Emulsifiers and the gut barrier

References

1. Independent research

   Sellem L, Srour B, Javaux G, Chazelas E, Chassaing B, Viennois E, et al. Food additive emulsifiers and risk of cardiovascular disease in the NutriNet-Santé cohort: prospective cohort study BMJ, 2023.

   doi:10.1136/bmj-2023-076058PubMed 37673430

   Funding and finding

   Registration

   NCT03335644

   Participants

   95,442

   Follow-up

   median 7.4 years

   Funding

   NutriNet-Santé: Ministère de la Santé, Santé Publique France, INSERM, INRAE, Conservatoire National des Arts et Métiers and University Sorbonne Paris Nord. Project: European Research Council (grant agreement 864219), French National Cancer Institute (INCa_14059), French Ministry of Health, IdEx Université de Paris (ANR-18-IDEX-0001) and a Bettencourt-Schueller Foundation research prize 2021. Researchers were independent from funders. The funders had no role in the design; collection, analysis, and interpretation of data; writing of the report; and decision to submit the article for publication.

   Finding

   1995 cardiovascular events over 666,509 person-years. Hazard ratios per 1 SD of intake: total celluloses (E460-E468) 1.05 (95% CI 1.02 to 1.09) for cardiovascular disease and 1.07 (1.02 to 1.12) for coronary heart disease; carboxymethylcellulose (E466, SD 32.0 mg/day) 1.03 (1.01 to 1.05) and 1.04 (1.02 to 1.06); total mono- and diglycerides of fatty acids (E471 and E472) 1.07 (1.04 to 1.11) for cardiovascular disease. Supplementary eTable2: total mono- and diglycerides of fatty acids (E471, E472, E472a, E472b, E472c and E472e; SD 287.5 mg/day) 1.07 (1.04 to 1.11), 1.08 (1.03 to 1.14) for coronary heart disease and 1.07 (1.01 to 1.13) for cerebrovascular disease; E471 alone (SD 208.6 mg/day) 1.03 (0.98 to 1.09), P = 0.2, for cardiovascular disease, and 1.03 (0.96 to 1.11) for coronary heart disease and for cerebrovascular disease. E471 was consumed by 81.6%, mean 161.2 mg/day. Diphosphates (E450) were consumed by 72.6%, mean 244.5 (SD 338.2) mg/day; eTable2 hazard ratios per SD (349.7 mg/day) were 0.99 (0.93 to 1.04) for cardiovascular disease, 0.96 (0.89 to 1.04) for coronary heart disease and 1.01 (0.93 to 1.09) for cerebrovascular disease. Trisodium phosphate (E339) was associated with coronary heart disease, 1.06 (1.00 to 1.12) per SD (58.4 mg/day), P = 0.03, not significant after correction for multiple testing (adjusted P = 0.3). Carrageenans and lecithins were not associated. Mean E466 intake 3.8 mg/day, consumed by 10.8%; E433 consumed by 1.1% and not analysed individually. Absolute risks by intake level are not reported.

2. Regulator

   EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), Younes M, Aggett P, Aguilar F, Crebelli R, Dusemund B, et al. Re-evaluation of mono- and di-glycerides of fatty acids (E 471) as food additives EFSA Journal, 2017.

   doi:10.2903/j.efsa.2017.5045PubMed 32625340

   Funding and finding

   Funding

   European Food Safety Authority; requestor: European Commission.

