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Objectives. Carrageenan is well known to cause inflammation and is used in laboratory experiments to study mediators and treatments of inflammation. However, carrageenan is added to hundreds of processed foods to improve texture. Previous work indicated that low concentrations of carrageenan in drinking water caused marked glucose intolerance and insulin resistance in a mouse model. This exploratory, clinical study tested the impact of the no-carrageenan diet in prediabetes. Research Design and Methods. Participants with prediabetes (n=13), defined as HbA1c of 5.7%-6.4%, enrolled in a 12-week, randomized, parallel-arm, feeding trial. One group (n=8) was provided all meals and snacks with no carrageenan. A second group (n=5) received a similar diet with equivalent content of protein, fat, and carbohydrate, but with carrageenan. Blood samples were collected at baseline and during oral glucose tolerance tests at 6 and 12 weeks. The primary outcome measure was changed in %HbA1c between baseline and 12 weeks. Statistical analysis included paired and unpaired t-tests, correlations, and 2×2 ANOVAs. Results. Subjects on no carrageenan had declines in HbA1c and HOMA-IR (p=0.006, p=0.026; paired t-test, two tailed). They had increases in C-peptide (p=0.029) and Matsuda Index (2.1±0.7 to 4.8±2.3; p=0.052) and declines in serum IL-8, serum galectin-3, and neutrophil phospho-(Ser307/312)-IRS1 (p=0.049, p=0.003, and p=0.006; paired t-tests, two tailed). Subjects on the diet with carrageenan had no significant changes in these parameters. Significant differences between no-carrageenan and carrageenan-containing diet groups for changes from baseline to 12 weeks occurred in C-peptide, phospho-Ser-IRS1, phospho-AKT1, and mononuclear cell arylsulfatase B (p=0.007, p=0.038, p=0.0012, and p=0.0008; 2×2 ANOVA). Significant correlations were evident between several of the variables. Conclusions. Findings indicate improvement in HbA1c and HOMA-IR in participants on no-carrageenan diets, but not in participants on carrageenan-containing diets. Significant differences between groups suggest that removing carrageenan may improve insulin signaling and glucose tolerance. Larger studies are needed to further consider the impact of carrageenan on development of diabetes.

Exposure to low concentration of the common food additive carrageenan (10 mg/L) for only six days led to glucose intolerance and insulin resistance in the C57BL/6J mouse. Longer exposure produced fasting hyperglycemia but with no increase in weight, in contrast to the HFD. Glucose intolerance was attributable to carrageenan-induced inflammation and to increased expression of GRB10. Both HFD and carrageenan increased p(Ser32)-IκBα and p(Ser307)-IRS1, and the increases were greater following the combined exposure. The effects of carrageenan were inhibited by the combination of the free radical inhibitor Tempol and BCL10 siRNA, which had no impact on the HFD-mediated increase. In contrast, the PKC inhibitor sotrastaurin blocked the HFD-induced increases, without an effect on the carrageenan-mediated effects. HFD had no impact on the expression of GRB10. Both carrageenan and high fat increased hepatic infiltration by F4/80-positive macrophages. Serum galectin-3 and galectin-3 binding to the insulin receptor increased by carrageenan and by HFD. Tyrosine phosphorylation of the insulin receptor declined following either exposure and was further reduced by their combination. Carrageenan reduced the activity of the enzyme N-acetylgalactosamine-4-sulfatase (ARSB; arylsulfatase B), which was unchanged following HFD. Dietary exposure to both high fat and carrageenan can impair insulin signaling through both similar and distinct mechanisms.

Aims. Major aims were to determine whether exposure to the commonly used food additive carrageenan could induce fasting hyperglycemia and could increase the effects of a high fat diet on glucose intolerance and dyslipidemia. Methods. C57BL/6J mice were exposed to either carrageenan, high fat diet, or the combination of high fat diet and carrageenan, or untreated, for one year. Effects on fasting blood glucose, glucose tolerance, lipid parameters, weight, glycogen stores, and inflammation were compared. Results. Exposure to carrageenan led to glucose intolerance by six days and produced elevated fasting blood glucose by 23 weeks. Effects of carrageenan on glucose tolerance were more severe than from high fat alone. Carrageenan in combination with high fat produced earlier onset of fasting hyperglycemia and higher glucose levels in glucose tolerance tests and exacerbated dyslipidemia. In contrast to high fat, carrageenan did not lead to weight gain. In hyperinsulinemic, euglycemic clamp studies, the carrageenan-exposed mice had higher early glucose levels and lower glucose infusion rate and longer interval to achieve the steady-state. Conclusions. Carrageenan in the Western diet may contribute to the development of diabetes and the effects of high fat consumption. Carrageenan may be useful as a nonobese model of diabetes in the mouse.