Randomized triple blind placebo controlled clinical trial examining the effects of alpha-lipoic acid supplement on the spermatogram and seminal oxidative stress in infertile men

Three months of supplementation with alpha-lipoic acid improved sperm quality in infertile men. Medical therapy with oral antioxidants can improve quality of semen parameters.

Hossein Khadem Haghighian, Fatemeh Haidari, Ph.D., Javad Mohammadi-asl, Ph.D., Mohammadreza Dadfar, M.D.

Volume 104, Issue 2, Pages 318-324


To evaluate effects of supplementation with alpha-lipoic acid (ALA) on the spermatogram and seminal oxidative stress biomarkers.

Randomized, triple-blind, placebo-controlled clinical trial.

Infertility clinic.

Infertile men.

ALA (600 mg) or placebo for 12 weeks.

Main Outcome Measure(s):
Semen analysis, anthropometric, dietary, and physical activity assessments, total antioxidant capacity, and malondialdehyde.

At the end of study, the total sperm count, sperm concentration, and motility in the intervention group were significantly higher than in the control group. In the ALA group, the total sperm count, sperm concentration, and motility levels were also significantly increased at the end of study compared with baseline values. However, there were no significant differences in ejaculate volume, normal morphology percentage, and live sperm between groups. ALA supplementation also resulted in a significant improvement in seminal levels of total antioxidant capacity (TAC) and malondialdehyde compared with the placebo.

According to the results, medical therapy of asthenoteratospermia with ALA supplement could improve quality of semen parameters. However, further investigation is suggested in this regard.

Clinical Trial Registration Number:

  • Jason M. Franasiak

    The authors are commended on their RCT. Supplementation studies are challenging at times due to patient compliance (has been seen significantly in literature surround oral contraceptive use). How was medication adherence monitored for this study?

  • The authors must be commended for presenting Level I evidence. Despite some of the shortcomings in the study addressed by Dr. Ko, the study attempted to study one supplement as opposed combinations that lead to more confusing results. It would be interesting to know if the authors looked at end points other than improvement in semen parameters (could be from mere variation) such as doubling of sperm density, # of men that reached normal (5%) thresholds according to WHO and such.

  • This is a supplement study with Alpha lipoic acid, an antioxidant. As with any supplement study, there was no control for dietary intake of food products. ALA is found in many foods (spinach, broccoli, brussel sprouts, red meat, carrots, etc,). After 3 months, there was statistically significant improvements in men on the supplements in terms of count, concentration, and motility. TAC was also improved.

    There are so many supplement studies that demonstrate that if you take the product, x or y parameter will improve. However, it must be noted that diet is very hard to control outside of the study.

    This study shows improvement and potentially be utilized. We must always ask the question, however, of what happens if you are already getting enough of the said supplement in your diet? If some is good, is it always better if you get more?

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