Randomized controlled pilot study: effect of carrageenan emulsifier on inflammation and gastrointestinal symptoms in quiescent ulcerative colitis

Reijo Laatikainen; Markku Lehto; Noora Mäkelä-Salmi; Markku Hillilä; Per-Henrik Groop; Hanne Salmenkari

doi:10.29219/fnr.v67.9575

Reijo Laatikainen Booston Oy Ltd, Helsinki, Finland
Markku Lehto Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
Noora Mäkelä-Salmi Department of Food and Nutrition, University of Helsinki, Helsinki, Finland
Markku Hillilä Clinic of Gastroenterology, University of Helsinki and Helsinki University, Hospital Jorvi, Espoo, Finland
Per-Henrik Groop Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; and Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia
Hanne Salmenkari Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; and Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland

DOI: https://doi.org/10.29219/fnr.v67.9575

Keywords: carrageenan, ulcerative colitis, IBD, inflammatory bowel disease, emulsifier

Abstract

Background: Animal models have provided some evidence of the pro-inflammatory effects of the commonly used emulsifier carrageenan. However, the effects of food-grade carrageenan among people with ulcerative colitis (UC) are largely unknown.

Methods: A randomized, placebo-controlled cross-over study comparing high molecular carrageenan and oat-based beta-glucan preparation (placebo) among patients (n = 7) with quiescent UC was performed. Primary endpoint was Simple Clinical Colitis Activity Index (SCCAI) at the end of the treatment (7th day). Secondary analyses included biochemical biomarkers of inflammation, intestinal permeability, detoxification of intestinal lipopolysaccharide (LPS), and gastrointestinal symptoms measured by visual analog scale.

Results: There were no statistically significant differences in SCCAI or any biochemical markers between carrageenan and placebo periods, nor were there any significant differences when comparing either period to baseline. Gastrointestinal symptoms were higher during the placebo period; the sum of all symptoms and borborygmi was statistically significantly higher at the end of the placebo period than at the end of the carrageenan period (20.8 ± 18.6 vs. 13.3 ± 16.4; P = 0.031, and 29.7 ± 28.6 vs. 17.9 ± 23.6; P = 0.016).

Conclusions: Our study suggests that at least short-term usage of food-grade carrageenan is safe among people with UC, but given the limitations of the current study, robust human studies are still urgently needed.

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References

1.
Jussila A, Virta LJ, Salomaa V, Mäki J, Jula A, Färkkilä MA. High and increasing prevalence of inflammatory bowel disease in Finland with a clear North-South difference. J Crohn’s Colitis 2013; 7(7): e256–62. doi: 10.1016/j.crohns.2013.01.001

2.
Levine A, Sigall Boneh R, Wine E. Evolving role of diet in the pathogenesis and treatment of inflammatory bowel diseases. Gut 2018; 67(9): 1726–38. doi: 10.1136/gutjnl-2017-314968

3.
Baker P, Machado P, Santos T, Sievert K, Backholer K, Hadjikakou M, et al. Ultra-processed foods and the nutrition transition: global, regional and national trends, food systems transformations and political economy drivers. Obes Rev 2020; 21(12): e13126. doi: 10.1111/obr.13126

4.
Albenberg L, Brensinger CM, Wu Q, Gilroy E, Kappelman MD, Sandler RS, et al. A diet low in red and processed meat does not reduce rate of Crohn’s disease flares. Gastroenterology 2019; 157(1): 128–36.e5. doi: 10.1053/j.gastro.2019.03.043

5.
Wedlake L, Slack N, Andreyev HJ, Whelan K. Fiber in the treatment and maintenance of inflammatory bowel disease: a systematic review of randomized controlled trials. Inflamm Bowel Dis 2014; 20(3): 576–586. doi: 10.1097/01.MIB.0000440919.02606.f1

6.
Marion-Letellier R, Amamou A, Savoye G, Ghosh S. Inflammatory bowel diseases and food additives: to add fuel on the flames! Nutrients 2019; 11(5): 1111. doi: 10.3390/nu11051111

7.
McKim JM. Food additive carrageenan: Part I: a critical review of carrageenan in vitro studies, potential pitfalls, and implications for human health and safety. Crit Rev Toxicol 2014; 44(3): 211–43. doi: 10.3109/10408444.2013.859292

8.
EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Re-evaluation of carrageenan (E 407) and processed Eucheuma seaweed (E 407a) as food additives. EFSA J 2018; 16(4): e05238. doi: 10.2903/j.efsa.2018.5238

9.
Chazelas E, Druesne-Pecollo N, Esseddik Y, De Edelenyi FS, Agaesse C, De Sa A, et al. Exposure to food additive mixtures in 106,000 French adults from the NutriNet-Santé cohort. Sci Rep 2021; 11(1): 19680.

