Melatonin is a hormone that the pineal gland in the brain produces naturally. It regulates the sleep-wake cycle and has antioxidant and anti-inflammatory effects in the body. Melatonin levels naturally rise in the evening and stay elevated throughout the night, then decrease in the morning as the body prepares to wake up. We will explore melatonin’s synthesis into supplement form, its historical discovery, research surrounding the compound, potential health outcomes from consumption, and, in particular, the potential for melatonin to support metabolic health. Through this process we will uncover a relationship between melatonin, sleep, and metabolic performance.

Figure A: 

Chemical reactions synthesize melatonin in the laboratory into a supplement. The process starts with the amino acid tryptophan and ends with the formation of melatonin. The exact process varies depending on the manufacturer but typically involves several steps, including converting tryptophan to 5-HTP, then to serotonin, and finally to melatonin. The final product usually comes in the form of a tablet, capsule, or liquid.

Historical Discovery of Melatonin

Researchers began studying the pineal gland’s role in regulating biological rhythms and discovered melatonin in the early 20th century. In the 1950s, researchers discovered that the pineal gland of cows and chickens contained a substance that could lighten the skin of frogs. This substance was later identified as melatonin, and its structure was determined in the 1960s. Since then, thousands of studies have been conducted on its effects on sleep, circadian rhythms, and various physiological processes in the body. Melatonin supplements have become increasingly popular as a natural sleep aid and antioxidant.

Research Surrounding Melatonin

Melatonin supplementation continues to be studied extensively for its effects on sleep and circadian rhythms. One particular study showed that it can improve sleep quality and duration, especially in people with insomnia or jet lag. Another study showed that melatonin helps to regulate circadian rhythms in people who work night shifts or have disrupted sleep schedules. Melatonin is also actively being studied for its potential role in preventing or treating various diseases, including cancer, cardiovascular disease, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. 

Potential Health Outcomes from Consumption

Melatonin supplementation may offer several health benefits, particularly for individuals experiencing sleep disturbances or age-related melatonin level declines. As noted in Figure B below, melatonin levels naturally decline as we age. 

Figure B:

Melatonin and sleep quality

Aging individuals and individuals who have insomnia and increased oxidative stress may benefit from melatonin supplementation. For instance, one study concludes that melatonin supplementation improves sleep quality and decreases oxidative stress in elderly people with insomnia, while another found it reduced daytime fatigue and improved sleep quality in healthy elderly individuals. 

Melatonin and blue light exposure

Additionally, individuals exposed to blue light from electronic devices, such as smartphones and computers, may benefit from melatonin supplementation. Blue light exposure can suppress melatonin production, disrupt the sleep-wake cycle, and cause health problems. Wearing blue light blocking glasses to filter out blue light from electronic screens may help maintain healthy melatonin levels and improve sleep quality. One study finds that individuals with sleep disorders who wear blue light blocking glasses for two hours before bedtime improve sleep quality and reduce insomnia symptoms. 

Melatonin and metabolic health

Recent research suggests that melatonin supplementation may improve metabolic health by affecting glucose metabolism, insulin sensitivity, and lipid metabolism. Melatonin has been found to have anti-inflammatory and antioxidant properties, which can contribute to its potential benefits for metabolic health. Studies show that melatonin supplementation can improve insulin sensitivity, reduce fasting blood glucose levels, and lower lipid levels in people with metabolic disorders. Melatonin has also been found to regulate the activity of brown adipose tissue (BAT), which is responsible for burning calories and producing heat in the body. The regulation of BAT activity by melatonin may contribute to increased calorie burn and improved metabolic function.

Potential consumption outcomes

Although appropriate use of melatonin is generally safe, it has potential side effects and risks. Common side effects include headache, dizziness, and drowsiness, while interactions with certain medications, such as blood thinners and immunosuppressants, may occur. There is also concern that melatonin supplementation may affect fertility and hormone levels, though research results have been mixed. Overdosing on melatonin can lead to nausea, vomiting, and diarrhea, so it is essential to follow the recommended dosage instructions and seek advice from a healthcare provider beforehand, particularly if taking any medications or having any underlying medical conditions.

Conclusion

Melatonin is a hormone that is naturally produced in the pineal gland of the brain. It helps regulate the sleep-wake cycle and has antioxidant and anti-inflammatory effects in the body. Melatonin supplements are widely available and are often used to help people sleep, especially those with insomnia or jet lag.

While melatonin is generally considered safe when used in appropriate doses, there are some potential side effects and risks associated with its use. If you are considering using melatonin supplements, it is important to follow the recommended dosage instructions and to talk to your healthcare provider to determine if it is right for you. 

