Melatonin is a naturally occurring hormone produced primarily by the pineal gland in the brain. This hormone plays a pivotal role in regulating the sleep-wake cycle, also known as the circadian rhythm. Melatonin production is closely tied to the light-dark cycle: it is secreted in larger amounts during the night and diminishes when exposed to light. This rhythmic secretion helps signal to the body that it is time to prepare for sleep, thereby promoting a healthy sleep pattern.

In addition to its primary role in sleep regulation, melatonin exhibits various other physiological functions. It is also involved in the modulation of immune responses, antioxidant activity, and the regulation of seasonal biological rhythms. Melatonin's antioxidant properties make it a potent scavenger of free radicals, thereby helping to protect cells from oxidative damage. These diverse roles underscore the hormone's significance beyond merely being a sleep aid.

Melatonin is not confined to the brain; it is also produced in smaller amounts by other tissues and organs, including the gastrointestinal tract and bone marrow. In the gastrointestinal system, melatonin aids in the regulation of digestive processes and provides a protective effect against gastrointestinal lesions and ulcers. The presence of melatonin in various bodily systems highlights its multifaceted nature and broad biological impact.

Given its critical functions, melatonin is also available as a dietary supplement, commonly used to address sleep disorders such as insomnia and jet lag. These supplements are synthesized to mimic the natural melatonin produced by the body and are often used to help regulate sleep patterns in individuals experiencing disruptions. Understanding melatonin's various roles and mechanisms can provide deeper insights into how it can be effectively utilized for improving health and well-being.

In summary, melatonin is a versatile hormone integral to maintaining the body's internal clock and overall physiological balance. Its production is intricately linked to the light-dark cycle, making it essential for promoting restful sleep and supporting various other bodily functions. As a supplement, it offers potential benefits for those struggling with sleep disturbances and other related conditions.

Melatonin is primarily used as a sleep aid to help manage various sleep disorders, including insomnia and jet lag. Its ability to regulate the sleep-wake cycle makes it particularly effective for individuals who have difficulty falling asleep or maintaining sleep. Research has shown that melatonin supplementation can significantly improve sleep quality and reduce sleep onset latency, making it easier for individuals to fall asleep more quickly.

One notable study published in the journal Sleep Medicine explored the efficacy of melatonin for sleep disturbances in middle-aged patients with primary insomnia. The randomized, double-blind, placebo-controlled trial found that melatonin supplementation significantly decreased early wake time and improved some aspects of sleep quality, such as total sleep time and percentage of rapid eye movement (REM) sleep. The study concluded that melatonin is effective and safe for improving sleep quality in this population (Xu et al., 2020).

Melatonin is also used to alleviate symptoms of jet lag, a condition that occurs when the body's internal clock is misaligned with a new time zone. A meta-analysis published in Sleep Medicine Reviews reviewed the effects of exogenous melatonin on sleep and concluded that melatonin significantly reduces sleep onset latency, increases sleep efficiency, and extends total sleep duration. These findings suggest that melatonin can help travelers adjust to new time zones more quickly and with fewer disruptions to their sleep patterns (Brzezinski et al., 2005).

Beyond sleep disorders, melatonin has shown promise in other areas of health. For instance, studies have indicated its potential role in reducing symptoms associated with tinnitus, improving sleep quality in cancer patients, and even in managing the side effects of certain medications like chemotherapy agents. A study in the Journal of Pineal Research found that melatonin, when combined with omeprazole, accelerated the healing of gastroduodenal ulcers, suggesting its protective role in gastrointestinal health (Celinski et al., 2011).

In summary, melatonin is widely used for its sleep-regulating properties, making it an effective treatment for insomnia and jet lag. Studies consistently demonstrate its efficacy in improving sleep quality and reducing sleep onset latency. Additionally, melatonin shows potential benefits in managing tinnitus, enhancing sleep in cancer patients, and protecting gastrointestinal health, expanding its utility beyond just a sleep aid.

Melatonin works by regulating the body's circadian rhythms, which are the internal processes that follow a roughly 24-hour cycle and respond primarily to light and darkness in an organism's environment. The pineal gland in the brain produces melatonin in response to darkness, signaling to the body that it is time to prepare for sleep. This hormone's production peaks during the night and diminishes with the onset of daylight, helping to synchronize the sleep-wake cycle.

At the molecular level, melatonin exerts its effects through binding to specific receptors known as MT1 and MT2, which are found in various tissues, including the brain. These receptors play a crucial role in modulating sleep and circadian rhythms. Activation of the MT1 receptor primarily influences the onset of sleep, while the MT2 receptor is involved in the regulation of the sleep-wake cycle and resetting the circadian clock. By binding to these receptors, melatonin can help initiate and maintain sleep.

Melatonin's influence extends beyond sleep regulation. It has potent antioxidant properties, enabling it to neutralize free radicals and reduce oxidative stress within cells. This antioxidant activity helps protect cellular structures, including DNA, proteins, and lipids, from damage caused by reactive oxygen species. Studies have shown that melatonin can enhance the activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, further contributing to its protective effects. For instance, a study in the Journal of Pineal Research highlighted melatonin's ability to scavenge hydroxyl radicals and other reactive oxygen species, thereby mitigating oxidative damage (Reiter et al., 2005).

In addition to its antioxidant properties, melatonin has anti-inflammatory effects. It can modulate the immune response by downregulating pro-inflammatory cytokines and upregulating anti-inflammatory cytokines. This immunomodulatory function is particularly beneficial in conditions where inflammation plays a key role, such as in certain neurodegenerative diseases and gastrointestinal disorders. A study published in Molecular Medicine Reports demonstrated melatonin's capability to reduce inflammation and oxidative stress, thereby protecting against gastric injury in a model of acute pancreatitis (Liang et al., 2014).

Melatonin also interacts with various neurotransmitter systems, including gamma-aminobutyric acid (GABA), serotonin, and dopamine, which are involved in mood regulation and stress response. By influencing these neurotransmitters, melatonin can contribute to improved mood and reduced anxiety, further enhancing its benefits for sleep and overall well-being.

In summary, melatonin works by regulating the body's circadian rhythms through its action on MT1 and MT2 receptors, promoting sleep onset and maintaining the sleep-wake cycle. Its antioxidant and anti-inflammatory properties protect cells from damage and modulate immune responses. Additionally, melatonin's interaction with neurotransmitter systems supports its role in mood regulation and stress reduction, making it a multifaceted hormone with broad physiological impacts.

Melatonin's role in regulating sleep and circadian rhythms is universally applicable to both men and women, but its effects and applications can vary based on gender-specific health issues. This variation arises from differences in hormonal cycles, reproductive health, and the prevalence of certain conditions that affect men and women differently.

In women’s health, melatonin has been studied for its potential benefits in managing menstrual-related sleep disturbances and symptoms of menopause. Hormonal fluctuations during the menstrual cycle and menopause can significantly impact sleep quality. For instance, a study published in Menopause found that melatonin supplementation improved sleep quality and reduced symptoms such as night sweats and hot flashes in menopausal women. Additionally, melatonin has been explored for its role in reproductive health, including its potential to improve outcomes in assisted reproductive technologies (ART). Research indicates that melatonin may enhance ovarian function and egg quality by reducing oxidative stress, thereby supporting fertility treatments (Tamura et al., 2013, Journal of Pineal Research).

For men, melatonin's antioxidative and anti-inflammatory properties have shown promise in protecting against age-related decline in testosterone levels and supporting overall reproductive health. Studies suggest that melatonin may help mitigate oxidative stress in the testes, thereby preserving testicular function and improving sperm quality. A study in Endocrinology reported that melatonin supplementation in middle-aged male rats restored youthful levels of testosterone and other reproductive hormones, highlighting its potential benefits for male reproductive health (Rasmussen et al., 1999).

