Autophagy Fasting: What You Should Know Before Starting Your Fast

Explore the science of autophagy and learn how it helps prevent diseases like cancer and diabetes through intermittent fasting, diet, and exercise.

Diana Licalzi
By Diana Licalzi
Lucia Gcingca
Edited by Lucia Gcingca

Published March 6, 2024.

a woman holding a knife and fork over a plate of food

Our cells go through a normal, physiological mechanism in which they quite literally feed on themselves—a process known as autophagy (pronounced aa-TAA-fuh-jee). The word autophagy stems from the Greek prefixes auto- (self) and -phagy (feed on). This form of cellular housekeeping allows our body to remove damaged parts of cells while recycling others. [1]

Inducing autophagy, especially through extended fasts, has become a popular habit among the longevity and biohacking crowds as a way to improve healthspan and live longer. But is this safe? How long is too long of an extended fast? Where does the current literature stand in humans? Let's dive into the popular (but still relatively uncharted) field of autophagy.

What is autophagy

Autophagy is a form of cellular housekeeping where misfolded proteins, damaged organelles, and pathogens are degraded and removed from cells.

How autophagy starts

  1. Formation of autophagosome: When autophagy kicks off, something called an "autophagosome" begins to take shape.
  2. Fusion with lysosome: This autophagosome combines with a tiny cell part filled with enzymes that break things down.
  3. Creation of autolysosome: The fusion of these two creates an "autolysosome," a place where cellular parts get broken down and recycled. [2]

Autophagy's role in your health

Cellular health

Autophagy plays a vital role in maintaining cellular health by leading to the removal of damaged and dysfunctional cells.

Disease prevention

Autophagy is critical in preventing various diseases, including:

  • Cancer
  • Diabetes
  • Infections
  • Autoimmune disorders
  • Neurodegenerative illnesses
  • Cardiovascular disease

Aging and longevity

Although autophagy naturally declines with age, animal and cell studies suggest that increasing autophagy activation may contribute to improved longevity and a longer lifespan. [3, 4]

» Can you increase longevity? Uncover the science behind living longer

Is autophagy good or bad?

Autophagy is like a delicate balancing act within our cells. If it's dysregulated—either too little or too much—it can have harmful consequences, potentially leading to abnormal cell growth or cell death.

  • Too little autophagy: When autophagy is halted for an extended period, it can disrupt normal cell growth and even contribute to the development of disorders like tumors.
  • Too much autophagy: In certain situations like cancer, excessive autophagy in tumor cells can act as a survival mechanism, allowing them to endure challenging conditions such as chemotherapy and low oxygen levels. [3]

Note: While current research is promising, further studies in humans are needed to gain a comprehensive understanding of the outcomes of induced autophagy.

How to induce autophagy

Autophagy can be induced by various safe and practical stress conditions, including calorie restriction (CR), fasting, and exercise. [3] Understanding when autophagy starts and how to induce it is essential for leveraging its benefits.

Calorie restriction

CR, involving a 10-40% reduction in overall caloric intake, emerges as a significant autophagy inducer. This approach aligns with the concept of an autophagy diet, where long-term CR (spanning 3-15 years) increases the expression of autophagy genes and the levels of molecules that remove dysfunctional proteins and organelles. [5]

Intermittent and extended fasting

In a 2019 crossover study, researchers analyzed numerous markers related to longevity, including the expression of autophagy genes. A group of 11 overweight adults followed an early time-restricted feeding (eTRF) schedule and a normal eating schedule.

The eTRF schedule improved longevity outcomes, including a 22% increase in the production of the autophagy gene LC3A after just four days. A handful of human studies also show extended fasts lead to increased autophagic activity through various mechanisms. [6, 7, 8]

How long do you need to fast for autophagy?

Evidence suggests that anywhere between 18 hours (as evidenced by the eTFR study) to four days will trigger autophagy. [6, 7. 8]

» Discover how intermittent fasting impacts longevity

Exercise and autophagy

Exercise triggers autophagy in muscle tissue. [9, 11] Autophagy markers increase after short, intense exercise sessions and longer moderate-intensity training. One study found that exercise intensity was a more significant factor for inducing autophagy than fasting, providing insights into achieving maximum autophagy through physical activity. [10]

What foods inhibit autophagy?

Interestingly, protein-based beverages may decrease autophagy activity. In a randomized control crossover trial, eight males were administered different protein/carb beverages after completing a 36-hour fast.

A marker of autophagy activity (LC3II/LC3I ratio) was measured during the fasting vs. the non-fasting periods. A decrease in autophagy occurred when the men sipped on the protein-rich beverages (leucine-rich whey or soy-based protein) but not the carbohydrate-rich ones.

The researchers noted that these findings align with rodent studies where branched-chain amino acids tend to suppress autophagy during catabolic conditions (like fasting). Glucose, on the other hand, doesn't impact autophagy. [8]

Does coffee stop autophagy?

Current research suggests that coffee does not stop autophagy. Research done in mice indicates that coffee stimulates autophagy in several tissues. [12]

a poster with different foods that promote autophagy

Foods that promote autophagy

Polyphenols, beneficial compounds found in plants, may play a role in inducing autophagy. Polyphenols stimulate various pathways, leading to autophagy and a longer lifespan. [4] For example, resveratrol is a common autophagy inducer in grape skins and nuts.

Other polyphenols include quercetin, green tea catechins, and curcumin. The following foods contain polyphenols that promote autophagy:

  • Green tea
  • Grape skin (red wine)
  • Nuts
  • Onions
  • Apples
  • Berries
  • Turmeric
  • Soybeans
  • Milk thistle

The power of balance

We've delved into autophagy, a natural process where your cells clean house. Fasting, especially intermittent fasting and calorie restriction, seems to be the key to activating autophagy, offering health benefits like reducing inflammation. But remember, balance is important—too much or too little autophagy can be harmful.

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