Emulsionantes y barrera intestinal

Qué son estas moléculas

De los 95 442 adultos franceses estudiados, la mayoría consumía lecitinas (E322), mono- y diglicéridos (E471) y carragenano (E407), pero pocos consumían carboximetilcelulosa (E466) o polisorbato 80 (E433) ¹.

Qué les ocurre en la digestión

Las enzimas digestivas descomponen los mono- y diglicéridos y las lecitinas, mientras que la carboximetilcelulosa llega intacta al colon ²³⁴. En varias especies, las heces contienen entre el 98 % y el 100 % del carragenano ingerido, y en voluntarios humanos, entre el 90 % y el 97 % de la fracción polioxietilénica del polisorbato 80 ⁵⁶.

La barrera en cuestión

En el colon del ratón, la capa interna de moco carece de bacterias ⁷.

Qué se midió en los ensayos con personas

En adultos sanos, la ingesta de 15 g diarios de carboximetilcelulosa durante 11 días modificó la composición de las bacterias intestinales sin alterar los marcadores de inflamación ⁸. Las bacterias alcanzaron la capa interna de moco en 2 de 7 participantes, frente a 0 de 9 controles (p = 0,175) ⁸. En la enfermedad de Crohn, la proporción de pacientes en remisión a las 4 semanas no difirió entre una dieta rica en emulsionantes y otra pobre en ellos (9 de 12 y 7 de 12; p = 0,67) ⁹. En la colitis ulcerosa, se produjo una recaída en el plazo de un año en 3 de 5 pacientes que recibieron carragenano y en 0 de 7 que recibieron placebo (prueba de rangos logarítmicos, p = 0,046) ¹⁰.

Qué se observó en las cohortes

En cohortes francesas, algunos emulsionantes se asociaron con pequeños aumentos del riesgo de enfermedad cardiovascular, cáncer y diabetes ¹¹¹¹². Durante una mediana de seguimiento de 7,4 años, los cocientes de riesgos instantáneos de enfermedad cardiovascular por cada aumento de una desviación estándar en la ingesta fueron de 1,03 (IC del 95 %: 1,01 a 1,05) para la carboximetilcelulosa y de 1,07 (1,04 a 1,11) para el conjunto de los mono- y diglicéridos ¹. Durante una media de seguimiento de 6,7 años, el riesgo absoluto de cáncer a los 60 años, estimado con un modelo, fue del 11,2 %, del 11,8 % y del 12,4 % según la categoría de ingesta de E471 ¹¹. En el tercil de mayor ingesta, el cociente de riesgos instantáneos de cáncer fue de 1,15 (1,04 a 1,27) ¹¹. Durante una media de seguimiento de 6,8 años, el cociente de riesgos instantáneos de diabetes de tipo 2 fue de 1,03 (1,01 a 1,05) por cada 100 mg diarios de carragenano ¹².

Estudios en animales y de laboratorio

En ratones, la carboximetilcelulosa o el polisorbato 80 añadidos al agua de bebida en una concentración del 1,0 % durante 12 semanas redujeron a menos de la mitad la distancia entre las bacterias intestinales y el revestimiento del intestino ¹³. Los ratones presentaron una inflamación de bajo grado ¹³. Los ratones axénicos, criados sin microorganismos, no se vieron afectados ¹³. La dosis del 1,0 % es muy superior a la exposición humana a los polisorbatos ⁶.

Límites reglamentarios

Los evaluadores europeos de riesgos establecieron una ingesta diaria admisible únicamente para los polisorbatos, de 25 mg por kg de peso corporal, y para el carragenano, de 75 mg con carácter temporal ⁶⁵⁴²³. En el escenario de fidelidad a una marca, la exposición al carragenano en el percentil 95 era hasta unas diez veces superior a ese valor ⁵.

Referencias

Independiente
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-2023-076058 PubMed 37673430
Financiación y resultado
Registro
NCT03335644
Participantes
95.442
Seguimiento
median 7.4 years
Financiación
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.
Resultado
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.
Regulatorio
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.2017.5045 PubMed 32625340
Financiación y resultado
Financiación
European Food Safety Authority; requestor: European Commission.
Resultado
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.
Regulatorio
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.2017.4742 PubMed 32625454
Financiación y resultado
Financiación
European Food Safety Authority; requestor: European Commission.
Resultado
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.
Regulatorio
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.2018.5047 PubMed 32625652
Financiación y resultado
Financiación
European Food Safety Authority; requestor: European Commission.
Resultado
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.
Regulatorio
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.2018.5238 PubMed 32625873
Financiación y resultado
Financiación
European Food Safety Authority; requestor: European Commission.
Resultado
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.
Regulatorio
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.2015.4152 PubMed 42109790
Financiación y resultado
Financiación
European Food Safety Authority; on request from the European Commission.
Resultado
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.
Independiente
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.0803124105 PubMed 18806221
Financiación y resultado
Financiación
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.
Resultado
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.
Independiente
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.2021.11.006 PubMed 34774538
Financiación y resultado
Registro
NCT03440229
Participantes
16
Seguimiento
11 days of intervention (14 days for the first 3 participants)
Financiación
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.
Resultado
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).
Independiente
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.70041 PubMed 39967287
Financiación y resultado
Registro
ACTRN12619001099112
Participantes
24
Seguimiento
4 weeks
Financiación
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.
Resultado
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.
Independiente
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-170023 PubMed 28447072
Financiación y resultado
Registro
NCT01065571
Participantes
12
Seguimiento
up to 1 year
Financiación
The study was supported by the Broad Medical Research Program.
Apoyo en especie
Food-grade carrageenan obtained from FMC Biopolymer; capsules prepared by the Chau Center for Industrial Pharmacy and Contract Manufacturing.
Resultado
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.
Independiente
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.1004338 PubMed 38349899
Financiación y resultado
Registro
NCT03335644
Participantes
92.000
Seguimiento
mean 6.7 years
Financiación
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.
Resultado
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.
Independiente
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-X PubMed 38663950
Financiación y resultado
Registro
NCT03335644
Participantes
104.139
Seguimiento
mean 6.8 years
Financiación
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.
Resultado
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.
Independiente
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/nature14232 PubMed 25731162
Financiación y resultado
Financiación
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).
Resultado
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.
Consenso
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.2020.01.046 PubMed 32068150
Financiación y resultado
Financiación
not stated
Resultado
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%.
Financiado por la industria
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:10.1080/10408398.2018.1481822 PubMed 29902080
Financiación y resultado
Financiación
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.
Resultado
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.
Independiente
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.18172 PubMed 39072856
Financiación y resultado
Registro
ACTRN12619000980134
Participantes
22
Seguimiento
28 days on each diet with at least 3 weeks of washout
Financiación
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.
Resultado
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).
Financiación no determinada
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.2025.08.005 PubMed 40816342
Financiación y resultado
Registro
NCT06552156
Participantes
60
Seguimiento
2 weeks of emulsifier-free diet, then 4 weeks of supplementation
Financiación
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.
Resultado
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.

Actualizado 2026-10-21