Written by Christopher Kelly
Dec. 5, 2018
Tommy: Hello and welcome to the Nourish Balance Thrive Podcast. My name is Tommy Wood and today, I'm joined by Dr. Bill Lagakos. Hi, Bill!
Bill: Hi, Tommy!
Tommy: I've been following your work for several years, probably at least five years, and there are many of your articles that you've written over that time period that I still refer to and refer others to, and I think most of the Nourish Balance Thrive team subscribes to your Patreon as well because we're big fans of your work and I'm very happy that we've finally had a chance to chat. Before we get into some of the topics that I know you're passionate about and very well read on, I'd love to hear a bit more about your story, your career trajectory particularly. Can you tell us a bit about your training, what made you interested in starting the original Calories Proper blog, which is where you got going, and what you're doing now?
Bill: Okay, sure. Well, I don't have an epic back story. I just got interested in nutrition really early on. I didn't have any disease condition that I had to battle to cure. I just really liked it. I like the topic. I started out in college in an engineering class that I didn't like. I took a nutrition class just on a whim. I really enjoyed it, so I changed my major and that started that, then I decided to go to graduate school to pursue a PhD in Nutritional Biochemistry and Physiology and I got to teach a couple of nutrition classes, so that's when I decided I really liked teaching. When I stopped teaching, I think that's when I decided that I had an urge to teach and that's where the Calories Proper blog started because I could still continue to teach basic, intermediate, and advanced nutrition levels, but in a blog format.
After I completed the PhD there, I went out to do some post-doctoral research in California studying -- endocrinology and metabolism was the general umbrella, so it was generally endocrinology and metabolism, but the real focus was studying inflammatory contributions to Type 2 diabetes. We did that with various animal models, genetically knocking out certain inflammatory molecules and different tissues and measuring out effective glucose tolerance with oral glucose tolerance tests or the hyperinsulinemic-euglycemic clamps, and all of this was animal work.
During that time, I started to get very interested in circadian rhythms because it seems like anyone who works a shift job has a huge increased risk for diabetes. They have increased inflammation. My interest in that just kept increasing and increasing, so then I went for a secondary post-doctoral study at the Mayo Clinic. Again, it was in animals and this time, we were looking at different diets, doing a ketogenic diet, low carb diet, low sugar diet, high carbohydrate diets, and various feeding schedules like whether you're feeding during the day, feeding during the night, having various access changes to the food to see how that affected the circadian rhythms, and if we could disrupt the circadian rhythms, how that would influence insulin sensitivity. That brings me up to pretty much today where I focus a lot on writing and researching about pretty much a broad range of topics and keeping up with what's new.
Tommy: Are you still in formal academic research or have you moved out there?
Bill: Now, I'm just doing a lot of writing and I'm still working on papers like writing papers from the experiments that I did.
Tommy: What are your long-term plans? I'm always really interested in academics that leave academia and what their long-term goals are.
Bill: I like writing. I like doing things of this nature, so I'm just going to keep doing this for the time being.
Tommy: Awesome! Well, we're certainly big fans of that, so let's dig in to some of this stuff. I think the circadian timing thing is something that's been a thread that's gone through several years of your writing. I was wondering if we could just start with the circadian control of metabolism, why is that so central to health. You particularly say many times that metabolism is gimped at night, so how does this all come together and then how does that start? So put together a picture that we can maybe use to help people with their long-term health.
Bill: Very broadly speaking, I think that circadian rhythms are extremely important. When people try and say, "Oh, well, that doesn't matter. What about diet?" I say if you compare circadian biology to diet, circadian rhythms are highly dependent on the light-dark cycle, your sleeping cycle. You can go a day without food. You can go a week without food. Heck, you can go a whole month without food. Try doing that with sleep. You will literally die and that's just because I think even for all of history for hundreds of thousands of years, people have survived on many, many different types of diets all around the world. They eat different grains, different animal foods, different fruits and vegetables. It varies seasonally. It varies geographically. What's the one thing that's been constant during all of this time? The light-dark cycle, so that's something we can't really get around. We can't hack it.
When I say metabolism is gimped at night, there has been a couple of studies showing, for example, you have impaired thermic effect of feeding after the same meal eating at night then you eat in the morning, which means basically if you choose to eat at night instead of in the morning, you're going to be eating fewer calories to maintain the same body weight. There are other studies showing metabolic health that you're better able to nutrient-partition food intake that's been taken in the morning than it's been taken at night. At night, you're more prone to store excess calories as fat than you are in the morning. In the morning, you're more prone to put those calories into lean tissue, so those are things that are -- they seem to be truly circadian in nature about the metabolic processing of nutrients.
