# Pasteur effect

Category: Metabolism

The normal response of cells to restrain glycolysis in the presence of adequate oxygen.

6 passages · 1 author · 1972–2016 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/pasteur-effect

## Synthesis

**Pasteur effect** is the normal physiological mechanism by which oxygen suppresses glycolysis, preventing the conversion of glucose to lactic acid. [Source 1, 6] In the presence of adequate oxygen, cells restrain fermentation and instead oxidize glucose to carbon dioxide. [Source 6] Peat described this as a logical control system in which respiration limits glycolysis to the rate that allows its product to be consumed oxidatively. [Source 4]

The failure of the Pasteur effect constitutes a *respiratory defect* that Otto Warburg identified as central to cancer. [Source 1, 5] When the effect fails, cells exhibit **aerobic glycolysis**—the continued production of lactic acid even in the presence of oxygen—which Warburg considered a reversion to a primitive form of life. [Source 1, 6] Peat argued that this defect consists largely of the failure to produce carbon dioxide in the mitochondria, and that **lactic acid** itself may be the *cause* of the respiratory defect in cancer, acting as an irritant that shifts the cell further away from oxygen use. [Source 2, 4, 5] Szent-Györgyi contributed the insight that something keeps the cancer cell in an excited state, preventing it from turning off the excitatory process even when oxygen is present. [Source 5]

Estrogen is known to lower the Pasteur effect, partly through an apparent oxygen-wasting effect of an estrogen-activated NADH oxidase function of peroxidase. [Source 3] This enzyme activity is stimulated by estradiol within two hours, before net protein synthesis can be detected, and the resulting reduction in oxygen tension would help account for the shift away from oxidative metabolism. [Source 3] The diversion of pyruvate to oxaloacetate under estrogen's influence would also tend to inhibit succinic dehydrogenase, further compromising respiration. [Source 3]

The Pasteur effect is often contrasted with the **Crabtree effect**, the inhibition of cellular respiration by an excess of glucose. [Source 1, 4] While the Pasteur effect is a normal regulatory system, the Crabtree effect tends to lower cellular energy and adaptability, and Peat considered it a maladaptive process that becomes a very general phenomenon during stress, when respiration is shut down while glycolysis is activated. [Source 4] On the organismic level, Peat saw the respiratory derangement of hyperventilation—driven by excess lactic acid and leading to edema, vascular leakiness, and multiple organ failure—as analogous to a *systemic Crabtree effect*. [Source 4] The **Randle effect**, the inhibition of glucose oxidation by an excess of fatty acids, represents another related metabolic disturbance that lowers efficiency and is promoted by estrogen. [Source 1]

## People also ask

### How does the Pasteur effect normally regulate glucose metabolism?

Peat described it as a control system where respiration limits glycolysis so that its product can be consumed oxidatively, with oxygen suppressing the conversion of glucose to lactic acid.

### What happens when the Pasteur effect fails in cancer?

The failure constitutes a respiratory defect leading to aerobic glycolysis, and Peat argued that the resulting lactic acid may itself cause further respiratory damage by acting as an irritant.

### How does the Pasteur effect differ from the Crabtree effect?

The Pasteur effect is a normal regulatory system where oxygen suppresses glycolysis, while the Crabtree effect is a maladaptive inhibition of respiration by excess glucose that Peat considered a stress phenomenon.

## Related concepts

- [Crabtree effect](https://bioenergeticoracle.com/md/concepts/crabtree-effect/index.md)
- [Acidosis](https://bioenergeticoracle.com/md/concepts/acidosis/index.md)
- [Alzheimer's and Dementia](https://bioenergeticoracle.com/md/concepts/alzheimer-s-and-dementia/index.md)
- [Cancer metabolism](https://bioenergeticoracle.com/md/concepts/cancer-metabolism/index.md)
- [Cori Cycle](https://bioenergeticoracle.com/md/concepts/cori-cycle/index.md)
- [Electron transport chain](https://bioenergeticoracle.com/md/concepts/electron-transport-chain/index.md)

