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What is Melatonin and how does it work as a Natural Sleep Aid?

Melatonin is one of the most important hormones in the human body, but its importance was not fully understood until fairly recently. It was first discovered in the early 1900s when scientists were researching changes in pigmentation on tadpoles.[1] They found that feeding tadpoles extracts from cow pineal gland caused the tadpoles to turn a lighter shade.[2] However, it wasn’t until the mid-1970s that researchers figured out its role in maintaining the human circadian rhythm[3], and its antioxidant effects were only discovered in the early 1990s![4]

In fact, it wasn’t until the mid-1990’s that researchers discovered this hormone’s presence in plants, and they’re still trying to figure out all its functions in plant species. So far, they've worked out that it is also involved in regulating the circadian rhythm, protecting plant cells, and that it might be involved in regulating plant growth.[5]

what is melatonin for sleep?

Melatonin supplements are sold in a number of countries around the world as a safe and natural sleep aid. Research has shown that it has a good bioavailability, and numerous benefits in the body – including helping to reduce the time taken to fall asleep, to prevent jet lag, and to support a healthy immune system. Unfortunately, not all countries allow the sale of this natural sleep aid over the counter, with some governments insisting that it be sold only by prescription.

In this article, we explore some of the top information about this natural compound, to give you a better idea of Melatonin supplements and why people are talking about them today!

 

Melatonin in the Human Body

Melatonin (also known by its scientific name, N-acetyl-5-methoxytryptamine) is a hormone and neurotransmitter found in plants and most animal species. It is produced in the human brain to regulate the sleep-wake cycle (the circadian rhythm). Although our brain is capable of synthesizing the hormone, recent studies have indicated that a substantial amount of its production requires consumption of L-Tryptophan or Melatonin-rich foods. In fact, research shows that fasting for 2-7 days causes a drop in concentrations of up to 20%![6] Further research has indicated that people who eat plant-based diets that are rich in fruits and vegetables tend to have higher concentrations of Melatonin.[7]

Melatonin is produced by the pineal gland from L-Tryptophan (which is also used to produce serotonin). Its production is strictly regulated through the use of intermediate compounds. For example, norepinephrine (released throughout the day) suppresses Melatonin production. Blue-light also prevents the production of this hormone and reduces sleepiness. In contrast, dim, yellowish light (often associated with sunset colours) signals for the resumed production of Melatonin.

In terms of its ability to help promote sleep, after it has been synthesized, Melatonin binds to receptors in the brain called M1 and M2 receptors.[8] These receptors send signals to a wide variety of areas in the body to get ready for sleep. Reduced levels of Melatonin are associated with a number of ailments and illnesses. These include neurodegenerative diseases like Alzheimer’s and dementia. Most importantly, low levels of Melatonin at night are an important indicator of difficulties with sleep.[9]

melatonin helps regulate the circadian rhythm

What is Melatonin? The Pineal Gland

The pineal gland is a small endocrine gland located directly in the centre of the vertebrate brain. Its functions are still not completely understood. However, it is understood that this is the gland responsible for synthesizing and secreting Melatonin. Its name is related to its shape, which resembles a pinecone. It was first described by Rene Descartes, the grandfather of modern science, as the “seat of the soul”, and has been a subject of pseudoscience for decades.[10]

It was recently discovered that the human pineal gland is capable of secreting N,N-Dimethyltryptamine (DMT), a compound found in almost all plants and animals, with powerful hallucinogenic effects.[11] It is the active component of the Ayahuasca drink – an ancient shamanic cocktail originating from tribes in the Amazonian jungle.[12] The role of DMT in the human body is still not fully understood.

