Oat Beta-Glucan: Its Role in Health Promotion and Prevention of Diseases

Authors

  • Cheickna Daou,

    1. Author Daou is with State Key Laboratory of Food Science and Technology, 1800 Lihu Road, Wuxi 214122, PR China, School of Food Science and Technology, Jiangnan Univ., 1800 Lihu Road, Wuxi 214122, PR China, and Faculty of Science and technology, dept. of biology, Univ. of Science and technology of Bamako (USTTB), Rep. Mali. Author Zhang is with State Key Laboratory of Food Science and Technology, 1800 Lihu Road, Wuxi 214122, PR China and School of Food Science and Technology, Jiangnan University. Direct inquiries to author Daou (E-mail: rimma504@yahoo.fr ) and author Zhang (E-mail: zhanghui@jiangnan.edu.cn ).
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  • Hui Zhang

    1. Author Daou is with State Key Laboratory of Food Science and Technology, 1800 Lihu Road, Wuxi 214122, PR China, School of Food Science and Technology, Jiangnan Univ., 1800 Lihu Road, Wuxi 214122, PR China, and Faculty of Science and technology, dept. of biology, Univ. of Science and technology of Bamako (USTTB), Rep. Mali. Author Zhang is with State Key Laboratory of Food Science and Technology, 1800 Lihu Road, Wuxi 214122, PR China and School of Food Science and Technology, Jiangnan University. Direct inquiries to author Daou (E-mail: rimma504@yahoo.fr ) and author Zhang (E-mail: zhanghui@jiangnan.edu.cn ).
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Abstract

Abstract:  This article presents an overview of the recent advances into the health promoting potentials of oat β-glucan. Oat β-glucan (OβG) consists mainly of the linear polysaccharide (1→3), (1→4)-β-D-glucan and is often called β-glucan. This soluble oat fiber is able to attenuate blood postprandial glycemic and insulinemic responses, to lower blood total cholesterol and low-density lipoprotein (LDL) cholesterol, and to improve high-density lipoprotein (HDL) cholesterol and blood lipid profiles as well as to maintain body weight. Thus, OβG intake is beneficial in the prevention, treatment, and control of diabetes and cardiovascular diseases. In addition, OβG can stimulate immune functions by activating monocytes/macrophages and increasing the amounts of immunoglobulin, NK cells, killer T-cells, and so on, which will improve resistance to cancer and infectious and parasitic diseases, as well as increase biological therapies and their prevention. All these health benefits of OβG may be explained by its physicochemical properties (such as viscosity, molecular weight) which can be affected by extraction methods and its behavior in gastrointestinal tract. Articles documenting these health benefits and effects are reviewed.

Introduction

The common oat (Avena sativa) is species of cereal grain mainly grown for its utilization for human consumption as oatmeal as well as for livestock feed. Oat has always been regarded as a health-promoting food without clear knowledge of its specific health-related effects. However, today it is known for its effects on satiety and retarded absorption of nutrients as well as a deterrent of various disorders of the gastrointestinal tract. These beneficial effects are chiefly due to the soluble fiber content of oats. Today oats is among the richest and most economical sources of soluble dietary fiber The present interest in soluble oat fiber originated from reports that showed that dietary oats can help in lowering cholesterol (Braaten and others 1994; Hsing-Hsien and Ming-Hoang 2000; Bae and others 2010; Drozdowski and others 2010; Tiwari and Cummins 2011), postprandial blood glucose level (Wood and others 2000; Hooda and others 2010; Regand and other 2011; Dong and others 2011; Tiwari and Cummins 2011) as well as modifying immune response and reducing risk of colon cancer (Mälkki 2001; Yang 2008).

Following reports of research findings that oat dietary fiber could effectively lower cholesterol and blood glucose, and protect and prevent against various diseases, the use of oats as food in the United States of America increased. Thus, the popularity of oatmeal and other oat products also increased after the January 1998 decision by the Food Drugs Administration (FDA) issued its final rule allowing a health claim to make on the labels of foods containing soluble fiber from whole oats. Whole oats products such as oat bran, oat flour, and rolled oats can supply up to 3 g of soluble fiber daily and, when consumed in conjunction with a diet low in saturated fat, cholesterol, and fat, it may reduce the risk of heart disease. Moreover, it is allowed by the FDA to claim health benefits for oat products when 0.75 g of β-glucan is consumed in a serving portion (FDA 1997).In other industrialized countries the interest in the effects of oat-soluble fiber has followed the same trend, but changes in the demand of oat have been more modest. The principal component of the soluble fiber in whole oats comprises a class of polysaccharides known as beta-D-glucan. Beta-D-glucan, often referred to as beta-glucan is a nondigestible polysaccharide (a chain of glucose molecules that is found in foods such as oats, barley, mushrooms, and yeasts). In cereal (oat and barley) beta-glucan is composed of mixed-linkage (1, 3) (1, 4)-β-D-glucose units, while it is composed of mixed-linkage of (1, 3) (1, 6)-β-D-glucose units in mushrooms and yeasts (di Luzio and others 1979; Tohamy and others 2003).

Whereas oat is an inexpensive source, and extraction of beta-glucan is very difficult, oat beta-glucan becomes the more inexpensive beta-glucan.

