Acute metabolic effects of melatonin—A randomized crossover study in healthy young men
Abstract
Melatonin regulates circadian rhythm, but may also have effects on glucose homeostasis. A common G-allele in the MTNR1B locus has been associated with an increased risk of type 2 diabetes (T2DM). We aimed to examine acute effects of high doses of melatonin on glucose metabolism with attention to MTNR1B genotype. Twenty men were examined in a double-blinded, randomized crossover study on two nonconsecutive days with four doses of 10 mg oral melatonin or placebo. Insulin sensitivity and insulin secretion were assessed by an intravenous glucose tolerance test (IVGTT) and a hyperinsulinaemic-euglycaemic clamp (HEC). Blood samples were drawn to determine the metabolic profile and MTNR1B rs10830963 genotype. Indirect calorimetry and blood pressure measurements were also performed. Insulin sensitivity index was significantly reduced on the melatonin day (P = .028) in the whole group and in homozygous carriers of the rs10830963 C-allele (P = .041). Glucose during the IVGTT was unaffected, but there was a tendency towards lower insulin and C-peptide levels in the first minutes after glucose administration in G-allele carriers. Systolic blood pressure decreased and lipid oxidation increased significantly on the melatonin day in rs10830963 G-allele carriers. Overall, our study reports that acute administration of melatonin in supra-physiological doses may have a negative impact on insulin sensitivity. Clinical trial registration number (clinicaltrial.gov): NCT03204877.
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The mechanisms underlying the association between melatonin administration and glycemic control remain unclear.
“While a few other studies (9–14) have examined the effects of melatonin administration on glycemic control, the mechanisms underlying such association remain unclear (7).”
From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [10]
The two prior human in vivo studies did not observe differences in insulin responses, but their measures (acute insulin response to glucose or AUC) relied on circulating insulin concentrations and did not take into account hepatic insulin extraction, whole-body insulin clearance, and prevailing glucose levels, and thus did not independently determine β-cell function.
“Neither of the aforementioned human in vivo studies observed differences in insulin responses (9,10). However, the measures of those two studies (acute insulin response to glucose or AUC) relied on circulating insulin concentrations and did not take into account hepatic insulin extraction, whole-body insulin clearance, and prevailing glucose levels and, thus, did not independently determine β-cell”
From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [10]
Only two prior human studies examined the effects of a single dose of exogenous melatonin on SI and insulin secretion in vivo: one in nine postmenopausal women using FSIGT and one in 20 young men using hyperinsulinemic-euglycemic clamp after FSIGT.
“Only two prior human studies examined the effects of a single dose of exogenous melatonin on SI and insulin secretion in vivo (9,10), one report in nine postmenopausal women using FSIGT (9), the other report in 20 young men using hyperinsulinemic-euglycemic clamp after FSIGT (10).”
From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [10]
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Melatonin in type 2 diabetes mellitus and obesity
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Increased melatonin signaling is a risk factor for type 2 diabetes
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Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening
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Minich, D. M., Henning, M., Darley, C., Fahoum, M., Schuler, C. B., & Frame, J. (2022) · Nutrients · doi:10.3390/nu14193934 · Cited by 176 · see citing works
Lauritzen, E. S., Kampmann, U., Pedersen, M. G. B., Christensen, L., Jessen, N., Møller, N., & Støy, J. (2022) · Journal of Pineal Research · doi:10.1111/jpi.12809 · Cited by 29 · see citing works
Self-citationQian, J., Stefanovski, D., Andersen, P. A. K., Vujovic, N., Kelly, L., Lepson, J., Nguyen, H., Byrne, S., Wang, W., Mandrup-Poulsen, T., et al. (2026) · Diabetes Care · doi:10.2337/dc26-0164
- Authors
- Kampmann, U., Lauritzen, E. S., Grarup, N., Jessen, N., Hansen, T., Møller, N., & Støy, J.
- Affiliations
- Aarhus University Hospital (DK)
- Aarhus University (DK)
- University of Copenhagen (DK)
- Corresponding author
- Kampmann, Ulla
- ORCID
- Venue
- Journal of Pineal Research
- Publisher
- Wiley
- Published
- 2020-12-06
- Volume
- 70
- Issue
- 2
- Pages
- e12706-e12706
- ISSN
- 0742-3098 (ISSN-L)
- 1600-079X
- OpenAlex
- W3110220429
- Cited by
- 24
- References
- 6
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 5
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pineal Research (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Danish Diabetes Academy (DDA10228201)
- Novo Nordisk Fonden (NNF16OC0022280, NNF18CC0034900)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- melatonin, insulin sensitivity, insulin secretion, MTNR1B, rs10830963, type 2 diabetes risk, glucose metabolism, hyperinsulinemic-euglycemic clamp, intravenous glucose tolerance test, C-peptide, blood pressure, lipid oxidation, circadian rhythm, healthy young men
- MeSH terms
- Adolescent, Adult, Blood Pressure, Calorimetry, Indirect, Child, Child, Preschool, Humans, Insulin, Insulin Resistance, Male, Melatonin, Lipid Peroxidation, Cross-Over Studies, Receptors, Melatonin, Young Adult
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