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Thomas P. Erlinger, MD, MPH; Eliseo Guallar, MD, DrPH; Edgar R. Miller III, MD, PhD; Rachael Stolzenberg-Solomon, PhD, RD; Lawrence J. Appel, MD, MPH

Arch Intern Med. 2001;161:1903-1908.

Background  Low serum levels of ß-carotene have been associated with increased risk of cancer and cardiovascular disease. However, in clinical trials, supplementation of the diet with ß-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 ß-carotene level and disease risk.

Methods  We used data from 14 470 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 ß-carotene and markers of inflammation (C-reactive protein and white blood cell count).

Results  After adjustment for ß-carotene intake and other factors, geometric mean levels of serum ß-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 ß-carotene concentration (P<.05 for all).

Conclusions  The strong and inverse association of serum ß-carotene level with C-reactive protein level and white blood cell count suggests that the relationship between serum ß-carotene concentration and disease risk might be confounded by inflammation. More broadly, for ß-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.

From the Welch Center for Prevention, Epidemiology, and Clinical Research (Drs Erlinger, Guallar, Miller, and Appel) and the Departments of Medicine (Drs Erlinger, Miller, and Appel) and Epidemiology (Drs Guallar and Appel), Johns Hopkins Medical Institutions, Baltimore, Md; and the National Cancer Institute, National Institutes of Health, Bethesda, Md (Dr Stolzenberg-Solomon).

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