Polysaccharide Ingredients: Carrageenan

William R Blakemore, Celtic Colloids Inc., Topsham, ME, USA

Ó 2016 Elsevier Inc. All rights reserved.

Introduction 1
Raw Materials 1
Manufacturing 1
Regulation 2
Molecular Structure 3
Chemistry 4
Solubility and Hydration 4
Gelation 4
Protein Reactivity 5
Acid Stability 5
Synergies 5
Applications 6
Toxicology 6
References 7

Introduction

For centuries, red seaweeds (Rhodophyceae) have been harvested and used as foods in the Far East and Europe. Carrageenan
(CGN) is a natural high molecular weight carbohydrate polymer present interstitially in the plant structure of specific species
of these red seaweeds, which are native to the shores of the North Atlantic and South America, and which are cultivated in
the tropics. Each species produces a unique CGN which results in a wide spectrum of functional attributes (Blakemore and
Harpell, 2010).
CGN is not absorbed across the gastrointestinal tract (GIT) and hence not systemically available to the human body, providing
only fiber with no nutritional value (Weiner, 2014). CGN has been widely used as a food additive for decades for its gel formation,
stabilization, thickening, and water-binding functionalities to improve the palatability of processed foods. Of primary importance is
the interaction of CGN with proteins (dairy, soy, meat, etc.), which has resulted in multiple applications, such as ice cream, choc-
olate milk, puddings, desserts, infant formulations, deli meats, etc. In addition to conventional foods, CGN is used in ‘Kosher,’
‘Halal,’ and ‘organic’ labeled processed foods. Also, CGN is used as an excipient for drug products such as capsules, coatings,
and syrups, and it is also used to formulate personal care products such as toothpastes, lotions, and creams.

Raw Materials

Although there are thousands of global carrageenophyte species, less than 20 are used commercially to produce CGN.
The primary commercial warm water–cultivated species list includes Kappaphycus alverezii (‘Cottonii’) and Eucheuma denticulatum
(‘Spinosum’), these species producing kappa-CGN and iota-CGN, respectively. These are spiny, bushy seaweeds that grow to about
50 cm high in reef or lagoon regions primarily in the Philippines, Indonesia, and East Africa. These species are farmed in tropical
waters with an 8- to 12-week harvest cycle and available year round. Only one CGN type is extracted from each of these two species.
In contrast, cold-water species are harvested annually during the summer months. The primary commercial species includes
Chondrus crispus/Gigartina stellata (‘Irish Moss’), which comprise small bushy seaweeds about 10 cm high and widely distributed
around the coasts of the North Atlantic ocean, and the much larger Gigartina species harvested off the West Coast of South America
(primarily Chile). These wild-harvested seaweeds comprise both haploid and diploid plants which grow together and appear iden-
tical. Haploid plants produce kappa-CGN; diploid plants produce lambda-CGN. Consequently, CGN extracted from cold-water
species is a mix of kappa-CGN and lambda-CGN in variable ratio depending on the season and location.
All commercial seaweed species are immediately and thoroughly dried to target moisture in the range 18–35% depending on the
species and natural salt content from the seawater. The dried seaweeds are baled and shipped to the CGN manufacturing plants.

Manufacturing

There are two basic seaweed extracts produced commercially as shown in Figure 1.
CGN is extracted as detailed in the left-hand column, and there are two dewatering processes: alcohol and gel-press. The alkalis
used are sodium, potassium, and calcium hydroxides, singly or in combination. Alcohol precipitation can be used for all CGN

Reference Module in Food Sciences http://dx.doi.org/10.1016/B978-0-08-100596-5.03251-0 1

2 Polysaccharide Ingredients: Carrageenan

Carrageenan PES

Seaweed Seaweed

Water Wash Water Wash

Alkaline Extraction Alkali Soak

Coarse Filtration Chopping

Gel-press Fine Filtration Alcohol Bleaching

Process Process
Concentration Water Wash

Potassium Chloride Precipitation Alcohol Precipitation

Pressing +/– Freeze-thaw Cycle

Drying Drying

Grinding Grinding

Blending Blending

Figure 1 Manufacturing processes for carrageenan and Processed Eucheuma Seaweed (PES). Reproduced with kind permission from FMC
Corporation.

