The Keto Study That Wasn't About Keto | Dr Nicola Guess

0:03Let me set the stage here for the listeners. So roughly one in three adults today have excess fat in their liver and many of those adults don't know about it yet. That excess fat in the liver tends to travel with blood work that's drifting out of range. And perhaps that is something that people are more familiar with. They go and see their doctor and their HbA1c or their fasting glyphs. glucose, and even biomarkers like ApoB or LDL cholesterol, which is a bit more commonly tested, can be somewhat out of range. And of course, when people go and see their doctor and they get told that these things are out of range, they want to know what they can do about this, particularly with their diet and specifically beyond just losing weight.

0:53Because of course, we know that losing weight can help these things, but is there anything else that people can do with regards to their diet? Should they eat more or less carbs? Should they eat more or less protein, more or less fat? And then ultimately, beyond these macronutrients, just what foods more or less up, because ultimately that's what people are thinking about when they're at the grocery store, which is why I wanted to get you back on the show, because there has been a new study from Sam Klein's group at Washington University that was published that I thought was really interesting.

1:28It compared three different diets looking at weight loss and some of these cardiometabolic markers and liver fat. And I'll get you to walk us through the details of this study. But first, I'd like to get your kind of first reaction. When you saw that this study was published, I have to imagine knowing your interest and the research that you do, that you were somewhat excited to see that this study had been done. For sure. So one of the things you want to know as a dietitian, what helps me be a dietitian, is knowing what nutrients do in the body. What is the effect if someone changes their dietary intake on, for example, liver fat?

2:14Historically, what we've done is free living trials. So you might do low carb versus high protein, whatever it might be. And people don't really follow those diets, first of all. You always end up with markedly different weight loss at the end. So it can't really tell you anything. There's no what we call internal validity. So lots of previous, let's broadly say low carb trials, have been interpreted as reducing carbohydrate does or doesn't affect outcome X. But that's not correct. It's more advising people to reduce carbohydrates doesn't or does something, right? What I want more of is trials like this one where stuff is controlled.

2:56They controlled the weight loss beautifully and it reduces changes in weight as a confounding factor. And then you can have more confidence as saying, okay, it's the macronutrient changes here. And the other thing is that they provided all of the food in this study. They also collected biomarkers for fidelity to the intervention. So for example, the low carb pattern, we'll get into this, but it was more of a high protein low carb pattern, but they measured a nitrogen in the urine. That's a really good robust marker of if someone's increased their protein intake. And they also measure ketones. So it gives you some confidence that people are reducing carbs.

3:36So all of that was so exciting because it's rare, because it's expensive. But it, for the first time, I think, enabled us to say, okay, if people lose 10 % weight loss and they have markedly different diets, what is the effect of those diets on certain outcomes? It was a great, really well done stay. So just to underscore that point about the advantage of providing food. So the difference being that if you just have dietitians telling people to eat one of three diets, what happens in the real world is not always in line with what the recommendations were because behavior and just dietary adherence overall is not going to be the same as if you give these people the food.

4:23A hundred percent. So there's a meta-analysis on trials. I think it was for weight loss and it was like low carb, less than 50 grams a day. That's what these trials aim to test. And in this meta-analysis, they report what people actually did. And at the end of it, some people were having 180 grams of carb a day. So you're not testing what happens when people have less than 50 grams of carb a day. You're testing what happens when you advise people to have less than 50 grams a day. So the beautiful thing about providing food, It's not a ward-based study. So we have to acknowledge that even if you provide food, in the real world, life will get in the way.

5:00Many of these participants, they'll have food delivered and they probably on occasion went out to a restaurant and had something different. But that's why the addition of these biomarkers, looking at the amount of nitrogen in the urine and looking at ketones, it tells you broadly people were following these dietary patterns. So this was a good study from a reputable group of researchers, scientists, Washington University, a well-controlled study, well-designed, able to measure adherence. The headline result was that a keto diet, which had 23 % of its energy from saturated fat, quite a lot, cut liver fat by 67%.

5:42And that was more than the reduction in liver fat that was seen on the Mediterranean diet or the third kind of plant-rich diet. I'll get you to go into the details. And this was, I think, shared not by everyone but by a lot of people as kind of evidence or proof that in folks with prediabetes who are looking to kind of come into remission, clear that liver fat, restore insulin sensitivity, that a ketogenic diet is clearly best, cutting carbohydrates is clearly best. And this study's evidence that that was better than even a Mediterranean diet, which is generally thought to be a very healthy diet.