Furthermore, melatonin's role in managing cardiovascular health may also present gender-specific benefits. Men tend to have a higher prevalence of cardiovascular diseases at a younger age compared to women, and melatonin's cardioprotective effects, such as reducing blood pressure and improving lipid profiles, can be particularly beneficial. A systematic review in Hormone and Metabolic Research found that melatonin supplementation significantly reduced systolic and diastolic blood pressure, which is crucial for cardiovascular health in men (Hadi et al., 2019).

In addition to reproductive and cardiovascular health, melatonin's impact on neurodegenerative diseases shows gender-specific nuances. Women, for example, have a higher lifetime risk of developing Alzheimer's disease. Melatonin's neuroprotective properties, including its ability to reduce oxidative stress and inflammation in the brain, may offer protective benefits against cognitive decline. Research in Frontiers in Neuroendocrinology suggests that melatonin could play a role in mitigating the risk or progression of neurodegenerative diseases, particularly in women (Pandi-Perumal et al., 2013).

In summary, while melatonin's primary function in regulating sleep applies to both genders, its applications in reproductive health, cardiovascular protection, and neurodegenerative disease management exhibit gender-specific benefits. In women, melatonin can improve menstrual and menopausal symptoms, support reproductive health, and potentially protect against cognitive decline. In men, it aids in preserving reproductive function and offers cardiovascular benefits, highlighting its versatile role in addressing gender-specific health concerns.

The appropriate dosage of melatonin can vary widely depending on the individual's needs, age, and the specific condition being addressed. Generally, melatonin supplements are available in doses ranging from 0.5 mg to 10 mg. It is essential to start with the lowest effective dose and gradually increase it if necessary, to minimize potential side effects.

For adults looking to improve sleep quality or manage insomnia, a common starting dose is between 1 mg and 3 mg taken about 30 to 60 minutes before bedtime. Studies have shown that even low doses can be effective in improving sleep onset and quality. For instance, a study published in the Journal of Sleep Research found that a 2 mg dose of prolonged-release melatonin significantly improved sleep quality and morning alertness in adults aged 55 and older (Lemoine et al., 2007). If the initial dose is not effective, it can be gradually increased up to 5 mg or 10 mg, but higher doses should be approached with caution.

In the case of jet lag, melatonin can be particularly beneficial. The recommended dose for adults ranges from 0.5 mg to 5 mg taken close to the target bedtime at the destination for a few days after arrival. Research published in Sleep Medicine Reviews indicates that melatonin is effective in reducing symptoms of jet lag and helping travelers adjust to new time zones more quickly (Brzezinski et al., 2005).

For children, melatonin should be used under the guidance of a healthcare provider, as the appropriate dosage can vary based on the child's age and specific needs. Pediatric doses typically range from 0.5 mg to 3 mg, with lower doses often being sufficient for improving sleep onset and quality. A study in the Journal of the American Academy of Child and Adolescent Psychiatry found that a dose of 3 mg to 6 mg of melatonin improved sleep onset and total sleep time in children with ADHD and chronic sleep onset insomnia (Van der Heijden et al., 2007).

It's also worth noting that melatonin is used in various other contexts, such as managing symptoms of tinnitus, supporting reproductive health, and protecting against oxidative stress. In these cases, the dosage may vary based on the specific condition and individual response.

In summary, the appropriate melatonin dosage depends on the individual's age, condition, and response to the supplement. For most adults, a starting dose of 1 mg to 3 mg before bedtime is recommended, with adjustments made as needed. For jet lag, doses between 0.5 mg and 5 mg are effective. Children should use melatonin under medical supervision, with typical doses ranging from 0.5 mg to 3 mg. Always start with the lowest effective dose to minimize potential side effects and consult a healthcare provider for personalized guidance.

While melatonin is generally considered safe for short-term use, it can cause side effects in some individuals. The most commonly reported side effects are relatively mild and include symptoms such as daytime drowsiness, dizziness, and headaches. These effects are usually transient and may diminish as the body adjusts to the supplement.

Daytime drowsiness is perhaps the most frequently reported side effect. This can occur if the dose of melatonin is too high or if it is taken too late at night, leading to residual effects the following day. It is advisable to start with a low dose and take melatonin 30 to 60 minutes before bedtime to minimize the risk of daytime sleepiness.

Dizziness and headaches are also common side effects. These symptoms are usually mild but can be bothersome for some users. They may be related to the body's adjustment to the supplement or to the dose being too high. If these symptoms persist, it may be helpful to reduce the dosage or consult a healthcare provider for further advice.

In some cases, melatonin can cause gastrointestinal symptoms such as nausea and stomach cramps. These effects are less common but can occur, particularly when higher doses are used. If gastrointestinal discomfort persists, it may be beneficial to take melatonin with food or to switch to a lower dose.

Melatonin can also interact with the body's hormonal balance, potentially affecting reproductive hormones. For example, it can influence levels of estrogen and testosterone, which may have implications for menstrual cycles in women and sexual health in men. However, these effects are typically seen with long-term use and higher doses. Short-term use of melatonin at recommended doses is less likely to cause significant hormonal changes.

Though rare, some users may experience mood changes, such as feelings of depression or anxiety. These mood alterations are not common and may be related to individual differences in how melatonin affects neurotransmitter systems in the brain. If mood changes occur, it is crucial to discontinue use and consult a healthcare provider.

In summary, while melatonin is generally safe for most people, it can cause side effects such as daytime drowsiness, dizziness, headaches, gastrointestinal symptoms, and, in rare cases, mood changes and hormonal imbalances. These side effects are usually mild and can often be managed by adjusting the dose or timing of the supplement. If persistent or severe symptoms occur, it is important to seek medical advice.

While melatonin is generally safe for most people, there are certain groups who should avoid using it or consult a healthcare provider before starting supplementation. This is due to the potential for interactions with existing conditions or medications, and the need for careful management of specific health concerns.

Firstly, pregnant and breastfeeding women should use melatonin with caution. There is limited research on the safety of melatonin during pregnancy and lactation, so it is generally recommended to avoid its use unless advised by a healthcare provider. The potential effects of melatonin on the developing fetus or nursing infant are not well understood, making it prudent to err on the side of caution.

Individuals with autoimmune disorders, such as rheumatoid arthritis, lupus, or multiple sclerosis, should also exercise caution when considering melatonin supplementation. Melatonin can influence the immune system, and while it has anti-inflammatory properties, its impact on autoimmune conditions is not fully understood. Consulting a healthcare provider is essential to determine whether melatonin is appropriate in these cases.

People with depression or other mood disorders should be cautious with melatonin use. While melatonin can have mood-regulating effects, it may also exacerbate symptoms in some individuals. A study in the Journal of Clinical Psychiatry found that melatonin could have varying effects on mood, potentially worsening symptoms in some cases (Papadimitriou et al., 2010). Therefore, it is crucial for individuals with mood disorders to consult their healthcare provider before using melatonin.

Individuals taking certain medications should avoid melatonin or use it under medical supervision due to potential interactions. For example, melatonin can interact with anticoagulant medications like warfarin, increasing the risk of bleeding. It can also interact with medications that affect the immune system, such as corticosteroids. Additionally, melatonin may interfere with blood pressure medications, diabetes medications, and other drugs that affect the central nervous system, such as benzodiazepines.

Children and adolescents should use melatonin only under the guidance of a healthcare provider. While melatonin is sometimes used to help manage sleep disorders in children, especially those with ADHD or autism, the long-term effects of melatonin use in this age group are not well studied. A healthcare provider can help determine the appropriate dosage and monitor for any potential side effects.

Lastly, individuals with epilepsy or other seizure disorders should be cautious with melatonin use. There is some evidence that melatonin may influence seizure activity, although the effects can vary. A healthcare provider can help assess the risks and benefits of using melatonin in individuals with seizure disorders.

In summary, while melatonin is generally safe for many people, certain groups should avoid its use or consult a healthcare provider before starting supplementation. These include pregnant and breastfeeding women, individuals with autoimmune disorders, depression or mood disorders, those taking specific medications, children and adolescents, and individuals with seizure disorders. Consulting a healthcare provider ensures that melatonin use is safe and appropriate for individual health needs.

