In this episode, Dr. Mike T. Nelson pulls back the curtain on some common keto myths, including how it’s connected to fat loss, athletic performance, and even ancestral eating patterns. You might be surprised to learn that smart athletes will do anything to win—except go keto.
In this myth-busting conversation, you’ll discover why the high-fat-eating Inuit peoples probably weren’t in ketosis, how keto can slash your power output by up to 8%, and why metabolic flexibility—not extreme diets—is the real key to optimal health.
After 20-plus years in the field, Dr. Nelson shares his unfiltered take on everything from exogenous ketones to the carbohydrate hypothesis of obesity, delivering the nuanced truth that diet influencers won’t tell you.
Table of Contents
In this podcast, Dr. Mike and I discuss:
- Why the Hadza scale trees and get hundreds of bee stings for honey
- The interesting reason why the Inuit aren’t in ketosis, even with a fat-heavy diet
- How keto cuts athletic speed and power output by at least 8%
- Why some elite athletes consume 120 grams of carbs per hour
- The metabolic enzyme cluster that explains keto’s performance problem
- The true meaning of the term “metabolic flexibility and why 50 million Americans are metabolically inflexible
- Why muscle glycogen—glucose stored in muscle tissue—can’t physiologically drop below 30-40%
- The major differences between starvation ketosis and dietary ketosis
- How ketones work for brain injuries and concussions
- The “non-pathological insulin resistance” keto creates
- How “fat bombs” and other hyperpalatable foods killed the effectiveness of the keto diet
- Why your brain might prefer ketones after a traumatic brain injury or any state where it’s glucose-impaired
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Transcript
Keto for fat loss
Ari: Perfect. I think that’s all pretty accurate. I think another big factor was probably we had- I think that that swinging from poles, one thing was the big low-fat trend back in what, starting in the ’70s, maybe the ’80s. Low-fat was all the rage, and then the whole food industry promoted all these low-fat, very high-refined carbohydrate foods, but the idea was that they were healthy by virtue of being low-fat or not likely to make you fat, at least. Fat makes you fat. I think the paleo movement came out, and then the paleo movement was conflated with the idea that our hunter-gatherer ancestors were all eating relatively low-carb diets.
Then low-carb became a thing. Then you had Gary Taubes in the mix and the carbohydrate hypothesis of obesity and the idea that carbs stimulate insulin. Insulin is this fat-storing hormone, and fat-storing hormone obviously is what makes you fat. Therefore, carbohydrates, by virtue of insulin, is the critical thing that makes us fat and that regulates body fatness and is the cause of the obesity epidemic. Gary Taubes and others wrote books basically promoting that story of how the obesity epidemic came to be in the Western world.
There are lots of data points that you can cite. The increase in refined sugar consumption, the increase in refined grain, and processed foods that are rich in carbohydrates. All of that being very much linked with obesity, so there’s lots of plus insulin fat-storing hormone. Seems like you’ve got the biochemical mechanism in place to explain everything, and everything comes together in this very logical puzzle. There’s a long history and lots of details to that as well.
I think part of it is that people started going low-carb and then started to think, “If carbs are this thing that’s really bad for us and what’s making us fat, then maybe we should go even lower carb and maybe being low enough in carbohydrate intake that we actually enter this state of ketosis.” Maybe that’s the real key to unlocking the extraordinary health benefits and the fat loss benefits of keto. I think later on, then there started to be the discovery of many layers to that story. A lot of which debunked the carbohydrate hypothesis of obesity and the idea that insulin regulates body fatness.
Then there was the discovery, as you mentioned, about how ketogenic diets do increase satiety and decrease hunger and therefore contribute, at least in a portion of people, to better fat loss by virtue of that, by virtue of simply eating less food overall. Then there’s also the element, which I think this probably contributed a lot to the virality of the keto trend was the fact that when you go keto initially, you lose a lot of water weight as stored glycogen gets out of your system and then you drop whatever 5 pounds or 8 pounds or 10 pounds of water weight in a couple of days.
Then people experiencing that, weighing themselves on a scale, going, “Wow. The keto diet is amazing. My fat is just melting off. I’m losing 10 pounds of fat in two days,” and not realizing that so much of that instant effect is just water loss. I think just maybe those add some additional layers to that story as well.
Dr. Nelson: The calories thing, the group that Gary Taubes is associated with sponsored a study that basically disproved his whole hypothesis via Kevin Hall’s study that, using highly, highly controlled conditions, showed that, oops, yes, calories still matter. Sorry. [laughs]
Were our ancestors really keto?
Ari: Actually, maybe we’ll come back to the fat loss-specific claims. Maybe let’s address the ancestral side of this, because there’s a notion, not just from popular keto advocates, but there are a number of people who promoted the idea. For example, I can think of in the chronic fatigue space, there’s a doctor named Dr. Sarah Myhill, who I’ve had on the podcast a couple of times. Very lovely, very smart physician who argues in her work, and this is a point of strong disagreement that I have with her work, but she argues that basically the human ancestral diet is a ketogenic diet. That all of our ancestral humans ate extremely low-carb diets.
There are a number of people who have promoted that idea that a ketogenic diet is the ancestral human diet, that ketones are the preferred fuel of the body or of the brain and so on and so forth. What do you think of those kinds of claims?
Dr. Nelson: My bias is I think in some places, yes, you definitely have populations that were definitely more ketogenic. The Inuits obviously being one. You go all the way to the Kitavans ate a ton of carbohydrates. You can look at the Hadza. They had some carbohydrates, not a ton, but in essence, in almost every place, it had more to do with what foods they had available more than anything else. If everything around you is frozen and you’ve got polar bears walking around, carbohydrates are just nonexistent. Hopefully, you’re good with a ketogenic diet.
There are some cool studies of the Inuit showing they may have some genetic things that allow them to use fat more efficiently and stuff like that. Again, you go closer to the equator, where carbohydrates tend to be a lot more plentiful. Most of those groups of people tend to eat a fair amount of carbohydrates. The other part that also whenever I did lectures in this area, I’d always point out this video of– I can’t remember what tribe it was. I think it was in more of a jungle setting of this crazy guy scaling up this whole tree, just getting stung a ton of times to get honey because honey was super prized as a source of carbohydrates.
Ari: A lot of tribes do that. Certainly, there’s videos online of the Hadza tribesmen doing that.
Dr. Nelson: Hadza have done that. Almost every place that there was honey, you could find a tribe that was willing to scale these massive trees and get stung a shitload of times to get it because carbohydrates were valuable. I think it depends on the area that you look at. My bias, again, is through metabolic flexibility. If you mostly have only fat around, you better be really good at using fat. When carbohydrates are present in almost every circumstance, there weren’t people that were like, “Oh, honey. We’re going to pass that. Oh, tropical fruits, we’re doing keto. We’re not doing that.” No. They were eating usually as much as they could.
A lot of times those were very sacred things; they would go out of their way to try to get also, which usually tells you that there’s probably some importance to that. Again, in a lot of places, calories were not super plentiful all the time. Not like we have now. The Hadza spend most of their time, like Chakar, getting food to eat. That is a big portion of their day spend is to get enough calories to eat.
Ari: It’s been many years since I delved deeply into this topic. Close to a decade is when I was really into all this research. I remember actually a study that came out even on the Inuit, showing that even they were not in a ketogenic diet. They were not in a state of ketogenesis. The reason, if I remember correctly, someone could probably Google this and fact-check me real quick. What I remember of that study was that they were saying that when you eat fresh meat, there’s enough glycogen in that fresh meat that they were still eating enough carbohydrate to keep them out of ketosis, as a result of just harvesting a seal or something like that.
The fresh meat, as opposed to meat that’s been for days in transport or something, has a lot more glycogen. I don’t know if you’ve seen that as well.
Dr. Nelson: If I remember right, I think the study you’re referring to showed that it was periodic ketosis that depending on again, back to availability. If they had a fresh animal that had a lot of glycogen, obviously, they’re going to consume the portions; they’re not going to keep as much as soon as they can, so they would dip out of ketosis. Then, when food became more scarce, oils and things like that were easier to keep. We were visiting my uncle, who lives in Alaska. He’s lived up there pretty much his whole life. I was asking him because he used to do plumbing work way Northern Alaska for a lot of the smaller villages and stuff. He would be there, living with the locals for sometimes months on end.
