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Complementary and Alternative Medicine - Cam

Search Health Information    Melatonin

Melatonin

Uses

What Are Star Ratings?

Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people.

For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.

2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

This supplement has been used in connection with the following health conditions:

Used for Why
2 Stars
Cluster Headache
Take under medical supervision: 10 mg daily in the evening
Taking melatonin before bedtime has been shown to reduce the frequency of cluster headaches.

Researchers have found low levels of the hormone melatonin in cluster headache patients.2 , 3 , 4 , 5 In a small double-blind trial, a group of cluster headache sufferers took a 10 mg evening dose of melatonin for 14 days. About half of the group saw a significant decrease in the frequency of their headaches within three to five days, after which no further headaches occurred until melatonin was discontinued.6 Melatonin appears to be effective against both types of cluster headache (e.g., episodic and chronic). 7 More research is needed to establish the long-term effects of melatonin supplementation on cluster headache.

2 Stars
Depression
.25 to 10 mg daily under medical supervision
Melatonin might help relieve depression. However, there is a possibility that it could exacerbate depression, so it should only be used for this purpose under a doctor’s supervision.

Melatonin might help some people suffering from depression. Preliminary double-blind research suggests that supplementation with small amounts of melatonin (0.125 mg taken twice per day) may reduce winter depression .8 People with major depressive disorders sometimes have sleep disturbances. A timed-release preparation of melatonin (5–10 mg per day for four weeks) was shown to be effective at improving the quality of sleep in people with major depression who were taking fluoxetine (Prozac), but melatonin did not enhance its antidepressant effect.9 There is a possibility that melatonin could exacerbate depression, so it should only be used for this purpose under a doctor’s supervision.

2 Stars
Hypertension
Take under medical supervision: 2 mg daily of sustained-released supplment at night
For people with nighttime hypertension, supplementing with melatonin may reduce nighttime systolic blood pressure.

In a double-blind study, supplementation with 2 mg of sustained-release melatonin each night for four weeks significantly reduced nighttime systolic blood pressure, compared with a placebo, in people with nocturnal hypertension.10 Normally, blood pressure declines at night. People with hypertension who do not have this nighttime blood pressure decline are at increased risk of developing and dying from heart disease. Melatonin supplementation may therefore be beneficial for this subgroup of people with hypertension.

2 Stars
Insomnia
Take under medical supervision: 0.5 to 3.0 mg daily one to two hours before bedtime
Taking melatonin before bedtime may help reset your body’s internal clock.

Caution: Melatonin is a potent hormone and its long-term safety is not established. Melatonin should only be taken with medical supervision.

Melatonin is a natural hormone that regulates the human biological clock. The body produces less melatonin with advancing age, which may explain why elderly people often have difficulty sleeping11 and why melatonin supplements improve sleep in the elderly.12

Middle-aged adults (average age, 54 years) with insomnia also have lower melatonin levels, compared with people of the same age without insomnia.13 However, there is not much research on the use of melatonin for sleep problems in middle-aged people.

Double-blind trials have shown that melatonin facilitates sleep in young adults without insomnia,14 but not in young people who suffer from insomnia.15However, one trial found that children with sleep disturbances stemming from school phobia had improved sleep after taking 1 mg of melatonin per night for one week, then 5 mg per night for one week, then 10 mg per night for a third week.16

The results of one double-blind trial also indicate that a controlled release melatonin supplement providing 2 mg per day improves sleep quality in people with schizophrenia.17

Normally, the body makes melatonin for several hours per night—an effect best duplicated with controlled-release supplements. Trials using timed-release melatonin for insomnia have reported good results.18 Many doctors suggest taking 0.5 to 3 mg of melatonin one and a half to two hours before bedtime. However, because melatonin is a potent hormone, the long-term effects of which are unknown, it should be taken only with the supervision of a doctor.

2 Stars
Insomnia and Tinnitus
Take under medical supervision: 3 mg dailly at bedtime
Supplementing with melatonin may improve sleep quality and relieve other symptoms of severe tinnitus.

Caution: Melatonin is a potent hormone and its long-term safety is not established. Melatonin should only be taken with medical supervision.

Melatonin is a natural hormone that regulates the human biological clock. The body produces less melatonin with advancing age, which may explain why elderly people often have difficulty sleeping19 and why melatonin supplements improve sleep in the elderly.20

Middle-aged adults (average age, 54 years) with insomnia also have lower melatonin levels, compared with people of the same age without insomnia.21 However, there is not much research on the use of melatonin for sleep problems in middle-aged people.

Double-blind trials have shown that melatonin facilitates sleep in young adults without insomnia,22 but not in young people who suffer from insomnia.23However, one trial found that children with sleep disturbances stemming from school phobia had improved sleep after taking 1 mg of melatonin per night for one week, then 5 mg per night for one week, then 10 mg per night for a third week.24

The results of one double-blind trial also indicate that a controlled release melatonin supplement providing 2 mg per day improves sleep quality in people with schizophrenia.25

Normally, the body makes melatonin for several hours per night—an effect best duplicated with controlled-release supplements. Trials using timed-release melatonin for insomnia have reported good results.26 Many doctors suggest taking 0.5 to 3 mg of melatonin one and a half to two hours before bedtime. However, because melatonin is a potent hormone, the long-term effects of which are unknown, it should be taken only with the supervision of a doctor.

2 Stars
Irritable Bowel Syndrome
Take under medical supervision: 3 mg daily at bedtime
Melatonin helps regulate gastrointestinal function and sensation. In one trial, people with irritable bowel syndrome who took melatonin experienced significantly less severe abdominal pain.

Melatonin plays a role in the regulation of gastrointestinal function and sensation. In a double-blind trial, people with irritable bowel syndrome and associated sleep disturbances received 3 mg of melatonin or a placebo at bedtime for two weeks. Compared with the placebo, melatonin significantly decreased the severity of abdominal pain, although it did not affect bloating, stool frequency, or sleep patterns.27 Melatonin was also effective in another double-blind trial.28

2 Stars
Jet Lag
Take under medical supervision: 0.5 mg daily at bedtime for four days after arriving at your destination
Taking melatonin at bedtime may improve sleep quality and daytime alertness.

Melatonin is a natural hormone that regulates the human biological clock and may be helpful in relieving symptoms of jet lag, according to some,29 , 30 though not all,31 , 32 double-blind studies. One double-blind trial, involving international flight crew members, found that melatonin supplementation was helpful when started after arriving at the destination but not when started three days before leaving.33 Another double-blind study compared various amounts and forms of melatonin taken at bedtime for four days after the flight by people who traveled through six to eight time zones.34 Fast-release melatonin supplements were found to be more effective than the controlled-release supplements. A 5 mg and 0.5 mg fast-release melatonin were almost equally effective for improving sleep quality, time it took to fall asleep, and daytime sleepiness.

2 Stars
Macular Degeneration
Take under medical supervision: 3 mg daily at bedtime
In one trial, melatonin improved eye abnormalities in the majority of cases. It appears to work by regulating eye pigmentation and by functioning as an antioxidant.

In a preliminary trial, supplementation with melatonin (3 mg per day at bedtime for at least three months) resulted in an improvement in the abnormalities observed on eye examination in the majority of cases.35 Melatonin is believed to work by regulating eye pigmentation (and, consequently, the amount of light reaching the retina) and by functioning as an antioxidant.

2 Stars
Schizophrenia and Sleep Disturbances
Take under medical supervision: 2 mg daily of a controlled-release preparation before bedtime
Supplementing with melatonin appears to improve sleep quality and duration in people with schizophrenia.

The results of one double-blind trial indicate that melatonin supplementation improves sleep quality in people with schizophrenia.36 In one study, all patients with a diagnosis of schizophrenia were found to have low melatonin output. Replacement of melatonin with 2 mg of a controlled-release supplement per day for three weeks improved sleep duration and quality compared to placebo. When patients receiving placebo were crossed over to the melatonin group, they too experienced improved sleep quality.

2 Stars
Tardive Dyskinesia
Take under medical supervision: 10 mg daily at bedtime
Taking melatonin may help reduce abnormal movements.

In a double-blind trial, supplementation with 10 mg of melatonin each night for six weeks reduced abnormal movements by 23.8% in patients with TD, compared with 8.4% in the placebo group, a statistically significant difference.37

1 Star
Age-Related Cognitive Decline
Refer to label instructions
Cognitive function is linked to adequate sleep and normal sleep-wake cycles, which are partially regulated by the hormone melatonin. The long-term effects of melatonin are unknown, use under a doctor’s supervision.

