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Your Health Leveraging Ketosis as a Path to Healthy Aging
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The Keto Diet

Leveraging Ketosis as a Path to Healthy Aging

By Brady Holmer
The ketogenic diet is a popular way to lose weight and boost metabolic health. Regularly getting the body into ketosis through fasting, diet, or using ketone supplements might also help to slow down aging and improve healthspan.

Think about your current hobbies, relationships, and physical activity goals. Now picture yourself engaged in these activities in 20 years, or maybe even further into the future. Are you still doing them with the same vigor?

Wouldn’t it be great to keep up with your “younger self” all throughout life?

The concept of healthy aging is that the activities we love and enjoy should be achievable throughout life. Rather than the wear and tear of time, healthy aging is all about maintaining or even improving our capacity as we get older. Obviously, advancing in years is inevitable, but biological “aging” can be partially delayed using the right strategies.

One of these “strategies” might be entering a physiological state called ketosis. It’s a hot research topic, and science is revealing that this evolutionary program might have some pretty remarkable benefits for health and longevity.

WHAT IS KETOSIS?

Throughout human history, food wasn’t always as plentiful as it is now in an era of 24/7 fast food and access to nearly unlimited calories. Our ancestors went through periods of feast and famine; times where food was available and times where it was scarce. Somehow they survived, and this wasn’t by some stroke of luck. In order to keep fueled when carbs couldn’t cut it, we needed an alternative mechanism to provide energy. This was achieved through ketosis.

When someone is in ketosis, energy — in the form of adenosine triphosphate (ATP) — is being produced through the breakdown of ketone bodies rather than glucose, our “first-line” energy source. Ketosis is a “fat burning state.” Our body has virtually limitless stores of body fat, in contrast to the mere ~2000 calories that we can store as glucose in the form of glycogen.1. When outside sources of energy run low, stored fat can be broken down for energy and used to synthesize ketones. Ketone bodies are synthesized in the liver from the breakdown of fat. The two “primary” ketones circulating in the blood are beta-hydroxybutyrate (BHB) and acetoacetate (AcAc). Once produced, ketones can be circulated throughout the body, where they are broken down and used to produce ATP, helping meet the energetic demands of tissues.


...new research shows that ketosis might be leveraged in otherwise healthy individuals to help optimize things like cognitive function, metabolic health, and longevity.

A “definition” of ketosis has been accepted as a blood ketone concentration of ≥0.5 millimolar (mM).2 Ketosis can be achieved through dietary means like fasting or a ketogenic diet (this is known as “nutritional ketosis”) or through the use of exogenous supplements like ketone esters, ketone salts, and medium chain triglyceride (MCT) oil (MCT oil).

Once a mechanism to survive starvation, we now know that ketosis has important therapeutic effects on human health including helping to promote healthy weight management, maintaining blood sugar levels, and promoting cardiovascular health.3

Perhaps even more interesting — new research shows that ketosis might be leveraged in otherwise healthy individuals to help optimize things like cognitive function, metabolic health, and longevity.

HOW TO GET INTO KETOSIS

There are a few ways to get your body into ketosis.

Fasting: Fasting is an ancient practice that has regained popularity among health-conscious and longevity-focused individuals. Fasting — going extended periods of time without food — is one of the best known ways to induce ketosis because it deprives the body of glucose and activates conserved metabolic pathways, ketosis being one of them.4

Three popular fasting “regimens” include the 5:2 fast (fasting for 2 days each week), alternate day fasting (fasting or drastically reducing calories every other day), and time-restricted feeding (TRF).

How long does it take to get into ketosis while fasting? An overnight fast can elevate ketones to around 0.1-0.5mM — just under the “threshold” used to define ketosis.4 Extending a fast to 48 hours can raise ketones to around 1-2 mM, 2-3 days to 3mM, and a 5-day fast to 7-8mM.5,6

You might not even need to completely fast to enter ketosis. Reducing calories for a few days each week is enough. In one study, restricting calorie intake by ~20% every other day (alternate-day calorie restriction) elevated ketones by 4 to 6-fold on the “fasting” days.7 Similarly, limiting calories for 2 days each week increases blood ketones, and one week of a “hypocaloric diet” (1200kcal/day) also raises blood BHB.8, 9 This is the idea behind the “fasting mimicking diet (FMD)” popularized by scientist Dr. Valter Longo — dramatically reduce calories on a few days each week and achieve the benefits of fasting, without really “fasting.”

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Ketogenic Diet: Another method of inducing ketosis is by consuming a low-carb/high-fat diet, also known as a ketogenic diet, or keto for short. Today, uses for keto are wide-ranging, and even some athletes are using ketogenic diets to optimize performance.6

Keto diets contain around 80% of total calories from fat, 15% of calories from protein, and very limited carbohydrates — typically under 50g per day .6 Sources of dietary fat on keto are wide ranging and may include fatty cuts of meat, cheeses, eggs, high-fat dairy, nuts and seeds, avocados, and low-starch vegetables.

