Melatonin: the body's natural sleep aid

Melatonin is a natural hormone produced in your body by the pineal gland located in the brain.  Melatonin is responsible for regulating our circadian rhythm in the management of our natural sleep cycle.

In addition to improving sleep, melatonin is also involved in managing immune function, blood pressure and cortisol levels.

Melatonin, Sleep and Circadian Rhythm

We all have a natural flow that regulates our sleep and wake cycle called the circadian rhythm.  Not everyone’s circadian rhythm is the same. This is why some people are early risers and others prefer to stay up late.

Our circadian rhythm works on a 24-hour cycle and tells us to go to sleep when it gets dark and wake up when it’s light out.

Melatonin is the hormone that regulates the body’s circadian rhythm and it is at its lowest throughout the day and peaks in the evening, telling us that it’s time for bed.

Circadian rhythm disruption occurs with travel and can be experienced as “jet lag”.  Shift work can also have a dramatic impact our circadian rhythm.  Once disrupted, it can take time to get our melatonin levels back to normal.

Melatonin and Sleep

There are a number of research studies that have demonstrated that melatonin can support better sleep.

A large meta-analysis included nineteen studies involving 1,683 adults and children with sleep disorders.

Melatonin demonstrated significant efficacy in reducing sleep latency and increasing total sleep time. Trials with longer duration and using higher doses of melatonin demonstrated greater effects on decreasing sleep latency and increasing total sleep time. Overall sleep quality was significantly improved in subjects taking melatonin compared to placebo. No significant effects of trial duration and melatonin dose were observed on sleep quality.

This meta-analysis demonstrated that melatonin decreases sleep onset latency, increases total sleep time and improves overall sleep quality. While the effects of melatonin on sleep for some are modest, they do not appear to dissipate with continued use.

In a double-blind, placebo-controlled study, cancer patients, who frequently have trouble with sleep, were given melatonin.  In 50 patients taking melatonin two hours before bed, subjects fell asleep faster and enhanced overall sleep quality.

In another randomized, placebo-controlled study, 791 adults were given melatonin nightly.  Results showed that patients provided melatonin fell asleep faster and experienced improved sleep.

In addition to improving sleep, melatonin is also involved in managing immune function, blood pressure and cortisol levels.

Melatonin is a Powerful Antioxidant

Beyond its role in sleep, melatonin provides antioxidant health benefits. It increases antioxidant enzymes in the body that maintain health on a cellular level.

Melatonin binds to free radicals like reactive oxygen and nitrogen species, neutralizing them, and rendering them less harmful. Free radicals are harmful because they damage cell structure, which can include damage to our genetic material like DNA.

Cellular damage that includes DNA can lead to aging, infertility and other chronic conditions. As an antioxidant, melatonin protects the body from free radical damage. This process takes place in many parts of the body, particularly the eyes, bone marrow, the brain, as well as the digestive and the reproductive organs.

One study in particular showed that one single molecule of melatonin has the power to neutralize up to 10 molecules of hydrogen peroxide. This study describes melatonin as a, kind of “scavenger” that detoxifies the body, one cell at a time by keeping free radical concentrations under control.

Mitochondrial Protection

The mitochondria are the parts of the cell responsible for generating energy. When they produce energy, ROSs (reactive oxygen species) and RNSs (reactive nitrogen species) are its by-products.

As already mentioned above, these ROSs and RNSs damage mitochondrial DNA and proteins, leading to cell death.  Melatonin is naturally occurring in the parts of the body that need it the most, including the heart, brain and nervous system.

By acting as an antioxidant, it protects and cleans up the mitochondria of the cells and prevents disease in these parts of the body when present in healthy amounts.

Immune Support

Research indicates that melatonin assists in regulating our immunity.  Some evidence suggests that it is an immune-stimulant, while other studies suggest it has anti-inflammatory properties.

One study concluded:

The immunomodulatory properties of melatonin are well known; it acts on the immune system by regulating cytokine production of immunocompetent cells. Experimental and clinical data showing that melatonin reduces adhesion molecules and pro-inflammatory cytokines and modifies serum inflammatory parameters. As a consequence, melatonin improves the clinical course of illnesses which have an inflammatory etiology. Moreover, experimental evidence supports its actions as a direct and indirect antioxidant, scavenging free radicals, stimulating antioxidant enzymes, enhancing the activities of other antioxidants or protecting other antioxidant enzymes from oxidative damage. Several encouraging clinical studies suggest that melatonin is a neuroprotective molecule in neurodegenerative disorders where brain oxidative damage has been implicated as a common link.

In this review article, the authors examine the effect of melatonin on several neurological conditions and conclude that melatonin provides a safe and nontoxic intervention in central nervous system (CNS) conditions.

Melatonin and Travel

Melatonin has been studied extensively as a treatment for jet lag. Much of the research regarding melatonin and jet lag has been positive.

One research article reviewed melatonin as a treatment for jet lag in 10 different studies. In 9 out of 10 of the studies reviewed, melatonin was found to decrease jet lag in people crossing five or more time zones. The benefits of melatonin, as in a decrease in jet lag symptoms, was noted when taken close to the local bedtime of the destination.  In this way, the melatonin was believed to act to supplementally adjust the natural circadian rhythm to match the new destination time zone.

