Ray Peat on Mitochondria

Importance of Nutrients for Mitochondrial Function and Aging

In old age, the walls of blood vessels tend to harden with calcium. In at least some tissues, calcification is known to begin in degenerating mitochondria, and mitochondria tend to degenerate in aging tissue. Nutrients such as iodine, vitamin E, magnesium, and vitamin B2 are especially important for maintaining the function of mitochondria, which produce most of our energy.

Nutrition For Women

Role of Mitochondrial Oxygen Consumption in Body Temperature

A high rate of mitochondrial oxygen consumption generates heat, allowing the organism to maintain an optimal body temperature. When body temperature drops, reactive oxygen species like superoxide increase; mitochondrial superoxide production rises slightly while elimination decreases sharply.

November 2020 – Ray Peat's Newsletter

Regulation of Body Temperature through Mitochondrial Energy Production

"Our body temperature is maintained by the rate of energy production, which is mainly the result of fuel oxidation by the mitochondria."

November 2020 – Ray Peat's Newsletter

The Role of Aspirin in Mitochondrial Oxygen Consumption and Fever

"Probably due to aspirin's fever-reducing effect, medical culture tends to view it as antithermogenic, despite its known stimulation of mitochondrial oxygen consumption. Like thyroid hormone, aspirin prevents the stress-related loss of sodium, which is an important part of our system for regulating temperature and energy."

November 2020 – Ray Peat's Newsletter

Low Cholesterol Levels and Effects on Mental Health

"A low serum cholesterol level has been linked to depression, suicide, violence, and increased cancer mortality. Since statins enter the brain and inhibit cholesterol synthesis there, reduced mitochondrial function is undoubtedly a factor in the mental side effects they can cause."

November 2018 – Ray Peat's Newsletter

Effects of Stress Hormones on the Mitochondria

"The levels of aldosterone and parathyroid hormone are increased by stress, with serotonin acting on the adrenal cortex and parathyroid gland to boost their secretion. All three of these hormones affect the mitochondria and reduce oxidative energy production."

May 2019 – Ray Peat's Newsletter

Factors for Healthier Pregnancies and the Postpartum Period

"The most important factors that can be optimized with available resources. Healthier pregnancies lead to a healthier and happier life after birth. These factors include sunlight, vitamin D, milk, cheese, eggs, fruit, as well as well-cooked vegetables, fiber-rich foods, and optimizing thyroid function along with pregnenolone and progesterone (which support mitochondrial function and protect against aldosterone, parathyroid hormone, excess serotonin, CRK, and cortisol, as well as increase allopregnanolone), and the use of the safest anti-inflammatory and antiserotonergic medications like aspirin and cyproheptadine when needed."

May 2019 – Ray Peat's Newsletter

Intercellular Communication through Protein and Mitochondrial Transfer

"Human cells of different types are capable of communicating by passing proteins, nucleic acids, and even mitochondria. Microvesicles containing these macromolecules and shed by cells from various organs can travel through body fluids."

May 2016 – Ray Peat's Newsletter

The Influence of Various Factors on Mitochondrial Oxygen Utilization

"When cells breathe intensely, all the oxygen reaching the mitochondria is immediately consumed, so the oxygen concentration near the respiratory enzymes is nearly zero. If something disrupts mitochondrial oxygen consumption (for example, a thyroid hormone deficiency or the presence of too much polyunsaturated fat or nitric oxide or carbon monoxide), the local oxygen concentration rises because it is not being used."

March 2021 – Ray Peat's Newsletter

Deterioration of Animal Mitochondria in Darkness

"Animal studies have found that their mitochondria gradually deteriorate during the hours of darkness."

March 2018 – Ray Peat's Newsletter

The Role of Mitochondria in Nighttime Brain Function

"Optimizing mitochondrial function at the beginning of the night makes the brain's inhibitory signals more effective, preserves glycogen stores, and reduces nighttime catabolism."

March 2018 – Ray Peat's Newsletter

The Diverse Influences and Effects of Nitric Oxide

"Nitric oxide is, like endotoxin and rotenone, a strong inhibitor of mitochondrial respiration. Endotoxin and other harmful stimuli can increase the production of nitric oxide, but it is also produced during normal excitatory nerve processes. When there is overexcitation relative to energy production and inhibitory influences, it can become the central trigger of excitotoxicity."

