Researcher Bias vs Independent Research

Is carrageenan bad for you? When considering the answer to that question, it’s useful to follow the money.

For example, industry consultant TOXpertise, LLC has painted research pointing to the potential health risks of this controversial food additive as faulty science. However, the company’s analyses were funded by FMC Corporation, which has “over 60 years of experience in the development and production of carrageenan products…”

Yet in a letter published as early as 1980 in The Lancet, one of the world’s leading medical journal, scientists expressed their concern with the safety of carrageenan in food.

Those scientists are in good company. Research showing that consumption of carrageenan is a health risk is typically conducted by academic institutions and funded through those institutions or sources like the National Institute of Health. On the other hand, if you investigate the source of studies insisting that carrageenan is safe for human consumption, you’ll find that they are often conducted or funded by the carrageenan industry or industry consultants

This type of “researcher bias” is rampant in safety testing for food and products, when a researcher is often funded or employed by the industry producing that product. Outcomes can be influenced by study design choices, including who is chosen to include in a study and how data is interpreted.

The Cornucopia Institute believes the discussion concerning carrageenan must take into account the evolving research, the institutions behind that research, and increasing awareness and concern of consumers in the marketplace. An increasingly common presence in the typical Western diet, carrageenan deserves scrutiny. (Learn more about the use of carrageenan in organic food.)

Summary of Research

In the following summary of carrageenan studies, Cornucopia identifies the source of funding (when known) and the affiliations of researchers and commenters. While thousands of studies exist, we identify those most applicable to the question of human health implications.  Scroll down for the research after 2017, when the studies extended to actual clinical trials that investigate carrageenan’s effect on human populations, as opposed to cell-line or animal experiments. 

 Over the last decade, industry-funded experts have falsely accused Cornucopia of confusing the kind of carrageenan that’s used in food (undegraded) with poligeenan (degraded carrageenan). We believe this accusation is meant to sow consumer confusion.  

 1970s 

 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, Center of Experimental Pathology and Toxicology, Albany Medical College (Albany, New York) 

 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 (Albany, New York) 

 Watanabe K, Reddy BS, Wong CQ, Weisburger JH (1978) “Effect of dietary undegraded carrageenan on colon carcinogenesis in F344 rats treated with azoxymethane or methylnitrosourea.” Cancer Research 38:4427–4430. 

 Summary of findings: This study found higher rates of tumors in rats fed undegraded carrageenan in the diet. 

 Funding: National Cancer Institute (National Institutes of Health) 

 Author affiliations: Naylor Dana Institute for Disease Prevention, American Health Foundation 

1980s 

 Watt J and Marcus R (1980) “Potential hazards of carrageenan.” The Lancet 315(8168): 602-603. 

 Letter to The Lancet: Leading carrageenan researchers R. Marcus and James Watt publish two letters in The Lancet, titled “Danger of Carrageenan in Foods” and “Potential Hazards of Carrageenan,” pointing out health concerns with the consumption of carrageenan. Highly respected, The Lancet is one of the world’s leading medical journals. . 

 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. 

 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 (Nagoya, 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. 

 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 often used as an alternative to carrageenan). 

 Funding: Food and Drug Administration 

 Author affiliations: Food and Drug Administration 

1990s 

 Weiner M. (1991) “Toxicological properties of carrageenan.” Agents and Actions 32(1-2): 46-51. 

 Summary of findings: Carrageenan is safe based on the author’s review of various animal feeding studies. 

 Author affiliation: FMC Corporation (a chemical corporation and leading carrageenan manufacturer). 

 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 

 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 three 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 

 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 myoepithelial cells after exposure to lambda-carrageenan.” Cancer Research 57:2823-2826. 

 Summary of findings: Mammary myoepithelial 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 (Iowa City, Iowa). 

2000s 

 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 (East Lansing, Michigan). 

 Tobacman JK (2001) “Review of Harmful Gastrointestinal Effects of Carrageenan in Animal Experiments.” Environmental Health Perspectives 109(10): 983-994. 

 Review summary: 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.” 

 Author affiliation: University of Iowa, College of Medicine, The University of Iowa (Iowa City, Iowa). 

 Hagiwara A, Miyashita K, Nakanishi T, Sano M, Tamano S, Asai I, Nakamura M, Imaida K, Ito N and Shirai T. (2001) “Lack of Tumor Promoting Effects of Carrageenan on 1,2-Dimethylhydrazine-induced Colorectal Carcinogenesis in Male F344 Rats.” Journal of Toxicologic Pathology 14; 37. 

