Relationship between systemic markers of inflammation and serum β-carotene levels

Background: Low serum levels of β-carotene have been associated with increased risk of cancer and cardiovascular disease. However, in clinical trials, supplementation of the diet with β-carotene either had no benefit or caused harm. This pattern of findings raises the possibility that confounding by other factors might explain the association between serum β-carotene level and disease risk. Methods: We used data from 14470 current smokers, ex-smokers, and never smokers aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey to assess the relationship between serum β-carotene and markers of inflammation (C-reactive protein and white blood cell count). Results: After adjustment for β-carotene intake and other factors, geometric mean levels of serum β-carotene for individuals with undetectable (<0.22 mg/dL), mildly elevated (0.22-0.99 mg/dL), and clinically elevated (≥ 1.0 mg/dL) C-reactive protein levels were 18.0, 16.1, and 13.6 μg/dL, respectively, in never smokers; 18.1, 15.7, and 13.9 μg/dL in ex-smokers; and 11.3, 10.2, and 9.4 μg/dL in current smokers (P<.001 for all). In corresponding analyses, white blood cell count was also inversely related to serum β-carotene concentration (P<.05 for all). Conclusions: The strong and inverse association of serum β-carotene level with C-reactive protein level and white blood cell count suggests that the relationship between serum β-carotene concentration and disease risk might be confounded by inflammation. More broadly, for β-carotene and likely other nutrients, it seems unwise to interpret biomarker data as prima facie evidence of dietary intake without a more complete understanding of the physiologic processes that affect nutrient levels.