Melatonin is a hormone secreted by the pineal gland in the brain. It is partially responsible for regulating sleep-wake cycles. Cognitive function is linked to adequate sleep and normal sleep-wake cycles. Cognitive benefits from melatonin supplementation have been suggested by preliminary research in a variety of situations and may derive from the ability of melatonin to prevent sleep disruptions.38 , 39 , 40 , 41 A double-blind trial of ten elderly patients with mild cognitive impairment showed that 6 mg of melatonin taken two hours before bedtime significantly improved sleep, mood, and memory, including the ability to remember previously learned items.42 However, in a double-blind case study of one healthy person, 1.6 mg of melatonin had no immediate effect on cognitive performance.43

The long-term effects of regularly taking melatonin supplements remain unknown, and many healthcare practitioners recommend that people take no more than 3 mg per evening. A doctor familiar with the use of melatonin should supervise people who wish to take it regularly.

1 Star
Epilepsy
Refer to label instructions
A small, preliminary trial found that melatonin improved sleep and improved seizure symptoms among children with one of two rare seizure disorders.

A small, preliminary trial found that 5 to 10 mg per day of melatonin improved sleep and provided “clear improvement of the seizure situation” among children with one of two rare seizure disorders.44 More research is needed to determine whether or not melatonin could benefit other people with epilepsy.

1 Star
Fibromyalgia
Refer to label instructions
In one study, supplementing with melatonin reduced tender points and improved sleep in people with fibromyalgia.

Melatonin supplementation may be useful in the treatment of fibromyalgia. In a preliminary trial, 3 mg of melatonin at bedtime was found to reduce tender points and to improve sleep and other measures of disease severity, though pain and fatigue improved only slightly.45

1 Star
Glaucoma
Refer to label instructions
Supplementing with melatonin lowered intraocular pressure of healthy people in one study.

Supplementing with 0.5 mg of melatonin lowered intraocular pressure of healthy people,46 but there have been no studies on the effects of melatonin in people with glaucoma.

1 Star
Migraine Headache
Refer to label instructions
Pineal gland function and melatonin secretion may be disturbed in people with migraine headaches. Taking melatonin may correct this problem and reduce symptoms.

The function of the pineal gland and its cyclic secretion of melatonin may be disturbed in people with migraine headaches.47 Preliminary evidence suggests that 5 mg per day of melatonin, taken 30 minutes before bedtime, may reduce symptoms of migraine headache.48 However, a double-blind trial found that taking 2 mg of melatonin 1 hour before bedtime each day for 8 weeks was not more effective than a placebo for decreasing migraine frequency.49

How It Works

How to Use It

Normally, the body secretes melatonin for several hours per night—an effect best duplicated with time-release supplements. Studies using timed-release melatonin for insomnia have reported good results.50 Many doctors suggest 1–3 mg of melatonin taken one to two hours before bedtime. Studies with people suffering from sarcoidosis or cancer have used very high amounts of melatonin—typically 20 mg per night. Such levels should never be taken without the supervision of a doctor. Melatonin should not be taken during the day.

Where to Find It

Melatonin is produced by the pineal gland, located within the brain. Levels of melatonin in the body fluctuate with the cycles of night and day. The highest melatonin levels are found at night. Melatonin is present in foods only in trace amounts.

Possible Deficiencies

Although elderly people often have difficulty sleeping51 and melatonin supplements have been shown to improve sleep in the elderly,52 melatonin secretion does not appear to decline in healthy older adults to a significant degree, despite many preliminary reports to the contrary.53 Most of these preliminary studies failed to verify that older subjects were healthy and not using drugs that suppress melatonin secretion (e.g., aspirin , ibuprofen , beta-blockers). Routine replacement of melatonin in elderly persons is, therefore, not recommended.

Adults with insomnia have been shown to have lower melatonin levels.54 Frequent travelers and shift workers are also likely to benefit from melatonin for the resynchronization of their sleep schedules,55 though a melatonin “deficiency” as such does not exist for these people. Patients with heart disease have been reported to have low melatonin levels, but whether this abnormality increases the risk of heart disease or whether heart disease leads to the low melatonin level is not yet known.56 People with schizophrenia were found to have low melatonin output and experienced significantly improved sleep following melatonin replacement supplementation.57

Interactions

Interactions with Supplements, Foods, & Other Compounds

At the time of writing, there were no well-known supplement or food interactions with this supplement.