extracts, but gel-press is limited to only kappa-CGN. The alkaline extraction is necessary to preserve molecular weight and maximize
extract functionalities. CGN produced by this process has all solids removed resulting in clear solutions when redissolved.
Processed Eucheuma Seaweed (PES) is processed as detailed in the right-hand column and applies only to Cottonii and Spino-
sum species. The alkali used is potassium hydroxide. This is a much simpler and lower-cost process. However, the CGN remains as
an integral component of the seaweed algal structure and these cellulosic solids (8–15%) remain in the final product. PES requires
high thermal treatment to extract the CGN into solution, which remains cloudy with the insoluble cellulosic particulates, and limits
the feasible applications for PES. PES is also known as Philippine natural grade (PNG), semirefined carrageenan, and alternatively
refined carrageenan.
Finished commercial products are made by blending one or more extracts, with or without standardizing agents (e.g., dextrose),
in order to maintain consistent functional quality from lot to lot and meet the agreed customer specifications.

Regulation

CGN has a long history of use in food. Reviews of the extensive CGN literature by regulatory agencies and scientific experts have
resulted in CGN and PES being permitted globally for use in food.
Health Canada and the US Food and Drug Administration make no distinction between CGN and PES and regulate both as
‘carrageenan.’
In the European Union, CGN and PES are approved food additives and assigned the numbers E407 and E407a, respectively, in
the list of permitted emulsifiers, stabilizers, and thickeners. Unless otherwise specified, CGN and PES are permitted for use quantum
satis, the concentration required to achieve a given technological benefit.
Both CGN and PES have been reviewed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and are included
in Codex Alimentarius International Food Standard 1992–1995 (and subsequent revisions). They are listed as permitted for use in
food in general (unless specified otherwise) in accordance with good manufacturing practices.
Specifications for CGN vary by compendia (i.e., Food Chemicals Codex, Commission Regulation (EU) No. 231/2012, JECFA
Specifications, National Formulary, etc.). National regulations determine which specifications apply.
CGN must not be confused with ‘poligeenan’ (PGN), also identified in some literature as ‘degraded carrageenan.’ PGN is man-
ufactured from CGN by deliberate acid-hydrolysis at pH1 and 90  C for up to 6 h. This reduces the weight average molecular
weight (Mw) from the commercial CGN range of 200 000–800 000 Da to the PGN range of 10 000–20 000 Da. CGN and PGN are
two completely different and separate materials, with different toxicological properties, specifications, and applications. PGN is
used primarily in clinical diagnostics to suspend barium sulfate for X-ray imaging purposes. PGN has no functional utility in
food. There is no PGN in CGN (Blakemore et al., 2014). This will be discussed in more detail later in this article.
 Polysaccharide Ingredients: Carrageenan 3

