The large majority of the medical establishment, and especially cardiologists, are going to have a knee-jerk reaction and say this diet's going to kill you. You know, you should get off this diet and alter the diet. But a lot of people who follow a ketogenic diet get so many great benefits from it, they don't want to get off of it. So, you have two options.
Welcome back to the Health Longevity Secrets Show, where we push the limits of human potential and unlock the secrets to our health and longevity with your host, Dr. Robert Lufkin.
Ketosis isn't a fat diet, it's a metabolic weapon. Today, Dr. Dom explains why ketones are like a magic shotgun against obesity, heart disease, cancer, even aging itself. From Navy SEALs to NASA astronauts, this is how the world's elite use ketosis to push human biology beyond its limits. And now, so can you.
And now, please enjoy this week's episode.
Thank you, Rob. It's great to be on. Appreciate it.
I'm so excited to talk about a subject near and dear to my heart, ketosis and ketogenic diets. But before we dive into it, maybe just start. What exactly do we mean when people say ketosis? What exactly is that?
Yeah, ketosis is defined by an objective biomarker that we can measure in our urine, in our blood, or even in our breath. And that's the ketone bodies: beta-hydroxybutyrate, acetoacetate, or acetone. So you can achieve ketosis through fasting. You could achieve it through manipulating macronutrient ratios, and that's called the ketogenic diet. And you can also achieve it, more recently, with exogenous ketones, ketone esters, ketone salts, or even medium-chain triglycerides, which is a type of ketogenic fat.
Now, are most people in ketosis, or what is the alternative to ketosis, I guess?
The alternative to ketosis would be not in ketosis. So the standard American diet, and pretty much what we're told to eat, silences or suppresses a metabolic state that has enormous favorable effects on our physiology. So if we adhere to the standard American diet, one really never achieves ketosis. That means an elevation of blood ketones, 0.5 millimolar. And this is in contrary to how we evolved evolutionarily through limited food availability and limited carbohydrate availability. We were undoubtedly going in and out of ketosis all the time. So it's rather unnatural not to ever achieve a state of ketosis, which the large majority of the population never really enters a state of ketosis. So historically, prior to the agricultural revolution at least, our natural state is in and out of this ketosis. But today, through the diet largely, people are no longer in it, and this has effects on our health, presumably.
What's good about ketosis, or what's bad about not being in ketosis ever?
Well, the ketogenic diet mimics the state of ketosis through a dietary manipulation that involves eating a sufficient amount of calories that are isocaloric, meaning that you're not gaining weight or losing weight. And what that does—in the 1920s, it was developed for epilepsy and other seizure disorders. So the clinical use of the ketogenic diet starts there. Maybe you could go back to like the Banting diet. Actually, it was used for type 1 diabetes prior to the advent of insulin therapy to help keep type 1 diabetics alive, essentially. And I think we've known, you know, well, if we want to take a big step back in millennia since the time of Hippocrates, and even, you know, the Gospel of Mark talks about fasting for seizures. So we've known about the benefits of ketosis achieved through fasting. And then in the 1920s, the ketogenic diet was developed that is restricted in carbohydrates, very high in fat, and adequate in protein. And then this diet mimics the state of fasting or some aspects of fasting. And it not only changes our metabolic physiology, it changes our brain neurochemistry and neuropharmacology in a way that can have a neuroprotective effect and have an anti-seizure effect. And that's kind of like what we study in the lab, you know, trying to understand fundamentally, you know, how changing our metabolic physiology changes other aspects of our brain health, including neurotransmitter systems, you know, antioxidant status, inflammation, things like that. And I think over the last 15 years, there has been an explosion of emerging applications of therapeutic ketosis. So that's a big thrust of what we do.
Yeah, I mean, it's amazing what this ketogenic therapy can do for, like you say, for seizure patients or in the past for type 1 diabetics. But, you know, most of us don't have seizures or type 1 diabetes. So what are the benefits to, like, everyday people? You talked about brain health, and what are some of the things—what are some of the benefits of being in ketosis through either a ketogenic diet or fasting or exogenous ketones, as you mentioned?
