Table 2 Characteristics of the representative epidemiological studies on the effect of melatonin supplementation on exercise-induced oxidative stress in humans

Ochoa et al. 2011 [115]

Highly trained performing regular exercise amateur athletes (n = 20): experimental group (n = 10) supplemented with MT and control group (n = 10) receiving placebo

Oral intake of five tablets of 3 mg MT: one tablet two days before the exercise test, three tablets on the previous days and one tablet 1 h before beginning the test

High intensity constant run with several degrees of high effort on total distance 50 km with permanent climbing, altitude changing from 640 to 3393 m

Significantly increased blood levels of TNF-α, IL-6, IL-1Ra, urine 8-OHdG and isoprostane concentrations in both tested groups. Efficiently reduced lipid peroxides, TNF-α and 8-OHdG before and after exercise in the MT group vs placebo group

MT supplementation can reduce muscle damage via modulation of OS and preventing overexpression of proinflammatory cytokines

Maldonado et al. 2012 [116]

16 young male football players (experimental group n = 8, control group n = 8)

Experimental group treated with 6 mg MT, control group treated with placebo, 30 min prior to exercise

Acute sport training of high intensity (heart rate 135 beats per minute)

Exercise increased MDA in both groups, but significantly decreased in MT group after 60 min of training. Decreased triglyceride and increased serum IgA levels after training in MT group

Supplementation with MT in acute sport training decreased the OS generated by exercise, enhanced the serum TAS, and improved metabolism of lipids

Leonardo-Mendonça et al. 2017 [122]

Randomized double-blind study of 24 resistance trained students (males). MT-treated men n = 12, placebo-treated men n = 12 (control group)

Experimental group supplemented with MT (100 mg daily, 30 min before bedtime for 4 weeks)

8 sessions a week (about 10 h/week): 5 sessions-resistance training (3 sessions between 60–75% of maximal strength and 2 sessions between 80 and 90% of maximal strength), 2 sessions—weight training and 1 session—aerobic running

Increased ORAC levels by MT vs placebo after exercise. Reduced LPO, iNOS, GSSG/GSH and GPx/GRd ratios, CK, LDH, creatinine, cholesterol. Prevention against AOPP increase in MT group vs placebo group

MT enhanced potency of the endogenous antioxidant system, restored redox equilibrium state and protected against OS damage

Ortiz-Franco et al. 2017 [117]

14 male healthy athletes (age: 20–37 years) engaged in a 2-week randomized, double-blinded trial (MT-treated group and placebo-treated group)

20 mg MT/day or placebo administered before exercise during the controlled study period (MT group)

Training program combined strength and high intensity interval trainings (6 sessions/week 60–75 min/day. \(V{\text{O}}_{2}^{\max }\): 70%, 90%)

Significantly increased MT level, TAC and GPx levels, decreased DNA damage in MT-treated group vs placebo group after 2-week exercise

MT treatment strengthens antioxidant state of athletes and protects DNA from damage caused by high intensity exercise

Ziaadini et al. 2017 [118]

Two groups of sedentary women: involved in exercise training and treated with MT (n = 10) and only training (n = 10), mean age: 24.2 ± 1.03 and 23.4 ± 1.83 years, respectively

3 mg/day MT supplementation before exercise training

8-week (3 days/week) exercise training of increasing intensity and volume from 60 to 80% HRmax through 15 to 45 min

Significantly increased levels of MDA after long-lasting aerobic exercise training. Suppression of post-exercise increased MDA in the exercising and supplemented group

Supplementation with MT may decrease ROS levels, thus improve lipid profile

Beck et al. 2018 [119]

11 males moderately active, mean age: 24.18 ± 3.92 years

MT (6 mg) or placebo ingestion 30 min before exercise

Exercise on cycloergometer with initial workloads of 75 W and increments of 15 W each 3 min till exhaustion

Maximal aerobic capacity 120.88 ± 18.78 W

A time to exhaustion significantly lower in placebo group compared to that with MT administered by approximately 19%

MT supplementation enhanced aerobic tolerance but was without effect on the biochemical and hematological parameters

Brandenberger et al. 2018 [120]

Ten cyclists long-distance training, mean age 25.0 ± 4.0 years

5 mg MT administered 15 min before time trial. Controls: placebo 15 min before time trial

32.2 km cycling time trial performance at \(V{\text{O}}_{2}^{\max }\) 62.7 ± 6.8 (mL kg⁻¹ min⁻¹) on ergometer. Mean powers (190.4 ± 40.4 W and 190.0 ± 45.7 W, respectively)

No statistically significant differences between both groups in duration (completion times: MT group 64.94 ± 5.95 min, placebo group 65.26 ± 6.85)

Supplementation of MT did not exhibit of significant effect on performance in thermoneutral environment

Czuczejko et al. 2019 [123]

Professional athletes: 47 football players, 19 rowers, 15 adults non-training males (control group)

5 mg MT administered before sleep through 30 days in the preparatory period for athlete’s competition

Athletes: exercise on a cycle ergometer at 75% \(V{\text{O}}_{2}^{\max }\)

Decreased blood MT levels in footballers and rowers vs controls before MT intake. Increased serum MT level in footballers and in rowers after a 30-day MT intake. Reduced OS markers: MDA, IL-6, CRP, and low-density lipoproteins

Supplementation of MT in professional athletes during intense training may protect against the toxic action of ROS/RNS and inflammation

Souissi et al. 2018 [121]

Eight healthy moderately trained male students, mean age: 21.8 ± 0.9 years

6 mg MT supplementation or placebo at 09:00 a.m. in a randomized order 50 min before exercise

Running at 60% \(V{\text{O}}_{2}^{\max }\) for 45 min on a treadmill, starting at a speed of 8 km/h and increasing by 0.5 km/h after every minute

Exercise elevated inflammatory markers: CRP, LDH, ALAT, ASAT in both placebo or MT intake groups

MT ingestion before moderate prolonged submaximal exercise showed no anti-inflammatory action

Cheikh et al. 2020 [124]

Randomized double-blind trial of 14 healthy-trained male athletes, mean age 154 ± 0.3 years

10 mg MT or placebo ingestion (control) after vigorous late-evening exercise (10:00 p.m.)

Two-test sessions (separated at least one week) Running-Based Anaerobic Sprint Test at 8:00 p.m. and in the following morning (7:30 a.m.)

Reductions of: WBC, NE, LY, CRP, muscle and hepatic damage enzymes (CK, ASAD), LDH, MDA and homocysteine before and after strenuous exercise vs placebo group

MT intake after strenuous late-evening exercise diminished transient leukocytosis and protected against lipid peroxidation and muscle damage in teenage athletes

Farjallach et al. 2019 [125]

20 soccer players mean age 18.81 ± 1.3 years, MT group (n = 10), placebo group (n = 10)

Nocturnal oral MT (5 mg) or placebo ingestion in a double-blind manner

Intensive 6-day training-repeated sprint ability test: sprints 6 × 40 m with a 20 s of passive recovery between repetitions

Decreased resting OS markers: AOPP, leukocytosis and CK. Decreased post-exercise leukocytosis and markers of cellular damage (CK, ASAT, ALAT), increased GPx and GR activities in MT-treated group vs placebo group

Nocturnal MT intake during intensive training decreased OS, leukocytosis, cellular damage, and improved exercise performance