The Cornucopia Institute Carrageenan Citations

January 26, 2016

These sources were cut and pasted from an email to me from The Cornucopia Institute – January 2017

Fahoum L, Moscovici A, David S, Shaoul R, Rozen G, Meyron-Holtz EG, and Lesmes U. (2016) Digestive fate of dietary carrageenan: Evidence of interference with digestive proteolysis and disruption of gut epithelial function. Molecular Nutritional Food Research (accepted manuscript online Oct 8) DOI: 10.1002/mnfr.201600545Summary of findings: Food grade carrageenan may reduce protein and peptide bioaccessibility, disrupt normal epithelial function, promote intestinal inflammation and compromise consumer health.

 

Shumard T, Xie H, Dodda A, Feferman L, Halline A, Goldstein JL, Hanauer SB (2016) Mo1792 Effects of the No Carrageenan Diet on Ulcerative Colitis Disease Activity: A Pilot and Feasibility Study. Gastroenterology 105(4):S777. Summary of findings: An association between carrageenan intake and earlier relapse in ulcerative colitis was found. Restriction of dietary carrageenan consumption benefits patients with ulcerative colitis.

 

Tobacman JK (2015) The Common Food Additive Carrageenan and the alpha-gal epitope. Journal of Allergy and Clinical Immunology 136(6): 1708-9. Summary of findings: Antibodies to the oligosaccharide epitope galactose-a-1,3- galactose (alpha-gal) are of considerable interest because they are so prevalent, include all isotypes, and are specific to humans and Old World apes. Alpha-gal–mediated responses, including immediate and delayed anaphylaxis, appear to be increasing. In the recent review ‘‘The alpha-gal story: lessons learned from connecting the dots,’’ sources of exposure to the alpha-gal epitope were presented, with particular attention to cetuximab, mamma- lian meat products, and tick bites. This communication is intended to bring attention to including carrageenan, a very commonly used food additive, to the list of sources of exposure to the alpha-gal epitope. Author affiliations: Department of Medicine, University of Illinois at Chicago 

 

Coleman MR and Coleman MT (2015) “Dairy-free” dietary substitute, abdominal pain, and weight loss. Clinical Medical Reviews and Case Reports 2:8. Summary of findings: Elimination of carrageenan containing almond milk from the diet of a patient that had substituted it for cow’s milk several months prior resulted in stabilization of weight and resolution of abdominal pain. Certain food substitutions for dairy products may expose patients to additives like carrageenan, for which there is evidence of its contribution to gastrointestinal disturbances. Considering an etiology for gastrointestinal symptoms brought on by dietary additives in the diagnostic differential gives the practitioner avenues to pursue prior to ordering expensive testing and treatments. Author affiliations: Louisiana State University School of Medicine

 

Bhattacharyya S, Feferman L, and Tobacman JK (2015) Carrageenan inhibits insulin signaling through GRB10-mediated Decrease in Tyr(p)- ISR1 and through Inflammation-induced Increase in Ser(P)307-IRS1. Journal of Biological Chemistry 290(17): 10764-10774. Summary of findings: Inflammation induced by exposure to the common food additive carrageenan leads to insulin resistance by increase in Ser(P) (307)-insulin receptor substrate 1 (IRS1) and subsequent decline in the insulin-stimulated increase in Ser(P)(473)-AKT. Studies were performed in human HepG2 cells and in C57BL/6J mice. and indicate that carrageenan inhibited insulin signaling by two mechanisms. These mechanisms provide internal feedback, mediated by Ser(P)(473)-AKT, Ser(P)(401)- GATA2, and nuclear GATA2, which modulates insulin responsiveness. Author affiliations: University of Illinois at Chicago; Jesse Brown Veterans Affairs Medical Center

 

Bhatacharyya S, Feferman L, Unterman T, and Tobacman JK (2015) Exposure to common food additive carrageenan alone leads to fasting hyperglycemia and in combination with high fat diet exacerbates glucose intolerance and hyperlipidemia without effect on weight. Journal of Diabetes Research Volume 2015, Article ID 513429. Summary of findings: Mice exposed to 10mg/L foodgrade lambda and kappa carrageenan in drinking water and fed an 8% fat diet for 1 year showed glucose intolerance after 6 days and earlier onset of fasting hyperglycemia, higher glucose levels, and exacerbated dyslipidemia compared with the control. This suggests that carrageenan exposure may exacerbate harmful effects of a high fat diet and contribute to development of diabetes. Author affiliations: Department of Medicine, University of Illinois at Chicago

