What are the side effects of exogenous melatonin (melatonin hormone replacement)?

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From the Guidelines

Exogenous melatonin can cause several side effects, though they are generally mild and temporary, with common side effects including drowsiness, headaches, dizziness, and nausea, as reported in a 2015 study 1. The side effects of exogenous melatonin are typically mild and temporary, but can include:

  • Drowsiness
  • Headaches
  • Dizziness
  • Nausea
  • Vivid dreams or nightmares
  • Short-term feelings of depression, irritability, or mild tremors Less common side effects include confusion or disorientation, especially in older adults, and reduced alertness the following day. Melatonin may also cause mild anxiety, abdominal cramps, and mild allergic reactions in some individuals. It can interact with certain medications, including blood thinners, immunosuppressants, diabetes medications, and birth control pills, as noted in a 2023 study 1. The typical dosage ranges from 0.5-5mg taken 30-60 minutes before bedtime, with lower doses often being effective with fewer side effects, as suggested in a 2023 study 1. Melatonin works by binding to receptors in the brain that help regulate the sleep-wake cycle, essentially signaling to the body that it's time to sleep. If side effects persist or are bothersome, users should consult a healthcare provider, especially before long-term use, as recommended in a 2015 study 1. It is also important to note that melatonin is considered a dietary supplement and is not subject to the same scrutiny as FDA-approved medications, which can raise concerns about the purity of available preparations and the reliability of stated doses, as mentioned in a 2015 study 1. Therefore, it is recommended to use melatonin with caution and under the guidance of a healthcare provider, especially for long-term use or in combination with other medications, as suggested in a 2023 study 1.

From the Research

Side Effects of Exogenous Melatonin

The side effects of exogenous melatonin have been studied in various research papers. According to the studies, the most frequently reported side effects are:

  • Daytime sleepiness (1.66%) 2
  • Headache (0.74%) 2
  • Other sleep-related side effects (0.74%) 2
  • Dizziness (0.74%) 2
  • Hypothermia (0.62%) 2
  • Agitation, fatigue, mood swings, nightmares, skin irritation, and palpitations (although these are rare and considered serious or of clinical significance) 2

Safety of Melatonin

The safety of melatonin has been evaluated in several studies. It has been found that:

  • Short-term use of melatonin is safe, even in extreme doses 3
  • Long-term melatonin treatment causes only mild side effects comparable to placebo 3
  • Melatonin is well tolerated and has no obvious short- or long-term adverse effects 4
  • Melatonin offers an alternative treatment to currently available pharmaceutical therapies for sleep disorders with significantly less side effects 4

Special Considerations

There are some special considerations to be taken into account when using melatonin:

  • Long-term safety of melatonin in children and adolescents requires further investigation 3
  • Pregnant and breast-feeding women should not take exogenous melatonin due to a lack of human studies 3
  • The most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The Safety of Melatonin in Humans.

Clinical drug investigation, 2016

Research

A review of sleep disorders and melatonin.

Neurological research, 2017

Research

Melatonin in sleep disorders.

Neurologia, 2022

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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