Ever since the 1st report on the health-promoting potentials of oat beta-glucan, several studies have been carried on the subject matter on various health problems. Moreover, consumption and utilization of the material have increased greatly among consumers, especially in the developed societies where issues of chronic diseases continue to be of major health concern. In order to provide current information on the subject matter, this article is an attempt to review recent advances into the general health benefits of oat beta-glucan.

Sources, chemistry, and isolation

Oat β-glucan, a viscous polysaccharide made up of units of the monosaccharides D-glucose, comes from oat kernels. About 20%–30% of the total weight of oat kernels of common cultivar varieties consists of hulls. In its unprocessed state, the oat kernel contains approximately 85% insoluble dietary fiber. Exceptions are naked cultivar varieties, where the hull content is less than 5%. Hulls can be further processed to obtain oat hull fiber, which has a dietary fiber content of more than 90%, all of it being insoluble (Cho 2001).

In the remaining edible part, the groat, the total content of dietary fiber is usually 6%–9%, about half of which is insoluble fiber, located mainly in the tissues outside the aleurone layer. The principal component of oat soluble fiber is the linear polysaccharide (1, 3), (1, 4)-β-D-glucan, usually called β-glucan. It is located in the endosperm cell walls, which are thickest adjacent to the aleurone layer, in the subaleurone layer. However, the size of endosperm cells, the thickness of the cell walls throughout the groat, and thus the distribution of β-glucan vary widely among the different cultivar varieties (Fucher and Muller 1993).

The principal oat species cultivated and marketed today are Avena sativa (white oats) and Avena byzantine (red oats). The major oat-producing areas are in Russia, the European Union (Finland and Poland are the biggest in the European Union), Canada, the United States, and Australia (Welch 1995).

Chemically speaking, oat (1, 3), (1, 4)-β-D-glucan is a linear polysaccharide and composed mainly of (1, 3)-linked cellotriosyl and cellotetraosyl units (>90%). The (1→3)-link prevents close packing of the molecule and makes the molecule partly soluble in water, unlike cellulose which is built entirely of β-(1→4)-linked D-glucanosyl units and is capable of close packing to crystalline structures (Morgan 2000). The relative amounts of oligosaccharides released from β-glucans by hydrolysis with (1, 3), (1, 4)-β-D–glucan-4-glucanohydrolase (lichenase), which specifically cleaves the (1, 4)-linkage of a 3-o-substituted β-D-glucopyranosyl residue, constitute a fingerprint of the structure of the β-glucans (Figure 1). The molar ratio of tri/ tetra oligosaccharides 2.1–2.4 is characteristic for oat (Cui and Wood 2000).

Figure 1–.

Structure of β-D-glucan.

Johansson and others (2000) emphasized that the nuclear magnetic resonance (NMR) structural analysis of β-glucan and HPLC analysis of its oligosaccharide indicates that cello-oligosaccharides are joined by (1, 3) and (1, 4) linkages only and the HPLC analysis showed that the main components of β-glucan are cellotri- and cellotetrasaccharides (95% of the whole).

Oat β-glucan produces very viscous solutions. It segregates into gelling and nongelling fractions (Johansson 2000), but the factors controlling gelation behavior of oat β-glucans have not been well studied. Clearly, molecular weight influences not only flow viscosity, but also gelation (Wood and others 2000).

The process of isolation and purification of oat β-glucan is extremely difficult; however, it has continued to be developed over the years. The extraction methodologies are based on the solubility of β-glucan in hot water and in alkaline solutions, separation of the dissolved proteins by isoelectric precipitation, and precipitation of the β-glucan by ammonium sulfate, 2-propanol, or ethanol (Wood and others 1978). In further purification, for research purposes, repeated precipitations and enzymatic hydrolysis of residual starch are used, and a purity of 99% has been reached (Wood and others 1991; Westerlund and others 1993). Bhatty (1993) used distilled water, adjusted to pH 10 with 20% sodium carbonate, to extract beta-glucan from oat bran. The yield from oat bran was higher, 61%, and the separated fraction contained 84% beta-glucan. Beer and others (1996) used a similar method to extract oat beta-glucan and purified the preparations further with dialysis, ultrafiltration, or alcohol precipitation. It was possible to produce preparations with beta-glucan content of 60%–65% with all 3 methods. However, dialysis gave a preparation with higher viscosity than the other methods. The authors concluded that alcohol precipitation would be the method of choice if large quantities of oat beta-glucan are to be prepared. Asif and others (2010) performed acid, alkaline, and enzymatic extraction and purification of oat β-glucan (Figure 2). They reported that enzymatic extraction was the best because it not only gave the highest yield but also removed more starch, fat, and pentosans during the extraction of β-D-glucan gum, along with a fair amount of minerals, without significantly affecting its physicochemical properties.

Figure 2.

–Extraction and purification of oat β-D-glucan. (Asif and others 2010)

Gastrointestinal effects of oat β-glucan

Both soluble and insoluble oat fibers have gastrointestinal effects: soluble fiber mainly due to its high swelling and water-binding ability, and as a substrate in colon fermentations and insoluble fiber due to its bulking effect.

The gastrointestinal effects of oat β-glucan were well reviewed by Mälkki and Virtanen (2001). However, in this article we intend to emphasize some solution behavior of oat β-glucan under gastrointestinal conditions. In the stomach, oat β-glucan has a smaller hydrodynamic size; its aggregates seem to be reduced or disrupted. Low pH could be responsible for that because no change was observed when pepsin was absent in the stomach (Ulmius and others 2012).

