Melatonin – biochemistry, role in the body, impact on sleep, and natural ways to support its production

What is Melatonin? – Biochemistry and Role in the Body

Description of Melatonin’s Chemical Structure

Melatonin, also known as N-acetyl-5-methoxytryptamine, is a lipophilic indole hormone synthesized from the amino acid tryptophan. Its molecular weight is approximately 232 daltons, and its chemical structure includes an indole ring, characteristic of many neurotransmitters and neuroendocrine hormones, along with two key functional groups – a methoxy group (-OCH₃) at position 5 of the indole ring and an N-acetylethyl side chain. This unique structure allows melatonin to penetrate biological membranes, including the blood-brain barrier, which is crucial for its regulatory functions in the central nervous system.

Due to its small size and lipophilic nature, melatonin acts both as a hormone and as a paracrine and autocrine factor, exhibiting a broad spectrum of biological activities. Its antioxidant properties and immune-modulating effects stem directly from its specific chemical structure, enabling it to neutralize free radicals and influence the expression of genes involved in cellular protection.

Where and How It Is Produced in the Body

Melatonin is primarily synthesized in the pineal gland (corpus pineale), a small gland located centrally in the brain between the two hemispheres. The pineal gland serves as the main regulator of the circadian rhythm, converting light signals received by the retina into rhythmic melatonin secretion. This process is regulated by the light–dark pathway: light inhibits the activity of the melatonin-synthesizing enzyme – N-acetyltransferase (AA-NAT), resulting in decreased melatonin production during the day, while synthesis intensifies at night.

Besides the pineal gland, melatonin is also produced in other tissues on a smaller scale, such as the skin, retina, gastrointestinal tract, and leukocytes. In the skin, melatonin acts locally as a powerful antioxidant protecting cells from damage caused by UV radiation and oxidative stress. In the retina, it modulates photoreceptors and influences the eye’s adaptive processes to changing light conditions.

Melatonin synthesis in the pineal gland begins with the conversion of tryptophan to serotonin, followed by enzymatic acetylation of serotonin by arylalkylamine N-acetyltransferase (AANAT) and methylation by hydroxyindole O-methyltransferase (HIOMT). This precise enzymatic activity allows rapid and rhythmic adjustment of melatonin levels according to environmental conditions and internal physiological needs.

Mechanism of Action – How Melatonin Regulates the Circadian Rhythm

Melatonin serves as a key mediator of signals related to the light–dark cycle, coordinating the biological clock that regulates the sleep-wake circadian rhythm. Its effects are primarily mediated through activation of specific melatonin receptors MT1 and MT2, which are G-protein coupled and located mainly in the suprachiasmatic nucleus (SCN) of the hypothalamus – the central biological clock of the body.

Upon binding of melatonin to MT1 receptors, the activity of SCN neurons is inhibited, producing calming effects and facilitating sleep onset. MT2 receptors are responsible for phase-shifting the circadian rhythm, allowing the body to adapt its biological clock to changing environmental conditions (e.g., time zone changes). Thanks to this, melatonin synchronizes numerous physiological processes such as body temperature, hormone secretion (e.g., cortisol), and immune system functions.

Beyond circadian rhythm regulation, melatonin possesses antioxidant, anti-inflammatory, and immunomodulatory properties, making it an important factor in maintaining body homeostasis. Research indicates melatonin also has neuroprotective effects and may exert anticancer activity by regulating the cell cycle and inducing apoptosis in cancer cells.

“Melatonin is not only a regulator of the circadian rhythm but also a powerful modulator of oxidative and immune processes, making it a hormone with a broad spectrum of biological activities.” – Reiter RJ, Rosales-Corral S, Tan DX et al., 2016

“Melatonin receptors MT1 and MT2 in the suprachiasmatic nucleus coordinate circadian rhythms by modulating neuronal activity, enabling adaptation to variable environmental conditions.” – Dubocovich ML, Markowska M., 2005

Melatonin and the Regulation of Sleep and Circadian Rhythm

How Melatonin Affects Sleep Stages

Melatonin plays a key role in sleep modulation, primarily by synchronizing the circadian rhythm and facilitating sleep initiation. By activating MT1 and MT2 receptors in the brain, melatonin reduces neuronal activity in the wakefulness system, which promotes the transition from wakefulness to NREM (non-rapid eye movement) sleep. Its action on the N3 stage, known as deep sleep, is particularly important, as this phase is responsible for body regeneration and memory consolidation.