Yeah, there are many. We tend to study—we research things that have a fundamental mechanism associated with that particular pathology that therapeutic ketosis can treat. But if we talk about the general population, is what you're asking. I think—I think I saw statistics yesterday. I was reading a systematic meta-analysis review. It was something like 72.7% of the population is overweight and/or, like, have, like, you know, pre-obesity, essentially. So they're, like, right on—they're either obese or they fit in that category that they're overweight or obese. So that's significant, and it increases as the age increases. So one could say that low-carb diets, which kind of create a mild state of ketosis, or ketogenic diets, by virtue of increasing our body's metabolic flexibility and our ability to burn fat as fuel and suppress the hormone insulin. So, you know, 72% of people who are, you know, overweight and obese undoubtedly have—although it's not part of a comprehensive metabolic panel—have hyperinsulinemia, which actually occurs prior to getting type 2 diabetes. So if we were to measure hormones throughout, you know, longitudinally throughout the trajectory of someone's metabolic health as they age, by the time they have type 2 diabetes, that could have been predicted years before as an increasing level of insulin. The insulin level—your pancreas is secreting more and more insulin to basically dispose of the glucose over time. So I know it's like a long-winded version to answer your question, but I think there are—we have a situation where, at least in the US and even abroad, where we have type 2 diabetes, obesity, people are overweight, and nutritional ketosis and even just a low-carb, carbohydrate-restricted diet or intermittent fasting or time-restricted feeding are all ways to improve insulin sensitivity, but also to create a caloric deficit, which in and of itself basically restores our health, you know, our insulin sensitivity. We tend to lose weight. You can lose weight through many different ways, but, you know, we're of the opinion that if you improve insulin sensitivity, lower blood glucose, lower insulin, that's going to fundamentally change the neural circuitry and reward mechanisms in the brain to allow someone to comfortably lose weight over time instead of having blood glucose fluctuations and cravings associated with eating carbohydrates, which can be a trigger for many people—not all people, but for the majority of people.
Yeah. I mean, it's so fascinating, like, from a medical perspective. Look at, like you say, obesity. Most adult Americans are either overweight or obese. And a ketogenic diet will cause people to lose weight. Half of adult Americans have hypertension. A ketogenic diet will, you know, low carb—even a low-carb diet will lower blood pressure and reverse hypertension in many patients. The number one killers for us all, cardiovascular disease, heart attack, and stroke. A ketogenic diet will medicate against endovascular disease and atherosclerosis. Cancer is a big killer. Ketogenic diets now being used, as you know, secondary treatments, as we can talk about, for cancer. Alzheimer's disease. Ketogenic diet in a significant number of patients, not all, but reverses the effects of Alzheimer's disease. And then psychiatric disease. What is it about a ketogenic diet that applies to every disease that I can think of—that is, every significant chronic disease that is, you know, epidemic in the population today? What's the underlying—what's going on there?
Yeah. Okay. All these things that you mentioned are true. Just go to—well, if you go to PubMed, a lot of people ask, you know, they're like, 'Well, what happened to the ketogenic diet? I heard about it, but I don't hear much about it anymore. It's not that popular.' Well, I evaluate the interest in ketogenic diet based on peer-reviewed research on PubMed. So just go to PubMed, and there were something like 503 articles in 2002, and this year it's like 626 or something. So it's exponentially increasing. So the peer-reviewed publications on PubMed, if you just type in ketogenic diet, is increasing. And I think what I'm more excited about is if you go to clinicaltrials.gov and type in the word ketogenic diet, you will find hundreds of—do you—hundreds of research, registered clinical trials on the ketogenic diet. Now, about a third of them, if you look deep, they're also using some kind of ketone supplementation that could be MCT or ketone ester or something like that. And it's an interesting avenue of, you know, innovation in the diet. But the general nutrition person, who basically—if you ask that question—they would say, well, there's nothing magical about the ketogenic diet. It does nothing special at all. The only reason that it works for these things, type 2 diabetes, weight loss, and even other neurologic—the only reason that it works, they'll tell you, is because a ketogenic diet is hypopalatable. It tastes bad. So people eat less. And I think some may argue, you know, it is satiating. It's, you know, fat and protein is satiating relative to carbohydrate feedings. So that's what they would say. But I would say—I would argue that the ketogenic diet is unique and unlike any other diet because no other diet that you can follow can control drug-resistant epilepsy. Like a vegan diet doesn't do it. You know, a paleo diet doesn't do it. A vegetarian—you know, the only diet that can fundamentally change our metabolic physiology to change our brain neurocircuitry and neuropharmacology is a ketogenic diet. And that's why so many, you know, pharmaceutical companies are interested in the mechanism of this. I've spoken at many pharmaceutical companies. They want me to give like one answer. But the thing is that the ketogenic diet's not a magic bullet. It's like a magic shotgun. So it's changing brain energy. It's changing the glutamate to GABA ratio. It's changing inflammatory mechanisms. It's changing—our lab studies the epigenetic effects of ketones. So we look at something called beta-hydroxybutylation, where beta-hydroxybutyrate can directly interact with histones and cause histone modifications. That's really going down the rabbit hole, but it just gives you a little bit of a sense of the pleiotropic effects associated with being in a state of ketosis.
