Medical Studies on Melatonin – Sleep


Modern science recognises more than 100 diseases related to sleep, because sleep disorders that are left undiagnosed or untreated can result in drastic consequences for health. Experts estimate that roughly one in ten suffers from some kind of sleep disorder. This proportion is even higher among older people, with around 60 to 70 per cent of people over the age of 65 suffering from sleep disorders to differing extents. A sleep disorder is defined as such if a person sleeps for less than six hours a night in three out of seven nights over a period of six months.

Sleep deprivation and its health consequences

Studies have been finding for years that people who sleep too little or have to sleep at the wrong times, for example, suffer from flu-like infections four times as often, as their immune system is weakened as a result of the sleep deprivation. People who have been working shifts for more than 10 years are at particular risk; the WHO (World Health Organisation) has classified night shift work as carcinogenic. The risk of breast cancer can increase by up to 65 per cent, while the risk of intestinal and prostate cancer also rises drastically.

Other effects

The likelihood of digestive system disorders, heart attack, stroke, diabetes, vascular diseases, and also cancer, dementia and obesity is also increased many times over. A lack of sleep can also result in impaired memory, lack of drive and mood swings. In the worst cases, this may result in hallucinations or depression.

Melatonin as a key hormone

The benefits of melatonin in regulating and optimising the sleep/wake cycle have long been proven. Especially as a chronotherapeutic drug, its value has been very successfully proven, providing support in mitigating the risk of one of the aforementioned diseases. And it has also been demonstrated that melatonin is highly tolerable over a longer period time, even at higher dosages. There is also no risk of addiction and/or dependency.

Medical Studies on Melatonin – Sleep

Evening home lighting adversely impacts the circadian system and sleep

2020-11 Cain SW, McGlashan EM, Vidafar P, Mustafovska J, Curran SPN, Wang X, Mohamed A, Kalavally V, Phillips AJK

The regular rise and fall of the sun resulted in the development of 24-h rhythms in virtually all organisms. In an evolutionary heartbeat, humans have taken control of their light environment with electric light. Humans are highly sensitive to light, yet most people now use light until bedtime. We evaluated the impact of modern home lighting environments in relation to sleep and individual-level light sensitivity using a new wearable spectrophotometer.

Predictions of melatonin suppression during the early biological night and their implications for residential light exposures prior to sleeping

2020-08 Rea MS, Nagare R, Figueiro MG

The magnitude of nocturnal melatonin suppression depends upon the spectrum, amount, and duration of light exposure. The functional relationship between melatonin suppression and the light spectrum and amount have been previously described. Only one duration-dependent parameter was needed to extend this functional relationship to predict nocturnal melatonin suppression during the early biological night from a variety of published studies.

Clinical Impact of Melatonin on Breast Cancer Patients Undergoing Chemotherapy; Effects on Cognition, Sleep and Depressive Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial.

2020-04 Palmer ACS, Zortea M, Souza A, Santos V, Biazús JV, Torres ILS, Fregni F, Caumo W

This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment.

Effectiveness of Complementary and Alternative Medicine Interventions for Sleep Quality in Adult Intensive Care Patients: A Systematic Review.

2020-03 Cooke M, Ritmala-Castrén M, Dwan T, Mitchell M

Pharmacological interventions for sleep (analgesic, sedative and hypnotic agents) can both disrupt and induce sleep and have many negative side effects within the intensive care population. The use of complementary and alternative medicine therapies to assist with sleep has been studied but given the variety of modalities and methodological limitations no reliable conclusions have been drawn.

Short Sleep Is Associated With Low Bone Mineral Density and Osteoporosis in the Women’s Health Initiative.

2020-02 Ochs-Balcom HM, Hovey KM, Andrews C, Cauley JA, Hale L, Li W, Bea JW, Sarto GE, Stefanick ML, Stone KL, Watts NB, Zaslavsky O, Wactawski-Wende J

Short sleep duration, recognized as a public health epidemic, is associated with adverse health conditions, yet little is known about the association between sleep and bone health. We tested the associations of usual sleep behavior and bone mineral density (BMD) and osteoporosis.

Circadian rhythm and its association with birth and infant outcomes: research protocol of a prospective cohort study.

2020-02 Kaur S, Teoh AN, Shukri NHM, Shafie SR, Bustami NA, Takahashi M, Lim PJ, Shibata S

Circadian rhythm plays an important role as our internal body's clock that synchronizes behavior and physiology according to the external 24-h light-dark cycle. Past studies have associated disrupted circadian rhythm with higher risk of miscarriages, preterm birth and low birth weights. This paper described the protocol of a prospective cohort study which aims to determine the circadian rhythm in pregnant women, identify its association with maternal factors during pregnancy, gestational weight gain, birth and infant outcomes.

Influence of Dietary Sources of Melatonin on Sleep Quality: A Review.

2020-01 Pereira N, Naufel MF, Ribeiro EB, Tufik S, Hachul H

Sleep is an essential biological phenomenon, being a physiological and behavioral process necessary for quality of life. Melatonin is a circadian hormone produced at night by the pineal gland, regulated by the light/dark cycle, under the control of the suprachiasmatic nucleus. Melatonin is an indoleamine, synthesized from the essential amino acid tryptophan via serotonin. Melatonin is also found in plants, where it helps fight oxidative stress. To present a systematic review on the ability of food sources of melatonin to promote healthy sleep.

The Effects of Melatonin on the Descending Pain Inhibitory System and Neural Plasticity Markers in Breast Cancer Patients Receiving Chemotherapy: Randomized, Double-Blinded, Placebo-Controlled Trial.

2019-11 Palmer ACS, Souza A, Dos Santos VS, Cavalheiro JAC, Schuh F, Zucatto AE, Biazus JV, Torres ILDS, Fregni F, Caumo W

Adjuvant chemotherapy for breast cancer (ACBC) has been associated with fatigue, pain, depressive symptoms, and disturbed sleep. And, previous studies in non-cancer patients showed that melatonin could improve the descending pain modulatory system (DPMS).

Reduced melatonin synthesis in pregnant night workers: Metabolic implications for offspring.

2019-11 Nehme PA, Amaral F, Lowden A, Skene DJ, Cipolla-Neto J, Moreno CRC

Several novel animal studies have shown that intrauterine metabolic programming can be modified in the event of reduced melatonin synthesis during pregnancy, leading to glucose intolerance and insulin resistance in the offspring. It is therefore postulated that female night workers when pregnant may expose the offspring to unwanted health threats.

An integrated approach to diagnosing and managing sleep disorders in menopausal women.

2019-10 Caretto M, Giannini A, Simoncini T

Sleep disorders increase in prevalence during the menopausal transition and they constitute a complex phenomenon. Insomnia, the main sleep disorder, can be a primary disorder or it can be secondary to hot flushes (HF), mood disorders, psychosocial factors, medical conditions, and other sleep disturbances, such as obstructive sleep apnoea (OSA) or restless legs syndrome (RLS).

The Circadian Syndrome: is the Metabolic Syndrome and much more!

2019-08 Zimmet P, Alberti KGMM, Stern N, Bilu C, El-Osta A, Einat H, Kronfeld-Schor N

The Metabolic Syndrome is a cluster of cardio-metabolic risk factors and comorbidities conveying high risk of both cardiovascular disease and type 2 diabetes. It is responsible for huge socio-economic costs with its resulting morbidity and mortality in most countries. The underlying aetiology of this clustering has been the subject of much debate.

Healthier rhythm, healthier brain? Integrity of circadian melatonin and temperature rhythms relates to the clinical state of brain-injured patients.

2019-08 Blume C, Angerer M, Raml M, Del Giudice R, Santhi N, Pichler G, Kunz AB, Scarpatetti M, Trinka E, Schabus M

Healthy circadian rhythmicity has been suggested to relate to a better state of brain-injured patients and to support the emergence of consciousness in patient groups characterized by a relative instability thereof such as patients with disorders of consciousness (DOC).

Pregnancy Induces an Earlier Chronotype in Both Mice and Women.

2019-06 Martin-Fairey CA, Zhao P, Wan L, Roenneberg T, Fay J, Ma X, McCarthy R, Jungheim ES, England SK, Herzog ED

Daily rhythms generated by endogenous circadian mechanisms and synchronized to the light-dark cycle have been implicated in the timing of birth in a wide variety of species. Although chronodisruption (e.g., shift work or clock gene mutations) is associated with poor reproductive outcomes, little is known about circadian timing during pregnancy.

Melatonin MT1 receptor as a novel target in neuropsychopharmacology: MT1 ligands, pathophysiological and therapeutic implications, and perspectives.

