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Theoretically, much like other nutrients, several factors could affect the bioavailability of a melatonin supplement, including overall reduced digestion and absorption capacity, the composition of the gut microbiome, genetic variability in enzymes that metabolize melatonin, and/or the excipient profile of the dietary supplement, to name a few. It is well accepted that melatonin in tablet or capsule form is generally not very bioavailable (1 to 74%) and can be influenced by multiple variables (1). A systematic review by researchers at the University of Copenhagen cited an average of 15% bioavailability from oral melatonin, which was highly variable (range: 9–33%) and affected by age, illness, caffeine, smoking, and medications (2).


From a pharmacokinetic standpoint, Vasey, McBride, and Penta (3) indicated that melatonin administered in tablet or capsule forms follows first-order or concentration-dependent kinetics. This implies that the kinetic absorption of melatonin is, in fact, not saturable, meaning that larger doses would produce higher plasma concentrations. Oral melatonin has been studied to reach peak plasma concentration after forty-one minutes of administration, although it was reported that melatonin pharmacokinetics varied greatly between individuals (3).


Because of its well-recognized low bioavailability, scientific innovations are underway to develop formulations that bypass the gastrointestinal tract, have a longer half-life, and/or leverage nanotechnology (4–6). Overall, more research is needed to better understand the bioavailability of various formats and sources of melatonin, as well as innovative developments to optimize its physiological effects (7). Another area of research to investigate is how the different sources of supplemental melatonin may vary in uptake. For example, whether a phytomelatonin form in its natural plant complex is more readily absorbed than one chemically synthesized. At this junction, these questions remain unanswered.


Authors: Deanna Minich, Ph.D., Melanie Henning, ND, Catherine Darley, ND, Mona Fahoum, ND, Corey B. Schuler, DC, James Frame

Reviewer: Peer-review in Nutrients Journal

Last updated: September 22, 2022




1. Savage R, Zafar N, Yohannan S, Miller JM. Melatonin. Treasure Island (FL): StatPearls Publishing; 2022.

2. Harpsøe NG, Andersen LPH, Gögenur I, Rosenberg J. Clinical pharmacokinetics of melatonin: A systematic review. Vol. 71, European Journal of Clinical Pharmacology. 2015.

3. Vasey C, McBride J, Penta K. Circadian rhythm dysregulation and restoration: The role of melatonin. Vol. 13, Nutrients. 2021.

4. Molska A, Nyman AKG, Sofias AM, Kristiansen KA, Hak S, Widerøe M. In vitro and in vivo evaluation of organic solvent-free injectable melatonin nanoformulations. European Journal of Pharmaceutics and Biopharmaceutics. 2020;152.

5. Mistraletti G, Paroni R, Umbrello M, Moro Salihovic B, Coppola S, Froio S, et al. Different routes and formulations of melatonin in critically ill patients. A pharmacokinetic randomized study. Clin Endocrinol (Oxf). 2019;91(1).

6. Zetner D, Andersen LPH, Rosenberg J. Pharmacokinetics of Alternative Administration Routes of Melatonin: A Systematic Review. Vol. 66, Drug Research. 2016.

7. Salehi B, Sharopov F, Fokou PVT, Kobylinska A, de Jonge L, Tadio K, et al. Melatonin in medicinal and food plants: Occurrence, bioavailability, and health potential for humans. Vol. 8, Cells. 2019.

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