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Dr. Stephen Phinney on Nutritional Ketosis and Ketogenic Diets (Part 1)

– Hi, I’m Steve Phinney, and I am the chief medical officer of Virta Health. This is going to be the first of four talks I’m gonna be presenting on ketogenic diets and how they are effective and safe in treatment of various conditions. This first talk will be an introduction to nutritional ketosis. What led me to this field to begin with was that I’m a recreational cyclist. I like riding a bicycle long distances. I’ve been doing it for over 50 years. And very early on I discovered that if when riding a bike for more than an hour or two if I didn’t eat when riding I would hit the wall, which is what happens when the body runs out of carbohydrates when it’s carbohydrate-dependent. And you feel really lousy, and your performance drops. So I very quickly became a carbohydrate advocate. Interestingly, at this time 40 or so years ago was when the Atkins diet first became popular.

And Atkins said, you know, you don’t need carbs to feel well and function well. Well, I was a newly minted young doctor, and I was feeling my oats. And I was set out to prove Bob Atkins wrong. And, guess what, proved myself wrong. Now, actually, it wasn’t quite that simple because if you go on a ketogenic diet for a week, or two weeks, your performance does drop. My experience had been only in short-term restrictions in carbs. So we did a study that lasted six weeks, and by the third week of the six week study people’s performance was coming back up.

And by 6 to 12 weeks their performance was back to or above where they’ve started. The body becomes capable of burning almost all of its energy from fat. In my research I actually make a habit, sometimes successfully, of trying to prove myself wrong. And you say wait a minute, why wouldn’t you try to prove yourself right? If you prove yourself wrong that’s how medical advances are made. If you assume that something’s right, and you find out it’s wrong, you can now change your understanding and change medical knowledge. And that’s something that I, and my co-founder and collaborator in this, Dr. Jeff Volek, have made a habit of doing over the past multiple decades. In this process back in 1980 I coined a term nutritional ketosis, and another term, keto-adaptation. The first thing you have to consider when listening to someone talk about nutritional ketosis or ketogenic diets is, how can you trust what they are saying? The reason is that they are a lot of self-appointed experts out there, but very few people in the medical arena have much training in nutrition. And most of them have absolutely no training or research experience in nutritional ketosis.

That is most people get their expertise by reading what other people have done. Now, why should you trust me? I mean, I’m an MD, and I can tell you I had no training in nutrition in medical school back when I went through that process. But after I completed my medical education curiosity drove me back to school, and I spent four years doing a PhD in nutritional biochemistry because I realized there were a bunch of paradoxes between what I was taught to believe and what the evidence seemed to present.

After completing that, my PhD, I went on to do two years of formal training in clinical nutrition. Since then I published 80 papers, I’ve co-authored three books. I’ve been studying and prescribing ketogenic diets for 40 years. The first point I want to make is that nutritional ketosis is a very powerful tool when properly done, but it’s not simple. It’s not just a matter of cutting out carbs. And the other point is that particularly in people that have medical conditions, it’s not always safe. So my goal in presenting this information to you is to share the power of nutritional ketosis, share the fact that it can reverse, and, or prevent very significant medical diseases.

Oftentimes taking away the medications that are currently being used for those conditions. With this power comes risk, particularly as it relates to having being on medication because if you’ve reversed the disease, and you don’t take away the medication, you can have major side effects. The other important point is that this is much more complex than just taking away sugars, bread, rice, pasta, potatoes, and other things. For a ketogenic diet to be safe, it has to be much more scripted than that. Getting the diet right in terms of the other nutrients in the diet is pretty complex. And it’s not something that a simple slide, or even this simple talk is gonna be adequate in order to do it safely. The other important point is there are some medical conditions where people should not do this type of diet. And I’ll mention those briefly in this talk, and more completely in later talks.

Let’s discuss what’s a ketone. It turns out that there are two compounds that the body makes from fat. And the body, meaning the liver, makes two compounds from fat which are classified as, and I put this in air quotes, ketones. Now, I won’t get into the details of the technicalities of that. Now, these can either be made from body fat, that is fat we’ve eaten before and stored, or fat that we eat, and that circulates through the blood after digestion. Fats that are eaten or stored when they circulate through the blood are difficult to transport. They’re in what are called lipoprotein particles. And these are the things that you were measuring when we measure cholesterol, and triglycerides, and things like that. And because doctors worry about these things you might imagine that having too much of them is a problem. Well, it turns out that when fats in the liver are made into ketones you no longer have to worry about lipoproteins because these are water-soluble particles, and they float through the blood. They move into cells easily, so it’s a much more efficient fuel for the body to use. Once it’s in the bloodstream in adequate levels it can feed the brain, it can feed your heart, and it can feed your muscles.

And as we’ll mention in a few minutes it can do other important things as well. Now, how do we know it can feed the brain? Well, there are actually some, let’s say dangerous experiments done back in the 1960’s where patients who’d been fasting for weeks, so they had quite high ketone levels, were then infused with insulin, which drove the blood sugar down to an extremely low level, to the point where it should cause people to pass out.

And as long as there were ketones in the blood the brain functioned just fine. So we know that ketones are a very efficient and effective brain fuel. We’ve discovered in the last five years that ketones are a very potent signal that talks to our genes. And some of the genes it’s talked to are the genes that protect us from things that we call oxidative stress, or free radicals. And this is really important because these are the root causes of a number of diseases, including type 2 diabetes, heart disease, inflammatory bowel disease, high blood pressure. Also, people with seizures oftentimes have dramatic results when they get in a well-formulated ketogenic diet. And it’s not so much about fuel as it is about reducing oxidative stress and inflammation.

This is a very, very important topic in terms of understanding how ketogenic diets can be used to markedly improve some chronic diseases. We understand not just what they do, but how they do it at the molecular level. And this is important in terms of moving this field forwards, and making optimum use of this state we call nutritional ketosis. Where did nutritional ketosis come from, and why did we have to define that as a term? Over a century ago doctors figured out that when people with what’s called type 1 diabetes, the diabetes typically of younger folks where the pancreas stops making any insulin at all, they can’t use glucose at all for fuel, and the body overproduces ketones. The ketones build up to very high levels, and that’s called ketoacidosis. When ketones build to very high levels you can actually smell them on a person. It’s like a (sniffs) smell that these ketones, then say, ah, you know, this is uncontrolled diabetes. And they realize that that changes the acid levels in the blood, and that’s ketoacidosis. But these are vastly elevated levels of ketones.

So figure let’s say a number of 20 would be a extremely high level of ketones. But if you’re eating a well-formulated ketogenic diet your blood levels are not 20, your blood levels will be in a range of .5 to 3. So it’s one-tenth that very high level. Yet if you eat say orange juice and bagel for breakfast, after breakfast your ketone levels will not be .5 to 3, they’ll be .1 or .2. So one-tenth, 10 times higher is nutritional ketosis. 10 times higher to that is ketoacidosis. So we define this state of nutritional ketosis as being a safe blood level where ketones function to feed vital organs in the body when you’re not eating a whole lot of carbohydrate. You can see that in the green zone between .5, and 3, or 4, that’s what we call the optimum ketone zone. That’s when ketones have beneficial effects in terms of feeding the brain and other organs in the body.

And as you can see, if you were in total starvation, which we don’t recommend because of negative effects on lean tissue and organ function, total starvation ketones will go up as high as seven. And you don’t get anywhere near the risk of ketoacidosis until the numbers are above 10. These are very distinct states differentiating nutritional ketosis from diabetic ketoacidosis. So by 1970 all of this stuff was well-defined, and has been in the medical literature. And we kind of assumed that, you know, if we can just tell people that ketones are good for heart, and muscle, and brain that that would be a good thing. But really exciting things have happened in the last five years. The reason we know that this is not a rumor, word of mouth, there were some very solid scientific papers in the medical literature now indicating not just that, gee, looks like inflammation goes down, we actually know precisely how.

The beta hydroxybutyrate, this primary ketone we have in our blood, makes inflammation and oxidative stress go down, and provides optimized control for some inflammatory diseases. Let’s kind of get to a little bit more practical information. How does one get into nutritional ketosis? People who have reason to want to have benefit if they have type 2 diabetes, or they’re severely overweight, or have hypertension, very often those people have what we call insulin resistance. That is their body has begun to lose its responsiveness to this hormone, insulin, which is the hormone that causes blood sugar to go into cells, and also manages body fat metabolism.

So if you’re insulin-resistant you probably have to get your daily total carbohydrate intake down somewhere between 20 and 50 grams of carbohydrate per day. If you want to think about that in terms of macronutrients that’s less than 10%, and oftentimes less than 5% of your total daily energy intake comes from carbs. So that’s very carb-restricted. And the more insulin-resistant the person is the lower they have to go to initially get into a state of nutritional ketosis.

