Melatonin

Melatonin: Overview

Melatonin is a key hormone in the body's regulation of daily, monthly, yearly and possibly even life-long bodily functions.  A hormone produced in the pineal gland, it affects many other organ systems in the body.

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Melatonin comes form the remnant of the body of our 'third eye'.  This, our pineal gland, contains light-sensitive cells and monitors our environment.  It keeps our body in tune with daily and seasonal rhythms and changes.  Hence, we are synchronous with nature; rest and sleep when it is dark and active and awake when it is light; and in lower animals, the sense of when to migrate, mate and hibernate.

Melatonin is not really a food supplement.  It is a hormone, just like estrogen, thyroid, or cortisone, but without the obvious side-effects seen on overdosing.  While melatonin is widely touted as an antioxidant, the current evidence suggests that it is not an important antioxidant when typical concentrations are used.

Much information and marketing abounds concerning melatonin supplementation, the long-term consequences of which have not been determined.  It seems that our pineal glands release melatonin in ever increasing amounts in the evening, possibly in response to decreasing light, promoting the duration and "quality" of sleep.  Some reports suggest that as humans age, the pineal gland produces less melatonin; affecting not only the sleeping pattern, but other factors as well.

Source

Melatonin is produced by the pineal gland and is not a part of your daily diet (unless you are in the habit of eating pineal glands!)

Melatonin levels are 10 to 20 times higher at night than during the day and one to two times higher in late spring/summer (the Solstice) than in late fall/winter.  Melatonin is passed through the placenta before birth, in mother's milk in the early part of our lives and gradually increases until age seven, when it greatly increases.  At puberty, there is a temporary decline, which signals the pituitary to release the sex stimulating hormones.  At about the age of 40, our pineal gland shrinks and later becomes calcified.  By age 60, our melatonin production is half of what it was at age 20.

Melatonin pills come in varying sizes, but include a 3mg oral preparation and a 2.5mg and 5mg under the tongue product.

Function; Why it is Recommended

In addition to extending our youthful life, melatonin restores normal sleep patterns, is an antioxidant, strengthens our immune system and enhances sexual vitality, as well as preventing jet lag.

Melatonin is appropriate for supplementation when low melatonin levels are suspected, or when specific conditions are being treated with higher doses.

If melatonin excites instead of calms, this may indicate a hormone imbalance in women.  Inositol at low doses (650mg, which is contained in 3 tbsp of lecithin) at bedtime may help.  When depression is also present, 5-HTP, St. John's Wort or tryptophan may help as well.

Elderly patients using 2mg of controlled-release melatonin are much more successful at weaning themselves off of medications such as alprazolam, oxazepam, brotizolam, and lorazepam.  In one study, 14 out of 18 patients were able to completely discontinue their benzodiazepine treatment after 4 to 6 weeks of melatonin therapy.

One particular use of melatonin seems to be quite rational; the short-term use of melatonin to overcome jetlag.  Since jetlag is essentially a phenomenon of your body trying to realign its 24 hour clock with the abnormal day light cycle change, a dose of melatonin seems to be excellent at helping.  Taking 0.5 to 3 mg a few hours before the desired time of sleep should decrease the adjustment period of jetlag.  Short-term treatment of insomnia can be treated the same way.  Each individual will respond differently to different dosages of melatonin.  What is adequate for one individual may have no effect on another and may cause even another to have a morning "hang-over".

One Dutch study suggested that 30mg of melatonin daily could even act as a contraceptive.

Instructions

Generally speaking, melatonin should not be taken during the day as it may disrupt circadian rhythms and cause drowsiness.  There is no evidence that one method of delivery is substantially better than another (tablet, capsule, sublingual), but the sustained-release form might best duplicate the body's normal pattern of release.  Generally the sublingual form is preferable when used to help with sleep or anxiety.  It is faster-acting, better absorbed, and doesn't remain in the system as long so it is less likely to cause a 'morning hangover'.

Dosages of 1-3mg one hour before bedtime are more than sufficient to achieve its sleep-inducing quality.  Doses as low as 0.1mg have produced a sedative effect when melatonin levels are low.  Doses in the range of 10-50mg are used in cancer treatment and possibly other conditions.

Others recommend 3 to 9mg one hour before desired sleep (3mg at ages 30 to 40; 6mg at ages 40 to 60; and 9mg after age 60).  Melatonin is available in the form of sublingual tablets, in which case it is 2.5mg from ages 30 to 40; 5mg from ages 40 to 60; and 7.5mg after age 60.

