Abstract
BACKGROUND: Despite the significant increase in omega-6 fatty acid consumption, evidence regarding their health impacts remains inconsistent. This study performs an umbrella review and updated meta-analysis to evaluate the association between dietary and circulating omega-6 levels and the risks of cardiovascular diseases (CVDs), cancer, and mortality. METHODS: A systematic search was conducted in PubMed, Scopus, and Web of Science until January 2024 to identify eligible meta-analyses of prospective observational studies. The Cochrane risk of bias and GRADE tools were used to assess the risk of bias and certainty of the evidence, respectively. RESULTS: Analysis of 150 publications revealed that higher dietary intake and circulating levels of omega-6 were associated with lower risks of CVDs, cancer incidence, and all-cause mortality in the general population, particularly for coronary heart disease and stroke. While omega-6 intake was linked to lower risks of lung and prostate cancers, it was associated with higher risks of ovarian and endometrial cancers. Subgroup analyses revealed that these protective associations were more pronounced in cohort studies and absent in populations with pre-existing health conditions. CONCLUSIONS: Higher dietary intake and circulating levels of omega-6 fatty acids were associated with lower risks of CVDs, cancers, and all-cause mortality. However, the associations vary by cancer type and are less evident in individuals with pre-existing health conditions. These findings highlight the potential benefits of omega-6 fatty acids for public health while underscoring the need for further research to address specific risks and underlying mechanisms. TRIAL REGISTRATION: Registration number (PROSPERO): CRD42024522842.