Introduction to Andrew Koutnik
Dr. Eric Westman: It’s my great pleasure to have Dr. Andrew Koutnik with me today.
Andrew Koutnik: It’s great to be here, and it’s an honor to get to speak with you today.
Who Andrew Koutnik is, where he is from, his diagnosis and how he got into the keto world
Dr. Eric Westman: You’re in the midst of learning what ketones are, and what ketones do, and I just tell people to stop eating carbs and enjoy the wonders of ketones. So it’s my great pleasure to have you here. Who are you? Where are you from? How’d you get into this world? And, what’s on your mind lately?
Andrew Koutnik: I’m a research scientist studying the impact of lifestyle, with a strong focus on nutrition, on diabetes or those at risk for diabetes. We have a health and performance-based mindset, trying to understand and uncover how these nutritional strategies work, and then how the unique effects they have on metabolism and the metabolites themselves can actually translate to meaningful, actionable change in patients. That’s where I’m at right now.
I started my journey on a personal level with obesity. I had obesity during adolescence as a kid and appreciated the struggles and difficulties that come along with being in the current food environment and Western culture’s impact on the risk for obesity. After years and years of failing, I know you’ve helped many people on their journey to weight loss, I was finally successful. I didn’t do anything particularly novel, I just had some accountability. It was very hard, not easy. I probably could have done it a better way with the knowledge I have today, but I eventually did lose the weight.
Amazingly, a year later, I was diagnosed with type 1 diabetes. That diagnosis was revolutionary for me, not only in my personal life but also in my career. It completely changed my interest in how food and lifestyle interacted with my body composition. Now, every single meal had a direct impact on not only glucose levels and insulin but also how I felt in a very short period after eating. I started drawing associations between glucose, insulin, and these other components of lifestyle. That really changed my entire path in life, leading me to research.
Not just because I always found science fascinating, getting real answers to questions was such an intellectually stimulating path, but what fascinated me most was the translation of that knowledge to real, meaningful outcomes. I had lived the experience myself and knew how powerful things like nutrition and exercise could be for how you feel. That level of awareness, especially with type 1 diabetes, was hard to compare to anything else in my life.
Dr. Eric Westman: How old were you when you had the diagnosis?
Andrew Koutnik: I wasn’t officially diagnosed, but when I was a little after 12 years, I was coming up on overweight and obesity. I was officially obese in late adolescence, and then my type 1 diabetes diagnosis came when I was 16, going on 17 years, back in June 2006. It’s been almost 17 years now, creeping up around those numbers. I almost forget at this stage.
Diagnosed with type 1 diabetes
Dr. Eric Westman: I’m sure you remember it well. How did you know something was wrong? How did you get diagnosed with type 1?
Andrew Koutnik: I was on a family trip. We were on our way to Washington, D.C., and I was in high school at the time. I had just finished my second-to-last year before heading off to college, or at least, maybe going to college. I didn’t know at that stage what I was going to do. We were in the summer between school periods, and we went on a trip to Washington, D.C., to see what I was learning about in school. I had become very fascinated with learning and education at that stage, which was a major pivot for me.
Right before we got on the flight, I felt my stomach start to hurt, and I got nauseous. I made the mistake of thinking, “Bread and sugary drinks are going to help make my stomach feel better”, you know, the old wives’ tale. Unfortunately, I didn’t realize that my body was quickly losing the ability to actually metabolize glucose and carbohydrates. I was rapidly consuming them, thinking I was going to help my situation, but I didn’t know. I was unaware of the internal devastation and the attack on my cells that was taking place in my body.
It was about 24 hours later, when we got to DC, and we started walking around. In DC, there are a lot of opportunities to walk around and see different sites, and I never felt more exhausted in my entire life. I didn’t realize that it was because I was not able to actually take any of the food I was consuming and convert it into energy due to the complete or near absence of insulin in my body. I felt horrible. That night, I drank 14 to 16 typical glasses of water, 16 ounces, I forget the exact amount, but I was drinking them one after the other and urinating at excessive levels. Obviously, I wasn’t feeling good. I was very fatigued.
The next night, we did the same thing, but they brought out pitchers, like the actual pitcher they pour at each table. I drank two and a half of those, and that night I threw up for 14 hours straight and ended up in the hospital. My mouth felt like cardboard because I’d been throwing up for so long. I’ve never been so dehydrated in my entire life. Luckily, we were thinking, “Okay, this is super sick,” but it got to dangerous levels of dehydration. I wasn’t able to consume anything for hours, almost over half a day at this point, and was vomiting up everything in me.
