Ketogenic diet – what does the scientific evidence say about it?

Diet fads seem to test the limits of science since forever. I’m an ancient feathered dinosaur, and I’ve seen it all from the popcorn diet to the South Beach diet to the paleo diet to the ketogenic diet.

I’m sure that the ancient Romans had some diet fad diet that the aristocracy followed to keep themselves healthy – oh wait, the Roman upper class followed the Mediterranean diet, which may be one diet fad that stood the test of time and science.

Outside of the aforementioned Mediterranean diet, which includes whole grains, olive oil, seafood, legumes, and nuts, most of these diets lack robust scientific evidence supporting their usefulness in weight loss or maintaining some unbiased standard of health. But they certainly make a lot of money for those promoting them. It was a US$66 billion market in the USA alone in 2017.  Wait, maybe I should invent the Raptor Diet?

One of the current fads is the ketogenic diet, which is all the rage among those looking to lose weight, improve their health, and, I’m sure, prevent cancer. Before someone thinks it really prevents cancer, it does not. In fact, it may increase the risk of cancer. But that’s another story for another day.

Let’s get into this ketogenic diet fad. Is it supported by any robust, repeated, published evidence? Or, like most diet fads, is it mostly supported by testimony and anecdotes? 

ketogenic diet
Nom nom, steak. Credit: Paul Hermann
@plhrmnn from Unsplash

Science of diets

Dieting, which for the purpose of this article strictly means losing weight, is an important health care issue. Obesity is linked to a large number of chronic health issues – type 2 diabetes, increased risk of all cancers, cardiovascular disease, osteoarthritis, and many other diseases and conditions.

According to the Centers for Disease Control and Prevention (CDC), a person who has a Body Mass Index (BMI) > 30.0 is considered obese, whereas someone with a BMI of 25.0-30.0 is considered overweight. These are not subjective measurements, they are objective values based on vast amounts of epidemiological evidence that shows the BMI points where many chronic and acute diseases increase significantly.

And, of course, the USA and many other “developed” countries have an obesity epidemic. Nearly 40% of Americans are considered obese. Around 20% of Europeans are considered obese, and about 50% are considered overweight. Around 28% of Australians are obese. And in each of these countries, the rates are increasing, not decreasing, despite the overwhelming public health messages that obesity is bad.

This has led to the cottage industry of diet fads, including the keto diet, over the past few decades. Obese and overweight individuals are looking for the easiest, but occasionally difficult, methods to lose weight fast. During the 1990s, there were are a number of prescription, and over-the-counter, medications to lose weight. Some of them worked to lose a few kilograms, usually with significant risks from the medication themselves.

The science of weight loss is very basic – calories consumed must be less than calories expended. I know that the pseudoscience weight loss industry wants to convince us that certain foods “burn” more calories than others. Or the body doesn’t get calories from some food. Or many other ideas not based on actual physiology.

From a physiological standpoint, all calories consumed is energy in, no matter if it’s a celery stick or a Big Mac. Of course, it’s easier to get more calories from a Big Mac than a bunch of celery, but technically you could gain weight from an all-celery diet, though my brain would rebel against that.

You burn calories through your basal metabolic rate (BMR), or your resting energy use that runs everything in your body, and through exercise beyond your basal rate. So, you can sit in your chair surfing the internet for 8 hours, and you’ll still burn energy. Ironically, the heavier you are the higher your BMR.

This isn’t rocket science – calories in must be less than calories out. And, as far as the scientific evidence shows, that basic formula cannot be violated.

You can adjust parts of the equation by increasing your BMR, like exercising a lot, but it’s kind of a myth that exercise actually leads to weight loss. For many people, not having a bag of potato chips (or crisps for those of you who use that word) reduces 400 calories on the input side. Burning those 400 calories on the output side of the equation would require a 1.5-hour brisk walk or jog.

And it takes 7700 kcal to lose 1 kg of weight (or about 3500 kcal for one pound). So, to lose 1 kg per week, one must have a calorie deficit of about 1000 kcal every single day.

Again, there are no magical formulas here. Almost every food fad I read about relies upon special pleading to make claims that are just not biologically plausible. No, there are no foods that can “trick” the digestion to not absorb calories. No there are no foods that increase your BMR sufficiently so that you burn more calories (and even if it did, it is improbable that it could cause your metabolism to burn an extra 1000 calories per day without causing undue harm to the individual).

