Low Folate Levels Linked to Poor Sperm Quality in Healthy Young Men
Men with lower folate levels had significantly fewer sperm and higher odds of abnormal semen analysis, a new cross-sectional study finds.
Summary
A Spanish cross-sectional study of 197 healthy men aged 18–40 found that those with the lowest plasma and red blood cell folate levels had significantly lower sperm counts and over three times the odds of an abnormal semen analysis compared to those with the highest folate levels. Cobalamin and homocysteine levels were not significantly linked to sperm quality. Additionally, men carrying the MTHFD1 1958AA genetic variant — which impairs folate metabolism — showed reduced sperm motility and higher odds of an abnormal seminogram. These findings suggest that folate status and related genetic factors meaningfully influence sperm production and function, even in men without apparent fertility problems.
Detailed Summary
Male fertility is declining globally, and nutritional factors may play a bigger role than previously appreciated. Folate-mediated one-carbon metabolism is fundamental to DNA synthesis, methylation, and genomic stability during sperm production — processes that are highly sensitive to micronutrient availability. Yet evidence linking folate status to sperm quality in healthy, non-infertile men has remained limited.
Researchers from Universitat Rovira i Virgili in Spain conducted the Led-Fertyl cross-sectional study, recruiting 197 healthy men aged 18–40 between 2021 and 2023. They measured plasma folate, red blood cell folate (RBCF), plasma cobalamin, total homocysteine, and key genetic polymorphisms affecting folate and cobalamin metabolism. Sperm quality was assessed using WHO 2010 criteria.
The results were striking for folate. Men in the lowest tertile of plasma folate (below 11.9 nmol/L) had significantly lower sperm counts compared to those in the highest tertile (17.0 nmol/L or above), and were over three times more likely to have an abnormal seminogram (OR 3.37). Similar patterns held for red blood cell folate. Neither cobalamin deficiency nor elevated homocysteine were independently associated with sperm parameters in this cohort.
Genetics added another dimension: men carrying the MTHFD1 1958AA genotype — a variant that reduces efficiency of folate-mediated one-carbon metabolism — showed nearly 8 percentage points lower progressive sperm motility and more than four times the odds of an abnormal seminogram compared to GG carriers.
These findings suggest that even folate levels within the non-deficient range may meaningfully affect sperm production and motility. Clinicians evaluating male fertility or preconception health may benefit from assessing folate status routinely. Limitations include the cross-sectional design, which precludes causal inference, and the summary is based on the abstract only, as the full text was not available.
Key Findings
- Men with the lowest plasma folate had 3.4x higher odds of an abnormal semen analysis versus highest-folate men.
- Low red blood cell folate was independently associated with lower sperm count and 2.3x greater odds of abnormal seminogram.
- The MTHFD1 1958AA genotype was linked to ~8% lower progressive sperm motility and 4.4x higher odds of abnormal seminogram.
- Cobalamin deficiency and elevated homocysteine were not significantly associated with sperm quality parameters.
- Folate deficiency was uncommon (4.6% plasma, 2.6% RBCF), yet even lower-normal levels correlated with worse sperm quality.
Methodology
This was a cross-sectional study of 197 healthy men aged 18–40 recruited in Spain from 2021–2023. Biomarkers included plasma and red blood cell folate, cobalamin, total homocysteine, and relevant SNPs; sperm quality was assessed by WHO 2010 criteria. Associations were analyzed using multivariable linear and logistic regression.
Study Limitations
The cross-sectional design prevents causal inference — it is unknown whether increasing folate would improve sperm quality. The sample of 197 men from a single Spanish region may limit generalizability. This summary is based on the abstract only, as the full text was not available; complete methodology, covariates, and supplementary data could not be reviewed.
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