Carrageenan

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Carrageenans or carrageenins (/ˌkærəˈɡnənz/ KARR-ə-GHEE-nənz from Irish carraigín, "little rock") are a family of linear sulphated polysaccharides that are extracted from red edible seaweeds. They are widely used in the food industry, for their gelling, thickening, and stabilizing properties. Their main application is in dairy and meat products, due to their strong binding to food proteins. There are three main varieties of carrageenan, which differ in their degree of sulphation. Kappa-carrageenan has one sulphate group per disaccharide. Iota-carrageenan has two sulphates per disaccharide. Lambda carrageenan has three sulphates per disaccharide.

Gelatinous extracts of the Chondrus crispus (Irish Moss) seaweed have been used as food additives since approximately the 1400s.[1] Carrageenan is a vegetarian and vegan alternative to gelatin in some applications, although it cannot replace gelatin in confectionery such as jelly beans.

Carrageenan has undergone many long-term dietary studies under defined regulatory conditions en route to its current global regulatory status. While some indicate that carrageenan safely passes through rat GI tracts without adverse effect when it is a dietary ingredient,[2] other animal dietary studies have observed colitis-like disease and tumour promotion.[3] In the late 2000s[clarification needed], some scientists raised concerns about whether the amount of "degraded carrageenan" (poligeenan) in food-grade carrageenan may lead to health problems, leading to a debate in the research literature.[4] It is yet to be determined whether such observations are pertinent to dietary safety considerations.

The use of carrageenan in infant formula, organic or otherwise, is prohibited in the EU for precautionary reasons, but is permitted in other foodstuffs.[5] In the US, it is permitted in organic and non-organic foods, including juices, chocolate milk, and organic infant formula.

Properties[edit]

The molecular structures of different types of carrageenan

Carrageenans are large, highly flexible molecules that curl forming helical structures. This gives them the ability to form a variety of different gels at room temperature. They are widely used in the food and other industries as thickening and stabilizing agents.

All carrageenans are high-molecular-weight polysaccharides made up of repeating galactose units and 3,6 anhydrogalactose (3,6-AG), both sulfated and nonsulfated. The units are joined by alternating α-1,3 and β-1,4 glycosidic linkages.

There are three main commercial classes of carrageenan:

  • Kappa forms strong, rigid gels in the presence of potassium ions; it reacts with dairy proteins. It is sourced mainly from Kappaphycus alvarezii.[6]
  • Iota forms soft gels in the presence of calcium ions. It is produced mainly from Eucheuma denticulatum.[6]
  • Lambda does not gel, and is used to thicken dairy products.

The primary differences that influence the properties of kappa, iota, and lambda carrageenan are the number and position of the ester sulfate groups on the repeating galactose units. Higher levels of ester sulfate lower the solubility temperature of the carrageenan and produce lower strength gels, or contribute to gel inhibition (lambda carrageenan).

Many red algal species produce different types of carrageenans during their developmental history. For instance, the genus Gigartina produces mainly kappa carrageenans during its gametophytic stage, and lambda carrageenans during its sporophytic stage.

All are soluble in hot water, but in cold water, only the lambda form (and the sodium salts of the other two) are soluble.

When used in food products, carrageenan has the EU additive E-number E407 or E407a when present as "processed eucheuma seaweed".[7] Technically carrageenan is considered a dietary fibre.[8][9]

In parts of Scotland and Ireland, where it is known by a variety of local and native names, Chondrus crispus is boiled in milk and strained, before sugar and other flavourings such as vanilla, cinnamon, brandy, or whisky are added. The end-product is a kind of jelly similar to pannacotta, tapioca, or blancmange.

Production[edit]

Eucheuma denticulatum being farmed for iota-carrageenan in an off-bottom cultivation in Tanzania.

