I've written about melatonin in the past year, as a natural sleep aid, so, to be honest, I didn’t expect to be revisiting the subject so soon. But melatonin is becoming a hot corner of the anti-aging research world. A lot of folks are taking a second or third look at melatonin, including me.

Melatonin 101  

As you’re probably aware, melatonin is a big deal in the supplement market. The products that jump out at you at the drugstore or supermarket are a synthesized version of the human hormone, which we thought was mainly produced by the pineal gland inside the brain, and that plays an important role in regulating our sleep. During the day, our primary stress hormone cortisol keeps the energy fires burning, then come evening, cortisol declines and melatonin levels rise, lowering body temperature and blood pressure rate, and generally preparing the body to fall and stay asleep. It’s our hormonal mechanism to keep us in synch with the natural light/dark cycle of the day, or, to sum it up in a single term, our circadian rhythms. That can be especially useful when we’re trying to counteract the sleep disruptive effects of jet lag.

Melatonin, the new vitamin D?    

It was always thought that the majority of melatonin was produced by the pineal gland mainly at night, in the dark. But we are now discovering that the vast majority of it is actually synthesized in the mitochondria of all cells, 24 hours a day. It seems to be much more than a sleep hormone and not solely impacted by the light/dark cycle as we had always assumed. In fact, it is a hormone that is involved in the workings of a particularly huge swath of our physiology, as is vitamin D. And, medical researchers keep coming up with the same finding – people with naturally high D levels, and similarly high melatonin levels – are generally healthy and more resistant to the so-called diseases of aging. Unfortunately, levels of D and melatonin naturally decline as we age. In other words, just when we need them most, to counter the downward gravitational pull of aging, there’s less to go around. That’s a strong theoretical argument for supplementing with melatonin for all-round health (just as many of us do with supplemental D), even if I’m waiting for more clinical trials before I routinely recommend it to my patients for long-term use.

The Advanced Anti-Aging Course  

A few decades ago, the first experiments were published that showed that feeding melatonin to lab animals could extend their life by up to 20%. That generated a buzz at the time -- some media coverage and a least one best-selling book. But the bigger question that older research raised went largely unanswered: what did any of this have to do with humans?  Well, the intervening years have seen an explosion in our understanding of what drives human aging. As best we know now, aging isn’t a single thing, but rather a series of changes that happen at the cellular and molecular level that work together to make you look and feel different at 70 than when you did when you were 20. Researchers are now able to map out what’s going on, including: inflammaging, the decay of our cells’ “power plants,” the mitochondria; the wear and tear caused by “free radicals” generated by the cell’s energy production; harmful mutations in the DNA inside the cell nucleus; the decline of our immune system. That’s a lot of science to take in, I know, but here’s the point. The properties of melatonin that researchers have pinned down – it’s an antioxidant, it reduces energy waste products (“oxidative stress”), it’s anti-inflammatory – should help counteract those drivers of aging. That’s the theory and we’re beginning to put together the clinical evidence to back up that theory. Think of it this way: melatonin has a lot of keys that can open up a lot of anti-aging “locks.”

“Good for What Ails You?”

While we all might like to fantasize about some fountain-of-youth pill, the research to date is showcasing melatonin’s promise as an ally to help combat some of the most serious age-related conditions which, all too often, turns a healthy senior into a candidate for assisted living. I mentioned the “oxidative stress” that drives a lot of the damage at the cellular and molecular level. The two most important and vulnerable areas where that damage manifests are the brain and the cardiovascular system.

Your brain on melatonin…  

Small clinical studies suggest that melatonin can have a brain-protective effect, even helping to delay the onset of Alzheimer’s Disease. Animal studies have shown that it can help block the production of the amyloid plaque that gums up the neural machinery and can lead to Alzheimer’s. Because melatonin shores up the mitochondria by helping clean up the waste products of energy production – and mitochondrial “dysfunction” helps drive neurological diseases – it may prove out as a therapy for a whole range of debilitating brain conditions.

Your heart on melatonin…  

The cardiovascular system is a similar story. Studies have shown melatonin can improve the health of the heart vessels by helping to counter the effect of the free radicals which weaponize LDL cholesterol, causing it to form artery-clogging plaque.  One interesting study showed it had a positive effect on the strength of the heart muscle, in patients with heart failure, a life-threatening weakening of the heart’s ability to pump blood.

Melatonin and the immune system.  

For a number of years now, researchers have been looking at the contribution melatonin can make as a cancer fighter. It seems to work on two fronts, supporting the immune system’s battle against malignant cancer cells and softening the toxic effects of chemotherapy. Melatonin’s potential role in helping to tame an out-of-control immune system has been highlighted during the pandemic. Integrative practitioners often recommend it to their patients for COVID protection, along with vitamin D, quercetin, NAC and zinc. The working theory is that it can help tamp down the immune’s system tendency to overreact to the virus, the so-called “cytokine storm” that can cause far more damage than the virus itself.

What isn’t it good for?

I would quickly run out of space if I tried to tick off all the areas of melatonin health research. Here are a few of my “honorable mentions,” to consider alongside the research on neurological diseases, heart disease and cancer. As an anti-inflammatory, melatonin shows promise as protection against metabolic problems like metabolic syndrome and type 2 diabetes. Ditto on issues involving the female reproductive tract, like endometriosis and PCOS. There is less known about how supplemental melatonin might positively impact gut disorders but the potential is intriguing to say the least. Consider that cells in the gut  naturally produce the hormone by breaking down the amino acid tryptophan, a supply that actually  far outstrips what the pineal gland in the brain produces, even if it doesn’t seem to have a role in regulating our circadian rhythms.

More than a sleep aid.  

While the melatonin sold as a sleep aid is usually in the 3-5 mg. range, the medical researchers have found that a much smaller dosage, a tenth as small, in the .3-.5 mg range, are often just as or more effective for sleep. But as I imagine a future when long-term melatonin supplementation is routine to support aging well, I’m thinking of dosages which correspond to the amounts of the hormone produced in the brain by a young person, before the age-related decline sets. To use the technical language, it’s a “physiologic” dose. I recommend starting somewhere between 5-10mg/day, because our body’s melatonin production gradually decreases over time. I’m not especially worried about side-effects, as melatonin has surprisingly low toxicity, especially at doses less than 10mg/day. If you experience morning grogginess that you occasionally see at the bigger “pharmacological” doses, cut back on your dose. Still, with any long-term hormonal supplementation, caution should rule. Discuss with your health care provider.

Extra-credit homework.  

If you’re as intrigued by melatonin as I am, you may want to take a look at a recent academic paper that has stimulated a lot of this new interest within the integrative health world: The research was sponsored by the company that makes a melatonin product, Herbatonin, the only one I’m aware of that is made from a plant extract, not by chemical synthesis. The article is a review piece that pulls together a huge amount of scientific research (323 footnotes!). I also recommend a recent piece in Life Extension Magazine which does an excellent job digesting that same research in a shorter, less technical form for the layperson:

Stay tuned to the melatonin research (I know I will) and we’ll see how this story develops.