Food-junk and some mystery ailments: Fatigue, Alzheimer’s, Colitis, Immunodeficiency.
Check Your Labels – Guar Gum
Carrageenan: A pseudo-latex allergy
Progesterone and Protection from Carrageenan
Doubts surface about safety of common food additive, carrageenan
Carrageenan: How a “Natural” Food Additive is Making Us Sick
THE PHENOMENON OF PERSORPTION
Is common food additive to blame for rising rates of bowel disease?
Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome
Carrageenan is a toxic food additive and allergen that should be avoided at all costs. Check your labels!
Carrageenan is a used as a fat substitute; it assists in making a myriad of products more creamy. Its use centers around a false phobia of saturated fat as well a means to market low calorie foods. The food industry removes protective saturated fat and replaces it with a food additive that is provided to lab animals to intentionally induce inflammation, tumors, and immunodeficiency.
Carrageenan is considered safe because it’s said not to enter the blood stream through the intestinal wall, however, its harmful interaction with intestinal bacteria is ignored. Additionally, the little known phenomenon called persorption allows a variety of microparticles, including carrageenan, into the blood stream. The intestinal ramifications of carrageenan consumption set up an inflammatory cascade, digestive problems, and immune system burden.
Quotes by Ray Peat, PhD:
“Carrageenan has been found to cause colitis and anaphylaxis in humans, but it is often present in baby “formulas” and a wide range of milk products, with the result that many people have come to believe that it was the milk-product that was responsible for their allergic symptoms. Because the regulators claim that it is a safe natural substance, it is very likely that it sometimes appears in foods that don’t list it on the label, for example when it is part of another ingredient.
In the 1940s, carrageenan, a polysaccharide made from a type of seaweed, was recognized as a dangerous allergen. Since then it has become a standard laboratory material to use to produce in-flammatory tumors (granulomas), immunodeficiency, arthritis, and other in-flammations. It has also become an increasingly common material in the food industry.”
“The food industry is promoting the use of various gums and starches, which are convenient thickeners and stabilizers for increasing self-life, with the argument that the butyric acid produced when they are fermented by intestinal bacteria is protective. However, intestinal fermentation increases systemic and brain serotonin, and the short-chain fatty acids can produce a variety of inflammatory and cytotoxic effect. Considering the longevity and stress-resistance of germ-free animals, choosing foods (such as raw carrots or cooked bamboo shoots or cooked mushrooms) which accelerate peristalsis and speed transit through the bowel, which suppressing bacterial growth, seems like a convenient approach to increasing longevity.”
“But if you allow bacteria to break down the carrageenan into smaller fragments that more easily get into cells, that WILL cause cancer. And our intestine contains bacteria that are able to do that breakdown.”
“Persorption refers to a process in which relatively large particles pass through the intact wall of the intestine and enter the blood or lymphatic vessels. It can be demonstrated easily, but food regulators prefer to act as though it didn’t exist. The doctrine that polymers–gums, starches, peptides, polyester fat substitutes–and other particulate substances can be safely added to food because they are “too large to be absorbed” is very important to the food in-dustry and its shills.
When the bowel is inflamed, toxins are absorbed. The natural bacterial endotoxin produces many of the same inflammatory effects as the food additive, carrageenan. Like inflammatory bowel disease, the incidence of liver tumors and cirrhosis has increased rapidly. Liver damage leads to hormonal imbalance. Carrageenan produces inflammation and immunodeficiency, synergizing with estrogen, endotoxin and unsaturated fatty acids.”
Pathol Biol (Paris). 1979 Dec;27(10):615-26.
[Biological and pharmacological effects of carrageenan (author’s transl)].
[Article in French]
Roch-Arveiller M, Giroud JP.
Carrageenan is sulfated polysaccharide which has been extensively used as emulsifier and thickening agent in the food industry, for its ability to induce acute inflammation in pharmacology and for its selectively toxic effect for macrophages in immunology. Carrageenan is a complex substance which displays various biological properties. The authors have shown the extent of these actions and reviewed the latest investigations on this subject.
