# Autophagy

Category: Metabolism

Autophagy is a catabolic cellular process activated by stress that Ray Peat viewed as a double-edged survival mechanism, not an unqualified good. Peat defined it as the activation of lysosomal enzymes to degrade damaged proteins into amino acids for reuse, a process that occurs…

8 passages · 3 authors · 2017–2023 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/autophagy

## Synthesis

**Autophagy** is a catabolic cellular process activated by stress that Ray Peat viewed as a double-edged survival mechanism, not an unqualified good. [Source 1, 3] Peat defined it as the activation of **lysosomal enzymes** to degrade damaged proteins into amino acids for reuse, a process that occurs steadily under normal conditions but becomes drastic under duress. [Source 2] He argued that autophagy is triggered by *glucose deprivation*, hypoxia, heavy metal poisoning, lipid peroxidation, and irradiation, allowing individual cells to survive at the expense of the organism's organized function. [Source 1, 3] When prolonged, this defensive state leads to *loss of tissue function*, fibrosis, or cancerization, as cells prioritize their own survival without regard to the whole. [Source 1, 3]

Peat detailed the biochemical cascade linking stress to autophagy, centering on the enzyme **heme oxygenase**. [Source 1] Stress induces heme oxygenase to produce carbon monoxide (CO), which, alongside estrogen, prevents apoptosis and promotes autophagy for short-term survival. [Source 1] The accumulation of **polyunsaturated fats (PUFA)** with aging amplifies this reaction, as their peroxidation produces toxins including CO, and stress-induced prostaglandin E2 further activates heme oxygenase and aromatase, increasing estrogen synthesis. [Source 1] Peat emphasized that the cholinergic nervous system, active during the night, also activates heme oxygenase, meaning even normal cyclic stress can, when combined with continuous low-level harmful factors, create *systemic inflammation and fibrosis*. [Source 1]

Peat explicitly cautioned against the popularization of autophagy induction, particularly through fasting. [Source 2] He stated that while autophagy is part of normal cell turnover, drastically intensifying it can prepare cells for either destruction or *cancerization*, and he advised against drugs known to amplify the process because some also promote tumor survival. [Source 2] Georgi Dinkov extended this critique, citing evidence that autophagy is a strong **tumor promoter** in a majority of cancers, with autophagy-inhibiting drugs now in clinical trials. [Source 6] Dinkov noted that fasting initially slows tumor growth but subsequently makes tumors highly aggressive and resistant to therapy. [Source 6] He characterized autophagy as an ancient evolutionary mechanism, akin to parathyroid hormone and serotonin, whose upregulation is generally undesirable. [Source 4]

Dinkov and Danny Roddy have argued that the benefits of fasting-induced autophagy are misrepresented, as the process is simply a *recycling of raw materials* during starvation, accompanied by damaging events like fatty acid release, stress system activation, and lipid peroxidation. [Source 5, 7] They highlighted that **thyroid hormone (T3)**, **fructose**, **glucose**, and **trehalose** can also increase autophagy, undermining the claim that fasting is the sole or optimal trigger. [Source 4, 7] Roddy summarized the perspective by stating that the body's stress response during fasting, including autophagy, is a sign of damage being framed as useful, a concept tied to a disrupted redox balance that promotes proliferation without serving the organism's overall health. [Source 8]

## People also ask

### How does heme oxygenase connect stress to autophagy?

Peat described a cascade where stress induces heme oxygenase to produce carbon monoxide, which, along with estrogen, blocks apoptosis and promotes autophagy for short-term cell survival, a process amplified by PUFA peroxidation and prostaglandin E2.

### Why did Peat warn against fasting to trigger autophagy?

Peat cautioned that drastically intensifying autophagy through fasting can prepare cells for destruction or cancerization, and Dinkov added that fasting initially slows tumor growth but later makes tumors highly aggressive and therapy-resistant.

### Can substances other than fasting increase autophagy?

Dinkov and Roddy noted that thyroid hormone (T3), fructose, glucose, and trehalose can also increase autophagy, undermining the claim that fasting is the sole or optimal trigger for the process.

