Questionable benefit of dietary supplements for men with fertility concerns

The benefit of nutritional supplements is limited, despite their popularity. There’s sound reasoning for preconception folate supplementation for women but evidence of benefits of supplements for men is lacking.

In “Micronutrient Antioxidants for Men (Menevit®) Improve Sperm Function by Reducing Oxidative Stress, Resulting in Improved Assisted Reproductive Technology Outcomes”, Ogawa et al. address the hypothesis that “micronutrient antioxidants reduce ROS [reactive oxygen species]-induced sperm quality damage, thereby improving male fertility and pregnancy outcomes”.

The study included 136 men (of a total of 171 recruited) from infertile couples. Eighty-four men chose to take Menevit® (some with high semen ‘static oxidation-reduction potential’ (sORP) levels and very low sperm concentrations, and others with lower sORP), and 52 men declined to take the supplement. Semen parameters and outcomes of assisted reproductive technology (ART) cycles were measured at baseline and after six months, with an interim semen analysis at three months.

The researchers conclude that “this prospective interventional study revealed significant improvements in sperm characteristics and pregnancy outcomes following IVF/ICSI-ET when micronutrient antioxidants were used”. Their statement is unjustifiable based on their presented data.

The only semen parameter that was ‘improved’ by the dietary supplement was sperm concentration (a measure of sperm quantity, not quality), in a subset of the men (those who began with high semen sORP and very low sperm concentrations). Even so, this variable remained below the WHO reference range in this group. The “statistically significant” change (using a simplistic approach to statistical analysis) in sperm concentration is therefore of questionable biological relevance.

Similarly, ‘pregnancy outcomes’ (this is a misnomer: pregnancy outcomes were not measured; implantation, clinical pregnancy and miscarriage rates were) showed only higher implantation and clinical pregnancy rates for partners of men with high sORP values who took the supplement. Other ART outcome variables were not different.

The investigators’ rationale for measuring and reporting oocyte retrieval numbers, and the number of retrieved oocytes in metaphase II, is not provided but these are outcomes that could not possibly be affected by men’s use of a supplement. The biological processes that underlie these measurements occur in the bodies of the female partners of the men in the study.

The inclusion of these data helps to illustrate an important point. The number of oocytes, and the number of these oocytes in metaphase II, retrieved from the partners of men who had low sORP and took the supplement were lower at the end of the study than at the beginning. The researchers do not discuss this ‘statistically significant’ observation; presumably because it’d be difficult to explain, other than just by chance. There is nothing about this observation that makes it any less valid than the results used to claim benefits for “sperm function” or ART outcomes. Changes in sperm concentration, and in implantation and clinical pregnancy rates, may be false discoveries, despite them being ‘statistically significant’.

The authors’ overinterpretation of the results in their study is suspicious.

“The authors declare no conflicts of interest” in this article, yet in another study published less than a year ago, it is declared that one of the authors “received honoraria for speaker bureaus from Bayer Yakuhin, Ltd”. Bayer make the supplement that is the subject of this study.

Bias, selective reporting and the undeclared conflict of interests makes “Micronutrient Antioxidants for Men (Menevit®) Improve Sperm Function by Reducing Oxidative Stress, Resulting in Improved Assisted Reproductive Technology Outcomes” an article with a title that is misleading and incorrect, and open to misuse for promotion of a product with no proven benefit.