Department of Nutrition, Harvard T H Chan School of Public Health, Boston, MA, USA; Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA, USA.
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
Lancet Diabetes Endocrinol. 2024 Jun;12(6):404-413. doi: 10.1016/S2213-8587(24)00096-2. Epub 2024 May 3.
Use of melatonin supplements has been increasing substantially in both children and adults in the USA; however, their long-term cardiometabolic effects remain unclear. We aimed to assess the associations between regular use of melatonin supplements and the risk of developing type 2 diabetes or cardiovascular disease in adults.
In this study, we included individuals from three US cohorts: the Nurses' Health Study (women only), the Health Professionals Follow-up Study (men only), and the Nurses' Health Study II (women only). Women aged 25-55 years and men aged 45-75 years at baseline, who had no diagnosis of cancer at baseline, and who responded to the question about melatonin supplement use (yes or no) were included. We excluded baseline prevalent cardiovascular disease and baseline prevalent type 2 diabetes for the main analyses. The main outcomes were cardiovascular disease and type 2 diabetes incidence. In secondary analyses, we stratified by duration of rotating night shift work in the Nurses' Health Study and Nurses' Health Study II to examine whether the associations with melatonin supplement use differed by rotating night shift work.
For the cardiovascular disease analysis, we included 67 202 women from the Nurses' Health Study (follow-up 1998-2019, mean age at baseline: 63·6 years [SD 7·1]), 26 629 men from the Health Professionals Follow-up Study (1998-2020, 62·9 years [8·8], and 65 241 women from the Nurses' Health Study II (2003-19, 48·2 years [4·7]). Follow-up for incident type 2 diabetes was from 1998 to June 30, 2021, for the Nurses' Health Study; 2003 to Jan 31, 2023, for the Nurses' Health Study II; and from 1998 to Jan 31, 2020, for the Health Professionals' Follow-up Study. Melatonin supplement use in the study cohorts doubled over recent decades from less than 2% in 1998-2007 to 4% or higher in 2014-15 (4·0% in men and 5·3% in women). We documented 16 917 incident cardiovascular disease events during 2 609 068 person-years of follow-up and 12 730 incident cases of type 2 diabetes during 2 701 830 person-years of follow-up. In a pooled analysis of the three cohorts, comparing users with non-users of melatonin supplements, the pooled multivariable-adjusted hazard ratios were 0·94 (95% CI 0·83-1·06, p=0·32) for cardiovascular disease and 0·98 (0·86-1·12, p=0·80) for type 2 diabetes. In secondary analyses, melatonin supplement use appeared to attenuate the positive association between long-term shift work (>5 years) and risk of cardiovascular disease (p=0·013) among the female nurses.
With up to 23 years of follow-up of three large prospective cohorts of middle-aged and older men and women, self-reported melatonin supplement use was not associated with risk of type 2 diabetes or cardiovascular disease. Further research is warranted to assess if melatonin supplement use could mitigate the potential risks of type 2 diabetes and cardiovascular disease associated with rotating night shift work.
US National Institutes of Health.
褪黑素补充剂在美国的儿童和成人中使用量大幅增加；然而，其长期的心脏代谢影响仍不清楚。我们旨在评估成年人定期使用褪黑素补充剂与 2 型糖尿病或心血管疾病发病风险之间的关系。
在这项研究中，我们纳入了来自三个美国队列的个体：护士健康研究（仅限女性）、健康专业人员随访研究（仅限男性）和护士健康研究 II（仅限女性）。基线时年龄在 25-55 岁的女性和 45-75 岁的男性，基线时无癌症诊断，并且回答了褪黑素补充剂使用问题（是或否）的人被纳入。我们排除了主要分析中的基线现患心血管疾病和基线现患 2 型糖尿病。主要结局是心血管疾病和 2 型糖尿病的发病情况。在二次分析中，我们根据护士健康研究和护士健康研究 II 中轮班夜班工作的持续时间进行分层，以检查褪黑素补充剂使用与心血管疾病之间的关联是否因轮班夜班工作而有所不同。
对于心血管疾病分析，我们纳入了来自护士健康研究的 67202 名女性（1998-2019 年随访，基线时平均年龄：63.6 岁[7.1]）、来自健康专业人员随访研究的 26629 名男性（1998-2020 年，62.9 岁[8.8]）和来自护士健康研究 II 的 65241 名女性（2003-19 年，48.2 岁[4.7]）。2 型糖尿病发病的随访时间为护士健康研究的 1998 年至 2021 年 6 月 30 日；护士健康研究 II 的 2003 年至 2023 年 1 月 31 日；以及健康专业人员随访研究的 1998 年至 2020 年 1 月 31 日。在最近几十年中，研究队列中褪黑素补充剂的使用量翻了一番，从 1998-2007 年的不足 2%增加到 2014-15 年的 4%或更高（男性为 4.0%，女性为 5.3%）。我们记录了 16917 例心血管疾病事件，发生在 2609068 人年的随访中，12730 例 2 型糖尿病事件发生在 2701830 人年的随访中。在三个队列的汇总分析中，与褪黑素补充剂使用者相比，非使用者的多变量调整后的风险比为 0.94（95%CI：0.83-1.06，p=0.32），心血管疾病为 0.98（0.86-1.12，p=0.80）。在二次分析中，褪黑素补充剂的使用似乎减弱了女性护士中长时轮班夜班工作（>5 年）与心血管疾病风险之间的正相关关系（p=0.013）。
通过对三个大型中年和老年男性和女性前瞻性队列进行长达 23 年的随访，自我报告的褪黑素补充剂使用与 2 型糖尿病或心血管疾病的发病风险无关。需要进一步研究以评估褪黑素补充剂的使用是否可以减轻与轮班夜班工作相关的 2 型糖尿病和心血管疾病的潜在风险。
美国国立卫生研究院。