6:21What's your kind of high level reaction to that take from this single study? My interpretation of the data is that there is something about this reduction in carbohydrate and I think in particular increase in protein that is reducing the liver fat and potentially improving liver metabolism. The design of this study can't tell us anything really about saturated fat in any other context. It might actually be irrelevant here in terms of like the power of the reduced carbohydrate and increased protein at reducing triglyceride in the liver might be so great that the saturated fat is sort of meaningless.

7:04But what I would like to see, and whenever I support patients to follow a low-carb or a high-protein diet, I always emphasize poly and monounsaturated fats. I'll never go out of my way to recommend saturated fats. But I reckon if someone compared low-carb, high-protein, one with high poofers and moofers and one with high saturated fat, I think you'd probably get slightly better results with the MUFAs and the POOFAs. Because we do have data like there are controlled studies which aimed to test saturated versus poly or MUFAs and it's the unsaturated fats that seem to help protect the liver from fat deposition.

7:42I want to put a pin in that and make sure we come back to that, the differences in fat type and how they affect liver and some of those other trials and how we reconcile those trials with this trial. Because broadly, and we'll put a pin in this, my understanding is that sometimes the context is different in terms of are the subjects losing weight is it at weight maintenance is it in a calorie surplus and i think there are some interesting things that we can chat about there but i do want to just further set the stage here you and i have covered this before and i've since spoken with professor alexander crag and we spoke about this as well but i think it's worth tracing back over why does liver fat sort of sit at the center of insulin resistance or does it?

8:28And is liver fat itself driving the insulin resistance and this problem that people are having with regards to getting glucose into cells? So this is really difficult to answer for a couple of reasons. One, this is super in-depth whole body physiology, which is crazy complicated and I'm not a physiologist. But broadly, the folks who work in this area would say, yes, liver fat seems to be causally related to insulin resistance. For example, we have some Mendelian randomization studies that look at these pathways that suggest that liver fat is causal for developing insulin resistance. But with the complexity of this, once you develop insulin resistance, you then are more likely to deposit probably fat in the liver.

9:17So there is this kind of vicious cycle that you get. But what I would kind of say is whether it's causal or not, if you've got lots of fat in your liver, that is a marker of an unhealthy metabolism period. And it's also the case, and again, let me emphasize, this is not my area of research, fat in the liver can develop further on. So you can get fibrosis and then it, I believe, increases the risk of certain liver cancers. So if you've got fat in the liver, regardless of where it's going to go, I would almost call it a marker like a highway circumference. It's something people should want to address.

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10:55Do you know at all if the type of fat that's stored in the liver affects that mechanism? Is there a fat that's more harmful or less harmful? I don't know. Yeah, I mean, that's my short answer is I don't know. I mean, I can't imagine it would. I think if you've got triglyceride deposited in an organ, which regulates everything, it regulates micronutrient metabolism, fat, carbohydrate, amino acid metabolism, I can't imagine it would make a difference. I think if you've got too much triglyceride in the liver, and it starts at a very small percentage, that does start to impair the overall function of the liver.

11:32I asked that question, and this is well above my pay grade, But in doing some reading around saturated fats in particular, it seemed that one of the proposed mechanisms by which saturated fats might be different to polyunsaturated fats in the liver is that saturated fats increase the production of these compounds called ceramides. I've heard that too, yeah. I don't know to what extent that's true. I mean, I would say that when we look, and I know you said we'd come back to this, but the overfeeding trials that are like two weeks or some of them might be longer, comparing saturated palm oil versus polyunsaturated fat, you see greater deposition of fat.

12:09Also acutely, there's a couple of studies where it's just literally acutely comparing, I think again it might be palm oil and unsaturated fats, and you see it start to impair glucose and lipid metabolism. the exact molecular pathways. I don't know. I'm not sure whether anyone's characterized that really well. As I understand it, if someone's sitting here and thinking, where does this fat come from that ends up in the liver? And when I think about this, there seems to be a few different places it could come from. It could be fat from our meals. Is that what's ending up in the liver? Is it fat that was in our adipose tissue stored elsewhere that then ends up in the liver?