Yes, melatonin supplements are known to interact with several medications, which can affect their efficacy and safety. Understanding these interactions is crucial for individuals considering melatonin supplementation, especially those who are on prescription medications. Always consult a healthcare provider before starting melatonin if you are taking any other medications.

One of the primary concerns with melatonin supplementation is its interaction with anticoagulant medications, such as warfarin and other blood thinners. Melatonin can enhance the effects of these medications, increasing the risk of bleeding. A study in the Journal of Clinical Pharmacology highlighted this potential interaction, indicating that melatonin might increase the anticoagulant effect of warfarin, necessitating close monitoring of blood clotting parameters (Srinivasan et al., 2011).

Melatonin can also interact with medications that affect the central nervous system, such as benzodiazepines, antidepressants, and antipsychotics. For example, combining melatonin with benzodiazepines like diazepam or lorazepam can enhance the sedative effects, leading to excessive drowsiness or impaired coordination. Similarly, melatonin may interact with certain antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), potentially altering their efficacy and side effect profile. A study in the Journal of Clinical Psychiatry emphasized the need for caution when combining melatonin with these medications due to the potential for additive sedative effects (Papadimitriou et al., 2010).

Individuals taking medications for hypertension should also be cautious with melatonin. While melatonin can help lower blood pressure, it may interact with antihypertensive medications, such as beta-blockers or calcium channel blockers, potentially leading to an excessive decrease in blood pressure. Monitoring blood pressure closely and adjusting the dosage of either the medication or melatonin may be necessary under medical supervision.

For those managing diabetes, melatonin can interact with medications that regulate blood sugar levels. Melatonin has been shown to affect glucose metabolism, and its use in conjunction with diabetes medications like insulin or metformin may require careful monitoring of blood sugar levels to avoid hypoglycemia or hyperglycemia. A study in Diabetes, Obesity and Metabolism noted that melatonin could influence insulin sensitivity, highlighting the importance of monitoring for potential interactions (Peschke et al., 2006).

Melatonin can also interact with immunosuppressive medications, such as corticosteroids or drugs used in organ transplantation. Given that melatonin has immune-modulating properties, it may counteract the effects of these medications, potentially reducing their efficacy. Consulting a healthcare provider is essential to ensure that melatonin does not interfere with the intended effects of immunosuppressive therapy.

Lastly, melatonin can interact with medications that influence the cytochrome P450 enzyme system in the liver, which is responsible for metabolizing many drugs. For instance, melatonin may affect the metabolism of certain medications, potentially altering their plasma levels and effects. This interaction underscores the importance of consulting a healthcare provider to assess the risk of interactions and adjust medication dosages if necessary.

In summary, melatonin supplements can interact with various medications, including anticoagulants, central nervous system drugs, antihypertensives, diabetes medications, immunosuppressants, and drugs metabolized by the cytochrome P450 enzyme system. These interactions can affect the efficacy and safety of both melatonin and the medications being taken. Therefore, it is crucial to consult a healthcare provider before starting melatonin supplementation to ensure safe and effective use.

Melatonin can be sourced both naturally through certain foods and synthetically in the form of supplements. Understanding these sources can help individuals make informed choices about how to incorporate melatonin into their routines to support sleep and overall health.

Natural food sources of melatonin include a variety of fruits, vegetables, grains, and nuts. Tart cherries, in particular, are one of the richest natural sources of melatonin. Studies have shown that consuming tart cherry juice can significantly increase melatonin levels and improve sleep quality. A study published in the European Journal of Nutrition found that tart cherry juice supplementation improved sleep duration and quality in adults (Howatson et al., 2012). Additionally, other fruits such as grapes, strawberries, and kiwis also contain melatonin, albeit in smaller amounts.

Nuts, especially walnuts and almonds, are another good source of melatonin. Walnuts, for example, not only provide melatonin but also contain other nutrients like magnesium and omega-3 fatty acids that support sleep and overall health. Vegetables such as tomatoes, bell peppers, and mushrooms also contain melatonin, making them valuable additions to a melatonin-rich diet. Grains like rice, barley, and oats have been found to contain melatonin as well, providing another avenue for natural intake.

In addition to these natural sources, melatonin is available as a dietary supplement. These supplements are typically synthesized to mimic the natural melatonin produced by the body and are available in various forms, including tablets, capsules, gummies, and liquid formulations. Supplements offer a convenient and controlled way to increase melatonin intake, especially for individuals with significant sleep disturbances or those who need a more consistent dose.

When selecting melatonin supplements, it's important to consider the quality and purity of the product. Look for supplements that have been third-party tested for quality assurance and are free from contaminants and additives. Products with certifications from reputable organizations, such as the United States Pharmacopeia (USP) or NSF International, can provide additional assurance of quality.

In summary, the best sources of melatonin include natural foods such as tart cherries, grapes, strawberries, kiwis, walnuts, almonds, tomatoes, bell peppers, mushrooms, rice, barley, and oats. For those needing a more consistent or higher dose of melatonin, dietary supplements offer a practical solution. When choosing supplements, prioritize quality and purity by selecting products that have been third-party tested and certified by reputable organizations. Combining these natural and supplemental sources can help support healthy melatonin levels and improve sleep quality.

Melatonin is available in various forms, providing flexibility in how it can be administered to suit individual preferences and needs. Each form has its advantages and may be more suitable for different situations or specific health conditions.

One of the most common forms of melatonin is oral tablets or capsules. These are widely available and come in various dosages, typically ranging from 0.5 mg to 10 mg. Tablets and capsules are convenient and easy to take, making them a popular choice for individuals looking to improve their sleep quality. They are designed to be taken 30 to 60 minutes before bedtime to help promote sleep onset. Some tablets are formulated as immediate-release, providing a quick surge of melatonin, while others are extended-release, offering a gradual release of the hormone throughout the night to help maintain sleep.

Melatonin is also available in gummy form, which can be an appealing option for those who dislike swallowing pills or prefer a more palatable method of supplementation. Gummies come in various flavors and dosages, and they are especially popular among children and adults who find traditional tablets or capsules difficult to take. However, it is important to check the sugar content and other additives in gummies, as these can vary between brands.

Liquid melatonin is another form that offers flexibility in dosing. It is typically administered using a dropper, allowing for precise measurements and easy adjustments of the dose. This form is particularly useful for children or individuals who have difficulty swallowing pills. Liquid melatonin can be mixed with a small amount of water or juice, making it easier to consume.

For those who prefer not to take oral supplements, melatonin is also available in sublingual tablets or lozenges. These are designed to dissolve under the tongue, allowing the melatonin to be absorbed directly into the bloodstream through the mucous membranes. This method can provide a faster onset of action compared to oral tablets, making it a good option for individuals who need quick relief from sleep disturbances.

In addition to these common forms, melatonin is available as a transdermal patch. These patches are applied to the skin and deliver melatonin gradually over several hours. Transdermal patches can be particularly beneficial for individuals who require a steady release of melatonin throughout the night. They are also an option for those who have gastrointestinal issues or prefer a non-oral route of administration.

Finally, melatonin can be found in combination with other supplements or ingredients designed to support sleep, such as magnesium, valerian root, or L-theanine. These combination products can offer a synergistic effect, enhancing the overall benefits for sleep and relaxation.

In summary, melatonin is available in various forms, including oral tablets and capsules, gummies, liquid, sublingual tablets or lozenges, transdermal patches, and combination products with other sleep-supporting ingredients. Each form offers unique advantages, allowing individuals to choose the method that best suits their preferences and specific needs. Consulting with a healthcare provider can help determine the most appropriate form and dosage for optimal results.

