What we are now learning about melatonin

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When you think about melatonin what do you think of? Chances are you think of a dietary supplement for sleep that 3 million people in the U.S. take in any given month.

In fact, any search engine will yield melatonin coming in a variety of products, combinations with herbs, and different ways of ingesting it.  You may also know that melatonin is a hormone that has a role in sleep and is mostly produced in the brain’s pineal gland. What you may not know is that melatonin is found extensively in the animal kingdom, plants (leaves, fruit, seeds) and even bacteria. It is a ubiquitous ancient molecule derived from an amino acid with antioxidant activity that was probably one of the first compounds that appeared on earth to coordinate basic events of life. And yet, melatonin was only first isolated in 1958 with the observation that it seemed to lighten the color of a frog’s skin when bovine pineal gland extracts were injected into it. Further research into the 1970s began to shed some light into melatonin’s role as the timekeeper for the body and how it is primarily driven by the body’s circadian system and secondarily light. In this article, I will highlight some take away points from current research that you should know if you are taking melatonin including very recent studies on how there appears to be an adverse effect of taking melatonin with food.

Is it safe to take melatonin?

According to the National Center for Complementary and Integrative Health in the NIH, melatonin is safe to take in the short term but there is data lacking for long term use. Of course, since melatonin is classified as a dietary supplement it is not regulated or approved by the FDA for any indication.  Studies have shown that when you buy melatonin, there is often a discrepancy between the  label dose and what’s actually inside.  Side effects include daytime drowsiness, dizziness, weakness, confusion, vivid dreams, or nightmares but the frequency of these side effects is generally low (<1-2%).  Melatonin is not fundamentally sedating and it works by quieting down a region of the brain called the suprachiasmatic nucleus (i.e. suppressing circadian rhythm arousal) to facilitate sleep. Melatonin secretion that our body produces is generally low in the daytime, high in the nighttime, and declines at the end of the normal sleep period in the morning. We don’t believe taking supplemental melatonin suppresses our own production of melatonin. Studies have shown in different populations that a melatonin supplement will decrease the sleep onset time by about 10 minutes for insomnia, will improve overall sleep duration by about 13 minutes, and yields a small improvement in the quality of sleep. However, it has not been shown to be particularly effective in treating most primary sleep disorders or secondary sleep disorders (such as jet lag, shift work).  It’s most likely to be helpful for people with circadian rhythm phase delay (night owls), non-24 hour sleep/wake disorder (blind adults), and irregular sleep/wake rhythm disorder (children with neurologic disorders).

The new concern about melatonin

There have been several studies in the last 5 years that have shown that when there is a later time of food intake and increased melatonin levels in the body either because of taking a supplement or the circadian timing (evening hours when the body’s melatonin secretion is increased), there is a clear association with increased body fat and decreased glucose tolerance (that’s bad!!) which is what happens in diabetes.  The question being raised is should we not mix meals and melatonin? If we’re following a normal pattern of eating during the daytime, and then sleeping and fasting during the nighttime, melatonin is serving us well but when we cross those boundaries that can be problematic physiologically so we need to keep in mind the timing.  Researchers stated in a July 2020 article: “Shift workers, night eaters, and melatonin users are susceptible to the adverse effect brought about by the concurrence of food intake and high melatonin levels.”

Take away points about melatonin supplements

  • Melatonin is usually well tolerated and safe for short term use and it might help with sleep onset but unlikely to help sleep maintenance issues. It is not intended for long term use (maximum=2 months) and caution is advised due to the uncertainty about metabolic effects mentioned above.

  • Most likely helpful for people with circadian rhythm phase delay (night owls) and non-24 hour disorders. Limited support for jet lag and shift work.

  • Start low, and go slow: try 0.5 MG and work your way up to 3 MG—more is not better with melatonin (due to a flat response curve > 3 MG).

  • Use strategically timed. Take prior to bedtime (1-2 hours) but not too early—at least 2 hours after last meal.

  • Avoid eating late in the evening, even if you’re not taking melatonin (because your own body’s melatonin level is coming up by that time).

  • Melatonin poses little risk when taken with psychiatric medications with the exception of the SSRI antidepressant, fluvoxamine, which can result in elevated levels of melatonin in the body.  Melatonin may also interact with certain blood pressure and diabetes medications.

  • When purchasing melatonin look for third party testing approval on label which includes: GMP (Good Manufacturing Practices), NSF International, USP (US Pharmacopeia), or CL (ConsumerLab.com).  They provide some peace of mind that a product contains what’s on the label.

  • Don’t overlook your own body’s melatonin production and how you can promote it by limiting bright lights and other sleep hygiene measures discussed in my previous article from June 2019, How Can I Sleep Better.