The Physiological, Microbiological, and Cellular Effects of Fasting

A quite a long list of conditions might be made better by fasting, and now we delve into why. Much of this research is new, and further studies are needed to solidify exactly what is happening on a cellular level. But, some concepts have already been delineated and understood, and we are well on the way.

So let’s go through some of how fasting has changed the physiology of clinical trial participants and experimental animals and see what this could mean for the future of fasting and health. Let’s learn the physiological, microbiological, and cellular effects of fasting.

Fasting and cancer

For this particular case, we’ll be talking about calorie reduction rather than fasting (though fasting is a way to reduce your calories). Reduction of calories results in reduced inflammation, oxidative stress, reduction of insulin levels, and many other metabolic changes. The direct result of these changes is cellular adaptations that occur downstream (1).

Your body is designed to protect and modulate itself, but this process could be helped by fasting
Your body is designed to protect and modulate itself, but this process could be helped by fasting.

One of these changes is that immunosurveillance, which is your immune system “watching” for problems, starts to increase. A major cause of cancer is DNA mutations and changes, but DNA repair processes increase when caloric intake decreases. Cancer means your cells in some areas of your body are reproducing out of control, but this cell replication also decreases as caloric intake decreases (1).

Finally, carcinogen-detoxification enzymes, which are compounds in our body that attempt to reduce cancer-causing changes to our DNA and our cells. For all these reasons, researchers are now focused on clinical trials that can observe these cellular changes, as many of these concepts are based on cellular or animal models in a laboratory rather than human clinical observations.

There is much more to come as we continue to learn about how caloric restriction and its effect on cancer formation and progression, and the future is looking quite exciting to nutritionists and oncologists alike (1).

Autophagy

Autophagy literally translates to “self-eating” and occurs when the body needs to get rid of old, damaged, or dying cells. Essentially, the body breaks down and recycles the different proteins and cellular components and readies them to be used again in new cellular material.

The AMPK pathway (AMP-activated protein kinase) is the pathway that activates autophagy, allowing it to take place. AMPK regulates our metabolism at the mitochondrial level and is one of our energy-production moderators. AMPK is extremely important for our aging process, which is directly linked to mitochondria and metabolism. Our mitochondrial health is central to how we age and, ultimately, our lifespan (2).

Many theorize if we decrease our caloric intake and reduce our metabolic rate, then we might live longer. Of course, studies are ongoing, and no definitive answers have yet been found. But it’s a fascinating concept. Fasting is also thought to increase autophagy (2). By more efficiently ridding our body of cells that are nonfunctional or damaged, we may avoid diseases like cancer, which arise from damaged or altered cells.

Apoptosis

Apoptosis is related to autophagy, which we’ve already talked about. Where autophagy is the process of naturally recycling old cells and is part of a healthy body, apoptosis is a last resort strategy. Essentially a “cellular suicide,” apoptosis occurs when an unfixable error has been found within a cell, and the cell destroys itself before the problem can spread to neighboring cells (3).

For example, if a cell develops cancer and realizes it has a problem, then it destroys itself before cancer spreads to other cells, causing tumor formation and eventual cancer progression. Apoptosis is a last-ditch effort to prevent problems from becoming multi-cell when they begin to spread and become a serious health risk to the entire body.    

Fasting reduces activation of AKT and mTOR pathways in our body, which leads to autophagy and cell death, rather than an accumulation of body problems. This essentially means our body can better monitor itself before reaching the point when apoptosis and cell problems are becoming too prevalent or problematic. Its cellular monitoring and prevention at the most fundamental level.

Fasting also increases our ability to monitor DNA for damage, which induces mitochondrial changes that can result in apoptosis of unhealthy cells, eliminating future problems before they accumulate (4). For all these reasons, clinicians interesting in fasting as a medical intervention and aid suggest that fasting might be a way to improve our body’s ability to maintain its own health in a more efficient and self-driven way, reducing the need for external interventions (such as pharmaceutical treatments for disease, once they’ve become a problem the body cannot solve on its own).

