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Melatonin is secreted by the pineal gland in the brain and is important in
the regulation of many hormones in the body. Among its key roles, melatonin
controls the body's circadian rhythm, an internal 24-hour time-keeping system
that plays an important role in when we fall asleep and when we wake up.
Darkness stimulates the release of melatonin and light suppresses its activity.
Normal melatonin cycles are disrupted when we are exposed to excessive light in
the evening or too little light during the daytime. For example, jet lag, shift
work, and poor vision can disrupt melatonin cycles. In addition, some experts
claim that exposure to low-frequency electromagnetic fields (as is common in
household appliances) may disrupt normal cycles and production of melatonin.
Melatonin is also one of the hormones that controls the timing and release of
female reproductive hormones. As a result, melatonin helps determine when
menstruation begins, the frequency and duration of menstrual cycles, and when
menstruation ends (menopause). Many researchers also believe that levels of
melatonin in the body are related to the aging process. For example, young
children have the highest levels of nighttime melatonin and these levels are
thought to diminish progressively with age. This decline likely contributes to
why many older adults suffer from disrupted sleep patterns and tend to go to bed
earlier and wake up earlier in the morning than when they were younger. However,
emerging research is bringing the idea of diminished melatonin levels in the
elderly into some question. Therefore, those considering use of this supplement
should first talk to their healthcare provider about having blood levels of
melatonin checked.
In addition to its hormone actions, melatonin also has strong antioxidant
properties and preliminary evidence suggests that it may help strengthen the
immune system. Because melatonin is a potent hormone, it's advisable to check
with a healthcare provider before using it as an antioxidant supplement.
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Melatonin for Insomnia
Although results are still controversial, studies suggest that melatonin
supplements help induce sleep in people with disrupted circadian rhythms (such
as those suffering from jet lag or poor vision or those who work the night
shift) and those with low melatonin levels (such as some elderly and individuals
with schizophrenia). In fact, a recent review of scientific studies found that
melatonin supplements help prevent jet lag, particularly in people who cross
five or more time zones.
A few studies suggest that when taken for short periods of time (days to
weeks) melatonin is significantly more effective than placebo in decreasing the
amount of time required to fall asleep, increasing the number of sleeping hours,
and boosting daytime alertness. In addition, at least one study suggests that
melatonin may improve the quality of life in people who suffer from insomnia and
some experts suggest that melatonin may be of value for children with learning
disabilities who suffer from insomnia.
Although research suggests that melatonin may be modestly effective for
treating certain types of insomnia as described, few studies have investigated
whether melatonin supplements are safe and effective over the long term.
Osteoporosis
Melatonin has been shown in laboratory studies to stimulate cells called
osteoblasts that promote bone growth. Given that melatonin levels may also be
lower in some older individuals such as postmenopausal women, current studies
are investigating whether or not decreased melatonin levels contribute to the
development of osteoporosis, and whether treatment with melatonin can help
prevent this condition.
Menopause
Melatonin supplements may benefit menopausal women by promoting and sustaining
sleep. Peri- or postmenopausal women who use melatonin supplements to regulate
sleep patterns should do so only for a short period of time since long term
effects, as indicated earlier, are not known.
Melatonin for depression (Melotonin for SAD)
In one small study of 10 people with a particular type of depression known as
seasonal affective disorder (depressive symptoms that develop during the winter
months when exposure to light is lessened), those who received melatonin
supplements had significant improvement in their symptoms compared to those who
received placebo. Given the small size of this study, however, more research is
needed before conclusions can be drawn regarding use of melatonin for either
seasonal affective disorder or any other type of depression. This is
particularly true since one study from the 1970s suggested that symptoms of
depression may worsen when taking melatonin.
Melatonin for Eating Disorders
Melatonin levels may play a role in the symptoms of
anorexia. For example,
abnormally low melatonin levels may cause depressed mood in people with this
condition. However, it is not known whether supplementation will change the
course of the disease. Some researchers speculate that low melatonin levels in
people with anorexia may indicate who is likely to benefit from
antidepressant
medications (a treatment often used for eating disorders).