J Allergy Clin Immunol. 1995 May;95(5 Pt 1):933-6.
Anaphylaxis to carrageenan: a pseudo-latex allergy.
Tarlo SM, Dolovich J, Listgarten C.
Toronto Hospital, Western Division, Ontario, Canada.
Anaphylactic reactions during a barium enema have been attributed to allergy to latex on the barium enema device. The observation of anaphylaxis during barium enema without latex exposure or latex allergy led to the performance of an allergy skin test to the barium enema solution.
Individual components of the barium enema solution were obtained for double-blind skin testing. A RAST to identify specific IgE antibodies to the skin test active agent was established.
Carrageenan, a component of the barium enema solution, produced positive reactions to allergy skin test and RAST. Gastrointestinal symptoms for which the patient was being investigated by the barium enema subsequently disappeared with a diet free of carrageenan.
Carrageenan is a previously unreported cause of anaphylaxis during barium enema. It is an allergen widely distributed in common foods and potentially could account for some symptoms related to milk products or baby formula.
Food Addit Contam. 1989 Oct-Dec;6(4):425-36.
Intestinal uptake and immunological effects of carrageenan–current concepts.
Nicklin S, Miller K.
Carrageenans are a group of high molecular weight sulphated polygalactans which find extensive use in the food industry as thickening, gelling and protein-suspending agents. Although there is no evidence to suggest that the persorption of small amounts of carrageenans across the intestinal barrier poses an acute toxic hazard, they are known to be biologically active in a number of physiological systems and extended oral administration in laboratory animals has been shown to modify both in vivo and in vitro immune competence. Whereas this effect could be attributed to carrageenan having a selective toxic effect on antigen-processing macrophages, additional studies suggest that macrophages can also influence immune responses by the timed release of immunoregulatory mediators. Evidence in support of this comes from in vitro studies which demonstrate that carrageenan-treated macrophages can, depending on conditions and time of administration, release either stimulatory or inhibitory factors. The former is known to be the immunostimulatory agent interleukin 1 (IL-1). The inhibitory factor, which is produced at an early stage following exposure to non-toxic doses of carrageenans, has yet to be formally identified but it is believed to be a prostaglandin because of its specific mode of action and short biological half-life. At present it is impossible to relate these studies to the human situation. Although it is established that carrageenans can cross the intestinal barrier of experimental animals, there is no evidence to suggest that the limited uptake that may occur in man in any way interferes with normal immune competence. Nevertheless, increased exposure may occur in the neonate during weaning, and adults and children following allergic reactions and episodes of gastrointestinal disease. Further studies under such conditions now seem warranted in order to elucidate the possible immunological consequences which may be associated with enhanced uptake of carrageenans in vulnerable groups.
Environ Health Perspect. 2001 October; 109(10): 983–994.
Review of harmful gastrointestinal effects of carrageenan in animal experiments.
J K Tobacman
In this article I review the association between exposure to carrageenan and the occurrence of colonic ulcerations and gastrointestinal neoplasms in animal models. Although the International Agency for Research on Cancer in 1982 identified sufficient evidence for the carcinogenicity of degraded carrageenan in animals to regard it as posing a carcinogenic risk to humans, carrageenan is still used widely as a thickener, stabilizer, and texturizer in a variety of processed foods prevalent in the Western diet. I reviewed experimental data pertaining to carrageenan’s effects with particular attention to the occurrence of ulcerations and neoplasms in association with exposure to carrageenan. In addition, I reviewed from established sources mechanisms for production of degraded carrageenan from undegraded or native carrageenan and data with regard to carrageenan intake. Review of these data demonstrated that exposure to undegraded as well as to degraded carrageenan was associated with the occurrence of intestinal ulcerations and neoplasms. This association may be attributed to contamination of undegraded carrageenan by components of low molecular weight, spontaneous metabolism of undegraded carrageenan by acid hydrolysis under conditions of normal digestion, or the interactions with intestinal bacteria. Although in 1972, the U.S. Food and Drug Administration considered restricting dietary carrageenan to an average molecular weight > 100,000, this resolution did not prevail, and no subsequent regulation has restricted use. 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.
