"Conclusion
Inflammatory bowel disease and colorectal malignancy represent major sources of morbidity and mortality in the United States. A possible factor in the etiology of these pathologies is exposure to carrageenan.
Several investigators have expressed their concerns about the use of undegraded carrageenan in food products (6-10), yet no legislative protection to restrict incorporation of low molecular weight fractions has been enacted. In fact, there has been no substantive review by the Food and Drug Administration of carrageenan since the studies undertaken more than two decades ago. However, there has been increased evidence regarding the cancer-promoting activity of undegraded carrageenan and further confirmation of the carcinogenic potential of degraded carrageenan.
Evidence for the role in carcinogenesis of carrageenan appears to support a nongenotoxic model based on direct toxic effects, for carrageenan has been nonmutagenic in Salmonella mutagenicity testing and nongenotoxic by DNA repair tests (60,102). A model of cellular destruction--from disruption of lysosomes by accumulation of carrageenan by-products or by interference with normal cellular oxidation-reduction processes from sulfate metabolites--emerges from review of the experimental studies. The impact of sulfatases, of either bacterial or human origin, on the metabolism of carrageenan requires further investigation. By interference with the normal intracellular feedback mechanisms associated with arylsulfatase activity, including steroid sulfatase, the highly sulfated carrageenan may have an impact on the availability of active, unsulfated hormones, such as dehydroepiandrosterone, derived from dehydroepiandrosterone-sulfate, and estrone-1, derived from estrone-1 sulfate.
Genetic characteristics that affect sulfatase and hydrolysis reactions as well as the individual intestinal microflora may influence how carrageenan is metabolized and how its effects are manifested. These factors may determine how carrageenan is metabolized differently by different individuals, but these characteristics may not be accessible to manipulation. A basic factor that can be controlled is the intake of carrageenan, which is amenable to dietary modification or food additive regulation.
Although carrageenan is widely used as a food additive for its texture-enhancing properties, other gums, some of which are used in combination with carrageenan, such as locust bean gum, gum arabic, alginate, guar gum, or xanthan gum, potentially can be used alone or in different combinations as substitutes for carrageenan (41,46). Alternatively, higher fat composition can lead to changes in food properties that may compensate for exclusion of carrageenan. Other hydrocolloids that are used as stabilizers and thickeners have not been associated with harmful gastrointestinal effects, and it is reasonable to expect that they could replace carrageenan in many food products. Although the dietary fibers pectin and psyllium affect intestinal motility, ulcerations or neoplasms have not been induced with either these or the other water-soluble polymers used as food additives. In contrast, other highly sulfated polysaccharides, amylopectin sulfate and dextran sulfate sodium, have induced ulcerations and neoplasia, suggesting that the degree of sulfation and polysaccharide molecular weight may be critical for induction of the observed effects (102).
The major pieces of evidence that support an argument to reconsider the advisability of use of carrageenan as a GRAS food additive are:
* Degraded carrageenan is a known carcinogen in animal models
* Undegraded carrageenan is a known co-carcinogen in animal models of carcinogenesis
* In animal models, both degraded and undegraded carrageenan have been associated with development of intestinal ulcerations that resemble ulcerative colitis
* Hydrolysis such as may occur by exposure to gastric acid in the human stomach can lead to the depolymerization of undegraded carrageenan and the availability of degraded carrageenan
* Food-grade carrageenan may be contaminated with low molecular weight, degraded carrageenan that may arise during food processing
* The use of a viscosity measurement to characterize a carrageenan sample is insufficient because the presence of a small number of large molecules (and undegraded carrageenan may have molecular weight in the millions) may obscure a significant low molecular weight fraction.
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."