Melatonin use is rising sharply post-pandemic and is often polarising in its effects. Some find it gives them what they need, while others don’t.
In an article written earlier this year, I promised I would dive deeper into this remarkable hormone, and here we are.
We’re going to look at how melatonin works in the body, how it interacts with other hormones such as cortisol, some things about it you didn’t know (Melatonin and IBS?!) and, of course, some guidelines on how to take it.
How is melatonin created in the body?
One of the first things I offer patients about melatonin is its relationship to the natural rhythms of light over the day. As your eyes notice the change in the light spectrum at sunset, this triggers a message via the optic nerve to the pineal gland to begin melatonin production.
Melatonin production and distribution are enhanced by darkness and diminished by light.[1] It peaks in the middle of the night, often between 2 am and 4 am, and decreases gradually during the second part of the night.[2]
Already this natural ebb and flow can give you clues as to how melatonin can help to manage sleep disturbances. If you find you are waking up “earlier than my alarm,” as many of my patients put it, this can signify that your melatonin levels could benefit from supplementation.
A study published in 2020 confirmed that melatonin significantly decreased early wake time in elderly adults using a 3mg dose over four weeks.[3]
Melatonin’s primary function is regulating circadian rhythms, including your sleep-wake rhythms, neuroendocrine rhythms or body temperature cycles.
First, you might be asking what a circadian rhythm is.
Circadian rhythm is the twenty-four-hour internal clock in our brain that manages alertness and sleepiness based on the light spectrum in our environment. The sleep-wake cycle alone influences eating habits, digestion, body temperature, hormone release and other functions.[4]
Due to the wide variety of functions influenced by the sleep-wake cycle, it’s easy to see how a lack of sleep or poor sleep patterns can affect what feels like everything. In contrast, restoring circadian rhythms can positively influence our behaviour, mood, memory consolidation and metabolism.[5]
One of the deeper, more fascinating parts of this beyond sleep is melatonin’s role as an “internal time giver” for other organs. For example, by helping an organ or system to “know what time it is”, melatonin influences cortisol and insulin levels in the morning so we are awake and ready to draw energy from our breakfast.[6]
Chronobiology, or the effects of time on our bodies, is definitely worth its own article. It has recently led to a Nobel prize award for researchers investigating its impact on our health. For now, though, understanding melatonin’s role in helping us to merge with our environment is a great start to gaining some insights into this remarkable hormone.
Melatonin can play a significant role in protecting the brain from rust caused by oxidation.
Oxidation is a naturally occurring and necessary process in our bodies, but the byproducts it creates can accelerate an ageing-like process called “oxidative stress.” Melatonin is known for its antioxidant action in the brain as a protective mechanism.[7]
This protective action also spans out to the digestive system.
Melatonin’s effects on receptors in the gut protect it from ulceration by reducing hydrochloric acid and the effects of bile acids from the gall bladder on the gut lining.[8] This protective quality sees melatonin potentially help in many digestive conditions, such as ulcerative colitis and irritable bowel syndrome.
One of the bonus influences outside of sleep for melatonin is a proposed role in IBS.
True to our theme at philipwatkins.health, we are all about bringing the gut and brain together. Melatonin’s role in IBS might be a perfect example of this.
Visceral pain and abdominal discomfort are frequent and typical in IBS, and a review published in 2021 suggests that melatonin’s anti-inflammatory effects may work on assisting with these symptoms.[9]
In my opinion, one of the most interesting reviews released in 2022 explored how circadian rhythms influence the digestive system.
For example, the same circadian rhythms that melatonin influences regulate digestion and absorption of nutrients, motility (the transit of your food through the digestive system) and even the activity of the microbes in your gut.[10]
The review goes on to mention that disruptions in your circadian rhythms may be responsible for the origin of functional digestive disorders such as IBS!
Melatonin’s role in all of this is exciting. The melatonin concentration in the gut is four hundred times higher than in the brain’s pineal gland.[11] Furthermore, these levels are independent of what the brain produces, suggesting that melatonin plays a precise role in balancing the digestive system.
Melatonin directly enhances components of the immune system.
Or at least this is how it seems in animal studies.
Melatonin enhances nearly all parts of the host or innate immunity. The innate or host immune system is the generalised line of defence between the body and the outside world.[12]
It does this via increasing T-helper immune responses (think general responses to infection) and reducing nitric oxide formation, which helps decrease inflammation.[13]
Melatonin may also assist with bone formation.
Once again, though, the primary studies here are in animals, with some pilot studies in humans. Sometimes though, this can be a guide on what’s to come.
One animal study found melatonin supplementation increased the bone mass of rats and also saw a reduction in bone resorption, a process that breaks down bone tissue.[14]
These significant results have led to some small human studies assessing whether melatonin could help bone health in peri-menopausal women. The melatonin group didn’t change bone density scores over six months. There did seem to be a downward trend in bone resorption, suggesting that it may help prevent bone loss.[15]
Another lesser known of melatonin is its influence on energy metabolism and body mass.
