Association Between Adiposity and Low Total Serum Bilirubin Concentration: A Retrospective, Cross‐Sectional Study

Background and Aims: Bilirubin, an antioxidant and anti-inflammatory agent, has been shown to negatively correlate with adiposity. However, the extent to which adiposity level influences total bilirubin (TBili) concentration remains unclear. We sought to evaluate the associations of body mass index (BMI; kg/m²) and waist circumference (WC) with low TBili concentration. Methods: We included adults ≥ 20 years of age without elevated liver enzymes, excess alcohol use, iron overload, anemia, TBili ≥ 1.2 mg/dL, low albumin, or positive hepatitis serology from the 1999-2018 National Health and Nutrition Examination Survey. The primary outcome was low TBili, defined as < 0.4 mg/dL. We used multivariable logistic regression to determine the odds ratios of low TBili by BMI and WC categories, stratified by gender. We additionally explored associations between past 1-year, maximum lifetime, and non-linear continuous BMI on low TBili. Results: Among 13,953 participants (mean age 47.3 years, 49% men, 69% non-Hispanic White), 17% were ≥ 65 years, 32% had BMI ≥ 30, and 12% had low TBili. Women with a BMI ≥ 27.5 had at least a 42% increased odds of low TBili compared to women with a BMI ≥ 23 and < 25. Women with a normal BMI but elevated WC of ≥ 88 cm had increased odds of low TBili (OR: 2.74 [1.61-4.66]) than those with a normal WC. A BMI 1 year prior to survey ≥ 35 (OR: 1.59 [1.05-2.40]) and lifetime maximum BMI ≥ 25 (OR: 1.60 [1.13-2.28]) were independently associated with low TBili in women. Similar point estimates, but no significant associations were found in men. Conclusion: Elevated BMI and an elevated WC but normal BMI were associated with higher likelihood of low TBili in women, potentially reflecting a consequence or indirect biomarker of clinical obesity. Further studies should determine the long-term impact of low TBili on cardiometabolic disease risk and mortality.