Basic Facts

Medical Studies on Melatonin – Basic Facts

Basic Facts

Melatonin (N-acetyl-5-methoxytryptamine) is mainly produced in the pineal gland, located in the brain – especially during the night in complete darkness. This is when the melatonin level rises to eight times of the level during the day. This signals to the organism that it is time for the organs and bodily functions to rest, but also to initiate vital repair mechanisms. This makes melatonin the most important internal timer.

Disruptions to cycles caused by light

On the other hand, even the slightest flash of light can affect this critical process, especially the blue light from TVs and smartphones, the light from an alarm clock or street lighting. These everyday appliances have proven to be highly disruptive to our internal cycles and have a substantially adverse impact on our melatonin balance.

Melatonin keeps our internal clock ticking

Each flash of light passes through the retina to reach the suprachiasmatic nucleus (SCN), which is connected to the pineal gland and serves as a control centre and “master clock” for the brain. Melatonin provides the timing for this internal clock, not only letting the brain know that it should switch to “night mode”, but also passing this information on to every other organ and cell in the body. If this natural mechanism is disrupted by light during the night, this has serious consequences not only for the day/night cycle, but also for the function of the organs and the development and course of many diseases.

Every cell contains melatonin

Only recently did it become known that the “powerhouses” of each cell, the mitochondria, are also capable of producing melatonin. This melatonin is not passed into the blood, but rather is used to regulate certain functions in each of the cells. This production is also partly controlled by the melatonin in the pineal gland, meaning that disorders of the pineal gland can also result in changes in how these cells function, which may result in organ damage, for example.

Medical Studies on Melatonin – Basic Facts

Biological correlates of altered circadian rhythms, autonomic functions and sleep problems in autism spectrum disorder

2022-05 Dell'Osso L, Massoni L, Battaglini S, Cremone IM, Carmassi C, Carpita B

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by a complex and multifaceted neurobehavioral syndrome. In the last decades, several studies highlighted an increased prevalence of sleep problems in ASD, which would be associated with autonomic system and circadian rhythm disruption.

Melatonin ameliorates tau-related pathology via the miR-504-3p and CDK5 axis in Alzheimer’s disease

2022-05 Chen D, Lan G, Li R, Mei Y, Shui X, Gu X, Wang L, Zhang T, Gan CL, Xia Y, Hu L, Tian Y, Zhang M, Lee TH

Intracellular accumulation of the microtubule-associated protein tau and its hyperphosphorylated forms is a key neuropathological feature of Alzheimer's disease (AD). Melatonin has been shown to prevent tau hyperphosphorylation in cellular and animal models. However, the molecular mechanisms by which melatonin attenuates tau hyperphosphorylation and tau-related pathologies are not fully understood.

Melatonin, macrophages and microbiota: Interactions

2022-03 Reiter RJ

This commentary summarizes and highlights the recent research reports of the group headed by Professor Wenkai Ren. Their research has been focused in two important investigative areas, namely, the role of melatonin in the regulation of macrophage polarization and the functional implications of melatonin for the gastrointestinal microbiota. Both these subjects are of high interest to melatonin biologists since both have significant implications in clinical and veterinary medicine.

SARS-CoV-2 and other coronaviruses negatively influence mitochondrial quality control: beneficial effects of melatonin

2021-03 Mehrzadi S, Karimi MY, Fatemi A, Reiter RJ, Hosseinzadeh A

Coronaviruses (CoVs) are a group of single stranded RNA viruses, of which some of them such as SARS-CoV, MERS-CoV, and SARS-CoV-2 are associated with deadly worldwide human diseases. Coronavirus disease-2019 (COVID-19), a condition caused by SARS-CoV-2, results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with high mortality in the elderly and in people with underlying comorbidities.

Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder

2021-02 Lalanne S, Fougerou-Leurent C, Anderson GM, Schroder CM, Nir T, Chokron S, Delorme R, Claustrat B, Bellissant E, Kermarrec S, Franco P, Denis L, Tordjman S

The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin’s effects in ASD and the choice of formulation type require further study.

Melatonin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-related Diseases

2021-02 Xie WQ, Chen SF, Tao XH, Zhang LY, Hu PW, Pan WL, Fan YB, Li YS

Cartilage is a relatively simple connective tissue that plays a variety of roles in the human body, including joint support and protection, load bearing of the intervertebral discs, joint lubrication, formation of the external structure of the ears and nose and support of the trachea. The maintenance of cartilage homeostasis is therefore crucial. Cartilage-related diseases are difficult to diagnose and treat because their molecular and pathological mechanisms are not fully understood.

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.

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.

Melatonin: action as antioxidant and potential applications in human disease and aging.

2010-11 Bonnefont-Rousselot D, Collin F.

This review aims at describing the beneficial properties of melatonin related to its antioxidant effects. Oxidative stress, i.e., an imbalance between the production of reactive oxygen species and antioxidant defences, is involved in several pathological conditions such as cardiovascular or neurological disease, and in aging. Therefore, research for antioxidants has developed. However, classical antioxidants often failed to exhibit beneficial effects, especially in metabolic diseases.

Melatonin signaling and cell protection function.

2010-10 Luchetti F, Canonico B, Betti M, Arcangeletti M, Pilolli F, Piroddi M, Canesi L, Papa S, Galli F

Besides its well-known regulatory role on circadian rhythm, the pineal gland hormone melatonin has other biological functions and a distinct metabolism in various cell types and peripheral tissues. In different tissues and organs, melatonin has been described to act as a paracrine and also as an intracrine and autocrine agent with overall homeostatic functions and pleiotropic effects that include cell protection and prosurvival factor.

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.

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