Authored by Sumeet Sharma • 
July 10, 2016
 • 3 min read

Take Home Points

  • Melatonin is a hormone produced in the pineal gland of the brain that promotes sleep and regulates the circadian rhythm (sleep-wake cycle).

  • Safe and effective way to regulate your sleep cycle via supplementation

  • There is good evidence that melatonin is helpful in improving memory under stress and decreasing inflammation


Melatonin, also known as n-acetyl-5-methoxytryptamine, circadin


In the body, the starting material for making melatonin is the dietary amino acid L-tryptophan. It undergoes a series of reactions with enzymes to become melatonin as seen below.

Melatonin Biosynthesis Pathway Biosynthetic pathway of melatonin.


Melatonin is naturally produced by the pineal gland in the brain.

Melatonin supplements are synthetically manufactured and are molecularly identical to the natural form.

How to take

Take a dose of 0.5 up to 5 mg of melatonin daily about 30 minutes prior to bedtime for jet lag or sleeping difficulty. It is important to note that the effects of melatonin are not dose dependent, which means the more you take doesn't help you fall asleep necessarily faster. Adjust the dosage accordingly.

Effects on the Brain


Melatonin primarily regulates the sleep-wake cycle. As melatonin levels rise, so does your drive to fall asleep. Two important parameters of sleep are improved by melatonin: sleep efficiency, the quality of the sleep you get, and sleep latency, or time required to fall asleep.1

Melatonin Circadian Rhythm The top graph shows wakefulness, measured by video recording, and the bottom shows melatonin levels at these same times. Notice that melatonin peaks when wakefulness is at its lowest level.

Melatonin is thought to promote sleep by acting directly in the brain as well as causing cooling by acting on the peripheral blood vessels. Melatonin may reduce blood pressure in elderly individuals, particularly between 3 am - 8 am, when the risk for cardiovascular complications is highest.2

Melatonin levels also decrease with aging, correlating with reduced sleep quality in older individuals.3

The Howard Hughes Medical Institute has a wonderful animation describing the regulation of your "biological clock" in the brain.

Anatomy of the Pineal Gland and the Suprachiasmatic Nucleus The pineal gland is where melatonin is produced. The suprachiasmatic nucleus is where it acts to regulate sleep.

Insomnia is difficulty in falling and/or staying asleep. Melatonin has been shown to improve outcomes in elderly patients with insomnia.4In another study, prolonged-release melatonin improved sleep quality and morning alertness in insomnia patients aged 55 years and older. No withdrawal effects were noted.5

Another important use of melatonin is rescuing sleep-wake cycles that have been perturbed by light exposure. For those of us who spend countless hours in front of a computer, the blue light of the screen is particularly disruptive of our normal circadian rhythm. Melatonin at night may be beneficial for both maintaining desired sleep-walk cycle and resuscitating it after environmental disruption.

Melatonin supplementation at or near bedtime has been shown to be a powerful method to pre-set your sleep wake-cycle and reduce jet lag, according to a 2002 meta-analysis.6

Side Effects

Melatonin is categorized as generally regarded as safe (GRAS) by the FDA. Long term studies have shown that it is not habit forming and does not have deleterious effects with frequent use, even in adolescents.7Developing tolerance is also not an issue.


Avoid taking melatonin in close proximity to a meal, as melatonin acutely may reduce glucose tolerance.8

Do not drive or operate heavy machinery 5-6 hours after taking melatonin

Melatonin may interact with blood thinning medications (anticoagulants), immunosuppressants, diabetes medications, and birth control pills. Please see your doctor before taking melatonin if you are taking one of these types of medications, or are unsure.s

  1. Tuli, H. S., Kashyap, D., Sharma, A. K., & Sandhu, S. S. (2015). Molecular aspects of melatonin (MLT)-mediated therapeutic effects. Life Sci, 135, 147-157. doi:10.1016/j.lfs.2015.06.004

  2. Gubin, D. G., Gubin, G. D., Gapon, L. I., & Weinert, D. (2015). Daily Melatonin Administration Attenuates Age-Dependent Disturbances of Cardiovascular Rhythms. Curr Aging Sci.

  3. Olbrich, D., & Dittmar, M. (2011). Older poor-sleeping women display a smaller evening increase in melatonin secretion and lower values of melatonin and core body temperature than good sleepers. Chronobiol Int, 28(8), 681-689. doi:10.3109/07420528.2011.599904

  4. Luthringer, R., Muzet, M., Zisapel, N., & Staner, L. (2009). The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia. Int Clin Psychopharmacol, 24(5), 239-249. doi:10.1097/YIC.0b013e32832e9b08

  5. Lemoine, P., Nir, T., Laudon, M., & Zisapel, N. (2007). Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res, 16(4), 372-380. doi:10.1111/j.1365-2869.2007.00613.x

  6. Herxheimer, A., & Petrie, K. J. (2002). Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev(2), Cd001520. doi:10.1002/14651858.cd001520

  7. van Geijlswijk, I. M., Mol, R. H., Egberts, T. C., & Smits, M. G. (2011). Evaluation of sleep, puberty and mental health in children with long-term melatonin treatment for chronic idiopathic childhood sleep onset insomnia. Psychopharmacology (Berl), 216(1), 111-120. doi:10.1007/s00213-011-2202-y

  8. Rubio-Sastre, P., Scheer, F. A., Gomez-Abellan, P., Madrid, J. A., & Garaulet, M. (2014). Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. Sleep, 37(10), 1715-1719. doi:10.5665/sleep.4088

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