Association between saturated and polyunsaturated fatty acid proportions in total fat intake and mortality risk: mediation by the neutrophil percentage-to-albumin ratio.

Background: For over half a century, dietary guidelines have consistently advocated for the substitution of saturated fatty acids (SFA) with monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) as a cornerstone strategy for health life, but evidence on independent associations between specific fatty acids and mortality remains inconsistent.

Methods: This prospective cohort study from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 analyzed 21,823 participants aged 20-80 years. Survey-weighted Cox regression assessed associations between SFA, MUFA, PUFA intake, and their ratios to the total fat (TFAT) intake quantity, and all-cause mortality. Mediation analyses examined whether the neutrophil percentage-to-albumin ratio (NPAR) mediated the effects of fatty acid-related parameters on mortality risk.

Results: In multivariable-adjusted models, no significant trends were observed for all-cause mortality across tertiles of SFA, MUFA, or PUFA intake. In multivariable-adjusted Cox models, the highest tertile of SFA/TFAT ratio was significantly associated with elevated mortality risk (HR = 1.23, p for trend < 0.01). Conversely, the highest PUFA/TFAT tertile demonstrated a protective association (HR = 0.86, p for trend < 0.01). However, the MUFA/TFAT ratio showed no significant mortality association across tertiles (p for trend = 0.137). Mediation analysis revealed that NPAR mediated 9.8% and 11.8% of SFA/TFAT and PUFA/TFAT effects on mortality risk, suggesting partial mediation through a shared inflammatory pathway.

Conclusion: This study provides the novel evidence that the proportional composition of dietary fatty acids within total fat intake-rather than their absolute intake levels-is a critical determinant of longevity. By demonstrating that replacing SFA with PUFA reduces mortality risk through NPAR-mediated inflammatory pathways, our findings inform the World Health Organization's 2023 guidelines on dietary fat modification. These results shift the paradigm from isolated nutrient restrictions to balanced fatty acid ratios, offering a novel mechanistic basis for public health strategies aimed at extending healthy lifespan.