Melatonin is a hormone related to the biological clock, also known as the body’s “timing factor”, which is often used to regulate sleep.
What is Melatonin?
Melatonin is a hormone produced in the pineal gland and also exists in plants and microorganisms. It was discovered and named by American dermatologist Aaron Lerner in 1958, mainly related to circadian rhythms and seasonal reproduction regulation.
In most animals, melatonin is synthesized and secreted primarily at night (converted from tryptophan), and it is also synthesized in many tissues and cells, including retina, bone marrow cells, platelets, gastrointestinal tract, skin, or lymphocytes.
Dispersed throughout the body, melatonin receptors appear to be multipurpose physiological signals involved in the control of many physiological processes that affect responses such as sleep, reproduction, molting, immune responses, energy balance, and behavior.
In addition, it has direct and indirect antioxidant properties, and there is strong evidence that this compound can counteract the harmful effects of reactive oxygen species and nitrogen in different systems.
When to take melatonin (dose)?
If you want to try melatonin, it’s best to start with low doses. For example, take 0.5 mg/mg (500 mcg) or 1 mg 30 minutes before bedtime.
If this dose doesn’t help you fall asleep, try increasing it to 3 to 5 mg.
But taking more melatonin may not help you fall asleep faster, the goal is to find the lowest dose that will get you to sleep.
Does Melatonin Help Whiten Skin?
It is generally believed that melatonin can achieve whitening effect by inhibiting epidermal melanin, but according to the current available research, oral melatonin has no effect on human skin pigmentation, so it is not helpful for skin whitening. Note 1
What is the difference between Melatonin and Melanin?
Melatonin is a hormone responsible for the body’s biological clock, while melanin is a pigment responsible for skin color. This is the main difference between the two.
Melanin is one of the main pigments found in human skin, and it determines the color of the skin. In humans, melanin exists in three forms: eumelanin, pheomelanin, and neuromelanin.
In its different forms, melanin has a variety of biological functions, the most important being the protection of the skin and eyes from the sun’s ultraviolet radiation.
What are the proven efficacy (benefits) of melatonin?
1. Improve the success rate of IVF
Techniques involving the manipulation of oocytes in vitro are called assisted reproductive technologies, of which in vitro fertilization/IVF is the most common form.
In July 1978, Robert Edwards and Patrick Steptoe, MD, reported the first IVF babies in England, an achievement that later earned Edwards the Nobel Prize in Medicine in 2010.
Initially, IVF was used for infertile women with bilateral blocked fallopian tubes. In later years, IVF was also used in couples with unexplained subfertility, cervical factors, failed ovulation induction, endometriosis or unilateral Lateral fallopian tube pathology.
A meta-analysis of the literature (including 7 randomized controlled trials) indicated that oral melatonin during IVF treatment increased the number of mature oocytes and increased clinical pregnancy rates. pregnancy rate), although not significant. Note 1
＊Conclusion: For IVF treatment, melatonin may bring positive help, but limited by the small sample size, more research is needed for further verification
2. Good for weight control
Obesity has become one of the most important public health problems in the world, associated with type 2 diabetes, myocardial infarction, stroke, osteoarthritis, obstructive sleep apnea, depression, and some types of cancer, such as breast cancer, Ovarian, prostate, liver, kidney and colon cancers are closely related.
The rise in obesity rates over the past few decades is reflected in the industrialization of the food system, including the production and sale of highly processed foods. These types of foods are usually higher in calories than unprocessed foods like fruits, vegetables, and fish, and are far less healthy.
A systematic literature review and meta-analysis (including 23 randomized controlled trials) indicated that melatonin supplementation (dose ranging from 3 to 10 mg per day, and intervention duration from 3 to 48 weeks) compared with placebo ) reduced body weight but had no significant effect on BMI and waist circumference. Note 1
*Conclusion: Melatonin supplementation may have positive effects on weight control, but limited by possible selection bias, more research is needed to confirm its efficacy and safety.
3. Relieve surgery-related anxiety
Surgery is a traumatic treatment, often with risks of bleeding, pain or death, so patients admitted to the hospital for surgery often experience some level of anxiety.
Anxiety can be defined as varying degrees of tension, restlessness, fear, and a high degree of involuntary feeling.
Patients with high anxiety require higher doses of anesthesia inducers and have poorer recovery. Without realizing it, prolonged anxiety can create stress that can subsequently harm the patient and delay recovery.
