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Melatonin

Nutrient Name: Melatonin.

Summary Table
nutrient description

Chemistry and Form

Melatonin is an amino acid–based (indole) hormone, produced in the brain by the pineal gland. It is synthesized from the amino acid tryptophan, which is converted to the neurotransmitter serotonin, which is then converted to melatonin.

Physiology and Function

Melatonin is the central hormone involved in the regulation of numerous environmental and body cycles. As the biological timekeeper of hormone secretion, melatonin functions as a hormonal interface between the body and the environment. The greatest regulatory influence involves the daily cycle of light and darkness; melatonin production by the pineal gland begins to rise slowly with nightfall, reaching its maximum between midnight and 3AM. After its synthesis is triggered by various external environmental cues, melatonin integrates the environmental feedback of daily and seasonal cycles, sets the biological clock, and activates bodily functions associated with these cues. The most notable example is the circadian (24-hour) cycle of sleep and waking, in which darkness triggers melatonin production, which helps to engender a feeling of sleepiness, and light suppresses secretion. Thus, melatonin possesses both phase-shifting and sleep-promoting properties. Many other cycles influence melatonin production as well, such as the annual cycle of longer and shorter days and the monthly female reproductive cycle, and many events tied to these cycles are linked to melatonin. Melatonin is metabolized by the liver after a half-life of 30 to 50 minutes.

Melatonin acts on multiple systems, appears to be high on the hierarchy of regulatory hormones (i.e., it regulates hormones that regulate hormones), and demonstrates antioxidant, antiestrogenic, and oncostatic activity. For example, melatonin appears to be such as powerful regulator of the secretion of growth hormone (GH) and gonadotropic hormones (the hormones that regulate production of sex hormones such as estrogen and progesterone) that it is a crucial element in the timing of the female reproductive cycle; rising melatonin levels may bring on menstruation, and their decline may induce a surge of luteinizing hormone (LH) and ovulation. Thus, melatonin influences menarche; the frequency, timing, and duration of menstrual cycles; and menopause. It also introduces subtle changes according to external rhythms; for example, varying melatonin levels over the course of the year result in higher estrogen in the spring and summer and higher progesterone in the fall and winter.

Human lymphocytes synthesize and release large amounts of melatonin. This melatonin appears to play a central role in the regulation of the human immune system, possibly by acting as an intracrine, autocrine, and paracrine substance. Receptors have been reported on T and B lymphocytes, and melatonin has demonstrated immune-enhancing properties in many animal studies. Physiologically, melatonin opposes the degeneration caused by elevated levels of endogenous corticosteroids (e.g., protein catabolism, suppressed immune function, and altered blood glucose metabolism). The immunosuppressive activity of exogenous corticosteroids may also be moderated by melatonin.

Various studies have shown a correlation among melatonin, aging, and life span. One proposed rationale is that the ratio of serotonin to melatonin increases as a person ages, increasing the production of various chemicals that are linked with aging. Onset of melatonin's rhythmic patterns starts at approximately 3 months of age, and young children have the highest levels of nighttime melatonin. Levels rise and then gradually start to decline during adolescence. Adults generally exhibit a 37% decline, approximately, in daily melatonin output between 20 and 70 years of age. However, controversy surrounds whether such declines are as prominent in healthy adults. These secretion patterns may contribute to sleep disruption and the tendency to shift to earlier sleep in the evening and earlier rising in the morning in the elderly population.

Numerous researchers and clinicians have suggested that the increased use of artificial light and resulting extension of the daily photoperiod of light exposure over the past century has depressed melatonin secretion and elevated the incidence of cancer in industrialized societies. 1,2

Melatonin also functions as a powerful antioxidant, particularly in neutralizing hydroxyl, the most damaging of all oxygen-based free radicals. Administration for this purpose may be inappropriate, however, because the antioxidant effects may be offset by hormonal disruption caused by taking large doses.

Studies have also shown that melatonin decreases the internal carotid pulsability index of premenopausal women 3 and, applied topically, can reduce skin damage inflicted by ultraviolet (UV) radiation. 4 Research does not support administration as a remedy for the effects of aging; it is probably more beneficial to protect oneself from influences that inhibit melatonin.

nutrient in clinical practice

Known or Potential Therapeutic Uses

As a self-prescribed nutraceutical, melatonin is primarily used to induce sleep or adjust sleep cycles, especially with travel and schedule changes. Practitioners of nutritional therapeutics, particularly within the context of integrative medicine, often prescribe melatonin in the treatment of some forms of depression and hyperactivity, at low dosages, and as part of multimodality cancer treatment protocols, using high dosages.

Historical/Ethnomedicine Precedent

None known.

Possible Uses

Age-related cognitive decline, Angelman's syndrome (sleep disturbances only), attention deficit–hyperactivity disorder (ADHD), breast cancer, cluster headaches, colon cancer, coronary heart disease, depression, epilepsy, essential hypertension, glaucoma, insomnia, jet lag, lung cancer, migraine headaches, multiple sclerosis, myoclonus, nocturnal hypertension, oxidative stress in dialysis patients (preventive), postmenopausal osteoporosis, prostate cancer, sarcoidosis, seasonal affective disorder (SAD), sudden infant death syndrome (SIDS), sleep cycle disruption, tardive dyskinesia, tinnitus.

Deficiency Symptoms

Insomnia 5 and other sleep disturbances.

Dietary Sources

Melatonin appears in foods only in trace amounts.

Nutrient Preparations Available

Time-release forms may best approximate normal physiological secretion of melatonin, 6 which typically occurs over several hours during the night. Further, a limitation of non-time-release forms is that the half-life of oral melatonin is approximately 30 to 50 minutes.

Dosage Forms Available

Capsule, tablet, sublingual tablet, time-release tablet and capsule.

Source Materials for Nutrient Preparations

Melatonin used in preparations for oral administration is derived from animals or produced synthetically.

Dosage Range

Adult

Supplemental/Maintenance: Melatonin is usually not taken on a long-term basis as a general nutritional supplement, that is, outside situational appropriateness or therapeutic strategy.

Pharmacological/Therapeutic: 0.5 to 6.0 mg nightly; up to 40 mg per day in cancer therapy.

Toxic: Melatonin is generally considered nontoxic when used in accordance with proper dosing guidelines for appropriate conditions.

Pediatric (<18 Years)

Supplemental/Maintenance: Melatonin is generally not appropriate for children, other than short-term situational use (e.g., travel, jet lag).

Pharmacological/Therapeutic: Generally not appropriate, except with managed therapeutic protocols.

Toxic: Melatonin is generally considered nontoxic for children when used in accordance with proper dosing guidelines for appropriate conditions.

Laboratoary Values

Salivary melatonin concentration, urinary 6-hydroxymelatonin sulphate excretion rate, serum melatonin concentration. 7

Note: Melatonin in a physiological setting is problematic to study, because a blood sample needs to be obtained between 3 and 4AMwithout exposing the patient to light, in order to obtain a relevant measurement. Accurate interpretation of the assay requires a collection of normal levels arranged by age.

safety profile

Overview

Melatonin use is generally considered safe when used for appropriate conditions in accordance with standard dosage levels. Although certain predictable effects may occur, no substantive and consistent patterns of adverse effects or toxicity, based on clinical trials or qualified case reports, have been confirmed in the scientific literature. Long-term human studies on toxicity or subtle adverse effects have not been conducted. Evidence is lacking at this time of a feedback loop in which augmentation or replacement causes suppression. Nevertheless, as with administration of any exogenous hormone, regular use of melatonin over an extended period may interfere with self-regulatory mechanisms in hormonal systems.

Nutrient Adverse Effects

General Adverse Effects

Drowsiness is an expected outcome of taking melatonin, and being drowsy at inopportune times represents the most common adverse effect. Overuse or incorrect use of melatonin may disrupt circadian rhythms and sleep cycles. Morning sedation or drowsiness may indicate that the dosage used is excessive; if so, a lower dosage should reduce adverse symptoms. Somnambulism, disorientation, and vivid dreams have also been reported. Sleep disruption was observed in one small study. 8 Anxiety and irritability may occur in some individuals. Nocturnal asthma may be aggravated. 9,10

Scattered and unqualified case reports have suggested exogenous melatonin intake as a factor in a variety of adverse phenomena, including transient psychosis, headache, abdominal cramps, decreased libido, infertility, and painful gynecomastia. 11-14Subsequent investigation has yet to document and confirm significant patterns of adverse effects consistent with these reported individual reactions. 15-17

Pregnancy and Nursing

Melatonin readily crosses the placenta, and its fetal effects are unknown; therefore, melatonin is not recommended during pregnancy. Given the intimate relationships between melatonin and reproductive hormones, use of melatonin by women who are pregnant is further contraindicated, pending substantive evidence of safety. The lack of research on the effects and safety of melatonin in infants warrants avoidance by mothers who are breastfeeding.

Infants and Children

An increased incidence of seizures in children with neurological disorders after melatonin administration has been reported but not confirmed. 18 Monitoring by a qualified health care professional is warranted when use in such populations is otherwise appropriate.

Contraindications

Driving and operation of machinery should be avoided while under the influence of melatonin. Daytime use may result in fatigue and decreased alertness; other contraindications include pregnancy and nursing; fibromyalgia (if elevated melatonin), 19 insulin sensitivity or diabetes, 3 and SAD.

Some highly experimental animal trials suggest that melatonin may be contraindicated for patients with autoimmune disorders such as rheumatoid arthritis, lupus, or multiple sclerosis.

Precautions and Warnings

General

Caution is advised given the limited knowledge of hormones and their interactions and the multiple influences melatonin exerts on other regulatory hormones.

Regular use for extended periods is not advised without supervision by a health care professional experienced in nutritional therapies.

Specific Populations

Elevated melatonin levels may inhibit ovulation; prudence suggests that melatonin should generally be avoided by women attempting to conceive.

Individuals diagnosed with depression, diabetes, fibromyalgia, or schizophrenia, especially when not deficient; adolescents; individuals undergoing corticosteroid therapy for anti-inflammatory or immune suppressive effects; individuals with nocturnal asthma may experience increased inflammation with elevated melatonin levels.

Many clinicians have observed a paradoxical effect, causing alertness and insomnia, from melatonin administration in approximately 5% of patients. With those individuals, melatonin can often be successfully dosed in the morning with no adverse effects (i.e., no drowsiness).

interactions review

Strategic Considerations

In most clinical settings, and in the vast majority of self-prescribed use by the general public, melatonin is used to treat sleep disorders (3 mg time-release form) or regulate sleep cycles (e.g., travel across multiple time zones, changing work shift). Assays for deficiency status (or excess) are available, but most experienced practitioners use sleep quality (after correcting sleep hygiene as much as possible, and ruling out sleep apnea/nocturnal myoclonic leg jerks as problems) and response to melatonin (3 mg time-release form) as the primary criteria in clinical evaluation for melatonin sufficiency.