There were a couple of funny studies that show they compared one meal a day, breakfast versus dinner, and in the initial studies, the people that were eating breakfast only tended to lose a little bit of weight or lose a little bit more than the people that were eating dinner only. So then they had dieticians come in and calculate exactly what they were eating and it turns out that people that were eating breakfast only tended to eat a little bit less, so it made sense that they would lose a little bit more weight. I don't know if you do show notes, but if you don't, these are studies by Jacobs and Hirsch. You can search either my blog for that or go to PubMed.
Tommy: Yeah, we'll get all of that. We have some pretty extensive show notes that people can go and dig into these studies if they want to.
Bill: They did some follow-up studies where they actually controlled the calories because that's a major confounder in a study like this, so they locked in the calories and they found the same thing that the people that were eating breakfast only actually lost a little bit more weight than the people that were eating dinner only, which just seems to be like a true circadian phenomenon.
Tommy: This reminds me of an old argument you had with Keifer of Carb Back-Loading fame. I was wondering if you could maybe just tell us a little bit about that because the more work that's come out on circadian biology and circadian rhythm management over the last few years basically suggests that that approach to stack calories at the end of the day, particularly carbohydrates at the end of the day, is pretty much like the antithesis of what would constitute normal circadian rhythm management, so do you mind digging into that a little bit?
Bill: Actually, me and John, I was on his podcast once and we agree on a lot of things. If your solution to body recomposition or weight loss really depends on a big dinner at night then you really do have to exercise a lot to make up for that, but if you want to optimize things, I would say frontloading your calories. A lot of studies show this that even -- I'm not talking about skipping dinner, but some studies show that having 70% of your calories in our early half of the day versus 70% of the calories in later half of the day, the people that are frontloading the calories always seem to do better in these studies regardless of whether they're totally controlling your food intake or if they're letting you feed in an ad libitum context, which is basically just directing people to say, "Have a bigger breakfast. We don't care what you eat."
The frontloading phenomenon seems to be pretty consistent and this also seems to be true with the intermittent fasting. There have been a lot of studies on intermittent fasting where the default seem to just be skipping breakfast, so that prolongs the overnight feeding window. My take on looking at all of these intermittent fasting studies is pick one, pick any of them, and none of them show great effects. I was just like, okay, well, they lost weight. Well, what if we compared them to just a regular lower calorie diet? The results were basically the same, so intermittent fasting didn't add anything to the picture, even the most recent ones.
There was one recent one -- I think the lead author was named Dr. Gasmi -- showing skipping breakfast and having maybe a late lunch and a big dinner and this was ad libitum, so the people that were doing that ended up taking in a higher amount of protein, which you would think would improve body composition effects. However, it had no effect on -- they were looking at muscle parameters and it had no effect on muscle strength or size or muscle performance, physical performance, which suggests to me that if you increase the protein of the diet, those things should've improved, but if they didn't improve, well, what would've happened if you didn't increase the protein? Well, those parameters have declined. My take-home from that study was skipping breakfast means you have to increase the amount of protein required to maintain nitrogen balance and physical function.
Tommy: In that specific study, do you know if the time period and the metrics they were using, were they going to be powered to see change in any of that, or it's part of the lack of effects in either direction just because a lot of support science studies just aren't particularly well controlled or designed? Is that part of it as well?
Bill: They did mention the power calculation. I didn't look at it. They cited some earlier studies that showed that they should've had the power to affect something. In my opinion, 12 weeks is pretty long. Most studies are like a month long. I think we're lucky to get these 12 weeks. That's not an isolated finding. There was another recent one by Dr. Panda and Varady. Basically, the general study outline was skipping breakfast and the skipping breakfast group in this study actually ended up eating less overall. They exercised more or had higher physical activity than the other group, but didn't seem to lose any more body fat, which again makes me wonder, well, what if they didn't do more exercise? Would skipping breakfast actually make you gain body fat? In the first study, the increased protein offset the potentially negative effects of skipping breakfast. In the second study, the increased exercise compensated for some sort of negative effects of skipping breakfast.
Tommy: Is this something that you think explains a lot of the issues? When people go to something like a ketogenic diet or low carb diet and then they often gravitate towards one meal a day and it's usually in the evening and it never seems to quite solve all the problems that they expected it to solve, do you think this is part of it?
Bill: Yes, and it's really hard to get around this because dinnertime is family time, and when do you ever get to sit down with everybody altogether? It's really hard. When I've worked with clients in real life trying to do this, I say you have to do gradual shifts. Start having a lighter dinner a little bit earlier than usual. You don't have to just skip dinner altogether. A lot of people say that they're not hungry in the morning and that's because you had a big dinner basically. Try skipping dinner once. Believe me. You'll be hungry for breakfast the next morning.