Although carrageenans were introduced on an industrial scale in the 1930s, they were first used in China around 600 B.C. (where Gigartina was used) and in Ireland around 400 A.D.[citation needed] Carrageen gelatin can be prepared at home using the traditional recipe found in Diderot's encyclopedie and used for centuries. 5oz rinsed Irish moss is cooked with 8 quarts of water for 10 minutes, stirred as it boils. Hard water should be mixed with 1/2 oz of borax. Two quarts of cold water are rapidly added to the hot brew, and after the mixture has cooled it is strained through a cloth. It is then cooled for 24 hours and becomes gelatinous.[citation needed]

As of 2011, global sales of carageenan were estimated at $640 million.[10] The largest producer of industrial carrageenan was the Philippines, where cultivated seaweed produces about 80% of the world supply,[11] while China is the main exporter to global markets in the US and Europe.[10] The most commonly used sources are E. cottonii (Kappaphycus alvarezii, K.striatum) and E. spinosum (Eucheuma denticulatum), which together provide about three-quarters of the world production. These grow from the sea surface to a depth of about 2 metres. The seaweed is normally grown on nylon lines strung between bamboo floats, and it is harvested after three months or so, when each plant weighs approximately 1 kg.

The E. cottonii variety has been reclassified as Kappaphycus cottonii by Maxwell Doty (1988), thereby introducing the genus Kappaphycus, on the basis of the phycocolloids produced (namely kappa carrageenan).[citation needed]

After harvest, the seaweed is dried, baled, and sent to the carrageenan manufacturer. There the seaweed is ground, sifted to remove impurities such as sand, and washed thoroughly. After treatment with hot alkali solution (e.g., 5–8% potassium hydroxide), the cellulose is removed from the carrageenan by centrifugation and filtration. The resulting carrageenan solution is then concentrated by evaporation. It is dried and ground to specification.

There are three types of industrial processing:

Semi-refined[edit]

This is only performed using E. cottonii or E. spinosum. The raw weed is first sorted and crude contaminants are removed by hand. The weed is then washed to remove salt and sand, and then cooked in hot alkali to increase the gel strength. The cooked weed is washed, dried, and milled. E. spinosum undergoes a much milder cooking cycle, as it dissolves quite readily. The product is called semi-refined carrageenan, Philippines natural grade or, in the U.S., it simply falls under the common carrageenan specification.[12]

                           cleaned and washed seaweed 
                                   ↓
                                extraction
                                   ↓
                             coarse filtration   → seaweed residue
                                   ↓ 
                              fine filtration    → used filter aids
                                   ↓
                ------------ concentration --------↓
 preparation with KCl                         preparation with alcohol
         ↓                                          ↓
   gel pressing                                      alcohol recovery 
         ↓                                          |
      drying                                        |
         ↓                                          ↓ 
        milling                                   drying 
         ↓                                          ↓ 
      blending                                    milling
         ↓                                          ↓
     gel refined carrageenan                     blending
                                                    ↓
                                             refined carrageenan

Refined[edit]

The essential difference in the refining process is that the carrageenan is first dissolved and filtered to remove cell wall debris. The carrageenan is then precipitated from the clear solution either by isopropanol or by potassium chloride.[13]

Mixed processing[edit]

A hybrid technology in which seaweed is treated heterogeneously as in the semirefined process exists, but alcohol or high salt levels are used to inhibit dissolution. This process is often used on South American seaweeds and gives some of the cost benefits of semirefined processing, while allowing a wider range of seaweeds to be processed, however, the naturally low cellulose levels in some South American seaweeds allow them to be heterogeneously processed and still be sold under the EU refined specification.

Uses[edit]

Food and other domestic uses[edit]

  • Desserts, ice cream, cream, milkshakes, salad dressings, sweetened condensed milks, and sauces: gel to increase viscosity
  • Beer: clarifier to remove haze-causing proteins
  • Pâtés and processed meats (ham, e.g.): substitute for fat, increase water retention, and increase volume, or improve sliceability
  • Toothpaste: stabilizer to prevent constituents separating
  • Fruit Gushers: ingredient in the encapsulated gel
  • Fire fighting foam: thickener to cause foam to become sticky
  • Shampoo and cosmetic creams: thickener
  • Air freshener gels
  • Marbling: the ancient art of paper and fabric marbling uses a carrageenan mixture on which to float paints or inks; the paper or fabric is then laid on it, absorbing the colours
  • Shoe polish: gel to increase viscosity
  • Biotechnology: gel to immobilize cells/enzymes
  • Pharmaceuticals: used as an inactive excipient in pills/tablets
  • Soy milk and other plant milks: used to thicken, in an attempt to emulate the consistency of whole milk
  • Diet sodas: to enhance texture and suspend flavours
  • Pet food
  • Personal lubricants
  • Vegetarian hot dogs