Yeah. I mean, my personal favorite mechanism is mTOR and turning down mTOR—turning off or turning down mTOR to autophagy, turning down inflammation, turning down hyperfunction, and thus not only the chronic diseases but slowing down aging, you know, as an effect as well, and improving longevity. Now, when we talked about a ketogenic diet before, we talked about it for—you mentioned for epilepsy or some of these like as treatments and that sort of thing. Are any people going on ketogenic diets and just switching to ketogenic diets? Or is it like, oh, I have epilepsy, I'll do it for a week and then I'll stop? Or, I mean, is it realistic to be on a ketogenic diet for the rest of your life and not make it a diet but just a lifestyle?
Yeah, good question. I probably should have started off with this. A ketogenic diet is a clinical intervention that is prescription strength, right? So there's different types of diets. I would label a ketogenic diet as a prescription-strength metabolic therapy, meaning that it should involve—it should require close medical supervision. By, for example, in epilepsy, you have a neurologist that's working with a registered dietitian that's trained in ketogenic therapies to manipulate the macronutrient ratios and to measure the person's blood or urine ketones to induce and sustain therapeutic ketosis to metabolically manage that particular disorder. So that is unlike any diet that I know of. So it's unique in that way, and also an objective biomarker to help guide the clinician and the patient to manage it. However, you know, you can use versions of a—like our keynote speaker at the Metabolic Health Summit that just happened a few weeks ago was Dr. Valter Longo, and he is an advocate of the fasting-mimicking diet, which is a type of a ketogenic diet in that, you know, in his presentation, he basically showed that, you know, it produces a state of ketosis, but it's only like five days out of a month. And what's very interesting about this intermittent ketosis is that you get sustained effects—metabolic effects that occur for weeks. I think he said like three weeks after like a fasting-mimicking diet and just like a short phase like five days could be achieved. So for the everyday person—and I mean, he's using it to treat different disorders and stuff too—but I think there's a lesson to learn here, that intermittently entering a state of ketosis can produce long-lasting beneficial effects on many different—on our physiology. And this could be inflammation, this could be insulin sensitivity, it could be body weight, blood glucose control. So I think that's an important message too, that there are many types of ketogenic diets, macronutrient ratios-wise. There's the modified Atkins diet that's used for adult epilepsy. There's the fasting-mimicking diet. There's even, you know, the very first article I ever wrote in the Keto Nutrition blog, which is our website, Keto Nutrition, was a plant-based ketogenic diet, just because I get so many questions about people that are vegan or vegetarian that want to follow a ketogenic diet. So it sent me down the rabbit hole, it's like, okay, this is an important topic. So you can even, you know, follow a plant-based version of a ketogenic diet if you want to.
