The Benefits Of Melatonin Supplements

Melatonin is a hormone related to the physiological clock, also known as the body’s “timing factor”, is often used to regulate sleep. Do you know the benefits of melatonin supplements?

The following will introduce the benefits and related side effects of melatonin.

Table of Contents

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 the American dermatologist Aaron Lerner in 1958. It is mainly related to circadian rhythm and seasonal reproduction regulation.

In most animals, melatonin is mainly synthesized and secreted at night (converted from tryptophan), and it is also synthesized in many tissues and cells, including the retina, bone marrow cells, platelets, gastrointestinal tract, skin, or lymphocytes.

Melatonin receptors are scattered throughout the body and seem to be multi-purpose physiological signals that participate in the control of many physiological processes, thereby affecting sleep, reproduction, molting, immune response, energy balance, and behavior.

In addition, it has direct and indirect antioxidant properties, and there is strong evidence that this compound can offset the harmful effects of reactive oxygen species and nitrogen in different systems.

When should melatonin be taken (dose)?

If you want to try melatonin, it is best to start with a low dose.

For example, take 0.5 mg/mg (500 mcg) or 1 mg 30 minutes before going to bed.

If this dose does not 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 make you fall asleep.

What are the benefits of melatonin?

1. Melatonin improves primary sleep disorders

Primary Sleep Disorders is a type of insomnia not caused by medical, mental or environmental reasons, according to the diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).

The main symptoms of primary insomnia are difficulty starting or maintaining sleep, or suffering from non-restorative sleep that lasts for at least 1 month.

The second criterion is that sleep disturbance (or related daytime fatigue) causes significant pain or damage in social, occupational, or other important functional areas.

The third criterion is sleep disorders that do not completely occur in narcolepsy, respiratory-related sleep disorders, circadian rhythm sleep disorders or abnormal sleep

The fourth criterion is that incompletely occurs in the process of another mental disorder (such as major depressive disorder, generalized anxiety disorder, delirium).

Finally, the fifth criterion is not caused by the direct physiological effects of substances (such as drug abuse, drug treatment) or general medical conditions.

A meta-analysis of 19 randomized placebo-controlled trials (a total of 1683 patients with primary insomnia) indicated that melatonin helps to reduce the waiting time before going to bed and increases compared to placebo Total sleep time improves overall sleep quality.

In addition, although melatonin’s sleep disturbance improvement benefits are lower than those for treating insomnia, it has relatively few side effects.

*Conclusion: For primary sleep disorders, oral melatonin can improve the sleep state of patients, but it is limited to a small number of samples, and more large-scale experiments are still needed to corroborate

2. Melatonin improves secondary sleep disorders

In addition to the primary factors mentioned above, chronic insomnia has secondary sleep disorders, usually caused by medical conditions, neurological, environmental, pharmaceutical, 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 hypoxic 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 tics, RLS).

Environmental factors include excessive noise, harmful odors, strong light, or extreme ambient temperature. Drugs and mental factors include alcoholism, anxiety disorder, emotional disorder, panic disorder, and other mental disorders.

A literature review and meta-analysis (including 7 randomized controlled trials with a total of 205 patients with secondary sleep disorders) pointed out that exogenous melatonin reduced the time to sleep compared to placebo, and The total sleep time is increased, but it does not significantly help sleep efficiency.

*Conclusion: For secondary sleep disorders, oral melatonin is positive for improving symptoms, but limited by the small sample size and potential bias, more design and accurate tests are still needed to support.

3. Melatonin is beneficial for blood pressure regulation

Blood pressure is defined as the pressure of blood circulation on the blood vessel wall, and the human body can adjust blood pressure as needed, so the change in blood pressure reading is normal. However, if the blood pressure is too high for too long, it will damage blood vessels over time, increasing the risk of various health problems.

Long-term hypertension can increase the possibility of cardiovascular disease and lead to organ damage. Possible long-term effects include poor blood circulation to the legs, heart failure, stroke, kidney failure, etc.

