Caffeine

Caffeine is a methylxanthine alkaloid found in coffee, tea, and cocoa that acts as a competitive antagonist of adenosine A1 and A2A receptors, inhibiting the adenosine-mediated signalling that promotes drowsiness and reduces neuronal activity. Receptor blockade disinhibits dopamine, glutamate, and acetylcholine release, producing increases in alertness, reaction time, and sustained attention. Plasma half-life averages 5–6 hours in healthy adults but extends with age, liver impairment, or oral contraceptive use, so a late-afternoon dose can suppress slow-wave and REM sleep. Habitual coffee consumption shows an inverse association with all-cause mortality: the NIH-AARP Diet and Health Study (Freedman et al. 2012, N ≈ 400,000) found 4–5 cups/day associated with hazard ratios of ~0.88 (men) and ~0.84 (women), with reduced risk across cardiovascular, respiratory, stroke, diabetes, and infection-related causes; a meta-analysis of 23 prospective studies (Malerba et al. 2013) corroborated an inverse trend at moderate intake. A2A antagonism is linked to lower Parkinson's disease incidence in prospective data and underpins the approved drug istradefylline, though caffeine is neither approved as a therapeutic nor proven causally protective — residual lifestyle confounding cannot be excluded. A 2025 narrative review (Carbone et al.) notes moderate intake may support alertness and offer neuroprotective effects in aging, while excessive use can cause anxiety, sleep disturbances, and cognitive or motor impairment in older adults.