Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements

Abstract

Melatonin has become a popular dietary supplement, most known as a chronobiotic, and for establishing healthy sleep. Research over the last decade into cancer, Alzheimer’s disease, multiple sclerosis, fertility, PCOS, and many other conditions, combined with the COVID-19 pandemic, has led to greater awareness of melatonin because of its ability to act as a potent antioxidant, immune-active agent, and mitochondrial regulator. There are distinct similarities between melatonin and vitamin D in the depth and breadth of their impact on health. Both act as hormones, affect multiple systems through their immune-modulating, anti-inflammatory functions, are found in the skin, and are responsive to sunlight and darkness. In fact, there may be similarities between the widespread concern about vitamin D deficiency as a “sunlight deficiency” and reduced melatonin secretion as a result of “darkness deficiency” from overexposure to artificial blue light. The trend toward greater use of melatonin supplements has resulted in concern about its safety, especially higher doses, long-term use, and application in certain populations (e.g., children). This review aims to evaluate the recent data on melatonin’s mechanisms, its clinical uses beyond sleep, safety concerns, and a thorough summary of therapeutic considerations concerning dietary supplementation, including the different formats available (animal, synthetic, and phytomelatonin), dosing, timing, contraindications, and nutrient combinations.

Melatonin: A Potential Candidate for the Treatment of Experimental and Clinical Perinatal Asphyxia

“…Serotonin is, in turn, converted into N-acetylserotonin and then into melatonin; the finished melatonin is released into the blood and cerebrospinal fluid [ 21 , 78 , 79 , 80 , 81 , 82 , 83 ]. Melatonin is an evolutionarily preserved substance found in all microorganisms, plants, animals and humans [ 18 , 20 ].…”

“…Several factors contribute to the bioavailability of melatonin, including reduced digestive and absorption capacity, the composition of the intestinal microbiome, genetic variation in melatonin-metabolizing enzymes, dietary excipient profile and more [ 18 ]. It is generally accepted that melatonin in capsule or tablet form is generally not very bioavailable (1–74%) [ 18 ].…”

“…Several factors contribute to the bioavailability of melatonin, including reduced digestive and absorption capacity, the composition of the intestinal microbiome, genetic variation in melatonin-metabolizing enzymes, dietary excipient profile and more [ 18 ]. It is generally accepted that melatonin in capsule or tablet form is generally not very bioavailable (1–74%) [ 18 ]. A systematic review showed an average of 15% oral bioavailability of melatonin, which was highly variable (9 to 33%) and dependent on age, smoking, caffeine, diseases and medications used [ 153 ].…”

“…In dogs, after oral administration of melatonin at a dose of 1 mg/kg, the bioavailability was reduced to 17%, indicating a dose-dependent bioavailability [ 155 ]. Due to low bioavailability, research is being conducted to develop preparations bypassing the gastrointestinal tract, with a longer half-life or developed with the use of nanotechnology [ 18 , 156 , 157 , 158 ]. In addition, demonstrating whether plant-derived phytomelatonin is more easily digestible than the synthetic form [ 18 ].…”

“…Recently, there has been growing interest in studying the therapeutic properties of melatonin due to the fact that it is a safe, inexpensive, accessible, long-acting substance with minimal side effects [ 17 ]. Melatonin can be of synthetic as well as natural origin, isolated from plants, vegetables and fruits in the treatment of neurological disorders [ 18 ]. Melatonin, irrespective of its origin, has a protective effect in several models of experimental neurological disorders [ 19 , 20 , 21 ].…”