Is melatonin as an ergogenic hormone a myth? a systematic review and meta-analysis.

PURPOSE: Melatonin supplementation has been disclosed as an ergogenic substance. However, the effectiveness of melatonin supplementation in healthy subjects has not been systematically investigated. The present study analyzed the effects of melatonin supplementation on physical performance and recovery. In addition, it was investigated whether exercise bout or training alter melatonin secretion in athletes and exercise practitioners. METHODS: This systematic review and meta-analysis were conducted and reported according to the guidelines outlined in the PRISMA statement. Based on the search and inclusion criteria, 21 studies were included in the systematic review, and 19 were included in the meta-analysis. RESULTS: Melatonin supplementation did not affect aerobic performance relative to time trial (-0.04; 95% CI: -0.51 to 0.44) and relative to VO2 (0.00; 95% CI: -0.57 to 0.57). Also, melatonin supplementation did not affect strength performance (0.19; 95% CI: -0.28 to 0.65). Only Glutathione Peroxidase (GPx) secretion increased after melatonin supplementation (1.40; 95% CI: 0.29 to 2.51). Post-exercise melatonin secretion was not changed immediately after an exercise session (0.56; 95% CI: -0.29 to 1.41) and 60 min after exercise (0.56; 95% CI: -0.29 to 1.41). CONCLUSION: The data indicate that melatonin is not an ergogenic hormone. In contrast, melatonin supplementation improves post-exercise recovery, even without altering its secretion.

Photoperiod and Melatonin Supplementation: Variable Effects on the Quality of Chilled Dog Semen.

The addition of melatonin in seminal extenders due to its antioxidant properties and its beneficial role in sperm preservation has been previously described, especially in seasonal species. The aim of this study was to study a potential seasonal effect based on photoperiod duration when adding a physiological concentration of melatonin in the canine ejaculate. A total of 24 ejaculates were obtained from 10 healthy dogs during the increasing photoperiod (from December 21 to June 21), whereas 12 ejaculates were collected from five healthy individuals during the decreasing photoperiod (from June 22 to December 20). Each ejaculate was separated into two aliquots, and one of them remained as a control, whereas melatonin (100 pM) was added to the other one (C and M treatment groups, respectively). Diluted semen was refrigerated at 5°C. On days 0, 1, 2, 3, and 6, sperm motility analyses were performed using a CASA system and hypoosmotic swelling test (HOST), osmotic resistance test (ORT), and flow cytometry analysis. No effect of melatonin on motility was detected in either photoperiod. Negative effects of melatonin were found for acrosomal defects, apoptosis, and viability in the decreasing photoperiod. The addition of melatonin to sperm in the decreasing photoperiod could create such a high level that it would cause the described negative effects. We found a beneficial effect of melatonin in the increasing photoperiod on acrosomal defects and apoptosis during 0-6 days. Melatonin treatment also increased viability in the short term (days 1 and 2) for both photoperiods. Also, melatonin can provide certain beneficial effects on mitochondrial activity in the medium term (days 2 and 3) in the decreasing photoperiod.

The effects of melatonin administration on carotid intima-media thickness and pulse wave velocity in diabetic nephropathy: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Previous studies have reported that melatonin intake is inversely associated with reduced markers of atherosclerosis development such as carotid intima-media thickness (CIMT). OBJECTIVE: This study was designed to assess the effects of melatonin administration on CIMT and pulse wave velocity (PWV) in patients with diabetic nephropathy (DN). MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial was conducted on 32 DN patients. Subjects were assigned to receive melatonin or placebo (starch) for 24 weeks. Individuals in the melatonin group (n = 19) received 10 mg/day. CIMT and PWV levels were taken at the study baseline and after 24 weeks of intervention. RESULTS: After 24 weeks of intervention, melatonin intake did not affect mean levels of left (P = 0.51) and right (P = 0.16) CIMT and maximum levels of left (P = 0.76) and right (P = 0.15) CIMT, and PWV (P = 0.55) compared with the placebo. In addition, within-group difference demonstrated a significant reduction in mean levels of right CIMT (P = 0.01) in the melatonin group. We did not observe any significant change in C-reactive protein (CRP) concentrations after melatonin intake (P = 0.81). CONCLUSIONS: Melatonin intake did not affect mean levels of left and right CIMT and maximum levels of left and right CIMT, PWV, CRP levels compared with the placebo. In addition, within-group difference demonstrated a significant reduction in mean levels of right CIMT in the melatonin group. This trial was registered at www.irct.ir as http://www.irct.ir: IRCT20200527047584N2.

Protective Effects of Melatonin on Saccharomyces cerevisiae under Ethanol Stress.

