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How Long Do You Need to Fast for Autophagy?

Reviewed on 3/22/2021

What is autophagy?

Autophagy
Autophagy may engulf non-specific cell components, or selectively remove damaged components or invasive bacteria and other pathogens.

Autophagy is a natural cellular mechanism by which the cells in our body degrade unnecessary or damaged components within the cell. The process of autophagy helps maintain normal functioning (homeostasis) in the cell. The term “autophagy” literally means “self-eating.”

Though autophagy sounds like self-destruction, the process actually helps clean up harmful material inside the cells and rejuvenates them. Autophagy may completely destroy damaged molecules, or recycle them into new components which can be used for cellular repair.

In times of stress, when cells are deprived of nutrients or oxygen, autophagy can provide an alternate source of energy from the recycled cellular material to help them survive. Autophagy can help the immune system by cleaning up toxins and infectious agents.

Under certain conditions, autophagy can also induce programmed cell death (apoptosis). In short, autophagy is a part of a cellular process that maintains cell homeostasis by finding a balance between making and breaking cellular components.

What is the process of autophagy?

Autophagy forms a part of the metabolic process which helps cells convert food into a form of energy that cells can use to grow and divide. Metabolism balances between two opposing activities, anabolism, and catabolism.

Anabolism is a process that synthesizes molecules and builds cellular structures, while catabolism breaks them down. Autophagy is a catabolic process.

A human cell is composed of a nucleus, surrounded by a semifluid substance known as cytoplasm, enclosed within a cellular membrane. The cytoplasm is made up of a solution known as cytosol, protein molecules, and structures known as organelles, which are essential for the survival and functioning of the cell.

During autophagy, a semicircular membrane known as phagophore forms and closes around some of the molecules and organelles in the cytoplasm and becomes what is known as an autophagosome.

The autophagosome fuses with an organelle known as the lysosome. The lysosome contains digestive enzymes that break down the contents of the autophagosome. The resulting molecules are released back into the cytosol to be recycled and used in the metabolic process.

Autophagy is a natural process that occurs all the time in the cell, less when well-fed, and more when under stress. Autophagy may engulf non-specific cell components, or selectively remove damaged components or invasive bacteria and other pathogens.

What is autophagy in fasting?

Intermittent fasting is a possible way to induce autophagy. Under normal conditions, when the cell has sufficient nutrients, autophagy degrades damaged components in the cell. When fasting starves the cells, autophagy helps digest some of the cell components, to provide the necessary energy for survival.

The liver stores excess glucose as glycogen. When glucose levels drop with fasting, the liver converts glycogen into glucose and releases it. After the stored glucose is depleted, the liver breaks down fat to make a substance known as ketones to provide energy. This process is known as ketosis.

Many people follow intermittent fasting and calorie restriction diets for weight reduction. A currently popular diet known as the ketogenic diet, in which 75% of the daily calories come from fat, is believed to induce ketosis and autophagy. There are insufficient studies on the long-term effects of the ketogenic diet.

Research indicates that intermittent fasting, calorie restriction, and ketosis can all trigger autophagy. However, a majority of studies have so far been conducted only on animals. It is also not clear what type of cells initiate autophagy in response to fasting. For instance, fasting may induce autophagy in any type of cell and not necessarily in fat cells.

How long do you need to fast for autophagy?

Depending on the individual’s metabolism, significant autophagy may take two to four days of fasting in humans. Autophagy is believed to begin when glucose and insulin levels drop considerably. Animal studies have shown evidence of autophagy after 24 hours of fasting, which starts peaking at around 48 hours of fasting.

Some studies have detected autophagy in human cultured neutrophils (the most abundant type of immune cell in the blood) after 24 hours. There are, however, no conclusive studies on humans that indicate an optimal period of fasting to achieve autophagy. However, do not attempt to fast to induce autophagy without discussing this method with your doctor.

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How do you increase autophagy?

Research suggests that autophagy may increase from activities that cause stress to the cells, such as:

  • Lack of nutrients due to prolonged fasting for two to three days
  • Physical exercise, which can cause damage to the cells, triggering autophagy
  • Certain diets like the ketogenic diet deprive the body of carbohydrates

Some foods believed to trigger autophagy include the following:

Is autophagy good or bad?

Current research does not provide a full picture of the effects of autophagy or how best to induce it. Studies show that autophagy can be both good or bad depending on the situation. 

Following are some examples to show how autophagy can be good or bad:

  • Cancers: Autophagy can prevent the development of cancer by getting rid of damaged cell components, but can also help tumor cells survive under stress at later stages. Inhibiting autophagy has been found to cause death in only certain types of tumor cells which depend on autophagy for survival.
  • Infections: In bacterial and viral infections, autophagy has been found to be good with certain species and bad with others. Autophagy is able to kill some pathogens, but some bacteria and viruses subvert the autophagy process to replicate and spread.
  • Neurodegenerative diseases: Autophagy may have a protective effect in neurodegenerative diseases such as Alzheimer’s and Parkinson’s, by breaking down harmful proteins that accumulate in the brain. Autophagy, however, may also facilitate the generation of certain proteins inside the nerve cell which can lead to its degeneration.
  • Cell death: Autophagy plays a role in cell death, but studies show that different cells react differently. Autophagy promotes cell death when treated with chemotherapy in some cancers, but helps the cell survive in some cancers.

Autophagy may be a method of treatment in many diseases in the future but requires more research to understand the many dimensions of autophagy and the specific ways it works.

The best ways to induce autophagy, and its particular benefits in weight loss are not fully understood and must not be attempted without consulting with your doctor. Prolonged fasting, calorie restriction, and diets that restrict food groups may pose higher risks for people with chronic conditions such as diabetes or heart disease.

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References
https://www.news-medical.net/life-sciences/What-is-Autophagy.aspx

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196727/

https://www.nature.com/scitable/topicpage/the-discovery-of-lysosomes-and-autophagy-14199828/

https://naomiw.com/blogs/nutrition/how-long-for-autophagy-to-kick-in-when-fasting

https://lifeapps.io/fasting/the-5-stages-of-intermittent-fasting/

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