Medical uses[edit]

Personal lubricant made from carrageenan

A 2006 in vitro study and a 2007 mouse study at the National Cancer Institute in the United States suggested that carrageenans might function as a topical microbicide.[14][15] A 1987 in vitro study in Spain revealed a broad spectrum antiviral activity of carrageenan.[16]

HSV[edit]

There are indications a carrageenan-based gel may offer some protection against HSV-2 transmission by binding to the receptors on the herpes virus, thus preventing the virus from binding to cells. Research has shown a carrageenan-based gel effectively prevented HSV-2 infection at a rate of 85% in a mouse model.[17]

HPV[edit]

Laboratory studies have shown carrageenans inhibit HPV infection in vitro and in mouse challenge models.[14][15] A substudy of a South African HIV-prevention clinical trial found a lower prevalence of high risk HPV infection in users of a carrageenan-based vaginal microbicide, Carraguard, versus placebo users at the end of the trial—prevalence of high risk HPV infection at the beginning of the trial was not ascertained.[18][19]

HIV[edit]

A phase 3 clinical trial by the Population Council examined whether a carrageenan-based product was effective as a topical microbicide for blocking HIV infection in women.[17] The trial ran from 2004 to 2007, with more than 4,000 South African women completing the study, but found no statistical difference in infection between those having used the lubricant and those not having used the lubricant.[20][21] The trial also provided information about usage patterns and showed that the gel does not increase infection any more than the baseline or cause significant side-effects. As such, it is expected to be used as a stable delivery vehicle for experimental antiretrovirals in future studies.

Concurrent studies in macaques found the same carrageenan gels used in clinical trials to be effective against SIV challenge. This was in direct contrast with in vitro findings, where the compound was found to enhance HIV and SIV infections in various assays. Although compliance was believed to be one issue in clinical versus animal trials, the high viscosity and controlled nature of animal-viral inoculations (atraumatic introduction of virus using a French catheter) may be why the latter animal study observed a positive outcome.[22]

Common cold[edit]

Clinical studies have shown coating the insides of the nose with carrageenans to be preventative against common cold virus infections.[23]

Animal models[edit]

Dilute lambda carrageenan solution (1–2%) injected subcutaneously causes swelling and pain. It is used in animal models of inflammatory pain e.g. to test efficacy of analgesics. A murine (mouse) model of ulcerative colitis is induced by feeding mice degraded carrageenan (poligeenan).[24]

Health concerns[edit]

Cancer and gastrointestinal effects[edit]

There have been several peer-reviewed animal studies suggesting tumor promotion or initiation by carrageenan.[25][26][27][28] In an industry-funded study, Cohen & Ito discuss methodological problems with four such studies, along with several evaluations of genotoxic activity, and conclude that there is no credible evidence that carrageenan contributes to tumor promotion or colon cancer.[29] In contrast, Tobacman's review of 45 publicly funded studies concludes that "the potential role of carrageenan in the development of gastrointestinal malignancy and inflammatory bowel disease requires careful reconsideration of the advisability of its continued use as a food additive."[3] As of 2011, Kanneganti et al. note that "the role of both CGN [carrageenan] and dCGN [degraded carrageenan] as carcinogens still remains controversial".[30]

Studies conducted with isolated cells and human intestinal epithelial cells in tissue culture as models for in vivo conditions have suggested carrageenan may trigger a number of responses in the body that lead to inflammation of the intestines or bind to and activate several membrane receptor signaling pathways.[31][32]

Carrageenan is commonly used to induce inflammatory responses in mice. Notably, the air pouch inflammation model is based on administration of 1% carrageenan into sub-cutaneous air pouches in mice and strong inflammatory reactions are observed as early as 4 hours post administration. This in vivo inflammation model has been widely used to study the effect of anti-inflammatory compounds.[33]

