Melatonin Supplements for Sleep and Anti-Aging?

Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

Some experts recommend melatonin as a first-line agent to treat insomnia in older adults. The World Sleep Society disagrees due to its low efficacy. Subjectively, people report better sleep, though objectively a meta-analysis of studies found that melatonin only helped people get to sleep four minutes faster, and extend overall sleep duration by about 13 minutes.

If you do want to try melatonin to help with sleep, older adults are advised to use the smallest effective dose an hour before bedtime, starting perhaps at 0.3 mg. The 12 mg supplements on the market could produce levels in the bloodstream that can be 200 times higher than normal nightly levels, which raises safety concerns. After all, melatonin used to be known as the anti-gonad hormone, with human-equivalent doses of just a milligram or two reducing the size of sex organs, and impairing fertility in laboratory animals.

Furthermore, due to poor regulation of dietary supplements in the U.S., you never know what you’re going to get. An analysis of 31 different brands of melatonin supplements found that the actual melatonin content varied up to nearly 500 percent compared to what was listed on the bottle. Even within a single brand, different lots of the same product suffered similar variability. Given that there is no guarantee of the strength or purity of melatonin supplements, many countries have banned over-the-counter melatonin, making it prescription-only so the authenticity could be ensured. U.S. citizens can get certified melatonin by sending a prescription to an online Canadian pharmacy (though it’s technically illegal), or can get melatonin from their diet.

Interestingly, the rise in melatonin blood levels or metabolites in the urine consistently exceed the amount of melatonin that’s actually ingested in these foods. You can even get a spike in melatonin by eating fruit that doesn’t even appear to have any detectable melatonin at all. The answer to the puzzle may lie in the gut.

The first site outside the pineal gland where melatonin production was discovered was the human appendix. Although we now know melatonin can be produced throughout the body, the greatest accumulation appears to be in the gastrointestinal tract––estimated to contain more than 400 times more melatonin than the pineal gland. So, perhaps the consumption of certain foods can cause the release of some of this bounty into the bloodstream. This may be how magnesium supplements (500 mg a day for eight weeks) were able to improve sleep quality and quantity over placebo, given the effect was accompanied by a rise in melatonin levels.

What’s more intriguing are its purported anti-aging benefits. In addition to regulating sleep and our circadian rhythms (when properly timed, it can be used to treat jet lag), melatonin can have antioxidant and anti-inflammatory properties. However, secretion of melatonin appears to progressively decline with age, dropping as much as 70 percent between middle and older age. This has led some to speculate that “aging is a syndrome of relative melatonin deficiency resulting from the gradual failure of the pineal gland.”

A variety of age-related diseases, such as Alzheimer’s, are associated with particularly low levels of melatonin. But we have yet to determine if this is a cause or consequence of disease. Melatonin supplementation extends the lifespan of fruit flies, but shortens the lifespan of C. elegans. Mice after having their pineal glands removed appeared to age more rapidly. But when put to the test, melatonin prolonged survival of some strains of mice, but shortened the lives of others (by inducing cancer). So, are we more like New Zealand bIack mice or Bagg albino mice? Sometimes the same research group went on to publish opposite results, showing melatonin both increasing and decreasing lifespan. Not surprisingly, a meta-analysis found no overall effect when all of the mouse studies were considered together. In rats, melatonin significantly improved survival, but so did a melatonin-blocking drug.

Please consider volunteering to help out on the site.

