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19 Mar 15
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Many of melatonin's biological effects in animals are produced through activation of melatonin receptors,[6] while others are due to its role as a pervasive and powerful antioxidant,[7] with a particular role in the protection of nuclear and mitochondrial DNA.[8]
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There have been few long-term clinical trials in the use of melatonin in humans.
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The legal availability of melatonin varies widely among countries, ranging from being available without prescription (e.g. in most of North America and Finland)
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Formerly, melatonin was derived from animal pineal tissue, such as bovine. It is now synthetic and does not carry a risk of contamination or the means of transmitting viral material.
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13 Oct 14
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principally blue light, around 460 to 480 nm, that suppresses melatonin
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t light containing only wavelengths greater than 530 nm does not suppress melatonin in bright-light conditions
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13 Jul 14
ralawamiEXOGENOUS supplementation effects not yet confirmed
CIRCADIAN rhythyms are not entrained -
23 Feb 14
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20 Dec 13
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The incandescent light bulb widely used in the twentieth century produced relatively little blue light.[37] Wearing glasses that block blue light in the hours before bedtime may decrease melatonin loss. Kayumov et al. showed that light containing only wavelengths greater than 530 nm does not suppress melatonin in bright-light conditions.[38] Use of blue-blocking goggles the last hours before bedtime has also been advised for people who need to adjust to an earlier bedtime, as melatonin promotes sleepiness.[39]
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Melatonin has been studied as a potential treatment of gastroesophageal reflux disease,[70] cancer, immune disorders, cardiovascular diseases, depression, seasonal affective disorder (SAD), circadian rhythm sleep disorders, sexual dysfunction[71] and insomnia in the elderly.[71][72][73][74] Prolonged release melatonin has shown good results in treating insomnia in older adults (2007).[75] It may improve circadian misalignment and SAD.[76][77] Basic research indicates that melatonin may play a role in modulating the effects of drugs of abuse such as cocaine.[78][79] Melatonin is also a geroprotector.[80]
A 2004 review found that melatonin significantly increased total sleep time in people suffering from sleep restriction.[33]
For many types of sleep disorders, melatonin is not effective. A 2006 review found that although it is safe for short term use (of three months or less), there is "no evidence that melatonin is effective in treating secondary sleep disorders or sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder."[81]
In a 2005 study, researchers concluded that while "there is some evidence to suggest that melatonin is effective in treating delayed sleep phase disorder (DSPD), there is evidence to suggest that melatonin is not effective in treating most primary sleep disorders with short-term use (4 weeks or less)."[82]
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Circadian rhythm disorders[edit]
Further information: Circadian rhythmExogenous melatonin taken in the evening is, together with light therapy upon awakening, the standard treatment for delayed sleep phase disorder (DSPD) and non-24-hour sleep–wake disorder where circadian rhythms are not entrained to the environmental cycle. It appears to have some use against other circadian rhythm sleep disorders as well, such as jet lag and the problems of people who work rotating or night shifts. Melatonin reduces sleep onset latency to a greater extent in people with DSPD than in people with insomnia.[33]
A very small dose taken several hours before bedtime in accordance with the phase response curve for melatonin in humans (PRC) doesn't cause sleepiness but, acting as a chronobiotic (affecting aspects of biological time structure),[83] advances the phase slightly and is additive to the effect of using light therapy upon awakening. Light therapy may advance the phase about one to two-and-a-half hours and an oral dose of 0.3 or 3 mg of melatonin, timed correctly some hours before bedtime, can add about 30 minutes to the ~2 hour advance achieved with light therapy. There was no difference in the average magnitude of phase shift induced by the 2 doses.[40]
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Learning, memory and Alzheimer's[edit]
Melatonin receptors appear to be important in mechanisms of learning and memory in mice,[84] and melatonin can alter electrophysiological processes associated with memory, such as long-term potentiation (LTP). The first published evidence that melatonin may be useful in Alzheimer's disease was the demonstration that this neurohormone prevents neuronal death caused by exposure to the amyloid beta protein, a neurotoxic substance that accumulates in the brains of patients with the disorder.[85] Melatonin also inhibits the aggregation of the amyloid beta protein into neurotoxic microaggregates that, it seems, underlie the neurotoxicity of this protein, causing death of neurons and formation of neurofibrillary tangles, the other neuropathological landmark of Alzheimer's disease.[86]
Melatonin has been shown to prevent the hyperphosphorylation of the tau protein in rats. Hyperphosphorylation of tau protein can also result in the formation of neurofibrillary tangles. Studies in rats suggest that melatonin may be effective for treating Alzheimer's disease.[87] These same neurofibrillary tangles can be found in the hypothalamus in patients with Alzheimer's, adversely affecting their bodies' production of melatonin. Another study has implicated heightened afternoon agitation found in many Alzheimer's patients, called sundowning, with a phase delay in core body temperature.[88] This may suggest a possible connection to melatonin production.