My mom called my grandmother, who was a nurse at the time, and she said, “You need to take him to the hospital right now.” We went to the hospital, and my blood sugar, for those in the audience who are probably very familiar, as part of the community, are likely to get this, but normal blood sugar is 70 to 120 mg/dL. Whatever is optimal within that is up for debate, but that’s what’s medically defined as normal. For those outside the United States, that’s around 4.5 to 6.67 mmol/L.
I was 596 (mg/dL), about six times higher than normal. They walked into the room and said, “Andrew, you have type 1 diabetes, and you’re going to have it for the rest of your life.” I had no idea what this meant. I just wanted to get out of the hospital. Over the next two weeks, they rapidly took me into a complete, face-first plunge into understanding that everything I eat, for the rest of my life, I would now be the master dictator of my metabolism. I would now control everything I was consuming. I would need to know everything about it, and not only that, I would have to understand how much insulin I would need to give to control my blood sugar levels.
I wasn’t completely educated on this at the time, but what I soon found out was that they tell you to keep your blood sugar levels as controlled as possible. As a researcher who has studied for years the impact of type 1 diabetes and the impact nutrition and other lifestyle factors can have on it, glucose levels are the key risk factor not only for how you feel today but also for the long-term complications associated with the disease if you’re not able to control it. Unfortunately, the vast majority of people are not able to control it. 99% of people with my disease don’t have what’s termed “normal metabolic glycemic control,” so they live their entire lives outside of normal, and it has pretty significant implications.
Ultimately, that is why I went on the path I have, from studying the body’s response to exercise and nutrition, to actually looking at it in petri dishes and model systems that replicate human responses. You can use these more novel, innovative strategies, and ultimately apply the tools we’ve studied early on, translating and understanding how they work in humans. That’s what we’ve been doing for almost a decade now, and that’s ultimately what led me here.
Carb counting
Dr. Eric Westman: Did you run across Dr. Bernstein’s work?
Andrew Koutnik: What’s interesting is that I did not come across Dr. Bernstein until about halfway through grad school. But the irony here is that I had actually come across something very similar to the Bernstein protocol inadvertently and had done it a few years after my diagnosis.
When I was diagnosed with type 1 diabetes, and it still is the case, they often tell you not to eat processed foods, to eat whole food-based foods. You do these things called carb counting, where you count the amount of carbs you consume and give a proportional amount of insulin with it. We know that strategy does not work. The evidence says, based on meta-analysis, that carb counting does nothing for glycemic control or does not help you improve glycemic control. But at the time, and still today, this is like the gold standard strategy for managing this disease.
Ultimately, it is not up for debate that when you consume carbohydrates, they raise your blood sugar, and you will need insulin to bring it into a normal range. However, I had found some time ago that I had come across something called the Atkins diet. I went from being this obese adolescent child to then wanting to be the opposite of that, as big, strong, and fast as I possibly could. After being diagnosed with type 1 diabetes, I became so interested in how everything I consumed was affecting my body. I tracked my macronutrients, progress in the gym, weight, body composition, and all these things over time.
For about five years, I was doing what is typically the gold standard approach to bodybuilding, which is these high-protein, whole-food-based strategies. I was very hyper-focused so I was able to achieve relatively good results, in the sixes (6.0 HbA1c), which is not normal by any means.
The meaning of A1C
Dr. Eric Westman: A1C
Andrew Koutnik: Yes. For your audience members who may be unfamiliar with A1C, it averages your blood sugar over a two-to-three-month period, which is usually able to reflect or associate with certain average glucose levels. The more glucose you have in circulation, the more it sticks to hemoglobin cells, and the higher your blood sugar is. I was regularly in the low 6’s, which most endocrinologists today would even say is amazing, but it wasn’t normal.
I had heard of the Atkins diet because it was hyped for its ability, at the time, I didn’t know, I was ignorant of the ability to eat this way, hold muscle, and lose fat. I thought, “Well, that sounds great if I’m trying to change my physique and improve my performance.” So, I shifted.
Interestingly, at the time I had got hold of a professional athlete who I knew had type 1 diabetes. I found their email and reached out to them. They got back to me and actually got on the phone with me. This person also happened to be a registered dietitian in their previous background.
