Spread of damage through bystander effects"Severe stresses in one part of the body spread their influence throughout the entire body, in a process now called the bystander or off-target effect. Serotonin, nitric oxide, and ATP are among the substances known to spread damage." September 2019 – Ray Peat's Newsletter |
Questioning Neo-Darwinism Through Analysis of Hormetic Toxins"If toxins like CO and NO are hormetically beneficial when present in urban air, then they must obviously be very beneficial when produced in the body by enzymes that have evolved through natural selection of things that support survival – there is a clear Panglossian aspect of neo-Darwinism: Everything exists because of its utility." November 2017 – Ray Peat's Newsletter |
Thymus Gland Atrophy: Causes and Restorative Substances"Factors causing thymus gland atrophy include cortisol and other glucocorticoid hormones, estrogen, prostaglandins, polyunsaturated fatty acids, lipid peroxidation, nitric oxide, endotoxin, hypoglycemia, and ionizing radiation. Progesterone and thyroid hormone support thymus gland restoration and provide protection by counteracting all these atrophy-inducing factors. Increasing sugar in the diet can correct some of the metabolic changes of aging." November 2016 – Ray Peat's Newsletter |
Nitric Oxide in the Treatment of Coronavirus and Its Consequences"Nitric oxide is a strong oxidizing agent that can destroy viruses, and it randomly dilates blood vessels. Doctors have almost unanimously recommended it for treating coronavirus infection; however, it is associated with inflammation (Weidinger, et al., 2015) and promotes fibrosis, with fibrosis being a secondary condition of coronavirus disease." May 2020 – Ray Peat's Newsletter |
Correlation of Exhaled Nitric Oxide and Altitude Sickness"An increased amount of nitric oxide in exhaled breath is a clear predisposing factor for altitude sickness." May 2020 – Ray Peat's Newsletter |
Stress, Metabolic Energy, and System Integration"The stimulation of CRH production by histamine, serotonin, endorphins, IL-1, nitric oxide, and/or estrogen in good health leads to the activation of complex and appropriate anti-stress responses. When the stress is very intense or prolonged, or nutrition has been inadequate, all activating signals, CRH itself, and the anti-stress-promoting glucocorticoids can produce effects that are not integrated into the organism's functions while it copes with its problems, causing symptoms and eventually degenerative processes and aging. This failure of integration is almost always the result of insufficient metabolic energy." May 2019 – Ray Peat's Newsletter |
Environmental factors that may contribute to autism"Among the environmental factors or substances that arise in response to environmental stress and could cause autism are prenatal and neonatal radiation exposure, including isotopes from the energy industry, bomb tests, Chernobyl, and Fukushima; exposure to air pollution, including nitrogen oxides, ozone, carbon monoxide, sulfur dioxide, and particulates (Jung, et al., 2013); aluminum (Mold, et al., 2018), lead, mercury, manganese, arsenic, cadmium, chromium, manganese, and nickel (Windham, et al., 2006); acetaminophen, infections, endotoxin, exogenous and endogenous estrogens, hypothyroidism, progesterone deficiency, agmatine deficiency, serotonin excess, endogenous nitric oxide (Sweeten, et al., 2004), and vitamin D deficiency." May 2018 – Ray Peat's Newsletter |
Influence of various factors on mitochondrial oxygen use"When cells respire intensively, 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 use (for example, thyroid hormone deficiency, too many polyunsaturated fats, nitric oxide, or carbon monoxide), the local oxygen concentration rises because it is not being used." March 2021 – Ray Peat's Newsletter |
The role of endotoxins in activating inflammatory processes"The endotoxin lipopolysaccharide has a generally excitatory effect, activating cellular inflammatory processes and damaging energy production, mediated by cellular products such as nitric oxide, carbon monoxide, serotonin, histamine, prostaglandins, estrogens, and various cytokines (interleukins and tumor necrosis factor, TNF). Some of these substances enter the bloodstream from the gut, others are produced elsewhere in the body, but some are formed directly in the brain when endotoxin reaches the brain." March 2017 – Ray Peat's Newsletter |
Diverse influences and effects of nitric oxide"Nitric oxide, like endotoxin and rotenone, is a strong inhibitor of mitochondrial respiration. Endotoxin and other harmful stimuli can increase the production of nitric oxide, but it is also produced in normal excitatory nerve processes, and when excitation exceeds energy production and inhibitory influences, it can become the central factor in excitotoxicity." March 2017 – Ray Peat's Newsletter |
Hypoglycemia induces excitotoxicity via nitric oxide"Hypoglycemia activates the excitatory glutamatergic system, leading to increased nitric oxide, which causes excitotoxicity when there is simultaneous energy deficiency." March 2017 – Ray Peat's Newsletter |
Nitric oxide causes a metabolic shift to glycolysis"Nitric oxide causes a metabolic shift toward glycolysis even in the presence of oxygen, wastefully producing lactate from glucose." March 2017 – Ray Peat's Newsletter |