10.
Watt J, Marcus R. Experimental ulcerative disease of the colon in animals. Gut 1973; 14(6): 506–510. doi: 10.1136/gut.14.6.506

11.
Yin Y, Li M, Gu W, Zeng B, Liu W, Zhu L, et al. Carrageenan oligosaccharides and associated carrageenan-degrading bacteria induce intestinal inflammation in germ-free mice. J Genet Genomics 2021; 48(9): 815–24. doi: 10.1016/j.jgg.2021.07.002

12.
Bhattacharyya S, Shumard T, Xie H, Dodda A, Varady KA, Feferman L, et al. A randomized trial of the effects of the no-carrageenan diet on ulcerative colitis disease activity. Nutr Healthy Aging 2017; 4(2): 181–92. doi: 10.3233/NHA-170024

13.
Bancil AS, Sandall AM, Rossi M, Chassaing B, Lindsay JO, Whelan K. Food additive emulsifiers and their impact on gut microbiome, permeability, and inflammation: mechanistic insights in inflammatory bowel disease. J Crohns Colitis 2021; 15(6): 1068–79. doi: 10.1093/ecco-jcc/jjab036

14.
Walmsley RS, Ayres RC, Pounder RE, Allan RN. A simple clinical colitis activity index. Gut 1998; 43(1): 29–32. doi: 10.1136/gut.43.1.29

15.
Lin L, Wyness SP, Jensen R, Bird J, Norgyal T, Jensen G, et al. Comparison of next-generation assays for fecal calprotectin vs the PhiCal assay. Am J Clin Pathol 2022; 157(2): 252–6. doi: 10.1093/ajcp/aqab017

16.
Lassenius MI, Fogarty CL, Blaut M, Haimila K, Riittinen L, Paju A, et al. Intestinal alkaline phosphatase at the crossroad of intestinal health and disease – a putative role in type 1 diabetes. J Intern Med 2017; 281(6): 586–600. doi: 10.1111/joim.12613

17.
Thies F, Masson LF, Boffetta P, Kris-Etherton P. Oats and bowel disease: a systematic literature review. Br J Nutr 2014; 112(suppl 2): S31–S43. doi: 10.1017/S0007114514002269

18.
Hallert C, Björck I, Nyman M, Pousette A, Grännö C, Svensson H. Increasing fecal butyrate in ulcerative colitis patients by diet: controlled pilot study. Inflamm Bowel Dis 2003; 9(2): 116–21. doi: 10.1097/00054725-200303000-00006

19.
Ispiryan L, Kuktaite R, Zannini E, Arendt EK. Fundamental study on changes in the FODMAP profile of cereals, pseudo-cereals, and pulses during the malting process. Food Chem 2021; 343: 128549. doi: 10.1016/j.foodchem.2020.128549

20.
Laito S, Valkonen N, Laaksonen O, Kalliomäki M, Tuure T, Linderborg KM. Effect of oat or rice flour on pulse-induced gastrointestinal symptoms and breath hydrogen in subjects sensitive to pulses and controls – a randomised cross-over trial with two parallel groups. Br J Nutr 2022; 128(11): 2181–92. doi: 10.1017/S0007114522002020

21.
Adolph TE, Zhang J. Diet fuelling inflammatory bowel diseases: preclinical and clinical concepts. Gut 2022; 71(12): 2574–86. doi: 10.1136/gutjnl-2022-326272

22.
Sandall AM, Cox SR, Lindsay JO, Gewirtz AT, Chassaing B, Rossi M, et al. Emulsifiers impact colonic length in mice and emulsifier restriction is feasible in people with Crohn’s disease. Nutrients 2020; 12(9): 2827. doi: 10.3390/nu12092827