I said, “Look, I have type 1 diabetes, and I’m really interested in improving performance, how I feel, and all these other things.” It had nothing to do with glycemic control at the time because that’s not the hyperfocus when you go to the doctor. The philosophy is often, “Live your life and don’t let diabetes affect your life,” which is understandable to a degree, but it also fails to inform the patient that they need to be making decisions that will affect how they feel and will affect their life.
At that time, my locus of control was very internal, and I wanted to figure out what I could do to improve myself. Over time, after they called me, I started communicating with them and actually worked with them. They helped. I said, “I want to try this Atkins diet. I heard it could really help me.” They replied, “I’m not going to tell you what to do, but if you want to try it, here’s how you do it.”
They knew about regular insulin, and the different strategies with food, and gave me a master rapid course on how to do it. I had never heard of Dr. Bernstein. For your audience who may not be aware, Dr. Bernstein is a legendary figure in the type 1 diabetes community for writing essentially the handbook and guidebook on how to regulate glycemic control on insulin with a very low-carbohydrate approach, which some people used to call the Atkins approach or ketogenic diet. All these names have been used over the years for that approach.
Ultimately, I use the word Atkins because that’s how I got introduced to it.
Three months later, following this individual’s guidance, similar to the Bernstein approach, I had personalized my treatment, almost like a titration process they were assisting me with. When I visited my doctor after those three months, who also happened to be the American Diabetes Association president at the time, I never knew. I go in, and I get my A1C values back, and he just looks at me and says, “What are you doing?” I ask, “What do you mean?” He responds, “This is the best HbA1C I’ve ever seen in my office.”
I was so empowered at that moment. I said, “Guess what? Here’s what I’m doing!” I was all jazzed because what I also found was, it wasn’t just that one metric. I actually started feeling better. I wasn’t as likely to go outside of feeling normal. I felt very stable. I would check my blood sugar because I didn’t have a CGM (continuous glucose monitor) at the time. This was outside of having any CGM, just a finger stick. I would find that when I checked my blood sugar with a finger stick, I wasn’t in the high 100s or 200s, or going low all the time. I was consistently finding numbers in this range, and I started to feel better.
Ironically, I also started performing better in the gym, too. At the time, I was probably not eating a diet as rich in essential fatty acids as I should have, but once I switched, my strength went through the roof, and I looked leaner. This was all great for me. I was in my late teens or early twenties, thinking, “This is all good stuff for me!” Without any intent of improving my glycemic control, it just so happened that I walked in and my glycemic control was the best it had ever been in my entire life.
That’s when it clicked for me. I thought, “Here’s something special about this.” It was fascinating how nutrition was able to completely revolutionize my meal-by-meal experience, and my day-to-day experience, and ultimately change the course of my disease management and my career path in life. I haven’t looked back since.
Ketosis
Dr. Eric Westman: Are you in ketosis too when you eat this way?
Andrew Koutnik: I recently did a case report, published in the American Journal of Physiology and Journal of Clinical Endocrinology & Metabolism, actually looking at myself – the first-ever longitudinal report over 10 years.
Dr. Eric Westman: with Watts, et al.
Andrew Koutnik: Yes, Joe Watts was a friend of mine at Florida State University. That’s where I did my undergraduate studies and researched the impact of things like cardiovascular health and mental health at the time. Originally, my research focused on the cardiovascular implications of mental health status. Later, I went on to study nutrition, and all this came together for me, ultimately focusing on disease, specifically diabetes.
With Watts et al., we decided to do a follow-up report. I had been on this diet for 10 years, and I had Dexa scans from Florida State. I had blood work from back then, and I knew exactly what I was eating because I tracked everything, including insulin and food. I knew my exercise routine and essentially had all the data from over the years. I suggested we do a follow-up report, given all the controversy surrounding this diet in the context of type 1 diabetes.
There’s been all this concern about high lipids, cardiovascular risk, and hypoglycemia if you don’t eat carbs. There are also concerns about ketoacidosis (DKA) risk with a ketogenic diet. We conducted a medical health history review, pulling up medical records. We did pre- and post-Dexa scans, checked lipid values, tracked HbA1C levels throughout, and, because CGMs weren’t available at the time, conducted a 60-day CGM assessment at the end. We did advanced lipid tests and looked for early signs of adverse risks that were hypothesized not just in the context of ketogenic diets and type 1 diabetes, but also in the general population.
