Antioxidants Fail to Improve Male Fertility in Landmark Trial

Daily intake of a widely marketed antioxidant supplement showed no improvement in ongoing pregnancy rates compared to placebo after six months of use. Notably, during the window when treatment effects should be optimal, pregnancy rates were significantly lower in the antioxidant group, raising concerns about the supplement’s effectiveness (1^✔ ✔Trusted Source
Antioxidant Treatment and the Chance to Conceive in Men Seeking Fertility Care

Go to source). The randomized trial, conducted across 21 centers in the Netherlands and published in JAMA Network Open, included 1,171 men aged 18 to 50 seeking fertility support. Participants were given either a placebo or a supplement called Impryl, containing nutrients like zinc, folic acid, betaine, and vitamins B2, B6, and B12. Results suggest antioxidant use may not just be ineffective, it may be counterproductive for male fertility.

Oxidative Stress Theory and Antioxidant Hype

Male factor infertility contributes to approximately 50% of all infertility cases, with oxidative stress often suspected as a key culprit. Reactive oxygen species, which damage sperm DNA and membranes, have led to widespread use of antioxidant supplements aimed at neutralizing them.

Despite the physiological basis, clinical trials testing antioxidant efficacy have yielded conflicting results due to small sample sizes and inconsistent designs. As demand for over-the-counter fertility boosters grows, there remains a critical need for large-scale, reliable clinical trials to validate or refute their claims.

Fertility Techniques Used Among Male Participants

The SUMMER trial was a double-blind, placebo-controlled, randomized clinical trial that followed participants from May 2018 through December 2024. Men enrolled were undergoing assisted reproductive techniques such as intrauterine insemination, in vitro fertilization, or intracytoplasmic sperm injection.

The study measured the ongoing pregnancy rate, defined as a viable pregnancy at 12 weeks, within six months of treatment initiation. Secondary metrics included sperm characteristics, DNA fragmentation, and fertility outcomes at various points throughout the trial period.

No Benefits and Potential Harms Observed

After six months, the antioxidant group had a 33.8% pregnancy rate compared to 37.5% in the placebo group. Even more striking, during the 4–6 month sperm production window, pregnancy rates dropped further in the antioxidant group to 15.5% versus 21.5% with placebo.

Among couples using in vitro fertilization or intracytoplasmic sperm injection, pregnancy rates after fresh embryo transfer were also lower in the antioxidant group. No significant difference was observed with frozen-thawed embryo transfers or in fertilization and embryo utilization rates.

Sperm Health and Adverse Signals

Semen analysis found no differences in volume, motility, or concentration between groups. However, sperm vitality decreased in the antioxidant group over time. DNA fragmentation remained unchanged, but the drop in vitality raises concerns about the biological impact of long-term antioxidant use.

Adverse effects were rare and similar across groups, but adherence to the supplement was modest at just 58%. Live birth outcomes and certain neonatal measures were not available at the time of publication. The findings were released early due to emerging concerns and ethical reasons.

Implications for Fertility Treatment Practices

This trial is among the first to rigorously test antioxidant supplementation’s effects on male fertility in a large population. Despite widespread marketing claims, the supplement failed to enhance pregnancy outcomes and may even reduce fertility during the most critical period.

These findings suggest that routine antioxidant use in men seeking fertility treatment could be misguided. Given the potential for unintended harm, caution is advised when considering these supplements. The trial was funded by Goodlife Pharma BV, maker of Impryl, though the company had no role in study design or publication.

To sum up, this large-scale clinical trial challenges the widespread belief that antioxidant supplements can enhance male fertility. Not only did the supplement fail to improve pregnancy outcomes, but it also potentially reduced fertility during the key treatment window. Clinicians and patients should reconsider the routine use of such supplements and await stronger evidence before incorporating them into fertility care.

Reference:

1. Antioxidant Treatment and the Chance to Conceive in Men Seeking Fertility Care - (https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2839329)

Source-Medindia