Effect of oral melatonin treatment on insulin resistance and diurnal blood pressure variability in night shift workers. A double-blind, randomized, placebo-controlled study

Hannemann J, Laing A, Middleton B, et al. Effect of oral melatonin treatment on insulin resistance and diurnal blood pressure variability in night shift workers. A double-blind, randomized, placebo-controlled study. Pharmacol Res. 2024;199:107011. doi:10.1016/j.phrs.2023.107011

Overview

This randomized, placebo-controlled, prospective 12-week study aimed to see if melatonin supplementation at 2 mg could improve insulin resistance markers, sleep quality, circadian melatonin, cortisol levels, and blood pressure in night shift workers.

At the study's conclusion, sleep quality significantly improved from the baseline in the shift work group. The other markers measured were not significantly impacted.

SNHI’s Advisory Council comments/takeaway from the article

Changes to metabolic health (insulin, blood pressure, and cortisol) generally require substantial time to be positively influenced by supplementation, and often multiple aspects of lifestyle care (diet, exercise, stress management, etc.) are required. The study included generally healthy individuals; therefore, we would not expect to see a significant impact of melatonin on their cardiometabolic health in the 12-week period of the study. However, the study further supports the use of melatonin in shift workers to help restore better quality and support a healthy circadian rhythm.

Article summary including Results

It is well known that shift workers carry an increased burden of diabetes and other cardiometabolic disease as compared to non-shift workers. This is largely thought to be due to the circadian rhythm disturbances from this type of work. Individuals (night shift workers, N=24 and non-night shift workers, N=12) were evaluated at baseline for a number of health markers, including blood pressure, oral glucose tolerance testing, and serial melatonin and cortisol levels, among others. Participants also completed two validated sleep questionnaires during the study. The shift workers were then assigned to a melatonin or placebo group and treated for 12 weeks, with a repeat exam at the conclusion of 12 weeks and again after a 12-week washout period.

At baseline, insulin and glucose were similar between shift and non-shift workers and did not significantly change after 12 weeks of melatonin treatment from baseline or compared to placebo. This result is also true for the HOMA index, though the night shift group showed a significantly higher baseline insulin resistance level as compared to non-night shift workers.

Similarly, blood pressure, serum melatonin, and cortisol levels were not significantly different in the two groups at baseline. No significant change was noted in the shift worker group at 12 weeks.

Significantly, at baseline, 71% of those in the shift worker group reported poor quality sleep, while only 17% in the non-shift worker group reported this. During the 12-week trial, 50% of the shift worker group receiving 2 mg melatonin reported improvements, while there were no changes observed in the placebo group.

Limitations noted by Author(s)

The authors noted the small sample size as a limitation, though they compensated for this in statistical analyses. Additionally, they noted that the workers on a rotating shift work schedule had no baseline differences in circadian rhythm parameters, which may indicate that those who have a permanent or more intense night-shift schedule could be impacted by melatonin administration. This study also identified pre-diabetic participants, while other studies showing the positive effects of melatonin have been done in established Type 2 diabetics. Lastly, they noted that the short duration of the study could impact the findings.

Other limitations noted in this review (anything we noted as a limitation)

• Measurable or significant changes in healthy individuals to health markers, including blood pressure, insulin, and cortisol, would not be expected in a short duration of time, if at all.

• Research suggests that higher doses of melatonin are more impactful for blood pressure and glucose regulation.

• Likewise, research suggests higher doses, 3 mg, may be most appropriate for shift work.

Article review completed by Mona Fahoum, ND

Content reviewed by Kim Ross, DCN

Date: June 6, 2024