Research Blog

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?

Melatonin

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.

Oral Contraceptives Exert Influence on Exercise Physiology

birth control or oral contraception


Oral contraceptives have been found to hinder aerobic performance, but a new study suggests low-dose monophasic oral contraception may not have an effect on endurance performance.




Athletes put in countless hours in practice to achieve minute, but consequential improvements in performance. Therefore, reports that oral contraception may compromise athletic performance have steered many elite female athletes away from using oral contraception. The studies are not conclusive; some studies demonstrated that oral contraception causes measurable declines in performance, while others found no significant difference.  

Three studies published between 2000 and 2003 indicated an oral contraceptive mediated decline in maximal aerobic capacity. However, a study published this month using low-dose monophasic oral contraceptives as the form of birth control found no differences in aerobic capacity (Maximal fat oxidation, but not aerobic capacity, is affected by oral contraceptive use in healthy women, 2014. Laurie Isaco, et al.). Low-dose monophasic oral contraceptives are popular today (e.g. microgestin) and provide a constant dose of estrogen and progesterone over the menstrual cycle.

The researchers looked at twenty-one recreationally active women who were either taking monophasic oral contraception or who were not taking any oral contraception. They found that women on oral contraceptives showed no measurable difference in aerobic capacity. Furthermore, there was no difference in cardiorespiratory parameters between the women on oral contraceptives and women not on oral contraceptives at maximal aerobic capacity. However, the maximum lipid oxidation rate was higher in women taking oral contraceptives. The women on oral contraceptives had a higher %VO2max (percentage of maximum aerobic capacity) at which the maximum lipid oxidation rate was reached (also referred to as Lipoxmax). The figure below demonstrates the effect of low-dose monophasic oral contraceptives on lipid oxidation during exercise.

Influence of oral contraceptive use (OC+ or OC−) on (A) intensity of exercise at which maximum lipid oxidation rate occurs (Lipoxmax, expressed as %VO2max) and (B) maximal lipid oxidation rate (MLOR) in healthy women. Data is displayed as mean ± SD. **, *** is p<0.01 and p<0.001, respectively. MLOR is milligrams of lipids oxidized per minute per kg of fat-free mass (FFM).

The increased lipid oxidation is difficult to interpret in regards to athletic performance. Endurance athletes generally have higher lipid oxidation rates at sub-maximal paces to conserve carbohydrates. Carbohydrates provide more oxygen efficient energy and their depletion is responsible for “the wall” marathoners hit late in the marathon race. As the figure below demonstrates, women on the low-dose monophasic contraception showed no significant difference in VO2Max. However, there is a decreased VO2Max trend in the women on oral contraceptives relative to the women not on oral contraceptives.

Influence of low dose monophasic oral contraceptives (OC+ and OC-) on VO2Max (maximum ml of oxygen consumed in a minute, a measure of aerobic capacity). Data displayed as mean ± SD. NS is no significant difference between groups.

The authors warn against extrapolating this data to trained athletes. It would also be interesting to use a different assay to measure aerobic capacity. For example, higher lipid oxidation may decrease VO2Max, which reflects a race of 7-10 minutes, but might it have the opposite effect at longer races where carbohydrate depletion is a constraint?

The question remains, does oral contraception hinder endurance performance? The best oral contraceptive option for women appears to be low-dose monophasic oral contraception. The jury is still out on whether the low-dose monophasic oral contraception hinders endurance, but any effect would be relatively minor.

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