Carrageenan – It’s Just Science and Seaweed, WebMD – 2/1/16

Dr. Roger Clemens on carrageenan science

This article was written by Roger A. Clemens, DrPH.

Carrageenan is sourced from red seaweed and widely used as a food additive. It has a very unique property that gives us a smooth mouth-feel in food. It also has a suspension property. It keeps things, like beverages, from separating. How do you keep the chocolate from separating from the milk in chocolate milk? Food processors add carrageenan. Carrageenan has a long history of use in a lot of different products.

There is no evidence that this food additive poses any health risk when consumed at intended levels as part of a normal human diet. Despite the overwhelming and sustained body of research that supports carrageenan safety, including in infant formula up to 1000 ppm (JECFA 2015), a series of publications over the last decade from a single group of investigators (Tobacman 2008) continues to drive further studies on public health and safety concerns about carrageenan (Weiner 2016; McKim et al 2015).

Media interpretations of the alleged risks posed by carrageenan have motivated the food industry to begin removing it from food products, an example of economic policy shaped by compromised research and consumer fear. To critically evaluate the science involved, it is important to carefully evaluate both the fundamental and specific threats to validity of this work.

In general, exposure of an isolated cell line to any substance must be seen in light of the limitations of any in vitro study. In particular, the use of a now recognized faulty (NCM460) experimental cell line further threatens the validity of any carrageenan conclusion. In vitro lab work, while valuable in formulating questions and designing future investigation, has little relevance to dietary exposure in free-living human beings.

In classic toxicology, animal studies can provide a better natural laboratory for evaluation of safety, even though there are profound genomic differences between rodents and human beings. However, even at the level of cell biology there are questions that often facilitate translation of mouse data to human physiology.

Route of administration is another potential source of error in drawing conclusions from the lab research, i.e., injecting virtually any substance into

the foot pad or peritoneal cavity of an animal will likely result in a local inflammatory response. Food gums such as carrageenan are eaten, not injected. Moreover, like most nutrients, carrageenan is a component of, and integrated within a food matrix with a constellation of functional properties. With respect to nutrients, this means that exposure to any tissue surface and subsequent absorption and digestion are markedly different than exposure of tissue to a solitary and inevitably exaggerated dose of the compound in question. Importantly, carrageenan is not absorbed. Thus, the carrageenan dissolved or dispersed in drinking water is another threat to validity; this is not a chemically or behaviorally relevant dosing vehicle for human exposure (Weiner et al 2016).

In a 2002 review on the toxicological effects of carrageenan, Cohen and Ito suggested that putative carrageenan effects on the immune system are not pertinent to orally administered carrageenan (Cohen & Ito, 2002). They suggest that poligeenan, a different substance than carrageenan, exhibits toxicological properties at high doses that do not occur with the food additive carrageenan and do not occur in the food supply. The point is made that in long-term bioassays, carrageenan has not been found to be carcinogenic, and there is no credible evidence supporting a carcinogenic effect or a tumor-promoting effect on the colon in rodents.

Finally, the identity and purity of a substance used in laboratory work must be verified (Tsuji et al, 2003). Much of the questionable and contradictory work with carrageenan fails to validate the source and purity of the tested carrageenan (McKim, 2014).

In particular, one minority study suggests carrageenan contributes to fasting hyperglycemia by interfering with insulin signaling and induces inflammation (Bhattacharyya et al, 2015a; Bhattacharyya et al, 2015b). This minority-opinion group reported that the induced inflammation is attributed to elevated TNF-α (tumor necrosis factor) and that carrageenan inhibits apoptosis, an important characteristic associated with cancer (Bhattacharyya et al, 2010; Tobacman et al, 2001). This research was not replicated in any other laboratory, and in fact was dramatically contradicted in a meticulous study reported by McKim et al (2015).

Another key issue is that food grade carrageenan is inert to hydrolysis in the human GI tract and that of monogastric animals is not absorbed systemically. In addition, there is strong evidence that carrageenan does not penetrate or is transported beyond mucosal surfaces (Harmuth-Hoene & Schwerdtfeger 1979; Cummings et al, 1976). Therefore, the oral administration of carrageenan as typically consumed would not be expected to provoke a local or systemic inflammatory response.