Ulmius and others (2011) reported in their study that the release of oat-β-glucan was mainly due to gastric digestion. They further observed that the process of milling to smaller particles could improve the releasability of β-glucan from 20% to 55%. Moreover, it reduced protein and starch matrices to 5% and fat to 45%. Wang and others (2002) have reported that the rate of recovery of β-glucan increased to 90% after microwave heating compared to 75% for samples treated by conventional dissolution. This was due to the large particle size of β-glucan aggregates in the sample which was reduced or disrupted after microwave heating leading to increased recovery of β-glucan.

Dikeman and others (2006), in their study to quantify the viscosity of soluble and insoluble fibers at various concentrations in solution, determined the effects of altering shear rate on the viscosity of these solutions as well as the effects of fibers source, incubation time, and shear rate on the viscosity of solution in a two-stage in vitro digestion simulation model. The authors reported that a short exposure time (1–2 h) of oat bran to gastric fluids in vitro, and in pigs, increased the viscosity. Increase of viscosity was due to the hydration of the substrate. However, a longer exposure decreased the viscosity, which could have been caused by gastric conditions and resulted in a breakdown of the polymeric structure.

Oat dietary fiber when ingested, starts to imbibe water, swell, and dissolve in relationship to its size and previous hydrothermal treatments, the increased volume causes a distension of the stomach, thus affecting satiety. Data on the effect of oat fiber on stomach emptying are controversial. A concept often referred to is that viscous dietary fibers reduce the rate of gastric emptying and that coarse particles leave the stomach sooner (Mälkki and others 2001).

In the small intestine of humans, β-glucan remains intact, since no mammalian enzymes are capable of hydrolyzing it and thereby increase the viscosity. However, the viscosity was also elevated by increased mucin (Mälkki and others 2001). Some insoluble and soluble fibers sources can enhance mucin production (Begin and others 1989; Satchithanandam and others 1990). In pigs, the molecular weight of β-glucan decreases, especially in the distal end, due to the effect of bacterial enzymes (Johansen and others 1997). Due to physical barriers to hydration and enzymatic action, intact remnants of plant tissues can still be observed, and individual variations in viscosity ranged from 2 to 195 mPa.s, with the highest mean value (90 mPa.s) in the distal third of the small intestine 3 h postprandial (Johansen and others 1997). In human ileal effluents (Lia and others 1996), 88.5% of the β-glucan ingested could be recovered.

This increase of viscosity during small intestine digestion is possibly a result of the reformed aggregates (Dikeman and others 2006). Ulmius and others (2011) also observed that the pure β-glucan fractions showed an extensive increase in size during small intestine digestion. The reason could be that the pure β-glucan was partly depolymerized during gastric digestion and the smaller polymers increased the degree of aggregation due to their higher rate leading to more condensed aggregates and, ultimately, gels in neutralized pH (Li and others 2011). Several other human and animal studies have shown depolymerization of β-glucan in the gastrointestinal tract (Lazaridou and Biliaderis 2007), but Johansson and others (2006) did not detect any degradation of oat β-glucan polymers by conditions similar to the ones of the human stomach.

After small intestine digestion, the β-glucan molar mass increases irrespective of whether bile acids or enzymes are present or not, this means that no binding of β-glucan to bile acids or pepsin/pancreatin can be observed; instead, the increase in aggregate size is probably a result of the normalized pH (6.8). The reformed aggregates resulted in a range of Mw (200–700 ×106 g/mol for oat bran b-glucans, 10–100 × 106 g/mol for pure β-glucans), indicating that β-glucan aggregation can lead to aggregates with different sizes (Ulmius and others 2012).

The behavior of β-glucan during gastrointestinal digestion indicates that different fiber fractions have different optimal acidification levels at which polymers are released and the viscosity increases. Beyond these levels, polymers break down and lose their viscous effects (Dikeman and Fahey 2006). Ulmius and others (2011) have confirmed that β-glucan from pure fractions and oat bran behaves differently in the gastrointestinal tract and may have different mechanisms of action. The β-glucan aggregate from oat bran contributes to the viscosity in the intestinal tract, but the possible gel formation of pure β-glucans may instead decrease the viscosity of the surrounding medium.

In the large bowel, oat dietary fiber is fermented as well as other dietary fiber sources. The main products of its fermentation are short chain fatty acids (SCFAs) composed of acetic, propionic, and butyric acids. Oat dietary fiber differs from other source by high fermentability and by yielding higher amounts of butyric acid (Casterline and others 1997).

Oat β-glucan behaves as a prebiotic: a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one strain or a limited number of bacterial strains in the colon and thus improves host health (Gibson and Roberfroid 1995). β-Glucan as such decomposes in the large intestine. The increase in dry weight of colon contents it caused mainly by an increase in microbial cells, as shown with animal studies (Bach Knudsen and others 1990). The microbial cell material also retains more water than insoluble fiber, which increases the water content of the feces.

In summary, in the large intestine β-glucan behaves as a substrate, favoring production of SCFAs. Its oligosaccharides have been demonstrated to act as selective factors, favoring growth of some bacterial strains. The favorable effect on colon function is based partly on the enhanced production of microbial mass with good water retention properties, partly by the bulking effect of insoluble components of the fiber (Mälkki and others 2001).

