A meta-analytic approach to quantify the dose-response relationship between melatonin and core temperature

A melatonin-mediated reduction in body temperature could be useful as a "pre-cooling" intervention for athletes, as long as the melatonin dose is optimised so that substantial soporific effects are not induced. However, the melatonin-temperature dose-response relationship is unclear in humans. Individual studies have involved small samples of different sexes and temperature measurement sites. Therefore, we meta-analysed the effects of exogenous melatonin on body core temperature to quantify the dose-response relationship and to explore the influence of moderating variables such as sex and measurement site. Following a literature search, we meta-analysed 30 data-sets involving 193 participants and 405 ingestions of melatonin. The outcome was the mean difference (95 % confidence limits) in core temperature between the melatonin and placebo-controlled conditions in each study, weighted by the reciprocal of each standard error of the difference. The mean (95 % confidence interval) pooled reduction in core temperature was found to be 0.21 C (0.18-0.24 C). The dose-response relationship was found to be logarithmic (P < 0.0001). Doses of 0-5 mg reduced temperature by ~0.00-0.22 C. Any further reductions in temperature were negligible with doses >5 mg. The pooled mean reduction was 0.13 C (0.05-0.20 C) for oral temperature vs 0.26 C (0.20-0.32 C) for tympanic and 0.22 C (0.19-0.25 C) for rectal temperature. In conclusion, our meta-regression revealed a logarithmic dose-response relationship between melatonin and its temperature lowering effects. A 5-mg dose of melatonin lowered core temperature by ~0.2 C. Higher doses do not substantially increase this hypothermic effect and may induce greater soporific effects.