Free fatty acids and mortality among adults in the United States: a report from US National Health and Nutrition Examination Survey (NHANES)

BACKGROUND: The relationship between free fatty acids (FFAs) and the risk of mortality remains unclear. There is a scarcity of prospective studies examining the associations between specific FFAs, rather than total concentrations, of their effect on long-term health outcomes. OBJECTIVE: To evaluate the correlation between different FFAs and all-cause and cardiovascular mortality in a large, diverse, nationally representative sample of adults in the US, and examine how different FFAs may mediate this association. METHODS: This cohort study included unsaturated fatty acids (USFA) and saturated fatty acids (SFA) groups in the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 and provided blood samples for FFAs levels. Multiple model calibration was performed using Cox regression analysis for known risk factors to explore the associations between FFAs and all-cause and cardiovascular mortality. RESULTS: In the group of USFA, 3719 people were included, median follow-up, 6.7 years (5.8-7.8 years). In the SFA group, we included 3900 people with a median follow-up, 6.9 years (5.9-8 years). In the USFA group, myristoleic acid (14:1 n-5) (hazard ratio (HR) 1.02 1.006-1.034; P = 0.004), palmitoleic acid (16:1 n-7) (HR 1.001 1.001-1.002; P < 0.001), cis-vaccenic acid (18:1 n-7) (HR 1.006 1.003-1.009; P < 0.001), nervonic acid (24:1 n-9) (HR 1.007 1.002-1.012; P = 0.003), eicosatrienoic acid (20:3 n-9) (HR 1.027 1.009-1.046; P = 0.003), docosatetraenoic acid (22:4 n-6) (HR 1.024 1.012-1.036; P < 0.001), and docosapentaenoic acid (22:5 n-6) (HR 1.019 1.006-1.032; P = 0.005) were positively associated with the all-cause mortality, while docosahexaenoic acid (22:6 n-3) had a statistically lower risk of all-cause mortality (HR 0.998 0.996-0.999; P = 0.007). Among the SFA group, palmitic acid (16:0) demonstrated a higher risk of all-cause mortality (HR 1.00 1.00-1.00; P = 0.022), while tricosanoic acid (23:0) (HR 0.975 0.959-0.991; P = 0.002) and lignoceric acid (24:0) (HR 0.992 0.984-0.999; P = 0.036) were linked to a lower risk of all-cause mortality. Besides 23:0 and 24:0, the other FFAs mentioned above were linearly associated with the risks of all-cause mortality. CONCLUSIONS: In this nationally representative cohort of US adults, some different FFAs exhibited significant associations with risk of all-cause mortality. Achieving optimal concentrations of specific FFAs may lower this risk of all-cause mortality, but this benefit was not observed in regards to cardiovascular mortality.