# Crabtree effect

Category: Metabolism

Crabtree effect, observed originally in yeast, refers to the inhibition of respiration in the presence of glucose. This occurs in cancers (e.g., Miralpeix, et al., 1990) and in rapidly proliferating normal cells (e.g., Guppy, et al., 1993).

6 passages · 2 authors · 2009–2025 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

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

## Synthesis

The **Crabtree effect** is the inhibition of cellular respiration by an excess of glucose, a phenomenon originally observed in yeast but now recognized as a central feature of cancer and rapidly proliferating normal cells. [Source 2, 3] Ray Peat described it as the suppression of respiration by glycolysis, often framed as the simple opposite of the *Pasteur effect*, in which oxygen limits glycolysis to the rate that allows its product to be consumed oxidatively. [Source 1, 4] However, Peat argued that unlike the logical, normal control system of the Pasteur effect, the Crabtree effect tends to lower cellular energy and adaptability, representing a maladaptive state. [Source 4] He noted that embryonic tissues sometimes behave in this manner, leading to the suggestion that glycolysis is closely related to growth. [Source 1]

While the Crabtree effect is usually thought of as something that happens in tumors and some highly glycolytic tissues when given large amounts of glucose, Peat expanded its relevance by considering the role of **lactate**. [Source 1, 4] He argued that lactate, produced by normal tissues when deprived of oxygen or disturbed by a stress reaction, makes the Crabtree effect a very general phenomenon. [Source 1] The "respiratory defect" seen on the organismic level during hyperventilation is very similar to a "systemic Crabtree effect" that happens during stress, in which respiration is shut down while glycolysis is activated. [Source 1, 4] Since oxidative metabolism is many times more efficient for producing energy than glycolysis, Peat considered it maladaptive to shut it down during stress. [Source 1, 4] He went so far as to propose that lactate is not merely a sign of the respiratory defect in cancer, as Otto Warburg thought, but a *cause* of it, just as it is the immediate cause of the respiratory derangement of hyperventilation. [Source 4]

Mechanistically, lactate formation from glucose increases when anything interferes with respiratory energy production, but lactate itself can suppress cellular respiration through a variety of mechanisms, creating a vicious cycle. [Source 5] Peat identified **nitric oxide** and **calcium excess** as the main endogenous antirespiratory factors in stress, though free unsaturated fatty acids are also clearly involved. [Source 1] The presence of lactate also mobilizes free fatty acids, which then suppress the oxidation of glucose, a phenomenon known as the *Randle effect*. [Source 1, 2] Peat noted that estrogen promotes this effect, and Danny Roddy has specified that estrogen shifts cellular metabolism over to glycolysis, such that even if oxygen is present, the cell cannot use it, an effect he identified as the Crabtree effect. [Source 2, 6] When the mitochondrion's ability to consume pyruvate and NADH is limited, pyruvate itself accepts hydrogen from NADH, forming lactic acid. [Source 5] If too much lactate accumulates, it slows glycolytic ATP production, and a cell with defective respiration will die unless an alternative electron sink, such as the synthesis of fatty acids via **fatty acid synthase (FAS)**, is available. [Source 5]

Peat contrasted the toxic effects of lactic acid with the protective effects of carbon dioxide, noting they have opposing effects. [Source 2] He traced a wide range of pathologies to an excess of lactic acid and the related features of hyperventilated physiology, including the panic reaction, shock lung, vascular leakiness, brain swelling, and ultimately multiple organ failure. [Source 4] He was critical of the medical use of **lactated Ringer's solution**, arguing it is toxic and that its use as a buffer is a matter of convenience rather than physiology, as it damages mitochondria. [Source 2, 4] The Crabtree effect, in Peat's framework, is thus not an isolated quirk of tumor metabolism but a fundamental, systemic derangement of energy production driven by glycolytic stress, with lactate acting as both a product and a central toxin that perpetuates a *respiratory defect*. [Source 1, 4]

## People also ask

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

Peat described the Crabtree effect as the suppression of respiration by glycolysis, often framed as the opposite of the Pasteur effect, but argued it represents a maladaptive state that lowers cellular energy, unlike the logical control system of the Pasteur effect.

### What role does lactate play in the Crabtree effect?

Peat argued that lactate is not just a sign of the respiratory defect but a cause of it, as it can suppress cellular respiration through various mechanisms, creating a vicious cycle that makes the Crabtree effect a very general phenomenon during stress.

### Why did Peat consider lactated Ringer's solution harmful?

Peat argued that lactated Ringer's solution is toxic and damages mitochondria, criticizing its medical use as a matter of convenience rather than physiology, since lactate acts as a central toxin that perpetuates a respiratory defect.

