Therapeutic Potential of the 4 Strategies to SUlfide-REduction (4-SURE) Diet in Adults with Mild to Moderately Active Ulcerative Colitis: An Open-Label Feasibility Study

Abstract

Background Diet therapy may bridge the therapeutic gap in ulcerative colitis (UC). Objectives The novel 4-SURE diet (4-strategies-to-SUlfide-REduction), designed to modulate colonic fermentation and influence production of excess hydrogen sulfide, was examined in a feasibility study for tolerability, clinical efficacy and effects on microbial end-points. Design Adults ≥ 18 years old with mild to moderately active UC were advised to increase intake of fermentable fibers, restrict total and sulfur-containing proteins and avoid specific food additives for 8-weeks. The primary outcome was tolerability of diet (100-mm visual analogue scale (VAS) with 100-mm being intolerable). Secondary exploratory outcomes were self-reported adherence (always adherent ≥ 76–100%), clinical and endoscopic response (reduction in partial Mayo ≥ 2 and Mayo endoscopic sub-score ≥ 1), modulation of fecal characteristics including markers of protein and carbohydrate fermentation, and food-related quality of life (IBD-FRQoL-29). Primary analysis was by intention to treat, performed using paired t and Wilcoxon signed-rank statistical tests. Results 28 adults with UC, mean age 42 (range 22–72) years, 15 female, 3 proctitis, 14 left-sided and 11 extensive, were studied. Prescribed dietary targets were achieved overall. The diet was well tolerated (VAS: 19 mm; 95% CI 7, 31 mm) with 95% frequently or always adherent. Clinical response occurred in 13/28 (46%) and endoscopic improvement in 10/28 (36%). Two (7%) worsened. Fecal excretion of short-chain fatty acids (SCFA) increased by 69% (p < 0.0001) while the proportion of branched-chain to SCFA were suppressed by 27% (-1.34%; 95% CI: -2.28, -0.40; p = 0.007). FRQoL improved by 10 points (95% CI: 4, 16; p < 0.001). Conclusions The 4-SURE dietary strategy is considered tolerable and an acceptable diet by adults with mild to moderately active UC. The dietary teachings achieved the prescribed dietary and fecal targets. Given signals of therapeutic efficacy, further evaluation of this diet is warranted in a placebo-controlled trial. Trial registration number: Australian New Zealand Clinical Trials Registry ACTRN12619000063112.

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“…Lastly, the 4-SURE diet (4-strategies-to-SUlfide-REduction) designed to modulate colonic fermentation and influence production of excess hydrogen sulfide in UC showed endoscopic improvement, an increase in stool short chain fatty acids and an increase in food-related QoL 74. Since this was an uncontrolled feasibility trial, these promising results need further confirmation in an RCT as well.…”

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“…These results are promising, but comparing this low-emulsifier diet with a control diet in a larger clinical trial is necessary to rule out a placebo-effect. Another dietary intervention feasibility study advised 28 adults with UC to increase their intake of fibers, restrict total and sulfur-containing proteins, and avoid specific food additives, including CGN, for 8 weeks ( 53 ). The dietary intervention achieved clinical improvement in 46% of the participants, endoscopic improvement in 36% of the participants, and improvement in quality of life in 43% of the participants.…”

Impact of diet on hydrogen sulfide production: implications for gut health

“…Two recent studies provide useful insights into the effects of diet on H 2 S production and the inflammatory activity of ulcerative colits in adults (median age of participants in both studies was 42 years) [10 ▪▪ ,24]. The 4-SURE study was an 8-week open-label trial aimed primarily at determining diet tolerability with secondary outcomes assessing clinical response and microbial metabolites, including SCFAs, in patients with mild-to-moderately active ulcerative colits [10 ▪▪ ]. No H 2 S-specific variables were captured, but the 4-SURE diet targeted a lower H 2 S production through an increased fiber intake (10–15 g/day of resistant starch and 5 g/day slowly fermentable nonstarch polysaccharide), moderate protein intake (≤1.2 g/kg/day total protein and ≤1.5–2.0 g/day sulfur-containing amino acids), and avoidance of specific food additives (sulfite/sulfate, nitrite/nitrate, and carrageenan).…”

“…Two recent studies provide useful insights into the effects of diet on H 2 S production and the inflammatory activity of ulcerative colits in adults (median age of participants in both studies was 42 years) [10 ▪▪ ,24]. The 4-SURE study was an 8-week open-label trial aimed primarily at determining diet tolerability with secondary outcomes assessing clinical response and microbial metabolites, including SCFAs, in patients with mild-to-moderately active ulcerative colits [10 ▪▪ ].…”

“…In the colon, microbiota-generated H 2 S is capable of stimulating colonic muscle contractions [7] and can have anti-inflammatory effects [8]. However, excess quantities of H 2 S can negatively impact the integrity of the intestinal barrier [9] and contribute to the development of ulcerative colitis [10 ▪▪ ] and early onset colorectal cancer [11]. The amount of H 2 S produced in the intestine is dependent on nutrient flow to the gut microbiota, as well as its metabolic potential.…”