I know, someone will claim in the comments that they lost 10 kg with the all V8 diet or something. These claims were always made by advocates of the Atkins diet back in the early 1990s. What was discovered, like with all of these diets, is that initially there were successful not because of any amazing diet design, but because the patient consumed less food. Eating bacon by the plateful may sound like a great way to lose weight, but there’s only so many fatty foods one is willing to eat, and eventually, the calories in are less than the calories out.

And anecdotes are not scientific evidence.

ketogenic diet
Steak is part of the ketogenic diet. Yum. Credit: rawpixel
@rawpixel from Unsplash.

What is the ketogenic diet?

The ketogenic diet, which is often called the keto diet, is a high-fat, average-protein, low-carbohydrate diet that was originally is used primarily to treat difficult-to-control (refractory) epilepsy in children. The ketogenic diet forces the cells of the body to utilize fats for energy rather than glucose.

Normally, when carbohydrates are consumed, they are broken down into three basic monosaccharides, glucose, fructose, and galactose, then they are absorbed into the blood. Fructose and galactose are used for a lot of biochemical processes in cells, but glucose circulates throughout the body where insulin signals cells to absorb the glucose for energy.

Glucose is not only extremely important to fueling brain metabolism, but also for just about every cell in the body.

However, if one’s diet reduces the amount of carbohydrates, and thus glucose, the liver is signaled to convert fats into fatty acids and ketone bodies. The ketone bodies in the blood replace glucose as the energy source for the brain, which can lead to a reduction in the incidence of epileptic seizures. However, better medications to control these seizures have been developed and the usefulness for the diet in epilepsy has become limited.

During the past couple of years, the ketogenic diet became the new fad diet, endorsed by the usual woo-pushing celebrities.

However, like the gluten-free diet nonsense, where people claim they can have a little gluten (individuals with diagnosed celiac disease have an on/off situation with gluten – even a little can be harmful), the ketogenic diet is, in reality, very difficult to implement. Even a little carbohydrate can reduce the ketosis effect.

Irrespective of anecdotes and testimonies, is there much evidence that it works?

Scientific evidence for the ketogenic diet – cancer

The published scientific evidence supporting the ketogenic diet for weight loss is rather limited. In fact, most of the evidence seems to indicate that it is no better than other fad diets, and there is potential for some risks.

But let’s start with one of the most ridiculous claims about the diet – it prevents cancer. This claim is pushed by a Dr. Thomas Seyfried, Ph.D., a “cancer researcher” at Boston College.  He makes this outlandish claim:

The low-carb, high-fat ketogenic diet can replace chemotherapy and radiation for even the deadliest of cancers, said Dr. Thomas Seyfried, a leading cancer researcher and professor at Boston College.

In an exclusive interview, Dr. Seyfried discussed why the ketogenic diet has not been embraced by the medical community to treat cancer despite its proven track record both clinically and anecdotally.

“The reason why the ketogenic diet is not being prescribed to treat cancer is purely economical,” said Dr. Seyfried, author of Cancer as a Metabolic Disease. “Cancer is big business. There are more people making a living off cancer than there are dying of it.”

Oh, this garbage again.

Dr. Seyfried, who appears to be a well-published researcher in cancer, makes this claim based on a couple of mouse studies. And as I’ve said about mice in cancer research, they’re not humans, and we’ve “cured” cancer in mice hundreds of thousands of times. The loquacious Orac examined these studies and opines thusly:

Dr. Seyfried presents mouse studies that are interesting and suggestive that there might be something to this whole ketogenic diet thing, at least in brain tumors, such as this one. However, this is what we in the oncology biz would call pretty preliminary data, worthy of further investigation but not supporting the grandiose claims that Dr. Seyfried makes.

Dr. Seyfried, using these preclinical studies, is trying to make an argument that diets that change the metabolism can kill cancers without chemotherapy or radiation. Much of it based on some outrageous conclusions from some early studies on cancer, and there is no clinical evidence supporting the belief that a ketogenic diet is going to have some effect on cancer. Back to Orac:

In the meantime Dr. Seyfried and other advocates who so passionately believe that ketogenic diets will greatly help patients with brain cancer do no one any favors by claiming unequivocally that cancer is a metabolic disease and saying that ketogenic diets are more beneficial than chemotherapy for patients with brain tumors.