March 2017 – Ray Peat's Newsletter

Evaluation of L-DOPA and Alternative Treatments for Parkinson's

"Despite its toxicity, L-DOPA remains the main treatment for Parkinson's disease, although the better-suited drugs bromocriptine, amantadine, and memantine are also widely used. Anticholinergics, similar to hyoscyamine and belladonna, which Charcot used, are sometimes employed to control excessive saliva flow. Amantadine and memantine incidentally protect against nitric oxide, serotonin, inflammation, and endotoxins and protect the mitochondria."

March 2017 – Ray Peat's Newsletter

The role of progesterone in the brain's energy processes

"It seems likely that a fundamental part of progesterone's ability to protect the brain from stress is its support of the high-energy mitochondrial oxidation of glucose to carbon dioxide."

January 2018 – Ray Peat's Newsletter

Activation of the NMDA receptor and the state of pseudohypoxia

"The NMDA receptor (like many other regulatory proteins, e.g., COX, TLR, NOS, aromatase) is activated by the reduction of its thiol groups. The reduced state that activates this excitatory system can arise from actual oxygen deficiency but also from inhibition of mitochondrial function, creating a state of pseudohypoxia."

January 2017 – Ray Peat's Newsletter

Reductive stress and its self-reinforcing biochemical cycles

"The reduced state caused by hunger or hypoglycemia, an excess of lactate or fat, or oxygen deficiency activates the release of glutamate. The resulting excitation can shut down mitochondrial oxidation and amplify the state of pseudohypoxia. Nitric oxide synthase activated by reductive stress is an important factor in suppressing mitochondrial oxidation."

January 2017 – Ray Peat's Newsletter

The overlooked inhibition of mitochondrial oxygen use by nitric oxide

"Only a very small minority of publications on the physiology of nitric oxide address the fact that it inhibits mitochondrial oxygen use for energy production."

January 2016 – Ray Peat's Newsletter

Estrogen-induced anti-respiratory substances and their effects

"One of the anti-respiratory substances produced by estrogen is carbon monoxide (Tschugguel, et al., 2001). Another inhibitor of mitochondrial oxidation, hydrogen sulfide, is also increased by estrogen (Lechuga, et al., 2015)."

January 2016 – Ray Peat's Newsletter

Nutrition and stress resistance in age-related oxidative changes

"Avoiding oxidatively toxic heavy metals and maintaining respiration while simultaneously lacking highly peroxidizable unsaturated fats in the diet (and a lower content in storage tissues) would likely lead to animals tolerating stress better (EFA-deficient mitochondria are more resistant to oxidative damage, and vitamin E prevents many stress-related problems) and could inhibit age-related oxidative changes in serum albumin, red blood cells, and other tissues."

Generative Energy Restoring The Wholeness Of Life

Mitochondrial damage affects hormone production and energy

"Since protective hormones depend on the mitochondria's ability to convert cholesterol into pregnenolone, it is clear that mitochondrial damage impairs our supply of protective hormones, simultaneously with the decline of our energy supply, forcing us to switch to atrophy-inducing stress hormones, including cortisol."

Generative Energy Restoring The Wholeness Of Life

The role of mitochondrial protection in age-related pathologies

"Simple factors that protect mitochondria are known to have profound therapeutic effects. At some point, I think we will understand mitochondrial protection well enough to prevent and cure the fundamental pathologies of aging."

Generative Energy Restoring The Wholeness Of Life

The potential of mitochondrial protection to increase biological energy

"I think it is likely that our current knowledge of mitochondrial protection could provide the average adult with about a 50% increase in biological energy. To go beyond this level, it might be necessary to start at an earlier age to allow proper development of body proportions."

Generative Energy Restoring The Wholeness Of Life

Calcium and iron deposits in mitochondria and diseases

"Calcium and iron tend to be deposited together, and mitochondria are usually the starting points for their deposition. Iron overload is associated with heart disease, cancer, diabetes, and many other degenerative diseases, including brain disorders."

February 2001 

The toxic effects of serotonin and nitric oxide on brain cells

"Serotonin does not cure depression, and both serotonin and nitric oxide impair blood flow and are toxic to brain cells. Both poison mitochondrial respiration."

February 2001 

Cellular excitation and hydration as fundamental properties

"I think the only way to understand the general nature of cellular excitation is to consider it in terms of the fundamental properties of living material. Only something as general and basic as the hydration state of the cell, its moisture, can explain the coherent way cells are activated, with related processes occurring at all levels – from chromosomes through mitochondria and enzymes to the structural protein network of the cytoskeleton and sensory functions."

March 2000 

Neuroprotective and mitochondrial restorative effects of progesterone

"Besides its antiestrogenic effect, progesterone is a neurosteroid, an antiexcitotoxin, and an inhibitory modulator. These effects in the nervous system have parallels in the immune system, where it modulates the activities of many cells, protects the thymus, inhibits mast cell degranulation, and prevents shock reactions. It acts as an antitoxin, stabilizes cell structure and function. In mitochondria, it preserves or restores respiratory efficiency."

