Autophagy is how our cells recycle their components. Most of the time it runs quietly in the background. But when cells are stressed (such as during starvation or in the presence of dysfunctional proteins) it is increased in order to protect us.

Learn how you can maximize autophagy for your own health benefit.

Autophagy benefits

What is Autophagy?

Autophagy (from the Greek for self-eating) is the regulated process by which a cell degrades its dysfunctional or foreign components. The cell can then recycle useful chemical components for further purposes [R].

This allows autophagy to regulate the balance of protein composition in a cell, prevent the buildup of toxic waste products, maintain cellular organelle function, remove invading pathogens, and help sustain cells during periods of starvation [R].

The scientific importance of understanding autophagy was highlighted when the 2016 Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy.

Watch the video below for a quick introduction to how autophagy works:

Essentially, autophagy is the creation of a ‘garbage bag’ (autophagosome) that collects cellular components and then takes them to the cell’s ‘recycling center’ (lysosome) to be broken down into their parts which can then be recycled into new components.

Autophagy_process1-PMID26567363-compressed

Source: https://www.ncbi.nlm.nih.gov/pubmed/26567363

Autophagy-related genes (ATG) are responsible for creating the structures that carry out autophagy. The VPS34 complex initiates the autophagosome, ATG9 contributes to its expansion, and the ATG12-ATG5ATG16L1 complex recruits ATG8 proteins which complete formation and are involved in targeted capture [R].

Other genes are involved in turning autophagy on and off. In particular, genes that can detect changes in the cell. mTOR responds to the level of nutrients in a cell and decreases autophagy (by disrupting ULK1 preventing formation of the VPS34 complex) when there are plenty of nutrients available. AMPK monitors the energy levels in a cell (the amount of ATP) and activates autophagy when they are low. HIF1A detects oxygen levels and turns on autophagy (targeting mitochondria) when they are low (hypoxia) [R1, R2].

Sirtuin genes (activated by resveratrol) can inhibit mTOR which increases autophagy [R]. Low levels of NAD+ are also reported to increase autophagy [R].

To learn about how your own genetic makeup influences autophagy go to SelfDecode for further information.

The Benefits of Autophagy

Autophagy benefits

Source: https://www.ncbi.nlm.nih.gov/pubmed/25654554

When things are running smoothly in a cell, autophagy occurs at a low level, helping to recycle worn-out cellular components. It’s a type of ‘maintenance’ mode.

But when things become stressed in a cell (not enough nutrients or energy, dysfunctional components, or invasion by microbes), autophagy is turned up in order to help protect us. A ‘stress response’ mode.

Autophagy Can Extend Lifespans

Activation of autophagy counteracts the age-associated accumulation of damaged cellular components and enhances the metabolic efficiency of cells [R].

Autophagy is a response to stress that helps cells to become more resilient and conservative with their energy.

In particular, autophagy can be activated to remove dysfunctional mitochondria (mitophagy) which produce a lot of harmful reactive oxygen species (ROS) that degrade the cell [R].

These processes are reported to extend the lifespan of several species [R].

Autophagy Protects Against Psychiatric Disorders

Typical functioning of autophagy provides protection against the development of psychiatric disorders. Disruptions to autophagic processes have been associated with increased risk for some psychiatric conditions [R].

Post mortem studies of the brains of individuals with depression and schizophrenia identified deficiencies in essential autophagy pathways [R1, R2].

Autophagy Prevents Neurodegenerative Disorders

Many neurodegenerative disorders stem from accumulation of deformed proteins in and around neurons, inducing gradual brain cell death and subsequent loss of mental faculties [R].

Autophagy protects us by removing these proteins.

In Huntington disease it removes the huntingtin (HTT) protein [R], in Alzheimer’s disease it removes amyloid ꞵ (created from the APP protein) [R], in Parkinson disease it removes ⍺-synuclein (SNCA), and in dementia it removes microtubule associated protein tau (MAPT) [R].