 

Jung TW, Lee SY, Hong HC, Choi HY, Yoo JH, Baik SH, and Choi KM (2014) AMPK activator-mediated inhibition of endoplasmic reticulum stress ameliorates carrageenan-induced insulin resistance through the suppression of selenoprotein P in HepG2 hepatocytes. Molecular and Cellular Endocrinology 382(1):66-73. Summary of findings: Carrageenan causes inflammation through toll-like receptor 4, which plays an important role in insulin resistance and type 2 diabetes mellitus. Carrageenan induces endoplasmic reticulum (ER) stress in a time- and dose-dependent manner. ER stress plays a crucial role in selenoprotein P regulation. Salsalate relieves ER stress and is a new therapeutic strategy to treat insulin resistance. Author affiliations: Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital 

 

Bhattacharyya S, Feferman L, and Tobacman JK (2014) Regulation of Chondroitin-4-Sulfotransferase (CHST11) Expression by Opposing Effects of Arylsulfatase Bon BMP4 and Wnt9A. Biochim Biophys Acta 1849(3): 342-352. Summary of findings: Exposure to the common food additive carrageenan, which reduces ARSB activity, reduced expression of bone morphogenetic protein (BMP)-4 in colonic epithelium and increased Wnt9A expression and Wnt/β-catenin signaling. Funding: University of Illinois at Chicago Author affiliations: Department of Medicine, University of Illinois at Chicago

 

Bhattacharyya S, Feferman L, Borthakur S and Tobacman JK (2014) Common Food Additive Carrageenan Stimulates Wnt/β-Catenin Signaling in Colonic Epithelium by Inhibition of NucleoredoxinReduction. Nutrition and Cancer 66(1): 117-127.Summary of findings: Exposure to carrageenan may be a risk factor in development of colorectal cancer. The findings indicate that environmental exposure stimulates both Wnt signaling and suggest that carrageenan exposure in vivo may contribute to development of colonic neoplasia (uncontrolled growth of cells). Average daily intake of carrageenan in the U.S. in the 1970s was calculated to be 108 mg by the National Academy of Sciences, but recently the average daily carrageenan intake was reported to be 250 mg/day. Increased attention to the effects of carrageenan on vital cell processes, including the Wnt/β-catenin pathway, may lead to significant clinical benefit, as well as increased understanding of relationships between environmental exposures and human disease. Funding: Veterans Affairs Merit Award Author affiliations: University of Illinois at Chicago; Jesse Brown Veterans Affairs Medical Center

 

Bhattacharyya S, O-Sullivan I, Katyal S, Unterman T and Tobacman JK (2012) Exposure to the common food additive carrageenan leads to glucose intolerance, insulin resistance and inhibition of insulin signalling in HepG2 cells and C57BL/6J mice. Diabetologia 55(1): 194-203. Summary of findings: Carrageenan in the diet may contribute to diabetes. Carrageenan impairs glucose tolerance, increases insulin resistance, and inhibits insulin signalling in vivo in mouse liver and human HepG2 cells. These effects may result from carrageenan-induced inflammation. Funding: National Institutes of Health; American Diabetes Association Author affiliations: University of Illinois at Chicago

 

Yang B, Bhattacharyya S, Linhardt R and Tobacman JK (2012) Exposure to common food additive carrageenan leads to reduced sulfatase activity and increase in sulfated glycosaminoglycans in human epithelial cells. Biochimie 94(6): 1309-16. Summary of findings: Exposure to small amounts of food-grade carrageenan reduces the activity of sulfatase enzymes, which are critical for many vitalcellular processes. Funding: National Institute of General Medical Sciences, National Institutes of Health Author affiliations: University of Illinois at Chicago; Jesse Brown Veterans Affairs Medical Center; Rensselaer Polytechnic Institute 

 

Borthakur A, Bhattacharyya S, Anbazhagan AN, Kumar A, Dudeja PK and Tobacman JK (2012) Prolongation of carrageenan-induced inflammation in human colonic epithelial cells by activation of an NFκB-BCL10 loop. Biochimica and Biophysica Acta 1822(8): 1300-7. Summary of findings: Inflammation of the colon caused by exposure to low levels of food-grade carrageenan persists beyond the initial period of exposure. Funding: National Institutes of Health Author affiliations: University of Illinois at Chicago

