Nitric oxide

Nitric oxide is a free radical gas that Ray Peat treated as a fundamental metabolic toxin, analogous in its action to carbon monoxide and cyanide. 2 Peat argued that its primary mechanism of harm is the poisoning of mitochondrial respiration, specifically by blocking the enzyme cytochrome c oxidase and other electron transport components, which shuts down oxidative energy production. 2 This interruption causes electrons to back up, shifting the entire cell into a reduced chemical state and creating a condition of reductive stress that promotes the leakage of electrons and further free radical damage. 2 Although the body produces nitric oxide endogenously, Peat emphasized that it was first known as a toxic component of smog, and its internal production should be viewed as a dangerous, primitive adaptation rather than a health-promoting molecule. 2

The physiological role of nitric oxide is that of an emergency vasodilator, deployed when the organism cannot produce sufficient carbon dioxide to properly relax blood vessels. 4 Georgi Dinkov has explained that both gases regulate vascular tone by controlling calcium levels in cells, but carbon dioxide is the preferred, non-pathological mechanism, while nitric oxide is a compensatory response to a perceived state of hypoxia when oxidative metabolism is failing. 4 Peat documented that this emergency system becomes destructive when chronically activated, as nitric oxide is a central damaging agent in the dopamine system in Parkinson's disease, a killer of insulin-producing beta cells in the pancreas leading to diabetes, and a promoter of cancer growth by stimulating cell division in the absence of sufficient energy. 3 The muscle growth touted by bodybuilders using arginine supplements is, in Peat's view, an inflammatory and hypoxic process akin to putting a tourniquet on a limb, forcing cells to divide because they lack the energy to perform differentiated functions. 5

Peat traced a distinct chronology in the scientific perception of nitric oxide, noting that from its discovery in the body in the late 1980s until the mid-1990s, research clearly demonstrated its toxicity, including massive documentation of its role in killing pancreatic beta cells. 2 He argued that this understanding was abruptly inverted around 1997 when the patent and marketing for Viagra (sildenafil) created a financial incentive to reframe nitric oxide as a wonder molecule associated with virility, leading to a flood of publications touting its protective effects. 3 After the initial wave of publicity subsided, Peat observed that research began to re-acknowledge its role in producing diabetes, heart failure, and the fibrotic degeneration of aging. 2 He noted that the age-related loss of muscle, gain of fat, decreased insulin sensitivity, and collagen deposition in arteriosclerotic arteries are all produced by increased nitric oxide. 6

The body's natural regulation of nitric oxide is hormonally controlled, with estrogen exciting and activating the nitric oxide synthase enzyme, while progesterone and related neurosteroids like pregnenolone inhibit its production and stabilize the cell. 2 Peat highlighted that nitric oxide impairs the oxidation of glucose, creating a state of aerobic glycolysis that mimics cancer metabolism, and that its excitatory effects on the parasympathetic nervous system can paradoxically lead to vascular spasms, variant angina, and transient ischemic attacks. 2 The accumulation of nitric oxide, combined with the reductive stress from blocked respiration, is implicated in the pathology of Alzheimer's disease and other degenerative conditions. 6 Peat suggested that therapeutic intervention involves using substances that block these energy-limiting systems to restore full oxidative energy production. 7