Science 101

The Science Behind The Ketogenic Diet

The keto craze is more than just popular. Many argue it’s science.


Unless you’ve been living under a rock, you’ve heard about the ketogenic diet. Over the past few years, everyone from celebrities to self-appointed lifestyle gurus from Silicon Valley have hopped on to the “keto” craze, which exploded into mainstream popularity starting around 2017, according to Google Trends. In fact, keto devotees have hyped the extreme low-carb, high-fat diet’s supposed benefits — such as weight loss, clearer focus, and more even energy —  so much that the “global ketogenic foods market” is now a multibillion dollar industry.

Today’s proponents of “keto,” as it’s known for short, have even promised that it can help solve everything from acne to cancer to aging. But of course, as is usually the case for fad diets,  there’s much more to going keto than simply adding MCT oil to your coffee, or eating as many avocados as you can stomach. For starters, following the diet can be pretty tricky. Generally, the macronutrient breakdown for keto is 55% to 60% fat, 30% to 35% protein and 5% to 10% carbohydrates. That means if you’re aiming for 2,000 calories per day, you only get between between 20 to 50 g of carbohydrates per day. (For reference, a single banana has 27 grams of carbs.)

Also, the science supporting its usage is far from settled. “Keto shouldn’t be viewed as snake oil. There is definitely research behind it, but it varies from theoretical to proven,” says Angela Poff, PhD, a research associate at Department of Molecular Pharmacology and Physiology at the University of South Florida.

Ahead, we’ll dive into everything you should know about what science has to say about this trendy diet, from the history of its discovery to where the research is at now.

The History of the Ketogenic Diet

In 2021, the ketogenic diet will celebrate its 100th birthday. So in fact, though it seems new, it’s nothing new in scientific circles.

Scientists first came upon what would become the ketogenic diet by starting with an ancient remedy for seizures: fasting. For centuries, dating all the way back to the Ancient Grecce, various time periods of not eating had been used to limit the occurrence of seizures. “It’s even mentioned in the Bible,” Poff says. But the problem with fasting as a treatment, of course, is that one can only go without eating for so long. So, in the early 1920s, scientists began studying fasting in epileptic children. What they found was that after a few days of not eating, the body started breaking down fat to fuel your body’s processes — and for whatever reason, this metabolic shift was the key to fasting’s minimizing effect on seizures.

Keto shouldn’t be viewed as snake oil. There is definitely research behind it, but it varies from theoretical to proven.

What they realized was that “in a sense, when you’re fasting, you are eating a high-fat diet— it’s just that the fat is coming from storage, not the food you’re eating,” Poff says. And this idea ultimately led one Mayo Clinic physician, named Russel Wilder, to an interesting idea for a workaround of fasting’s fatal flaw: Perhaps they could design a specialized diet, one that was high in fat and low in carbs, that could starve the body of its normal fuel and thereby mimic the state of fasting. 

From there, the scientists “basically took a shot in the dark and guessed what this diet would look like,” Poff says. After testing out a formula that was roughly 5% to 10% carbohydrates, 30% to 35% protein and 55% to 60% fat they found that this diet — which they termed “ketogenic” for the way it mimicked the body’s fasting state, “ketosis”  — could significantly reduce and or even stop seizures in their young patients, no hunger (or muscle wasting) required.

How Does the Ketogenic Diet Work?

Put simply, the ketogenic diet works by forcing your body into a state of ketosis. This refers to the metabolic state your body is in during the process of breaking down fat into byproducts, known as ketones, that your body can use as fuel.

The ketogenic diet works by forcing your body into a state of ketosis. This refers to the metabolic state your body is in during the process of breaking down fat into byproducts, known as ketones, that your body can use as fuel.

When you’re eating a normal American diet, full of plenty of carbohydrates, your body is breaking these down into glucose that can enter your bloodstream and be used as fuel for all of your body’s processes. But when you become starved of carbohydrates, your body can’t make enough glucose to meet your energy needs. At this point, your body will then turn to a workaround: It will begin to look for fat it can break down into what’s known as ketones. 