Tommy: Just that is a great piece of practical advice. Then you would suggest in that kind of scenario that to get into it, you'd skip one night of dinner. You'd be hungry the next morning. You can eat a bigger breakfast. I think you used that old adage of breakfast like a king, lunch like a prince, and dinner like a pauper, so that's how you'd start to recommend people shift their eating habits?
Bill: I think it's a good avenue to try. It's a hard habit to form. There was one recent study. It hasn't been followed up. The authors said they were going to follow up on it. It was called early time-restricted feeding where they basically had one rule, frontload your calories and stop eating at around four o'clock or something. To me, that seems a little bit strict. If you're going to have a light early dinner and you want to spend family time, that's fine. You don't have to have such a strict rule, but I like this study because one, it wasn't a weight loss study, but all of the participants reported less hunger in the evening. There have been other examples of studies where they'll do a short-term study and it's not a weight loss study, but they report lower hunger, and then the authors will follow up with a longer term study and find out that the group that reported lower hunger actually does lose weight if the study had gone long enough and they were allowed to lose weight.
In this study, if they started losing weight, the authors told them to eat a little bit more because they wanted to study the independent effects of the earlier feeding window. So if any fasting, intermittent fasting regimen showed beneficial effects, I think it was this study because they showed a variety of metabolic improvements, improved glucose tolerance, improved insulin sensitivity independent of weight loss just by switching the feeding window to the early time restricted feeding. People say that I'm against testing. Well, that's not exactly true. I think it has to do with the meal timing, the timing of the feeding window, not necessarily the duration.
Tommy: One part of that, the intermittent fasting versus caloric restriction comes up, I was talking to Dr. Satchin Panda and he mentioned that in caloric restriction studies, often there becomes a time-restricted feeding component because you give a small amount of food and then it's eaten in a small window. Do you think that is maybe part of why intermittent fasting versus caloric restriction often shows similar effects? Or at least intermittent fasting, does it show any benefit over caloric restriction?
Bill: Maybe. There has been a couple of studies that have compared to just continuous energy restriction to intermittent fasting and the reason why I think they don't show great effects is because when you're skipping breakfast, it's just basically the calorie intake, CiCo model of weight loss. It's not really fixing your circadian rhythms. You're better at nutrient partitioning with the frontloading of the calories, so that's why I think if they did a proper study, a long-term study on early time-restricted feeding versus continuous energy restriction, I think that would be important. These authors say they are going to be following up with a study along those lines and I'm being patient.
Tommy: If we zoom out and just think about the effects of circadian rhythm disruption on overall health, can you talk about some of the increased disease risks and where that data is coming from?
Bill: Sure. A lot of it is epidemiology because you can't really force somebody to do shift work and wait until they develop cancer, but there are highly increased risks for a wide variety of diseases that is seen in these shift work populations. Shift work is basically a huge circadian disruption. You have police officers that work the night shift. You have a lot of nurses that do rotating shift work, which I think is a little bit worse. Sometimes they have a day shift, sometimes they have a night shift, so when do you sleep, when do you eat. It's difficult. You're seeing a lot of mental disorders like neuropsychiatric conditions, bipolar disorder being more prevalent or being exaggerated in the shift workers.
A lot of these things are also I think going to become a lot, lot worse because of things like kids playing on their iPad until late hours of the night because that's another thing. It's a huge circadian disruptor. The iPads, the smartphones and smart devices, they put out a special kind of blue light that really specifically disrupts your circadian rhythms. This has been linked to all sorts of things, obesity, diabetes, breast cancer, prostate cancer.
In some cases, they've tried to figure out the mechanisms so that it's not just epidemiological studies. In the case of the cancers, there were a couple of studies showing that this blue light, this artificial light at night, seems to really disrupt the melatonin. You need melatonin to properly set your circadian rhythms. You need it every day, which is why you need to have darkness at night or at least install the blue light blockers on your smart devices or wear the blue blocking glasses. I do both of those things regularly.
They showed that when they're taking these human breast cancer cells and bathing them in melatonin or giving them a solution that has no melatonin, melatonin seems to block the uptake of alpha-linolenic acid, which tumor cells, if they do take it up, they will rapidly convert it into these mitogenic compounds that drive tumor growth. So if somebody is exposed to the artificial light at night, they're not getting that melatonin hit, which means if you have any precancerous cells, they're going to be more likely to proliferate into cancerous cells. I'm not sure what the mechanisms are for other disease conditions, but that was just one example for the breast cancer.