Yeah, it's fascinating. Valter's a friend of mine and he's on this program. But, you know, as you mentioned, they have this five-day fasting-mimicking diet, and he says, 'Great, you got to try it.' And I go, 'Hey, Valter, I'm in ketosis almost all the time. I eat one meal a day, and the meal I eat is basically protein and fat, very, very little refined carbs at least. So I'm in ketosis. Why would I want to do a fasting-mimicking diet?' And he goes—well, he pointed out something I hadn't thought of: ketosis is very different than fasting. I mean, there are a lot of similarities and there's a lot of overlap, but he says, 'Sure, you're going to be in ketosis all the time, but you're not fasting.' And his whole fasting-mimicking diet, it's basically—it's like a ketogenic diet, but hypocaloric to the point of, you know, 500 calories, 800 calories a day. So it drops you into this nonsustainable, you know, sort of artificial stress hypocaloric state for at least five days. And I mean, nobody really knows—certainly I don't know it, you know—but there appear to be benefits from it that are above and beyond what I would get from my daily 20-hour fast or something, which really only kicks in some of the autophagy for short periods, if at all, really. But yeah, there's so many fascinating things to look at this. But what's the pushback on a ketogenic diet? I mean, you hear negative things about it. 'Oh, don't do that. You'll kill your kidneys,' or, you know, you'll—what do you think? What's the message people need to understand about the dangers of the ketogenic diet? What do we need to watch out for, if there are any, versus what's out there in the press?
Yeah. Well, like any really strict medical or dietary intervention, it can have some side effects. The side effects of ketogenic diets are typically transient and manageable. From the epilepsy world, you know, if you have a fatty acid oxidation disorder, if you have pancreatitis, if you have liver dysfunction, if you have carnitine deficiency—primary carnitine deficiency—if you follow a ketogenic diet, a lot of labs I've seen actually show you end up being low in carnitine, especially if you don't have a lot of meat in the diet. That's because carnitine transports fat into the mitochondria, and it tends to deplete because you're burning so much fat. So these are some of the things that show up in the lab. Also, low calcium and low magnesium and electrolytes especially, that can contribute to the brain fog or the keto flu in the beginning. Suppressing the hormone insulin has a natriuretic effect and also a diuretic effect. So you'll excrete more sodium, and then if you're not hydrating and getting in extra electrolytes, then you're going to be hyponatremic, and you could have things like orthostatic hypotension if you stand up. That's quite common, especially if you're on blood pressure medication probably. And there's good literature to support dietary therapies can help lower blood pressure, but low-carb ketogenic diets lower blood pressure more than any other type of diet. That's important because you could have side effects if you are on blood pressure-lowering medication. So you need to adjust the medication. That's going to be important. But in regards to pushback, I think the biggest pushback comes from cardiologists and from advocates of plant-based diets or lower-fat diets, in that the fat could be atherogenic, especially if it's saturated fat, the elevation of LDL and ApoB. Even in the context of improving other biomarkers like triglycerides, hemoglobin A1C, insulin levels go down. I would say in about maybe a third of the people who follow a strict ketogenic diet and lose weight and sustain it, they may have an—well, if you start off with your LDL very high and you go on a ketogenic diet, it tends to come down. However, if you're healthy and lean and follow a ketogenic diet and become fat-adapted, what we typically see in some people could fit what's called the lean mass hyperresponder phenotype, where you have low triglycerides under 60, high HDL over 60, but then your LDL is like above 190 or above 200. So I actually fit into that category. So this is the large majority of the medical establishment, and especially cardiologists, are going to have a knee-jerk reaction and say this diet's going to kill you. You know, you should get off this diet and alter the diet. But a lot of people who follow a ketogenic diet get so many great benefits from it, they don't want to get off of it. So you have two options. You can lower the saturated fat and see what that does, and just include monounsaturated, polyunsaturated fat. Or you could take a lipid-lowering medication. That could be ezetimibe. That could be a PCSK9 inhibitor or a statin. The last one I think has too many side effects to consider unless you have a high atherogenic risk, or unless you've had a heart attack, unless you have, you know, high heart disease in the family. So that's probably the biggest pushback. And a lot of people