Breast Cancer
Several studies indicate that melatonin levels may be linked with breast cancer
risk. For example, women with breast cancer tend to have lower levels of
melatonin than those without the disease. In addition, laboratory experiments
have found that low levels of melatonin stimulate the growth of certain types of
breast cancer cells and adding melatonin to these cells inhibits their growth.
Preliminary laboratory and clinical evidence also suggests that melatonin may
enhance the effects of some chemotherapy drugs used to treat breast cancer. In a
study that included a small number of women with breast cancer, melatonin
(administered 7 days before beginning chemotherapy) prevented the lowering of
platelets in the blood. This is a common complication of chemotherapy, known as
thrombocytopenia, that can lead to bleeding.
In another study of a small group of women whose breast cancer was not
improving with tamoxifen (a commonly used chemotherapy medication), the addition
of melatonin caused tumors to modestly shrink in over 28% of the women. People
with breast cancer who are considering taking melatonin supplements should first
consult a healthcare provider who can help construct a comprehensive treatment
approach to be administered together with conventional care.
Prostate Cancer
Similar to breast cancer, studies of people with prostate cancer suggest that
melatonin levels are lower compared to men without cancer, and test tube studies
have found that melatonin inhibits the growth of prostate cancer cells. In one
small-scale study, melatonin (when used in conjunction with conventional medical
treatment) improved survival rates in 9 out of 14 patients with metastatic
prostate cancer. Interestingly, meditation appears to be a valuable addition to
the treatment of prostate cancer. The positive effects of meditation may be due
to a rise in levels of melatonin in the body. Although these early results are
intriguing, more research is needed.
Cancer-related Weight Loss
Weight loss and malnutrition are of great concern for people with cancer. In one
study of 100 people with advanced cancer that had spread throughout the body,
those who received melatonin supplements were less likely to lose weight than
those who did not receive the supplement.
Sarcoidosis
Some physicians use melatonin to help treat sarcoidosis (a condition where
fibrous tissue develops in the lungs and other tissues). Two case reports
suggest that melatonin may be helpful for those who do not improve from
conventional steroid treatment.
Rheumatoid Arthritis
In a group of patients with rheumatoid arthritis, melatonin levels were low
compared to healthy individuals without arthritis. When treated with the
anti-inflammatory medication indomethacin, melatonin levels returned to normal.
The chemical structure of melatonin resembles indomethacin, so researchers
speculate that melatonin supplements may work similarly to this medication for
people with rheumatoid arthritis. This theory has not been tested, however.
Melatonin for attention deficit/hyperactivity disorder (ADHD)
Although melatonin supplementation does not appear to improve the key behavioral
symptoms of attention deficit/hyperactivity disorder (ADHD), it may be effective in managing sleep disturbances in children
with this condition.
Melatonin for Epilepsy
Preliminary research suggests that melatonin reduces the number of seizures in
certain animal species and may reduce seizures in people with epilepsy. However,
not all experts agree with these findings. In fact, concern has been raised that
melatonin (1 to 5 mg per day) may actually induce seizures, particularly in
children with neurologic disorders. Given that the research is in a very
premature stage, some experts suggest that melatonin should be administered by
healthcare providers to only a select group of people who suffer from seizures
that cannot be controlled by any other type of therapy.
Sunburn
A few small-scale studies suggest that gels, lotions, or ointments containing
melatonin may protect against redness (erythema) and other skin damage when used
either alone or in combination with topical
vitamin E prior to exposure to UV
radiation from the sun.
Viral Encephalitis
Although melatonin has not been scientifically evaluated for use in treating
human encephalitis (inflammation of the brain), some studies suggest that this
supplement may protect animals from serious complications associated with the
condition and even increase their survival rates. In one study of mice infected
with Venezuelan equine virus (a type of organism that causes viral
encephalitis), melatonin supplements significantly lowered the presence of virus
in the blood and reduced death rates by more than 80%. More studies are needed,
however, to determine whether similar treatment may offer the same protection to
people with viral encephalitis.
