Melatonin Does More Than Put You to Sleep

melatonin puts woman to sleep

Melatonin, often sold as an over-the-counter sleep aid, can fight inflammation and oxidative damage in muscle tissue following a strenuous bout of exercise.

We have all experienced the satisfaction of a night of deep sleep after a day of strenuous activity. Thus, it comes as no surprise that exercisers report sleeping better than non-exercisers. American marathon great Meb Keflezighi stresses the importance of sleep with daytime naps on top of 8.5 hours of nighttime sleep. Why do our bodies crave sleep after strenuous activity?


One potential explanation may come from melatonin. Melatonin is our bodies' natural regulator of the circadian rhythm; higher doses at nighttime induce sleepiness and low doses during the day keep us awake. As we age, melatonin production from the pineal gland wanes. Thus, melatonin is often used by the elderly to cure insomnia. In addition to its role in regulating the circadian rhythm, melatonin is a powerful antioxidant.

A study published this month in the Journal of Pineal Research found that melatonin treatment could reduce muscle inflammation and oxidative stress in rats following strenuous exercise (Melatonin decreases muscular oxidative stress and inflammation induced by strenuous exercise and stimulates growth factor synthesis, 2014. Leandro da Silva Borges, et al.).  The Brazilian study exercised the rats to exhaustion for 50 minutes and muscles were looked at immediately following, and two hours after, the conclusion of the exercise protocol.  Half the rats were treated with melatonin intraperitoneally for ten days, while the other half were not administered melatonin.

TNF-α, IL-1β and IL-6 skeletal muscle concentrations expressed as ratios of integrated cytokine release with or without melatonin treatment. The values represent the mean ± SE. *P < 0.05 between the melatonin-treated and control groups and ***P < 0.001 between the melatonin-treated and control groups.

A variety of markers for inflammation and oxidative stress were measured. Plasma levels of IL-1ß (an inflammatory signal) were found to increase immediately following exercise: only 2-fold in the melatonin-treated rats and 3.1-fold in the rats not treated with melatonin.  The exercised rats saw an immediate and maintained increase in plasma L-selectin (a chemical marker for inflammatory cells), but melatonin treatment negated the immediate increase and produced a decrease in L-selectin at 2 hours. In the muscle tissue, melatonin mediated a decrease in TNF-alpha, IL-1ß and IL-6. Thus, the anti-inflammatory effects of melatonin were both systematic and localized. The decrease in inflammatory cytokines in muscle is illustrated in the figure above.

Ratios of integrated VEGF release in skeletal muscle with or without melatonin treatment. The values represent the mean ± SE. *P < 0.05 between the melatonin-treated and control groups.

Melatonin increased VEGF, a potent regulator of angiogenesis. VEGF is also known to play a role in regulating oxidation as it is regulated by oxidative stress through reactive oxygen species. The figure to the right demonstrates the ability of melatonin to increase VEGF concentrations in the skeletal muscle following strenuous exercise.

Superoxide dimutase (SOD) activity in skeletal muscle was also found to increase in the melatonin-treated rats following exercise relative to the exercised rats that did not receive melatonin treatment.  SOD is an antioxidant enzyme that removes the harmful superoxide anion. The figure below illustrates the ability of melatonin to increase the levels of SOD in skeletal muscle.

Ratios of superoxide dimutase (SOD) enzyme activity in skeletal muscle with or without melatonin treatment. The values represent the mean ± SE. ***P < 0.001 between the melatonin-treated and control groups.

Oxidative damage is a major cause of pathogenesis in patients with diabetes mellitus, and can lead to tissue necrosis. Interestingly, melatonin treatment has been shown to reduce oxidative damage in exercising rats with diabetes (Protective effect of melatonin on lipid peroxidation in various tissues of diabetic rats subjected to an acute swimming exercise, 2012. Bicer M, et al.). This Turkish study may highlight the therapeutic effects of melatonin following exercise in patients who are sensitive to oxidative stress (i.e. G6PD deficiency).

The mechanism of how melatonin induces anti-inflammatory effects in skeletal muscle following strenuous exercise is still unknown. However, inflammation and oxidation are directly linked, with oxidative damage in the cell being a signal for an inflammatory response to clear out the damaged tissue. Melatonin is a natural substance made from the amino acid tryptophan and is non-toxic even in high doses. For the athlete, melatonin apparently can do more than put him or her to sleep.

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