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## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — From 'heroic medicine' to 'hormesis': First deny that harm is done

Ray Peat · Newsletter · 2017

> Autophagy is activated by stresses such as starvation, glucose deprivation, hypoxia, heavy metal poisoning, lipid peroxidation, and irradiation, allowing cells to survive. When the process is a direct response of cells to harmful environmental factors, while the nervous system is in a defensive state, the survival of individual cells will occur without regard to the pattern of the whole organism, and if the process is prolonged, the result will be loss of function of a tissue or organ, fibrosis, or cancerization.
>
> Part of the basic cellular defense reaction involves enzymes that process toxins in ways that improve the immediate situation, but that can create new problems for the organism if they become chronic. For example, stressed tissues produce carbon monoxide and estrogen, which prevent apoptosis and promote autophagy, with short-term survival value. Surviving in the stressed condition under the influence of CO and estrogen, the cells produce cytokines that affect the sensitivity of surrounding cells to stress and inflammation, and progressively undergo “epigenetic” changes, tending to become cells of a different type, with different types of metabolism, producing collagen to make the tissue more resistant to mechanical stresses, or becoming mobile cells, able to replace cells that have been destroyed, healing wounds.
>
> The autonomic nervous system controls the organism’s reactions to stress, with the cholinergic parasympathetic system tending to reduce glucose oxidation. Exaggerated activation of this system produces shock, with extreme inhibition of respiratory metabolism, but in normal circumstances, this system’s activity increases during the night and decreases during the day. Even under the normal cyclic activity of the nervous system, increased activity of heme oxygenase occurs during the night. Cholinergic chemicals activate heme oxygenase (Espada, et al., 2009; Hui, et al., 2012).
>
> This is very convenient when there are distinct wounds, and necessary for survival; but when the harmful factors are continuously present in small amounts, the continuing activation of these enzymes has a cumulative effect, creating systemic inflammation and systemic fibrosis, even in the brain, weakening the organized functioning of the organism.
>
> With aging, the accumulation of polyunsaturated fats intensifies those changes. Reacting with oxygen, the peroxidation of PUFA produces many toxins, including carbon monoxide (Wolff, 1976), and one of the basic enzymes induced by stress is cyclooxygenase, producing prostaglandins.

### Source 2 — One Radio Network: The True Nature of a Virus (September 21, 2020)

Ray Peat · Interview · Sep 21, 2020

> **Patrick Timpone:** What is Dr. Peat's opinion on autophagy, A-U-T-O-P-H-A-G-Y? What is that?
>
> **Ray Peat:** It's a new term for activating the lysozymes internal revision breakdown proteins. When a protein is damaged, it will get put into the lysosome and enzymes will degrade it into amino acids and it'll go back as a nutrient. So it's a process that goes on steadily but when it happens drastically and you get a sudden breakdown of the substance of the cell that can be preparation either for destroying cancer cells or for destroying normal cells and letting them turn into cancer cells so It has become kind of a fad, but it's just part of the normal cell turnover process, internal revision. And I think it's best not to take any drugs that are known to intensify the process because some of them also promote tumor survival instead of destruction.
>
> **Patrick Timpone:** We're very fortunate to have Dr. Peat on once a month, and he doesn't do medical advice and stuff, but he can give you his opinion on things. And if you'd like to join in, Patrick at OneRadioNetwork.com. This is from Harish. Could you please ask Dr. Peat? You mentioned in one of your interviews that you could not take sufficient thyroid when you had been in Florida because of the high heat and humidity. Does that mean that people living in tropical countries will not be able to take enough thyroid to fully fix their hypothyroid symptoms?

