Every zero-result search is logged — it is how we decide what to curate next.
Also: caffiene
Four separate measurements, never averaged. Independent evidence counts only studies with no sponsor attached. Methodology version v2.0-2026-10 · how we grade evidence
Claimed to improve endurance, strength, power and alertness, increase metabolic rate and fat oxidation, and promote fat loss and appetite suppression. The performance effects are small, reproducible and correctly sized in the literature: strength SMD 0.20 (95% CI 0.03–0.36), power SMD 0.17 (0.00–0.34) with a lower bound of exactly zero, and endurance improvements of about 2–3% — genuinely valuable to a competitive athlete and essentially irrelevant to a general-health user. Across 46 endurance studies, two reported slower time-trial performance and five lower mean power output with caffeine, so a meaningful minority of individuals do not respond.
No high-quality meta-analysis showing clinically meaningful weight or fat-mass loss was located. The best available evidence addresses fat oxidation, a surrogate: the pooled effect is ES 0.39 (0.30–0.47), and the measure closest to whole-body fat burning — expired-gas analysis — gave the smallest effect, ES 0.26 (0.16–0.37), against ES 0.55 (0.43–0.67) for blood biomarkers. No included study measured fat loss. That analysis was funded by The Coca-Cola Foundation.
Safety is established and the lethal dose is quantified: NIH ODS states an acute oral dose of about 10–14 g can be fatal and at least two young men have died after taking pure powdered caffeine. Heavy use may reduce performance and causes sleep disturbance, irritability and anxiety. No hepatotoxicity signal. The principal product-level hazard is concentration rather than caffeine itself, which is what the FDA’s action against bulk powders addresses. Note the regulatory inversion: the European Union authorises no health claim for caffeine at all, while authorising claims for compounds with weaker evidence.
At a glance
Competitive antagonism of adenosine A1 and A2A receptors in the central nervous system, which reduces perceived effort and increases central drive, with secondary catecholamine release and lipolysis. Both the adenosine antagonism and its ergogenic consequence are demonstrated in human randomised trials. The lipolytic step is also measurable, but an increase in fat oxidation is not the same as fat loss, and the distinction is where the thermogenic marketing claim fails.
Dated determinations, each flagged for whether it is final and whether it covers safety only. A safety review is not an efficacy finding, and most reporting in this category conflates the two.
Recorded in the NIH ODS fact sheet, which also notes the AMA recommends limits of 500 mg/day for adults and 100 mg/day for adolescents. ODS states an acute oral dose of about 10–14 g (150–200 mg/kg) can be fatal and that at least two young men have died after taking pure powdered caffeine. Heavy use at or above 500 mg/day may *reduce* performance and causes sleep disturbance, irritability and anxiety.
Guidance of 16 April 2018, directed at containers holding hundreds or thousands of servings. FDA said "even a small dose can be toxic or deadly", noted bulk caffeine has been linked to two deaths, and doubted consumers can accurately measure a 200 mg serving (about 1/16 teaspoon). The hazard being regulated is concentration and product format, not caffeine itself.
EFSA Scientific Opinion on the safety of caffeine, EFSA Journal 2015;13(5):4102 (DOI not verified; stakeholder presentation dated 5 March 2015). Thresholds: single doses up to 200 mg (about 3 mg/kg body weight) and habitual intake up to 400 mg/day (about 5.7 mg/kg) for healthy adults; up to 200 mg/day for pregnant women; about 3 mg/kg body weight per day for children and adolescents.
Verified directly against the Annex: there is no caffeine entry at all. EFSA’s proposed caffeine performance claims were never adopted. The compound with the most reproducible performance effect in this cluster carries no European efficacy claim, while glucomannan — pooled weight effect −0.22 kg, non-significant — carries an authorised weight-loss claim.
Educational information only
Educational information only. Not medical advice, not a diagnosis, and not a substitute for your clinician. Never start, stop, or change a prescription medication based on anything you read here. We do not sell, prescribe, dispense or recommend any medication, peptide or supplement, and we do not link to anyone who does. If you are having a medical emergency, call 911.
Published by Nu Link, 10111 Clodine Rd, Richmond, TX 77407.