Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action

Posadzki, Paul; Bajpai, Ram; Kyaw, Bhone Myint; Roberts, Nicola; Brzezinski, Amnon; Christopoulos, George I.; Divakar, Ushashree; Bajpai, Shweta; Soljak, Michael; Dunleavy, Gerard; Järbrink, Krister; Nang, Ei Ei Khaing; Soh, Chee Kiong; Car, Josip

doi:10.1186/s12916-017-1000-8

Cited by 76 publications

(61 citation statements)

References 165 publications

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“…Its secretion exhibits diurnal variation: it is low during the day since the pineal melatonin production is powerfully suppressed by light exposure. During the night, melatonin concentrations increase several times with a peak in the middle of the night (9). Several studies revealed that a proportion of individuals with ASD have lower levels of melatonin (5), as well as that deviations in biorhythm of melatonin secretion were observed (6).…”

Section: Introductionmentioning

confidence: 99%

Urinary levels of 6-sulphatoxymelatonin and their associations with sleep disorders and behavioural impairments in children with autism spectrum disorder

Babinská¹,

Siklenková²,

Stebelová³

et al. 2019

BLL

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BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with sleep disturbances that may result from abnormalities in melatonin production. The correlations of melatonin levels with the severity of sleep disorder and/or severity of ASD were reported. OBJECTIVES: To evaluate urinary levels of the melatonin metabolite, 6-sulphatoxymelatonin (aMT6s), in children with ASD, and their associations with sleep abnormalities and behavioural impairments. METHODS: Study involved 77 children with ASD and 84 controls aged 2.5-15.5 years. Sleep disorders were assessed by Children's Sleep Habits Questionnaire. Morning and afternoon levels of aMT6s were determined by radioimmunoassay method. Urinary creatinine levels were assessed by an enzymatic method. RESULTS: The urinary aMT6s/creatinine values indicate that the night-time melatonin levels are signifi cantly lower in ASD than in controls, but there are no signifi cant differences in the daytime levels. In the ASD group, on average, a 6.8-fold difference between night-time and daytime values of urinary aMT6s/creatinine was found, whereas for the controls a 12.5-fold difference was observed, indicating a lower night-time increase in melatonin levels. In ASD group, the difference in night-time-daytime aMT6s/creatinine value correlated with some types of sleep problems, but not with the severity of ASD. CONCLUSION: The results indicate that in ASD there are differences in the patterns of melatonin secretion that may be associated with sleep impairment (Tab. 4, Fig. 2, Ref. 28).

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Section: Introductionmentioning

confidence: 99%

Urinary levels of 6-sulphatoxymelatonin and their associations with sleep disorders and behavioural impairments in children with autism spectrum disorder

Babinská¹,

Siklenková²,

Stebelová³

et al. 2019

BLL

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“…Adenosine acts through the A 1 AR and A 2A AR in the brain, to promote sleep. Melatonin receptors are involved in regulation of circadian rhythm and the sleep cycle, based partly on larval exposure to 3 and 18 (50 and 30 µM, respectively) [104]. Gandhi et al [105] found that melatonin 60 promotes sleep in part through Ars, using A 2A AR KO mice and ADK inhibition with ABT-702 18.…”

Section: Pain Antidepressant Sleep and Other Behavioral Interventionmentioning

confidence: 99%

Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

Reitman

2020

Cells

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Many ligands directly target adenosine receptors (ARs). Here we review the effects of noncanonical AR drugs on adenosinergic signaling. Non-AR mechanisms include raising adenosine levels by inhibiting adenosine transport (e.g., ticagrelor, ethanol, and cannabidiol), affecting intracellular metabolic pathways (e.g., methotrexate, nicotinamide riboside, salicylate, and 5-aminoimidazole-4-carboxamide riboside), or undetermined means (e.g., acupuncture). However, other compounds bind ARs in addition to their canonical ‘on-target’ activity (e.g., mefloquine). The strength of experimental support for an adenosine-related role in a drug’s effects varies widely. AR knockout mice are the ‘gold standard’ method for investigating an AR role, but few drugs have been tested on these mice. Given the interest in AR modulation for treatment of cancer, CNS, immune, metabolic, cardiovascular, and musculoskeletal conditions, it is informative to consider AR and non-AR adenosinergic effects of approved drugs and conventional treatments.

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“…Adenosine acts through the A1AR and A2AAR in the brain to promote sleep. Melatonin receptors are involved in regulation of circadian rhythm and the sleep cycle (Posadzki et al, 2018). Gandhi et al (2015) found that melatonin 60 promotes sleep in part through ARs using A2AAR KO mice and ADK inhibition with ABT-702 18.…”

Section: Pain Antidepressant Sleep and Other Behavioral Interventionmentioning

confidence: 99%

Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

Reitman

2020

Preprint

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Many ligands directly target adenosine receptors (ARs). Here we review the effects on adenosinergic signaling of other drugs that are not typically identified as binding ARs. Non-AR mechanisms include raising adenosine levels by inhibiting adenosine transport (e.g. ticagrelor, ethanol, cannabidiol), affecting intracellular metabolic pathways (e.g. methotrexate, nicotinamide riboside, salicylate, AICA riboside), or undetermined means (e.g. acupuncture). Yet other compounds bind ARs, in addition to their canonical 'on-target' activity (e.g. mefloquine). The strength of experimental support varies widely. AR knockout mice are the 'gold standard' method for investigating an AR role, but few drugs have been tested in these mice. Given the interest in AR modulation for treatment of cancer, CNS, immune, metabolic, cardiovascular, and musculoskeletal conditions, it is informative to consider AR and non-AR adenosinergic effects of approved drugs and conventional treatments.

show abstract

Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action

Cited by 76 publications

References 165 publications

Urinary levels of 6-sulphatoxymelatonin and their associations with sleep disorders and behavioural impairments in children with autism spectrum disorder

Urinary levels of 6-sulphatoxymelatonin and their associations with sleep disorders and behavioural impairments in children with autism spectrum disorder

Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

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