Although consideration of its physiological role raises suspicions that many medications may interfere with melatonin secretion, human research into such effects and their clinical implications is sparse and early in its evolution. Depletion of melatonin by some pharmaceutical agents can be easily corrected with coadministration, usually at low doses, if deficiency results. In a more proactive sense, melatonin may play an important role as a component of integrative care strategies in the treatment of hormone-related cancers and sleep disturbances.

nutrient-drug interactions
Benzodiazepines
Beta-1-Adrenoceptor Antagonists (Beta-1-Adrenergic Blocking Agents)
Chemotherapy and Radiotherapy
Corticosteroids, Oral
Fluoxetine
Fluvoxamine
Haloperidol and Related Antipsychotic Medications
Interleukin-2 (IL-2)
Mirtazapine
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Acetylsalicylic Acid (Aspirin)
Tamoxifen
Triptorelin
Verapamil
Verapamil (Calan, Calan SR, Covera-HS, Isoptin, Isoptin SR, Verelan, Verelan PM). Extrapolated, based on similar properties: Verapamil combination drug: trandolapril and verapamil (Tarka).
Drug-Induced Nutrient Depletion, Supplementation Therapeutic, Not Requiring Professional Management

Probability: 2. Probable
Evidence Base: Preliminary

Effect and Mechanism of Action

Verapamil influences the renal and hepatic handling of melatonin, resulting in increased urinary melatonin excretion.

Research

After noting that individuals with primary hyperparathyroidism have higher serum melatonin concentrations during active disease than after surgical cure, Wikner et al. 80 conducted a three-part experiment to determine whether exogenous hypercalcemia, as induced by calcium channel blockers such as verapamil, would similarly inhibit nocturnal melatonin secretion. After eight healthy volunteers were treated, on separate occasions, with oral verapamil and placebo, verapamil increased urinary melatonin excretion significantly (by 67%), but did not alter excretion of 6-sulphatoxymelatonin, the primary melatonin metabolite excreted by the kidneys. Verapamil did not affect nocturnal melatonin secretion.

Nutritional Therapeutics, Clinical Concerns, and Adaptations

Although the mechanism of this proposed depletion pattern appears consistent with known research and pharmacological principles, its clinical significance remains undetermined at this time. Larger, well-designed clinical trials are warranted, preferably involving subjects with medical conditions for which verapamil would normally be prescribed. Pending such evidence, physicians prescribing verapamil or other calcium channel blockers may want to query relevant patients regarding sleep disruption as a potential adverse effect and discuss the option of corrective melatonin intake, usually 2 to 3 mg daily, before bedtime. Although evidence is lacking to indicate a significant risk from melatonin administration, close supervision and regular monitoring may be warranted in the event that the option to supplement is chosen, preferably within an integrative care context.

theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Anticoagulants
Bupropion, Desipramine, Tranylcypromine
Clonidine; Methoxamine
Cyclosporine
Cytochrome 1A2 lsoenzyme Substrates
Cytochrome 2C9 lsoenzyme Substrates
Estrogens, Progestins, and Estrogen-Progestin Combinations
Indomethacin
Vitamin B 6 –Depleting Drugs
Sedative Medications
nutrient-nutrient interactions
Alcohol/Ethanol
Tryptophan
Vitamin B 6 , Pyridoxine
Vitamin B 12
herb-nutrient interactions
Hypnotic Herbs
Citations and Reference Literature
  • 1.Kerenyi NA, Pandula E, Feuer G. Why the incidence of cancer is increasing: the role of “light pollution.” Med Hypotheses 1990;33:75-78.View Abstract
  • 2.Regelson W, Pierpaoli W. Melatonin: a rediscovered antitumor hormone? Its relation to surface receptors; sex steroid metabolism, immunologic response, and chronobiologic factors in tumor growth and therapy. Cancer Invest 1987;5:379-385.View Abstract
  • 3.Cagnacci A, Arangino S, Renzi A et al. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (Oxf) 2001;54:339-346.View Abstract
  • 4.Fischer T, Bangha E, Elsner P, Kistler GS. Suppression of UV-induced erythema by topical treatment with melatonin: influence of the application time point. Biol Signals Recept 1999;8:132-135.View Abstract
  • 5.Attenburrow ME, Dowling BA, Sharpley AL, Cowen PJ. Case-control study of evening melatonin concentration in primary insomnia. BMJ 1996;312:1263-1264.View Abstract
  • 6.Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 1995;346:541-544.View Abstract
  • 7.Nowak R, McMillen IC, Redman J, Short RV. The correlation between serum and salivary melatonin concentrations and urinary 6-hydroxymelatonin sulphate excretion rates: two non-invasive techniques for monitoring human circadian rhythmicity. Clin Endocrinol (Oxf) 1987;27:445-452.
  • 8.Middleton BA, Stone BM, Arendt J. Melatonin and fragmented sleep patterns. Lancet 1996;348:551-552.View Abstract
  • 9.Martin JG, Suzuki M, Maghni K et al. The immunomodulatory actions of prostaglandin E2 on allergic airway responses in the rat. J Immunol 2002;169:3963-3969.View Abstract
  • 10.Martins E Jr, Ligeiro de Oliveira AP, Fialho de Araujo AM et al. Melatonin modulates allergic lung inflammation. J Pineal Res 2001;31:363-369.View Abstract
  • 11.Guardiola-Lemaitre B. Toxicology of melatonin. J Biol Rhythms 1997;12:697-706.View Abstract
  • 12.Force RW, Hansen L, Bedell M. Psychotic episode after melatonin. Ann Pharmacother 1997;31:1408.View Abstract
  • 13.Shannon M. Alternative medicines toxicology: a review of selected agents. J Toxicol Clin Toxicol 1999;37:709-713.View Abstract
  • 14.De Bleecker JL, Lamont BH, Verstraete AG, Schelfhout VJ. Melatonin and painful gynecomastia. Neurology 1999;53:435-436.View Abstract
  • 15.Bornman MS, Schulenburg GW, Reif S et al. Seminal plasma melatonin and semen parameters. S Afr Med J 1992;81:485-486.View Abstract
  • 16.Porter LM. Can melatonin cause severe headaches? RN 1996;59:75.
  • 17.Lamberg L. Melatonin potentially useful but safety, efficacy remain uncertain. JAMA1996;276:1011-1014.
  • 18.Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998;351:1254.View Abstract
  • 19.Korszun A, Sackett-Lundeen L, Papadopoulos E et al. Melatonin levels in women with fibromyalgia and chronic fatigue syndrome. J Rheumatol 1999;26:2675-2680.View Abstract
  • 20.Wakabayashi H, Shimada K, Satoh T. Effects of diazepam administration on melatonin synthesis in the rat pineal gland in vivo. Chem Pharm Bull (Tokyo) 1991;39:2674-2676.View Abstract
  • 21.McIntyre IM, Norman TR, Burrows GD, Armstrong SM. Alterations to plasma melatonin and cortisol after evening alprazolam administration in humans. Chronobiol Int 1993;10:205-213.View Abstract
  • 22.Monteleone P, Forziati D, Orazzo C, Maj M. Preliminary observations on the suppression of nocturnal plasma melatonin levels by short-term administration of diazepam in humans. J Pineal Res 1989;6:253-258.View Abstract
  • 23.Ferini-Strambi L, Zucconi M, Biella G et al. Effect of melatonin on sleep microstructure: preliminary results in healthy subjects. Sleep 1993;16:744-747.View Abstract
  • 24.Cardinali DP, Gvozdenovich E, Kaplan MR et al. A double blind-placebo controlled study on melatonin efficacy to reduce anxiolytic benzodiazepine use in the elderly. Neuroendocrinol Lett 2002;23:55-60.View Abstract
  • 25.Dagan Y, Zisapel N, Nof D et al. Rapid reversal of tolerance to benzodiazepine hypnotics by treatment with oral melatonin: a case report. Eur Neuropsychopharmacol 1997;7:157-160.View Abstract
  • 26.Steinlechner S, King TS, Champney TH et al. Comparison of the effects of beta-adrenergic agents on pineal serotonin N-acetyltransferase activity and melatonin content in two species of hamsters. J Pineal Res 1984;1:23-30.View Abstract
  • 27.Rommel T, Demisch L. Influence of chronic beta-adrenoreceptor blocker treatment on melatonin secretion and sleep quality in patients with essential hypertension. J Neural Transm Gen Sect 1994;95:39-48.View Abstract
  • 28.Stoschitzky K, Sakotnik A, Lercher P et al. Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol 1999;55:111-115.View Abstract
  • 29.Maestroni GJ, Hertens E, Galli P et al. Melatonin-induced T-helper cell hematopoietic cytokines resembling both interleukin-4 and dynorphin. J Pineal Res 1996;21:131-139.View Abstract
  • 30.Lissoni P, Rovelli F, Meregalli S et al. Melatonin as a new possible anti-inflammatory agent. J Biol Regul Homeost Agents 1997;11:157-159.View Abstract
  • 31.Neri B, de Leonardis V, Gemelli MT et al. Melatonin as biological response modifier in cancer patients. Anticancer Res 1998;18:1329-1332.View Abstract
  • 32.Lissoni P. Modulation of anticancer cytokines IL-2 and IL-12 by melatonin and the other pineal indoles 5-methoxytryptamine and 5-methoxytryptophol in the treatment of human neoplasms. Ann N Y Acad Sci 2000;917:560-567.View Abstract
  • 33.Liu F, Ng TB, Fung MC. Pineal indoles stimulate the gene expression of immunomodulating cytokines. J Neural Transm 2001;108:397-405.View Abstract
  • 34.Rosales-Corral S, Tan DX, Reiter RJ et al. Orally administered melatonin reduces oxidative stress and proinflammatory cytokines induced by amyloid-beta peptide in rat brain: a comparative, in vivo study versus vitamin C and E. J Pineal Res 2003;35:80-84.View Abstract
  • 35.Neri B, Fiorelli C, Moroni F et al. Modulation of human lymphoblastoid interferon activity by melatonin in metastatic renal cell carcinoma: a phase II study. Cancer 1994;73:3015-3019.View Abstract
  • 36.Brackowski R, Zubelewicz B, Romanowski W et al. Preliminary study on modulation of the biological effects of tumor necrosis factor-alpha in advanced cancer patients by the pineal hormone melatonin. J Biol Regul Homeost Agents 1994;8:77-80.View Abstract
  • 37.Lissoni P, Meregalli S, Nosetto L et al. Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology 1996;53:43-46.View Abstract
  • 38.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.View Abstract
  • 39.Lissoni P, Paolorossi F, Ardizzoia A et al. A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non–small cell lung cancer patients in a poor clinical state. J Pineal Res 1997;23:15-19.View Abstract
  • 40.Lissoni P, Tancini G, Barni S et al. Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin. Support Care Cancer 1997;5:126-129.View Abstract
  • 41.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;35:1688-1692.View Abstract
  • 42.Lissoni P, Malugani F, Bukovec R et al. Reduction of cisplatin-induced anemia by the pineal indole 5-methoxytryptamine in metastatic lung cancer patients. Neuroendocrinol Lett 2003;24:83-85.View Abstract
  • 43.Cerea G, Vaghi M, Ardizzoia A et al. Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations. Anticancer Res 2003;23:1951-1954.
  • 44.Agapito MT, Antolin Y, del Brio MT et al. Protective effect of melatonin against Adriamycin toxicity in the rat. J Pineal Res 2001;31:23-30.View Abstract
  • 45.Parlakpinar H, Sahna E, Ozer MK et al. Physiological and pharmacological concentrations of melatonin protect against cisplatin-induced acute renal injury. J Pineal Res 2002;33:161-166.View Abstract
  • 46.Liu X, Chen Z, Chua CC et al. Melatonin as an effective protector against doxorubicin-induced cardiotoxicity. Am J Physiol Heart Circ Physiol 2002;283:H254-263.View Abstract
  • 47.Birdsall TC, Alschuler LN, Martin J et al. Effect of concomitant naturopathic therapies on clinical tumor response to external beam radiation therapy for prostate cancer. Society of Integrative Oncology’s Third International Conference. Boston; 2006.
  • 48.Mori W, Aoyama H, Mori N. Melatonin protects rats from injurious effects of a glucocorticoid, dexamethasone. Jpn J Exp Med 1984;54:255-261.View Abstract
  • 49.Demisch L, Demisch K, Nickelsen T. Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects. J Pineal Res 1988;5:317-322.View Abstract
  • 50.Zawilska JB, Sadowska M. Prolonged treatment with glucocorticoid dexamethasone suppresses melatonin production by the chick pineal gland and retina. Pol J Pharmacol 2002;54:61-66.View Abstract
  • 51.Pawlikowski M, Kolomecka M, Wojtczak A, Karasek M. Effects of six months melatonin treatment on sleep quality and serum concentrations of estradiol, cortisol, dehydroepiandrosterone sulfate, and somatomedin C in elderly women. Neuroendocrinol Lett 2002;23 Suppl 1:17-19.View Abstract
  • 52.Yu AM, Idle JR, Byrd LG et al. Regeneration of serotonin from 5-methoxytryptamine by polymorphic human CYP2D6. Pharmacogenetics 2003;13:173-181.
  • 53.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;166:196-198.View Abstract
  • 54.Walsh HA, Daya S. Influence of the antidepressants desipramine and fluoxetine on tryptophan-2,3-dioxygenase in the presence of exogenous melatonin. Life Sci 1998;62:2417-2423.View Abstract
  • 55.Miller HL, Ekstrom RD, Mason GA et al. Noradrenergic function and clinical outcome in antidepressant pharmacotherapy. Neuropsychopharmacology 2001;24:617-623.View Abstract
  • 56.Von Bahr C, Ursing C, Yasui N et al. Fluvoxamine but not citalopram increases serum melatonin in healthy subjects—an indication that cytochrome P450 CYP1A2 and CYP2C19 hydroxylate melatonin. Eur J Clin Pharmacol 2000;56:123-127.
  • 57.Hartter S, Wang X, Weigmann H et al. Differential effects of fluvoxamine and other antidepressants on the biotransformation of melatonin. J Clin Psychopharmacol 2001;21:167-174.View Abstract
  • 58.Facciola G, Hidestrand M, von Bahr C, Tybring G. Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes. Eur J Clin Pharmacol 2001;56:881-888.View Abstract
  • 59.Grozinger M, Hartter S, Wang X et al. Fluvoxamine strongly inhibits melatonin metabolism in a patient with low-amplitude melatonin profile. Arch Gen Psychiatry 2000;57:812-813.View Abstract