I was asking him, I was like, “How was it?” He’s like, “It was pretty good. It was pretty interesting. When wailing season happens, everybody drops everything. That’s the big thing, and everyone goes wailing, you get a huge whale.” The other part, he said is, I said, “How was the food?” He is like, “It’s pretty variable.” I said, “What didn’t you like about it?” He’s like, “I never got used to the taste of seal oil.” I’m like, “Seal oil?” He’s like, “Yes, they put it on everything. Tastes horrible.” [laughs]
Ari: Wow, [crosstalk]
Dr. Nelson: If you think about it, I’m like, “Any type of concentrated oil is going to be probably a stable, huge amount of calories you can keep for a long time.”
Ari: This point of periodic ketosis, I think it’s worth making the distinction between a state of ketosis that you’re entering in as a result of lack of food versus a state of ketosis that is driven by a calorie-sufficient diet that is very rich in fat and low in carbohydrate.
Dr. Nelson: Yes. The hard part is they are different states because one, you could be at maintenance level or calories, or maybe even a little bit higher. Again, there’s been some studies looking at more on the physique athlete spectrum of is it best for muscle gain? Things like that. The short version is it can work; it’s probably not best, but it’s just hard to eat a surplus of calories doing that, so there is some truth to the satiety metrics. If you’re in a starvation condition, you might be able to get pretty high levels of ketones after a period of time, but you’re also in a massive caloric deficit.
My buddy Ben [unintelligible 00:11:47] has a saying I like is that whether you’re in a caloric surplus or a caloric deficit, caloric deficit is like this big trump card, and you can get away with a lot of, I’ll say, sins and air quotes by being in a caloric deficit. Usually, you’re doing a fair amount of movement exercise at that point too, whether it’s low-level or higher-intensity stuff. I think that’s the big thing that gets overlooked because you could come up with a scenario where maybe like three, four days into starvation, your ketone levels are maybe 2½, 3 millimolar.
If you’re doing a really hardcore ketogenic diet, you’re taking in a fair amount of fat. Maybe you’re doing a little bit of exercise. I have seen people register 2 or 3 millimolar who’ve been doing it for a while. Looking at blood levels of ketones, you might say, “Oh, those are both equivalent,” but yet in my opinion, those are two very different metabolic states to be in because one is a big caloric deficit and one is probably closer to maintenance.
The benefits of ketosis brought forth by caloric deficit
Ari: What would be expected to be maybe a benefit of the state of ketosis that results from being in a caloric deficit versus one that is from a ketogenic diet? In terms of the actual practical benefits that one might expect to get from being in a state of ketosis, what are the key distinctions there?
Dr. Nelson: Let me know if this answers your question, but the biggest thing is just fat loss. Obviously, if you want to lose fat, you have to be in a caloric deficit. How you do the caloric deficit, in my opinion, makes a big difference into how sustainable and how much you’re going to basically try to white knuckle your way through everything. You could make an argument, which I would agree with, that one of the ways to do a caloric deficit is to have higher levels of ketones because you do get some of the appetite blunting effects that can be used for the brain, cardiac tissue, muscle, et cetera.
The caveat that you run into then is, what kind of foods do you like? Usually, people ask me, you’ll be on a plane, or they’ll be like, “Oh, so what do you think of the keto diet?” Which is usually a loaded question because they either hate the keto diet or they’ve already been doing it. They’ve already made up their mind. They just want you to agree with whatever thing they’re doing. The first question I’ll ask them is, “Oh, do you like doing it, or how is it working for you?” They’re like, “Oh, I love doing it. It’s great.”
Ari: You got to make sure to ask that question if you’re going to be seated next to them for the next several hours, make sure you’re not going to say something that makes them think–
Dr. Nelson: Yes, pretty much. Again, you could make a rational argument that, hey, if you can get higher levels of ketones during a normal diet, that’s probably going to be easier. Yes. Now, the caveat is I’ll always ask people if they want an honest opinion, should I do a ketogenic diet? They’re not really predisposed one way or the other. I’m like, “What are your favorite foods?” If it’s bacon and fatty steaks, and I love putting butter in my coffee, a ketogenic diet for weight loss might be pretty good for you. If it’s donuts, hoho, and pasta, ketogenic diet’s probably going to be pretty hard for you because you’re going to definitely have to severely restrict or eliminate those particular types of foods.
Again, most of the data shows that weight loss is easier. Staying in that state and keeping the weight off is by far the biggest issue. If you want to do a ketogenic diet and your favorite food is donuts and white rice, yes, you can do it, but it’s going to take a lot of gonadal fortitude just to keep doing it, and that’s probably going to make your life pretty hard.
Ari: Gonadal fortitude. I’ve never heard that expression. That’s a good one. I’m going to steal that from you. There’s an important distinction in what you’re saying there, and this relates to the carbohydrate hypothesis of obesity as well which is certainly back in the day, and I think this is true to a large extent still, though I don’t really have my finger on the pulse of general public perception of the keto diet and carbs and insulin these days. I think it’s broadly true that at least a lot of people are still operating in the model of the carbohydrate hypothesis of obesity. The idea that carbs and insulin are a key cause or regulator of body fatness.
Therefore, the thinking was that– a lot of proponents of low carb and keto diets directly stated this years ago, was that basically calories don’t matter. They were mocking the idea of calories in, calories out is like, “Oh, that’s a bunch of pseudoscience.” Really, it’s about hormones. When we say hormones, we specifically really mean insulin, most of all, and insulin is all about carbohydrates, and so really this story isn’t so much about calories, it’s about carbs and insulin.
Hormones are the key thing that determine body fatness. What is embedded into what you just explained is a more modern understanding of things that reconciles these two views by saying, “Actually, no, that perspective is wrong. We have all this evidence to say that carbohydrates and insulin aren’t the thing that regulates body fatness, calories do matter, but there is this way that ketogenic diets interplay with the calories in, calories out equation.
Dr. Nelson: I would say the studies that Kevin Hall has done, other people have replicated these, where if we do highly, highly controlled experiments, where we put people in what’s called a metabolic chamber. Everything is measured, the amount of movement is measured, the food they get is measured, how much they eat of the food is measured, they’re looking at all the gases that go in and the gases that go out to see what their body is using for fuel.
Every time we run these studies, what we find is, yes, thermodynamics still works. I had to suffer through all those classes. I did my master’s in mechanical engineering, thermodynamics still works, calories do matter. However, that is a highly controlled environment, and we’re externally monitoring everything. Now the hard part is, humans don’t live in that type of environment. They live in a more open or free environment. When we try to replicate studies in that type of environment, it gets tricky because how do we accurately measure how much movement they do?
Maybe they didn’t move a lot, but they’re tapping their fingers a lot. They have a high level of what’s called NEAT, non-exercise activity thermogenesis.
People are horrible at telling you how many calories they ate, even when you try to get them to weigh stuff and do different things. A lot of those studies get really, really messy because again, you have humans living in a free-living society making their own choices. Now, some of those choices and some of those responses are actually subconscious, meaning the humans in your study may not actually be trying to lie to you, but they still are. For example, movement related to NEAT, like the non-exercise activity thermogenesis, walking, moving, twitching, those things are highly subconsciously regulated and changed by hundreds of calories sometimes per day or per week.
People are horrible at reporting those things again, because they are subconscious. I think that’s what adds to a lot of these misnomers with thing. There is some truth to insulin. Insulin, as I said, if you do lower insulin, you do push the body to use more fat as a fuel. However, you can definitely out-eat that, and you could probably out-eat it pretty fast.
Ari: Especially if you’re consuming fat bombs.
Dr. Nelson: Yes, especially. It is true that if you consume more dietary fat, in general, it is much easier for that fat to get stored. Atkinson has done some really cool studies, just overfeeding people in an acute sense, massive amounts of carbohydrates. I want to say, I think it was 400 grams or something like that. I’d have to look. It was just a massive amount of carbs. What he found was that in these people, they generally started oxidizing more carbohydrates. Insulin went up. Insulin pushed their body to start using more carbs as a fuel.
They did oxidize more of these carbohydrates. However, when you overfeed people fat, fat may have some effect upon satiety mechanisms. It seems to be very individual. Increasing dietary fat coming in does not upregulate fatty acid oxidation, or the burning of fat in and of itself. Now again, if you’re doing that in a ketogenic diet, because insulin is lower, you will still be oxidizing more fat, but that’s because you’re already in a low insulin state.