Molecular Structure

CGN is a natural high molecular weight linear hydrophilic copolymer based on repeating but varying disaccharide galactose units,
which are partially sulfated. These ester sulfate units are negatively charged (polyanionic) and require association with cations, most
commonly sodium, potassium, calcium, and magnesium. Thus, CGNs are natural polymer salts. All CGN linear molecular back-
bones comprise alternating a-(1,3) and b-(1,4) glycosidic links.
The primary ideal (theoretical) disaccharide units are shown in Figure 2 along with the effect of alkali treatment as detailed in the
manufacturing section.
Ideal kappa-CGN comprises the disaccharide galactose-4-sulfate (G-4-S) and 3,6-anhydrogalactose (3,6-AG). The ideal disaccha-
ride precursor is mu-CGN comprising G-4-S and G-6-S. The CGN in native Cottonii seaweed during growth is a random copolymer
of ideal kappa-CGN and ideal mu-CGN in the approximate ratio of 70:30. Alkaline extraction converts most of the mu-CGN to
kappa-CGN and reduces the mu-CGN content from about 30% to about 5%, which increases and optimizes the gel strength.
Thus, commercial kappa-CGN extracted from Cottonii seaweed is a random copolymer of 95% ideal kappa-CGN and 5% ideal
mu-CGN.
Ideal iota-CGN differs from ideal kappa-CGN only by the presence of an ester sulfate on the 2 position of the 3,6-AG unit. Thus,
the repeating disaccharide structure of ideal iota-CGN is G-4-S and 3,6-AG-2-S, and its precursor, nu-CGN, is G-4-S and G-2,6-S.
Similar to commercial kappa-CGN, commercial iota-CGN from Spinosum seaweed is a random copolymer of 95% ideal iota-
CGN with 5% nu-CGN for optimum gel strength.
Lambda-CGN is nongelling and comprises G-2-S and G-2,6-S. Alkaline extraction results in partial conversion of lambda-CGN
to theta-CGN with the formation of the 3,6-anhydride ring structure (G-2-S and 3,6-AG-2-S). Commercial lambda-CGN is a random
copolymer of about 90% ideal lambda-CGN and 10% ideal theta-CGN.
Kappa-CGN extracts from cold-water species such as Chondrus and Gigartina deviate from the previously described ideal structure
of G-4-S and 3,6-AG. There is a continuum of ester sulfate content on the 2 position of the 3,6-AG. These kappa-CGN extracts have
between 5% and 50% 3,6-AG-2-S. As ideal iota-CGN has 100% 3,6-AG-2-S, these kappa-CGN extracts are copolymers of ideal
kappa-CGN, ideal mu-CGN, ideal iota-CGN, and ideal nu-CGN, mostly randomly distributed, but some block distribution occurs
when the 3,6-AG-2-S content reaches 30–50%. The kappa-CGN in this 30–50% range is known as ‘kappa-2-CGN.’ The ratio of these
four ideal structures varies by species and alkaline extraction conditions. An even higher level of complexity is caused by the variable
haploid (kappa-CGN) to diploid (lambda-CGN) plant ratio during harvesting. Thus, commercial CGN extracts from cold-water
species are challenging with respect to maintaining consistent functionalities and generally require standardizing agents for consis-
tent applications performance.
CGN and PES are high molecular weight polydisperse polysaccharide salts within the Mw range of 200 000–800 000 Da
(Blakemore and Harpell, 2010). The molecular weight profile of CGN extracts shows Gaussian distribution, with minor frac-
tions below 100 000 Da and above 800 000 Da. These fractions are naturally occurring inherent synthesis components of the
growing seaweed plant. As already indicated, these natural lower molecular weight fractions should not be confused
with PGN.

CH2OH CH2OSO3– CH2OH CH2

–O3SO O –O3SO O
O O OH– O O
O
OH
O O
OH OH OH OH
mu kappa

CH2OH CH2OSO3– CH2OH CH2

–O3SO O –O3SO O
O O O O
OH
OH– O
O O
OH nu OSO3– OH OSO3–
iota

CH2OH CH2OSO3– CH2OH CH2

HO O HO O
O O O O
OH– O
30%-H O 30%-H O
O 70%-SO3– OSO3– O 70%-SO3– OSO3–
lambda theta

Figure 2 Ideal disaccharide structures of carrageenan. Reproduced with kind permission from FMC Corporation.
4 Polysaccharide Ingredients: Carrageenan

Chemistry
Solubility and Hydration
All CGN types are soluble in water; lambda-CGN is soluble in cold water, but gel types, such as kappa-CGN and iota-CGN generally
require a heat–cool cycle (e.g. 80  C for 15 min) for full solubility. Kappa-CGN and iota-CGN particles hydrate and swell when
contacted by cold water. These stable swollen particles demonstrate their water-binding properties and their use in applications
such as delicatessen meats to retain water during cooking (Blakemore and Harpell, 2010).

