Across 105,563 females from UK Biobank and Biobank Japan followed up to 10 years, higher plasma acetate — the dominant short-chain fatty acid produced by gut microbial fermentation of dietary fibre — was associated with a 11.3% lower 10-year MACE risk (HR=0.887, p=0.002). Critically, acetate above the population median neutralised the elevated MACE hazard in women with early menopause (HR=1.155, p=0.075) versus those below the median (HR=1.431, p<0.001), a protective interaction replicated in the Japanese cohort. The top acetate quartile corresponded to roughly 27+ grams of daily dietary fibre. Proteomics pointed to suppression of pro-inflammatory signalling as the mechanistic driver.
This finding arrives at a clinically important intersection: early menopause affects roughly 5% of women and confers disproportionate lifetime cardiovascular burden, yet hormone therapy remains contraindicated or declined by many. The acetate-inflammation axis has biological plausibility — short-chain fatty acids activate G-protein coupled receptors (GPR41/43) and inhibit histone deacetylases, dampening NF-κB-mediated inflammation. The dual-biobank replication across European and East Asian cohorts meaningfully strengthens confidence. However, this is an observational study; plasma acetate is influenced by diet, gut microbiome composition, and metabolic health simultaneously, making causal attribution difficult. Dietary fibre supplementation trials are needed to confirm whether raising acetate intentionally reproduces these outcomes. As a preprint not yet peer-reviewed, these results should be treated as preliminary — methodology and effect estimates may shift during review. Still, the large sample size and biological coherence make this incrementally important for CVD prevention in menopausal women.