Tommy: This suddenly makes me think of basically all in vitro or cell culture work where there's going to be a complete absence of normal circadian external cues to the cell that the cell might normally expect if it was inside a healthy body. I wonder if there's going to have to be a lot of in vitro work that we'll just have to throw out because this is going to be so important for those --
Bill: Yeah, and when it comes to circadian biology, when I was at the Mayo Clinic studying this, we had some very expensive equipment that would -- we'd have the cell culture in there and it would give it melatonin for 12 hours and then it would drain it out and put it in a new solution for 12 hours. We could add certain compounds that would entrain the circadian rhythms, so I think the in vitro cell culture studies are important for determining the mechanisms. However, your point was exactly head on. We have to have the equipment to do it right.
Tommy: Did you notice any differences between what happens in these cell lines when they do or don't get -- you talked about the uptake of some of the compounds that can then affect tumorigenesis, but are there any general effects on just the health of the cell when it does or doesn't have some kind of time circadian input?
Bill: I don't know. I know that when we were doing the circadian studies, we could add compounds that would start the circadian rhythms and then you could measure them like every four or 12 hours and it would go for a couple of days, so you just have to want to set up your study designed accordingly like when do you want to do these studies. You have to entrain the circadian rhythms of these different cells lines at the same time so that you're not seeing differences, "Oh, it's this one" just because you switched around the daylight cycle.
The same thing with animal studies, it was very difficult to design these studies because we want to see a good difference in the morning or at night. Well, was this right at the end of their feeding period or was this right after they were fasting for 12 hours? Animals generally eat at night, so then if you did your study in the morning then they had just been eating for 12 hours, but then if you did your study at night, they've been fasting all day. For those studies, we would train a group of animals to eat during the day so that if we wanted to do the studies at night, we could at least control for when they're exposed to food and the fasting windows, so we were trying to delineate true circadian effects, but this is in its infancy.
Tommy: It's increasingly seeming like it's going to have to create a reexamination of all the stuff we know from animal work. It might explain a lot of the reasons why various animal models of disease science study brain injury. They don't always translate to the human and maybe this is a big part of it.
Bill: I agree with that entirely.
Tommy: In terms of general circadian rhythms, I'm interested in your thoughts on something like chronotypes. What do you think about the idea that some people are just designed or end up being more of the morning light versus the night owl? How does that fit into the picture of circadian rhythm and health?
Bill: My feeling in general is that chronotypes are a species level distinction whereas humans are the morning types. Mice are the evening types. I have never seen a study showing a positive effect of a human being on the night owl type. Those people tend to have more depressive disorders, increased risk for a variety of diseases, and I just think that that's just not the human thing. People have said the argument, well, during Paleolithic times, somebody had to guard the camp at night and maybe that was the night owl. Well, maybe it was just the person that drew the shortest stick, the person with the bad luck that just got chosen to do that, or maybe we had bonfires to keep away the predators, which makes sense because when I say artificial light at night disrupts your melatonin, well, that's artificial light. Bonfires don't do that, the moonlight doesn't disrupt your melatonin, so I think that we're just a morning species for humans, on a human level.
Tommy: Yeah. I often wonder if the night owl phenomenon describes people who are more susceptible to all these poor light cues that we're giving ourselves and then they are more likely to become affected by the light at night or that creates a greater circadian shift in them for whatever reason, something like that.
Bill: Yeah. It's one of these snowball effects. Once you start staying up later playing with your artificial devices, you're more tired. You're sleeping later in the morning. It's going to shift a lot of things. Your food intake patterns are probably going to follow. If you're staying up later, you might be hungrier later. It's a snowball effect.
Tommy: Then when you're working with people or if you had any general thoughts, I'd be interested in terms of the kind of advice that you'd give to people in various scenarios. One thing that I think about a lot simply -- because I'm half Icelandic, I have family in Iceland and in the summer, there's no darkness. In the winter, there's no light. There's about three hours of daylight in the middle of the day. I sometimes wonder how people do such a good job of staying healthy and maintaining a robust rhythm with such potentially wonky light cues. Do you have any thoughts on how that is set up or would you have any specific advice for people at those latitudes?
Bill: I was in Sweden for a couple of weeks a few years back and it was the weirdest thing that I have ever experienced because we were leading up to go out at night and leave the hotel at about nine o'clock and it was still bright as day, but what I did notice is the people have adapted accordingly with a lot of blackout shades, so it's not that they were used to having 24 hours of daylight, but at night when they went home, their windows were completely covered. I think that's sort of the smart way to get around it.
Tommy: Then what about during the winter?
Bill: In the winter, have bright lights in your house.
Tommy: Do you have any specific recommendations? Do you use light boxes or anything else like that?
Bill: A lot of people report that the GO light, Philips, is a good one. There was one called Circadian Blue, which was cool because some people were saying that they were leaving to work before the sunrise, before the sun even came up, and they could put this to the visor in their car. You could also bring it into work and clip it onto your computer monitor, so I thought that was cool and helpful for people that couldn't just get -- I mean, it's not very practical for everybody to get an hour of sunlight in the morning.
