Caffeine

Caffeine is a purine alkaloid that Ray Peat considered to function analogously to progesterone and carbon dioxide, stabilizing the cell to expel calcium and sodium, suppress glycolysis, and shift metabolism toward an oxidizing state through a shared structural electron-attracting effect. 2 This fundamental action underlies its broad protective effects, including blocking pro-inflammatory, pro-glycolytic, and reductive processes involved in carcinogenesis from radiation, chemical carcinogens, or viral processes. 1 Peat argued that caffeine's ability to restore respiratory energy production, partly by inhibiting nitric oxide formation, allows it to inhibit vascular endothelial growth factor (VEGF) and consequently suppress neovascularization and cancer growth. 10

Mechanistically, caffeine increases the cellular level of cyclic AMP (cAMP), a regulatory substance mediating its inhibition of cancer cell multiplication, and opposes the effects of adenosine secreted by stressed, energy-depleted cells. 3 By raising cAMP and decreasing serotonin in thyroid cells, caffeine tends to locally activate thyroid secretion, and it synergizes with thyroid and progesterone to increase their production or compensate for their deficiency. 4 Peat noted that caffeine's effect on the breast resembles that of progesterone, opposing estrogen's actions, and he dismissed the claim that it causes fibrocystic breast disease as a logical error, since the elevated cAMP in diseased tissue is a protective response that caffeine supports. 3 Caffeine also restrains the enzyme xanthine oxidase, which in stress can become a dangerous source of free radicals, and it inhibits the energy-depleting PARP enzyme to prevent a characteristic form of cell death without preventing normal cellular turnover. 2

The metabolic context of caffeine consumption is critical. Peat emphasized that caffeine increases the cellular consumption of glucose, so drinking it on an empty stomach confounds its intrinsic effects by causing a drop in blood sugar and a compensatory increase in adrenaline. 3 He advised taking coffee with a meal, with cream or milk and sugar, to avoid the anxiety and shakiness associated with hypoglycemia, and reported that people previously intolerant to coffee could become happy drinkers within days using this method. 2 When consumed adequately, caffeine increases blood volume in the brain while decreasing vascular resistance, an effect consistent with its stimulation of brain metabolism and the consequent increase in vasodilating carbon dioxide. 3 In the context of rosacea, caffeine can decrease vasodilation caused by a mismatch between energy supply and demand, though it does not inhibit the physiological vasodilation from carbon dioxide. 8

Peat viewed the habitual consumption of coffee as a rational, homeostatic self-medication rather than a destructive addiction, noting that his own intake spontaneously dropped from 50 cups to about five per day after he began thyroid supplementation. 9 He cited epidemiological evidence that five or more cups per day were associated with the lowest rates of liver disease, dementia, and cancer, and that coffee and tea together provide roughly 20% of several essential nutrients in some national diets, including B vitamins and manganese. 3 Caffeine also protects against iron overload by inhibiting intestinal iron absorption, and coffee drinkers have been found to have lower levels of cadmium in their kidneys. 2 Peat argued that caffeine's protective effects, including stimulation of DNA repair processes and the immune system, are so profound that they override the harmful effects of the smoky junk in coffee. 2