A Cochrane Database of Systematic Reviews (Cochrane Database of Systematic Reviews, consisting of 27 randomized controlled trials involving 2319 patients undergoing any surgical procedure requiring the use of anesthesia) noted that compared with placebo, melatonin as a premedication ( tablet or sublingual) may reduce preoperative anxiety in adults (measured 50 to 120 minutes after dosing). Note 1
Melatonin also reduced immediate and delayed anxiety, but to a lesser extent, compared with placebo (measured in the recovery room and 6 hours after surgery).
Compared to benzodiazepines, melatonin is almost indistinguishable from anxiolytics. Therefore, melatonin may have similar effects to benzodiazepines in reducing preoperative and postoperative anxiety in adults.
*Conclusion: Oral melatonin may positively help with surgery-related anxiety.
4. Adjuvant COVID-19 Treatment
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread rapidly around the world and was declared a pandemic in early 2020.
The virus can cause a wide range of clinical manifestations, ranging from mild symptoms (such as fever, cough, and myalgias) to moderate symptoms (pneumonia and local inflammation) requiring hospitalization, and severe symptoms can lead to death.
In COVID-19, interactions between epithelial and immune cells produce high levels of pro-inflammatory cytokines, linking cytokine storms with severe complications and poor prognosis in this infection.
A single-center, double-blind, randomized clinical trial of 74 hospitalized patients with confirmed mild to moderate COVID-19 over a 14-day period showed that, compared with a control group (receiving standard care), the intervention group (standard care plus Clinical symptoms such as cough, dyspnea, fatigue, CRP level, and lung damage in patients with melanin) were significantly improved. Note 1
In addition, patients in the intervention group had significantly shorter mean time to discharge and time to return to baseline health compared to the control group.
＊Conclusion: In response to COVID-19, adjuvant melatonin therapy may be of positive help in improving clinical symptoms, but limited by the small sample size, more studies are still needed for further verification.
5. Beneficial for children with autism
Autism Spectrum Disorder is a neurodevelopmental disorder characterized by persistent lack of social communication and interaction, limitations in behavior, interests, or activities, or repetitive behaviors, with a prevalence of up to 116 per 10,000 children .
Its etiology is generally thought to be related to heterogeneous genetic influence. According to statistics, up to 89% of patients have sleep problems, and the presence of sleep disorders may have a negative impact on prognosis.
A systematic literature review and meta-analysis (including 5 randomized, double-blind, placebo-controlled studies in children with autism) found that melatonin use improved sleep parameters (including: sleep duration/sleep duration and the time it takes to fall asleep/sleep onset latency) Note 1
In addition, melatonin appears to improve daytime behavior in people with autism with few side effects.
＊Conclusion: For children with autism, oral melatonin may bring positive help, but limited by the small sample size, more research is needed for further verification.
6. Improve postoperative pain and opioid use
More than 230 million people worldwide undergo surgery every year. Surgery often causes postoperative pain, which should be relieved as soon as possible to reduce pain, promote the healing process and recovery, and prevent complications.
Traditionally, opioid analgesic therapy has been the mainstay of treatment for acute postoperative pain. However, the recent rise in morbidity and mortality associated with opioid abuse has led to the need for additional efforts to develop pain treatment strategies.
A systematic literature review and meta-analysis (Meta-analysis of 15 RCTs with 1,102 participants) showed that melatonin use slightly reduced postoperative pain scores (trial order analysis = conclusive), reduced surgical Post-opioid consumption (trial-order analysis = indeterminate), decreased number of patients requiring analgesics, and did not increase or decrease the incidence of adverse events (dizziness, headache, nausea, and paresthesia). Note 1
*Conclusion: Given the low quality of the available evidence, the mild reduction in pain visual analog scale scores, and the uncertainty of the trial-order analysis of postoperative opioid consumption, this analysis neither supports nor disagrees with melatonin for postoperative pain. Impact.
7. Anti-inflammatory effect
Inflammation, derived from the Latin word “inflammare” (meaning burning), is an important process necessary for animal cells to defend against certain injuries or microbial infections.
The mechanism of inflammation is an organized, dynamic chain of reactions involving cellular and vascular events with specific humoral secretions. These pathways include changes in the physical location of leukocytes (monocytes, basophils, eosinophils, and neutrophils), plasma, and fluid at sites of inflammation. Uncontrolled inflammation can lead to tissue damage and chronic disease (neurodegenerative diseases, cancer and cardiovascular disease).