Food Chem Toxicol. 1990 Dec;28(12):807-11.
The effects of carrageenan on drug-metabolizing enzyme system activities in the guinea-pig.
Pintauro SJ, Gilbert SW.
Carrageenans are seaweed extracts comprising high molecular weight sulphated polygalactosides. They are used in foods at concentrations of up to 2.5% as thickening and gelling agents. When degraded to lower molecular weight forms, they have been shown to induce ulcerative colitis and colon cancer in laboratory animals. Furthermore, undegraded carrageenan (CG) has been shown to promote azoxymethane and methylnitrosourea initiated carcinogenesis, but the promotion mechanism is unclear. To determine if this mechanism involves alterations of tissue drug-metabolizing enzyme system (DMES) activities, six groups of five guinea-pigs each were administered 0.2% kappa undegraded, 0.2% i undegraded, 1% kappa degraded or 1% i degraded CG, or control solutions in the drinking-water for 8 wk. Microsomal and cytosolic DMES activities of the liver, small intestine and colon were determined. The kappa undegraded CG group exhibited significant (P less than 0.05) increases in small intestine cytochrome P-450 levels and benzo[a]pyrene hydroxylase activities. These data suggest that undegraded CG may selectively induce DMES activities in the small intestine mucosa.
J Pharm Pharmacol. 1989 Jun;41(6):423-6.
Rapid production of ulcerative disease of the colon in newly-weaned guinea-pigs by degraded carrageenan.
Marcus AJ, Marcus SN, Marcus R, Watt J.
In a dose-response study, degraded carrageenan (Eucheuma spinosum) was supplied in the drinking fluid at 1.2 and 3% concentrations over two weeks to young adult guinea-pigs. Ulceration of the large bowel was produced in 100% of animals, the severity and extent of damage probably being dose-related. In a time-course study, 3% degraded carrageenan solution supplied to newly-weaned guinea-pigs produced in 100% of animals ulceration in the caecum by four days and in the ascending colon by seven days. The onset of ulceration occurred as early as the second day. This model is convenient and economic for the screening of drugs of potential therapeutic value in human ulcerative colitis.
Gut. 1971 Feb;12(2):164-71.
Carrageenan-induced ulceration of the large intestine in the guinea pig.
Watt J, Marcus R.
A 5% aqueous solution of degraded carrageenan derived from the red seaweed Eucheuma spinosum was fed to guinea pigs in their drinking water over a period of 20-45 days. Occult blood in the faeces and multiple ulcers in the caecum, colon and rectum occurred in 100% of animals by the 30th day. The clinical and pathological features bear a close resemblance to human ulcerative colitis. The method provides a simple experimental model for the study of various aspects of the pathology of ulcerative lesions in the large intestine as well as the effects of therapeutic agents.
Int J Exp Pathol. 1992 Aug;73(4):515-26.
The pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea-pig.
Marcus SN, Marcus AJ, Marcus R, Ewen SW, Watt J.
The pre-ulcerative phase of carrageenan-induced colonic ulceration was investigated in guinea-pigs supplied 3% degraded carrageenan as an aqueous solution as drinking fluid for 2 or 3 days during which no ulceration of the bowel was observed with the naked eye or dissecting microscope. Mucosal microscopic changes, from caecum to rectum, were multifocal and included cellular infiltrates, dilatation of glands, crypt abscesses, micro-ulcers and sulphated polysaccharide in the lamina propria. Sulphated polysaccharide was also demonstrated histologically for the first time within the surface epithelium and showed ultrastructural features similar to carrageenan. The results indicate that colonic epithelium in the guinea-pig is capable of macromolecular absorption. Carrageenan, a highly active polyanionic electrolyte, within the surface epithelial cells is most likely a primary factor in the breakdown of mucosal integrity. Macromolecular absorption causing enteropathy of the large bowel is a new pathophysiological concept which may have implications in man, particularly in the pathology of large bowel disease.
Methods Achiev Exp Pathol. 1975;7:56-71.