Side-Effects; Counter-Indicators and Warnings

Melatonin is non-addictive and, if taken at the proper dosage, has little downside except its expense.  It has shown itself to be virtually free of any significant adverse effects; a lethal dose of melatonin cannot be identified which is a rare event in toxicology studies.  However, more mild side-effects, such as headache, morning sleepiness/grogginess, fatigue, intense dreaming or nightmares, are experienced by average individuals when they try melatonin.  Perhaps it is because these people do not require supplementation.  In spite of the non-existence of serious side-effects, it is a cautious and generally made recommendation that melatonin should only be taken when your own production is low unless a serious condition is being treated with higher doses.

Melatonin is almost certainly safe for occasional use (such as in plane travel), but some concerns do exist about using it on a regular basis.  Because the body's own production of melatonin is probably the equivalent of only 0.1mg daily, when you take melatonin for sleep, you may tremendously exceed the body's own production.  The consequences of doing so on a regular basis are completely unknown.

If you take too much melatonin, you may experience the following effects:

  • Drowsiness upon arising
  • Wild, not just vivid, (bad) dreams
  • An excess of the thyroid hormone (T3), resulting in waking up nervous, sweating, and with palpitations
  • Decreased estrogen and progesterone levels.  If melatonin excites instead of calms, this may indicate a hormone imbalance in women.  Inositol at low doses (650mg, which is contained in 3 tbsp of lecithin) at bedtime may help.

On the basis of theoretical ideas about how melatonin works, some authorities specifically recommend against using it for depression, schizophrenia, autoimmune diseases and other serious illnesses, or by pregnant or nursing women.  Do not drive or operate machinery for several hours after taking melatonin.

Doses over 10mg per day can decrease ovarian activity & suppress sex hormone function.

Melatonin helps with the conversion of the inactive thyroid (T4) to the active thyroid (T3).  If you are on thyroid and start to regularly take melatonin, you may need to adjust your thyroid dosage.

Melatonin can help with the following:

Aging

Premature/Signs of Aging

Melatonin helps to restore metabolic function and 'reset the metabolic clock' that has been disrupted by aging.

Parkinson's Disease

Melatonin is one of the most powerful antioxidants in the brain, and can help to gradually slow down chronic degenerative brain diseases such as Parkinsons.

Autoimmune

Sarcoidosis

At least two cases of sarcoidosis have been successfully treated with 20mg of melatonin per day.  These were chronic sarcoidosis cases unresponsive to long-term steroidal therapy. [The Lancet November 4, Vol 346, pp.1229-30, 1995]

Not recommended for
Autoimmune Tendency

Melatonin enhances the immune system and therefore those with autoimmune diseases should use melatonin only in very low doses.

Environment / Toxicity

Female-Specific

Not recommended for
Motherhood Issues

On the basis of theoretical ideas about how melatonin works, some authorities specifically recommend against using it for depression, schizophrenia, autoimmune diseases and other serious illnesses, and in pregnant or nursing women.

Pregnancy-Related Issues

On the basis of theoretical ideas about how melatonin works, some authorities specifically recommend against using it for depression, schizophrenia, autoimmune diseases and other serious illnesses, and in pregnant or nursing women.

Glandular

Not recommended for
Low Adrenal Function / Adrenal Insufficiency

Since melatonin helps to control excess cortisol production, those with low adrenal function and low cortisol levels need to be careful about taking too much melatonin: it can make them even more tired.

Habits

Lack of Sleep

Melatonin improves the quality of sleep.

Hormones

Immunity

Chronic Fatigue / Fibromyalgia Syndrome

A randomized, placebo-controlled study found that melatonin supplementation (either alone or in conjunction with fluoxetine/Prozac) significantly reduced fibromyalgia symptoms.

Weakened Immune System

Melatonin is an immune system enhancer and modulator.

HIV/AIDS

Melatonin slows HIV replication in cell cultures.

Lab Values

High Total Cholesterol

Melatonin helps to decrease total cholesterol and "bad" LDL cholesterol levels.

LDL/HDL Ratio, High

Melatonin helps to decrease total cholesterol and "bad" LDL cholesterol levels.

Mental

Stress

Melatonin can protect against stress by controlling overproduction of the stress hormone cortisol.

Cluster Headaches

A drop in nocturnal melatonin has been linked with cluster headaches, and melatonin supplementation has shown a low but significant preventive capacity for cluster headaches.  In a blinded trial, 10mg of melatonin was given to 10 subjects and a placebo was given to 10 controls for 14 days.  5 out of 10 treated patients reported a decline in attack frequency after 3-5 days of treatment and then experienced no further attacks until melatonin was discontinued.  The melatonin was taken in a single evening dose. [Cephalalgia. 1996;16: pp.494-496]

Not recommended for
Depression

On the basis of theoretical ideas about how melatonin works, some authorities specifically recommend against using it for depression, schizophrenia, autoimmune diseases and other serious illnesses, and in pregnant or nursing women.

