# Oxidative phosphorylation

Category: Metabolism

Also known as: OXPHOS

Oxidative phosphorylation (OXPHOS) is the mitochondrial process of fully oxidizing fuel—primarily glucose—to carbon dioxide, water, and ATP, and its impairment is the central metabolic defect underlying cancer and virtually all chronic disease. Peat argued that the efficiency…

11 passages · 2 authors · 1972–2025 · Most-cited: [Georgi Dinkov](https://bioenergeticoracle.com/md/voices/georgi-dinkov/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/oxidative-phosphorylation

## Synthesis

**Oxidative phosphorylation (OXPHOS)** is the mitochondrial process of fully oxidizing fuel—primarily glucose—to carbon dioxide, water, and ATP, and its impairment is the central metabolic defect underlying cancer and virtually all chronic disease. [Source 6, 10] Peat argued that the efficiency of this coupling increases with higher evolutionary development and alertness, suggesting that a *less wasteful use of oxygen* is a crucial factor in longevity. [Source 3] Dinkov has written that when forward electron flow through the OXPHOS complexes is blocked, **reverse electron flow** commences, generating an excess of **reactive oxygen species (ROS)**; this occurs predominantly when metabolism is low or obstructed, not when it is high. [Source 10] A properly functioning system, producing optimal amounts of CO₂ and water, generates negligible ROS because the rapid flow of electrons exerts a pulling effect that prevents electron leakage. [Source 5, 9]

The degradation of OXPHOS is a common adaptive response to a hostile cellular environment. Dinkov explains that under chronic stress—whether from viral infection, poor diet, or environmental factors—the cell begins dismantling its oxidative apparatus, reverting to a primitive *anaerobic energy production* state identical to the **Warburg effect** seen in cancer. [Source 2] This shift involves a loss of cellular differentiation; Dinkov notes that any differentiated cell can de-differentiate into a stem-like state if mitochondrial ROS production rises beyond a threshold, a finding that reframes cancer as a reversible metabolic condition rather than an irreversible genetic one. [Source 10] Peat identified specific landmarks vulnerable to disruption, including **phosphofructokinase-1 (PFK1)**, **pyruvate dehydrogenase (PDH)**, and **cytochrome c oxidase**, with fat oxidation inherently biasing the system toward inefficiency by overproducing FADH₂ relative to NADH, which reduces the availability of ubiquinone at Complex I and backs up electron flow. [Source 5]

Estrogen and other stressors directly interfere with OXPHOS. Peat’s early work noted that estrogen’s action might occur through a disruption of oxidative phosphorylation, leading to altered intracellular potassium-to-sodium ratios and a phase change in cytoplasmic structure. [Source 1] Dinkov has extended this by identifying specific interventions that restore electron flow through blocked complexes. The quinone **coenzyme Q10**, which is deficient in cancer patients, acts as a critical electron carrier, and other quinones like **methylene blue** can substitute for it, functioning as an oxidant that paradoxically acts as an antioxidant by enabling proper electron transit and preventing ROS formation. [Source 4, 5] B vitamins such as **riboflavin**, **thiamine**, and **niacin** serve as essential cofactors for the OXPHOS complexes, and their administration—along with agents like aspirin metabolites or pregnenolone—has shown promise in restoring oxidative metabolism in cancer cells without triggering the systemic inflammation caused by cytotoxic therapies. [Source 7, 11]

The systemic consequences of OXPHOS failure extend beyond the initial site of injury. Dinkov describes how killing cancer cells with chemotherapy or radiation spills mitochondrial debris into the bloodstream, triggering inflammatory pathways that signal the entire body to shut down oxidative phosphorylation, thereby creating a permissive environment for metastatic dissemination. [Source 8] This reinforces the principle that *metabolic modulation*—raising the low metabolic rate characteristic of disease—is the therapeutic goal, not cellular destruction. [Source 10] Peat maintained that the faster the oxidative apparatus runs, the more it creates an electron-withdrawing effect that protects surrounding cells, making the maximally efficient production of CO₂ a form of structural insurance against degeneration. [Source 5]

## People also ask

### How does oxidative phosphorylation relate to cancer development?

Peat and Dinkov described cancer as a reversible metabolic condition where cells dismantle their oxidative phosphorylation apparatus under chronic stress, reverting to anaerobic energy production in a process identical to the Warburg effect.

### Why does high oxidative metabolism produce fewer reactive oxygen species?

The entry explains that a properly functioning system generates negligible ROS because the rapid flow of electrons exerts a pulling effect that prevents electron leakage, meaning ROS overproduction occurs when metabolism is low or obstructed, not when it is high.

