Melatonin is a relatively well known compound that is often mentioned in congruence with sleep deprivation or sleeping, in general. Interestingly, although melatonin is widely used, people typically know little about it. Luckily, this article will delve into what melatonin is, if and where it is synthesized in the body, the multiple functions of its use, basic physiology, as well as dosages and effectiveness – so, without further ado, let us begin!

What is melatonin?

Melatonin is a protein based hormone [1][2].

Where does it come from?

Melatonin is primarily synthesized endogenously (aka, inside the body) via the pineal gland located in the brain (other sites are bone marrow, skin, retina, gut, and likely other unknown sites) [1][2][3]. It can also be found in certain plants in inconsequential quantities; as well, as taken exogenously (aka, outside from the body – via pill form, for example)[3]. Melatonin, however, is extremely variable in its synthesis between people – some synthesize high, some normal, and some lower than average amounts [3].

Synthesis Maturation?

Melatonin production via the pineal gland begins after the first 3 months of life after birth with it reaching its highest levels around ages 1-6 years and from there a steady decline until 80% less melatonin relative to bodyweight is seen in adulthood [3][6]. This is likely due to pineal gland production remaining steady while body size increasing; however, melatonin may be mediated through hormonal changes in puberty, but this has not been fully understood [3]. In adulthood, serum melatonin (aka, found in the blood) ranges between 10 – 80 ug/night; rates may decline in later life due to calcification of the pineal gland, but not necessarily to sub-normal levels [3].

How does melatonin work? Function?

This section could easily be an entire mechanistic article, but we’ll spare ourselves the trouble of learning enzymatic activity to understand the interesting basics.

If we investigate the synthesis of melatonin, we will see that melatonin is highly regulated by eye sight, and more specifically, the retina [3]. The retina senses darkness, then neurons linking between the retina and the suprachiasmatic nuclei (SCN) located on the hypothalamus of the brain fire to send the signal for “night time”, at which point, the SCN sends a neural signal to the pineal gland to secrete melatonin via the synthesis of the amino acid tryptophan (found in most proteins) which is then further synthesized into the neurotransmitter serotonin and then melatonin for secretion [3]. Once the pineal gland secretes melatonin into the blood stream, because melatonin is hydrophilic, it is highly soluble and can easily pass through the body to act on a variety of cells; most melatonin binds with blood albumin (a protein) as it travels through the body system, but some free melatonin can also be found in the saliva, urine, and other places [3][7][8]. Interestingly, it is so prevalent, it is also found in amniotic fluid and breast milk, making it a key to infant sleeping in the first few months before the pineal gland activates within the infant [3].

Melatonin’s secretion pattern at night, when sleep is most probable, tends to come in rapid pulses going from almost no release at a given time to sudden jumps in release from the pineal gland [1][3]. These pulses have been measured to be as quick as every 10-20 minutes and tend to be most abundant in release around 3 am [3]. This all makes sense as we understand melatonin to be a huge component of circadian rhythms; circadian rhythms being the “internal clock” or mechanism that regulate the body through waking and sleeping – more on this shortly [9].

Melatonin is well known for its sleep benefits, but melatonin is actually considerably more important than just a sleep aid. The hormone may have a noticeable impact on reducing cancer risk as it acts as a strong anti-oxidant (check out the Oxidative Stress article for more on that), which may be one of the reasons sleep offers such healing benefits as the removal of free radicals (aka, cancer causing agents) is imperative to health [3]. Not only that, melatonin is related to immune function; however, in what capacity is still unknown, we do know there is a link between healthy melatonin levels and a strong immune system [3]. In terms of health, melatonin seems to also have some connection to sex hormone health for both men and women, and while these mechanisms are clear in seasonal animals, they are less clear in humans – so, we will leave it at “there is a connection”, although the extent and in what way said connection occurs is unknown [3][10].

Finally, the most important facet of melatonin is its impact on circadian rhythms. This area extends beyond the sleep cycle, but it most well-known for its sleep factor. Melatonin is so specific, in fact, that it is a reliable indicator of circadian rhythm function as a whole. There is a strong connection between melatonin secretion, routine waking and sleeping, body temperature when slumbering, and may have some impact on cortisol secretion (another hormone, most commonly attributed to stress)[3]. This melatonin secretion is so specific and well-timed that the only long term effective means of reducing melatonin output and keeping wakefulness is through light exposure (presumably, because light – especially blue light – makes the body believe it is daylight)[3]. To be clear, it is the retina (primarily) that informs the pineal gland, via the SCN, that melatonin is to be released.

How effective is melatonin?

