Melatonin, a rhythmic hormone secreted by the pineal gland, plays a crucial “molecular switch” role in regulating the human biological clock, and its secretion is closely related to the “light-dark cycle.” As night falls and the external environment darkens, the retina senses this change and transmits the signal to the pineal gland through complex neural pathways, stimulating it to synthesize and secrete melatonin. Melatonin enters the bloodstream and circulates throughout the body, with some reaching the suprachiasmatic nucleus (SCN). The SCN is the core pacemaker of the human biological clock; when melatonin binds to it, it’s like pressing the “sleep start button,” triggering a series of physiological changes. It inhibits the transmission of arousal signals in the SCN, causing the brain to receive the “it’s time to rest” instruction; simultaneously, the body’s core temperature begins to slowly decrease, and the level of cortisol, a hormone related to stress and arousal, gradually decreases, creating a suitable physiological environment for sleep and smoothly initiating the sleep preparation process. Clinical studies have provided strong evidence for the efficacy of melatonin in regulating the biological clock and improving sleep. A study of shift workers found that these individuals, who frequently experience disrupted sleep schedules, saw an average 23% reduction in sleep latency (the time interval between preparing to fall asleep and actually falling asleep) after supplementing with exogenous melatonin. This allowed them to fall asleep more quickly and alleviate sleep disturbances caused by irregular work hours to some extent. Melatonin also proves beneficial for travelers crossing time zones, helping them adapt more quickly to the day-night cycle of a new time zone, reducing jet lag-related sleep disturbances, and enabling their biological clock to synchronize rapidly with the new environment.
Receptor-Mediated Regulation of Sleep Depth
Melatonin’s regulation of sleep extends beyond initiating sleep; it extends to the depth of sleep, primarily through the activation of MT1/MT2 receptors. MT1 receptors are widely distributed in brain regions closely related to sleep regulation, such as the preoptic area of the hypothalamus. When melatonin binds to and activates MT1 receptors, it acts like a “pause button” on neuronal activity in the preoptic area, inhibiting over-excitation. The preoptic area plays a crucial role in sleep-wake regulation; its calmness facilitates the gradual transition from wakefulness to sleep, helping people smoothly begin their sleep journey.
MT2 receptors, on the other hand, play a key role in regulating the sleep cycle. When MT2 receptors are activated, they act like precise time managers, finely regulating the sleep cycle and effectively prolonging slow-wave sleep (deep sleep). Deep sleep is the most critical stage of sleep, during which the body receives ample rest and recovery, and important physiological processes such as cell repair and immune regulation proceed efficiently. Functional MRI (Magnetic Resonance Imaging) technology provides a direct visual demonstration of the effects of melatonin on sleep-related areas of the brain: After melatonin intervention, MRI scans revealed an 18% decrease in prefrontal cortex activity, indicating a reduction in brain excitability and the initiation of a relaxed sleep state. Simultaneously, sleep-related EEG activity in the hippocampus was significantly enhanced. The hippocampus is closely linked to functions such as memory consolidation and emotion regulation. This enhanced sleep-related EEG activity further demonstrates that melatonin can improve sleep quality, promote memory consolidation and emotional stability during sleep, and leave people feeling energetic and emotionally stable upon waking.
Analysis of the Dual Effects of Melatonin on Improving Sleep
(I) Empirical Advantages of Short-Term Intervention
Rapid Adjustment to Jet Lag: In modern life, long-distance travel is becoming increasingly frequent, and jet lag has become a major problem for travelers. For travelers crossing more than 5 time zones, the huge difference between their biological clock and the destination time can lead to sleep disturbances, daytime sleepiness, fatigue, and other discomfort symptoms, seriously affecting the travel experience and work efficiency. Melatonin has shown significant advantages in addressing jet lag. Studies have shown that taking 2-3 mg of melatonin 2 hours before bedtime can regulate the biological clock, accelerate the body’s adaptation to the new time zone, and significantly shorten the jet lag adaptation period by 40%-60%. Travelers no longer need to spend several days adjusting and can integrate into the local rhythm of life more quickly. At the same time, the number of awakenings at night will decrease by 35%, and sleep will be more restful, allowing travelers to have good sleep quality even in foreign countries and start their journey with plenty of energy.
Rhythm Restoration for Shift Workers: Shift workers, such as medical staff, police officers, firefighters, and factory assembly line workers, have irregular working hours and reversed day-night cycles, disrupting their normal circadian rhythms and easily leading to sleep disorders. Taking melatonin 30 minutes before the designated sleep window, combined with light therapy, can effectively improve this situation. Melatonin can regulate the body’s biological clock, increasing sleep efficiency by 28% for shift workers, allowing them to get more sleep within their limited rest time. Furthermore, melatonin can regulate hormone secretion, normalizing diurnal cortisol fluctuations. As a stress hormone, normal cortisol fluctuations are crucial for maintaining the body’s physiological balance. For shift workers, normalized cortisol fluctuations mean reduced stress response, decreased fatigue, improved concentration, and increased work efficiency, thus better ensuring work quality and safety.
Auxiliary Intervention for Mild Insomnia: In today’s fast-paced society, life stress and unhealthy lifestyle habits make difficulty falling asleep a common sleep problem for many. For non-chronic insomniacs with difficulty falling asleep (sleep latency > 30 minutes), melatonin is an effective adjunctive intervention. It can reduce brain excitability by regulating neurotransmitter release, thereby shortening sleep onset time by 15-20 minutes and helping insomniacs fall asleep faster. Compared to traditional sleeping pills, melatonin has no residual sedative effect the next day, and will not cause dizziness or fatigue, affecting work and daily life. Users can maintain a clear mind and good mental state after waking up, and can normally engage in daily activities, solving the problem of difficulty falling asleep without causing additional disruption to daily life.
