Bone Health
Based on cell and preclinical data, it has been suggested that melatonin acts on both anabolic and catabolic aspects of bone metabolism (1). Melatonin has been noted to increase osteoprotegerin (an osteoblastic protein) and procollagen type I C-peptide (part of the bone matrix) (2).
Over the years, limited published clinical trials using a relatively small number of study subjects have demonstrated melatonin’s role in rebalancing bone remodeling in perimenopausal women (3) and increasing bone density in postmenopausal women with osteopenia (4). In these studies, up to 3 mg of supplemental melatonin was used. According to findings from the year-long clinical trial referred to as Melatonin-micronutrients Osteopenia Treatment Study (MOTS), a combination of melatonin (5 mg), strontium (citrate) (450 mg), vitamin D3 (2000 IU/50 mcg) and vitamin K2 (MK7) (60 mcg) may be able to favorably impact bone markers such as bone mineral density in postmenopausal, osteopenic women, compared with placebo (1). In addition to beneficially modifying bone markers, the intervention improved quality of life measures such as mood and sleep quality (1). Of course, it cannot be inferred that melatonin was responsible for these effects since it was given as a combination supplement.
In a Letter to the Editor, Cardinali & Reiter highlight that most studies use chronobiotic doses of melatonin (less than 10 mg daily), though doses showing benefits from animal studies (1-1.5 mg/kg/day) are rarely used clinically. They suggest it is plausible that higher doses of melatonin may provide further understanding and utilization of melatonin’s role in bone health and osteoporosis (2).
Investigators reviewed melatonin as a pivotal compound in age-related skeletal muscle disorders because of its involvement in mitochondrial function through its antioxidant potential (5). Any research findings in this direction may be helpful for those with cachexia or sarcopenia. Furthermore, these authors suggested that it would be interesting to explore melatonin’s effect on the gut microbiome as it relates to skeletal muscle (the ‘gut-muscle axis’) (5).
Authors: Deanna Minich, Ph.D., Melanie Henning, ND, Catherine Darley, ND, Mona Fahoum, ND, Corey B. Schuler, DC, James Frame
Reviewer: Peer-review in Nutrients Journal
Last updated: October 24, 2024
References
1. Zhao Y, Shao G, Liu X, Li Z. Assessment of the Therapeutic Potential of Melatonin for the Treatment of Osteoporosis Through a Narrative Review of Its Signaling and Preclinical and Clinical Studies. Vol. 13, Frontiers in Pharmacology. Frontiers Media S.A.; 2022.
2.Cardinali DP, Reiter RJ. Clinical use of melatonin in osteoporosis: Expectations still unmet. Osteoporosis International. 2024 Oct 18; https://doi.org/10.1007/s00198-024-07261-8
3. Kotlarczyk MP, Lassila HC, O’Neil CK, D’Amico F, Enderby LT, Witt-Enderby PA, et al. Melatonin osteoporosis prevention study (MOPS): A randomized, double-blind, placebo-controlled study examining the effects of melatonin on bone health and quality of life in perimenopausal women. J Pineal Res. 2012;52(4).
4. Amstrup AK, Sikjaer T, Heickendorff L, Mosekilde L, Rejnmark L. Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial. J Pineal Res. 2015;59(2).
5. Stacchiotti A, Favero G, Rodella LF. Impact of melatonin on skeletal muscle and exercise. Vol. 9, Cells. 2020.