There had been concerns about bone mineral density potentially decreasing on one of these diets, and so on.
Atherosclerotic risk
Dr. Eric Westman: Did you get the arteries checked? The carotid?
Andrew Koutnik: Yes, I sent in a prescription.
Here’s what happened. Over that period, I controlled my calories and kept my body weight within plus or minus 5% the entire decade. I adhered to a ketogenic diet and had confirmed elevated ketone bodies. I knew I had almost complete control over that period – levels of control that are rarely seen in reports like this. I had Dexa scans to confirm this, including bone mineral density and body composition assessments, both pre and post, and they were nearly identical.
We wanted to do an advanced assessment of future atherosclerotic risk and present atherosclerotic risk. This was important because not only did we want to assess safety and efficacy, but we also wanted to see if there were early signs of deterioration in cardiovascular health, something people often hypothesize would happen.
Dr. Eric Westman: In my clinic, and for those who’ve listened to me on the channel, I go directly to measuring the arteries because relying solely on blood tests for prediction isn’t good enough. Have you had the arteries checked?
Andrew Koutnik: Yes, I’ve had a CT angiogram and a calcium scan. However, we didn’t include this in the report.
Dr. Eric Westman: I didn’t see it in the report; that’s why I asked.
Andrew Koutnik: I wish we had added it. It’s actually on my desk right now.
Dr. Eric Westman: How about an addendum for it?
Andrew Koutnik: That is a good idea. It’s highly relevant. I recently had the angiogram and calcium score done, and my total score was zero. That’s a major win.
As your audience will appreciate the calcium score is the gold standard for assessing the progression of atherosclerotic disease. We didn’t initially anticipate this result. What we thought was that within the context of type 1 diabetes, we might see changes in how the vasculature responds to stress. This would be an early sign of future atherosclerosis progression.
We focused on things like arterial stiffness and compliance. Some might debate this approach, but the weight of the evidence consistently shows that, in type 1 diabetes, vascular stress responses deteriorate even in children within four years. Arterial stiffness increases, which is what we monitored. Later, after the report was released, I did the calcium scan, and it came back as zero, which is highly relevant.
What ketones do for health
Dr. Eric Westman: You always have to study the context. In the MESA study (Multi-Ethnic Study of Atherosclerosis), for example, if you’re a carb eater and your calcium score is zero, the likelihood of a heart attack over the next 10 years is almost zero. However, we hypothesize that by not being a carb eater, we might do even better.
This reminds me of 20 years ago when I had a visiting student who was a patient of Dr. Bernstein. I watched his LDL levels rise really high, and I didn’t know what to do at the time. I told him I wasn’t sure he should be following that regimen. In my first study, a randomized trial, we dropped someone because their LDL went up so high. But now, 20 years later, we’re following a group of people with high LDLs who aren’t eating carbs, and it seems they don’t develop the vascular disease that one would predict from LDL elevation.
It’s like if an alien came to Earth, and there was just one alien, we’d study it up and down instead of dismissing it as anecdotal. I came across that paper in August of this year, and I wanted to talk about it.
What I want to dive into now is what ketones do for health. Based on your experience with these papers, whether for exercise, cancer, or supplementation, what practical takeaways have you learned? My patients often ask, “Should I get that ketone gummy, pills, or the drinks?” From your perspective right now, what have you learned about ketones and just any actionable things that we could learn from that?
Andrew Koutnik: We’ve been studying the application of either nutritionally induced ketones through a diet or through these tools called exogenous ketone bodies. There are several ways to increase ketone bodies, but those are the two most reliable methods. I worked in a lab with a gentleman I’m sure most of your audience is familiar with, named Dominic D’Agostino, where we were actually in the process of trying to develop novel, new formulations of these ketone bodies and ultimately look at the signaling ramifications of their application in various settings, both in disease and non-disease contexts.
A lot of the work in our lab originally started because there was an interest in the application of exogenous ketone bodies or the ketogenic diet and its ability to potentially alter the progression of cancer. We used this very aggressive metastatic cancer model from something called a glioblastoma multiforme, which is one of the most aggressive forms of cancer that we know of. We looked at metastatic progression, so the model not only had this aggressive form of cancer but also rapidly metastasized.