March 2000

Defective Mitochondrial Respiration in Various Organ Diseases

"It is now widely recognized that defective mitochondrial respiration is a central factor in diseases of muscles, brain, liver, kidneys, and other organs."

July 2000

Mitochondrial Functions and Energy Concentration

"Warburg believed that mitochondria support specialized cell functions by concentrating at the sites where energy is needed."

July 2000

The Role of Carbon Dioxide in the Existence of Mitochondria

"Could carbon dioxide, a main product of mitochondria, help bring mitochondria to life? My answer to that is yes."

July 2000

Skepticism Regarding the Exchange of Organelles and the Origin of Mitochondria

"Although I have no hesitation in accepting that organelles can be exchanged between species and that it is conceivable that mitochondria could derive from symbiotic bacteria, I hesitate to believe that something happens just because it could happen."

July 2000

Theory of the Spontaneous Formation of Cells and Organelles

"Since I have an idea of how cells originated under the conditions prevailing on Earth, I should check whether this idea can reasonably explain their various components. Sidney Fox's proteinoid microspheres provide a good model for the spontaneous formation of primitive cells: variations of this idea can explain the origin of organelles (such as mitochondria and nuclei within cells, as well as chromosomes within nuclei). The value of this idea, a self-stimulating process in mitochondrial formation, lies in that it reveals many possibilities to test the idea experimentally and provides explanations for developmental and disease processes that otherwise would have no coherent explanation."

July 2000

Mitochondrial Metabolism as the Core Problem in Aging and Disease

"Mitochondrial metabolism is now considered the fundamental issue in aging and several degenerative diseases."

July 2000

Energy Supply and Reversal of Genetic Mitochondrial Damage

"Providing energy while simultaneously reducing stress seems to be all that is needed to reverse the accumulated genetic damage of mitochondria."

July 2000

The Role of Carbon Dioxide in Mitochondrial Stability

"Just as carbon dioxide changes the shapes and electrical affinities of hemoglobin and other proteins, I propose that it increases the stability of the mitochondrial coacervate, thereby recruiting additional proteins from its surroundings as well as from its own synthesis machinery to enlarge both its structure and its functions."

July 2000

The involvement of lactic acid in mitochondrial degradation

"In the relative absence of carbon dioxide or an excess of alternative solvents and adsorbents, such as lactic acid, the stability of the mitochondrial phase would decrease, and the mitochondria would degrade in both structure and function. As a counterpart to the idea that carbon dioxide stabilizes and activates mitochondria, the idea that lactic acid is involved in mitochondrial degradation can also be experimentally tested and is already supported by a considerable amount of indirect evidence."

July 2000

The influence of light on glucose oxidation and respiratory efficiency

"Light promotes glucose oxidation and is known to activate the key enzyme of respiration. Winter fatigue (including lethargy and weight gain) and nighttime stress must be included in the concept of respiratory defect, which leads to the anti-respiratory production of lactic acid and damages the mitochondria."

July 2000

Natural factors for correcting edema and cell functions

"Thyroid, proteins, sodium, and magnesium correct most edemas. Progesterone, which acts on the mitochondria to increase respiratory efficiency and on structural proteins to alter their ion affinities, works synergistically with other natural factors to correct permeability and water regulation."

January 2000 - Ray Peat's Newsletter

The role of calcium in mitochondrial damage and cellular excitotoxicity

"Calcium, released into the cytoplasm by excitotoxins, triggers the release of fatty acids, activation of nerves and muscles, and the release of various transmitter substances in a cascade of excitatory processes, but at the same time impairs mitochondrial metabolism and tends to accumulate increasingly in the mitochondria, leading to their calcification and death. This is further promoted by the anti-respiratory effects of unsaturated fatty acids and the lipid peroxidation they induce."

December 1999 - Ray Peat's Newsletter

The role of sodium in regulating water and ions in cells

"Sodium binds water to itself, and this property causes it to be excluded from the normal cell. CO₂, when in water, especially in the presence of carbonic anhydrase enzymes, combines with water. Since it is produced in the mitochondria, this means it transports water (as well as calcium and sodium) into the cytoplasm and out of the cell."

1998 – Ray Peat's Newsletter – 4

Treatment of scleroderma with thyroid, magnesium, and progesterone

"Men diagnosed with scleroderma have reported to me that their symptoms improved with the use of thyroid and magnesium supplements, Epsom salt baths, as well as topical progesterone and vitamin E. I suspect that the carbon dioxide produced in the mitochondria is the main factor for removing calcium from them."