### What substances can help restore blocked oxidative phosphorylation?

Dinkov identified coenzyme Q10 and methylene blue as electron carriers that can substitute for deficient quinones, while B vitamins like riboflavin, thiamine, and niacin serve as essential cofactors for the OXPHOS complexes.

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## Cited passages

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

### Source 1 — Age-related oxidative changes in the hamster uterus

Ray Peat · Article · Sep 1972

> Oxidative Phosphorylation (Strickland, et al., 1955) is apparently necessary for maintaining high intracellular K/Na ratios though possibly not for maintaining the resting potential (Ling, 1962), so it is possible that estrogen might have its early action either on the cytoplasmic structure (Nemetchek-Gansler, 1967; Peat and Soderwall, 1972), i.e., producing a permeability or phase change, and thus affecting oxidation by modifying structural relationships and diffusion rates and solubilities, or on oxidative phosphorylation, with a phase change 36—Ct (i.e., a salt ratio change) resulting from a reduction of the energy charge. Merely incubating uterus in Eagle's medium mimics estrogen action (Mueller, et al., 1958), and hypo-osmolarity duplicates some effects (Adams and Haynes, 1969). Progesterone has an opposite effect on sodium retention (Tomlinson, 1971; Jones, 1972). Sex hormone effects seem to be universal and specific; even yeast "sexual" types are selectively affected by the mammalian hormones (fakao, et al., 1971; Yanagishima, et al., 1970). The best known scheme for estrogen action (Jensen, et al., 1968; Mueller, et al., 1958) suggests that estrogen binds to a cytoplasmic "transport" protein and then enters the nucleus where it modifies the chromosomes so that certain mRNAs are transcribed, leading to synthesis of new proteins which then produce all other effects by membrane and enzymic changes. This theory igmores the fact that lipids are the first substances (by several hours) to show net "synthesis (Mueller, 1958), and the observations that salt ratio changes are sufficient to initiate, stop, or modify synthesis of DNA and RNA (Allfrey, et al., 1964; Lezzi, 1969). Engel (1970) suggests that certain enzymes have estrogen affinity sufficient.
>
> make them "receptors." Although the 9.55 and the 4-65 receptors” are not known to have enzyme activity, this may simply reflect the fact that the leading investigators of these proteins are not interested in their potential enzyme activity.

### Source 2 — #31: Estrogen for Libido? | PUFA and Hypogonadism | Overpopulation Hoax | Parabiosis | Cancer with Georgi Dinkov

Georgi Dinkov · Interview · Jul 19, 2020 · https://open.spotify.com/episode/6mO0fuDYLfG6rZQYQs1oT5

> **Georgi Dinkov:** So multiple, so different pathways, but they all converge into one, which is after the cell has been stressed by any agent, be that a virus, or like, you know, stress, chronic stress from the environment, or like poor diet, or anything else that's impeding the cell's metabolism, over time this tells the cell that the environment is so, basically so harsh and so inhospitable to life that the cell starts dismounting, dismantling actually, its apparatus for oxidative phosphorylation. That's the exact same thing happens in cancer. And actually they say this is the exact same thing that happens in COVID. But here's the thing. If this is the exact same process in cancer and in COVID, and we're seeing this happen, this is an entirely metabolic thing. Nobody's talking about mutations and genetic damage here. So it's the exact same process in infectious disease and in cancer. Should we be treating cancer as an infectious disease? Because they already proposed a mechanism here. They're saying like, oh, look, because HIF-1-alpha is elevated. These people are not getting enough oxygen to the tissues. Doing anything possible to put more oxygen inside of the tissues should reverse this metabolic state and has already been shown to be highly therapeutic. So to me, that means, so you just found a cure for cancer, right? Because you just said you can reverse the cancer metabolism completely because there's been no genetic damage. Everything is metabolic. So if you found the cure for the cytokine storm that's killing people from sepsis, and they actually say it's the exact same thing as what we're seeing in cancer, and you reverse that thing in COVID-19, why wouldn't it work in cancer?