### Source 3 — From 'heroic medicine' to 'hormesis': First deny that harm is done

Ray Peat · Newsletter · 2017

> From a very early stage of development, the nervous system coordinates the interactions of tissues. The rate of growth and function of each tissue is adapted to the availability of the needed materials. Tissues in action consume resources, and idle tissues can dedifferentiate, redifferentiate, or disintegrate, according to the needs of the system. The parts of the developing organism are kept in balance by a hierarchy of mechanisms, intracellular, electronic-redox, mechanical, hormonal, nervous, and perceptual; Buckminster Fuller’s architectural concept of tensional integrity, “tensegrity,” is a better metaphor for physiology than the mechanistic medical concepts.
>
> “Defense” is only one specialized aspect of stress. In some species, prolonged deprivation leads to hibernation or estivation, decreasing energy needs during the time of dearth. Defensive reactions that simply assure survival often degrade functioning of the individual. In any organism, prolonged deprivation has epigenetic effects that are likely to become transgenerational. Growth of the brain, the organ with the highest requirement for oxidative energy production, is disproportionately affected by gestational stress, with its growth being retarded more than the growth of the rest of the body. For example, exposure to lead early in life (Cragg and Rees, 1984), at levels that aren’t directly neurotoxic, inhibits the growth of the brain, while stimulating the growth of the rest of the body, producing adults with a smaller brain/body ratio.
>
> In mediating adaptation, the brain orients the organism toward aspects of the environment that are most likely to satisfy its needs, and this involves making judgments of possible future situations. In the absence of good prospects, the brain concerns itself with defensive changes, increasing the stress hormones, the fight-or-flight mechanisms, and begins to convert some of its own tissues to energy and materials needed for the construction of brain and heart. Cortisol, for example, selectively breaks down proteins in muscles and thymus, and activates their conversion to glucose.
>
> The catabolic turnover of cell materials, including the process of autophagy, is an alternative to the organized disintegration of a cell, “apoptosis,” during stress. Autophagy is activated by stresses such as starvation, glucose deprivation, hypoxia, heavy metal poisoning, lipid peroxidation, and irradiation, allowing cells to survive.

### Source 4 — #100: Autophagy | mRNA in Food? | Bank Collapse | Elon Musk | Obesity Epidemic with Georgi Dinkov

Georgi Dinkov (with Georgi Dinkov) · Interview · May 15, 2023 · https://open.spotify.com/episode/1PoHaJpfNhJYWNn3o7qNuI

> **Georgi Dinkov:** Right. I mean, I would worry in the sense of like, I don't want to promote it, right? It's a process that's there. It's very ancient evolutionary. And I'm always wary of these ancient things because we came from like basically the slime, the shapeless slime that used mostly glycolysis. So anytime you activate an ancient mechanism like parathyroid hormone, serotonin, prolactin, these are not good things to upregulate. And autophagy seems to be one of the earliest processes that we evolved with.
>
> **Danny Roddy:** There was a certain doctor, I won't name names, but I remember maybe like five years ago. He was like, he posted an article, maybe I've mentioned this, I often repeat myself on here, but he posted a study on lower blood sugar increasing growth hormone on Twitter. And he was like, this is what those Ray, like P-tards will never understand that lower blood sugar equals higher growth hormone. Which promotes cancer, by the way.
>
> **Georgi Dinkov:** Yeah, it's like,
>
> **Danny Roddy:** yeah, the Ray people tend to think that growth hormone is bad stuff because everything that comes from the pituitary in excess is bad stuff, basically.

### Source 5 — Danny Roddy & Kyle Mamounis; carnivore diet, joe rogan's carnivore anger, paul saladino's honey

Danny Roddy · Interview · Oct 21, 2020 · https://www.youtube.com/watch?v=UPfqamxPmU4

> **Danny Roddy:** And your body's just like fighting tooth and nail. It doesn't care like what book you just read, like from some whack job about like a weird diet. It has these set points all over your body and a constant monitoring system. So anyway, it's just a real long explanation to say, I don't think there's anything magical about fasting-induced autophagy. And it makes total sense that it would get turned up in fasting because it's a way of getting

### Source 6 — #100: Autophagy | mRNA in Food? | Bank Collapse | Elon Musk | Obesity Epidemic with Georgi Dinkov

Georgi Dinkov · Interview · May 15, 2023 · https://open.spotify.com/episode/1PoHaJpfNhJYWNn3o7qNuI

