Are total omega-3 and omega-6 polyunsaturated fatty acids predictors of fatal stroke in the Adventist Health Study 2 prospective cohort?

INTRODUCTION: The effects of omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) on cerebrovascular disease remain unsettled. However, most studies have focused on marine sourced n-3 PUFA rather than total n-3 PUFA, of which the majority in the American diet is plant derived. This study therefore intended to investigate these effects in a cohort for which the vegetarian diet was more prevalent than the general public. METHODS: Cox proportional hazards with fatal stroke as the outcome was performed on the approximately 96,000 subject Adventist Health Study 2 prospective cohort. Stratification by race and sex was performed on models with a priori covariables, comparing 90(th) to 10(th) percentile daily intakes of energy-adjusted total n-3 PUFA, total n-6 PUFA, and the n-6 / n-3 PUFA ratio as variables of interest. RESULTS: For the main analytical group (78,335 subjects), the hazard ratio (95% confidence interval) for total n-3 PUFA was 0.65 (0.51–0.83), and for total n-6 PUFA was 1.37 (1.02–1.82), while adjusting for both fatty acids in the model. The n-6 / n-3 PUFA ratio was harmful with a HR of 1.40 (1.16–1.69), whereas the inclusion of total n-3 PUFA slightly attenuated the HR to 1.33(1.02–1.74). Effects were similar for the non-black sex-combined and sex-specific analyses. CONCLUSION: In most analytic groups, subjects with greater total n-3 PUFA intakes have lower risk of fatal stroke, and those with a higher n-6 / n-3 PUFA ratio had higher risk. However, the n-6 / n-3 PUFA ratio remains statistically significant even after adjusting for total n-3 PUFA or total n-6 PUFA, suggesting that the ratio is of epidemiologic interest for cerebrovascular disease research.