You notice this as keto progressed. What I saw was the more keto foods people used, it was just an easier way for them to get calories in. If you went and said, “Don’t use a lot of whole processed foods,” not that I’m against processed foods. You’re going to eat actual meat, fibrous vegetables, maybe add some olive oil, add some oils to your meat. Most people their calories would be pretty well controlled at that point. Now you start adding in fat bomb 460 and three things of fat in your coffee. There’s just all these other sneaky ways of just getting more calories into your body. [crosstalk]
Ari: As keto became popular, there was a whole industry-
Dr. Nelson: Oh, yes.
Ari: -that popped up. Similar to the low-fat foods industry back in the day, now we had the high-fat low-carb food, but made delicious. Based on basically, if consumers are operating under the premise that calories don’t matter, and really what matters is this proportion of fat and carbohydrates in my diet. I have a free pass with fat. Really, as long as I keep my carbs low, then I can eat all these delicious treats from the keto food industry, making these hyperpalatable fat bombs. As long as I keep my insulin low, I’m safe. Then people started to discover– all of a sudden, as that industry popped up, the keto diet became much less effective in terms of helping people lose fat.
Dr. Nelson: They killed their own industry, which is ironic. [laughs]
Do ketones make you perform better?
Ari: Exactly. I think that’s one really important distinction with fat loss. There’s another element of this, which is the claims around performance and athletic performance in particular. There were a number of claims that have been made over this over many many years by advocates of the keto diet that by making your body fat-adapted, by doing this kind of diet, you have superhuman energy, you have superhuman endurance, superhuman athletic performance, everything just skyrockets. What’s the true story as far as how the research has played out on that front?
Dr. Nelson: The very short answer is, in my biased opinion, it hasn’t panned out real well. Now the caveat to that is, historically, with people using a ketogenic-based diet– we can talk a little bit about ketogenic supplements, which you could do on top of a higher carbohydrate diet, but that’s a whole separate, different topic. In general, using a ketogenic diet, the premise was that, “Hey, if I’m doing this keto diet, I am increasing the body’s ability to use fat. Oh, if I do long-duration stuff like endurance events, fat should be the primary fuel. Therefore, if I can increase my body’s ability to use fat, I should have better performance.”
Again, like all things, there is some truth to that. If you do run more fat through your system, you are more highly trained. You can increase your body’s ability to use fat. You can measure this with a metabolic card called MFO or maximal fat oxidation. It’s just at what rate can you run fat through your system? A lot of people would point to Jeff Volek did the FASTER study, where he took people had been doing ketogenic diets for a long period of time. Gave them some fat, put them on a treadmill. Lo and behold, they could go very long distances for a long time on the treadmill. They saw a massive increase in their body’s ability to use fat.
When athletes try doing this, for high-level athletes, it didn’t go so well. There’s a study that they looked at athletes running a competitive half-marathon. They chemically blocked their body’s ability to use fat as a fuel. Their race times almost did not change whatsoever. What does that tell us? That tells us even in a half-marathon, the pace that they’re running, again, these are highly competitive half-marathon athletes, they’re using almost all entirely carbohydrates.
If you go to the extreme of the extreme, you look at Kipchoge trying to break the four-hour marathon– or I’m sorry, the two-hour marathon. I believe he was taking in 120 grams of carbohydrates per hour. He was running through carbohydrates like there’s no tomorrow. Again, because the rate at which he was running, even though he’s running a marathon, he’s ungodly fast compared to us mere mortals. What you find is that even in a marathon pace, the rate at which those athletes who are highly competitive have to run can’t really be powered by fat.
Now if you go to someone who doesn’t want to be an elite-level athlete and they’re like, “Hey, man, I just want to complete a marathon,” which is great. I have had some of those athletes use more of a lower-carbohydrate approach because it is easier. You have a fair amount of fat to use. You’re not being highly competitive, so you’re not running at this blistering fast speed. It does make it easier with potentially GI upset, you can get with carbohydrates coming in, and things like that.
In some of those cases, from their previous performance, they did way better. Again, the context of what we look at matters. Then if you get to another extreme was, I worked with a guy who was working to be the first solo person to cross Antarctica unassisted. He didn’t quite make it. He actually did really, really well. One of the discussions we had multiple times was because he literally had to pull all his own equipment and all of his own food. In that point, you could make a very good argument that ketones might be a really good fuel because they’re relatively high-energy output. For the same amount of weight, you can get a fair amount of higher levels of energy out of it.
From an efficiency standpoint, if you got– I’ve worked with some people who do two or three-day races where they have to carry all their own stuff and things like that, I think ketones and that small niche area have a very unique perspective. In terms of highly competitive athletes, in my opinion, just hasn’t really panned out to what all the experts were clamoring. Then last part, they would always say, “Oh, but you did that study. You just didn’t allow them enough adaptation. You only allowed them six or eight weeks on a keto diet. They need a year.” Then it was a year and a half, and then it was two years.
I’m like, “Man, if I need two years to be fully adapted to a keto state,” which may be a real thing. There’s some data to support that. That better be one hell of a massive adaptation, I get performance-wise from that, because I just gave up two years of crappy ass training. That better be one hell of an adaptation when I get there.
Ari: Absolutely. Two years of limited carbohydrate intake as well.
Dr. Nelson: Exactly.
Ari: Not just process for fine carbs, but-
Dr. Nelson: Total carbs.
Ari: -in a keto diet, you have to limit even things like, let’s say, sweet potatoes and fruit. One thing that I think should be maybe clarified, and we can add one layer to everything you just described there is higher intensity versus lower intensity, and how that affects how the body uses different kinds of fuel in both of those states. I think a lot of listeners probably aren’t familiar with the basics of exercise physiology and nutrition as it pertains to performance. Then, very much related overlapping with that is sports that are either endurance in nature, which was the focus of what you just described, versus let’s say something more like soccer or tennis that involves much more bursts of high-intensity effort.
Dr. Nelson: The classic thing in exercise too, is what’s called the crossover effect just from Brooks and Mercier, which is 1992. You can find data going back previous to that. The premise is that at lower levels of exercise intensity and healthy people, you are primarily running fat as the main fuel source. As the exercise intensity goes up, which can be measured by RPE, which is called Rated Perceived Exertion, or just simple output. You’re doing a higher-level output, but you’re doing that for less time. People think about the Olympics. The 100-meter sprint is way faster than the 200-meter, which is way faster than the 400, which is way fast than 1600.
The longer distance you go, you’re just going to be able to perform a little bit at a slower speed. We know if you’re going really high on speed and power, the time of which you can do it is very, very compressed. World records, obviously, 100 meters are under 10 seconds. That is almost all entirely powered by carbohydrates. There’s some, what they call ATP-PC and all that kind of stuff. In terms of fat and carbohydrates, the higher you go on intensity, the more higher percentage of that is being powered by carbohydrates. The lower you go, the more is powered by fat.
Fat has the advantage of if we take the same amount of fat compared to the exact same amount of carbohydrates, your body can extract way more ATP or just simply energy from fat than it can from carbohydrates. Now, the caveat is, the extraction of the process through fat, through the whole processes and beta oxidation, all the biochem stuff, is slower. You can’t sustain really high levels of output because it takes too long to get energy from that. If you go to higher levels of performance and speed, and power, the time component is very, very short. Carbohydrates can provide more ATP, more energy in a shorter amount of time, but again, the time is your rate limiter there, and they produce less of it.
Carbohydrates can’t produce as much pure energy, but they can do it at a faster rate. When you are looking for high output, rate is probably going to be the limiting effect. Now, it has other downstream effects. You produce lactate plus hydrogen ions, you get the burning sensation and all that other kind of stuff going on too. Low levels, that can produce a ton of energy, but it can’t sustain the high-level output. If we go back to our ketogenic friends, yes, you will still have some stored glycogen. Yes, you will still have some stored glycogen in the liver, but two factors are working against them. One, they’re not probably consuming any carbohydrates, and their stores are going to be more limited.
Also, for whatever reason, a muscle, you can’t drive it like a gas tank all the way to zero. The lowest levels I’ve ever seen on biopsies in muscle is probably 30% to 40% glycogen. You can’t drive it completely all the way to zero.
Ari: I did not know that.
Dr. Nelson: Yes, it can’t go to zero.
Ari: Is that relatively new knowledge? I don’t remember ever learning that.
Dr. Nelson: It’s been around for a while.
Ari: Maybe I just missed that part in all my exercise physiology courses. [chuckles]
Dr. Nelson: I was always taught, oh, it’s fat and then carbs and ATP, and each one lasts for this specific period of time. It’s all a complete mess now because they’re all working together, and that the theory is your body still probably has to run some through the carbohydrate end of the spectrum, even for lower to moderate level activities. The theory is that we can’t drive muscle glycogen all the way to zero because everything would be completely halted at that point. That it’s almost like imagining you have a bucket that’s being passed to the next person, to the next person, to the next person.