12:48or is it the liver making new fat from carbohydrates? Do we kind of understand what is the greatest source of that? I think it would depend on the individual, the degree of hepatic insulin resistance already. The person who could answer that question would be Leanne Hotson. You should get Leanne Hotson because you know why this is so difficult? People might think, gee, surely you can figure this out. The reason this is so difficult is the liver is so difficult to study and you need to use isotopes. and they are expensive as hell. And you need to measure everything. You need to measure, like you say, fat coming out of the liver, whether it's coming from food.

13:26So we don't have that many studies, but one person who does those studies is Leanne Hodgson. These are difficult questions and they're more mechanistic. And in all honesty to the person who's just trying to figure out what diet to adopt and what foods to eat more or less of to restore insulin sensitivity and normalize those markers, it kind of doesn't matter to them. It's more of a scientific academic kind of pursuit. Yeah and I think it will help us to understand what diet is doing. So like I said when I interpret this new Sam Klein study when I look at the rest of the literature I think it is particular the protein that is very protective.

14:05How the jiggins it does that I don't think anyone knows. But we have some clues like when you give a high protein diet, and there are several high protein diets where they reduce carbohydrates by different amounts, you do get a reduction in liver fat, even if people don't lose weight. And we see that people with overweight, with or without type 2 diabetes. How is it doing it? I don't think we know. I think Sam Klein would say, and I think they discussed this in their paper, it's the combination of decreased glucose and insulin with an increase in glucagon. So reducing carbohydrate whether you replace it with fat or protein is going to reduce glucose and insulin usually more or less but it doesn't increase the glucagon that's what protein does and it's very interesting to me there have been a number of studies done which is just low carb and they didn't increase protein and without weight loss you don't really see a significant reduction in liver fat not to me that's convincing over the long term you do when you combine low carb with high protein and I would also just add we have again this is rare in nutrition research that you get this confirmation from all of these kind of study designs we also have studies where they overfed calories with either fat or fructose when you provide excess calories particularly with fat or fructose you get fat deposited in the liver if you do that and then add amino acids like branch chain amino acids they are protected from a fat deposition in the liver so the whole picture to me is that protein is really important for preventing fat deposition in the liver.

15:43But then to come back to your question about the academic side of it, that's the kind of work that someone like Leanne would do when we think about mechanism. Well, how? But one of the hypotheses there, and you alluded to it, is that amino acids, which are the constituents, the components of protein, raise glucagon levels, and glucagon is kind of promoting the liver or pushing the liver towards utilizing fat rather than making it from carbohydrate? So that's one of the hypotheses, but there's something else as well, is that there are studies which were matched for total protein where they gave a proprietary mix of specific amino acids that lowered liver fat compared to the equal amount of general protein.

16:26So basically what that signals to me is that amino acids, some of them may actually be signaling molecules, like telling the liver not to deposit fat. So there used to be a company called Acceler in Massachusetts where they tested amino acids and one of their areas of interest was liver fat. And so they were developing these proprietary mixes of amino acids. And it's more than just protein. It's more than just nitrogen. There is something about individual amino acids that are signaling the liver, I think. There's a trial called CARBFUNC out of Norway. And maybe you were just speaking to it there.

17:02But I found that trial, and it kind of speaks to what you're saying here, it was a one year, I believe, maybe two, but they had one year data randomized, nearly a couple hundred adults. Large sample size, yeah. Large sample size. And there was a low carb diet and then a couple of higher carb diets. But the interesting thing - Protein was the same, wasn't it? Protein was the same across these three different diets, about 16 to 17 % of calories, which is kind of a typical amount where people typically land. And yet, despite having varying amounts of carbohydrates and also the same amount of weight loss, which was important, the liver fat, which was measured by CT, not MRI, and it was a secondary outcome.

17:44So take that for what it's worth. But the liver fat did not appear to be different between these diets despite the differences in carbohydrate. And that speaks to what you're saying here, that maybe protein is having a big say in that. And also, I will add, if it is, and you're right on this, it kind of throws a spanner in the works for the whole protein restriction longevity conversation. I always think this stuff is really difficult. And I'm sure as we get to the end of this conversation and we'll talk about, okay, does this new Sam Klein study mean this diet's the best diet and what does that mean?