A systematic literature review and meta-analysis (13 randomized controlled trials with a total of 749 participants) found that melatonin supplementation significantly reduced TNF-α (tumor necrosis factor) compared with placebo and IL-6 (interleukin-6) levels, but had little effect on CRP (C-type reactive protein) levels. Note 1
In addition, a subgroup analysis showed that melatonin supplementation was more effective in improving TNF-α and IL-6 levels in studies with a daily dose of ≥10 mg for ≥12 weeks.
＊Conclusion: Melatonin supplementation can help reduce pro-inflammatory mediators and may bring positive help in fighting inflammation, but limited by the small sample size and heterogeneity, more research is needed to confirm.
8. Good for migraine
The word Migraine comes from the Greek word “hemicrania”, meaning “half of the head”, and it represents one of the most striking features of the disease (pain affects only one half of the head), but the pain is actually felt May also occur on both sides, less commonly on the face or body.
Most migraine attacks are severe, or at least moderate, with 10 to 20 percent of migraine sufferers experiencing aura symptoms, including abnormal vision, tingling, and numbness (often spreading to hand, arm, face, lips, and tongue on one side of the body), weakness, and difficulty swallowing.
A meta-analysis of the literature (25 randomized controlled trials involving 4499 patients with migraine) found that oral melatonin improved migraine attack frequency. Note 1
In addition, taking into account improvements in migraine attack frequency, response rate, dropout rate, and adverse event rate, melatonin 3 mg orally at bedtime (immediate-release) was the most ideal of all investigated interventions Pharmacological intervention with the best improvement.
*Conclusion: For migraine, oral melatonin may reduce the frequency of attacks, but is limited by insufficient statistical data (eg, heterogeneity of participant characteristics and small number of trials in some treatment groups), more research is needed to confirm Optimal dosage and duration of treatment.
9. Improve primary sleep disorders
Primary Sleep Disorders is a type of insomnia that is not due to medical, psychiatric, or environmental causes, according to the diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).
The main symptoms of primary insomnia are difficulty initiating or maintaining sleep, or having non-restorative sleep, lasting at least 1 month.
The second criterion was that sleep disturbance (or associated daytime fatigue) caused significant distress or impairment in social, occupational, or other important functional areas.
The third criterion is a sleep disorder that does not occur entirely in narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder, or sleep disturbance.
The fourth criterion is incomplete occurrence in the course of another mental disorder (eg, major depressive disorder, generalized anxiety disorder, delirium).
Finally, the fifth criterion is not due to the direct physiological influence of the substance (eg, substance abuse, drug treatment) or general medical condition.
A meta-analysis of the literature (including 19 randomized placebo-controlled trials involving 1683 patients with primary insomnia) found that melatonin helped reduce the time to sleep and increased sleep latency compared with placebo. Total sleep time and improve overall sleep quality. Note 1
In addition, although melatonin is less effective than insomnia drugs for improving sleep disturbances, it causes relatively few side effects.
＊Conclusion: For primary sleep disorders, oral melatonin can improve the sleep state of patients, but limited by the small number of samples, more large-scale experiments are still needed to prove it.
10. Improve secondary sleep disorders
In addition to the primary factors mentioned above, chronic insomnia also has secondary sleep disorders, usually caused by medical conditions, neurological, environmental, drug or psychiatric causes.
Medical causes include pain, thyroid disease, acid reflux, coronary artery disease, lung disease (chronic obstructive pulmonary disease, asthma, sleep apnea, central alveolar hypoxia syndrome), chronic renal insufficiency, eating disorders, thyroid dysfunction , fibromyalgia, menstrual-related sleep disorders, and pregnancy.
Neurological causes include headache, Parkinson’s disease, and sleep-related movement disorders (nocturnal muscle twitches, RLS).
Environmental factors include excessive noise, noxious odors, bright light or extreme ambient temperatures, and drug and psychiatric factors include: alcoholism, anxiety disorders, mood disorders, panic disorders and other psychiatric disorders.
A literature review and meta-analysis (7 randomized controlled trials involving 205 patients with secondary sleep disorders) found that exogenous melatonin reduced sleep onset time compared with placebo, and Increases total sleep time, but does not significantly help sleep efficiency. Note 2
＊Conclusion: For secondary sleep disorders, oral melatonin has a positive effect on improving symptoms, but limited by the small sample size and potential bias, more well-designed trials are still needed to prove it.