   Finding

   Mono- and diglycerides are very likely hydrolysed by gastrointestinal lipases to glycerol and fatty acids. No need for a numerical ADI and no safety concern at reported uses. At mean exposure E 471 supplies 0.8 to 3.5% of the recommended daily fat intake of adults. Specific studies of E 471 and the gut microbiota were not available. Monoglycerides and diglycerides are esters of glycerol in which one or two hydroxyl groups are esterified with a long-chain fatty acid; the JECFA definition states that E 471 is usually manufactured by glycerolysis of edible fats and oils but may also be prepared by esterification of fatty acids with glycerol, and glycerolysis of natural or hydrogenated fats and oils runs at 200 to 250 °C under alkaline catalysis. In Mintel's GNPD, E 471 was labelled on 33,090 EU food and beverage products in 2012 to 2017, mainly chilled desserts, edible ices, bread and bread products, sandwiches, baking ingredients and mixes, pasta and margarines, and on up to about 75% of dairy ice cream and frozen yoghurt. E 471 is authorised in Group I and at quantum satis in 77 of 84 food categories. Rats absorbed 97.8 ± 0.4% of cottonseed-oil monoglycerides, and in a model digestive system 1,3-diolein was nearly completely hydrolysed to free fatty acids. Glycidyl esters form mainly from diglycerides when vegetable oils are heated above 200 °C and are hydrolysed in the gastrointestinal tract to free glycidol, classified as probably carcinogenic to humans (IARC 2A) and as genotoxic and carcinogenic by the EFSA CONTAM Panel. Chronic studies of diacylglycerol oil at up to 7,800 mg/kg bw per day in mice and 2,000 mg/kg bw per day in rats showed no carcinogenic potential. JECFA established an ADI 'not limited' in 1973. Mean adult exposure in the non-brand-loyal scenario was 10 to 26 mg/kg bw per day. The Panel recommended specification limits for toxic elements, glycerol impurities, residual solvents, trans fatty acids, glycidyl esters and erucic acid, and more data on 3-MCPD and glycidyl esters.

3. Regulator

   EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), Mortensen A, Aguilar F, Crebelli R, Di Domenico A, Frutos MJ, et al. Re-evaluation of lecithins (E 322) as a food additive EFSA Journal, 2017.

   doi:10.2903/j.efsa.2017.4742PubMed 32625454

   Funding and finding

   Funding

   European Food Safety Authority; requestor: European Commission.

   Finding

   Phosphatidylcholine is absorbed intact or as lysophosphatidylcholine or choline after intestinal hydrolysis; dietary lecithins are hydrolysed by phospholipases to liberate choline. No need for a numerical ADI and no safety concern at reported uses, including for choline from lecithins. Lecithins (E 322) are used as emulsifying and stabilising agents of water-oil/fat mixtures in a wide range of foods. Identity: lecithins (E 322) are mixtures or fractions of phosphatides obtained by physical procedures from animal or vegetable foodstuffs, including hydrolysed products; JECFA treats lecithin (INS 322i) and partially hydrolysed lecithin (INS 322ii) as separate additives with distinct specifications; the main source is soya bean oil, with cottonseed, maize, sunflower, rapeseed and egg yolk of minor importance; JECFA set no numerical ADI (ADI 'not limited') in 1974. Food-grade lecithin from soya or other sources contains about 60% phospholipids and 40% triglycerides, sterols and carbohydrates; the phospholipid composition of soya bean lecithin on an oil-free basis is 21% phosphatidylcholine, 22% phosphatidylethanolamine, 19% phosphatidylinositol, 10% phosphatidic acid, 1% phosphatidylserine and 12% glycolipids, while 31P-NMR data from the European Lecithin Manufacturers Association give 12.69 to 22.23% phosphatidylcholine for liquid and de-oiled soya lecithin. Choline that can theoretically be released is 13.2% for phosphatidylcholine with two linoleate groups and up to 3.38% for commercial lecithins. Authorisation: Group I additive at quantum satis in most food categories, among them cocoa and chocolate products, bread and rolls, and fine bakery wares; 30,000 mg/kg in fats and oils essentially free from water; 1,000 mg/L in infant and follow-on formulae and in the corresponding foods for special medical purposes; 10,000 mg/kg in processed cereal-based and baby foods and other foods for young children. Bread and rolls and fine bakery wares were the largest contributors to exposure in most surveys for all groups above infancy, and formulae in infants. Refined brand-loyal mean exposure ranged from 7 mg/kg body weight per day in adolescents to 82 mg/kg bw per day in children, with 95th percentiles of 15 to 187; dietary lecithin from the regular diet is about 1 to 5 g/day, 14 to 71 mg/kg bw per day for a 70 kg adult. On trimethylamine, the Panel states that high doses of choline cause a fishy body odour through excretion of trimethylamine formed by bacterial action, but that lecithin does not present that risk because intestinal bacteria in general cannot cleave the esters and hence do not form major amounts of trimethylamine from choline, citing Zeisel et al. (1983) as cited in IOM (1998). Toxicology: no concern for genotoxicity; no adverse effects in chronic or carcinogenicity studies in rats up to 3,750 mg/kg bw per day; no reproductive toxicity study available; indications of altered brain development at 5% soya lecithin and above in the diet during gestation, lactation and post-weaning, in studies of limited relevance, for which a study to OECD TG 426 was recommended. The opinion does not assess trimethylamine N-oxide and cites no study of lecithins with cardiovascular outcomes.