18:19The really tough thing about diet is you have to deal with trade-offs. like there's broadly a healthy dietary pattern but if we think about excess or having extra protein maybe there are some downsides to that i know nothing about the longevity research i think it's kind of rubbish the whole high protein thing affecting longevity i mean if the protein is feeding your muscles and the muscles are helping your independence and exercise and it's keeping liver fat low surely that's that's that's what you want to summarize i think it's protein that has been forgotten here when we call these diets low carb or in this paper they call it a ketogenic diet and I wouldn't call this that.

18:58The headlines were a ketogenic diet is best for liver fat. I think a better characterization is a high protein, low carbohydrate diet, possibly in the context of weight loss though not necessarily helps lower liver fat. That's my take of this study. Okay, so let's come back to this study because we've kind of skipped through parts of it but What else do people need to know about this trial to kind of intimately understand what the researchers were setting out to test? So I think you described it well in the beginning. They called it a ketogenic diet. I call it a high-protein, low-carb diet, compared to two other good diets, like a plant-forward, plant-predominant diet and a Mediterranean diet, which were both much higher in carbohydrates and lower in protein.

19:42There were clear differences in the macronutrients. And the results weren't surprising to me because I know the high protein research, but they basically found that most other outcomes, you know, with a 10 % weight loss were pretty much the same, you know, same reduction in LDL cholesterol and all of the other markers. But the big difference was in liver fat and what they describe as liver insulin sensitivity. This has been sort of interpreted by some as being, oh, it's the ketogenic diet is the best diet. I think that's context dependent. I don't think it's the ketones because the ketones weren't even very high in this study.

20:16They were about 0.5 millimole per litre, which is probably at the absolute bottom end of ketones that you get from a proper ketogenic diet, which might be 1.5 or above. So I don't think the ketones are relevant here. I don't think we should be calling it a ketogenic diet. I think we should be saying a high protein reduced carbohydrate lowers liver fat because that's what this study shows and it's consistent with the rest of the literature. It's probably the same for all of the other outcomes that they mentioned but there's a couple of others that I think are important that I didn't find in the paper.

20:48They said they were going to look at vascular function so like flow mediated dilation, FMD, and blood vessel function particularly and this is really important because some critics of this study have rightly said well we're not looking at hard outcomes here it's just liver fat. And when we think about the cardiovascular disease like prevention trials with diet, if we consider Predimed, what they found is the significant effect on cardiovascular events, a proper outcome trial. And it happened through blood pressure. It happened through improving the function of our blood vessels. So we can't lose sight of that, that regardless of what is happening in the liver and reducing liver fat is really important, that we would also want any diet for good cardiovascular health to help our blood vessels too.

21:35I didn't see the blood vessel function reported in this paper, so I hope they do in the next. But look, I'm a dietician. My take would be, okay, if I had someone with high liver fat, I would definitely put them on a high protein, low carb diet or recommend it. And I use that a lot. But I always say, well, let's add the Mediterranean diet components into that, right? Like let's make sure in a high protein, low carb, we're getting extra virgin olive oil, we're getting seeds, we're getting plants and all of that. Yeah, that's where I landed too. I think that you can combine the best parts of these different dietary strategies.

22:12And also that kind of lower carbohydrate, high protein Mediterranean diet is a diet that can be kind of adapted to various cultures. And from an adherence point of view, I can see it being easier than going on a really, really strict ketogenic diet or a vegan diet on the other end of the spectrum. And that comes back to, again, understanding everyone's meals were provided in this study. But what you say as a dietician in clinic, then all of a sudden adherence and behavior becomes really important to that person's outcome. Yeah, 100%. And you personalise it. Like I have had, you know, anecdotally, I have had some vegans in my clinic and they would acknowledge themselves they were not healthy vegans.

23:00So it was a lot of processed carb, very little protein and not much healthy plants. I've had a couple of those people with really high liver fat, even though they were quite lean. And when I recommend more protein, and I started to because I was getting into this literature and many of my patients do go for MRIs, like if they've got really fatty liver, they go for MRIs. And it does reduce, even if someone's lean and they've got high liver fat, increasing the protein in my clinical experience, and this is what I think the scientific literature shows, it reduces liver fat. So like you say, if I have a vegan patient, like tofu's great, because tofu's got some phytonutrients in there.

