Evaluation of the toxicity of concentrated barley β-glucan in a 28-day feeding study in Wistar rats

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Abstract

β-Glucans are water-soluble cell-wall polysaccharides consisting of (1→3,1→4)-linked β-d-glucopyranosyl monomers that comprise a considerable proportion of soluble fiber from certain grains including oats and barley. Consumption of foods containing β-glucan or β-glucan-enriched fractions prepared from these grains lower serum cholesterol concentrations in humans and in animal models of hypercholesterolemia. The present study was conducted to evaluate the toxicity of β-glucan-enriched soluble fiber from barley in Wistar rats on dietary administration at concentrations of 0.7, 3.5 and 7% β-glucan for 28 days. There were no adverse effects on general condition and behavior, growth, feed and water consumption, feed conversion efficiency, red blood cell and clotting potential parameters, clinical chemistry values, and organ weights. Necropsy and histopathology findings revealed no treatment-related changes in any organ evaluated. A dose-dependent increase in full and empty cecum weight was observed. This is a common physiological response of rodents to high amounts of poorly digestible, fermentable carbohydrates, and was of no toxicological concern. The only finding of possible biological relevance was an increase in the number of circulating lymphocytes observed in males. However, the increase was not dose-dependent and was not observed in females. Results of this study demonstrated that consumption of concentrated barley β-glucan was not associated with any obvious signs of toxicity in Wistar rats even following consumption of large quantities.

Introduction

Oats and barley have long been known to lower serum cholesterol concentrations in animal models of hypercholesterolemia (De Groot et al., 1963). Consumption of these cereal grains has also demonstrated cholesterol-lowering activity in humans (Judd and Truswell, 1981, Anderson et al., 1984, Newman et al., 1989a, Newman et al., 1989b, Kestin et al., 1990, McIntosh et al., 1991, Ripsin et al., 1992, Lupton et al., 1994, Ikegami et al., 1996, Kahlon and Chow, 1997). However, consumption of relatively large amounts is required to produce clinically relevant reductions (Braaten et al., 1994). Therefore, many studies have been conducted to identify components present in these grains to which cholesterol-lowering activity could be attributable. Several substances have been identified that possess cholesterol-lowering activities (e.g. tocotrienols: Peterson and Qureshi, 1997, Qureshi et al., 1980, Qureshi et al., 1986). However, it is the bran fractions to which the cholesterol-lowering activity has most consistently been associated (Kirby et al., 1981, Anderson et al., 1984, Anderson et al., 1990, Anderson et al., 1991), more specifically, to the β-glucan component (Davidson et al., 1991, Braaten et al., 1994).

Relative to other cereal grains, oat bran contains high concentrations of soluble fiber of which a considerable proportion is β-glucan (>50%: Asp et al., 1992, Aman and Graham, 1987). The concentration of β-glucan in barley appears to be even higher than that of oats (Aman and Graham, 1987, Newman et al., 1992). Chemically, β-glucans are a heterogeneous group of water-soluble endospermic cell-wall polysaccharides consisting of (1→3,1→4)-β-d-linked glucose units (Wood et al., 1989). The β-glucan from barley and oats appears to be chemically indistinguishable (Jeraci and Lewis, 1989).

Concentrated preparations of oat β-glucan have demonstrated cholesterol-lowering activity in humans and animal models of hypercholesterolemia (Kirby et al., 1981, Davidson et al., 1991, Knuckles et al., 1992, Jonnalagadda et al., 1993, Kahlon et al., 1993, Braaten et al., 1994, Zhang et al., 1994, Yokoyama et al., 1998, Onning et al., 1999), as have similar products prepared from barley (Newman et al., 1989a, Newman et al., 1989b, Knuckles et al., 1992, Wang et al., 1992, Kahlon et al., 1993, German et al., 1996, Maqueda de Guevara et al., 2000). A recent study comparing β-glucan-enriched fractions from oats and barley in hypercholesterolemic hamsters demonstrated that the cholesterol-lowering activity of β-glucan from oats and barley was nearly identical (B. Delaney et al., unpublished data, 2002).

These studies suggest that β-glucan-enriched soluble fiber from barley may be useful in controlling elevated serum cholesterol concentrations in humans and an interesting commercial product. Although barley itself and foods containing soluble fibers are not considered unsafe, little toxicological information is available regarding the safety following repeated exposure to concentrate enriched in β-glucan. In the present study, the toxicity of a water-extracted β-glucan-enriched soluble fiber from barley (Barley Betafiber) was evaluated in a 28-day feeding study in Wistar rats. This study was conducted in accordance with OECD Guideline for Testing Chemicals n. 407 (adopted July 27, 1995) and in compliance with the OECD Principles of Good Laboratory Practice.

Section snippets

Preparation of β-glucan enriched soluble fiber concentrate

β-Glucan from hulless barley (Azhul variety) was extracted by a process similar to that of Aman and Hesselman (1985) but without the amyloglucosidase treatment step. The composition of the concentrated β-glucan product (Barley Betafiber, Cargill, Inc., Wayzata, MN) is presented in Table 1.

Analysis of β-glucan in barley concentrate and rat feed

β-Glucan in the barley concentrate was quantified enzymatically (McCleary, 1985) using a Megazyme β-glucan mixed linkage assay kit. β-Glucan-enriched soluble fiber samples were milled to pass through a 0.5-mm

Analysis of β-glucan in rat feed

The concentration of β-glucan was determined in the different feed samples blended with the indicated concentration of the (Barley Betafiber). Limited specificity of the analytic method was observed since control diets appeared to possess approximately 0.7% β-glucan (Table 2). This observation indicated either that a small amount of glucose was released by the enzymatic treatment during the analysis or that the dietary blend did contain a small amount of β-glucan. Following correction for the

Discussion

Oats and barley lower serum cholesterol concentration in humans (Judd and Truswell, 1981, Anderson et al., 1984, Newman et al., 1989a, Newman et al., 1989b, Kestin et al., 1990, McIntosh et al., 1991, Ripsin et al., 1992, Lupton et al., 1994, Ikegami et al., 1996, Kahlon and Chow, 1997). This activity is attributable to the soluble fiber fraction of these cereal grains, more specifically, to the β-glucan component (Davidson et al., 1991, Braaten et al., 1994). The β-glucan in oats and barley

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    Present address: Land O'Lakes, Inc., PO Box 64101, St. Paul, MN 55164-0101, USA.

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