The Case Against Melatonin (White Paper)

Dr. Shawn Talbott (Ph.D., CNS, LDN, FACSM, FACN, FAIS) has gone from triathlon struggler to gut-brain guru! With a Ph.D. in Nutritional Biochemistry, he's on a mission to boost everyday human performance through the power of natural solutions and the gut-brain axis.

Here is my narrated video about this post.

In the U.S., melatonin use has increased 5-fold since 1999, and sky-rocketed during the pandemic to include millions of kids, teens, and adults – leaving many struggling with “melatonin dependence” – described as the feeling that they “need” melatonin to fall asleep.

It has been known for at least 20 years that melatonin is not very effective for improving sleep quality – and add to that the growing concerns for dependence, grogginess, gut problems, and interference with puberty, it may be obvious that health-minded consumers are starting to look for non-melatonin sleep aids.

The European Sleep Research Society says “melatonin is not generally recommended for the treatment of insomnia because of low efficacy”. Two recent meta-analyses (one in 1,700 participants and another in ~44,000 people across 150+ trials) found that melatonin supplements can reduce the time it takes to fall asleep (“sleep latency”) by 7 minutes and increase total sleep time by 8 minutes. In kids, the effect of melatonin is a little better – improving time to fall asleep by 11 minutes and total time asleep by 15 minutes, which may not be a great trade-off for potential future problems? Importantly, even if melatonin supplements might give you a few minutes “more” sleep, none of these studies show any improvement in “sleep quality” – which is calculated from the amount of time spent in deep sleep (where your body recovers) and REM sleep (where your brain recuperates).

More than just a “sleep” hormone

Most people think of melatonin as the “sleep hormone” (which it is, but it also does so much more) – and millions think nothing of popping a few milligrams to help them sleep at night (which probably needs some more thought because of the potential problems associated with synthetic melatonin supplements).

Far from being “just” related to sleep, melatonin is actually involved in many more aspects of overall mental wellness and physical health – including regulation of our entire circadian rhythm, energy metabolism, body weight, insulin sensitivity, and glucose tolerance (which is why poor sleep is associated with diabetes and obesity – and why getting better sleep can help with weight loss).

Approximately 80% of the body’s melatonin is produced in the gut and this “gut-produced” melatonin is thought to have several potential roles, including:

    1. Gastrointestinal Regulation: Melatonin produced in the gut is believed to play a role in regulating various gastrointestinal functions, including motility (movement of food through the digestive system), secretion of digestive juices, and protecting the lining of the gut from inflammation and oxidative stress.

    1. Circadian Rhythm: Just like melatonin produced in the brain helps regulate the sleep-wake cycle, gut-produced melatonin may contribute to the circadian rhythms of the digestive system and the rest of the body. This can impact processes like nutrient absorption and metabolism.

    1. Immune System: Some research suggests that melatonin produced in the gut may have immune-modulatory effects, helping to regulate the immune responses in the gastrointestinal tract (which is home to 70% of our immune system).

    1. Microbiota Interaction: Gut-produced melatonin might also interact with the gut microbiota, which is the community of microorganisms living in the digestive system. There’s emerging evidence that the gut microbiota can influence melatonin production and vice versa.

Taking Melatonin (synthetically) versus Making Melatonin (naturally)

Because melatonin is such a vital hormone for myriad aspects of mental wellness and physical health – we need to ensure that our bodies are naturally MAKING the right amounts at the right times. But we also want to be aware that TAKING synthetic forms can be associated with common side effects such as headaches, irritability, dizziness, dry mouth, and night sweats, with the most common problem being the “melatonin hangover” grogginess experienced by many users the day after using melatonin (caused because your body has not fully metabolized the entire melatonin dose – so your brain still thinks it is night).

Taking melatonin supplements can theoretically interfere with your body’s normal production of melatonin, but the extent of this interference can vary from person to person and depends on several factors. Just ask any former bodybuilder or power athlete about their experience with anabolic steroids and subsequent testosterone problems. It is simple biology that taking an external synthetic hormone – when you don’t need it – will change your internal natural metabolism of that hormone. This is a different scenario to hormone “replacement” therapy (HRT) where you are restoring an absent hormone back to a normal level – as in the case of estrogen after menopause.

The handful of studies that have been done on melatonin supplements (“exogenous” = coming from outside the body) and subsequent production of the body’s own melatonin (“endogenous” = produced within the body) have been short (1 week to 1 month) – and conducted in people with jet lag or who are blind (and have disrupted melatonin production and abnormal circadian rhythms) – and not among people using melatonin supplements as a nightly sleep supplement for months or years (as so many people are doing lately).

Because melatonin helps regulate your sleep-wake cycle (circadian rhythm), there is a natural daily/nightly fluctuation between day/night and also between different phases/cycles of sleep that cannot be adequately replicated with single-dose melatonin supplements (even the “time-released” versions). When you take melatonin supplements, you’re introducing an external source of melatonin, which can affect your body’s natural production in a number of potential ways:

    1. Suppression of Natural Production: Taking melatonin supplements can signal to your body that it doesn’t need to produce as much melatonin naturally. This can potentially lead to a reduction in your body’s own production of melatonin.