Tommy: Of course, yeah.
Bill: But if you are at increased risk for one of these circadian-related disorders then it's something wise to consider.
Tommy: What about people doing shift work, night shifts, and then swing shifts? Obviously, going back between the night shifts and day shifts, do you have any thoughts on the best way to work around some of the negative consequences of that?
Bill: It's hard. It's very difficult to do this healthfully. I would say instead of saying morning and evening, just switch the terminologies to your subjective morning and your subjective evening, so if you're working the night shift then your subjective morning is going to be 8:00 p.m. That's the time when you get the light exposure. When I say frontload calories then that would be the time to do it because you want to do that in your subjective morning. If you are at risk for any of these mental disorders or obesity or diabetes then it's when I would really consider if this is the best career thing to do. You'd want to weigh the pros and cons like if you're at risk for developing these conditions, do you want to stay in this career forever?
Tommy: For a lot of the mental health disorders, obviously just adequate sleep goes a long way, so anything that improves the quality or length of sleep is probably going to be important as well.
Bill: Absolutely. It's this whole country and I think sleep problem is with the whole world basically. Nobody is really focusing on sleep quality.
Tommy: And then in this area, do you have any thoughts on genetic polymorphisms as they pertain to circadian rhythms? People are really interested in 23andMe and looking at the SNPs, and often the promise of looking at that really underperforms what you actually see in real life. Things like the MTNR gene, which can affect how melatonin affects insulin signaling at night, do you have any thoughts on where or if genetic polymorphisms might be useful in terms of looking at this kind of stuff?
Bill: Yeah. The MTNR example, you gave us a very good one because pharmaceutical companies wouldn't be so interested in that if nothing is off. A lot of pharmaceutical companies are looking into exploiting these melatonin receptor polymorphisms because we're a sleep-deprived nation and there are no good sleep drugs whether it's prescription, over-the-counter. If you go to any of these big conferences where they're talking about sleep, they don't even talk about the sleep drugs because basically, whether it's over-the-counter or prescription strength, they just knock you out. They do nothing to mimic the natural sleep cycle.
When I work with clients, fixing sleep is usually the low hanging fruit. We will have a couple of conversations about diet, about exercise, and then I'll find out that they're only sleeping for four hours a night. Well, that's a huge problem because -- and there are a couple of go-to studies that I'd like to cite that if I just tell people these studies, the design and the results, I don't have to convince them any further to fix their sleeping habits. One of them was basically take a group of people and allot them to having five hours of sleep at night or eight-and-a-half-hour sleep at night. I do that for a couple of days and then expose them to a buffet, which basically eat as much as you want. They found that the group that was sleeping with a shorter sleep duration ended up eating about 300 calories more than the group that had the longer sleeping duration. The reason why I found this so interesting is because they did a bunch of questionnaires and it turns out that the people that were sleeping less and eating more weren't hungrier, so they were basically passively, mindlessly overeating, which I think that was so weird. If you're hungry, you eat more, but these people weren't even hungry. They were just passively putting food in their piehole.
There was another study that had a similar design, but this was a weight loss study where they were very strictly controlling the food intake, so both groups were eating the same amount of calories. It was at a slight deficit because they wanted them to lose weight and it was again five hours versus a little bit more than eight hours of sleep. The group that was getting short sleep ended up losing more muscle mass and less fat mass than the people that were sleeping longer. This is they were controlling food activity and food intake, so this is just simply getting better sleep, you're setting yourself up to make better food decisions. You're better nutrient-partitioning of the foods that you do eat. It's a very low hanging fruit, in my opinion, to get your sleep in order.
Tommy: I think you're right that it starts with sleeping right and this is exactly why.
Bill: Yeah. Once you get that in order, other things effortlessly fix themselves.
Tommy: We've often joked amongst ourselves within the company about how you often see people on Facebook arguing about various aspects of a low carb diet and what supplements you need to get the most out of it. Actually, they probably wouldn't need a low carb diet if they weren't awake at two in the morning staring at a computer screen arguing about supplements.
Bill: Sure. Absolutely.
Tommy: We've covered how you would improve sleep, how you would maybe focus on the size of meals throughout the day, how they will be timed. I know you have a lot of thoughts on macronutrients as well, which is obviously something that people are often focused on. How would you think through some of this in terms of talking somebody through macronutrient contributions or composition of the diet?