23:40And then you'd make sure they were getting some greens, you'd get some blueberries in there, you know, nuts and seeds. And you've got all of those components. You've got the Sam Klein, I think, great protein result on liver fat, maybe reduce carbohydrate a bit. But then you take the Predimed findings and you add in some phytonutrients in there. This episode is proudly brought to you by IronMate. Over the past decade, I've seen what's possible when you stay consistent. I stopped binge drinking. I started eating a plant-based diet, I prioritized sleep, and I changed how I trained. At 40 today, I am the healthiest I've ever been, stronger, leaner, faster with my best ever blood work and VO2 max.

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26:35The pod is not a medical device and should not be used as a substitute for professional medical advice, diagnosis or treatment, and individual results may vary. Use code theproof at 8sleep.com forward slash theproof for up to$200 off the pod 6. That's 8sleep.com forward slash theproof. the glucose tolerance test that they did in this study. There was really no difference between the diets. So if they were on keto, I believe that they weren't necessarily tolerating glucose better than those on the Mediterranean or that plant forward diet. What does that tell you about how their physiology has changed their ability to tolerate carbohydrate load?

27:20So in general, like if we think back to the direct studies where people with type 2 diabetes lost about 10 kilograms and their glucose handling seemed to normalize. So when they looked at first phase insulin secretion, et cetera, after it, that was pretty normalized by just the weight loss. Now these were people with pre-diabetes and you could hypothesize that the earlier you catch type 2 diabetes and pre-diabetes is early type 2, 10 % weight loss would normalize glucose handling. Maybe that's what's happening here. It's always difficult, though, to run a glucose tolerance test when someone has been following a low-carb diet because they do become very acutely glucose tolerant because their insulin secretion goes down and their insulin clearance goes up.

28:08So I don't think, I think weight loss is doing most of this. If people have got prediabetes, the best evidence we have is that weight loss is the way to go. And I think because all groups lost a whacking amount of weight, we would expect glucose to normalize. Do people with prediabetes have beta cell dysfunction? Yeah. It's about, like if we think about the first phase insulin secretory response, depending on which group you look at, people with prediabetes have lost 30 to 60 % of it. And is there any data that was collected and published in this study that would have you believe that the beta cells, their function was preferentially kind of improved on one of the specific diets that they tested?

28:54Not from memory, no. That didn't jump out at me. Okay, so coming back to dietary fat, early on you made it clear that in some trials, it seems like there is an advantage to unsaturated fats, particularly polyunsaturated fats, over saturated fats when it comes to storing liver fat, which then might seem counterintuitive to the person listening to this who hears that the ketogenic diet resulted in the greatest reduction in liver fat, but it was the highest in saturated fat. Right. So how do you reconcile the broader body of evidence that we have, where there's a signal that polyunsaturated fats have an advantage over saturated fats for liver fat, with the findings of this Sam Klein trial?

29:43Some of the best trials are ones which are overfeeding. So they gave people excess calories. And as I mentioned, that will reliably cause people to deposit fat into the liver. And if you overfeed with polyunsaturated fat, you are less likely to deposit fat compared to saturated fat. Several groups have shown that. And there are also isocaloric trials or when people are just eating the same amount of calories, they're not losing or gaining weight. Again, which shows slightly reduced liver fat with the PUFA compared to the saturated fat. So it's a statistically significant effect. It's been replicated, but I don't think the effect size, the magnitude of effect is as big as we see with protein.

30:25So I don't think, like I said to you, that we can interpret what saturated fat means from this Sam Klein study alone, because I think it is the high protein and low carb that is really, I mean, it was a threefold difference, for goodness sakes. And this is pretty consistent with what we see in the literature. Even without weight loss, you increase protein and reduce carb and you reduce liver fat. I think that effect is so great that even if saturated fat was increased in this high-protein, low-carb diet didn't make a difference. But I do think, I hypothesize, it would have been even better if they'd had high-protein, low-carb, unsaturated fat.

31:05So saturated fat might not be as much of a problem in the context of weight loss. But is this important for people to understand in that people go through a weight loss phase, they're not losing weight forever. Eventually, they do get back to maintenance or a lot of people that lose weight go into regain? And at that point in time, does that ketogenic diet that has 23 % saturated fat start to look a little different in terms of some of these outcomes? I would imagine so. But like I said, even if you are in weight loss maintenance or you gained a bit of weight, and again, go back to those studies where they overfed people with fructose or fat and protein protected the liver to a certain extent, I do think it's the high protein and low carb that's doing the heavy lifting.