Autophagy protects neurons.

Autophagy Protects Neurons.

Autophagy Helps Fight Against Infectious Diseases

Autophagy contributes to fighting infectious diseases in three ways; [R]

  1. Direct removal of microbes from inside of cells (xenophagy)
  2. Removal of toxins created by infections
  3. Modulation of the immune response to infections

Infectious microbes such as Mycobacterium tuberculosis and the Group A Streptococcus, along with viruses such as HIV and protozoans are removed by autophagy [R1, R2, R3, R4].

Autophagy Helps to Regulate Inflammation

Autophagy can both increase and decrease inflammation responses within the body.

It increases inflammation by presenting evidence of pathogen invasion and turning on the immune response.

Autophagy then decreases the inflammation brought about by an immune response by clearing the cell of antigens that are stimulating the response. Additionally, autophagy also removes pro-immune response molecules produced by the cell in response to an invasion [R].

Autophagy Improves Muscle Performance

When exercising we place a stress on our cells, energy use goes up and components get worn out faster.

Autophagy is increased in response to this in order to: [R]

  • maintain energy use balance within the cell
  • reduce the amount of external energy required (by more efficiently recycling existing energy molecules)
  • ensure that degraded cellular components are removed before they begin to cause any trouble
Autophagy Benefits Muscles

Autophagy Benefits Muscles

Autophagy Involvement in Cancer Prevention

Autophagy plays a role in preventing the onset of cancer and inhibiting growth of early stage cancers.

Autophagy suppresses pro-cancer processes such as chronic inflammation, DNA damage response, and genome instability [R].

Mice genetically engineered to have impaired autophagy are reported to have increased rates of cancer [R].

Unfortunately the protective roles of autophagy may also be harnessed by cancerous cells within tumors.

Autophagy in health and disease

Source: https://www.ncbi.nlm.nih.gov/pubmed/18706940

Cons of Autophagy

Autophagy Can Support Tumor Growth

While autophagy is useful for preventing the onset of cancer it can later be used by advanced cancerous cells. As tumors grow the cells in the middle become isolated from the blood supply and begin to undergo nutrient and energy stress. Activation of autophagy can provide support to these cancerous cells [R].

How You Can Increase Autophagy

Autophagy is an essential cellular process that can be activated in order to provide benefits to the body and mind.

There are basically two options; you can induce a bit of stress on your body to activate autophagy or you can ingest something that turns it on.

Stressing the body:

Artificially turning on autophagy:

  • Diet/Foods
  • Herbal remedies
  • Supplements
  • Traditional Chinese Medicine constituents
  • Cancer therapy drugs

Lifestyle Choices That Can Increase Autophagy

1) Autophagy is Activated by Aerobic Exercise

Aerobic exercise has been demonstrated to induce autophagy in muscle tissues and the brain. This is due to the prolonged stress placed upon cells which leads to autophagy activation [R].

Not only does exercising make you feel great and increase your fitness, it also activates autophagy to ensure your cells fully recover from the process.

The benefits of increased autophagy can thus be harnessed through exercising.

For example, the observation that aerobic exercise activates autophagy in the brain suggests that going for a run may help with protecting against the onset of neurodegenerative disorders by clearing out any malformed proteins in your neurons.

2) Autophagy is Increased by Intermittent Fasting and Caloric Restriction

Intermittent fasting and caloric restriction activate autophagy [R].

A lack of nutrient influx activates autophagy to increase the recycling of cellular components, ensuring cells continue to properly function with less requirement from external resources.

This can be achieved either by going for a period without any food (fasting) or by reducing the amount of food you eat (caloric restriction).

Short-term fasting has been demonstrated to induce profound neuronal autophagy and may be a good method for combating neurological conditions [R].

3) Autophagy is Promoted by the Ketogenic Diet

The ketogenic diet reduces carbohydrate intake and increases fat intake resulting in a shift of energy use from glucose to ketones.