• Matheson E, Hainer BL. Insomnia: pharmacologic therapy. Am Fam Physician. 2017;96(1):29-35.
• Morin CM, Inoue Y, Kushida C, et al. Endorsement of European guideline for the diagnosis and treatment of insomnia by the World Sleep Society. Sleep Med. 2021;81:124-126.
• Fatemeh G, Sajjad M, Niloufar R, Neda S, Leila S, Khadijeh M. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials. J Neurol. 2022;269(1):205-216.
• Brzezinski A, Vangel MG, Wurtman RJ, et al. Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev. 2005;9(1):41-50.
• Vural EMS, van Munster BC, de Rooij SE. Optimal dosages for melatonin supplementation therapy in older adults: a systematic review of current literature. Drugs Aging. 2014;31(6):441-451.
• Lathrop NJ, Lentz M. Melatonin, light therapy, and jet lag. Air Med J. 2001;20(5):30-34.
• Grigg-Damberger MM, Ianakieva D. Poor quality control of over-the-counter melatonin: what they say is often not what you get. J Clin Sleep Med. 2017;13(2):163-165.
• Erland LAE, Saxena PK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. J Clin Sleep Med. 2017;13(2):275-281.
• Bhosle MJ, Balkrishnan R. Drug reimportation practices in the United States. Ther Clin Risk Manag. 2007;3(1):41-46.
• Kennaway DJ. Melatonin rich foods in our diet: food for thought or wishful thinking? Food Funct. 2020;11(11):9359-9369.
• Gonzalez-Flores D, Velardo B, Garrido M, et al. Ingestion of Japanese plums (Prunus salicina Lindl. cv. Crimson Globe) increases the urinary 6-sulfatoxymelatonin and total antioxidant capacity levels in young, middle-aged and elderly humans: nutritional and functional characterization of their content. J Food Nutr Res. 2011;50(4):229-236.
• Huether G. Melatonin synthesis in the gastrointestinal tract and the impact of nutritional factors on circulating melatonin. Ann N Y Acad Sci. 1994;719:146-158.
• Majidinia M, Reiter RJ, Shakouri SK, Yousefi B. The role of melatonin, a multitasking molecule, in retarding the processes of ageing. Ageing Res Rev. 2018;47:198-213.
• Abbasi B, Kimiagar M, Sadeghniiat K, Shirazi MM, Hedayati M, Rashidkhani B. The effect of magnesium supplementation on primary insomnia in elderly: a double-blind placebo-controlled clinical trial. J Res Med Sci. 2012;17(12):1161-1169.
• Melatonin for jet lag. Drug Ther Bull. 2020;58(2):21-24.
• Favero G, Franceschetti L, Bonomini F, Rodella LF, Rezzani R. Melatonin as an anti-inflammatory agent modulating inflammasome activation. Int J Endocrinol. 2017;2017:1835195.
• Waldhauser F, Weiszenbacher G, Tatzer E, et al. Alterations in nocturnal serum melatonin levels in humans with growth and aging. J Clin Endocrinol Metab. 1988;66(3):648-652.
• Rozencwaig R, Grad BR, Ochoa J. The role of melatonin and serotonin in aging. Med Hypotheses. 1987;23(4):337-352.
• Hardeland R. Melatonin in aging and disease -multiple consequences of reduced secretion, options and limits of treatment. Aging Dis. 2012;3(2):194-225.
• Bonilla E, Medina-Leendertz S, Díaz S. Extension of life span and stress resistance of Drosophila melanogaster by long-term supplementation with melatonin. Exp Gerontol. 2002;37(5):629-638.
• Bakaev VV, Efremov AV, Anisimov VN. An attempt to slow aging in C. elegans. 8. Melatonin reduces life span of C. elegans. The Worm Breeder Gazette. 1997;15(1):36.
• Reiter RJ, Tan DX, Rosales-Corral S, Galano A, Zhou XJ, Xu B. Mitochondria: central organelles for melatonin’s antioxidant and anti-aging actions. Molecules. 2018;23(2):509.
• Pierpaoli W, Dall’Ara A, Pedrinis E, Regelson W. The pineal control of aging. The effects of melatonin and pineal grafting on the survival of older mice. Ann N Y Acad Sci. 1991;621:291-313.
• Poeggeler B. Melatonin, aging, and age-related diseases: perspectives for prevention, intervention, and therapy. Endocrine. 2005;27(2):201-212.
• Oaknin-Bendahan S, Anis Y, Nir I, Zisapel N. Effects of long-term administration of melatonin and a putative antagonist on the ageing rat. Neuroreport. 1995;6(5):785-788.

Motion graphics by Avo Media

• aging
• Alzheimer’s disease
• anti-aging
• fruit
• longevity
• magnesium
• melatonin
• sleep
• supplements