Fat is still running in the background to create energy, and it’s kind of kicking it over to the carbohydrate end of the system in terms of the carbon skeletons that are used. Carbohydrate end of the spectrum is kicking it over to the ATP-PC, and then you’ve got different rate limiters in there. All fuel systems turn on at the same time, but because of the rate at which they can produce energy, they’re producing it at different rates, and it’s like this game of handing the baton off to the next person, to the next person, and this circle goes on forever on that.
If you go back to our ketogenic friend who’s trying to do some speed and power stuff, what you’ll see in the literature is, you can probably lop off at least 8% of speed and power right off the top end. Now, again, that may not necessarily be because they don’t have as many stored carbohydrates because that output may only be– let’s say, 100 meter race, may only be 10 seconds, but because they’ve been so low carbohydrate, the carbohydrate end of the spectrum, or fancy word is glycolysis, hasn’t really been run or exercised that much because they’re primarily running on fat.
What you find is that that system then will downturn just like the old use it or lose it. In essence, you haven’t used it for quite a while, so the body is going to lose some of that performance. This has to do with an enzyme called PDH, Pyruvate Dehydrogenase, which is a gatekeeper to glycolysis, blah, blah, blah. All it means is that when you run ketones more often in a ketogenic diet, it doesn’t directly appear to be the ketones themselves. It appears to be the fact that you’re running a low-carbohydrate environment that changes this PDH enzyme, that then limits how many carbohydrates can be thrown into the glycolysis end of the spectrum.
The studies that show confirmation of this are– initially, when this came out, there was like, “Okay, great, we’re going to do marathons. We’re going to create freak athletes. We’re going to have them do ketones, we’re going to have them do ketogenic diet for six months, and then 12 months, and then we’re going to destroy all the records.” Didn’t happen. Then they started looking and going, “Oh, crap, they need carbohydrates in order to run these events, so aha, we got a great idea. One or two days before the event, we’re going to give them piss ton of carbohydrates. We’re going to make sure that their livers are saturated, their muscle is saturated.
Hell, we’ll even try giving them carbohydrates during the race without being– we’ve got this high level of fatty acid oxidation, but they will not be substrate limited because we’re going to give them all the carbohydrates back these two days before the race and even during the race. That’s great. We’re going to create freaks.” No, no freaks, didn’t happen. Why? Because the PDH enzyme was still being inhibited, so even though they had enough of the substrate they had enough of the stored carbohydrates present, they were missing some of that high-end machinery.
It would be like if you have a V8 Corvette engine, but you’re only running seven cylinders. You’re just not getting the maximum amount of power out of the engine because of that downturn a little bit. What they found was, for high speed and power, carbohydrates are still going to be your friend. If you’re low to moderate, then ketones and things like that, lower-carbohydrate environments can be beneficial.
Ari: Has there been any research? Again, this has been years for me since I’ve really had my finger on the pulse of all this research, that I suspect there’s been at least a handful, if not many dozens of studies that have come out on this topic since I last paid attention to it. Has there been any research that has confirmed an advantage for ketogenic diets in any sort of athletic discipline? Whether we’re talking about 100-mile races? Based on everything you described, we know it’s extraordinarily unlikely to happen in anything that’s more high-intensity or sprint-based, but what about in the ultra-endurance type of context? Is there any advantage there?
Dr. Nelson: The short answer from everything I’ve seen would say no. [chuckles] The only time–
Ari: Even like let’s say somebody’s got to do a multi-day race and they’ve got to go long periods where they don’t have access to carbs on the go. Maybe does it prevent them from bonking because they’re able to more easily transition into using stored body fat for fuel or anything to that effect?
Dr. Nelson: Yes. I would say the only exception is the cases where, exactly what you said, you are either carrying all your own food, so then you get into weight and efficiency and all that kind of stuff. I would make a very hard argument that being in a state of ketosis and bringing stored fat and things like that that are very energy dense but do not take up a lot of weight, nor do they take up a ton of space, probably the best way to go. In cases where you cannot get calories exogenously, so you can’t get them outside.
You’re like, “Okay, I’m going to go do this race, but I really want to maximize efficiency. I don’t have any stations where I can stash food, or I’m not taking in any drinks or anything like that, and it’s a three-day race.” There are all sorts of crazy races and stuff now. I would agree. Definitely doing a ketogenic-type approach because of the efficiency factor, I would say, probably beneficial. Years ago, I was a support person for the race across America, which is biking. We were on a four-person team. You start in San Diego, California, which you’re very familiar with, and you pedal your ass on your bike all the way to Atlantic City, New Jersey.
We were on a team of four people. At some point, one of those four people is riding. We’d have two people switch back and forth. They would take four hours off, the next two would go back, switch back and forth. I was one of the support people for it. I can tell you, none of those people use a ketogenic approach because there is some support, you can get fuel. There is a certain thing where day three, a lot of the fuels we had planned for the racers, one guy in particular, I showed him up. I won’t say the name of the carbohydrate supplement. He’s like, “If you even show me that container again, I’m going to throw up all over you. I never want to see that taste again. It’s so foul.”
It’s all he lived on for three days, and he was tired of it. I’m like, “Oh, man.” We’re in Nebraska. I’m like, “Shit, what do I do with this guy?” I’m like, “What do you want to eat?” He’s like, “Fig Newtons.” I’m like, “Fig Newtons?” I’m like, “Okay.” He literally–
Ari: Oh, that’s right. Fig Newtons are real popular, or at least they used to be among endurance athletes, right?
Dr. Nelson: Yes. I’m trying to get some protein in him and he lived on Fig Newtons for four days. Did fine. We got third place. [laughs] I don’t recommend it.
Ari: You just punctured my memory of something I must have read maybe a decade ago of, I forget who said this, probably a Google search could bring it up. It was some trainer of elite athletes who basically made the point of, you know how we know that ketogenic diets don’t provide a performance advantage? If you look at elite athletes who are you setting world records in any given sport, basically, none of them or close to none of them are using ketogenic diets, and these are people who are basically willing to sell their mother’s car to win or willing to drink a gallon of paint thinner. Whatever you told them to do that was going to help them win the race, they would do anything.
Dr. Nelson: Oh, yes.
Ari: Even they’re not doing it, so therefore it must not provide a performance advantage. That’s the true test.
Dr. Nelson: Yes. Other than a few of those outlanding endurance sports because the efficiency thing, I can’t name a single person at a high level, an actual elite level, who won or even placed top three doing a ketogenic diet. I literally can’t in 20-some years of doing this. I can’t name one. [laughs]
Ari: We’ve covered the weight loss aspect of things, the performance side, as far as athletics is concerned. One thing which we briefly spoke about earlier, with regards to epilepsy, that is important, and where there is some real good evidence that ketogenic diets do have benefits, is in the context of specific medical disorders. Epilepsy being the most well-researched one, but there are some emerging findings of– I know there are some trending psychiatrists who are promoting low-carb ketogenic diets for a variety of different psychiatric disorders.
Obviously, Dale Bredesen promoted this heavily with regards to Dementia and Alzheimer’s. He used a ketogenic or a modified ketogenic diet of some kind. I’ve had him on the podcast, but I forget the details of his diet to help people with mild cognitive impairment, showing that you can actually reverse that, and he’s a big proponent of that. I should say there is quite a bit of discussion around some of the metabolic diseases and impaired metabolic flexibility, which I know that you’re an expert in.
That results in some of these metabolic states of prolonged metabolic dysfunction over many decades, people lose some of that. In that context, I think there is some evidence of benefit of, at least, maybe intermittent or at least a period of ketogenic dieting. Take listeners through those key distinctions thereof, understanding where this diet may have very good applications.
Dr. Nelson: I got this question so much, not as much now. I think I still have it on my website somewhere of a flowchart of, “Hey, should I do a keto diet?” For a while, that was the number one question I got. I got, not annoyed by it, but being an engineer, I drew out a flowchart.
Ari: [chuckles]
Dr. Nelson: The first question at the top of the flowchart is, “Are you a healthy individual, or are you trying to treat a pathology via your physician?” Those are two completely separate different pathways. If they’re like, “Oh, I’m a healthy person.” Great. I’m like, “What do you do for a sport?” Great. “Are you competitive or not?” It’s like, “Yes, I’m competitive.” It’s like, “What sport do you do?” “CrossFit.” “Stop, do not go to do a keto. Go eat a sweet potato.”