Gelation
Gelation of kappa-CGN and iota-CGN requires a heat–cool cycle and the presence of specific salts: potassium ions for kappa-
CGN and calcium ions for iota-CGN. Hot solutions of kappa- and iota-CGN set when cooled below the gel temperature, which
is between 30 and 70  C depending on the CGN type and concentration of cations present. The mechanism of gelation is shown
in Figure 3.
In hot solution, kappa- and iota-CGN are in a random coil conformation. On cooling, Gel I (Figure 3) shows double helix
formation and the building of a three-dimensional (3-D) gel network. At this point CGN gels are firm and elastic, and this is
the final stage for iota-CGN, even with further cooling. Additional cooling of kappa-CGN gels results in Gel II, which shows
helical aggregation. This results in significant increase of gel strength and an aesthetic change to hard and brittle textures. This
is the final stage for kappa-CGN gels. Note that these gels are thermo-reversible. Gel combinations of kappa- and iota- CGN
will produce a wide range of textures and are the basis for their use in dessert gels, including as a vegetable alternative to
gelatin.
Note that the length of the helices is determined by the concentration of mu-CGN in kappa-CGN and nu-CGN in iota-CGN,
which interrupts the helix formation from blocks of ideal kappa-CGN or ideal iota-CGN. This is why alkaline extraction of CGN
optimizes gel strength.
Also, the 2-S of iota-CGN is external to the helices in Gel I (Figure 3), resulting in a strong negative charge along the helix, which,
in turn, repels other helices. This explains why iota-CGN will not proceed to Gel II. As kappa-CGN has no 2-S, the helices aggregate
to Gel II. Note that as the 3,6-AG-2-S content of the kappa-CGN from cold-water species increases, the corresponding negative
charge on each individual helix also increases, resulting in less efficient helical aggregation and weaker gel strengths (Blakemore
and Harpell, 2010).
Kappa-CGN gels that progress from Gel I to Gel II conformation will exhibit syneresis, the release of water as the gel structure
tightens and shrinks. Iota-CGN gels remain at Gel I conformation which has no syneresis. The level of syneresis of dessert gels can be
controlled through appropriate mixtures of kappa and iota CGNs.
All CGN gels exhibit hysteresis; the melting temperature of gels is up to about 20  C higher than the setting or gelling temper-
ature. For example, kappa-CGN gels at about 35  C, but does not melt until over about 50  C. Similarly, iota-CGN gels and melts at
about 10  C higher than kappa-CGN gels. This means that CGN gels do not melt in the mouth (like gelatin) and cannot melt in the
GIT, this having favorable toxicological significance for CGN (Weiner, 2014).

Figure 3 Thermo-reversible gel mechanism of carrageenan. Reproduced with kind permission from FMC Corporation.
 Polysaccharide Ingredients: Carrageenan 5

Protein Reactivity
As CGN is a negatively charged polyanionic molecule, it will interact strongly with all proteins at neutral pH or lower. Some of
CGN’s first uses were in milk gels, evaporated milk, ice cream, and chocolate milk. Its reactivity with milk proteins, and specifically
with kappa-casein, allows for stabilization use levels as low as 0.01%. Kappa-CGN is the primary CGN used in protein applications,
and the interaction with casein is shown in Figure 4 (Blakemore and Harpell, 2010).
In hot solution in milk, kappa-CGNs react electrostatically with kappa-casein (and other proteins), either by direct bonding to
positively charged sites on proteins, or indirect bridging via divalent calcium cations forming a weak initial network. On cooling, the
structural network is enhanced by helical formation of the CGN resulting in stabilization at low CGN concentrations
(e.g., 0.01–0.05%) and gelation at higher concentrations (e.g., 0.1–0.3%). This is the basis for the application of CGN in dairy prod-
ucts such as stabilized milks, puddings, and flans.
The interaction of CGN with other proteins (e.g., soy, almond, etc.) is not as strong as with casein, requiring higher concentra-
tions of CGN to offset the weaker bonding capability of these proteins. The quality of the protein is critical to this interaction. For
example, fresh soy milk is much more reactive to CGN than processed soy protein. This means that the ratio between direct protein
bonding (CGN–protein interaction) and helical formation (CGN–CGN interaction) requires a shift toward helical formation to
maintain functional stability, which, in turn, necessitates an increase in CGN concentration.
Note that the interaction between CGN and protein is highly pH sensitive, particularly when lowering the pH below 5. When
approaching the iso-electric point (IEP) of proteins (e.g., pH 4.5) and lower, the positive charge on the protein is significantly
increased. This results in precipitation of a CGN–protein complex rather than the creation of a stabilizing structural network as
described above for neutral pH values.

