.

[00:03:28] Jonathan Wolf: That's amazing. And I did not know that. Thank you, Chris. The final question will cutting out carbs. Stop your body's ability to process them? 

[00:03:36] Christopher Gardner: No. 

[00:03:38] Jonathan Wolf: 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 of 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 that suggests there's something interesting there. And so I think it 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?

[00:04:15] Christopher Gardner: 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, and diabetes, because a lot of that has to do with excessive carbohydrate intake and the inability to process those carbs. So if you wipe carbs outta 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, and you will lose some weight. 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.

[00:05:16] Jonathan Wolf: Brilliant. And before we go on to that, because you mentioned the 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? 

[00:05:31] Christopher Gardner: If you think about this, the normal person on an average day is gonna burn a combination of carbohydrates and fats all day long. I think everybody, at least in the US learns this phrase. The mitochondria are the powerhouse of the cell. That is the basis of biology in the US. 

[00:05:48] Jonathan Wolf: I think my son told me he learned that this month. So there you go. I think it's universal. 

[00:05:53] Christopher Gardner: I think it's universal. And it has to do with the thing called the Kreb cycle or the TCA cycle is another name for it. 

[00:06:00] Jonathan Wolf: So you've lost me now. So, so explain. 

[00:06:03] Christopher Gardner: It's a cycle where carbs feed in at one end and fats feed in at the other end. Carbohydrates are usually 5 or 6 carbon atoms bound together. And fats are anywhere from 4 to 26. And you feed in as fats break down little 2 car units and you feed in as glucose breaks down little 3 and 4 car units, and you spit out carbon dioxide.

You breathe in oxygen and as you breathe in oxygen, you breathe out CO2. What happened? Ugh. You added carbon to the oxygen. You just breathe 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 carbohydrates 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 the energy that usually gets 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 into single carbs and can generate energy.

But it's in a slightly different pathway that excludes the use of carbohydrates. And a lot of people probably do this actually overnight. If you haven't eaten for 6, 8, 10, or 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 doesn'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. 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.

[00:08:23] Jonathan Wolf: Got it. So it's an unusual situation to be in for our sort of normal historical diets to be in this ketosis. 

[00:08:31] Christopher Gardner: That is my strong opinion. 

[00:08:33] Jonathan Wolf: 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?

[00:08:43] Christopher Gardner: 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 do 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 were not really similar levels of carbs and fats. They used completely different ones. They used different sources of food 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 are some people who are fanatical about it and some people who are appalled. 

[00:09:54] Jonathan Wolf: Many of them on the west coast are I think definitely one of the hotspots 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 and, it's almost a swing back, which as well if that case maybe carbs or 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, how low carb is that? What fraction of my diet is actually coming from carbs? 

[00:10:25] Christopher Gardner: 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. 

[00:10:35] Jonathan Wolf: I was gonna say, how many pieces of toast am I allowed with that, Christopher?

[00:10:38] Christopher Gardner: Yeah, so, I mean, most people have about 400 grams of carbs a day. 

[00:10:44] Jonathan Wolf: It's not a lot. It's not a lot of toast!

[00:10:46] Christopher Gardner: Carbohydrates have 4 calories per gram, that if you were eating 400 grams of carbs, times 4 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 1200 calories. And if you're eating 2000 calories a day, that'll be 60%. Most people's diet is more than half carbs. So to go to 20 to 50 grams means cutting back from 300 or 400 grams a day to 20 or 50 grams a day. There are not many choices. 

[00:11:30] Jonathan Wolf: 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. 

[00:11:39] Christopher Gardner: Not a chance. 

[00:11:42] Jonathan Wolf: 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, the 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 are 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? 

[00:12:16] Christopher Gardner: 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 'em 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 watch 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 are 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 with 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 fewer supplements. You do have people with different weights and physical capacities, 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 no 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. 

[00:13:58] Jonathan Wolf: Got it. So it doesn't answer all things. It. This very specific ketogenic diet, this very specific alternative diet, and comparing 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. 

[00:14:15] Christopher Gardner: Yep. So I know some of the headlines are gonna appear and say keto and Mediterranean, do this and do that. And I'm just gonna cringe. And I'm gonna 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. 

[00:14:33] Jonathan Wolf: Well so the good news is this is a podcast. We 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. 

[00:14:42] Christopher Gardner: 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 if 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, that it exceeded what was for a long time in us that cut off 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 five or 10% calories, 30, 35, or 40%.

[00:15:36] Jonathan Wolf: Got it. So in comparison to what you're talking about to be ketogenic, you've gotta 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 like 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. 

[00:16:05] Christopher Gardner: Yeah. And so our idea here was that we would make the Mediterranean and a ketogenic diet that was 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 avoid 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 starch here. The absence of added sugar and refined grain.