31:50And I guess my interpretation, like you can't tell too much about saturated fat from this one trial, but my view would be almost like whatever your goal is, there is no reason to have atherogenic saturated fat over unsaturated fats. Because like even if you wanted to go into ketosis, there's data that PUFAs are better, when you go on a high fat diet, better generating more ketones, so you get a higher concentration of ketones than saturated fat. You think about cardiovascular disease, you'd want to have more like poofers and moofers and saturated fats. There's just no reason to. Like when I'm talking to people like cheese, the signal is we don't need to worry so much about cheese.

32:29High fat yogurt, we don't need to worry so much. It seems pretty neutral. Those are also nutrient rich foods. But apart from deliciousness, I can't think of any nutritional reason why I would ever recommend someone, hey, have more butter, have more cream or coconut oil. There's no nutritional reason to do that. I'm going to steel man that position and push back as if I was someone that's listening and perhaps has a different view. I have the same view as you on this, but I'm thinking of what might come up here. So I think someone might say, Nicola, fair points. And broadly, the literature pretty consistently shows as you increase saturated fat, and certainly we could break that down to particular types of saturated fat that you see predictable increases in LDL cholesterol and ApoB and these atherogenic lipoproteins that are thought to be instigating and very much kick-starting that atherosclerosis kind of cascade where people build up plaque in their arteries and it predisposes them to having a heart attack or stroke, these types of events.

33:33However, in this study, a surprising finding was that the ketogenic diet, they actually had a reduction in their ApoB across the six-month period. In fact, all diet groups did and there was no significant differences between the groups. The Mediterranean group had the highest reduction in ApoB in absolute numbers, but there was no significant difference and they all had a reduction in ApoB. So, doesn't that mean that in this context, this ketogenic diet kind of lowered their risk of atherosclerosis, if anything? Oh yeah, that's a really good question and a really fair question. Yes, it did. But again, I would say based on all of the rest of the literature, we can only speculate about what might have been if that high protein, low carb diet also was much higher in poofers and moofers compared to saturated fat.

34:27So I almost think this is kind of missing the main point of the message that you want to get across to people. Like one follow a diet that can help you achieve weight loss because that's going to reduce all of your cardiovascular risk and liver fat. It looks like if you can increase protein and decrease carbohydrate, that has better advantages for liver fat. With all of that, and if you're losing 10 kilograms of weight, if you get quite a lot of saturated fat, it's tiny. But if we're talking about what you would advise someone based on everything we know, you'd say, hey, if you could tweak that a bit more, I hypothesize it would be even better for you if you try to reduce the cream, butter, and replaced it with nut seed, sunflower oil.

35:09I think that's a really important point because this is another one where APOB and LDL cholesterol on this high saturated fat ketogenic diet, again, I think it was masked by the weight loss, by the high protein and the carb restriction because the LDL cholesterol and APOB level, when you measure it, it's a summation of how much cholesterol is being produced and exported from the liver and how much is being cleared at the liver. And we know that saturated fat down regulates the LDL receptor. So it reduces your liver's ability to clear these particles. But what was happening at the same time on that ketogenic diet, or if I was to hypothesize, protein's having its effect and the carb restriction is having its effect on the liver.

35:53There's less fat in the liver, less triglycerides. So you get less export of VLDL and LDLs. So because there's less of these lipoproteins getting poor dumped into the bloodstream, it doesn't matter so much that clearance goes down from the saturated fat. And so the net effect is during that weight loss phase, at least, you don't see a significant effect on ApoB or perhaps the effect that you might otherwise predict from that amount of saturated fat in the diet. Does that make sense? Yeah, it does make sense. And what's quite interesting, and again, it comes back to what is protein doing to lipid metabolism.

36:31It's been really understudied. But if you look at a low-carb diet, which is high fat without adding protein, you get much greater increases in postprandial and day-long triglycerides. If you give a low-carbohydrate diet and you increase the protein, you don't get nearly as great a rise in triglycerides. So again, it comes back to the protein, like I said. It might just be high protein, low carb is doing so much to modify these lipid pathways that whatever the amount, whatever the saturated fat in the diet, it just doesn't have an effect. But again, I would go back to what you said, what happens when maybe people aren't following this diet so strictly or they're in weight maintenance, but also what I said with, well, would it have been even better if it had been high protein, low carb with a focus on unsaturated fats?