Acid Stability
CGN solutions lose viscosity and gel strength through autohydrolysis when subjected to acidic environments below about pH 5.5,
but not significantly until below about pH 4.5. Treatment at pH 3.5 is manageable, but requires specific care. The molecular back-
bone is cleaved by acid at the 3,6-AG units. The rate of hydrolysis is increased as solution temperatures are raised. However, after
gelation, the CGN is in the helical conformation, which ends the autohydrolysis, and the gels will remain acid-stable for many
months. This is the basis for using CGN in ready-to-eat dessert gels, these being stored on supermarket shelves for up to 6 months.
For most gel applications at lower pH, the acid is added last to the gel mix, generally during the filling process, and then immediately
cooled to form the gel as soon as possible. Table 1 shows the gel processing times and temperatures necessary to limit gel strength
reduction to 25%.
The acid and temperature sensitivities of CGN are clearly demonstrated. Most commercial dessert-manufacturing targets are
about pH 4.0–4.2 and filled aseptically at about 70–75  C. From the table, these conditions would lose 25% gel strength in about
1 h, but cooling for gel formation normally requires less than about 10 min.

Synergies
Kappa-CGN is strongly synergistic with konjac (glucomannan) and locust bean gum (LBG, galactomannan) when forming gels,
these mannan molecules associating with the gel helices. For konjac the distance between acetyl groups on the molecular backbone

Figure 4 Carrageenan reactivity with casein, a two-step process. Reproduced with kind permission from FMC Corporation.
6 Polysaccharide Ingredients: Carrageenan

Table 1 Carrageenan gel processing times

Final pH

Temperature ( C) 3.0 3.5 4.0 4.5 5.0 5.5 6.0

120 2s 6s 20 s 1 min 3 min 10 min 30 min

110 6s 20 s 1 min 3 min 10 min 30 min 1.5 h
100 20 s 1 min 3 min 10 min 30 min 1.5 h 5.0 h
90 1 min 3 min 10 min 30 min 1.5 h 5.0 h 15.0 h
80 3 min 10 min 30 min 1.5 h 5.0 h 15.0 h 2.0 days
70 10 min 30 min 1.5 h 5.0 h 15.0 h 2.0 days 6.0 days
60 30 min 1.5 h 5.0 h 15.0 h 2.0 days 6.0 days 20.0 days
50 1.5 h 5.0 h 15.0 h 2.0 days 6.0 days 20.0 days 60.0 days
40 5.0 h 15.0 h 2.0 days 6.0 days 20.0 days 60.0 days 200.0 days

Gel process times are the approximate times at the various pH and temperatures to reduce gel strength by 25%.
Reproduced with kind permission from FMC Corporation.

is similar to the helical length of kappa-CGN. For LBG, the length of mannan blocks between the galactose side groups is similar to
the helical length of kappa-CGN. This allows these mannan gums to line up with the kappa-CGN helices, fill the voids between
aggregated helices, and increase gel strength (Blakemore and Harpell, 2010).
Iota-CGN is mildly synergistic with starches, the combination allowing reduction of the starch content for the same gel charac-
teristics, improvement of gel texture (less pasty), and elimination of syneresis.
CGN is compatible with other hydrophilic gums, including guar gum, sodium carboxymethyl cellulose, and xanthan.

Applications

Primary water-based food applications are shown in Table 2, and protein-based food applications are detailed in Table 3. Approx-
imate usage levels and adjunct gums are included.
CGN is not an emulsifier, but will stabilize emulsions once formed.
The primary personal care application for CGN is toothpaste, which uses iota-CGN (use level about 1%), often in combination
with CMC and xanthan. Many toothpastes are cold-processed to avoid flavor loss and for improved economics which requires the
excellent hydration, swelling, and water-binding properties of iota-CGN to build the required rheology to suspend the abrasive and
maintain compositional integrity in the tube. Other personal care products include creams, lotions, and shampoos.
Oral drug applications include capsules (gelatin replacement), syrups, and coatings.

Toxicology

CGN is one of the most widely studied natural polysaccharide food additives for toxicity with research literature starting in the
1960s and continuing today. Unfortunately, publications in the early years did not distinguish between ‘carrageenan’ and ‘degraded

Table 2 Carrageenan water-based applications

Application Use level (%) Adjunct gums

Cake glaze 0.60–0.70

Imitation cheese 2.20–2.70
Water gel desserts 0.50–1.00
Fabricated foods 2.00–3.00
Deli meats 0.30–0.50
Jams and jellies 1.00–2.00
Pet food 0.20–1.00 LBG, guar, cassia
Sorbet 0.15–0.30 Pectin
Sour cream 0.10–0.20 LBG
Surimi 0.20–0.30 Starch
Batter mixes 0.10–0.30
Salad dressings 0.20–0.50
Toothpaste 0.50–1.00 CMC, xanthan
Air-freshener gels 1.00–3.00 CM-guar, LBG
 Polysaccharide Ingredients: Carrageenan 7