Melatonin also influences the REM (rapid eye movement) sleep phase, although its role is more complex and still under investigation. Melatonin’s effect on the circadian rhythm causes REM sleep to occur at regular intervals, which is crucial for a proper sleep cycle and good mental well-being. Melatonin deficiency may lead to shortened total sleep time and fragmentation of sleep stages, resulting in decreased rest quality.

The Importance of Melatonin in Treating Sleep Disorders, e.g., Insomnia, Jet Lag

Melatonin is widely used in the treatment of sleep disorders, especially in cases of insomnia in older adults and in regulating sleep for people working or traveling across different time zones (jet lag). As a dietary supplement, melatonin helps shorten the time to fall asleep, improve sleep quality, and increase its efficiency.

In circadian rhythm disorders such as delayed sleep phase syndrome, melatonin is used to advance the sleep phase to an earlier time, helping synchronize the biological clock with social schedules. In jet lag therapy, melatonin supplementation reduces symptoms such as fatigue, concentration difficulties, and sleep disturbances, accelerating adaptation to the new time zone.

Review of Clinical Studies Confirming Melatonin’s Effectiveness in Improving Sleep Quality

Numerous clinical studies confirm melatonin’s effectiveness as a sleep-enhancing agent. A meta-analysis conducted by Ferracioli-Oda et al. (2013) showed that melatonin supplementation shortens sleep onset latency by an average of 7 minutes and increases total sleep time by about 8 minutes, which has significant clinical relevance on a population level.

Other studies emphasize the benefits of melatonin use in idiopathic insomnia patients and in those with sleep disorders related to shift work. For example, a study by Lewy et al. (1992) documented a phase shift in sleep timing in people with circadian rhythm disorders under melatonin influence, leading to improved subjective sleep quality and reduced fatigue symptoms.

Expert Quotes and Meta-Analyses on Melatonin Supplementation

“Melatonin is one of the best-studied sleep-supporting supplements, effectively improving both sleep initiation and quality, especially in people with circadian rhythm disorders.” – Brzezinski A., 1997

“Meta-analyses of clinical trials indicate statistically and clinically significant benefits of melatonin in treating insomnia, particularly regarding improvements in sleep onset latency and sleep quality.” – Ferracioli-Oda E., Qawasmi A., Bloch M.H., 2013

“Melatonin supplementation is an effective strategy in jet lag therapy and sleep disorders in shift workers, contributing to faster adaptation and reduction of fatigue symptoms.” – Herxheimer A., Petrie K.J., 2002

Health Benefits of Melatonin Beyond Sleep

Impact on the Immune System and Antioxidant Action

Melatonin is not only a hormone regulating sleep but also a powerful modulator of the immune system. Numerous studies have shown that melatonin increases the activity of T lymphocytes, NK (natural killer) cells, and macrophages, which contributes to a more effective immune response to pathogens. Additionally, melatonin possesses strong antioxidant properties – it neutralizes free radicals, protecting cells from oxidative stress, which is a risk factor for many chronic diseases.

By reducing oxidative stress, melatonin supports cardiovascular health, counteracts inflammatory processes, and may slow down cellular aging. In vitro and animal model studies confirm that melatonin has a protective effect on mitochondria, key structures responsible for energy production and regulation of cellular metabolism.

Potential Neuroprotective Effects (e.g., Alzheimer’s, Parkinson’s)

Increasing evidence points to the neuroprotective properties of melatonin. Thanks to its ability to cross the blood-brain barrier, melatonin can act directly on nervous tissue, reducing oxidative stress and inflammation in the brain. In the context of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, melatonin helps reduce the accumulation of toxic proteins, e.g., beta-amyloid, and protects neurons from apoptosis.

Clinical and experimental studies suggest that melatonin supplementation may slow neurodegeneration progression, improve cognitive functions, and alleviate sleep disturbances often accompanying these diseases. Although these results are promising, further large-scale studies are needed to fully confirm these properties.

Support in Treating Metabolic and Hormonal Disorders

Melatonin also influences glucose metabolism and regulates hormones responsible for energy balance. Studies indicate that it may improve tissue sensitivity to insulin, which is beneficial in preventing and treating type 2 diabetes. Moreover, melatonin regulates the secretion of sex and thyroid hormones, which translates into improved hormonal functions and regulation of the menstrual cycle.

