Spread of damage through bystander effects"Severe stress in one part of the body spreads its influence throughout the entire body, in a process now known as 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 the analysis of hormetic toxins"If toxins like CO and NO are hormetically beneficial when they are present in city air, then they must obviously be very beneficial when produced in the body by enzymes that have evolved through the natural selection of things that support survival – there is a clear panglossic aspect to neo-Darwinism: everything exists because of its expediency." November 2017 – Ray Peat's Newsletter |
Thymus atrophy: causes and restorative substances“Factors that cause thymus atrophy include cortisol and other glucocorticoid hormones, estrogen, prostaglandins, polyunsaturated fatty acids, lipid peroxidation, nitric oxide, endotoxin, hypoglycemia, and ionizing radiation. Progesterone and thyroid hormones support thymus restoration and offer protection by counteracting all of these atrophy-inducing factors. Increasing dietary sugar may correct some of the metabolic changes associated with aging.” November 2016 – Ray Peat's Newsletter |
Nitric oxide in the treatment of coronavirus and its consequences"Nitric oxide is a powerful oxidizing agent that can destroy viruses, and it also happens to dilate blood vessels. Doctors have almost unanimously recommended it for the treatment of coronavirus infection; however, it is associated with inflammation (Weidinger et al., 2015) and promotes fibrosis, which is 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"In good health, the stimulation of CRH production by histamine, serotonin, endorphins, IL-1, nitric oxide, and/or estrogen leads to the activation of complex and appropriate anti-stress responses. However, when stress is very intense or prolonged, or when nutrition has been inadequate, all the activating signals, CRH itself, and the anti-stress-promoting glucocorticoids can produce effects that are not integrated into the organism's functions as it copes with its problems, causing symptoms and ultimately degenerative processes and aging. This failure of integration is almost always a consequence of insufficient metabolic energy." May 2019 – Ray Peat's Newsletter |
Environmental factors that may contribute to autism“Environmental factors or substances that may be produced in response to environmental stress and could cause autism include 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 particulate matter (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 utilization"When cells are breathing intensively, all the oxygen that reaches the mitochondria is immediately consumed, so the oxygen concentration near the respiratory enzymes is almost zero. If something disrupts mitochondrial oxygen utilization (for example, a deficiency of thyroid hormones, too many polyunsaturated fats, nitric oxide, or carbon monoxide), the local oxygen concentration increases because it is not being used." March 2021 – Ray Peat's Newsletter |
The role of endotoxins in the activation of inflammatory processes"The endotoxin lipopolysaccharide has a generally excitatory effect that activates cellular inflammatory processes and impairs energy production, mediated by cell 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 intestines, others are produced in other parts of the body, but some are formed directly in the brain when endotoxin enters the brain." March 2017 – Ray Peat's Newsletter |
Diverse influences and effects of nitric oxide"Nitric oxide, like endotoxin and rotenone, is a potent inhibitor of mitochondrial respiration. Endotoxin and other harmful stimuli can increase the production of nitric oxide, but it is also produced in the normal excitatory processes of the nerves, and when there is an excess of excitation relative to 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, in the presence of energy deficiency, causes excitotoxicity." March 2017 – Ray Peat's Newsletter |
Nitric oxide causes a metabolic switch to glycolysis."Even in the presence of oxygen, nitric oxide leads to a metabolic shift towards glycolysis, wastefully producing lactate from glucose." March 2017 – Ray Peat's Newsletter |
Parkinson's disease: Increase in iron, nitric oxide, and prostaglandins"Elevated levels of iron, nitric oxide, and prostaglandins have been observed in people with Parkinson's disease." March 2017 – Ray Peat's Newsletter |
Age-related changes in the brain are exacerbated by estrogen."With increasing age, iron and polyunsaturated fats accumulate in the brain. Estrogen slows the removal of dopamine, thereby increasing its potential to react toxically with iron and highly unsaturated fats, particularly arachidonic acid and DHA; it also tends to increase the production 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 disease"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 belladonna, which Charcot used, are sometimes employed to control excessive salivation. 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 the support of a shift away from a highly reduced state towards an oxidized-energized equilibrium.” March 2016 – Ray Peat's Newsletter |