 

Bhattacharyya S, Dudeja PK and Tobacman JK (2010) Tumor necrosis factor alpha-induced inflammation is increased but apoptosis is inhibited by common food additive carrageenan. Journal of Biological Chemistry 285(50): 39511-22. Summary of findings: This study examines the particular mechanisms by which food-grade carrageenan cause inflammation. Funding: Veterans Administration Author affiliations: University of Illinois at Chicago; Jesse Brown Veterans Affairs Medical Center 

 

Bhattacharyya S, Borthakur A, Tyagi S, Gill R, Chen ML, Dudeja PK, Tobacman JK (2010) B-cell CLL/lymphoma 10 (BCL10) is required for NF-kappaB production by both canonical and noncanonical pathways and for NF-kappaB-inducing kinase (NIK) phosphorylation. Journal of Biological Chemistry. 1;285(1):522-30. Summary of findings: Carrageenan stimulates innate immune-mediated pathways of inflammation. Funding: National Institutes of Health; Veterans Administration Author affiliations: University of Illinois at Chicago

 

Bhattacharyya S, Liu H, Zhang F, Jam M, Dudeja PK, Michel G, Linhardt RJ, and Tobacman JK (2010) Carrageenan-induced innate immune response is modified by enzymes that hydrolyze distinct galactosidic bonds. Journal of Nutritional Biochemistry 21(10): 906-13. Summary  of findings: This study examines the immune response by which food-grade carrageenan causes inflammation. Funding: Veterans Administration Author affiliations: University of Illinois at Chicago; Jesse Brown Veterans Affairs Medical Center; Rensselaer Polytechnic Institute; University Pierre and Marie Currie/Sorbonne University, Paris, France

 

Bhattacharyya S, Dudeja PK and Tobacman JK (2008) Carrageenan-induced NFkappaB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10. Biochimica and Biophysica Acta 1780(7-8): 973-82. Summary of findings: Exposure to human colonic epithelial cells in tissue culture to small quantities of food-grade carrageenan produced inflammatory responses. Funding: National Institutes of Health Author affiliations: University of Illinois at Chicago 

 

Bhattacharyya S, Borthakur A, Dudeja PK and Tobacman JK (2008) Carrageenan induces cell cycle arrest in human intestinal epithelial cells in vitro. Journal of Nutrition 138(3): 469-75. Summary of findings: Exposure of human colonic epithelial cells in tissue culture to small quantities of undegraded (food-grade) carrageenan produced an increase in cell death with cell cycle arrest, effects that can contribute to ulcerations. Funding: National Institutes of Health Author affiliations: University of Illinois at Chicago and Jesse Brown Veterans Affairs Medical Center 

 

Bhattacharyya S, Gill R, Chen ML, Zhang F, Linhardt RJ, Dudeja PK and Tobacman JK (2008) Toll-like receptor 4 mediates induction of the Bcl10- NFkappaB-interleukin-8 inflammatory pathway by carrageenanin human intestinal epithelial cells. Journal of Biological Chemistry 283(16): 10550-8. Summary of findings: Exposure of human colonic epithelial cells in tissue culture to small quantities of food-grade carrageenan was associated with changes in molecular signaling pathways that resemble the changes found in human colonic polyps. Untreated polyps can develop into colon cancer. Funding: National Institutes of Health; Veterans Administration Author affiliations: University of Illinois at Chicago; Jesse Brown Veterans Affairs Medical Center; Rensselaer Polytechnic Institute 

 

Borthakur A, Bhattacharyya S, Dudeja PK and Tobacman JK (2007) Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells. American Journal of Physiology, Gastrointestinal and Liver Physiology 292(3): G829-38. Summary of findings: Exposure of human colonic epithelial cells in tissue culture to small quantities of undegraded (food-grade) carrageenan produced inflammation by a second pathway of reactive oxygen species, as well as by the innate immune pathway. Funding: Department of Veterans Affairs; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Author affiliations: University of Illinois at Chicago and Jesse Brown Veterans Affairs Medical Center 

 