  • 60.Shamir E, Barak Y, Shalman I et al. Melatonin treatment for tardive dyskinesia: a double-blind, placebo-controlled, crossover study. Arch Gen Psychiatry 2001;58:1049-1052.View Abstract
  • 61.Lissoni P, Barni S, Cazzaniga M et al. Efficacy of the concomitant administration of the pineal hormone melatonin in cancer immunotherapy with low-dose IL-2 in patients with advanced solid tumors who had progressed on IL-2 alone. Oncology 1994;51:344-347.View Abstract
  • 62.Bregani ER, Lissoni P, Rossini F et al. Prevention of interleukin-2-induced thrombocytopenia during the immunotherapy of cancer by a concomitant administration of the pineal hormone melatonin. Recenti Prog Med 1995;86:231-233.
  • 63.Lissoni P, Barni S, Brivio F et al. Treatment of cancer-related thrombocytopenia by low-dose subcutaneous interleukin-2 plus the pineal hormone melatonin: a biological phase II study. J Biol Regul Homeost Agents 1995;9:52-54.View Abstract
  • 64.Lissoni P, Barni S, Fossati V et al. A randomized study of neuroimmunotherapy with low-dose subcutaneous interleukin-2 plus melatonin compared to supportive care alone in patients with untreatable metastatic solid tumour. Support Care Cancer 1995;3:194-197.View Abstract
  • 65.Lissoni P, Barni S, Brivio F et al. A biological study on the efficacy of low-dose subcutaneous interleukin-2 plus melatonin in the treatment of cancer-related thrombocytopenia. Oncology 1995;52:360-362.View Abstract
  • 66.Lissoni P, Pittalis S, Rovelli F et al. Interleukin-2, melatonin and interleukin-12 as a possible neuroimmune combination in the biotherapy of cancer. J Biol Regul Homeost Agents 1995;9:63-66.View Abstract
  • 67.Lissoni P, Bolis S, Brivio F, Fumagalli L. A phase II study of neuroimmunotherapy with subcutaneous low-dose IL-2 plus the pineal hormone melatonin in untreatable advanced hematologic malignancies. Anticancer Res 2000;20:2103-2105.View Abstract
  • 68.Lissoni P, Mandala M, Brivio F. Abrogation of the negative influence of opioids on IL-2 immunotherapy of renal cell cancer by melatonin. Eur Urol 2000;38:115-118.View Abstract
  • 69.Lissoni P, Malugani F, Malysheva O et al. Neuroimmunotherapy of untreatable metastatic solid tumors with subcutaneous low-dose interleukin-2, melatonin and naltrexone: modulation of interleukin-2-induced antitumor immunity by blocking the opioid system. Neuroendocrinol Lett 2002;23:341-344.View Abstract
  • 70.Palazidou E, Papadopoulos A, Sitsen A et al. An alpha 2 adrenoceptor antagonist, Org 3770, enhances nocturnal melatonin secretion in man. Psychopharmacology (Berl) 1989;97:115-117.
  • 71.Murphy PJ, Myers BL, Badia P. Nonsteroidal anti-inflammatory drugs alter body temperature and suppress melatonin in humans. Physiol Behav 1996;59:133-139.View Abstract
  • 72.Blask DE, Wilson ST, Zalatan F. Physiological melatonin inhibition of human breast cancer cell growth in vitro: evidence for a glutathione-mediated pathway. Cancer Res 1997;57:1909-1914.View Abstract
  • 73.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 progressing under tamoxifen alone. Br J Cancer 1995;71:854-856.View Abstract
  • 74.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;74:1466-1468.View Abstract
  • 75.Garcia JJ, Reiter RJ, Ortiz GG et al. Melatonin enhances tamoxifen’s ability to prevent the reduction in microsomal membrane fluidity induced by lipid peroxidation. J Membr Biol 1998;162:59-65.
  • 76.Rato AG, Pedrero JG, Martinez MA et al. Melatonin blocks the activation of estrogen receptor for DNA binding. FASEB J 1999;13:857-868.View Abstract
  • 77.Hermann R, Podhajsky S, Jungnickel S, Lerchl A. Potentiation of antiproliferative effects of tamoxifen and ethanol on mouse hepatoma cells by melatonin: possible involvement of mitogen-activated protein kinase and induction of apoptosis. J Pineal Res 2002;33:8-13.View Abstract
  • 78.Czeczuga-Semeniuk E, Wolczynski S, Anchim T et al. Effect of melatonin and all-trans retinoic acid on the proliferation and induction of the apoptotic pathway in the culture of human breast cancer cell line MCF-7. Pol J Pathol 2002;53:59-65.View Abstract
  • 79.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;31:178-181.View Abstract
  • 80.Wikner J, Wetterberg L, Rojdmark S. Does hypercalcaemia or calcium antagonism affect human melatonin secretion or renal excretion? Eur J Clin Invest 1997;27:374-379.
  • 81.Weekley LB. Melatonin-induced relaxation of rat aorta: interaction with adrenergic agonists. J Pineal Res 1991;11:28-34.View Abstract
  • 82.Esrefoglu M, Kurus M, Sahna E. The beneficial effect of melatonin on chronic cyclosporin A nephrotoxicity in rats. J Int Med Res 2003;31:42-44.View Abstract
  • 83.Singh P, Bhargava VK, Garg SK. Effect of melatonin and beta-carotene on indomethacin induced gastric mucosal injury. Indian J Physiol Pharmacol 2002;46:229-234.View Abstract
  • 84.Raskin NH, Fishman RA. Pyridoxine-deficiency neuropathy due to hydralazine. N Engl J Med 1965;273:1182-1185.View Abstract
  • 85.Haspels AA, Bennink HJ, Schreurs WH. Disturbance of tryptophan metabolism and its correction during oestrogen treatment in postmenopausal women. Maturitas 1978;1:15-20.
  • 86.Bermond P. Therapy of side effects of oral contraceptive agents with vitamin B6. Acta Vitaminol Enzymol 1982;4:45-54.View Abstract
  • 87.Shimizu T, Maeda S, Arakawa H et al. Relation between theophylline and circulating vitamin levels in children with asthma. Pharmacology 1996;53:384-389.
  • 88.Mydlik M, Derzsiova K, Zemberova E. Metabolism of vitamin B6 and its requirement in chronic renal failure. Kidney Int Suppl 1997;62:S56-S59.View Abstract
  • 89.Ekman AC, Leppaluoto J, Huttunen P et al. Ethanol inhibits melatonin secretion in healthy volunteers in a dose-dependent randomized double blind cross-over study. J Clin Endocrinol Metab 1993;77:780-783.View Abstract
  • 90.Honma K, Kohsaka M, Fukuda N et al. Effects of vitamin B12 on plasma melatonin rhythm in humans: increased light sensitivity phase-advances the circadian clock? Experientia 1992;48:716-720.
  • .Agapito MT, Antolin Y, del Brio MT, et al. Protective effect of melatonin against adriamycin toxicity in the rat. J Pineal Res 2001;31(1):23-30.
  • .Allegra M, Reiter RJ, Tan DX, et al. The chemistry of melatonin’s interaction with reactive species. J Pineal Res 2003;34(1):1-10. (Review)
  • .Andlauer P, Reinberg A, Fouree L, et al. Amplitude of the oral temperature circadian rhythm and the tolerance to shift-work. J Physiol 1979;75:507-512.
  • .Anisomov VN, Bondarenko LA, Khavinson VK, et al. The pineal peptides: interactions with indoles and the role in aging and cancer. Neuroendocrinol Lett 1989;11:235.
  • .Anton-Tay F. Melatonin: effects on brain function. Adv Biochem Psychopharmacol 1974;11:315-324.
  • .Arangino S, Cagnacci A, Angiolucci M, et al. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol 1999;83:1417-1419.
  • .Arendt J. Melatonin. Clin Endocrinol 1998;29:205-229.
  • .Arendt J. Melatonin assay in body fluids. J Neural Transm Suppl 1978;13:265-278.
  • .Arendt J. Safety of melatonin in long-term use? J Biol Rhythms 1997;12:673-681. (Review)
  • .Arendt J, Aldhous M, English J, et al. Some effects of jet-lag and their alleviation by melatonin. Ergonomics 1987;30:1379-1393.
  • .Arendt J, Aldhous M, Wright J. Synchronisation of a disturbed sleep-wake cycle in a blind man by melatonin treatment. Lancet 1988;1:772-773. (Letter)
  • .Arendt J, Bojkowski C, Franey C, et al. Immunoassay of 6-hydroxymelatonin sulphate in human plasma and urine: abolition of the urinary 24-hour rhythm with atenolol. J Clin Endocrinol Metab 1985;60:1166-1173.
  • .Arendt J, Marks V. Can melatonin alleviate jet lag? Br Med J 1983;287:426.
  • .Arendt J, Wirz-Justice A, Bradtke J. Annual rhythm of serum melatonin in man. Neurosci Lett 1977;7:327-330.
  • .Attele AS, Xie JT, Yuan CS. Treatment of insomnia: an alternative approach. Altern Med Rev 2000;5(3):249-259.
  • .Attenburrow ME, et al. Low dose melatonin improves sleep in healthy middle-aged subjects. Psychopharmacology (Berl) 1996;126(2):179-181.
  • .Avery D, Lenz M, Landis C. Guidelines for prescribing melatonin. Ann Med 1998;30(1):122-130.
  • .Bangha E, Elsner P, Kistler GS. Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine): a dose response study. Arch Dermatol Res 1996;288(9):522-526.
  • .Barchas J, DaCosta F, Spector S. Acute pharmacology of melatonin. Nature 1967;214:919-920.
  • .Bardia A, Tleyjeh IJ, Cerhan JR, et al. Does antioxidant supplementation reduce primary cancer incidence and mortality? Systematic review and meta analysis. Abstract A159. American Association for Cancer Research, Frontiers in Cancer Prevention Research meeting. Boston, Nov 13, 2006.
  • .Barlow-Walden L, Chuang J, Ortiz GG, et al. A review of the evidence supporting melatonin’s role as an antioxidant. J Pineal Res 1995;18(1):1-11.
  • .Barlow-Walden LR, Reiter RJ, Abe M, et al. Melatonin stimulates brain glutathione peroxidase activity. Neurochem Int 1995;26(5):497-502.
  • .Bartsch C, Bartsch H. Significance of melatonin in malignant disease. Wien Klin Wochenschr 1997;109(18):722-729.
  • .Bartsch C, Bartsch H. The anti-tumor activity of pineal melatonin and cancer enhancing life styles in industrialized societies. Cancer Causes Control 2006;17(4):559-571. (Review)
  • .Bartsch C, Bartsch H, Blask DE, et al, eds. The pineal gland and cancer: neuroimmunoendocrine mechanisms in malignancy. 1st ed. Berlin: Springer Verlag; 2001.
  • .Bartsch C, Bartsch H, Jain AK, et al. Urinary melatonin levels in breast cancer patients. J Neural Transm 1981;52:281-294.
  • .Baumgaertel A. Alternative and controversial treatments for attention-deficit/hyperactivity disorder. Pediatr Clin North Am 1999;46(5):977-992.
  • .Bazil CW, Short D, Crispin D, et al. Patients with intractable epilepsy have low melatonin, which increases following seizures. Neurology 2000;55(11):1746-1748.
  • .Beck-Friis J, Kjellman BF, Aperia B, et al. Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome. Acta Psychiatr Scand 1985;71(4):319-330.
  • .Beck-Friis J, Ljunggren JG, Thoren M, et al. Melatonin, cortisol and ACTH in patients with major depressive disorder and healthy humans with special reference to the outcome of the dexamethasone suppression test. Psychoneuroendocrinology 1985;10(2):173-186.
  • .Bekaroglu M, Aslan Y, Gedik Y. Relationships between serum free fatty acids and zinc, and attention deficit hyperactivity disorder: a research note. J Child Psychol Psychiatry 1996;37(2):225-227.
  • .Bellipanni G, Bianchi P, Pierpaoli W, et al. Effects of melatonin in perimenopausal and menopausal women: a randomized and placebo controlled study. Exp Gerontol 2001;36(2):297-310.
