As Melatonin is also an antioxidant, an immune system modulator and a core temperature regulator it is being
tested for various other health applications:
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a. Tension and cluster headaches - Some preliminary, double-blind studies suggest that Melatonin supplementation
may help in certain cases (1-3 mg at night).17,18 This af ect has been at ributed to Melatonin’s ability to prevent a
rise in core temperature, which is linked to cluster headaches.35,36
b. Sarcoidosis - Preliminary evidence has shown improvement in patients with sarcoidosis (20 mg at night).19
c. Adjunctive Cancer Treatment - Early trials indicate that Melatonin supplementation, as an adjunct to cancer
treatment may help inhibit the progression of breast cancer, reduce the PSA levels in prostate cancer patients and
improve disease-free survival in melanoma patients, as well as patients with brain and lung cancer (20 mg at night).
Of course, more research is required before any conclusive statements can be made about this application.20-27 In
a study of cancer patients with solid tumors in various organs the intake of Melatonin (40 mg per day) enhanced the
ef ectiveness of interleukin-2 therapy by enhancing its anti-tumor immune ef ect or by increasing susceptibility of
cancer cells to the cytolysis by cytotoxic lymphocytes.37
d. Immune System and AIDS - Maestroni and Conti demonstrated in 1995 that T-helper-2 lymphocytes possess
Melatonin receptors. When Melatonin docks with its receptor on the T-helper cell, a cascade of events is set in
motion releasing important signalling agents (cytokines) that strengthen immune function in various ways. For
example, natural killer cell production rose by 240 percent in healthy young men taking 20 mg of Melatonin each
night for a period of two months.
Melatonin may also inhibit viral replication and has been shown to increase T-helper cell numbers and natural killer
cell numbers in HIV-infected individuals. Further research is underway to substantiate these findings (20 mg at
night).28,29
e. Birth Control/Contraceptive - Very high doses of Melatonin inhibits ovulation in animals and women. A new birth
control is now being tested known as B-Oval. It contains no estrogen, but rather high dose Melatonin (75 mg) and
0.3 mg of progestin.30
Dosage Ranges
Insomnia and Jet Lag (Shift Workers) - 0.1 mg to 3.0 mg (note 0.1 mg equals 100 mcg), one to two hours before
bedtime. It is best to start with a small dose and work up, based upon improved sleep with no awakening and morning
drowsiness.
N.B. Taking a high dosage of Melatonin (5 – 75 mg) should only be undertaken with knowledge of a physician, who is
able to monitor blood work and other parameters, as these dosages are still experimental and long-term safety is
unknown at this time.38
Adverse Side Effects and Toxicity
Taking doses that are too high can result in morning grogginess, headaches and/or abdominal cramps.31,32
Melatonin testing in humans and animals indicate that it is very non-toxic.1,33
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Contraindications and Drug-Nutrient Interactions
Some cases of depression can be aggravated by Melatonin supplementation.34 Some antidepressant drugs stimulate
the production of Melatonin and others, such as fluoxetine (Prozac), may lower Melatonin levels. It is probably best at
this time not to combine Melatonin with any other drug that targets brain chemistry or neurotransmitter levels.35,36
A number of drugs have been shown to deplete Melatonin levels. Some of these include aspirin, ibuprofen, beta-
blockers, calcium channel blockers, sleeping pills, tranquillizers, fluoxetine (Prozac), caffeine, steroids and tobacco.1
The clinical significance of this is yet to be determined, in regards to whether or not patients on these substances
require Melatonin supplementation to compensate for the depletion of Melatonin (author’s note).
1. Reitar RJ, Robinson J. Melatonin. New York, NY: Bantam Books; 1995. p. 3-30.
2. Shida CS, Castrucci AML, Lamy-Freund MT. High melatonin solubility in aqueous medium. J Pineall Res 1994;16:198-201.
3. Waldhauser F, Saletu B, Trinchard-Lugan I. Sleep laboratory investigations on hypnotic properties of melatonin. Psychopharmacol
1990;100:222-6.
