A 2006 paper by researchers at the N.N. Petrov Research Institute of Oncology in St. Petersburg, Russia, reviewed the scientific literature on melatonin supplements and found that they show promise for the extension of life and health.
The pineal gland in humans (and some animals) produces melatonin naturally, partly to regulate the circadian rhythms involved in sleep. Older adults experience insomnia partly because the body’s natural melatonin production declines over the span of a human life. That’s why adults commonly use melatonin supplements to aid sleep.
In addition to regulating sleep, melatonin is an antioxidant and stimulates production of other natural antioxidants in the body. Antioxidants protect cells from damage by neutralizing chemicals called “free radicals” in your cells that can damage your DNA. According to the “free radical theory of aging,” the cumulative damage caused by free radicals causes the physical decline we associate with old age. So in fighting free radicals, antioxidants also fight age-related physical decline.
Melatonin also helps regulate gene expression. As we’ve learned from the emerging science of epigenetics, genes can be turned on or off, up or down, by chemical triggers in the body. Melatonin turns out to trigger quite a few different genes. The effects are complicated and still poorly understood, but they may include better metabolism of calcium and increased energy production within the body’s cells.
Melatonin first showed promise for life extension in the early 1990s, when researchers transplanted pineal glands from young mice into older mice. The young mice’s pineal glands produced more melatonin than the older mice’s own pineal glands would have, so the transplant increased melatonin levels in the older mice. Amazingly, the researchers found that the transplant extended the average length of the mice’s lives.
Another round of studies, mostly published in the late 1990s, found that melatonin protected mice from genetic damage. For instance, three studies exposed mice to X-rays, and found that mice with higher melatonin levels suffered less gene damage from the radiation. Other studies replaced X-rays with toxic chemicals like safrole and chromium and found that melatonin protected the mice’s genes from those as well.
In addition to genetic damage, free radicals and other toxins can also trigger a process called apoptosis, or programmed cell death. Over a dozen different studies have found that melatonin slows toxin-induced cell death in rodents’ brains, colons, and livers.
Attempts to replicate the original finding that melatonin increases rodents’ lifespans have produced mixed results. Lifespan increased in 12 of 20 experiments (60%) and had no effect on lifespan in the other 8 experiments (40%). The authors of the review paper blame the negative results on poor experimental design and the different melatonin sensitivities of different strains of mice.
Melatonin has also been tested in fruit flies. In naturally short-lived fruit fly strains, it tends to increase lifespan, but in longer-lived varieties it has either no effect or a negative effect on lifespan.
Studies of melatonin supplementation in human cancer patients have found it to be associated with a slight increase in survival at 1 year.
In addition to life span, researchers have also found that melatonin inhibits certain kinds of tumors in mice and that it stimulates their immune systems. Additional research is required to determine whether it could benefit humans in similar ways.
While melatonin generally acts as an antioxidant and extends animals’ lifespans, it can sometimes have pro-oxidant effects and may be toxic at very high doses. 4 experiments found that high doses of melatonin increased the incidence of certain types of cancer in certain strains of mice. High concentrations of melatonin can also damage DNA in a petri dish.
Melatonin should be generally safe at the dosage levels usually sold for human consumption, ranging from 1 to 12 mg. It’s been used in a number of long-term clinical trials with no adverse events. I personally wouldn’t exceed those dosages, however.
Melatonin may pose particular risks to patients at risk of diabetes. Some studies show that melatonin increases blood sugar levels and inhibits insulin. However, other researchers come to opposite conclusions, finding that melatonin ameliorates diabetes and obesity risk. The difference may be in your genes. A 2016 study found that melatonin’s regulation of insulin is exaggerated in patients with a certain gene, putting them at risk of type-2 diabetes. In the future, perhaps your 23andMe report will tell you whether it’s safe for you to use melatonin. Until then, maybe stay away if you’re at risk for diabetes.
So to summarize, melatonin appears possibly useful as a supplement for life extension and immunity boost, but keep in mind that what works in animals may not work in humans. Some people may experience adverse effects, and everyone should consult a physician before and during use of all supplements.
Anisimov VN, Popovich IG, Zabezhinski MA, Anisimov SV, Vesnushkin GM, Vinogradova IA. Melatonin as antioxidant, geroprotector and anticarcinogen. BBA Biochim. et Biophys. Acta. 2006;1757(5–6):573–589. https://doi.org/10.1016/j.bbabio.2006.03.012.
Tuomi T, Nagorny CLF, et al. Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes. Cell Metab. 2016;23(6):1067–1077. https://doi.org/10.1016/j.cmet.2016.04.009.