During grad school, one thing I assessed was this form of cancer and the application of exogenous ketones throughout the post-administration of the cancer, once we knew it was present, and the ramifications on various tissues. We know some of the consequences that come with cancer are loss of muscle mass and other factors. The short cliff notes version of this for your audience is that we found these exogenous ketones not only statistically reduced the cancer burden in these animals but also attenuated the loss of muscle mass in the animals. We wrote multiple papers on this, and after this report, we’ve actually seen human clinical physiology studies where they have taken individuals into a clinic, induced these rapid forms of muscle wasting using things like endotoxin, sleep deprivation, or caloric deprivation, and then infused ketone bodies. They found that you’re able to preserve muscle mass turnover.
This work has since matured into clinical studies, but these are some of the things we focused on originally. Since that work, the interest has blown up for several reasons in all these other domains, whether it be performance, both physical and cognitive, neurological disorders, metabolic health, and diabetes. The reason this has happened is because, as this research was coming together, not just the formulation of exogenous ketone bodies, but also considering things like medium-chain triglycerides as exogenous ketones. They’ve been clinically administered since the 1950s for children with malabsorption disorders, and they worked, they were effective in helping these children over half a century ago.
If you think about the more novel formulations, the reason people are now interested is because there are all these well-done signaling and mechanistic studies that have shown the ability for ketone bodies to attenuate inflammation and oxidative stress by actually changing your epigenetic methylation components. Ketones have all these unique effects, not only metabolically but also through their signaling effects, which are often described as positive. For example, reducing inflammation is often seen as positive in most contexts, as is reducing oxidative stress.
Now, they’ve been administered in randomized control trials over some time to potentially improve early cognitive decline or other settings. One thing that we’ve studied over the years is their application not only in disease model systems, like cancer and muscle wasting but also in seizure contexts. We found that ketones were able to attenuate seizures as well. I was leading a study that looked at this. The ability for ketone bodies, and this was just published two weeks ago, in military personnel is fascinating for their ability to actually alter brain energy metabolism and attenuate the drop in cognitive performance that we see when oxygen availability is reduced.
For those in the audience thinking, “What is he talking about?”, imagine you go up to altitude and experience reduced oxygen, which is something called hypoxia. We know hypoxia reliably reduces cognition. What we wanted to understand in the military context is whether you could take military personnel, reduce the oxygen available to them (equivalent to going to the tip of Mount Kilimanjaro), and see what happens when you do that, both at rest and during exercise.
What was fascinating, and this was just published two weeks ago, is that we’re starting to appreciate that these molecules (ketones) aren’t just metabolites used for energy. We know they have signaling properties and can change whole-system physiology. In this study, we administered ketones, exposed individuals to normal oxygen levels, and then dramatically reduced the available oxygen to simulate super high altitudes, peaking at some of the highest mountains in the world, thus inducing hypoxia. What we found is that individuals were able to retain higher levels of cognitive performance while on these ketone molecules when exposed to oxygen deprivation. Normally, oxygen deprivation reduces the body’s ability to have ATP turnover, but here we were able to improve cognition.
What was also fascinating was that it also increased SpO2 (blood oxygen saturation), which was not expected to happen. We had this very neuro-focused approach, and we’ve known that ketones may change neurological energy metabolism since George Cahill’s work in the 1960s. Here we are, over half a century later, exploring the broader impacts.
Explaining Sp02
Dr. Eric Westman: Explain what this means in layman’s terms:
Andrew Koutnik: Back in the 1960s, a group led by George Cahill and Owen et al. discovered that during chronic fasting, you are able to supplement the brain’s energy needs without being completely dependent on glucose. They discovered that the brain could use ketone bodies as fuel.
Subsequent studies revealed that even in the complete absence of nutrients, individuals remained coherent and cognitively intact. They also discovered that if you induced hypoglycemia in these individuals, they still retained cognitive capacity. This demonstrated that glucose is not the only fuel for the brain, and ketones can also be a fuel source.
Over the last few decades, further studies have shown that ketones might be a more efficient fuel and that the brain may take up ketones in a dose-dependent manner: the more ketones available, the more the brain might use them. When administering these molecules before inducing energetic deficits by lowering available oxygen (through hypoxia), we found that ketone bodies not only retained cognition at a higher level but also appeared to increase the amount of oxygen the body was able to take in. This was completely unexpected and has since been replicated.
There was a recent paper published just this week, after our work, showing that you could actually attenuate acute mountain sickness using ketones. So, someone might ask, “What does this have to do with me? Maybe I’m dealing with obesity or type 2 diabetes, or I’m just trying to feel better and adapt my life.”
This is relevant because what it’s saying is that these molecules have profound effects on physiology that might improve not only your cognition and supplement your brain’s need for glucose but also have very potent and rapid impacts on physiology that translate outside of just cognition, potentially affecting performance as well.
Administering ketones in a medical procedure or intervention
Dr. Eric Westman: The brainstorming I’ve heard people do, actually started when I first heard Richard Veech years ago at the first ketone or low-carb/keto meeting. He got up and said, in front of the audience, “When I have my heart attack, if I have one, I want to be infused with ketones.” I thought, “This guy is nuts!” The idea has since gained traction, with other doctors suggesting that when you have a heart attack, you should take an aspirin and try to reduce platelet aggregation and clotting. But to give a ketone when someone has a threatened stroke, heart attack, or traumatic brain injury? I’ve heard people suggest that you could be on a football field, someone gets a concussion, and you give them ketones. In these conditions, you’re running low on oxygen and fuel. If ketones could enhance that, what’s the state-of-the-art on administering ketones under circumstances like a medical procedure or intervention? Is there anything in that?
Andrew Koutnik: That’s a great question. It’s interesting you mention that because I was actually working on a project in that domain. About three years ago, we were just starting to appreciate, through the work of people like Steven Cunnane, who took the work of George Cahill to a whole new level. Cunnane was infusing ketone bodies and actually tracking their metabolism in the brain. He discovered that glucose usage in the brain appears to depend on energy needs, but the amount of ketones available seems to be used in a dose-dependent manner. Essentially, the brain can use as many ketones as are available.
Subsequently, he and others have shown that not only a ketogenic diet but also exogenous ketone bodies could help with age-related cognitive decline and Alzheimer’s-like conditions. But what about other domains, like concussions, traumatic brain injury, or when there’s an insult to the brain, such as a stroke?
I studied stroke over 10 years ago, looking at the ramifications of things that could improve the vasculature in patients who already had a stroke. This is a very interesting area because, in the context of concussions and traumatic brain injury, almost all the work up until three years ago was in animals. That research showed tremendous benefits of ketone bodies or a ketogenic diet – some way of inducing ketosis, on various forms of neurological injury. Stroke, whether hemorrhagic or ischemic, could also be included in that category.
All the animal data was remarkably positive. It showed the ability to resolve the insult to the brain more quickly, reduce inflammation, and ultimately recover more rapidly. But at that stage, there was almost nothing in the context of humans. The human work had really underdosed individuals; they were giving things like MCTs (medium-chain triglycerides) at doses that would not be considered meaningful. So, we had very little evidence.
I was initially involved in a study trying to understand how ketones could be applied in the context of traumatic brain injury, although I wasn’t part of its final completion. Much of that work was focused on the acute application of ketones. What we don’t yet know is the truth of if and when we should apply them in these contexts. All the data to date suggests that, if you had to choose, and I’ll use my own example: If I were diagnosed with a concussion or traumatic brain injury, the data tells me today that I would want to apply ketones rapidly. This could help reduce inflammation, and oxidative stress, and supplement brain energy needs, as glucose metabolism is acutely dysregulated in neurological assaults.
What that means for the average audience or lay person unfamiliar with medical terminology is that your ability to metabolize glucose (the primary fuel on a standard high-carb diet) is dramatically impaired in inflammatory conditions in the brain, such as concussion, traumatic brain injury, or stroke. Supplementing with ketones, which may be more efficient and don’t appear to be impaired by these inflammatory conditions, could be very beneficial. Most evidence suggests that in age-related conditions with chronic inflammation, applying ketone bodies leads to efficient metabolism, unaffected by these issues.
Right now, I feel confident saying that, in the absence of stronger evidence, the weight of the evidence we do have suggests that ketones would be an incredibly powerful tool to apply in these domains. We don’t yet have the evidence from randomized control trials to definitively say, “We know it is effective in this domain.” We don’t have that yet. However, we do have a lot of encouraging evidence that suggests if you had to make a choice, I would personally choose to apply ketones. But it’s up to each individual to figure that out, and we’ll see what the evidence eventually shows.
Exercise – fat, ketones and glucose
Dr. Eric Westman: It sounds like Dr. Veech still could be exonerated at some point. He said, “Infuse me with ketones!”
Switching gears again, you’re involved in so many interesting areas. It’s great! Let’s talk about exercise.
