▶︎ Introduction

Melatonin is a hormone secreted by the pineal gland in accordance with the circadian rhythm when the light level decreases. Reduction of melatonin secretion with age may be associated with physiological aging in neurodegenerative diseases by affecting the suprachiasmatic nucleus or of the neuronal pathways of transmission to the pineal gland. A significant decrease in melatonin synthesis has been reported in various disorders and diseases, including cardiovascular diseases, metabolic disorders (particularly diabetes type 2), cancer and endocrine diseases. In addition to the fact, that melatonin is a sleep inducer, it also exerts cytoprotective properties as an antioxidant and free radical scavenger. The therapeutic role of melatonin has been demonstrated in sleep disorders, eye damage and cardiovascular disease. The association between melatonin and β-blockers has had a positive impact on sleep disorders in clinical trials.

Previous studies have reported the anti-inflammatory effect of melatonin by adjusting levels of pro-inflammatory cytokines, including interleukin (IL)-6, IL-1β and tumor necrosis factor-α. Melatonin treatment has been demonstrated to decrease IL-6 and IL-10 expression levels and efficiently attenuate T-cell proliferation.

Melatonin is mainly produced by the pineal gland and secreted into the blood (2). Melatonin secretion is affected by the circadian rhythm, namely the dark light cycle. Artificial illumination during the night can decrease the natural release of melatonin and thus can disrupt the body's internal circadian rhythm with consecutive sleep disorders and immunity (2). It has been reported that melatonin plays important roles in various biological processes, including sleep, ageing, stress response and immunity (3). Although skepticism exists in the scientific community regarding melatonin as a ‘cure for all’, previous studies have reported the benefits of melatonin supplementation, such as antioxidant, analgesic and anxiolytic effect, thus slowing age-related diseases (1,3,4).

Melatonin physiology

Melatonin is a hormone secreted by the pineal gland under nerve modulation of the suprachiasmatic nucleus (9). Although melatonin is predominantly secreted by the pineal gland in mammals, some studies have reported that melatonin is produced in most cells, tissues and organs (9-11). Melatonin or N-acetyl-5-methoxytryptamine is an acetamide, synthesized from tryptophan, with the intermediate chemical compound serotonin and N-Acetylserotonin (10).

Dosage and side effects of melatonin

The maximal effective doses of melatonin range from 0.5-10.0 mg, although some studies have suggested that effect doses range from 1-6 mg (14). Higher than physiological concentrations may cause desensitization of melatonin receptors, thus others have recommend low doses ranging from 0.3-2.0 mg (14,15). Notably, the European Food Safety Authority recommends the use of maximum doses of 0.3-1.0 mg (15). However, further studies are required to identify the minimal effective dose.◀︎[1]

References:

[1] [2022] Benefits and adverse events of melatonin use in the elderly (Review)