This shift mimics the process that occurs during fasting and can lead to the increase of autophagy [R].

Ketogenic diets are reported to be particularly effective at promoting autophagy in the brain [R].

The ketogenic diet is a good alternative for individuals who struggle with fasting or caloric restriction approaches.

Read this post for more information about ketosis and the ketogenic diet.

Foods that Boost Autophagy

4) Autophagy is Induced by Coffee

Coffee has been demonstrated to increase autophagy throughout the body [R].

The health benefits of coffee have provided some contrasting results. With some studies reporting chronic consumption reducing overall mortality while others suggest coffee may increase inflammation.

5) Autophagy is Increased by Green Tea

Active ingredients in green tea activate autophagy. In particular, polyphenols such as epigallocatechin-3-Gallate (EGCG) are reported to have strong pro-autophagic effects [R].

Read this post to learn more about the health benefits of green tea.

Autophagy is Increased by Green Tea

Autophagy is Increased by Green Tea

6) Autophagy is Stimulated by Coconut Oil

Coconut oil consumption may stimulate autophagy by increasing ketone levels [R].

For more information on how coconut oil can add to your health check out this post.

7) Autophagy can be Activated by Ginger

An active constituent of ginger (6-shagol) can induce autophagy [R].

It is reported to block mTOR which in turn activates autophagy.

This post reviews the other health benefits of ginger.

8) Autophagy is Increased by Galangal

Galangal rhizomes are used in traditional southeast Asian dishes.

Galangin, a constituent of galangal, has been reported to induce autophagy via deacetylation of LC3 by SIRT1 [R].

9) Autophagy is Activated by Extracts of the Reishi Mushroom

Reishi mushroom (Ganoderma lucidum) has many health benefits, particularly relating to the immune system [R].

Extract of Reishi mushroom were demonstrated to induce autophagy and inhibit breast and colon cancer [R1, R2].

Read this post for more ways Reishi mushrooms can increase your health.

Natural Supplements that Increase Autophagy

10) Autophagy is Activated by Resveratrol

Resveratrol is a polyphenol found at low dosages in grapes, wine, peanuts, and soy [R].

Several studies have reported autophagy inducing activity for resveratrol [R1, R2, R3].

In order to ingest similar dosage levels to those in the reports it may be necessary to use resveratrol supplements.

The interaction between resveratrol and sirtuin genes is thought to facilitate the long-life benefits observed in some species.

Read this article outlining the many health benefits associated with resveratrol.

11) Autophagy is Turned Up by Medium-chain Triglycerides (MCTs)

MCTs have fatty acid tails that are 6-12 carbons in length. Ingesting them can significantly contribute to ketone levels in the body helping to boost autophagic processes [R].

MCTs can be purchased in an oil form.

12) Autophagy is Increased by Curcumin

Curcumin is the most active phytochemical in turmeric and has many health benefits [R].

Autophagy is reported to be activated by curcumin (via the AMPK signaling pathway) [R].

Go here for one of the most comprehensive posts about curcumin on the internet.

Autophagy is Increased by Curcumin

Autophagy is Increased by Curcumin

13) Autophagy is Activated by Vitamin D

Vitamin D is obtained through diet, supplements, and synthesized in the skin upon exposure to sunlight [R].

Research has shown that vitamin D induces autophagy and potentially plays a role in protecting pancreatic β‑cells, providing a possible avenue for diabetes therapeutics [R].

14) Autophagy is Promoted by Omega 6 and 3 Polyunsaturated Fats

Supplements containing omega 6 and 3 polyunsaturated fats can increase autophagy [R1, R2].

A study showed that inclusion of omega 6 polyunsaturated fatty acids in the diet of the nematode C. elegans significantly increased its lifespan [R].

An excellent source of omega fatty acids is fish oil. Read this post for more ways that fish oil can keep you healthy.