Carrageenan's function as a food additive relates to its large molecular weight (200,000–800,000 Da) and tight binding to food protein, but also influences carrageenan's fate as it passes through the GI tract. Oral feeding studies with laboratory animals indicate dietary carrageenan is excreted quantitatively [34][35] and is not accumulated in body organs such as the liver or colon;[36] studies disagree with respect to whether it triggers gastrointestinal tract inflammation or contributes to tumor promotion.[3][37] Long-term oral feeding studies found no adverse effects on male or female infant baboons reared from birth to 112 days of age on infant formula containing carrageenan at 5-times the concentration typically present in human infant formula as their only diet,[38] but did observe histopathologic changes in rhesus monkey colon after drinking solution containing 1% undegraded carrageenan.[39] Similarly, while no adverse effects were observed for multi-generations of rats fed up to 5% dietary carrageenan,[40][41] or on hamsters and rats fed for a lifetime diets containing up to 5% carrageenan,[42][43] administration of carrageenan to rodents in drinking water has resulted in some observations of GI-tract effects.[44][45][46] Tight binding of carrageenan to ingested food proteins is considered less available than in drinking water for interaction with the absorptive cells of the GI tract, although some studies have linked food-grade carrageenan to gastrointestinal disease in laboratory animals, including ulcerative colitis-like disease, intestinal lesions, and ulcerations.[47][48][49][50][51]

Carrageenan is inert to hydrolysis by intestinal enzymes in both humans and monogastric animals.[52][53] Many older studies and a few recent studies have been based on the use of "degraded carrageenan," a fraction of low-molecular weight segments of the carrageenan molecular backbone called "poligeenan." To resolve this within the scientific community, the U.S. Adopted Names Council assigned the name "poligeenan" to the fragments with molecular weight of 10,000 to 20,000 Da.[54][55] Approximately 8% of the fragments of food-grade carrageenan are of molecular mass less than 50,000 Da, in excess of the recommended minimum of 5% set by the European Scientific Committee on Food to ensure that the presence of poligeenan is kept to a minimum.[4] The proportion of this 8% that consists of poligeenan is unknown.

Regulatory status[edit]

In the U.S., carrageenan is allowed under FDA regulations[56] as a direct food additive and is considered safe[57] when used in the amount necessary as an emulsifier, stabilizer, or thickener in foods, except those standardized foods that do not provide for such use. FDA also reviewed carrageenan safety for infant formula.[58] The National Organic Program (NOP) added carrageenan to the National List;[59] reviewed and reauthorized in 2008[60] as "critical to organic production and handling operations".[61] The European Food Safety Authority concluded "there is no evidence of any adverse effects in humans from exposure to food-grade carrageenan, or that exposure to degraded carrageenan from use of food-grade carrageenan is occurring",[62] Furthermore, the Joint FAO/WHO expert committee on food additives stated in a July 2014 review of carrageenan "that the use of carrageenan in infant formula or formula for special medical purposes at concentrations up to 1000 mg/L is not of concern".[63]

Effects of radiation[edit]

Environmental advocate Dr. Helen Caldicott has drawn attention to the effect of radiation effects from the Fukushima Daiichi nuclear disaster on ocean life, arguing that seaweeds coming from the Pacific Ocean must be looked at carefully.[64] Concerns include the potential presence of carcinogenic radionuclides and the degradation of carrageenan by radiation; radiation degrades carrageenan,[65] and degraded carrageenan has been more closely associated with adverse health outcomes than undegraded carrageenan in animal studies.[3] No studies have yet been conducted to determine whether radiation-exposed Pacific seaweeds pose a danger to human health.

Grades[edit]

See also: Food grading

There are two basic grades of carrageenan: refined carrageenan (RC) and semi-refined carrageenan (SRC). In the United States both grades are labeled as carrageenan. In the European Union, refined carrageenan is designated by the E number E-407, and semi-refined carrageenan as E-407a.[7] Refined carrageenan has a 2% maximum for acid insoluble material and is produced through an alcohol precipitation process or potassium chloride gel press process. Semi-refined carrageenan contains a much higher level of cellulosic content and is produced in a less complex process. Indonesia, the Philippines, and Chile are three main sources of raw material and extracted carrageenan.