1997 – Ray Peat's Newsletter

Thyroid and magnesium in normalizing mitochondria

"Thyroid and magnesium are often the factors needed to normalize mitochondria and prevent calcification. In general, depleted cells take up calcium and lose magnesium."

1997 – Ray Peat's Newsletter

The role of the aging pigment in supporting mitochondrial respiration

"The aging pigment mainly consists of lipid peroxidation products, heme, and iron. It has the adaptive function of keeping NADH oxidized in a low-oxygen environment where mitochondrial respiration is insufficient, so that NADH can continue to drive the glycolytic sequence."

June 1994 – Ray Peat's Newsletter

Effects of stress on glucose and fat utilization

"When tissue oxygenation is insufficient, glucose is rapidly consumed. During prolonged stress, the liver's gluconeogenic response to glucocorticoids is reduced, as is its ability to form and store glycogen. As glucose becomes less available, adrenaline levels in the blood increase, and fat is mobilized from storage depots as an alternative energy source. Free fatty acids, especially unsaturated fats, are toxic to the mitochondrial respiratory system, blocking both the ability to use oxygen and energy production. The increased use of fats instead of glucose leads to an increase in lipid peroxidation."

June 1992 – Ray Peat's Newsletter

Effects of endotoxins on mitochondrial respiration and pregnenolone

"Bacterial endotoxins inhibit mitochondrial respiration, and this respiration is required for the intramitochondrial conversion of cholesterol into pregnenolone."

August/September 1992 – Ray Peat's Newsletter

The role of succinic acid in tissue respiration and regeneration

"Succinic acid was discovered by Szent-Györgyi as a stimulant of tissue respiration. Others found that it promotes the production of protective steroids, and recently it was found to be the best agent to chelate and remove aluminum from mitochondria. Succinic acid was identified as a main component of Vladimir Filatov's biogenic stimulants for tissue regeneration. It would be desirable to find food sources rich in this substance, especially in combination with the closely related butyric acid."

January 1991 – Ray Peat's Newsletter

Mitochondrial Damage Impairs Pregnenolone Production

"When mitochondria are damaged, the protective steroid pregnenolone (produced in the mitochondria from cholesterol) cannot be produced."

January 1991 – Ray Peat's Newsletter

The importance of copper for mitochondrial respiration and aging

"Copper is an essential component of cytochrome oxidase, which occupies the crucial final position in the mitochondrial respiratory system. Copper is also part of the cytoplasmic SOD enzyme, whose levels decline with age. Ceruloplasmin, an important copper-containing protein, helps keep iron in its safe oxidized form. Copper is involved in the production of melanin (itself an antioxidant) and elastin. The loss of melanin, elastin, and respiratory capacity, so characteristic of aging, is also caused by excessive cortisol load."

October 1990 – Ray Peat's Newsletter

The Role of Lipofuscin in Energy Production During Respiratory Failures

"When copper-dependent mitochondrial respiration fails, lipofuscin has the ability to maintain energy production through glycolysis (by keeping the coenzyme NAD, nicotinamide adenine dinucleotide, relatively oxidized). Therefore, it is possible that lipofuscin represents a primitive form of stress defense."

October 1990 – Ray Peat's Newsletter

The Conversion of Cholesterol in Mitochondria Influences Hormones

"Within the mitochondria, a cytochrome P-450 converts cholesterol into pregnenolone. The loss of both energy and steroid hormones would have significant consequences."

January 1989 – Ray Peat's Newsletter

Toxic effects of unsaturated oils on health and metabolism

"Research showing the toxic effects of unsaturated oils goes back more than 60 years. An article published in my 1985 newsletter lists some of the key references. These substances inhibit many enzymes (e.g., in digestion, the immune system, clot dissolution, thyroid function), disrupt mitochondrial energy production, and impair communication between cells. Little is heard about these toxic effects, and there is not much funding for further research in these areas."

February/March 1989 – Ray Peat's Newsletter

Therapeutic Effects of Radiation and Mitochondrial Protection

"Since long-wave infrared radiation and microwaves of longer wavelength can penetrate walls to some extent, it could be that the absence of this type of radiation in winter is the stressor causing these changes and mitochondrial damage in winter. It might be that some of the therapeutic effects of natural thermal springs are caused by gently matching radiation from the large masses of hot earth in the surroundings. I think these longer waves could also have an anti-free-radical effect, possibly by acting on solvated electrons."

February 1986
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