[laughter]
Dr. Nelson: Basically, if you’re competitive in any form, eat carbohydrates. If you’re just general weight loss and you like fat, great, that might be an option. Beyond the pathology side, there’s some super interesting data on exactly all the areas that you mentioned. All of them, again, this is my opinion that I think if we look at the root cause of it, there’s probably multiple root causes, but one of the main issues, and almost all of them, is that the mitochondria are just not very good at using carbohydrates.
If you have a brain and you’re just not getting enough energy, shocker. All sorts of bad stuff happens to you. We know this has been pretty clearly demonstrated in concussion or post-TBI, traumatic brain injury. If you take a walk to the skull, it basically sends your glucose metabolism almost offline, almost instantly. All sorts of bad stuff happen to it. You also start spinning up more inflammatory processes. You could have the blood-brain barrier that normally keeps all these other compounds out of the brain. That can be broken down.
Now you’ve got all these other compounds flowing into the brain that are causing more inflammation, that’s screwing up the metabolism even more. In that case and in some of the other cases, ketones can still serve as an energy source. If you look post-concussion, you’ve got high amount of inflammation, but you also have a brain that needs more energy in order to try to repair and to do its job, but you’ve got an energy impairment because the glucose metabolism just gets all screwy.
The ketone metabolism and lactate metabolism doesn’t appear to get messed up. It’s like George Brooks’ lab is in a lot of work with lactate infusions. There’s some interesting pilot work now done with ketone supplements or ketogenic diets. What they find is that the ketones themselves appear to be anti-inflammatory, they do cross the blood-brain barrier, and they also serve to create energy in the brain. The brain can still use ketones, and it can actually still use lactate.
For years, I’ve carried exogenous ketones in my bag for kiteboarding, because if I unfortunately get dropped 20, 30 feet out of the sky or take a whack to my head, for me personally, I’m going to put myself in a state of ketosis as fast as possible-
Ari: Wow, that’s interesting.
Dr. Nelson: -and I’m probably going to stay there and call my neurologist and be like, “Hey, man, what do I do now?” [laughs] It’s anecdotal at this point, but there’s some anecdotal case studies where that’s been extremely beneficial. There’s some very interesting preclinicals, some animal data. One of them was where you take mice and you whack them on the head and you basically give them a TBI, and you can put them in different states to see what’s beneficial.
The hard part is that there’s not a lot of human data because, as you can imagine, no IRB in the face of the planet is going to approve a study where we whack people on the head and give them a concussion or a TBI and try to look to see what’s going on. There’s some anecdotal data–
Ari: I’m going to resist the urge to get into the whole ethical debates around how we treat our own species, versus how we treat other species, and animal testing and all that.
Dr. Nelson: Oh, yes.
Ari: I would actually love to do a podcast separately on that subject, but I don’t want to digress into that subject here.
Dr. Nelson: No, for sure. It’s just hard to do those on humans. My argument and I did a whole program for the Kerrigan Institute on training neurologists on this is that we don’t really know all the upsides to being in a state of ketosis. We have technology now where you can use supplements to literally put you in a state of ketosis within 20 minutes. We have very good data showing that that generally is very safe. We’re very good at knowing what the downsides are. There really isn’t too many downsides.
My argument is, again, it’s not medical advice; talk to your neurologist, talk to your physician. For me personally, I think being in a state of ketosis there only potentially has upsides that are not well-defined, and I’m personally pretty comfortable that I’m not worried about the downsides in that case.
Ketones and brain health
Ari: What about some of these other disorders, whether we’re talking metabolic dysfunction, insulin resistance, metabolic syndrome, or whether we’re talking brain health problems like dementia and Alzheimer’s, or whether we’re talking psychiatric disorders, what do you think the overall data is? I don’t know if you can paint with broad brushstrokes here, but what are your thoughts in that area?
Dr. Nelson: My bias in that area, I know Dr. Chris Palmer, I’ve talked to him a fair amount, he’s got a great book on this area. I’d encourage people to check it out. From talking to him, my understanding is he’s more of biased towards the ketogenic diet for a lot of neurologic conditions, depression, things of that nature. I do think we’re realizing that a lot of these states are more whole body states, and while the brain is super important, the rest of the body and how well that is maintained makes a big difference, too.
You can probably find isolated cases where neurologically you have more issues than you do metabolically, but most of the time they go hand in hand. If you see someone who has a high risk of type 2 diabetes because they’re going to have issues with their blood vessels, those blood vessels small vessels occur in the extremities, and they also occur in the brain. It’s not that surprising that they’re going to have a higher rate of neurologic issues.
Also, depending on what theory of neurology you ascribe to, I think a lot of the psychiatric issues are probably more on a spectrum than they are completely separate. You can look up Dr. Robin Carhart-Harris has a thing called the
entropic brain theory. His argument is that the amount of entropy or disorder that you can put a lot of these pathologies on a scale. If someone is extremely obsessive compulsive, they probably don’t have enough entropy. They need a little bit more entropy. If you have someone on the other extreme end who’s schizophrenic, they have too much entropy. It’s hard for them to even figure out what world they’re in because of their senses, giving them all sorts of bad information. His argument through that theory is that you can put them all on a spectrum, and that they’re more related to each other than these two opposing ends appear to be completely opposite of each other. If that’s true, then maybe things that modify the level of entropy are some things we can go after in terms of targeting that.
Again, that would go back to what is the metabolic state of your brain in that particular case? I think anything you can do to increase better energy, have your brain function better, is going to give you the opportunity to move in the direction you need to move, then it’s a decision of what direction do you need to go? Do you probably need to add more entropy or do you need to decrease the amount of entropy?
Keto and metabolic flexibility
Ari: That’s a really interesting way of explaining that. Are there any other disorders or diseases that come to mind in this discussion of ketogenic diets?
Dr. Nelson: The other part that comes up all the time is they’re like, “Oh, so I heard metabolic flexibility is a great thing, so I’m going to do a ketogenic diet to increase metabolic flexibility because expert guru so-and-so said that’s the thing to do,” and it’s half true. If you look at metabolic flexibility, how well do you use carbohydrates on one end? The second part is how well do you use fat? The third part is, how well can you switch back and forth between those two?
Like we said, if I’m going to go do a high intensity exercise, I want the ability to use carbohydrates. Or if I have a large carbohydrate ability to upregulate my body to burn some of those carbohydrates to start running my metabolism or carbohydrates.
Ari: Mike, can you repeat that last sentence? You cut out. At least for me, you cut out.
Dr. Nelson: Oh, yes. The third part is, how well can I switch back and forth between carbohydrates in order to fat? If I go do some high intensity exercise, I want the ability to upregulate, to use carbohydrates as the main fuel. If I’m doing a fasting or a ketogenic type diet, yes, I want the ability to then use more fat. When people do a ketogenic diet, on one hand of the spectrum, they do increase their body’s ability to use more fat. They also produce ketones as a byproduct.
On one side of the spectrum for metabolic flexibility, they may be increasing it. Now the hard part is that they’re actually decreasing their body’s ability to use carbohydrates. Part of that is, we talked about the PDH enzyme. Part of that is, if you want to get really technical in the weeds, you can have what’s called a non-pathological insulin resistance at the muscle level. There’s a whole bunch of crazy gobbledygook that means your muscle may temporarily be insulin resistant. Which at first blush sounds like, oh my God, this is a horrible thing. I’ve been told insulin resistance is this big, bad bugaboo thing. What it is, it’s a temporary change because in the face of a ketogenic diet, carbohydrates are extremely limited.
Your brain says, I’m greedy, I get all the carbohydrates first before any of the muscles do. If I make the muscles more insulin resistant, they’re sparing glucose for the brain. Now, the issue where that shows up is this has happened to multiple people, they go to their doc or they do an oral glucose tolerance test. They take 80 grams of glucose and they see their glucose levels spike through the roof temporarily, because their body is having a harder time adapting to those high amounts of carbohydrates.
All that to say is that they increased metabolic flexibility on the end of fat, but they didn’t increase it on the end of carbohydrates. Actually they made it worse on the carbohydrate end. Now again, if you stay compliant and do a ketogenic diet, there really isn’t many issues with that. Because you don’t have a lot of carbohydrates, you don’t have much to worry about.
