Dom D'Agostino -- how ketosis can maximize fat loss, increase athletic performance, and optimize longevity.
Dom D'Agostino -- how ketosis can maximize fat loss, increase athletic performance, and optimize longevity.
From April through June last year, I did a 2 month long experiment. I ate no more than 30g of carbohydrates each day, while loading up on all the fat I could. I continued my CrossFit workouts and olympic lifting workouts with almost zero glycogen to run off, and consistently hit the wall. So why the heck would I want to do that? The goal was to transition to a ketogenic diet. A ketogenic diet is one that shifts the body’s fuel from carbs to fat. During this process, the body creates molecules called ketone bodies (like beta-hydroxybutyrate) to fuel the muscles and brain for fast fuel. And it turns out that many of today’s top athletes do some variation of a ketogenic diet. And after Dr. Jeff Volek’s FASTER study came out last year, ketogenesis has exploded in popularity among the athletic community. But being in a state of ketosis isn’t just for athletes. It’s been shown to help with weight loss, most metabolic markers, oxygen efficiency, and longevity. And while the ketogenic diet was originally prescribed to epileptic patients in the 1930s, there’s promising evidence to suggest it may be massively useful in the treatment of cancer, most metabolic diseases such as diabetes, and Alzheimer’s prevention. The science around a ketogenic diet is new and exciting, which is why I jumped at the chance to interview Dr. Dominic D’Agostino, a PhD and one of the world’s few expert in subjects. Dominic (Dom) is a recently tenured professor at University of South Florida where he studies the intricacies of the diet, and studies the most cutting edge exogenous ketones. The conversation was awesome as it was nerdy. Please enjoy! Show notes + TL;DR: 3:18 How Dom's PhD in neuroscience and physiology turned into a career in pharmacology, and eventually led to his fascination with dietary and supplemental ketones. Had to understand oxygen toxicity seizures related to Navy SEALS research. 6:10 - What is oxygen toxicity, and how is it affected by ketosis? Oxygen is essential for life, but it metabolizing oxygen naturally makes free radicals, or reactive oxidation species (ROS) like super-oxide anion. Having too much oxygen is called oxygen toxicity and is is toxic for the cells because of the dangerous amounts of free radicals. When you're using too much oxygen, you're naturally going to produce a bunch free radicals. They are powerful signaling molecules that tell your body something's potentially not right with the situation. They also disrupt brain energy metabolism. Ketones preserves the bioenergetic capacity of the brain under either too much or too little oxygen, and cause less free radicals than does glucose. 10:04 Why ketones are a high-octane fuel that burn with greater efficiency than does glucose. Through the use of oxygen, both glucose and ketones are converted into ATP within the mitochondria, which is the energetic currency of the cell. What’s is that, within the heart, ketones create 20-30% more ATP per oxygen molecule than does glucose. This means that during a low oxygen state, like working out, it’s beneficial to be fueled by ketones rather than glucose. Unfortunately no study directly shows this in the brain because the brain is hard to measure, but in vitro studies confirm this is likely. 12:50 How ketone metabolites can prevent cells from injury and programmed cell death. Cells are like little batteries that use charge gradients to convert chemical energy to electric energy. If the membrane potential is messed up, then the it'll create this apoptosis, which is basically like hitting the self-destruct button on a cell. This occurs during low oxygen states, but what’s interesting is that ketones have a neuro-protective effect and can prevent hypoxia and ischemia. 15:22 How ketosis allows endurance athletes to push harder, while also reducing the oxidative stress. Your brain is a moderator of energy output. If you have a steady flow of energy to your brain through ketones, your brain won’t send a signal that you’re under stress, allow you to push through even harder. Ketones function as a signaling molecule. They are histone deacetylase (HDAC) inhibitors. HDAC regulate gene expression, and what ketones do is that are actually have some calorie restriction. This is promising in terms of being a potential anti-cancer compound. The ketone beta-hydroxybutyrate, is also being tested for the prevention alzheimer's, and for the treatment of depression and anxiety. 22:40 How the led by Dr. Jeff Volek turned around what we thought endurance athletes should be eating for performance, and fat loss, and how ketosis plays into this. High carb athletes still burn a lot of fat compared to sedentary people, but compared with fat adapted athletes, it’s not even close. Fat oxidation was 2-3x higher in the fat adapted people, and this happened even at rest. In addition the fat adapted person also benefits in the long run in terms of longevity. This is because ketosis improves mitochondrial function and biogenesis, reduces inflammation, may even impact telomere length, though more research in that domain is required. In fact, this metabolic effects look super similar to the benefits of fasting. 