Melatonin itself is the primary active compound responsible for its efficacy in regulating sleep and circadian rhythms. However, the effectiveness of melatonin can be influenced by its interaction with various sub-compounds and metabolites that either enhance its activity or contribute to its overall physiological effects. Understanding these sub-compounds can provide a deeper insight into the mechanisms through which melatonin exerts its benefits.

One of the critical metabolites of melatonin is N-acetylserotonin (NAS). NAS is an intermediate in the biosynthesis of melatonin from serotonin and possesses its own biological activities. NAS has been shown to exhibit antioxidant properties and neuroprotective effects, similar to melatonin. Additionally, NAS can activate TrkB receptors, which are involved in neurotrophic signaling and neuronal survival. This activation can contribute to the overall neuroprotective and mood-regulating effects of melatonin (Jang et al., 2017, Journal of Pineal Research).

Another important sub-compound is 6-sulfatoxymelatonin (6-SMT), the primary metabolite of melatonin excreted in the urine. Measuring levels of 6-SMT can provide a reliable indicator of melatonin production and metabolism in the body. While 6-SMT itself does not exert direct physiological effects, its measurement is critical for assessing melatonin's efficacy in clinical and research settings, particularly in studies evaluating sleep disorders, circadian rhythm disturbances, and endocrine functions.

Melatonin also interacts with other endogenous compounds that can modulate its activity. For example, melatonin's antioxidant effects are enhanced by its interaction with glutathione, a major intracellular antioxidant. Melatonin can stimulate the synthesis of glutathione and, together, these compounds work synergistically to neutralize reactive oxygen species and protect cells from oxidative damage. This interaction underscores the importance of maintaining optimal levels of both melatonin and glutathione for effective cellular protection (Reiter et al., 2005, Journal of Pineal Research).

Additionally, melatonin's interaction with serotonin should be noted. Serotonin is a precursor to melatonin, and adequate levels of serotonin are necessary for the synthesis of melatonin. This relationship is particularly important in the regulation of mood and sleep, as both serotonin and melatonin play crucial roles in these processes. Disruptions in serotonin levels can impact melatonin production and, consequently, affect sleep quality and circadian rhythms.

In some formulations, melatonin is combined with other compounds to enhance its efficacy or provide additional benefits. For instance, melatonin supplements may include magnesium, which can support relaxation and sleep quality by promoting muscle relaxation and reducing stress. Valerian root and L-theanine are other common additions that can enhance the calming effects of melatonin and improve sleep onset and duration.

In summary, while melatonin itself is the primary active compound responsible for its sleep-regulating effects, its efficacy can be influenced by critical sub-compounds and metabolites such as N-acetylserotonin and 6-sulfatoxymelatonin. Additionally, interactions with endogenous compounds like glutathione and serotonin, as well as synergistic effects with supplemental ingredients like magnesium, valerian root, and L-theanine, can enhance melatonin's overall benefits. Understanding these relationships can help optimize melatonin supplementation for improved sleep and overall health.

Melatonin is known by several names, abbreviations, and chemical identifiers, reflecting its widespread recognition and various forms of reference in scientific literature, supplements, and common usage. Here are some of the most common names and terms associated with melatonin:

1. N-Acetyl-5-methoxytryptamine: This is the chemical name for melatonin, describing its molecular structure. It is often used in scientific research and pharmacological contexts.
2. MT: Melatonin is sometimes abbreviated as "MT" in scientific literature, particularly when discussing its receptors, such as MT1 and MT2 receptors.
3. MEL: Another common abbreviation used in research papers and clinical studies.
4. Hormone of Darkness: Melatonin is sometimes referred to colloquially as the "hormone of darkness" because its production is closely tied to the absence of light and the onset of darkness.
5. Sleep Hormone: This is a common layman's term that highlights melatonin's primary role in regulating sleep cycles.
6. Pineal Hormone: Melatonin is often called the pineal hormone because it is primarily synthesized and secreted by the pineal gland in the brain.
7. C13H16N2O2: This is the molecular formula for melatonin, indicating its chemical composition.
8. Circadin: This is a brand name for a prolonged-release melatonin tablet used in the treatment of primary insomnia characterized by poor quality of sleep in patients aged 55 or older.
9. Mela-T: Sometimes, melatonin supplements are marketed under different brand names or slight variations, such as Mela-T, which can also be a shorthand in some contexts.
10. Melatonine: A common misspelling, especially in non-English speaking countries, where the spelling might reflect the local language's phonetic rules.
11. Melatonina: The Spanish and Italian name for melatonin, reflecting its usage in those languages.
12. Melatoninum: The Latin-based term that may be used in certain pharmacological references or in countries where Latin nomenclature is common in medical contexts.

Understanding these various names and terms can help individuals recognize melatonin in different contexts, whether shopping for supplements, reading scientific literature, or discussing it with healthcare providers. Regardless of the name or abbreviation used, they all refer to the same hormone that plays a crucial role in regulating sleep and circadian rhythms.

When selecting a melatonin supplement, it's crucial to ensure product quality, safety, and efficacy by paying close attention to the information provided on the label. Here are key elements to look for:

1. Dosage and Concentration: The label should clearly state the amount of melatonin per serving, which typically ranges from 0.5 mg to 10 mg. Choose a dosage that aligns with your specific needs and consult a healthcare provider if you're uncertain about the appropriate amount.
2. Third-Party Testing and Certifications: Look for supplements that have been independently tested by third-party organizations to verify their purity, potency, and safety. Certifications from reputable organizations such as the United States Pharmacopeia (USP), NSF International, or ConsumerLab.com indicate that the product meets high standards for quality and does not contain harmful contaminants.
3. Ingredient List: Check the ingredient list for any additional components. High-quality melatonin supplements should contain minimal fillers, binders, or artificial additives. If the supplement includes other active ingredients, such as magnesium, valerian root, or L-theanine, ensure these are clearly listed and their amounts specified.
4. Form of Melatonin: The label should specify whether the melatonin is immediate-release, extended-release, or sublingual. Immediate-release melatonin helps you fall asleep faster, while extended-release formulations are designed to help maintain sleep throughout the night. Sublingual tablets or lozenges dissolve under the tongue for quicker absorption.
5. Serving Size and Instructions: The label should provide clear instructions on how to take the supplement, including the recommended serving size, timing (e.g., 30 to 60 minutes before bedtime), and any specific conditions or instructions for optimal use.
6. Manufacturer Information: Reliable manufacturers will provide their contact information and may offer additional details about their quality control processes. Check for a reputable company name, address, and customer service contact information.
7. Expiration Date and Lot Number: Ensure the product has an expiration date and a lot number on the label, which indicates that the manufacturer tracks their batches for quality control and recalls if necessary. Avoid purchasing supplements that are near or past their expiration date.
8. Allergen Information: If you have any allergies or dietary restrictions, check the label for potential allergens such as gluten, dairy, soy, or nuts. Many high-quality supplements will be labeled as free from common allergens and may also be labeled as non-GMO, vegan, or organic.
9. Warnings and Contraindications: The label should include any warnings or contraindications, such as advising against use during pregnancy or while operating heavy machinery. This information is essential for ensuring the safe use of the supplement.
10. Country of Origin: Knowing where the supplement is manufactured can provide additional assurance of quality. Supplements made in countries with stringent manufacturing regulations, such as the United States, Canada, or those in the European Union, are generally more reliable.

In summary, to ensure the quality of a melatonin supplement, look for clear dosage information, third-party testing and certifications, a minimal and transparent ingredient list, specific form details, clear instructions for use, reputable manufacturer information, expiration date and lot number, allergen information, warnings, and the country of origin. These elements collectively help verify that the supplement you choose is safe, effective, and of high quality. Always consult with a healthcare provider before starting any new supplement regimen.

