Melatonin

Overview

Melatonin is a hormone that is produced by the pineal gland in the brain. For years, scientists have known that melatonin's main function was in the control of our sleep patterns. However, more recent research has revealed that it also functions as an important antioxidant. (1) After puberty melatonin output begins a gradual steady decline. Adults experience about a 37 percent decline in daily melatonin output between the ages of 20 and 70 with the majority of the decline occurring after age 40. In 1994, melatonin became a sensation when studies revealed that supplementation provided significant life extension in several different species of laboratory animals. Although long-term studies on humans have not been conducted, melatonin became a popular product in health food stores and pharmacies throughout the country.

Dosage Info

Dosage Range

0.5-3mg nightly.

Most Common Dosage

3mg nightly.

Dosage Forms

Tablets, capsules, sublingual tablets, and timed release tablets and capsules.

Adult RDI

None established

Adult ODA

None established

RDA

  • : None Established

Interactions and Depletions

Depletions

Active Forms

Melatonin.

Absorption

Melatonin is easily absorbed when taken orally.

Toxicities & Precautions

General

There is no known toxicity associated with melatonin.

Functions in the Body

Antioxidant

Melatonin directly scavenges both hydroxyl and peroxyl free radicals, and it does so more effectively than most other antioxidants and it also greatly potentiates the efficiency of other endogenous and exogenous antioxidants. (2) Melatonin is especially important for the inhibition of peroxynitrite free radical reactions the protection of cellular DNA against peroxynitrite damage. Peroxynitrite is a dangerous free radical oxidant that many other antioxidants are not able to neutralize. (3)

Sleep Trigger

Melatonin’s primary function seems to be its role in regulating sleep/wake cycle. When darkness falls melatonin levels rise, which triggers the sleep cycle. (4)

Circadian Rhythm

Melatonin is a hormone responsible for regulating circadian rhythms. (5)

Enhanced Immunity

Melatonin stimulates T-helper lymphocytes to increase production of interleukin-4 (IL4), which produces a number of effects that strengthen immunity. (6)

Growth and Sex Hormones

Melatonin controls the output of growth hormone (7) and it may also play an important role in regulating the production of the sex hormones. (8)

Clinical Applications

Chemotherapy

Melatonin enhances the effectiveness of interleukin 2 therapy in a variety of solid-tumor cancers. (9)

Jet Lag

Double-blind studies confirm that melatonin is an effective treatment for people who experience jet lag after long airline flights. (10) , (11)

Circadian Rhythm

Melatonin has both phase-shifting and sleep-promoting properties that helps improve sleep cycles for millions of night shift and rotating shift workers and for people who are blind. (12) Melatonin supplementation seems to normalize circadian variation in human physiology, therefore, having a strong effect on general health. (13)

Breast Cancer

Melatonin inhibits the growth of breast cancer cells. (14) Also, women who are estrogen or progesterone receptor positive are found to have low levels of melatonin and this finding may have implications for prognosis and treatment in the future. (15) Factors that lower melatonin levels, such as exposure to light at night, and exposure to electromagnetic fields, may be a contributing factor in the incidence of breast cancer. (16) , (17)

Insomnia

Low melatonin levels is a frequent cause of insomnia in the elderly. (18) Several double-blind studies report that melatonin is effective at inducing sleep in individuals who have low melatonin levels. (19) , (20) , (21)

Tinnitus

47.6 percent of people with tinnitus reported improvement in a double-blind, placebo-controlled crossover trial where 3mg of melatonin was taken nightly for 30 days. (22)

Symptoms and Causes of Deficiency

A deficiency of melatonin can cause sleep problems and possibly a weakened immune system. Various kinds of drugs can inhibit the synthesis of melatonin including beta-blockers, benzodiazepines, estrogen-containing medications, hydralazine vasodilators, loop diuretics, and theophylline.

Dietary Sources

Melatonin does not occur in foods.