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 carbs 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. 

[00:17:21] Jonathan Wolf: And your issue is that these high-fiber foods also inevitably have carbohydrates in them. So you just can't eat them and stay within this very, very tight, daily limit.

[00:17:32] Christopher Gardner: And being the microbiome lover that you are Jonathan. And I know you are a recent convert to the microbiome, if we're gonna feed the microbiome with fiber, the main sources are gonna 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 that pretty much every public health recommendation that's out there. And so Jonathan, I wanna be very specific about how we frame this question. We wanna design our specific diets. We're calling it the keto med study, but it's really a well-formulated ketogenic diet, according to Phinney and Volek, 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. 

[00:18:46] Jonathan Wolf: If you're in nutrition, people talk about the Mediterranean diet all the time, but I think if you're outside of nutrition, particularly, maybe if you're living in Europe somewhere, then you're a bit confused because like there's a lot of countries and I've been to Spain and I've been to France and Italy, 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. 

[00:19:16] Christopher Gardner: So it's funny cuz 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 called the 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 wanna do an absence of yogurt. Quite a few of them say less meat. Some of them say, to switch red meat for poultry and fish. Most of them say fish is the Mediterranean. So those would be the major categories.

Alcohol's a really odd one. Alcohol in all the Mediterranean diet scores. Hopefully, this will sound the 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. 

[00:20:12] Jonathan Wolf: 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, you know, even with all those variations, that sounds, that's sort of one of the big things that seems like it's in common and very different from what most of us are eating.

[00:20:35] Christopher Gardner: 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 fruit. And beans.

So three things are similar and three things are different. And so the way the question is framed Jonathan is if we take people with type two diabetes or prediabetes, 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?

Getting rid of the whole grains and the fruits and the beans would seem counter to health professionals' advice. So we were looking to see if there was an additional benefit. 

[00:21:31] Jonathan Wolf: 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? 

[00:21:40] Christopher Gardner: No. So people lost weight on both diets. We can get into some of the pros and cons and there are some fun nuances to get into here. So the main outcome in terms of all of the 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 a sort of 90-day marker of how well you've been managing your glucose. So when you say glycosylated Hemoglobin, the hemoglobins from your red blood cell. And it means some glucose molecules randomly stuck on the red blood cells and it sounded 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 the 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 the point for keto. 

[00:23:03] Jonathan Wolf: And I think just to make sure we explain that for listeners, right? That's really surprising. Cause that triglycerides are just like all the fat 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 fat in your blood went down, is rather remarkable. Right? 

[00:23:20] Christopher Gardner: 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 car, 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 repeat these storage depots for glucose. So some are in your liver, some are 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 fact 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. 

[00:24:16] Jonathan Wolf: And so the summary of your results, if I understand right is that if you go onto 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. 

[00:24:34] Christopher Gardner: So it's a wash. I would say it's a wash between the two. They both worked for weight loss and get a point for one and a point against the other. But we looked beyond that. So a couple of the key issues here are adherence in being able to maintaining the diet. And another factor given that our study periods were only 12 weeks long is what happens to other nutrient intakes. What might happen over years and years of doing this? 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 Sonenberg 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. 

[00:25:32] Jonathan Wolf: Yeah. Let's talk about exactly that. So adherence is like science word for the sort of like how sustainable this is, right?

Like, is this something that I can keep doing? Like I, and here 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, 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've just explained that's already blown my day, but you've now done this real study. What have you seen in terms of sustainability?

[00:26:15] Christopher Gardner: Yeah. So, 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 a kickstart everybody and get them to be as adherent or compliant in following the directions as much as they could use whatever term you want. And for 4 of the 12 weeks of each phase, they had food delivered to them. 

[00:26:36] Jonathan Wolf: Which sounds great. Having said all of this. If you deliver the food to me, I'd eat almost anything! 

[00:26:43] Christopher Gardner: There you go. And then by design, we left the last 8 weeks for them to prepare food on their own. So that we could see how well they were and, 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, and 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 0 to 10 and 10 was perfect. And 0 was lousy. We kind of assumed that when we delivered the food, everybody would be at a 9 or a 10. Both groups, on average, when we were feeding them food, got a 7.5 out of 10. So they didn't do a very good job, but they went from, you know, a couple of points before the study to 7.5 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 2, 3, and 4 levels when we were delivering food.

Some of them were 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 enroll 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 was difficult to do. Fast forward now to when they do 8 weeks on their own.

And when they did 8 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, 5 of them on their own kicked butt on keto, they were all in the 9 to 10 range, but about 5 of them were from 0 to 2.

