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Melatonin

Topic Contents

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.¹ ^{, 2} ^{, 3} ^{, 4} 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.⁵ Melatonin appears to be effective against both types of cluster headache (e.g., episodic and chronic). ⁶ More research is needed to establish the long-term effects of melatonin supplementation on cluster headache.
2 Stars Colon Cancer 20 mg at bedtime	If you have colon cancer, taking melatonin under medical supervision may help improve prognosis and quality of life. The hormone melatonin is available as a supplement and is believed by some researchers to have anticancer activity because of its effects on the immune system.⁷ In research trials, melatonin has been evaluated as a potential agent for use in connection with treatment for cancer patients—not to protect healthy people from getting cancer. Patients with advanced colon cancer who had either not responded to chemotherapy, or who had relapsed after a response to chemotherapy, were given either no additional treatment (control group) or a combination of interleukin-2 and 40 mg of melatonin per day.⁸ Nine of 25 patients given melatonin plus interleukin-2 survived for a year compared with only three of 25 patients in the control group, a difference that was statistically significant. Many other controlled trials suggest that melatonin may extend survival, disease-free survival, and/or quality of life in cancer patients.⁹ ^{, 10} ^{, 11} ^{, 12} ^{, 13} ^{, 14} ^{, 15} ^{, 16} ^{, 17} ^{, 18} ^{, 19} ^{, 20} ^{, 21}Most of these trials used 20 mg of melatonin taken at bedtime. Taking such a high amount of melatonin should be done only under the supervision of a doctor familiar with its use. Animal research suggests that the anticancer effects of this hormone may be reversed if melatonin is taken during the day. Therefore, melatonin should be taken only at night.
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 .²² 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.²³ 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.²⁴ 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 sleeping²⁵ and why melatonin supplements improve sleep in the elderly.²⁶ Middle-aged adults (average age, 54 years) with insomnia also have lower melatonin levels, compared with people of the same age without insomnia.²⁷ 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,²⁸ but not in young people who suffer from insomnia.²⁹However, 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.³⁰ 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.³¹ 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.³² 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 sleeping³³ and why melatonin supplements improve sleep in the elderly.³⁴ Middle-aged adults (average age, 54 years) with insomnia also have lower melatonin levels, compared with people of the same age without insomnia.³⁵ 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,³⁶ but not in young people who suffer from insomnia.³⁷However, 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.³⁸ 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.³⁹ 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.⁴⁰ 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.⁴¹ Melatonin was also effective in another double-blind trial.⁴²
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,⁴³ ^{, 44} though not all,⁴⁵ ^{, 46} 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.⁴⁷ 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.⁴⁸ 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.⁴⁹ 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.⁵⁰ 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 Sunburn (Vitamin C, Vitamin E) Apply a formula containing 2% vitamin E, 5% vitamin C, and 1% to 2.5% melatonin before sun exposure	A topically applied combination of melatonin, vitamin C, and vitamin E may boost the protection from traditional sunscreens. Antioxidants have been studied as topical agents for protection against sunburn. Animal studies have found sunscreen-like effects from topical application of a vitamin C and vitamin E combination, and a controlled human study reported ultraviolet protection from the use of a lotion containing 0.02% to 0.05% of the selenium -containing amino acid known as selenomethionine.⁵¹ ^{, 52} The topical use of the hormone melatonin has been shown to protect human skin against ultraviolet rays in double-blind research.⁵³ ^{, 54} A double-blind human trial tested topical vitamins C and E and melatonin , alone and in combinations, and found the highest degrees of protection from combination formulations containing 2% vitamin E, 5% vitamin C, and 1% to 2.5% melatonin.⁵⁵ Other studies in which topical antioxidants were applied after ultraviolet exposure have found no benefits.⁵⁶ ^{, 57}
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.⁵⁸
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.⁵⁹ ^{, 60} ^{, 61} ^{, 62} 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.⁶³ However, in a double-blind case study of one healthy person, 1.6 mg of melatonin had no immediate effect on cognitive performance.⁶⁴ 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.⁶⁵ 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.⁶⁶
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,⁶⁷ but there have been no studies on the effects of melatonin in people with glaucoma.
1 Star Lung Cancer Refer to label instructions	In patients with advanced lung cancer who were given melatonin in one study, survival time was almost twice as long as survival in those not given melatonin. Years ago, a preliminary study suggested that melatonin may help stabilize the condition of some people with advanced cancers.⁶⁸ Since then, Italian researchers have been investigating the effects of melatonin in cancer patients, often with partial success.⁶⁹ ^{, 70} ^{, 71} ^{, 72} ^{, 73} ^{, 74} ^{, 75} ^{, 76} ^{, 77} ^{, 78} ^{, 79} ^{, 80} In patients with advanced lung cancer who were given 10 mg of melatonin at night in cycles of three weeks on followed by one week off, survival time was almost twice as long as survival in those not given melatonin—a statistically significant increase.⁸¹ Melatonin supplementation was not helpful to patients whose cancer had spread to the liver.⁸²
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.⁸³ Preliminary evidence suggests that 5 mg per day of melatonin, taken 30 minutes before bedtime, may reduce symptoms of migraine headache.⁸⁴ 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.⁸⁵
1 Star Prostate Cancer Refer to label instructions	Melatonin may help stabilize the condition of some people with advanced cancers. Years ago, a preliminary study suggested that melatonin may help stabilize the condition of some people with advanced cancers.⁸⁶ Since then, Italian researchers have been investigating the effects of melatonin in cancer patients, often with partial success.⁸⁷ ^{, 88} ^{, 89} ^{, 90} ^{, 91} ^{, 92} ^{, 93} ^{, 94} ^{, 95} ^{, 96} ^{, 97} ^{, 98} Patients with advanced prostate cancer who had previously not responded to drug therapy (triptorelin) were given melatonin plus triptorelin in a preliminary trial.⁹⁹ PSA scores, a marker of disease progression, fell (i.e., improved) more than 50% in 8 of 14 patients. Patients with advanced cancer have been reported to have improved survival and fewer side effects from taking chemotherapy when given melatonin plus chemotherapy vs. chemotherapy alone.¹⁰⁰