  • .Ben-Nathan D, Maestroni GJ, Lustig S, et al. Protective effects of melatonin in mice infected with encephalitis viruses. Arch Virol 1995;140(2):223-230.
  • .Beni SM, Kohen R, Reiter RJ, et al. Melatonin-induced neuroprotection after closed head injury is associated with increased brain antioxidants and attenuated late-phase activation of NF-kappaB and AP-1. FASEB J 2004;18(1):149-151.
  • .Benshushan A, Brzezinski A. Hormonal manipulations and breast cancer. Obstet Gynecol Surv 2002;57(5):314-323. (Review)
  • .Blaicher W, Speck E, Imhof MH, et al. Melatonin in postmenopausal females. Arch Gynecol Obstet 2000;263(3):116-118.
  • .Blask DE, Cos S, Hill SM, et al. Melatonin action on oncogenesis. In: Fraschini F, Reiter RJ, eds. Role of melatonin and pineal peptides in neuroimmunomodulation. New York: Plenum; 1991:233-240.
  • .Blask DE, Dauchy RT, Sauer LA. Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal. Endocrine 2005;27(2):179-188. (Review)
  • .Blask DE, Hill SM. Melatonin and cancer: basic and clinical aspects. In: Miles A, Philbrick DRS, Thompson C, eds. Melatonin: clinical aspects. Oxford: Oxford University Press; 1988:125-173.
  • .Blau JN, Engel HO. A new cluster headache precipitant: increased body heat. Lancet 1999;354:1001-1002.
  • .Block KI. Why integrative therapies? Integr Cancer Ther 2006;5(1):53-56. (Editorial)
  • .Block KI, Koch AC, Mead MN, et al: Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials. Cancer Treat Rev 2007;33(5):407-418. Epub 2007 March 23.
  • .Bonilla E, Valero-Fuenmayor N, Pons H, et al. Melatonin protects mice infected with Venezuelan equine encephalomyelitis virus. Cell Mol Life Sci 1997;53(5):430-434.
  • .Bonnefont-Rousselot D, Cheve G, Gozzo A, et al. Melatonin related compounds inhibit lipid peroxidation during copper or free radical-induced LDL oxidation. J Pineal Res 2002;33:109-117.
  • .Borjigin J, Deng J. Diurnal 5-HT production and melatonin formation. In: Pandi-Perumal SR, Cardinali D, eds. Melatonin: biological basis of its function in health and disease. Georgetown, TX: Landes Bioscience; 2004.
  • .Brouwer CAJ, Gietema JA, van den Berg MP, et al. Long-term cardiac follow-up in survivors of a malignant bone tumour. Ann Oncol 2006;17(10):1586-1591.
  • .Brzezinski A. Melatonin in health and disease. Fertil Steril 1991;55(5):1025. (Review)
  • .Brzezinski A. Melatonin in humans. N Engl J Med 1997;336(3):186-195. (Review)
  • .Brzezinski A. “Melatonin replacement therapy” for postmenopausal women: is it justified? Menopause 1998;5(1):60-64. (Review)
  • .Brzezinski A. The “darkness hormone”. Fertil Steril 1993;60(5):927-928.
  • .Brzezinski A, Cohen M, Ever-Hadani P, et al. The pattern of serum melatonin levels during ovarian stimulation for in vitro fertilization. Int J Fertil Menopausal Stud 1994;39(2):81-85.
  • .Brzezinski A, Fibich T, Cohen M, et al. Effects of melatonin on progesterone production by human granulosa lutein cells in culture. Fertil Steril 1992;58(3):526-529.
  • .Brzezinski A, Lynch HJ, Seibel MM, et al. The circadian rhythm of plasma melatonin during the normal menstrual cycle and in amenorrheic women. J Clin Endocrinol Metab 1988;66(5):891-895.
  • .Brzezinski A, Lynch HJ, Wurtman RJ, et al. Possible contribution of melatonin to the timing of the luteinizing hormone surge. N Engl J Med 1987;316(24):1550-1551.
  • .Brzezinski A, Seibel MM, Lynch HJ, et al. Melatonin in human preovulatory follicular fluid. J Clin Endocrinol Metab 1987;64(4):865-867.
  • .Brzezinski A, Vangel MG, Wurtman RJ, et al. Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev 2005;9(1):41-50.
  • .Brzezinski A, Wurtman RJ. The pineal gland: its possible roles in human reproduction. Obstet Gynecol Surv 1988;43(4):197-207. (Review)
  • .Brown GM. Light, melatonin and the sleep-wake cycle. J Psychiatr Neurosci 1994;19(5):345-351.
  • .Brown R, Kocsis JH, Caroff S, et al. Differences in nocturnal melatonin secretion between melancholic depressed patients and control subjects. Am J Psychiatry 1985;142:811-813.
  • .Brugger P, Mark HW, Harold M. Impaired nocturnal secretion of melatonin in coronary heart disease. Lancet 345(8962):1408.
  • .Bubenik GA. Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci 2002;47:2336-2348.
  • .Bubenik GA. Localization, physiological significance and possible clinical implications of gastrointestinal melatonin. Biol Signals Recept 2001;10:350-366.
  • .Buscemi N, Vandermeer B, Hooton N, et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ 2006;332(7538):385-393. (Meta-analysis)
  • .Buscemi N, Vandermeer B, Hooton N, et al. The efficacy and safety of exogenous melatonin for primary sleep disorders: a meta-analysis. J Gen Intern Med 2005;20(12):1151-1158. (Meta-analysis)
  • .Bylesjo I, Forsgren L, Wetterberg L. Melatonin and epileptic seizures in patients with acute intermittent porphyria. Epileptic Disord 2000;2(4):203-208.
  • .Cagnacci A. Melatonin in relation to physiology in adult humans. J Pineal Res 1996;21:200-213. (Review)
  • .Cagnacci A, Arangino S, Angiolucci M, et al. Influences of melatonin administration on the circulation of women. Am J Physiol 1998;274(2 Pt 2):R335-R338.
  • .Cagnacci A, Arangino S, Angiolucci M, et al. Potentially beneficial cardiovascular effects of melatonin administration in women. J Pineal Res 1997;22(1):16-19.
  • .Cagnacci A, Arangino S, Malmusi S, et al. Melatonin in aged women: possible modulation by estrogens. Aging (Milano) 1997;9(4 Suppl):62-63. (Review)
  • .Cagnacci A, Cannoletta M, Renzi A, et al. Prolonged melatonin administration decreases nocturnal blood pressure in women. Am J Hypertens 2005;18(12 Pt 1):1614-1618.
  • .Cagnacci A, Krauchi K, Wirz-Justice A, et al. Homeostatic versus circadian effects of melatonin on core body temperature in humans. J Biol Rhythms 1997;12(6):509-517. (Review)
  • .Cagnacci A, Soldani R, Yen SS Exogenous melatonin enhances luteinizing hormone levels of women in the follicular but not in the luteal menstrual phase. Fertil Steril 1995;63(5):996-999.
  • .Cagnacci A, Soldani R, Yen SS. Melatonin enhances cortisol levels in aged women: reversible by estrogens. J Pineal Res 1997;22(2):81-85.
  • .Cagnoni ML, Lombardi A, Cerinic MC, et al. Melatonin for treatment of chronic refractory sarcoidosis. Lancet 1995;346(4):1299-1230. (Letter)
  • .Capsoni S, Stankov BM, Fraschini F. Reduction of regional cerebral blood flow by melatonin in young rats. Neuroreport 1995;6:1346-1348.
  • .Cardinali DP, Bortman GP, Liotta G, et al. A multifactorial approach employing melatonin to accelerate resynchronization of sleep-wake cycle after a 12 time-zone westerly transmeridian flight in elite soccer athletes. J Pineal Res 2002;32(1):41-46.
  • .Cardoso SM, Oliveira CR. Glutathione cycle impairment mediates A beta-induced cell toxicity. Free Radic Res 2003;37(3):241-250.
  • .Carlson LE, Speca M, Patel KD, et al. Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate (DHEAS) and melatonin in breast and prostate cancer outpatients. Psychoneuroendocrinology 2004;29(4):448-474.
  • .Carman JS, Post RM, Roswell R, et al. Negative effects of melatonin on depression. Am J Psychiatry 1976;133:1181-1183.
  • .Carrillo-Vico A, Calvo JR, Abreu P, et al. Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance. FASEB J 2004;306:941-1111.
  • .Cauffield JS, Forbes HJ. Dietary supplements used in the treatment of depression, anxiety, and sleep disorders. Lippincotts Primary Care Pract 1999;3(3):290-304.
  • .Chase JE, Gidal BE. Melatonin: therapeutic use in sleep disorders. Ann Pharmacother 1997;31:1218-1225.
  • .Chuang JI, Chen SS, Lin MT. Melatonin decreases brain serotonin release, arterial pressure and heart rate in rats. Pharmacology 1993;47:91-97.
  • .Citera G, Arias MA, Maldonado-Cocco JA, et al. The effect of melatonin in patients with fibromyalgia: a pilot study. Clin Rheumatol 2000;19(1):9-13.
  • .Claustrat B, Brun J, Chiquet C, et al. Melatonin secretion is supersensitive to light in migraine. Cephalalgia 2004;24(2):128-133.
  • .Claustrat B, Brun J, David M, et al. Melatonin and jet lag: confirmatory result using a simplified protocol. Biol Psychiatry 1992;32(8):705-711.
  • .Cohen M, Small RA, Brzezinski A. Hypotheses: melatonin/steroid combination contraceptives will prevent breast cancer. Breast Cancer Res Treat 1995;33(3):257-264.
  • .Coker KH. Meditation and prostate cancer: integrating a mind/body intervention with traditional therapies. Semin Urol Oncol 1999;17(2):111-118.
  • .Cornelissen G, Halberg F, Burioka N, et al. Do plasma melatonin concentrations decline with age? Am J Med 2000;109(4):343-345.
  • .Cos S, Gonzalez A, Guezmes A, et al. Melatonin inhibits the growth of DMBA-induced mammary tumors by decreasing the local biosynthesis of estrogens through the modulation of aromatase activity. Int J Cancer 2006;118(2):274-278.
  • .Cos S, Gonzalez A, Martinez-Campa C, et al. Estrogen-signaling pathway: a link between breast cancer and melatonin oncostatic actions. Cancer Detect Prev 2006;30(2):118-128. (Review)
  • .Cos S, Sanchez-Barcelo EJ. Melatonin and mammary pathological growth. Front Neuroendocrinol 2000;21:133-170.
  • .Cos S, Sanchez-Barcelo EJ. Melatonin, experimental basis for a possible application in breast cancer prevention and treatment. Histol Histopathol 2000;15:637-647.
  • .Crasson M, Kjiri S, Colin A, et al. Serum melatonin and urinary 6-sulfatoxymelatonin in major depression. Psychoneuroendocrinology 2004;29:1-12. (Abstract)
  • .Dahlitz M, Alvarez B, Vignau J, et al. Delayed sleep phase syndrome response to melatonin. Lancet 1991;337(8750):1121-1124.
  • .Das Gupta TK. Influence of the pineal gland on the growth and spread of malignant tumors. Surg Forum 1965;19:83-84.
  • .Das Gupta TK, Terz J. Influence of the pineal gland on the growth and spread of malignant tumors. Surg Forum 1967;27:1306-1311.
  • .Danforth DN Jr, et al. Plasma melatonin and the hormone-dependency of human breast cancer. J Clin Oncol 1985;3(7):941-948.
  • .Daya S, Nonaka KO, Buzzell GR, et al. Heme precursor 5-aminolevulinic acid alters brain tryptophan and serotonin levels without changing pineal serotonin and melatonin concentrations. J Neurosci Res 1989;23(3):304-309.
  • .Delagrange P, Jockers R. Melatonin and energy homeostasis: peripheral versus central regulation. Minerva Endocrinol 2003;28(4):313-320.
  • .Dolberg OT, Hirschmann S, Grunhaus L. Melatonin for the treatment of sleep disturbances in major depressive disorder. Am J Psychiatry 1998;155:1119-1121.
  • .Dollins AB, Lynch HJ, Wurtman RJ, et al. Effect of pharmacological daytime doses of melatonin on human mood and performance. Psychopharmacology (Berl) 1993;112(4):490-496.
