Exposure to common food additive carrageenan leads to reduced sulfatase activity and increase in sulfated glycosaminoglycans in human epithelial cells

Bo Yang,Sumit Bhattacharyya,Robert Linhardt,Joanne Tobacman

doi:10.1016/j.biochi.2012.02.031

Abstract

The commonly used food additive carrageenan, including lambda (λ), kappa (κ) and iota (ι) forms, is composed of galactose disaccharides linked in alpha-1,3 and beta-1,4 glycosidic bonds with up to three sulfate groups per disaccharide residue. Carrageenan closely resembles the endogenous galactose or N-acetylgalactosamine-containing glycosaminoglycans (GAGs), chondroitin sulfate (CS), dermatan sulfate (DS), and keratan sulfate. However, these GAGs have beta-1,3 and beta-1,4 glycosidic bonds, in contrast to the unusual alpha-1,3 glycosidic bond in carrageenan. Since sulfatase activity is inhibited by sulfate, and carrageenan is so highly sulfated, we tested the effect of carrageenan exposure on sulfatase activity in human intestinal and mammary epithelial cell lines and found that carrageenan exposure significantly reduced the activity of sulfatases, including N-acetylgalactosamine-4-sulfatase, galactose-6-sulfatase, iduronate sulfatase, steroid sulfatase, arylsulfatase A, SULF-1,2, and heparan sulfamidase. Consistent with the inhibition of sulfatase activity, following exposure to carrageenan, GAG content increased significantly and showed marked differences in disaccharide composition. Specific changes in CS disaccharides included increases in di-sulfated disaccharide components of CSD (2S6S) and CS-E (4S6S), with declines in CS-A (4S) and CS-C (6S). Specific changes in heparin-heparan sulfate disaccharides included increases in 6S disaccharides, as well as increases in NS and 2S6S disaccharides. Study results suggest that carrageenan inhibition of sulfatase activity leads to re-distribution of the cellular GAG composition with increase in di-sulfated CS and with potential consequences for cell structure and function.

Highlights

The common food additive, carrageenan, is consumed in the average diet in sufficient quantities to have biological effects
IDS activity in the T84 cells was similar to the activity in the NCM460 cells and primary colonocytes and greater than in the CaCO2 cells, in contrast to the arylsulfatase B (ARSB) activity which was highest in the CaCO2 cells and least in the T84 cells
Exposure to the common food additive significantly reduced the activity of multiple sulfatase enzymes in human colonic and mammary epithelial cells

Summary

Introduction

The common food additive, carrageenan, is consumed in the average diet in sufficient quantities to have biological effects. In contrast to the glycoside digoxin, which is generally prescribed in doses of 0.25 mg daily, average daily ingestion of carrageenan in the typical diet is estimated to be 250 mg/day [1,2]. Containing foods may ingest several grams of carrageenan per day [3,4]. Carrageenan is found in a wide range of processed foods, including ice cream, whipped cream, infant formula, deli meats, sour cream, puddings, soymilk, yogurt, and dietary supplements. Carrageenan is used in pharmaceuticals as an excipient, and in room air fresheners, cosmetics, and pet foods, due to its ability to improve the texture and solubility of ingredients. The Joint Expert Committee (Food and Agriculture Organization of the UN and the WHO) on Food Additives has recommended that carrageenan be excluded from infant formula and that current intake of carrageenan in the diet be re-evaluated [5]

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