,
turmeric
[likely to be from GM Bacteria]
,
turmeric
[likely to be from GM Bacteria],
pimaracin]]]]
(synthetic) [possibly GM]
(synthetic) [possibly GM]
(synthetic) [possibly GM]
[Colour Retention Agent] [possible allergic reaction]
and gastrointestinal malignancy
have been major causes of morbidity and mortality in the USA. Even with
improvements in treatment and cancer screening, colorectal cancer remains
the second leading cause of cancer mortality in the United States. The
Western diet has been considered a possible source of inflammatory bowel
disease and colorectal malignancy, and intensive efforts have been undertaken
to study the impact of specific constituents of the Western diet, such
as fiber and fat (1-3). One food additive, carrageenan, has been associated
with induction and promotion of intestinal neoplasms and ulcerations in
numerous animal experiments; however, carrageenan remains a widely used
food additive. In 1982, the International Agency for Research on Cancer
(IARC) (4) designated degraded carrageenan as Group 2B, noting sufficient
evidence for the carcinogenicity of degraded carrageenan in animal models
to infer that "in the absence of adequate data on humans, it is reasonable,
for practical purposes, to regard chemicals for which there is sufficient
evidence of carcinogenicity in animals as if they presented a carcinogenic
risk to humans" (p. 90). The National Research Council has noted this designation
for degraded carrageenan in their 1996 monograph (5). Recognizing the impact
of carrageenan in animal models, several European and British investigators
have advised against the continued use of carrageenan in food (6-11). Several
reports have called attention to the problems associated with carrageenan
consumption (6-11). Extracted from red seaweed, carrageenan has been
used in food products for centuries and was patented as a food additive
for use in the USA in the 1930s. It has been used widely as a food additive,
contributing to the texture of a variety of processed foods. It has also
been used as a laxative,
as treatment for peptic
ulcer disease,
and as a component of pharmaceuticals, toothpaste, aerosol sprays, and
other products (12-15). In 1959, carrageenan was granted GRAS (Generally
Regarded as Safe) status in the USA. GRAS substances are permitted to be
incorporated into food products as long as good manufacturing processes
are used and the substance is used only in sufficient quantity to achieve
the desired effect (16,17). In the USA, the status of carrageenan was reconsidered
by the FDA, and an amendment to the Code of Federal Regulations for the
food additive carrageenan was proposed in 1972 (18). To diminish the
public's exposure to degraded carrageenan, the amendment supported inclusion
of an average molecular weight for carrageenan of 100,000 and a minimum
viscosity of 5 centipoises (cps) under specified conditions. However,
the actual regulation was not amended, although several publications indicated
that it had been modified (7,8,19-23). In 1979, the proposal to include
the average molecular weight requirement of 100,000 and the associated
viscosity requirement in the Code of Federal Regulations was withdrawn.
It was anticipated that a new rule-making proposal on carrageenan that
would comprehensively address all food safety aspects of carrageenan and
its salts would be published in about a year, but this has not been forthcoming
(24,25). The proposal withdrawal referred to interim specifications for
food-grade carrageenan using the Food Chemical Codex; these include a viscosity
stipulation, but no average molecular weight requirement (26). In the Food
Chemicals Codex and supplements, carrageenan is described with attention
to specific requirements for its identification and tests of its properties,
including its sulfate content, heavy metal content, solubility in water,
content of acid-insoluble matter, and viscosity [a 1.5% solution is to
have viscosity >= 5 cps at 75°C] (26,27). Although the viscosity is
stipulated, viscosity may not adequately protect food-grade carrageenan
from contamination by the lower molecular weight degraded carrageenans
that IARC has denoted as Group 2B. Because undegraded carrageenan may have
molecular weight in the millions, the actual viscosities of commercial
carrageenans range from about 5 to 800 cps when measured at 1.5% at 75°C
(14). Native carrageenan has molecular weights of 1.5 106-2
107 (28); poligeenan or degraded carrageenan is described as having
average molecular weight of 20,000-30,000 (4). The average molecular weight
of poligeenan has been described elsewhere as 10,000-20,000, but extending
up to 80,000 (29). Food-grade carrageenan has been described as having
average molecular weight of 200,000-400,000 (29), and elsewhere as having
molecular weight of 100,000-800,000 (19). Furcelleran (or furcellaran),
a degraded carrageenan of molecular weight 20,000-80,000, has a sulfate
content of 8-19% (12,17). No viscosity or minimum average molecular weight
was designated for furcelleran in the 1972 or 1979 Federal Register documents
(18,24). In the Food Chemical Codex (fourth edition), a 1.5% solution of
furcelleran at 75°C is described as having minimum viscosity of 5 cps
(27). Today, carrageenan is still included among the food additives designated
GRAS in the Code of Federal Regulations. The stipulations for its use include
the following: a) it is a sulfated polysaccharide, the dominant hexose
units of which are galactose and anhydrogalactose; b) range of sulfate
content is 20-40% on a dry-weight basis; c) the food additive is used or
intended for use in the amount necessary for an emulsifier, stabilizer,
or thickener in foods, except for those standardized foods that do not
provide for such use; d) to assure safe use of the additive, the label
and labeling of the additive shall bear the name of the additive, carrageenan.
Also included are similar standards for carrageenan salts and for furcelleran
and furcelleran salts (30). In 1999-2000, approved uses for carrageenan
were extended to include additional incorporation into food and medicinal
products, including both degraded and undegraded carrageenan in laxatives
(31-33). For use in experimental models, degraded carrageenan (poligeenan)
is derived from carrageenan by acid hydrolysis, frequently by a method
developed by Watt et al. (34). This method is expected to yield a degraded
carrageenan of average molecular weight 20,000-30,000 (35).Experiments
demonstrate that reaction conditions similar to those of normal digestion
can lead to the formation of degraded carrageenan (9-11). In addition,
experimental data have revealed the contamination of food-grade carrageenan
by substantial amounts of degraded carrageenan (10). Also, some bacteria
are known to hydrolyze carrageenan and form low molecular weight derivatives
(36-40). The sections that follow and the accompanying tables
summarize many experimental observations with regard to the intestinal
effects of carrageenan. In addition, I review possible mechanisms for production
of degraded carrageenan from undegraded carrageenan under physiologic conditions,
as well as evidence that provides a basis for the mechanism of carrageenan's
effects and for the reconsideration of the safety of carrageenan in the
human diet.
]]]
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