The effect on the blood lipid profile of soy foods combined with a prebiotic: a randomized controlled trial.

The value of soy protein as part of the cholesterol-lowering diet has been questioned by recent studies. The apparent lack of effect may relate to the absence of dietary factors that increase colonic fermentation and potentiate the cholesterol-lowering effect of soy. Therefore, unabsorbable carbohydrates (prebiotics) were added to the diet with the aim of increasing colonic fermentation and so potentially increasing the hypocholesterolemic effect of soy. Twenty-three hyperlipidemic adults (11 male, 12 female; 58 +/- 7 years old; low-density lipoprotein cholesterol [LDL-C], 4.18 +/- 0.58 mmol/L) completed three 4-week diet intervention phases-a low-fat dairy diet and 10 g/d prebiotic (oligofructose-enriched inulin, a fermentable carbohydrate), a soy food-containing diet (30 g/d soy protein, 61 mg/d isoflavones from soy foods) and 10 g/d placebo (maltodextrin), and a soy food-containing diet with 10 g/d prebiotic--in a randomized controlled crossover study. Intake of soy plus prebiotic resulted in greater reductions in LDL-C (-0.18 +/- 0.07 mmol/L, P = .042) and in ratio of LDL-C to high-density lipoprotein cholesterol (-0.28 +/- 0.11, P = .041) compared with prebiotic. In addition, high-density lipoprotein cholesterol was significantly increased on soy plus prebiotic compared with prebiotic (0.06 +/- 0.02 mmol/L, P = .029). Differences in bifidobacteria, total anaerobes, aerobes, and breath hydrogen did not reach significance. Soy foods in conjunction with a prebiotic resulted in significant improvements in the lipid profile, not seen when either prebiotic or soy alone was taken. Coingestion of a prebiotic may potentiate the effectiveness of soy foods as part of the dietary strategy to lower serum cholesterol.

Effect of a low-glycemic index or a high-cereal fiber diet on type 2 diabetes: a randomized trial.

CONTEXT: Clinical trials using antihyperglycemic medications to improve glycemic control have not demonstrated the anticipated cardiovascular benefits. Low-glycemic index diets may improve both glycemic control and cardiovascular risk factors for patients with type 2 diabetes but debate over their effectiveness continues due to trial limitations. OBJECTIVE: To test the effects of low-glycemic index diets on glycemic control and cardiovascular risk factors in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: A randomized, parallel study design at a Canadian university hospital research center of 210 participants with type 2 diabetes treated with antihyperglycemic medications who were recruited by newspaper advertisement and randomly assigned to receive 1 of 2 diet treatments each for 6 months between September 16, 2004, and May 22, 2007. INTERVENTION: High-cereal fiber or low-glycemic index dietary advice. MAIN OUTCOME MEASURES: Absolute change in glycated hemoglobin A(1c) (HbA(1c)), with fasting blood glucose and cardiovascular disease risk factors as secondary measures. RESULTS: In the intention-to-treat analysis, HbA(1c) decreased by -0.18% absolute HbA(1c) units (95% confidence interval [CI], -0.29% to -0.07%) in the high-cereal fiber diet compared with -0.50% absolute HbA(1c) units (95% CI, -0.61% to -0.39%) in the low-glycemic index diet (P < .001). There was also an increase of high-density lipoprotein cholesterol in the low-glycemic index diet by 1.7 mg/dL (95% CI, 0.8-2.6 mg/dL) compared with a decrease of high-density lipoprotein cholesterol by -0.2 mg/dL (95% CI, -0.9 to 0.5 mg/dL) in the high-cereal fiber diet (P = .005). The reduction in dietary glycemic index related positively to the reduction in HbA(1c) concentration (r = 0.35, P < .001) and negatively to the increase in high-density lipoprotein cholesterol (r = -0.19, P = .009). CONCLUSION: In patients with type 2 diabetes, 6-month treatment with a low-glycemic index diet resulted in moderately lower HbA(1c) levels compared with a high-cereal fiber diet. Trial Registration clinicaltrials.gov identifier: NCT00438698.

Comparison of a dietary portfolio diet of cholesterol-lowering foods and a statin on LDL particle size phenotype in hypercholesterolaemic participants.

