melatonin is widely associated with sleep, jet lag and occasional insomnia, but research describes the hormone as part of a broader system involved in immune regulation, inflammation and tissue protection. Studies cited in the source indicate that melatonin acts as a potent antioxidant and may help limit tissue damage, while evidence also suggests a possible role in preventing certain cancers.
The hormone, also known as N-acetyl-5-methoxytryptamine, regulates the body’s circadian rhythm. It is produced mainly in the pineal gland from serotonin, which in turn is derived from the amino acid tryptophan. Melatonin production rises in darkness and declines during daylight, when exposure to light suppresses its release into the bloodstream.
A 2025 review of 59 studies published between 2000 and 2025 examined the relationship between melatonin production, sleep and immune function. Its findings linked chronic sleep deprivation with impaired immune responses, greater susceptibility to infections and increased inflammation.
The immune system’s activity also changes across the sleep-wake cycle. During sleep, pro-inflammatory molecules known as cytokines help mobilize responses against infections and other foreign pathogens. Increased cytokine activity during illness can promote sleepiness, an adaptive response that supports recovery. Research published in 2024 found that lower melatonin levels were associated with increased secretion of pro-inflammatory cytokines.
According to the cited studies, persistent sleep loss may contribute to systemic low-grade inflammation and has been associated with potential risks involving cardiovascular disease, cancer, atherosclerosis, diabetes and autoimmune conditions. Chronically elevated cytokine levels have also been linked to fatigue and immunosuppression.
Wakefulness involves a different part of the body’s regulatory cycle. Cortisol, an anti-inflammatory hormone with immunosuppressive effects, is generally highest in the morning and decreases during the day. During sleep, cortisol levels fall as melatonin levels rise. Chronic sleep deprivation can disrupt cortisol secretion, potentially affecting immunity and susceptibility to infections.
The research supports melatonin or its precursor tryptophan for some short-term sleep disruptions, but the American Academy of Sleep Medicine does not recommend melatonin as a long-term treatment for chronic insomnia. The academy emphasizes identifying underlying causes and using behavioral strategies, including maintaining a regular sleep schedule, avoiding electronic devices for 30 to 60 minutes before bed, and exercising caution with caffeine and alcohol.
For chronic insomnia, which the source says affects about 10% of adults, cognitive behavioral therapy for insomnia is recommended. Medication is generally considered only after behavioral approaches have been tried.
Long-term supplementation has also raised safety questions. Research presented at the 2025 American Heart Association conference examined 130,828 adults diagnosed with insomnia and found that those who used melatonin for at least 12 months had a higher likelihood of being diagnosed with heart failure or dying from any cause during the following five years. The findings showed a correlation rather than proof of cause and effect, but they point to possible cardiovascular risks and the need for further research into prolonged use.
Sources: Psychology Today.