In the context of obesity and metabolic syndrome, melatonin may limit fat accumulation, inhibit inflammatory processes, and support the proper functioning of the hypothalamic-pituitary-adrenal axis, leading to better metabolic homeostasis.

Quotes from Scientific Studies and Expert Opinions

“Melatonin exhibits a wide spectrum of immunomodulatory and antioxidant actions, making it an important protective factor in chronic diseases and aging processes.” – Reiter R.J., Mayo Clin Proc, 2016

“Experimental studies have demonstrated melatonin’s neuroprotective potential, especially in models of neurodegenerative diseases, opening new therapeutic perspectives.” – Pandi-Perumal S.R. et al., CNS Neurosci Ther, 2017

“Melatonin supplementation may be a valuable adjunct in treating metabolic disorders, improving insulin sensitivity and regulating hormones responsible for energy balance.” – Cipolla-Neto J., Amaral F.G., Endocr Rev, 2018

Melatonin Supplementation – Indications, Dosage, and Safety

When and for Whom is Melatonin Supplementation Recommended?

Melatonin supplementation is especially recommended for people having difficulty falling asleep, suffering from insomnia, and those experiencing circadian rhythm disorders such as jet lag or shift work. Older adults, whose natural melatonin production decreases with age, may also benefit from supplementing this hormone. Melatonin is sometimes used as a supportive treatment for patients with certain neurological, metabolic, or immune disorders, but in these cases, supplementation should be supervised by a physician.

It is important to emphasize that melatonin is not a standard sleeping medication and should not be used long-term without medical consultation, especially in people with chronic illnesses or those taking other medications.

Possible Side Effects and Contraindications

Melatonin is generally well tolerated; however, adverse effects may occur, especially at higher doses or with prolonged use. The most common side effects include:

• sleepiness or drowsiness during the day, especially with improper dosing
• dizziness
• headaches
• nausea
• allergic reactions (rare)

Contraindications to melatonin supplementation include:

• pregnancy and breastfeeding (due to insufficient safety data)
• autoimmune diseases (due to possible immune system effects)
• use of medications affecting the nervous or immune system – supplementation should be supervised by a doctor

Melatonin in the context of lifestyle – how to naturally support its production?

The importance of exposure to light and darkness

Melatonin production in the body is strongly dependent on the light-dark cycle, which forms the basis of the natural circadian rhythm. The pineal gland starts releasing melatonin at dusk, signaling to the body that it is time to sleep. Exposure to bright light, especially blue light emitted by phone, computer, and TV screens, inhibits melatonin synthesis, delaying sleep onset and disturbing the sleep rhythm.

Therefore, it is crucial to limit exposure to blue light 1–2 hours before bedtime and use warm-colored lighting in the evening. Regular exposure to daylight, especially in the morning, helps synchronize the biological clock and improves melatonin production at night.

Diet and substances supporting natural melatonin production

Certain dietary components may support natural melatonin production or provide it directly. For example, tryptophan — an amino acid precursor to serotonin, from which melatonin is derived — is found in foods such as turkey, nuts, seeds, eggs, and bananas.

Additionally, some foods naturally contain melatonin, such as Montmorency cherries, walnuts, rice, tomatoes, and oats. Antioxidants and B vitamins (especially B6) also support the enzymatic processes involved in melatonin synthesis.

The importance of sleep hygiene and evening practices

Sleep hygiene includes habits that promote natural melatonin secretion and a healthy circadian rhythm. It is important to set consistent sleep and wake times, avoid intense physical activity and stress right before bedtime, and create a dark, quiet, and cool bedroom environment.

Evening rituals such as reading a book by warm light, meditation, or gentle stretching can help the body transition into a state ready for sleep.

“Evening exposure to blue light significantly lowers melatonin levels, leading to sleep and circadian rhythm disturbances.” – Chang A.-M. et al., Proceedings of the National Academy of Sciences, 2015

“A diet rich in tryptophan and a regular sleep schedule promote natural melatonin synthesis and improve sleep quality.” – Peuhkuri K. et al., Nutrition Research, 2012

Summary

Melatonin plays a key role in regulating the circadian rhythm and sleep quality, and its production is closely linked to natural light and darkness cycles. We can support it by consciously managing light exposure, maintaining a healthy diet rich in tryptophan and melatonin, and practicing good sleep hygiene with evening relaxation rituals. Melatonin supplementation is an effective tool in selected situations, but natural methods remain the foundation of a healthy circadian rhythm.