Heart Disease
Low levels of melatonin in the blood have been associated with heart disease,
but it is not clear whether melatonin levels are low in response to having heart
disease or if low levels of melatonin predispose people to developing this
condition. In addition, several studies in rats suggest that melatonin may
protect the hearts of these animals from the damaging effects of ischemia
(decreased blood flow and oxygen that often leads to a heart attack). It is not
known from this information, however, whether melatonin supplements may help
prevent or treat heart disease in people. More research and scientific
information is needed before conclusions can be drawn.
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Melatonin is available as tablets, capsules, cream, and lozenges that
dissolve under the tongue.
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There is currently no recommended dose range for melatonin supplements.
Different people will be more sensitive or less sensitive to its effects. For
those especially sensitive, lower doses may work effectively while a higher dose
could cause anxiety and irritability. The best approach for any condition is to
begin with very low doses of melatonin that match the amounts our bodies
normally make on a daily basis (< 0.3 mg) and keep the dose to a minimum. Your
healthcare provider can help guide what is best and most appropriate, including
how to increase the amount as needed.
Pediatric
Although studies including small numbers of children suggest that doses of
1-10 mg melatonin have little to no side effects, there is not enough
information at this point to clearly say that doses greater than 0.3 mg per day
are safe in children under age 15. In fact, doses between 1 to 5 mg may cause
seizures in this age group. Until more information is available, it is safest to
keep the dose close to the amount that our bodies normally produce (< 0.3 mg per
day).
Adult
- Insomnia: 3 mg one hour before bedtime is usually effective, although
doses as low as 0.1 to 0.3 mg may improve sleep for some people. If 3 mg per
night is not effective after three days, try 5-6 mg one hour before bedtime.
An effective dose should produce restful sleep with no daytime irritability
or fatigue.
- Jet lag: 0.5 to 5 mg of melatonin one hour prior to bedtime at final
destination has been successful in several studies. Another approach that
has been used clinically is 1 to 5 mg one hour before bedtime for two days
prior to departure and for 2 to 3 days upon arrival at final destination.
- Sarcoidosis: 20 mg per day for 4 to 12 months. Use of melatonin to treat
this specific health condition should only be done under medical
supervision. Do not take melatonin supplements long-term without consulting
your healthcare provider.
- depression: 0.125 mg twice in the late afternoon, each dose four hours
apart (for example, 4 PM and 8 PM). People with depression tend to be
particularly sensitive to the effects of melatonin -- meaning that a very
low dose is generally enough to get the desired outcomes.
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Because of the potential for side effects and interactions with medications,
dietary supplements should be taken only under the supervision of a
knowledgeable healthcare provider.
Some people may experience vivid dreams or nightmares when they take
melatonin. Overuse or incorrect use of melatonin could disrupt circadian
rhythms. Melatonin can cause drowsiness if taken during the day. Individuals
experiencing morning drowsiness after taking melatonin at night should take less
of the supplement. Additional side effects that have been reported from
melatonin include stomach cramps, dizziness, headache, irritability, decreased
libido, breast enlargement in men (called gynecomastia), and decreased sperm
count.
Melatonin could interfere with fertility and also should not be taken by
pregnant or nursing women.
A 1973 study including only 4 people with depression found that melatonin
supplements actually worsened symptoms of the condition. For this reason,
individuals with depression should consult a healthcare practitioner before
using melatonin supplements.
Although many researchers believe that levels of melatonin diminish with age,
emerging evidence has brought this theory into question. Given these
inconsistent findings, people older than 65 years of age should consult a
healthcare practitioner before taking melatonin supplements so that blood levels
of this hormone can be monitored appropriately.
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If you are currently being treated with any of the following medications, you
should not use melatonin without first talking to your healthcare provider.
antidepressant medications
In an animal study, melatonin supplements reduced the antidepressant effects of
desipramine and
fluoxetine. More research is needed to determine whether these
effects would occur in people. In addition,
fluoxetine (a member of a class of
drugs called selective serotonin reuptake inhibitors or SSRIs) has led to
measurable depletion of melatonin in people.