### Source 3 — Age-related oxidative changes in the hamster uterus

Ray Peat · Article · Sep 1972

> The well-known actuarial data that show that short people Live longer than tall ones might be relevant to this question, because of their proportionately larger brain size; the same would apply to the greater longevity of women. Energy production has been proposed as a crucial factor in life-span (Hershey, 1970; Calloway, 1971a).
>
> Palladin (1964) has made a possibly related observation concerning evolutionary level" (which in this case corresponded to brain size) and efficiency of oxidative phosphorylation. The efficiency of coupling was found to increase with higher evolutionary level, as well as with alertness. This observation suggests an interesting secondary factor to consider in relation to "rate of living" and Sacher's idea--the reason for Sacher's correlation might be metabolic efficiency, i.e., a less wasteful use of oxygen, possibly even a less destructive use of it.
>
> Thefree-radical theory of aging has become very popular recently, probably partly as a result of radiation studies and partly because of the observation (Harman, 1968; Kohn, 1971) that antioxidants such as BHT added to the diet of mice increased their lifespan by several percent. It has been pointed out by other investigators that the mice ate less of the diet, probably because of the smell of the antioxidant, and that the restricted food intake alone could account for the increased life span (Comfort, 1972), Restricted intake of calories has recently been found to slow the aging of collagen in rats (Everitt, 1971).
>
> ### Relations of the Senescent Physiology to Other Physiological Processes
>
> Other Physiological Processes Other studies (Lee et al., 1952; Visscher et al., 1952) have shown that limitation of caloric and protein intake lengthens the life span of mice, delays development of cancer in a susceptible strain, suppresses estrus and delays onset of both reproductive maturity and reproductive senescence. These observations will be discussed further below.
>
> Smith and Soderwall's (1962) finding that supplementing the diet with vitamin E delayed reproductive senescence in hamsters, and similar observations in rats tempt one in this context to suggest that excess free radicals from an overactive metabolism are the gent of alteration in the collagen, which in turn leads to acceler« ated functional senescence.

### Source 4 — #73: PUFA is Estrogenic | Endotoxin, Cancer, and Inflammation | Serotonin Causes Digestive Disease? with Georgi Dinkov

Georgi Dinkov · Interview · Nov 15, 2021 · https://open.spotify.com/episode/5RtrzF47VPqZLigRN7m53d

> **Georgi Dinkov:** reversal of this effect was strongly cytotoxic to acute myeloid leukemia, indicating the direct oxidative phosphorylation regulation by the delta of the difference of the ATP between cytosol and mitochondria, confers a survival advantage during hematopoietic clonal cell expression. So, yeah, that's what they're saying, is that interventions that target the oxidative phosphorylation, they're saying are basically viable therapies, at least for this cancer.

### Source 5 — Generative Energy #35: CO2, Ketosis, and Mitochondria | PUFA, Sugar, Iron, and AGEs | Progesterone and Cell Stability

Ray Peat (with Danny Roddy) · Interview · Aug 29, 2020 · https://open.spotify.com/episode/2Iz99Wy5JmrbohNj4OZCxP

> ## Metabolic Landmarks: PFK, PDH, and Cytochrome C
>
> **Danny Roddy:** A shout out to Jay Feldman for making me more aware of this. He says glucose oxidation produces about 25% more NADH and half as much FADH2 as fat oxidation. FADH2 donates electrons at complex II and reduces the amount of ubiquinone available to accept electrons at complex I. This backup of electrons is the main place where metabolism is shifted.
>
> **Ray Peat:** It might be the biggest factor, but I think everything tends to work together. Essentially everywhere a process is working, it tends to get biased when you're not overproducing carbon dioxide. Wasteful energy—in the sense of pouring out carbon dioxide and producing heat as your only product—is insurance.
>
> **Danny Roddy:** He also mentioned complex I is one of the major sources of superoxide, which combines to produce nitric oxide. So fat metabolism is inherently increasing the production of nitric oxide?
>
> **Ray Peat:** Unless you get the whole stream going, pulling the electrons out at a maximum rate at the oxygen end. That attracts electrons that would otherwise make superoxide. The faster you run the apparatus, it creates an electron-withdrawing effect from the surrounding cells—an inclination towards a more carbon dioxide-like condition of the structure.

### Source 6 — Episode 244 - Interview with Georgi Dinkov: Causes of Insulin Resistance, Obesity is an Endocrine Problem, and Problems with Excess Cortisol