During alcoholic fermentation, Saccharomyces cerevisiae is subjected to several stresses, among which ethanol is of capital importance. Melatonin, a bioactive molecule synthesized by yeast during alcoholic fermentation, has an antioxidant role and is proposed to contribute to counteracting fermentation-associated stresses. The aim of this study was to unravel the protective effect of melatonin on yeast cells subjected to ethanol stress. For that purpose, the effect of ethanol concentrations (6 to 12%) on a wine strain and a lab strain of S. cerevisiae was evaluated, monitoring the viability, growth capacity, mortality, and several indicators of oxidative stress over time, such as reactive oxygen species (ROS) accumulation, lipid peroxidation, and the activity of catalase and superoxide dismutase enzymes. In general, ethanol exposure reduced the cell growth of S. cerevisiae and increased mortality, ROS accumulation, lipid peroxidation and antioxidant enzyme activity. Melatonin supplementation softened the effect of ethanol, enhancing cell growth and decreasing oxidative damage by lowering ROS accumulation, lipid peroxidation, and antioxidant enzyme activities. However, the effects of melatonin were dependent on strain, melatonin concentration, and growth phase. The results of this study indicate that melatonin has a protective role against mild ethanol stress, mainly by reducing the oxidative stress triggered by this alcohol.

Dim Light Exposure or Melatonin Ingestion Lowers a Type 2 Diabetic's Blood Glucose Removal Rate: A Single Case.

The purpose of this case study is to compare a Type 2 diabetic's postprandial glucoregulatory ability under two different room lighting conditions. The subject was a 56-year-old physically active male with well controlled blood glucose levels (HbA1c ≤ 6% for 5 y) from a combination of diet, exercise, and medication. Two hours post evening meal (380 kcal, 18 g fat, 44 g carbohydrate, 12 g protein), a 45 g carbohydrate challenge was given, and blood glucose was measured every 30 minutes for 2.5 hours under three conditions: dim light (<50 lux) (DL), bright light (>40000 lux) (BL), and bright light plus 6 mg melatonin (BLM). Each condition was repeated 3 times over a period of 6 months with each trial a minimum of seven days apart. The area under the average glucose concentration vs. time plot was different between the three conditions (BL = 909 ± 76; DL = 1078 ± 106; and BLM = 1130 ± 45 mmol·min·l-1). Visual inspection of the average blood glucose vs. time plot suggested that DL and BLM displayed very similar patterns and magnitude, with both DL and BLM having the blood glucose concentrations at each time point that are noticeably greater than BL. Additionally, the average (± standard deviation) blood glucose concentrations for DL (8.8 ± 0.9 mmol·l-1) and BLM (9.1 ± 1.1 mmol·l-1) were respectively 18% and 22% greater than BL (7.5 ± 0.5 mmol·l-1). Melatonin and/or dim light can reduce a Type 2 diabetic's glucoregulatory ability.

Melatonin supplementation improves oxidative and inflammatory state in the blood of professional athletes during the preparatory period for competitions.

Melatonin supplementation has been proved to have antioxidant and anti-inflammatory effects in humans. The aim of the study was to estimate the influence of a 30-day melatonin supplementation on oxidative and inflammatory state in the blood of intense training professional athletes. The study was conducted in 47 football players, 19 rowers, and 15 adults who did not practice sports (control group). Blood samples were taken once from the control group and twice from the athletes: before and after 30-day melatonin administration (5 mg daily before sleep). Serum levels of melatonin, isoprostanes, antiox-LDL antibodies, interleukin-6, and C-reactive protein were measured. In erythrocytes, the concentrations of reduced glutathione (GSH) and malondialdehyde (MDA), and the activities of glutathione peroxidase (GSH-Px), cytoplasmic superoxide dismutase (SOD-1), and glutathione reductase (GR) were determined. Melatonin supplementation caused a significant decrease in markers of oxidative stress and a significant increase in melatonin concentration and the activities of SOD-1 and GSH-Px in athletes. The obtained data showed increased oxidative stress and inflammatory processes in professional athletes during intense training and indicated that supplementation of melatonin in their daily diet may have a beneficial effect on the protection of tissues against the adverse action of RONS and inflammatory processes.

The effects of melatonin supplementation on mental health, metabolic and genetic profiles in patients under methadone maintenance treatment.

This investigation was designed to determine the effect of melatonin supplementation on mental health parameters, metabolic and genetic profiles in patients under methadone maintenance treatment (MMT). This randomized, double-blind, placebo-controlled, clinical trial was conducted among 54 patients under MMT. Participants were randomly allocated to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 26) or placebo (n = 28) once a day, 1 hour before bedtime for 12 weeks. Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (ß -4.08; 95 percent CI, -5.51, -2.65; P < 0.001), Beck Depression Inventory index (ß -5.46; 95% CI, -8.92, -2.00; P = 0.003) and Beck Anxiety Inventory index (ß -3.87; 95% CI, -5.96, -1.77; P = 0.001) and significantly increased International Index of Erectile Functions (ß 5.59; 95% CI, 1.76, 9.42; P = 0.005) compared with the placebo. Subjects who received melatonin supplements had significantly lower serum insulin levels (ß -2.53; 95% CI, -4.48, -0.59; P = 0.01), homeostasis model of assessment-insulin resistance (ß -0.56; 95% CI, -1.03, -0.09; P = 0.01) and higher quantitative insulin sensitivity check index (ß 0.01; 95% CI, 0.004, 0.02; P = 0.009) and HDL-cholesterol levels (ß 3.71; 95% CI, 1.77, 5.64; P = 0.002) compared to placebo. Additionally, melatonin intake resulted in a significant reduction in serum high sensitivity C-reactive protein (ß -0.15; 95% CI, -0.27, -0.02; P = 0.02), malondialdehyde (ß -0.31; 95% CI, -0.57, -0.05; P = 0.02) and protein carbonyl (ß -0.06; 95% CI, -0.09, -0.04; P < 0.001). This trial indicated that taking melatonin supplements for 12 weeks by patients under MMT had beneficial effects on their mental health metabolic profiles.