Interactions with Medicines

Certain medicines interact with this supplement.

Types of interactions: Beneficial Adverse Check

Replenish Depleted Nutrients

  • Cortisone

    A controlled trial found that a single dose of the synthetic corticosteroid dexamethasone suppressed production of melatonin in nine of 11 healthy volunteers.73 Further research is needed to determine if long-term use of corticosteroids interferes in a meaningful way with melatonin production, and whether supplemental melatonin would be advisable for people taking corticosteroids.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Dexamethasone

    A controlled trial found that a single dose of the synthetic corticosteroid dexamethasone suppressed production of melatonin in nine of 11 healthy volunteers.77 Further research is needed to determine if long-term use of corticosteroids interferes in a meaningful way with melatonin production, and whether supplemental melatonin would be advisable for people taking corticosteroids.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Methylprednisolone

    A controlled trial found that a single dose of the synthetic corticosteroid dexamethasone suppressed production of melatonin in nine of 11 healthy volunteers.108 Further research is needed to determine if long-term use of corticosteroids interferes in a meaningful way with melatonin production, and whether supplemental melatonin would be advisable for people taking corticosteroids.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Prednisolone

    A controlled trial found that a single dose of the synthetic corticosteroid dexamethasone suppressed production of melatonin in nine of 11 healthy volunteers.112 Further research is needed to determine if long-term use of corticosteroids interferes in a meaningful way with melatonin production, and whether supplemental melatonin would be advisable for people taking corticosteroids.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Prednisone

    A controlled trial found that a single dose of the synthetic corticosteroid dexamethasone suppressed production of melatonin in nine of 11 healthy volunteers.113 Further research is needed to determine if long-term use of corticosteroids interferes in a meaningful way with melatonin production, and whether supplemental melatonin would be advisable for people taking corticosteroids.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Reduce Side Effects

  • Bicalutamide

    In preliminary research, large amounts of melatonin were used successfully in combination with tamoxifen in a few people with breast cancer for whom tamoxifen had previously failed.59 The amounts used in this study should be taken only under the supervision of a doctor.

  • Busulfan

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.61

  • Capecitabine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.64

  • Carboplatin

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.65

  • Carmustine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.68

  • Chlorambucil

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.69

  • Cladribine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.71

  • Cyclophosphamide

    High amounts of melatonin have been combined with a variety of chemotherapy drugs to reduce their side effects or improve drug efficacy. One study gave melatonin at night in combination with the drug triptorelin to men with metastatic prostate cancer.74 All of these men had previously become unresponsive to triptorelin. The combination decreased PSA levels—a marker of prostate cancer progression—in eight of fourteen patients, decreased some side effects of triptorelin, and helped nine of fourteen to live longer than one year. The outcome of this preliminary study suggests that melatonin may improve the efficacy of triptorelin even after the drug has apparently lost effectiveness.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Cytarabine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.76

  • Docetaxel

    High amounts of melatonin have been combined with a variety of chemotherapy drugs to reduce their side effects or improve drug efficacy. One study gave melatonin at night in combination with the drug triptorelin to men with metastatic prostate cancer.80 All of these men had previously become unresponsive to triptorelin. The combination decreased PSA levels—a marker of prostate cancer progression—in eight of fourteen patients, decreased some side effects of triptorelin, and helped nine of fourteen to live longer than one year. The outcome of this preliminary study suggests that melatonin may improve the efficacy of triptorelin even after the drug has apparently lost effectiveness.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Erlotinib

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.82

  • Etoposide

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.84

  • Floxuridine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.86

  • Fludarabine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.88

  • Fluorouracil

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with 5-FU plus folinic acid and 5-FU plus cisplatin.91

  • Hydroxyurea

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.93

  • Irinotecan

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.94

  • Lomustine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.97

  • Mechlorethamine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.99

  • Melphalan

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.103

  • Mercaptopurine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.105

  • Methotrexate

    High amounts of melatonin have been combined with a variety of chemotherapy drugs to reduce their side effects or improve drug efficacy. One study gave melatonin at night in combination with the drug triptorelin to men with metastatic prostate cancer.106 All of these men had previously become unresponsive to triptorelin. The combination decreased PSA levels—a marker of prostate cancer progression—in eight of fourteen patients, decreased some side effects of triptorelin, and helped nine of fourteen to live longer than one year. The outcome of this preliminary study suggests that melatonin may improve the efficacy of triptorelin even after the drug has apparently lost effectiveness.

