Acheson · The American journal of clinical nutrition 2004 · controlled crossover clinical trial · n=8

Metabolic effects of caffeine in humans: lipid oxidation or futile cycling?

Cited 239 times in the scientific literature.

Level 2 - randomized trial

Controlled clinical trial evaluating metabolic tracer kinetics across three conditions

PubMed 14684395 · doi:10.1093/ajcn/79.1.40 · record verified 2026-08-29

What was done

Respiratory gas exchange and [1-13C]palmitate tracer methods were used to measure lipid oxidation and free fatty acid (FFA) turnover in 8 healthy, young men. Measurements were collected across 90 minutes before and 240 minutes after the ingestion of placebo, caffeine (10 mg/kg), or caffeine administered during beta-adrenoceptor blockade.

What was found

During fasting baseline conditions, measured metabolic variables did not differ between the 3 tests. During the final hour after caffeine intake, lipid turnover increased 2-fold (P < 0.005) and energy expenditure increased by 13.3 +/- 2.2% (P < 0.001), both higher than after placebo or caffeine with beta-blockade. Caffeine increased oxidative FFA disposal by 44% (from 236 +/- 21 to 340 +/- 16 micromol/min), while nonoxidative FFA disposal increased 2.3-fold (from 455 +/- 66 to 1054 +/- 242 micromol/min; P < 0.01). Under postabsorptive conditions, 34% of lipids were oxidized and 66% were recycled; following caffeine, 24% were oxidized and 76% were recycled. Beta-adrenoceptor blockade blunted, but did not eliminate, these metabolic responses.

Why it matters

This study shows that the acute lipolytic effect of high-dose caffeine primarily drives futile cycling between triacylglycerol and free fatty acids rather than large increases in actual fat oxidation, with effects partly mediated by the sympathetic nervous system.

Limits

The study evaluated a very small cohort (n = 8) consisting exclusively of healthy young men under acute, resting postabsorptive conditions. The caffeine dose tested (10 mg/kg) is relatively large, and the abstract does not report long-term metabolic outcomes or findings in other demographic groups.

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