Recent research indicates that the pineal gland is subject to calcification, even in children of very young ages.[13] This is thought to be due to a number of factors and is partly because the pineal gland is not separated from the rest of the body by the blood-brain barrier, allowing the deposition of minerals.[14] In some studies, researchers have found that the pineal gland contains the highest concentrations of fluoride in the body, greater than bones or teeth.[15]

Calcification of the pineal gland results in reduced Melatonin production and is associated with an increased risk of dementia and Alzheimer’s disease.[16] Interestingly, the theory that calcification increases with age is strongly contested by the age independence theory (that calcification is not related to age).[17] Prevalence of pineal gland calcification is high, with a recent study finding that, of 500 brain scans reviewed, 58.8% showed significant signs of calcification.[18]

pineal-gland-melatonin-illustration-vector

Melatonin in Plants - a new discovery

Today, Melatonin is mostly thought of in terms of its effects on sleep in humans, and until 1995, scientists didn’t realize that it occurs in plants as well as animals. However, recent studies have found that this amazing hormone actually occurs in varying concentrations in ALL plants that have been tested to-date.[19] In general, it occurs in greater concentrations in the seeds and leaves of plants, while fruit tends to contain the least amounts.[20]

Some medicinal herbs contain such high levels of Melatonin that it could actually be considered to be a part of the biochemical mechanism behind their effects. Examples include St. John’s wort, feverfew, and a number of Chinese medical herbs.[21]

In plants, this hormone is used to regulate reproductive systems and the circadian rhythm, just like in animals. In early studies, researchers found that the highest levels of Melatonin occur after dark.[22] It also helps to protect plant cells from toxins (as a powerful antioxidant) and from environmental stresses.[23] Finally, researchers believe that this amazing hormone might also be partly responsible for regulating vegetative growth because of its similarity to Indole-3-acetic acid (IAA), a plant hormone that stimulates growth. [24]

melatonin-in-plants-circadian-rhythm

Melatonin Supplements for Sleep

melatonin from liftmodeMelatonin is legally sold in many countries around the world as a supplement. In the United States, the Food and Drug Administration (FDA) has labelled this natural hormone as a dietary supplement, and it can be sold by registered vendors, so long as they meet the current good manufacturing processes (cGMP) as outlined by the FDA. This requires that accurate labels and information be provided and that all supplements be properly standardized.

 

In Canada, the status of Melatonin as a dietary supplement is somewhat contested. For a long time, it could be sold as a dietary supplement, but it was rescheduled to a prescription-only compound. However, recent amendments allow it to be sold as a dietary supplement, in small amounts. Countries like the United Kingdom (UK), European Union, Japan, and Australia do not allow over-the-counter sales of Melatonin without a prescription.[25]

Luckily for those people who live in countries where this natural hormone can be easily purchased online or imported without difficulties at customs, it is highly effective when taken as a supplement. When taken orally, it tends to have good bioavailability at the recommended serving size. It takes around 1.5 hours to reach the maximum concentration and has a half-life of around 2 hours.[26] This is why people recommend taking Melatonin supplements around 2 hours prior to sleep.

 

Research has found that this supplement has the potential to offer a number of great benefits when used correctly. There has been a robust amount of high-quality research conducted on its effects, most of which point towards positive benefits in reducing the time taken to fall asleep, regardless of age or sex.[27] Furthermore, research shows that this supplement can help to reduce the symptoms of jet-lag, and to help with sleep issues for shift-workers.[28] Finally, it is a powerful antioxidant that helps to support a healthy body.[29]

 

Warnings when Taking Melatonin Supplements

melatonin helps to regulate sleepMelatonin has been studied by many high-level researchers for its effects in humans. It is safe for use by most people when taken at the recommended serving size. In a 2016 review, researchers found that only mild adverse effects like dizziness, headache, nausea and sleepiness had been reported, in all studies up to that date – even in those using very large servings. According to the authors, there is no evidence that Melatonin should induce any serious side effects. However, long-term safety in children and adolescents needs to be investigated further.[30]

According to WebMD, a good resource for information on supplements, Melatonin may not be safe for use by pregnant and nursing women, and due to a lack of research on this population, it would be better to avoid using it. This supplement may also have negative effects on people who suffer from bleeding disorders, diabetes, depression, high blood pressure, or seizures. If you have any underlying medical conditions, please speak to your doctor before using this supplement.[31]

One important consideration is the quality of the supplement itself. Recent studies have found that the actual content of many supplements varies widely from what is on the label. In more than 71% of Melatonin supplements tested, the actual content varied from between 83% less to 438% more than what was on the label. [25] Always purchase supplements from reputable vendors who supply a valid Certificate of Analysis (preferably from a 3rd-party, independent laboratory) testifying to the contents of the supplement.

Conclusion - What is Melatonin and how can it help with sleep?

So, what is Melatonin, really? Well, it is a hormone found in both animals and plants, that helps to regulate the circadian rhythm (the natural body-clock). It was first discovered in animals but has since been found to occur in all plant species tested. In humans, it is secreted by the pineal gland – a small pinecone-shaped gland in the centre of the brain – in response to detected changes in light and dark. It binds to receptor proteins that send signals to the rest of the body to prepare for sleep.

When used as a dietary supplement, Melatonin is effective in helping to reduce the time taken to fall asleep, and to prevent symptoms of jet-lag. There is evidence that it might be helpful for people who work night-shifts, as well as helping to support a healthy body and immune system. Melatonin supplements are safe for use by most people and do not tend to produce any serious adverse effects. People with underlying medical conditions should speak to their doctor before using any supplements, including Melatonin.

melatonin chemical structure

 
 

Medical Disclaimer


Not intended to treat, diagnose, or cure any disease or ailment. Please read and fully understand potential adverse effects before using this product. These statements have not been reviewed by the FDA and are not written by a medical professional. Please consult your doctor before using any supplements, especially if you have any medical conditions.

 

References:

[1] Filadelfi AM, Castrucci AM. Comparative aspects of the pineal/melatonin system of poikilothermic vertebrates. J Pineal Res. 1996 May;20(4):175-86.

[2] Coates PM, Blackman MR, Cragg GM, Levine M, Moss J, White JD (2005). Encyclopedia of dietary supplements. New York, N.Y: Marcel Dekker. pp. 457–66. ISBN 0-8247-5504-9.

[3] Lynch HJ, Wurtman RJ, Moskowitz MA, Archer MC, Ho MH (January 1975). Daily rhythm in human urinary melatonin. Science. 187 (4172): 169–71

[4] Poeggeler B, Reiter RJ, Tan DX, Chen LD, Manchester LC (May 1993). Melatonin, hydroxyl radical-mediated oxidative damage, and aging: a hypothesis. J. Pineal Res. 14 (4): 151–68.

[5] Hardeland R. Melatonin in Plants – Diversity of Levels and Multiplicity of Functions. Frontiers in Plant Science. 2016;7:198.

[6] Röjdmark S, Wetterberg L. Short-term fasting inhibits the nocturnal melatonin secretion in healthy man. Clin Endocrinol (Oxf). (1989)

[7] Nagata C, et al. Association of vegetable intake with urinary 6-sulfatoxymelatonin level. Cancer Epidemiol Biomarkers Prev. (2005)

[8] Doghramji K. Melatonin and Its Receptors: A New Class of Sleep-Promoting Agents. Journal of Clinical Sleep Medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2007;3(5 Suppl):S17-S23.

[9] Hardeland R. Neurobiology, Pathophysiology, and Treatment of Melatonin Deficiency and Dysfunction. The Scientific World Journal. 2012;2012:640389.

[10] Descartes and the Pineal Gland, Stanford Encyclopedia of Philosophy, First published Mon Apr 25, 2005; substantive revision Wed Sep 18, 2013, available online from https://plato.stanford.edu/entries/pineal-gland/ [Accessed May 31, 2018]

[11] Gallimore AR, Strassman RJ. A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience. Frontiers in Pharmacology. 2016;7:21 .

[12] Frecska E, Bokor P, Winkelman M. The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization. Frontiers in Pharmacology. 2016;7:35.