Delirium[edit]
A randomized placebo-controlled trial showed that low-dose melatonin supplementation to 72 elderly patients admitted to acute medicine services significantly reduced delirium.[89]
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Light therapy may advance the phase about one to two-and-a-half hours and an oral dose of 0.3 or 3 mg of melatonin, timed correctly some hours before bedtime, can add about 30 minutes to the ~2 hour advance achieved with light therapy. There was no difference in the average magnitude of phase shift induced by the 2 doses.[40]
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Stimulants[edit]
Research shows that after melatonin is administered to ADHD patients on methylphenidate, the time needed to fall asleep is significantly reduced. Furthermore, the effects of the melatonin after three months showed no change from its effects after one week of use.[90]
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Headaches[edit]
Several clinical studies indicate that supplementation with melatonin is an effective preventive treatment for migraines and cluster headaches.[91][92]
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Mood disorders[edit]
Melatonin has been shown to be effective in treating seasonal affective disorder,[93] a form of depression, and is being considered for bipolar and other disorders in which circadian disturbances are involved.[94] It was observed in 1985 that bipolar disorder might have elevated sensitivity to light, i.e., a greater decrease in melatonin secretion in response to light exposure at night, as a "trait marker" (a characteristic of being bipolar, which does not change with state).[95] This could be contrasted with drug-free recovered bipolar patients showing normal light sensitivity.[96]
Cancer[edit]
A systematic review of unblinded clinical trials involving a total of 643 cancer patients using melatonin found a reduced incidence of death but that blinded and independently conducted randomized controlled trials are needed.[97] The National Cancer Institute's review of the evidence found that it remains inconclusive.[98]
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Gallbladder stones[edit]
Melatonin presence in the gallbladder has many protective properties, such as converting cholesterol to bile, preventing oxidative stress, and increasing the mobility of gallstones from the gallbladder.[99] It also decreases the amount of cholesterol produced in the gallbladder by regulating the cholesterol that passes through the intestinal wall. In guinea pigs, melatonin administration restored normal function by reducing inflammation after induced cholecystitis, whether administered before or after onset of inflammation.[99] Concentration of melatonin in the bile is 2–3 times higher than the otherwise very low daytime melatonin levels in the blood across many diurnal mammals, including humans.[100]
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Amyotrophic lateral sclerosis[edit]
In animal models, melatonin has been shown to ameliorate glutamate-induced neuronal death, it is presumed due to its antioxidant effects. In a clinical safety study involving 31 ALS patients, high-dose rectal melatonin (300 mg/day for 2 years) was shown to be tolerated well.[101]
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Obesity[edit]
Melatonin is involved in energy metabolism and body weight control in small animals. Many studies show that chronic melatonin supplementation in drinking water reduces body weight and abdominal fat in experimental animals, especially in the middle-aged rats[102] and the weight loss effect did not require the animals to eat less and to be physically more active. A potential mechanism is that melatonin promotes the recruitment of brown adipose tissue (BAT) as well as enhances its activity.[103] This effect would raise the basal metabolic rate by stimulating thermogenesis, heat generation through uncoupling oxidative phosphorylation in mitochondria. Whether the results of animal studies can be extrapolated to human obesity is a matter of future clinical trials, since substantially active BAT has been identified in adult humans. [104]
Protection from radiation[edit]
Both animal[105] and human[106][107] studies have shown melatonin to be potentially radioprotective. Moreover, it is a more efficient protector than amifostine,[108] a commonly used agent for this purpose. The mechanism of melatonin in protection against ionizing radiation is thought to involve scavenging of free radicals.[43] It is estimated that nearly 70% of biological damage caused by ionizing radiation is attributable to the free radical, especially the hydroxyl radical that attacks DNA, proteins, and cellular membranes. Melatonin has been suggested as a radioprotective agent, with the proposed advantages of being broadly protective, readily available, orally self-administered, and without major known side effects.[109]
Tinnitus[edit]
Several medical studies involving adult patients indicate that melatonin can be beneficial in the treatment of tinnitus.[110][111][112][113]
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Other[edit]