Parkinson's disease: increase in iron, nitric oxide, and prostaglandins"In people with Parkinson's disease, increased amounts of iron, nitric oxide, and prostaglandins have been observed." March 2017 – Ray Peat's Newsletter |
Age-related changes in the brain amplified by estrogen"With increasing age, iron and polyunsaturated fats accumulate in the brain. Estrogen slows the removal of dopamine, increasing its potential to react toxically with iron and highly unsaturated fats, especially arachidonic acid and DHA; it also tends to increase the formation of prostaglandins and nitric oxide. The opposing effects of progesterone likely explain the lower prevalence of Parkinson's disease in women compared to men." 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 more suitable drugs bromocriptine, amantadine, and memantine are also widely used. Anticholinergics, similar to hyoscyamine and deadly nightshade, which Charcot used, are sometimes employed to control excessive saliva flow. Amantadine and memantine also protect against nitric oxide, serotonin, inflammation, and endotoxins and protect the mitochondria." March 2017 – Ray Peat's Newsletter |
Stress buffers: substances that stabilize metabolism"Several of these substances inhibit the release of free fatty acids and the formation of prostaglandins and reduce nitric oxide, lactate production, inflammation, excitation, and cholinergic activity. What they all have in common is supporting a shift away from a highly reduced state toward an oxidized-energized balance." March 2016 – Ray Peat's Newsletter |
Various substances that increase respiration and reduce essential CO₂"In addition to ammonia and lactate, other stress-related substances can also increase respiratory drive and thus reduce essential CO₂ – for example endotoxin, acetylcholine, serotonin, hydrogen sulfide, nitric oxide, carbon monoxide, angiotensin, and estrogen." July 2017 – Ray Peat's Newsletter |
Reductive stress triggers regenerative cellular processes"Reductive stress activates multiple levels of regenerative processes (as an alternative to the protective functions of carbon dioxide) to stimulate respiration, increase blood flow, and provide energy and materials for the renewal of cell structures. Prostaglandins, cytokines, estrogen, and nitric oxide are produced in a coordinated manner, and cell behavior changes defensively. The structures of the cytoskeleton are modified as reductive chemistry converts protein disulfides into sulfhydryls, thereby altering the shapes and especially the solubility properties of the cell material." July 2017 – Ray Peat's Newsletter |
Enzymatic Breakdown of Active Hormones“The active thyroid hormone T3 is locally destroyed by a specific deiodinase, prostaglandins are formed by cyclooxygenase, estrogen by aromatase, and nitric oxide by its synthase. These enzymes are activated by chemical reduction of their disulfide groups, converting them into thiol groups.” July 2016 – Ray Peat's Newsletter |
Aspirin and Inflammation: The Lesser-Known Pro-Oxidant Effect“The fact that the pro-inflammatory enzymes aromatase, cyclooxygenase, and nitric oxide synthase – which are inhibited by an oxidizing environment – are also inhibited by aspirin suggests that aspirin and salicylic acid act as pro-oxidants.” July 2016 – Ray Peat's Newsletter |
Reductive stress and its self-reinforcing biochemical cycles“The reduced state caused by starvation or hypoglycemia, an excess of lactate or fat, or oxygen deficiency activates glutamate release, and the resulting excitation can shut down mitochondrial oxidation, intensifying the state of pseudohypoxia. Nitric oxide synthesis activated by reductive stress is a key factor in suppressing mitochondrial oxidation.” January 2017 – Ray Peat's Newsletter |
Reevaluation of the Role of Nitric Oxide in Cell Stress“If we called nitric oxide an anti-respiratory, pro-inflammatory substance mainly produced by stressed cells, we would be very cautious with medical methods that increase its production.” January 2016 – Ray Peat's Newsletter |
Nitric Oxide: Central Factor in Shock States“Nitric oxide was a central factor in shock, and inhibiting its production could alleviate the shock state. Shock was often described as circulatory failure caused by excessive vasodilation, so the role of vasodilating nitric oxide in circulatory collapse was easy to recognize.” January 2016 – Ray Peat's Newsletter |
Overlooked Effect of Nitric Oxide on Mitochondrial Oxygen Use“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, Injury, and Energy Metabolism“The remarkable fact that both estrogen and nitric oxide are produced in virtually every injury has been barely mentioned, and their closely linked effects on energy metabolism have been largely ignored.” January 2016 – Ray Peat's Newsletter |
Adaptive Role of Estrogen in Hibernation“The increase in nitric oxide and/or hydrogen sulfide caused by estrogens is an adaptation for an animal in hibernation, as it lowers body temperature and metabolic rate.” January 2016 – Ray Peat's Newsletter |
Epigenetic Changes through Stress Adaptation"All these forms of stress adaptation involve epigenetic changes to DNA, with nitric oxide working together with estrogen and other hormones in DNA methylation, histone modification, and a variety of other biochemical, long-lasting changes." January 2016 – Ray Peat's Newsletter |
