Acetate, a short-chain fatty acid, has recently drawn scientific interest because of its seemingly contradictory roles in human health, with research suggesting it may help protect the cardiovascular system while also promoting the development of certain cancers, especially those influenced by sex hormones. Despite these observations, its impact has rarely been examined in large-scale population studies. To explore this further, researchers conducted a Mendelian randomization analysis to assess the potential causal relationships between acetate and ischemic heart disease, diabetes, and several cancers related to sex hormones. They selected genetic variants strongly associated with acetate levels that showed no linkage disequilibrium and applied these variants to extensive genome-wide association data covering ischemic heart disease (up to 154,373 cases), diabetes (109,731 cases), and five cancers, including breast, colorectal, prostate, ovarian, and endometrial cancers, with case numbers ranging from 8,679 to 122,977. Using a range of analytical approaches, such as penalized inverse variance weighting, inverse variance weighting, weighted mode, and weighted median methods, the study found that higher acetate levels were linked to a reduced risk of ischemic heart disease, showing an odds ratio of 0.62 per standard deviation increase and a 95% confidence interval between 0.39 and 0.98. In contrast, acetate was associated with an increased risk of breast cancer, with an odds ratio of 1.26 and a 95% confidence interval of 1.08 to 1.46, and this link remained consistent across multiple sensitivity analyses. These findings suggest that acetate and the biological pathways it influences could become potential targets for developing new treatments aimed at breast cancer prevention and cardiovascular disease management.