I get really worried about people who go on and off or a hardcore ketogenic for Monday through Friday, and then Saturday and Sunday it’s like donuts and Ho Hos and the wheels are off. Then, oh my God, I got to get my head back into it. Monday, hardcore keto again, and this flip-flop back and forth. I don’t know. I don’t have any data to show this, but I think that would be very hard on your metabolism. [laughs]
Ari: I definitely went through my phase where I was doing that. Fun fact, I was doing the keto diet way before it became popular.
Dr. Nelson: Oh, nice.
Ari: Not before the Atkins diet, because I think that was when I was very, very young, or even maybe that even started before I was born. There was, I think, a guy from New Zealand, either Australia or New Zealand, who, geez, what is that guy’s name? He promoted basically, essentially what is a ketogenic diet, but he didn’t call it that. This was when I was a teenager, when I was 16 or 17, I remember doing this diet that he was promoting, and that was the first iteration that I saw popularized for people who were into fitness and building muscle.
Dr. Nelson: Was it a cyclical ketogenic diet?
Ari: It might have been. I want to say his last name was Flanagan or so something like that.
Dr. Nelson: Could be. Zumpano was the first guy to do a cyclical ketogenic diet for athletes, but there’s been a couple of people.
Ari: I remember when I was 16 or 17, zero carbs, just drinking cream and protein. Basically nothing else, just fat and protein, and carbs were out. I think it was cyclic. I think that every fourth day or something, I would binge on carbs. It was something like that. Can’t say that I ever noticed any particular benefits from doing it, but it was one of many, many extreme diets that I did in my younger years, starting in my teenage years, well through my 20s.
Dr. Nelson: I tried a cyclic years ago. God, this is probably almost 30 years ago now. I tried a cyclical ketogenic diet because at the time on paper it made sense. I was like, “Oh, okay, Monday through Friday, I burn a ton of fat. I get used to using fat on the weekends. I refill glycogen stores.” I even tried using it with clients again probably 20 years ago. With the rare exception of one dude, it was just a debacle.
You feel like crap until about Wednesday to maybe Thursday, then you feel pretty good. Then you get excited to eat a bunch of carbohydrates and then you feel really tired all weekend, your training’s better, and then you feel like ass come Monday and then just the cycle just starts over again.
[laughter]
Ari: It’s fun for maybe two or three months maximum, and then you’re pretty much over it when you realize there’s no gold pot at the end of the rainbow of that one.
Dr. Nelson: No. Even with drugs, there’s no physiologic free lunch. There’s a pro and a con to just everything. There’s a push, there’s a pull. It’s just how it works.
Ari: Hence the nature of side effects. This is a principle that a lot of people, we’ve become so normalized to this, but whenever you go tinkering with a complex biological system, whenever you’re operating from these simplistic principles of X mechanism causes Y effect, and let’s just create in a lab, let’s go create a man-made synthetic chemical that targets this receptor or this enzyme and just blocks it, we’re surprised that there’s side effects. I’m like, yes, that’s the nature of tinkering with a complex biological system. This is why all drugs will have side effects.
Dr. Nelson: Oh, yes. Even drugs we’ve known about for years that are relatively safe. I’ll pick on metformin. I mean, shit, we’re still looking, we’re still trying to figure out what exact– To this day, I don’t know what the exact mechanism metformin is. I’ve heard top physiologists say, “Oh, it’s because it’s bypassing this part of electron transport chain,” whatever.
I’ve heard literally people who have published on bioenergetics say, “No, that’s not true because at the levels you need to do that, that’s only in an animal model, that’s never been shown in a human model. The levels in a human model, it’d actually be toxic. There’s no way that’s actual mechanism.” A drug we’ve had around forever that is relatively safe, we still don’t really know how it works. [laughs]
Ari: I would argue, I’ve been getting very deep into systems theory and system science.
Dr. Nelson: Oh, nice.
Ari: Understanding biological systems through that lens, systems biology. I would argue that that same thing that you just said about the metformin is true of almost everything.
Dr. Nelson: Oh, sure.
Ari: That’s the whole nature of what we call side effects are just other mechanisms. It’s just that our way of speaking about this thing is we like to impose these very simplistic models of things where we imagine that our drug is only creating this one effect through this one mechanism. Whereas the reality of a biological system is it’s actually operating through many mechanisms and creating many effects. It’s just we’re focused on and talking about and seeking only one of those things. Then the other ones that are the bad stuff that we don’t want, we call them side effects and act like those aren’t also mechanisms.
Dr. Nelson: They’re just mechanisms we don’t like.
Ari: Yes, exactly.
[laughs]
Ari: Anyway, we could we could probably talk about that for five hours, so we’ll leave that one. Let’s see, what other important points do we need to address on metabolic flexibility? I know this is a big thing. This is something that we want, so what are keys that people should be aware of to actually get that? Maybe that’s a subject for a whole other podcast, but give people a brief overview of that.
Dr. Nelson: I think one reason I like the concept of metabolic flexibility not only was it my PhD studies, but to me, it’s from a marketing standpoint, you can say, “Hey, you can give them one term,” but we just talked about that one term envelops carbohydrate use, fat use, switching. It’s a little bit more complicated. The reality is at a simplistic level, that is how your physiology of a healthy person works.
You should be able to use carbohydrates well, you should be able to use fat. You should be able to switch back and forth between them, depending upon what you’re actually doing at that time. What’s having this conversation right now, a better fuel source would be fats. There’s no need to create a whole bunch of energy at a fast rate. We’re at rest, we’re not doing a lot of exercise. However, if we go do exercise, then yes, we want to use carbohydrates because we want, even I’d argue for general population, you want a performance adaptation from your exercise. It should not only be a caloric drink.
Yes, you’re going to burn calories. Yes, that is a benefit. Yes, that’s a It’s a good thing, but you want the chronic adaptations of improved aerobic metabolism, more muscle, more strength, increased grip strength, cardiovascular components. Those are the things that are helpful to maintain everything long term. You want the ability to use carbohydrates because you want the ability to increase performance, to get a little bit better output, to get the positive adaptations of exercise and everything else.
Negative side effects of very low carb ketogenic diet
Ari: Very well explained. Let me ask you this, what about side effects? Speaking of side effects, what about negative effects? Let me put it that way. Negative effects of being on a very low carb ketogenic diet. What comes to mind there. The reason I ask this is, again, I don’t know what new research has emerged in the years since I have explored this, but I do remember seeing some studies and certainly lots of anecdotes of people on the keto diet that were talking about poor thyroid hormones and low T3 and things like that.
It just so happens that just a few days ago, July 12th, I saw on Facebook on SuppVersity, he was publishing a little story of a study that was talking about low T3 syndrome. This is a name of basically low T3 levels. What was interesting about this is it’s basically talking about more of a hypothesis that is yet to be thoroughly proven by researchers.
Basically, they’re saying in people on low carbohydrate diet, particularly those who are doing a lot of physical activity, they might end up in this low T3 state. The way that this was talked about in the past was this was just a bad outcome. Certainly, in lots of functional medicine practices, they might say, oh, this low T3 is no good. Let’s give you exogenous thyroid hormones to get your levels up to the normal or optimal ranges. What this was talking about is, seeing this low T3 syndrome in this context of low carb diets and lots of exercise, actually as an intelligent adaptive state. Because basically, they’re saying the adrenal glands are pumping out lots of cortisol in this state to free glucose from the muscles, from the liver, to keep blood glucose levels stable.
In that state of higher levels of cortisol, the body intelligently lowers thyroid hormone output, so that you don’t get too much tissue wasting. That therefore, based on that premise, that actually someone who responds to that low T3 by just taking exogenous thyroid hormones to ‘bump’ their levels up to the optimal range where their T3 ‘should be’, would actually be working against their biology’s intelligent adaptation to that state of low carb intake, high exercise, high cortisol. What are your thoughts on that?
Dr. Nelson: I would generally agree, although back to the systems point of view, I don’t know if I would pin that much weight on cortisol. I think it’s a factor. I definitely think it’s going to be affected. I would view it more as a maladaptation to exercise in the face of probably not the right substrate or calories. I would be willing to bet those people, their intensity level is probably more moderate to the high level. They’re probably just not only doing zone two stuff and walking.
I would bin it more under the, not really, I would say, acute overtraining syndrome, but probably overreaching. The same idea, though. Your body is like, “Hey, you’ve been pushing the gas pedal pretty hard and we’re trying to recover, but, oh, wait, you’re pushing the gas pedal and you’re giving us this shitty octane fuel engine. Oh, but you’re pushing the gas pedal harder again.” You’re trying to get that next level of performance, but not providing the best substrate for it.
