medwireNews: Self-reported melatonin supplement use is not associated with the risk for type 2 diabetes or cardiovascular disease (CVD), suggest long-term follow-up data from three large prospective cohorts of middle-aged and older men and women.
“However, there was some suggestive evidence that regular use of melatonin supplement might attenuate adverse effects of long-term night shift work on cardiovascular disease risk among female nurses,” report Yangping Li (Harvard T H Chan School of Public Health, Boston, Massachusetts, USA) and co-authors in The Lancet Diabetes & Endocrinology.
They explain that the use of melatonin supplements has increased substantially in the USA. The supplements are primarily advertised as a natural sleep aid for general use, but also for improving sleeping difficulties due to circadian rhythm disturbances in night shift workers, or for easing jet lag.
In the three cohorts included in the current study – the Nurses’ Health Study (1998–2019), the Health Professionals Follow-up Study (1998–2020), and the Nurses’ Health Study II (2003–2019) – less than 2% of men and women reported taking melatonin during 1998–2007. By 2014–2015, the rate was 4.0% in men and 5.3% in women.
This growing melatonin use “prompts a careful consideration of potential negative side effects,” the researchers remark.
They therefore investigated whether there was a link between self-reported melatonin use and the risk for type 2 diabetes and CVD in 67,202 women (mean age at baseline 63.4 years) from the Nurses' Health Study, 26,629 men (mean age 62.8 years) from the Health Professionals Follow-up Study, and 65,241 women (mean age 49.0 years) from the Nurses' Health Study II. The participants had up to 23 years of follow-up data and none had type 2 diabetes, CVD, or cancer at baseline.
Li et al report that there were 12,730 incident cases of type 2 diabetes during 2,701,830 person–years of follow-up and 16,917 incident CVD events during 2,609,068 person–years of follow-up.
In a pooled analysis of the three cohorts adjusted for age, sex, socioeconomic factors, lifestyle factors, baseline complications, and sleep-related factors, there was no significant increased or decreased risk for type 2 diabetes or CVD among melatonin users relative to non-users.
The investigators also carried out a secondary analysis among Nurses' Health Study and Nurses' Health Study II participants to examine whether rotating night shift work impacted the relationship between melatonin use and type 2 diabetes or CVD risk.
They found that for type 2 diabetes, nurses with more than 5 years’ history of rotating shift work who did not use melatonin had a significantly higher risk than melatonin non-users who had no experience of working night shifts (hazard ratio [HR]=1.11), but there was no attenuated risk among shift workers who used melatonin, at a nonsignificant HR of 0.91.
And compared with nurses who had no experience of rotating night shift work and did not report regular use of melatonin supplements, the HR for CVD among nurses who had more than 5 years of shift work was a significant 1.10 without regular use of melatonin supplements and a significant 0.62 with regular use of melatonin supplement.
The interaction between the two outcomes was statistically significant, suggesting that melatonin supplement use appeared to “attenuate the positive association between long-term shift work (>5 years) and risk of cardiovascular disease,” Li et al remark.
The authors note that they “did not collect detailed information on melatonin supplements, such as age at initiation of use, frequency and duration of use, supplement dosage and brand, and whether the usage was related to night shift work,” which is a limitation of the study.
They therefore conclude that “[f]urther research is warranted to assess whether melatonin supplement use has the potential to mitigate the elevated risks of chronic disease associated with rotating night shift work.”
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Lancet Diabetes Endocrinol 2024; doi:10.1016/S2213-8587(24)00096-2