Autophagy Fasting | Start | Stop | Induce | Methods | Diet | Benefits
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 characterized by too much growth.
Autophagy is a process on the cell level induced by fasting, which we hardly use anymore.
Nevertheless, it’s precisely autophagy that can recycle cell waste and prevent those modern diseases ranging from obesity to cancer.
What Is Autophagy Fasting?
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. After the glucagon injection, these specific organelles broke down cell components in rats’ liver cells.
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:
- Atherosclerosis (heart attack and stroke)
- Fatty liver disease
- Polycystic kidney disease
- Polycystic ovary syndrome (PCOS)
- Type 2 diabetes
Definition of Autophagy
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 of cellular waste.
Damaged subcellular parts and redundant proteins are marked for destruction and then sent to lysosomes.
Autophagy is 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 speaking.
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. The dysfunctional cell parts are sent to lysosomes as part of the process. 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 began decisive yeast cell experiments 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 discovering 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, fasting benefits 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 aging process, as the body screens for dysfunctional cell parts and replaces them with new ones.
As we often witness in nature, autophagy also has a certain balance. Because even from the best things, one can sometimes get too much.
Therefore both too much and too little autophagy can harm health. In times of abundance, humans have forgotten 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 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?
Autophagy starts after 14 to 16 hours if you are used to fasting.
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 crucial 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 one.
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.
Autophagy starts if you do not stimulate these three nutrient sensors for about 14 hours (Yang et al. 20174).
Hence, even 16/8 intermittent fasting induces autophagy. Moreover, you can induce autophagy faster through exercise and nutrition.
What Can Stop Autophagy While Fasting?
Autophagy stops when we eat or drink nutrients that break a fast. Even chewing gum might affect autophagy.
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 rest.
As AMPK responds to all forms of energy, any macronutrient can activate both mTOR and AMPK:
Therefore, even a tiny amount of glucose or amino acids can break autophagy.
With this in mind, autophagy occurs only when fasting. Simple calorie restrictions or diets cannot activate autophagy.
When the nutrient sensors are activated, we signal our body to grow. Thus, nutrient sensors stop autophagy.
For this reason, autophagy is a catabolic (degrading) and not an anabolic (building) mechanism. However, there is a low basal level of autophagy at any given time because it is our bodies’ maintenance service.
Hence, excess nutrients put the body into growth mode via mTOR. On the other hand, fasting – the absence of nutrients – puts your body in maintenance mode.
How to Induce Autophagy
You can induce autophagy through fasting, a keto diet, exercise, and special foods.
These scientifically proven ways activate autophagy or accelerate the timeline to induce autophagy through the most potent method, fasting:
As we know, fasting is the primary tool to induce autophagy.
Autophagy kicks in if you do not directly or indirectly activate the central nutrient sensor mTOR for at least 14 hours (Yang et al. 20175).
According to animal studies, fasting can induce neural autophagy, which is 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, skipping breakfast is the easiest way to start fasting.
If you eat twice daily (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.
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 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 regularly trained on the treadmill (He et al. 201210).
#4: Intense Exercise
According to studies, exercise intensity is more decisive for muscle autophagy than a fasted state (Schwalm et al. 201511).
Accordingly, HIIT (High-Intensity Interval Training) is probably the best way to induce autophagy quickly.
#5: Autophagy Diet Foods
Furthermore, certain nutrients in food can induce autophagy:
Caffeinated and decaffeinated coffee activates autophagy in muscle tissue, the liver, the 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 induce autophagy through coffee quickly.
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 more significant 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 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, green tea’s primary catechin epigallocatechin gallate (EGCG) 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 a better choice than black tea, concerning autophagy and general mortality (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, occur 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.
Curcumin is the primary phytonutrient in turmeric.
It is instrumental 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.
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 food supplements like powder or pills.
Benefits of Autophagy Fasting
As we have already experienced, too much growth and protein accumulation harm health.
Thus, modern diseases are all characterized by excessive growth – from atherosclerosis over cancer to polycystic ovary syndrome.
All these diseases are treatable through dietary intervention, especially fasting, which fights causes instead of symptoms, unlike drugs.
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 excrete toxic proteins that contribute to dementia.
As they stick to neurons in the brain, accumulating these toxic proteins (β-Amyloid and Tau) significantly contributes 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 (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, fasting or resveratrol’s positive effect on life expectancy disappeared (Nakamura et al. 201824).
Hence, scientists derive that autophagy is the leading cause that slows the aging process.
On the one hand, autophagy precisely repairs damaged proteins that contribute to tumor formation – 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 could use EGCG – the primary polyphenol in green tea – as a new treatment method to induce autophagy that triggers apoptosis, which means the death of cancer cells (Prasanth et al. 201926).
Furthermore, studies suggest that influencing autophagy through intermittent fasting may improve cancer therapies’ effectiveness 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, 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 indicates autophagy can slow systematic aging (Jiao et al. 201730).
Autophagy can counteract not only muscle atrophy but also bone loss.
Thus, studies suggest that autophagy also does 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.
Thus, researchers conclude that autophagy can significantly reduce cardiovascular diseases (Sasaki et al. 201732).
Consistent Fasting Helps 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 makes 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.
Learn how to successfully integrate fasting into your daily routine in my new book:
Induce Autophagy Fasting FAQ
How long does it take for autophagy to start?