15) Autophagy is Increased by Nicotinamide

Nicotinamide is a member of the vitamin B family and an ingredient for making the essential energy molecule nicotinamide adenine dinucleotide (NAD).

It has been reported to forestall Alzheimer’s through increasing autophagy in neurons [R].

In particular, its ability to induce autophagic recycling of mitochondria is beneficial to cellular health [R].

For more information about where to find nicotinamide supplements and further health benefits check out this post on Nicotinamide Riboside.

16) Autophagy is Activated by Melatonin

Melatonin is a hormone that regulates many aspects of the body in relation to your circadian rhythm and sleep/wake cycles [R].

Melatonin induces autophagy and subsequently provide protection from neuropsychiatric disorders, prion diseases, and cancer [R1, R2, R3].

This post has detailed information about ways melatonin can be beneficial for your health.

17) Autophagy is Enhanced by Ginseng

Ginseng contains ginsenosides that have been reported to promote autophagy [R].

These activities are suggested to produce in anti-cancer effects [R].

sliced ginseng

Autophagy is Enhanced by Ginseng

18) Autophagy is Increased by Lithium

Lithium is a chemical element that is reported to have many health benefits when used as a supplement.

Lithium induces autophagy by inhibiting inositol triphosphate (IP3) [R].

IP3 is important to cellular Ca2+ transport and plays a role in neuronal plasticity.

Lithium has been reported to enhance degradation of aggregate-prone proteins that cause Huntington’s disease, Alzheimer’s and dementia [R].

Read this post for more information on how lithium can help with your health.

19) Autophagy is Boosted by Spermidine

Spermidine is a polyamine compound found in wide range of foods [R].  

It has been reported to assist with age-related declines and prolong the lifespan of several organisms through the activation of autophagy [R].

Foods with the highest reported levels of spermidine are soybean (dried) and one-year-old cheddar cheese [R].

20) Autophagy is Induced by Sulforaphane

Sulforaphane is a sulfur-containing organic compound found in cruciferous vegetables such as broccoli, cabbage, cauliflower, brussels sprouts and kale [R].

Sulforaphane induces autophagy in neuronal cells and has been reported to prevent prion protein-mediated neurotoxicity [R1, R2].

21) Autophagy is Promoted by Trehalose

Trehalose is a sugar that contributes to protecting the body.

It induces autophagy and has been reported to inhibit cytomegalovirus infection and have neuroprotective properties [R1, R2].

22) Autophagy is Induced by Ursolic Acid

Ursolic acid is a substance that comes from a variety of plants and herbs. It has been reported to have a variety of health benefits.

Ursolic acid has been shown to increase autophagy and contribute to cell death of breast cancer cells [R].

Read this post to learn more about the benefits of ursolic acid.

23) Other Natural Supplements that Increase Autophagy

  • Corynoxine, isolated from Uncaria rhynchophylla, promotes the clearance of alpha-synuclein via mTOR pathway [R].
  • Cedrol, found in the essential oil of conifers, induces autophagy and cell death of lung carcinoma cells [R].
  • Amla extract from Indian gooseberry (Emblica officinalis) induces autophagy and inhibits ovarian cancer proliferation [R].
  • Black hoof mushroom (Phellinus linteus) extract induces autophagy and inhibits breast cancer cell growth [R].
  • Extract of European black nightshade (Solanum nigrum) induces autophagy and inhibits colorectal carcinoma cells [R].
  • East Indian sandalwood oil induces autophagy and cell death in proliferating keratinocytes [R].
  • Neferine from the Indian Lotus (Nelumbo nucifera) induces autophagy through the inhibition of PI3K/Akt/mTOR pathway [R].
  • Anacardic acids, found in the shell of the cashew nut (Anacardium occidentale), induce autophagy and inhibit lung carcinoma (A549) cells [R].
  • Naringin, found in citrus fruits (especially grapefruit), induces autophagy-mediated growth inhibition of cancer cells [R].
  • Astin B, from Aster tataricus, induces apoptosis and autophagy in liver cells [R]
  • Oridonin, purified from the herb Rabdosia rubescens, induces autophagy and cell death in prostate cancer cells [R].

