BACKGROUND:

Inflammatory mediators regulate key aspects of lipid metabolism. We hypothesized that inflammation could diminish the cholesterol-lowering effect of a reduced-fat/low-cholesterol diet.

METHODS AND RESULTS:

After a 2-week run-in period on a control diet (37% total fat, 16% saturated fat), 100 participants were randomized to the control or DASH diet (27% total fat, 6% saturated fat) for 12 weeks. Median C-reactive protein (CRP) at baseline was 2.37 mg/L (interquartile range, 1.20, 3.79). The DASH diet, net of control, had no effect on CRP. Overall, there were significant net reductions in total (-0.34 mmol/L), LDL (-0.29 mmol/L), and HDL (-0.12 mmol/L) cholesterol from the DASH diet (each, P<0.001) and little change in triglycerides (+0.05 mmol/L, P=0.21). Baseline CRP was strongly associated with lipid responsiveness to the DASH diet. Total and LDL cholesterol were reduced to a greater degree in those with a "low" (below median) compared with a "high" (above median) baseline CRP (total, -9.8% versus -3%; P for interaction=0.006; LDL cholesterol, -11.8% versus -3%; P for interaction=0.009). Reductions in HDL cholesterol (-8.8%) were similar in persons with low versus high CRP. Triglycerides were increased in those with a high CRP but not in those with a low CRP (19.8% versus +0%; P for interaction=0.019).

CONCLUSIONS:

In this study, the presence of increased CRP was associated with less total and LDL cholesterol reduction and a greater increase in triglycerides from a reduced-fat/low-cholesterol diet. These findings document an additional mechanism by which inflammation might increase cardiovascular disease risk.