Bilirubin as a Protective Factor for Rheumatoid Arthritis: An NHANES Study of 2003 - 2006 Data

Daniel Fischman, Ashok Valluri, Venkata Subhash Gorrepati, Megan E. Murphy, Ian Peters, Pramil Cheriyath


Background: Rheumatoid arthritis(RA) is a chronic inflammatory, autoimmune polyarthritis, with a prevalence estimated at  one percent of the United States(US) population. Serum bilirubin, because of its antioxidant nature, has been conjectured to exert an anti-inflammatory biologic effect. The objective of this study is to discern whether higher serum Total Bilirubin(TBili) levels are protective against RA.

Methods: This is a secondary analysis of  National Health and Nutrition Examination Survey (NHANES) data collected between 2003-2006. Study participants completed a comprehensive questionnaire regarding their health history, underwent a physical examination, and had body fluids collected for laboratory studies. In NHANES, to assess for the presence of RA, the following questions were asked: “Doctor ever said you had arthritis?" If so, “Which type of arthritis”. Statistical analysis was performed, using SAS version 9.1, proc survey methods. Participant data were adjusted for demographic characteristics as well as risk factors for RA.

Results: NHANES 2003-2006 included 20,470 individuals, chosen as a representative sampling of  the entire US population. Exclusion criteria included  age less  than twenty years or liver dysfunction, defined as history of abnormal liver function tests or liver disease.   8,147 subjects did not have any exclusion criteria and were included in the data analysis. RA is inversely related to the serum level of TBili with an odds ratio of 0.679 (95% CI 0.533-0.865) and remained significant even after adjusting for age, gender, race, education, and tobacco history, with an odds ratio 0.749 (95% CI 0.575 - 0.976).

Conclusions: Our study supports the hypothesis that higher TBili levels are protective against RA. A plausible mechanism for this association would be that the anti-oxidant effects of TBili exert a physiologic anti-inflammatory effect, which provides protection against RA. This explanation is supported by prior studies which show that higher TBili levels are protective against stroke, atherosclerosis, and vasculitis.  Further studies are needed to delineate the exact nature of the protective properties of TBili.



Bilirubin; Rheumatoid arthritis ; Antioxidant; Protective

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