Yes, without being too hyperbolic, it may actually contribute to keeping you slim.
Once again, the jury isn’t in on this one. Early studies that found melatonin reduced body weight in animals[16]didn’t transfer over to human studies.
Positive studies have cropped up in other research where weight gain was a simultaneous part of a mental health condition or menopause.
For example, a systematic review that pools studies together to draw broader conclusions found potential in using 5-8mg of melatonin for six to twelve months was associated with decreased BMI. This dose is something that I wouldn’t go out and do straight away, but it does speak to the span of melatonin’s action in the body.
Whilst the jury is out on melatonin and weight loss, another metabolic condition has some important pre-clinical research.
If you are a regular reader on the site, you would know how frequently non-alcoholic fatty liver disease (NAFLD) pops up in numerous clinical landscapes. Notably, predictions see China experiencing the most significant increase in NAFLD in the coming years, making this more of a global disease than a western one.[17]
With NAFLD being a precursor to diabetes, more and more people are encountering this illness as part of their annual blood checks. It seems melatonin affects all the key markers over twelve weeks, along with other effective natural medicine interventions.
A randomised, controlled, double-blind clinical trial found that 6mg of melatonin significantly improved many markers associated with fatty liver. For example, liver enzymes, hs-CRP (highly sensitive C-reactive protein), blood pressure and the grade of fatty liver itself all changed for the better.
I’ve said this before, but melatonin is remarkable if these effects turn out to be clinically relevant.
Let’s be honest, though. You’re probably here to use melatonin to help you sleep.
So, let’s get into it.
A systematic review released at the beginning of this year brought together twenty-three randomised controlled trials looking at sleep quality and various diseases. Melatonin had a positive effect on sleep issues associated with respiratory diseases, metabolic disorders and primary sleep issues but not on sleep problems brought on by mental health conditions.[18]
This difference in action goes a long way to explain why melatonin may work for some but not others.
Interestingly, when it comes to mental health conditions, increased melatonin levels were seen in the blood and urine of people who had a successful treatment following the administration of antidepressants.[19]
This change in levels somewhat makes sense, considering that melatonin is derived from serotonin; in saying that, though, there was an interesting hypothesis proposed in the eighties called low melatonin syndrome and its relationship to depression that didn’t seem to get much traction.[20]
Other studies back up its use in sleep with a little more detail about its effects on poor sleep specifically. For example, a meta-analysis published in 2013 brought together nineteen studies for a total of 1683 subjects and found numerous effects. These positive effects included reducing the time it took to get to sleep and increasing sleep duration.[21]
The study did mention that melatonin, in comparison to other sleep interventions, compared to placebo, did have a lower absolute benefit but was still appropriate because of its low side effect profile.[22]
I would take that a little further. Even considering that the absolute sleep benefit is lower, hopefully, after getting this far in the article, you’ll agree that melatonin’s broader effects on the body outside of sleep, especially in the metabolic and immune landscapes, are significant bonuses to its sleep influence.
A note on using melatonin, especially for your children and teenagers.
Sleep patterns, especially in Hong Kong, have changed with children and teenagers going through different phases of lockdown and isolated education. According to a report from RTHK, students who went to bed later, primarily down to less optimal levels of physical exercise and activity, had lower melatonin levels.[23]
However, this lower level doesn’t mean that giving your child melatonin, especially in doses above the 3mg dose available over the counter, is a good idea. Lower doses are available, but children who have trouble sleeping often respond better to higher levels of physical activity[24] for sleep or herbal medicine before moving towards melatonin.
That’s not all in 2024, it’s important to take a serious interest in the types of melatonin supplements you are exposing your children too.
A JAMA study released in April 2023 investigated some popular brands of melatonin supplements, some of which were combined with CBD. In a surprising result, some of the formulas investigated had none at all and only CBD and other formulas contained melatonin levels ranging from one to thirteen milligrams! [1]
Now, this is quite alarming when it comes to children’s dosing, as even just 0.1-0.3mg of melatonin can increase nighttime blood levels.[2]
The study then went on to express that, in some cases, these formulas could expose children to quantities from forty to one hundred and thirty times higher than advertised on the label.
Now this is not unusual in supplements from the US. Apologies to our US followers, but it is a reminder that often the cheaper brands may cost you more in the long-run.
So what do you think?
In a world where it seems as if it’s hard to get a straight answer, I’m hoping articles like this help to demystify when things like melatonin might help and where in the case of mental health sleep issues, it doesn’t.
It’s fair to say, though, that in a world dominated by bright lights from our screens, it may have a more significant role to play beyond our sleep that will be exciting to follow.
Hope this helps x
References
[1] Touitou Y. La mélatonine: hormone et médicament [Melatonin: hormone and medication]. C R Seances Soc Biol Fil. 1998;192(4):643-657.
[2] Karasek M, Winczyk K. Melatonin in humans. J Physiol Pharmacol. 2006;57 Suppl 5:19-39.
