Is the Relationship Between Serum β-carotene and Cardiovascular Disease (CVD) Risk Confounded by Inflammation?
Background: In observational studies, low serum β-carotene levels have been associated with an increased risk of CVD and cancer. However, in clinical trials, supplementation of diet with β-carotene has had no benefit. This pattern of findings raises the possibility that confounding with other factors may explain the association of serum β-carotene with disease risk. Objective: To determine the association between serum β-carotene levels and markers of inflammation. Setting: 14,470 participants, ages 17 years and older, in NHANES III. Results: In multivariate models that adjusted for β-carotene intake and other factors associated with serum β-carotene, the geometric means of serum β-carotene for those with undetectable (<0.22 mg/dl), mildly elevated (0.22-0.99 mg/dl) and clinically elevated (≥ 1.0 mg/dl) CRP were 18.0, 16.1 and 13.6 μg/dl in never smokers (P-value for trend < 0.001), 18.1, 15.7 and 13.9 μg/dl in ex-smokers (P-value for trend < 0.001), and 11.3, 10.2 and 9.4 ìg/dl in current smokers (P-value for trend < 0.001). In corresponding analyses, WBC count was inversely related to serum β-carotene (P-value for trend <0.05 in each group). Conclusions: Serum β-carotene is strongly and inversely related to systemic inflammation. These results suggest that the relationship between serum β-carotene and disease risk is confounded by inflammation, which itself is a risk factor for CVD and perhaps cancer. More broadly, these results highlight the potential limitations of using serum nutrient levels as a surrogate for dietary intake.