## Cited passages

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

### Source 1 — Mitochondria and mortality

Ray Peat · Article · 2016 · https://raypeat.com/articles/articles/mitochondria-mortality.shtml

> **Crabtree effect**: Inhibition of cellular respiration by an excess of glucose; excess of glucose promotes calcium uptake by cells.
>
> **Pasteur effect**: Inhibition of glycolysis (fermentation) by oxygen.
>
> **Randle effect**: The inhibition of the oxidation of glucose by an excess of fatty acids. This lowers metabolic efficiency. Estrogen promotes this effect.
>
> **Lactated Ringer's solution**: A salt solution that has been used to increase blood volume in treating shock; the lactate was apparently chosen as a buffer in place of bicarbonate, as a matter of convenience rather than physiology. This solution is toxic, partly because it contains the form of lactate produced by bacteria, but our own lactate, at higher concentrations, produces the same sorts of toxic effect, damaging mitochondria.
>
> **Estrogenic phytotoxins** damage mitochondria, kill brain cells; tofu is associated with dementia.
>
> Since reading Warburg's publications in the late 1960s and early 70s, and doing my own research on tissue respiration, I have been convinced that Warburg was on the right track in seeing mitochondrial respiration as the controlling influence in cell differentiation, and in seeing cancer as a reversion to a primitive form of life based on a "respiratory defect." Harry Rubin's studies of cells in culture have expanded Warburg's picture of the process of cancerization, showing that genetic changes occur only after the cells have been transformed into cancer.
>
> It is now well recognized that defective mitochondrial respiration is a central factor in diseases of muscles, brain, liver, kidneys, and other organs. The common view has been that the mitochondrial defects are produced by genetic defects, that are either inherited or acquired, and are irreversible.
>
> Mitochondria depend on some genes in the nuclear chromosomes, but they also contain some genes, and mutations in these specific mitochondrial genes have been associated with various diseases, and with aging. Although these aren't the genes that the cancer establishment has focussed on as "the cause" of cancer, for people interested in the achievements of Warburg and Rubin, it is important to know whether mutations in these mitochondrial genes are the *cause* of respiratory defects, or whether a respiratory defect causes the mutations. Recent research seems to show that physiological problems precede and cause the mutations.
>
> Warburg believed that mitochondria supported specialized cell functions by concentrating themselves in the places where energy is needed. This idea has some interesting implications.

### Source 2 — Townsend Letter — December 1999

Ray Peat · Newsletter · Dec 1, 1999

> The “respiratory defect” in which the Pasteur effect (suppression of lactic acid formation in the presence of oxygen) fails to operate, consists largely of the failure to produce carbon dioxide in the mitochondria.
>
> Simple hyperventilation causes muscle spasms and paresthesia (prickling of the skin), in an experiment anyone can perform in a few minutes. When a large amount of carbon dioxide is blown off, the blood’s pH increases very slightly, because of systemic adjustments. The “calcium deficiency” theory of tetany would suggest that increased alkalinity of the blood decreases the “availability” of ionized calcium, and that (somehow) the “decreased availability of ionized calcium” interrupts a relaxed state of the nerves and muscles. At least, that’s the explanation that I have heard many times, though I am stating it in a way that makes it sound fairly crazy. (See Stadler, et al., 1995.) But, in fact, everywhere calcium is studied, it is an activator, an excitant, a goad to activity, when it enters the cytoplasm. The evidence is that hyperventilation, which changes the serum concentration of bicarbonate, magnesium, potassium, chloride, and phosphate, does not change the serum calcium concentration, while it does increase the intracellular calcium content. (Fujimoto, et al., 1987; Stadler, et al., 1995.)
>
> The combination of the calcium ion, Ca2+, with the bicarbonate ion, HCO3-, forms a very soluble complex ion with a single positive charge. In the saliva, there is more carbon dioxide than in the mouth, and this situation is believed to explain the fact that calcium which is dissolved in the saliva tends to be deposited in an insoluble form as it loses its solubilizing bicarbonate, and the insoluble form contributes to dental plaque. (Presumably, this physical principle would account for the deposition of calcium in the walls of blood vessels or in any tissue which is relatively deficient in carbon dioxide.) Similarly, when serum bicarbonate decreases, the calcium escapes from its soluble complex, and in effect the available calcium—the forms of calcium which are not bound to bicarbonate—has increased, exactly the opposite of what the Carlson school has argued.