  • Polifeprosan 20 with Carmustine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.111

  • Thioguanine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.116

  • Thiotepa

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.119

  • Uracil Mustard

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.124

  • Vinblastine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.125

  • Vincristine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.128

Support Medicine

  • Anastrozole

    In preliminary research, large amounts of melatonin were used successfully in combination with tamoxifen in a few people with breast cancer for whom tamoxifen had previously failed.58 The amounts used in this study should be taken only under the supervision of a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Bicalutamide

    In preliminary research, large amounts of melatonin were used successfully in combination with tamoxifen in a few people with breast cancer for whom tamoxifen had previously failed.60 The amounts used in this study should be taken only under the supervision of a doctor.

  • Busulfan

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.62

  • Capecitabine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.63

  • Carboplatin

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.66

  • Carmustine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.67

  • Chlorambucil

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.70

  • Cladribine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.72

  • Cytarabine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.75

  • Diethylstilbestrol

    In preliminary research, large amounts of melatonin were used successfully in combination with tamoxifen in a few people with breast cancer for whom tamoxifen had previously failed.78 The amounts used in this study should be taken only under the supervision of a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Docetaxel

    High amounts of melatonin have been combined with a variety of chemotherapy drugs to reduce their side effects or improve drug efficacy. One study gave melatonin at night in combination with the drug triptorelin to men with metastatic prostate cancer.79 All of these men had previously become unresponsive to triptorelin. The combination decreased PSA levels—a marker of prostate cancer progression—in eight of fourteen patients, decreased some side effects of triptorelin, and helped nine of fourteen to live longer than one year. The outcome of this preliminary study suggests that melatonin may improve the efficacy of triptorelin even after the drug has apparently lost effectiveness.

  • Erlotinib

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.81

  • Estramustine
    In preliminary research, large amounts of melatonin were used successfully in combination with tamoxifen in a few people with breast cancer for whom tamoxifen had previously failed.83 The amounts used in this study should be taken only under the supervision of a doctor.
    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Etoposide

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.85

  • Floxuridine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.87

  • Fludarabine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.89

  • Fluorouracil

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with 5-FU plus folinic acid and 5-FU plus cisplatin.90

  • Hydroxyurea

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.92

  • Irinotecan

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.95

  • Leuprolide

    In preliminary research, large amounts of melatonin were used successfully in combination with tamoxifen in a few people with breast cancer for whom tamoxifen had previously failed.96 The amounts used in this study should be taken only under the supervision of a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Lomustine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.98

  • Mechlorethamine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.100

  • Megestrol

    In preliminary research, large amounts of melatonin were used successfully in combination with tamoxifen in a few people with breast cancer for whom tamoxifen had previously failed.101 The amounts used in this study should be taken only under the supervision of a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Melphalan

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.102

  • Mercaptopurine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.104

  • Methotrexate

    High amounts of melatonin have been combined with a variety of chemotherapy drugs to reduce their side effects or improve drug efficacy. One study gave melatonin at night in combination with the drug triptorelin to men with metastatic prostate cancer.107 All of these men had previously become unresponsive to triptorelin. The combination decreased PSA levels—a marker of prostate cancer progression—in eight of fourteen patients, decreased some side effects of triptorelin, and helped nine of fourteen to live longer than one year. The outcome of this preliminary study suggests that melatonin may improve the efficacy of triptorelin even after the drug has apparently lost effectiveness.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Nilutamide

    In preliminary research, large amounts of melatonin were used successfully in combination with tamoxifen in a few people with breast cancer for whom tamoxifen had previously failed.109 The amounts used in this study should be taken only under the supervision of a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Polifeprosan 20 with Carmustine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.110

  • Tamoxifen

    In preliminary research, large amounts of melatonin were used successfully in combination with tamoxifen in a few people with breast cancer for whom tamoxifen had previously failed.114 The amounts used in this study should be taken only under the supervision of a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Testolactone

    In preliminary research, large amounts of melatonin were used successfully in combination with tamoxifen in a few people with breast cancer for whom tamoxifen had previously failed.115 The amounts used in this study should be taken only under the supervision of a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Thioguanine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.117

  • Thiotepa

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.118

  • Toremifene

    In preliminary research, large amounts of melatonin were used successfully in combination with tamoxifen in a few people with breast cancer for whom tamoxifen had previously failed.120 The amounts used in this study should be taken only under the supervision of a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Triazolam

    A preliminary study showed that taking melatonin and triazolam together produces better quality of sleep than occurs when the drug is taken alone. The results also indicated that less triazolam is needed when melatonin and triazolam are taken together, which might reduce side effects such as morning grogginess.121 Additional research is needed to determine whether individuals taking triazolam should also take melatonin.