11. Beneficial for NAFLD
Non-alcoholic fatty liver disease (NAFLD) is caused by accumulation of fat in liver cells and is associated with diabetes, dyslipidemia, obesity, cardiovascular disease and metabolic syndrome. Poor control may lead to cirrhosis , liver failure, hepatocellular carcinoma.
About 30% of adults in Western countries have NAFLD, and first-line treatment is lifestyle interventions, including diet, exercise, and weight loss. Of these, weight loss is key, but only a minority of patients are able to reach the target threshold.
A systematic literature review and meta-analysis (5 randomized controlled trials involving 260 participants with nonalcoholic fatty liver disease) indicated that supplementation with melatonin (6 to 18 mg per day, intervening during the trial) from 4 to 56 weeks) helps reduce aspartate aminoalaninase (AST), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT). Note 3
＊Conclusion: For non-alcoholic fatty liver disease, melatonin supplementation may improve liver index, but limited by the small sample size, more research is needed to prove it.
12. Good for blood pressure regulation
Blood pressure is defined as the pressure of blood circulation on the walls of blood vessels, and the body can adjust blood pressure as needed, so changes in blood pressure readings are normal. However, if blood pressure is too high for too long, it can damage blood vessels over time, increasing the risk of various health problems.
Long-term high blood pressure can increase the likelihood of cardiovascular disease and lead to organ damage, and possible long-term effects include: poor circulation in the legs, heart failure, stroke, kidney failure, etc.
A meta-analysis (Meta-Analysis, including 5 randomized controlled trials with a total of 340 participants) indicated that oral melatonin reduced systolic blood pressure (−3.43 mm Hg) and diastolic blood pressure (Diastolic Blood Pressure, − 3.33 mm Hg). Note 1
The underlying mechanism may be related to melatonin altering suprachiasmatic nucleus function, regulating autonomic nervous system, anti-oxidation, anti-inflammatory and increasing nitric oxide production.
＊Conclusion: Oral melatonin can bring positive help for blood pressure regulation, but the relevant results still need to be confirmed by more precise clinical trials.
13. Beneficial for Fibromyalgia
Fibromyalgia syndrome is a chronic disorder (estimated prevalence of 0.5% to 5.8%) characterized by generalized pain, fatigue, sleep disturbance, cognitive impairment, and anxiety of unknown etiology that can be associated with hypothyroidism and Chronic autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus coexist.
The underlying pathophysiological factors include biological and genetic influences, environmental triggers, neuroendocrine and autonomic nervous system dysfunction.
A systematic review (including 4 clinical trials) found that taking melatonin helped improve disease impact, sleep quality, pain level, and pain point count. Note 2
However, results have been inconsistent regarding the effects of melatonin on anxiety, fatigue and depression levels.
*Results: Oral melatonin may be helpful for improving fibromyalgia, but due to the high heterogeneity between studies, more high-quality randomized controlled clinical trials are needed for further verification.
14. Beneficial for blood lipid regulation
Dyslipidemia is a disorder of lipid metabolism that results in abnormal lipid levels in the blood and is a major risk factor for cardiovascular disease, stroke, and type 2 diabetes.
Studies have shown that for every 10 mg/dL increase in total cholesterol, total and cardiovascular mortality increases by 5% and 9%, respectively.
A systematic literature review and meta-analysis (12 randomized, placebo-controlled trials with a total of 641 participants) found that melatonin improved low-density lipoprotein cholesterol (SMD: -0.31 mmol/L) and triglyceride level (SMD: -0.45mmol/L). Note 1
The underlying mechanism may be related to melatonin reducing the number of LDL-C receptors, reducing free fatty acids, and reducing LDL-C oxidation.
＊Conclusion: Oral melatonin has a positive effect on the improvement of blood lipid indexes, but limited by the small sample size and sample heterogeneity, more research is needed to further verify.
15.Good for blood sugar control
Type 2 diabetes mellitus is a disease that affects more than 400 million people worldwide, and by 2040, there will be more than 640 million people with diabetes worldwide.
Common symptoms of hyperglycemia include polyuria, polydipsia, weight loss, and sometimes polyphagia and blurred vision.
Long-term complications include: retinopathy, nephropathy, foot ulcers, amputations, Charcot joints, and autonomic neuropathy causing gastrointestinal, genitourinary, cardiovascular symptoms, and sexual dysfunction.