4. Regulator

   EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), Younes M, Aggett P, Aguilar F, Crebelli R, Di Domenico A, et al. Re-evaluation of celluloses E 460(i), E 460(ii), E 461, E 462, E 463, E 464, E 465, E 466, E 468 and E 469 as food additives EFSA Journal, 2018.

   doi:10.2903/j.efsa.2018.5047PubMed 32625652

   Funding and finding

   Funding

   European Food Safety Authority; requestor: European Commission.

   Finding

   Modified celluloses, including sodium carboxymethylcellulose (E 466), are not absorbed intact, not fermented and are excreted intact in faeces. No need for a numerical ADI and no safety concern at reported uses; indicative total exposure of 660 to 900 mg/kg bw per day for all celluloses. The Panel noted that microbiota and inflammation endpoints reported in mice (Chassaing et al., 2015) are not systematically studied in guideline toxicity studies.

5. Regulator

   EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), Younes M, Aggett P, Aguilar F, Crebelli R, Filipič M, et al. Re-evaluation of carrageenan (E 407) and processed Eucheuma seaweed (E 407a) as food additives EFSA Journal, 2018.

   doi:10.2903/j.efsa.2018.5238PubMed 32625873

   Funding and finding

   Funding

   European Food Safety Authority; requestor: European Commission.

   Finding

   Carrageenan, sulphated galactose and 3,6-anhydrogalactose polysaccharides, is not absorbed intact; 98 to 100% of high molecular weight carrageenan is excreted in faeces in several species. Poligeenan (weight-average 10 to 20 kDa) is not an authorised food additive. The existing group ADI of 75 mg/kg bw per day was made temporary, with the database to be improved within 5 years; brand-loyal 95th percentile exposure exceeded it by up to about 10-fold. Uncertainties included the low molecular weight fraction and the relevance for existing inflammatory bowel disease.

6. Regulator

   EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Scientific Opinion on the re-evaluation of polyoxyethylene sorbitan monolaurate (E 432), polyoxyethylene sorbitan monooleate (E 433), polyoxyethylene sorbitan monopalmitate (E 434), polyoxyethylene sorbitan monostearate (E 435) and polyoxyethylene sorbitan tristearate (E 436) as food additives EFSA Journal, 2015.

   doi:10.2903/j.efsa.2015.4152PubMed 42109790

   Funding and finding

   Funding

   European Food Safety Authority; on request from the European Commission.

   Finding

   Group ADI 25 mg/kg bw per day for polysorbates, from a NOAEL of 2500 mg/kg bw per day in a long-term rat study and an uncertainty factor of 100; toddler exposure in the highest non-brand-loyal scenario 24.5 mg/kg bw per day. The fatty acid ester bond is hydrolysed in the gastrointestinal tract and the fatty acids are metabolised like dietary fatty acids; only small amounts of polyoxyethylene sorbitans are absorbed. In four volunteers given 4.5 g polysorbate 80 per day, 90 to 97% of the polyoxyethylene moiety was recovered in faeces and 2.3 to 3.1% in urine. The 1% dose of Chassaing et al. (2015) was taken as equivalent to 1500 mg/kg bw per day.

