What is Melatonin?
Melatonin is a hormone secreted by the pineal gland in the brain that is used by the body to help regulate its internal body clock and induce sleep. Melatonin is readily available over-the-counter to support normal circadian rhythms/sleep-wake cycles, typically through oral pill or liquid solutions - acting both quickly and over a period several hours after ingestion. Melatonin is commonly used in medical practice for treatment of insomnia.







The body also produces melatonin through metabolism of the neurotransmitter serotonin. Melatonin secretion is regulated by hormone/neurotransmitter norepinephrine. Exposure to light environments (such as daylight) reduces melatonin synthesis by stopping stimulation of norepinephrine, whereas exposure to dark environments does the opposite.



Thus, it is easier for people to fall asleep when it’s dark outside as opposed to bright, sunny times of the day. This is why normal circadian rhythms are imperative for proper melatonin production and a healthy sleep cycle. Night shift workers may struggle to sleep for more than several hours per day as their body is essentially on an inverse schedule in terms of normal circadian rhythms.



Melatonin Supplementation
There are a host of benefits that arise from supplementing with melatonin thanks to its ability to correct irregular sleep patterns; when circadian rhythms and sleep patterns are askew, a wide variety of health problems and premature aging are more likely to occur.[1]



Therefore, individuals with sleep disorders (such as insomnia) and those that work night shifts and/or get jet lag from traveling may benefit from melatonin supplementation. Extended-release melatonin may also prove worthwhile for individuals who have trouble getting to, and staying, asleep at night.





Melatonin as an Antioxidant
Melatonin appears to be a potent antioxidant with immune-enhancing properties.[2] Antioxidants are molecules that reduce oxidative stress induced by reactive oxygen species in the body; excessive oxidative stress has been linked to a multitude of deleterious health conditions.[3]



N-acetyl-L-cysteine (NAC) is a common ingredient used for glutathione synthesis in humans; glutathione is a peptide that exhibits antioxidant functions throughout the body. Reduced glutathione and its related enzymes glutathione peroxidase and reductase are the main mitochondrial antioxidant system.







Since glutathione is a crucial endogenous antioxidant, reduced levels of it are associated with increased oxidative stress and ramifications in practically all body systems.[4],[5] A recent study, however, suggests that melatonin is an even more efficacious substance than NAC for supporting glutathione status in brain and liver mitochondria.



A recent study shows for the first time that melatonin, but not other endogenous antioxidants such as vitamins C and E, regulates glutathione redox status in brain and liver mitochondria, correcting it when it was disrupted by oxidative stress.[6] In baseline conditions, melatonin increased mitochondrial reduced glutathione (GSH) pool, decreasing oxidized glutathione (GSSG) content. Moreover, melatonin reduced the mitochondrial hydroperoxide level and stimulated the activity of the two enzymes involved in the GSH-GSSG balance: Glutathione reductase and peroxidase.



These data and the results of the suggest an important role for melatonin in maintaining mitochondrial GSH homeostasis, simultaneously removing reactive oxygen species (ROS) produced during oxidative stress. Of the other antioxidants evaluated (vitamins C, E, and the pharmaceutical agent Trolox), only Trolox showed some effect, but at a dose 104 times higher than that of melatonin.



The use of NAC in this study served as a negative control. As aforementioned, NAC displays antioxidant properties because it is used for glutathione synthesis by the cell. Since glutathione synthesis takes place in the cytosol where mitochondria obtain it by transport, NAC had no effect in this study (which was on isolated mitochondria).



Therefore, melatonin is a much more efficient antioxidant than Trolox, conceivably because melatonin stimulates the activity of the glutathione-related enzymes. Another key finding of this study is that melatonin not only maintains a good redox status in baseline conditions, but is able to counteract the oxidative damage induced by t-butyl hydroperoxide (t-BHP) on mitochondria, recovering GSH levels and scavenging ROS.



Melatonin also recovers the activity glutathione-related enzymes that are typically inhibited by t-BHP. Thus, supplementation with melatonin, but not other antioxidants, recovers mitochondria from otherwise irreversible oxidative damage due to t-BHP.



Extended Benefits of Melatonin Supplementation
Some melatonin supplements also contain vitamin B6 (pyridoxal phosphate), which facilitates conversion of the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).



A major plus of supplemental melatonin is that it’s non-habit forming and is primarily recommended for supplementing with to decrease the time it takes for you to fall asleep and to promote healthy sleep-wake cycles.



Curiously, some research suggests that melatonin can be taken during the day to help manage stress, among a variety of other beneficial properties. Overall, clinical research suggests the benefits of melatonin supplementation may include:



Supports proper sleep cycles and circadian rhythms[7]
Support glutathione production and immune function
Support healthy growth hormone production[8]
May help treat insomnia and jet lag[9],[10]
Support relaxation and calmness
How to Use Melatonin
To support healthy sleep patterns, taking about 5mg of melatonin, one hour before bedtime, is best. As little as 2mg of melatonin can be taken for antioxidant purposes (glutathione production) that has been touched on. Overall, almost any gym goer stands to benefit from melatonin, even if it's just to get better sleep on occasions where you feel restless.

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