Drugs that Activate Autophagy

24) 6 Drugs that Increase Autophagy

Some drugs target the autophagic pathway in order to create their beneficial effect.

They can increase autophagy to help clear troublesome targets (e.g. bacteria and dysfunctional proteins) from within cells or they can use autophagy as a means of inducing the death of cancer cells.

Always consult a physician before taking any medication.

  • Sirolimus, also known as rapamycin, induces autophagy by inhibiting mTOR [R].
  • Fentanyl is a potent, synthetic opioid pain medication that induces autophagy via activation of the ROS/MAPK pathway [R].
  • Carbamazepine, a medication used primarily in the treatment of epilepsy and neuropathic pain, induces autophagy and has been shown to act on multidrug-resistant Mycobacterium tuberculosis [R].
  • Metformin, a diabetes drug, is an autophagic promoter that has been trialed in Alzheimer’s treatment and reported to improve anxiety-like behaviors [R1, R2].
  • Imatinib, a chemotherapy medication used to treat cancer, induces autophagy in chronic leukemia cells [R].
  • Bortezomib, an anticancer drug, induces autophagy in head and neck carcinoma cells [R].

How to Decrease Autophagy

While eating lots of protein and not exercising will prevent extra activation of autophagy it won’t actively decrease the basal level of autophagy in cells either.

6 Supplements that Decrease Autophagy

  • Epigallocatechin-3-Gallate (EGCG), a flavonoid found in green tea, has been reported to reduce autophagy in type-2 diabetic rats [R].
  • Eugenol, a phenolic acid found in clove (Syzygium aromaticum), was identified from a screen of 86 traditional Chinese medicines to have the strongest ability to decrease autophagy [R].
  • Bafilomycin A1, a macrolide antibiotic derived from Streptomyces griseus, has been reported to inhibit autophagy [R].
  • Elaiophylin was identified from a screen of North China Pharmaceutical Group Corporation’s pure compound library of microbial origin to have the best ability to decrease autophagy [R].
  • Oblongifolin C, a phenolic acid from the Asian tree Garcinia yunnanensis, inhibits autophagy and has been described as having anticancer properties [R].
  • Matrine, an alkaloid found in plants from the Sophora genus, is reported to be an autophagy inhibitor (via modulation of the lysosomal process) [R].

6 Drugs that Decrease Autophagy

Technical Details:

The Genetics of Autophagy

Autophagy Process with Key Genes

Autophagy Process with Key Genes (Source: https://www.ncbi.nlm.nih.gov/pubmed/24064518)

Autophagy is tightly controlled by turning on and off autophagy related genes (Atg). Individual genetic differences can strongly influence this process.

Go to SelfDecode to learn how you can have your own genetic makeup analysed for autophagy related conditions.

Genes Involved in the Mechanism of Autophagy

Autophagy begins with the creation of a phagophore from membranes enriched with phosphatidylinositol 3-phosphate (PI3P) [R].).

This enrichment is assisted by a group of proteins called the ‘VPS34 complex’ (VPS34, the regulatory subunit p150, BECLIN 1, and ATG14) [R].

Expansion of this membrane region is facilitated by ATG9 which cyclically introduces more lipids to the bi-lipid membrane [R].

The phagophore structure takes shape via the action of the proteins CapZ and WHAMM [R].

During maturation the ATG12-ATG5-ATG16L1 complex recruits ATG8 proteins (particularly cleaved LC3B and GABARAP). These assists with morphing into the ‘bag’ shape of the autophagosome [R].

Among the ATG8 family members, LC3A, B, and C are mostly involved in autophagosome formation while GABARAP, GABARAL1, and GATE-16 are involved later in the maturation step [R].

