Background: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are
heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with
metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between
plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways.
Methods: We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain:
C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals
from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort
study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential
confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic
markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI)
and alcohol consumption, were tested.Results: Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC),
triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT),
aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated
with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio,
triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA
group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C,
TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption.
Conclusions: Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver
function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and
even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs.
The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.