A meta-analysis of literature (including 5 randomized controlled trials, a total of 340 participants) pointed out that oral melatonin has a reduction in systolic blood pressure and diastolic blood pressure.

The underlying mechanism may be related to melatonin changing the suprachiasmatic nucleus function, regulating the autonomic nervous system, antioxidant, anti-inflammatory and increasing nitric oxide production

*Conclusion: Oral melatonin can bring positive help to blood pressure regulation, but related results still need to be supported by more accurate clinical trials.

4. Melatonin beneficial fibromyalgia

Fibromyalgia syndrome is a chronic disease (estimated prevalence rate is 0.5% to 5.8%), characterized by systemic pain, fatigue, sleep disturbance, cognitive impairment and anxiety, the etiology is unknown and can be associated with hypothyroidism and chronic autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus coexist.

The potential pathophysiological factors include biological and genetic influences, environmental triggers, neuroendocrine, and autonomic nervous system abnormalities.

A systematic review (including 4 clinical trials) pointed out that taking melatonin can help improve the impact of the disease, sleep quality, pain level, and pain point count.

However, the results of melatonin on anxiety, fatigue, and depression levels are not consistent.

*Result: Oral melatonin may be helpful in improving fibromyalgia, but it is limited by the high heterogeneity between studies, and more high-quality randomized controlled clinical trials are still needed for further verification.

5. Melatonin lowers blood fat

Dyslipidemia is a disorder of lipid metabolism that leads to 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 mortality and cardiovascular mortality increase by 5% and 9%, respectively.

A systematic literature review and meta-analysis (including 12 randomized, placebo-controlled trials with a total of 641 participants) pointed out that melatonin can improve low-density lipoprotein cholesterol (SMD: -0.31 mmol/L) and triglyceride level (SMD: -0.45 mmol/L).

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 index, but it is limited by the small sample size and sample heterogeneity, and more studies are still needed to further verify.

6. Melatonin helps blood sugar control

Type 2 diabetes mellitus is a disease that affects more than 400 million people worldwide. By 2040, there will be more than 640 million people with diabetes worldwide.

Common symptoms of hyperglycemia include polyuria, polydipsia, weight loss, sometimes accompanied by polyphagia and blurred vision.

Long-term complications include retinopathy, nephropathy, foot ulcers, amputation, Charcot joints, and autonomic neuropathy that causes gastrointestinal tract, urogenital system, cardiovascular symptoms, and sexual dysfunction.

A systematic literature review and meta-analysis (including 12 randomized controlled trials) pointed out that melatonin supplementation (daily doses between 3 mg and 10 mg) can reduce fasting blood glucose and improve the quantitative insulin sensitivity test index (QUICKI ), but it does not significantly help to improve insulin levels, insulin resistance homeostasis model evaluation (HOMA-IR), and glycated hemoglobin levels.

*Conclusion: Melatonin may have a positive effect on blood sugar control, but due to publication bias, more long-term trials are needed to corroborate.

7. Melatonin-assisted cancer treatment

Cancer is a disease of uncontrolled proliferation of cells in an organism, resulting in the invasive decline of normal cells or tissues.

Current cancer treatment is based on radiotherapy, chemotherapy, and surgery. Radiotherapy and chemotherapy inhibit the proliferation of cancer cells by destroying DNA. However, DNA damage can interfere with normal cells throughout the body and is accompanied by many side effects

A meta-analysis of literature (including 20 randomized controlled trials) pointed out that the combined use of melatonin in addition to cancer treatments (including chemotherapy, molecular target therapy, radiotherapy, and supportive treatment) can further improve tumor remission Rate and overall survival rate.

In addition, melatonin can also reduce the incidence of neurotoxicity, thrombocytopenia, and asthenia due to chemotherapy.

*Conclusion: Melatonin adjuvant therapy can help improve the tumor remission rate and overall survival rate of cancer patients while reducing the incidence of chemotherapy side effects. However, due to possible publication bias, more research is still needed to confirm its clinical benefit.