 Summary of findings: This study found no statistically significant increases in malignant tumors in rats given food-grade carrageenan in the diet. The study was terminated as higher rates of tumors in the carrageenan group were detected. The rats were killed after 90 days (a rat’s natural lifespan is 2 years). When the study was terminated, tumor rates were higher, but not yet high enough to be statistically significant. 

 Author affiliations: Nagoya City University, Daiyukai Institute for Medical Science and San-Ei Gen FFI, Inc. One of the authors has a work history with SanEi Gen FFI, Inc., a Japanese carrageenan manufacturer. 

 Uno Y, Omoto T, Goto Y, Asai I, Nakamura M and Maitani T. (2001) “Molecular weight distribution of carrageenans studies by a combined gel permeation/inductively coupled plasma (GPC/ICP) method.” Food Additives and Contaminants 18: 763-772. 

 Summary of findings: The study measured the molecular weight of 29 samples of food-grade carrageenan and concluded that no sample had a significant level of degraded carrageenan. The detection limit was 5%. However, the lowest average molecular weight detected over the three days was 718 kDa, indicating that some degradation of the carrageenan did occur 

 Author affiliations: San-Ei Gen FFI, Inc, a Japanese food additive manufacturer. In addition to carrageenan, San-Ei Gen FFI manufactures flavors, colors, preservatives and the artificial sweetener sucralose. 

 Cohen SM and Ito N. (2002) “A critical review of the toxicological effects of carrageenan and processed euchema seaweed on the gastrointestinal tract.” Critical Reviews in Toxicology 32(5): 413-44. 

 Summary of findings: The authors of this review criticized research studies pointing to gastrointestinal harm from consuming carrageenan. The authors conclude that “there is no credible evidence supporting a carcinogenic effect or a tumor-promoting effect on the colon in rodents.” 

 Author affiliations: Department of Pathology/Microbiology, University of Nebraska Medical Center (Omaha, Nebraska) and Nagoya City University Medical School (Japan).  

 Weiner M, Nuber D, Blakemore WR, Harriman JF and Cohen SM. (2007) “A 90-day dietary study on kappa-carrageenan with emphasis on the gastrointestinal tract.” Food and Chemical Toxicology 45(1): 98-106. 

 Summary of findings: The study found no clinical signs in rats fed high doses of food-grade carrageenan with up to 12% degraded carrageenan, other than soft stool. The authors reported that the gastrointestinal tract “appeared normal,” even in the rats given high doses of carrageenan in the diet. 

 Funding: FMC Corporation (a leading carrageenan manufacturer). 

 Author affiliations: FMC Corporation. In addition to manufacturing carrageenan, FMC Corporation produces pesticides and industrial chemicals. 

 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 and Jesse Brown Veterans Affairs Medical Center (Chicago, Illinois). 

 Bhattacharyya S, Borthakus 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 (Chicago, Illinois). 

 Tobacman JK, Bhattacharyya S, Borthakur A, Dudeja PK. (2008) “The carrageenan diet: not recommended.” Science 321(5892):1040-1041. 

 NOTE: this research was cited in the Subcommittee summary review. 

 Summary of findings: Concluded that efforts at cultivation of carrageenan-producing seaweed have demonstrated how a “natural product” can produce harmful effects to the marine environment; similarly, harmful effects to humans may be attributable to carrageenan exposure. 

 Author affiliations: Department of Medicine, University of Illinois (Chicago, Illinois). 

 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 (Chicago, Illinois). 

 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 (Chicago, Illinois). 

 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 carrageenan in 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 (Chicago, Illinois); Jesse Brown Veterans Affairs Medical Center (Chicago, Illinois); and, Rensselaer Polytechnic Institute (Troy, New York). 

 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 (Chicago, Illinois). 

 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 (Chicago, Illinois); Jesse Brown Veterans Affairs Medical Center (Chicago, Illinois); Rensselaer Polytechnic Institute (Troy, New York); University Pierre and Marie Currie/Sorbonne University (Paris, France). 

 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 (Chicago, Illinois) and Jesse Brown Veterans Affairs Medical Center (Chicago, Illinois). 

 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 (Chicago, Illinois). 

 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. https://pubmed.ncbi.nlm.nih.gov/22410212/ 

 Summary of findings: Exposure to small amounts of food-grade carrageenan reduces the activity of sulfatase enzymes, which are critical for many vital cellular processes. 

 Funding: National Institute of General Medical Sciences, National Institutes of Health. 

 Author affiliations: University of Illinois (Chicago, Illinois); Jesse Brown Veterans Affairs Medical Center (Chicago, Illinois); Rensselaer Polytechnic Institute (Troy, New York). 