  • Triptorelin Pamoate

    In preliminary research, large amounts of melatonin were used successfully in combination with tamoxifen in a few people with breast cancer for whom tamoxifen had previously failed.122 The amounts used in this study should be taken only under the supervision of a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Uracil Mustard

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.123

  • Vinblastine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.126

  • Vincristine

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.127

Reduces Effectiveness

  • none

Potential Negative Interaction

  • none

Explanation Required

  • Cisplatin

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.129

  • Doxorubicin

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with doxorubicin.130

  • Fluoxetine

    Administration of fluoxetine for six weeks significantly lowered melatonin levels in people with seasonal affective disorder (SAD) and in healthy persons as well.131 Further study is needed to determine if this might interfere with sleeping or whether melatonin supplementation might be appropriate.

  • Fluvoxamine

    Fluvoxamine has been shown to significantly raise the amount of melatonin in the blood after oral administration.132 Researchers suggest that fluvoxamine may inhibit elimination of melatonin, but the clinical significance of this finding is as yet unclear.

  • Ifosfamide

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.133

  • Mirtazapine

    Taking mirtazapine results in enhanced secretion of melatonin at night;134 this may explain part of the mechanism of the effects of mirtazapine. Controlled research is needed to determine whether melatonin supplementation might enhance either the beneficial or the adverse effects of mirtazapine.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Paclitaxel

    Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with paclitaxel.135

The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers’ package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a supplement with your doctor or pharmacist.

Side Effects

Side Effects

Melatonin is associated with few side effects. However, morning grogginess, undesired drowsiness, sleepwalking, and disorientation have been reported. Researchers have hypothesized that certain people should not use melatonin supplements, including pregnant or breast-feeding women, people with depression or schizophrenia , and those with autoimmune disease, including lupus , at least until more is known.136 , 137

In one study, administration of 3 mg per day of melatonin for three months resulted in a marked decline in sperm counts and a decline in sperm quality in two of eight healthy young men.138 In one of these two men, sperm count and quality became normal after melatonin was discontinued. Although this was a small study, it raises the possibility that long-term use of melatonin could lead to infertility.

In a group of children suffering from neurological disorders, 1–5 mg of melatonin per night led to an increase in the rate of seizures despite the fact that sleep improved.139 Until more is known, children with neurological conditions should take melatonin only under medical supervision.

Many other side effects have been attributed to melatonin supplementation, including inhibition of sex drive, severe headaches, abdominal cramps, and formation of rudimentary breasts in men.140 , 141 However, these associations have not been supported by solid evidence.142 , 143 , 144 , 145 Since none of these claims have been well documented or independently confirmed, these problems may not have been due to melatonin.

Though most research reports that melatonin improves the quality of sleep, at least one trial has found that four of fifteen men given melatonin had their sleep patterns disturbed by supplemental melatonin.146

One case of painful gynecomastia (enlarged breasts) has been reported involving a 56-year-old man who had been suffering from amyotrophic lateral sclerosis (Lou Gehrig’s disease), and was taking 1–2 mg melatonin per day for one and a half years.147 As the signs and symptoms disappeared after melatonin was discontinued, the authors of the report suspected that melatonin caused this side effect.

According to a preliminary report, blood levels of melatonin may be elevated in women with fibromyalgia .148 Data in this report did not indicate toxicity from melatonin, nor did the report suggest that melatonin causes or exacerbates the symptoms of fibromyalgia. It did suggest there is no current rationale for melatonin supplementation in people with fibromyalgia.

One-time oral administration of 1 mg of melatonin to post- menopausal women reduced glucose tolerance and insulin sensitivity when tested 45 minutes after administration.149 This finding suggests that people with diabetes should use melatonin with caution and only under the supervision of a doctor.

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