When Does Autophagy Start: 10 Ways to Induce Autophagy

Article based on science

How can we induce autophagy? And when does it start? Learn about methods and foods that promote autophagy backed by science.

Initially, there was a balance in humankind between feasting and fasting. Accordingly, almost every religion includes a fasting custom.

However, we experience an endless summer in terms of nutrition today. Thus, our endless feasting causes modern diseases, which are characterized by too much growth.

Autophagy is a process on cell level induced by fasting, which we hardly use any more.

Nevertheless, it’s precisely autophagy that can recycle cell waste and prevent those diseases ranging from obesity to cancer.

What Is Autophagy Fasting?

The word autophagy is derived from the Greek words auto (self) and phagein (to eat). Therefore it means “to eat oneself.”

Autophagy was first described in 1962 when researchers observed an increase in the number of lysosomes. These specific organelles broke down cell components in the liver cells of rats after the injection of glucagon.

In short, autophagy is a type of cell cleanse mechanism. In this process, the body identifies old and dysfunctional cell components and marks them for elimination.

Accordingly, autophagy can counteract the accumulation of old and broken cell parts responsible for the significant effects of aging and age-related diseases. These include, among others:

  • Alzheimer
  • Atherosclerosis (heart attack and stroke)
  • Fatty liver disease
  • Obesity
  • Cancer
  • Parkinson
  • Polycystic kidney disease
  • Polycystic ovary syndrome (PCOS)
  • Type 2 diabetes

Autophagy: Definition

Autophagy is the mechanism in our body that sorts out or recycles disused organelles, proteins, and cell membranes.

Moreover, autophagy starts when there is a lack of energy to maintain these decayed cell parts. With this in mind, it’s a regulated and structured process of degradation and recycling cellular waste.

Damaged subcellular parts and redundant proteins are marked for destruction and then sent to lysosomes.

Autophagy is very similar to what is perhaps better known as programmed cell death, or apoptosis.

Apoptosis programs cells to die after a certain number of divisions. Although this sounds a bit harsh, this process is essential for health.

Also, this process exists on a subcellular level – autophagy. Accordingly, it is the maintenance service in our cells, metaphorically spoken.

Instead of replacing the whole device (apoptosis), only the defective part is replaced (autophagy).

Thus, autophagy destroys subcellular organelles and builds new ones to replace them. As part of the process, the dysfunctional cell parts are sent to lysosomes. And these lysosomes are unique organelles that contain enzymes to break down proteins.

In this sense, autophagy has three essential tasks in our cells:

  • Remove dysfunctional proteins and organelles
  • Remove pathogens
  • Prevent atypical protein accumulation

Nobel Prize for Autophagy

Even Two Nobel Prize winners accompanied the term autophagy.

Since he discovered that lysosomes could break down cell components, the Belgian biochemist Christian de Duve was the first to shape the term autophagy.

Furthermore, he won the Nobel Prize in 1974 for this fundamental discovery.

However, a Japanese scientist started the decisive experiments on yeast cells in the early 1990s.

Lastly, it was Yoshinori Ohsumi that showed precisely how the processes in autophagy work and how crucial they are for health.

Therefore, he was awarded the Nobel Prize in Medicine in 2016 for his discovery of the mechanism induced by fasting.

Moreover, Yoshinori Ohsumi called his Nobel Lecture: “Autophagy – an intracellular recycling system” (Levine et al. 20171).

Autophagy and Intermittent Fasting

However, the advantages of fasting are not limited to autophagy. Because in principle, fasting induces two substantial mechanisms:

  • Activation of autophagy: Disposal of proteins and cell parts
  • Activation of growth hormone: Production of new, more powerful parts

Therefore, the combination of these mechanisms of fasting represents a complete renovation of the household in which we live.

Thus, fasting can reverse the entire aging process, as the body screens for dysfunctional cell parts and replaces them with new ones.

As we can often witness in nature, there is also a certain balance to autophagy. Because even from the best things, one can sometimes get too much.

Therefore both too much and too little autophagy can harm health. What we humans have forgotten in times of abundance is a healthy balance between eating and fasting.

And intermittent fasting is the simplest way to restore this balance. Thus, intermittent fasting enables cell growth during eating and cell cleansing during fasting.

Accordingly, you can even use this simple principle to build muscle sustainably.