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.¹⁰¹ 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 sleeping¹⁰² and melatonin supplements have been shown to improve sleep in the elderly,¹⁰³ melatonin secretion does not appear to decline in healthy older adults to a significant degree, despite many preliminary reports to the contrary.¹⁰⁴ 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.¹⁰⁵ Frequent travelers and shift workers are also likely to benefit from melatonin for the resynchronization of their sleep schedules,¹⁰⁶ 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.¹⁰⁷ People with schizophrenia were found to have low melatonin output and experienced significantly improved sleep following melatonin replacement supplementation.¹⁰⁸

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.

What Are Drug Interactions

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.¹²⁴ 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.¹²⁸ 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.¹⁵⁹ 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.¹⁶³ 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.¹⁶⁴ 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.¹¹⁰ 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.¹¹²
Capecitabine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹¹⁵
Carboplatin

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

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

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹²⁰
Cladribine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹²²
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.¹²⁵ 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.¹²⁷
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.¹³¹ 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.¹³³
Etoposide

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹³⁵
Floxuridine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹³⁷
Fludarabine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹³⁹
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.¹⁴²
Hydroxyurea

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁴⁴
Irinotecan

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁴⁵
Lomustine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁴⁸
Mechlorethamine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁵⁰
Melphalan

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁵⁴
Mercaptopurine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁵⁶
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.¹⁵⁷ 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.¹⁶²
Thioguanine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁶⁷
Thiotepa

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁷⁰
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.¹⁷⁵
Vinblastine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁷⁶
Vincristine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁷⁹

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.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.
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.¹¹¹ 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.¹¹³
Capecitabine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹¹⁴
Carboplatin

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

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

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹²¹
Cladribine

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

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹²⁶
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.¹²⁹ 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.¹³⁰ 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.¹³²
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.¹³⁴ 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.¹³⁶
Floxuridine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹³⁸
Fludarabine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁴⁰
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.¹⁴¹
Hydroxyurea

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁴³
Irinotecan

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁴⁶
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.¹⁴⁷ 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.¹⁴⁹
Mechlorethamine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁵¹
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.¹⁵² 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.¹⁵³
Mercaptopurine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁵⁵
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.¹⁵⁸ 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.¹⁶⁰ 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.¹⁶¹
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.¹⁶⁵ 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.¹⁶⁶ 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.¹⁶⁸
Thiotepa