  • .Dollins AB, Zhdanova IV, Wurtman RJ, et al. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci U S A 1994;91(5):1824-1828.
  • .Dreher F, Denig N, Gabard B, et al. Effect of topical antioxidants on UV-induced erythema formation when administered after exposure. Dermatology 1999;198(1):52-55.
  • .Dreher F, Gabard B, Schwindt DA, et al. Topical melatonin in combination with vitamins E and C protects skin from ultraviolet-induced erythema: a human study in vivo. Br J Dermatol 1998;139(2):332-339.
  • .Dubbels R, Reiter RJ, Goebel A, et al. Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography-mass spectrometry. J Pineal Res 1995;18:28-31.
  • .Eck-Enriquez K, Kiefer TL, Spriggs LL, et al. Pathways through which a regimen of melatonin and retinoic acid induces apoptosis in MCF-7 human breast cancer cells. Breast Cancer Res Treat 2000;61(3):229-239.
  • .Fauteck J, Schmidt H, Lerchl A, et al. Melatonin in epilepsy: first results of replacement therapy and first clinical results. Biol Signals Recept 1999;8(1-2):105-110.
  • .Fellenberg AJ, Phillipou C, Seamark RE. Measurement of urinary production rates of melatonin as an index of human pineal function. Endocr Res Comm 1980;7:167-175.
  • .Fevre-Montange M, van Cauter E, Refetoff S, et al. Effects of ’jet lag’ on hormonal patterns: II: adaptation of melatonin circadian periodicity. J Clin Endocrinol Metab 1981;52:642-649.
  • .Folkard S, Arendt J, Clark M. Can melatonin improve shift workers’ tolerance of the night shift? Some preliminary findings. Chronobiol Int 1993;10:315-320.
  • .Forsling ML, Williams AJ. The effects of exogenous melatonin on stimulated neurohypophysial hormone release in man. Clin Endocrinol (Oxf) 2002;57:615-620.
  • .Forsling ML, Wheeler MJ, Williams AJ. The effect of melatonin administration on pituitary hormone secretion in man. Clin Endocrinol (Oxf) 1999;51(5):637-642.
  • .Fountoulakis KN, Karamouzis M, Iacovides A, et al. Morning and evening plasma melatonin and dexamethasone suppression test in patients with nonseasonal major depressive disorder from northern Greece (latitude 40-41.5 degrees). Neuropsychobiology 2001;44(3):113-117.
  • .Fowler G, Daroszewska M, Ingold KU. Melatonin does not “directly scavenge hydrogen peroxide”: demise of another myth. Free Radic Biol Med 2003;34:77-83.
  • .Fraschini F, Demartini G, Esposti D, et al. Melatonin involvement in immunity and cancer. Biol Signals Recept 1998;7(1):61-72.
  • .Gagnier JJ. The therapeutic potential of melatonin in migraines and other headache types. Altern Med Rev 2001;6(4):383-389. (Review)
  • .Garfinkel D, Zisapel N, Wainstein J, et al. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med 1999;159(8):2456-2460.
  • .Gibb JW, Bush L, Hanson GR. Exacerbation of methamphetamine-induced neurochemical deficits by melatonin. J Pharmacol Exp Ther 1997;283:630-635.
  • .Glazer WM, Woods SW, Goff D. Should sisyphus have taken melatonin? Arch Gen Psych 2001;58(11):1054-1055.
  • .Golden RN, Markey SP, Risby ED, et al. Antidepressants reduce whole-body norepinephrine turnover while enhancing 6-hydroxymelatonin output. Arch Gen Psychiatry 1988;45A:150-154.
  • .Gooneratne NS, Metlay JP, Guo W, et al. The validity and feasibility of saliva melatonin assessment in the elderly. J Pineal Res 2003;34:88-94.
  • .Gordon N. The therapeutics of melatonin: a paediatric perspective. Brain Dev 2000;22(4):213-217.
  • .Grad BR, Rozencwaig R. The role of melatonin and serotonin in aging: update. Psychoneuroendocrinology 1993;18(4):283-295.
  • .Grin W, Grüberger W. A significant correlation between melatonin deficiency and endometrial cancer. Gynecol Obstet Invest 1998;45:62-65.
  • .Grossman E, Laudon M, Yalcin R, et al. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med 2006;119(10):898-902.
  • .Grundman M, Grundman M, Delaney P. Antioxidant strategies for Alzheimer’s disease. Proc Nutr Soc 2002;61(2):191-202.
  • .Guardiola-Lemaître B. Toxicology of melatonin. J Biol Rhythms 1997;12:697-706.
  • .Guerrero J, Reiter AR. A brief survey of pineal gland-immune system interrelationships. Endocr Res 1992;18:91-113.
  • .Haimov I, Lavie P. Potential of melatonin replacement therapy in older patients with sleep disorders. Drugs Aging 1995;7(2):75-78.
  • .Haimov I, Laudon I, Zisapel N, et al. Sleep disorders and melatonin rhythms in elderly people. BMJ 1994(9120);309:167.
  • .Hariharasubramanian N, Nair NPV, Pilapil C. Circadian rhythm of plasma melatonin and cortisol during the menstrual cycle. In: Brown GM, Wainwright SD, eds. The pineal gland, endocrine aspects. Oxford: Pergamon Press; 1985:31-36.
  • .Hartter S, Wang X, Weigmann H, et al. Differential effects of fluvoxamine and other antidepressants on the biotransformation of melatonin. J Clin Psychopharmacol 2001;21(2):167-174.
  • .Hartter S, Grozinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67(1):1-6.
  • .Herrera J, Nava M, Romero F, et al. Melatonin prevents oxidative stress resulting from iron and erythropoietin administration. Am J Kidney Dis 2001;37(4):750-757.
  • .Herxheimer A, Petrie KJ. Melatonin for preventing and treating jet lag. Cochrane Database Syst Rev 2001;(1):CD001520.
  • .Herxheimer A, Waterhouse J. The prevention and treatment of jet lag. BMJ 2003;326(7384):296-297.
  • .Hughes RJ, Sack RL, Lewy AJ. The role of melatonin and circadian phase in age-related sleep maintenance insomnia: assessment in a clinical trial of melatonin replacement. Sleep 1998;21:52-68.
  • .Iguchi H, Kato KI, Ibayashi H. Age-dependent reduction in serum melatonin concentrations in healthy human subjects. J Clin Endocrinol Metab 1982;55:27-29.
  • .Illnerova H, Buresova M, Presl J. Melatonin rhythm in human milk. J Clin Endocrinol Metab 1993;77:838-841.
  • .Ivanenko A, Crabtree VM, Tauman R, et al. Melatonin in children and adolescents with insomnia: a retrospective study. Clin Pediatr (Phila) 2003;42(1):51-58.
  • .Jacob S, Poeggeler B, Weishaupt JH, et al. Melatonin as a candidate compound for neuroprotection in amyotrophic lateral sclerosis (ALS): high tolerability of daily oral melatonin in ALS patients. J Pineal Res 2002;33:186-187.
  • .Jacobson JS, Workman SB, Kronenberg F. Research on complementary/alternative medicine for patients with breast cancer: a review of the biomedical literature. J Clin Oncol 2000;18(3):668-683. (Review)
  • .James SP, Sack DA, Rosenthal NE, et al. Melatonin administration in insomnia. Neuropsychopharmacology 1990;3(1):19-23.
  • .Jan JE, Connolly MB, Hamilton D, et al. Melatonin treatment of non-epileptic myoclonus in children. Dev Med Child Neurol 1999;41:255-259. (Review)
  • .Jan JE, Espezel H, Appleton RE. The treatment of sleep disorders with melatonin. Dev Med Child Neurol 1994;36(2):97-107.
  • .Jan JE, Espezel H, Freeman RD, et al. Melatonin treatment of chronic sleep disorders. J Child Neurol 1998;13(2):98.
  • .Jockovich M, Cosentino D, Cosentino L, et al. Effect of exogenous melatonin on mood and sleep efficiency in emergency medicine residents working night shifts. Acad Emerg Med 2000;7(8):955-958.
  • .Kaptanoglu E, Palaoglu S, Demirpence E, et al. Different responsiveness of central nervous system tissues to oxidative conditions and to the antioxidant effects of melatonin. J Pineal Res 2003;34:32-35.
  • .Karasek M, Fraschini F. Is there a role for the pineal gland in neoplastic growth? In: Fraschini F, Reiter RJ, eds. Role of melatonin and pineal peptides in neuroimmunomodulation. New York: Plenum; 1991:243-251.
  • .Karasek M, Reiter RJ. Melatonin and aging. Neuroendocrinol Lett 2002;23(Suppl 1):14-16.
  • .Kayumov L, Brown G, Jindal R, et al. A randomized, double-blind, placebo-controlled crossover study of the effect of exogenous melatonin on delayed sleep phase syndrome. Psychosom Med 2001;63(1):40-48.
  • .Keifer T, Ram PT, Yuan L, et al. Melatonin inhibits estrogen receptor transactivation and cAMP levels in breast cancer cells. Breast Cancer Res Treat 2002;71:37-45.
  • .Kennaway DI, Royles P. Circadian rhythms of 6-sulphatoxy melatonin, cortisol and electrolyte excretion at the summer and winter solstices in normal men and women. Acta Endocrinol (Copenh) 1986;113:450-456.
  • .Kennedy SH. Melatonin disturbances in anorexia nervosa and bulimia nervosa. Int J Eating Disord 1994;16:257-265.
  • .Kennedy SH, Garfinkel PE, Parienti V, et al. Changes in melatonin levels but not cortisol levels are associated with depression in patients with eating disorders. Arch Gen Psychiatry 1989;46:74-79.
  • .Kirkwood CK. Management of insomnia. J Am Pharm Assoc 1999;39(1):688-696.
  • .Klein T, Martens H, Dijk DJ, et al. Circadian sleep regulation in the absence of light perception: chronic non-24-hour circadian rhythm sleep disorder in a blind man with a regular 24-hour sleep-wake schedule. Sleep 1993;16(4):333-343.
  • .Knobil E. The neuroendocrine control of the menstrual cycle. Recent Prog Horm Res 1980;36:53-88.
  • .Kostoglou-Athanassiou I, Treacher DF, Wheeler MJ, et al. Melatonin administration and pituitary hormone secretion. Clin Endocrinol (Oxf) 1998;48(1):31.
  • .Kostrzewa RM, Segura-Aguilar J. Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. a review. Neurotoxicol Res 2003;5(6):375-383. (Review)
  • .Kunz D, Mahlberg R, Muller C, et al. Melatonin in patients with reduced REM sleep duration: two randomized controlled trials. J Clin Endocrinol Metab 2004;89(1):128-134.
  • .Lagneux C, Joyeux M, Demenge P, et al. Protective effects of melatonin against ischemia-reperfusion injury in the isolated rat heart. Life Sci 2000;66(6):503-509.
  • .Lee YM, Chen HR, Hsiao G, et al. Protective effects of melatonin on myocardial ischemia/reperfusion injury in vivo. J Pineal Res 2002;33:72-80.
  • .Leger D, Laudon M, Zisapel N. Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy. Am J Med 2004;116(2):91-95.
  • .Leibenluft E, Feldman-Naim S, Turner EH, et al. Effects of exogenous melatonin administration and withdrawal in five patients with rapid-cycling bipolar disorder. J Clin Psychiatry 1997;58(9):383-388.
  • .Leone M, D’Amico D, Moschiano F, et al. Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups. Cephalalgia 1996;16(7):494-496.
  • .Lewy AJ, Bauer VK, Cutler NL, et al. Melatonin treatment of winter depression: a pilot study. Psychiatr Res 1998;77(1):57-61.
  • .Lewy AJ, Sack RL, Singer CM, et al. Winter depression and the phase-shift hypothesis for bright lights therapeutic effects: history, theory, and experimental evidence. J Biol Rhythms 1988;3(2):121-134.
  • .Lewy AJ, Wehr TA, Goodwin FK, et al. Light suppresses melatonin secretion in humans. Science 1980;210:1267-1269.
