Table 3.

Effects of emulsifiers in human studies based on trials restricting emulsifiers or trials of diets restricting emulsifiers as part of other diets.

Study	Design	Participants	Intervention	Outcome
				Tolerance	Disease Activity	Microbiome	Inflammatory Markers
Diets Free of Emulsifiers
Bhattacharyya et al. ref. 42	Randomized, double-blind, placebo-controlled trial	12 CUC	Carrageenan-free diet for 12 months vs carrageenan-containing diet (resupplementation)	3 patients declined further participation due to reluctance to comply with the diet	At the 1-year endpoint, 3/5 patients in the carrageenan-containing diet group relapsed; only 1/7 relapsed in the no-carrageenan diet (p=0.046)	Not measured	At end of study (compared to baseline), there was increase in IL-6 and fecal calprotectin in the carrageenan-containing diet group, but not in the carrageenan-free diet
Sandall et al. ref. 43	Uncontrolled feasibility study	20 Crohn’s in remission	Low emulsifier diet for 2 weeks: ≥75% reduction in frequency of emulsifier intake between baseline and intervention was achieved in 19/20	FR-QOL improved significantly on the low emulsifier diet	Crohn’s disease-related symptoms (measured using the PRO-2 Questionnaire) as well as perceived disease control (assessed by the IBD Control-8 Questionnaire) improved significantly between baseline and the low emulsifier diet.	Not measured	Not measured
Diets Restricting Emulsifiers as Part of Other Diet
Sigall-Boneh et al. ref. 44	Uncontrolled retrospective study	47 children and young adults with active Crohn’s disease (PCDAI >7.5 or HBI ≥4)	CDED plus 50% PEN, or CDED alone for 6 weeks; then an additional 6-week stepdown diet	5 patients were not compliant (2 did not comply at all; 3 complied most of the time, with 2/3 achieving full remission)	Remission occurred in 70% of children and 69% of adults. Seven patients used the diet without PEN, with 6/7 entering remission.	Not measured	Normalization of previously elevated CRP in 70% of patients in remission
Levine et al. ref. 45	Randomized controlled trial	78 children with mild to moderate CD (PCDAI ≥10 and ≤40)	Group 1 (n=40): CDED plus 50% of energy from PEN for 6 wk (stage 1), followed by CDED with 25% PEN from weeks 7 to 12 (stage 2) Group 2 (n=38): EEN for 6 wk, followed by a free diet with 25% PEN from weeks 7 to 12	Combination of CDED and PEN was tolerated by 39 children (97.5%), whereas EEN was tolerated by 28 children (73.6%) (P=0.002)	At week 12, 28 of 37 (75.6%) children given CDED plus PEN were in corticosteroid-free remission compared with 14 of 31 (45.1%) given EEN and then PEN (P=0.01).	CDED plus PEN was associated with reduction of fecal Proteo-bacteria	In children given CDED plus PEN, corticosteroid-free remission was associated with sustained reductions in CRP and fecal calprotectin
Svolos et al. ref. 46	Randomized open-label pilot study	5 children with active Crohn’s disease (PCDAI ≥ 12.5) and 28 healthy adults received CD-TREAT diet for 8 weeks	CD-TREAT restricts components such as gluten, lactose, emulsifiers, fiber, CHO, and alcohol for 8 weeks	In healthy adults, CD-TREAT was easier to comply with than EEN. 4 children completed the 8-wk trial; 1 child withdrew due to symptom exacerbation	4 children (80%) experienced a clinical response and 3 (60%) entered remission	Total fecal bacteria decreased with both diets plus similar changes to β-diversity and fecal bacterial metabolites	Children receiving CD-TREAT had significant decrease in fecal calprotectin (mean change −918±555 mg/kg; P=0.002)

CDED=Crohn’s disease exclusion diet; CD-TREAT=Crohn’s disease TReatment with EATing; CHO=carbohydrates; CRP=C-reactive protein; EEN=exclusive enteral nutrition; FR-QOL=food-related quality of life; HBI=Harvey-Bradshaw Index; IL=interleukin; PCDAI=Pediatric Crohn’s Disease Activity Index; PEN=partial enteral nutrition