Melatonin administration lowers biomarkers of oxidative stress and cardio-metabolic risk in type 2 diabetic patients with coronary heart disease: A randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Melatonin may benefit diabetic people with coronary heart disease (CHD) through its beneficial effects on biomarkers of oxidative stress and cardio-metabolic risk. This investigation evaluated the effects of melatonin administration on metabolic status in diabetic patients with CHD. METHODS: This randomized, double-blind, placebo-controlled trial was conducted and involved 60 diabetic patients with CHD. Subjects were randomly allocated into two groups to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day for 12 weeks. RESULTS: Compared with the placebo, melatonin supplementation resulted in significant increases in plasma glutathione (GSH) (+64.7 ± 105.7 vs. -11.1 ± 137.6 µmol/L, P = 0.02) and nitric oxide (NO) (+0.9 ± 4.7 vs. -3.3 ± 9.6 µmol/L, P = 0.03), and significant decreases in malondialdehyde (MDA) (-0.2 ± 0.3 vs. +0.1 ± 0.5 µmol/L, P = 0.007), protein carbonyl (PCO) (-0.12 ± 0.08 vs. +0.03 ± 0.07 mmol/mg protein, P < 0.001) and serum high sensitivity C-reactive protein (hs-CRP) levels (-1463.3 ± 2153.8 vs. +122.9 ± 1230.4 ng/mL, P = 0.001). In addition, taking melatonin, compared with the placebo, significantly reduced fasting plasma glucose (-29.4 ± 49.0 vs. -5.5 ± 32.4 mg/dL, P = 0.03), serum insulin concentrations (-2.2 ± 4.1 vs. +0.7 ± 4.2 µIU/mL, P = 0.008), homeostasis model of assessment-estimated insulin resistance (-1.0 ± 2.2 vs. +0.01 ± 1.6, P = 0.04), total-/HDL-cholesterol ratio (-0.18 ± 0.38 vs. +0.03 ± 0.35, P = 0.02) and systolic (-4.3 ± 9.6 vs. +1.0 ± 7.5 mmHg, P = 0.01) and diastolic blood pressure (-2.8 ± 7.3 vs. +0.1 ± 3.6 mmHg, P = 0.04). Melatonin treatment also significantly increased quantitative insulin sensitivity check index (+0.006 ± 0.01 vs. -0.004 ± 0.01, P = 0.01) and serum HDL-cholesterol (+2.6 ± 5.5 vs. -0.01 ± 4.4 mg/dL, P = 0.04). Supplementation with melatonin had no significant effect on other metabolic parameters. CONCLUSIONS: Overall, melatonin intake for 12 weeks to diabetic patients with CHD had beneficial effects on plasma GSH, NO, MDA, PCO, serum hs-CRP levels, glycemic control, HDL-cholesterol, total-/HDL-cholesterol ratio, blood pressures and parameters of mental health. Registered under ClinicalTrials.gov Identifier no. http://www.irct.ir: IRCT2017051333941N1.

Melatonin has a protective effect against lipid peroxidation in the bone tissue of diabetic rats subjected to acute swimming exercise.

Aim The present study aimed to examine the effects of melatonin supplementation on lipid peroxidation in the bone tissue of diabetic rats subjected to acute swimming exercise. Methods The study was conducted on 80 Sprague-Dawley type adult male rats which were equally allocated to eight groups: group 1, general control; group 2, melatonin-supplemented control; group 3, melatonin-supplemented diabetic control; group 4, swimming control; group 5, melatonin-supplemented swimming; group 6, melatonin-supplemented diabetic swimming; group 7, diabetic swimming; group 8, diabetic control. In order to induce diabetes, the animals were subcutaneously injected with 40 mg/kg streptozotocin (STZ). The animals were supplemented with 3 mg/kg/day melatonin intraperitoneally (IP) for 4 weeks. At the end of the study, the animals were decapitated to collect bone tissue samples which were examined to find out the malondialdehyde (MDA) (nmol/g/protein) and glutathione (GSH) (mg/dL/g protein) levels. Results The highest MDA values in the bone tissue were found in groups 7 and 8. MDA levels in the bone tissue in groups 3 and 6 were lower than the levels in groups 7 and 8, but higher than those in all other groups. Groups 3, 5 and 6 had the highest bone tissue GSH values. On the other hand, the lowest GSH level was established in groups 7 and 8. Conclusion The results of the present study indicated that the cell damage caused by acute swimming exercise and diabetes in the bone tissue could be prevented by melatonin supplementation.