A randomized trial of the effects of the no-carrageenan diet on ulcerative colitis disease activity

Abstract

BACKGROUND: Carrageenan is a very common food additive in Western diets, but predictably causes inflammation in thousands of cell-based and animal experiments. OBJECTIVE: To assess the impact of carrageenan exposure on the interval to relapse in patients with ulcerative colitis in remission. METHODS: A randomized, double-blind, placebo-controlled, multicenter, clinical trial was conducted to assess if patients with ulcerative colitis in remission would have a longer interval to relapse if they followed a diet with no carrageenan. All participants were instructed in the no-carrageenan diet and were randomized to either placebo capsules or carrageenan-containing capsules. The carrageenan in the capsules was less than the average daily carrageenan intake from the diet. Relapse was defined as an increase of two or more points on the Simple Clinical Colitis Activity Index (SCCAI) and intensification of treatment for ulcerative colitis. Participants were followed by telephone calls every two weeks until relapse or one year of participation. The occurrence of relapse and inflammatory biomarkers were compared between the two groups. RESULTS: Twelve patients completed study questionnaires. Three patients who received carrageenan-containing capsules relapsed, and none of the patients who received placebo-containing capsules relapsed (p = 0.046, log-rank test). Laboratory tests showed increases in Interleukin-6 (p = 0.02, paired t-test, two-tailed) and fecal calprotectin (p = 0.06; paired t-test, two-tailed) between the beginning and the end of study participation in the carrageenan-exposed group, but not in the placebo-group. CONCLUSION: Carrageenan intake contributed to earlier relapse in patients with ulcerative colitis in remission. Restriction of dietary carrageenan may benefit patients with ulcerative colitis.

Keywords: Colitis; Interleukin-6; carrageenan; food additive; inflammation.

Fig.1

Study flow diagram. This flow chart presents the number of subjects approached in enrollment, the number of subjects allocated to carrageenan or placebo capsules, and the number of participants in follow-up and analysis. Group 1 received the carrageenan-containing capsules, and Group 2 received similar-appearing placebo capsules.

Fig.2

Average SCCAI and SIBDQ scores for placebo and carrageenan-supplemented groups. (A) Mean SCCAI scores were similar for both groups at the onset of study participation. At the conclusion of participation, SCCAI scores were higher in the carrageenan-supplemented group, consistent with the occurrence of relapses in this group. Mean SCCAI scores at the endpoints were 0.86±1.46 (n = 7), compared to 4.20±3.70 in the group who received carrageenan supplements (p = 0.05, unpaired t-test, two-tailed, n = 5). (B) Initial and final scores on the SIBDQ were similar in both groups, with mean values of 63.6±5.6 at onset and 63.3±4.3 at conclusion in the placebo group (n = 7). In the carrageenan- supplemented group (n = 5), initial mean score was 59.0±5.2, and final average score was 61.6±6.5.

Fig.3

Kaplan-Meier curves comparing the carrageenan-supplemented group (Group 1) and the placebo group (Group 2). Kaplan-Meier curves indicate significant differences between the two study groups. Three dropouts in the control group occurred, at 5, 10, and 39 weeks. Relapses in the carrageenan supplement group occurred at 5, 32, and 42 weeks.

Fig.4

Scatterplot of fecal calprotectin and Interleukin-6. (A) The initial and final values for fecal calprotectin are shown in the scatterplot by placebo controls and carrageenan-exposed participants. Two of the controls and four of the carrageenan-exposed subjects had increases (p = 0.06 for carrageenan-exposed group, paired t-test, two-tailed; n = 5). (B) Interleukin-6 values for the study subjects increased in all of the carrageenan-exposed participants and in one of the control subjects (p = 0.02 for carrageenan-exposed group, paired t-test, two-tailed; n = 5).