A more recent article from 2014, reviewed studies of the use of melatonin in various health conditions, including preventing jet lag. This review of eight randomized clinical trials looking at jet lag, with a total of more than 900 participants, found that six of the eight trials favored melatonin over the control for counteracting the effects of jet lag.

Melatonin:  A Proven Sleep Aid with Multiple Benefits

From a functional and a research perspective, it is clear that melatonin plays an important role in sleep hygiene. As a means for assisting in situations where sleep is disrupted, melatonin is a natural, non-toxic supplement which clearly helps to bring on sleep and support a more restful night.  In situations of travel, where normal sleep patterns and circadian rhythms may be interrupted, melatonin is the perfect way to help your body align to a new time zone and get the rest you need to be at your best.

References

1. 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
2. Kurdi MS, Muthukalai SP. The Efficacy of Oral Melatonin in Improving Sleep in Cancer Patients with Insomnia: A Randomized Double-Blind Placebo-Controlled Study. Indian J Palliat Care. 2016;22(3):295-300. doi:10.4103/0973-1075.185039
3. Costello RB, Lentino CV, Boyd CC, et al. The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature. Nutr J. 2014;13:106. Published 2014 Nov 7. doi: 10.1186/1475-2891-13-106
4. Wade AG, Ford I, Crawford G, McConnachie A, Nir T, Laudon M, Zisapel N. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo-controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Med. 2010 Aug 16;8:51. doi: 10.1186/1741-7015-8-51. PMID: 20712869; PMCID: PMC2933606.
5. Tan DX, Manchester LC, Reiter RJ, Plummer BF, Limson J, Weintraub ST, Qi W. Melatonin directly scavenges hydrogen peroxide: a potentially new metabolic pathway of melatonin biotransformation. Free Radic Biol Med. 2000 Dec;29(11):1177-85. doi: 10.1016/s0891-5849(00)00435-4. PMID: 11121726.
6. Esposito E, Cuzzocrea S. Antiinflammatory activity of melatonin in central nervous system. Curr Neuropharmacol. 2010;8(3):228-242. doi:10.2174/157015910792246155
7. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev. 2002;(2):CD001520. doi: 10.1002/14651858.CD001520. PMID: 12076414.
8. Pandi-Perumal S, Srinivasan V, Spence D, Cardinali D. Role of the melatonin system in the control of sleep: therapeutic implications. CNS Drugs. 2007;21:995–1018. doi: 10.2165/00023210-200721120-00004.
9. Pevet P, Challet E. Melatonin: both master clock output and internal time-giver in the circadian clocks network. J Physiol Paris. 2011;105:170–182. doi: 10.1016/j.jphysparis.2011.07.001.
10. Zhdanova I. Melatonin as a hypnotic: Pro. Sleep Med Rev. 2005;9:51–65. doi: 10.1016/j.smrv.2004.04.003.
11. Rajaratnam SM, Dijk DJ, Middleton B, Stone BM, Arendt J. Melatonin phase-shifts human circadian rhythms with no evidence of changes in the duration of endogenous melatonin secretion or the 24-hour production of reproductive hormones. J Clin Endocrinol Metab. 2003;88:4303–4309. doi: 10.1210/jc.2003-030460.
12. Rajaratnam SM, Middleton B, Stone BM, Arendt J, Dijk DJ. Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans. J Physiol. 2004;561:339–351. doi: 10.1113/jphysiol.2004.073742.
13. Arendt J, Aldhouse M, English J, Marks V, Arendt J, Marks M, Folkard S. Some effects of jet-lag and their alleviation by melatonin. 1987;30:1379–1393. doi: 10.1080/00140138708966031.
14. Spitzer RL, Terman M, Williams JB, Terman JS, Malt UF, Singer F, Lewy AJ. Jet lag: clinical features, validation of a new syndrome-specific scale, and lack of response to melatonin in a randomized, double-blind trial. Am J Psychiatry. 1999;156:1392–1396.
15. Claustrat B, Brun J, David M, Sassolas G, Chazot G. Melatonin and jet lag: confirmatory result using a simplified protocol. Biol Psychiatry. 1992;32:705–711. doi: 10.1016/0006-3223(92)90300-O.
16. Petrie K, Conaglen JV, Thompson L, Chamberlain K. Effect of melatonin on jet lag after long haul flights. 1989;298:705–707. doi: 10.1136/bmj.298.6675.705.
17. Suhner A, Schlagenhauf P, Johnson R, Tschopp A, Steffen R. Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag. Chronobiol Int. 1998;15:655–666. doi: 10.3109/07420529808993201.
18. Petrie K, Dawson AG, Thompson L, Brook R. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatry. 1993;33:526–530. doi: 10.1016/0006-3223(93)90007-Z.
19. Almeida Montes LG, Ontiveros Uribe MP, Cortes Sotres J, Heinze Martin G. Treatment of primary insomnia with melatonin: a double-blind, placebo-controlled, crossover study. J Psychiatry Neurosci. 2003;28:191–196.