Soluble Fiber and Cholesterol: The Functionality of Oat -Glucan

Kimberly L. Scannevin The Sage Colleges

INTRODUCTION Coronary heart disease, stroke, and heart attack; what these three medical conditions have in common is that they are leading causes of death in the United States. But numerous deaths may be prevented, and health can be improved, by focusing on one controllable risk factor; high cholesterol. According to the American Heart Association, high cholesterol increases the risk of coronary heart disease (2012), hence lowering cholesterol levels is a major health concern, both nationally and internationally (http://www.heart.org/HEARTORG/). Seeking an alternative to drug therapy for cholesterol lowering benefits, there has been many studies on functional foods which may promote cardiovascular health. Oat - glucan, a soluble fiber, is one such food that has cholesterol-lowering properties (Othman, Moghadasian, & Jones, 2011, p. 299). Soluble fiber can be defined as, plant gums and pectic substances that undergo some digestion and absorption in the large intestine (McWilliams, 2012, p. 536). Soluble fiber (glucans), may have specific cholesterol-lowering abilities, with much research pointing towards lowering LDL cholesterol levels and total blood cholesterol levels (Othman et al., 2011, p. 299). Examples of beta-glucans can be found in graminaceous crops, including barely and rye, or in fungi and bacteria (Chen & Huang, 2009, p. 154). Oat - glucan is the most prominent example, and can be found primarily in oat endosperm cell walls. As cited by Othman et al., it is classified as a soluble fiber, which is highly viscous (Butt, Tahir-Nadeem, Khan, Shabir & Butt, 2008, p. 70). Beta-glucans are described as polysaccharides which consist of glucose residues joined by beta linkage (Chen & Huang, 2012, p. 154). Further information regarding the composition of the glucose molecules is that they have mixed -(14) and -(13) bonds (see Figure 1 for the -glucan chemical structure) (Othman et al., 2011, p. 299). The -glucan

chemical structure promotes viscosity and solubility, both which impact cholesterol metabolism (Othman et al., 2011, p. 299). Other important characteristics of beta-glucans are their watersolubility (Birklund, Holm & nning, 2008, p. 83), gel-forming properties (Rondanelli et al., 2011, p. 869), and stability to heat (Chen & Huang, 2009, p. 155).

PROPOSED MECHANISMS OF ACTION The mechanism of the cholesterol-lowering ability of the beta-glucan is that the fiber portion escalates the viscosity of the intestinal contents, delaying absorption of triacylglycerols and glucose, while inhibiting cholesterol and bile acid from absorption as well as resorption (Birklund et al., 2008, p. 83). Thus, the first step in the action plan of the beta-glucan is to inhibit intestinal uptake via the formation of a viscous layer, which prevents uptake of cholesterol. As cited by Othman et al. (2011, p. 299), without bile acid resorption, bile acids are synthesized from cholesterol, which leads to a decrease in circulating low-density lipoprotein levels (Butt et al., 2008, p. 70). Bile acid delivery is increased in the feces; beta-glucans actually entrap bile-acid containing micelles (Chen & Huang, 2009, p. 155).

CYP7A1 Cholesterol 7 -hydroxylase or CYP7A1 is important bile acid metabolizing enzyme. CYP7A1 catalyzes the rate-limiting step in bile acid synthesis and thus speeds up cholesterol elimination (Chen & Huang, 2009, p. 155-156). Cholesterol conversion into bile acids is increased (Chen & Huang, 2009, p. 156). This is confirmed by results of the Ellegrd and Andersson study, as subjects who were fed oat bran had an increase in CYP7A1 product 7 hydroxycholesterol. CYP7A1 expression increased 114% in oat-bran fed subjects, as compared

to the control subjects whose diet excluded oat bran (Chen & Huang, 2009, p. 156). A major pathway for cholesterol elimination is via bile acid synthesis and excretion (Ellegrd & Andersson, 2007, p. 938), hence the importance of the findings.