just—some people just can't tolerate the level of fat needed to be on a ketogenic diet. So what I have done over the years is I've gravitated more towards a low-carb Mediterranean diet, a type of diet that puts me in a very mild state of ketosis, but then I'll put like MCT oil, MCT powder, and I'll use a ketone electrolyte product maybe once or twice a day, and I'm always running about 1 to 1.5 millimolar ketones. And I think a lot of the benefits you get from being in ketosis, you could achieve that. Or alternatively, certain days I'll do intermittent fasting, but intermittent fasting caused me to lose lean body mass over time and strength because it was hard for me to get the amount of calories that I needed if I did intermittent fasting every day. So it becomes like I pull the trigger on intermittent fasting if I need to be my best and I need to—like, you know, if I have a big talk coming up or I need to—if I'm writing a grant or a paper, I'll not eat breakfast in the morning, and then I'll do that maybe like twice a week. And I have to admit, they're the two days that I feel the best. So I'd like to do it all the time, but at the same time, if I intermittent fast and I just have a meal at the end of the day, I tend to overeat and I just get the munchies at night. So I did intermittent fasting for many years, and I still use it. I think it's an amazing tool, but I don't want to lose any more weight now, especially as I'm, you know, approaching 50 years old. And I look at my DEXA scans over the years. I could see, you know, since I was—I don't know, 10 years ago, I lost 18 pounds of lean body mass. And I'm still training. I don't train like I did before, but that's a little bit alarming. And I want to stabilize and slow things down. So, and I think intermittent fasting, it was really hard for me to maintain a certain level of muscle and strength. Not that I'm trying to, you know, be really big like a bodybuilder or a powerlifter or something like that. But I do feel it's important as we age to prioritize that lean body mass and strength as we age.
Yeah, absolutely. Just one point. I love my vegan audience and I love my carnivore audience. And just to be clear, you can be on a ketogenic diet with plant-based fats as well as animal-based fats. It's, you know, maybe more challenging on a plant-based, but you can find them if you're willing to do it. And absolutely. Now, one of the great things about social media is you reach out, you meet all these different people. I have a friend I met who's an Inuit in Alaska, and his grandmother—he has pictures of it. She literally—they lived in an igloo, and they were very far north, and he has all these pictures of them. And he said they were in ice for like nine months of the year, and they basically were on a carnivore diet most of the time. And even the rest of the year, it was before, you know, civilization really came to them. So they were on a carnivore diet most of the time. Are people on a carnivore diet—I mean, excluding honey and, you know, if you don't eat those sweet things—are people on a carnivore diet in ketosis?
Yeah, there's a couple groups that advocate for a pure animal-based carnivore diet or a ketogenic carnivore diet. So Paleo Medicina comes to mind. They're in Budapest, Hungary. I actually visited their clinic, and they pulled out a lot of records, including people with cancer, with type 1 diabetes, type 2 diabetes, and showed me a lot, and they published a number of publications too. So I think that is—I mean, an animal-based ketogenic diet will give you all the micronutrients that you need. You're not going to be—I mean, even vitamin C you get from meat, and there are—you're not going to be deficient in anything, and the blood work looks pretty good. On the other hand, I am of the opinion—I follow more of an omnivore-based ketogenic diet. Although I will say the last three or four days I completely ran out of vegetables. I just didn't have time to shop. So I was eating steak, eggs, pork, fish with no vegetables. Actually had a little bit of blueberries at nighttime, but basically almost pure carnivore aside from like a quarter cup of blueberries. And I felt great, you know, but I feel better if I—and my go-to vegetable would be broccoli florets, you know, and I cut it up also to give it to my dogs. But they're basically—it probably makes up 5% of the calories for me. It makes up—carbs may make up 5, maybe 10% of the calories, but probably 5, just because I pick high-fiber carbohydrates. I pick wild blueberries, broccoli, a little bit of like pistachios, maybe macadamia nuts, maybe some walnuts here and there, and salads here and there. But basically it's like eggs, steak, and a lot of fish. Over the last couple years, I've gravitated—a lot of beef. But also I eat mackerel, sardines, and tuna fish, and salmon too, probably makes up almost half of my protein from fish sources. And then shrimp, and then oysters and clams and, you know, things like that as well, but not as much.
