Melatonin is a principal hormone of the vertebrate pineal gland. It is synthesized endogenously by the pinealocytes of the pineal gland.
In the biosynthesis of melatonin, tryptophan is first converted by tryptophan hydroxylase to 5-hydroxytryptophan, which is then decarboxylated to serotonin. The synthesis of melatonin from serotonin is catalyzed by two enzymes (arylalkylamine N-acetyltransferase and hydroxyindole-O-methyltransferase) both which are largely confined to the pineal gland.
The synthesis of melatonin displays a circadian rhythm that is reflected in serum melatonin concentrations. Synthesis and release of melatonin are stimulated by darkness and inhibited by light.
As synthesis of melatonin increases the hormone enters the bloodstream through passive diffusion. Melatonin secretion increases soon after darkness peaks and then gradually falls during the second half of the night.
Melatonin can be found in plants and animals, although concentration in plants is a much lower than in animals.
Infants younger than three months of age secrete very little melatonin. The secretion of melatonin peaks from age one to three (325 pg per milliliter) and then declines gradually with age (adult: 10 and 60 pg per milliliter).
Melatonin is rapidly metabolized, mainly in liver, by hydroxylation and after conjugation with sulfuric or glucuronic acid it is secreted into the urine. The bioavailability of oral melatonin varies widely.
Many blind individuals with no pupillary light reflexes and no conscious visual perception have light-induced suppression of melatonin secretion.
Supplemental melatonin may have a hypnotic action. It is a hormone that has biological effects and that activates through a family of G protein-coupled receptors. The putative effect of melatonin as a hypnotic may be accounted for by receptor-mediated action on the limbic system.
At high doses, melatonin may have antioxidant properties. It may inhibit metal ion-catalyzed oxidation processes, specifically in the Fenton reaction.
Melatonin may have anti-apoptotic activity in the thymus, possibly by down-regulating the glucocorticoid receptor.
Melatonin may be used in the treatment of some forms of sleep disturbances or insomnia.
Melatonin may be used to treat some symptoms of jet lag, although research results are mixed.
Melatonin may be used in the treatment of cancer and immune disorders. Some findings are promising, but they are preliminary.
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen [Motrinâ] and aspirin (ASA), can decrease melatonin secretion in the body.
Beta-blockers, such as propranolol [Inderalâ], inhibit the nocturnal rise in melatonin concentrations.
Tricyclics (amitriptyline [Elavilâ]), monoamine oxidase inhibitors (MAOIs) (isocarboxazid [Marplanâ]), and some other antidepressants increase the concentrations of brain melatonin.
Benzodiazepines, such as diazepam [Valiumâ], interfere with synthesis of melatonin.
Diuretics such as furosemide [Lasixâ] and calcium-channel blockers such as amlodipine [Norvascâ] can interfere with melatonin production.
Vitamin B12 concentrations influence melatonin secretion in the body. Taking melatonin (1.5 mg of methylcobalamin per day) can improve sleeping disorders.
Alcohol and caffeine can decrease melatonin production. Avoid these substances before taking melatonin right before going to sleep.
Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature. In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship.
Sleep or Insomnia: Sleep disturbance is very common among the elderly population. Fifty percent of people over 65 years of age complain of sleep disturbance. Healthy elderly take longer to fall asleep, awake more often and have more difficulty returning to sleep after midnight awakenings. Impaired melatonin secretion is associated with sleep disorders and old age.
In a study done on elderly melatonin-deficient insomniacs, patients were given 1 to 2 mg of melatonin formulations or placebo for 7-day periods. In the preliminary study, 1week treatment of 2 mg of fast-release melatonin was as effective as the two-month treatment of 1 mg of sustained release melatonin. Researchers concluded that melatonin deficiency seemed to be linked to sleep disorders in the elderly. Melatonin replacement may be beneficial in the initiation and maintenance of sleep in the elderly.5
Six healthy male volunteers participated in a study that included a total of 9 test sessions with at least 5 days between sessions. Subjects were given oral doses of 0.3 or 1.0 mg of melatonin at 3 time points. Researchers found that sleep onset provoked by a single dose of melatonin, resulted not from its effect on biological timing mechanisms, but from a direct action of elevated circulating melatonin concentrations.6
Antioxidant: Melatonin may be an effective free radical scavenger. In vivo and in vitro studies have indicated that melatonin directly scavenges highly toxic hydroxyl radical and other oxygen centered radicals. It is speculated that melatonin may provide protection against diseases that involve degenerative or proliferative changes by shielding macromolecules from free radical damage.
