Melatonin

Latest Edit: Iva Lloyd, ND 2017-05-05 (EDT)

See Also	Food Supplements

Melatonin is a hormone made from serotonin and is released from the pineal gland which is a small gland found at the base of the brain. Over many years of studying melatonin, scientists have come to realize melatonin's essential role in regulating circadian rhythms. Circadian rhythm refers to the natural pattern of hormone secretion in the body which aid in proper body function regulation. Melatonin is the "timekeeper" of this rhythm and helps control sleep-wake cycles. Melatonin secretion is greater during times of darkness and is less during the day light and is stimulated by a pathway that travels from the retina to the pineal gland. Imbalances in proper melatonin release is very common in our society where we no longer let the sun's movement dictate our activity and can lead to such conditions as insomnia and jet lag.

Other beneficial aspects of melatonin are related to its antioxidant and anticancer actions.

Article	Melatonin Chronosynergy, Women and Aging, NDNR [1], 2012 February

Food Sources

Melatonin can be found in olive oil, wine and beer. It is also found in many common fruits and vegetables including tomatoes, grape skins, tart cherries and walnuts.

The amount of melatonin found in food is significantly less than that typically found in a supplement.

Uses

The following is a list of the primary uses for melatonin.,

Article	Melatonin: Clinical applications, IHP, June/July 2009

• Jet Lag: Melatonin has been used to relieve the symptoms of jet lag. One study shows that it is best to take melatonin supplementation in the evening at the new destination for 5 days.
• Insomnia: Melatonin plays an important role in the sleep-wake cycle and therefore, when it is not secreted in sufficient amounts at night as it should, it can lead to insomnia. It proves to be effective only in those individuals who have low levels at night. Low melatonin is a common cause of insomnia in the elderly. Waking up exhausted can also indicate melatonin deficiency.

Article	Benefits of Melatonin in Solid Tumors When Used Concurrently With Chemotherapy, NMJ, [2], 2012 August

• Cancer: Melatonin has an anticancer effect on several types of cancers, especially those that are hormonally related such as prostate cancer and breast cancer. Exposure to artificial electromagnetic fields suppresses the production of melatonin and is considered a risk factor for cancer. Melatonin administered with interleukin 2, interferon, tumor necrosis factor, and tamoxifen show promising anticancer effects and have increased survival time and quality of life. Furthermore, low melatonin levels due to night-time shift work has been linked to higher rates of breast cancer. Low levels of melatonin at night is induced by night-time light and increases the amount of estrogen that is exposed to breast tissue.
• Depression: It was once believed that melatonin levels were lower in individuals with depression. The low levels of melatonin which were demonstrated in individuals with depression in these initial studies were actually a result of antidepressant medications and other factors. It is now believed that it is more likely that the release time of melatonin is not as it should be in patients with depression. Melatonin supplementation may be able to alter the peak time of release of melatonin which was found to be 77 minutes after the control group in one study. It is not likely that melatonin will have a major positive impact on the treatment of depression but may be able to play a role. A word of caution comes after a study done in 1973 found that melatonin supplementation can worsen depression in some cases. This may have been a result of administering melatonin several times during the day when melatonin is usually lowest.
• Multiple Sclerosis: Declining levels of melatonin may be involved in the pathophysiology and the course of MS. The exact role melatonin plays is unknown but declining levels are seen when symptoms get worse. The benefit of melatonin therapy during the treatment of MS is not yet known.
• Coronary Heart Disease: Melatonin levels are also lower in individuals with coronary heart disease. This can lead to increased nocturnal sympathetic activity which means that there is more circulating epinephrine and norepinephrine which can damage vessel walls and this can lead to atherosclerotic plaque formations. One study shows that melatonin inhibits platelet aggregation and may play a role in preventing heart disease.
• Alzheimer's Disease: There is some evidence to suggest that melatonin serves a protective role for neuronal cells, in fact, melatonin replacement can reverse some of the cognitive loss associated with Alzheimer's Disease. Melatonin acts as antioxidant for grey matter. It is not clear if melatonin is beneficial to all with Alzheimer's Disease.
• Weight Loss: Melatonin supplementation increases weight loss

Assessment Procedure

Way to detect low melatonin:

• Salivary melatonin concentration
• Urinary 6-hydroxymelatonin sulphate excretion rate
• Serum melatonin concentration

Prescribing Considerations

• Melatonin is available in tablet, capsule, and sublingual tablet forms. Some argue that the sublingual form is superior.
• Melatonin is not taken long-term as a nutritional supplement and is only prescribed in certain situations which warrant it.
• Adult: doses range from 0.1-3mg (a therapeutic dose varies greatly from person to person depending on level of deficiency); higher doses are likely needed for anti-cancer effects.

