Abstract
BACKGROUND: The associations between changes in fatty acid intake over time and subsequent mortality are unclear. OBJECTIVES: The objective of this study was to prospectively examine associations between changes in fatty acid intake (as percentage of total energy) and mortality. METHODS: Among 65,179 adults from the Nurses' Health Study and Health Professionals Follow-up Study, free from cardiovascular disease, cancer, and diabetes at baseline in 1994, we documented 20,571 deaths through 2020 (1,334,603 person-years). Diets were assessed every 4 years using validated questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality risk were estimated from Cox proportional hazards models. RESULTS: A 5% energy increment in total fat intake was associated with 5% lower all-cause mortality (HR: 0.95; 95% CI: 0.93, 0.96; isocaloric comparison was total carbohydrate). The HRs of all-cause mortality (95% CI) were 0.83 (0.78, 0.89) and 0.91 (0.87, 0.94) for a 5% increment in energy intake from polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA), respectively, and was 1.10 (1.04, 1.17) for a 1% increase in energy intake from trans fatty acid (TFA; all P(trend) ≤ 0.001). Changes in saturated fatty acid (SFA) were not associated with all-cause mortality. Increases in intakes of linoleic acid, marine n-3 PUFA, and MUFA from plant sources were each significantly associated with lower all-cause mortality. In substitution analyses, replacing 5% energy from SFA with PUFA was associated with 19% lower all-cause mortality (HR: 0.81; 95% CI: 0.75, 0.87), whereas replacing 0.3% of energy from SFA with marine n-3 PUFA was associated with 11% lower all-cause mortality (HR: 0.89; 95% CI: 0.84, 0.93). Isocaloric substitution of SFA by PUFA, particularly marine n-3 PUFA, was associated with lower mortality due to cardiovascular, neurodegenerative, and respiratory diseases. CONCLUSIONS: These findings support replacing SFA with unsaturated fatty acids (especially from plant sources) and eliminating dietary TFA to reduce premature death.