7. Independent research

   Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria Proceedings of the National Academy of Sciences of the United States of America, 2008.

   doi:10.1073/pnas.0803124105PubMed 18806221

   Funding and finding

   Funding

   Swedish Research Council Grants 7461, 8646 and 20680, the Swedish Cancer Foundation, the Swedish Foundation for Strategic Research-Mucosal Immunobiology and Vaccine Center, and the IngaBritt and Arne Lundberg Foundation.

   Finding

   Mouse colonic mucus extended about 150 µm above the epithelium in two layers: a loose outer layer of about 100 µm that could be aspirated, and a firmly adherent inner layer about 25 µm thick after fixation. Fluorescence in situ hybridisation with a 16S rRNA probe detected bacteria in the outer layer and none in the inner stratified layer; both layers require Muc2.

8. Independent research

   Chassaing B, Compher C, Bonhomme B, Liu Q, Tian Y, Walters W, et al. Randomized controlled-feeding study of dietary emulsifier carboxymethylcellulose reveals detrimental impacts on the gut microbiota and metabolome Gastroenterology, 2022.

   doi:10.1053/j.gastro.2021.11.006PubMed 34774538

   Funding and finding

   Registration

   NCT03440229

   Participants

   16

   Follow-up

   11 days of intervention (14 days for the first 3 participants)

   Funding

   National Institutes of Health grants DK115180, 5UL1TR001878 and P30-DK050306, and the Max Planck Society; laboratory support from the European Research Council, IdEx Université de Paris, the Kenneth Rainin Foundation, the French Research Agency, INSERM and the USDA National Institute of Food and Agriculture. The funders had no role in the design of the study and data collection, analysis and interpretation, or in manuscript writing.

   Finding

   Double-blind: an emulsifier-free diet (n = 9) or the same diet with 15 g/day carboxymethylcellulose (n = 7), given in brownies and sorbet. Carboxymethylcellulose modestly increased postprandial abdominal discomfort (P = 0.019), shifted microbiota composition with lower diversity and lower relative abundance of Faecalibacterium prausnitzii, and depleted faecal short-chain fatty acids and free amino acids; faecal lipocalin-2, serum cytokines and appetite did not change. Microbiota encroachment into the inner mucus layer appeared in 2 of 7 versus 0 of 9 participants (P = 0.175).

9. Independent research

   Fitzpatrick JA, Gibson PR, Taylor KM, Anderson EJ, Friedman AB, Ardalan ZS, et al. Clinical trial: the effects of emulsifiers in the food supply on disease activity in Crohn's disease: an exploratory double-blinded randomised feeding trial Alimentary Pharmacology & Therapeutics, 2025.

   doi:10.1111/apt.70041PubMed 39967287

   Funding and finding

   Registration

   ACTRN12619001099112

   Participants

   24

   Follow-up

   4 weeks

   Funding

   This work was supported by JAF receiving the Crohn's and Colitis Australia PhD Scholarship. EPH was supported through research grants from the National Health & Medical Research Council Investigator Grant and Crohn's and Colitis Foundation Litwin Pioneers Program. The study was supported by a grant from the Eva and Tom Breuer Foundation.

   Finding

   High-emulsifier versus low-emulsifier diet, both following Australian healthy eating guidelines, with all food provided. Clinical remission (Harvey-Bradshaw Index below 5) in 9 of 12 versus 7 of 12 (P = 0.67); IBUS-SAS fell on both diets; faecal calprotectin did not change; no outcome differed between diets.

10. Independent research

    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 Nutrition and Healthy Aging, 2017.

    doi:10.3233/NHA-170023PubMed 28447072

    Funding and finding

    Registration

    NCT01065571

    Participants

    12

    Follow-up

    up to 1 year

    Funding

    The study was supported by the Broad Medical Research Program.

    In-kind support

    Food-grade carrageenan obtained from FMC Biopolymer; capsules prepared by the Chau Center for Industrial Pharmacy and Contract Manufacturing.

    Finding

    Double-blind capsules of 100 mg food-grade carrageenan or dextrose placebo. Relapse in 3 of 5 participants given carrageenan and 0 of 7 given placebo (log-rank P = 0.046); interleukin-6 rose in the carrageenan group (P = 0.02). EFSA (2018) judged the study of limited relevance because of the small number of patients.