You can get away doing that for a while, but I think over time, your governor is just basically going to start lowering you down. It’s going to be like, “Hey, man, you’re not going to get to that high level. You’re just not going to get to those RPMs you want to get.” One of those systems that is going to regulate that is obviously cortisol. One of them is going to regulate it is anabolic hormones. Another big one is going to regulate it is the thyroid.
Within thyroid, obviously, you can look at T3, T4, reverse T3, blah blah blah, all the different ones. But T3 is the main one because that is the active one. I’d be super curious to see what are the rest of their other hormone, and especially, what is their output of training over time? Then I’d look at also a nervous system cost, like resting heart rate, heart rate variability. I would look at those markers also.
Again, you can look at cortisol levels. I think that’s probably useful. The cortisol levels are notorious to fluctuate a massive amount with exercise and stress. It’s a little harder to get your arms around what’s going on with that system.
Exogenous ketones
Ari: Maybe last couple of questions here, and I want to make sure there’s nothing that comes to your mind that you think is important that I haven’t guided us into. One thing I want to make sure to ask is about exogenous ketones, which you’ve mentioned a couple of times, and it sounds like you use, not only in a potential emergency context, but it sounds like you use in other contexts. I’m curious what your thoughts are on the benefits of those and what specific benefits those are, and in what context someone might get them.
Dr. Nelson: It’s like an area that I’ve been interested in since they came out. The fact that you could take a substance and get into a state of ketosis measured by blood levels of ketones within 20 minutes, it’s to me just fascinating. Because you basically bypass all the other things that involve fasting or high fat or other. Like we said, I think a lot of the negative parts of the performance part are probably more from the low carbohydrate environment that you have to be in to get ketones more so than the ketones themselves. That’s probably a little bit debatable.
Years ago, I was talking to Dom D’Agostino, and he was doing a project where for the military, they were trying to figure out a way that Special Forces could use non-rebreathers masks, but limiting the risk of oxygen toxicity. They realized that there’s some old data that ketones can help with that. Having them do a ketogenic diet is just not really applicable, so he was hired to try to find, is there a supplement that we can give these people to get them into a state of ketosis?
Long story short, there are some compounds that actually can do that. Now, normally you would think, okay, great. We have the ketone. We know the main ketone used for fuel is BHB, beta-hydroxybutyrate. Why don’t we just consume that? When you do, it’s not toxic, but your stomach just breaks it down and it doesn’t get anywhere at all.
The only two ways to get it across into the bloodstream are you have to bond it to something. The two main categories are ketone salts. They’ll covalently bond it to sodium, calcium, potassium, and magnesium, I think. The original one, which is done by Patrick Arnold, was just the BHB molecule and sodium. It worked, but, man, did you get a massive amount of sodium? What you also realize, I may have tested this myself, if you take in a huge amount of that because of the massive amount of sodium, you will be in the bathroom doing the Wilford-Brimley two-step for quite a while. Your guts do not like that whatsoever. They just– [crosstalk]
Ari: Who is that, the Wilford Brimley two-step?
Dr. Nelson: I call it the Wilford Brimley two-step. You remember the guy from the oatmeal box? [laughs]
Ari: Okay.
Dr. Nelson: Your guts will not be happy- [crosstalk]
Ari: I have no idea what it is, but it sounds bad enough that I don’t want to take that ketone salt.
Dr. Nelson: It’s like everything must go now, and it’s coming out. [laughs] Because you’ve changed the osmolality so much, your body’s like, “Just get it out. Just get it the hell out of here. We don’t want that. This is not going to be good.” Then they said, “Okay, if we’re using salt, let’s bond it to different receptors. Let’s put some on calcium, magnesium, et cetera,” or what they have a quad salt.”
That was better, but that ion dose is still limited. You could get maybe like two millimolar. Then there was a whole other line of research that was using basically what’s called ketones. They would have a different bond of different molecules. One of the early ones they used, this was something called 1,3-Butanediol. It was actually investigated as a potential food for NASA astronauts years ago. What happens with this molecule is it crosses and it goes to the liver and part of it gets metabolized via alcohol pathway, and the other part does get converted to ketones. At low levels, you kind of get some– [crosstalk]
Ari: These are ketone esters?
Dr. Nelson: These are ketone ester, yes. What HVMN uses in their product now is 1,3-Butanediol. That’s all that’s in the product. You do get some levels of ketones because now we solve the problem of getting them across digestion, but when you use 1,3-Butanediol because of the diol pathway, it literally goes to an alcohol pathway. If you’ve taken, let’s say, more than one serving of them, it’s a weird feeling. It feels like you spent a little time at a funky bar. It is not anything I would say is performance enhancing.
If you want to use it as an alcohol alternative, then I think that makes complete sense to me. That makes sense, and there is some potential stress, some animal studies showing stress in the liver. The other forms that came out with was, how do we get this across? There’s a company in the UK, they have their own version. I do some consulting work for a company called Tekton. They went to the company in the UK and they said, “Hey, your product really seems to work, but it not only tastes bad, butanediol is bad too.” They both taste like, I’ve never had jet fuel in my life, the first time I tried it, I literally thought I had poisoned myself.
Ari: Just to be clear, you have thus far not successfully sold me on taking any of these exogenous ketones.
Dr. Nelson: Correct.
Ari: I hope there better be something really good at the end of it.
Dr. Nelson: Yes, there is hope at the end of it. A certain chemist sent me some, in a little vial with no CoA, no nothing with a little container from good grips. I’m like, “Oh God, do I really want to try this?” He is like, “Whatever you do, don’t throw it up because the vial I sent you is like two grand.”
Ari: Wow.
Dr. Nelson: I remember taking it over my kitchen sink, there’s no smell to it, and immediately I was like, this tastes like jet fuel would taste. It was not just bad, but a stringently horribly bad. Fast forward, Tekton, they said, “Well, what if we just take the BHP molecule and we just bind it to glycerol, right?” Glycerol is the backbone of free fatty acids, and they were able to find a way to make it actually tastes pretty darn good. The properties are, when it gets split, you just literally have free BHB and glycerol. Glycerol is already normal product in the body just gets metabolized by the liver.
Early studies show does appear to be a little bit better molecule, and the good part is it actually tastes pretty decent. The new one that comes out will be pretty darn good. Now we have a way of getting ketones, which allow you to get much higher levels. You can get 2, 3, 4 millimolar ketones in your bloodstream within 20 minutes. We can bypass maybe three or four days of fasting or a long ketogenic diet, and have high levels of ketones even in the face of high levels of carbohydrates and no downturn in potentially the BHB mechanism.
In English, what does any of all that mean? You might be able to get some of the appetite suppressant effects, some of the cognitive effects and maybe reduction in fatigue. Those studies are still mixed. By just consuming the ketones in and of themselves, you probably need some type of ketone ester in order to get high enough levels to be effective. A lot of the ones in the market right now taste pretty bad, and I’m not convinced the butanediol versions are all they’re cracked up to be.
Full disclosure, I do some work for Tekton, I am an ambassador for them, so I am probably biased in that direction.
Ari: You’re a shill.
Dr. Nelson: I’m a shill, yes, I’ve been converted.
Ari: Tell us the truth, Mike. Does it really work? [laughs]
Dr. Nelson: It does, but it’s for weird things. Again, I don’t make that much money from them, but it’s fascinating because I’ve had a couple days where I’ve done grip stuff and I may have had three cans, which is 30 grams, pretty high dose. I’ll be darned if my output on the grip stuff was pretty good. I’ve replicated that many times now. There’s no data to say that that should be in effect. That’s a high output, high intensity thing. Most literature would say that shouldn’t be a thing, but I think there’s more going on in the central nervous system than what we realize at higher doses.
Ari: Interesting.
Dr. Nelson: Some people respond really well to them and some people are like, “Yes, it was okay.” I think the more not tuned to glucose as well as your brain is, the more ketones are going to be beneficial. I think that’s going to vary across the board.
Ari: I have heard a number of anecdotes of people saying that it does improve brain function or improves the ability to focus that sort of thing. Is there any data to support that or what’s your experience with that?
Dr. Nelson: There is data to support it, but it’s super mixed. Just flat out cognitive function, there is some data to support it. There’s better data that support cognition under fatigue. It’s like Brendan Egan has done some of these studies where you may do like a 2K row and have to do a cognitive task right after it. What are they doing? They’re trying to simulate like athletics because athletics, the fourth quarter of a game, you’ve got a high amount of fatigue, but you still have to be cognitively intact. There is some data showing that in those cases, it’s probably beneficial.