In addition to restricting carbs, this is not a high protein diet. Protein, like carbohydrates, stimulates insulin production, and exacerbates insulin resistance. So it has to be moderate in protein, enough protein to maintain healthy function of our organs, but not so much that it raises insulin levels. Then the other key point of a well-formulated ketogenic diet is this is not a calorie-restricted, stop eating when you eat x-number of calories per day. This is a diet when is done right is eaten to satiety. That is when you finish a meal you should be satiated, and you shouldn’t be hungry until it’s time for your next meal. And the way you do that if you’re eating very little carbohydrate and moderate protein is the majority of your dietary calories have to come from fat. And we’ll come back to the safety issues around, is it okay to eat that much fat if it’s more than half my calories? And the answer is yes, and hopefully I can convince you of that later on.

The other thing that is very important in a well-formulated ketogenic diet is getting enough vegetables, provide enough minerals, maybe fiber to provide satiety. Rather than coming from pills it should come from fresh real food. So we suggest three to five servings of non-starchy vegetables per day. Now, realize this is just an overview, it’s not a prescription. Don’t just say, okay, I know how to do it, I’m gonna go do it. So this is something where you need to understand the serving sizes, that we adjust the protein to the size and gender. So a small woman’s gonna need less protein than a very tall guy.

There are variations in this that require individualization. So this is not a cookie cutter or one size fits all diet. I want to point out that there are lots of low carbohydrate diet strategies out there, but not all of them are either ketogenic or involve keto-adaptation. For instance, a paleo diet, or a primal diet, or a low carbohydrate, Mediterranean, and certainly not intermittent fasting. Those do not allow for keto-adaptation. Either they’re not sustained enough or they have too much protein. So if you look at this slide here where on the vertical access it’s the amount of carbohydrates this percent per day, and the horizontal is protein. You can see that the standard American diet, I think SAD, you know, sad is a good term for that, which is high in carbohydrate, moderate in protein, and relatively low in fat, is way above the low carbohydrate level.

If you cut some carbs out of the diet, and add more fat, that would be a Mediterranean diet, but it’s still not low carb. But as a general rule most people in the nutrition field will call anything under 30% of calories as carbohydrate, a low carb diet. So a paleo diet typically is about 30% protein, about 20 to 30% carbohydrate, and only 50% or less fat. So it’s not that high in fat. But the combination of the carbohydrate and protein are enough that it prevents the body from making ketones. So that doesn’t fall into the ketogenic diet range. So you can see that to get to a well-formulated ketogenic diet it’s kind of a small island of keeping protein in moderation between roughly 10 to 20%, keeping carbohydrates under 10%. So if you’re 20% protein and 10% carbs, and you’re holding your weight stable, that is after a period of time, you’re in weight maintenance, that means that 70% of your energy has to come from fat. That can be pretty scary, but that’s how one does a ketogenic diet. And that can be done not just for weeks or months, that can be done for years and decades. And the best way to measure it is to, you know, be tough, prick your finger like people with type 2 diabetes, or diabetes to measure blood sugar.

And there are special strips for ketone meters that can actually measure your blood ketones, and they’re very accurate. And you don’t need to do that forever, you need to do that long enough just to know what level you get to if you’re eating a certain range of foods. One of the keys to success here is you have to be sure that this is safe. If you do this, and do it in a way that’s not safe, then you’re not gonna be successful. You’re either not gonna feel well, or it’s gonna make you ill, or actually carry significant risk. So as a general rule, even if you’re otherwise healthy, and you just want to lose some weight, or improve your energy level, you should let your doctor know what you’re doing. If you have type 1 diabetes, which is a case where the body is not able to make enough insulin, you’ll need specialized medical support. There are some people who advocate using this type of diet with type 1 diabetes.

But it takes a specially trained physician who knows how to do this to guide you. And this is something that has to be done with very close supervision. The same is true with type 2 diabetes, but oftentimes with type 2 diabetes we can get people off of some, or most of their medications. And, again, that has to be done by a physician, but then the supervision doesn’t have to be quite so close because you’re no longer taking the medications that carry risk.