The information provided on this website, including any text, images, or other material contained within, is for informational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition. This page was created by the SuppCo editiorial team, with AI summarization tools, including data from but not limited to following studies:

1. S. P. James, D. Sack, N. Rosenthal, W. Mendelson (1990). Melatonin administration in insomnia.. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 3 1,
   19-23 . Link:
2. C. M. Ellis, Gilbert Lemmens, J. D. Parkes (1996). Melatonin and insomnia. Journal of Sleep Research, 5, . Link: 10.1046/j.1365-2869.1996.00003.x
3. Huajun Xu, Chujun Zhang, Y. Qian, J. Zou, Xinyi Li, Yupu Liu, Huaming Zhu, L. Meng, Suru Liu, Wei-tian Zhang, H. Yi, J. Guan, Zhengnong Chen, S. Yin (2020). Efficacy of melatonin for sleep disturbance in middle-aged primary insomnia: a double-blind, randomised clinical trial.. Sleep medicine, 76,
   113-119 . Link: 10.1016/j.sleep.2020.10.018
4. P. Lemoine, T. Nir, M. Laudon, N. Zisapel (2007). Prolonged‐release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. Journal of Sleep Research, 16, . Link: 10.1111/j.1365-2869.2007.00613.x
5. L. Palagini, R. Manni, E. Aguglia, M. Amore, R. Brugnoli, S. Bioulac, P. Bourgin, J. Micoulaud Franchi, P. Girardi, L. Grassi, R. Lopez, C. Mencacci, G. Plazzi, J. Maruani, A. Minervino, P. Philip, Sylvie Royant Parola, I. Poirot, L. Nobili, G. Biggio, C. Schroder, P. Geoffroy (2021). International Expert Opinions and Recommendations on the Use of Melatonin in the Treatment of Insomnia and Circadian Sleep Disturbances in Adult Neuropsychiatric Disorders. Frontiers in Psychiatry, 12, . Link: 10.3389/fpsyt.2021.688890
6. C. Andrade, B. Srihari, K. Reddy, L. Chandramma (2001). Melatonin in medically ill patients with insomnia: a double-blind, placebo-controlled study.. The Journal of clinical psychiatry, 62 1,
   41-5 . Link: 10.4088/JCP.V62N0109
7. A. Brzezinski, M. Vangel, R. Wurtman, Gillian Norrie, I. Zhdanova, A. Ben-Shushan, I. Ford (2005). Effects of exogenous melatonin on sleep: a meta-analysis.. Sleep medicine reviews, 9 1,
   41-50 . Link: 10.1016/J.SMRV.2004.06.004
8. F. Auld, Emily L. Maschauer, I. Morrison, D. Skene, R. Riha (2017). Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders.. Sleep medicine reviews, 34,
   10-22 . Link: 10.1016/j.smrv.2016.06.005
9. Kristiaan B. Van, Der, Heijden, Marcel G. Smits, E. Someren, Richard Ridderinkhof, W. B. gunning (2007). Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia.. Journal of the American Academy of Child and Adolescent Psychiatry, 46 2,
   233-41 . Link: 10.1097/01.CHI.0000246055.76167.0D
10. Azar Jafari-Koulaee, Masoumeh Bagheri-Nesami (2021). The effect of melatonin on sleep quality and insomnia in patients with cancer: a systematic review study.. Sleep medicine, 82,
    96-103 . Link: 10.1016/j.sleep.2021.03.040
11. J. Zeitzer, J. Duffy, S. Lockley, D. Dijk, C. Czeisler (2007). Plasma melatonin rhythms in young and older humans during sleep, sleep deprivation, and wake.. Sleep, 30 11,
    1437-43 . Link: 10.1093/SLEEP/30.11.1437
12. M. Rios-Lugo, P. Cano, V. Jiménez‐Ortega, M. P. Fernández-Mateos, P. Scacchi, D. Cardinali, A. Esquifino (2010). Melatonin effect on plasma adiponectin, leptin, insulin, glucose, triglycerides and cholesterol in normal and high fat–fed rats. Journal of Pineal Research, 49, . Link: 10.1111/j.1600-079X.2010.00798.x
13. F. Raygan, Vahidreza Ostadmohammadi, F. Bahmani, R. Reiter, Z. Asemi (2019). Melatonin administration lowers biomarkers of oxidative stress and cardio-metabolic risk in type 2 diabetic patients with coronary heart disease: A randomized, double-blind, placebo-controlled trial.. Clinical nutrition, 38 1,
    191-196 . Link: 10.1016/j.clnu.2017.12.004
14. Vahidreza Ostadmohammadi, A. Soleimani, F. Bahmani, E. Aghadavod, Reza Ramezani, R. Reiter, M. Mansournia, Zarrin Banikazemi, M. Soleimani, Marsa Zaroudi, Z. Asemi (2020). The Effects of Melatonin Supplementation on Parameters of Mental Health, Glycemic Control, Markers of Cardiometabolic Risk, and Oxidative Stress in Diabetic Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation, , . Link: 10.1053/j.jrn.2019.08.003
15. Linfeng Wang, J. McFadden, Gaiqing Yang, He-Shui Zhu, Hongxia Lian, T. Fu, Yu Sun, T. Gao, Ming Li (2021). Effect of melatonin on visceral fat deposition, lipid metabolism and hepatic lipo-metabolic gene expression in male rats.. Journal of animal physiology and animal nutrition, , . Link: 10.1111/jpn.13497
16. R. P. Junior, L. Chuffa, Vinícius Augusto Simão, N. M. Sonehara, R. Chammas, R. Reiter, D. Zuccari (2022). Melatonin Regulates the Daily Levels of Plasma Amino Acids, Acylcarnitines, Biogenic Amines, Sphingomyelins, and Hexoses in a Xenograft Model of Triple Negative Breast Cancer. International Journal of Molecular Sciences, 23, . Link: 10.3390/ijms23169105
17. S. W. Rajaratnam, B. Middleton, B. Stone, J. Arendt, D. Dijk (2004). Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans. The Journal of Physiology, 561, . Link: 10.1113/jphysiol.2004.073742
18. Anna Tarocco, N. Caroccia, G. Morciano, M. Wieckowski, G. Ancora, G. Garani, P. Pinton (2019). Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical implications for newborn care. Cell Death & Disease, 10, . Link: 10.1038/s41419-019-1556-7
19. D. Rasmussen, B. M. Boldt, C. Wilkinson, S. Yellon, A. Matsumoto (1999). Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels.. Endocrinology, 140 2,
    1009-12 . Link: 10.1210/en.140.2.1009
20. M. Navarro-Alarcón, F. Ruiz-Ojeda, R. Blanca-Herrera, A. Kaki, A. Adem, A. Agil (2014). Melatonin administration in diabetes: regulation of plasma Cr, V, and Mg in young male Zucker diabetic fatty rats.. Food & function, 5 3,
    512-6 . Link: 10.1039/c3fo60389j
21. O. Pechanova, L. Paulis, F. Simko (2014). Peripheral and Central Effects of Melatonin on Blood Pressure Regulation. International Journal of Molecular Sciences, 15, 17920 - 17937. Link: 10.3390/ijms151017920
22. A. Hadi, E. Ghaedi, S. Moradi, M. Pourmasoumi, A. Ghavami, M. Kafeshani (2019). Effects of Melatonin Supplementation On Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Hormone and Metabolic Research, 51, 157 - 164. Link: 10.1055/a-0841-6638
23. Macarena Ramos Gonzalez, Michael R. Axler, Kathryn E. Kaseman, Andrea J Lobene, W. Farquhar, Melissa A H Witman, D. Kirkman, S. Lennon (2023). Melatonin Supplementation Reduces Nighttime Blood Pressure But Does Not Affect Blood Pressure Reactivity in Normotensive Adults on a High Sodium Diet.. American journal of physiology. Regulatory, integrative and comparative physiology, , . Link: 10.1152/ajpregu.00101.2023