A systematic literature review and meta-analysis (including 12 randomized controlled trials) indicated that melatonin supplementation (daily doses ranging from 3 mg to 10 mg) reduced fasting blood glucose and improved the quantitative insulin sensitivity test index (QUICKI). ), but did not significantly help improve insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR), and glycated hemoglobin levels. Note 1
*Conclusion: Melatonin may have positive effects on blood sugar control, but limited by publication bias, more long-term trials are still needed to confirm.
16.Adjuvant cancer treatment
Cancer is a disease in which the uncontrolled proliferation of cells in an organism leads to the invasive decline of normal cells or tissues.
Current cancer treatment is based on radiation, chemotherapy and surgery. Radiation and chemotherapy inhibit the proliferation of cancer cells by damaging DNA. However, DNA damage interferes with normal cells throughout the body, with many side effects.
A meta-analysis of the literature (including 20 randomized controlled trials) found that the addition of melatonin to cancer treatments (including chemotherapy, molecularly targeted therapy, radiotherapy, and supportive care) further improved tumor response rate and overall survival rate. Note 1
In addition, melatonin reduces the incidence of chemotherapy-induced neurotoxicity, thrombocytopenia, and asthenia.
＊Conclusion: Adjuvant melatonin therapy can help improve the tumor remission rate and overall survival rate of cancer patients, while reducing the incidence of chemotherapy side effects, but limited by possible publication bias, more studies are still needed to confirm its clinical benefits.
17. Improve jet lag syndrome (adjust jet lag)
Jet Lag, also known as circadian rhythm disorder, is a sleep disorder caused by a mismatch between the body’s natural circadian rhythm and the external environment caused by rapid travel across multiple time zones.
Jet lag is characterized by sleep disturbance, daytime fatigue, decreased performance, gastrointestinal problems, and general malaise.
This general problem affects all age groups, but the impact may be more pronounced in older adults, who take longer to adjust than younger adults.
A Cochrane Database of Systematic Reviews (9 studies) noted that oral melatonin (in doses ranging from 500mcg to 5mg) helps prevent or reduce jet lag and appears to be safe for occasional short-term use.
And the more time zones you cross (especially eastward flight 2 to 4 time zones), the greater the benefit may be, while westward flight is generally less of a benefit. Note 3
＊Conclusion: Oral melatonin can improve the circadian clock imbalance caused by jet lag syndrome and help sleep.
18. Improve mood disorders
Mood disorders are common mental illnesses and are estimated to affect 8% to 20% of the world’s population. Depression is the most common. The main symptoms are never-ending sadness, loss of interest in things, and negative beliefs about oneself. , suicidal thoughts, and pattern changes in sleep, appetite, and libido.
Although drug therapy and other adjuvant therapy can help the condition, 30%-40% of depression patients still resist treatment,
A systematic review (including 8 clinical studies) pointed out that, so far, there is no evidence that the use of melatonin can bring about a significant improvement in mood disorders (depression, seasonal affective disorder). Note 1
＊Conclusion: Oral melatonin cannot significantly improve depression symptoms. Since the current results are still inconsistent, more research is needed to confirm.
19. Beneficial for pain relief
Pain is defined as a multi-faceted entity that includes nociception, CNS afferents, modulation, affective responses, endogenous analgesia, behavioral regulation, and changes in social roles.
Despite advances in medical treatment, chronic pain remains beyond the reach of health professionals because it is an unmanageable disease
Part of the reason is that the pathogenesis of pain consists of three aspects: including: pain sensation (local condition), emotional (fear and depression), and behavioral factors (catastrophic, vigilance, and body awareness).
A literature review and meta-analysis (19 randomized controlled trials with a total of 1053 participants) found that exogenous melatonin significantly reduced the intensity of various types of pain, including surgery-related pain under local anesthesia, generalized Surgery-related pain, inflammatory pain, procedural pain, and experimental pain under anesthesia. Note 6
In addition, melatonin also reduces patients’ need for analgesics, but its effect on total analgesic intake remains to be confirmed.
The mechanism behind may be related to melatonin’s lowering of BDNF levels
*Conclusion: Exogenous melatonin can bring positive help in anti-pain, but limited by the heterogeneity of the included studies, more research is needed to confirm.
20. Beneficial for Alzheimer’s Disease
Alzheimer’s disease is the most common cause of dementia in the elderly. Typically characterized by progressive decline in memory, language, and intelligence.