We were always taught, and I believe textbooks still say, that when you reach a certain level of anaerobic activity, like sprinting, your body has to use glucose. I remember Professor Tim Noakes, relatively recently, although it’s probably some years ago now, who’s known for teaching people how to run marathons through his book, The Lore of Running, from Cape Town, South Africa, and is now a major editor on ketogenic research. He and Jeff Volek, doing work with exercise, began saying that the body might be able to sprint and use fatty acids or ketones when it was previously thought it couldn’t.
What’s the latest on the idea that your muscles can use fat, ketones, and glucose? What’s the current thinking there?
Andrew Koutnik: It’s important to always provide some context. What we’ve discovered really upends prior assumptions. In the field of exercise physiology, we used to believe that as exercise intensity increased, you would shift your energetic needs from very low carbohydrate needs at low intensities, with high-fat use, to a point where you’d hit what’s called the “crossover effect.” At this point, the ability to utilize fat rapidly diminishes, and carbohydrate usage rapidly increases as exercise intensity rises.
The traditional thinking was that during high-intensity exercise, like sprints, oxygen availability decreases. Since fat metabolism requires oxygen, it was believed that glucose became the essential fuel, as it could be metabolized into lactate even in the absence of oxygen (anaerobic conditions).
We challenged that assumption. It had always been thought that sprinting or short-duration high-intensity efforts required carbs as the essential fuel, and this idea goes back decades. However, the studies that had been done to support this conclusion had focused on periods of less than four weeks on a low-carb or ketogenic diet. This was important because performance does initially drop off when you begin these types of diets, as the body adapts to new dietary and energy needs.
The question became: what happens after four weeks? There was a hypothesis that after four weeks, the body might “flip the switch,” so to speak. We know that certain metabolic changes occur almost immediately when you reduce carbohydrate intake – insulin drops, glucose levels in the bloodstream decrease, and ketones start to appear as early as the 18-hour mark. The body’s oxidation of fuels also begins to change within the first couple of weeks.
However, the four-week mark was thought to be significant because studies on elite athletes following a ketogenic diet for less than four weeks showed impaired performance. As a result, people believed that carbs were essential for high-level performance. However when we reviewed the evidence on performance and low-carb ketogenic diets, we found that studies lasting four weeks or longer showed that the performance deficits weren’t as clear-cut. In fact, the evidence didn’t fully support the idea that high-carbohydrate diets were necessary for optimal performance.
So, we challenged that assumption. We took high-level athletes, lean athletes running over 50 kilometers per week, many of whom were competing with high VO2 max values in middle age. These were experienced athletes. We wanted to see what happens if the same person, in a randomized control fashion, controls their body composition, calories, and physical activity for the whole duration. We had them go on a high-carb diet for four weeks, take a break, and then go on a low-carb ketogenic diet for four weeks. Afterward, they performed highly demanding, short-duration, high-intensity exercises, like running a mile as fast as they could or doing 6 x 800-meter sprints.
Number one, we found no difference in performance for the same person when they adhered to the diet for at least four weeks while controlling all the confounding variables that could interfere with our interpretation of whether the diet was actually causing the effect. We really tried to isolate the question: is the diet causing any negative effect on performance? What we found was that when we controlled these other confounders and did it for four weeks, there was no impairment, even in these high-intensity exercise bouts.
What was also fascinating was that we showed that even at the highest levels of intensity, around 60% of VO2 max, maybe up to 70%, where you’d expect fat oxidation to drop dramatically and carb oxidation to rise, individuals who adhered to the low-carb diet for four weeks and performed these super-high-intensity exercises were oxidizing levels of fat never recorded before, north of 85% of their VO2 max!
What does that mean for the average person listening? It means that not only did a low-carb diet not impair performance, even during very intense exercise, but the way they maintained their performance was by oxidizing fat at intensity levels where we previously thought meaningful fat oxidation wasn’t possible. We actually saw record levels of fat oxidation.
Oftentimes in science, we make assumptions based on prior evidence, because that’s what we do. But here we tested the question directly and found that the assumptions were wrong. You can follow a low-carb, ketogenic diet and still perform comparably during intense exercise bouts.