While autophagy is generally viewed as a random process, engulfing cellular components indiscriminately, it appears to also have the ability to target specific components for degradation [R].  

LC3 is reported to have a second function wherein it selectively incorporates cellular components that are exposing a specific structure (the LIR motif) [R].

Targeting of old parts of the endoplasmic reticulum and nuclear membrane is facilitated by FAM134 reticulon protein family [R].

NDP52 and OPTN are the main molecules involved in targeting mitochondria [R].

Components (proteins and bacterium) tagged for degradation (with ubiquitin) are targeted by p62 [R].

The cargo of an autophagosome is broken down and recycled by the contents of a lysosome. Attachment and fusing together of the two is facilitated by an interaction between ATG14, STX17, and SNAP-29 [R]-.

Genes Involved in Turning Autophagy On and Off

The majority of autophagy is controlled by mammalian target of rapamycin (mTOR). When nutrients are limited, mTOR is inactivated, which in turn induces autophagy [R].

mTOR suppresses the ULK complex (ULK1/2, ATG13, FIP200) which turns on the VPS34 complex and initiates phagophore ‘budding’ [R].

AMPK is a key sensor of intracellular energy under conditions of starvation or environmental stress. It can turn on autophagy by acting upon the ULK complex [R].

AMPK can also inactivate mTOR via the tuberous sclerosis complex (TSC) which prevents mTOR from blocking autophagy [R].

There are additional mechanisms for turning on and off autophagy that do not involve mTOR/AMPK. The inhibition of inositol monophosphatase and disruptions to the endoplasmic reticulum (causing the creation of faulty proteins) can both turn on autophagy [R1, R2].

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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12 COMMENTS

  • Robert Landry

    That’s what it sounds like but with fasting diet protocols, the overwhelming influence of all the autophagic processes, provided all the parameters are in fact adhered to, would dictate that that the autophagic decrease aspect of ECGC would have little to no effect on decreasing overall autophagy.

  • Dennis

    This web site: http://www.mdpi.com/1422-0067/18/7/1412/htm lists several herbs and the type of cancer it affects. I thought it was helpful for natural autophagy.

  • Tanya

    doesn’t autophagy cause some viruses to replicate?

  • Nathan

    So apparently Green Tea promotes autophagy but L-Theanine, which is in Green Tea, inhibits autophagy, or rather, EGCG inhibits mTOR while L-Theanine activates it. Talk about trying to lift the stool you’re sitting on. I was about to go on a fast and drink nothing but water and green tea, but nevermind I guess I can’t.

  • blue

    I noticed this too; it’s number 5 on the list of things that increase autophagy but also listed among supplements that reduce autophagy. It’s possible that, like melatonin, it suppresses autophagy in some circumstances and increases it in others. That may turn out to be true for all of these, actually, and since autophagy itself is desirable in some circumstances and potentially damaging in others, I suppose it makes sense that there’s no simple, uncomplicated answer. (Unfortunately for us)

  • Traci

    What about heavy cream or half and half in your coffeee? Butter is made from cre after all.

  • Luis Moreira

    Please explain the paradox concerning ECGC. Does it promote autophagy or does it exhibit an inhibitory effect on autophagy?

  • Dara

    Does intermittent fasting with coffee, butter & MCT oil increase autophagy? I’ve been looking for an objective source to answer this question. Thanks.

    1. Nattha Wannissorn, PhD

      Yes

      1. Dara

        Thank you Nattha. Could you share your source or reference? I can’t find anyone who says yes except for Dave Asprey. I like Dave, but don’t consider him objective about the topic of Bulletproof coffee.

        1. Nattha Wannissorn, PhD

          Just the idea that if you are in ketosis, you don’t turn on mTOR and you still have the benefits of autophagy. I’m not speaking for or against BP coffee.

  • Hisoo Park

    Ironically ECGC has both effect? (Increase and Decrease autophagy)

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