  • .Lima AC, Louzada PR, De Mello FG, et al. Neuroprotection against Abeta and glutamate toxicity by melatonin: are GABA receptors involved? Neurotoxicol Res 2003;5(5):323-327.
  • .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;49:336-339.
  • .Lissoni P, Barni S, Cattaneo G, et al. Clinical results with the pineal hormone melatonin in advanced cancer resistant to standard antitumor therapies. Oncology 1991;48(6):448-450.
  • .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(12):1688-1692.
  • .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(1):196-199.
  • .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;21:239-242.
  • .Lissoni P, Chilelli M, Villa S, et al. Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial. J Pineal Res 2003;35(1):12-15.
  • .Lissoni P, Giani L, Zerbini S, et al. Biotherapy with the pineal immunomodulating hormone melatonin versus melatonin plus aloe vera in untreatable advanced solid neoplasms. Nat Immunol 1998;16(1):27-33.
  • .Lissoni P, Malugani F, Bukovec R, et al. Reduction of cisplatin-induced anemia by the pineal indole 5-methoxytryptamine in metastatic lung cancer patients. Neuro Endocrinol Lett 2003;24(1-2):83-85.
  • .Lissoni P, Mandala M, Rossini F, et al. Growth factors: thrombopoietic property of the pineal hormone melatonin. Hematology 1999;4(4):335-343.
  • .Lissoni P, Meregalli S, Fossati V, et al. A randomized study of immunotherapy with low-dose subcutaneous interleukin-2 plus melatonin vs chemotherapy with cisplatin and etoposide as first-line therapy for advanced non-small cell lung cancer. Tumori 1994;80(6):464-467.
  • .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(8):1340-1343.
  • .Lissoni P, Rovelli F, Pittalis S, et al. [Therapy with melatonin does not suppress its endogenous production in healthy volunteers.] Recenti Prog Med 1999;90(2):84-85.
  • .Lissoni P, Tancini G, Paolorossi F, et al. Chemoneuroendocrine therapy of metastatic breast cancer with persistent thrombocytopenia with weekly low-dose epirubicin plus melatonin: a phase II study. J Pineal Res 1999;26(3):169-173.
  • .Lissoni P, Vigore L, Rescaldani R, et al. Neuroimmunotherapy with low-dose subcutaneous interleukin-2 plus melatonin in AIDS patients with CD4 cell number below 200/mm3: a biological phase-II study. J Biol Regul Homeost Agents 1995;9:155-158.
  • .Low Dog T, Riley D, Carter T. Traditional and alternative therapies for breast cancer. Alt Ther 2001;7(3):36-47. (Review)
  • .Lusardi P, Piazza E, Fogari R. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. Br J Clin Pharmacol 2000;49(5):423-427.
  • .MacFarlane JG, Cleghorn JM, Brown GM, et al. The effects of exogenous melatonin on the total sleep time and daytime alertness of chronic insomniacs: a preliminary study. Biol Psychiatry 1991;30(4):371-376.
  • .MacIntosh A. Melatonin: clinical monograph. Q Rev Nat Med 1996;47-60. (Review)
  • .Maestroni G, Conti A, Pierpaoli W. Role of the pineal gland in immunity: melatonin antagonizes the immuno-suppressive effects of acute stress via an opiatergic mechanism. Immunology 1988;63:465-469.
  • .Malhotra S, Sawhney G, Pandhi P. The therapeutic potential of melatonin: a review of the science. Medscape Gen Med 2004;6(2).
  • .Manev H, Uz T. Oral melatonin in neurologically disabled children. Lancet 1998;351:1963. (Letter)
  • .Martin V, Sainz RM, Antolin I, et al. Several antioxidant pathways are involved in astrocyte protection by melatonin. J Pineal Res 2002;33:204-212.
  • .Martins E Jr, Ligeiro de Oliveira AP, Fialho de Araujo AM, et al. Melatonin modulates allergic lung inflammation. J Pineal Res 2001;31(4):363-369.
  • .Massion AO, Teas J, Hebert JR, et al. Meditation, melatonin and breast/prostate cancer: hypothesis and preliminary data. Med Hypotheses 1995;44:39-46.
  • .Mayo JC, Sainz RM, Antolin I, et al. Melatonin regulation of antioxidant enzyme gene expression. Cell Mol Life Sci 2002;59:1706-1713.
  • .Mazzoccoli G, Carughi S, De Cata A, et al. Melatonin and cortisol serum levels in lung cancer patients at different stages of disease. Med Sci Monitor 2005;11(6):CR284-CR288.
  • .Mazzoccoli G, Giuliani A, Carughi S, et al. The hypothalamic-pituitary-thyroid axis and melatonin in humans: possible interactions in the control of body temperature. Neuro Endocrinol Lett 2004;25(5):368-372.
  • .Mazzoccoli G, Giuliani A, De Cata A, et al. [Melatonin in the international literature of the last twenty years.] Recenti Prog Med 2003;94(4):172. [Italian] (Review)
  • .McArthur AJ, Budden SS. Sleep dysfunction in Rett syndrome: a trial of exogenous melatonin treatment. Dev Med Child Neurol 1998;40(3):186-192.
  • .McIntyre IM, Norman TR, Burrows GD, et al. Human melatonin suppression by light is intensity dependent. J Pineal Res 1990;6:149-156.
  • .Mcintyre IM, Norman TR, Burrows GD, et al. Melatonin supersensitivity to dim light in seasonal affective disorder. Lancet 1990;335:488.
  • .McIntyre I, Trevor R. The pineal hormone melatonin in panic disorder. J Affect Disorder 1987;12:203-206.
  • .Megwalu UC, Finnell JE, Piccirillo JF. The effects of melatonin on tinnitus and sleep. Otolaryngol Head Neck Surg 2006;134(2):210-213.
  • .Miles A, Philbrick DRS. Melatonin and psychiatry. Biol Psychiatry 1998;23:405-425.
  • .Mills E, Wu P, Seely D, et al. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res 2005;39(4):360-366. (Review)
  • .Mirmiran M, Swaab DF, Kok JH, et al. Circadian rhythms and the suprachiasmatic nucleus in perinatal development, aging and Alzheimer’s disease. Prog Brain Res 1992;93:151-162.
  • .Molis TM, Spriggs LL, Jupiter Y, et al. Melatonin modulation of estrogen-regulated proteins, growth factors, and proto-oncogenes in human breast cancer. J Pineal Res 1995;18(2):93-103.
  • .Moretti RM, Marelli MM, Maggi R, et al. Antiproliferative action of melatonin on human prostate cancer LNCaP cells. Oncol Rep 2000;7(2):347-351.
  • .Moss RW. Should patients undergoing chemotherapy and radiotherapy be prescribed antioxidants? Integr Cancer Ther 2006;5(1):3-6.
  • .Munoz-Hoyos A, Sanchez-Forte M, Molina-Carballo A, et al. Melatonin’s role as an anticonvulsant and neuronal protector: experimental and clinical evidence. J Child Neurol 1998;13(10):501-509.
  • .Murphy P, Myers B, Badia P. NSAIDs suppress human melatonin levels. Am J Nat Med 1997;iv:25.
  • .Nagtegaal JE, Smits MG, Swart ACW, et al. Melatonin-responsive headache in delayed sleep phase syndrome: preliminary observations. Headache 1998;38:303-307.
  • .Nowak R. The salivary melatonin diurnal rhythm may be abolished after transmeridian flights in an eastward but not a westward direction. Med J Aust 1988;149:340-341. (Letter)
  • .Nunnari G, Nigro L, Palermo F, et al. Reduction of serum melatonin levels in HIV-1-infected individuals’ parallel disease progression: correlation with serum interleukin-12 levels. Infection 2003;31(6):379-382.
  • .Okatani Y, Morioka N, Wakatsuki A. Changes in nocturnal melatonin secretion in perimenopausal women: correlation with endogenous estrogen concentrations. J Pineal Res 2000;28(2):111-118.
  • .Okatani Y, Sagara Y. Amplification of nocturnal melatonin secretion in women with functional secondary amenorrhea: relation to endogenous estrogen concentration. Clin Endocrinol 1994;41(6):763-770.
  • .Okatani Y, Sagara Y. Enhanced nocturnal melatonin secretion in women with functional secondary amenorrhea: relationship to opioid system and endogenous estrogen levels. Horm Res 1995;43(5):194-195.
  • .Olde Rikkert MG, Rigaud AS. Melatonin in elderly patients with insomnia: a systematic review. Z Gerontol Geriatr 2001;34(6):491-497. (Review)
  • .Olcese J, ed. Hanseatic Endocrine Conference on Melatonin after four decades: melatonin after four decades: an assessment of its potential (advances in experimental medicine and biology, 460). New York: Plenum Pub Corp; 2000.
  • .Oosthuizen JM, Bornman MS, Barnard HC, et al. Melatonin and steroid-dependent carcinomas. Andrologia 1989;21(5):429-431.
  • .Oxenkrug G, Requintina P, Bachurin S. Antioxidant and antiaging activity of N-acetylserotonin and melatonin in the in vivo models. Ann N Y Acad Sci 2001;939:190-199.
  • .Pappolla MA, Simovich MJ, Bryant-Thomas T, et al. The neuroprotective activities of melatonin against the Alzheimer beta-protein are not mediated by melatonin membrane receptors. J Pineal Res 2002;32(3):135-142.
  • .Parfitt A, Klein DC. Increase caused by desmethylimipramine in the production of [3H] melatonin by isolated pineal glands. Biochem Pharmacol 1977;26:904.
  • .Partonen T. Involvement of melatonin and serotonin in winter depression. Med Hypotheses 1994;43:165-166.
  • .Partonen T. Short note: melatonin-dependent infertility. Med Hypotheses 1999;52(5):487-488.
  • .Pawlikowski M, Kolomecka M, Wojtczak A, et al. Effects of six months melatonin treatment on sleep quality and serum concentrations of estradiol, cortisol, dehydroepiandrosterone sulfate, and somatomedin C in elderly women. Neuroendocrinol Lett 2002;23(Suppl 1):17-19.
  • .Peled N, Shorer Z, Peled E. et al. Melatonin effect on seizures in children with severe neurologic deficit disorders. Epilepsia 2001;42(9):1208-1210.
  • .Peres MF, del Rio MS, Seabra ML, et al. Hypothalamic involvement in chronic migraine. J Neurol Neurosurg Psychiatry 2001;71(6):747-751.
  • .Peres MF, Seabra ML, Zukerman E, et al. Cluster headache and melatonin. Lancet 2000;355:147. (Letter)
  • .Peres MF, Zukerman E, da Cunha Tanuri F, et al. Melatonin, 3 mg, is effective for migraine prevention. Neurology 2004;63(4):757.
  • .Perreau-Lenz S, Kalsbeek A, Pevet P, et al. Glutamatergic clock output stimulates melatonin synthesis at night. Eur J Neurosci 2004;19(2):318-324.
  • .Petrie K, Dawson AG, Thompson L, et al. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatry 1993;33:526-530.
  • .Pillar G, Shahar E, Peled N, et al. Melatonin improves sleep-wake patterns in psychomotor retarded children. Pediatr Neurol 2000;23(3):225-228.
  • .Poeggeler B, Miravalle L, Zagorski MG, et al. Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the Alzheimer amyloid Abeta peptide. Biochemistry 2001;40(49):14995-15001.
  • .Poeggeler B, Sazrela S, Reiter R, et al. Melatonin: a highly potent endogenous radical scavenger and electron donor; new aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci 1994;738:419-420.
  • .Rabe-Jablonska J, Szymanska A. Diurnal profile of melatonin secretion in the acute phase of major depression and in remission. Med Sci Monitor 2001;7(5):946-952.
  • .Ram PT, Yuan L, Dai J, et al. Differential responsiveness of MCF-7 human breast cancer cell line stocks to the pineal hormone, melatonin. J Pineal Res 2000;28(4):210-218.