8. Melatonin improves jet lag syndrome (adjusting jet lag)

Jet Lag, also known as circadian rhythm disorder, is a sleep disorder caused by the rapid traversal of multiple time zones, resulting in a mismatch between the body’s natural circadian rhythm and the external environment.

The jet lag syndrome is characterized by sleep disturbances, daytime fatigue, decreased performance, gastrointestinal problems, and general malaise.

This common problem affects all age groups, but the impact on the elderly may be more pronounced because older people have a longer adaptation time than the younger ones.

A Cochrane Database of Systematic Reviews (including 9 studies) pointed out that oral melatonin (dose between 500mcg to 5mg) helps prevent or reduce jet lag syndrome, and occasionally short-term use seems to be safe.

The more time zones that are crossed (especially when flying east to 2 to 4 time zones), the greater the benefit maybe, while the benefits of flying west are generally smaller.

*Conclusion: Oral melatonin can improve the dysregulation of physiological clock caused by jet lag syndrome and help fall asleep.

9. Melatonin improves mood disorders

Emotional disorders are common mental disorders. It is estimated that about 8% to 20% of the world’s population is affected, especially depression is the most common. The main symptoms are endless sadness, loss of interest in things, and negative beliefs in self. , Suicidal thoughts, and patterns of sleep, appetite, and sexual desire.

Although drug therapy and other adjuvant therapies can help the disease, 30%–40% of depression patients still resist treatment.

A systematic review (including 8 clinical studies) pointed out that as of now, there is no evidence to prove that the use of melatonin can have a significant improvement effect on mood disorders (depression, seasonal mood disorders).

*Conclusion: Oral melatonin can not significantly improve the symptoms of depression. Since the current results are still inconsistent, it needs to be confirmed by more studies.

10. Melatonin prevents primary headache

Headache is one of the most common neurological diseases, with an incidence of 48.9% in the general population.

Primary Headache Disorders refers to headaches that occur independently and are not caused by other diseases, accounting for almost 98% of all headaches, and can be divided into four categories: migraine, tension headache, cluster headache, and trigeminal autonomy Headache and other primary headaches.

A systematic review (including 4 randomized controlled trials with a total of 351 participants) pointed out that for migraine, oral melatonin may have the following effects compared to placebo or analgesics, such as: reducing pain, reducing The use of analgesics, reduced headache intensity, and headache days (but according to the grading method, the quality of the evidence is very low).

In addition, for cluster headache, melatonin can reduce the use of analgesics, but there is no difference in the number of daily attacks.

*Conclusion: Due to insufficient research volume and poor methodological quality, the existing evidence is still insufficient to support melatonin in the prevention of primary headaches.

11. Melatonin relieves pain

Pain is defined as a multi-faceted entity, including nociception, central nervous system afferent, regulation, emotional response, endogenous analgesia, behavioral regulation, and changes in social roles.

With the advancement of medical treatment, despite the perfect treatment, chronic pain is still beyond the reach of health experts, because it is an uncontrollable disease.

Part of the reason is that the pathogenesis of pain includes three aspects: including pain (local conditions), emotions (fear and depression), and behavioral factors (disaster theory, alertness, and physical awareness).

A literature review and meta-analysis (including 19 randomized controlled trials with a total of 1053 participants) pointed out that exogenous melatonin can significantly reduce the intensity of various pains, including surgery-related pain under local anesthesia, systemic Surgery-related pain, inflammatory pain, programmed pain, and experimental pain under anesthesia.

In addition, melatonin also reduces the patient’s demand for analgesics, but its impact on total analgesic drug intake still needs further confirmation.

The underlying mechanism may be related to the reduction of BDNF levels by melatonin.

*Conclusion: Exogenous melatonin can have a positive effect on anti-pain, but it is limited by the heterogeneity of the studies included, and more studies are needed to corroborate.

12. Melatonin benefits Alzheimer’s disease

Alzheimer’s disease is the most common cause of dementia in the elderly. The typical characteristic is the gradual decline of memory, language, and intelligence.