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40:05And then ultimately at the individual level, Or would you agree that the sensible thing would be you're monitoring your body weight and your blood work? So you're looking to see how are you responding during weight loss and after weight loss and specifically looking at ApoB in your blood work, looking at HbA1c, fasting glucose, all of these biomarkers with your physician, of course, to see what your metabolism looks like. That would be great. Like in an ideal world, that kind of information, like relevant information, relevant biomarkers and data are good. In the real world for lots of people, that's not going to be possible.

40:42And I would again draw on the rest of the literature. Like even today with this really amazing study, and I was really pleased to see it, but I wasn't that surprised by the liver fat data. It wouldn't change my recommendations for people to have lots of plant foods, fruits, even in the context of a low-carb diet and emphasizing unsaturated fats. Like if people individually, if you happen to really like butter and you want to eat a high saturated fat diet, and you for whatever, you know, let's say this diet in the way that we're hypothesizing does modulate lipid metabolism in such a way that you don't get an increase in LDL cholesterol.

41:18Like if that's true, great. But it still wouldn't change the advice I would give now based on the data that we have. What we would need is like we've been discussing, let's compare high protein, low carb, high saturated fat, high protein, low carb, high unsaturated fat in weight loss and then during an extended period of weight loss maintenance. And if that doesn't negatively impact APOB or LDL cholesterol, great, we have that data. But if people can't measure biomarkers or go and get their GP to measure this stuff frequently, I would just go with high protein, low carb, heart healthy. There we go.

41:54So Sam Klein or Max Peterson, if you guys are listening, there's a study idea for you. They really did a great job with this. Yeah. I'm sure they're already onto that, but we'll see. Fingers crossed. So just to leave the listeners here with something very practical. You've described the kind of advice that you would give someone in clinic, but if we bring that back to food, what does that look like on a weekly basis? What types of food and food groups would you want to see people leaning into? Okay. So this sort of comes with translating this very tightly controlled trial into real world. And let me just state one other research question that I would like answered, and I think it would be helpful to get this clarity, is I don't think based on the existing literature, you need to go as low carb as they did in this study.

42:42I think it's the protein doing the heavy lifting. How much protein you need, I don't think we know. Is there a dose response? Like, do you need to like max out at 20 % of calories? Does it me to be a certain amount based on mass, we don't know this. So what I try and do in my practice is move the needle. So what I would look for if I had someone who was a patient, like they had participants here, someone with obesity, someone with pre-diabetes and fatty liver, I would be wanting to increase the protein in their diet by at least 30%. And I would do that by, let's say they were a meat eater, like you would want like chicken and fish, I would increase that to have a larger serving size, then rather than lots of white or processed carbohydrate, I would be adding in legumes because that's going to give you a bit more protein and it's giving you those phytonutrients.

43:33And what you would want to try to get, I think 35 grams of protein a meal is a good starting point for most people. So with the combination of if you're a meat eater, have chicken, fish, tofu if you're not, plant-based meat alternatives you're not, then have some legumes, that's going to get you the protein. Have a small amount of carbohydrate if you want, like rice, potatoes, but keep it small. Have loads of veggies, whatever you happen to like, and get some healthy fat on there. Whether it's sunflower, canola, olive oil, that would be a very healthy main meal. How do you feel about cooking and cooling potatoes and rice to kind of reduce the glycemic load?

44:14Is that helpful? Personally, I find it a bit of a faff. I mean, you know, if people cook it up and, you know, you've got it in the fridge and you can add it to a salad to have the next day, great. But in general, when you are reducing the carbohydrate and increasing the protein, that alone is going to significantly reduce, it's going to make, it's like low glycemic load meal, it's going to significantly lower your glucose. So if people do this kind of high protein, low carb diet approach, if you've got loads of fish or tofu and some legumes. I think if you just want a small bit of white rice, don't worry about it.

44:50Like everything else is going to slow that absorption down. The high protein will help that person tolerate, it will make use of the carbohydrates in the meal. It will just keep the glycemic excursion low. And what are your thoughts on nuts and seeds and cooking oils? Nuts and seeds are great unless you have an allergy, obviously. Very nutritious. And again, it goes back to let's think about all important blood pressure and vascular function. That was one of the key findings of Predimed, the difference between the control diet that was a typical Mediterranean diet, light diet, and the nut group, because the nut groups had walnuts, almonds, another kind of nut, that was it.