Experimental ulcerative disease of the colon.
Watt J, Marcus R.
The oral administration to guinea-pigs of an aqueous solution of carrageenan derived from the red seaweed, Eucheuma spinosum, provides a useful, readily available experimental model for the study of ulcerative disease of the colon. Two types of ulcerative disease can be produced within a 4-6 week period, viz., ulceration localised mainly to the caecum by using 1% undegraded carrageenan in the drinking fluid, and extensive ulceration involving caecum, colon, and rectum by using 5% degraded carrageenan. Ulceration is probably due to the local action of carrageenan in the bowel.
J Natl Cancer Inst. 1977 Apr;58(4):1171-2.
Promotion of incidence of adenovirus type 12 transplantable tumors by carrageenan, a specific antimacrophage agent.
Lotzová E, Richie ER.
Carrageenan, a sulfated polygalactose with known macrophage-toxic properties, was used to ascertain the role of macrophages in resistance to adenovirus type 12 transplantable tumors. A single ip injection of 5 or 10 mg carrageenan led to increased incidence and more rapid growth of tumors in C3H mice. Carrageenan was most effective if given 1 day before tumor inoculation; the effectiveness decreased with increasing intervals before or after tumor cell injection. The macrophage stabilizer poly-2-vinylpyridine N-oxide injected sc (150 mg/kg) 1 day before carrageenan was given reduced the incidence of tumors. These data lend further support to the importance of macrophages in tumor immunity.
Biomedicine. 1975 Sep;22(5):387-92.
Involvement of macrophages in genetic resistance to bone marrow grafts. Studies with two specific antimacrophage agents, carrageenan and silica.
Lotzova E, Gallagher MT, Trentin JJ.
Carrageenans and silica, agents toxic for macrophages, were used in this study to examine the role of macrophages in resistance of irradiated mice to inbred parental and rat bone marrow grafts. Administration of 2.5 mg of carrageenans or 2.5-5 mg of silica particles intravenously to prospective graft recipients resulted in a prompt abrogation of hybrid and xenogeneic resistance. The macrophage stabilizer poly-2-vinylpyridine N-oxide (PVNO) injected subcutaneously in the dose of 150 mg/kg, 24 hr before silica prevented or reduced the suppression of resistance. PVNO, however, did not antagonize the suppression of resistance by carrageenen, horse anti-mouse thymocyte serum and cyclophosphamide. These results suggest that a) a subpopulation is involved in marrow graft rejection by irradiated mice; b) carrageenan and silica apparently act on macrophages by different mechanisms c) horse anti-mouse thymocyte serum and cyclophosphamide may act on cells other than macrophages or they act on macrophages by a different mechanism than silica, to resistance to bone marrow transplantation.
Agents Actions. 1981 May;11(3):265-73.
Carrageenan: a review of its effects on the immune system.
Thomson AW, Fowler EF.
Carrageenans (kappa, lambda and iota) are sulphated polysaccharides isolated from marine algae that can markedly suppress immune responses both in vivo and in vitro. Impairment of complement activity and humoral responses to T-dependent antigens, depression of cell-mediated immunity, prolongation of graft survival and potentiation of tumour growth by carrageenans have been reported. The mechanism responsible for carrageenan-induced immune suppression is believed to be its selective cytopathic effect on macrophages. This property of carrageenan has led to its adoption as a tool for analysing the role of these cells in the induction and expression of immune reactivity. Systemic administration of carrageenan may, however, induce disseminated intravascular coagulation and inflict damage on both the liver and kidney. This is an important consideration in the interpretation of the effects of carrageenan in vivo and precludes its use as a clinical immune suppressant.
Biomedicine. 1978 May-Jun;28(3):148-52.
Carrageenan and the immune response.