Georgi Dinkov · Interview · Apr 14, 2023

> **Georgi Dinkov:** It starts to work less efficiently and you'll still produce the energy, but through other means that are not as beneficial for you. And if this extends throughout time, you essentially, the body adapts and you're sending a signal to the body that something's off and the body will say, well... If that's the only way I can produce energy, I'm going to stick with it until something in the environment shows me that we're back to the optimal situation and I can go back to producing the energy the way I want to. And the boundary review says every disease that we know of, whether it's acute or chronic, ultimately stems from this, you know, initially benign, looking benign, you know, interference with the so-called process of oxidative phosphorylation, which is fully oxidizing, primarily glucose, to carbon dioxide and water, and ATP. If you interfere with that process, any of the steps, and if you do this for long enough, you're actually going to get a problem. Several Nobel laureates actually stated this openly in regards to cancer, Otto Warburg, a Nobel Prize winner, and he gave his name to the infamous so-called Warburg effect. He was of the opinion that cancer is a metabolic disease. A metabolic disease is just another name for a functional disease. In other words, for a bioenergetic disease, your cancer develops when something in the body interferes with the production of energy. And cancer is like a desperate attempt to correct that. But because the energy that's being produced in the body is not produced in the proper manner, cancer cannot differentiate back into normal tissue. So cancer is not an attempt to kill you. Cancer is an attempt to repair a problem under very suboptimal circumstances. And Otto Warburgs was, up until he died, was of the opinion that if you can restore, if you can remove this oxidative phosphorylation defect, as he called it, then you should be able to cure cancer.

### Source 7 — Why Modern Cancer Treatment Might Be Making Things Worse w/ Georgi Dinkov

Georgi Dinkov · Interview · May 22, 2025 · https://www.youtube.com/watch?v=gh1aWw_CCwA

> **Ashley:** So, okay, glycolysis outside the mitochondria and then oxidative phosphorylation inside mitochondria through the electron transport chain. And it's important for people to understand that there's a lot of processes and complexes and steps along this chain. And there are various cofactors such as the vitamins and the minerals that we consume in our food, right? So the whole goal of metabolism is to take the energy that we consume in our food and then convert it into cellular energy. So it's an energy conversion process. So we want to convert high energy electrons into ATP for our cells to use. And we need various cofactors and vitamins along the way to do that. So Georgi's previous studies have shown that, you know, having aspirin and then the metabolite of aspirin can help restore that electron flow but also various b vitamins such as vitamin b1 and vitamin b3 can help restore energy production because maybe those were missing cofactors maybe those cancer cells didn't have enough of those very important vitamins which are critical cofactors to this oxidative phosphorylation process. So you have recent updates on your studies, your cancer studies. What have you recently been investigating and what have you found for improvement of restoring oxidative phosphorylation?
>
> **Georgi Dinkov:** So the screenshots that I sent you, I guess last week, they were on the breast cancer study and on a prostate cancer study. These two combined are probably responsible for the majority of cancers in both men and women in the United States, actually most of the developed world. And specifically, the breast cancer study is on the estrogen receptor positive cell line known as MCF-7. It's one of the most studied cell lines out there. More than 80% of the new cancer diagnosis are estrogen receptor positive. And I just wanted to do a study with it because it's such a relevant disease for all women around the world. And so far, it looks like basically there were several groups in the study, one with the combination of B vitamins plus aspirin, and then there's one just with the metabolite of aspirin, 2,6-DHPA, and then there's one with pregnenolone. and there were because of previous studies with the b vitamins and aspirin and 26 dhba that's why i had these two groups pregnant alone comes from a i haven't mentioned this anywhere but about four or five years ago um this lab that i'm currently doing the studies with we did an in vitro study with them with the mcf7 line with any pregnant alone and uh Pregnilo did the best compared to all of the other standard treatments, such as tamoxifen, clomiphene, aromatase inhibitors that were basically currently used at the time. So not only it was more effective at lower concentrations, but unlike all the other chemicals that were used, Pregnenol didn't cause any cell toxicity. There was no cell rupture. There was no leakage of cellular internals, including the mitochondria into the environment, into the buffer. So the lab said, we think that pregnenol, based on the results, should be able to treat breast cancer, the AMCF satellite. with the same cell line back then.

### Source 8 — Why Modern Cancer Treatment Might Be Making Things Worse w/ Georgi Dinkov

Georgi Dinkov · Interview · May 22, 2025 · https://www.youtube.com/watch?v=gh1aWw_CCwA