4. Zhdanova IV, Wurtman RJ, Morabito C, Piotrovska VR, Lynch HJ. Sleep-inducing effects of low doses of melatonin ingested in the
evening. Clin Pharmacol Ther 1995;57:552-8.
5. Dahlitz M, Alverez B, Vignau J, English J, Arendt J, Parkes JD. Delayed sleep phase syndrome response to melatonin. Lancet
1991;337:1121-4.
6. MacFarlane JG, Cleghorn JM, Brown GM, Streiner DL. The effects of exogenous melatonin on the total sleep time and day-time
alertness of chronic insomniacs: A preliminary study. Biol Psychiatry 1991;30:371-6.
7. James SP, et al. Melatonin administration in insomnia. Neuropsychopharmacology 1990;3:19-23.
Comment [c32]: Could not find other authors
8. Nave R, Peled R, Lavie P. Melatonin improves evening napping. Eur J Pharmacol 1995;275:213-6.
9. Haimov I, Laudon M, Zisapel N, Souroujon M, Nof D, Shlitner A, et al. Sleep disorders and melatonin rhythms elderly people. BMJ
1994;309:167.
10. Hughes RJ, Sack RL, Lewy AJ. The role of melatonin and circadian phase in age-related sleep maintenance insomnia: assessment in a
clinical trial of melatonin replacement. Sleep 1998;21:52-68.
11. Arendt J, Aldhous M, English J, Marks V, Arendt JH, Marks M, et al. Some effects of jet-lag and their alleviation by melatonin.
Ergonomics 1987;30:1379-98.
12. Claustrat B, Brun J, David M, Sassolas G, Chazot G. Melatonin and jet lag: Confirmatory result using a simplified protocol. Biol
Psychiatry 1992;32:705-11.
13. Petrie K, Conaglen JV, Thompson L, Chamberlain K. Effect of melatonin on jet lag after long haul flights. Br Med J 1989;298:705-7.
14. Lino A, Silvy S, Condorelli L, Rusconi AC. Melatonin and jet lag: Treatment schedule. Biol Psychiatry 1993;34:587.
15. Petrie K, Dawson AG, Thompson L, Brook R. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol
Psychiatry 1993;33:526-30.
16. Folkard S, Arendt J, Clark M. Can melatonin improve shift workers’ tolerance of the night shift: Some preliminary findings. Chronobio
Intern 1993;10,5:315-20.
17. Nagtegaal JE, Smits MG, Swart AC, Kerkhof GA, van der Meer YG. Melatonin-responsive headache in delayed sleep phase syndrome:
Preliminary observations. Headache 1998;38:303-7.
18. Leone M, D’Amico D, Moschiano F, et al. Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with
parallel groups. Cephalagia 1996;16:494-6.
19. Cagnoni ML, Lombardi A, Cerinic MC, Dedola GL, Pignone A. Melatonin for treatment of chronic refractory sarcoidosis [letter]. Lancet
1995;346(4):1229-30.
20. Lissoni P, et al. A randomized study with subcutaneous low-dose interleukin 2 alone vs interleukin 2 plus the pineal neurohormone
Comment [c33]: Could not find the other authors
melatonin in advanced solid neoplasms other than renal cancer and melanoma. Br J Cancer 1994;69:196-9.
21. Lissoni P, Barni S, Fossati V, Ardizzoia A, Cazzaniga M, Tancini G, et al. A randomized study of neuroimmunotherapy with low-dose
subcutaneous interleukin-2 plus melatonin compared to supportive care alone in patients with untreatable matastatic solid tumor. Support
Care Cancer 1995;3(3):194-7.
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22. Neri B, Fiorelli C, Moroni F, Nicita G, Paoletti MC, Ponchieatti R, et al. Modulation of human lymphoblastoid interferon activity by
melatonin in metastatic renal cell carcinoma: A phase II study. Cancer 1994;73(12):3014-9.
23. Lissoni P, Barni S, Meregalli S, Fossati V, Cazzaniga M, Esposti D, et al. Modulation of cancer endocrine therapy by 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-