Melatonin was used to treat periodic limb movement disorder, a common neurological condition, which, when severe, adversely affects sleep and causes excessive daytime fatigue, in a small trial conducted by Kunz D and Bes F. In this condition, the sufferer is affected by mini arousals during sleep and limb movements that occur in a frequent rhythmic fashion. This often involves leg kicking, but sometimes also involves arm movement. Those affected are often not aware of the condition, and partners are often the first to notice the condition. 7 out of the 9 participants in the trial showed significant improvement.[114]
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In recent trial for use in irritable bowel syndrome treatment, melatonin relieved some symptoms, as published in 2010.[115]
A research team in Italy has found that melatonin supplementation in the evening in perimenopausal women produces an improvement in thyroid function and gonadotropin levels, as well as restoring fertility and menstruation and preventing the depression associated with the menopause.[116] One study reported that melatonin taken in the evening raised prolactin levels in six out of seven women.[117]
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In recent trial for use in irritable bowel syndrome treatment, melatonin relieved some symptoms, as published in 2010.[116]
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22 Aug 13
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Production of melatonin by the pineal gland is inhibited by light to the retina and permitted by darkness. Its onset each evening is called the dim-light melatonin onset (DLMO).
It is principally blue light, around 460 to 480 nm, that suppresses melatonin,[36] proportional to the light intensity and length of exposure.
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When used several hours before sleep according to the phase response curve for melatonin in humans, small amounts (0.3 mg[40]) of melatonin shift the circadian clock earlier, thus promoting earlier sleep onset and morning awakening.[
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24 Apr 13
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30 Aug 12
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04 Jun 12
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In mammals, melatonin is biosynthesized in four enzymatic steps from the essential dietary amino acid tryptophan, with serotonin produced at the second step. Melatonin is secreted into the blood by the pineal gland in the brain.
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In humans, melatonin is produced by the pineal gland, a small endocrine gland[24] located in the center of the brain but outside the blood–brain barrier. The melatonin signal forms part of the system that regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature, but it is the central nervous system (specifically the suprachiasmatic nuclei, or SCN)[24] that controls the daily cycle in most components of the paracrine and endocrine systems
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09 Feb 12
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sic research indicates that melatonin may play a significant role in modulating the effects of drugs of abuse such as cocaine
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aken 30 to 90 minutes before bedtime, melatonin supplementation acts as a mild hypnotic. It causes melatonin levels in the blood to rise earlier than the brain's own production accomplishes. This usage is now common in sleep and relaxation drinks
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The World Health Organization in 2007 named late night shift work as a probable cancer-causing agent
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he first published evidence that melatonin may be useful in Alzheimer's disease was the demonstration that this neurohormone prevents neuronal death caused by exposure to the amyloid beta protein, a neurotoxic substance that accumulates in the brains of patients with the disorder.[24
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Those Alzheimer's patients with this specific affliction often show heightened afternoon agitation, called sundowning, which has been shown in many studies to be effectively treated with melatonin supplements in the evening.[27]
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It has been observed that bipolar disorder might have, as a "trait marker" (something that is characteristic of being bipolar, that does not change with state), supersensitivity to light, i.e., a greater decrease in melatonin secretion in response to light exposure at night.[39] This could be contrasted with drug-free recovered bipolar patients not showing light hypersensitivity.[40
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During the night, melatonin regulates leptin, lowering the levels; see leptin.
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The melatonin signal forms part of the system that regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature, but it is the central nervous system (specifically the suprachiasmatic nuclei, or SCN)[82] that controls the daily cycle in most components of the paracrine and endocrine systems[83][84] rather than the melatonin signal (as was once postulated).
