Tier 4 — mechanistic

Effects of the reduced form of coenzyme Q10 (ubiquinol) on semen parameters in men with idiopathic infertility: a double-blind, placebo controlled, randomized study

Mohammad Reza Safarinejad, Shiva Safarinejad, Nayyer Shafiei, Saba Safarinejad
The Journal of Urology 2012 188(2):526-531

Bibliography

PubMed
PMID 22704112
DOI
10.1016/j.juro.2012.03.131
Funding
The original article is indexed as non-U.S. government-supported research. The tested compound was ubiquinol; secondary literature identifies Kaneka as the commercial source/context for this research line. Exact original funding wording was not available in the accessible PubMed record checked.
Competing interests
CRITICAL INTEGRITY NOTICE: The Journal of Urology issued a formal Expression of Concern in 2023 regarding this 2012 paper (PMID 36626336; DOI 10.1097/JU.0000000000003143). The efficacy findings should therefore be treated as unreliable/low-certainty until the journal resolves the concern. A contemporaneous published letter also commented on the article.

Study snapshot

DesignDouble-blind placebo-controlled randomized trial; Expression of Concern issued 2023
ModelRandomized, double-blind, placebo-controlled trial in men with idiopathic oligoasthenoteratozoospermia; publication is under a formal Expression of Concern.
Sample228 men randomized 1:1: 114 ubiquinol and 114 placebo.
InterventionUbiquinol 200 mg/day versus placebo for 26 weeks, followed by a 12-week off-treatment observation period.
Duration26 weeks treatment + 12 weeks off-drug follow-up.
EndpointsSperm density; Sperm motility; Strict sperm morphology; FSH; Inhibin B; Seminal antioxidant capacity; Off-treatment persistence; Treatment-duration correlations; Publication integrity / Expression of Concern

What the study showed, in plain terms

This 2012 randomized double-blind trial reported substantial improvements in sperm density, motility and morphology after 26 weeks of ubiquinol 200 mg/day in 228 men with idiopathic infertility, with some persistence during a 12-week off-treatment period.

The originally reported end-of-treatment means were sperm density 28.7 ± 4.6 vs 16.8 ± 4.4 million/mL (p=0.005), motility 35.8 ± 2.7% vs 25.4 ± 2.1% (p=0.008), and normal morphology 17.6 ± 4.4% vs 14.8 ± 4.1% (p=0.01), favoring ubiquinol.

However, these efficacy results must not be presented as dependable evidence without a prominent warning: The Journal of Urology issued a formal Expression of Concern about this paper in January 2023. Accordingly, Biohack Blueprint treats this record as compromised/uncertain evidence and does not rely on its effect sizes as proof that ubiquinol improves male fertility.

Key findings

INTEGRITY STATUS: Formal Expression of Concern issued by The Journal of Urology in 2023 (PMID 36626336; DOI 10.1097/JU.0000000000003143). This status overrides otherwise favorable study design when grading confidence.

Originally reported sperm density at week 26: 28.7 ± 4.6 million/mL with ubiquinol vs 16.8 ± 4.4 with placebo; p=0.005.

Originally reported sperm motility: 35.8 ± 2.7% vs 25.4 ± 2.1%; p=0.008.

Originally reported strict normal morphology: 17.6 ± 4.4% vs 14.8 ± 4.1%; p=0.01.

Reproductive hormones: FSH reportedly decreased (p=0.02) and inhibin B increased (p=0.01) during treatment.

Off-treatment phase: semen parameters reportedly moved back toward baseline, while differences remained significant for density and motility at the reported follow-up (both p=0.03).

These numerical findings are catalogued for completeness, not endorsed as reliable, because the formal Expression of Concern materially lowers confidence in the paper.

What this study can and cannot tell us

The central limitation is publication integrity: a formal Expression of Concern was issued by the journal in 2023. Until resolved, all efficacy estimates require substantial skepticism.

The study reported semen parameters and hormones rather than pregnancy/live-birth outcomes.

A published 2013 letter/comment also questioned aspects of the paper, adding to the need for cautious interpretation.

The reported dose-duration correlations are post-randomization/exploratory associations and do not independently validate causality.

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Editorial review

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology