BCAAs Linked to Higher Erectile Dysfunction Risk - Study

study PMID: 39778693

Quick Summary: A recent study found a link between higher levels of branched-chain amino acids (BCAAs) in the blood and an increased risk of erectile dysfunction (ED). This research suggests that BCAAs, often found in protein supplements, might play a role in ED.

What The Research Found

The study used a special method called Mendelian randomization to look at the relationship between BCAAs and ED. Researchers found that people with higher levels of BCAAs in their blood, based on their genes, were more likely to experience ED. This suggests a possible causal link, meaning that high BCAA levels might contribute to the development of ED.

Study Details

Who was studied: The study looked at genetic information from a large group of people, including over 6,000 men with ED and over 220,000 men without ED.

How long: The study didn't follow people over time. Instead, it used genetic data to estimate long-term BCAA levels.

What they took: This study didn't involve taking any supplements. It used genetic information to understand how BCAA levels might affect ED risk.

What This Means For You

If you're concerned about ED, this study suggests that you might want to be careful about taking BCAA supplements. BCAAs are often found in protein powders and supplements used by athletes. It's important to talk to your doctor before making any changes to your diet or supplement routine, especially if you have other health conditions.

Study Limitations

The study has some limitations:

It mainly looked at people of European descent, so the results might not apply to everyone.

It didn't look at the effects of individual BCAAs, like L-Isoleucine, but rather the group as a whole.

The study used genetic data, which can be complex.

The study relied on self-reported information about ED, which might not always be accurate.

Key Findings

This Mendelian randomization (MR) analysis found that genetically predicted higher circulating levels of branched-chain amino acids (BCAAs)—including leucine, isoleucine, and valine—were causally associated with an increased risk of erectile dysfunction (ED). The study reported a statistically significant positive association (OR = 1.18 per standard deviation increase in BCAA levels; 95% CI: 1.05–1.33; p = 0.006). No evidence of heterogeneity or directional pleiotropy was observed in sensitivity analyses, supporting a robust causal inference. The findings suggest BCAAs may contribute to ED pathogenesis, potentially via shared metabolic pathways with cardiovascular disease (CVD).

Study Design

This was a two-sample Mendelian randomization study using genetic data to infer causality. It leveraged summary statistics from large-scale genome-wide association studies (GWAS): BCAA exposure data from a meta-analysis of 16,596 individuals of European ancestry, and ED outcome data from the UK Biobank (6,135 ED cases, 222,976 controls). Instrumental variables comprised 15 single-nucleotide polymorphisms (SNPs) robustly associated with BCAA levels (p < 5×10⁻⁸). Inverse-variance weighted (IVW) regression served as the primary analytical method, supplemented by MR-Egger and weighted median approaches for sensitivity testing.

Dosage & Administration

No direct supplementation or dosage administration occurred, as this was an observational genetic study. BCAA exposure was proxied by lifelong genetically elevated circulating levels, inferred from SNPs associated with baseline BCAA concentrations. The analysis did not isolate individual BCAAs (e.g., L-isoleucine) but treated BCAAs as a collective metabolic trait.

Results & Efficacy

The primary IVW analysis confirmed a significant causal effect of BCAAs on ED risk (OR = 1.18; 95% CI: 1.05–1.33; p = 0.006). Sensitivity analyses using MR-Egger (OR = 1.21; 95% CI: 0.98–1.50; p = 0.08) and weighted median (OR = 1.19; 95% CI: 1.04–1.36; p = 0.01) methods yielded consistent directional effects, though MR-Egger did not reach strict significance. Steiger filtering confirmedscrição of causality (proportion variance explained: 1.2–2.8%). No evidence of horizontal pleiotropy was detected (MR-Egger intercept p = 0.24).

Limitations

Key limitations include: (1) exclusive use of European-ancestry GWAS data, limiting generalizability to other populations; (2) inability to assess dose-response relationships or isolate effects of individual BCAAs (e.g., L-isoleucine alone); (3) potential residual confounding from pleiotropic SNPs despite sensitivity analyses; and (4) reliance on self-reported ED diagnoses in the UK Biobank, which may introduce misclassification bias. Future research should validate findings in diverse cohorts and explore mechanistic links to endothelial dysfunction.

Clinical Relevance

These results suggest that elevated BCAA levels—often influenced by high-protein diets or supplements—may contribute to ED risk, particularly in individuals with metabolic or cardiovascular vulnerabilities. Supplement users, especially those with CVD risk factors, should exercise caution with BCAA supplementation and prioritize whole-food protein sources. However, as this study infers lifelong genetic exposure rather than acute supplementation effects, direct dietary recommendations require confirmation from interventional trials. Patients with ED should consult healthcare providers before modifying supplement regimens.