24. M. Akbari, Vahidreza Ostadmohammadi, N. Mirhosseini, K. Lankarani, R. Tabrizi, Z. Keshtkaran, R. Reiter, Z. Asemi (2019). The effects of melatonin supplementation on blood pressure in patients with metabolic disorders: a systematic review and meta-analysis of randomized controlled trials. Journal of Human Hypertension, 33, 202-209. Link: 10.1038/s41371-019-0166-2
25. F. Scheer, G. V. van Montfrans, E. V. Van Someren, Gideon Mairuhu, R. Buijs (2004). Daily Nighttime Melatonin Reduces Blood Pressure in Male Patients With Essential Hypertension. Hypertension: Journal of the American Heart Association, 43, 192-197. Link: 10.1161/01.HYP.0000113293.15186.3b
26. A. Cagnacci, Maria G Cannoletta, A. Renzi, F. Baldassari, S. Arangino, A. Volpe (2005). Prolonged melatonin administration decreases nocturnal blood pressure in women.. American journal of hypertension, 18 12 Pt 1,
    1614-8 . Link: 10.1016/J.AMJHYPER.2005.05.008
27. Lusardi, Preti, Savino, Piazza, Zoppi, Fogari (1997). Effect of bedtime melatonin ingestion on blood pressure of normotensive subjects.. Blood pressure monitoring, 2 2,
    99-103 . Link:
28. M. Możdżan, M. Możdżan, M. Chałubiński, Katarzyna Wojdan, M. Broncel (2014). The effect of melatonin on circadian blood pressure in patients with type 2 diabetes and essential hypertension. Archives of Medical Science : AMS, 10, 669 - 675. Link: 10.5114/aoms.2014.44858
29. S. Arangino, A. Cagnacci, M. Angiolucci, A. M. Vacca, G. Longu, A. Volpe, G. Melis (1999). Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men.. The American journal of cardiology, 83 9,
    1417-9 . Link: 10.1016/S0002-9149(99)00112-5
30. F. Simko, L. Paulis (2007). Melatonin as a potential antihypertensive treatment. Journal of Pineal Research, 42, . Link: 10.1111/j.1600-079X.2007.00436.x
31. Julio J. Ochoa, J. Díaz-Castro, N. Kajarabille, C. García, I. Guisado, C. de Teresa, Rafael Guisado (2011). Melatonin supplementation ameliorates oxidative stress and inflammatory signaling induced by strenuous exercise in adult human males. Journal of Pineal Research, 51, . Link: 10.1111/j.1600-079X.2011.00899.x
32. M. Cheikh, Khouloud Makhlouf, Kais Ghattassi, A. Graja, Salyma Ferchichi, C. Kallel, Mallek Houda, N. Souissi, O. Hammouda (2019). Melatonin ingestion after exhaustive late-evening exercise attenuate muscle damage, oxidative stress, and inflammation during intense short term effort in the following day in teenage athletes. Chronobiology International, 37, 236 - 247. Link: 10.1080/07420528.2019.1692348
33. M. A. Farjallah, Kais Ghattassi, A. Kamoun, A. Graja, L. Ben Mahmoud, T. Driss, K. Jamoussi, Z. Sahnoun, N. Souissi, P. Żmijewski, O. Hammouda (2022). Melatonin supplementation alleviates cellular damage and physical performance decline induced by an intensive training period in professional soccer players. PLoS ONE, 17, . Link: 10.1371/journal.pone.0273719
34. Rafael Ishihara, M. P. Barros, Cristiano José da Silva, L. Borges, E. Hatanaka, R. Lambertucci (2021). Melatonin improves the antioxidant capacity in cardiac tissue of Wistar rats after exhaustive exercise. Free Radical Research, 55, 677 - 692. Link: 10.1080/10715762.2021.1939024
35. H. Marzougui, M. Turki, I. Ben Dhia, R. Maaloul, H. Chaker, Rihab Makhlouf, I. Agrebi, K. Kammoun, K. Jamoussi, F. Ayadi, M. Ben hmida, O. Hammouda (2023). Melatonin intake before intradialytic exercise reverses oxidative stress and improves antioxidant status in hemodialysis patients. The International Journal of Artificial Organs, 46, 264 - 273. Link: 10.1177/03913988231165324
36. L. Borges, A. Dermargos, Edenilson Pinto da Silva Junior, Eleine Weimann, R. Lambertucci, E. Hatanaka (2015). Melatonin decreases muscular oxidative stress and inflammation induced by strenuous exercise and stimulates growth factor synthesis. Journal of Pineal Research, 58, . Link: 10.1111/jpi.12202
37. J. Kruk, Basil H. Aboul-Enein, Ewa Duchnik (2021). Exercise-induced oxidative stress and melatonin supplementation: current evidence. The Journal of Physiological Sciences : JPS, 71, . Link: 10.1186/s12576-021-00812-2
38. M. Mansouri, S. Abbasian, M. Khazaie (2018). Melatonin and Exercise: Their Effects on Malondialdehyde and Lipid Peroxidation. Melatonin - Molecular Biology, Clinical and Pharmaceutical Approaches, , . Link: 10.5772/INTECHOPEN.79561
39. I. Ben Dhia, R. Maaloul, H. Marzougui, S. Ghroubi, C. Kallel, T. Driss, M. Elleuch, F. Ayadi, M. Turki, O. Hammouda (2022). Melatonin reduces muscle damage, inflammation and oxidative stress induced by exhaustive exercise in people with overweight/obesity.. Physiology international, , . Link: 10.1556/2060.2022.00126
40. R. C. Leonardo-Mendonça, Javier Ocaña-Wilhelmi, T. de Haro, Carlos de Teresa-Galván, E. Guerra-Hernández, I. Rusanova, Marisol Fernández-Ortiz, Ramy K. A. Sayed, G. Escames, D. Acuña-Castroviejo (2017). The benefit of a supplement with the antioxidant melatonin on redox status and muscle damage in resistance-trained athletes.. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 42 7,
    700-707 . Link: 10.1139/apnm-2016-0677
41. I. Brzozowska, M. Strzałka, D. Drozdowicz, S. Konturek, T. Brzozowski (2014). Mechanisms of esophageal protection, gastroprotection and ulcer healing by melatonin. implications for the therapeutic use of melatonin in gastroesophageal reflux disease (GERD) and peptic ulcer disease.. Current pharmaceutical design, 20 30,
    4807-15 . Link: 10.2174/1381612819666131119110258
42. I. Brzozowska, P. Konturek, T. Brzozowski, S. Konturek, S. Kwiecień, R. Pajdo, D. Drozdowicz, M. Pawlik, A. Ptak, E. Hahn (2002). Role of prostaglandins, nitric oxide, sensory nerves and gastrin in acceleration of ulcer healing by melatonin and its precursor, L‐tryptophan. Journal of Pineal Research, 32, . Link: 10.1034/j.1600-079x.2002.1o811.x
43. Konturek Pc, S. Konturek, J. Majka, M. Zembala, E. Hahn (1997). Melatonin affords protection against gastric lesions induced by ischemia-reperfusion possibly due to its antioxidant and mucosal microcirculatory effects.. European journal of pharmacology, 322 1,
    73-7 . Link: 10.1016/S0014-2999(97)00051-4
44. K. Kato, I. Murai, S. Asai, Y. Takahashi, Y. Matsuno, S. Komuro, H. Kurosaka, A. Iwasaki, K. Ishikawa, Y. Arakawa (1998). Central nervous system action of melatonin on gastric acid and pepsin secretion in pylorus-ligated rats.. Neuroreport, 9 11,
    2447-50 . Link:
45. J. Jaworek, T. Brzozowski, S. Konturek (2005). Melatonin as an organoprotector in the stomach and the pancreas. Journal of Pineal Research, 38, . Link: 10.1111/j.1600-079X.2004.00179.x