27:51 There is an adaptation period to get into ketosis. How do we switch to oxidizing fat, and what is physiologically going on during this state? Initially: Since you're no longer eating carbs, there's the suppression of the hormone insulin. Less spikes and lower baseline levels forces the body to release fat for fuel. Since carbohydrate stores in liver tend to get depleted, and the brain then gets hungry for fuel. This is why the first few days of adaptation aren’t very fun! Insulin retains sodium so you'll lose a lot of sodium and water, so you’ll need to increase fluids and salts. Short-term adaptation (first couple days) Your liver is going to increase the beta oxidation of fats. More fats you have the more ketones you create (fat —> acetyl-CoA --> acetoacetate --> beta-hydroxybutyrate). Your liver is usually a greedy organ, so if you're starving and you get glucose, your liver holds onto it. But since it can’t use ketones, it pushes them out to the blood. This state is called hyperketonemia, which is managed well by the body. Ketone bodies go throughout the bloodstream, being used by the muscles. They can also pass the blood brain barrier and help preserve brain metabolism. During this process, the liver is upregulating the enzymes to make ketone production faster, and the ketone transporters ( (like monocarboxylic acid) in the brain and muscles increase as well Long-term adaptation (a couple weeks to 6 months) After 2 weeks, you’ll get 30-50% upregulation of the these ketone transporters that shuttle ketones into the brain. 33:28 So does that mean that athletes are faster to adapt to ketosis? Dominic’s observation is that athletes adapt quicker, however, because athletes have so much more need for fuel, they may actually require 4-6 months to fully adapt to a ketogenic diet. 34:45 Can you talk about how carbohydrate needs, and adaptation period, vary between different groups of people? It’s really important for the athlete to train hard in the state of ketosis and fully adapt. They’ll deplete glycogen stores very quickly, but after 1-2 months, they'll end up to fill out again, as their body gets good at replenishing glycogen In fact, within his studies, keto-adapted athletes had the same glycogen as the carb-adapted people. This is because fats are really glycogen sparing. However, because sprint athletes and fast-twitch athletes put higher demands on their anaerobic pathways, they should supplement with creatine monohydrate and BCAAs. 40:46 Is there a minimum level of carbohydrate for required for people? How should people dial up or down their carbs to maintain safe and effective implementation of a ketogenic diet? It depends on the person. Since carbohydrates are anabolic and anti-catabolic, it may make sense for people who are doing fast-twitch exercises like sprints or weightlifting to take 20-30g of pre-and intra-workout carbohydrates. The other key is to train in ketosis and use low glycemic carbs for at least a couple months as you're adapting. But ultimately, it does depend on the person. For instance: People who train really hard may be able to get away with more grams of carbs while staying in a state of ketosis. Big guys with a lot of muscle create a lot of lactate, which then goes to the liver and is recycled back into glucose. This means they may have a harder time getting into ketosis. Also, they especially need to be sure to not have too much protein, which can shut off ketosis. This is why bigger guys may benefit more from the exogenous ketones that are on the market. 48:10 Does supplementing exogenous ketones change a person's ability to create their own endogenous ketones? Not that Dominic has seen. 51:21 With ketosis, many people make a distinction between medium chain triglycerides (MCTs) and long chain triglycerides (LCTs). What's the difference, and are there benefits to each? Long chain fats are packaged into chylomicrons and shuttled throughout the lymph system to provide long-term, sustained energy for the heart and muscles, before they end up within the liver. It's just a controlled, slow delivery system, and there is nothing wrong with this. Since MCTs are not packaged into these chylomicrons, and are shuttled straight to the liver, which “overloads” the liver with more than it needs, and then creates ketones. MCTs don't require as much emulsification as LCTs, and are obligate beta-oxidators, meaning they are almost completely gone down the acetyl-CoA pathway to get created into ketones. 55:22 Why L-carnitine amino acid is gets depleted with most ketogenic diets, and how it should be supplemented to avoid deficiency. 56:00 New unpublished data: the liver can store fat like it can store glycogen, in a healthy way. 1:00:52 What is the impact of a ketogenic diet on the gut microbiome? Ketogenic diet varies a ton between people. Diversity of the gut microbiome is dependent on the diversity of the diet. Total mass may decrease. 1:03:44 What effect does fiber have on ketogenesis? Fibers can actually can have a ketogenic effect, but because peoples’ gut microbiomes are different, and the fibers they report are different, we don't yet know what “optimal” fiber intake looks like. 1:06:23 How should women do ketosis differently or safely? What are the differences? Women should not over-exercise and certainly don't under-eat, as well as add liberal amounts of salt and fluids. Add 10-20% of the calories to really make sure to really force your bodies into metabolizing fat. 1:08:11 Should we be adding potassium or magnesium to the diet? Adding potassium is unnecessary as long as you eat the occassional avocado and salads. However, potassium salt may be a good idea, and Dom would always recommend a good magnesium supplement: citrate or glycinate before bed. 1:09:40 What are the go-to snacks to make the ketogenic diet easy? Macadamia nuts, coconut cream, dark chocolate and 1/4 to 1/3 cup blueberries plus cinnamon whipped together to make a great “keto pudding”. Organic sour cream and Wild Planet sardines are staples of his at Whole Foods. Resources Food/Supplements packed in olive oil. Exogenous ketones MCT oil ketones BCAAs Creatine monohydrate Magnesium citrate or glycinate Books Jeff Volek & Stephen Phinney , by Tom Seyfried. Find out more about Dominic on his blogs: