True story: I discovered some shocking information regarding ketones while doing the research and writing for my keto web-blog which examines how we may increase the generation of mitochondrial energy and, as a result, increase our levels of energy. The body’s metabolic requirements weren’t being supplied by these molecules, despite their longstanding reputation as a fantastic source of cellular energy. That brought up a crucial question: What exactly were ketones doing, and for what purpose, if they weren’t acting as a substitute fuel source for the body and brain?
I discovered myself going down a data rabbit hole. I learned the exact purpose of ketones after re-examining the most recent study, and it was right under my nose the entire time. Even though I’ve been practicing restorative medicine for more than 12 years, I, like many of my colleagues, couldn’t see the wood for the trees. When I opened my eyes, it became abundantly evident to me that ketones are not an amazing fuel but rather activate the crucial molecular process known as mitochondrial uncoupling, which underlies all we previously knew about how to promote lifespan, health, and well-being.
I am well aware that proponents of ketogenic diets would regard my findings as unorthodox. I anticipate some opposition from those who have succeeded on a ketogenic diet, whether by losing excess weight or treating a variety of health issues. That includes many of my own patients who gladly lost a few pant sizes and had a significant improvement in their general health after implementing the ketogenic versions of my programs.
Instead of advocating that we completely disregard ketones, my aim in this book is to challenge long-held beliefs about their function in the body and explain what I’ve discovered about how they affect mitochondrial health. My patients were using the power of ketones without adhering to the standard high-fat ketogenic diet, just like Ester did, after I realized what we’d been getting wrong about keto. In fact, according to the statistics, following a traditional ketogenic diet can occasionally be detrimental to long-term health, as we witnessed with Diana.
I’m going to encourage you to open your mind and think bigger and braver as we go forward, and I’m going to urge you to suspend your present views about what it means to be “keto.” You’re going to finally get why all the diets you’ve tried both keto and non-keto didn’t live up to your expectations. But before we examine how to go correctly, we must first examine what went wrong. Let’s start by looking more closely at ketones.
WHAT EXACTLY ARE KETONES?
First discovered in the urine of diabetic patients in Germany in the 1880s, these water-soluble short-chain carbon compounds were thought to be little more than a sign of metabolic disorder at the time. But a few decades later, medical professionals working in France and the United States who just so happened to be studying childhood epilepsy made an incredible finding. Children with epilepsy who were fed a diet high in fat (80%), protein (10%), and carbohydrates (10%) experienced a significant decrease in the frequency and intensity of their seizures. This approach completely eliminated the seizures in several kids. The only other nutritional strategy that even came close to being as beneficial was a water fast, in which the kids only drank water for stretches of 18 to 24 hours at a time to prevent seizures. As you can understand, it was simply not a practical or humane long-term solution to force growing children to abstain from food.
The diet was an effective treatment for at least 50% of children who could not find relief from their seizures by any other approach, but doctors were baffled as to the mechanism at work. Yet why? Why might eating a lot of fat (or not eating anything at all) cause seizures to decrease?
Time travel to 1921, when Rollin Turner Woodyatt, an endocrinologist at Northwestern University, made an unexpected discovery while studying diabetes. Woodyatt discovered that ketones aren’t always produced by the body as a result of metabolic disorders. Instead, he found that when an animal is either hungry or eating a diet high in fat but low in protein and carbohydrates, the liver creates ketones. The liver accomplishes this by converting free fatty acids (FFAs), which are lipids that originate straight from the fats that we make and store in our fat cells, into ketones. The three unique forms of ketones that Woodyatt’s research identified are acetone, beta-hydroxybutyrate (BHB), and acetoacetate (AcAc).
Less than a year later, Dr. Russell Wilder, a leading expert on diabetes and nutrition at the Mayo Clinic, used Woodyatt’s discoveries to create a high-fat, low-carb diet he dubbed the “ketogenic diet” and used it to treat children with epilepsy. The diet in these young kids not only assisted in seizure management but also enhanced the children’s sleep and appeared to give them more vitality. Before anti-seizure drugs like phenobarbital and Dilantin were created, the ketogenic diet was the go-to treatment for infantile epilepsy.
It’s important to remember that the ketogenic diet first gained popularity in the 1960s as a preferred method of treating epilepsy. Advocates of the diet advocated consuming lots of medium-chain triglyceride, or MCT, oil, a unique kind of saturated fat that is metabolized differently than other types of lipids. The patients were able to consume more protein and carbohydrates while still reducing their intake of fat, which helped to control their seizures. If you’re wondering how that may possibly work, read on pause to reflect. We’ll talk more about MCTs later on, including how they affect the production of ketones.
What we believed ketones to do
When you combine all the information, it becomes obvious that there are three distinct times when ketones are produced: during feasts (high-fat meals), during famines (starvation), and when there is diabetes (a metabolic condition). What connects the three together?
The quick response is “carbohydrates.” Carbohydrates are transformed by the body into glucose, which is subsequently used by our mitochondria to create ATP, the energy that drives our cells. Diabetes patients’ bodies struggle to manufacture ATP when they don’t have enough insulin, either because their bodies can no longer produce it (in the case of type 1 diabetes) or because they have developed a resistance to the hormone (in the case of type 2 diabetes). Insulin aids in bringing glucose into our cells. On the other hand, if you’re undernourished or consuming a diet low in carbohydrates, your body won’t have access to the glucose it needs to produce ATP. That begs the important question of what might be acting as an alternative fuel for producing ATP in the absence of glucose, given the significance of glucose for keeping our systems fueled and prepared for work.
Our cells first turn to glycogen, the form of glucose stored in the liver and muscles, to keep us alive when food is not available. But what occurs after that is gone? That topic was finally resolved in the 1960s by Dr. Richard Veech, a scientist and trained physician. Veech was studying the subtleties of human metabolism when he made an unusual discovery. Researchers were already aware that when fasting or following a high-fat, low-carb diet, the liver creates ketones. Veech and his mentor, Harvard University-based diabetes specialist Dr. George Cahill, found that one type of ketone body, beta-hydroxybutyrate (BHB), could not only replace the missing glucose to aid in ATP production but also set off a number of downstream effects unrelated to energy production. They proposed that BHB and other types of ketones might serve as an alternate fuel. But let’s get back to the history lesson, shall we? (I later learned that it’s those downstream consequences that actually give ketones their strength.)
Veech and Cahill made the hypothesis that the liver produces ketones as a backup fuel source when carbohydrate-rich dietary sources are scarce as a result of their discovery. After all, to function, our bodies require energy. Heck, only our brains consume 20% of the total energy produced by our bodies. Veech and Cahill postulated that the body would burn stored fat, releasing FFAs to be transformed into ketones, in order to survive periods of low glucose availability (famine). The essential energy would subsequently be produced by the body using ketones. They went so far as to claim that ketones were a type of “super fuel” a source of cellular nutrition that might help cells especially brain cells work much better than they already did.
After all, even in the chilly, gloomy winter months, our ancestors had to obtain sustenance wherever they could. When the hunting was bad or the fields were fallow, they didn’t die since they could use ketones instead of glucose for energy. Our bodies, unlike those of many animals, were well-built for any situation thanks to this fail-safe system. When food was relatively easy to locate or grow, we could feast ourselves, but we could also get by during times of famine and drought. In order to keep us alive until we could kill the next gazelle or forage for the next tuber, having a backup food supply meant that our bodies could function, possibly even at a greater level.
Ketones are still regarded as a wise insurance policy that keeps us afloat in today’s society. Some proponents of ketones may even go so far as to claim that ketones are miraculous a highly effective sort of “super fuel” for our bodies and minds. I used to be one of those ardent supporters, telling patients like Ester that their weight loss was due to becoming an incredibly effective fat burner. But like so many of my contemporaries, I had a fundamental misunderstanding of how ketones functioned. Ketones may work miracles, but not in the manner that we all once thought.
HOW WE BELIEVED KETOGENIC DIETARY METABOLISM WORK
More than a century ago, when the first ketogenic diet was recommended, it was unclear how it may benefit people with seizures or other neurological conditions. All that mattered was that it worked.
The first scientist to attribute BHB to helping prehistoric humans live when food was scarce was Dr. Veech. It was a theory that made some sense: early man could survive far longer on this alternate metabolism during hunger than he could on glucose, supplied by carbohydrates and protein alone. And Veech’s research, which demonstrated that people could still produce ATP after weeks without meals, seemed to tie things up nicely. The side effects of prolonged fasting are quite dangerous, and include increased stress on the heart, muscle deterioration, and malnutrition. This is not a healthy path to weight loss or longevity. (In fact, we now know that humans can survive for quite a long time without food â for example, in 1971, Angus Barbieri, an extremely obese British man, successfully completed a 382-day water-only fast under medical supervision.)2
The premise of the ketogenic diet is that the body must use stored fat as fuel when there is no glucose available. The FFAs created as fat breaks down can act as an alternate fuel source for the majority of the cells in your body after fasting for roughly 12 hours (remember this figure, please!) or restricting carbs to 20 grams or fewer per day, providing you are not insulin resistant. Your energy hog of a brain, however, cannot be fed by those FFAs. You may be aware that the blood-brain barrier, a unique network of tissues, serves as the brain’s defense mechanism. Only a few substances, such as water, sugar, and oxygen, may flow through readily; its purpose is to keep harmful substances away from this priceless organ. Larger molecules in particular are rejected in favor of smaller molecules. FFAs cannot support your brain cells for this reason. They can’t easily penetrate the blood-brain barrier and reach to where they are most required because they are just too big and not water-soluble enough.
Let’s be clear: most of your cells convert to utilize FFAs as fuel instead of glucose when you’re famished. However, your brain is unable to consume these chemicals. So where does it acquire the fuel that it uses to generate energy? We now know that some of the FFAs generated from your fat cells travel to the liver, where they are changed into ketone bodies (another name for ketones), which are smaller and water-soluble, allowing them to readily bridge the blood-brain barrier to reach the brain. This is in contrast to FFAs, which are not as easily able to do so. There, the ketones can be utilized by your brain cells as “emergency” fuel, assisting the mitochondria in your neurons to make the ATP they require to remain in optimal functioning. (Interestingly, although the liver produces ketones, it is unable to utilize them as fuel and instead excretes them into the bloodstream.)
So far, so good, I suppose. Ketones are made by the liver. In the absence of glucose, ketones can be transported to the brain and used as fuel. And if Veech is right, every cell in the body may absorb and use this “most excellent” energy source (with the exception of those in the liver). If so, then we should aim to be in a state of constant ketosis and, in essence, starvation. Every organ and system in our body will be content as our bodies will burn fat and produce ketones. Please pardon the pun, but hold on!
In the late 1960s, Dr. Oliver Owen, a different George Cahill protégé at Harvard who studied diabetes and human metabolism, contradicted that idea by showing that ketones only meet up to 70% of the brain’s overall energy needs. Humans who fast for an extended period not only experience muscle deterioration but also possible and actual cognitive damage. This implies that ketones simply cannot replace all the glucose the brain needs to function at its best, even when the body is fully operating in a state of ketosis, the basis of the ketogenic diet.
Veech’s “super fuel” idea has still another kink, which Owen and Cahill discovered. During a three-day fast, ketones were the preferred fuel source for muscles, but after twenty-four days of fasting, study participants shifted to burning FFAs. In the end, Owen informed the scientific world that ketones are insufficient as an energy source to keep the body and brain functioning at peak levels after conducting a number of further experiments. In fact, he showed in 2004 that only around 30% of the body’s energy-production requirements may be satisfied by ketones while the body is in full ketosis.
Review what you just read. The brain isn’t pleased with the abundance of ketones produced by the body, despite them being billed as a miracle fuel. It desires, no, it need glucose. Ketones also don’t completely satiate your muscles. Yes, they will utilize them first, but eventually they will move to FFAs. Less than one-third of your body’s entire energy requirements will be satisfied even if you are able to maximize your ketone synthesis.
This begs the question of how exactly experts continue to advocate using ketones as our primary source of fuel rather than glucose for our bodies’ metabolic processes.
A KEOGENIC DIET TO LOSE WEIGHT
You may have observed that Veech, Cahill, and Owen didn’t really talk much about weight loss in general. How did medical professionals and researchers transition from emphasizing ketones as an energy source to advocating a ketogenic diet for weight loss? I’ll explain.
When using the ketogenic diet to treat epilepsy, scientists discovered an intriguing phenomenon. People who consume a lot of fat tend to lose weight quickly. This outcome was contrary to the nutritional theory that was in vogue at the time, which claimed that consuming a high-fat diet could only lead to weight increase.
Then, in 1972, cardiologist Dr. Robert C. Atkins released Dr. Atkins’ Diet Revolution. The Drinking Man’s Diet, a treatise by photographer Robert Cameron that discussed the advantages of a low-carb, high-animal-protein diet (with a lot of alcohol thrown in for good measure), served as the inspiration for the book. In essence, this fad diet forbade the ingestion of carbs. Atkins believed there was substance to the idea of restricting carbohydrates, even though doctors and nutritionists at the time mainly disregarded Cameron’s book as being rubbish.
With his cardiac patients, Atkins detected a concerning trend: they were becoming more and more obese. He understood the connection between this extra weight and cardiovascular problems and blamed America’s rising waistlines on an overabundance of carbohydrate consumption. He immediately came up with what he dubbed a “controlled carb approach” to weight management, promoting the consumption of protein and fats, particularly saturated fats, rather than the traditional plate’s abundance of cereals and grains. While Dr. Atkins did not refer to his weight loss plan as a ketogenic diet, he did claim that eating this manner allowed the body to use fat rather than glucose for energy. His weight loss plan restricted daily carbohydrate intake to 20 grams and excluded most grains, vegetables, and fruits.
Since the publication of Dr. Atkins’ Diet Revolution decades ago, the eating regimen has been altered to incorporate more fruits, vegetables, and other complex carbohydrates as a person approaches their weight loss objective. However, the fact was that weight reduction (and, more often than not, maintenance of that weight loss) only persisted as long as the carbohydrate restriction was in place, both with the Atkins diet and the various imitators that came after it. The weight usually returned once they started eating a more balanced diet, frequently with an additional 5 to 10 pounds. A low-carb, high-fat “keto” and/or high-protein diet typically promotes more rapid weight reduction and correction of insulin resistance than low-fat diets, although the benefit wears off rapidly, according to numerous human studies. In reality, when Danish scientists from the University of Copenhagen directly studied the long-term health impacts of these different diets, they discovered few variations in the outcomes seen after a year.
But as we all know, the ketogenic diet has recently had yet another comeback. Similar to other carb-restricted diets, its theory is that by making the body produce ketones and use them as fuel, it will cause rapid and “magical” weight loss. How is this accomplished?
Ketones in the urine, according to Dr. Atkins, indicated wasted energy and aided in the promotion of weight loss. Other proponents of high-fat diets have hypothesized that this may be effective because ketones “waste” calories in some manner, causing weight reduction. Others have promoted the idea that ketones may suppress the appetite or, as demonstrated in research by David Raubenheimer and Stephen Simpson, leading authorities in nutritional ecology from the University of Sydney, that eating this way makes you feel full faster, so you ultimately eat less.6 Of course, there remains the popular theory that ketones help the body become more ketogenic. (It turns out, these people are correct, just not for the reasons they think!) This is what I used to think because I did inform Ester that she had developed into a really effective fat burner.
Even if the medical community didn’t fully comprehend the connection between weight loss and ketosis, the majority of well-known books on the ketogenic diet weren’t afraid to make outlandish claims. Here is a selection of quotes from some of the most well-known keto “experts” (names have been changed to protect the innocent!)
- ”You are using fat as fuel, thus losing weight will be simple.”
- Fat is burned for fuel, and the byproduct of that process is ketones.”
- ”The body actually prefers to use ketones as fuel.”
- “The most effective fuel is ketones.”
- “Glucose is a dirty fuel, whereas ketones are a clean fuel.”
- ”Ketones are actually the ideal fuel supply for the brain, liver, heart, and muscles. The handling of carbs by these organs is poor.”
- “You can adapt to the ketogenic diet in a few days.”
- ”The fourth macronutrient and the fourth ATP production method is ketones.”
- ”Up to 75% of people worldwide are intolerant to carbohydrates.”
It makes sense why so many people want to try the keto diet. You could be motivated to stop eating carbohydrates tomorrow after reading these claims (or believe you might like to try it, if it didn’t include eating all that fat). There is only one issue: ketones are a poor fuel source. The majority of professionals were completely mistaken about all they believed they knew about ketosis and weight loss.
A TRADITIONAL KETO DIET’S CONTRAINS
After emphasizing all those amazing keto weight loss claims, I’d be negligent if I didn’t also point out that a ketogenic diet has a number of disadvantages. First of all, not all carbohydrates are made equally. A brownie and Swiss chard are both regarded as foods that contain carbohydrates. One of those foods is bursting with fiber and phytonutrients, or nutrients derived from plants like polyphenols. The other categorically isn’t. It is nearly impossible to consume the nutrients your body needs to function at its best on a long-term eating plan that severely restricts how much carbohydrate you can consume.
And the reason for this is that your general well-being is greatly influenced by the health of your microbiome, which is the community of bacteria and microorganisms that lives in the human gut. Your microbiome can’t obtain the nutrients it need to support your well-being if there isn’t a wide variety and ample supply of fiber, polyphenols, and nutrients in the form of veggies and other plant foods.
When all carbohydrates are treated equally, important nutritional variations in fruits, vegetables, and grains as well as how each of these items affects your metabolism are also overlooked. For instance, complex carbohydrates like nuts, properly prepared legumes, and fibrous vegetables are digested considerably more slowly than simple carbohydrates like sugar and processed grains. When grouped together, carbohydrates cover a vast range of foods, including both animals and plants.
Strict carb restriction has another drawback that must be considered. While some keto gurus will claim that 75 percent of us are “carbohydrate intolerant,” such claim is complete hogwash. Carbohydrates are necessary for all living things. Animal brains even have a built-in sensor to monitor our intake of carbs, ensuring that our bodies have the glucose they require to produce ATP and survive.
These diets present a number of important difficulties in addition to the uncertainty about carbs that comes with turning keto:
Elevated fat content.
I’m obviously pro-fat and am known for claiming that the primary goal of eating is to consume more olive oil, but a ketogenic diet that includes all fats without restriction is not a good strategy. We’ll look into the key distinctions between dietary fats in following articles here on my blog.
High level of cholesterol.
The traditional ketogenic diet’s consumption of long-chain fats almost always raises LDL cholesterol, which may cause your local doctor to reach for their prescription pad if you subscribe to the cholesterol theory of coronary artery disease, which holds that high cholesterol is to blame for heart disease. Although I disagree with this hypothesis, my regimen shouldn’t cause a sharp increase in your LDL levels.
Animal protein and fat.
Because plant protein sources typically contain carbohydrates, the classic keto diet is unworkable for the majority of vegans and vegetarians. That makes it extremely difficult to adhere to the classic keto diet’s requirement for a 10 percent content in terms of both protein and carbohydrate energy sources. For reasons related to their health, ethics, or the environment, other people favor a plant-based diet.
Boredom.
Even eating foods high in healthful carbohydrates must be severely restricted, which might result in bland meals. This is probably a major factor in the failure of 60% of people to maintain a ketogenic diet for even a brief length of time.
Poor athletic performance.
Although the evidence is conflicting, several studies claim that being in ketosis does not affect performance. The results of the trials Jeff S. Volek and Stephen D. Phinney did with athletes for The Art and Science of Low Carbohydrate Performance revealed that a high-fat diet was not harmful to performance. In other, more recent ketogenic diet experiments, researchers found elite race walkers could retain their peak performance on a high-fat diet, but doing so required more oxygen (i.e., they had to breathe harder and faster to produce the same amount of ATP as when they were consuming a more carbohydrate-rich diet). However, even they concede that athletic performance tanks initially and that it may take weeks to get “keto adapted.” At least in these top athletes, carbohydrate is able to give more ATP per unit of oxygen use than fat. This poses a challenge for the conventional view of keto: if ketones were the super fuel that so many claim they are, one would expect to observe an increase in athletic performance rather than a decrease, or at least little change.
Heart problems and increased inflammation.
It’s a big “if,” but it’s possible that maintaining a state of ketosis for an extended period of time could endanger your health. A combined investigation by Columbia University and the NIH found that following a ketogenic diet was associated with both higher cholesterol and more widespread inflammation. And despite all the claims that it would assist to control metabolism, it instead seemed to make diet-following subjects more insulin resistant!9 One of my more ardent keto practitioners was astonished to see that these identical problems were evident in his own blood work just this week.
Let’s assume you can get beyond these challenges and adapt keto to work for you. The majority of keto specialists guarantee that your body will become an effective fat-burning powerhouse once ketones start to produce! But think about that assertion for a second. If ketones are actually improving your body’s ability to burn fat, you should be producing more energy with less food, according to Merriam-Webster’s definition of “efficient” as “capable of producing desired results with little to no waste.” A hybrid automobile like a Toyota Prius clearly burns fuel more effectively than, say, a Ferrari sports car. A Prius can go around 50 miles on one gallon of gas. No matter how attractive it is, that Ferrari will only get you around 10 miles per gallon. Therefore, I would choose the Ferrari if I wanted to literally squander a lot of gas. (Okay, I might want to go about in the Ferrari for other reasons, but let’s stick with this efficiency analogy.)
Each gram of protein and carbohydrates has roughly 4 calories. Contrarily, fat has roughly 9 calories per gram. That amounts to over twice as many calories! As a result, you shouldn’t be losing weight if your diet is primarily made up of fat and contains twice as many calories as your previous diet. Those extra calories ought to be stored as fat. You should have plenty of extra calories since, as an effective fat burner (or someone who uses body fat to produce more energy), you should be able to put on weight more quickly.
In other words, if ketones were turning me into an effective fat burner, they would also turn me into a very effective fuel burner, similar to a Prius. And not more, but less, fat would be used as a result. On the other hand, I would get into the Ferrari, a very effective fuel waster, if I wanted to squander fuel (or fat). The main paradox of the keto diet is that, when it is effective, it seems to be making people and their mitochondria terribly fuel inefficient exactly the opposite of what its proponents claim!
I have one more thing to add. Researchers recently conducted a meta-analysis of high-fat ketogenic and/or modified Atkins-style diets and found no advantage for type 2 diabetes reversal or weight loss, in addition to no effect for weight loss. In fact, these researchers discovered that this kind of diet raised inflammation and heart disease risk factors. It’s yet another illustration of how keto, at least as it’s currently understood, is not the healthy choice that many proponents of the diet claim it to be.
Contrary to what I and many other proponents of the ketogenic diet once may have believed, eating a diet high in fat does not make you a more effective fat burner. Diana and a great deal of the patients I treat consequently experience the complete reverse of what the keto diet promises. Ketogenic diets’ theories for why they effectively burn fat just don’t hold up.
TIME TO RETAKE A LOOK
Approximately 80% of those who visit my clinics with the intention of losing weight say they are either on a ketogenic diet or, like my patient Diana, have bravely attempted the diet without success. Despite the popularity of ketogenic diets, only a small percentage of users actually see the expected outcomes. On the surface, it would appear that they are merely failing to adhere to the program.
But I was certain that there had to be another factor at play if the keto diet was failing to work for certain people. There is nothing new to learn, as my mentor Dr. Gernshtain would frequently remind me when I was first a research fellow at the NIH. Dr. Andvile characterized research as “to look again; to literally re-search,” but there is still plenty to discover.
He has such an impact on me that I now actively seek out explanations for why I might be mistaken. I discovered that ketones operate as signaling molecules, sending important instructions to our mitochondria, the energy-production factories in our cells, as I combed through literature on mitochondria with the aim of explaining how these organelles work. You might think this is a minor distinction a footnote in a research paper but there is a significant distinction between these two roles. According to the current view, ketones act as the premium fuel that keeps our bodies functioning smoothly and effectively. They are, however, a long way from being a super fuel, as was previously demonstrated. However, in their capacity as messengers, they instruct mitochondria to “uncouple” and figuratively squander fuel in order to safeguard themselves from undue strain. This ground-breaking new knowledge of ketones can help you reach your full potential for healthy health as well as weight loss.
You’ll discover that you can and will improve your weight and health while decreasing the aging process once you understand how the foods you choose to eat can assist you in harnessing the power of your mitochondria. You’ll never again view “keto” in the same way. Better still? There is no need for all that fat, as this new science supports a nutritional plan that is much more permissive, pleasurable, and long-lasting than conventional keto diets and much better outcomes.
Without a doubt, you are eager to discover more. But as in all my other works, some familiarity with our subject is necessary before we get to the program itself. It’s time to review how your mitochondria function and why your health depends so much on them. Let’s move forward.