46. Konturek Pc, Stanisław J. Konturek, K. Celinski, M. Slomka, H. Cichoż-Lach, W. Bielański, Russel J. Reiter (2010). Role of melatonin in mucosal gastroprotection against aspirin‐induced gastric lesions in humans. Journal of Pineal Research, 48, . Link: 10.1111/j.1600-079X.2010.00755.x
47. T. Brzozowski, P. Konturek, K. Żwirska-Korczala, S. Konturek, I. Brzozowska, D. Drozdowicz, Z. Śliwowski, M. Pawlik, W. Pawlik, E. Hahn (2005). Importance of the pineal gland, endogenous prostaglandins and sensory nerves in the gastroprotective actions of central and peripheral melatonin against stress‐induced damage. Journal of Pineal Research, 39, . Link: 10.1111/j.1600-079X.2005.00264.x
48. K. Celinski, P. Konturek, M. Slomka, H. Cichoż-Lach, M. Gonciarz, W. Bielański, R. Reiter, S. Konturek (2009). Altered basal and postprandial plasma melatonin, gastrin, ghrelin, leptin and insulin in patients with liver cirrhosis and portal hypertension without and with oral administration of melatonin or tryptophan. Journal of Pineal Research, 46, . Link: 10.1111/j.1600-079X.2009.00677.x
49. K. Kirsz, M. Szczesna, E. Molik, D. Zieba (2017). Effects of ghrelin on nocturnal melatonin secretion in sheep: An in vitro and in vivo approach.. Journal of animal science, 95 9,
    4101-4112 . Link: 10.2527/jas2017.1737
50. L. F. Nogueira, E. Marqueze (2021). Effects of melatonin supplementation on eating habits and appetite-regulating hormones: a systematic review of randomized controlled clinical and preclinical trials. Chronobiology International, 38, 1089 - 1102. Link: 10.1080/07420528.2021.1918143
51. J. Jaworek (2006). Ghrelin and melatonin in the regulation of pancreatic exocrine secretion and maintaining of integrity.. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 57 Suppl 5,
    83-96 . Link:
52. A. Mustonen, P. Nieminen, H. Hyvärinen (2001). Preliminary evidence that pharmacologic melatonin treatment decreases rat ghrelin levels. Endocrine, 16, 43-46. Link: 10.1385/ENDO:16:1:43
53. Y. Djeridane, Y. Touitou (2005). Lack of effect of ghrelin treatment on melatonin production in rat pineal and Harderian glands.. Life sciences, 76 20,
    2393-401 . Link: 10.1016/J.LFS.2004.12.006
54. Zhihai Liang, M. Qin, G. Tang, Hui-ying Yang, Juan Su, Jie-An Huang (2014). Melatonin reduces inflammation and recovers endogenous ghrelin in acute necrotizing pancreatitis in rats.. Molecular medicine reports, 9 6,
    2599-605 . Link: 10.3892/mmr.2014.2132
55. R. Bułdak, Katarzyna Pilc-Gumuła, Ł. Bułdak, D. Witkowska, M. Kukla, R. Polaniak, K. Żwirska-Korczala (2015). Effects of ghrelin, leptin and melatonin on the levels of reactive oxygen species, antioxidant enzyme activity and viability of the HCT 116 human colorectal carcinoma cell line.. Molecular medicine reports, 12 2,
    2275-82 . Link: 10.3892/mmr.2015.3599
56. Hoon Jang, Y. Na, Kwonho Hong, Sangho Lee, Sohyeon Moon, M Cho, Miseon Park, Ok-Hee Lee, E. Chang, Dong Ryul Lee, J. Ko, W. Lee, Youngsok Choi (2017). Synergistic effect of melatonin and ghrelin in preventing cisplatin‐induced ovarian damage via regulation of FOXO3a phosphorylation and binding to the p27Kip1 promoter in primordial follicles. Journal of Pineal Research, 63, . Link: 10.1111/jpi.12432
57. A. Ibáñez-Costa, J. Cordoba-Chacon, M. Gahete, R. Kineman, J. Castaño, R. Luque (2015). Melatonin regulates somatotrope and lactotrope function through common and distinct signaling pathways in cultured primary pituitary cells from female primates.. Endocrinology, 156 3,
    1100-10 . Link: 10.1210/en.2014-1819
58. A. Schneider, Ana Carolina de Moura, F. Carvalho, Thiago Alves, F. Meurer, M. Porawski, T. R. da Silveira (2021). Effect of Melatonin on the Reduction of Hepatic Steatosis and Intestinal Leptin Expression in Zebrafish Exposed to Fructose.. Zebrafish, , . Link: 10.1089/zeb.2020.1910
59. S. Aspengren, H. Sköld, G. Quiroga, L. Mårtensson, M. Wallin (2003). Noradrenaline- and melatonin-mediated regulation of pigment aggregation in fish melanophores.. Pigment cell research, 16 1,
    59-64 . Link: 10.1034/J.1600-0749.2003.00003.X
60. M. Franklin, E. M. Clement, G. Campling, P. Cowen (1998). Effect of venlafaxine on pineal melatonin and noradrenaline in the male rat. Journal of Psychopharmacology, 12, 371 - 374. Link: 10.1177/026988119801200407
61. D. Skene, C. Bojkowski, J. Arendt (1994). Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans.. British journal of clinical pharmacology, 37 2,
    181-6 . Link: 10.1111/J.1365-2125.1994.TB04258.X
62. Z. S. Ferreira, P. Fernandes, D. Duma, J. Assreuy, M. Avellar, R. Markus (2005). Corticosterone modulates noradrenaline‐induced melatonin synthesis through inhibition of nuclear factor kappa B. Journal of Pineal Research, 38, . Link: 10.1111/j.1600-079X.2004.00191.x
63. V. N. Iartsev, O. V. Karachentseva, D. P. Dvoretskii (2004). [Effects of exogenic noradrenaline and melatonin on the neurogenic vasoreactivity].. Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova, 90 11,
    1363-9 . Link:
64. C. Torres-Farfan, F. Valenzuela, Mauricio Mondaca, Guillermo J. Valenzuela, B. Krause, E. Herrera, R. Riquelme, A. Llanos, M. Seron-Ferre (2008). Evidence of a role for melatonin in fetal sheep physiology: direct actions of melatonin on fetal cerebral artery, brown adipose tissue and adrenal gland. The Journal of Physiology, 586, . Link: 10.1113/jphysiol.2008.154351
65. W. Drijfhout, A. Linde, J. B. Vries, C. Grol, B. Westerink (1996). Microdialysis reveals dynamics of coupling between noradrenaline release and melatonin secretion in conscious rats. Neuroscience Letters, 202, 185-188. Link: 10.1016/0304-3940(95)12245-1
66. J. Axelrod, H. Shein, R. Wurtman (1969). Stimulation of C14-melatonin synthesis from C14-tryptophan by noradrenaline in rat pineal in organ culture.. Proceedings of the National Academy of Sciences of the United States of America, 62 2,
    544-9 . Link: 10.1073/PNAS.62.2.544
67. P. Cowen, A. Green, D. Grahame-Smith, L. Braddock (1985). Plasma melatonin during desmethylimipramine treatment: evidence for changes in noradrenergic transmission.. British journal of clinical pharmacology, 19 6,
    799-805 . Link: 10.1111/J.1365-2125.1985.TB02717.X
68. E. Palazidou, A. Papadopoulos, H. Ratcliff, S. Dawling, S. Checkley (1992). Noradrenaline uptake inhibition increases melatonin secretion, a measure of noradrenergic neurotransmission, in depressed patients. Psychological Medicine, 22, 309 - 315. Link: 10.1017/S0033291700030257
69. D. Garfinkel, M. Laudon, D. Nof, N. Zisapel (1995). Improvement of sleep quality in elderly people by controlled-release melatonin. The Lancet, 346, 541-544. Link: 10.1016/S0140-6736(95)91382-3