Some studies showing melatonin to be an effective treatment for depression were flawed.  Melatonin is unlikely to produce significant positive effects in the treatment of depression in most patients, especially if the patient is not already melatonin-deficient.  Badly timed use of melatonin can worsen depression.  However, some patients with SAD (seasonal affective disorder, a form of depression associated with the shortening of the days in autumn and winter) have been shown to have disrupted melatonin cycles, and have been treated effectively with light therapy.

Tendency Toward Postpartum Depression

On the basis of theoretical ideas about how melatonin works, some authorities specifically recommend against using it for depression, schizophrenia, autoimmune diseases and other serious illnesses, and in pregnant or nursing women.

Metabolic

Nervous System

Seizure Disorder

In a preliminary study, 6 children with severe intractable seizures were given a 3mg tablet of melatonin 30 minutes before bedtime in addition to their usual anti-seizure medication for three months.  A reduction in seizure activity, particularly during the night, was experienced by 5 out of 6 starting 3 days after treatment began.  The mean seizure rate decreased from 3.6 per day to 1.5 per day.  According to the parents, daytime behavior also improved.  This therapy should be monitored closely as a previous study with melatonin found increased seizure activity in some children. [Epilepsia 2001;42: pp.1208-10]

Tardive Dyskinesia

A double-blind study demonstrated that 10mg of melatonin given at 8pm for 6 weeks is an effective treatment for tardive dyskinesia, although the magnitude of the effect was only modest.  Other natural substances that have been reported to improve tardive dyskinesia include vitamin E, manganese and vitamin B6.  It is possible that using these compounds in combination would be more effective than using any one individually. [Arch Gen Psychiatry 2001;58: pp.1049-52]

Unresolved Chronic Pain

Melatonin can help to reduce pain.

Sleep

Insomnia

The body uses the hormone melatonin as part of its normal control of the sleep-wake cycle: melatonin plays an important role in the induction of sleep.  The pineal gland – a tiny gland at the base of the brain – makes serotonin and then turns it into melatonin when light decreases.  Strong light (such as sunlight) turns off melatonin production.  Completely darkened rooms increase melatonin levels more than partially darkened rooms, and weak light doesn't completely shut down melatonin production as does strong light.

Taking melatonin as a supplement seems to stimulate sleep when the natural cycle is disturbed.  It is most dramatically effective for jet lag and for those who work night shifts and want to change their hours of sleep on the weekends.

Sustained-release melatonin may provide sleep enhancement for those who have difficulty remaining asleep.  Several double-blind trials show melatonin supplementation to be very effective in promoting sleep.  However, it appears that the sleep-promoting effects of melatonin supplementation are most apparent if an individual's melatonin levels are low.  Melatonin supplementation does not act as a simple sedative like a sleeping pill; only if this sleep-producing hormone is deficient will supplementation be helpful.  Furthermore, melatonin acts to regulate or alter sleep rhythms, so its effect may be stronger with problems getting to sleep initially than with sleep disturbances once asleep.

One week of supplementation with melatonin (0.1mg, 0.3mg or 3mg before bedtime) in 30 patients with insomnia over 50 years old with reduced melatonin levels, improved sleep in a double-blind, placebo-controlled, cross-over study.  The 3mg per day dose induced hypothermia and caused plasma melatonin to remain elevated into the daylight hours. [J Clin Endocrinol Metab 2001;86(10): pp.4727-4730]

One double-blind study enrolled 320 people who were given 5mg of standard melatonin, 5mg of slow-release melatonin, 0.5mg of standard melatonin, or a placebo for 4 nights following plane travel.  The results showed improvements only with 5mg of standard melatonin.  Benefits were noted in time to fall asleep, quality of sleep, and daytime drowsiness and fatigue.  Positive results were seen in several other studies but at least one study failed to find a significant sleep-inducing effect for melatonin.  On balance, the evidence is strongly positive that melatonin can help sleep.

According to one review of the literature, treatment is most effective for those with significant jet lag, such as those who have crossed more than 8 time zones.  However, melatonin also seems to be help induce sleep for other people, including those with no sleep problems to begin with.