Another point, which I think is highly relevant to your audience, is that 30% of these middle-aged, super-fit individuals, with high VO2 max, lean body composition, on the high-carb approach showed glycemic values consistent with pre-diabetes. We did not anticipate this. These were healthy, non-diagnosed individuals. But when we put continuous glucose monitors on them, multiple monitors, not just one, we controlled for fasting glucose and conducted analogous testing. This wasn’t just over a short period. We looked at fasting, 24-hour readings over a 31-day average.
This is important because continuous glucose monitors give insights into over 240 full-time points in a single day and tens of thousands over a month. We took the average of these glucose values and found that 30% of those on the high-carb diets had values consistent with pre-diabetes.
However, when these same individuals switched to the low-carb diet, they were able to resolve their pre-diabetic glycemic values. This did two things: it upended the idea that high-carb is essential, even at high intensities, and it also challenged the philosophy that you can get away with anything as long as you’re lean and exercise. What we were seeing was quite the opposite.
Those individuals were developing early signs of what appeared to be adverse metabolic health status through glycemic values when you actually use advanced testing that wouldn’t normally pick it up through one of these single snapshots when they were eating a high-carb diet. What that told us is that, if you had to choose and you could perform the same on either diet, maybe it’s not so much about performance anymore for the average person, for 99% of people out there. Maybe there’s a health-related question for athletes that they have to consider when they make a dietary choice. It’s not just about performance.
Dr. Eric Westman: I think that was Peter Attia’s experience. He was a swimmer, and he developed, in the video that he did at Human and Computer Cognition, which is a great teaching video, I still use it with my students and residents. He was able to swim back and forth in the Maui Channel, but he said his belly looked as big as his wife’s, and his wife was pregnant. That’s a wonderful video to watch. It goes through his understanding of how he got into it and then the biochemistry behind it. Then he ends up saying, “We biked all of the peaks of Colorado,” and here he is at the top holding his bike up high. He felt like he did it with less exertion because of the idea that you’d have more oxygen and all that. He’s evolved in his thinking since then, but it was a brilliant snapshot of his time.
Are you still at the institute?
The Human and Machine Cognition Institute
Andrew Koutnik: Which one?
Dr. Eric Westman: The Human and Machine Cognition?
Andrew Koutnik: I’m a visiting research scientist at the Florida Institute of Human and Machine Cognition. I’m not involved in active projects with them right now, but I do retain a position with them in a visiting capacity.
Dr. Eric Westman: The thought occurred to me. I interviewed Stephen Cunnane recently. Do you know French, or could you learn it really quickly?
Andrew Koutnik: No, I couldn’t learn quickly.
Dr. Eric Westman: Could you learn quickly, and then you could go up and be the professor of ketone therapeutics?
Andrew Koutnik: If I could learn a new language as fast as my wife, it would be no problem, It’d be done instantly!
Dr. Eric Westman: Maybe if it’s a couple. He says he needs someone who is francophone or just a little Duolingo for a while. It’s the only endowed chair I’m aware of that is specific for ketone therapeutics in the world.
Thank you so much for sharing this really important information. For those watching, you’re at a point of watching the science in animals and then humans and ketones and MCTs. It affects every part of the body. The metabolism is so different. I wish you all the best. Thank you for the work that you’re doing. I really appreciate it.
Andrew Koutnik: I appreciate the legacy of the effect you’ve had on the entire field and what you’ve done over time. I encourage everyone to stay tuned. I can promise you some of what we spoke about here today, we have more stuff coming on this front that I think will address everything, each component, both diabetes and performance and beyond. I believe it’s going to be quite revolutionary in how we view not only disease management but also performance applications when it comes to these dietary strategies.
Where to find Andrew Koutnik
Dr. Eric Westman: How do people find you, or where can they get the latest on what you’re doing?
Andrew Koutnik: I have a website, AndrewKoutnik.com. I’m going to keep that updated soon with more information and keep people informed. It’s largely free-based information to help individuals, and I stay active on Twitter and Instagram. I just made a TikTok. I’m @AndrewKoutnik on Twitter (X). I’m AndrewKoutnikPhD on Instagram, and on TikTok, I’m sure if you search Andrew Koutnik, you’ll find me. I don’t actually know my handle. I think it’s the same as my Instagram, but I’m trying to ultimately translate as much of the information we have and study to actually impact people in a positive way. If you stay tuned, you’ll hopefully get a lot of useful information.
Dr. Eric Westman: Thanks for sharing your own personal experience, and goes beyond the normal what I ask folks. I really appreciate that.
You can watch the full video here.