### Source 3 — Estrogen-Stimulated Pathway Changes and Cold-Inactivated Enzymes

Ray Peat · Newsletter · 1972

> Engel 38 has reported that one of his estrogen activated transhydrogenases has an affinity and specificity for estrogen comparable to that of the "receptor" protein, although the 17f3-estradiol dehydrogenase has a lower affinity. If an intracellular enzyme binds estrogen and has its function modified by it, it is a receptor, but there is no evidence that the well known "9 S" receptor has enzyme activity.
>
> One of the seemingly well established "coenzyme" functions of estrogen is in the estrogen activated NADH oxidase function of peroxidase. 39 Peroxidase is "induced" in the uterus by estrogen treatment. 40 Temple et al. 41 found that the oxidase behaved "like an induced enzyme," except that "oxidase activity was stimulated by the administration of estradiol to oophorectomized rats in two hours, when net protein synthesis cannot be detected." "Receptor" protein is also "induced" by estrogen. 42 ,43 Whatever the relation of "receptor" to estrogen activated enzymes might be, the apparent oxygen wasting effect of the estrogen activated oxidase would help account for estrogen's ability to lower the Pasteur effect 44 and to lower the pO2 of the uterine lumen, 45 and this effect would be compatible with the above mentioned diversion of pyruvate to oxaloacetate (which would tend to inhibit succinic dehydrogenase) and with the shift 45 toward M isozymes of LDH, which appears to correspond to hypoxia and would also divert pyruvate from oxidation. A consequent reduction of the energy charge might cause the phase change, or damage to structure as suggested by Warburg. 46 Racker 47 has recently proposed that increased temperature or altered pH may be involved in activation of the glycolytic pathway in cancer, and suggests increased hydrolysis of ATP as a possible cause. It was Racker who first observed that mitochondrial ATPase is cold-inactivated, and he has also pointed out that damage to mitochondria can reveal very high levels of ATPase activity.

### Source 4 — Mitochondria and mortality

Ray Peat · Article · 2016 · https://raypeat.com/articles/articles/mitochondria-mortality.shtml

> The Crabtree effect, which is the suppression of respiration by glycolysis, is often described as the simple opposite of the Pasteur effect, in which respiration limits glycolysis to the rate that allows its product to be consumed oxidatively. But the Pasteur effect is a normal sort of control system; when the Pasteur effect fails, as in cancer, there is glycolysis which is relatively independent of respiration, causing sugar to be consumed inefficiently. Embryonic tissues sometimes behave in this manner, leading to the suggestion that glycolysis is closely related to growth. Unlike the logical Pasteur effect, the Crabtree effect tends to lower cellular energy and adaptability. Looking at many situations in which increasing the glucose supply increases lactic acid production and suppresses respiration, leading to maladaptive decrease in cellular energy, I have begun thinking of lactic acid as a toxin. The use of Ringer's lactate solution in medicine has led many people to assume that lactate must be beneficial, or they wouldn't put it in the salt solution that is often used in emergencies; however, I think its use here, as a buffer, is simply a convenience, because of the instability of some bicarbonate solutions.
>
> On the organismic level, it is clear that lactic acid is "the essence of hyperventilation," and that it produces edema and malfunction on a grand scale: The panic reaction, shock lung, vascular leakiness, brain swelling, and finally multiple organ failure, all can be traced to an excess of lactic acid, and the related features of hyperventilated physiology.
>
> Otto Warburg apparently thought of lactate as simply a sign of the respiratory defect that characterizes cancer. V. S. Shapot at least hinted at its possible role in turning on the catabolic reactions leading to cancer cachexia (wasting). I think a good case can be made for lactate as the *cause* of the respiratory defect in cancer, just as it is usually the immediate cause of the respiratory derangement of hyperventilation on the organismic level.
>
> The Crabtree effect is usually thought of as just something that happens in tumors, and some tissues that are very active glycolytically, and some bacteria, when they are given large amounts of glucose.