SUMMARY OF IMPACAT Potential methods by which blood cholesterol levels are lowered by oat -glucans are summarized in Table 1 (Othman et al., 2011, p. 306). Increased viscosity in the small intestine leads to decreased absorption of cholesterol as the beta-glucans basically bind cholesterol and bile acids in the intestine (Chen & Huang, 2009, p. 155). As bile-acid resorption is lowered, cholesterol, through hepatic conversion is transformed into bile acids, thus lowering free cholesterol pools. There is an increase (upregulation) in LDL-receptor (hepatic) synthesis, leading to LDL-transportation increases from the blood to the hepatocytes. This chain of events leads to the eventual serum LDL cholesterol decrease (Othman et al., 2011, p. 306).

INFLUENCES ON CHOLESTEROL-LOWERING ACTIONS Molecular weight and structure affects the viscosity produced by beta-glucans. As cited by Chen & Huang (2009, p. 155), a prior study determined that the best viscosity is formed by beta-glucans with molecular weights of 2.68 x 104 to 3.00 x 106 daltons (Doublier & Wood, 1995, p. 335-340). The Wolever et al. clinical trial also agrees that molecular weight is important to viscosity (2010, p. 723), and adds that storage and method of processing influence effects as well, as gathered from a prior studys results (Regand, Tosh, Wolever, & Wood, 2009, p. 8831-8838). The food microstructure, or food matrix form, influences -glucan functioning as

well. Whether the beta-glucan has been added to a solid versus a liquid vehicle influences the level of cholesterol-lowering impact (Othman et al., 2011, p. 305). The beta-glucan dosage effects the final changes in total and LDL cholesterol from baseline amounts. Charlton et al. found that lower doses of oat -glucan were just as effective as higher dosages when provided in varying food formats (all formats delivered similar amounts of soluble beta-glucan) (2012, p. 1037). Oat porridge, cereal bars and oat-flaked breakfast cereal were trialed on adults who were mildly hypercholesterolaemic; all resulted in total cholesterol and LDL level reduction, but no difference was found in reduction between the groups (Charlton et al, 2012, p. 1039-1040).

OAT -GLUCAN AND CHOLESTEROL-LOWERING CLAIMS Food claims from manufacturing companies to promote the functionality of oat glucans cholesterol lowering properties were a huge push in the mid 1990s. The Quaker Oats company, in 1995, submitted the Food and Drug Administration (FDA) with a petition for approval of a health claim for their product, which stated that whole oat products had beneficial cholesterol lowering effects (Othman et al., 2011, p. 300). The FDA recognized the

relationship between soluble fiber (specifically oat -glucan) and a decrease in cholesterol in 1997; this health claim was approved for oats on a basis of data collected from thirty-three clinical studies. A significant decrease in blood cholesterol was found in twenty-one out of the thirty-three studies (Othman et al., 2011, p. 300). The approved authorized claim states, that soluble fiber from foods such as oat bran, as part of a diet low in saturated fat and cholesterol, may reduce the risk of coronary heart disease (Othman et al., 2011, p. 300). Whole oat products inclusive of this health claim are whole oats, oat bran, and whole oat flour (Othman et al., 2011,

p. 300). Other agencies worldwide allowed this claim on their countrys products as well. The French Food Safety Agency and the United Kingdoms Joint Health Claims Initiative both supported and approved health claims on food products containing oat -glucan, in regards to the reduction of blood cholesterol (Wolever et al., 2010, p. 723). The recommended amounts approved by these food and health governing agencies, in conclusion, was that 3 grams a day, as a minimum dose, is required for a benefit in the blood cholesterol lowering abilities of oat -glucan. In addition, the food should contain at least 0.75 g -glucan soluble fiber per serving in order for the food claim to be allowed on the product (Othman et al., 2011, p. 300). This dosage of oat -glucan can lower cholesterol by 510 %, via 3 g per day of bran or rolled oats (Charlton et al., 2011, p. 1038).

