CAN BUTYRATE PREVENT COLON CANCER? THE AUSFAP STUDY: A RANDOMISED, CROSS-OVER CLINICAL TRIAL

Background and aims: Butyrate produced by large bowel fermentation of dietary fiber may reduce the risk of colon cancer. Dietary butyrylated high amylose maize starch (HAMSB) delivers butyrate to the colon. This clinical trial evaluated the effects of HAMSB on polyp burden in participants with Familial Adenomatous Polyposis (FAP).
Methods: The study was a double-blind, randomised, placebo-controlled, cross-over trial. Participants were randomly assigned to 2 groups that ingested 40g HAMSB (Ingredion Inc, USA) or low amylose starch (Melogel; Ingredion Inc, USA) for 6 months, followed by the alternative product for 6 months, and then a 6 month washout with no treatment. The participants underwent video-recorded colonoscopies at baseline, 6, 12 and 18 months to assess polyp number and size, and for collection of polyp and mucosal biopsies. At baseline two colonic tattoos were placed: tattoo 1 where polyps were cleared at each scope to assess polyp initiation; and tattoo 2 where polyps were left in situ the entire study, when safe, to assess polyp growth or recession. Global polyp burden was assessed by the CIA, with 2 gastroenterologists independently reviewing polyp burden in tattoo sites. The primary endpoint was the number of colonic polyps. A subset of 14 participants collected faecal samples for analysis.
Results: A total of 72 participants were randomised to sequence (39 male, 33 female) with 49 completing the study. The mean age at baseline was 37.6 years. Generalised linear mixed models were used to estimate the ratio of the mean polyp counts in the intervention period compared to the placebo period. HAMSB did not affect number (0.9-fold reduction, 95% confidence interval, CI: 0.77–1.06), nor size (0.88-fold reduction, 95% CI: 0.71-1.1 for polyps <2.4mm) of colonic polyps. However HAMSB did reduce the mean total polyp count in tattoo 1 (0.72-fold reduction, 95% CI: 0.53-0.98, P=0.037) and tended to reduce the number of small polyps <2.4mm (0.73-fold reduction, 95% CI: 0.51-1.05, P=0.089). Polyp burden in tattoo 2 was not affected by dietary intervention. HAMSB increased mean faecal butyrate concentration compared to LAMS. The average intake of HAMSB provided participants an estimated 20.5 g resistant starch/d and the average intake of LAMS provided 1.8 g resistant starch/d.
Conclusion: This study represents the first clinical evaluation of a novel and cost-effective food supplement in FAP that delivers significant quantities of butyrate to the large bowel. Ingestion of HAMSB reduced the initiation of polyp growth without causing regression or growth of existing polyps. Analysis of tissue biopsies may determine if this effect was due to responses in cellular apoptotic or proliferative pathways to colonic butyrate. The effects of HAMSB have potential to lower the risk of sporadic colorectal cancer in the wider community.