In addition to this, sleep and circadian rhythm disturbances are common in Alzheimer’s disease (especially in the early stages), and sleep problems have been reported in up to 45% of patients.
The most common sleep disturbances reported by patients were: excessive awakening (23%), early morning awakening (11%), extreme daytime sleepiness (10%), and daytime napping for more than 1 hour (14%).
A meta-analysis of the literature (7 randomized controlled trials involving 462 patients with Alzheimer’s disease) found that melatonin treatment increased total nighttime sleep time, but not improved cognition. Help (measured by the Short Intelligence Test MMSE and the Alzheimer’s Disease Assessment Scale ADAS-Cog). Note 7
*Conclusion: In Alzheimer’s disease patients, melatonin can help improve sleep status.
Does melatonin have side effects?
For most adults, short-term low-dose use of melatonin is safe, but long-term use has not been rigorously tested to confirm its safety.
Possible side effects that have been mentioned include: nausea, headache, diarrhea, joint pain, short-term depression, daytime sleepiness, dizziness, stomach cramps, etc. Note 8
A population observation suggests that long-term use of melatonin and sleep aids (zolpidem, zopiclone) may be associated with an increased risk of fractures. Note 9
A double-blind, randomized, placebo-controlled study found that oral melatonin may increase reactive aggression (an aggressive response to a potential threat or provocation). Note 10
Safety Precautions
- If additional melatonin supplementation is considered due to sleep disorders, it is best to seek medical attention to confirm the relevant hormone levels and the cause of sleep problems.
- May have more lucid dreams, that is, when you are dreaming, you can realize that you are dreaming.
- Pregnant women, children, breastfeeding mothers, and those with liver and kidney insufficiency are not recommended to use, because the relevant safety is still unknown.
- Do not use it in patients with hypotension or taking antihypertensive drugs (melatonin has the effect of lowering blood pressure and may also interfere with the effect of drugs).
- Do not drive or operate machinery after taking it (it will cause drowsiness and decreased concentration).
- Animal studies have found that (using subcutaneous injection) may affect testicular and ovarian function, but more research is needed to confirm.
- Do not use it together with anticoagulants, immunosuppressants, non-steroidal anti-inflammatory drugs NSAIDs, radiotherapy and chemotherapy drugs (may interfere with the effect of drugs, please confirm with your doctor before use).
- Some claim that taking too much melatonin prevents the body from producing melatonin naturally, but short-term studies have shown no such effect. Note 11
- Do not use with birth control pills (because birth control pills may increase melatonin levels, if additional use will exceed the normal safe amount).
- Do not use in combination with sedative and sedative drugs (central nervous system depressants), which may cause excessive drowsiness. The related drug names are: clonazepam, lorazepam, phenobarbital, zolpidem (Zuo Pei Mian), diazepam (Stable).
- Do not use in combination with caffeine, because caffeine may reduce the level of melatonin in the body, and if used together will reduce the effect of supplements.
- Do not use together with the antidepressant MELATONIN (fluvoxamine), it may increase the absorption of melatonin, thereby increasing the chance of adverse reactions or side effects.
- Do not use it in combination with hypoglycemic drugs or insulin, which may affect the efficacy of glucose control drugs. Related drug names are: glimepiride, glyburide, pioglitazone, rosiglitazone. ketone, chlorpropamide, glipizide, tolbutamide.
- Do not use it in combination with immunosuppressants, as it may reduce the efficacy of the drug (because melatonin may enhance the immune system). The related drug names are: azathioprine, basiliximab, cyclosporine, daclizumab (xeniguat), muromonab-CD3, mycophenolate, tacrolimus, sirolimus (rapamycin) , prednisone, corticosteroids.
- Do not use in combination with drugs with anticoagulant effects, which may increase the chance of bruising and bleeding (because melatonin may slow blood clotting), related drug names are: aspirin, clopidogrel , diclofenac, ibuprofen, naproxen, dalteparin, enoxaparin, heparin, warfarin.
- Do not use in combination with the blood pressure lowering drug Nifedipine GITS, it may reduce the efficacy of the drug.
- Do not use Verapamil, a drug that lowers blood pressure and prevents angina pectoris. It may reduce the effectiveness of melatonin (because the process of metabolizing this drug will consume melatonin).
- Do not combine with the CNS drug Flumazenil, which may reduce the effectiveness of melatonin supplements.