CURRENT ADVANCES IN RESEARCH Furthers studies surrounding the exact amounts and mode of administration of the glucans are currently being researched. The exact molecular weight of the oat -glucan necessary to see beneficial health effects was the main focus of two recent studies. The findings of one current study suggest that a smaller quantity (1.5g/d) of medium-molecular-weight oat -glucan with high solubility may be equally as effective as a higher quantity (3g/day) of highmolecular-weight -glucan (Charlton et al., 2012, p. 1046). The researchers agree that further studies are needed to confirm and determine the lowest effective oat -glucan dosage, and as to which food formats work best, but this new data is promising. Another study examined the molecular weight (MW) and dosage more in depth; a randomized clinical trial tested the differences between the consumption of 3g of high-MW, 4g medium-MW, 3g-medium MW and 4 g low-MW oat -glucan (Wolever et al., 2010, p. 723).

The study results concluded that it is important to determine the serving amount, the MW and bioavailability (source) of the oat -glucan. Differences were found on low-density lipoprotein cholesterol lowering abilities; the high and medium MW 3g cereals had a similar lowering effect (5%), but there was a 50% reduction in efficacy when a low MW oat -glucan is used (Wolever et al., 2010, p. 731). Advanced research has investigated the mode of administration of oat -glucans, and whether this affects cholesterol-lowering properties. One study found that the consumption frequency of the -glucans influenced the reduction of lipid concentrations more profoundly; that more frequent servings (several times a day versus once or twice daily) is preferable (Birklund et al., 2008, p. 88). Comparison of diets enriched with beta-glucans versus rice bran has been studied in other recent research; specifically on hypercholesterolemic men. A crossover clinical trial compared the effects of soluble fiber (barley beta-glucans) versus insoluble fiber (rice bran) on serum lipid levels. The results indicated that the foods enriched with beta-glucan clearly had statistically significant LDL-cholesterol reducing effects when compared to rice bran-enriched foods (Rondanelli et al., 2011, p. 869). This research insinuated that functional foods could be a potential treatment for mildly hypercholesterolemic persons (Rondanelli et al., 2011, p. 869), instead of the use of statins, which have side effects that include muscle abnormalities (weak and stiff muscles) and liver enzyme elevations (Kostapanos, Milionis, & Elisaf, 2010, p. 14, 19).

FUTURE RESEARCH Further clinical studies and research is needed to correlated more closely physiochemical characteristics and understand their association. Important concepts include -glucans

molecular weight and exact cholesterol lowering effects (Othman et al., 2011, p. 306). Another issue that needs further investigation is if consumption by the public is in high enough quantities to actually achieve the dosage needed for beneficial health effects (Birklund et al., 2008, p. 84). If this functional food is adapted, and supplemented into products as a cholesterol-lowering additive, concern is that it might affect the palatability of the products, possibly negatively impacting the sensory qualities of the foods (Birklund et al., 2008, p. 84). Further research is deemed necessary.

FINAL RECOMMENDATIONS Oat -glucans have beneficial effects on lowering cholesterol; including 3 grams a day or more as part of a healthy diet will promote cardiovascular health (Othman et al., 2011, p. 307), potentially lowering low-density lipoprotein levels and total plasma levels by 5-10% (Othman et al., 2011, p. 299). The optimal candidates to benefit from this functional food are people with borderline high cholesterol levels who do not want to go on medication, but can adopt slight diet changes to potentially lower their levels into the desirable category. While soluble fiber has been used as a selling point and marketing tool for food manufacturers, it has been confirmed and proven to have cholesterol-lowering effects and can be accepted as a functional food which has heart-healthy properties.

FIGURES & TABLES Figure 1 Oat -glucan chemical structure.

Source: Othman et al., 2011, p. 300

Table 1 Suggested mechanisms for cholesterol-lowering impact of -glucan. Viscosity in the gastrointestinal tract Intestinal uptake of dietary cholesterol Hepatic conversion of cholesterol into bile acids Reabsorption of bile acids and its return to the liver Hepatic bile acid concentrations results in: Hepatic cholesterol pools Activity of CYP7A1 enzyme, which converts cholesterol into bile acids Upregulation of hepatic synthesis of 3-hydroxy-3-methylglutaryl coenzyme A reductase Upregulation of hepatic LDL-receptors synthesis Transportation of LDL-cholesterol from the blood into hepatocytes Plasma LDL cholesterol removal (-) Cholesterol synthesis independent of bile acid Production of short-chain fatty acids Abbreviation and symbols: CYP7A1, cholesterol 7 -hydroxylase; LDL, low-density lipoprotein; (-) inhibition; , increase; , decrease.

