What is the highest safe dose of melatonin (melatonin)?

From the Guidelines

The highest safe dose of melatonin for adults is generally considered to be up to 15 mg per day, as indicated by the most recent study 1, which suggests that immediate-release melatonin can be titrated up to 15 mg at bedtime to address dream enactment in patients with isolated REM sleep behavior disorder. When considering the use of melatonin, it's essential to prioritize the lowest effective dose to minimize potential side effects, such as headaches, dizziness, nausea, and daytime drowsiness.

• The starting dose of immediate-release melatonin is usually 3 mg taken at bedtime, which can be titrated up in 3-mg increments as needed, according to the 2023 study 1.
• Melatonin is a hormone naturally produced by the pineal gland that helps regulate sleep-wake cycles, and supplementation can help with insomnia, jet lag, and certain sleep disorders.
• While melatonin is generally considered safe for short-term use, long-term safety data is limited, and some individuals, including pregnant women, those with autoimmune disorders, and people taking certain medications, should consult a healthcare provider before using melatonin.
• It's also important to note that melatonin is available over the counter in the United States and Canada, but its bioavailability and content may be less consistent across formulations, as mentioned in the 2023 study 1.
• If sleep problems persist despite melatonin use, it's crucial to consult a healthcare professional to address underlying causes, rather than simply increasing the dose or relying on melatonin as a long-term solution.

From the Research

Melatonin Dosage and Safety

• The highest safe dose of melatonin is not explicitly stated in the provided studies, but the effective melatonin doses varied according to each age group, from 0.5 to 3 mg in children, 3 to 5 mg in adolescents, 1 to 5 mg in adults, and 1 to 6 mg in elderly people 2.
• Daily melatonin doses ranged from 0.15 mg to 12 mg in a systematic review of 37 randomized controlled trials (RCTs) 3.
• A systematic review and meta-analysis of high-dose melatonin (≥10 mg) in adults found that melatonin did not cause a detectable increase in serious adverse events (SAEs) or withdrawals due to adverse events (AEs), but did appear to increase the risk of AEs such as drowsiness, headache, and dizziness 4.
• Melatonin doses ranged from 0.5 mg to 6 mg in a systematic review of melatonin in elderly patients with insomnia, with most patients taking a single dose 30-120 min before bedtime 5.

Adverse Events and Safety Profile

• The most frequently reported adverse events (AEs) associated with melatonin were daytime sleepiness, headache, other sleep-related AEs, dizziness, and hypothermia 3.
• Very few AEs considered to be serious or of clinical significance were reported in a systematic review of 37 RCTs 3.
• Melatonin was generally regarded as safe and well tolerated in a systematic review of 37 RCTs 3.
• A systematic review and meta-analysis of high-dose melatonin found that melatonin appears to have a good safety profile, but better safety reporting in future long-term trials is needed to confirm this 4.

Age-Specific Considerations

• The effective melatonin doses varied according to each age group, with higher doses used in adults and elderly people 2.
• Melatonin was found to be effective in elderly insomniacs who chronically used benzodiazepines and/or had documented low melatonin levels during sleep 5.
• Exogenous melatonin was found to be useful in patients with a stabilized psychiatric disorder or in remission, to prevent relapse in case of associated complaints of insomnia, poor quality sleep, or delayed sleep phase syndrome 6.