Antipsychotic Medications
A common side effect of antipsychotic medications used to treat schizophrenia is
a condition called tardive dyskinesia, a movement disorder of the mouth
characterized by a constant chewing motion and darting action of the tongue. In
a study of 22 people with schizophrenia and tardive dyskinesia caused by
antipsychotic medications, those who took melatonin supplements had
significantly reduced mouth movements compared to those who did not take the
supplements.
Benzodiazepines
The combination of melatonin and triazolam (a benzodiazepine medication used for
the treatment of anxiety and sleep disorders) improved sleep quality in one
study. In addition, there have been a few reports suggesting that melatonin
supplements may help individuals stop using long-term benzodiazepine therapy.
(Benzodiazepines are highly addictive.)
Blood Pressure Medications
Melatonin may reduce the effectiveness of blood pressure medications like
methoxamine and clonidine. In addition, medications in a class called calcium
channel blockers (such as nifedipine, verapamil, diltiazem, amlodipine,
nimodipine, felodipine, nisoldipine, and bepridil) may decrease melatonin
levels.
Use of beta-blockers (another class of high blood pressure medications
including propranolol, acebutolol, atenolol, labetolol, metoprolol, pindolol,
nadolol, sotalol, and timolol) may reduce melatonin production in the body.
Blood-thinning Medications, Anticoagulants
Melatonin may increase the risk of bleeding from anticoagulant medications such
as warfarin.
Interleukin-2
In one study of 80 cancer patients, use of melatonin in conjunction with
interleukin-2 led to more tumor regression and better survival rates than
treatment with interleukin-2 alone.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
NSAIDs such as ibuprofen may reduce the levels of melatonin in the blood.
Steroids and Immunosuppressant Medications
Melatonin should not be taken with corticosteroids or other medications used to
suppress the immune system because the supplement may cause them to be
ineffective.
Tamoxifen
Preliminary research suggests that the combination of tamoxifen (a chemotherapy
drug) and melatonin may benefit certain patients with breast and other cancers.
More research is needed to confirm these results.
Other Substances
Caffeine, tobacco, and alcohol can all diminish levels of melatonin in the body
while cocaine and amphetamines may increase melatonin production.
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Attele AS, Xie JT, Yuan CS. Treatment of insomnia: an alternative
approach.Altern Med Rev. 2000;5(3):249-259.
Avery D, Lenz M, Landis C. Guidelines for prescribing melatonin. Ann Med.
1998;30(1):122-130.
Baumgaertel A. Alternative and controversial treatments for
attention-deficit/hyperactivity disorder. Pediatr Clin N Am. 1999;46(5):977-992.
Bazil CW, Short D, Crispin D, Zheng W. Patients with intractable epilepsy
have low melatonin, which increases following seizures. Neurology.
2000;55(11):1746-1748.
Bekaroglu M, Aslan Y, Gedik Y. Relationships between serum free fatty acids
and zinc, and attention deficit hyperactivity disorder: a research note. J Child
Psychol Psychiatry. 1996;37(2):225-227.
Ben-Nathan D, Maestroni GJ, Lustig S, Conti A. Protective effects of
melatonin in mice infected with encephalitis viruses. Arch Virol.
1995;140(2):223-230.
Bonilla E, Valero-Fuenmayor N, Pons H, Chacin-Bonilla L. Melatonin protects
mice infected with Venezuelan equine encephalomyelitis virus. Cell Mol Life Sci.
1997;53(5):430-434.
Brzezinski A. "Melatonin replacement therapy" for postmenopausal women: is it
justified? Menopause. 1998;5:60-64.
Bylesjo I, Forsgren L, Wetterberg L. Melatonin and epileptic seizures in
patients with acute intermittent porphyria. Epileptic Disord. 2000;2(4):203-208.
