Circulating Bile Acids and Adenoma Recurrence in the Context of Strict Adherence to a High-Fiber, High-Fruit and -Vegetable, and Low-Fat Dietary Intervention

OBJECTIVES: Diet may affect BA metabolism and signaling, and, in turn, chronically higher bile acid (BA) concentrations may be associated with colorectal cancer risk. Further evidence regarding these interrelationships among human populations is needed. Therefore, we investigated 1) the effect of strict adherence to a high-fiber, high-fruit and -vegetable, low-fat dietary intervention on serum BA concentrations; and 2) associations of BA concentrations with adenoma recurrence. METHODS: The Polyp Prevention Trial is a 4-year randomized dietary intervention that investigated the effect of a high-fiber, high-fruit and vegetable, and low-fat diet on colorectal adenoma recurrence. We used targeted, quantitative liquid chromatography–tandem mass spectrometry panels to measure 13 BAs in serially collected serum at baseline, year-2, and year-3 of the trial among 170 intervention participants who strictly adhered to the intervention and 198 comparable control arm participants. We estimated the effect of the dietary intervention on mean year-2 and year-3 BA concentrations using repeated-measures linear mixed-effects models. We estimated associations of BA concentrations with adenoma recurrence 3–4 years after baseline using multivariable logistic regression. We estimated temporal variability of BA concentrations over 3 years using intraclass correlation coefficients (ICCs). RESULTS: We found no effects of the high-fiber, high-fruit and -vegetable, low-fat diet intervention on serum BA concentrations; however, pre-trial dietary fiber intake was inversely associated with total BAs (Spearman = −0.15; P(FDR)( )= 0.03). Baseline total BA concentrations were positively associated with adenoma recurrence (OR(Q3 vs. Q1 )= 2.17; 95% CI = 1.19–4.04; P-trend(FDR)( )= 0.05). These findings were inconsistent when considering BA concentrations at year-2 and year-3, potentially reflecting our findings of moderate temporal stability of BAs over 3 years (ICC for total BAs = 0.53; 95% CI = 0.46–0.59) and underlying changes in adenoma status across the follow-up period. CONCLUSIONS: A high-fiber, high-fruit and -vegetable, low-fat diet may not modify serum BA concentrations; however, BAs concentrations may be positively associated with risk of adenoma recurrence. FUNDING SOURCES: Intramural Research Program, National Cancer Institute, NIH.