See also[edit]

References[edit]

  1. ^ FAO Agar and Carrageenan Manual. Fao.org (1965-01-01). Retrieved on 2011-12-10.
  2. ^ Weiner ML, Nuber D, Blakemore WR et al., (2007) A 90-day dietary study of kappa carrageenan with emphasis on the gastrointestinal tract. Fd Chem Toxicol 45:98-106
  3. ^ a b c d Tobacman JK (2001) Review of harmful gastrointestinal effects of carrageenan in animal experiments.Environ Health Perspect 109(10):983-984.
  4. ^ a b Spichtig, V., & Austin, S. (2008). Determination of the low molecular weight fraction of food-grade carrageenans. Journal of Chromatography B, 861(1), 81-87.
  5. ^ European Commission, Scientific Committee on Food. Opinion of the Scientific Committee on Food on Carrageenan (2003). http://ec.europa.eu/food/fs/sc/scf/out164_en.pdf.
  6. ^ a b [1], FAO Fisheries Technical Paper No. 441
  7. ^ a b "Current EU approved additives and their E Numbers". Food Standards Agency. 26 November 2010. Retrieved 12 August 2014. 
  8. ^ http://www.marine-science.co.jp/english/goods/carra.html, Marine Science Co. Ltd.
  9. ^ DeSilver, Drew (April 1993). "Answering Machine: Carra-what?". Vegetarian Times: 28. Retrieved 12 August 2014. 
  10. ^ a b Carrageenan Industry Report 2012 Contents (Report). CyberColloids Ltd.. 2012. http://www.cybercolloids.net/sites/default/files/private/downloads/Carrageenan%20market%20report%202012%20contents.pdf. Retrieved 6 April 2014.
  11. ^ Pareño, Roel (14 September 2011). "DA: Phl to regain leadership in seaweed production". The Philippine Star. Retrieved 6 April 2014. 
  12. ^ CyberColloids: E407 Specification Carrageenan, CyberColloids, Hydrocolloids research and development webpage.
  13. ^ CyberColloids: E407a Specification Procesed Eucheuma Seaweed, Hydrocolloids research and development webpage.
  14. ^ a b Buck, Christopher B.; Thompson, Cynthia D.; Roberts, Jeffrey N.; Müller, Martin; Lowy, Douglas R.; Schiller, John T. (July 2006). "Carrageenan is a potent inhibitor of papillomavirus infection". PLoS Pathogens 2 (7): 671–680. doi:10.1371/journal.ppat.0020069. PMC 1500806. PMID 16839203. "Some, but not all, carrageenan-containing over-the-counter sexual lubricant gels we tested were extremely effective for blocking the infectivity of an HPV16 reporter pseudovirus in vitro. These results raise the possibility that use of such lubricant products, or condoms lubricated with carrageenan based gels, could block the sexual transmission of HPV. However, in the absence of clinical efficacy data, it would be inappropriate to recommend currently available products for use as topical microbicides." 
  15. ^ a b Roberts, Jeffrey N.; Buck, Christopher B.; Thompson, Cynthia D.; Kines, Rhonda; Bernardo, Marcelino; Choyke, Peter L.; Lowy, Douglas R.; Schiller, John T. (July 2007). "Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan". Nature Medicine 13 (7): 857–861. doi:10.1038/nm1598. PMID 17603495. 
  16. ^ González, María Eugenia; Alarcón, Balbino; Carrasco, Luis (September 1987). "Polysaccharides as antiviral agents: antiviral activity of carrageenan". Antimicrobial Agents and Chemotherapy 31 (9): 1388–1393. doi:10.1128/AAC.31.9.1388. PMC 174948. PMID 2823697. 
  17. ^ a b Population Council (August 17, 2009). "Microbicides program". New York: Population Council. Archived from the original on November 3, 2009. Retrieved September 5, 2007. 
