What is the difference between exogenous and endogenous ketones?
Exo- means ‘outside’, like an exoskeleton, where the skeleton is on the outside of a creature, like a crab (or certain insects). We humans have an endoskeleton – it is inside our bodies. Endogenous ketones, therefore, are ketones that come from within. Exogenous ketones are ketones that have to be consumed through a drink, a pill, or a product. (They come from outside the body.) Exogenous ketones are this new type of product that can be consumed to raise your ketone levels, but endogenous ketones are ones that your body makes by itself.
Most people don’t know that when you are on a keto diet with real food, you don’t have to eat or drink ketones. Your body makes the ketones by itself from fat burning! Fat burning— which is what you want to do if you’re trying to lose weight—generates your own ketones (endogenous ketones). That’s the big difference, and it’s confusing to folks, because on the internet there are a lot of ads that come up (for exogenous ketones), which are pretty compelling.
These ketones your body produces actually cause a physiological change inside your body, which is incredible. Every other diet out there is just telling you to eat a certain way, but there’s no physiological change, whereas with a keto diet, these ketones get produced and it’s just from limiting the carbs.
It’s a different metabolic state, if you will. It’s called nutritional ketosis, which is to differentiate it from diabetic ketoacidosis or some other type of ketosis. Nutritional ketosis happens when you just limit the carbohydrates to a very low level. A lot of people smarter than me have looked at the history of what humans eat and they argue that humans probably were in ketosis for longer than they were not in ketosis. If you eat a carb, you have to burn the carb, which turns off the fat burning and the ketones. You’re not in ketosis if you eat a lot of carbs. Humans probably didn’t eat many carbs until just very relatively recently, so it’s been argued that the natural way we’ve been adapted as humans is to actually eat a keto diet. I think that’s part of why it’s become so popular – because the science is solid. The research has been done. The people who’ve been talking about the ancestral diet, the hunter-gatherer diet, all compared notes and said, “Well, we’ve all been saying the same thing—that not eating carbohydrates (which is the key to getting ketones) is probably a very healthy thing to do.”
Around five years ago, exogenous ketones started to become a buzzword. Companies popped up everywhere selling these products. In your opinion, are there any benefits to these types of products?
There’s a difference between a perceived benefit and a scientifically proven benefit. I wait to recommend things until they have a scientifically proven benefit beyond a placebo. I’m waiting until these new ketones—these exogenous ketones—have been studied with rigorous science to say that we know for sure they’re better than placebo.
Those studies haven’t been done. I was hoping there’d be, by now, study after study after study showing how great these are, because certainly, people purchase these products. But those studies haven’t been done, so I’ve been reluctant so far to recommend exogenous ketones. I have a method where you get your ketones from within, without having a product. The studies I’m waiting for may have been done and not published, because they didn’t work, which is always a suspicion when you don’t see positive studies. I’m not even aware of any buzz about studies that have been done that have been negative.
There’s no question that exogenous ketones can raise your ketone level, so a lot of people will think that’s all they need to do. They drink ketones, measure their ketone level, and think, “Oh, I’m great!” No. I want to have it studied in the context of an entire dietary pattern of eating to show that there’s benefit beyond just the foods.
If our bodies make ketones, why would we need to buy these products?
There’s been some fascinating lectures about human behavior and the belief that we need to take things to get better. There’s a percentage of the population who believe in taking vitamins. It’s just human nature to want to take something to get better. A lecture that I saw explained that if all you do is take something away, people think nothing’s changing, or if anything, the change is a bad thing. On a keto diet, when you take away carbohydrates, you’re basically depriving people of certain foods, so they often feel like they need to take a drink or a powder or a pill. (They want to be given something rather than only have something taken away.) That’s called the psychology of subtraction. A lot of people will take pills for weight loss and keto pills that don’t work, because they’ll see it on TV or on an ad, and they won’t learn about changing the food in a way where you don’t need the pills at all, like I do with my patients.
With your method there may be a waiting period – it could take anywhere from three days to four weeks to get into nutritional ketosis. People want instant gratification, so they take these exogenous ketones and within a few minutes they can be in ketosis.
Right. You’ll get that positive reinforcement very quickly. I’m a physician; I’m used to having things evaluated at a level that drugs are evaluated, with FDA (Food * Drug Administration) approval. It’s all well and good that there’s a perceived benefit, but that doesn’t mean I’m going to be endorsing it for that purpose.
With the products, it’s fascinating, because this has opened a new area of research into ketone and nutritional ketosis metabolism. For example, the early research of just drinking ketones without changing the diet at all can change things. There’s some early research on neurologic diseases. I saw a study on the tremor that goes with Parkinson’s disease. The study didn’t change this individual’s diet; they just had him drink some ketones. The tremor went away for a little while and then came back. What’s fascinating is that you might be able to have someone drink or eat or or swallow a pill to raise ketone levels and you may experience a benefit from that by itself, but that’s entirely different from me saying I’m going to help you lose weight and I’m going to teach you a method that you’ll be able to sustain for the rest of your life, because you’ve learned how to lose the weight in the same way that you maintain the weight loss.
It depends on what you’re trying to accomplish. I think it’s exciting and I’m enthusiastic and optimistic about using exogenous ketones, but I haven’t seen studies saying that adding exogenous ketones improves the endogenous ketones you get from just changing your diet. I’d like to do that study. I have a lot of patients who follow keto diets without those products. It would be interesting to add them in to see if there is a benefit beyond just the diet alone.
A lot of people continue on their high-carb diets, but then take the ketones to try and lose weight, almost like a hack.
I don’t think that’s going to work very well for weight loss or fixing diabetes. A commonsense takeaway is to try a new diet or a medicine and if it’s not working in a couple weeks, go on to something new. A low-carb keto diet works that fast. In the first couple days, the hunger goes away for most people – that’s when the ketosis is kicking in without drinking or eating or popping a pill with ketones in it.
There have been some studies done on mice. What is your opinion on mouse studies versus human studies?
I think animal studies that use animals other than humans are interesting and fascinating and they can get you into the mechanisms of things. Animal models have been very encouraging about using ketones or a diet that leads to nutritional ketosis for things like cancer, Alzheimer’s, and other neurodegenerative issues, but there’s a big leap to go from the animal models to humans. Most of the time, things don’t work in humans like they do in mice or rats, so you want to be careful to not blindly follow someone who’s just talking about a mouse model of ketosis. I see people thinking that because the ketone level and the glucose ketone index is a certain way in an animal, that that’s the way it will work in a human. But we just don’t know that. The ketosis metabolism in mice is very different, because their brains are very different, so you want to be careful to not immediately think that what happened in a mouse will happen in a human. Those studies need to be done again, with people being the research subjects.
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