During nighttime, both melatonin and total antioxidant status (TAS) decreased to basal daytime values and with aging, day to night differences in melatonin and TAS change. A study on healthy volunteers from ages 2 to 89 looked at whether physiological concentrations of melatonin contribute to the antioxidant capacity of human serum. Results showed physiological melatonin concentrations in human serum, especially at night, exhibited significant antioxidative properties.7
Ethanol-induced, gastro-duodenal damage is thought to be mediated by the generation of free radicals. Melatonin protection against ethanol-induced gastroduodenal injury was investigated in rats given 10 mg/kg of melatonin intraperitoneal in a single dose. Melatonin administration before ethanol treatment greatly reduced macroscopic and histological gastroduodenal damage. Melatonin administration reduced indomethacin-ethanol-induced polymorphonuclear leukocyte infiltration rise by 57% in the stomach and 40% in the duodenum. Results from these experiments show a significant protection by melatonin against ethanol-induced gastroduodenal injury. 8
Bone Formation: Studies have shown that melatonin can increase expression of the response element of rat bone sialoprotein (BSP) as well as several other essential bone marker proteins, including alkaline phosphatase (ALP) and osteocalcin (OC). In addition, it has shown to stimulate both osteoblast differentiation and mineralization.
A study looked at whether melatonin could modulate expression of BSP in two cell lines. Concentrations of 10 nm of melatonin were able to stimulate transcription of genes when cells were grown in the presence of beta-glycerophosphate and ascorbic acid. Melatonin-induced gene expression of bone marker proteins occurred on the 5th day after seeding the culture dishes. The results demonstrated that melatonin is capable of promoting osteoblast differentiation and mineralization of matrix in culture and it may play an essential role in regulating bone growth. 9
Blindness: A majority of completely sight-impaired individuals have circadian rhythms that are not synchronized to environmental time cues and that oscillate on a cycle slightly longer than 24 hours. This can cause recurrent insomnia and sleepiness during the day.
A study on 7 sight-impaired subjects with free running circadian rhythms were given 10 mg of melatonin or placebo daily 1 hour prior to bedtime for 3 to 9 weeks. Subjects were found to spend less time awake after the initial onset of sleep and sleep efficiency was higher. Researchers found free-running circadian rhythms in blind people can be entrained to a 24-hour cycle with a daily dose of melatonin and possibly preventing a sleep disorder. 10
Perimenopause and Menopause: Nocturnal administration of melatonin may postpone endocrine aging and maintain or reconstitute more juvenile sexual function in women during perimenopause or menopause. It may also enhance and improve efficiency of hormone replacement therapy and add more years to a woman's fertile life.
A study done on perimenopausal and menopausal women ages 42 to 62 took 3 mg of melatonin or placebo at bedtime for 3 and 6 months. Melatonin produced a significant diminution of luteotropic hormone in the women aged 43 to 49, but no effect was seen in the 52 to 62 year old women. The women receiving melatonin reported a general improvement in mood, a significant mitigation of depression and a recovery of pituitary and thyroid functions. Overall, researchers concluded that this showed a more juvenile pattern of regulation. 11
For sleep disturbance or jet lag no more than 0.3 to 3 mg of melatonin should be taken at bedtime and it should not be taken for longer than 2 weeks. Higher doses or for prolonged periods should be done under medical supervision.
Information regarding the precise dose of melatonin is insufficient. Reported dose range has been from 0.3 to 80 mg, but the correct timing of the dose is unclear.1
Forms available: capsules, liquid, lozenges, sublingual tablets, tea and time released tablets.
The dietary supplement information contained on this site has been compiled from published sources thought to be reliable, but it cannot be guaranteed. Efforts have been made to assure this information is accurate and current. However, some of this information may be purported or outdated due to ongoing research or discoveries. The authors, editors and publishers cannot accept responsibility for errors or omissions or for any consequences from applications of the information in this site and make no warranty, expressed or implied, with respect to the contents herein.
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