 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 signaling in HepG2 cells and C57BL/6J mice.” Diabetologia 55(1): 194-203. https://pubmed.ncbi.nlm.nih.gov/22011715/  

 Summary of findings: Carrageenan in the diet may contribute to diabetes. Carrageenan impairs glucose tolerance, increases insulin resistance, and inhibits insulin signaling in vivo in mouse liver and human HepG2 cells. These effects may result from carrageenan-induced inflammation. 

 Funding: National Institutes of Health and American Diabetes Association. 

 Author affiliations: University of Illinois (Chicago, Illinois). 

 Bhattacharyya S, Feferman L, and Tobacman JK (2014) “Increased Expression of Colonic Wnt9A through Sp1-mediated Transcriptional Effects involving Arylsulfatase B, Chondroitin 4-Sulfate, and Galectin-3.” The Journal of Biological Chemistry 289(25): 17564-17575. 

 Summary of findings: Mechanism by which Wnt expression was increased by carrageenan exposure was unknown. This study showed that Sp1 activated Wnt9A transcription through changes in arylsulfatase B, chondroitin 4-sulfation, and galectin-3. 

 In conclusion, a decline in arylsulfatase B leads to transcriptional effects mediated by Sp1 and galectin-3. The significance is that extracellular events can regulate transcription through changes in arylsulfatase B and chondroitin 4-sulfation. 

 Author affiliations: University of Illinois (Chicago, Illinois) and Jesse Brown Veterans Affairs Medical Center (Chicago, Illinois). 

 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 Nucleoredoxin Reduction.” 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 (Chicago, Illinois) and Jesse Brown Veterans Affairs Medical Center (Chicago, Illinois). 

 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 (Chicago, Illinois). 

 Author affiliations: Department of Medicine, University of Illinois (Chicago, Illinois). 

 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 

 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 (Chicago, Illinois). 

 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. https://pubmed.ncbi.nlm.nih.gov/25883986/  

 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 (Chicago, Illinois) and Jesse Brown Veterans Affairs Medical Center (Chicago, Illinois). 

 Tobacman JK (2015) “The Common Food Additive Carrageenan and the alpha-gal epitope.” Journal of Allergy and Clinical Immunology 136(6): 1708-9. https://pubmed.ncbi.nlm.nih.gov/26518095/  

 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, mammalian 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 (Chicago, Illinois). 

 Coleman MT. (2015) “Dairy-free” dietary substitute, abdominal pain, and weight loss.” Clinical Medical Reviews and Case Reports 2:8. https://clinmedjournals.org/articles/cmrcr/clinical-medical-reviews-and-case-reports-cmrcr-2-079.pdf  

 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 (New Orleans, Louisiana). 

 Weiner, M. (2016) “Parameters and pitfalls to consider in the conduct of food additive research, Carrageenan as a case study.” Food and Chemical Toxicology, 87: 31-44. https://pubmed.ncbi.nlm.nih.gov/26615870/  

 Summary of findings: FMC Corporation announced that this analysis found significant weaknesses in food additive research, using carrageenan as a primary example. 

 Funding: FMC Corporation, an agricultural sciences company and stakeholder in the carrageenan industry. 

 Author affiliations: Dr. Myra L. Weiner, is the owner and president of TOXpertise, LLC, a firm that consults for the carrageenan industry.  

 Weiner M, McKim J, and Blakemore W. “Addendum to Weiner, M.L. (2016) “Parameters and Pitfalls to Consider in the Conduct of Food Additive Research, Carrageenan as a Case Study.” Food Chemical Toxicology 87, 31-44. https://pubmed.ncbi.nlm.nih.gov/28651808/  

 Summary: This paper is an addendum to a 2016 paper outlining pitfalls and parameters to consider in the conduct of food additive research with carrageenan. 

 Author affiliations: TOXpertise, LLC; IONTOX, LLC; and Celtic Colloids, Inc. As previously noted, all of these are associated with the carrageenan industry. 

 McKim Jr JM, Heidi Baas, Rice G, Willoughby Sr J, Weiner M, Blakemore W. (2016) “Effects of carrageenan on cell permeability, cytotoxicity, and cytokine gene expression in human intestinal and hepatic cell lines.” Food and Chemical Toxicology, 96: 1-10. https://www.sciencedirect.com/science/article/pii/S0278691516302265  

 Summary of findings: Three common forms of the food additive carrageenan were tested in vitro cell lines, looking for permeability, cytotoxicity, and induction of cytokines. Carrageenan was negative in all endpoints evaluated. 