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁶⁹
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.¹⁷¹ 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.¹⁷² 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.¹⁷³ 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.¹⁷⁴
Vinblastine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁷⁷
Vincristine

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.¹⁷⁸

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.¹⁸⁰
Doxorubicin

Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with doxorubicin.¹⁸¹
Fluoxetine

Administration of fluoxetine for six weeks significantly lowered melatonin levels in people with seasonal affective disorder (SAD) and in healthy persons as well.¹⁸² 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.¹⁸³ 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.¹⁸⁴
Mirtazapine

Taking mirtazapine results in enhanced secretion of melatonin at night;¹⁸⁵ 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.¹⁸⁶

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

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.¹⁸⁷ ^{, 188}

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.¹⁸⁹ 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.¹⁹⁰ 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.¹⁹¹ ^{, 192} However, these associations have not been supported by solid evidence.¹⁹³ ^{, 194} ^{, 195} ^{, 196} 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.¹⁹⁷

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.¹⁹⁸ 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 .¹⁹⁹ 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.²⁰⁰ This finding suggests that people with diabetes should use melatonin with caution and only under the supervision of a doctor.

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70. Lissoni P, Barni S, Crispino S, et al. Endocrine and immune effects of melatonin therapy in metastatic cancer patients. Eur J Cancer Clin Oncol 1989;25:789–95.

71. Lissoni P, Barni S, Ardizzoia A, et al. A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms. Cancer 1994;73:699–701.

72. Lissoni P, Barni S, Ardizzoia A, et al. Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin. Oncology 1992;49:336–9.

73. Lissoni P, Paolorossi F, Tancini G, et al. Is there a role for melatonin in the treatment of neoplastic cachexia? Eur J Cancer 1996;32A:1340–3.

74. Lissoni P, Barni S, Tancini G, et al. A randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma. Br J Cancer 1994;69:196–9.

75. Lissoni P, Brivio F, Ardizzoia A, et al. Subcutaneous therapy with low-dose interlekin-2 plus the neurohormone melatonin in metastatic gastric cancer patients with low performance status. Tumori 1993;79:401–4.

76. Aldeghi R, Lissoni P, Barni S, et al. Low-dose interlekin-2 subcutaneous immunotherapy in association with the pineal hormone melatonin as a first-line therapy in locally advanced or metastatic hepatocellular carcinoma. Eur J Cancer 1994;30A:167–70.

77. Lissoni P, Paolorossi F, Tancini G, et al. A phase II study of tamoxifen plus melatonin in metastatic solid tumour patients. Br J Cancer 1996;74:1466–8.

78. Lissoni P, Barni S, Mandalà, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

79. Lissoni P, Brivio O, Brivio F, et al. Adjuvant therapy with the pineal hormone melatonin in patients with lymph node relapse due to malignant melanoma. J Pineal Res 1996;21:239–42.

80. Neri B, Fiorelli C, Moroni F, et al. Modulation of human lymphoblastoid interferon activity by melatonin in metastatic renal cell carcinoma. Cancer 1994;73:315–9.

81. Lissoni P, Barni S, Ardizzoia A, et al. Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin. Oncology 1992;49:336–9.

82. Lissoni P, Barni S, Ardizzoia A, et al. Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin. Oncology 1992;49:336–9.

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86. Lissoni P, Barni S, Crispino S, et al. Endocrine and immune effects of melatonin therapy in metastatic cancer patients. Eur J Cancer Clin Oncol 1989;25:789–95.

87. Neri B, De Leonardis V, Gemelli MT, et al. Melatonin as biological response modifier in cancer patients. Anticancer Res 1998;18:1329–32.

88. Lissoni P, Barni S, Crispino S, et al. Endocrine and immune effects of melatonin therapy in metastatic cancer patients. Eur J Cancer Clin Oncol 1989;25:789–95.

89. Lissoni P, Barni S, Ardizzoia A, et al. A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms. Cancer 1994;73:699–701.

90. Lissoni P, Barni S, Ardizzoia A, et al. Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin. Oncology 1992;49:336–9.

91. Lissoni P, Paolorossi F, Tancini G, et al. Is there a role for melatonin in the treatment of neoplastic cachexia? Eur J Cancer 1996;32A:1340–3.