> **Georgi Dinkov:** Yeah. So they basically, there's been a lot of talk about autophagy, I guess, in, in all circles, including medical and the dietary scene. And of course the, the, the proponents of autophagy are saying you cannot get into autophagy unless you fast. That's not true. Yeah. First of all, second of all, you got to be careful with autophagy. Autophagy is now known actually, and I think I've kind of mentioned it too on Paul Saladino's show as well, is that it's known to be a strong tumor promoter. And it kind of depends on the tumor type and stage. But basically, there's a large number of tumors. And I will probably, I'll go on a limb and say the majority of them, where autophagy is upregulated. And the reason we know it's contributing to the tumor growth is because there's several drugs that inhibit autophagy. And they're now in clinical trials for basically for treating the cancer. So they've already been proven to work in animal models and now they're in human clinical trials. So I don't think autophagy is something you want to mess with. You know, just the whole thing of like one cell eating another. It just reminds me actually of what cancer cells do. If you remember that study that cancer cells steal mitochondria from neighborhood cells around them. Well, that is a process that's very, very similar to autophagy. And in fact, it's probably like a cancer specific type of autophagy. So another study basically did a review of autophagy and promoting and inhibiting it and said that most cases of heart failure, autophagy is upregulated. Now, somebody can say, well, of course, you have a lot of dead cells in the heart and they need to be cleaned up and whatnot. But again, once you do the intervention part, right, you form a hypothesis that autophagy is bad. It's contributing to the heart disease. So you try to inhibit it and see if there's a good result. There was.

### Source 7 — #02: Zero-Carb and Carnivore Diet Critique with Ex-Carnivore Kyle Mamounis

Danny Roddy · Interview · May 17, 2019 · https://open.spotify.com/episode/5ngFPotpHRqRbU6OmcHpbB

> **Danny Roddy:** I don't want to speak for him. I think Ray's perspective was that all these other bad things are happening during the autophagy. So you can't really say, oh, there's that good thing when the fatty acids are being released, the activation of the stress systems, lipid peroxidation, et cetera. And I think that maybe that was his argument for ketones, but I think that might apply for the autophagy.
>
> **Kyle Mamounis:** Right, ketones are good, but how you get to them is bad.
>
> **Danny Roddy:** Yeah, exactly. Maybe I'm actually being a little bit confused, but, uh, uh, and also I think he is somewhere in one of his papers said that thyroid increased autophagy. And so does like Trehalose, the, some chemical and mushrooms or something. So I don't know if that's necessarily like the only way to do it is to fast or go on a keto or zero carb diet.

### Source 8 — #05: Global Warming, Serotonin, Dopamine, Nitric Oxide, Depression, and BPA with Georgi Dinkov

Georgi Dinkov · Interview · Jun 29, 2019 · https://open.spotify.com/episode/3IH5gP5oQMxEcgEikcoiEs

> **Danny Roddy:** Well, while we're on this subject, I forgot who, it might've been Nicholas Simpson. Do you know who that is? He's a very intelligent, um, he's definitely like on your level. He's a very smart guy. He, he has like a weightlifting thing, whatever. He's a, uh, interested in Ray Peat's work, but I think he commented on something about talking about, uh, long-term fasting or whatever. And you know how people are always saying this is beneficial for the auto. Um, how do you say it? Auto, auto faggy or. Autophagy.
>
> **Georgi Dinkov:** Autophagy or autophagy or whatever. Yes. Yes.
>
> **Danny Roddy:** And, and also like the stem cell recruitment, but like the, like in his interpretation was like, this was just a sign of damage basically, but it's being, it's being framed as something useful. And it gets back to that redox balance of promoting. Like you could promote proliferation through shifting the redox balance towards reduction. Exactly. But that necessarily wouldn't serve the... Like death by a thousand cuts. You're not going to want to do that in any situation where you're already likely... I mean, the environment... is putting us in that reduced redox balance. And so shifting things over in that direction is not necessarily going to be helpful, especially to increasing that proliferation and things.

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