Bhattacharyya S, Borthakur A, Dudeja PK and Tobacman JK (2007) Carrageenan reduces bone morphogenetic protein-4 (BMP4) and activates the Wnt/ beta-catenin pathway in normal human colonocytes. Digestive Diseases and Sciences 52(10): 2766-74. Summary of findings: This study identified mechanisms by which food-grade carrageenan influences the development of human intestinal polyps. Untreated intestinal polyps can develop into colon cancer. Funding: National Institutes of Health Author affiliations: University of Illinois at Chicago 

 

Tobacman JK (2001) Review of Harmful Gastrointestinal Effects of Carrageenan in Animal Experiments. Environmental Health Perspectives 109(10): 983-994. Review study: This study examined existing research done to date (2001). The author concluded: “Because of the acknowledged carcinogenic properties of degraded carrageenan in animal models, and the cancer-promoting effects of undegraded carrageenan in experimental models, the widespread use of carrageenan in the Western diet should be reconsidered.” Funding: None Author affiliation: University of Iowa College of Medicine

 

Suzuki J, Na HK, Upham BL, Chang CC and Trosko JE (2000) Lambda-carrageenan-induced inhibition of gap-junctional intercellular communication in rat liver epithelial cells. Nutrition and Cancer 36(1): 122-8. Summary of findings: This study aimed to better understand the role of food-grade carrageenan in carcinogenesis. The experiments in this study were designed to test the hypothesis that carrageenan might function as a tumor-promoting chemical by inhibiting GJIC (Gap-junctional intercellular communication is believed to help healthy cells fight cancer). The data revealed inhibition of GJIC by carrageenan similar to that by the well-documented tumor promoter phorbol ester. Author affiliations: Michigan State University

 

Corpet DE, Taché S, and Préclaire M (1997) Carrageenan given as a jelly does not initiate, but promotes the growth of aberrant crypt foci in the rat colon. Cancer Letters 114:53–55. Summary of findings: Consumption of food-grade carrageenan promotes the growth of aberrant crypt foci in the rat colon. Aberrant crypt foci are abnormal glands in the colon that are precursors to polyps and are one of the earliest changes seen in the colon that may lead to cancer. Author affiliations: French National Institute of Agronomic Research, Toulouse, France 

 

Tobacman JK (1997) Filament disassembly and loss of mammary myopithelial cells after exposure to lambda-carrageenan. Cancer Research 57:2823- 2826. Summary of findings: Mammary myopeithelial cells exposed to lambda-carrageenan at rates as low as 0.00014% exhibited disruption of the internal cellular architecture and cell death. Destruction of these cells in tissue culture by a low concentration of a widely used food additive suggests a dietary mechanism for mammary carcinogenesis not considered previously. Author affiliations: Department of Internal Medicine, College of Medicine, The University of Iowa

 

Capron I, Yvon M, Muller G (1996) In-vitro gastric stability of carrageenan. Food Hydrocolloids 10(2):293–244. Summary of findings: This study analyzed the rate of degradation in an artificial stomach which simulated realistic conditions for human digestion, wherein the pH gradually decreases from 5 to 1.5 over 3 hours prior to gastric emptying. The findings showed that, under the most unfavorable conditions of gastric digestion (slow emptying rate and rapid acidification), about 10” of the carrageenan had a molecular weight of less than 100 kDa. Funding: Proctor & Gamble Company Author affiliations: Proctor & Gamble Company 

 

Wilcox DK, Higgins J, Bertram TA (1992) Colonic epithelial cell proliferation in a rat model of nongenotoxin-induced colonic neoplasia. Laboratory Investigation 67:405–411. Summary of findings: This study shows an association between loss of epithelial cells (the cell membranes in the intestine) and the consumption of both undegraded and degraded carrageenan. Funding: Proctor & Gamble Company Author affiliations: Proctor & Gamble Company

 

Calvert RJ and Reicks M (1988) Alterations in colonic thymidine kinase enzyme activity induced by consumption of various dietary fibers. Proceedings of the Society for Experimental Biology and Medicine 189:45–51. Summary of findings: Researchers examined the reported effects of various dietary fibers on chemically induced colon carcinogenesis in rats. This study found a four-fold increase in thymidine kinase activity (a measure for malignant disease) in colonic mucosa following exposure to food-grade carrageenan. No differences were found following exposure to guar gum, a food additive used as an alternative to carrageenan. Funding: Food and Drug Administration Author affiliations: Food and Drug Administration