Bill: As a country as a whole, I think we eat way too much sugar and processed foods. I wrote the book "The Poor, Misunderstood Calorie". When I first was researching and writing that book, one of the things that I found a very positive thing of the low carbohydrate diets is if you look at 99% of the junk food that's most commonly people are eating, if you switch to a low carbohydrate diet, you're automatically cutting those foods out. I thought that that as a default was a very positive effect of the low carbohydrate in the ketogenic diets. If you wanted to follow a non-carbohydrate, restricted diet and you just cut out all the junk food, the carbs would probably go down and it would still be a healthy avenue.
I don't know who coined this phrase, but industrial foods. It just seems like step one should be cut the industrial foods. There's been a couple of studies, Ebbeling study -- I can't think of them off the top of my head -- that show that just by cutting these industrial foods, if you cut 300 or 400 calories of industrial foods out of the diet that people don't seem to need to replace those calories with other calories, so it turns into a little bit of a weight loss scenario even if that was not what was intended.
Tommy: Also, it reminds me of some of the primate studies on caloric restriction which basically suggested that if you are feeding your monkeys industrial foods, soybean oil and sucrose, then getting them to eat less of it is a good thing, but if you have monkeys eating what they're supposed to eat, more of a natural high quality diet, then the caloric restrictions seems to have less of an effect.
Bill: Absolutely. That was almost a scandal. I think over the past ten years, those studies came out and they showed exactly that. If you're eating a normal diet, a healthy diet, then calorie restriction probably doesn't really have a big effect, and that was a very interesting confounder.
Tommy: The problem is that those studies take decades and millions and millions of dollars, so they might not be repeated to the level that we want to really answer that question.
Tommy: What about protein? There's obviously a bit of or a lot of overlap between people talking about amino acid or protein restriction because of its effects on mTOR and that overlaps some of the caloric restriction stuff, but I know that you're a protein fan as I often tend to be as well, so can you maybe talk about how that stuff passes out?
Bill: I think this is also another species thing. I have yet to see a study where they vary the amount of protein in humans and they show a negative effect of higher protein. Every single study shows that whether it's a weight loss study, whether it's physical performance study, they all show beneficial effects of higher protein. The studies that show the negative effects are usually conducted in worms or fruit flies. Maybe there were some mice studies that are showing ultra high protein diets can be associated with reduced longevity, but I have not seen that in human studies. On the other hand, I think that a lot of people just don't eat enough protein even if we're not talking high protein diets. We're talking inadequate amount of protein.
Tommy: So what would you recommend to somebody working with you in terms of protein intake?
Bill: Well, protein intake varies a lot between people and one thing that happens if you drastically increase your protein intake then all of the enzymes involved in amino acid oxidation also increase. So if you're in a weight maintenance phase and you want to gain muscle and lose fat, just very gradually increase the amount of protein from whenever you're eating.
I don't like really giving grams per pound or grams per kilogram of lean mass recommendations because if somebody's habitually eating 200 grams of protein a day and somebody else is eating 150 grams, I don't want to make them a recommendation that would bring both of them to 175 because the guy who's eating 200 grams, if he goes down to 175, that's going to have a negative impact.
Tommy: But in terms of -- you mentioned inadequate, how the people ensure that they're getting adequate protein then I guess is a good place to start.
Bill: I would say a crude indicator would be body composition. If you're happy with your body composition and you have a good amount of lean mass and you're not carrying around excess adipose, you're probably consuming an adequate amount of protein. If you're the skinny-fat body type or obesity, you may want to consider -- well, if you're obese, you probably are eating enough protein or eating a lot of everything.
Tommy: Relevant to this is a few clients that we've worked with that have lost some muscle mass on a long-term low carb or ketogenic diet and almost always, the answer is either total calories or total protein. Is that where you might imagine the problem to be as well?
Bill: Yes, absolutely. This is true of basically every single low carb study. Lately, people are saying, "Oh, well, low carb is not superior to low fat if you control for protein and calories." I would say you have to take that a step further. If you're doing a low carbohydrate diet for body composition, the purpose of improving your body composition, you need to replace some of those carbohydrates with protein, so you can't keep having the same amount of protein, go to low carbohydrate diet, and expect to have better body composition. The studies just don't show that.
I would say lower carbohydrates replace half the calories with protein and fat. Make sure you're still at deficit so that you can be reducing the body fat, but you have to increase the protein a little bit to maintain the lean mass. The argument for that is simple. Protein is much more anabolic than dietary fat. I don't think anybody would really even argue that.
Tommy: What about the effects of ketones on sparing muscle tissue? We seem to go back and forwards on whether that's actually a thing. Where do you land on that?
Bill: It's not a thing. There's a very famous biological phenomenon called the glucose-sparing effect of fat-derived fuels and this is a phenomenon that's observed during starvation.