2019-06 Comai S, Lopez-Canul M, De Gregorio D, Posner A, Ettaoussi M, Guarnieri FC, Gobbi G

Melatonin (MLT), a neuromodulator mainly acting through two G-protein coupled receptors MT1 and MT2, regulates many brain functions, including circadian rhythms, mood, pain and sleep. MLT and non-selective MT1/MT2 receptor agonists are clinically used in neuropsychiatric and/or sleep disorders.

Effects of red light on sleep inertia.

2019-05 Figueiro MG, Sahin L, Roohan C, Kalsher M, Plitnick B, Rea MS

Sleep inertia, broadly defined as decrements in performance and lowering of alertness following waking, lasts for durations ranging between 1 min and 3 hrs. This study investigated whether, compared to a dim light condition (the control), exposure to long-wavelength (red) light delivered to closed eyelids during sleep (red light mask) and to eyes open upon waking (red light goggles) reduced sleep inertia.

Melatonin profiles during the third trimester of pregnancy and health status in the offspring among day and night workers: A case series.

2019-04 Nehme PA, Amaral FG, Middleton B, Lowden A, Marqueze E, França-Junior I, Antunes JLF, Cipolla-Neto J, Skene DJ, Moreno CRC

Successful pregnancy requires adaptation in maternal physiology. During intrauterine life the mother's circadian timing system supports successful birth and postnatal development. Maternal melatonin is important to transmit circadian timing and day length to the fetus.

Night workers have lower levels of antioxidant defenses and higher levels of oxidative stress damage when compared to day workers.

2019-03 Teixeira KRC, Dos Santos CP, de Medeiros LA, Mendes JA, Cunha TM, De Angelis K, Penha-Silva N,  de Oliveira EP, Crispim CA

The effects of circadian misalignment and work shift on oxidative stress profile of shift workers have not been explored in the literature. The present study aimed to evaluate the role of shift work (day and night) and social jetlag - a measure of circadian misalignment - with oxidative stress markers.

The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia.

2009-09 Luthringer R, Muzet M, Zisapel N, Staner L

Objectives of this study were to investigate the effects of prolonged-release melatonin 2 mg (PRM) on sleep and subsequent daytime psychomotor performance in patients aged > or =55 years with primary insomnia, as defined by fourth revision of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association.

Melatonin, synthetic analogs, and the sleep/wake rhythm.

2009-03 Escames G, Acuña-Castroviejo D

Melatonin, a widespread hormone in the animal kingdom, is produced by several organs and tissues besides the pineal gland. Whilst extrapineal melatonin behaves as a cytoprotective molecule, the pineal produces the hormone in a rhythmic manner. The discovery of melatonin in 1958, and the characterization of its synthesis somewhat later, let to the description of its photoperiodic regulation and its relationship with the biological rhythms such as the sleep/wake rhythm.

Role of the melatonin system in the control of sleep: therapeutic implications.

2007-12 Pandi-Perumal SR, Srinivasan V, Spence DW, Cardinali DP

The circadian rhythm of pineal melatonin secretion, which is controlled by the suprachiasmatic nucleus (SCN), is reflective of mechanisms that are involved in the control of the sleep/wake cycle. Melatonin can influence sleep-promoting and sleep/wake rhythm-regulating actions through the specific activation of MT(1) (melatonin 1a) and MT(2) (melatonin 1b) receptors, the two major melatonin receptor subtypes found in mammals.

Phase-dependent treatment of delayed sleep phase syndrome with melatonin.

2005-10 Mundey K, Benloucif S, Harsanyi K, Dubocovich ML, Zee PC

Delayed sleep phase syndrome (DSPS) is a circadian-rhythm sleep disorder characterized by abnormally late sleep and wake times. Melatonin, taken in the evening, advances sleep and circadian phase in patients with DSPS. However, little is known about the most effective dose or time of administration. In the present study, we tested the effectiveness of melatonin to advance the timing of sleep and circadian phase in individuals with DSPS.

Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach.

1999-11 Garfinkel D, Zisapel N, Wainstein J, Laudon M

Benzodiazepines are the most frequently used drug for the treatment of insomnia. Prolonged use of benzodiazepine therapy is not recommended. However, many patients, particularly older patients, have difficulties discontinuing therapy. Melatonin, a hormone that is produced at night by the pineal gland, promotes normal sleep in humans and augments sleep induction by benzodiazepine therapy.

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