Melatonin is appropriate for supplementation when low melatonin levels are suspected, or when specific conditions are being treated with higher doses.
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. While melatonin is widely touted as an antioxidant, the current evidence suggests that it is not an important antioxidant when typical concentrations are used.
Melatonin 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, fatigue 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.
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, and help those who fall asleep easily but awaken too soon.
Safety Issues
Melatonin is probably safe for occasional use (as in plane travel), but some real concerns exist about using it on a regular basis. It should be noted that 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. It is not a part of your daily diet, unless you are in the habit of eating pineal glands! 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 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 lorzepam. In one study, 14 out of 18 patients were able to completely discontinue their benzodiazepine treatment after 4 to 6 weeks of melatonin therapy.
In the elderly, 0.3mg melatonin before bed was an effective dose for enhancing sleep. Larger doses (3mg) had the same effect but also caused hypothermia and levels remained high during the day, not dropping as is normally the case.
Cautions, Contraindications and Side-Effects
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.
If you take too much melatonin, you may experience the following effects:
- Drowsiness upon arising
- Wild, not just vivid, 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.
One Dutch study suggested that 30mg of melatonin daily could even act as a contraceptive.
Melatonin can help with the following
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.1229-1230, 1995]
Hypertension
Researchers discovered that if men take melatonin before bedtime, their blood pressure may decrease as much as if they were taking a antihypertensive drug. The participants in the study took 2.5mg of melatonin for a three week period. As expected, melatonin also increased their quality and quantity of sleep. [Hypertension. 2004 Feb;43(2): pp.192-7]
The authors of this study caution that melatonin should not be used for treating hypertension based on this single trial, and that more studies are required.
Seasonal Affective Disorder (SAD)
Although it cannot be established that SAD is caused by abnormal melatonin metabolism, in some people melatonin makes the symptoms of SAD worse (Tarquini et al. 1998). These people should stop melatonin or reduce its dosage during the times of the year when darkness appears early in the day.
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.
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 has been used 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 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.
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 week of treatment with melatonin, either 0.1mg or 0.3mg given 30 minutes before bedtime, did improve sleep in a well controlled cross-over study in Austria of 20 patients with mental retardation and sleep deficits. [J Autism Dev Disorders 2003;33(4): pp.469-72]
Headaches, Cluster
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]
Headaches, Migraine/Tension
Three cases of idiopathic stabbing headache were reported in which melatonin (3 to 12mg at bedtime) was used successfully in their treatment. [Neurology 2003;61(6): pp.865-6]
Male Gynecomastia
One case of painful gynecomastia has been reported involving a 56 year old man who had been suffering from amyotrophic lateral sclerosis and was taking 1 to 2mg melatonin per day over a 1 1/2 year period. As the gynecomastia disappeared after melatonin use was discontinued, it was suspected that the melatonin caused this side effect.
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]
Cancer / Risk - General Measures
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.
Increased Risk of Alzheimer's / Dementia
Ensure normal melatonin levels. 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.
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 ß-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.
Prostate Cancer
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 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 percent of the patients taking anywhere from 10 to 50 milligrams daily (at 8pm) experienced improvements in survival time and quality-of-life assessments. (Lissoni et al, Brit J Cancer 7l(4): pp.854-56, 1995)
Possible 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.
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.
Key
| May do some good |
| Likely to help |
| Highly recommended |
| May have adverse consequences |
| Avoid absolutely |
Glossary
Melatonin
The only hormone secreted into the bloodstream by the pineal gland. The hormone appears to inhibit numerous endocrine functions, including the gonadotropic hormones. Research exists on the efficacy of melatonin in treating jet lag and certain sleep disorders. Dosages greater than l milligram have been associated with drowsiness, headaches, disturbances in sleep/wake cycles and is contraindicated in those who are on antidepressive medication. It also negatively influences insulin utilization.
Milligram
(mg): 1/1,000 of a gram by weight.
Sedative
Calming, quieting; drug that quiets nervous excitement.
Cancer
Refers to the various types of malignant neoplasms that contain cells growing out of control and invading adjacent tissues, which may metastasize to distant tissues.
Antioxidant
A chemical compound that slows or prevents oxygen from reacting with other compounds. Some antioxidants have been shown to have cancer-protecting potential because they neutralize free radicals. Examples include vitamins C and E, alpha lipoic acid, beta carotene, the minerals selenium, zinc, and germanium, superoxide dismutase (SOD), coenzyme Q10, catalase, and some amino acids, like cystiene. Other nutrient sources include grape seed extract, curcumin, gingko, green tea, olive leaf, policosanol and pycnogenol.
Sublingual
Situated or administered under the tongue, for example sublingual glands or sublingual tablets.
Hormones
Chemical substances secreted by a variety of body organs that are carried by the bloodstream and usually influence cells some distance from the source of production. Hormones signal certain enzymes to perform their functions and, in this way, regulate such body functions as blood sugar levels, insulin levels, the menstrual cycle, and growth. These can be prescription, over-the-counter, synthetic or natural agents. Examples include adrenal hormones such as corticosteroids and aldosterone; glucagon, growth hormone, insulin, testosterone, estrogens, progestins, progesterone, DHEA, melatonin, and thyroid hormones such as thyroxine and calcitonin.
Estrogen
One of the female sex hormones produced by the ovaries.
Thyroid
Thyroid Gland: An organ with many veins. It is at the front of the neck. It is essential to normal body growth in infancy and childhood. It releases thyroid hormones - iodine-containing compounds that increase the rate of metabolism, affect body temperature, regulate protein, fat, and carbohydrate catabolism in all cells. They keep up growth hormone release, skeletal maturation, and heart rate, force, and output. They promote central nervous system growth, stimulate the making of many enzymes, and are necessary for muscle tone and vigor.
Inositol
Usually considered part of the vitamin B complex. It is thought that along with choline, inositol is necessary for the formation of lecithin within the body. Involved in calcium mobilization.
Tablespoon
(Tbsp) Equivalent to 15cc (15ml).
Lecithin
A mixture of phospholipids that is composed of fatty acids, glycerol, phosphorus, and choline or inositol. Lecithin can be manufactured in the body. All living cell membranes are largely composed of lecithin.
Tryptophan
Essential amino acid. Natural relaxant and sleep aid due to its precursor role in serotonin (a neurotransmitter) synthesis. Along with tyrosine, it is used in the treatment of addictions.
Hypothermia
Abnormally low body temperature.
Schizophrenia
Any of a group of psychotic disorders usually characterized by withdrawal from reality, illogical patterns of thinking, delusions, and hallucinations, and accompanied in varying degrees by other emotional, behavioral, or intellectual disturbances. Schizophrenia is associated with dopamine imbalances in the brain and defects of the frontal lobe and is caused by genetic, other biological, and psychosocial factors.
Autoimmune Disease
One of a large group of diseases in which the immune system turns against the body's own cells, tissues and organs, leading to chronic and often deadly conditions. Examples include multiple sclerosis, rheumatoid arthritis, systemic lupus, Bright's disease and diabetes.