Furthermore, research has shown that even short fasting periods activate neuronal autophagy and thus protect the brain from neurodegenerative diseases such as Alzheimer’s or Parkinson’s (Alirezaei et al. 20102).

When Does Autophagy Start?

Accordingly, nature has provided a certain balance for humankind:

  • On the one hand, we grow in times of abundant food
  • On the other hand, we can live on body fat for weeks or months during food scarcity (Stewart et al. 19733)

When food is scarce, the body does not want to grow. Thus, it’s a nutrient deprivation that induces autophagy.

Therefore, the human body has nutrient sensors that shut down or induce autophagy. Accordingly, there are three primary nutrient sensors:

  • Insulin: Sensitive to carbohydrates and proteins
  • mTOR: Sensitive to proteins
  • AMPK: Sensitive to lack of energy in cells

As soon as nutrient sensors detect low nutrient availability, autophagy kicks in.

Accordingly, the storage hormone insulin decreases during fasting, and its opponent glucagon, which induces consumption of stored energy, increases.

As a result, the increase in glucagon activates autophagy. In short, increasing glucagon by fasting is the most potent activator of autophagy.

Furthermore, mTOR (mechanistic or mammalian target of rapamycin) regulates autophagy. And this enzyme is particularly important for growth.

Therefore, mTOR is extremely sensitive to proteins. When mTOR is low, it induces autophagy. However, when you stimulate mTOR, autophagy stops.

And the last primary activator of autophagy is AMP-activated protein kinase (AMPK). This enzyme indicates the energy stored in a cell. However, high AMPK means a low energy level, and low AMPK represents a high energy level.

So if the cell’s battery is empty, AMPK increases and activates autophagy.

When cells have no energy, they want to act sustainably and recycle old proteins to produce energy.

As long as you do not stimulate any of these three nutrient sensors for about 14 hours, autophagy kicks in (Yang et al. 20174).

Hence, even 16/8 intermittent fasting indcues autophagy. Moreover, you can induce autophagy faster through exercise and nutrition.

What Breaks Autophagy?

Autophagy stops when we eat.

Since mTOR is the most central nutrient sensor, it integrates the signals from insulin and AMPK to determine whether the cell should divide and grow or go into a resting state.

As AMPK responds to all forms of energy, any macronutrient can activate both mTOR and AMPK:

  • Carbohydrates
  • Proteins
  • Fat

Therefore, even a small amount of glucose or amino acids can break autophagy.

With this in mind, autophagy occurs only when fasting. Simple calorie restriction or diets cannot activate autophagy.

When the nutrient sensors are activated, we signal our body that we want to grow. Thus, nutrient sensors stop autophagy.

For this reason, autophagy is a catabolic (degrading) and not an anabolic (building) mechanism. However, at any given time, there is a low basal level of autophagy because it is the maintenance service in our bodies.

Hence, excess nutrients put the body into growth mode via mTOR. On the other hand, fasting – the absence of nutrients – puts your body into maintenance mode.

How to Induce Autophagy

There are several scientifically proven methods to activate autophagy or to accelerate the achievement of autophagy induced by fasting:

1. Fasting

As we know, fasting is the primary tool to induce autophagy.

If you do not directly or indirectly activate the central nutrient sensor mTOR for at least 14 hours, autophagy kicks in (Yang et al. 20175).

According to animal studies, fasting can induce neural autophagy, particularly useful in preventing neurodegenerative diseases such as dementia (Alirezaei et al. 20106).

For this reason, many people report a sharpened focus and mental clarity when fasting.

In this sense, the easiest way to start fasting is to skip breakfast.

If you eat twice a day (i.e., at noon and 8 PM) and stick to unsweetened tea, water, or coffee without milk during fasting, you have already established a 16/8 intermittent fasting schedule.

Since morning hunger is a learned habit, you will quickly unlearn it and begin to benefit from autophagy.

2. Keto Diet

If you are keto- or fat-adapted, fasting can help you reach a significant state of autophagy more quickly.

Since keto, like fasting, is based on lowering insulin, emptying carbohydrate stores, and burning fat as a primary fuel, you are already on the road to autophagy.

Additionally, a ketogenic diet also activates the AMPK signaling pathway, another primary sensor inducing autophagy (Paoli et al. 20157).

With this in mind, a keto diet in rats induced autophagy and protected their brains from possible seizures (Wang et al. 20188).