To be fair, there are ten clinical trials underway at this time that are evaluating the ketogenic diet and cancer – none of those trials, however, eliminate standard chemotherapy and radiotherapy treatments. The diet is added with standard treatments – it would be unethical to do otherwise.

There was one article published from those studies, and the results were fairly unremarkable. It was a very small study (n=17), and there may have been some improvement in some of the study participants, but it would be difficult to come to any conclusion.

Based on the preclinical evidence, there may be some reason to consider a ketogenic diet to possibly go hand-in-hand with standard cancer treatments for slightly improved outcomes. But as a replacement for standard cancer therapy? No.

And it certainly cannot prevent cancer.

Scientific evidence for the ketogenic diet – weight loss

There’s actually more intriguing evidence about cancer (even that is very weak and lacking in any clinical studies) than there is about weight loss. One of the best systematic reviews (the pinnacle of the hierarchy of biomedical research) on the effect of a ketogenic diet on weight loss came to this conclusion:

There is insufficient evidence to make recommendations for or against the use of low-carbohydrate diets, particularly among participants older than age 50 years, for use longer than 90 days, or for diets of 20 g/d or less of carbohydrates. Among the published studies, participant weight loss while using low-carbohydrate diets was principally associated with decreased caloric intake and increased diet duration but not with reduced carbohydrate content.

Before we move along here, I need to remind the reader of the Argument from ignorance, which states that if we haven’t disproved a hypothesis, then it’s entirely possible that it’s still true. No, the authors wrote that there is insufficient evidence, meaning there is nothing there to support the belief that a ketogenic diet causes weight loss directly.

In fact, the evidence seems to indicate that, like most diets, it works by reducing the number of calories consumed rather than by some magical metabolic process of carbohydrate reduction. And, the research also seemed to indicate that individuals would stay on the diet longer. I guess eating steak is easier than salads!

Another systematic review did appear to indicate that the ketogenic diet may reduce appetite, though it seems that any low-calorie diet could do the same thing. And another systematic review provided evidence that the ketogenic diet could produce excellent weight loss, but, once again, it seems to be directly related to reduced calories rather than any magical change in metabolism.

But now we come to some major issues with the ketogenic diet. There are many studies that show that the diet may be linked to higher mortality compared with other low-calorie diets. For example, a meta-analysis (also at the top of the hierarchy of research) of clinical studies showed that the diet can increase certain markers of cardiovascular diseases, such as the levels of low-density lipoprotein. 

Even more worrisome is another systematic review that concluded:

Our meta-analysis supported long-term harm and no cardiovascular protection with low-carbohydrate diets. However, the observational studies were limited and moderately heterogeneous. Our findings underscore the imminent need for large-scale trials on the complex interactions between low-carbohydrate diets and long-term outcomes.

The researchers also wrote:

Given the facts that low-carbohydrate diets are likely unsafe and that calorie restriction has been demonstrated to be effective in weight loss regardless of nutritional composition, it would be prudent not to recommend low-carbohydrate diets for the time being. Further detailed studies to evaluate the effect of protein source are urgently needed.

In other words, there are some serious health issues that appear to be linked to low carbohydrate diets like the ketogenic diet. In fact, the best diets, like the Mediterranean diet, have broad calorie types including carbohydrates like fruits, vegetables, grains, and legumes along with meats. And those diets may actually be linked to a lower risk of cancer.

Summary

There does not appear to be overwhelming evidence that the ketogenic diet actually has any advantage over any other diet for weight loss other than it may actually reduce calorie consumption and increase adherence to the diet. It has no magical properties to make the weight loss mechanism any better or worse than any other fad diet.

Furthermore, it does not prevent or cure cancer. I do wish this particular trope would go away, but I have no power over that.

Finally, there are some big risks to the ketogenic diet, including potential links to cardiovascular diseases and all-cause mortality. In other words, the benefits of weight loss, which is important, may be outweighed by the risks. But if it works for certain individuals who are younger and at lower risk to cardiovascular diseases and other mortality events, then maybe the benefits do outweigh the risks, especially if the weight loss is significant and long-term.

Michael Pollan gives the best advice for dieting – “eat food, not too much, mostly plants.” We’re overcomplicating dieting for little benefit and, in the case of the ketogenic diet, some large risks.

Citations



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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!