Training Compounds
Evidence: strong_human
Caffeine is a methylxanthine that primarily acts as a competitive adenosine A1 and A2A receptor antagonist. By blocking adenosine's inhibitory effects on neural activity, caffeine increases alertness, reduces perceived exertion, and delays fatigue. Downstream effects include: increased dopamine, norepinephrine, and acetylcholine release; enhanced calcium release from sarcoplasmic reticulum (direct muscle contraction enhancement); increased fat oxidation via enhanced lipolysis (HSL activation through cAMP/PKA pathway from PDE inhibition); and central drive enhancement (reduced RPE). Caffeine also inhibits phosphodiesterase (PDE), raising intracellular cAMP.
Standard: 100-400mg daily (1-3mg/kg bodyweight for cognitive; 3-6mg/kg for athletic performance)
Maintenance: 100-200mg/day for regular users
Administration: oral
Timing: 30-60 min before exercise or cognitive demand. Avoid within 8-10 hours of bedtime (half-life: 5-6 hours, but CYP1A2 polymorphisms cause wide variation). Morning preferred.
Duration: ongoing with periodic tolerance resets (1-2 weeks off every 8-12 weeks)
CYP1A2 genotype determines caffeine metabolism speed: -163C>A (rs762551) — AA homozygotes are 'fast metabolizers' who benefit most from pre-exercise caffeine, while AC/CC 'slow metabolizers' may experience more side effects and even reduced performance. Genetic testing is highly recommended before optimizing caffeine protocols. Tolerance develops in 7-14 days of regular use — periodic washouts (caffeine holidays) restore sensitivity. The lethal dose is approximately 10g for adults — bulk caffeine powder should NEVER be recommended. Coffee provides beneficial polyphenols beyond caffeine.
Caffeine anhydrous (pure, powdered) provides precise dosing vs coffee (~80-150mg variable per cup). Sustained-release caffeine (Infinergy/caffeine malate) reduces peak-trough fluctuations. Capsule form prevents accidental overdose (pure caffeine powder is dangerous — 10g can be lethal). Brands: Thorne Caffeine, ProLab Caffeine, Nutricost.
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