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Some supplemental melatonin users report an increase in vivid dreaming.
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esearch has supported the anti-aging properties of melatonin. Younger children hit their peak melatonin production at night, and some researchers believe that the level of melatonin peaks earlier as we get older. This may explain why older adults go to bed earlier, wake up earlier, and have more sleep problems than children do.[111]
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Stephanie Wubbenapossible sleep aid (all natural)
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regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature, but it is the central nervous system (more specifically, the suprachiasmatic nuclei, SCN) that controls the daily cycle in most components of the paracrine and endocrine system
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hormone of darkness
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melatonin promotes sleepiness
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melatonin as an antioxidant
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prevent the damage to DNA by some carcinogens, stopping the mechanism by which they cause cancer.
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melatonin may enhance cytokine production
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increased REM sleep time and dream activity
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30 Aug 09
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Studies from Massachusetts Institute of Technology have said that melatonin pills sold as supplements contain three to ten times the amount needed to produce the desirable physiologic nocturnal blood melatonin level for more a rapid sleep onset. Dosages are designed to raise melatonin levels for several hours to enhance quality of sleep, but some studies suggest that smaller doses (for example 0.3 mg as opposed to 3 mg) are just as effective.[74] Large doses of melatonin can even be counterproductive: Lewy et al.[75] provide support to the "idea that too much melatonin may spill over onto the wrong zone of the melatonin phase-response curve" (PRC). In one of their subjects, 0.5 mg of melatonin was effective while 20 mg was not.
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In individuals with auto-immune disorders, there is concern that melatonin supplementation may ameliorate or exacerbate symptoms due to immunomodulation.[81][82]
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12 Mar 09
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Products containing melatonin have been available as a dietary supplement in the United States since 1993.[7] However, over-the-counter sales of the hormone remain illegal in many other countries, and the U.S. Postal Service lists melatonin among items prohibited by Germany.[8]
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ADHD
Research shows that after melatonin is administered to ADHD patients on methylphenidate, the time needed to fall asleep is significantly reduced. Furthermore, the effects of the melatonin after three months showed no change from its effects after one week of use.[52]
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Headaches
Several clinical studies indicate that supplementation with melatonin is an effective preventive treatment for migraines and cluster headaches.[55][56]
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19 Jan 09
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but over-illumination can create significant reduction in melatonin production.
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Since it is principally blue light that suppresses melatonin,[23] wearing glasses that block blue light[24] in the hours before bedtime may avoid melatonin loss. Use of blue-blocking goggles the last hours before bedtime has also been advised for people who need to adjust to an earlier bedtime, as melatonin promotes sleepiness.
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Even low light levels inhibit melatonin production to some extent
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Extremely high doses of melatonin (50mg) dramatically increased REM sleep time and dream activity in both narcoleptics and those without narcolepsy.
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Many supplemental melatonin users have reported an increase in vivid dreaming.
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However, one factor that may influence this perception is that many over-the-counter melatonin tablets also include Vitamin B6 (pyroxidine), which is also known to be capable of producing vivid dreams
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Exogenous melatonin, used as a chronobiotic and usually taken orally in the afternoon and/or evening, is, together with light therapy upon awakening, the standard treatment for delayed sleep phase syndrome and non-24-hour sleep-wake syndrome.
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Research shows that after melatonin is administered to ADHD patients, the time needed to fall asleep is significantly reduced. Furthermore, the effects of the melatonin after three months showed no change from its effects after one week of use.
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Studies from Massachusetts Institute of Technology have said that melatonin pills sold as supplements contain three to ten times the amount needed to produce the desirable physiologic nocturnal blood melatonin level for enhancement of sleep. Dosages are designed to raise melatonin levels for several hours to enhance quality of sleep, but some studies suggest that smaller doses (for example 0.3 mg as opposed to 3 mg) are just as effective at improving sleep quality.[63]
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If taken several hours before bedtime according to the phase response curve (PRC) for melatonin, it merely advances the phase of melatonin production. If taken 30 to 90 minutes before bedtime, it advances the period of melatonin's presence in the blood.
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When taken several hours before bedtime in accordance with the PRC for melatonin in humans, the dosage should be so tiny as to not cause tiredness/sleepiness
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