While melatonin is widely used as a sleep aid, the long-term effects of its prolonged use remain unclear. Research suggests that while short-term use appears safe for most adults, extended melatonin supplementation may carry potential risks that warrant further investigation.
Melatonin's Role in Circadian Rhythm Regulation
Melatonin plays a crucial role in regulating the human circadian rhythm and sleep-wake cycle. As the "hormone of darkness," melatonin is primarily secreted by the pineal gland at night, with peak levels occurring around 3-4 AM[4]. Its production is controlled by the suprachiasmatic nucleus (SCN) in the hypothalamus, which acts as the body's central circadian pacemaker[4]. Melatonin functions as an endogenous synchronizer, helping to entrain the body's internal clock to the 24-hour solar day[4]. It does this through two main mechanisms: as a chronobiotic, shifting the circadian rhythm, and as a sleep promoter, facilitating sleep onset and continuity[2][4]. The hormone's effects are mediated primarily through MT1 and MT2 receptors, with MT2 being more involved in phase-shifting and MT1 in sleep initiation[4]. By signaling darkness to the body, melatonin helps regulate various physiological processes, including sleep propensity, body temperature, and other circadian rhythms[2][3].
Potential Hormonal Disruptions
Melatonin supplementation may potentially disrupt other hormonal systems in the body. Prolonged or excessive use of melatonin can affect the delicate balance of hormones, including cortisol, estrogen, and testosterone[1]. There are concerns that melatonin supplements could influence hormonal development, particularly in children and adolescents, potentially affecting puberty, menstrual cycles, and the production of prolactin[2]. Some studies suggest that melatonin may have suppressive effects on sex hormones and metabolic processes, similar to seasonal changes observed in animals with higher melatonin levels in winter[1]. Additionally, melatonin has been shown to impact insulin sensitivity and glucose tolerance, with evening supplementation decreasing insulin sensitivity and morning supplementation impairing glucose tolerance[1]. These findings highlight the complex interactions between melatonin and various hormonal and metabolic processes in the body.
Inconsistent Dosing in Melatonin Supplements
Recent studies have revealed significant inconsistencies in the melatonin content of over-the-counter supplements, particularly in gummy formulations. A 2023 study published in JAMA found that 22 out of 25 melatonin gummy supplements analyzed contained significantly different quantities than stated on their labels, with melatonin amounts ranging from 74% to 247% of the advertised dosage[1]. Similarly, a Canadian study showed that 71% of tested melatonin supplements had mislabeled doses[1]. This variability extends to lot-to-lot differences within the same product, with variations as high as 465%[2]. The inconsistency in dosing raises concerns about efficacy and safety, as lower doses might be ineffective while higher doses could lead to unexpected side effects or interactions[3]. To ensure more consistent dosing, experts recommend looking for supplements with third-party verification stamps from organizations like USP or NSF International[1].
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