  • .Reiter RJ. Oxidative damage in the central nervous system: protection by melatonin. Prog Neurobiol 1998;56(3):359-384.
  • .Reiter RJ, Melchiorri D, Sewerynek E, et al. A review of the evidence supporting melatonin’s role as an antioxidant. J Pineal Res 1995;18(1):1-11. (Review)
  • .Reiter RJ, Tan DX, Mayo JC, et al. Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochim Pol 2003;50(4):1129-1146.
  • .Riemann D, Klein T, Rodenbeck A, et al. Nocturnal cortisol and melatonin secretion in primary insomnia. Psychiatry Res 2002;113(1-2):17-27.
  • .Rogers NL, Dinges DF, Kennaway DJ, et al. Potential action of melatonin in insomnia. Sleep 2003;26(8):1058-1059.
  • .Rojansky N, Brzezinski A, Schenker JG. Seasonality in human reproduction: an update. Hum Reprod 1992;7(6):735-745. (Review)
  • .Rosenberg SI, Silverstein H, Rowan PT, et al. Effect of melatonin on tinnitus. Laryngoscope 1998;108:305-310.
  • .Roth JA, Kim B-G, Lin W-L, et al. Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem 1999;274:22041-22047.
  • .Sack RL, Brandes RW, Kendall AR, et al. Entrainment of free-running circadian rhythms by melatonin in blind people. N Engl J Med 2000;343(15):1070-1077.
  • .Sack RL, Hughes RJ, Edgar DM, et al. Sleep-promoting effects of melatonin: at what dose, in whom, under what conditions, and by what mechanisms? Sleep 1997;20(10):908-915.
  • .Sack RL, Lewy AJ. Desmethylimipramine treatment increase melatonin synthesis in humans. Biol Psychiatry 1986;21:406-410.
  • .Sack RL, Lewy AJ. Melatonin as a chronobiotic: treatment of circadian desynchrony in night workers and the blind. J Biol Rhythms 1997;12(6):595-603. (Review)
  • .Sakotnik A, Liebmann PM, Stoschitzky K. Decreased melatonin synthesis in patients with coronary artery disease. Eur Heart J 1999;20:1314-1317.
  • .Samples JR, Krause G, Lewy AJ. Effect of melatonin on intraocular pressure. Curr Eye Res 1988;7:649-653.
  • .Sanchez-Barcelo EJ, Cos S, Fernandez R, et al. Melatonin and mammary cancer: a short review. Endocr Relat Cancer 2003;10(2):153-159. (Review)
  • .Sandyk R. The pineal gland and the menstrual cycle. Intern J Neurosci 1992;63:197-204.
  • .Satomura T, Sakamoto T, Shirakawa S, et al. Hypnotic action of melatonin during daytime administration and its comparison with triazolam. Psychiatry Clin Neurosci 2001;55(3):303-304.
  • .Scheer FA, Van Montfrans GA, van Someren EJ, et al. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 2004;43(2):192-197.
  • .Scott GN, Elmer GW. Update on natural product-drug interactions. Am J Health-Syst Pharm 2002;59(4):339-347. (Review)
  • .Sener G, Sehirli AO, Ayanoglu-Dulger G. Protective effects of melatonin, vitamin E and N-acetylcysteine against acetaminophen toxicity in mice: a comparative study. J Pineal Res 2003;35:61-68.
  • .Sewerynek E. Melatonin and the cardiovascular system. Neuroendocrinol Lett 2002;23(Suppl 1):79-83.
  • .Shafii M, Shafii SL, eds. Melatonin in psychiatric and neoplastic disorders. Washington, DC: American Psychiatric Press; 1998.
  • .Shamir E, Barak Y, Shalman I, et al. Melatonin treatment for tardive dyskinesia: a double-blind, placebo-controlled, crossover study. Arch Gen Psychiatry 2001;58(11):1049-1052.
  • .Shamir E, Laudon M, Barak Y, et al. Melatonin improves sleep quality of patients with chronic schizophrenia. J Clin Psychiatry 2000;61(5):373-377.
  • .Sheldon SH. Oral melatonin in neurologically disabled children. Lancet 1998;351(9120):1964. (Letter)
  • .Singer C, McArthur A, Hughes R, et al. Melatonin and sleep in the elderly. J Am Geriatr Soc 1996;44:51. (Abstract)
  • .Skene DJ, Lockley SW, Arendt J. Use of melatonin in the treatment of phase shift and sleep disorders. Adv Exp Med Biol 1999;467:79-84.
  • .Skwarlo-Sonta K. Melatonin in immunity: comparative aspects. Neuroendocrinol Lett 2002;23(Suppl 1):67-72.
  • .Smits MG, Nagtegaal EE, van der Heijden J, et al. Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. J Child Neurol 2001;16(2):86-92.
  • .Spitzer RL, Terman M, Williams JB, et al. Jet lag: clinical features, validation of a new syndrome-specific scale, and lack of response to melatonin in a randomized, double-blind trial. Am J Psychiatry 1999;156(9):1392-1396.
  • .Stetinova V, Smetanova L, Grossmann V, et al. In vitro and in vivo assessment of the antioxidant activity of melatonin and related indole derivatives. Gen Physiol Biophys 2002;21:153-162.
  • .Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci 2001;107(1-2):77-85.
  • .Suhner A, Schlagenhauf P, Johnson R, et al. Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag. Chronobiol Int 1998;15(6):655-666.
  • .Sutherland ER, Martin RJ, Ellison MC, et al. Immunomodulatory effects of melatonin in asthma. Am J Respir Crit Care Med 2002;166(8):1055-1061.
  • .Szymanska A, Rabe-Jablonska J, Karasek M. Diurnal profile of melatonin concentrations in patients with major depression: relationship to the clinical manifestation and antidepressant treatment. Neuroendocrinol Lett 2001;22:192-198.
  • .Takahashi T, Sasaki M, Itoh H, et al. Melatonin alleviates jet lag symptoms caused by an 11-hour eastward flight. Psychiatry Clin Neurosci 2002;56(3):301-302.
  • .Tan DX, Manchester LC, Reiter RJ, et al. Ischemia/reperfusion-induced arrhythmias in the isolated rat heart: prevention by melatonin. J Pineal Res 1998;25:184-191.
  • .Terzolo M, Revelli A, Guidetti D, et al. Evening administration of melatonin enhances the pulsatile secretion of prolactin but not of LH and TSH in normally cycling women. Clin Endocrinol (Oxf) 1993;39(2):185-191.
  • .Thompson C, Franey C, Arendt J, et al. A comparison of melatonin secretion in depressed patients and normal subjects. Br J Psychiatry 1988;152:260-265.
  • .Touitou Y, Motohashi Y, Reinberg A, et al. Effect of shiftwork on the night-time secretory patterns of melatonin, prolactin, cortisol and testosterone. Eur J Appl Physiol 1990;60:288-292.
  • .Tsia PL, Hu MK. Free radical scavenging and antioxidative activity of melatonin derivatives. J Pharm Pharmacol 2003;55(12):1655-1660.
  • .Tzischinsky O, Dagan Y, Lavie P. The effects of melatonin on the timing of sleep in patients with delayed sleep phase syndrome. In: Touitou Y, Arendt J, Pevet P, eds. Melatonin and the pineal gland: from basic science to clinical application. Amsterdam: ExcerptaMedica; 1993:351-354.
  • .Tzischinsky O, Lavie P. Melatonin possesses time-dependent hypnotic effects. Sleep 1994;17:638-645.
  • .USDA: Composition of foods: USDA handbook #8. Washington, DC: ARS, USDA; 1976-1986.
  • .van der Helm-van Mil AH, van Someren EJ, van den Boom R, et al. No influence of melatonin on cerebral blood flow in humans. J Clin Endocrinol Metab 2003;88(12):5989-5994.
  • .van Heukelom RO, Prins JB, Smits MG, et al. Influence of melatonin on fatigue severity in patients with chronic fatigue syndrome and late melatonin secretion. Eur J Neurol 2006;13(1):55-60.
  • .Wagner DR. Circadian rhythm sleep disorders. Curr Treat Opt Neurol 1999;1(4):299-308.
  • .Wagner J, Wagner ML, Hening WA. Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia. Ann Pharmacother 1998;32:680-691.
  • .Waldhauser F, Saletu B, Trinchard-Lugan I. Sleep laboratory investigations on hypnotic properties of melatonin. Psychopharmacology (Berl) 1990;100(2):222-226.
  • .Weaver DR. Reproductive safety of melatonin: a “wonder drug” to wonder about. J Biol Rhythms 1997;12:682-689.
  • .Wehr TA, Duncan WC Jr, Sher L, et al. A circadian signal of change of season in patients with seasonal affective disorder. Arch Gen Psychiatry 2001;58:1108-1114.
  • .Weiss JF, Landauer MR. Protection against ionizing radiation by antioxidant nutrients and phytochemicals. Toxicology 2003;189(1-2):1-20. (Review)
  • .West Sk, Oosthuizen JM. Melatonin levels are decreased in rheumatoid arthritis. J Basic Clin Physiol Pharmacol 1992;3(1):33-40.
  • .Wetterberg L, Arendt J, Paunier L, et al. Human serum melatonin changes during the menstrual cycle. J Clin Endocrinol 1976;42:185-188.
  • .Wetterberg L. The relationship between the pineal gland and the pituitary-adrenal axis in health, endocrine and psychiatric conditions. Psychoneuroendocrinology 1983;8:75-80.
  • .Williams G, Waterhouse J, Mugarza J, et al. Therapy of circadian rhythm disorders in chronic fatigue syndrome: no symptomatic improvement with melatonin or phototherapy. Eur J Clin Invest 2002;32(11):831-837.
  • .Wilson N. Depression and its relation to light deprivation. Psychoanal Rev 2002;89:557-567.
  • .Wolfer A, Abuja PM, Linkesch W, et al. Questionable benefit of melatonin for antioxidant pharmacologic therapy. J Clin Oncol 2002;20:4127-4129.
  • .Wright J, Aldhous M, Franey C, et al. The effect of exogenous melatonin in endocrine function in man. Clin Endocrinol 1986;24:375-382.
  • .Wu YH, Feenstra MG, Zhou JN, et al. Molecular changes underlying reduced pineal melatonin levels in Alzheimer disease: alterations in preclinical and clinical stages. J Clin Endocrinol Metab 2003;88(12):5898-5906.
  • .Wurtman RJ, Zhdanova II. Oral melatonin in neurologicaly disabled children. Lancet 1998;351(9120):1963-1964. (Letter)
  • .Yen SSC. The human menstrual cycle. In: Yen SSC, Jaffe RB, eds. Reproductive endocrinology, physiology, pathophysiology and clinical management. Philadelphia: Saunders; 1986:200-236.
  • .Yie SM, Brown GM, Liu GY, et al. Melatonin and steroids in human pre-ovulatory follicular fluid: seasonal variations and granulosa cell steroid production. Human Reprod 1995;10(1):50-55.
  • .Zatta P, Tognon G, Carampin P. Melatonin prevents free radical formation due to the interaction between beta-amyloid peptides and metal ions [Al(III), Zn(II), Cu(II), Mn(II), Fe(II)]. J Pineal Res 2003;35(2):98-103.
  • .Zawilska JB, Nowak JZ. Melatonin: from biochemistry to therapeutic applications. Pol J Pharm 1999;51:3-23.
  • .Zeitzer JM, Daniels JE, Duffy JF, et al. Do plasma melatonin concentrations decline with age? Am J Med 1999;107:432-436.
  • .Zhadanova IV, Wurtman RJ, Lynch HJ, et al. Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther 1995;57:552-558.
  • .Zhdanova IV, Wurtman RJ, Morabito C, et al. Effects of low oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in normal young humans. Sleep 1996;19:423-431.
  • .Zhdanova IV, Wurtman RJ, Regan MM, et al. Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab 2001;86(10):4727-4730.
  • .Zhdanova IV, Wurtman RJ, Wagstaff J. Effects of a low amount of melatonin on sleep in children with Angelman syndrome. J Pediatr Endocrinol Metab 1999;12:57-67.
  • .Zeitzer JM, Daniels JE, Duffy JF, et al. Do plasma melatonin concentrations decline with age? Am J Med 1999;107:432-436.
  • .Zisapel N. The use of melatonin for the treatment of insomnia. Biol Signals Recept 1999;8(1-2):84-89.