Melatonin touted as glucose-metabolic–safe sleep aid in meta-analysis

Intake of melatonin before bedtime does not appear to harm glucose metabolism and may even be beneficial given its positive effect on insulin sensitivity, according to the results of a meta-analysis.

Pooled data from 11 studies showed that melatonin treatment did not significantly affect fasting plasma glucose levels in healthy adults and patients with glucose-metabolic diseases as compared with placebo (Hedges' g, −0.07, 95 percent confidence interval [CI], −0.22 to 0.08; n=603). [Clin Endocrinol 2021;95:91-701]

Of note, fasting insulin levels markedly decreased instead with melatonin, although the effect was small (g, −0.27, 95 percent CI, −0.50 to −0.04; n=278), and trended towards reduced insulin resistance (HOMA-IR; g, −0.20, 95 percent CI, −0.44 to 0.03).

Long-term melatonin treatment also exerted no meaningful impact on HbA1c levels, although only two studies were analysed.

The investigators acknowledged that the CIs were wide and stressed a need for larger studies to confirm the effect of melatonin treatment on fasting insulin levels, as well as on HbA1c levels and insulin sensitivity.

“Melatonin is a tryptophan-derived hormone, which serves as an endocrine signal for retinal light exposure in humans,” they said. “As [its] consumption of melatonin is rapidly increasing as a presumably safe sleep aid in both adults and children, it is important to clarify the effects of melatonin on glucose metabolism.” [Natl Health Stat Report 2015:79:1-16]

Previous studies reported that daytime administration of melatonin resulted in lower insulin sensitivity and, at high doses, reduced glucose-dependent insulinotropic polypeptide levels. In the current meta-analysis, the investigators included studies that evaluated the effects of daily immediate-release melatonin administration before bedtime for a minimum of 2 weeks. [Sleep 2014;37:1715-1719; J Pineal Res 2021;70:e12706; J Clin Endocrinol Metab 2021;doi:10.1210/clinem/dgab521]

“Obviously, there is a need to clarify whether [the said] negative glucose-metabolic effects of melatonin persist when melatonin is administered at a more physiological and pharmacological appropriate timing. The current study provides evidence that the timing of melatonin administration seems to be crucial, since no studies included in this systematic review and meta-analysis revealed any negative effects on glucose metabolism of melatonin administered before bedtime,” they pointed out.

In terms of the improvements seen in fasting insulin levels and the trend toward improved insulin sensitivity, the investigators noted that while it could look like the benefit might have been mediated by a reduction in body mass index (BMI) after melatonin treatment, this suggestion was unlikely, because subgroup analysis of BMI in the five studies that measured insulin and HOMA-IR showed a negligible effect of melatonin on BMI (g, −0.04, 96 percent CI, −0.27 to 0.20).

The meta-analysis had several limitations. First, the included patient populations across studies differed with respect to the type of metabolic disease investigated, while the participants in three studies were healthy. Also, the dosage of melatonin used varied between 1 and 10 mg, with treatment periods ranging from 2 weeks to 1 year.

Despite the limitations and given the current evidence and literature available, the investigators believed that immediate-release melatonin is a glucose-metabolic safe sleeping aid.