During starvation, you are losing muscle. You lose a lot of muscle at first and that declines. The rate of muscle loss declines. If the rate of muscle loss during starvation did not decline, you would die. I'm talking muscle mass like your heart's a muscle or your organs are muscles. In glucose-sparing effect of fat-derived fuels, the fat-derived fuels are the ketones and that offsets the body's use of glucose so that you can have more glucose for some tissues that require it for longer. This is an effect that occurs during starvation. It is not an effect that occurs during benign dietary ketosis or nutritional ketosis where people are maintaining their body weight and they have elevated ketones.
There's a study that show that the way to maintain lean mass during a ketogenic diet is you have to increase the protein. If ketones had an independent muscle-sparing effect then you wouldn't need to increase the protein.
Tommy: This is a warring thing in terms of people who go on ketogenic diets who think about total circulating ketones or beta-hydroxybutyrate if they're measured on a finger prick. That's the goal. Obviously, in that scenario, eating more protein might suppress some of those ketone levels, but in reality, the overall benefit is going to come from increasing protein.
Bill: Also, what is your goal? If your goal is body composition then you don't really need to measure. For some people, there are certain disease conditions like pediatric intractable epilepsy where they definitely need to be on ketogenic diet. The one thing with the ketogenic diet, if you want to determine adherence or if you're doing it right or wrong, there's a really easy way to test, to check for that, and it's just do the finger prick and test the blood levels.
Tommy: This transitions us nicely to something else that I want to talk about, which is the ketogenic diet -- so you've written about mental health. Obviously, neurological disease is something that I'm really interested in as well and you mentioned the classical case of intractable pediatric epilepsy. In those scenarios, the absolute level of your ketones is probably going to make a much bigger difference than somebody who just has body composition goals, so maybe you can tell us a little bit about why you got so interested in ketogenic diets and mental health, and then we can go from there.
Bill: Sure. I'm not entirely sure if it's an effect of the ketones themselves directly or people just giving up a lot of industrial junk foods. There are some cases to be made that the ketones have an effect. Very early studies show that humans that were early in dementia, just showing symptoms of mild cognitive decline, did show beneficial effects of a ketogenic diet suggesting that this way of eating may alter, biochemically alter the neurochemistry in the brain.
There was another study on more serious cases of dementia that showed a very positive effect, but the disappointing thing was adherence, of course. As these severity worsened, adherence declined, so the people that needed it the most were the least likely to be able to follow it. And then there were the intermediate studies that show a low-ish carbohydrate diet supplemented with something like coconut oil sort of mimics the effects of a ketogenic diet, which the field of the ketone supplements is sort of becoming a thing. I think this might be a case where that might be helpful, either the coconut oil, the MCT oils, or the ketones themselves.
Tommy: In terms of mental health, bipolar, depression, where else are you seeing the potential benefits from a ketogenic diet coming into play in terms of mental health?
Bill: I think it's promising. There were a couple good case studies on it. In bipolar, for example, it hasn't been very rigorously studied in a randomized trial. I think that should be done soon because these drugs, they're not good. You hear these horror stories of somebody trying like 12 different drugs before they find one that works. Well, that's because we don't really know what these drugs are doing and we don't really understand the conditions themselves very well. If you could just knock that out with a certain way of eating that we do understand, of course there are going to be cases where you're going to need pharmaceutical intervention, but you don't really want to go to that as a first line if you don't have to.
Tommy: Then when you work with somebody, if somebody comes to you and they do a consultation, which I know you're doing, everything that we've talked about, how do you start to integrate that? How do you figure out where the best intervention point is, where the lowest hanging fruit is? Are you looking at blood test or any other testing? How does this all start to come together as we start to figure out how to improve one individual's health?
Bill: I like the way you phrased that question because usually, the first one or two consultation sessions is just listening. I say, "Why are you contacting me? Tell me about your health?" and general things. While I'm listening, I'm doing exactly that. I'm looking for the low hanging fruit. If it takes than two conversations until they tell me that they have three cans of regular soda a day and they're munching on potato chips then that's going to be one of the first steps we take, or if I find out they have insomnia and they're playing on their smartphone, they're answering emails or something very late at night, I'm going to say, "Okay. Well, we need to look at that." I try to find things that people can adhere to.
One of my mantras with diet is, "What's the diet that somebody can adhere to?" and the answer is it's the diet that they've been eating their entire life. What would a healthier diet be? Well, let's just take the same thing that they've been adhering to and make small modifications to it because if it's just small modifications to something that you can adhere to, I think you're more likely to stay with it long term than if we radically change your diet.
Tommy: Is that something that you've seen or encountered hurdles with? So again, something else that we focus on a lot recently is the idea of behavior change, creating sustainable behavior change, and it sounds like that's something that you've been having to work through as well.
