Healthy KidsStress and Relaxation

From Childhood to the Elderly: Evidence for Melatonin

An array of clinical research shows the safety and efficacy of melatonin in healthy and compromised populations

Many a time in life when the stress hormones are flying, we also have the unfortunate experience of struggling to sleep. The experience of insomnia is not uncommon, with about one-third to two-thirds of adults experiencing insomnia symptoms of any severity, with 10 to 15% of individuals dealing with chronic insomnia.[1],[2] Sleep difficulties are more common in women and individuals who are single (widowed, divorced, or separated), and often coexist with psychiatric disorders such as depression, or more commonly, anxiety.[3] Insomnia can also be caused by medication side effects, including those used to treat anxiety and depression.[4] Many individuals who experience insomnia never receive a formal diagnosis, and self-medication with substances such as alcohol or over-the-counter medications is not uncommon.[5],[6] However, alcohol can be a contributing factor to poor sleep quality, and negatively affects the body’s circadian rhythm when consumed chronically, obliterating the perceived benefits one may attribute to its use.[7]

Melatonin – the body’s natural sleep regulator

Melatonin, primarily produced in the body by the pineal gland, is the body’s natural sleep promoting hormone. Melatonin levels have a circadian rhythm, rising at night and returning to low levels during the day, nearly opposite in profile to the cortisol pattern.[8] Light is one factor which mediates melatonin secretion, and bright light in particular can be used to shift its circadian pattern.[9] Decreased melatonin production and altered rhythms have been seen with increasing age, in individuals who experience conditions including depression, visual impairment, and neurodevelopmental disorders.[10],[11],[12],[13] The receptors activated by melatonin play not only a beneficial role in sleep, but also in mood disorders, learning and memory, drug abuse, and cancer.[14]

The receptors activated by melatonin play not only a beneficial role in sleep, but also in mood disorders, learning and memory, drug abuse, and cancer.

Melatonin also has importance in the body as an antioxidant that protects the brain and nervous system. It not only has antioxidant action on its own, but also stimulates the body’s production of other antioxidants that are important for detoxification, and recycling of our most common intracellular antioxidant glutathione.[15],[16],[17]

Clinical studies and meta-analyses support the use of melatonin

Melatonin has been studied clinically as a sleep-supportive agent in populations ranging from 2 to 84 years of age.[18],[19] In these studies, no serious side effects caused by melatonin supplementation were observed. Some mild side effects included morning drowsiness, headache, or nighttime awakening. Occasionally, a loss of therapeutic effect was seen with time and continued nightly melatonin use. In some studies, melatonin was even combined with multiple other psychotropic medications in the very young and elderly without any adverse events.[20],[21],[22] In clinical studies, the duration of treatment ranged from days to as long as four years.[23] Dosages in studies for the purpose of supporting sleep range from 0.75 to 15 mg,[19],[24] and often if higher the dosages were used, the dose was titrated gradually over time.[25]

Melatonin has been studied clinically as a sleep-supportive agent in populations ranging from 2 to 84 years of age. In these studies, no serious side effects caused by melatonin supplementation were observed.

In children with neurodevelopment disorders, melatonin was found to significantly improve total sleep time as well as shorten the time it took to fall asleep, although no difference was seen in nighttime awakenings.[26] Although many people argue that melatonin supplementation may reduce the body’s endogenous production of this important hormone, in adults and children with trouble falling asleep, melatonin supplementation was found not only to advance the sleep-wake rhythm but also to stimulate the brain’s own production of melatonin.[27] In patients with sleep disorders associated with dementia, a meta-analysis of seven clinical studies found that melatonin significantly prolonged total sleep time and marginally improved sleep efficacy, although no significant changes were seen in cognitive function.[28] In neurodegenerative disease including Parkinson’s disease and Alzheimer’s, melatonin was found to positively impact certain markers of sleep as evaluated by the Pittsburgh Sleep Quality Index (PSQI), as well as clinical and neurophysiological aspects of rapid eye movement sleep behavior disorder.[29]

The largest meta-analysis considered 19 studies involving 1,683 individuals with primary sleep disorders found that melatonin improved several measurements of healthy sleep and that the effects did not dissipate with continued use.[30] The authors conclude with the statement, “Although the absolute benefit of melatonin compared to placebo is smaller than other pharmacological treatments for insomnia, melatonin may have a role in the treatment of insomnia given its relatively benign side-effect profile compared to these agents,” which fairly well summarizes the majority of research surrounding melatonin.

Extended-release formats of melatonin may more closely mimic the brain’s natural release of melatonin, thus enabling lower dosing and reduced residual daytime sleepiness.

Outside of these selected meta-analyses which broadly assess the impact of melatonin on common conditions associated with altered sleep, melatonin has also been studied in the setting of traumatic brain injury (TBI). Many individuals who experience a TBI subsequently have fragmented or disrupted sleep, which can further negatively impact neuropsychiatric, physical and cognitive outcomes.[31] Altered sleep is in part due to a dramatic decline in the nocturnal melatonin production, but also may be due to oxidative stress and a disrupted blood-brain barrier.[32] In a study of patients with TBI-associated sleep disturbances, prolonged-release melatonin was found to significantly improve sleep efficiency, vitality, and mental health.[33] Again, no serious adverse events were reported, and additionally, patients did not experience increased daytime sleepiness. It has been suggested that melatonin also be considered for other events of trauma leading to intensive care hospitalization, as these conditions also are associated with declines in melatonin secretion.[34]

Consideration for an extended-release format

Although hereunto not discussed specifically, at times, an extended-release format of melatonin was used within some of these studies which were referenced explicitly or existed within the meta-analysis reviews.[33],[35] Prolonged-release formats may more closely mimic the brain’s natural release of melatonin, thus enabling lower dosing and reduced residual daytime sleepiness.[36] For the melatonin-naïve, children, elderly, and individuals who are sensitive to medications and supplemental therapies, this may be beneficial.

In many of these clinical settings, melatonin is not only indicated to support the body’s melatonin levels, but also for the antioxidant action it delivers. Adequacy of melatonin is one critically important thing to consider when supporting a normal, healthy sleep cycle, and volumes of clinical research support its use in a range of healthy and challenged individuals.

 

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Addressing Allergies: A Multi-Pronged Approach
Sleep and Relaxation Support – Stat!

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