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Melatonin

Herbals / Health Supplements
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Brand

Melatonin, Melatonix, Tranzone

Availability

Tablets: 1mg, 1.5mg, 3 mg
Capsules: 1mg, 3mg, 5 mg
Liquid: 500 mcg/mL, 1mg/mL

Pharmacology

Melatonin is an endogenous hormone produced in the brain by the pineal gland from the amino acid tryptophan , in mammals. However it is not stored by the pineal gland. Melatonin production is also not limited to just pineal secretion. Extrapineal sources of melatonin have been found not only in the retina and the immune system but the Harderian glands (of rats) as well. Norepinephrine stimulates the production of melatonin from serotonin. Serum Melatonin levels not only create our circadian rhythm, but help to regulate other hormones that control the seasonal clock (estrous in rats) in some animals, and our own biological clock. Its level rises during the period of darkness, and decreases with light coming through the retina.

Melatonin is shown to have strong antioxidant activity, as well as being a potent scavenger of free radicals. Studies indicate that melatonin may have an effect against some cancers including certain types of breast, skin, kidney, pituitary, some types of lung cancer, as well as partial response in the treatment of solid tumors.

The endogenous levels of melatonin are decreased as we age and by various diseases. People with insomnia have lower levels of melatonin. Lab studies have also shown that reduced levels of melatonin stimulates breast cancer cells in humans. This has lead to research in rats with mammary tumors.

In rats with mammary tumors survival time was lengthened when the rats were given daily doses of exogenous melatonin. The hormone didn’t reduce the number of tumors or their growth, but it stabilized the chemical/hormonal environment thus lengthening survival time. Melatonin acts as an anti-estrogen substance as well as inhibiting, suppressing, or reducing prolactin secretion from the pituitary gland.

Of note, although controversy continues, studies have shown some promise in the use of melatonin as adjunctive therapy potentiating the anticonvulsant effect of phenobarbital, in the treatment of seizures in rats. This may be due to its neuroprotective effects.

Melatonin is both synthetically produced chemically from 5-methoxyindole, and extracted from beef cattle pineal glands. The synthetic product is preferred in order to avoid viral contamination from the beef by-product. Classified as a nutritional supplement as defined by the U.S. Dietary Supplement Health and Education Act, Oct. 25, 1994, chemically produced melatonin can be obtained in health food stores.

Melatonin is rapidly metabolized and taken up by all tissues, and its metabolites are excreted through the kidney.

Melatonin supplementation should be avoided during pregnancy or planned mating based on possible hormonal effect. In animal studies, melatonin has been detected in breast milk and should therefore be avoided during lactation. Additionally studies have shown decreased sperm count and motility with the use of melatonin. However, there is very little evidence showing any major toxicity with the use of melatonin, even at high doses.

Indications

Used to inhibit the development of new benign mammary fibroadenomas in female rats that have previously had these tumors removed. It is a recommendation, as well, for those female rats to be spayed as this also decreases recurrence of these tumors.
Note: Melatonin does not treat existing tumors, so these should be removed whenever possible. Consultation with a veterinarian is advised before beginning Melatonin.

As adjunctive treatment in seizures.

Drug Interactions or Contraindications

Melatonin opposes the action of natural corticosteroids and corticosteroid drugs such as: dexamethasone, methylprednisolone , prednisolone and prednisone. Supplemental melatonin may decrease the effect of corticosteroid drugs if taken at the same time. It is advised to avoid using together.

Melatonin can increase sedative action when given with anticonvulsants, barbiturates, benzodiazepines, catnip, St. John’s Wort, Kava, or products containing diphenhydramine (Benadryl). Caution when using together.

Adverse Reactions

CNS:  sedation, hypothermia, irregular sleep/wake cycles

CV:  tachycardia, hypertension

Metabolic:  hyperglycemia

Skin:  pruritus (itching)

Dosage Recommendations

0.5 mg/kg to 20 mg/kg, PO, daily (empirical)

*Note: average dose reported when using to inhibit development of mammary tumors is 1mg/kg to 5 mg/kg  12

Considerations

  • Content of commercial products containing melatonin may not be uniform. Discuss product type with veterinarian.
  • In some cases may lower seizure threshold and increase the risk of seizure in the presence of neurologic disorders.
  • Avoid use in those rats having renal or hepatic insufficiency due to reduced clearance of drug.
  • Store supplement in closed container away from heat.
References
  • Bispink, G., Zimmermann, R., Weise, H., & Leidenberger, F. (1990). Influence of Melatonin on the Sleep-Independent Component of Prolactin Secretion. J Pin Res, 8, 97-106. Retrieved November 4, 2008, from the Medline database.
  • Jimenez-Jorge, S., Guerrero, J., Jimenez-Caliani, A., Naranjo, M., Lardone, P., Carrillo-Vico, A., Osuna, C., & Molinero, P. (2007). Evidence for melatonin synthesis in the rat brain during development. J Pin Res, 42(3), 240-6.
  • Forcelli, P., Soper, C., Duckles, A., Gale, K., & Kondratyev, A. (2013). Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats. Epilepsy Research, 107(3), 217-223. Retrieved January 20, 2015, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870145/
  • Jung, B., & Ahmad, N. (2006). Melatonin in cancer management: progress and promise. Cancer Res, 66(20), 9789-93. Retrieved November 4, 2008.
  • Lemus-Wilson, A., Kelly, P., & Blask, D. (1995). Melatonin blocks the stimulatory effects of prolactin on human breast cancer cell growth in culture. Br J Cancer, 72(6), 1435-40. Retrieved November 4, 2008, from the PubMed database.
  • Lemus-Wilson, A. (1995). Melatonin blocks the stimulatory effects of prolactin on human breast cancer cell growth in culture. Br J Cancer, 72(6), 1435-40.
  • Lynch, E. (2004). Le Magazine, January 2004 - Report: Melatonin And Cancer Treatment. Retrieved November 4, 2008, from http://www.lef.org/magazine/mag2004/jan2004_report_melatonin_04.htm.
  • Melatonin. (n.d.). Retrieved November 4, 2008, from http://www.drugdigest.org/DD/PrintablePages/herbMonograph/0,11475,4060,00.html.
  • Melatonin. (n.d.). Retrieved November 4, 2008, from http://www.umm.edu/altmed/articles/melatonin-000315.htm.
  • Tamarkin, L., Cohen, M., Roselle, D., Reichert, C., Lippman, M., & Chabner, B. (1981). Melatonin inhibition and pinealectomy enhancement of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in the rat. Cancer Res, 41(11 pt. 1), 4432-6. Retrieved November 4, 2008.
  • Wolden-Hanson, T., Mitton, D., Mccants, R., Yellon, S., Wilkinson, C., Matsumoto, A., & Rasmussen, D. (2000). Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. Endocrinology, 141(2), 487-97. Retrieved November 4, 2008.

Posted on October 8, 2008, 15:13, Last updated on January 20, 2015, 12:54 | Herbals / Health Supplements



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