 

Arakawe S, Okumua M, Yamada S, Ito M, Tejima S (1986) Enhancing effect of carrageenan on the induction of rat colonic tumors by 1,2-dimethylhydrazine and its relation to ß-glucuronidase activities in feces and other tissues. Journal of Nutritional Science and Vitaminology 32:481–485. Summary of findings: This study found higher rates of tumors in rats fed undegraded carrageenan in the diet. Author affiliations: Nagoya City University, Japan Nicklin S and Miller K (1984) Effect of orally administered food-grade carrageenans on antibody-mediated and cell-mediated immunity in the inbred rat. Food and Chemical Toxicology 22:615–621. Summary of findings: Researchers using undegraded carrageenan administered in the drinking water of rats showed that carrageenan penetrates the intestinal barrier. Author affiliations: The British Industrial Biological Research Association, a privately-owned consulting firm. 

 

Watt J and Marcus R (1981) Harmful effects of carrageenan fed to animals. Cancer Detection and Prevention 4(1-4): 129-34. Review article: The authors reviewed the scientific literature and found “an increased number of reports … describing harmful effects of degraded and undegraded carrageenan supplied to several animal species in their diet or drinking fluid.” “Harmful effects [of food-grade carrageenan] are almost certainly associated with its degradation during passage through the gastrointestinal tract. There is need for extreme caution in the use of carrageenan or carrageenan-like products as food additives in our diet.” Watt J and Marcus R (1981) Danger of carrageenan in foods and slimming recipes. The Lancet 317(8215): 338. Letter to The Lancet: Scientists repeat their concern with the use of carrageenan in food in a letter to The Lancet. 

 

Watt J and Marcus R (1980) Potential hazards of carrageenan. The Lancet 315(8168): 602-603. Letter to The Lancet: The authors of published research showing increased rates of ulcerative colitis like disease in laboratory animals given food-grade carrageenan wrote the letter to The Lancet. Highly respected, The Lancet is one of the world’s leading medical journals. The scientists express their concern with the safety of carrageenan in food. 

 

Engster M and Abraham R (1976) Cecal response to different molecular weights and types of carrageenan in the guinea pig. Toxicology and Applied Pharmacology 38:265–282. Summary of findings: In this short-term study, researchers administered different types of carrageenan in the diet and drinking water of guinea pigs for two weeks. They found ulceration of the intestines in guinea pigs given undegraded iota-carrageenan in the drinking water. No changes were observed in the other groups, and it is unclear what effects would have been seen if the experiment had been continued for longer than two weeks. Funding: National Institute of Environmental Health Sciences, National Institutes of Health Author affiliation: Albany Medical College

 

Pittman K, Golberg L, and Coulston F (1976) Carrageenan: The effect of molecular weight and polymer type on its uptake, excretion and degradation in animals.” Food and Cosmetics Toxicology 14 (2):85-93. Summary of findings: Food-grade carrageenan was given to guinea pigs, monkeys, and rats through drinking water or in the diet. Fecal and liver samples were examined by gel electrophoresis and carrageenans present in the feces were reduced to 100kDa or less. Carrageenans were also found in the liver, demonstrating that high molecular weight carrageenans are degraded after passing through the digestive tract and can be absorbed. Author affiliations: Institute of Comparative and Human Toxicology, Albany Medical College of Union University 

 

Grasso P, Sharratt M, Carpanini FMB, Gangolli SD (1973) Studies on carrageenan and large-bowel ulceration in mammals. Food and Cosmetics Toxicology 11:555–564. Summary of findings: The researchers administered both degraded and undegraded/food-grade carrageenan in the diet of several species of laboratory animals. Guinea pigs and rabbits experienced ulcerations in the large intestine, symptoms which were not detected in rats, squirrel monkeys, hamsters, and ferrets. Author affiliations: The British Industrial Biological Research Association, a privately owned consulting firm.

 

Watt J, Marcus R (1969) Ulcerative colitis in the guinea-pig caused by seaweed extract. Journal of Pharmacy and Pharmacology 21:187S–188S. Summary of findings: This study was one of the first to show that food-grade carrageenan contributes to ulcerative colitis-like disease in laboratory animals (guinea pigs). Author affiliations: University of Liverpool, United Kingdom

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