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 5.5 each. When they had been provided all their food, they were 7.5 each. Mediterranean group was yeah, kind of from 3 to 8. But interestingly, no one when they were feeding themselves in the Mediterranean was a 9 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 the refined grain. And there were a couple of other things it's like, God, I can't. Every day I gotta 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 for 12 weeks when the study was over, what were they eating? 

[00:30:12] Jonathan Wolf: 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?

[00:30:21] Christopher Gardner: So the thing they all remember 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 studies 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 9s and 10s for those 8 weeks. Yeah. They were gone. They couldn't do it 12 weeks after this 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.

[00:31:22] Jonathan Wolf: 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 you have to follow the ketogenic diet in order to be worth it. And we had lots of listers questions really on this because many, many of our listeners have tried this and many of them are there for 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? 

[00:31:51] Christopher Gardner: 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 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. To be in ketosis. 

[00:32:41] Jonathan Wolf: 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 manage to be compliant. And so that's different from this situation or is that, you know, most of our listeners are, are probably not injecting insulin with diabetes. So they're in a broader range. Are you saying ketogenic doesn't work for anybody? How should we interpret this? If you're listening right now and sort of trying to decide whether to give this a go? 

[00:33:26] Christopher Gardner: So I'll give a practical note here. The folks on keto toward the end, I think were better having anchored them so low in added sugar and refined grain.

I mean, for the cheating, wasn't a cupcake for them. Cheating was a piece of whole grain bread. 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 just some really interesting physiology there. So I think there are 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, a taste and a longevity perspective, I think a high fat, Mediterranean diet gives you more options, easier for social events.

[00:34:40] Jonathan Wolf: And so people were really sticking with this more, as I think just on that other side, the Mediterranean diet, although you may have 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, 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 its sort of like a diet and this Mediterranean is potentially a lifestyle that, that you can sustain permanently. Is that right? 

[00:35:11] Christopher Gardner: Yep. And then we saw multiple nutrients that were lower on the ketogenic diet than on 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.

[00:35:36] Jonathan Wolf: I was gonna say, can we talk about that for a few minutes?

Because I think, you know, I know your study, 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? 

[00:35:48] Christopher Gardner: 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 a 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 Fishbach 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 look 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 6 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. 

[00:37:07] Jonathan Wolf: So in your ketogenic group, the fiber intake is lower than in the Mediterranean group? 

[00:37:12] Christopher Gardner: Has to be by definition. Yes, it is. Yes. Significant. That is the most significant difference of all the nutrient differences. And there were a half dozen fibers was the one that stuck out the most. 

[00:37:22] Jonathan Wolf: 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 tradeoff. 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 shorter term nature is not gonna be able to see that impact. Is that fair? Am I putting words in your mouth?

[00:37:45] Christopher Gardner: Yeah. Nope. That's perfect. Getting started on it and you know, as well as that, it's a complicated issue, but we really are pinging away at it or we're making some progress. We're gonna know more soon. 

[00:37:56] Jonathan Wolf: 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 cuz there's been a lot of things, talked about maybe a transient effect on how you eat carbs when you just switch off a ketogenic diet. You would've 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?

[00:38:22] Christopher Gardner: 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.

Proteins are 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, and galactose, that's all. That's their starch long chains of glucose. You have these carbohydrases, A-S-E stands for an enzyme. You have, they digest carbohydrates. You wouldn't possibly be able to eliminate your ability to digest carbs. You would bounce right back. 

[00:39:10] Jonathan Wolf: So no real concern. You know, 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?

[00:39:21] Christopher Gardner: Not for carbohydrate metabolism. If, as the, my partner, my division chief as 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. 

[00:39:50] Jonathan Wolf: Amazing. Christopher. I am gonna 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 that the diet's actually been around for a long time, but only recently have people thought about 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 were 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 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 these fibers.

So conclusion with me is like, that I get to stick with my current ZOE diet that lets me indulge in bread in the occasional cake. And I don't need to move to 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'd just love to wrap up with this one because it made me laugh.

And her question is why is keto popular? It's horrendous. 

[00:41:55] Christopher Gardner: 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.

[00:42:13] Jonathan Wolf: 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'll come back again and we can talk about some of those as well, as some, as the following analysis that that comes from this. 

[00:42:26] Christopher Gardner: More to come Jonathan, happy to come back sometime soon.

[00:42:29] Jonathan Wolf: 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 by understanding the right food for each of us to improve our health and manage our weight. Each member starts with an at-home test, comparing them with participants in the world's largest nutrition science study.

If you're interested in learning more about ZOE, you can head to joinZOE.com/podcast and get 10% off your personalized nutrition program. As always. I'm your host, Jonathan Wolf. ZOE science and nutrition is produced by Fascinate Productions with support from Sharon Feder and Alex Jones here at ZOE. See you next time.

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