More research is needed to fully understand the long-term effects of melatonin supplementation on health outcomes. However, results thus far hint at a relationship between melatonin, sleep, and metabolic performance.

References:

Melatonin to treat sleep disorders, insomnia and jet lag:

• Rondanelli M, Opizzi A, Monteferrario F, Antoniello N, Manni R, Klersy C. The effect of melatonin, magnesium, and zinc on primary insomnia in long-term care facility residents in Italy: a double-blind, placebo-controlled clinical trial. J Am Geriatr Soc. 2011;59(1):82–90. doi:10.1111/j.1532-5415.2010.03232.x -> https://www.ncbi.nlm.nih.gov/pubmed/21226679 
• Cardinali DP, Srinivasan V, Brzezinski A, et al. Melatonin and its analogs in insomnia and depression. J Pineal Res. 2012;52(4):365–375. doi:10.1111/j.1600-079X.2012.00979.x -> https://www.ncbi.nlm.nih.gov/pubmed/22449079 
• Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One. 2013;8(5):e63773. doi:10.1371/journal.pone.0063773 -> https://www.ncbi.nlm.nih.gov/pubmed/23691095 
• Buscemi N, Vandermeer B, Pandya R, et al. Melatonin for treatment of sleep disorders. Evid Rep Technol Assess (Summ). 2004;(108):1–7. PMID: 15574200. -> https://www.ncbi.nlm.nih.gov/books/NBK11942/ 

Circadian Rhythm Regulation:

• Stothard ER, McHill AW, Depner CM, Birks BR, Moehlman TM, Ritchie HK, Guzzetti JR, Chinoy ED, LeBourgeois MK, Axelsson J. Circadian Entrainment to the Natural Light-Dark Cycle across Seasons and the Weekend. Curr Biol. 2017 Jun 19;27(12):1762-1768.e3. doi: 10.1016/j.cub.2017.05.018. Epub 2017 Jun 1. PMID: 28578928; PMCID: PMC5484187 -> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335920/
• James SM, Honn KA, Gaddameedhi S, Van Dongen HPA. Shift Work: Disrupted Circadian Rhythms and Sleep-Implications for Health and Well-Being. Curr Sleep Med Rep. 2017 Jun;3(2):104-112. doi: 10.1007/s40675-017-0071-6. Epub 2017 Apr 27. PMID: 29057204; PMCID: PMC5647832. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647832/ 

Improves sleep quality and decreases oxidative stress in elderly people with insomnia

• Lemoine P, Nir T, Laudon M, et al. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res. 2007;16(4):372–380. doi:10.1111/j.1365-2869.2007.00613.x -> https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2869.2007.00613.x 

Reducing daytime fatigue and assisting with sleep in elderly individuals

• Abad VC, Guilleminault C. Insomnia in Elderly Patients: Recommendations for Pharmacological Management. Drugs Aging. 2018 Sep;35(9):791-817. doi: 10.1007/s40266-018-0569-8. PMID: 30058034. https://pubmed.ncbi.nlm.nih.gov/30058034/ 
• Pierce M, Linnebur SA, Pearson SM, Fixen DR. Optimal Melatonin Dose in Older Adults: A Clinical Review of the Literature. Sr Care Pharm. 2019 Jul 1;34(7):419-431. doi: 10.4140/TCP.n.2019.419. PMID: 31383052. https://pubmed.ncbi.nlm.nih.gov/31383052/ 

Blocking blue light 2 hours before bed time

• Shechter A, Kim EW, St-Onge MP, Westwood AJ. Blocking nocturnal blue light for insomnia: A randomized controlled trial. J Psychiatr Res. 2018 Jan;96:196-202. doi: 10.1016/j.jpsychires.2017.10.015. Epub 2017 Oct 21. PMID: 29101797; PMCID: PMC5703049. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703049/ 

Melatonin can improve insulin sensitivity, reduce fasting blood glucose levels, and lower lipid levels in people with metabolic disorders

• Garaulet M, Qian J, Florez JC, Arendt J, Saxena R, Scheer FAJL. Melatonin Effects on Glucose Metabolism: Time To Unlock the Controversy. Trends Endocrinol Metab. 2020 Mar;31(3):192-204. doi: 10.1016/j.tem.2019.11.011. Epub 2020 Jan 1. PMID: 31901302; PMCID: PMC7349733. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349733/ 

Melatonin can regulate the activity of brown adipose fatty tissue

• Xu Z, You W, Liu J, Wang Y, Shan T. Elucidating the Regulatory Role of Melatonin in Brown, White, and Beige Adipocytes. Adv Nutr. 2020 Mar 1;11(2):447-460. doi: 10.1093/advances/nmz070. PMID: 31355852; PMCID: PMC7442421. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442421/