Melatonin offers slight benefits in a few key ways. In terms of sleep latency, which is described as the time going from wakefulness to sleep state, melatonin has a small benefit [2]. In terms of overall sleep time, melatonin also has a slight effect [2]. Finally, in terms of sleep quality, melatonin not only has an effect, but that level of effect is seen most consistently in all populations studied [2]. We could put out numbers, but since these numbers come from a variety of dosages and the level of variability between people would mean these numbers are inconsistent in applicable use and could be higher or lower (likely higher, as the averages were relatively low).

Bottom line, it works at the appropriate dosages for you. It should also be stated that a single, immediate release dose of melatonin may not be beneficial in maintaining sleep as we know melatonin is released in sharp waves throughout the night, and in such a case, it may be more of a simulation to ingest time-release melatonin or a combination of the two.

Finally, this seemed appropriate to add to this section, as melatonin intake during the day may be less impactful than in the evening; this is due to the body’s mechanism of “shutting off” melatonin production during the day and increasing secretion at night, meaning the supplement would not have the aid of endogenous production [13].


Melatonin is primarily cleared from the blood via the liver and then excreted in urine [3].


Dosing exogenous melatonin (aka, pills and/or shots, and/or cream, etc.) is relatively simple since it is so variable between people. Melatonin can be taken as needed with some dosages seen as low as 1mg total, 5mg total, 0.1mg/kg of bodyweight (.05mg/lb) all the way up to 50mg/kg of bodyweight (22.7mg/lb)[5][11]. It would be prudent to start on the lower end (1mg total) compared to the higher end [5][11]. It should also be noted, these numbers are assessed in adults, not children.

It might also be useful to note, again, that since melatonin is released by pulses throughout the night, an initial intake may get a person sleepier, but may not sustain sleep as melatonin has a short life within the body as these pulses are normally sustained throughout sleep; so, taking a timed release capsule may be more beneficial for sustained sleep [12].


The safety of melatonin is considered extremely high as studies done to assess toxicity went up as high as 800mg/kg of bodyweight (364mg/lb) with no serious adverse conditions in animals [4]. At worst, melatonin can cause an upset stomach or headache [4]. In humans, dosages up to 6mg/day were tested and also found no adverse effects aside from a bit of drowsiness – as expected [4]. Starting around 1mg/day and slowly moving up is likely prudent.

The only real issue would be in children where melatonin is especially high or supposedly high in which case, extra melatonin may have negative effects as harsh as, in rare cases, seizures [5]. This is likely due to the fact melatonin is a suppressant of excitation and continuous suppression could throw other glands off kilter – true of all ages, but especially important in times of brain and gonad development like childhood.

Overall, melatonin is considered safe, but be sure to take the smallest amount and slowly build up as to assess tolerance.


Although a lot of information was covered throughout the article, we now know that melatonin is a hormone secreted by the body via the pineal gland of the brain. We know that melatonin has important functions in sleep, as well as possible important functions in immunity (especially anti-cancer), and in hormone regulation. Its secretion is mediated, primarily, by light penetrating the retina of the eye – if light is present, melatonin is not secreted, and the opposite is true. Melatonin is most well-known for its proven impact on “wake to sleep” time, quality of sleep, and duration of sleep, but melatonin may be best administered, if administered via pill, shot, or cream, in a timed release form to simulate the body’s mechanism of release. Dosages vary widely and depend on the individual, but starting extremely low is usually prudent (1mg/day), although melatonin (in healthy adults) is considered safe at all tested doses.

Writer: Nicolas Verhoeven
This is educational material only and not meant to be prescripton, consult your physician before making any changes.


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[9] Circadian Rhythms Fact Sheet. (n.d.). Retrieved from National Institute of General Medical Sciences website:

[10] Luboshitzky, R., & Lavie, P. (1999). Melatonin and Sex Hormone Interrelationships - A Review. Journal of Pediatric Endocrinology and Metabolism, 12(3). Retrieved from

[11] Vural, E. M., Van Munster, B. C., & De Rooij, S. E. (2014). Optimal Dosages for Melatonin Supplementation Therapy in Older Adults: A Systematic Review of Current Literature.Drugs Aging, 31(6), 441-451. Retrieved from

[12] Leppämäki, S., Partonen, T., Vakkuri, O., Lönnqvist, J., Partinen, M., & Laudon, M. (2003). Effect of controlled-release melatonin on sleep quality, mood, and quality of life in subjects with seasonal or weather-associated changes in mood and behaviour. European Neuropsychopharmacology, 13(3), 137-145. Retrieved from

[13] Arendt, J., Bojkowski, C., Folkard, S., Franey, C., Marks, V., Minors, D., … Wright, J. (2008). Some Effects of Melatonin and the Control of its Secretion in Humans.Ciba/Photoperiodism, 266-283. Retrieved from

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