Health benefits of oat beta-glucan

Oat bran, the edible outermost layer of the oat kernel is rich in soluble fiber and is called beta-glucan. It is a natural polymer comprised of individual glucose molecules that are linked together by a series of beta-(1, 3) and beta-(1, 4) linkages, comprising a class of nondigestible polysaccharides called beta-D-glucans. This unique array of linking promotes several consumer health benefits.

Oat β-glucans lower cholesterol level and promote heart health

According to scientific research results it has been known to scientists for over 2 decades that β-glucan (oat β-glucan) has strong cholesterol and triglyceride lowering properties leading to reduced cardiovascular diseases. Maki and others (2003) in the Chicago Centre for Clinical Research experimented on 268 men and women with high cholesterol and reported the cholesterol-lowering effect. They consumed the TOP/β-glucan (TOP: tall oil-based phytosterols and β-glucan: from whole grain rolled oats), and control foods (the control cereal was corn flakes with some whole grain rolled wheat and crisp rice. The results showed that subjects with medium to moderate hypercholesterolemia reduced their LDL and total cholesterol levels by consuming a TOP/β-glucan-containing food as part of a diet low in satured fat and cholesterol. The main biomarkers for cardiovascular diseases are total and LDL-cholesterol concentrations. Epidemiological data and clinical trials suggest that each 0.026 mmol/L increment in LDL-cholesterol causes an increase in coronary risk of 1% (Anorldi 2004).

Anderson was among the 1st to bring through studies (Anderson 1984, 1990a, 1990b, and 1991) to public attention the potential cholesterol-lowering effects of oats. He demonstrated that oat bran contained β-glucan and was able to reduce total serum cholesterol in hypercholesterolemic subjects as much as 23% with no change in high-density lipoprotein (HDL) cholesterol. It was then suggested that β-glucan was the active component responsible for lowering serum cholesterol levels. Thus, U.S. Food and Drug Administration (U.S. FDA) then allowed a health claim that diets low in satured fat and cholesterol that include soluble fiber from whole oats “may” or “might” reduce the risk of heart disease (U.S. FDA 1997). Law and co-workers (1994) also reported that a prolonged difference in serum cholesterol of 0.6 mmol/L was associated with an almost 30% reduction in the risk of coronary heart disease. In the same vein, Kestin and others (1990) compared 3 different cereal brans (wheat, rice, oats) in mildly hypercholestero-lemic men. The bran was incorporated in bread and muffins and was given to the subjects for 4 wk in a cross-over design. In comparison with wheat and rice bran, oat bran significantly reduced the plasma cholesterol concentration by 5.6% and 3.8%, respectively. The main difference between the test products was that oat bran contained twice as much water-soluble fiber as rice and wheat bran. Many recent studies have confirmed these early statements. Kerckhoffs and others (2003) used enriched bread, cookies, and orange juice with oat β-glucan and investigated its effect on serum lipoproteins in mildly hypercholesterolemic subjects (mean daily intake of oat β-glucan was 5.9 g). They reported that bread and cookies enriched with oat β-glucan did not significantly change LDL-cholesterol compared to the control, while enriched orange juice decreased significantly LDL-cholesterol (0.26 mmol/L). However, Reyna-Villasmil and others (2007) have reported that subjects who consumed bread formulated with 6 g of oat β-glucan for 8 wk significantly increased their plasma HDL cholesterol from 39.4 to 49.5 mg/dL and total cholesterol, and LDL-cholesterol significantly decreased (from 231.8 to 194.2 mg/dL and 167.9 to 120.9 mg/dL, respectively). Biörklund and others (2005) also investigated the effects on serum lipoproteins and postprandial glucose and insulin concentrations with beverages enriched with 5 or 10 g of β-glucan from oat and barley. The results showed that the beverage with 5 g of oat β-glucans lowered the LDL concentration by 0.29 mmol/L (6.7%) and with 10 g oat β-glucan by 0.16 mmol/L (3.7%), while the corresponding reductions in the LDL-cholesterol for barley were only1.8% and 4.0%, respectively. For total cholesterol, beverages with oat β-glucan (5 and 10 g) showed better results than with barley. The reduction was only 7.4% and 4.5%, respectively. This reduction of LDL cholesterol was greater than that reported by Kerckhoffs (0.29 mmol /L and 0.26 mmol /L, respectively).

Some treatments like fermentation, hydrolysis, and others of β-glucan can affect its cholesterol-lowering activities. In this way, Bae and others (2010) reported that enzymatic hydrolysis of oat β-glucan improved its cholesterol-lowering activity more in than native β-glucan. Its hydrolysate significantly reduced weight gain of rats and improved feed efficiency and serum lipid profile, especially the level of triglycerides in serum which was significantly lower in rats when they were fed the diet supplemented with β-glucan hydrolysate, while the HDL cholesterol content in serum increased up to 42%–62%. Furthermore, the diet containing β-glucan hydrolysate substantially reduced the LDL and VLDL-cholesterol contents by 25%–31% and 0.2%–2.3%, respectively. Mårtenson and others (2002) found that the level of serum cholesterol was lower and level of triglycerides was significantly lower in rats fed with oat-based products fermented by microorganism.