Since the biological effects of carrageenan were reviewed in 1972 by Di Rosa it has become clear from a large number of reports that this algal polysaccharide markedly influences immune responses. Profound suppression of immunity evidenced by impaired antibody production, graft rejection, delayed hypersensitivity and anti-tumour immunity, has been observed in carrageenan-treated animals and the immunodepressive ability of carrageenan confirmed by in vitro studies. Efforts at analysis of carrageenan-induced immune suppression have focussed on the selective cytotoxic effect of this agent on mononuclear phagocytes. Faith in the ability of carrageenan to eliminate those cells has led to its use in examination of the role played by mononuclear phagocytes in various aspects of immune reactivity. This review documents and discusses the effects of carrageenan on immune responses and assesses the value of carrageenan as a useful tool in both current and future work aimed at broadening our knowledge of mechanisms underlying immune reactions.
Biomedicine. 1976 May;24(2):102-6.
Evaluation of carrageenan as an immunosuppressive agent and mediator of intravascular coagulation.
Thomson AW, Wilson AR, Cruickshank WJ, Horne CH.
Carrageenan suppressed antibody responses to SRBC in mice and rats, measured in terms of splenic IgM PFC production. The effect, in mice, was dependent on dose and on the temporal relationship between treatment and antigen administration. Carrageenan was found to alter the time course of the PFC response and also to produce disseminated intravascular coagulation. Some correlation between the observed effects and the use of chemically distinct carrageenans was found. The possible mode of actio2n of carrageenan is discussed in the light of these, and other findings.
J Pathol. 1980 Sep;132(1):63-79.
Histological and ultrastructural changes following carrageenan injection in the mouse.
Fowler EF, Simpson JG, Thomson AW.
Mice were injected intravenously with either uncharacterised potassium carrageenan or purified iota carrageenan and tissue was examined by light and electron microscopy 1 hr and 24 hr later. The survival of animals injected with these carrageenans was monitored over a 6-month period. Histological examination of liver and kidney was carried out on animals which died during this time and in the surviving mice at 28 weeks. Histological and ultrastructural evidence of disseminated intravascular coagulation was observed within 24 hr of carrageenan injection. The changes were more severe in animals given potassium carrageenan. Electro-microscopic examination of liver revealed carrageenan within membrane-bound vacuoles in Küpffer cells. These cells were largely unaffected by phagocytosis of iota carrageenan but uptake of potassium carrageenan resulted in marked ultrastructural changes and occasional damage to adjacent hepatocytes. Mice given potassium carrageenan had the poorer long-term survival and many animals in this group showed chronic renal damage with features which suggested obstructive nephropathy. A smaller proportion of mice injected with iota carrageenan displayed similar changes. There was no evidence of long-term hepatotoxicity in either group although both types of carrageenan persisted within liver macrophages for at least 6 months after injection.
Am J Pathol. 1971 Aug;64(2):387-404.
Spectrum and possible mechanism of carrageenan cytotoxicity.
Catanzaro PJ, Schwartz HJ, Graham RC Jr.
Carrageenan, a sulfated polygalactose which suppresses established delayed hypersensitivity in vivo, is shown to be cytotoxic to macrophages but not to lymphocytes in vitro. This cytotoxicity depends on the carrageenan concentration and degree of lysosomal differentiation but is independent of serum. Survival of macrophages in the presence of carrageenan can be enhanced temporarily by corticosteroids. Ultrastructural studies reveal that carrageenan is readily taken up by macrophages and stored in lysosomes, which subsequently swell and rupture, apparently resulting in cell death. The presence of corticosteroids temporarily retards lysosome swelling. It is suggested that carrageenan may exert its cytotoxic effect by causing osmotic rupture of lysosomes. The possible immunologic significance of these findings is discussed.
Cancer Lett. 1978 Mar;4(3):171-6.
Induction by degraded carrageenan of colorectal tumors in rats.
Ashi KW, Inagaki T, Fujimoto Y, Fukuda Y.
Degraded carrageenan derived from the red seaweed Eucheuma spinosum was given to Sprague—Dawley rats through the diet, in drinking water or by stomach tube for up to 24 months. Carrageenan-induced squamous cell carcinomas, adenocarcinomas and adenomas in the colorectum were observed. Some rats had metastases to the regional lymph nodes of squamous cell carcinomas. These results show that degraded carrageenan is carcinogenic to the colorectum of the rat.