Cagnoni ML, Lombardi A, Cerinic MC, Dedola GL, Pignone A. Melatonin for
treatment of chronic refractory sarcoidosis [letter]. Lancet.
1995;346(4):1299-1230.
Carman JS, Post RM, Buswell R, Goodwin FK. Negative effects of melatonin on depression. Am J Psychiatry. 1976;133:1181-1186.
Cauffield JS, Forbes HJ. Dietary supplements used in the treatment of depression, anxiety, and sleep disorders. Lippincotts Prim Care Pract. 1999;
3(3):290-304.
Chase JE, Gidal BE. Melatonin: Therapeutic use in sleep disorders. Ann
Pharmacother. 1997;31:1218-1225.
Coker KH. Meditation and prostate cancer: integrating a mind/body
intervention with traditional therapies. Sem Urol Onc. 1999;17(2):111-118.
Cornelissen G, Halberg F, Burioka N, Perfetto F, Tarquini R, Bakken EE. Do
plasma melatonin concentrations decline with age? Am J Med. 2000;109(4):343-345.
Cos S, Sanchez-Barcelo EJ. Melatonin and mamary pathological growth.
Frontiers Neuroendo. 2000;21:133-170.
Cos S, Sanchez-Barcelo EJ. Melatonin, experimental basis for a possible
application in breast cancer prevention and treatment. Histo Histopath.
2000;15:637-647.
Dagan Y, Zisapel N, Nof D, et al. Rapid reversal of tolerance to
benzodiazepine hypnotics by treatment with oral melatonin: a case report. Eur
Neuropsychopharmacol. 1997;7(2):157-160.
Dreher F, Denig N, Gabard B, Schwindt DA, Maibach HI. Effect of topical
antioxidants on UV-induced erythema formation when administered after exposure.
Dermatology. 1999;198(1):52-55.
Dreher F, Gabard B, Schwindt DA, Maibach HI. Topical melatonin in combination
with vitamins E and C protects skin from ultraviolet-induced erythema: a human
study in vivo. Br J Dermatol. 1998;139(2):332-339.
Eck-Enriquez K, Kiefer TL, Spriggs LL, Hill SM. Pathways through which a
regimen of melatonin and retinoic acid induces apoptosis in MCF-7 human breast
cancer cells. Breast Cancer Res Treat. 2000;61(3):229-239.
Fauteck J, Schmidt H, Lerchl A, Kurlemann G, Wittkowski W. Melatonin in
epilepsy: first results of replacement therapy and first clinical results. Biol
Signals Recept. 1999;8(1-2):105-110.
Ferini-Strambi L, Zucconi M, Biella G, et al. Effect of melatonin on sleep
microstructure: preliminary results in healthy subjects. Sleep.
1993;16(8):744-747.
Forsling ML, Wheeler MJ, Williams AJ. The effect of melatonin administration
on pituitary hormone secretion in man. Clin Endocrinol (Oxf).
1999;51(5):637-642.
Fraschini F, Demartini G, Esposti D, Scaglione F. Melatonin involvement in
immunity and cancer. Biol Signals Recept. 1998;7(1):61-72.
Garfinkel D, Laundon M, Nof D, Zisapel N. Improvement in sleep quality in
elderly people by controlled-release melatonin (see comments). Lancet.
1995;346(8974):541-544.
Garfinkel D, Zisapel N, Wainstein J, Laudon M. Facilitation of benzodiazepine
discontinuation by melatonin: a new clinical approach. Arch Intern Med.
1999;159(8):2456-2460.
Gibb JW, Bush L, Hanson GR. Exacerbation of methamphetamine-induced
neurochemical deficits by melatonin. J Pharmacol and Exp Ther. 1997;283:630-635.
Gordon N. The therapeutics of melatonin: a paediatric perspective. Brain Dev.
2000;22(4):213-217.
Haimov I, Laudon I, Zisapel N, Souroujon M, Nof D, Shiltner A, et al. Sleep
disorders and melatonin rhythms in elderly people. BMJ. 1994(9120);309:167.