70. Khadijeh Alizadeh Feremi, L. Alipoor, R. Esmaeili (2021). Effect of Melatonin on the Sleep Quality: A Systematic Review. Reviews in Clinical Medicine, 8, 60-68. Link: 10.22038/RCM.2021.55887.1356
71. A. Brzezinski, M. Vangel, R. Wurtman, Gillian Norrie, I. Zhdanova, A. Ben-Shushan, I. Ford (2005). Effects of exogenous melatonin on sleep: a meta-analysis.. Sleep medicine reviews, 9 1,
    41-50 . Link: 10.1016/J.SMRV.2004.06.004
72. Natalie A. Grima, S. Rajaratnam, D. Mansfield, T. Sletten, Gershon Spitz, J. Ponsford (2018). Efficacy of melatonin for sleep disturbance following traumatic brain injury: a randomised controlled trial. BMC Medicine, 16, . Link: 10.1186/s12916-017-0995-1
73. P. Lemoine, T. Nir, M. Laudon, N. Zisapel (2007). Prolonged‐release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. Journal of Sleep Research, 16, . Link: 10.1111/j.1365-2869.2007.00613.x
74. J. V. Gandolfi, Ana Paula Altimari Di Bernardo, Débora Augusto Valverde Chanes, D. F. Martin, V. B. Joles, C. P. Amendola, L. Sanches, G. Ciorlia, S. Lobo (2020). The Effects of Melatonin Supplementation on Sleep Quality and Assessment of the Serum Melatonin in ICU Patients: A Randomized Controlled Trial.. Critical Care Medicine, , . Link: 10.1097/CCM.0000000000004690
75. N. Pereira, M. F. Naufel, E. Ribeiro, S. Tufik, H. Hachul (2019). Influence of Dietary Sources of Melatonin on Sleep Quality: A Review.. Journal of food science, , . Link: 10.1111/1750-3841.14952
76. Gholami Fatemeh, Moradi Sajjad, Rasaei Niloufar, Soveid Neda, Setayesh Leila, Mirzaei Khadijeh (2021). Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials. Journal of Neurology, , . Link: 10.1007/s00415-020-10381-w
77. Yi Gao, Xuezhao Chen, Qi Zhou, Jiannan Song, Xizhe Zhang, Yi Sun, Miao Yu, Yun Li (2022). Effects of Melatonin Treatment on Perioperative Sleep Quality: A Systematic Review and Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials. Nature and Science of Sleep, 14, 1721 - 1736. Link: 10.2147/NSS.S381918
78. Azar Jafari-Koulaee, Masoumeh Bagheri-Nesami (2021). The effect of melatonin on sleep quality and insomnia in patients with cancer: a systematic review study.. Sleep medicine, 82,
    96-103 . Link: 10.1016/j.sleep.2021.03.040
79. Russel J. Reiter, D. Tan, J. Mayo, R. Sainz, Josefa León, D. Bandyopadhyay (2003). Neurally-mediated and neurally-independent beneficial actions of melatonin in the gastrointestinal tract.. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 54 Suppl 4,
    113-25 . Link:
80. C. Cho, S. Pang, Baobao Chen, C. J. Pfeiffer (1989). Modulating Action of Melatonin on Serotonin‐Induced Aggravation of Ethanol Ulceration and Changes of Mucosal Blood Flow in Rat Stomachs. Journal of Pineal Research, 6, . Link: 10.1111/j.1600-079X.1989.tb00406.x
81. D. Bandyopadhyay, A. Chattopadhyay (2006). Reactive oxygen species-induced gastric ulceration: protection by melatonin.. Current medicinal chemistry, 13 10,
    1187-202 . Link: 10.2174/092986706776360842
82. D. Bandyopadhyay, A. Bandyopadhyay, P. K. Das, R. Reiter (2002). Melatonin protects against gastric ulceration and increases the efficacy of ranitidine and omeprazole in reducing gastric damage. Journal of Pineal Research, 33, . Link: 10.1034/j.1600-079X.2002.01107.x
83. J. Jaworek, T. Brzozowski, S. Konturek (2005). Melatonin as an organoprotector in the stomach and the pancreas. Journal of Pineal Research, 38, . Link: 10.1111/j.1600-079X.2004.00179.x
84. H. Ayles, R. Ball, R. Friendship, G. Bubenik (1996). The effect of graded levels of melatonin on performance and gastric ulcers in pigs. Canadian Journal of Animal Science, 76, 607-611. Link: 10.4141/CJAS96-089
85. M. Magierowski, Katarzyna Jasnos, I. Brzozowska, D. Drozdowicz, Z. Śliwowski, Elizbieta Nawrot, U. Szczyrk, S. Kwiecień (2013). [Melatonin as a therapeutic factor in gastric ulcer healing under experimental diabetes].. Przeglad lekarski, 70 11,
    942-6 . Link:
86. H. Ayles, R. Friendship, G. Bubenik, R. Ball (1999). EFFECT OF FEED PARTICLE SIZE AND DIETARY MELATONIN SUPPLEMENTATION ON GASTRIC ULCERS IN SWINE. Canadian Journal of Animal Science, 79, 179-185. Link: 10.4141/A98-071
87. K. Celinski, S. Konturek, P. C. Konturek, T. Brzozowski, H. Cichoż-Lach, M. Slomka, Plonka Malgorzata, W. Bielański, R. Reiter (2011). Melatonin or l‐tryptophan accelerates healing of gastroduodenal ulcers in patients treated with omeprazole. Journal of Pineal Research, 50, . Link: 10.1111/j.1600-079X.2011.00855.x
88. G. Dion (2014). Commentary on "does melatonin have therapeutic use in tinnitus?".. Southern medical journal, 107 6,
    367 . Link: 10.14423/01.SMJ.0000450713.38550.1a
89. Agnes Hurtuk, C. Dome, C. Holloman, Kelly Wolfe, D. Welling, E. Dodson, Abraham Jacob (2011). Melatonin: Can it Stop the Ringing?. Annals of Otology, Rhinology & Laryngology, 120, 433 - 440. Link: 10.1177/000348941112000703
90. C. F. Sepmeijer, J. K. Langendoen, M. J. Middelweerd (2000). Melatonine for tinnitus. Clinical Otolaryngology, 25, 327-328. Link: 10.1046/J.1365-2273.2000.00358-20.X
91. A. Pirodda, M. C. Raimondi, G. Ferri (2010). Exploring the reasons why melatonin can improve tinnitus.. Medical hypotheses, 75 2,
    190-1 . Link: 10.1016/j.mehy.2010.02.018
92. Leah Merrick, D. Youssef, M. Tanner, A. Peiris (2014). Does Melatonin Have Therapeutic Use in Tinnitus?. Southern Medical Journal, 107, 362–366. Link: 10.14423/01.SMJ.0000450714.38550.d4
93. S. Albu, Felician Chirteş (2014). Intratympanic dexamethasone plus melatonin versus melatonin only in the treatment of unilateral acute idiopathic tinnitus.. American journal of otolaryngology, 35 5,
    617-22 . Link: 10.1016/j.amjoto.2014.06.009
94. Seyed Hamidreza Abtahi, S. M. Hashemi, Mahdi Mahmoodi, M. Nilforoush (2017). Comparison of Melatonin and Sertraline Therapies on Tinnitus: A Randomized Clinical Trial. International Journal of Preventive Medicine, 8, . Link: 10.4103/ijpvm.IJPVM_229_17
95. R. Reiter, D. Tan, A. Korkmaz, L. Fuentes-Broto (2011). Drug-mediated ototoxicity and tinnitus: alleviation with melatonin.. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 62 2,
    151-7 . Link:
96. A. Hosseinzadeh, S. K. Kamrava, B. Moore, R. Reiter, H. Ghaznavi, M. Kamali, S. Mehrzadi (2019). Molecular Aspects of Melatonin Treatment in Tinnitus; a Review.. Current drug targets, , . Link: 10.2174/1389450120666190319162147
97. U. Megwalu, Joshua Finnell, J. Piccirillo (2005). The Effects of Melatonin on Tinnitus and Sleep. Otolaryngology–Head and Neck Surgery, 134, 210 - 213. Link: 10.1016/j.otohns.2005.10.007