Animal studies show that ecosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are effective for the prevention and treatment of insulin resistance (IR). Data from human studies are contradictory. We sought to determine whether the relationships between plasma n-3 and n-6 polyunsaturated fatty acid (FA) levels and IR differ according to the presence or absence of metabolic syndrome (MS) in a coronary heart disease sample.

Clinical, metabolic parameters, plasma phospholipid FA profiles and indirect measurement of IR (homeostatic model assessment-HOMA) were measured in 734 subjects, 8 weeks following acute coronary syndrome. FA levels and their correlations with IR were compared in subjects with and without MS. MS patients had higher saturated (16:0, 18:0) and n-6 (18:3n-6, 20:3n-6, 22:4n-6, 22:5n-6) FA levels, and lower EPA and DHA levels. HOMA-IR correlated positively with total saturated (r=0.13, P=0.017) and n-6 (r=0.17, P=0.001) FA levels and negatively with total n-3 FA levels (r=-0.13, P=0.012), in MS subjects only. Total n-3 and n-6 FAs and n-6/n-3 ratio were associated with HOMA-IR levels in MS subjects independent of total saturated FA levels, age, sex, sedentary behaviour, smoking, waist circumference, triglycerides, HDL-cholesterol, and systolic blood pressure.

Relationships between polyunsaturated FA type and IR vary according to the presence or absence of MS. N-3 FAs including EPA and DHA are associated with lower HOMA-IR, while the opposite is true for n-6 FAs. Prospective studies are required to address the potential effects of intermediate dose EPA and DHA on glucose handling in MS patients.