Natural Products

Melatonin

N-acetyl-5-methoxytryptamine

Efficacy

• Indications with proven efficacy:
  Circadian rhythm sleep disorders in blind and in children and adolescents with mental retardation, autism and central nervous system disorders
• Indications with possible, but poorly documented efficacy - the use of this product cannot be recommended:
  Cancer
  Jet lag
  Various insomnias
• Also used for these other indications, but with no proof of efficacy:
  Benzodiazepine and nicotine withdrawal
  Contraceptive
  Insomnia due to shift-work (possibly ineffective)
  Migraine and cluster headache prevention
  Skin protection from ultraviolet radiation (topically)
  Tardive Dyskinesia
  To enhance the immune system
  To reduce the effects of aging

Security

• Risk of Drug Interactions: Low
• Adverse Effects: Not Frequent

What is it?

Melatonin is a naturally occurring hormone of the human body. It is secreted in the brain by the pineal gland and some other tissues. It is believed to regulate the circadian rhythm and sleep by interacting with receptors located in the brain. Light-sensitive receptors located in the eye influence the synthesis and release of this hormone. Melatonin levels increase in darkness and decrease in light. Melatonin may play a role in the control of body temperature, cardiac function and reproductive system.

Melatonin is available as immediate-release or controlled-release tablets.

Warning

In 2004, Canada adopted new regulations that control the manufacturing, packaging, labeling and importing of natural health products. The new regulations also include an adverse reaction reporting system. Products that conform to the regulation's criteria are identified with a natural product number (NPN) or homeopathic medicine number (DIN-HM) and can be legally sold in Canada. This number indicates that the product meets specific criteria for safety and purity, not that it is effective for any indication.

Medicinal plants content varies naturally from plant to plant – just as fruits from the same package may vary in taste and texture. There is no standard to measure the active content of each plant. Thus, efficacy of natural products should be expected to vary from brand to brand as well as from bottle to bottle of the same brand.

For more information about the Natural Health Products Regulations, or to check if a product has been assessed, visit the Health Canada website at http://www.hc-sc.gc.ca/dhp-mps/prodnatur/index-eng.php.

Does it work?

There is evidence that melatonin can reestablishing a normal sleep-waking cycle in the blind and in children and adolescents with mental retardation, autism and central nervous system disorders.

• Circadian rhythm sleep disorders in blind:
  In the absence of light, the blind's sleep-waking cycle elongates to 25 hours per day. After a few days, the individual finds himself awake during the night and tired and drowsy during the day. Melatonin helps to restores a more normal 24-hour cycle. Usually, people take 5 mg melatonin 2 to 3 hours before bedtime.
• Jet lag:
  Doses of 0.5 to 8 mg at bedtime have been recommended for this indication, with some success, but with poor documentation! Treatment should begin the night of departure or 3 day before and continue for up to 1 week.
• Insomnia:
  Insomniacs of all ages and healthy elderly people have reduced circulating melatonin levels. Small doses (0.3 to 6 mg at bedtime) have been used to restore melatonin levels, but melatonin's efficacy in this indication is poorly documented.
• Cancer:
  Laboratory studies have shown a reduced growth of cancerous tumors when exposed to melatonin. Administering 10 to 50 mg melatonin at bedtime appears to improve the survival rate of patients in association with radiotherapy, chemotherapy, or interleukin-2. It may also improve thrombocytopenia. However, its exact use in the treatment of cancer remains to be established.

Is it safe?

• Melatonin is not associated with any severe toxicity. There have been reports of headaches, dizziness, stomach ache, irritability, depressive symptoms and reduced alertness as well as daytime fatigue. Its long-term safety is still not established.
• Melatonin is contraindicated in depressive and epileptic patients or in case of liver disease. It should not be administered to children since it may interfere with sexual development.
• Since there is no safety data available concerning its use during pregnancy and breast-feeding, pregnant and lactating women should not take melatonin.
• Because it has sedative properties, melatonin may increase the drowsiness induced by other products such as alcohol, benzodiazepines (Valium, Ativan, etc.), kava, valerian, etc. Melatonin may affect the immune system and should not be used during immunosuppressive therapy. Before taking melatonin, check with your pharmacist to make sure that there are not interactions with your regular medication.
• Use of natural melatonin from animal pineal gland is controversial and should be avoided due to the possibility of contamination.

Clinical notes

• Melatonin has interesting properties combined with a reassuring adverse effect profile. Clinical information available on melatonin leads us to believe that it may be useful in some indications. However, its long-term safety profile is still unknown.

References

1. Facts & Comparisons, The Lawrence review of natural products, 1998
2. Natural Medicines Comprehensive Database, Therapeutic Research Faculty, 2007
3. Herbal Companion to AHFS DI, American Society of Health-System Pharmacists, 2001
4. Lininger S. et Al. The Natural Pharmacy, Prima Health, 1998
5. Passeportsanté.net. Mélatonine. http://www.passeportsante.net
6. Rotblatt M. et Ziment I. Evidence-Based Herbal Medicine, Hanley & Belfus, 2002