11. Independent research

    Sellem L, Srour B, Javaux G, Chazelas E, Chassaing B, Viennois E, et al. Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort PLoS Medicine, 2024.

    doi:10.1371/journal.pmed.1004338PubMed 38349899

    Funding and finding

    Registration

    NCT03335644

    Participants

    92,000

    Follow-up

    mean 6.7 years

    Funding

    NutriNet-Santé public institutions (Ministère de la Santé, Santé Publique France, INSERM, INRAE, CNAM, Université de Paris, University Sorbonne Paris Nord); European Research Council (grant agreement 864219); French National Cancer Institute (INCa_14059); French Ministry of Health; IdEx Université de Paris (ANR-18-IDEX-0001); Bettencourt-Schueller Foundation Research Prize 2021. Researchers were independent from funders. Funders had no role in the study design, the collection, analysis, and interpretation of data, the writing of the report, and the decision to submit the article for publication.

    Finding

    2604 incident cancers (750 breast, 322 prostate, 207 colorectal) over 615,749 person-years. Highest versus lowest intake of E471: overall cancer HR 1.15 (95% CI 1.04 to 1.27), breast 1.24 (1.03 to 1.51), prostate 1.46 (1.09 to 1.97); total carrageenans and breast cancer 1.32 (1.09 to 1.60). No emulsifier was associated with colorectal cancer. Modelled absolute risks at age 60 by intake category (eTable C): overall cancer 11.2%, 11.8% and 12.4% for E471; breast cancer 4.2%, 4.7% and 5.1% for E471 and 4.1%, 4.6% and 5.2% for total carrageenans; prostate cancer 3.6%, 4.2% and 4.9% for E471. E471 was coded in sex-specific thirds (cut-offs 34 and 187.3 mg/day in men, 40.4 and 177.8 mg/day in women; category means 7.16, 104.17 and 376.1 mg/day). eTable D, cases/participants by third of E471 intake: overall cancer 790/30,667, 1018/30,729 and 796/30,604, HR 1.00, 1.16 (1.05 to 1.27) and 1.15 (1.04 to 1.27), p-trend 0.01; breast cancer 211/24,090, 292/24,153 and 245/24,027; prostate cancer 86/6,577, 133/6,576 and 103/6,577. Total mono- and diglycerides of fatty acids (E471, E472, E472a, E472b, E472c, E472e) and overall cancer: HR 1.12 (1.02 to 1.23) and 1.03 (0.93 to 1.14), p-trend 0.4. Diphosphates (E450) were consumed by 72.6%, mean 246.7 (SD 341.0) mg/day, and coded in sex-specific thirds (cut-offs 47.3 and 259.5 mg/day in women, 28 and 264.3 mg/day in men; category means in women 4.85, 145.42 and 580.06 mg/day). eTable D, E450 by third: premenopausal breast cancer 61/16,560, 120/17,021 and 113/19,382, HR 1.00, 1.56 (1.13 to 2.15) and 1.45 (1.04 to 2.02), p-trend 0.03 (false-discovery-rate-adjusted p-trend 0.1); overall cancer 838/30,683, 1036/30,658 and 730/30,659, HR 1.00, 1.03 (0.94 to 1.13) and 0.98 (0.88 to 1.09), p-trend 0.97; breast cancer HR 1.14 (0.94 to 1.40) for the highest third, p-trend 0.08. eTable C modelled absolute risk of premenopausal breast cancer at age 40 by E450 third: 1.7%, 2.1% and 2.5%. Additive doses were estimated from laboratory assays, EFSA doses by food category or Codex GSFA doses; the study period was 2009 to 2021. The authors state that further human, epidemiological and preclinical studies are required to elucidate the potential underlying mechanisms.