The third situation where you would need careful medical support, and have your doctor be directly involved in what you’re doing, is if you have high blood pressure and you’re on medication. Because, again, oftentimes we need to withdraw those medications. If you have a heart condition, or if you have significant liver or kidney disease that needs to have careful evaluation to see if you have enough function of those organs in order to be able to manage the adaptation of this diet successfully. Most doctors aren’t taught how to do this.

Some of them will read books, hopefully our books, and understand how to do it. But beware of physicians who don’t have the experience in doing this. The final point about safety is this is not, as I said, not just about restricting carbs, and keeping protein moderate, but getting adequate minerals. The important minerals include sodium. If you don’t have enough salt, or sodium, in your diet you’ll have a bunch of symptoms, which include lightheadedness, dizziness, fatigue when exercising, and constipation.

Those are not side effects of nutritional ketosis. Those are side effects of not having enough salt. It just so happens that when you’re in nutritional ketosis your kidneys get much more efficient at getting rid of salt. And you have to provide it on a routine basis in order to maintain your well-being and function on this type of lifestyle. An additional mineral that’s very important, particularly for heart and muscle function, is potassium. And you get that from broth, you get that from vegetables, and you get that from eating unprocessed meats. We don’t normally have to supplement that. If you get the vegetables, meat, and hopefully make your own homemade broth in order to maintain adequate potassium intake. A third mineral we deal with a lot, particularly in people with diabetes is magnesium. This is a mineral that most Americans don’t get enough of. And it seems that people with diabetes have a significant problem maintaining adequate amounts.

A major sign of magnesium depletion or deficiency is muscle cramps, whether after exercise or occurring at night. And that’s easily managed if someone is knowledgeable on how to replace magnesium. But don’t just accept cramps as a necessary effect of this. That’s easily managed by someone who knows how to do this. Other minerals include calcium, which is necessary for bones, and nerve, and muscle function. That’s maintained by adequate vegetables, dairy, and cheese, also, from homemade broth. We rarely have to supplement calcium people when they have the normal food intake that’s appropriate for a well-formulated diet. And vitamins are sometimes a concern because people say, well, I’m not eating fruit, or I’m not eating enough fruit, and where are my vitamins gonna come from. It turns out that vegetables are an excellent source of the vitamins that you would normally attribute to fruit. So we find that people don’t need additional vitamins with this. But if one wants to take a standard multivitamin it’ll do no harm, but probably not necessary.

To wrap up, a well-formulated ketogenic diet and nutritional ketosis is a healthy normal metabolic state. This is not something that is abnormal. This is not something that you should only do for a week or two at a time because longer is unsafe. No, this is something one can do for months, years, and decades. It’s achieved by reducing sugar, and refined carbohydrates, and most starchy foods. But in the meantime you’re eating real foods, and plenty of foods, and eating those foods to satiety. This is as I mentioned a very effective disease reversing way of living. And if you have diseases that can be reversed with this you need medical supervision, particularly if you’re taking medications for those diseases. Because the good news is you have to take them away. The bad news is if you don’t take them away it can have serious side effects. So it has to be monitored by a knowledgeable physician. To do this right it results in improved well-being and function.

And the neat thing is this is not a calorie-restricted approach. You don’t have to go away from the table hungry, and you don’t have to count calories. You let your natural instincts empower you to succeed when you do a well-formulated ketogenic diet. This is a graphic that we use when we try to explain to doctors all the emerging things that happen when one goes into nutritional ketosis.

Across the top on the left-hand side are fat cells where we store energy. That energy can be released by the fat cells, circulate through the blood, get taken up by the liver. Made into ketones, and the ketones feed the brain. We didn’t put the heart on there. The other interesting thing, it appears to feed the digestive system, which is intriguing, and reduces inflammation. And that appears to be why inflammatory bowel disease oftentimes gets better on a well-formulated ketogenic diet. Clearly, ketones and fats can feed the muscles.

But it also reduces inflammation, including many people with asthma notice that their symptoms get better. There’s emerging science, not on people, but in little worms grown in test tubes, and in mice grown in cages, that a well-formulated ketogenic diet actually improves longevity by reducing oxidative stress. Then, many athletes now, particularly endurance athletes who go beyond marathon distances, like triathlons, or longer distance running, and more extreme duration sports, they’re turning to a ketogenic diet because the body can run mostly on fat. Then the person doesn’t run out of energy and doesn’t hit the wall. So, again, this has a multitude of effects, many of them beneficial. But I want to get across the idea it always has to be done with adequate information and adequate supervision to be safe. Thank you. .