There have been few attempts to establish a dose–response relationship which may differ among different subject groups and also depend upon the baseline level. Among others, Davidson and others (1991) have examined the effective dosage of oatmeal and oat bran on serum cholesterol levels in mildly hypercholesterolemic (about 7 mmol/L) subjects. They were receiving 88 g oatmeal, 56 g oat bran, and 84 g of oat bran corresponding to 3.6, 4.0 and 6.0 g of β-glucan, respectively. After 6 wk the authors reported there was an inverse correlation between cholesterol level and β-glucan dose.

Ripsin and others (1992) selected a number of oat studies for a meta-analysis from which it was concluded that a daily dose of more than 3 g β-glucan was needed for statistically and physiologically significant effects, and that the magnitude of response was greater for subjects with a greater than 5.9 mmol/L serum cholesterol level (Table 1). Queenan and others (2007) also reported that intake of 6 g oat β-glucan concentrate per day for 6 wk produced a significant reduction from the baseline of total cholesterol levels (0.03 mmol/L) and LDL-cholesterol (0.03 mmol/L). A more recent meta-analysis of the effect of β-glucan intake on blood cholesterol and glucose levels confirmed that previous statement. The daily dose of oat β-glucan (3 g) increased HDL-cholesterol (0.03 mmol/L) and decreased the total cholesterol (0.60 mmol/L), LDL-cholesterol (0.66 mmol/L), and triglycerides/triacylglycerol (0.04 mmol/L) (Tiwari and Cummins 2011).

Table 1. –Blood lipid values at the end of the diet period in different clinical studies on hypercholesterolemic subjects given oats. (Ripsin and others 1992).
InitialChange,Change,
cholesterol levelβ-glucan < 3g/dβ-glucan ≥3 g/d
<5.9 mmol/L−0.09 ± 0.10 mmol/L−0.13 ± 0.12 mmol/L
≥5.9 mmol/L−0.27 ± 0.04 mmol/L−0.41 ± 0.21 mmol/L

High blood pressure or hypertension is epidemic now in all societies. Hypertension is one of the leading causes of death in both men and women. Dietary fiber supplementations (average dose 11.5 g/d) have been reported to change systolic and diastolic blood pressure by 1.13 mm Hg and 1.26 mm Hg, respectively. This reduction in blood pressure tended to be larger in older and hypertensive populations than younger and normotensive ones (Streppel and others 2005). Saltzman and others (2001) and Pins and others (2002) reported that the consumption of a hypocaloric diet containing oats over 6 wk resulted in greater decreases in systolic blood pressure, total cholesterol, and LDL, which resulted in the prevention of cardiovascular diseases (CVD). This study confirmed the research work of Appel and others (1997) and Mertens and van Gall (2000). In the same trend, Keenan and others (2002) studied the antihypertensive effects of soluble fiber rich whole oat cereal when added to the standard American diet. They reported that the oat cereal group showed a 7.5 mm Hg reduction in systolic blood pressure and a 5.5 mm Hg reduction in diastolic blood pressure, while there was no change in both systolic and diastolic blood pressures in the control group. Oat β-glucan, when supplemented daily, significantly improved blood pressure by reducing both systolic and diastolic blood pressure, reduced greatly antihypertensive medication needs, and reduced the risk of cardiovascular disease in hypertensive patients (Keenan and others 2002; Biörklund and others 2005; Streppel and others 2005; Theuwissen and Mensink 2008; Chen and Huang 2009).

Mechanism of reduction of cholesterol by β-glucan

The reduction of cholesterol is evidently a sum of several effects. However, it is a commonly accepted concept that the main mechanism for β-glucans cholesterol-lowering effect is thought to be dependent on its ability to entrap whole micelles containing bile acid in the intestinal contents due to its viscosity and excluding them from the required interaction with the luminal membrane transporters on the intestinal epithelium, thereby decreasing the absorption or reabsorption of fats, including cholesterol and bile acid, which leads to an increased fecal output of these 2 components (Ellegard and others 2007; Theuwissen and Mensink 2008). As a result, hepatic conversion of cholesterol into bile acid increases, hepatic pools of free cholesterol decrease, and, to reach a new steady state, endogenous cholesterol synthesis will increase. This leads to increased activities of 7α-hydroxylase and HMG-CoA reductase to compensate for the losses of bile acid and cholesterol from liver stores. Furthermore, hepatic LDL-cholesterol receptors become upregulated to restore hepatic cholesterol stores which will lead to decreased serum LDL-cholesterol concentration (Jeon and Blacklow 2005; Ellegard and others 2007). Direct indications of this mechanism are an increase in excretion of bile acids via the feces. This excretion may vary from 35% to 65% (Lia and others 1995). There is no direct proof for a mechanism of the reduced absorption, but it is probably for the main part caused by the increased viscosity in the small intestine. This explanation is supported merely by the physical effect of the viscosity on the diffusion rates and the thickness of the unstirred layer on the site of absorption, but also by a study on cholesterol and galactose absorption in the small intestine of rat in vitro (Lund and others 1989). This is related to the effects of β-glucan and its viscosity on the absorption of glucose (Wood and others 1994). Due to a decrease in bile acid content in the small intestine, emulsification of fats is decreased, which in addition to the viscosity effects mentioned reduces fat absorption. As a result, excretion of fat is increased. In a study with ileostomics (Lia and others 1995), this excretion was 5.5 g/d, which does not significantly alter the amount of fat available daily but might have a positive long-term effect. Reduction and retardation of absorption of nutrients can also have effects via hormonal pathways (Chen and Huang 2009). In Table 2 there are some possible mechanisms for how β-glucans lower blood cholesterol levels.