[13] Whitehead MT, Oh C, Raju A, Choudhri AF. Physiologic pineal region, choroid plexus, and dural calcifications in the first decade of life. AJNR Am J Neuroradiol. 2015;36:575–580.

[14] Kaur C, Ling EA. The circumventricular organs. Histol Histopathol. 2017 Sep;32(9):879-892.

[15] Luke J. Fluoride deposition in the aged human pineal gland. Caries Res. 2001 Mar-Apr;35(2):125-8.

[16] Mahlberg R, Walther S, Kalus P, Bohner G, Haedel S, Reischies FM, Kühl KP, Hellweg R, Kunz D. Pineal calcification in Alzheimer's disease: an in vivo study using computed tomography. Neurobiol Aging. 2008 Feb;29(2):203-9. Epub 2006 Nov 13.

[17] Galliani I, Falcieri E, Giangaspero F, Valdrè G, Mongiorgi R. A preliminary study of human pineal gland concretions: structural and chemical analysis. Boll Soc Ital Biol Sper. 1990 Jul;66(7):615-22.

[18] Mutalik S, Tadinada A. Prevalence of pineal gland calcification as an incidental finding in patients referred for implant dental therapy. Imaging Science in Dentistry. 2017;47(3):175-180.

[19] Paredes SD, Korkmaz A, Manchester LC, Tan DX, Reiter RJ (2009-01-01). Phytomelatonin: a review. Journal of Experimental Botany. 60 (1): 57–69.

[20] Dubbels R, Reiter RJ, Klenke E, Goebel A, Schnakenberg E, Ehlers C, Schiwara HW, Schloot W. Melatonin in edible plants identified by radioimmunoassay and high performance liquid chromatography-mass spectrometry. J Pineal Res. 1995;18:28–31

[21] Chen G, Huo Y, Tan DX, Liang Z, Zhang W, Zhang Y. Melatonin in Chinese medicinal herbs. Life Sci. 2003;73:19–26.

[22] Wolf K, Erwin K, Witters E, van Dongen W van Onckelen H, Macháčková I. Daily profile of melatonin levels in Chenopodium rubrum L. depends on photoperiod. Journal of Plant Physiology, Volume 158, Issue 11, 2001, Pages 1491-1493

[23] Arnao MB, Hernández-Ruiz J. The Physiological Function of Melatonin in Plants. Plant Signaling & Behavior. 2006;1(3):89-95.

[24] Murch S, Saxena PK. Melatonin: A potential regulator of plant growth and development? In vitro Cell Dev Biol Plant. 2002;38:531–536.

[25]  Grigg-Damberger MM, Ianakieva D. Poor Quality Control of Over-the-Counter Melatonin: What They Say Is Often Not What You Get. Journal of Clinical Sleep Medicine: JCSM : Official Publication of the American Academy of Sleep Medicine. 2017;13(2):163-165.

[26] Gooneratne NS, Edwards AYZ, Zhou C, Cuellar N, Grandner MA, Barrett JS. Melatonin pharmacokinetics following two different oral surge-sustained release doses in older adults. Journal of pineal research. 2012;52(4):437-445

[27] Costello RB, Lentino CV, Boyd CC, et al. The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature. Nutrition Journal. 2014;13:106.

[28] Malhotra S, Sawhney G, Pandhi P. The Therapeutic Potential of Melatonin: A Review of the Science. Medscape General Medicine. 2004;6(2):46.

[29] Korkmaz A, Reiter RJ, Topal T, Manchester LC, Oter S, Tan D-X. Melatonin: An Established Antioxidant Worthy of Use in Clinical Trials. Molecular Medicine. 2009;15(1-2):43-50.

[30] Andersen LP, Gögenur I, Rosenberg J, Reiter RJ. The Safety of Melatonin in Humans. Clin Drug Investig. 2016 Mar;36(3):169-75.

[31] Melatonin, WebMD.com, available online from https://www.webmd.com/vitamins/ai/ingredientmono-940/melatonin [Accessed June 1, 2018]