## Related concepts

- [Glycolysis](https://bioenergeticoracle.com/md/concepts/glycolysis/index.md)
- [Mitochondria](https://bioenergeticoracle.com/md/concepts/mitochondria/index.md)
- [Pasteur effect](https://bioenergeticoracle.com/md/concepts/pasteur-effect/index.md)
- [Warburg effect](https://bioenergeticoracle.com/md/concepts/warburg-effect/index.md)
- [Acidosis](https://bioenergeticoracle.com/md/concepts/acidosis/index.md)
- [Adrenaline](https://bioenergeticoracle.com/md/concepts/adrenaline/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

> 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. But when we consider lactate, which is produced by normal tissues when they are deprived of oxygen or are disturbed by a stress reaction, the Crabtree effect becomes a very general thing. The "respiratory defect" that we can see on the organismic level during hyperventilation, is very similar to the "systemic Crabtree effect" that happens during stress, in which respiration is shut down while glycolysis is activated. Since oxidative metabolism is many times more efficient for producing energy than glycolysis is, it is maladactive to shut it down during stress.
>
> Since the presence of lactate is so commonly considered to be a normal and adaptive response to stress, the shut-down of respiration in the presence of lactate is generally considered to be caused by something else, with lactate being seen as an effect rather than a cause. Nitric oxide and calcium excess have been identified as the main endogenous antirespiratory factors in stress, though free unsaturated fatty acids are clearly involved, too. However, glycolysis, and the products of glycolysis, lactate and pyruvate, have been found to have a causal role in the suppression of respiration; it is both a cause and a consequence of the respiratory shutdown, though nitric oxide, calcium, and fatty acids are closely involved.
>
> Since lactic acid is produced by the breakdown of glucose, a high level of lactate in the blood means that a large amount of sugar is being consumed; in response, the body mobilizes free fatty acids as an additional source of energy. An increase of free fatty acids suppresses the oxidation of glucose. (This is called the Randle effect, glucose-fatty acid cycle, substrate-competition cycle, etc.) Women, with higher estrogen and growth hormone, usually have more free fatty acids than men, and during exercise oxidize a higher proportion of fatty acids than men do. This fatty acid exposure "decreases glucose tolerance," and undoubtedly explains women's higher incidence of diabetes. While most fatty acids inhibit the oxidation of glucose without immediately inhibiting glycolysis, palmitic acid is unusual, in its inhibition of glycolysis and lactate production without inhibiting oxidation.

### Source 2 — 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 3 — Glossary

Ray Peat · Glossary

> Crabtree effect
>
> Crabtree effect, observed originally in yeast, refers to the inhibition of respiration in the presence of glucose. This occurs in cancers (e.g., Miralpeix, et al., 1990) and in rapidly proliferating normal cells (e.g., Guppy, et al., 1993).

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

Ray Peat · Newsletter · Aug 3, 2009

> Lactate formation from glucose is increased when anything interferes with respiratory energy production, but lactate, through a variety of mechanisms, can itself suppress cellular respiration. (This has been called the Crabtree effect.) Lactate can also inhibit its own formation, slowing glycolysis. In the healthy cell, the mitochondrion keeps glycolysis working by consuming pyruvate and electrons (or “hydrogens”) from NADH, keeping the cell highly oxidized, with a ratio of NAD <sup>+</sup>/NADH of about 200. When the mitochondrion's ability to consume pyruvate and NADH is limited, the pyruvate itself accepts the hydrogen from NADH, forming lactic acid and NAD <sup>+</sup> in the process. As long as lactate leaves the cell as fast as it forms, glycolysis will provide ATP to allow the cell to survive. Oxygen and pyruvate are normally “electron sinks,” regenerating the NAD <sup>+</sup> needed to produce energy from glucose.
>
> But if too much lactate is present, slowing glycolytic production of ATP, the cell with defective respiration will die unless an alternative electron sink is available. The synthesis of fatty acids is such a sink, if electrons (hydrogens) can be transferred from NADH to NADP <sup>+</sup>, forming NADPH, which is the reducing substance required for turning carbohydrates and pyruvate and amino acids into fats.
>
> This transfer can be activated by the transhydrogenase enzymes in the mitochondria, and also by interactions of some dehydrogenase enzymes.
>
> The enzyme, fatty acid synthase (FAS), normally active in the liver and fat cells and in the estrogen-stimulated uterus, is highly active in cancers, and its activity is an inverse indicator of prognosis. Inhibiting it can cause cancer cells to die, so the pharmaceutical industry is looking for drugs that can safely inhibit it. This enzyme is closely associated with the rate of cell proliferation, and its activity is increased by both cortisol and estrogen.
>
> The first biochemical event when a cell responds to estrogen is the synthesis of fat. Estrogen can activate transhydrogenases, and early studies of estrogen's biological effects provided considerable evidence that its actions were the result of the steroid molecule's direct participation in hydrogen transfers, oxidations and reductions. E.V.

### Source 6 — Bioenergetic Helpline #3: Fifty Cups of Coffee Per Day, Fat Malabsorption, Reverse T3, Mushrooms

Danny Roddy · Interview · Dec 13, 2025 · https://www.youtube.com/watch?v=PXS_hNS3uis

> **Danny Roddy:** That's so granular, but that's my understanding of how estrogen works. It shifts things over to glycolysis. Even if oxygen is around, the cell can't use it. It's called the Crabtree effect or something. I can't recall the details, but that's the initiative to grow, to take up water and divide the cell and grow the cell for structural purposes to grow a biomass. don't have any papers that talk about estrogen and like a panic breathlessness but there are some papers about prolactin and prolactin is like a proxy for estrogen and one paper i have talks about like prolactin peaking and like a panic attack and so yeah dude anything anything stress related low thyroid is going to inhibit carbon dioxide interfere with oxygen utilization and then i mean that's why people breathe into a bag they're taking in their co2 so i mean what you laid out seems completely reasonable

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