In addition, sleep and circadian rhythm disturbances are very common in Alzheimer’s disease (especially in the early stages of the disease), and up to 45% of patients are reported to have sleep problems.

The most common sleep disturbances in patients are excessive waking (23%), early morning waking (11%), extreme daytime sleepiness (10%), and daytime nap for more than 1 hour (14%).

A meta-analysis (Meta-analysis, including 7 randomized controlled trials, 462 participants with Alzheimer’s disease) pointed out that melatonin treatment can prolong the total sleep time at night, but it is not obvious for improving cognitive ability Help (measured by the short intelligence test MMSE and Alzheimer’s Disease Assessment Scale ADAS-Cog).

*Conclusion: For patients with Alzheimer’s disease, the use of melatonin can help improve sleep.

Are there any side effects of melatonin?

For most adults, short-term use of melatonin in small doses is still 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.

A population observation pointed out that long-term use of melatonin and sleeping aids (zolpidem, zopiclone) may be associated with increased fracture risk.

A double-blind, randomized, placebo-controlled study found that oral melatonin may increase reactive aggression (a reactive response to potential threats or provocations).

Safety Precautions

1. If you consider additional melatonin supplementation due to sleep disorders, it is best to consult a doctor to confirm the level of hormones and the cause of sleep problems.

2. There may be more lucid dreams (lucid dreams), that is, when dreaming, you can realize that you are dreaming.

3. Pregnant women, children, nursing mothers, liver, and kidney dysfunction are not recommended for use, because the related safety is still unknown.

4. Do not use in patients with low blood pressure or taking antihypertensive drugs (melatonin has a blood pressure-lowering effect and may also interfere with the effect of drugs).

5. Do not drive or operate the machine after taking it (it will cause drowsiness and decreased concentration).

6. Animal studies have found that the use of subcutaneous injections may affect the testis and ovarian function, but more studies have yet to confirm.

7. Do not use with anticoagulants, immunosuppressants, non-steroidal anti-inflammatory drugs NSAIDs, radiochemotherapy drugs (may interfere with the role of drugs, you must first confirm with your doctor before use).

8. Some accounts suggest that taking too much melatonin will prevent the body from naturally producing melatonin, but short-term studies have shown no such effect.

9. Do not use birth control pills (because birth control pills may increase melatonin levels, it will exceed the normal safe amount if taken extra).

10. Do not use it in combination with a sleeping sedative (central nerve inhibitor), which may cause excessive drowsiness. The names of the related drugs are clonazepam, lorazepam, phenobarbital, zolpidem, diazepam.

11. Do not use in combination with caffeine, caffeine may reduce the level of melatonin in the body if used together will reduce the effect of supplements.

12. Do not use with the antidepressant MELATONIN (fluvoxamine), it may increase the absorption of melatonin, which will increase the chance of adverse reactions or side effects.

13. Do not use it in combination with hypoglycemic drugs or insulin, which may affect the efficacy of glucose control drugs. The names of related drugs are glimepiride, glyburide, pioglitazone, rosiglitazone, chlorpropamide, glipizide, tolbutamide.

14. Do not use in combination with immunosuppressants, it may reduce the efficacy of the drug (because melatonin may strengthen the immune system), the relevant drug names are azathioprine, basiliximab, cyclosporine, daclizumab, muromonab-CD3, mycophenolate, tacrolimus, sirolimus, prednisone, corticosteroids.

15. 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), the related drug names are aspirin, clopidogrel, diclofenac, ibuprofen, naproxen, dalteparin, enoxaparin, heparin, warfarin.

16. Do not use it in combination with Nifedipine GITS, which may reduce the effectiveness of the drug.

17. Do not use it in combination with Verapamil, a drug that lowers blood pressure and prevents angina, it may reduce the effectiveness of melatonin (because the process of metabolizing this medicine consumes melatonin).

18. Do not combine with the central nervous system drug Flumazenil, which may reduce the effectiveness of melatonin supplements.

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