References

  1. View Abstract: Oxenkrug G, Requintina P, Bachurin S. Antioxidant and antiaging activity of N-acetylserotonin and melatonin in the in vivo models. Ann N Y Acad Sci. Jun2001;939:190-9.
  2. View Abstract: Reiter RJ. Oxygen radical detoxification processes during aging: the functional importance of melatonin. Aging (Milano). Oct1995;7(5):340-51.
  3. View Abstract: Gilad E, Cuzzocrea S, Zingarelli B, Salzman AL, Szabo C. Melatonin is a scavenger of peroxynitrite. Life Sci. 1997;60(10):PL169-74.
  4. View Abstract: Brown GM. Light, melatonin and the sleep-wake cycle. J Psychiatry Neurosci. Nov1994;19(5):345-53.
  5. View Abstract: Sack RL, Lewy AJ, Hughes RJ. Use of melatonin for sleep and circadian rhythm disorders. Ann Med. Feb1998;30(1):115-21.
  6. View Abstract: Maestroni GJ. T-helper-2 lymphocytes as a peripheral target of melatonin. J Pineal Res. Mar1995;18(2):84-9.
  7. View Abstract: Coiro V, Vescovi PP. Alcoholism abolishes the effects of melatonin on growth hormone secretion in humans. Neuropeptides. Jun1998;32(3):211-4.
  8. View Abstract: Luboshitzky R, Lavie P. Melatonin and sex hormone interrelationships--a review. J Pediatr Endocrinol Metab. May1999;12(3):355-62.
  9. View Abstract: Lissoni P, et al. Efficacy of the Concomitant Administration of the Pineal Hormone Melatonin in Cancer Immunotherapy with Low-dose IL-2 in Patients with Advanced Solid Tumors who had Progressed on IL-2 Alone. Oncology. Aug1994;51(4):344-47.
  10. View Abstract: Petrie K, et al. A Double-blind Trial of Melatonin as a Treatment for Jet Lag in International Cabin Crew. Biol Psychiatry. Apr1993;33(7):526-30.
  11. View Abstract: Claustrat B, et al. Melatonin and Jet Lag: Confirmatory Result Using a Simplified Protocol. Biol Psychiatry. Oct1992;32(8):705-11.
  12. View Abstract: Sack RL, et al. Melatonin as a Chronobiotic: Treatment of Circadian Desynchrony in Night Workers and the Blind. J Biol Rhythms. Dec1997;12(6):595-603.
  13. View Abstract: Kunz D, Mahlberg R, Muller C, Tilmann A, Bes F. Melatonin in patients with reduced REM sleep duration: two randomized controlled trials. J Clin Endocrinol Metab. Jan2004;89(1):128-34.
  14. View Abstract: Molis TM, et al. Melatonin Modulation of Estrogen-regulated Proteins, Growth Factors, and Proto-oncogenes in Human Breast Cancer. J Pineal Res. Mar1995;18(2):93-103.
  15. View Abstract: Danforth DN Jr, et al. Plasma Melatonin and the Hormone-dependency of Human Breast Cancer. J Clin Oncol. Jul1985;3(7):941-48.
  16. View Abstract: Brainard GC, et al. The Relationship Between Electromagnetic Field and Light Exposures to Melatonin and Breast Cancer Risk: A Review of the Relevant Literature. J Pineal Res. Mar1999;26(2):65-100.
  17. View Abstract: Stevens RG, et al. The Melatonin Hypothesis: Electric Power and Breast Cancer. Environ Health Perspect. Mar1996;104(Suppl 1):135-40.
  18. Haimov I, et al. Sleep Disorders and Melatonin Rhythms in Elderly People. BMJ. Jul1994;309(6948):167.
  19. View Abstract: Waldhauser F, et al. Sleep Laboratory Investigations on Hypnotic Properties of Melatonin. Psychopharmacology. (Berl). 1990;100(2):222-26.
  20. View Abstract: Dahlitz M, et al. Delayed Sleep Phase Syndrome Response to Melatonin. Lancet. May1991;337(8750):1121-24.
  21. View Abstract: Attenburrow ME, et al. Low Dose Melatonin Improves Sleep in Healthy Middle-aged Subjects. Psychopharmacology. (Berl). Jul1996;126(2):179-81.
  22. View Abstract: Rosenberg SI, et al. Effect of Melatonin on Tinnitus. Laryngoscope. Mar1998;108(3):305-10.