“Ketones are basically an alternate energy fuel for your body, ” Poff explains. Also sometimes referred to as “ketone bodies,” they are simple compounds formed in the liver from the breakdown of fatty acids. “If you manipulate your diet into this high-fat, low-carb scenario, you will start making these ketones and they’ll rise to significant levels in your blood,” Poff says. From there, ketones will be further broken down to make adenosine triphosphate (ATP), the chemical that powers energy in your body’s cells, just as glucose would.

Ketogenic Diet and Weight Loss

The main reason for keto’s surging popularity today is its purported impacts on weight loss, and there is some evidence that keto can help people lose weight faster with minimal side effects than those on a more traditional low-fat diet. Studies have also shown keto to be particularly useful for those struggling to lose weight due to metabolic disorders like insulin resistance and even polycystic ovary syndrome.

That said, there are also side effects and risks to consider. Some report gastrointestinal distress, fatigue, and other symptoms during the transition to ketosis; this has become known as “keto flu.” People already taking insulin-controlling medications can suffer a severe complication known as ketoacidosis if their dosages are not adjusted before making the switch. 

All of this is why if you are going to give it a try, the best advice is to work with your doctor so your health can be monitored throughout. It’s also a good idea to involve a registered dietitian, who can make sure you’re still getting the vitamins, minerals, and other nutrition you need to support your health.

Ketogenic Diet and Aging

Beyond its usefulness in weight loss, the ketogenic diet has also garnered attention from scientists as a possible key to staving off aging and related diseases.

But also, it turns out ketones are not just a fuel source. “Ketones are also signalling molecules, meaning they can interact with receptors on the cell membrane,” Poff says. “They can also interact with other molecules present in the cells and in the blood.” For example, a 2015 study performed in mice found that ketones can stop the activation of certain inflammatory chemicals that become overactivated in many chronic diseases and in aging. Another mouse study from 2013 found that ketones may also have the ability to up-regulate our bodies natural antioxidant defense mechanism.

In yet another recent study, this one from 2018, rats fed a ketogenic diet “experienced a persistent elevation” in levels of the coenzyme nicotinamide adenine dinucleotide (NAD+), an essential protein that your cells can’t function without. It is known to decline with age, contributing to the cascade of breakdowns that occur in human aging. 

What this means is that theoretically, ketosis could contribute to the slowing of aging through a variety of different pathways: possibly by down-regulating oxidative stress and inflammation, and increasing the presence of key enzymes important for longevity. The theory that the ketogenic diet may help slow aging and lengthen healthspan is showing some promise in animal studies, but much more research is needed to see if this would translate to human aging.

What’s Next for the Ketogenic Diet?

Scientists are hopeful that one day the ketogenic diet may be used in treating way more than seizures. Currently, a variety of trials are ongoing to determine keto’s usefulness as part of treatment for certain types of cancer, as well as for other neurological disorders like Parkinson’s, Alzheimer’s, and multiple sclerosis. But at this point, all of this research is still in its infancy.

As for the benefits for healthy people, “the bulk of the evidence suggests there are definite benefits of experiencing ketosis for some periods of time,” Poff says. For example, animal and human studies of the diet’s effects have found improvements in obesity and type 2 diabetes but only for a limited time — though it’s unclear exactly how long — and sometimes with adverse side effects, like development of nonalcoholic fatty liver disease and insulin resistance.

We know that ketosis was key to our evolution as humans. “For a vast majority of human evolution, food scarcity was a major problem, so it was critical that even during scarcity, we would be able to support the energy needs of the brain. Ketones are a really big part of how we survived that. They’re really important because they’re the only other primary energy substrate for the brain outside of glucose.”

But there are still many unknowns. We don’t have studies on how keto affects your health if you stay on it for long periods of time, for example. And just because ketosis may have been useful to our ancestors, or work really well at controlling seizures, doesn’t mean it’s a cure-all. However, researchers are looking into ketosis in a variety of animal models to treat myriad diseases, including neurodegenerative disorders like Alzheimer’s, cancers and tumors. How these could translate to humans, and if, is yet to be understood. 

“It takes time to do the work,” Poff says. “We’re only just starting to see where the ketogenic diet might be useful and where it might not be. There’s a lot of emerging data and we still need longer, better studies in healthy individuals.”

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