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Table 2 Study outcomes involving oral supplementation of various antioxidants in men

From: Utility of antioxidants during assisted reproductive techniques: an evidence based review

Antioxidant Study type Patient population Intervention (daily dose x duration) Control group (daily dose) Study outcome (effect on sperm parameters) Reference
Vitamin E Double blind, placebo cross-over, RCT Healthy men with high seminal ROS levels (n = 30) 600 mg vitamin E x 3 months (n = 15) Placebo (n = 15) Improved in vitro sperm function (improved zona-binding assay) Kessopoulou et al. [101]
Vitamin E Double blind, placebo-controlled Men with (n = 110) asthenozoospermia or oligoasthenozoospermia 300 mg vitamin E x 6 months (n = 52) Placebo (n = 55) 1. Reduced MDA concentration (less LPO in spermatozoa) Suleiman et al. [102]
2. Improved sperm motility
3. 20% of those on therapy achieved pregnancy
Vitamin E + Anti-Estrogen (Clomiphene citrate) Prospective, placebo-controlled RCT Infertile men with idiopathic oligozoospermia (n = 60) 400 mg vitamin E +25 mg clomiphene citrate x 6 months (n = 30) Placebo (n = 30) 1. Improved sperm count and progressive motility Ghanem et al. [103]
2. Partners had higher incidence of pregnancy
Vitamin E + selenium Open, randomized Volunteers and infertile men (n = 54) 400 mg vitamin E +225 μg selenium x 3 months (n = 28) 4.5 g vitamin B x 3 months (n = 26) 1. Reduced MDA concentration (less LPO in spermatozoa) Keskes-Ammar et al. [104]
2. Improved sperm motility
Vitamin E + selenium Observational study Infertile men with idiopathic asthenozoospermia (n = 690) 400 IU vitamin E +200 μg selenium x 100 days None 1. Improvement in sperm motility/morphology or both (53%) Moslemi & Tavanbakhsh [105]
2. Increased spontaneous pregnancy rates (11%)
Vitamin E + Vitamin C Double blind, placebo-controlled, RCT Men (n = 31) with asthenozoospermia or moderate oligoasthenozoospermia 1000 mg vitamin C +800 mg vitamin E x 8 weeks (n = 15) Placebo (n = 16) No improvement in sperm parameters Rolf et al. [106]
No improvement in 24 h sperm survival rate
Vitamin E + Vitamin C Observational study, double-blind Men with elevated sperm DNA fragmentation (≥15%) who have unexplained infertility 1000 mg vitamin C +1000 mg vitamin E x 2 months (n = 32) Placebo (n = 32) Reduced percentage of DNA-fragmented sperm (TUNEL test) Greco et al. [107]
Vitamin E + Vitamin C Observational study involving assisted conception treatment Men with elevated sperm DNA fragmentation (≥15%) who failed their 1st ICSI attempt 1000 mg vitamin C +1000 mg vitamin E x 2 months (n = 38) None 1. Reduced percentage of DNA-fragmented sperm (TUNEL test) Greco et al. [108]
2. Marked improvement in implantation and clinical pregnancy rates in the 2nd ICSI attempt vs 1st attempt
Vitamin C   Men with sperm agglutination (>25%) (n = 30) 200 mg vitamin C or 1000 mg vitamin C Placebo Improved sperm motility, viability, morphology after 4 weeks (more prominent improvement in 1000 mg vitamin C vs. 200 mg vitamin C) Dawson et al. [109]
Vitamin C   Men who are heavy smokers (n = 75) with normal reproductive function 200 mg vitamin C or 1000 mg vitamin C Placebo 1. Improved sperm agglutination Dawson et al. [110]
2. Improved 24 h viability
3. Improved sperm morphology
Folic acid + zinc sulphate Double blind, placebo-controlled, RCT Fertile (n = 108) and subfertile men (n = 103) 5 mg folic acid, 66 mg zinc sulphate or 5 mg folic acid +66 mg zinc sulphate x 26 weeks Placebo or placebo + placebo Increased sperm concentration in subfertile and fertile males after combined treatment Wong et al. [111]
Folic acid + zinc sulphate Double blind, placebo-controlled Fertile (n = 47) and subfertile men (n = 40) 5 mg folic acid +66 mg zinc sulphate x 26 weeks Placebo Increased sperm concentration in infertile males, but not fertile males Ebisch et al. [112]
Folic acid + zinc sulphate Double blind, placebo controlled, RCT Subfertile men with OAT (n = 83) 5 mg folic acid +220 mg zinc sulphate x16 weeks Placebo Zinc sulfate + folic acid did not improve sperm quality in men with OAT (severely compromised sperm parameters) Raigani et al. [113]
Folic acid + zinc sulphate Prospective, randomized controlled Men with palpable varicocele (grade III) who underwent surgical repair of varicocele (n = 160) 5 mg folic acid (n = 26), 66 mg zinc sulphate (n = 32) or 5 mg folic acid +66 mg zinc sulphate (n = 29) x 6 months Placebo (n = 25) 1. Zinc sulfate + folic acid improved sperm parameters and improved varicocelectomy outcomes Azizollahi et al. [114]
2. Improved protamine content and halo formation rate
Coenzyme Q 10 Systematic review and meta-analysis (3 RCTs) Infertile men CoQ10 (n = 149) Controls (n = 147) 1. Improved seminal CoQ10 levels Lafuente et al. [115]
2. Increased sperm concentration
3. Increased sperm motility
4. No increase in pregnancy rates
5. Data on live births were lacking
Coenzyme Q 10 Double blind, placebo-controlled, RCT Men with iOT (n = 60) 200 mg CoQ10 x 3 months (n = 30) Placebo (Lactose) (n = 30) 1. Increased levels of CoQ10 in seminal plasma Nadjarzadeh et al. [116]
2. Decreased 8-isoprostane levels (biomarker of LPO) (attenuation of OS in seminal plasma)
3. Increased sperm forward and total motility
4. Increased catalase, SOD activity
Coenzyme Q 10 Double blind, placebo-controlled, RCT Men with iOAT (n = 47) 200 mg CoQ10 x 12 weeks Placebo 1. Reduced TBARS (reduced plasma MDA levels) Nadjarzadeh et al. [117]
2. Increased TAC in seminal plasma
Coenzyme Q 10 Double blind, placebo-controlled, RCT Men with iOAT (n = 228) 200 mg ubiquinol x 26 weeks (n = 114) Placebo (n = 114) Improved sperm quality (density, motility, normal strict morphology) Safarinejad et al. [118]
Coenzyme Q 10 Double blind, placebo-controlled, RCT Men with idiopathic infertility (n = 60) 200 mg CoQ10 x 6 months Placebo 1. Increase in CoQ10 and ubiquinol in seminal plasma and spermatozoa Balercia et al. [119]
2. Increase in spermatozoa motility
Coenzyme Q 10 Prospective Men with iOAT (n = 212) 300 mg CoQ10 x 26 weeks (n = 106) Placebo (n = 106) 1. Improved sperm density, motility, normal strict morphology Safarinejad [120]
2. Improved acrosome reaction
Coenzyme Q 10 Open-label, prospective Men with iOAT (n = 287) 600 mg CoQ10 x 12 months (n = 106) None 1. Improved sperm quality (concentration, progressive motility, normal morphology) Safarinejad [121]
2. Improved pregnancy rates