45:28And it reduced cardiovascular disease at about, from memory, 25 grams a day. So the evidence for having a small amount of nuts a day on cardiovascular disease is really good. So again, if you want to have a low-carb diet, high-carb diet, whatever your favorite or most suitable diet is, getting nuts in season is a great idea. And what cooking oil is in your pantry at home? Oh, I've got loads. So I cook with rapeseed oil a lot because it's neutral. I also have sunflower oil because that's the highest in linoleic acid. And I have olive oil. I like olive oil on bread, olive oil on salads. So people don't need to be concerned if they've come across information online that rapeseed or sunflower oil is going to increase inflammation?

46:11No. Like at this point, I know this is the thing that's all over the internet. At this point, if people are not convinced, if people are worried sunflower oils are going to do them harm and it could cause inflammation, they're going to believe that. You know, people, there's been so much good information put out by scientists, physicians, dieticians and others. yes the animal data suggests that they were inflammatory but human data consistently shows they're not if people don't believe it by now they never will and you know the worst thing in the world I'm a big NFL fan and there was a coach who started and I think I'm a Niners fan and I think it was the defensive coach joined another team and he said the first thing I'm doing is removing seed oils and you're like oh I like I love you as a coach but Robert Sala I think that's his name.

46:58Well, that's become a thing. There's seed oil-free restaurants. It's a sticker on Windows now. I mean, it's mad, isn't it? Yeah. I mean, like I said, I have sunflower oil in my pantry. I use it for cooking. Well, we can thank RFK Jr. for some of that. Now, last question here, fiber. You mentioned that targeting 35 grams of protein per meal is probably a good target for a lot of people. Is the 30 grams of daily fiber, broad recommendation, does that have a direct effect on glucose tolerance and liver fat? I think there is some evidence that like viscous or fermentable carbohydrates, because this was my PhD work, we looked at fermentable carbohydrates and liver fat, has a small effect on liver fat is it reduces it.

47:42But you need a lot of fermentable carbohydrate to do that. It does improve glucose tolerance as well. It improves glucose tolerance directly like viscous fibers do because it's almost like they slow down the absorption of glucose. but we also think via a secondary mechanism of like short-chain fatty acids of the products of fermentation alter favorably fat metabolism and glucose intolerance is as a result of impaired fat metabolism largely when you develop type 2 diabetes. So yes, it's all indirect and again I'll repeat what I think. I think the effect of high protein on liver fat is greater than fiber but again, I would always recommend a high fiber diet because the evidence is so good for everything else that it does.

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49:11Head to join.whoop.com forward slash Simon. That's join.whoop.com forward slash Simon to get one month off your first subscription. And to round this out, so you're basically saying if someone has pre-diabetes or they're a bit overweight and their HbA1c is elevated and triglycerides and fasting blood glucose are elevated, and they adopt this Mediterranean high-protein, slightly lower-carb style diet as you've explained it, whether that's chicken and fish or it's fish and tofu or whatever that exactly looks like. They're eating nuts and seeds. They're cooking with olive oil or sunflower oil and they're losing some weight with that diet.

50:01Reliably, most people will see an improvement in those biomarkers that are slightly out of range. Yeah. If you do that, blood pressure should improve, LDL cholesterol should improve, blood glucose should improve. If people are losing weight, typically C-reactive protein goes down. And what does that mean for that person's risk of cardiovascular disease or other complications? It goes down massively, yeah. Okay. Is there anything else before we kind of land the plane here that you want to add? I mean, again, I would just emphasize, I think this was not a ketogenic diet. I don't think this study should have been interpreted as testing a ketogenic diet because it wasn't the ketones, I don't think.

50:39And Sam Klein in the paper seems to agree. Wonderful. Well, thank you for coming back and hanging out with me. We'll keep this conversation going and get you back on soon. Great. Really appreciate it. It was fun. There you have it, friends. I hope you enjoyed this episode. If you did and want to stay up to date with future episodes, be sure to hit that subscribe button on YouTube and follow on Apple or Spotify. Finally, thank you for showing up and the effort that you're making to take control of your health. I look forward to hanging out with you again in the next episode.