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Melatonin does not start to be produced in the body until around three months, with infants initially receiving all their melatonin through breast milk. However, from this time forward, production dramatically increases into the teen years, before dropping and leveling out between 0.3 mg to 0.5 mg per day until around 55, when production drops again to 0.1 mg, highlighting how a physiological dose of about 0.3 mg would be indicated for many patients from age 50 onwards (1,2).


One of the most circulated pieces of misinformation relates to endogenous production being adversely impacted by exogenous (supplemental) melatonin. On the contrary, research studies have shown that melatonin from supplementation does not impact endogenous production (3-6). If this point was an issue, it would have been reported in the three decades’ worth of research studying high-dose melatonin supplementation (up to 50 mg) in cancer patients. However, as leading melatonin researcher Professor Richard Wurtman from MIT discussed in the 1990s, and many practitioners have observed since then, high-dose long-term use of melatonin could potentially reduce sensitivity of receptor sites and create a need for higher doses and even a dependence on exogenous melatonin. The caveat is that there may be a threshold in reducing sensitivity once receptor sites are saturated (7). Findings by one of the world’s leading melatonin researchers with several hundreds of publications on the topic, Professor Russell J. Reiter, would suggest that exogenous melatonin may help increase the cell’s production of melatonin, at least in cancer cells, by removing metabolic blocks to its synthesis (8).

Written by Deanna Minich, PhD

Last updated: February 20, 2023



  1. Grivas, T.B.; Savvidou, O.D. Melatonin the “light of night” in human biology and adolescent idiopathic scoliosis. Scoliosis 2007, 2, 6.

  2. Zhdanova, I.V.; Wurtman, R.J.; Regan, M.M.; Taylor, J.A.; Shi, J.P.; Leclair, O.U. Melatonin treatment for age-related insomnia. J. Clin. Endocrinol. Metab. 2001, 86, 4727–4730.

  3. Matsumoto M, Sack RL, Blood ML, Lewy AJ. The amplitude of endogenous melatonin production is not affected by melatonin treatment in humans. J Pineal Res. 1997 Jan;22(1):42-4. doi: 10.1111/j.1600-079x.1997.tb00301.x. PMID: 9062869.

  4. Mallo C, Zaidan R, Faure A, Brun J, Chazot G, Claustrat B. Effects of a four-day nocturnal melatonin treatment on the 24 h plasma melatonin, cortisol and prolactin profiles in humans. Acta Endocrinol (Copenh) 1988;119:474–480.

  5. Lemoine P, Garfinkel D, Laudon M, Nir T, Zisapel N. Prolonged-release melatonin for insomnia - an open-label long-term study of efficacy, safety, and withdrawal. Ther Clin Risk Manag. 2011;7:301-11. doi: 10.2147/TCRM.S23036. Epub 2011 Jul 26. PMID: 21845053; PMCID: PMC3150476.

  6. Lissoni P, Rovelli F, Pittalis S, Casati M, Giani L, Barni S, Fumagalli L, Laudon M. La terapia con melatonina non sopprime la sua produzione endogena nei volontari sani [Therapy with melatonin does not suppress its endogenous production in healthy volunteers]. Recenti Prog Med. 1999 Feb;90(2):84-5. Italian. PMID: 10208098.

  7. Dimah Sweis. The uses of melatonin. Arch Dis Child Educ Pract Ed 2005; 90:ep74–ep77. doi: 10.1136/adc.2004.066498.

  8. Reiter, R.J., Sharma, R., Ma, Q., Rosales-Corral, S., Acuna-Castroviejo, D. and Escames, G. 2019. Inhibition of mitochondrial pyruvate dehydrogenase kinase: a proposed mechanism by which melatonin causes cancer cells to overcome cytosolic glycolysis, reduce tumor biomass and reverse insensitivity to chemotherapy. Melatonin Research. 2, 3 (Aug. 2019), 105-119.

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