Bill: Yeah, and different things take different amounts of time. I'm always trying to do things gradually. One time, I wrote a blog post. Somebody came out with an estimate that said -- they're comparing the different sleep durations of different species. Humans, just for an optimal situation, we're supposed to be getting around nine hours and that freaks some people out. I'm saying, "Okay, Well, if you're sleeping seven hours a night, you don't need to jump to nine. For a week, try going to bed ten minutes earlier. If that's cool then the next week, try going to bed in additional ten minutes earlier and see where it works out to be."
For example, with the early time-restricted feeding study that we were discussing previously, they said -- I really like that study because in all diet studies, there's always attrition, people dropping out, people not following the plan. This study, after about 12 days, they had 100% adherence, which is amazing. By the end of the study -- I think it lasted 28 days -- they had all these questionnaires and the people were perfectly willing to keep doing this indefinitely. The question was, "Well, is this healthy or not?" The researchers didn't say this is healthy. They just told them, "This is what we want you to do and we're going to take these measurements" and the people said, "Oh! Well, yeah, I'll do it if you tell me that this is healthy" and I thought that was amazing that it took about on average 12 days.
There are other things like I've coached some people that are athletic, but really wanted to try the ketogenic diet. I said that's going to take a little bit longer because if you all of a sudden stop eating carbohydrates to get into the state of nutritional ketosis then your physical performance isn't going to decline. On the bright side, it really only takes about three weeks to get back to baseline, so then your training can go back. In that case, it's three weeks, not 12 days. You can't tell people to make a change overnight and you're going to have everything go into line. Some things take time.
Tommy: What kind of sports are these people doing? Because if somebody is a pure aerobic endurance sport then that certainly seems to be the case that you can adapt quite quickly to removing the majority of the carbohydrates in the diet, but we've had people who've tried ketogenic diets for months or maybe even years and they're doing a sport that requires some glycolytic power and bursts of intensity and they never quite get that top end back, so we have to iterate and bring back some carbohydrates into the diet. How does that look with the athletes that you're working with?
Bill: Most of the athletes I work with are just recreational, not competitive. There have been a couple of studies that are hard to define what constitutes that top end that you discussed. I've seen the Wingate studies where you have to be pretty crazy to participate in that study because -- yeah, there's a throw-up bucket next to the bike because they push these people at really high intensities and they show that you can support that high-end performance on a wide variety of diets.
Even recently, there was a study on Olympic weightlifters that showed as long as you give them adequate time to adapt -- and this study was over a month, which is more than enough time -- then they're still being able to perform a lot of these lifts at the high end. I'm not really seeing that study-wise. That said, I don't think carbs are going to hinder anyone's performance, so if you're on a ketogenic diet and you have some carbs the day of your event, that's not going to hinder you.
Tommy: Well, I guess based on the traditional Sports Science literature, they'd say that carbohydrates are ergogenic, but we do have to reframe that once we get some better understanding of how athletes perform on a ketogenic diet.
Tommy: As you continue your foray into writing and working with people, is there anything else that you're excited to learn and write about? We're obviously always excited when an email pops up with a new article from you, so where are you going to go with the blog?
Bill: Whenever there's a new study that people are buzzing about, I try to always reserve time either time during the day or at least one day a week where I can stay on top of that because I kind of consider myself like the antithesis to the journalists. When the recent study said that low carbohydrate diets will kill you, oh, it's not the carbohydrate content of the diet, it's if your fats and proteins are coming from animal sources or plant sources, blah, blah, blah, so I try to counter the journalists that grossly misinterpret those studies, but I also have my own interests like we were discussing in this podcast.
Circadian biology is of interest to me, various diets whether they should be ketogenic or vary seasonally geographically. I have a broad range of interests. I would encourage people to leave comments on the blog. I try and respond to as many comments on the blog. When people send me messages on Twitter, I try engaging as much as possible.
Tommy: But not after 8:00 p.m., right?
Bill: Correct, 8:00 p.m. Eastern Time.
Tommy: This has been a really nice overview of the great work that you've been doing and we're always very interested to follow what you write and I would absolutely encourage anybody listening to this to join your Patreon, which is the way to support your work and get access to your articles, but beyond that, you've mentioned Twitter. Is there anywhere else that people can find you and follow your work and interact with you?
Bill: Yeah, Twitter and my Patreon is pretty much the main two places where I like to engage with people and have discussions and challenges too. If you want to challenge my ideas, I like being challenged. I'm not unwilling to change, but yeah, this has been a great talk.
Tommy: Yeah. Great! Bill, thank you so much for your time. We'll put links to all the studies you've mentioned and all of your stuff so people can go and find it, and I again absolutely encourage people to support your work because it's always really good. Thanks so much for your time.
Bill: Thanks for having me.
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