    1. Tolerance: Over time, your body might become accustomed to the supplemented melatonin levels, leading to a decreased response to the supplement. This could result in needing higher and higher doses to achieve the same effect, further affecting your body’s natural melatonin production.

    1. Circadian Rhythm Disruption: If you take melatonin supplements at the wrong time or inappropriately, it could potentially disrupt your circadian rhythm. This might make it harder for your body to regulate its sleep-wake cycle naturally.

    1. Individual Variation: People have different sensitivities to melatonin supplements. Some might experience little to no disruption in their natural production, while others might notice significant changes.

Because of the relatively low-effectiveness and the theoretical potential for harm, several medical and health organizations have expressed concerns about the use of melatonin supplements:

    1. American Academy of Pediatrics (AAP): points out that U.S. Poison Control Centers saw a ~500% increase in melatonin ingestions over the past decade – and suggests that melatonin is not recommended as a treatment for sleep problems in children and adolescents.

    1. National Sleep Foundation (NSF): recommends that melatonin supplements be used cautiously if at all and never as a substitute for good sleep hygiene practices.

    1. American Academy of Sleep Medicine (AASM): suggests that melatonin supplements may be useful for certain sleep disorders, such as jet lag or shift work disorder, but they advise against the use of melatonin supplements.

    1. European Sleep Research Society (ESRS): has expressed concerns about the increasing use of melatonin supplements, including guidance about their low level of effectiveness.

    1. Canadian Sleep Society (CSS): advises against the regular use of melatonin supplements as a sleep aid.

Based on the poor “user experiences” of melatonin supplementation that are all over social media, it seems prudent to look for other non-drug natural approaches to improve sleep – and luckily we have a number of them to choose from – many of which you can read about in my Natural Sleep Guide.

Sources:

    1. American Academy of Sleep Medicine (AASM) Health Advisory: Melatonin Use in Children and Adolescents (Sept 9, 2022). https://aasm.org/advocacy/position-statements/melatonin-use-in-children-and-adolescents-health-advisory/

    1. Attia, A.M.; Montaser, B.A.; Abdallah, N.K. Role of Melatonin in Constitutional Delayed Puberty in Boys. Menoufia Med. J. 2020, 33, 283. Available online.

    1. Besag, F.M.C., Vasey, M.J., Lao, K.S.J. et al. Adverse Events Associated with Melatonin for the Treatment of Primary or Secondary Sleep Disorders: A Systematic Review. CNS Drugs 33, 1167–1186 (2019). https://doi.org/10.1007/s40263-019-00680-w

    1. Boafo A, Greenham S, Alenezi S, Robillard R, Pajer K, Tavakoli P, De Koninck J. Could long-term administration of melatonin to prepubertal children affect timing of puberty? A clinician’s perspective. Nat Sci Sleep. 2019 Jan 31;11:1-10. https://doi.org/10.2147/NSS.S181365

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    1. D. Blum. New York Times. Sept 6, 2022. Can You Get Hooked on Melatonin? The sleep supplement doesn’t cause physical dependence, but falling asleep without it can be tricky for some people. https://www.nytimes.com/2022/09/06/well/mind/melatonin-dependency.html

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    1. De Crescenzo et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. The Lancet. Vol 400, Issue 10347, P170-184, July 16, 2022. DOI: https://doi.org/10.1016/S0140-6736(22)00878-9

    1. Fatemeh, G., Sajjad, M., Niloufar, R. et al. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials. J Neurol 269, 205–216 (2022). https://doi.org/10.1007/s00415-020-10381-w

    1. Ferracioli-Oda E, Qawasmi A, Bloch MH (2013) Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders. PLoS ONE 8(5): e63773. https://doi.org/10.1371/journal.pone.0063773

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    1. Li J, Somers VK, Xu H, Lopez-Jimenez F, Covassin N. Trends in Use of Melatonin Supplements Among US Adults, 1999-2018. JAMA. 2022;327(5):483–485. doi:10.1001/jama.2021.23652 https://jamanetwork.com/journals/jama/fullarticle/2788539

    1. Minich, D.M.; Henning, M.; Darley, C.; Fahoum, M.; Schuler, C.B.; Frame, J. Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements. Nutrients 2022, 14, 3934. https://doi.org/10.3390/nu14193934

    1. National Center for Complementary and Integrative Health (NCCIH) = https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know

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    1. Talbott SM, Talbott JA, Brownell L, Yimam M. UP165, A Standardized Corn Leaf Extract for Improving Sleep Quality and Mood State. J Med Food. 2023 Jan;26(1):59-67. https://pubmed.ncbi.nlm.nih.gov/36179066/

About the Author

Exercise physiologist (MS, UMass Amherst) and Nutritional Biochemist (PhD, Rutgers) who studies how lifestyle influences our biochemistry, psychology and behavior - which kind of makes me a "Psycho-Nutritionist"?!?!

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