Various substances that increase respiration and reduce essential CO₂"Besides 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 several 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 to a defensive state. The structures of the cytoskeleton are modified as reductive chemistry converts protein disulfides into sulfhydryls, thereby altering the shapes and, most importantly, the solubility properties of the cellular material.” July 2017 – Ray Peat's Newsletter |
Enzymatic degradation 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, which converts them into thiol groups." July 2016 – Ray Peat's Newsletter |
Aspirin and inflammation: The lesser-known pro-oxidative 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 hunger or hypoglycemia, excess lactate or fat, or oxygen deficiency activates the release of glutamate, and the resulting excitation can shut down mitochondrial oxidation, thereby exacerbating the state of pseudohypoxia. Nitric oxide synthesis, activated by reductive stress, is a key factor in the suppression of mitochondrial oxidation." January 2017 – Ray Peat's Newsletter |
Reassessment of the role of nitric oxide in cell stress"If we were to describe nitric oxide as an anti-respiratory, pro-inflammatory substance produced mainly by stressed cells, we would be very cautious about medical methods that increase its production." January 2016 – Ray Peat's Newsletter |
Nitric oxide: A key factor in shock states"Nitric oxide was a key factor in the shock state, and inhibiting its production could alleviate the shock state. The shock state was often described as circulatory failure caused by excessive vasodilation, so the role of vasodilating nitric oxide in circulatory collapse was readily apparent." January 2016 – Ray Peat's Newsletter |
Overlooked effect of nitric oxide on mitochondrial oxygen utilization"Only a very small minority of publications on the physiology of nitric oxide address the fact that it inhibits the mitochondrial use of oxygen 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 related effects on energy metabolism have been largely ignored." January 2016 – Ray Peat's Newsletter |
Adaptive role of estrogen during hibernation"The increased levels of nitric oxide and/or hydrogen sulfide caused by estrogen 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, together with estrogen and other hormones, contributing to DNA methylation, histone modification, and a variety of other long-lasting biochemical 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 down 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 the metabolism"Since the metabolic rate must be in balance with the availability of energy, thyroid hormone, which directly activates respiratory enzymes, is particularly important. Just as it would be impossible for an animal to hibernate in a state of hyperthyroidism, a fundamental mechanism for coping with stress in non-hibernating animals is to reduce the production of thyroid hormone. Nitric oxide blocks the formation of thyroid hormone 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 may be beneficial for a species, it can be harmful to individual organisms." January 2016 – Ray Peat's Newsletter |
The metabolic consequences of nitric oxide exposure"The damage caused by nitric oxide creates a diabetes-like condition that forces the body to use 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 severely 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 associated with aging, such as muscle loss (Martinez-Moreno, et al., 2007), fat gain (Bahadoran, et al., 2015) and decreased 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 disease"People with an abnormal lipoprotein, ApoE4, are more likely to develop Alzheimer's disease, 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 being directly connected to the blood vessels. When the parasympathetic nerves act on the heart and slow down and weaken its contractions, they release nitric oxide, which reduces the heart's oxygen consumption and energy production." January 2016 – Ray Peat's Newsletter |
Reductive stress and effects of the parasympathetic nervous system"Normally, parasympathetic nerves produce relaxation, but in situations of prolonged or unavoidable stress, increased parasympathetic activity and the accumulation of nitric oxide lead to a state of reductive stress, causing pseudohypoxia." January 2016 – Ray Peat's Newsletter |
Linked biochemical reactions“Estrogen, nitric oxide, prostaglandins and parasympathetic nerve activity often occur simultaneously, and it is common for a substance that inhibits one of these components to also inhibit 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 think it makes sense to look for the simplest explanation rather than experimentally investigating 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 reduce energy production, could be triggered by a reduction in carbon dioxide, in a physical change even more fundamental than the energy level represented by ATP. The utilization of Krebs cycle substances for the synthesis of amino acids and other products would reduce CO₂ formation and create a situation in which 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 inflammatory factors released by estrogen contribute to its ability to produce 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, while carbon dioxide also has a protective effect." December 1999 – Ray Peat's Newsletter |
Ray Peat on nitric oxide
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