Arachidonic Acid

Arachidonic acid is a highly unsaturated fatty acid that Ray Peat identified as one of the most toxic stored fats in the body, acting as the primary precursor to the major inflammatory mediators known as prostaglandins, leukotrienes, and thromboxanes. 2 Even if not consumed directly, the body synthesizes it from dietary linoleic acid, and its spontaneous release from phospholipids and triglyceride storage triggers a cascade of inflammatory and degenerative processes. 1 Peat argued that this chronic, low-grade inflammation, driven by the continual liberation of small amounts of arachidonic acid, is a fundamental cause of conditions ranging from diabetes and osteoporosis to Alzheimer's disease and fibrosis. 3

The release of arachidonic acid is enzymatically controlled by phospholipase A2, an enzyme activated by virtually any inflammatory or stress signal, including estrogen, serotonin, and physical irritation. 2 Once liberated, arachidonic acid does not require enzymatic conversion to begin causing harm; its mere presence shifts a cell's affinity for water, causing cellular swelling that is sufficient to turn off oxidative phosphorylation and force a reliance on glycolysis. 11 Georgi Dinkov has written that intact arachidonic acid reliably causes decreased mitochondrial function and reduced oxygen consumption, and can even structurally reduce the expression of electron transport chain complexes, making its anti-metabolic effects harder to reverse. 2 This metabolic disruption is not tissue-specific, making arachidonic acid a pro-cancer agent both for the initiation and growth of tumors. 2

Peat detailed multiple self-reinforcing pathological loops involving arachidonic acid. It stimulates the secretion of prolactin, which in turn decreases thyroid activity and oxidative metabolism while increasing glycolysis and lactate production. 3 Dinkov has described a positive feedback cycle between arachidonic acid and serotonin, where arachidonic acid inhibits the serotonin transporter (SERT), leading to increased serotonin availability, which then activates phospholipase A2 to liberate more arachidonic acid. 8 This cycle implicates arachidonic acid as a known inducer of depression and suggests that SSRI drugs, by inhibiting SERT, are highly pro-inflammatory. 8 Furthermore, arachidonic acid and DHA increase the excitatory effect of glutamate on its receptor and decrease its uptake, directly contributing to excitotoxicity and nerve damage seen in epilepsy, Parkinson's disease, and Alzheimer's disease. 9

The accumulation of arachidonic acid in tissues is a hallmark of aging and stress. As fat tissues become more burdened with it, they release it more easily in response to lipolytic stress signals, explaining the increased levels of free fatty acids and lipid peroxidation with age. 10 Peat noted that the brain becomes increasingly enriched with polyunsaturated fats over time, leading to the spontaneous oxidation of these fats into neuroprostanes and isoprostanes, which are linked to the progression of Alzheimer's disease. 6 This burden is diet-dependent; Peat observed that in animals "deficient" in polyunsaturated fatty acids, adrenaline does not have the lipolytic effect it does in animals on a standard diet, highlighting how dietary choices directly modulate the body's stress-induced release of stored toxins. 10

The therapeutic countermeasures to arachidonic acid's toxicity center on inhibiting its release and opposing its downstream effects. Progesterone inhibits the phospholipase that liberates arachidonic acid, while estrogen activates it. 10 Aspirin exerts its broad protective effects partly by inhibiting the synthesis of prostaglandins from arachidonic acid, thereby reducing inflammation, stimulating bone formation, and protecting against excitotoxic nerve damage. 2 Peat maintained that the most fundamental intervention is dietary: consuming saturated fats instead of polyunsaturated fats prevents the initial storage of this toxin, as saturated fats are chemically unreactive and can even act as antioxidants to prevent the deterioration of unsaturated molecules. 2 He dismissed the concept of essential fatty acid deficiency as a misapplication of flawed experimental models, particularly when extrapolated to animals with higher metabolic rates. 4