I am not sure one way or another, as most studies see effects at very lose doses, so that’s why I was asking why they use such high doses. In adults, studies have found the benefits from melatonin are for people who have sleeping problems related to delayed sleep-wake phase disorder and jet lag. Evidence in small studies have indicated that melatonin may be useful in children with certain conditions including epilepsy and some neurodevelopmental disorders such as autism spectrum disorder and Angelman’s syndrome. High doses of melatonin increase sleep duration during nighttime and daytime sleep episodes in older adults.
In my understanding, we do see some age related decrease in melatonin synthesis, but the literature is mixed on this. I am fortunate to be able to learn from a great group of circadian rhythm field experts such as , Dr. Gianluca Tosini, who is a pioneer in the melatonin/circadian rhythm field. I talked to him about this issue before as we know the SCN and retina from older mice and humans a show a decrease in responsiveness to melatonin, and he said that as we age, it less so the effect of melatonin synthesis decreasing and more so the effect of melatonin receptor responsiveness decreasing that leads to disruption of sleep as we age. We also talked about melatonin’s antiaging effects, and the one study he knew of claimed to help in anti-aging and in the paper it was shown that if you give exogenous melatonin only at night, you can extend lifespan in mice. But his issue with the paper is that it is hard to distinguish between the effects of melatonin or if it is sleep that is causing this extension of lifespan.
There is a really good review on the aging clock that I will attach:
https://www.jci.org/articles/view/90328
What was interesting was their talk on melatonin:
" However, other evidence suggests that a “young” melatonin rhythm is in fact preserved in very healthy older adults, and a reduction in peak melatonin may occur only in older individuals whose total melatonin levels are at the lower end of the population distribution. For example, a 6-year longitudinal study found no evidence of a decrease in total melatonin secretion in healthy older adults (ages ranging from 55 to 74 years). This discrepancy in findings may suggest that a reduction in the melatonin rhythm is not a feature of a healthy aging process, and in fact may signal underlying pathology. To this end, Waller and colleagues reported a lower nightly melatonin peak in middle-aged men (mean age of 57 years) with cognitive impairment compared with age-matched healthy controls. Furthermore, significant reductions in melatonin synthesis and expression of melatonin receptors in the SCN have been documented in individuals with neurodegenerative diseases such as Alzheimer’s or Parkinson’s, or those with prodromal symptoms. "
I also know of Melatonin disruption leading to health disorders such as obesity, type 2 diabetes, insulin resistance, etc. A variant in MTNR1B is associated with increased risk of type 2 diabetes and impaired early insulin secretion. There have been some studies talking about melatonin over signaling being a risk factor for type 2 diabetes. In insulin secreting cells, melatonin seemed to reduce cAMP levels and MTNR1B overexpression exaggerated the inhibition of insulin released exerted by melatonin.
Personally, I don’t see much benefit in taking large doses of melatonin until we get much much older, and even then I would weigh the risk/reward in relation to the benefits of melatonin dosing vs how much longer you think you have left. I don’t see the harm in taking a large dose if your 70-80+ and you more than likely are heading toward your marginal decades, but if your younger than that, I would wait to see more research come out.