3. Regular Exercise

In motion-related autophagy, lifelong exercise induces the most remarkable effects.

Accordingly, one study shows that people who have played soccer throughout their lives have far more autophagy markers based on gene activity than people of the same age who have not exercised regularly throughout their lives (Mancini et al. 20199).

Also, scientists could detect autophagy in the liver, muscles, pancreas, and adipose tissue in mice that they regularly trained on the treadmill (He et al. 201210).

4. Intense Exercise

According to studies, exercise intensity is more decisive for autophagy in muscles than a fasted-state (Schwalm et al. 201511).

Accordingly, HIIT (High-Intensity Interval Training) is probably the best way to induce autophagy quickly.

Foods That Promote Autophagy

Furthermore, certain nutrients in food can induce autophagy:

1. Coffee

Both caffeinated and decaffeinated coffee activates autophagy in muscle tissue, liver, heart, and other vital organs – at least in mice (Pietrocola et al. 201412).

When they were fed, this effect occurred as well. Hence, the mice did not have to fast to induce autophagy through coffee.

Since decaffeinated coffee also works, it is probably the antioxidants in coffee that account for these benefits of autophagy.

2. Red Wine

Resveratrol, a polyphenol, can also induce autophagy (Park et al. 201613).

Polyphenols are bioactive, antioxidant components, known to be contained in red wine.

Although it is questionable whether you should drink larger amounts of red wine to induce autophagy due to its alcohol content, one glass per day isn’t harmful.

Accordingly, scientists say this amount promotes health benefits (Yuan et al. 199714).

3. Green Tea

Just like red wine, green tea is full of bioactive polyphenols.

Accordingly, green tea consists of about 4000 different active compounds, but the most vital health benefits of green tea come from a particular class of polyphenols called catechins.

Accordingly, a recent study confirmed that the polyphenols in green tea induce autophagy (Prasanth et al. 201915).

Furthermore, the primary catechin epigallocatechin gallate (EGCG) in green tea can combat insulin-induced aging effects, type 2 diabetes, fatty liver, and lung cancer (Thielecke et al. 200916).

Due to its degree of fermentation, green tea outperforms black tea as it contains more polyphenols. Thus, green tea is the better choice than black tea, not only concerning autophagy but also mortality in general (Kuriyama et al. 200617).

4. Olive Oil

A recent study suggests that the anti-cancer properties of the most crucial antioxidant in extra virgin olive oil, oleuropein, occurs by inducing autophagy (Przychodzen et al. 201918).

Hence, this represents further scientific evidence of the positive effect of the Mediterranean diet on life expectancy, of which olive oil is the cornerstone.

For example, in the southern Italian village of Acciaroli, more than 300 people are over 100 years old and have virtually no age-related diseases such as dementia or strokes.

5. Turmeric

Curcumin is the primary phytonutrient in turmeric.

It is particularly useful in activating mitophagy – autophagy in our cellular power plants, mitochondria (de Oliveira et al. 201619).

Therefore, if you use turmeric as a seasoning for your favorite dishes, always combine it with black pepper. Why?

Since pepper contains piperine, it can increase the autophagy inducing effects of curcumin by a factor of 20 (Shoba et al. 199820).

If you want to use a dietary supplement instead, although organic turmeric powder is a more sustainable way, it should also contain black pepper.

6. Berberine

Berberine is a bioactive ingredient that occurs naturally in barberry, tree turmeric, Oregon grape, goldenseal, or yellowroot.

According to studies, berberine can activate autophagy (Jin et al. 201721).

You will most likely find berberine in the form of food supplements, such as powder or pills.

7 Benefits of Autophagy

As we have already experienced, too much growth and protein accumulation harm health.

Thus, modern diseases are all diseases characterized by excessive growth – from atherosclerosis over cancer to polycystic ovary syndrome.

All these diseases are treatable through dietary intervention, especially fasting, which, unlike drugs, fights causes instead of symptoms.

Furthermore, fasting-induced autophagy can repair age-related defects in cells. Therefore, the following vital effects are among the health benefits of autophagy:

1. Brain, Alzheimer’s, and Parkinson’s

Autophagy can help brain cells to excrete toxic proteins that contribute to dementia.

As they stick to neurons in the brain, the accumulation of these toxic proteins (β-Amyloid and Tau) is a significant contributor to Alzheimer’s, Parkinson’s, and Huntington’s disease.