  18. ^ Marais, Dianne; Gawarecki, Daniel; Rutenberg, Naomi; Allan, Bruce; Ahmed, Khatija; Altini, Lydia; Cassim, Nazira; Gopolang, Felicity; Hoffman, Margaret; Williamson, Anna-Lise (July 2010). "P-107: Carraguard, a vaginal microbicide, protects women against HPV infection (poster)". Montreal, Canada: 26th International Papillomavirus Conference, July 3–8, 2010. Archived from the original on July 26, 2011. Retrieved July 20, 2010. 
  19. ^ Marais, Dianne; Gawarecki, Daniel; Allan, Bruce; Ahmed, Khatija; Altini, Lydia; Cassim, Nazira; Gopolang, Felicity; Hoffman, Margaret; Ramjee, Gita; Williamson, Anna-Lise (2011). "The effectiveness of Carraguard, a vaginal microbicide, in protecting women against high-risk human papillomavirus infection". Antiviral Therapy 16 (8): 1219–1226. doi:10.3851/IMP1890. PMID 22155903. 
  20. ^ "Trial Shows Anti-HIV Microbicide Is Safe, but does Not Prove it Effective". Population Council. 18 February 2008. Retrieved 2008-03-12. 
  21. ^ "Experimental Microbicide Carraguard Does Not Provide Protection Against HIV, Study Finds". kaisernetwork.org. 20 February 2008. Retrieved 2008-03-12. 
  22. ^ Turville, Stuart G.; Aravantinou, Meropi; Miller, Todd; Kenney, Jessica; Teitelbaum, Aaron; Hu, Lieyu; Chudolij, Anne; Zydowsky, Tom M. et al. (2008). "Efficacy of Carraguard-Based Microbicides In Vivo Despite Variable In Vitro Activity". In Kewalramani, Vineet N. PLoS ONE 3 (9): e3162. doi:10.1371/journal.pone.0003162. PMC 2525816. PMID 18776937. 
  23. ^ Eccles R, Meier C, Jawad M, Weinmüllner R, Grassauer A, Prieschl-Grassauer E (2010). "Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold". Respiratory Research 11: 108. doi:10.1186/1465-9921-11-108. PMC 2923116. PMID 20696083. 
  24. ^ Fath, RB Jr; Deschner, EE; Winawer, SJ; Dworkin, BM (1984). "Degraded carrageenan-induced colitis in CF1 mice. A clinical, histopathological and kinetic analysis". Digestion 29 (4): 197–203. doi:10.1159/000199033. 
  25. ^ Watanabe, K., Reddy, B. S., Wong, C. Q., & Weisburger, J. H. (1978). Effect of dietary undegraded carrageenan on colon carcinogenesis in F344 rats treated with azoxymethane or methylnitrosourea" Cancer Research 38(12), 4427–4430.
  26. ^ Taché, S, Peiffer, G, Millet, A-S, and Corpet, DE. Carrageenan gel and aberrant crypt foci in the colon of conventional and human flora-associated rats. Nutr Cancer 37:75–80, 2000.
  27. ^ Yasuyuki Oohashi, Tomonori Ishioka, Kazuo Wakabayashi, Noriyuki Kuwabara. (1981). A study on carcinogenesis induced by degraded carrageenan arising from squamous metaplasia of the rat colorectum. Cancer Letters, 14(3):267-272.
  28. ^ Corpet, DE, Taché, S, and Préclaire, M. Carrageenan given as a jelly, does not initiate, but promotes the growth of aberrant crypt foci in the rat colon" Cancer Lett 114:53–55, 1997b.
  29. ^ Cohen S and Ito N (2002) A critical review of the toxicological effects of carrageenan and processed eucheuma seaweed on the gastrointestinal tract.Crit Rev in Toxicol 32(5) 413-444
  30. ^ Kanneganti, M., Mino-Kenudson, M., & Mizoguchi, E. (2011). Animal models of colitis-associated carcinogenesis. BioMed Research International, 2011.
  31. ^ 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
  32. ^ 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
  33. ^ Duarte DB, Vasko MR, Fehrenbacher JC. (2012) Models of Inflammation: carrageenan air pouch. Current Protocols in Pharmacology, Chapter 5
  34. ^ Uno Y, Omoto T, Goto Y, et al., (2001) Molecular weight and fecal excreted quantity of carrageenan administered to rats in blended feed. Japanese Journal of Food Chemistry 45(1):98-106
  35. ^ Weiner ML (1988) Intestinal transport of some macromolecules in food. Fd Chem Toxicol 26:867-880
