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Melatonin is widely known as the substance that makes us sleepy . It is commonly used as an over-the-counter sleep aid to treat jet lag and bouts of insomnia . However, new research shows that melatonin plays a wider role in maintaining overall health. Melatonin is a potent antioxidant that can prevent tissue damage. Evidence suggests it could help ward off certain types of cancer (Proietti, Reiter & Bizzarriet, 2012). It plays an essential role in the immune system’s ability to fight infections and heal from injuries (Szataniak & Packi, 2025; Singh et al., 2024).
Melatonin (N-acetyl-5-methoxytryptamine) is known as a chronobiotic hormone, which means that it regulates circadian rhythm . Tryptophan, an amino acid ingested from certain foods, serves as a building block for the production of serotonin. Serotonin, a neurotransmitter involved in mood regulation, is converted to melatonin primarily in the brain’s pineal gland. Production of melatonin is increased during darkness at night and it is released directly into the bloodstream. Levels decline during the day as production is inhibited by light (Kamfar et al., 2024).
Sleep has long been known to promote healing. People need extra sleep to recover from physical ailments. Research published in 2025 by Szataniak et al. showed that immune responses are strongly affected by the sleep cycle. The authors analysed 59 studies published from 2000-2025 that examined how melatonin production affects the immune system. They found that chronic sleep deprivation impairs immune response which increases susceptibility to infections and inflammation (Szataniak, et al 2025).
Pro-inflammatory molecules of the immune system, called cytokines, mobilize aggressive responses to fight off viruses, infections or foreign pathogens. This process is most active during sleep. Elevated levels of cytokines during infections or inflammation promote increased sleepiness associated with illness. This is an adaptive response and serves to promote recovery (Singh et al., 2024).
In 2024, Singh et al. published results that showed decreased melatonin levels correlate with increased secretion of pro-inflammatory cytokines. They found that chronic sleep deprivation increases cytokine production, contributing to systemic low-grade inflammation. This imbalance potentially increases the risk for cardiovascular disease, cancer, atherosclerosis, diabetes, and autoimmune illnesses (Szataniak et al., 2025; Singh et al., 2024). Chronic elevation of these cytokines has also been found to be associated with fatigue and immunosuppression (Szataniak et al., 2025).
Another component of the immune response acts to quiet the system and heal from inflammation and infections. Anti-inflammatory molecules such as the hormone cortisol are enhanced during wakefulness and play an essential role in regulating sleep and immune function (Singh et al., 2024). Cortisol reduces inflammation in the body and has immunosuppressant effects. It increases the sense of alertness, and like melatonin it is released following a circadian rhythm (Hoyt, Zeiders, Ehrlich & Adam, 2016). Levels of cortisol are highest early in the morning and decrease throughout the day. During sleep, cortisol levels are decreased while melatonin levels are increased. Chronic sleep deprivation can disrupt cortisol secretion, leading to a negative impact on immunity and susceptibility to infections (Singh et al., 2024).
Getting enough sleep is essential for maintaining physical health. Screening for insomnia should be included in routine healthcare visits. Education and increased awareness regarding the importance of adequate sleep should be part of health and wellness initiatives (Szataniak et al., 2025). Recently, enhanced widespread screening for pain issues and depression have been incorporated into medical visits. This should be expanded to include regular sleep assessments.
Evidence supports the use of dietary supplements containing melatonin or its precursor tryptophan to treat certain types of short-term sleep disruption (Szataniak et al., 2025; American Academy of Sleep Medicine, 2021). However, melatonin supplementation is not recommended as a long-term strategy for treatment of chronic insomnia (AASM, 2021). The American Academy of Sleep Medicine emphasizes the importance of assessing underlying causes of insomnia. They recommend implementing behavioral routines to improve sleep. Collectively referred to as sleep hygiene, this includes strategies such as turning off electronic devices (for example phones, television, and computers) 30 to 60 minutes before bed, adhering to a consistent sleep schedule, and caution around substances such as caffeine and alcohol .
About 10% of adults meet criteria for chronic insomnia disorder (AASM, 2021). In these cases, a course of cognitive behavioral therapy for insomnia or CBT-I is recommended. Medications for insomnia are generally considered a last resort after behavioral options have been implemented (AASM, 2021).
More recent research presented at the 2025 American Heart Association conference examined long-term melatonin use in 130,828 adults diagnosed with insomnia. Results showed that the use of melatonin for 12 months or more was correlated with an increased likelihood of being diagnosed with heart failure or dying from any cause over the course of five years. Although cause and effect was not proven, it highlights potential cardiovascular risks and the need for further research to establish the safety of long-term melatonin use (American Heart Association, 2025).
Hormones, including melatonin, are part of a complex endocrine system that exert multiple effects on different organs. Maintaining balance promotes resilience and wellness. Adequate sleep is a critical component to maintaining long-term health and optimal immune function. (Singh et al., 2024).
American Academy of Sleep Medicine, Missing the mark with melatonin: Finding the best treatment for insomnia (2021). https://aasm.org/missing-the-mark-melatonin-finding-best-treatment-insomnia/
American Heart Association Scientific Sessions, Long-term use of melatonin supplements to support sleep may have negative health effects (2025). Abstract MP 2306. https://newsroom.heart.org/news/long-term-use-of-melatonin-supplements-to-support-sleep-may-have-negative-health-effects
Hoyt, L., Zeiders, K.H., Ehrlich, K.B., Adam, E.K., (2016). Positive upshots of cortisol in everyday life. Emotion 16(4):431-435.
Kamfar, W.W., Khraiwesh, H.M., Ibrahim, M.O., Qadhi, A.H., Azhar, W.F., Ghafouri, K.J., Alhussain, M.H., Aldairi, A.A., AlShahrani, A.M., Alghannam, A.F., Abdulal, R.H., Al-Slaihat, A.H., Qutob, M.S., Elrggal, M.E., Ghaith, M.M., Azzeh, FS (2024). Comprehensive review of melatonin as a promising nutritional and nutraceutical supplement. Heliyon Vol 10(2).
https://doi.org/10.1016/j.heliyon.2024.e24266
Proietti, S., Cucina, A., Reiter, R.J., Bizzarri, M., (2012). Molecular mechanisms of melatonin’s inhibitory actions on breast cancers. Cell Mol Life Sci 70(12): 2139-21-57 . https://doi.org/10.1007/s00018-012-1161-8
Singh, K.K., Ghosh, S., Bhola, A., Verma, P., Amist, AD., Sharma, ,H., Sachdeva, P., Sinha, J.K., (2024). Sleep and immune system crosstalk: Inflammatory homeostasis and disease pathogenesis. Ann Neurosci 32(3): 196-206. https://doi.org/10.1177/09727531241275347
Szataniak, I., Packi, K. (2025). Melatonin as the missing link between sleep deprivation and immune dysregulation: A narrative review, Int J Mol Sci, 26(14) 6731. https://doi.org/10.3390/ijms26146731
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Lori Plutchik, M.D., is a board-certified psychiatrist in New York City, who has been in practice for over 25 years.
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