Healthy choices for healthy living with Dominic D'Agostino (USA)

Mental health is highly correlated to our metabolic health. Constant eating results in what's called energy toxicity. Simple carbohydrate restriction can reverse a lot of problems that people have, and that could be everything from overeating to pre-diabetes.

Thank you for the invitation. I appreciate it. Great to be here.

Yeah, you know, we've worked in a diverse array of fields in my research, mostly neuroscience. I was trained as a neuroscientist with a postdoctoral fellowship to understand extreme environments, and mostly the undersea environment. So in the effort to develop new technologies to understand the undersea environment, I got the opportunity to investigate cells, tissues, animals, and humans, including myself, in extreme environments. So that research has been, you know, a big fulcrum of my career, looking at, you know, how people respond to extreme environments and even how a disease process like cancer can respond to high-pressure oxygen. So in the effort to understand human physiology, we went down many different paths, and one of them was, you know, looking at the undersea warfighter, but also the astronaut, and somewhere in between we started studying cancer as a metabolic disease from some of the observations we made under hyperbaric oxygen conditions.

Yeah, well, I think with the TED Talk, now that was over 10 years ago, but we developed a hyperbaric microscope to understand oxygen toxicity seizures, which is a limitation for hyperbaric oxygen therapy, which has 14 different FDA-approved applications. So in the effort, in the process of doing that, we discovered that we could develop a non-pharmacological anti-seizure approach, which is actually a ketogenic diet, to prevent oxygen toxicity seizures, which manifests as a grand mal seizure, also a tonic-clonic seizure. So in the process of doing research, some of the really key insights that we sort of stumbled upon was that if you give the brain a source of energy that can enhance brain energy metabolism and also reduce oxidative stress, that the brain can continue to function normally under conditions that it would otherwise produce a seizure.

Brain energy metabolism, cognition, and various aspects of neurological function. So we started studying ketogenic diets, and then we developed, tested, and published on exogenous ketone supplementation in the form of ketone esters and also exogenous ketone electrolyte salts and different formulations of such. And we've applied these technologies that we developed into, you know, about a dozen different applications. And that research was funded by the military, but then has gone into a number of other research projects that include, you know, projects funded by industry, by small foundations, by National Institutes of Health. So we have a range of different projects really focused on metabolic health and preserving and enhancing metabolic health, because that's sort of the root cause of the three major diseases that would kill us, that includes cardiovascular disease, of course, cancer, and neurodegenerative diseases like Alzheimer's disease. So we have research projects on all these different things, and I think, you know, the core of what I, with the TEDx Talk, was that we can develop, you know, food-based metabolic therapy and even supplements that sort of mimic our endogenous metabolites, and then we can, you know, sort of have control over our own destiny as it pertains to our metabolic health, which is central to our mental health. Mental health is highly correlated to our metabolic health, so that's another theme that we're working on, and it's an emerging field in the sciences called metabolic psychiatry. And for example, if we go down the other end of the spectrum, ultra-processed food is associated with a wide range of psychiatric disorders, or the overconsumption of that, and that's relatively new science, like in the last 10 years, but it's linked to, you know, the food that we eat dramatically impacts our metabolism and many functions associated with things that maybe we wouldn't otherwise think about, including our mood and our behavior and our overall mental health over time. So that's another theme, you know, that has emerged out of that early research.

Yeah, well, everybody, you know, may do a dietary intervention or change of diet for different reasons. The main thrust of our research started out looking at the clinically accepted application of a ketogenic diet, which was for seizures, and then that expanded into different applications, which are emerging applications. It's not the standard of care per se, but it is a standard of care for some of the things that we study. So if the everyday listener just wants to gain some information about ketogenic diets, our website ketonutrition.org is a, you know, a great website. We have a lot of articles written on there. I always have directed people to the first website that I found on ketogenic diets in 2008 or 2009, the Charlie Foundation, which is an amazing foundation by Jim Abrams and his son Charlie, you know, suffered from drug-resistant epilepsy, and that inspired a movie that Meryl Streep was in called First Do No Harm, which I also watched as I was getting into this area of research, and then later connected with the clinicians at Johns Hopkins and many other clinicians that had ketogenic diet clinics and were treating actual patients. So surprisingly, I went through a nutrition science program in college, and I really wasn't taught about ketogenic therapies for that, or I was basically, you know, ketogenic diets were more or less looked down upon, and we weren't really taught the clinical significance of it because they were mostly marginalized, you know, as kind of an esoteric or kind of fringe dietary therapy to only be used in extreme situations, because ketogenic diets are very difficult to follow. And for a pediatric population, it's relatively easier because, you know, the child will eat whatever the parent makes or what's in the formula bottle, right, for pediatric epilepsy. But for adults, I think the compliance is pretty low with following a ketogenic diet, for example, for adult epilepsy. So a big focus of our research was developing ketogenic technologies that would allow you to consume exogenous ketones, and then these can be used with or without a diet, because there are some situations where people are unwilling or unable to follow a ketogenic diet. And one of the disorders that we study is a fatty acid oxidation disorder, so a ketogenic diet could potentially quickly kill patients who have this, however, because they can't metabolize fat. However, exogenous ketones can reverse the cardiomyopathy and actually keep patients alive. So ketones are kind of water-soluble breakdown products of fat, but these patients, for example, like they can't tolerate a ketogenic diet, but the standard of care is sodium beta-hydroxybutyrate, which is, you know, a ketone body that can be administered orally or IV. So we work with a lot of different, you know, groups that have support rare disorders, and we look at the science and the application of different ketogenic therapies for these things.