(II) Potential Risks and Side Effects
Acute Adverse Reactions: Some individuals may experience acute adverse reactions such as headache, dizziness, and nausea after taking melatonin. Statistics show that approximately 12% of users experience headaches, 8% experience dizziness, and 5% experience nausea. This is mainly due to the cross-reaction of melatonin with central 5-HT receptors. 5-HT receptors play an important role in regulating nervous system function and gastrointestinal motility. When melatonin interacts with these receptors, it may interfere with normal signal transmission in the nervous system, causing headaches and dizziness; it may also affect normal gastrointestinal function, leading to nausea and other discomfort. Individuals with sensitive constitutions are more prone to these adverse reactions due to their stronger reactions to various substances; those with gastrointestinal disorders, whose gastrointestinal tracts are already more vulnerable, may experience aggravated symptoms due to melatonin’s stimulation of the gastrointestinal tract.
Circadian Rhythm Disruption: Long-term or inappropriate use of melatonin may lead to circadian rhythm disruption problems such as daytime sleepiness and abnormal dreams. This is because overactivation of melatonin receptors disrupts the body’s natural circadian rhythm. When melatonin receptors are overexcited, they continuously send “sleep signals” to the brain, causing drowsiness even during the day and affecting work and study efficiency. Furthermore, it can affect neural activity during sleep, leading to abnormal dreams, such as overly vivid dreams or nightmares, thus reducing sleep quality. Older adults have slower metabolisms and weaker melatonin metabolism, resulting in melatonin’s longer-lasting effect and a greater likelihood of daytime sleepiness. Those with slower metabolisms also face this risk; their bodies cannot eliminate melatonin in time, leading to its accumulation and adverse effects.
Long-term use risks: Continuous use of melatonin for more than 3 months may lead to endogenous secretion suppression and dependence. The pineal gland is responsible for secreting melatonin. When melatonin is supplemented exogenously for a long time, the body may mistakenly believe it no longer needs to secrete it, thus inhibiting pineal gland function through negative feedback, leading to endogenous secretion suppression. Once exogenous melatonin is discontinued, the body’s own melatonin secretion cannot recover in time, leading to sleep disorders and other problems. Users may develop a dependence on melatonin, becoming reliant on it for sleep. This dependence not only affects sleep quality but may also pose potential threats to health, increasing the difficulty of subsequent treatment of sleep problems.
Special Population Contraindications: Pregnant women, adolescents, and patients with autoimmune diseases should avoid using melatonin. During pregnancy, the endocrine system is in a special state of balance. Melatonin, through receptor-mediated endocrine regulation, may interfere with the hormonal balance in the pregnant woman’s body, affecting the normal development of the fetus. Adolescents are in a critical period of growth and development, and the pineal gland is constantly developing and maturing. Randomly supplementing with melatonin may interfere with the normal development of the pineal gland, affecting the secretion of growth hormones and other hormones, thus impacting the adolescent’s growth and development. Patients with autoimmune diseases already have a disordered immune system. The regulatory effect of melatonin on the immune system may further aggravate the condition, hindering disease control and recovery.
Scientific Controversy Regarding Long-Term Safety
The safety of long-term melatonin use has been a focus of attention in the academic and medical communities. Current clinical data shows that short-term (<3 months) low-dose use of melatonin has good safety, but the core controversy surrounding long-term use remains. One key issue is the suppression of endogenous melatonin. Studies have shown that serum endogenous melatonin levels may decrease by 15%-20% in those who take it continuously for more than 6 months. This is because the human body has a sophisticated endocrine regulatory mechanism. Long-term exogenous melatonin supplementation can mislead the body into believing that its own melatonin production is sufficient, thus inhibiting the normal secretory function of the pineal gland through negative feedback regulation. When endogenous melatonin secretion decreases, the body cannot adjust promptly upon stopping exogenous melatonin use, easily leading to the risk of “rebound insomnia.” Users will noticeably experience worsened sleep quality, with problems such as difficulty falling asleep and increased nighttime awakenings recurring, sometimes even more severely than before taking melatonin.
The impact on reproductive endocrine function is also a controversial aspect of long-term melatonin use. In animal studies, researchers have found that high doses of melatonin may inhibit the release of gonadotropins. Gonadotropins are crucial for maintaining normal reproductive function, promoting gonadal development and sex hormone secretion. Suppression of gonadotropin release can affect the normal functioning of the reproductive system. However, it is important to note that animal results cannot be directly extrapolated to humans. The long-term effects of melatonin use on human reproductive function still require large-scale studies for verification. Human physiological structure and metabolic mechanisms differ from those of animals, and various factors such as living environment and dietary habits can also influence the effects of melatonin. Currently, due to a lack of sufficient large-scale, long-term human study data, a definitive conclusion cannot be drawn regarding whether long-term melatonin use in humans will cause substantial damage to reproductive function. This has become one of the key areas for future research.
Rational Positioning and Scientific Choice
Melatonin, as a “natural rhythm regulator,” is valuable for short-term, precise intervention rather than long-term dependence. Users are advised to:
1. Prioritize addressing insomnia through sleep behavior adjustments (such as stimulus control therapy and sleep restriction therapy);
2. If supplementation is necessary, strictly adhere to the principle of “lowest effective dose + short-term use,” avoiding continuous use for more than 3 months;
3. Special populations (such as patients with chronic diseases and pregnant women) must assess the benefit-risk ratio under the guidance of a doctor.
Sleep health is essentially a multi-system coordinated physiological process. The scientific application of melatonin needs to return to its core positioning of “regulation rather than replacement,” forming precise synergy with lifestyle and medical interventions to truly optimize sleep quality.
