Melatonin is an important hormone that is secreted by the pineal gland in the brain. Since its identification in 1958, studies have shown that melatonin plays a crucial role in ordering the complex hormone secretion patterns that regulate the body's circadian rhythm. Melatonin also helps control sleeping and waking periods, because its release is stimulated by darkness and suppressed by light. It also controls the timing and release of female reproductive hormones, affecting menstrual cycles, menarche, and menopause.

Overall levels of melatonin in the body also contribute to the process of aging. The standard rhythmic pattern of melatonin levels are absent until about 3 months of age. After that, the nocturnal levels of melatonin are at their highest for the first few years and then begin to decline as puberty begins. After puberty, nocturnal melatonin levels are relatively stable throughout adulthood and then fall as people age. In old age, the nocturnal rise in melatonin may be barely detectable. Because melatonin opposes the degeneration caused by high levels of corticosteroids (e.g., protein catabolism, suppressed immune function, and altered blood glucose metabolism), higher melatonin levels may help promote health and extend life span.

Studies show that jet lag is most likely caused by a disrupted circadian rhythm that can be effectively adjusted by using melatonin. Insomnia that is seen in the elderly and in some children with sleeping disorders is usually caused by low melatonin levels. That, too, can be treated with the proper supplementation. Childhood diseases that may cause melatonin-related sleep disorders include autism, epilepsy, Down's syndrome, and cerebral palsy. Melatonin supplementation can also benefit blind people whose sleeping rhythms are disturbed. Melatonin is not effective as a sleeping aid for persons with normal melatonin levels.

Several studies have shown how melatonin levels shift during monthly menstrual cycles. Nocturnal melatonin is highest during the premenstrual period and lowest during the midmenstrual period. It is thought that rising melatonin levels may bring on menstruation and lowering ones may bring on a surge of luteinizing hormone and ovulation. Administering melatonin prior to the midcycle surge of luteinizing hormone appears to block ovulation, leading to speculation about the use of melatonin as a natural contraceptive.

Melatonin also has antioxidant, antiestrogenic, and may have oncostatic properties. As an antioxidant, melatonin appears to be able to neutralize hydroxyl, the most damaging of all oxygen-based free radicals. Studies show that melatonin may help prevent or treat some hormonally related cancers, such as breast cancer and prostate cancer.

Many studies have shown that some patients suffering from depression have lower-than-normal melatonin levels. Seasonal affective disorder (SAD) is often effectively treated with phototherapy, and research has shown that SAD patients often have delayed melatonin rhythms in the winter. While some forms of depression may have direct links to melatonin levels, other types of depression have not responded well to melatonin treatment. Exaggerated depressive symptoms have been reported in some cases of depressed patients receiving daytime melatonin supplements. Melatonin has increased psychotic behavior in some schizophrenic patients.

Melatonin is a hormone manufactured by serotonin and secreted by the pineal gland. It is an indole, like the simple amino acid, tryptophan.

Melatonin can be taken in tablet, capsule, and sublingual tablet form.

• Used to restore sleeping patterns and fatigue caused by jet lag
• As a sleeping aid for those who suffer from insomnia as a result of low melatonin levels (e.g., elderly and some children with sleep disorders)
• May be beneficial for treatment of depression related to low melatonin levels (e.g., SAD)
• Preliminary studies show it may be useful in multiple sclerosis, SIDS, coronary heart disease, epilepsy and postmenopausal osteoporosis.

Official dosage ranges have not yet been set for melatonin supplementation. Sensitivity to melatonin may vary from individual to individual. For those especially sensitive to it, lower doses may work more effectively than the standard amount. Higher doses could cause anxiety or irritability.

For treatment of insomnia, a dose of 3 mg taken an hour before bedtime is usually effective, although dosages as low as 0.1 to 0.3 mg may improve sleep for some people. If 3 mg a night is not effective after three days, try 6 mg one hour before bedtime. An individually effective dose should produce restful sleep and no daytime irritability or fatigue. For treatment of jet lag, take 5 mg of melatonin one hour before bedtime upon arrival at new location; repeat for the first five days. Long-term melatonin supplementation should not be carried out without a health care provider's supervision.

There are no known serious side effects to regulated melatonin supplementation. Some people may experience vivid dreams or nightmares. Overuse or incorrect use of melatonin could disrupt circadian rhythms. Long-term effects have not been well studied. In rats, melatonin decreases T4 and T3 uptake levels.

Melatonin can cause drowsiness if taken during the day. If morning drowsiness is experienced after taking melatonin at night, reduce dosage levels. In some cases of depression, daytime doses of melatonin can increase depression. May be contraindicated for those with autoimmune disorders and immune system cancers (e.g., lymphoma, leukemia). Because melatonin suppresses corticosteroid activity, those who are taking corticosteroids for anti-inflammatory or immune suppressive purposes (e.g., transplant patients) should exercise caution with melatonin supplementation. Melatonin could interfere with fertility. It is also contraindicated during pregnancy and lactation. Lack of sleep and insufficient exposure to darkness may suppress natural production of melatonin.

Melatonin impaired the efficacy of both methoxamine and clonidine by relaxing vascular smooth muscle through an undetermined mechanism in an ex-vivo experiment using thoracic aorta excised from male rats (Weekley 1991). It is not known whether exogenous melatonin can antagonize the effects of methoxamine and clonidine in humans.

In an experimental rat study, exogenous melatonin (0.25 mg/kg/day) abolished the antidepressant effects of desipramine and fluoxetine possibly through interference with tryptophan-2,3-dioxygenase activity (Walsh and Daya 1998). More research is needed to determine if exogenous melatonin counteracts the effects of antidepressants in humans.

Preliminary research suggests that tamoxifen plus high-dose melatonin may be of benefit in patients with metastatic solid tumors or breast cancer (Lissoni et al. 1995A; Lissoni et al. 1996). More research is needed to confirm these effects.

The combination of melatonin (100 mg/day) with triazolam improved subjective sleep quality in healthy subjects (Ferini-Strambi et al. 1993). Another case study reported that melatonin (1 mg/day controlled release) improved sleep quality and enabled a patient to cease long-term benzodiazepine therapy (Dagan et al. 1997).

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