Yeah, in studying a ketogenic diet, I was curious about, you know, what it felt like being on a ketogenic diet, and I reached out and bought a book by Dr. Eric Kossoff and the late John Freeman from Johns Hopkins, which was a very calculated ketogenic diet, the 4:1 ratio, and that's a diet that's, you know, very high in fat and with marginal amounts of protein that's adequate and essentially no carbohydrates. And I followed this diet and realized that the ketogenic diet is very hard to follow. So I sort of acknowledged that it would be important to develop ways to make ketogenic diets easier to follow. So that's why, you know, we focused a lot of time and effort into developing a whole portfolio of ketogenic technologies that can mimic and produce therapeutic ketosis. But over time, I kind of shifted to more of a modified ketogenic diet that's more liberal in protein and just have a level of carbohydrate restriction that produces a state of ketosis. So that varies depending upon, you know, your activity level, your individual physiology, that can vary significantly. And it's quite different than, I want to make the statement that this is very, very different than a medical ketogenic diet, which needs like really careful gram-level calculations with an electronic scale and very precise ratios of macronutrients to produce therapeutic ketosis. So it's a very calculated approach than the internet keto or whatever you call it, the non-clinical ketogenic diet. But simple carbohydrate restriction can reverse a lot of problems that people have, and that could be everything from overeating to, you know, pre-diabetes to, you know, just getting their weight under control, giving them more energy. So some level of carbohydrate restriction is probably therapeutic for the large majority of the US population that is over-consuming carbohydrates, especially in the context of a sedentary lifestyle. You know, if you're an athlete and you're very, you know, you're burning a lot of calories, you're probably okay with a high-carb diet. But the large majority of the population are obese, they have type 2 diabetes, and they want to lose some weight, and simple carbohydrate restriction, that's a non-ketogenic diet, is probably all that's needed. But ketogenic therapies are extremely therapeutic in the context of different disorders, and I can kind of go down the list on, you know, the different disorders that are being studied. For example, like on clinicaltrials.gov, for example, there's quite a few.

Well, it depends on why you want to fast, so that's like an important question that people have. So intermittent fasting and fasting in general is a way to produce a caloric deficit, an energy deficit that can put your body into fasting ketosis, and that can be therapeutic for a wide range of, you know, disorders. Eating within, it's all in the scientific community, it's called time-restricted eating or time-restricted feeding, and that could simply mean eating, at the least restrictive, is eating within a 12-hour window. So, you know, waking up at 6 and, you know, eating shortly after, and then stop eating at 6, you know, in the evening, and not... And surprisingly, about 90% or more of the population, you know, will eat within something like an 18 to 20-hour window, so they're essentially eating kind of all the time, and it's not really giving the body, the digestive system, a break. And our body is kind of inundated with having to, you know, enzymatically and mechanically break down food, and constant eating results in what's called like energy toxicity. And a large percent of the population probably have this energy toxicity, and simply doing time-restricted feeding and creating a fasting window of even 12 hours, you know, 14, 16 hours, can improve glycemic control, insulin sensitivity, and inadvertently cause you to eat less food, which can be beneficial overall, can create a caloric deficit that can help you sort of lose and maintain weight. Eating within that, it doesn't work for everybody, but it can be an effective way to eat. And then, you know, some people just like to eat breakfast, right, and maybe have their first meal later in the day. So it's, there's nothing magic to it. You could do it with a standard diet, you could do it with a processed food diet, you could do it with a ketogenic diet, but it's essentially eating within a certain window. And I think many of the benefits of a ketogenic diet can be further augmented by implementing ketogenic therapies with time-restricted feeding. And this is really a good tool for people who have weight to lose. However, if you are underweight, which is sometimes the case with ketogenic diet therapies, for example, in kids or cancer patients trying to maintain their weight due to things like cancer cachexia, age-related sarcopenia, or chemotherapy-induced muscle wasting, so you don't want to further initiate, you know, or augment weight loss. So time-restricted feeding can be contraindicated in those conditions, in that situation. However, in patients that are at higher BMI and have weight to lose, then that's another form of sort of, I like to call it, restriction, another thing that can be added to dietary therapies to help implement healthy weight loss over time. But eating, for example, one meal a day, which some people do, it may be okay for some people, but getting all the nutrition that you need in one meal per day is kind of a common trend. It would be hard to optimize your protein intake and protein metabolism by simply eating one meal a day. And I know that's a trend that a lot of people are doing. You know, super busy days, I may do that, but not every day. And I think some people have gone down that path, and I think what it ultimately results in is a loss of muscle over time, and that could be potentially detrimental to your metabolic health, the muscle loss that's associated with only, you know, eating one meal of protein per day or one meal total.