Herxheimer A, Petrie KJ. Melatonin for preventing and treating jet lag.
Cocharane Database Syst Rev. 2001;(1):CD001520.
Jacobson JS, Workman SB, Kronenberg F. Research on complementary/alternative
medicine for patients with breast cancer: a review of the biomedical literature.
J Clin Onc. 2000;18(3):668-683.
Jan JE, Espezel H, Appleton RE. The treatment of sleep disorders with
melatonin. Dev Med Child Neurol. 1994;36(2):97-107.
Jan JE, Espezel H, Freeman RD, Fast DK. Melatonin treatment of chronic sleep
disorders. J Child Neurol. 1998; 13(2):98.
Kaneko S, Okumura K, Numaguchi Y, Matsui H, Murase K, Mokuno S, et al.
Melatonin scavenges hydroxyl radical and protects isolated rat hearts from
ischemic reperfusion injury. Life Sciences. 2000;67(2):101-112.
Kennedy SH. Melatonin disturbances in anorexia nervosa and bulimia nervosa.
Int J Eating Disord. 1994;16:257-265.
Kirkwood CK. Management of insomnia. J Am Pharm Assoc. 1999;39(1):688-696.
Lagneux C, Joyeux M, Demenge P, Ribuot C, Godin-Ribuot D. Protective effects
of melatonin against ischemia-reperfusion injury in the isolated rat heart. Life
Sciences. 2000;66(6):503-509.
Lewy AJ, Bauer VK, Cutler NL, Sack RL. Melatonin treatment of winter depression: a pilot study. Psych Res. 1998;77(1):57-61.
Lissoni P, Barni S, Meregalli S, Fossati V, Cazzaniga M, Esposti D, Tancini
G. Modulation of cancer endocrine therapy to melatonin: a phase II study of
tamoxifen plus melatonin in metastatic breast cancer patients progressing under
tamoxifen alone. Br J Cancer. 1995;71(4):854-856.
Lissoni P, Barni S, Tancini G, Ardizzoia A, Ricci G, Aldeghi R, et al. A
randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin 2
plus the pineal neurohormone melatonin in advanced solid neoplasms other than
renal cancer and melanoma. Br J Cancer. 1994;69(1):196-199.
Lissoni P, Cazzaniga M, Tancini G, Scardino E, Musci R, Barni S, Maffezzini
M, Meroni T, Rocco F, Conti A, Maestroni G. Reversal of clinical resistance to
LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin:
efficacy of LHRH analogue plus melatonin in patients progressing on LHRH
analogue alone. Eur Urol. 1997;31(2):178-181.
Lissoni P, Paolorossi F, Tancini G, et al. A phase II study of tamoxifen plus
melatonin in metastic solid tumour patients. Br J Cancer. 1996;74(9):1466-1468.
Lissoni P, Paolorossi F, Tancini G, Barni S, Ardizzoia A, Brivio F,
Zubelewicz B, Chatikhine V. Is there a rold for melatonin in the treatment of
neoplastic cachexia? Eur J Cancer. 1996;32A(8):1340-1343.
Lissoni P, Tancini G, Barni S, Paolorossi F, Ardizzoia A, Conti A, Maestroni
G. Treatment of cancer chemotherapy-induced toxicity with the pineal hormone
melatonin. Support Care Cancer. 1997;5(2):126-129.
Lissoni P, Tancini G, Paolorossi F, Mandala M, Ardizzoia A, Malugani F, et
al. Chemoneuroendocrine therapy of metastatic breast cancer with persistent
thrombocytopenia with weekly low-dose epirubicin plus melatonin: a phase II
study. J Pineal Res. 1999;26(3):169-173.
Lissoni, P, Vigore L, Rescaldani R, et al. Neuroimmunotherapy with low-dose
subcutaneous interleukin-2 plus melatonin in AIDS patients with CD4 cell number
below 200/mm3: a biological phase-II study. J Biol Regul Homeost Agents.
1995;9:155–158.
Low Dog T, Riley D, Carter T. Traditional and alternative therapies for
breast cancer. Alt Ther. 2001;7(3):36-47.
