Caffeine: Effective Dose, Safe Limit and Side Effects

Antagonises adenosine receptors, blocking the signal that accumulates through the day and produces the sensation of tiredness. Downstream effects include increased catecholamine release, lower perceived exertion during exercise, and increased calcium release in muscle. Tolerance to the alertness effect develops within days; tolerance to the performance effect is less complete.

• Exercise performance: consistently improved at 3-6 mg per kg of body mass, per the International Society of Sports Nutrition position stand. Doses at or above 9 mg/kg add nothing.
• Alertness and reaction time: reliable, and partly a reversal of withdrawal in habitual users.
• Thermogenesis: a modest increase in energy expenditure, amplified when combined with green tea catechins.
• Minimum effective dose: may be as low as 2 mg/kg, lower than most pre-workouts assume.

The International Society of Sports Nutrition position stand on caffeine and exercise performance, updated in 2021, establishes the 3-6 mg/kg range and the absence of additional benefit at 9 mg/kg or more. The EFSA scientific opinion on the safety of caffeine sets the 400 mg/day and 200 mg single-dose reference points used by most regulators.

3-6 mg per kg of body mass for performance, which is 210-420 mg for a 70 kg adult, taken 30-60 minutes before exercise. EFSA concluded that habitual intakes up to 400 mg/day do not raise safety concerns for non-pregnant adults, and that single doses up to 200 mg are unlikely to cause adverse effects. Pregnant women should stay at or below 200 mg/day.

Anxiety, jitteriness, palpitations, raised blood pressure, GI upset and insomnia. The half-life is around five hours, so an afternoon dose still measurably affects sleep. Withdrawal headache and fatigue appear within 12-24 hours of stopping regular use. Caffeine anhydrous powder has caused fatalities through measurement error and should never be dosed by eye.

Additive with other stimulants including synephrine and yohimbine, which is how many fat-burner formulas produce cardiovascular complaints. Metabolised by CYP1A2, so fluvoxamine, ciprofloxacin and oral contraceptives markedly slow its clearance. Reduces absorption of iron and calcium. Adds to the blood-pressure effect of stimulant medication.