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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