Lusardi P, Piazza E, Fogari R. Cardiovascular effects of melatonin in
hypertensive patients well controlled by nifedipine: a 24-hour study. Br J Clin
Pharmacol. 2000;49(5):423-7.
MacIntosh A. Melatonin: clinical monograph. Q Rev Nat Med. 1996; 47–60.
Manev H, Uz T. Oral melatonin in neurologicaly disabled children [letter].
Lancet. 1998;351:1963.
Massion AO, Teas J, Hebert JR, Wertheimer MD, Kabat-Zinn J. Meditation,
melatonin and breast/prostate cancer: hypothesis and preliminary data. Med Hypo.
1995;44:39-46.
Moretti RM, Marelli MM, Maggi R, Dondi D, Motta M, Limonta P.
Antiproliferative action of melatonin on human prostate cancer LNCaP cells.
Oncol Rep. 2000;7(2):347-351.
Munoz-Hoyos A, Sanchez-Forte M, Molina-Carballo A, Escames G, Martin-Medina
E, Reiter RJ, et al. Melatonin's role as an anticonvulsant and neuronal
protector: experimental and clinical evidence. J Child Neurol.
1998;13(10):501-509.
Murphy P, Myers B, Badia P. NSAIDs suppress human melatonin levels. Am J Nat
Med. 1997; iv: 25.
Nagtagaal JE, Laurant MW, Kerkhof GA, Smits MG, van der Meer YG, Coenen AM.
Effects of melatonin on the quality of life in patients with delayed sleep phase
syndrome. J Psychosom Res. 2000;48(1):45-50.
Neri B, de Leonardis V, Gemelli MT, di Loro F, Mottola A, Ponchietti R,
Raugei A, Cini G. Melatonin as biological response modifier in cancer patients.
Anticancer Res. 1998;18(2B):1329-1332.
Oosthuizen JM, Bornman MS, Barnard HC, Schulenburg GW, Boomker D, Reif S.
Melatonin and steroid-dependent carcinomas. Andrologia. 1989;21(5):429-431.
Partonen T. Short note: melatonin-dependent infertility. Med Hypotheses.
1999;52(5):487-488.
Peled N, Shorer Z, Peled E. Pillar G. Melatonin effect on seizures in
children with severe neurologic deficit disorders. Epilepsia.
2001;42(9):1208-1210.
Petrie K, Conaglen JV, Thompson L, Chamberlain K. Effect of melatonin on jet
lag after long haul flights. BMJ. 1989;298:705–707.
Pillar G, Shahar E, Peled N, Ravid S, Lavie P, Etzioni A. Melatonin improves
sleep-wake patterns in psychomotor retarded children. Pediatr Neurol.
2000;23(3):225-228.
Ram PT, Yuan L, Dai J, Kiefer T, Klotz DM, Spriggs LL, et al. Differential
responsiveness of MCF-7 human breast cancer cell line stocks to the pineal
hormone, melatonin. J Pineal Res. 2000;28(4):210-218.
Rommel T, Demisch L. Influence of chronic beta-adrenoreceptor blocker
treatment on melatonin secretion and sleep quality in patients with essential
hypertension. J Neural Transm Gen Sect. 1994;95:39-48.
Roth JA, Kim B-G, Lin W-L, Cho M-I. Melatonin promotes osteoblast
differentiation and bone formation. J Biol Chem. 1999;274:22041-22047.
Sack RL, Brandes RW, Kendall AR, Lewy AJ. Entrainment of free-running
circadian rhythms by melatonin in blind people. N Engl J Med.
2000;343(15):1070-1077.
Sack RL, Hughes RJ, Edgar DM, Lewy AJ. Sleep-promoting effects of melatonin:
at what dose, in whom, under what conditions, and by what mechanisms? Sleep.
1997;20(10):908-915.
Sakotnik A, Liebmann PM, Stoschitzky K, Lercher P, Schauenstein K, Klein W,
et al. Decreased melatonin synthesis in patients with coronary artery disease.