Nitric Oxide: The Double-Edged Sword of Metabolic Regulation"Nitric oxide blocks the ability to use sugar but slows metabolism, so it could serve to adjust the size of developing organs and ensure survival when less energy is available." January 2016 – Ray Peat's Newsletter |
Thyroid hormone balances metabolism"Since the metabolic rate must be balanced with energy availability, thyroid hormone, which directly activates respiratory enzymes, is especially important. Just as an animal could not survive winter in a hyperthyroid state, a fundamental mechanism for coping with stress in non-hibernators is to lower thyroid hormone production. Nitric oxide blocks thyroid hormone formation in response to thyroid-stimulating hormone." January 2016 – Ray Peat's Newsletter |
The dual role of nitric oxide"Although a primitive adaptation mechanism like nitric oxide can be useful for a species, it can be harmful to individual organisms." January 2016 – Ray Peat's Newsletter |
The metabolic consequences of nitric oxide burden"Damage caused by nitric oxide creates a diabetes-like condition that forces the use of fats instead of glucose as an energy source." January 2016 – Ray Peat's Newsletter |
The role of nitric oxide in reductive stress and impaired glucose oxidation"When a particular cell or tissue is strongly reduced, nitrate and nitrite can be converted into nitric oxide, leading to a vicious cycle of blocked glucose oxidation and an even more reduced state." January 2016 – Ray Peat's Newsletter |
Age-related muscle loss, fat gain, and insulin sensitivity"Some of the obvious changes with age, such as muscle loss (Martinez-Moreno, et al., 2007), fat gain (Bahadoran, et al., 2015), and reduced insulin sensitivity (Ropelle, et al., 2013), are caused by increased nitric oxide." January 2016 – Ray Peat's Newsletter |
ApoE4 and the risk of Alzheimer's"People with an abnormal lipoprotein, ApoE4, are more likely to develop Alzheimer's, and this abnormal protein is known to increase the production of nitric oxide." January 2016 – Ray Peat's Newsletter |
Indirect effect of nitric oxide on the heart via the parasympathetic system"Nitric oxide acts on the heart without directly involving the blood vessels. When the parasympathetic nerves influence the heart and slow down and weaken its contractions, they release nitric oxide, which reduces the heart's oxygen consumption as well as its energy production." January 2016 – Ray Peat's Newsletter |
Reductive stress and effects of the parasympathetic nerves"Normally, parasympathetic nerves produce relaxation, but in situations of persistent or unavoidable stress, increased parasympathetic activity and the accumulation of nitric oxide lead to a state of reductive stress that causes pseudohypoxia." January 2016 – Ray Peat's Newsletter |
Linked Biochemical Reactions"Estrogen, nitric oxide, prostaglandins, and parasympathetic nerve activity often occur simultaneously, and it happens that a substance that inhibits one of these components often also inhibits the others." January 2016 – Ray Peat's Newsletter |
Serotonin and the Toxic Effects of 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 – Source |
Glycolysis, pyruvate, and mitochondrial function in cells"Glycolysis produces both pyruvate and lactate, and excess pyruvate produces almost the same inhibitory effect as lactate. Since the Crabtree effect involves nitric oxide and fatty acids as well as calcium, I consider it sensible to look for the simplest explanation rather than experimentally tracking all possible interactions of these substances; a simple physical competition between the products of glycolysis and carbon dioxide for binding sites, such as lysine, would correspond to a phase change in the mitochondrion." July 2000 – Source |
Glucose, glycolysis, and energy production in cells"Glucose and apparently glycolysis are required for the production of nitric oxide, as well as for the accumulation of calcium, at least in some cell types. These coordinated changes, which lower energy production, could be triggered by a reduction of carbon dioxide, in a physical change even more fundamental than the energy level represented by ATP. The use of Krebs cycle substances for the synthesis of amino acids and other products would reduce CO₂ formation and create a situation where the system has two possible states: one, the glycolytic stress state, and the other, the CO₂-producing, energy-efficient state." July 2000 – Source |
Influence of Estrogen on Histamine, Serotonin, and Edema"It is known that histamine, serotonin, and other inflammation factors released by estrogen contribute to its ability to cause edema. The excess nitric oxide produced under the influence of estrogen likely contributes to some edematous, inflammatory, and degenerative conditions." January 2000 – Ray Peat's Newsletter |
Excitotoxic Damage and the Protective Role of Carbon Dioxide"The release of histamine, nitric oxide, and carbon monoxide is largely involved in excitotoxic damage, and carbon dioxide also acts protectively against it." December 1999 – Ray Peat's Newsletter |
Ray Peat on Nitric Oxide
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