Again, does all the data agree across the board? No, but I think one of the issues is we’re not exactly sure what part of cognition is most impacted or beneficial. Different levels of fatigue are going to be different across people, and my base feeling is that, if your glucose metabolism in your brain isn’t quite up to par, by providing that alternative energy source, you’re going to perform even better. What I’ve noticed in people who have even more just frank pathologies of stuff, they tend to respond better to ketones.
For example, if I’m really sleep deprived and my stress load is really high, anecdotally, I respond much better to ketones than if my stress load is low, training’s moderate and I’ve gotten enough sleep.
Ari: Very, very interesting.
Dr. Nelson: I think that may account for a fair amount of the variability in the current data.
Ari: Quick question, what about MCTs, MCT oil, does that reliably increase ketone levels in the body?
Dr. Nelson: Yes, but not that much. MCTs could be, the main ones are C8 and C10. C10 probably doesn’t too much. C10 is just a chain of 10 carbons, C8 caprylic can, I haven’t seen people get above 1.2, 1.3 millimolar though. The good part is, C–
Ari: Is this the one that gives you olestra effect of–
Dr. Nelson: The good part is it’s less, so if you take a lot of–
Ari: Any linkage?
Dr. Nelson: Yes. If you take a lot of C10, I may have tested this too in my own home and, yes, you don’t want to go anywhere.
[laughter]
Too much C8 will do that too, but it’s not nearly as bad, a nine of doses it will still do it.
Ari: Is there anything that we didn’t touch on in this conversation that we should have?
Dr. Nelson: I would say no. To me, the most fascinating part in the future is, I think the use of ketones as a supplement because you can get potentially a lot of the benefits without as much of the, not really downside, but pain in the butt. For example, if I know I’ve got a fourth quarter game, I got to travel to get there, I might consider using ketones more often in that situation or we use them a lot for nurses and doctors who do shift work or like, “Hey man, I got like three hours left on my ER shift and I got to go home and sleep three and a half hours. I don’t want any more stimulants, I don’t want any more caffeine or anything.” In those cases, I think that has some pretty interesting properties.
I think the ketogenic diet for pathologies is fascinating. I do think there’s a lot we just don’t understand about that. I do think it’s probably a good alternative in a lot of those cases. Again, for the average person, if you really like putting butter in your coffee and bacon, I think, ketogenic diet could be a great solution. If you like rice and potatoes, probably not a good idea. The beauty is you don’t have to do a ketogenic diet for weight loss. There’s plenty of options for that, and I think we’ve gone past where people feel like they have to do a keto diet. Because maybe like seven years ago it was like, oh, I’m doing this because of weight loss. It’s the only thing that works, it’s like, no, there’s plenty of things that can work. It is an option, it might be a valid option, but it’s not the only option for that.
Ari: Now you have to eat only meat with no plant foods.
Dr. Nelson: Now I just do carnivore, right? Plants are evil and broccoli’s are to kill us, and oh God.
Ari: As I was walking through my garden earlier today in my backyard, the broccoli did jump out at me and tried to kill me. I had to defend myself, so there is some truth to that.
Dr. Nelson: Yes, I think I just mowed outside my yard very quick, but yes. The darn– I saw something the other day, I wanted to scream at my computer, I think I did, was that blueberries are now bad. Don’t get the wild blueberries because those are not organic and that these non-organic blueberries, those are the ones you got to watch out for now.
Ari: Yes.
Dr. Nelson: I’m like, oh my God. Most people don’t eat enough berries, period. There’s tons of data that did not use organic blueberries that shows beneficial effects. God forbid, everyone’s scared to eat anything now.
Ari: Yes. It’s amazing our species even survived, everything is out to kill us.
Dr. Nelson: Yes, how did we make it this far? To me, it’s fascinating that if I have a car and I put sugar in the gas tank, I’m probably not going to make it around the block, but you could have a human whose butt looks like a couch cushion, doesn’t exercise a whole lot, that eats 7, 11 Slurpees with no ice, and they can exist for a long period of time. That, to me, is fascinating.
Ari: I often remark on something similar, not only just eating, I mean certain groups of humans are raised from the time they’re kids just eating horrendous processed foods diets, smoking cigarettes, drinking. Growing up even from the time you’re a kid, breathing secondhand smoke and still many of these people will live into their 70s or 80s. We are an astoundingly resilient species that you can– I mean what other animal species could you do that with? That you could just feed it a horrendous diet that is completely inappropriate for that species, have it smoke and drink and be exposed to artificial light, and do almost everything wrong and still make it nearly to the age of a 100?
Dr. Nelson: To me, the resilience of the human organism is fascinating. Back to your thing about systems is, I’ve often joked the engineering like, physiology has every ‘bad’ engineering word associated with it. It’s nonlinear, it’s anisotropic, it’s chaotic. It’s like all this stuff that we have a really, really hard time modeling because there is backups to the backups, but the fact, like talking about ketones, the fact that you could take Bob, who’s never been in a state of ketosis his entire life, let’s say he is 50, you could lock Bob in a metabolic chamber and just give him water and electrolytes for three days, his body would still produce ketones and would still know what to do with them.
Or you could give him exogenous ketones, and the fact that those are so redundant, even though he is never really processed many ketones, he would still be able to use them at a pretty high degree because that pathway is needed for survival. It is so incredibly conserved without even being used. To me it’s just fascinating.
Ari: Yes, agreed. Mike, thank you for hanging out with me for so long. This went a lot longer than I anticipated.
Dr. Nelson: It was good.
Ari: I also had a whole bunch of questions that I formulated. I didn’t use any of them, maybe [laughs] except first one, just asking you what a ketogenic diet is. I just let the conversation flow naturally, which is always very easy to do with you, and really excellent stuff. This was a pleasure. I look forward to our next conversation, but tell people about the work that you do more broadly and give us a sales pitch. Give us like, what do you do? What kinds of stuff do you offer to the world, and how should people follow you, work with you? Tell us everything.
Dr. Nelson: Oh, thank you, I really appreciate it. This was super fun. Thank you for all the time, and the great questions. It was fun. Best ways to find me is just the website, miketnelson.com. I work one-on-one with a wide variety of people, from more high-end athletes to mostly trainers. I’ve got a few people right now that are post-cancer that have a fair amount of metabolic and movement stuff they’re trying to figure out.
I usually work with the people who, I don’t want to say the more complex cases, but more of the systems level thinking like, let’s think about your biomechanics, let’s think about your nutrition, let’s think about your recovery and try to figure those things out and how they all interplay with each other. The best place for more info is a website, which is miketnelson.com
I have a newsletter I tend to write for Daily, which has most of the information I put out, so you can get on that for free. Just go to miketnelson.com and there’s a newsletter above. I do have some stuff on the old Instagram, which is Dr. Mike T. Nelson. Then I do have some certifications, which is the Flex Diet certification, which is on metabolic flexibility combined with flexible dieting.
The Physiologic Flexibility Cert, which is more advanced stuff for recovery and like we talked about, trying to be really robust, anti-fragile stuff like temp differences, cold water, sauna, pH changes, breathing techniques. I have a course– [crosstalk]
Ari: I’m super excited to dig into that material with you. That’s actually the original reason that I wanted to reach out to you is because that’s one of my major areas of interest and I saw it was one of yours and I was like, “Wow, I got to talk to this guy.” I had actually been following your work since, geez, way back in the day when you were writing for T-Nation as well.
Dr. Nelson: Oh, yes. [laughs] That’s cool. We’ve got a course on hybrid variability, and then we have a course on flexible cardio for meatheads. If you’re a meathead who just likes to lift, but cardio’s also important, so how do you incorporate that? I have a course on that too.
Ari: Awesome. To listeners, I highly recommend all of Dr. Mike’s work. As you can tell from this episode and the previous one on heart rate variability, he’s a true expert through and through. I really enjoyed this conversation, Mike. Thank you so much for coming on the podcast, and I look forward to the next one.
Dr. Nelson: Thank you so much, I really appreciate it. That was great
Show Notes
00:00 – Intro
00:15 – Guest Intro – Dr. Mike T. Nelson
05:21 – Why is keto almost a religion?
15:49 – Keto for fat loss
20:11 – Were our ancestors really keto?
28:24 – The benefits of ketosis brought forth by caloric deficit
38:23 – Do ketones make you perform better?
1:03:51- Ketones and brain health
1:06:54 – Keto and metabolic flexibility
1:17:17 – Negative side effects of very low carb ketogenic diet
1:22:23 – Exogenous ketones
Links
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