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. 2017 Sep;6(Suppl 4):S734–S760. doi: 10.21037/tau.2017.08.20

Table 3. Review of studies examining the effect of antioxidant therapy on sperm DNA fragmentation.

Study (reference) Supplements (daily intake) Study design n Duration SDF testing method Result
Tunc et al. (202) Vitamin C (100 mg), E (400 IU), selenium (26 ìg), Zn (25 mg), folic acid (0.5 mg), lycopene (6 mg) and garlic oil (333 ìg) Prospective observational study 50 3 months TUNEL, CMA3 assay Significant decrease in SDF [pre-treatment: 22.2% (16.5–26.6%); post-treatment: 18.2% (13.4–23.1%), P=0.002] and protamine packaging [pre-treatment: 69.0% (63.5–73.1%); post-treatment: 73.6% (69.3–77.5%), P<0.001]. No significant improvement in semen parameters
Ménézo et al. (203) b-carotene (18 mg), vitamins C (400 mg), E (400 mg), Zn (500 µmol) and Se (1 µmol) Prospective observational study 58 3 months SCSA Significant decrease in SDF (−19.1%, P<0.0004)
Kodama et al. (204) Vitamins C (200 mg), E (200 mg), glutathione (400 mg) Prospective observational study for the treatment group 14 2 months 8-hydroxy-2'-deoxyguanosine Significant improvement in sperm concentration (7±1 million/mL, P<0.05). Significant decrease in oxidative DNA damage (−0.4%±0.1%, P<0.05)
Omu et al. (205) Group1: Zn (400 mg); group 2: Zn (400mg) + vitamin E (20 mg); group 3: Zn (400 mg) + vitamins E (20 mg) + C (10 mg) Randomized placebo-controlled study 45 treatment (group 1: n=11; group 2: n=12; group 3: n=14; 8 placebo group) 3 months SCSA Improvement in SDF measures with treatment*. Significant improvement in sperm motility with the treatment group (group 1: 25%±12%; group 2: 24%±6%; group 3: 25%±9%, P<0.01)
Greco et al. (206) Vitamin C (1,000 mg) + vitamin E (1,000 mg) Prospective observational study 29 (patients with high SDF and prior failed ICSI) 2 months TUNEL Significant decrease SDF levels (−15.8%±3.6%, P<0.001). Insignificant effect on semen parameters. Significant improvement in ICSI clinical pregnancy (48.2% versus 6.9%) and implantation (19.6% versus 2.2%; P<0.01) rates compared with the pre-treatment ICSI outcomes
Greco et al. (207) Vitamin C (1,000 mg) + vitamin E (1,000 mg) Randomized placebo-controlled study 64 men with unexplained infertility and high SDF levels 2 months TUNEL Significant decrease in SDF levels (−13%±0.5%, P<0.001). Insignificant effect on semen parameters
Martínez-Soto et al. (208) Docosahexaenoic acid (DHA) (1,500 mg) Randomized, double blind, placebo-controlled, parallel-group study 57 (32 treatment group and 25 placebo group) 10 weeks TUNEL Significant decrease in SDF levels (−17.2%±2.8%, P<0.001) in treatment group vs. (11.2%±1.9%, P>0.05) in the placebo group. Insignificant effect on semen parameters
Fraga et al. (209) Vitamin C (250 mg) Prospective observational study 10 15 weeks 8-hydroxy-2'-deoxyguanosine Vitamin C depletion/repletion was associated with inverse relationship with seminal vitamin C levels and oxo8dG measures (P<0.01)
Abad et al. (210) L-carnitine (1,500 mg); vitamin C (60 mg); coenzyme Q10 (20 mg); vitamin E (10 mg); zinc (10 mg); vitamin (200 ìg) B9 selenium (50 ìg); vitamin B12 (1 ìg) Prospective observational study 20 infertile patients diagnosed with asthenoteratozoospermia 3 months SCD measurement done following various periods of sperm storage (0, 2, 6, 8 and 24 h) at 37 °C Significant decrease in SDF levels (at 0 h: −8.4%±6.7%, P=0.004; at 2 h: −8.07%±5.03%, P=0.003; at 6 h: −8.58%±0.81%, P=0.004; at 8 h: −9.03%±2.79%, P=0.006; at 24 h: −20.95%±8.59%, P=0.0002). Significant improvement in DDS (−1.6%±0.9%, P=0.04). Significant improvement in sperm concentration (0.1±6.47 million/mL, P=0.04), motility (6.5%±2.8%, P=0.02) and morphology (1.5%±2.4%, P=0.04)
Vani et al. (211) Vitamin C (1,000 mg) 5 consecutive days in a week Prospective comparative study 240 (120 men exposed to lead, and 120 healthy human subjects) 3 months Comet Significant decrease in alkaline-labile sites and mean tail length of the comet when compared to the control group (P<0.001). Significant improvement in all semen parameters (P<0.001)
Gual-Frau et al. (212) L-carnitine (1,500 mg); vitamin C (60 mg); coenzyme Q10 (20 mg); vitamin E (10 mg); zinc (10 mg); vitamin B9 (200 ìg), selenium (50 ìg), vitamin B12 (1 ìg) Prospective observational study 20 infertile men with grade 1 varicocele 3 months SCD Significant decrease in SDF levels (−22.1%, P=0.02). 31.3% fewer highly degraded sperm cells (P=0.07). Significant increase in sperm concentration (P=0.04)
Piomboni et al. (213) Beta-glucan (20 mg), fermented papaya (50 mg), lactoferrin (97 mg), vitamin C (30 mg), and vitamin E (5 mg) Prospective observational study 36 men with leukocytospermia; 15 controls 3 months Acridine orange (AO) staining No significant decrease in SDF. Significant increase in sperm morphology (12.8%±1.3%, P<0.01) and total progressive motility (15.8%±1.1%, P<0.01). Significant reduction in leukocyte number (−1.3±0.7 million/mL, P<0.05)

, interquartile range; *, no values were provided. SDF, sperm DNA fragmentation; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; CMA3, chromomycin A3; SCSA, sperm chromatin structure assay; DDS, DNA degraded sperm.