Table 3 Carrageenan protein-based applications

Application Use level (%) Adjunct gums

Chocolate milk 0.02–0.05

Ice cream 0.01–0.03 LBG, guar, CMC
Cream cheese 0.05–0.08
Evaporated milk 0.005–0.020
Infant formula 0.02–0.03
Soy beverages 0.02–0.05
Puddings 0.20–0.60
Flans 0.20–0.30
Dressings 0.01–0.03
Nutritional beverages 0.10–0.15
Milk shakes 0.02–0.03
Sterilized milk 0.01–0.03

carrageenan’ (now called ‘poligeenan’ as previously explained), and, unfortunately, these publications continue to be misused as
references for issues with CGN. As CGN and PGN have vastly different toxicological profiles, these ongoing misnomers have caused
much confusion (Blakemore, 2015). In addition, most of these publications fail to characterize adequately the CGN used in their
experiments and to realize that their experiments do not mirror how CGN is used and present in food.
The CGN used in food products is either gelled or reacted with protein. Both these physical states result in extremely large aggre-
gated molecules with Mw values of at least 10 million Da, and more likely toward 100 million Da. Consequently, it has been shown
that CGN is not absorbed into the bloodstream from the GIT and is excreted unchanged in the feces (Weiner, 2014). CGN gels
cannot melt and disintegrate in the GIT, the gel particles remaining intact and acting as dietary fiber in the colon. CGN–protein
complexes will be precipitated in the acidic stomach (pH below IEP). No CGN is released from the structure with protein until
far down the GIT, and only after enzymatic activity in the colon breaks down the protein structures to release the CGN (Weiner,
2014).
Consequently, feeding studies orally dosing CGN solubilized in drinking water are not representative of how CGN is nor-
mally used or present in foods. In addition, studies in drinking water over a wide range of CGN concentrations
(e.g., 0.05–5.0%) will be subject to conformational changes of the CGN, from random coil at below about 0.1% to helical
conformation above about 0.1%. Obviously, CGN in random coil conformation will have more direct access to or contact
with specific in vivo cells of the GIT. However, this is not how CGN is used or present in foods. It is necessary to understand
the CGN conformation and interaction with proteins before drawing any conclusions from feeding and drinking water study
observations.
There have been multiple in vitro research publications on CGN using various biological cells to try to link CGN to cancer,
inflammation of the GIT, diabetes, and adverse effects on the immune system. However, the theories, conclusions, suggested meta-
bolic pathways, etc. proposed in these in vitro articles have been shown to be severely flawed in interpretation and study designs
(McKim, 2014, 2015).
CGN has an impressive, robust, and safe in vivo toxicological database. CGN is acutely nontoxic by oral, dermal, and inhalation
routes (Weiner et al., 2007; Weiner, 2014; Necas and Bartosikova, 2013). The only effects reported in animal subchronic and
chronic feeding studies at high dietary CGN concentrations (e.g., 5%) are loose stools and diarrhea, which are common occurrences
with such high levels of nondigestible dietary fiber. Results of animal feeding studies have shown CGN to be nongenotoxic, noncar-
cinogenic, not a tumor promoter, and not a developmental or reproductive toxicant. Based on a large number of dietary toxicity
studies, CGN has not been shown to cause adverse effects in the GIT or on the immune system in adults and neonates (Weiner,
2014; Weiner et al., 2015).
On the other hand, PGN at high concentrations has been shown to induce ulceration and irritation to the GIT. As PGN does not
gel and does not form helices (the molecules are not long enough) or other 3-D structures in the presence of proteins, it will always
be present in random coil conformation at all concentrations. Thus, the direct access to or contact with specific in vivo cells in the GIT
is significantly enhanced for PNG compared to CGN. These gel formation and protein reactivity functionalities of CGN are
extremely important for the interpretation of toxicological feeding study observations. They also explain why CGN is nontoxic
in subchronic and chronic dietary studies compared to PGN.

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