Such a drastic restriction of carbohydrates and a high provision of fat sets up the “ideal” conditions for the production of ketones. After about 2-4 days on a ketogenic diet, blood ketones can increase to around 1-2mM, which will be sustained as long as carbohydrate restriction continues.6

Workout on Empty: In addition to a keto diet, exercise after an overnight fast can also raise levels of ketone bodies. Studies have shown that after 2 hours of fasted exercise, blood ketones rise to around 0.5-1.0mM and might even increase further after exercise ends.6 Low-carbohydrate availability after an overnight fast and further reduction in muscle glycogen during exercise produce a state similar to fasting where the body is burning fat and producing ketones as an “alternative” source of energy. If you like working out on an empty stomach, keep it up.

Exogenous Ketones: Fasting may not be your cup of tea, and the ketogenic diet isn’t ideal for everyone. How then, can one achieve the benefits of ketosis? The relatively recent introduction of exogenous ketone supplements — ketone bodies that can be consumed as a “food source” — allows ketosis to be achieved even without fasting or a low-carb diet.

Exogenous ketones come in many forms, including ketone salts and ketone esters of different varieties. However, the most promising research and results are shown for esters of beta-hydroxybutyrate (BHB). BHB ketone esters can elevate blood ketones rapidly to around 3mM within 60 minutes of consumption and maintain ketone levels >1mM for up to 9 hours.11

Using exogenous ketones as a daily “supplement’ to maintain ketosis may also be beneficial, and has been shown to be safe in healthy adults. In fact, a recent study found that ketosis can be maintained over 28 days by ingesting 3 servings of a BHB ketone ester per day, without inducing any changes in body weight or causing negative side effects.12 Exogenous ketone supplements might be the next “keto mimicking diet.”

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HOW DOES KETOSIS AFFECT AGING?

We have many ways to naturally and artificially induce ketosis. People are beginning to use ketosis as a strategy to improve metabolic health and to boost mental and physical performance. It’s much more than a “weight loss” strategy.

While ketosis is particularly relevant for clinical conditions and general wellness, there is a growing interest in ketosis for healthspan and lifespan extension. It is well known that fasting and calorie restriction (CR) both increase lifespan in animals.13 Since fasting and CR also induce ketosis, this would suggest that ketones are responsible for some of the lifespan-enhancing effects of these regimens. It turns out, that is exactly the case.

Researchers, including Dr. Eric Verdin, MD and Dr. John Newman, MD, PhD from the Buck Institute for Research on Aging, are saying that BHB might be the molecule responsible for the healthy aging effects of ketosis.14

BHB is an energy substrate — this is well known. But studies show that BHB also acts as a signaling molecule in the body. BHB regulates the expression of genes, modifies proteins, and activates ancient genetic programs that enhance healthspan and prolong lifespan.14 Whether through BHB or some other pathway, studies find that ketosis is beneficial for optimizing healthy aging. Right now, most studies have been done in animals, but they still provide compelling and exciting evidence that ketosis might be the key to successful aging.

KETO DIETS AND HEALTHSPAN

Low-carb diets may be good for improving healthspan — that is the amount of “healthy years lived.” Mice who were put on a version of a low-carb/high-fat diet had an increase in their median lifespan, however, maximum lifespan wasn’t affected.15 They lived better, but not longer. These mice also aged more successfully. The keto diet mice had increased motor function and memory performance compared to the mice eating a control diet.15 This suggests that a ketogenic diet may preserve physiological and cognitive function with aging.

Another study, also in mice, showed that a cyclic ketogenic diet (keto every other week alternating with a control diet) reduced mid-life mortality and improved memory performance. Again, “healthspan” was increased, but not maximum lifespan.16

The decline in physical and cognitive function that is common to aging might be preventable by using a ketogenic diet. Unfortunately, the evidence isn’t clear if and how ketogenic diets might contribute to increasing the total number of years we can live. We will have to wait for the data on that.

EXOGENOUS KETONES AND HEALTHSPAN

The healthy aging effects of keto diets might be achievable through exogenous ketones. Since BHB is partly responsible for the lifespan-enhancing effects of calorie restriction and fasting, it has been hypothesized that providing BHB alone will have similar effects on longevity. 17

So far, this hypothesis has only been tested in worms. Giving the ketone BHB to a nematode known as C. elegans increased average lifespan by 20% and also improved heat tolerance, glucose control, and reduced the risk of neurodegenerative conditions, suggesting enhanced stress-resistance in these little crawlers.18

ADD KETOSIS TO YOUR TOOLKIT

The exciting new research on ketosis shows that this evolutionary energy pathway is likely beneficial for human healthspan and potentially for extending lifespan. More studies, eventually in humans, will tell us whether ketogenic diets and exogenous ketones are effective for maintaining youth and vitality. Now that exogenous ketone esters are commercially available, they may present a promising way to leverage ketosis for successful and healthy aging. So, whether you choose to eat a keto diet, intermittent fast, take exogenous ketones, or some combination of both, the research suggests you should be in ketosis at least occasionally — your health may depend on it.

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