Toxicol Lett. 1981 Jun-Jul;8(4-5):207-12.
Effect of degraded carrageenan on the intestine in germfree rats.
Hirono I, Sumi Y, Kuhara K, Miyakawa M.
The role of intestinal bacterial flora in display of the effect of degraded carrageenan was investigated by feeding 9 germfree and 12 conventional female Wistar rats on diet containing 10% carrageenan for 63 days. Animals were sacrificed 7, 20, 35, and 63 days after the start of feeding and histological changes induced by carrageenan were studied. The germfree rats showed mucosal lesions, such as macrophage aggregates, erosion, and squamous metaplasia of the large intestine, and these lesions were more extensive than those in the conventional rats. Therefore, it was concluded that bacterial flora are not essential for display of the biological effects of degraded carrageenan.
Food Chem Toxicol. 1987 Feb;25(2):113-8.
Intestinal permeability changes in rodents: a possible mechanism for degraded carrageenan-induced colitis.
Delahunty T, Recher L, Hollander D.
Rats and guinea-pigs were treated with degraded carrageenan (50 g/litre in the drinking-water) and their intestinal permeability was studied at weekly intervals over the last 4 wk of the test period by determining the recovery of orally administered tracer doses of [3H]polyethylene glycol (PEG-900) or D-[3H]mannitol in 16-hr urine collections. A freely diffusible dye, Azure A, was administered simultaneously to compensate for non-intestinal factors that could modify renal excretion. Animals were killed after a total treatment period of 5 months for rats and 6 wk for guinea-pigs. After 3 wk of carrageenan treatment, excretion of PEG-900 (expressed as a ratio of the Azure A excretion) in guinea-pigs showed a statistically significant increase over that in the control group. At autopsy, the caeca showed numerous macroscopically visible erosions of the entire mucosal surface and histological examination showed ulcerations largely in the mucosa with abscesses in the crypts. Although no such histological changes were seen in the intestines of the treated rats, even after 5 months, a statistically significant increase in PEG-900 excretion was again found compared with the control group. This increase did not occur when deoxycholate was administered with the carrageenan solution. No effect of carrageenan treatment on mucosal permeability to D-[3H]mannitol was demonstrated in either species. The results suggest that degraded carrageenan-induced colitis could be a result of increased intestinal permeability, since ingestion of this polysaccharide by rats increased PEG-900 absorption without causing mucosal damage.
Cancer Detect Prev. 1981;4(1-4):129-34.
Harmful effects of carrageenan fed to animals.
Watt J, Marcus R.
An increased number of reports have appeared in the literature describing the harmful effects of degraded and undegraded carrageenan supplied to several animal species in their diet or drinking fluid. The harmful effects include foetal toxicity, teratogenicity, birth defects, pulmonary lesions, hepatomegaly, prolonged storage in Kupffer cells, ulcerative disease of the large bowel with hyperplastic, metaplastic, and polypoidal mucosal changes, enhancement of neoplasia by carcinogens, and, more ominously, colorectal carcinoma. Degraded carrageenan as a drug or food additive has been restricted in the United States by the FDA, but undegraded carrageenan is still widely used throughout the world as a food additive. Its harmful effects in animals are almost certainly associated with its degradation during passage through the gastrointestinal tract. There is a need for extreme caution in the use of carrageenan or carrageenan-like products as food additives in our diet, and particularly in slimming recipes.
