Carrageenan in foods: response. (Correspondence).

Carrageenan has been the subject of significant investigation for several decades, and the complexity pertaining to it may have impeded our ability to form a clear impression about its harmful effects. In rodent models, there is clear evidence that degraded carrageenan can induce ulcerations and neoplasms. Also, there is clear evidence that food-grade carrageenan can be broken down to degraded carrageenan by acid hydrolysis and by bacteria, and degraded carrageenan is likely to contaminate food-grade carrageenan. Although most of our concerns about carcinogenic exposures arise in relation to the unmetabolized product, the situation with carrageenan requires some extension of our perspective to recognize that exposure to undegraded carrageenan is inevitably accompanied by exposure to degraded carrageenan. If we accept the Delaney standard of no known carcinogens in food or the pesticide standard of no more than one in part in a million (1), the use of carrageenan in food is clearly in excess.

Carthew has raised issues pertaining to the role of human intestinal flora on the effects related to carrageenan and the possibility of interspecies variation in the toxicity of carrageenan. The paper by Tache et al. (2) referred to by Carthew actually supports concerns about the availability of degraded carrageenan after exposure to food-grade carrageenan and human microflora. The authors report data on the average molecular weight of carrageenan recovered from stool samples in feeding experiments with rats in which human intestinal microflora had been introduced. The average molecular weight of the carrageenan extracted from feces was 346,000 [+ or -] 18,000 in the rats with the conventional intestinal flora and was slightly lower (307,000 [+ or -] 37,000) in the rats exposed to human intestinal microflora. This strongly suggests that metabolism of dietary carrageenan does not depend on the presence of rodent microflora.

Interpretation of Tache et al.'s (2) data on the number of crypt foci and the numbers of aberrant crypts is confounded by lack of a comparable control group, as noted by the authors. When they sought to expose a control population to similar conditions (life in an isolator, sawdust bedding), they found that the rats developed only 20 aberrant crypt foci per colon; this was far less than the previously reported controls that developed 86 [+ or -] 23 aberrant crypt foci per colon or the experimental animals with human intestinal microflora that developed 55 [+ or -] 18 aberrant crypt foci per colon (3), suggesting unresolved experimental issues pertaining to initiation. This confounds interpretation of the data about promotion. Also, Tache et al. (2) did not provide details about the actual composition of the microflora in their experimental rats, and we do not know if it was consistent throughout the experiment. Hence, these data cannot be used to declare that the colon cancer-promoting effect of food-grade carrageenan is a "rodent-specific phenomenon" and that it requires a rodent intestinal microbiologic flora.

When the Food and Drug Administration (FDA) considered the status of carrageenan in the early 1970s, their review included a study of 24 rhesus monkeys with appropriate controls (4,5). Investigators observed that monkeys fed 2% degraded carrageenan did not gain weight, had an immediate change in stool consistency, and consistently had blood in their stools, which was associated with a decline in hemoglobin, until approximately 10 weeks after the withdrawal of the carrageenan. In addition, they developed mucosal erosions and ulceration and multiple crypt abscesses. Pathologic changes were dose and duration dependent. Thus, these data indicate that degraded carrageenan can induce colitis in primates.

It is unfortunate that the June 2001 meeting of the FAO/WHO Expert Committee on Food Additives (JECFA) (6) rated the acceptable daily intake (ADI) of carrageenan as "not specified," as they had done previously, including at the 28th meeting in 1984 (7), rather than establishing a different position. In the 1999 report on carrageenan prepared as part of the World Health Organization Food Additives Series, Greig (8) stated that the JECFA ADI of "not specified" for carrageenan was temporary, pending review in 2001. Also, Greig (8) pointed out that degraded carrageenans and processed Eucheuma seaweed were not included by the JECFA in the specifications of food-grade carrageenan in 1984. Subsequently, a review of carrageenan was undertaken for the 2001 meeting. Greig (8; p. 16) noted that

   Maintenance of a restriction on the relative mass distribution in the
   specifications of carrageenan for food use provides protection against the
   adverse effects of carageenans (sp) of low relative molecular mass.

However, in 2001 the JECFA apparently did not endorse any specific restriction on the molecular weight of food-grade carrageenan. The report of Cohen and Ito to which Carthew refers and the full report of JECFA 2001 are not yet published.

I hope that the recommendations pertaining to carrageenan will be revised by regulatory groups. Clearly, there are significant economic issues and interests for the food industry and for populations involved in farming red seaweeds. In the United States, the FDA has ignored the harmful potential of carrageenan for over 20 years, but now is the time to reevaluate carrageenan and its potential harmful effects.

Joanne Tobacman
University of Iowa Health Care
Iowa City, Iowa
E-mail: [e-mail]

REFERENCES AND NOTES

(1.) Food Quality Protection Act of 1996. Public Law 104-170, 1996.

(2.) Tache S, Peiffer O, Millet A-S, Corpet DE. Carrageenan gel and aberrant crypt foci in the colon of conventional and human flora-associated rats. Nutr Cancer 37:193-198 (2000).

(3.) Corpet DE, Tache S, Preclaire 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 (1997).

(4.) Informatics, Inc. Monograph on Carrageenan. Vol 1. TR-72-1552-03. Rockville, MD:Informatics, Inc., 1972.

(5.) Benitz K-F, Golberg L, Coulston F. Intestinal effects of carrageenans in the rhesus monkey (Macaca mulatta). Food Cosmet Toxicol 11:565-575 (1973).

(6.) Joint FAO/WHO Expert Committee on Food Additives Fifty-seventh meeting, Rome, 5-14 June 2001. Summary and conclusions. Available: http://www.fao.org/es/ ESN/Jecfa/57corr.pdf [cited 15 February 2002].

(7.) Joint FAP/WHO Expert Committee on Food Additives. Specifications for Identity and Purity of Food Additives: Anticaking Agents, Buffering Agents, Salts, Emulsifiers, Enzymes, Extraction Solvents, Flavouring Agents, and Miscellaneous Food Additives: 28th Session of the Joint FAO/WHO Expert Committee on Food Additives, Rome, March 1984. Rome:Food and Agriculture Organization of the United Nations, 1984.

(8.) Greig JB. Carrageenan. WHO Safety Evaluation of Certain Food Additives. Food Additives Series 42. Geneva:World Health Organization, 1999. Available: http://www.inchem.org/documents/jecfa/jecmono/ v042je08.htm [cited 22 February 2002].