[1] Cohen PA, Avula B, Wang Y, Katragunta K, Khan I. Quantity of Melatonin and CBD in Melatonin Gummies Sold in the US. JAMA. 2023;329(16):1401–1402. doi:10.1001/jama.2023.2296
[2] Dollins AB, Zhdanova IV, Wurtman RJ, Lynch HJ, Deng MH. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci U S A. 1994;91(5):1824-1828. doi:10.1073/pnas.91.5.1824
[3] Xu H, Zhang C, Qian Y, et al. Efficacy of melatonin for sleep disturbance in middle-aged primary insomnia: a double-blind, randomised clinical trial. Sleep Med. 2020;76:113-119. doi:10.1016/j.sleep.2020.10.018
[4] Reddy S, Reddy V, Sharma S. Physiology, Circadian Rhythm. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519507/
[5] Arendt J. Melatonin: characteristics, concerns, and prospects. J Biol Rhythms. 2005;20(4):291-303. doi:10.1177/0748730405277492
[6] Tordjman S, Chokron S, Delorme R, et al. Melatonin: Pharmacology, Functions and Therapeutic Benefits. Curr Neuropharmacol. 2017;15(3):434-443. doi:10.2174/1570159X14666161228122115
[7] Reiter RJ, Tan DX, Maldonado MD. Melatonin as an antioxidant: physiology versus pharmacology. J Pineal Res. 2005;39(2):215-216. doi:10.1111/j.1600-079X.2005.00261.x
[8] Bubenik GA. Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci. 2002;47(10):2336-2348. doi:10.1023/a:1020107915919
[9] Savage RA, Zafar N, Yohannan S, et al. Melatonin. [Updated 2022 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534823/
[10] Fowler S, Hoedt EC, Talley NJ, Keely S, Burns GL. Circadian Rhythms and Melatonin Metabolism in Patients With Disorders of Gut-Brain Interactions. Front Neurosci. 2022;16:825246. Published 2022 Mar 9. doi:10.3389/fnins.2022.825246
[11] Huether G. Melatonin synthesis in the gastrointestinal tract and the impact of nutritional factors on circulating melatonin. Ann N Y Acad Sci. 1994;719:146-158. doi:10.1111/j.1749-6632.1994.tb56826.x
[12] Chaplin DD. Overview of the immune response. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S3-S23. doi:10.1016/j.jaci.2009.12.980
More references!
[13] Hardeland R, Pandi-Perumal SR. Melatonin, a potent agent in antioxidative defense: actions as a natural food constituent, gastrointestinal factor, drug and prodrug. Nutr Metab (Lond). 2005;2:22. Published 2005 Sep 10. doi:10.1186/1743-7075-2-22
[14] Koyama H, Nakade O, Takada Y, Kaku T, Lau KH. Melatonin at pharmacologic doses increases bone mass by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation. J Bone Miner Res. 2002;17(7):1219-1229. doi:10.1359/jbmr.2002.17.7.1219
[15] Kotlarczyk MP, Lassila HC, O’Neil CK, et al. Melatonin osteoporosis prevention study (MOPS): a randomized, double-blind, placebo-controlled study examining the effects of melatonin on bone health and quality of life in perimenopausal women. J Pineal Res. 2012;52(4):414-426. doi:10.1111/j.1600-079X.2011.00956.x
[16] Tan DX, Manchester LC, Fuentes-Broto L, Paredes SD, Reiter RJ. Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity. Obes Rev. 2011;12(3):167-188. doi:10.1111/j.1467-789X.2010.00756.x
[17] Wong WK, Chan WK. Nonalcoholic Fatty Liver Disease: A Global Perspective. Clin Ther. 2021;43(3):473-499. doi:10.1016/j.clinthera.2021.01.007
[18] Fatemeh G, Sajjad M, Niloufar R, Neda S, Leila S, Khadijeh M. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials. J Neurol. 2022;269(1):205-216. doi:10.1007/s00415-020-10381-w
[19] Beck-Friis J, Kjellman BF, Aperia B, et al. Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome. Acta Psychiatr Scand. 1985;71(4):319-330. doi:10.1111/j.1600-0447.1985.tb02531.x
[20] Beck-Friis J, Kjellman BF, Aperia B, et al. Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome. Acta Psychiatr Scand. 1985;71(4):319-330. doi:10.1111/j.1600-0447.1985.tb02531.x
[21] Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One. 2013;8(5):e63773. Published 2013 May 17. doi:10.1371/journal.pone.0063773
[22] Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One. 2013;8(5):e63773. Published 2013 May 17. doi:10.1371/journal.pone.0063773
[23] https://news.rthk.hk/rthk/en/component/k2/1668460-20220926.htm, viewed 21st October 2022.
[24] Lin YY, Lee WT, Yang HL, Weng WC, Tsai SY. Hu Li Za Zhi. 2021;68(4):53-63. doi:10.6224/JN.202108_68(4).07
