Prostaglandins

Prostaglandins are hormone-like inflammatory signaling substances synthesized from polyunsaturated fats (PUFAs), and Ray Peat argued that, contrary to the popular "yin and yang" theory of good and bad types, the accumulating evidence shows they all have seriously harmful effects, making their absence beneficial. 2 They are formed from linoleic acid and arachidonic acid via the cyclooxygenase (COX) pathway, and Peat noted that the body's own endogenously produced Mead acid (an omega-9 PUFA) yields anti-inflammatory prostaglandins, but this natural defensive system is blocked by the accumulation of dietary vegetable and fish oils. 3 Georgi Dinkov has reinforced that even mainstream medicine considers the ideal blood level of PGE2 to be zero, and that consuming PUFAs guarantees a certain amount of these metabolites will be produced, especially during stress-induced lipolysis when PUFAs are preferentially released from fat stores. 11

The pathological actions of prostaglandins form a central amplifying loop in degenerative disease. Peat detailed that PGE2 directly activates aromatase, the enzyme that synthesizes estrogen from androgens, and also activates heme oxygenase, which produces carbon monoxide and releases toxic free iron. 2 Dinkov has written that PGE2 was found to be directly responsible for inhibiting oxidative glucose metabolism in the brain, diverting glucose to glycogen synthesis and producing an "aged brain" phenotype with significant cognitive deterioration. 9 This metabolic suppression is compounded by prostaglandins' ability to synergize with estrogen, destroy the negative feedback mechanism of the adrenal axis to elevate cortisol, and activate tryptophan hydroxylase to increase serotonin synthesis. 2 Danny Roddy has highlighted that PGE2 is elevated in prostate and breast cancer, and that PGD2 was found to be significantly increased in the scalps of men with androgenic alopecia, linking these metabolites directly to pattern hair loss. 3

The production and effects of prostaglandins are intimately tied to systemic energy failure and inflammation. Peat explained that the stressed or injured cell becomes incontinent, releasing ATP and producing lactic acid, while the peroxidation of PUFAs produces toxins that amplify cellular stress reactions. 2 Dinkov described a positive-feedback loop where increased prostaglandin levels result in increased COX enzyme expression and activity, creating a self-reinforcing spiral of inflammation. 9 Roddy noted that many prostaglandins are anti-respiratory, directly inhibiting the production of useful energy, and that the liberation of free fatty acids into the blood promotes inefficient energy metabolism and inflammation. 7 This cascade connects prostaglandins to a broader degenerative context where Peat observed that the accumulation of PUFA is one reason why baldness, heart attacks, and prostate cancer are strongly associated. 8

Therapeutic intervention focuses on blocking prostaglandin synthesis and avoiding their dietary precursors. Peat listed aspirin, caffeine, progesterone, and methylene blue as safe substances that lower carbon monoxide production or protect against its effects, with aspirin being the most direct method to inhibit the COX pathway. 2 Dinkov has emphasized that blocking the effects of PGE2, even peripherally, was sufficient to restore glucose metabolism and reverse the aged brain phenotype in animal studies. 9 The foundational strategy, however, is the systemic avoidance of dietary PUFAs, as Peat argued that the relative absence of these fats improves fetal memory and development, and that non-metabolized PUFA itself suppresses glucose metabolism and increases inflammatory biomarkers independently of prostaglandin formation. 2