### Source 5 — Ask the Herb Doctor: The Metabolism of Cancer

Ray Peat · Interview · Jul 15, 2016

> ## Cancer, Excitation, and Oxygen
>
> **Andrew Murray:** Getting back to this energetic state, how should we understand cancer arising from a depletion of this state?
>
> **Ray Peat:** In the 1920s, David Keilin in England was working on cytochromes. He found that when an insect or bird flight muscle was contracting and highly stimulated, the pigment he was studying disappeared, showing there was no oxygen present. The extreme activity had consumed all the oxygen momentarily and shifted the cell into a reduced state of excess electrons. Szent-Györgyi and Keilin were simultaneously working on ideas that William Frederick Koch had developed independently: it is the flow of electrons through the system to oxygen which has to be continuous. When something overstimulates or irritates an area—and the irritating effect of things like estrogen was already known—that excitation exhausts the tissue oxygen. This was at the center of the idea of what cancer is. Warburg described it as a defect in respiration where the cancer lacks the Pasteur effect. The Pasteur effect, seen in yeast, is where oxygen normally causes the yeast to stop fermenting (stop producing lactic acid or ethanol). Szent-Györgyi said there is something wrong with the system that prevents cancer from turning off that excitatory process, even in the presence of oxygen. Something keeps the cell in the excited state.

### Source 6 — Lactate vs. CO2 in Wounds, Sickness, and Aging

Ray Peat · Newsletter · Aug 3, 2009

> Warburg, Koch, and Szent-Györgyi had a comprehensive view of biology, in which the aerobic production of lactate, resulting from a respiratory defect, itself was functionally related to the nature of cancer.
>
> A focus on correcting the respiratory defect would be relevant for all of the diseases and conditions (including heart disease, diabetes, dementia) involving inflammation and inappropriate excitation, not just for cancer.
>
> ## Glossary
>
> Aerobic glycolysis, the conversion of glucose to lactic acid even in the presence of oxygen. The presence of oxygen normally restrains glycolysis so that glucose is converted to carbon dioxide instead of lactic acid.
>
> Anaerobic glycolysis, the increased conversion of glucose to lactic acid when the supply of oxygen isn't sufficient, which is a normal event during intense muscle action.
>
> “Warburg Effect” refers to Otto Warburg's observation that cancer cells produce lactic acid even in the presence of adequate oxygen. Cancer cells don't “live on glucose,” since they are highly adapted to survive on protein and fats.
>
> Pasteur Effect, the normal response of cells to restrain glycolysis in the presence of adequate oxygen.
>
> Crabtree Effect, observed originally in yeast, refers to the inhibition of respiration in the presence of glucose. This occurs in cancers[[45](#ref045)] and in rapidly proliferating normal cells.[[21](#ref021)]
>
> “Cancer metabolism” or stress metabolism typically involves an excess of the adaptive hormones, resulting from an imbalance of the demands made on the organism and the resources available to the organism. Excessive stimulation depletes glucose and produces lactic acid, and causes cortisol to increase, causing a shift to the consumption of fat and protein rather than glucose. Increased cortisol activates the Randle effect (the inhibition of glucose oxidation by free fatty acids), accelerates the breakdown of protein into amino acids, and activates the enzyme fatty acid synthase, which produces fatty acids from amino acids and pyruvate, to be oxidized in a “futile cycle,” producing heat, and increasing the liberation of ammonia from the amino acids. Ammonia suppresses respiratory, and stimulates glycolytic, activity.
>
> [references]

_Generated 2026-07-20 from the Bioenergetic Oracle corpus._