92. Lissoni P, Barni S, Tancini G, et al. A randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma. Br J Cancer 1994;69:196–9.

93. Lissoni P, Brivio F, Ardizzoia A, et al. Subcutaneous therapy with low-dose interlekin-2 plus the neurohormone melatonin in metastatic gastric cancer patients with low performance status. Tumori 1993;79:401–4.

94. Aldeghi R, Lissoni P, Barni S, et al. Low-dose interlekin-2 subcutaneous immunotherapy in association with the pineal hormone melatonin as a first-line therapy in locally advanced or metastatic hepatocellular carcinoma. Eur J Cancer 1994;30A:167–70.

95. Lissoni P, Paolorossi F, Tancini G, et al. A phase II study of tamoxifen plus melatonin in metastatic solid tumour patients. Br J Cancer 1996;74:1466–8.

96. Lissoni P, Barni S, Mandalà, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

97. Lissoni P, Brivio O, Brivio F, et al. Adjuvant therapy with the pineal hormone melatonin in patients with lymph node relapse due to malignant melanoma. J Pineal Res 1996;21:239–42.

98. Neri B, Fiorelli C, Moroni F, et al. Modulation of human lymphoblastoid interferon activity by melatonin in metastatic renal cell carcinoma. Cancer 1994;73:315–9.

99. Lissoni P, Cazzanga M, Tancini G, et al. Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone. Eur Urol 1997;31:178–81.

100. Lissoni P, Barni S, Mandalà, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

101. Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 1995;346:541–4.

102. Haimov I, Laudon M, Zisapel N, et al. Sleep disorders and melatonin rhythms in elderly people. BMJ 1994;309:167.

103. Singer C, McArthur A, Hughes R, et al. Melatonin and sleep in the elderly. J Am Geriatr Soc 1996;44:51 [abstr #A1].

104. Zeitzer JM, Daniels JE, Duffy JF, et al. Do plasma melatonin concentrations decline with age? Am J Med 1999;107:432–6.

105. Attenburrow MEJ, Dowling BA, Sharpley AL, Cowen PJ. Case-control study of evening melatonin concentration in primary insomnia. BMJ 1996;312:1263–4.

106. Folkard S, Arendt J, Clark M. Can melatonin improve shift workers’ tolerance of the night shift? Some preliminary findings. Chronobiol Int 1993;10:315–20.

107. Sakotnik A, Liebmann PM, Stoschitzky K. Decreased melatonin synthesis in patients with coronary artery disease. Eur Heart J 1999;20:1314–7.

108. Shamir E, Laudon M, Barak Y, et al. Melatonin improves sleep quality of patients with chronic schizophrenia. J Clin Psychiatry 2000;61:373–7.

109. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: A phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progression under tamoxifen alone. Br J Cancer 1995;71:854–6.

110. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: A phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progression under tamoxifen alone. Br J Cancer 1995;71:854–6.

111. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: A phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progression under tamoxifen alone. Br J Cancer 1995;71:854–6.

112. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

113. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

114. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

115. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

116. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

117. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

118. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

119. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

120. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

121. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

122. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

123. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

124. Demisch L, Demisch K, Nickelsen T. Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects. J Pineal Res 1987;5:317–22.

125. Lissoni P, Cazzaniga M, Tancini G, et al. Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: Efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone. Eur Urol 1997;31:178–81.

126. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

127. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

128. Demisch L, Demisch K, Nickelsen T. Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects. J Pineal Res 1987;5:317–22.

129. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: A phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progression under tamoxifen alone. Br J Cancer 1995;71:854–6.

130. Lissoni P, Cazzaniga M, Tancini G, et al. Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: Efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone. Eur Urol 1997;31:178–81.

131. Lissoni P, Cazzaniga M, Tancini G, et al. Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: Efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone. Eur Urol 1997;31:178–81.

132. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

133. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

134. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: A phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progression under tamoxifen alone. Br J Cancer 1995;71:854–6.

135. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

136. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

137. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

138. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

139. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

140. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

141. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

142. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

143. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

144. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

145. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

146. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

147. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: A phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progression under tamoxifen alone. Br J Cancer 1995;71:854–6.

148. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

149. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

150. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

151. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

152. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: A phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progression under tamoxifen alone. Br J Cancer 1995;71:854–6.

153. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

154. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

155. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

156. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

157. Lissoni P, Cazzaniga M, Tancini G, et al. Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: Efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone. Eur Urol 1997;31:178–81.

158. Lissoni P, Cazzaniga M, Tancini G, et al. Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: Efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone. Eur Urol 1997;31:178–81.

159. Demisch L, Demisch K, Nickelsen T. Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects. J Pineal Res 1987;5:317–22.

160. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: A phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progression under tamoxifen alone. Br J Cancer 1995;71:854–6.

161. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

162. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

163. Demisch L, Demisch K, Nickelsen T. Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects. J Pineal Res 1987;5:317–22.

164. Demisch L, Demisch K, Nickelsen T. Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects. J Pineal Res 1987;5:317–22.

165. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: A phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progression under tamoxifen alone. Br J Cancer 1995;71:854–6.

166. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: A phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progression under tamoxifen alone. Br J Cancer 1995;71:854–6.

167. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

168. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

169. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

170. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

171. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: A phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progression under tamoxifen alone. Br J Cancer 1995;71:854–6.

172. Ferini-Strambi L, Zucconi M, Biella G, et al. Effect of melatonin on sleep microstructure: preliminary results in healthy subjects. Sleep 1993;16:744–7..

173. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: A phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progression under tamoxifen alone. Br J Cancer 1995;71:854–6.

174. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

175. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

176. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

177. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

178. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

179. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

180. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

181. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

182. Childs PA, Rodin I, Martin NJ, et al. Effect of fluoxetine on melatonin in patients with seasonal affective disorder and matched controls. Br J Psychiatry 1995;166:196–8.

183. Härtter S, Grözinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1–6.

184. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

185. Palazidou E, Papadopoulos A, Sitsen A, et al. An alpha 2 adenoceptor antagonist, Org 3770, enhances nocturnal melatonin secretion in man. Psychopharmacology (Berl) 1989;97:115–7.

186. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

187. Weaver DR. Reproductive safety of melatonin: a “wonder drug” to wonder about. J Biol Rhythms 1997;12:682–9.

188. Arendt J. Safety of melatonin in long-term use(?) J Biol Rhythms 1997;12:673–81.

189. Luboshitzky R, Shen-Orr Z, Nave R, Lavi S, Lavie P. Melatonin administration alters semen quality in healthy men. J Androl 2002;23:572–8.

190. Sheldon SH. Pro-convulsant effects or oral melatonin in neurologically disabled children. Lancet 1998;351:1254.

191. Shannon M. Alternative medicines toxicology: a review of selected agents. Clin Toxicol 1999;37:709–13.

192. Guardiola-Lemaître B. Toxicology of melatonin. J Biol Rhythms 1997;12:697–706.

193. Lamberg L. Melatonin potentially useful but safety, efficacy remain uncertain. JAMA 1996;276:1011–4.

194. Force RW, Hansen L, Badell M. Psychotic episode after melatonin. Ann Pharmacother 1997;31:1408 [letter].

195. Porterfield LM. Can melatonin cause severe headaches? RN 1996;59:75.

196. Bornman MS, Schulenburg GW, Reif S, et al. Seminal plasma melatonin and semen parameters. S Afr Med J 1992;81:485–6.

197. Middleton B. Melatonin and fragmented sleep patterns. Lancet 1996;348:551–2 [letter].

198. De Bleeker JL, Verstraete AG, Schelfhout VJ. Melatonin and painful gynecomastia. Neurology 1999;53:435–6 [letter].

199. Korszun A, Sackett-Lundeen L, Papadopoulos E, et al. Melatonin levels in women with fibromyalgia and chronic fatigue syndrome. J Rheumatol 1999;26:2675–80.

200. Cagnacci A, Arangino S, Renzi A, et al. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol2001;54:339–46.

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Complementary Medicine - Cam

Topic Contents

Melatonin

Uses

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

How It Works

How to Use It

Where to Find It

Possible Deficiencies

Interactions

Interactions with Supplements, Foods, & Other Compounds

Interactions with Medicines

Replenish Depleted Nutrients

Reduce Side Effects

Support Medicine

Reduces Effectiveness

Potential Negative Interaction

Explanation Required

Side Effects

Side Effects

Related Information

References