Food and Cosmetics Toxicology
Volume 14, Issue 2, 1976, Pages 85-93
Carrageenan: The effect of molecular weight and polymer type on its uptake, excretion and degradation in animals
K.A. Pittmana, L. Golberga, F. Coulstona
A variety of τ-, κ- and λ-carrageenans was given to guinea-pigs, monkeys and rats, either in the drinking-water, by gavage or in the diet. Faecal and liver samples were examined qualitatively by gel electrophoresis, to determine any changes in the apparent molecular weight of carrageenans after administration. Quantitative measurements of carrageenans were carried out on samples of liver and urine. That there was little or no absorption of carrageenans of high molecular weight was evidenced by the absence of carrageenan from the livers of guinea-pigs or rats or from the urine of guinea-pigs or monkeys. By contrast, substantial amounts of carrageenan were found in the livers of guinea-pigs and rats given low-molecular-weight carrageenans (Mn ⩽ 40,000). Intermediate amounts of carrageenan were found in livers of animals given carrageenans ranging in Mn between 40,000 and 150,000. Urinary excretion of carrageenan was limited to low-molecular-weight material (Mn ⩽ 20.000). Qualitative and quantitative evidence indicated that there was an upper limit to the size of carrageenan molecules absorbed, but estimates of this upper limit ranged from 10,000 to 85.000 depending upon the analytical approach. Absorption of carrageenan from the drinking-water may differ qualitatively from absorption from the diet. Analysis of faecal samples by gel electrophoresis showed that degradation of high-molecular-weight carrageenan had occurred, either in the gut or in the faeces.
Volume 14, Issue 3, December 1981, Pages 267-272
A study on carcinogenesis induced by degraded carrageenan arising from squamous metaplasia of the rat colorectum
Yasuyuki Oohashi, Tomonori Ishioka, Kazuo Wakabayashi, Noriyuki Kuwabara
We have undertaken studies on carcinogenesis arising from precancerous lesions, such as squamous metaplasia and ulcerative lesions of the rat colorectum, after termination of degraded carrageenan administration. Rates of tumor incidence in groups that were given a 10% diet of degraded carrageenan for 2, 6 and 9 months were 5 rats out of 39 (12.8%), 8 out of 42 (19.0%) and 17 out of 42 (40.5%), respectively. The colorectal squamous metaplasia persisted in all rats and progressed irreversibly. Degraded carrageenan was deposited not only in the colorectal propria mucosa, but also in the other reticuloendothelial organs. These results show that, even with short-term degraded carrageenan administration, degraded carrageenan is carcinogenic to the colorectum of the rat after a prolonged period.
Cancer Res. 1997 Jul 15;57(14):2823-6.
Filament disassembly and loss of mammary myoepithelial cells after exposure to lambda-carrageenan.
Carrageenans are naturally occurring sulfated polysaccharides, widely used in commercial food preparation to improve the texture of processed foods. Because of their ubiquity in the diet and their observed preneoplastic effects in intestinal cells, their impact on human mammary myoepithelial cells in tissue culture was studied. At concentrations as low as 0.00014%, lambda-carrageenan was associated with disassembly of filaments with reduced immunostaining for vimentin, alpha-smooth muscle-specific actin, and gelsolin; increased staining for cytokeratin 14; and cell death. The absence of mammary myoepithelial cells is associated with invasive mammary malignancy; hence, the 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.
Acta Pathol Microbiol Scand A. 1980 May;88(3):135-41.
Stereomicroscopic and histologic changes in the colon of guinea pigs fed degraded carrageenan.
Olsen PS, Poulsen SS.
A colitis-like state induced in Guinea Pigs fed degraded carrageenan orally. By means of a combined semimacroscopic and histologic technique the course of the disease was followed during 28 days. The changes were primarily seen and became most prominent in the caecum. The first lesions were observed following 24 hours of treatment as small rounded foci initially with degenerative changes and inflammation in the surface epithelium, later forming superficial focal ulcerations. Ulcerative changes gradually progressed during the experiment, forming linear and later large, geographical ulcerations. Topographically the ulcerative process was strongly related to the larger submucosal vessels. Nonulcerated parts of the mucosa were not changed until following 7-14 days of treatment. The mucosa became bulging, granulated and finally villus-like. Accumulation of macrophages was found under the surface epithelium after 7-17 days. Possible pathogenetic mechanisms are discussed, especially the development of the early lesions and the significance of the macrotphages.
Teratology. 1981 Apr;23(2):273-8.
Teratogenic effect of lambda-carrageenan on the chick embryo.
Monis B, Rovasio RA.