Table 2–.  Possible effects of beta-glucans on cholesterol homeostasis (Chen and Huang 2009).
 AlterationsConsequencesReferences
Bile acid absorptionDecreasedConversion of cholesterol into bile acids isEllegard and Andersson 2007
   increased and blood cholesterol level is decreased 
CYP7A1IncreasedConversion of cholesterol into bile acids is increasedEllegard and Andersson 2007
LDLRIncreasedCholesterol transport into hepatocytes is increasedWatkins 2004
CYP3A4Not knownCYP3A4 increased bile acid metabolismChen and Raymond 2006
HMG CoA reductaseIncreasedCholesterol synthesis is increasedEllegard and Andersson 2007
Cholesterol absorptionDecreasedBlood level of cholesterol is decreasedEllegard and Andersson 2007,
    and Watkins 2004

One suggested mechanism for cholesterol reduction is the action of short-chain fatty acids. Oat β-glucans have a mixed β-(1→3) and β-(1→4) linkage. Humans lack small intestine enzymes to separate the glucose molecules of β-glucans, and they pass into the large intestine undigested. Oat β-glucan is a fermentable, viscous fiber that decreases LDL cholesterol by decreasing enterohepatic recirculation of cholesterol and bile acids (Queenan and others 2007; Wood 2007).

Soluble fiber entering the colon is fermented nearly completely, the main end products being acetic, propionic, and butyric acids. Butyrate is metabolized by colonic mucosal cells while acetate and propionate are absorbed. Production of SCFAs, and especially the propionate: acetate ratio may influence lipid metabolism. Since propionic acid inhibits cholesterol synthesis in isolated rat hepatocytes at concentrations of 1.0–2.5 mM (Wright and others 1990), it has been suggested that it would have an inhibiting effect on liver cholesterol synthesis. However, in rats fed oat bran the concentration of propionate in the hepatic portal vein has been shown to be maximally 0.35 mmol/L (Illman and Topping 1985), and this mechanism seems thus to be unlikely or to have only a minor effect if any, in humans. Wolever and others (1996) stated there are significant positive relationships between the serum propionate: acetate ratio and with total and LDL-cholesterol in healthy men, but not in women.

Oat β-glucan increases intestinal viscosity and lowers the rate of glucose absorption, which results in lowered postprandial insulin concentrations and decreased insulin–stimulated hepatic HMG-CoA activity, and hence cholesterol synthesis.

Oat beta-glucan lowers postprandial glucose and insulin responses and prevents diabetes

Oat β-glucan plays a role in modulating the metabolic effects observed after fiber-rich meals. As a soluble fiber with viscous characteristics it modifies properties of chyme in the upper part of the gastrointestinal tract affecting gastric emptying, gut motility, and nutrient absorption, which are reflected in lower postprandial glycemic and insulin responses (Behall and others 2006). Thus, oat β-glucan intake is beneficial for healthy subjects and patients with type-2 diabetes (Charles 2005). However, the main biomarkers for the efficiency of a food to control diabetes are measurements of blood glucose and insulin after a standardized meal (glycemic index, GI, postprandial effects) or fasting glucose, insulin, or HbA1c levels (long-term effects). Both metabolic and epidemiological evidence suggest that replacing high-GI forms of carbohydrates with low-GI forms of carbohydrates would reduce the risk of acquiring type-2 diabetes (Willet and Manson 2002; Anorldi 2004).

Granfeldt and others (1995) investigated the postprandial effect of 2 oat products, namely flaked oats (muesli) and boiled oat flakes (oat porridge), in healthy subjects. Both products had a similar GI effect as white bread, while intake of boiled oat kernels tested at the same time gave lower glucose and insulin responses. Tappy and others (1996) gave diabetic subjects a cooked extruded oat bran concentrate for breakfast at different doses (4.0, 6.0, and 8.4 g beta-glucan). The maximum increases in plasma glucose for the oat bran meals were 67%, 42%, and 38%, respectively, compared with a continental breakfast (35 g available carbohydrates). Other studies (van der Sluijs and others 1999) also showed, that when a more concentrated oat extract (Oatrim) is consumed in cooked, boiled, or baked form, it lowers the glucose and insulin responses.

Battilana (2001) and colleagues have studied the mechanism of action of beta-glucan on postprandial glucose metabolism. Healthy men were given a diet with (8.9 g/ d), or without beta-glucan for 3 d. On the 3rd day the diet was administered as fractionated meals ingested every hour for 9 h. In this way it was possible to study effects on metabolism that were unrelated to delayed carbohydrate absorption, for example, fermentation effects. However, glucose metabolism (glucose and insulin concentrations) was similar for the diet with or without beta-glucan. Thus, the main effect of beta-glucan seems to be a delayed intestinal absorption of carbohydrates.