Safety

The safety precautions of melatonin include:

• Side-effects may include: drowsiness at inopportune times is most common; overuse can disrupt sleep cycles; high that are too high for an individual can lead to morning sedation and drowsiness; sleep walking, disorientation, and vivid dreams; sleep disruption; anxiety and irritability; aggravation of nocturnal asthma

Article	Safety and Efficacy of Melatonin in Children, NMJ, 2012 February

• Children: It has been reported that in increase in seizure activity has occurred in children with neurological disorders who have taken melatonin. Monitoring when using melatonin in children is warranted.

• Pregnancy and Breastfeeding

• Melatonin can cross the placenta; its effects on the fetus are unknown and therefore should not be used in pregnancy. Furthermore, melatonin has an effect on reproductive hormones and is further contraindicated in pregnancy for this reason. There is also a lack of research to suggest its safety to breast-feeding infants and therefore should be avoided by nursing mothers.

• Contraindications

• driving and operating machinery while under the influence of melatonin; day time use can lead to fatigue and decreased alertness
• pregnancy and nursing
• fibromyalgia (if melatonin is elevated)
• insulin sensitivity or diabetes
• Seasonal Affective Disorder (SAD)
• possibly for patients with [Autoimmune Conditions|autoimmune conditions]] such as rheumatoid arthritis, lupus, or MS.

• Precautions

• Chronic use of melatonin is not advised. Elevated melatonin may inhibit ovulation. Increased inflammation from elevated melatonin may be experienced by individuals with depression, diabetes, fibromyalgia, schizophrenia, individuals in their adolescence, individuals undergoing corticosteroid treatment, individuals with nocturnal asthma.
• About 5% of individuals will experience both alertness and insomnia from melatonin administration; in this population, melatonin can be dosed in the morning without adverse effects.

• Drug Interactions:

Supportive or Beneficial:

• Chemotherapy and Radiation - Co-administration of drug and high-dose melatonin can ameliorate adverse drug effects and enhance chemotherapy cytotoxicity.
• Fluvoxamine - Concomitant use can increase the effect of either or both agents having an additive effect.
• Haloperidol and Related Antipsychotic Medications - Melatonin may reduce symptoms of tardive dyskinesia (adverse drug effect).
• Interleukin-2 - Potentially mutually supportive antineoplastic activity and synergistic interaction between melatonin and IL-2 in oncology care. Possible reduction in adverse drug effects.
• Mirtazapine - Concomitant use can be beneficial, depending on the case, including facilitation of reduced drug dose or use in drug withdrawal. Adverse effects possible but unlikely.
• Tamoxifen - Co-administration of drug and high-dose melatonin can ameliorate adverse drug effects and enhance chemotherapy cytotoxicity.
• Triptorelin - Melatonin may enhance efficacy of drug and may re-establish response after patients have become refractory.

Addresses Drug-Induced Deficiency:

• Benzodiazepines - Drug can suppress and deplete melatonin. Furthermore, melatonin may be used for synergistic effect and/or to ameliorate withdrawal symptoms from benzodiazepine insomnia treatment by re-establishing a regular sleep cycle.
• Beta 1-Adrenoceptor Antagonists - With chronic use, drug may suppress melatonin synthesis.
• Nonsteroidal Anti-inflammatory Drugs (NSAIDs) - NSAIDs interfere with melatonin synthesis, suppress nocturnal melatonin levels, and may alter sleep patterns.
• Verapamil - Drug induces increased urinary melatonin excretion through its effect on liver and kidneys.

Contraindicated:

• Fluoxetine - Drug can decrease melatonin levels and melatonin can decrease drug activity. Avoid concomitant use.

Other:

• Corticosteroids, oral - Corticosteroid therapy may suppress melatonin synthesis. Melatonin may reduce adverse drug effects but could also suppress drug activity. Insufficient evidence to support generalized recommendations.

• Nutrient Interactions:

• Alcohol/Ethanol - Consumption of ethanol during the evening has been found to inhibit nocturnal melatonin secretion. Evidence is lacking to suggest if melatonin supplementation would be beneficial or problematic.
• Tryptophan - Tryptophan administration may help correct low-melatonin responses.
• Vitamin B6 - A B6 deficiency may affect the tryptophan-serotonin-melatonin pathway and thus inhibit the synthesis of melatonin.
• Vitamin B12 - The beneficial effects of melatonin on sleep-wake cycles may be enhanced with B12 co-administration, presumably because of improved melatonin secretion.