Notably, autophagy in the brain decreases significantly in the early stages of dementia (Li et al. 201722).

In contrast, fasting induces autophagy in the brain. Thus, fasting can protect against neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease (Raefsky et al. 201723).

2. Aging and Longevity

Both fasting and resveratrol induced autophagy and thus increased life expectancy in animals.

As soon as the scientists removed autophagy-stimulating genes in these animals, the positive effect on life expectancy by fasting or resveratrol also disappeared (Nakamura et al. 201824).

Hence, scientists derive that autophagy is the leading cause that slows the aging process.

3. Cancer

On the one hand, autophagy repairs precisely those damaged proteins that contribute to tumor formation –known as the tumor suppressor effect (Yang et al. 201725).On the other hand, dysfunctional autophagy can also contribute to cancer.

Since tumors can be suppressed or promoted depending on their stage of development and tumor type, research intensively investigates the modulation of autophagy for cancer treatment.

With this in mind, researchers were able to use EGCG –  the primary polyphenol in green tea –  in a new treatment method to induce autophagy that triggered apoptosis, the death of the cancer cells (Prasanth et al. 201926).

Furthermore, studies suggest that influencing autophagy through intermittent fasting may contribute to improving the effectiveness of cancer therapies while protecting healthy cells (Antunes et al. 201827).

4. Insulin Resistance and Diabetes

Autophagy protects the insulin-producing beta cells in the pancreas (Yang et al. 201728).

When autophagy stops working correctly, the beta cells of the pancreas become damaged and eventually stop producing insulin.

Therefore, the adverse impairment of autophagy is a possible trigger of type 2 diabetes. Thus, increased autophagy can already be a preventive measure against pre-diabetes.

Furthermore, intermittent fasting can reverse the pre-existing disease known as insulin resistance and type 2 diabetes itself, which diets alone hardly can (Halberg et al. 200529).

5. Muscle Atrophy

Scientists have found that autophagy maintains and protects muscle tissue.

Also, autophagy can prevent age-related muscle atrophy. This effect on skeletal muscles is another indication that autophagy can slow down the systematic aging process (Jiao et al. 201730).

6. Osteoporosis

Autophagy can counteract not only muscle atrophy but also bone loss.

Thus, studies suggest that autophagy is also doing the housekeeping in bone cells and thus recycles dysfunctional bone cells (Florencio-Silva et al. 201731).

7. Heart Health

Autophagy does not stop at heart either. In this sense, research shows more and more that autophagy can probably renew damaged proteins and organelles in heart cells as well.

Thus, researchers conclude that autophagy can significantly reduce cardiovascular diseases (Sasaki et al. 201732).

Consistency Will Induce Autophagy

The health benefits of autophagy open up an entirely new therapeutic potential.

If we do not activate our nutrient sensors for at least 14 hours, we can stop much of the growth that is now making us sick.

Since both carbohydrates, fat, and protein activate nutrient sensors, these are the crucial rules for autophagy fasting:

  • No eating, no snacking
  • Only water, tea, and coffee
  • No milk or milk substitutes
  • No sugar or sweeteners

With this in mind, even non-caloric sweeteners such as aspartame or stevia stimulate the nutrient sensor insulin (Anton et al. 201033).

Consistent fasting is the most effective way to prevent modern diseases of excessive growth, such as obesity, diabetes, PCOS, and cancer.

How to Induce Autophagy FAQ

How long does it take for autophagy to start?

According to studies, autophagy kicks in after about 14 hours. Exercise, a ketogenic diet, and certain foods can speed up the process, as you will learn in this article.

Does fat stop autophagy?

Yes, all kinds of macronutrients, such as fat, will stop autophagy.

Does coffee affect autophagy?

Coffee without sugar, sweetener, milk, or any kind of milk substitute can even increase autophagy. Mostly religious reasons prohibit coffee during fasting. Learn more in my guide to coffee on intermittent fasting.

Does exercise induce autophagy?

Research has shown that regular and particularly intensive exercise can induce autophagy.

Studies

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Mag. Stephan Lederer, Bakk., MSc

Stephan is a writer and a true man of science holding multiple diplomas and master degrees among different areas of research. Closing the gap between the conventional perception of health and the latest scientific evidence is his greatest analytical passion – always following the data.

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