12. Independent research

    Salame C, Javaux G, Sellem L, Viennois E, de Edelenyi FS, Agaësse C, et al. Food additive emulsifiers and the risk of type 2 diabetes: analysis of data from the NutriNet-Santé prospective cohort study The Lancet Diabetes & Endocrinology, 2024.

    doi:10.1016/S2213-8587(24)00086-XPubMed 38663950

    Funding and finding

    Registration

    NCT03335644

    Participants

    104,139

    Follow-up

    mean 6.8 years

    Funding

    NutriNet-Santé public institutions (Ministère de la Santé, Santé Publique France, INSERM, INRAE, CNAM, University Sorbonne Paris Nord); European Research Council (grant agreement 864219, ADDITIVES); French National Cancer Institute (INCa_14059); French Ministry of Health; IdEx Université de Paris (ANR-18-IDEX-0001); Bettencourt-Schueller Foundation Research Prize 2021. The funders had no role in study design; the collection, analysis, and interpretation of data; the writing of the report, or the decision to submit the manuscript for publication.

    Finding

    1056 incident cases of type 2 diabetes. Hazard ratios per 100 mg/day: total carrageenans 1.03 (95% CI 1.01 to 1.05), E407 1.03 (1.01 to 1.05); mean total carrageenan intake 59.0 mg/day. Associations were also reported for E340 (1.15, 1.02 to 1.31, per 500 mg/day), E472e, E331, E412, E414 and xanthan gum E415 (hazard ratio 1.08, 95% CI 1.02 to 1.14, per increment of 500 mg/day, p = 0.013). Xanthan gum was found in 5% of foods according to EFSA data cited by the authors. Appendix eTable3 (https://ars.els-cdn.com/content/image/1-s2.0-S221385872400086X-mmc1.pdf), per 500 mg/day, fully adjusted and mutually adjusted for other emulsifiers: E471 0.99 (0.91 to 1.08), p = 0.84, minimally adjusted 1.07 (0.98 to 1.16); total mono- and diglycerides of fatty acids 1.00 (0.95 to 1.05). E471 was consumed by 80.3%, mean 165.4 mg/day. eTable3, per 500 mg/day, fully adjusted: diphosphates E450 1.01 (0.98 to 1.04), p = 0.49; tripotassium phosphate E340 1.15 (1.02 to 1.31), p = 0.023, with a false-discovery-rate-adjusted p of 0.10 (Figure 4 legend); trisodium phosphate E339 1.03 (0.92 to 1.14), p = 0.64. E450 was consumed by 70.4%, mean 244.5 (SD 351.7) mg/day; E340 by 5.2%, mean 6.9 (SD 90.5) mg/day. Absolute risks by intake level are not reported.

13. Independent research

    Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome Nature, 2015.

    doi:10.1038/nature14232PubMed 25731162

    Funding and finding

    Funding

    This work was supported by NIH grant DK099071 and DK083890. BC is a recipient of the Research Fellowship award from the Crohn's and Colitis Foundation of America (CCFA).

    Finding

    Carboxymethylcellulose or polysorbate 80 at 1.0% in drinking water for 12 weeks reduced the mean distance of the closest bacteria to the epithelium by more than 50% from about 25 µm, raised faecal bioactive flagellin and lipopolysaccharide, caused low-grade inflammation, adiposity and raised fasting glucose in wild-type mice and colitis in Il10- and Tlr5-deficient mice. Germ-free mice were unaffected; microbiota transfer reproduced the effects. Effects appeared from 0.1%. Exposure was not blinded. A 2016 corrigendum (doi 10.1038/nature18000) corrected mouse ages to 5 to 7 weeks and group sizes without changing the conclusions.

14. Expert consensus

    Levine A, Rhodes JM, Lindsay JO, Abreu MT, Kamm MA, Gibson PR, et al. Dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases Clinical Gastroenterology and Hepatology, 2020.

    doi:10.1016/j.cgh.2020.01.046PubMed 32068150

    Funding and finding

    Funding

    not stated

    Finding

    Consensus of the IOIBD nutrition cluster (agreement above 75% required). In Crohn's disease and ulcerative colitis it may be prudent to reduce intake of processed foods containing carrageenan, carboxymethylcellulose and polysorbate 80; evidence level very low, agreement 92.3%.