Wood and others (1994, 2000, and 2007) suggested that the reductions in glucose and insulin responses after a meal are mainly due to the viscosity caused by oats. They studied mixtures of oat beta-glucans with different viscosity and there was a highly significant linear relationship between the viscosity and the glucose and insulin responses. Tapola and others (2005), in their study “glycemic responses of oat bran products in type-2 diabetic patients,” also concluded the same when they studied volunteers with type-2 diabetes fed on oat bran flour, oat bran crisp, and a glucose load providing 12.5 g glycemic carbohydrate (series 1) and 25 g glucose load alone, and 25 g glucose load with 30 g oat bran flour (series 2). In both series oat bran products rapidly lowered postprandial glucose concentrations than after the 12.5 g or 25 g glucose load during the 1st hour, but the glucose concentration was greater at 120 min after the oat bran products ingestion than after the glucose load. This decrease of glucose absorption will decrease insulin release and thereby attenuate pancreatic insulin response. Therefore, oat β-glucan has a greater effect at lowering peak glucose absorption concurrently with an attenuated insulin response, which has a high significance in control and prevention of type-2 diabetes (Hooda and others 2010). It was noted that the area under the plasma glucose curve (AUC) for the postprandial period after ingestion of the oat bran crisp was larger than the AUC after the oat bran flour. This means oat bran flour lowered more rapidly the postprandial glucose response than oat bran crisp. As explanation, the β-glucan content of oat bran flour is higher than oat bran crisp and the authors concluded that oat bran flour being high in β-glucan had a low-glycemic response and acted as an active ingredient, decreasing the postprandial glycemic response of an oral glucose load in subjects with type2-diabetes (Tapola and others 2005). Another test was carried on healthy volunteers who were given 4 different test meals: without added cereal fibers and enriched with 10 g cereal fibers (wheat bran, oat bran, and a combination of 5 g of each). The postprandial glucose and insulin responses were similar as previously (Juvonen and others 2011).

The effect on glucose metabolism of long-term intake of oat beta-glucan has also been investigated. An intake of oat beta-glucan (3 g in muesli) taken for breakfast for 4 wk in men with type 2-diabetes led to a decreased cholesterol level and lower postprandial glucose peaks but no effects on fasting plasma glucose, insulin, and HbA1c were observed (Kabir and others 2002).

Researchers have shown that obesity is one of the causes of type 2-diabetes. In the United States of America obesity affects approximately 9 million children over 6 y of age. This dramatic rise in childhood obesity has led to a predicted risk of between 30%–40% for children born in 2000 who will be diagnosed with noninsulin-dependent diabetes mellitus (NIDDM or Type 2-diabetes) during their lifetime (Koplan and others 2005).

Dietary fiber intake helps to decrease the prevalence of obesity. Howarth and others (2001) have reported that an increase in either soluble or insoluble fiber could play a key role in obesity control. Fiber intake increases postmeal satiety and decreases subsequent hunger. Then, the consumption of an additional 14 g/d fiber for >2 d is associated with a 10% decrease in energy intake and body weight loss of 1.9 kg over 3 mo, and obese individuals may even exhibit a greater suppression of energy intake. Slavin (2005) also reported strong epidemiologic support that dietary fiber intake prevents obesity and that fiber intake is inversely associated with body weight and body fat. The amount of fiber intake by adults that may help to decrease the prevalence of obesity should be >25 g/d (Howarth 2001).

Oat β-glucan prevents cancer

Beta-glucans have been used in immune-adjuvant therapy for cancers and tumors since 1980. The ability of β-glucan to inhibit tumor growth in a variety of experimental tumor models is well established (di Luzio 1979). Many of the scientific studies and published articles were done primarily in Japan. There is a large collection of research data that demonstrates beta-glucans have antitumor and anticancer activity. Generally, the (1, 3)-β-glucan was administered prophylactically and the end-point were tumor growth, tumor volume, degree of metastases, and /or survival. Moreover, the antitumor efficacy of (1, 3)-β-glucan seems to relate to the type of tumor, the genetic background of the host animal, the dose, the route, and timing of β-glucan administration, as well as the tumor load (Yan and others 2005). Antitumor and anticancer effect of β-glucan is not just macrophages that attack tumor cells and destroy them, but also modulation of lymphocyte, neutrophil, and natural killer (NK) cells activity and other components of the innate immune system (Hong and others 2004). Most of the studies on antitumor properties of β-glucan were carried out with various types of mushrooms and fungi, but all contained (1, 3)-β-glucan (Demir and others 2007, Liu and others 2009, Chen and others 2011). Murphy and others (2004) after examining the independent and combined effects of short-term exercise and oat β-glucan intake (raw oat β-glucan was fed in the drinking water) on the metastatic spread of injected tumor cells (B16 melanoma cells via intravenous injection), and macrophage antitumor cytotoxicity, reported that the metastatic spread of injected B16 melanoma cells was similar in all groups (group mice exercise plus water, group mice exercise plus oat β-glucan, and group mice control plus oat β-glucan) and was significantly different from the group control plus water. This decreased significantly the number of lung tumor foci (95, 102, and 92, respectively, and 189 for the control). There was also no statistical difference between them, thus no additive effects of moderate exercise and oat β-glucan. Macrophage antitumor cytotoxicity was also enhanced significantly in all group compared to the control, but not to the additive effects exercise plus oat β-glucan.