According to studies, autophagy kicks in after about 14 hours. As you will learn in this article, exercise, a ketogenic diet, and certain foods can speed up the process.
Does fat stop autophagy?
Yes, all macronutrients, such as fat, will stop autophagy.
Does coffee affect autophagy?
Coffee without sugar, sweetener, milk, or any milk substitute can even increase autophagy. Mainly 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.
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This Post Has 19 Comments
Extremely well written and informative article. Takes alot of information, out on the net, and brings it together. Great job.
Thanks for your time to submit feedback. I am delighted that the information was helpful, and you appreciated that the article is backed by more science-backed sources than the average one 🙂
Have a great day and br,
I just bought your book off of amazon to compliment the information from Dr. Fung. Thank you for your work. I am doing alternate day fasting and wondering if I need to be concerned about not meeting my DV% for nutrients on the fasting days. Can I make up for it on the eating days? So for example we need about 4000 mg of potassium a day but that would mean I have to hit 8000 on my eating day and double for all the other nutrients. Another question would taking 2.5 grams of camu powder on my fasting days throw off autophagy?
I am delighted my work was helpful to you – thanks for the cheerful words!
1) Yes, the human body can store nutrients – that’s why we do not need to eat round the clock, as the food industry has told us. Find this and other myths about fasting debunked by science here.
2) Technically, Camu Powder breaks a fast since it’s 70% sugar. Your serving since is not much, but it will at least diminish autophagy – so it’s up to you to decide.
Have a great day,
I am confused by this article.
It says that Autophagy stops we when we eat, ergo:
and yet a Keto diet, which is high fat, one of the nutrients listed above, can induce Autophagy.
So does eating fat stop Autophagy, or induce it… which is it?
Thanks for the question.
As the article states: If you are keto-adapted, fasting can help you reach a significant state of autophagy more quickly.
So if your regular diet is high-fat low-carb, your insulin levels are way lower (healthier), and you can reach autophagy with fasting or working out more quickly. In contrast, if you are on a Western Pattern Diet (WPD) high in carbs, you might need 30 hours to reach a significant state of autophagy with fasting or even more. For this reason, it is so hard to tell when autophagy starts individually since it depends on lifestyle factors.
Thank you for the very well compiled and explained article.
I have been reading on and off on autophagy and the related subjects but this is for the first time, I feel that I have got the gist.
Thanks again and have a good day.
Hi, thank you for the article. One section confused me and I’d like a little clarification please. Olive oil is listed specifically as inducing Autophagy. Then later the article says fat stimulates the nutrient sensing pathways which then stop Autophagy. How can olive oil both stimulate Autophagy AND stop Autophagy? Is it dose related? Perhaps you could clarify the situation for me. Again, please and thank you.
thank you for your kind words! 🙂
The thing about food inducing autophagy is that it usually has macro-nutrients and hence stimulates one of the nutrient sensors in our bodies. Olive oil, however, is one of the best choices since it can only have an impact through AMPK and won’t stop ketosis. While there is no 100% on and off switch regarding autophagy, I suggest consuming autophagy-enhancing food in your diet, especially with meals before starting a fast.
Interesting you say there is no on and off switch for autophagy as that brings back to mind a comment I heard on a podcast that it is more like a dimmer switch getting weaker or stronger. So does that mean when I do a 36 hour fast to get into the best autophagy that if I need some fasting aids like bone broth or a bit of cream in my coffee I haven’t ruined my efforts to induce autophagy? If I needed a fasting aid just to extend my fast as long as possible rather than quitting earlier what would you suggest (other than the usual coffee, tea, sparkling water)
The things I recommend in my fasting books are bone broth, bulletproof coffee, and golden milk 🙂
If I am understanding this correctly, I can’t put any kind of sweetener or creamer of any kind in my coffee or it will curtail autophagy? Is honey included in that? Is there anything I can put in my coffee that will not affect autophagy? Thank you for your consideration.
Hi, Julia, that is correct.
There is not enough research to say if erythritol inhibits autophagy, but most likely, since other sugar alcohols like xylitol can break a fast (*). Moreover, even non-nutritive sweeteners like stevia inhibit autophagy since they directly induce insulin production in the pancreas without the intense effect on blood sugar (*).
Although I prefer it to sweeteners, honey is mostly sugar – so that’s going to ruin autophagy.
What is sold as “creamer” is absolute junk (50%+ refined sugar) – I would not put these substances in my coffee. If you want to lose weight put some real cream into your coffee – it still affects autophagy but not ketosis.
Thanks but could you please suggest the amount of coffee or green tea to be taken?
thanks for the question. You can find the answers in my guide to drinks during fasting.
Here’s a question. Is the 14 hour delay for autophagy to start absolute? If I’ve been fasting for 48 hours and then have some bone broth, sure, that will kick me out of my fast. But does it take another 14 hours before autophagy will start back up again or will it restart sooner since my glycogen stores are so depleted and the bone broth represented a minimal caloric load? Is it time based (a neural shot clock) or calorie based?
If you only had bone broth, it would go faster 🙂
Several ways can speed up the process, like exercise or a ketogenic diet (both deplete glycogen stores).
Have a great day,
Just a quick note to let you know how much I appreciate this article!
Very informative & helpful!
Thanks for your positive message. I am delighted my work could help you 🙂
Have a great day,