  36. ^ Pittman KA, Golberg L, Coulston F (1976) Carrageenan: the effect of molecular weight and polymer type on its uptake, excretion and degradation in animals. Fd Cosmet Toxicol 14:85-93
  37. ^ Weiner ML, Nuber D, Blakemore WR et al., (2007) A 90-day dietary study of kappa carrageenan with emphasis on the gastrointestinal tract.Fd Chem Toxicol 45:98-106
  38. ^ McGill HC,Jr., McMahan CA, Wigodsky HS, Sprinz H. (1977) Carrageenan in formula and infant baboon development. Gastroenterology 73:512-517
  39. ^ Mankes & Abraham, 1975, as cited in Tobacman, J.K. (2001), Review of harmful gastrointestinal effects of carrageenan in animal experiments.Environ Health Perspect 109(10):983-984.
  40. ^ Collins TFX, Black TN, Prew JH (1977a) Long-term effects of calcium carrageenan in rats. 1. Effects on reproduction. Fd Cosmet Toxicol 15:533-538
  41. ^ Collins TFX, Black TN, Prew JH (1977b) Long-term effects of calcium carrageenan in rats. II. Effects on fetal development. Fd Cosmet Toxicol 15:539-545
  42. ^ Rustia M, Shubik P, Patil K (1980) Lifespan carcinogenicity test with native carrageenan in rats and hamsters. Cancer Letters 11(1):1-10
  43. ^ Abraham R, Benitz KF, Mankes R, Rosenblum I (1985) Chronic and subchronic effects of various forms of carrageenan in rats Ecotoxicology and Environmental Safety 10:173-183
  44. ^ Wilcox DK, Higgins J and Bertram TA (1992) Colonic epithelial cell proliferation in a rat model of nongenotoxin-induced colonic neoplasia Lab Invest 67(3):405-411
  45. ^ Calvert RJ and Satchithanandam S (1992) Effects of graded levels of high-molecular-weight carrageenan on colonic mucosal thymidine kinase activity Nutrition 8(4):252-257
  46. ^ Calvert RJ and Reicks M (1988) Alterations in colonic thymidine kinase enzyme activity induced by consumption of various dietary fibers Proc Soc Exp Biol Med 189(1)45-51
  47. ^ Watt J and Marcus R (1969) Ulcerative colitis in the guinea-pig caused by seaweed extract. Journal of Pharmacy and Pharmacology 21:187S–188S
  48. ^ 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
  49. ^ 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
  50. ^ 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
  51. ^ Review of harmful gastrointestinal effects of carrageenan in animal experiments J. K. Tobacman (2001)
  52. ^ Harmuth-Hoene AE and Schwerdtfeger E (1979) Effects of indigestible polysaccharides on protein digestibility and nitrogen retention in growing rats. Nutr Metab 23:399-407
  53. ^ Cummings JH, Jenkins DJA and Wiggins HS (1976) Measurement of the mean transit time of dietary residue through the human gut. Gut17:216-218
  54. ^ United States Adopted Names Council (1988)
  55. ^ CAS Number 53973-98-1
  56. ^ 21 Code of Federal Regulations 172.620
  57. ^ Generally Recognized As Safe 21 CRF §182.7255 GRAS ID Code 9000-07-1 (1973)
  58. ^ Federal Food, Drug, and Cosmetic Act 21 U.S.C. 350(a) §412
  59. ^ 68 FR 61993 (2003)
  60. ^ 65 FR 80548
  61. ^ 73 FR 59481
  62. ^ Opinion of the Scientific Committee on Food on Carrageenan (2003) [2] p. 5
  63. ^ Joint FAO/WHO Expert Committee on Food Additives. Who.int. Retrieved on 2014-8-11.
  64. ^ Caldicott, Helen. "The Medical Implications of Fukushima". Invited talk. International House of Japan in Roppongi, Tokyo, on July 7, 2013.
  65. ^ L. Rellevea, N. Nagasawab, L.Q. Luanc, T. Yagib, C. Aranillaa, L. Abada, T. Kumeb, F. Yoshiib, A. dela Rosaa (2005) Degradation of carrageenan by radiation. Polymer Degradation and Stability 87(3):403-410

Further reading[edit]

External links[edit]