Improving Metabolic Health with Fasting and Ketosis for Healthy Aging

Here is a list of modern/chronic diseases associated with metabolic damage (i.e., mitochondrial dysfunction, insulin resistance, and metabolic inflexibility):

• Neurodegenerative disease: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, ALS, multiple sclerosis
• Cancer
• Type-2 Diabetes
• Obesity
• Metabolic syndrome
• Cardiovascular disease
• Mental disorders (depression, anxiety, bipolar disorder, schizophrenia)
• Migraine

And I am sure I am missing others.

Now, I am not saying these conditions are caused by metabolic damage, but then again, I’m not saying they aren’t. I simply find it fascinating that despite the apparent differences between all of these conditions, they share many metabolic characteristics.

What if these conditions were downstream to accumulated metabolic damage? Would the key to disease prevention be to prevent these metabolic problems?

I am interested in how I can stack the cards in my favor to extend my healthspan.

Yes, healthspan, not lifespan.

I know medicine can keep me alive well beyond my health, so frankly, I am not interested in extending my life without extending my health.

My goal is to get old slowly and die fast.

I believe that supporting my metabolism and thus, the health of my mitochondria is my best bet of reaching this goal. All of these metabolic disorders are associated with impaired capacity to burn fat, and diseased states are associated with a shift towards greater energy production from glucose and less from fat likely as a consequence of reduced mitochondrial efficiency.

So, how do we prevent insulin resistance, mitochondrial dysfunction, and metabolic inflexibility?

In my opinion, cycling between the fed and fasted state (i.e., ketosis), and supporting the body’s ability to burn sugar AND fat (and ketones made from burning fat) is a good strategy. Metabolic flexibility essentially describes the ability to switch between fuel sources depending on availability, so if you eat some carbs, you’ll burn sugar, but once that’s exhausted, you can tap into your body fat.

There are practical ways to enhance fat metabolism → ketogenic diets, intermittent fasting, calorie restriction, and exercise.

Every single one of these practices facilitates glycogen depletion, lowering glucose availability, and triggering the body to vet out an alternative fuel. Relying on fat and ketone metabolism supports the health and efficiency of our mitochondria, and you can manipulate what and when you eat to take advantage of this.

When morning rolls around, most people are just on the edge of getting into this fat-burning state and then abruptly stop this process by eating breakfast, and then continuing to eat throughout the day until it’s time to go to bed. This can become much more of an issue if you are feeding yourself refined grains and sugar, mixed with vegetable oils packaged into something considered “food.” Over the years, not only are you likely accumulating more and more body fat, but you are also slowly losing your ability to even burn fat. We store fat with the intention of burning it, and ironically the very organ (fat tissue) that once permitted our survival is the very organ leading us to an early grave.

The ketogenic diet mimics the fasted state even in the fed state, metabolically speaking. Both a ketogenic diet and fasting suppress the hormone insulin causing an elevation in the hormone glucagon, which favors the breakdown of fat and the production of ketones. Ketosis is simply the result of low glucose availability, where the body has transitioned from a sugar-burner to a fat- and ketone-burner. The human brain demands a constant supply of energy and in the carbohydrate-fed state, relies almost exclusively on glucose. We essentially have an unlimited capacity to store fat, but a finite ability to store glucose. If glucose stores drop (glycogen depletion), the brain needs an alternative fuel. Fat alone cannot cross the blood-brain barrier, so the liver converts fat to ketones, which do enter the brain and can be used as fuel. This also spares our muscles from being broken down and converted to glucose, which would have preserved our strength and ability to hunt and gather food when food was scarce. Collectively, ketosis allowed us to survive periods of starvation throughout evolution and arguably is the reason we survived and evolved as a species. Today, strategies that activate these primordial pathways are appealing as modern science continues to expose the wide range of benefits we can derive from ketones and the fasted state. Our genes haven’t changed; our environment has.

Over time, going into ketosis (the fasted state) with either a ketogenic diet, fasting, or a combination of the two promotes adaptations in the body that support metabolic health and make us really good fat-burners. These adaptations also allow us to derive more benefits from ketosis over time, such as reduced inflammation, up-regulation of anti-oxidant capacity, and greater resilience against stress. While I am a proponent of low carb and ketogenic diets, and this is my default diet, I am not of the opinion that carbohydrates as a macronutrient are inherently evil. Of course they’re not. Instead, I believe that the issues around carbohydrate intake are rooted in the type of carbohydrate, the amount you eat, and the frequency in which you eat them. Eating a whole-foods diet with some carbohydrates from fruits or starches is very different from refined grains and sugar, and I think if you eat a whole-foods based diet you can get away with a lot of different macronutrient ratios when you add in a component of fasting and/or exercise.

I don’t think we are going to find the answers to which is the optimal diet for longevity by focusing on one single macro or micronutrient or arguing over plant foods vs animal foods. I have not come across any research to suggest humans existed on a solely vegan or carnivore diet. Humans are opportunistic. We likely ate what we could find, and our metabolism evolved to deal with these changes. The problem with today’s modern food environment is that we don’t cycle anything. Most people are chronically in the “carbohydrate-fed state,” or the “glycogen full” state. In the context of a healthy diet, there is nothing wrong with being in the “fed” state, so long as you vary it with periods in the “fasted” state, you just don’t want to be in one of these states all the time.

Research from Dr. Valter Longo, longevity expert, and creator of the “Fasting Mimicking Diet,” has shown that the re-feed phase is part of why his protocol works. In animal models, organs shrink during the “fasting” cycle, and these tissues are renewed and remodeled when returning to regular food intake. The immune system, as well, can undergo renovations and come out stronger than before. Cycling into the fasted state is essential, it triggers these renewal programs, but re-feeding with adequate nutrition, especially protein, is equally important to supply our cells with the growth signals and building blocks that support optimal repair and restoration.

Fasting = Breaking down (cellular clean up/breakdown and recycling of damaged cells/cell components (autophagy))

Feeding = Building up (renewal and regeneration)

Growth factors should be cycled, and if you are supporting metabolic flexibility with periods of ketosis, you are essentially cycling growth factors. In this way, focusing on the lifestyle that supports metabolic flexibility and mitochondrial health hits many of the individual targets that longevity experts focus on.

Here is what I think: Everyone should maintain some period in a state of ketosis with a ketogenic diet to promote the adaptations that will support their ability to burn fat and ketones (keto-adaptation). Assuming you are not following a ketogenic diet to manage a disease, this can become a lifestyle by incorporating higher carb/protein or simply higher calorie days. This will prevent your body from adapting to ketosis and ketosis only, and promote overall better metabolic flexibility. Although there are several benefits you can derive from being in a sustained state of ketosis, there is likely benefits to kicking yourself out periodically, too. If a ketogenic diet isn’t for you, then you could follow a whole-foods lower carb diet and implement intermittent ketosis with fasting or short-term ketogenic diets as your method of flipping the metabolic switch.

Most people adopt a diet for weight loss, which I get. Weight loss itself can reverse a lot of metabolic damage. With that said, I believe that by focusing on improving your metabolic health, you will be pleasantly surprised by how these same practices can improve your body composition. You would be hard-pressed to find someone who is obese with perfect metabolic health. Weight loss, improved sleep, improved mood, fat loss, mental clarity, better energy, insulin sensitivity, metabolic flexibility, and thus healthy aging are all side effects of a healthy metabolism and healthy mitochondria.