What are the risks associated with taking melatonin?

Risks Associated with Melatonin

Melatonin has a favorable safety profile with minimal serious adverse effects, though common side effects include drowsiness, headache, dizziness, and morning grogginess, particularly at higher doses (≥10 mg). 1

Common Adverse Effects

Dose-Related Side Effects

• Higher doses (≥10 mg) significantly increase risk of drowsiness, headache, and dizziness compared to placebo (Rate Ratio 1.40, p < 0.001). 1
• Morning grogginess and "hangover" effects occur more frequently with higher doses due to melatonin's half-life extending into morning hours. 2
• Gastrointestinal upset has been reported more frequently at higher melatonin doses. 2, 3
• Lower doses (3 mg) are often more effective than higher doses (10 mg), which may cause receptor desensitization or saturation. 2, 3

General Side Effects

• Morning sleepiness may occur in some patients, especially children. 2
• Impaired motor function can occur with higher doses of melatonin. 4

Serious Safety Concerns

Specific Patient Populations at Risk

• Patients with epilepsy may come to harm from melatonin based on case reports, warranting caution in this population. 5
• Patients taking warfarin may experience potential interactions requiring investigation and monitoring. 2, 5
• Patients with liver disease may experience enhanced sensitivity to melatonin, making lower doses more appropriate. 2

Cardiovascular Effects

• Melatonin has been associated with both hypotension and hypertension at higher doses, which could potentially affect patients with conditions like POTS. 3
• Blood pressure monitoring is advisable when initiating melatonin in patients with cardiovascular concerns. 3

Metabolic Concerns

• Melatonin has been associated with impaired glucose tolerance in healthy women after acute administration. 3

Special Population Considerations

Elderly Patients with Dementia

• The American Academy of Sleep Medicine recommends avoiding melatonin for irregular sleep-wake rhythm disorder in older people with dementia due to lack of benefit and potential for harm. 4
• Detrimental effects on mood and daytime functioning have been observed in dementia patients receiving melatonin. 4

Pediatric Safety

• No serious adverse reactions have been documented in children using melatonin at appropriate doses. 4, 2
• Long-term safety data in children is limited, though available evidence is reassuring. 2
• Concerns about effects on reproductive development have not been substantiated in follow-up studies showing no significant differences in pubertal development (Tanner stages) after approximately 3 years of use. 2

Product Quality and Regulatory Concerns

Manufacturing Issues

• Melatonin is regulated as a dietary supplement in the U.S., raising significant concerns about purity and reliability of stated doses. 2, 3
• No regulatory agency oversees its manufacturing or sale in the U.S. 6
• Melatonin concentration of marketed preparations varies widely between product labels and manufacturers. 6
• Choose United States Pharmacopeial Convention Verified formulations when possible for more reliable dosing and purity. 2, 3

Long-Term Safety Data

Evidence Limitations

• Long-term safety data beyond several months is limited, though available evidence suggests good tolerability. 2
• Much research on long-term melatonin administration has found no difference between exogenous melatonin and placebo in terms of long-term negative effects. 6
• It is widely agreed that long-term effects of taking exogenous melatonin have been insufficiently studied and warrant additional investigation. 6

Meta-Analysis Findings

• A systematic review of 79 studies (3,861 participants) found that 37% of studies made no mention of presence or absence of adverse events, indicating poor safety reporting. 1
• Based on limited high-quality evidence, melatonin did not cause detectable increase in serious adverse events (Rate Ratio 0.88, p = 0.64) or withdrawals due to adverse events (0.93, p = 0.92). 1

Drug Interactions

• Concurrent medications may interact with melatonin metabolism, potentially amplifying effects of higher doses. 2
• Potential interaction with stimulant medications should be monitored, though no specific contraindications exist. 3

Timing-Related Risks

• If melatonin is taken at the wrong time (early in the day), it is liable to cause sleepiness and delay adaptation to local time. 5
• The dim light melatonin onset (DLMO) represents a specific phase where melatonin can induce sleep but does not shift the circadian master clock. 7