Some Evidence-Based Answers to Your Frequently-Asked Questions: A 3-Part Series

Part 3: Ketogenic diet and aging

By Eric Verdin, President and CEO of the Buck Institute

This is the third and final installation of our series, “Some Evidence-Based Answers to Your Frequently-Asked Questions,” where I use up-to-date data and scientific research to answer the questions we get asked most  here at the Buck. In Part 1, we explored the health benefits of exercise on aging, and in Part 2, we discussed caloric restriction and intermittent fasting. In my concluding post, I will follow up on the topic of diet by discussing one that has exploded onto the scene in recent years, the ketogenic diet. What does the science tells us about its effects on health and aging?

What is a ketogenic diet and why are there so many cookbooks/meal-kits/blogs about it all of a sudden?

The ketogenic diet is a high-fat, low-carbohydrate diet. It has a long history as a therapeutic diet used in the treatment of pediatric epilepsy. More recently, it has gained widespread popularity as a diet to promote weight loss and athletic peak performance. Most relevant to the Buck, beneficial effects  of the keto diet have been suggested for chronic diseases including cancer, obesity, diabetes, and neurodegeneration.

The key nutritional aspect of the ketogenic diet is its high fat content relative to the carbohydrate content. A typical ketogenic has approximately 55% to 60% fat, 30% to 35% protein and 5% to 10% carbohydrates.

The reason low carbohydrates are so important for the ketogenic diet is because of how the body uses fuel. Metabolism is the process by which food is turned into energy for the body. The body preferentially uses carbohydrates as an energy source, breaking them down into simple sugar and burning that sugar to produce energy. When there are no carbs available, the body still needs energy. As an alternative fuel source, the liver turns stored fat into molecules called ketone bodies that can then be processed into usable energy for the heart, muscles, kidneys, and brain. Therefore, a diet that restricts carbohydrates in favor of fats will put the body into a constant state of ketosis, making use of an alternative metabolic pathway.

As noted, “doing keto” has recently exploded as a popular way to lose weight. There is indeed good evidence that a ketogenic diet can support weight loss, at least in the short term. There are several ways this may happen, including reduced hunger, decreased fat storage, and more calories devoted to burning energy.

How could the ketogenic diet be relevant to aging?

While the current popularity of the ketogenic diet is primarily due to its weight loss effects, there is also a growing body of literature suggesting potential long-term health effects.

Because the ketogenic diet emphasizes fat metabolism rather than sugar, insulin signaling is reduced while in ketosis. This may have positive benefits for diabetes and conditions related to inflammation, which underlies many age-related diseases.

A study that came out of my lab, with Buck faculty member Dr. John Newman as lead author, in 2017  demonstrated that feeding adult mice a ketogenic diet extended their median lifespan, improved physiological function, and prevented memory loss during aging compared to mice fed a calorie-matched, non-ketogenic diet. Ongoing studies are investigating the effect of the ketogenic diet on mouse models of chronic diseases including Alzheimer’s.

Are there any watch-outs concerning the keto diet?

The effects of a ketogenic diet on long-term human health are not yet clear. The ketogenic diet is associated with weight loss and improved cholesterol levels in obese patients, but whether this is attributable to overall reduction in calories or by other mechanisms is still unknown.

It is important to note that in some mammalian models, the ketogenic diet has been associated insulin resistance. Therefore, more research is needed to determine the appropriate applications of this diet. A careful assessment of existing risk factors by your physician is important before making any changes to your diet.

What’s the bottom line on keto?

The ketogenic diet is certainly a very exciting area of research. There is promising data about its impact on weight loss and long-term brain benefits in mice, but there is limited data on its long term health effects in humans. One concern is that it is critical to maintain a state of ketosis because  a high fat diet that doesn’t put you into ketosis is not too far off from the typical Western diet, which is associated with many chronic diseases of aging!  Intermittent fasting might be an effective way to introduce daily periods of ketosis, and here at the Buck we are investigating how ketone bodies might become an effective therapeutic without maintaining a ketogenic diet.

Thank you for following along in our series of frequently asked questions.  We have learned that there are no easy answers, especially in a topic as complex as aging. However, I will continue to provide my perspective on the evidence, as long as you keep the questions coming.