Senescent cells

Senescent cells are another interesting problem our body deals with constantly, and usually so efficiently that we don’t even notice. Cellular senescence occurs when a cell is “arrested,” meaning it has been stopped in its replication cycle. Senescent cells cannot replicate, cannot be destroyed by apoptosis or autophagy, and basically exist without a purpose (5). Getting rid of these is vital for healthy body functioning, no matter where they occur. They cannot repair themselves or function as they need to.

anti-ageing properties of fasting
Senescent cells can be reduced by fasting, which may have anti-aging properties.

Senescent cells have been linked to our aging process (particularly the development of age-related diseases) because a buildup of them tends to occur with age. For example, a buildup of proteins associated with senescent cells in the brain may be partially responsible for cognitive decline as we get older (6).

Dr. Ming-Hui Zou at Georgia State University has been trying to crack this relationship between senescent cells, aging, and fasting for much of his research career. He and his team recently found that β-Hydroxybutyrate is a ketone body producing during fasting or caloric restriction at a higher rate. Interestingly, this compound can prevent cellular senescence (7).

Much more research remains by Dr. Zou’s research team has been recently working diligently on trying to find a way to harness these findings and use them to reduce Alzheimer’s disease and other age-related diseases through modulation of senescence, stimulated by fasting.

Glycogen depletion

Glycogen is a form of glucose that is stored primarily in the liver. When our body is too low on energy and needs more than what our day’s food can provide, it extracts the glycogen from the liver and uses it as a backup energy source to keep our muscles running and body functioning in the absence of food (8). Clearly, glycogen depletion (removal from the liver for use) is directly related to fasting because fasting often results in glycogen depletion.

In a study done with rats, those rats that had fasted for 24 hours before exercising could run longer before becoming exhausted. The researchers suggest that fasting increased the rats’ ability to utilize fatty acids during exercise, thus increasing endurance (9).

This means fasting might have further impacts than we thought on glycogen depletion and endurance during exercise. Rather than simply switching us to using stored glycogen, fasting before exercise might make our body more readily able to use our stored fats, increasing the weight-loss benefit of exercise.

Ketone upregulation

Ketone bodies are a double-edged sword and are good and bad for our health in different contexts. Ketone bodies can be made out of fatty acids, transported in our blood, and used as an alternative energy source. When you look at diets focused on proteins rather than sugar and carbohydrates, these diets aim to switch your body to ketone metabolism rather than carbohydrate metabolism. By doing this, you’ll break down fatty acids and fat stores on your body instead of glycogen as a backup energy source.

Diabetic ketoacidosis is an unhealthy and dangerous state, but ketone bodies are not in themselves a bad thing
Diabetic ketoacidosis is an unhealthy and dangerous state, but ketone bodies are not in themselves a bad thing.

Those are all the great things about ketone bodies and why some desire to elevate their ketone counts. But, fundamentally, high levels of ketones are not healthy. People with diabetes can suffer from “diabetic ketoacidosis,” which means ketones build up in their blood as their body tries to get the energy of any kind into their sugar-starved cells (without insulin, the sugar can’t get into the cells).

Ketone levels of 15-25mM or higher result in pH imbalances (10), causing nausea and vomiting, abdominal pain, fatigue, confusion, and shortness of breath (11). But, a state of nutritional ketosis (simply switching your body over to protein-based metabolism, with no incidence of diabetes) typically results in ketone levels of 0.5-3mM (significantly lower than the dangerous levels resulting in the previously listed medical symptoms). So the good news is you likely won’t have these symptoms if you’re achieving ketosis through diet.

Fasting is known to cause ketosis, as your body attempts to find alternative energy sources (12). This is good for weight management because your body will eventually begin to break down its own fatty acid stores. However, starting to eat sugar again will likely undo the process, so accompanying this with a ketone-focused diet is often recommended for long-term health maintenance.

In rats, two days of fasting resulted in ketone body production, higher metabolic rates, and fat storage decrease (13). This could reduce the incidences of obesity and type 2 diabetes if applied properly (14). As with many health regimes, we always recommend consulting your healthcare team before drastically changing your diet and exercise or partaking in a fast longer than 24 hours.

Now that you know the physiological, microbiological, and cellular effects of fasting, check out “Satia’s Complete Guide to Fasting.”

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