 Author affiliations: All the authors hail from businesses and consultants associated with carrageenan manufactures. The specific affiliations include: IONTOX, LLC; Cyprotex; TOXpertise, LLC; Celtic Colloids, Inc. Dr. Myra L. Weiner, is the owner and president of TOXpertise, LLC, a firm that consults for the carrageenan industry.  

SINCE 2017 

 Sumit Bhattacharyya, et al. (2017) “A Randomized Trial of the Effects of the No-carrageenan Diet on Ulcerative Colitis Disease Activity.” 181 – 192. DOI: 10.3233/NHA-170023. https://content.iospress.com/articles/nutrition-and-healthy-aging/nha170023 

 Summary of findings: A randomized, double-blind, placebo-controlled, multicenter, clinical trial published in 2017 showed that people with colitis should avoid carrageenan. Patients who received carrageenan-containing capsules relapsed, and none of the patients who received placebo-containing capsules relapsed in their colitis disease. Laboratory tests showed increases in inflammatory biomarkers in those trial participants who received carrageenan. 

 Author affiliations: Department of Medicine, University of Illinois (Chicago, Illinois); Jesse Brown VA Medical Center (Chicago, Illinois); Department of Medicine, University of Chicago, (Chicago, Illinois); Division of Epidemiology and Biostatistics, University of Illinois at Chicago, (Chicago, Illinois) and Faculty of Health Sciences, Simon Fraser University (Burnaby, BC, Canada); Department of Kinesiology and Nutrition, University of Illinois at Chicago, (Chicago, Illinois). 

 John Vincent Martino, Johan Van Limbergen1, and Leah E. Cahill. (2017) “The Role of Carrageenan and Carboxymethylcellulose in the Development of Intestinal Inflammation.” Front. Pediatr., 1(5):96. doi:10.3389/fped.2017.00096. https://pubmed.ncbi.nlm.nih.gov/28507982/  

 Summary of findings: Research found that carrageenan may trigger or magnify an inflammatory response in the human intestine. The researchers determined that more study was needed because it seemed consumption of carrageenan was a risk factor, but did not seem to be the sole cause involved in the development of IBD or in disease recurrence after treatment. The researchers also highlighted the prevalence of carrageenan in pediatric diets as a cause for concern. 

 Author affiliations: Pediatric Gastroenterology, Hepatology and Nutrition, IWK Health Centre, (Halifax, NS, Canada); Medicine, Dalhousie University (Halifax, NS, Canada); and Department of Nutrition at the Harvard T.H. Chan School of Public Health (Boston, Massachusetts). 

 Bixler, HJ. (2017) “The carrageenan controversy.” Journal of Applied Phycology, 29:2201–2207. https://link.springer.com/article/10.1007/s10811-017-1132-4  

 Summary of article: (NOTE this is not a research paper) The article describes how the negative attitude toward carrageenan evolved, stating it came from research from a group at the University of Illinois who claim that carrageenan upregulates inflammatory genes of the intestinal epithelium. There is no evidence that this in vitro model applies in vivo and a growing body of research is showing it does not. Nevertheless, it was picked up by various bloggers feeding on contradictory issues and quickly went viral. This paper describes the evolution of the “carrageenan controversy” and provides information for food producers and consumers on new more robust studies confirming that it is safe to consume foods containing carrageenan. This article also presents actions being taken by carrageenan producers and users, to reduce the noise in the public domain from the controversy. 

 Author affiliations: Ingredients Solutions, Inc, a carrageenan supplier. The company calls themselves “The World’s Largest Independent Supplier of Carrageenan” and is a world leader in the development, design and marketing of Specialty Hydrocolloids. 

 Shlomit D, et al. (2019) “Revisiting the carrageenan controversy: do we really understand the digestive fate and safety of carrageenan in our foods?” Food Funct., 10, 1763. DOI: 10.1039/C9FO00018F. https://pubs.rsc.org/en/content/articlelanding/fo/2018/c7fo01721a#!divAbstract 

 Summary of findings: A review of carrageenan safety research in 2019 came to three conclusions. First, they concluded that there isn’t enough information about current consumption rates. Second, the link between carrageenan’s properties, its impact on digestion, and the colon microbiome and inflammation are yet to be fully resolved. Third, there is not enough research on carrageenan’s effect on predisposed populations, such as elderly people or IBD patients. The review of the existing concluded carrageenan has not been definitively determined as “safe” and more research needs to be done. 

 Author affiliations: Laboratory of Chemistry of Foods and Bioactives, Department of Biotechnology and Food Engineering, Technion, Israel Institute of Technology (Haifa, Israel). 