> **Georgi Dinkov:** And the only way you get out of this vicious cycle is if the mitochondria starts to work again, number one, or if the cell decides that it's too damaged and basically commits apoptosis. And that's really the only two things that can be approached therapeutically in cancer. This whole idea of killing the cancer cell, while that cell is still very much active and viable, I think it backfires terribly, and we see that, because once you start killing cells that are relatively healthy, and they basically spill their entrails, so to speak, into the bloodstream, multiple studies have demonstrated that this is a signal that becomes systemic, and the entire body decides that it's under attack. A lot of the mitochondrial debris and the debris from the nucleus trigger the exact same pathways and receptors that bacterial or viral infections trigger. So of course, when that happens, when you have an infection, you're under chronic inflammation because that's one way the foreign pathogen is being killed. But the problem with inflammation is that it also turns off... systemically the oxidative phosphorylation metabolism because the body needs to focus resources on fighting pathogens. So when you kill the cancer cells that are not yet damaged enough that they really deserve to die, when you kill all these cancer cells and then spill the entrails into the bloodstream, your entire body becomes inflamed, so it becomes a systemic issue, and the entire body says, I'm under attack, so I'm going to start turning off the oxidative phosphorylation everywhere, not just on the tumor side. So now you have basically your entire body capable of supporting new cancer cells. And I think that's really what explains the metastatic process. Once they cut out the tumor and blast that area with radiation and chemotherapy, and they spill all of these dead cells into the bloodstream, the entire body becomes basically shifting towards the cancer metabolism.

### Source 9 — #39: Low Testosterone and PUFA | Vitamin D is Anabolic and Anti-Cortisol | High Metabolism and Aging

Georgi Dinkov · Interview · Nov 15, 2020 · https://open.spotify.com/episode/1ydUK0ut0jy7L37VbyLUmX

> **Georgi Dinkov:** A person with high metabolism in general will have, and I think that study actually said that as a quote, has it as a quote, that a person with high rate of oxidative phosphorylation that produces the optimal amounts of CO2 and water as the final byproducts, right, they will not have many ROS in their tissues.

### Source 10 — Stress/Injury (mitochondrial dysfunction) sufficient to cause de-differentiation, even cancer

Georgi Dinkov · Article · Sep 6, 2023 · https://haidut.me/?p=2312

> One of the most pernicious myths in medicine is the “irreversibility” of several cellular processes related to aging, diabetes, fibrosis and, of course, cancer. Perhaps the most fundamental of those processes is cellular differentiation. To this day, the dominant opinion in medicine is that once a stem cell embarks on the process of differentiation that process cannot be reversed and it can only end with cellular death due to senescence or injury. This erroneous idea is used to support the dogma in oncology that a normal cell (differentiated) can never become a cancer cell (de-differentiated, stem-alike) under normal circumstances, so a cancerous mutation of some sort is conjured out of thin air to explain the cancerization. Conversely, the dogma also holds that once cancerous de-differentation occurs, the “cancer” cell can never become a “normal” cell again. Thus, the only hope for the “cancer” patient is to have those “cancer” cells killed by any means necessary – usually through the (in)famous combination of surgery (cut), chemotherapy (poison), and radiation (burn).
>
> Well, the study below not only pours cold water on these dogmatic medical myths, but also once again highlights the central role metabolism and mitochondria play in such processes. Namely, the study demonstrated that any type of differentiated cell can easily convert back to a de-differentiated (stem) cell if the mitochondrial production of reactive oxygen species (ROS) is elevated beyond a certain threshold. Unfortunately, another common medical dogma is that ROS are produced when the metabolic rate is high – i.e. when forward electron transport across the metabolic chain is high. However, as discussed on Dr. Mercola’s and Danny Roddy’s podcasts, this is completely false and, in fact, exactly backwards to what is happening in the cell. Namely, ROS are overproduced when forward electron flow is blocked at one or more of the OXPHOS steps and so-called “reverse electron flow” commences. In other words, ROS overproduction happens predominantly when metabolism is low/blocked, while less than 0.5% of ROS are generated when metabolism is functioning properly and forward flow is as fast as the cell can accommodate. The cellular “phenotype” of high ROS production is seen in virtually all diseases known to medicine – both chronic and acute alike.

### Source 11 — #17: Progesterone/DHEA Study Results, Field Biology, NAFLD, and Vitamin E with Georgi Dinkov

Georgi Dinkov · Interview · Feb 21, 2020 · https://open.spotify.com/episode/2Ari0W9sBDaSeJPiyQo5nb

> **Georgi Dinkov:** I think the dosage would be about, I know people think it's very high, like about 600 to 800 milligrams daily, but that's what they use to treat migraines, and it's been shown to be, so far, no serious side effects, despite hundreds of trials already being done. So I think that's another... Yet another confirmation that ALS is actually a mitochondrial slash metabolic disease. And I put some links into my post about like a few years ago, I posted another one showing that copper can actually treat, copper dissolved in DMSO can actually treat ALS. And they're trying to patent this formulation right now, even though you can get it over the counter. I mean, you can make it yourself at home. And there was another study which showed that lithium may potentially also treat ALS. And what all of these three things like the riboflavin, the lithium, and the copper have in common, is that they stimulate oxidative phosphorylation and specifically the activity of the electron transport chain fraction of it.

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