Carrageenans are widely used as food additives. Thus, it seemed of interest to test their possible teratogenic action. For this purpose, 530 chick eggs were injected in the yolk sac with 0.1 ml of a solution of 0.1% lambda-carrageenan in 0.9% sodium chloride. As controls, 286 eggs were injected with 0.1 ml of 9.0% sodium chloride. In addition, 284 eggs received no treatment. After incubation for 48–50 hours at 39 degrees C, embryos were fixed, cleared, and observed with a stereoscopic microscope. The frequency of abnormal embryos in the group receiving lambda-carrageenan was higher than in the controls (p less than 0.04). Partial duplication of the body, abnormal flexures of the trunk, anencephaly, a severely malformed brain, thickening of the neural tube wall, an irregular neural tube lumen with segmentary occlusion and a reduction in crown-rump length and number of somites were distinctly seen in the lambda-carrageenan-injected group. Moreover, the average number of anomalies per embryo in the lambda-carrageenan-injected group was nearly twice that in the controls. Present data indicate that lambda-carrageenan has teratogenic effects on early stages of the development of the chick embryo.
Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G829-38. Epub 2006 Nov 9.
Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells.
Borthakur A, Bhattacharyya S, Dudeja PK, Tobacman JK.
Carrageenan is a high molecular weight sulfated polygalactan used to improve the texture of commercial food products. Its use increased markedly during the last half century, although carrageenan is known to induce inflammation in rheumatological models and in intestinal models of colitis. We performed studies to determine its direct effects on human intestinal cells, including normal human intestinal epithelial cells from colonic surgeries, the normal intestinal epithelial cell line NCM460, and normal rat ileal epithelial cells. Cells were treated with high molecular weight lambda-carrageenan at a concentration of 1 mug/ml for 1-96 h. IL-8, IL-8 promoter activity, total and nuclear NF-kappaB, IkappaBalpha, phospho-IkappaBalpha, and Bcl10 were assessed by immunohistochemistry, Western blot, ELISA, and cDNA microarray. Increased Bcl10, nuclear and cytoplasmic NF-kappaB, IL-8 promoter activation, and IL-8 secretion were detected following carrageenan exposure. Knockdown of Bcl10 by siRNA markedly reduced the increase in IL-8 that followed carrageenan exposure in the NCM460 cells. These results show, for the first time, that exposure of human intestinal epithelial cells to carrageenan triggers a distinct inflammatory pathway via activation of Bcl10 with NF-kappaB activation and upregulation of IL-8 secretion. Since Bcl10 contains a caspase-recruitment domain, similar to that found in NOD2/CARD15 and associated with genetic predisposition to Crohn’s disease, the study findings may represent a link between genetic and environmental etiologies of inflammatory bowel disease. Because of the high use of carrageenan as a food additive in the diet, the findings may have clinical significance.
J Diabetes Res. 2015; 2015: 513429
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
Sumit Bhattacharyya, Leo Feferman, Terry Unterman, and Joanne K. Tobacman
Aims. Major aims were to determine whether exposure to the commonly used food additive carrageenan could induce fasting hyperglycemia and could increase the effects of a high fat diet on glucose intolerance and dyslipidemia. Methods. C57BL/6J mice were exposed to either carrageenan, high fat diet, or the combination of high fat diet and carrageenan, or untreated, for one year. Effects on fasting blood glucose, glucose tolerance, lipid parameters, weight, glycogen stores, and inflammation were compared. Results. Exposure to carrageenan led to glucose intolerance by six days and produced elevated fasting blood glucose by 23 weeks. Effects of carrageenan on glucose tolerance were more severe than from high fat alone. Carrageenan in combination with high fat produced earlier onset of fasting hyperglycemia and higher glucose levels in glucose tolerance tests and exacerbated dyslipidemia. In contrast to high fat, carrageenan did not lead to weight gain. In hyperinsulinemic, euglycemic clamp studies, the carrageenan-exposed mice had higher early glucose levels and lower glucose infusion rate and longer interval to achieve the steady-state. Conclusions. Carrageenan in the Western diet may contribute to the development of diabetes and the effects of high fat consumption. Carrageenan may be useful as a nonobese model of diabetes in the mouse.