Eur Heart J. 199;20(18):1314-1317.
Shamir E, Barak Y, Shalman I, Laudon M, Zisapel N, Tarrasch R, et al.
Melatonin treatment for tardive dyskinesia: a double-blind, placebo-controlled,
crossover study. Arch Gen Psych. 2001;58(11):1049-1052.
Shamir E, Laudon M, Barak Y, Anis Y, Rotenberg V, Elizur A, Zisapel N.
Melatonin improves sleep quality of patients with chronic schizophrenia. J Clin
Psychiatry. 2000;61(5):373-377.
Shannon M. Alternative medicines toxicology: a review of selected agents.
Clin Tox. 1999;37(6):709-713.
Sheldon SH. Oral melatonin in neurologicaly disabled children [letter].
Lancet. 1998;351(9120):1964.
Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically
disabled children[letter]. Lancet. 1998;351(9111):1254.
Skene DJ, Lockley SW, Arendt J. Use of melatonin in the treatment of phase
shift and sleep disorders. Adv Exp Med Biol. 1999;467:79-84.
Smits MG, Nagtegaal EE, van der Heijden J, Coenen AM, Kerkhof GA. Melatonin
for chronic sleep onset insomnia in children: a randomized placebo-controlled
trial. J Child Neurol. 2001;16(2):86-92.
Spitzer RL, Terman M, Williams JB, Terman JS, Malt UF, Singer F, et al. Jet
lag: clinical features, validation of a new syndrome-specific scale, and lack of
response to melatonin in a randomized, double-blind trial. Am J Psych.
1999;156(9):1392-1396.
Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis.
Int J Neurosci. 2001;107(1-2):77-85.
Stoschitzky K, Sakotnik A, Lercher P, Zweiker R, Maier R, Liebmann P, Lindner
W. Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol.
1999;55(2):111-115.
Tzischinsky O, Lavie P. Melatonin possesses time-dependent hypnotic effects.
Sleep. 1994;17:638–645.
van Wijingaarden E, Savitz DA, Kleckner RC, Cai J, Loomis D. Exposure to
electromagnetic fields and suicide among electric utility workers: a nested
case-control study. West J Med. 2000;173;94-100.
Wagner DR. Circadian rhythm sleep disorders. Curr Treat Opt Neurol.
1999;1(4):299-308.
Wagner J, Wagner ML, Hening WA. Beyond benzodiazepines: alternative
pharmacologic agents for the treatment of insomnia. Ann Pharmacother. 1998;
32:680-691.
Walsh HA, Daya S. Influence of the antidepressants desipramine and fluoxetine
on tryptophan-2,3-dioxygenase in the presence of exogenous melatonin. Life Sci.
1998;62(26):2417-2423.
Weekley LB. Melatonin-induced relaxation of rat aorta: Interaction with
adrenergic agonists. J Pineal Res. 1991;11:28-34.
West Sk, Oosthuizen JM. Melatonin levels are decreased in rheumatoid
arthritis. J Basic Clin Physiol Pharmacol. 1992;3(1):33-40.
Wurtman RJ, Zhdanova II. Oral melatonin in neurologicaly disabled children
[letter]. Lancet. 1998;351(9120):1963-1964.
Zawilska JB, Nowak JZ. Melatonin: from biochemistry to therapeutic
applications. Pol J Pharm. 1999;51:3-23.
Zeitzer JM, Daniels JE, Duffy JF, Klerman EB, Shanahan TL, Dijk DJ et al. Do
plasma melatonin concentrations decline with age? Am J Med. 1999;107(5):432-436.
Zhdanova IV, Wurtman RJ, Morabito C, Piotrovska VR, Lynch HJ. Effects of low
oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in
normal young humans. Sleep. 1996;19:423–431.
Zhdanova IV, Wurtman RJ, Lynch HJ, et al. Sleep-inducing effects of low doses
of melatonin ingested in the evening. Clin Pharmacol Ther. 1995; 57:552–558.
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