 Myra L. Weiner and James M. McKim, Jr. (2019) “Comment on ‘Revisiting the carrageenan controversy: do we really understand the digestive fate and safety of carrageenan in our foods?’ by S. David, C. S. Levi, L. Fahoum, Y. Ungar, E. G. Meyron-Holtz, A. Shpigelman and U. Lesmes, Food Funct., 2018, 9, 1344–1352. https://pubs.rsc.org/en/content/articlelanding/2019/fo/c8fo01282b  

 Summary: This piece is a comment rather than research or review. The comment is critical of the above paper. 

 Author Affiliations: TOXpertise, LLC and IONTOX, LLC. Both TOXpertise and IONTOX provide professional consulting services in the field of toxicology, and both businesses are known to be hired as consultants for the carrageenan industry. Note that previous “reviews” in this listing, including the same author (Weiner, M) that were critical of carrageenan research done through non-industry sources. 

 Ye Mi Y, et al. (2020) “Native κ-carrageenan induced-colitis is related to host intestinal microecology.” International Journal of Biological Macromolecules, 147: 284-294. DOI: 10.1016/j.ijbiomac.2020.01.072. https://www.sciencedirect.com/science/article/abs/pii/S0141813019390828  

 Summary of findings: Research into inflammation and carrageenan in 2020 found that inflammatory properties of carrageenan are related to carrageenan’s modification of the intestinal microbiome. In addition, researchers found that carrageenan can exacerbate chronic inflammation (which could explain why people with existing chronic conditions improve with a carrageenan-free diet). 

 Author affiliations: Human Health Research Laboratory, College of Food Science and Engineering, Ocean University of China (Qingdao, China); Institute of Ocean and Earth Sciences, University of Malaya (Kuala Lumpur, Malaysia). 

 Zhou J, et al. (2021) “Long-term kappa-carrageenan consumption leads to moderate metabolic disorder by blocking insulin binding.” Pharmacological Research, 165: 105417. https://www.sciencedirect.com/science/article/abs/pii/S1043661820317254  

 Summary of findings: The purpose of this study was to investigate the impact of κ-carrageenan (CGN) on glucose intolerance and insulin resistance from the perspective that κ-CGN may interfere with insulin receptor function and affect insulin sensitivity and signaling, thereby leading to body weight loss. The study concluded that κ-CGN reduced weight gain without affecting food intake, but impaired glucose metabolism in mice by interfering with insulin binding to receptors, causing non-diabetic weight gain reduction due to metabolic disorder. 

 Author affiliations: State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, (Ningbo, Zhejiang, China); Department of Laboratory Medicine, Ningbo Medical Center Lihuili Hospital, (Ningbo, Zhejiang, China); Department of Laboratory Medicine, Taipei Medical University Ningbo Medical Center, (Ningbo, Zhejiang, China). 

  Fang Liu, et al. (2021) “Food-grade carrageenans and their implications in health and disease.” Comprehensive Reviews in Food Science and Food Safety 20(1). https://onlinelibrary.wiley.com/doi/full/10.1111/1541-4337.12790  

 Summary of findings: This research reviewed the molecular mechanisms by which carrageenans exert their biological effects and examined the interactions between carrageenans and the gut microbiome in the pathogenesis of gastrointestinal disorders. This review argues for personalized guidance on carrageenan intake based on individuals’ health status. Future research efforts that aim to close the knowledge gap on the effect of low-dose and chronic carrageenan intake as well as interactions among food additives should be conducive to the improved safety profile of carrageenans in processed food products. 

 Author affiliations: College of Food Science and Engineering, Ocean University of China (Qingdao, China); Affiliated Hospital of Qingdao Binhai University, Qingdao, China; Laboratory of Marine Drugs and Biological Products, Pilot National Laboratory for Marine Science and Technology (Qingdao, China); USDA-ARS Animal Genomics and Improvement Laboratory (Beltsville, Maryland). 

 Ali AJ, Abdulla HI, Al-Nimer MS. (2021) “The Pharmacological Effects of Kappa Carrageenan on Different Human Cell Lines and Genomic DNA: An in vitro study.” Iraqi J Pharm Sci, Vol 30:1. https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/1229  

 Summary of findings: Kappa-carrageenan inhibited the cancer cell growth and fibroblast cell lines growth  in an experimental model because the carrageenan damaged the cells being studied outside their normal biological context (in vitro). The carrageenan solution completely and significantly damaged the DNA in the cancer cells.  

 Author affiliations: International Association for Dental Research (Alexandria, Virginia); Hawler Medical University (Erbil, Iraq).