The antitumor activity is caused by a unique killing mechanism that involves neutrophils (the most abundant type of white blood cells in human which form an essential part of the innate immune system) that are primed with betafectin, and that are not normally involved in the fight against cancer (Cheung and others 2002). Recent research by Hong and others (2003; 2004) have advanced the concept that orally administrered beta-glucan will exert an adjuvant effect when combined with exogenously administered antitumor antibodies that activate the components, and demonstrated that this mechanism of action is effective against a broad range of cancers when used in combination with specific monoclonal antibodies that activate or cause the complement to be bound to the tumor. The complement enables these primed neutrophils to find and bind to the tumor, which facilitates killing. Innate immune cells are the body's 1st line of defence and circulate throughout the body engaging in an immune response against “foreign” challenges (bacteria, fungi, parasites). Typically, neutrophils are not involved in the destruction of cancerous tissue because these immune cells view cancer as “self” rather than foreign or “nonself.” Current cancer immunotherapies involve monoclonal antibodies and vaccines, which stimulate the acquired immune response, but do nothing to change the innate immune system's view of cancer as “self.” As a result, the monoclonal antibodies alone do not engage or initiate the potential killing ability of the innate immune system, which is our primary mechanism of defence against bacteria and yeast (fungal) infections. Multinational research has successfully demonstrated that the oral form of yeast β-1, 3-D glucan has similar protective effects as the injected version, including defence against infectious diseases and cancer (Vetvicka and others 2002; Xiao and others 2004; Rice and others 2005). Recently, orally-delivered β-glucan was found to significantly increase proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer (Demir and others 2007).

Antimicrobial and immune effects of oat β-glucan

As much as fungi-derived β-glucans may have stimulatory effects on the immune system, leading to resistance against viral, bacterial, parasitic, and fungal pathogens, the cereal derived β-glucans have also been ascribed to have immune-stimulating properties. It was reported that natural β-glucan administration (intravenously or intramuscularly or taken orally) helps in the elimination of bacteria by increasing bacterial clearance, increasing bactericidal activity, increasing modulation of cytokine production, and increasing the number of monocytes and neutrophils, thereby resulting in an antibiotic potential (Liang and others 1998; Kaiser and others 2002), and enhances macrophage phagocytic activity and resistance to infection in mice (Estrada and others 1997; Yun and others 2003; Murphy and others 2008). Some scientists reported that oat β-glucan taken orally alone or in combination with sucrose has beneficial effects on susceptibility to HSV-1 respiratory infection and macrophage antiviral resistance following stressful exercise (Davids 2004a and b; Nieman 2008Murphy and others 2008, 2009). Oat β-glucans increase the activity of transcription factors in intestinal leukocytes and enterocytes of β-glucan treated mice (Volman and others 2010b).

Rodriguez and others (2009) have reported that intraperitoneal injection of β-glucan significantly enhanced the immune response and protection against infection by the bacterial pathogen Aeromonas hydrophila in zebrafish.

Soluble β-(1, 3)-glucan has been demonstrated to protect against infection and shock in rats and mice (Hetland and others 2000), and clinical studies suggest that administration of soluble glucans to trauma/surgical patients decreases septic complications and improves survival (Williams and others 1996). To confirm these studies, Sissener Engstad and others (2002) studied the effect of soluble β-(1, 3)-glucan and lipopolysaccharide (LPS) on cytokine production and coagulation activation in whole blood, and they reported that soluble yeast β-glucan is recognized by and interacts with cells of the innate immune system in humans, and that soluble glucan not only modulates, but (in most cases) upregulates leukocyte function, both on its own and in response to LPS.

Many studies have shown the antimicrobial effects of oat β-glucan, whereas Yun and others (1997) treated mice, immunosuppressed and infected with oocysts of Eimeria vermiformis, with oat β-glucan by intragastric or subcutaneous route. As result, oat β-glucan treated-groups showed reduced fecal oocyst shedding, minimal clinical signs of disease, no mortality, and a greater amount of total immunoglobulin in the serum. Immunomodulating agents such as IFN-gamma- and IL-4-secreting cells in response to sporozoite antigen were also detected in the mesenteric lymph of the oat β-glucan-treated groups. Therefore, oat beta-glucan treatment increased the resistance to E. vermiformis infection. The same author, in another study, confirmed that oat β-glucan treatment enhanced resistance to infection caused by Staphylococcus aureus and E. vermiformis (Yun 2003). Moreover, scientists have stated its antimicrobial effects against E.coli and B.subtilis, but a β-glucan derivative showed pronounced antimicrobial effects (Shin and others 2005). According to their results, underivatized oat β-glucan had inhibitory effects on both E. coli and B. Subtilis; up to around 35% depending on their concentration and that the β-glucan derivative inhibited their growth up to 80% at a concentration of 2000 μg/ml.

Oat β-glucan enhances resistance to microbial infections via cellular and antigen specific humoral immunity. These immune functions can be upregulated by both oral and parenteral administration of oat β-glucan. Therefore, oat β-glucan plays an important role in providing resistance to bacterial and parasitic infections.

Summary

In view of all these studies we can safely say that oat β-glucan plays an important role in promoting health and prevention against diseases. It is

  • • A good lowering agent of total and LDL cholesterol, and improves HDL cholesterol also;
  • • a good regulator of blood pressure and improves the blood lipid profile;
  • • a good regulator of blood postprandial glycemic and insulin responses;
  • • and reduces and maintains body weight.

Thus, it helps to treat and/or prevent cardiovascular diseases and diabetes. In addition, it improves the immune functions of an organism by increasing, in the blood, immunoglobulins, NK cells, killer T-cells, among others, and it improves the resistance to infectious and parasitic diseases. Moreover, it contributes to the decrease in the risk of cancer and improves the quality of chemotherapy. Most of these studies have been conducted with animals; it will be interesting to confirm them in humans, especially for cancer treatment.

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