15. Industry-funded

    McKim JM, Willoughby JA, Blakemore WR, Weiner ML. Clarifying the confusion between poligeenan, degraded carrageenan, and carrageenan: A review of the chemistry, nomenclature, and in vivo toxicology by the oral route Critical Reviews in Food Science and Nutrition, 2019.

    doi:10.1080/10408398.2018.1481822PubMed 29902080

    Funding and finding

    Funding

    Financial support for the preparation of this review was provided by FMC Corporation. The authors acknowledged the Manager of Global Regulatory Affairs of the FMC Health and Nutrition business unit for comments and support.

    Finding

    Narrative review. Food-grade carrageenan has a weight-average molecular weight of 200,000 to 800,000 Da; poligeenan of 10,000 to 20,000 Da, produced at pH 0.9 to 1.3 above 80 °C for several hours. The review states that gastric pH of 2 to 3, rising towards 5 with food, and gastric emptying of 3 to 4 hours provide insufficient time, temperature and acid for hydrolysis, that carrageenan has never been shown to be converted to poligeenan in vivo, and that carrageenan is not absorbed and does not cause gastrointestinal lesions.

16. Independent research

    Fitzpatrick JA, Gibson PR, Taylor KM, Halmos EP. The effect of dietary emulsifiers and thickeners on intestinal barrier function and its response to acute stress in healthy adult humans: A randomised controlled feeding study Alimentary Pharmacology & Therapeutics, 2024.

    doi:10.1111/apt.18172PubMed 39072856

    Funding and finding

    Registration

    ACTRN12619000980134

    Participants

    22

    Follow-up

    28 days on each diet with at least 3 weeks of washout

    Funding

    JAF is a recipient of the Crohn's and Colitis Australia PhD Scholarship. EPH was supported through research grants from the National Health & Medical Research Council Investigator Grant and Crohn's & Colitis Foundation Litwin Pioneers Program. The study was supported by a grant from the Eva and Tom Breuer Foundation.

    Finding

    Single-blinded cross-over feeding trial of high- against low-emulsifier diets, both with all food provided. Unstressed median 2 h urinary lactulose:rhamnose ratio 0.030 (IQR 0.018 to 0.042) on the high-emulsifier diet against 0.042 (0.029 to 0.078) on the low-emulsifier diet (P = 0.04), with lower lipopolysaccharide-binding protein (P = 0.026) and no difference in epithelial injury or inflammation markers. After intravenous corticotrophin-releasing hormone the ratio rose by 89% on the high-emulsifier diet (P = 0.004) and fell by 39% on the low-emulsifier diet (P = 0.009), the two differing (P = 0.001).

17. Funding unknown

    Wellens J, Vanderstappen J, Hoekx S, Vissers E, Luppens M, Van Elst L, et al. Effect of five dietary emulsifiers on inflammation, permeability, and the gut microbiome: a placebo-controlled randomized trial Clinical Gastroenterology and Hepatology, 2026.

    doi:10.1016/j.cgh.2025.08.005PubMed 40816342

    Funding and finding

    Registration

    NCT06552156

    Participants

    60

    Follow-up

    2 weeks of emulsifier-free diet, then 4 weeks of supplementation

    Funding

    not stated in an accessible source; the full text could not be read. Registry NCT06552156 names Universitaire Ziekenhuizen KU Leuven as lead sponsor and lists no collaborators.

    Finding

    Double-blind; brownies with carboxymethylcellulose, polysorbate 80, carrageenan, soy lecithin, native rice starch or no additive (registry doses: carboxymethylcellulose 2.75 g, carrageenan 375 mg and soy lecithin 3.55 g per day). Faecal short-chain fatty acids were lower with carboxymethylcellulose than placebo; faecal calprotectin, C-reactive protein, serum lipopolysaccharide-binding protein and metabolic markers did not differ from placebo; transcellular permeability rose from baseline with carrageenan (P = 0.04). Cholesterol fell after 2 weeks of the emulsifier-free diet.