Tumors, Malignant

Breast Cancer

Melatonin has been shown to inhibit several types of cancers, especially hormone-related cancers such as breast cancer.  This may be due to its ability to reduce the number of cellular estrogen receptors, which reduces the production of cell-multiplication factors.  The immune-modulating properties of melatonin appear to convey additional anti-cancer properties.  It has been shown to support the use of interleukin-2 in anti-cancer therapy, especially under conditions of controlled lighting.  Many animal studies have demonstrated an increase in tumor growth rates in animals whose pineal glands have been removed.

Positive results have been shown with melatonin on its own and in combination with interferon, tumor necrosis factor, and tamoxifen.  These preliminary results were quite encouraging as approximately 30% of the patients taking anywhere from 10-50mg daily (at 8pm) experienced improvements in survival time and quality-of-life assessments. [Brit J Cancer 7l(4): pp.854-56, 1995]

Cancer, General

Melatonin has been shown to inhibit several types of cancer, especially hormone-related cancers like breast cancer and prostate cancer.  This may be due to its ability to reduce the number of cellular estrogen receptors, which reduces the production of cell-multiplication factors.

The immune-modulating properties of melatonin seem to convey additional anti-cancer properties.  It has been shown to support the use of interleukin-2 in anti-cancer therapy, especially under conditions of controlled lighting.  Many animal studies have demonstrated an increase in tumor growth rates in animals whose pineal glands have been removed.

Various researchers report successes against solid tumors, colorectal cancer, non-small cell lung cancer, brain metastases, glioblastoma, estrogen receptor-negative breast cancer, prostate cancer, metastatic renal cancer and adenocarcinoma of the pancreas.  Furthermore, these effects seem to be substantial.

To select a typical example, people with solid tumors were given either just IL-2 (a regulator of the immune system), or IL-2 plus melatonin.  15% of the people receiving just IL-2 survived after one year, whereas 46% of the people also receiving melatonin survived.  One researcher reported no failures i.e. instances in which melatonin did not have a positive effect.  It has been proposed that melatonin might be useful for treating the general ill health found in cancer patients.

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Melatonin can help prevent the following:

Aging

Alzheimer's Disease

Melatonin, a powerful antioxidant and heavy-metal-chelating agent, has been shown to protect against heavy metal exposure which is in turn implicated in Alzheimer's Disease.  Ensuring normal melatonin levels therefore has a protective effect.

After exposing nerve cells to inorganic mercury, neurobiologists observed a toxic reaction that reduced cellular levels of the antioxidant glutathione by 30%, triggered the release of plaque-forming β-amyloid peptides, and spurred the hyperphosphorylation of tau-protein – all pivotal mechanisms in the development and progression of Alzheimer's.

However, they found that if the cells were first incubated with melatonin – a powerful antioxidant and heavy-metal-chelating agent – they were protected from these damaging effects.  In fact, despite being exposed to toxic doses of mercury, the cells treated with melatonin often showed metabolic status comparable to that of mercury-free cells.

These results provide strong experimental evidence that mercury toxicity may be involved in Alzheimer's development and that melatonin shows a marked potential to neutralize this toxic-induced pathology, by boosting antioxidant defense and binding to heavy metals.

Tumors, Malignant

Prostate Cancer

The body produces the most melatonin at night, when it is dark.  Bright lights at night or too little light during the day disrupt the production of melatonin.  A 2014 study of 928 Icelandic men without prostate cancer found that men who had higher levels of melatonin had a 75% reduced risk for developing advanced prostate cancer, and a 31% decreased risk for prostate cancer overall, compared with men who had lower levels of melatonin. [Eur Urol. 2015 Feb;67(2): pp.191-4]  This suggests that lowering one's risk for prostate cancer is as simple as getting enough sleep.

Melatonin has been shown to inhibit several types of cancers, especially hormone-related cancers like breast cancer and prostate cancer. [Bartsch and Bartsch]  This may be due to its ability to reduce the number of cellular estrogen receptors, which reduces the production of cell-multiplication factors.

The immune-modulating properties of melatonin seem to convey additional anti-cancer properties.  It has been shown to support the use of interleukin-2 in anti-cancer therapy, especially under conditions of controlled lighting.  Many animal studies have demonstrated an increase in tumor growth rates in animals whose pineal glands (which secrete melatonin) have been removed.

Positive results have been shown with melatonin on its own and in combination with interferon, tumor necrosis factor, and tamoxifen.  These preliminary results are quite encouraging because approximately 30% of the patients taking anywhere from 10 to 50mg daily (at 8pm) experienced improvements in survival time and quality-of-life assessments. [Lissoni et al, Brit J Cancer 7l(4): pp.854-6, 1995]

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