Examination of the Tobacman and Bhattacharyya research that suggests carrageenan is not safe also indicates a) the investigators associate poligeenan (PGN) with carrageenan, and b) that PGN is a typical degradation product of carrageenan exposed to classic thermal food processing. PGN has a different molecular weight profile than carrageenan, is not a food additive, has no functionality in food, is not found in foods and is not a product of normal thermal food processing.

Poligeenan production requires a naturalistic autoclave, the use of strong acids (pH 0.9-1.2) and high temperatures (>190°F) over an extended period of time. The average pH of an adult stomach around 3, and the body temperature of a healthy adult is 98.6°F. Equally important, the human body cannot degrade carrageenan to PGN. These factors were considered by JECFA before concluding carrageenan was safe for use in the food supply, including infant formula (JECFA 2015).

In conclusion, the preponderance of scientific research supports the safety of carrageenan as a safe food additive for human consumption.

Bhattacharyya S, Dudeja P, Tobacman JK. Tumor Necrosis Factor α-induced Inflammation Is Increased but Apoptosis Is Inhibited by Common Food Additive Carrageenan. J Biol Chem 2010;285:39511-22

Bhattacharyya S, Feferman L, Tobacman JK. Carrageenan Inhibits Insulin Signaling through GRB10-mediated Decrease in Tyr(P)-IRS1 and through Inflammationinduced Increase in Ser(P)307-IRS1. J Biol Chem 2015;290:10764-74

Bhattacharyya S, Feferman L, Unterman T, Tobacman JK. Exposure to Common Food Additive Carrageenan Alone Leads to Fasting Hyperglycemia and in Combination with High Fat Diet Exacerbates Glucose Intolerance and Hyperlipidemia without Effect on Weight. J Diab Res 2015a; doi: 10.1155/2015/513429

Campo VL, Kawano DF, da Silva Jr DB, Carvalho I. Carrageenans: Biological properties, chemical modifications and structural analysis – A review. Carbo Polymers 2009;77:167-80

Cohen SM, Ito N. A Critical Review of the Toxicological Effects of Carrageenan and Processed Eucheuma Seaweed on the Gastrointestinal Tract. Crit Rev Toxicol 2002;32:413-44

Cummings JH, Hill MJ, Jenkins DJA, Pearson JR, Wiggins HS. Changes in fecal composition and colonic function due to cereal fiber. Am J Clin Nutr 1976;29:1468-73

Harmuth-Hoene AE, Schwerdtfeger E. Effect of indigestible polysaccharides on protein digestibility and nitrogen retention in growing rats. Nutr Metab 1979;23:399-407

Joint FAO/WHO Expert Committee on Food Additives (JECFA), Safety evaluation of certain food additives. WHO Food Additive Series: 70, World Health Organization, Geneva, 2015; pp 3-44

McKim JM. Food additive carrageenan: Part I: A critical review of carrageenan in vitro studies, potential pitfalls, and implications for human health and safety. Crit Rev Toxicol 2014;44:211-43

McKim Jr JM, Wilga PC, Pregenzer JF, Blakemore WR. The common food additive carrageenan is not a ligand for Toll-Like-Receptor 4 (TLR4) in an HEK293-TLR4 reporter cell-line model. Food Chem Toxicol 2015;78:153-58

Tobacman JK. Review of harmful gastrointestinal effects of carrageenan in animal experiments. Environ Health Perspect 2001;109:983-94

Tobacman JK. The Carrageenan Diet: Not Recommended. Science 2008;321:1040-41

Tsuji RF, Hoshino K, Noro Y, Tsuji NM, Kurokawa T, Masuda T, Akira S, Nowak B. Suppression of allergic reaction by lambda carrageenan: Toll-like receptor 4/MyD88 dependent and independent modulation of immunity. Clin. Exp. Allergy 2003;33:249-58.

Weiner ML. Parameters and pitfalls to consider in the conduct of food additive research, Carrageenan as a case study. Food Chem Toxicol 2016;87:31-44

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Food Science Matters.

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