News | Antioxidant Fertility Supplements Ineffective? Large Clinical Trial Suggests They May Be Counterproductive
A large clinical trial published in JAMA Network Open challenges marketing claims that antioxidants improve male fertility. The study found that Impryl, widely promoted as a fertility supplement, did not increase pregnancy rates and may even have reduced them during a key treatment window.
The multicenter, randomized, double-blind, placebo-controlled SUMMER Trial was conducted at 21 hospitals and fertility centers in the Netherlands from May 2018 to December 2024. It enrolled 1,171 men aged 18 to 50 who were undergoing fertility treatment with their partners, including intrauterine insemination, intracytoplasmic sperm injection (ICSI), or in vitro fertilization (IVF).
The treatment group took Impryl daily, containing 200 mg betaine, 200 mg L-cystine, 16 mg niacin, 10 mg zinc, 1.4 mg vitamin B6, 1.4 mg vitamin B2, 400 micrograms folic acid, and 2.5 micrograms vitamin B12. The control group received an identical-looking placebo. The primary endpoint was ongoing pregnancy within six months, defined as a visible fetal heartbeat at 12 weeks.
At six months, there was no significant difference in pregnancy rates: 33.8% (193/571) in the antioxidant group and 37.5% (208/555) in the placebo group, with an adjusted odds ratio of 0.85 (95% CI, 0.66-1.09).
More notably, during the prespecified ‘optimal treatment-effect period’—months 4 to 6 of treatment, corresponding to the 72-day sperm production cycle—the pregnancy rate was significantly lower in the antioxidant group at 15.5%, compared with 21.5% in the placebo group (AOR 0.66, 95% CI, 0.47-0.94, P=0.02).
Further analysis showed that among couples undergoing IVF or ICSI, pregnancy rates after egg retrieval and fresh embryo transfer were significantly lower in the antioxidant group, while frozen embryo transfer outcomes did not differ. The groups showed no significant differences in fertilization rates, embryo utilization, or semen parameters, including concentration, motility, and total motile sperm count.
In a subset of participants, sperm motility in the antioxidant group declined from baseline, from 62.7% to 54.9%, while DNA fragmentation did not differ.
The researchers noted that although antioxidants can theoretically neutralize reactive oxygen species (ROS) and reduce sperm DNA damage, excessive use may cause ‘reductive stress,’ which can also disrupt normal redox balance and impair reproductive function.
Adherence was moderate at about 58%, and adverse events were rare and similar between groups. Final live birth results have not yet been released, but the team published the data early because of the potential negative signal and ethical considerations.
The lead researcher said: ‘These results clearly show that evidence currently does not support routine antioxidant supplementation in men to improve fertility. Instead, we must carefully assess its potential negative physiological effects.’
The study received unrestricted funding from Impryl manufacturer Goodlife Pharma BV, but the funder was not involved in study design, data analysis, or publication decisions.
News | Antioxidant Fertility Supplements Ineffective? Large Clinical Trial Suggests They May Be Counterproductive
News | Antioxidant Fertility Supplements Ineffective? Large Clinical Trial Suggests They May Be Counterproductive
A large clinical trial published in JAMA Network Open challenges marketing claims that antioxidants improve male fertility. The study found that Impryl, widely promoted as a fertility supplement, did not increase pregnancy rates and may even have reduced them during a key treatment window.
The multicenter, randomized, double-blind, placebo-controlled SUMMER Trial was conducted at 21 hospitals and fertility centers in the Netherlands from May 2018 to December 2024. It enrolled 1,171 men aged 18 to 50 who were undergoing fertility treatment with their partners, including intrauterine insemination, intracytoplasmic sperm injection (ICSI), or in vitro fertilization (IVF).
The treatment group took Impryl daily, containing 200 mg betaine, 200 mg L-cystine, 16 mg niacin, 10 mg zinc, 1.4 mg vitamin B6, 1.4 mg vitamin B2, 400 micrograms folic acid, and 2.5 micrograms vitamin B12. The control group received an identical-looking placebo. The primary endpoint was ongoing pregnancy within six months, defined as a visible fetal heartbeat at 12 weeks.
At six months, there was no significant difference in pregnancy rates: 33.8% (193/571) in the antioxidant group and 37.5% (208/555) in the placebo group, with an adjusted odds ratio of 0.85 (95% CI, 0.66-1.09).
More notably, during the prespecified ‘optimal treatment-effect period’—months 4 to 6 of treatment, corresponding to the 72-day sperm production cycle—the pregnancy rate was significantly lower in the antioxidant group at 15.5%, compared with 21.5% in the placebo group (AOR 0.66, 95% CI, 0.47-0.94, P=0.02).
Further analysis showed that among couples undergoing IVF or ICSI, pregnancy rates after egg retrieval and fresh embryo transfer were significantly lower in the antioxidant group, while frozen embryo transfer outcomes did not differ. The groups showed no significant differences in fertilization rates, embryo utilization, or semen parameters, including concentration, motility, and total motile sperm count.
In a subset of participants, sperm motility in the antioxidant group declined from baseline, from 62.7% to 54.9%, while DNA fragmentation did not differ.
The researchers noted that although antioxidants can theoretically neutralize reactive oxygen species (ROS) and reduce sperm DNA damage, excessive use may cause ‘reductive stress,’ which can also disrupt normal redox balance and impair reproductive function.
Adherence was moderate at about 58%, and adverse events were rare and similar between groups. Final live birth results have not yet been released, but the team published the data early because of the potential negative signal and ethical considerations.
The lead researcher said: ‘These results clearly show that evidence currently does not support routine antioxidant supplementation in men to improve fertility. Instead, we must carefully assess its potential negative physiological effects.’
The study received unrestricted funding from Impryl manufacturer Goodlife Pharma BV, but the funder was not involved in study design, data analysis, or publication decisions.
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