Source: Othman et al., 2011, p. 306

Kimberly Scannevin References American Heart Association. (2012). Why cholesterol matters. Retrieved from http://www.heart.org/HEARTORG/Conditions/Cholesterol/WhyCholesterolMatter s/Why-Cholesterol-Matters_UCM_001212_Article.jsp Birklund, M., Holm, J., & nning, G. (2008). Serum lipids and postprandial glucose and insulin levels in hyperlipidemic subjects after consumption of an oat -glucan containing ready meal. Annuals of Nutrition & Metabolism, (52), 83-90. doi: 10.1159/000121281 Butt, M.S., Tahir-Nadeem, M., Khan, M. K., Shabir, R., & Butt, M.S. (2008). Oat: unique among the cereals. European Journal of Nutrition, 47 (2), 68-79. doi: 10.1007/s00394-008-0698-7 Charlton, K.E., Tapsell, L.C., Batterham, M.J., OShea, J., Thorne, R., Beck, E., & Tosh, S. (2012). Effect of 6 weeks consumption of -glucan-rich oat products on cholesterol levels in mildly hypercholesterolaemic overweight adults. British Journal of Nutrition, 107 (7), 1037- 1047. http://dx.doi.org/10.1017/S0007114511003850 Chen, J., & Huang, X. (2009). The effects of diets enriched in beta-glucans on blood lipoprotein concentrations. Journal of Clinical Lipidology, 3 (3), 154-158. http://dx.doi.org/10.1016/j.jacl.2009.04.054 Doublier, J. & Wood, P. (1995). Rheological properties of aqueous solutions of (13)(14)--D-glucan from oats. Cereal Chem, 72 (4), 335-340. Ellegrd, L., & Andersson, H. (2007). Oat bran rapidly increases bile acid excretion and bile acid synthesis: an ileostomy study. European Journal of Clinical Nutrition, 61(8), 938-945. doi: 10.1038/sj.ejcn.1602607

Kostapanos, M.S., Milionis, H.J. & Elisaf, M.S. (2010). Rosuvastatin-associated adverse effects and drug-drug interactions in the clinical setting of dyslipidemia. Am J Cardiovasc Drugs, 10 (1), 11-28. http://dx.doi.org.library.sage.edu:2048/10.2165/13168600-000000000-00000 McWilliams, M. (2012). Foods: Experimental perspectives. Upper Saddle River, NJ: Prentice Hall. Othman, R.A., Moghadasian, M.H., & Jones, P.J. (2011). Cholesterol-lowering effects of oat glucan. Nutrition Reviews, 69 (6), 299-309. doi: 10.1111/j.1753-4887.2011.00401.x. Regand, A., Tosh, S.M., Wolever, T.M. & Wood, P. J. (2009). Physiochemical properties of glucan in differently processed oat foods influence glycemic response. Journal of Agricultural and Food Chemistry, 57, 8831-8838. Rondanelli, M., Opizzi, A., Monteferrario, F., Klersy, C., Cazzola, R. & Cestaro, B. (2011). Beta-glucan or rice bran enriched foods: a comparative crossover clinical trial on lipidic pattern in mildly hypercholesterolemic men. European Journal of Clinical Nutrition, (65), 864-871. doi: 10.1038/ejcn.2011.48 Wolever, T.M., Tosh, S.M., Gibbs, A. L., Brand-Miller, J., Duncan, A. M., Hart, V., . . . Wood, P.J. (2010). Physiochemical properties of oat -glucan influence its ability to reduce serum LDL cholesterol in humans: a randomized clinical trial. American Journal of Clinical Nutrition, 92 (4). 723-732. doi: 10.3945/ajcn.2010.29174