The effect of diet v. statins on LDL particle size as a risk factor for CVD has not been examined. We compared, in the same subjects, the impact of a dietary portfolio of cholesterol-lowering foods and a statin on LDL size electrophoretic characteristics. Thirty-four hyperlipidaemic subjects completed three 1-month treatments as outpatients in random order: a very-low saturated fat diet (control); the same diet with 20 mg lovastatin; a dietary portfolio high in plant sterols (1 g/4200 kJ), soya proteins (21.4 g/4200 kJ), soluble fibres (9.8 g/4200 kJ) and almonds (14 g/4200 kJ). LDL electrophoretic characteristics were measured by non-denaturing polyacrylamide gradient gel electrophoresis of fasting plasma at 0, 2 and 4 weeks of each treatment. The reductions in plasma LDL-cholesterol levels with the dietary portfolio and with statins were comparable and were largely attributable to reductions in the estimated concentration of cholesterol within the smallest subclass of LDL (portfolio - 0.69 (se 0.10) mmol/l, statin - 0.99 (se 0.10) mmol/l). These were significantly greater (P < 0.01) than changes observed after the control diet ( - 0.17 (se 0.08) mmol/l). Finally, baseline C-reactive protein levels were a significant predictor of the LDL size responsiveness to the dietary portfolio but not to the other treatments. The dietary portfolio, like the statin treatment, had only minor effects on several features of the LDL size phenotype, but the pronounced reduction in cholesterol levels within the small LDL fraction may provide additional cardiovascular benefit over the traditional low-fat diet of National Cholesterol Education Program Step II.

The glycemic index: methodology and use.

The glycemic index concept owes much to the dietary fiber hypothesis that fiber would reduce the rate of nutrient absorption and increase the value of carbohydrate foods in the maintenance of health and treatment of disease. However, properties and components of food other than its fiber content contribute to the glycemic and endocrine responses postprandially. The aim of the glycemic index classification of foods was therefore to assist in the physiological classification of carbohydrate foods which, it was hoped, would be of relevance in the prevention and treatment of chronic diseases such as diabetes. Over the past two decades low glycemic index diets have been reported to improve glycemic control in diabetic subjects, to reduce serum lipids in hyperlipidemic subjects and possibly to aid in weight control. In large cohort studies, low glycemic index or glycemic load diets (glycemic index multiplied by total carbohydrate) have also been associated with higher levels of high-density lipoprotein cholesterol, reduced C-reactive protein concentrations and with a decreased risk of developing diabetes and cardiovascular disease. More recently, some case-control and cohort studies have also found positive associations between the dietary glycemic index and the risk of colon, breast and other cancers. While the glycemic index concept continues to be debated and there remain inconsistencies in the data, sufficient positive findings have emerged to suggest that the glycemic index is an aspect of diet of potential importance in the treatment and prevention of chronic diseases.

Colonic health: fermentation and short chain fatty acids.

Interest has been recently rekindled in short chain fatty acids (SCFAs) with the emergence of prebiotics and probiotics aimed at improving colonic and systemic health. Dietary carbohydrates, specifically resistant starches and dietary fiber, are substrates for fermentation that produce SCFAs, primarily acetate, propionate, and butyrate, as end products. The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source and gut transit time. SCFAs are readily absorbed. Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues. Specific SCFA may reduce the risk of developing gastrointestinal disorders, cancer, and cardiovascular disease. Acetate is the principal SCFA in the colon, and after absorption it has been shown to increase cholesterol synthesis. However, propionate, a gluconeogenerator, has been shown to inhibit cholesterol synthesis. Therefore, substrates that can decrease the acetate: propionate ratio may reduce serum lipids and possibly cardiovascular disease risk. Butyrate has been studied for its role in nourishing the colonic mucosa and in the prevention of cancer of the colon, by promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme histone deacetylase and decreasing the transformation of primary to secondary bile acids as a result of colonic acidification. Therefore, a greater increase in SCFA production and potentially a greater delivery of SCFA, specifically butyrate, to the distal colon may result in a protective effect. Butyrate irrigation (enema) has also been suggested in the treatment of colitis. More human studies are now needed, especially, given the diverse nature of carbohydrate substrates and the SCFA patterns resulting from their fermentation. Short-term and long-term human studies are particularly required on SCFAs in relation to markers of cancer risk. These studies will be key to the success of dietary recommendations to maximize colonic disease prevention.

Assessment of the longer-term effects of a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia.

BACKGROUND: Cholesterol-lowering foods may be more effective when consumed as combinations rather than as single foods. OBJECTIVES: Our aims were to determine the effectiveness of consuming a combination of cholesterol-lowering foods (dietary portfolio) under real-world conditions and to compare these results with published data from the same participants who had undergone 4-wk metabolic studies to compare the same dietary portfolio with the effects of a statin. DESIGN: For 12 mo, 66 hyperlipidemic participants were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal), and almonds (23 g/1000 kcal). Fifty-five participants completed the 1-y study. The 1-y data were also compared with published results on 29 of the participants who had also undergone separate 1-mo metabolic trials of a diet and a statin. RESULTS: At 3 mo and 1 y, mean (+/-SE) LDL-cholesterol reductions appeared stable at 14.0 +/- 1.6% (P < 0.001) and 12.8 +/- 2.0% (P < 0.001), respectively (n = 66). These reductions were less than those observed after the 1-mo metabolic diet and statin trials. Nevertheless, 31.8% of the participants (n = 21 of 66) had LDL-cholesterol reductions of >20% at 1 y (x +/- SE: -29.7 +/- 1.6%). The LDL-cholesterol reductions in this group were not significantly different from those seen after their respective metabolically controlled portfolio or statin treatments. A correlation was found between total dietary adherence and LDL-cholesterol change (r = -0.42, P < 0.001). Only 2 of the 26 participants with <55% compliance achieved LDL-cholesterol reductions >20% at 1 y. CONCLUSIONS: More than 30% of motivated participants who ate the dietary portfolio of cholesterol-lowering foods under real-world conditions were able to lower LDL-cholesterol concentrations >20%, which was not significantly different from their response to a first-generation statin taken under metabolically controlled conditions.

Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants.

BACKGROUND: 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce serum cholesterol and are increasingly advocated in primary prevention to achieve reductions in LDL cholesterol. Newer dietary approaches combining cholesterol-lowering foods may offer another option, but these approaches have not been compared directly with statins in the same persons. OBJECTIVE: The objective was to compare, in the same subjects, the cholesterol-lowering potential of a dietary portfolio with that of a statin. DESIGN: Thirty-four hyperlipidemic participants underwent all three 1-mo treatments in random order as outpatients: a very-low-saturated-fat diet (control diet), the same diet plus 20 mg lovastatin (statin diet), and a diet high in plant sterols (1.0 g/1000 kcal), soy-protein foods (including soy milks and soy burgers, 21.4 g/1000 kcal), almonds (14 g/1000 kcal), and viscous fibers from oats, barley, psyllium, and the vegetables okra and eggplant (10 g/1000 kcal) (portfolio diets). Fasting blood samples were obtained at 0, 2, and 4 wk. RESULTS: LDL-cholesterol concentrations decreased by 8.5+/-1.9%, 33.3+/-1.9%, and 29.6+/-1.3% after 4 wk of the control, statin, and portfolio diets, respectively. Although the absolute difference between the statin and the portfolio treatments was significant at 4 wk (P=0.013), 9 participants (26%) achieved their lowest LDL-cholesterol concentrations with the portfolio diet. Moreover, the statin (n=27) and the portfolio (n=24) diets did not differ significantly (P=0.288) in their ability to reduce LDL cholesterol below the 3.4-mmol/L primary prevention cutoff. CONCLUSIONS: Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention. They may, therefore, bridge the treatment gap between current therapeutic diets and newer statins.

Resistant starches and health.

It was initially hypothesized that resistant starches, i.e., starch that enters the colon, would have protective effects on chronic colonic diseases, including reduction of colon cancer risk and in the treatment of ulcerative colitis. Recent studies have confirmed the ability of resistant starch to increase fecal bulk, increase the molar ratio of butyrate in relation to other short-chain fatty acids, and dilute fecal bile acids. However the ability of resistant starch to reduce luminal concentrations of compounds that are damaging to the colonic mucosa, including fecal ammonia, phenols, and N-nitroso compounds, still requires clear demonstration. As such, the effectiveness of resistant starch in preventing or treating colonic diseases remains to be assessed. Nevertheless, there is a fraction of what has been termed resistant (RS1) starch, which enters the colon and acts as slowly digested or lente carbohydrate in the small intestine. Foods in this class are low glycemic index and have been shown to reduce the risk of chronic disease. They have been associated with systemic physiological effects such as reduced postprandial insulin levels and higher HDL cholesterol levels. Consumption of low glycemic index foods has been shown to be related to reductions in risk of coronary heart disease and Type 2 diabetes. Type 2 diabetes has in turn been related to a higher risk of colon cancer. If carbohydrates have a protective role in colon cancer prevention this may lie partly in the systemic effects of low glycemic index foods. The colonic advantages of different carbohydrates, varying in their glycemic index and resistant starch content, therefore, remain to be determined. However, as recent positive research findings continue to mount, there is reason for optimism over the possible health advantages of those resistant starches, which are slowly digested in the small intestine.

Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein.

CONTEXT: To enhance the effectiveness of diet in lowering cholesterol, recommendations of the Adult Treatment Panel III of the National Cholesterol Education Program emphasize diets low in saturated fat together with plant sterols and viscous fibers, and the American Heart Association supports the use of soy protein and nuts. OBJECTIVE: To determine whether a diet containing all of these recommended food components leads to cholesterol reduction comparable with that of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). DESIGN: Randomized controlled trial conducted between October and December 2002. SETTING AND PARTICIPANTS: Forty-six healthy, hyperlipidemic adults (25 men and 21 postmenopausal women) with a mean (SE) age of 59 (1) years and body mass index of 27.6 (0.5), recruited from a Canadian hospital-affiliated nutrition research center and the community. INTERVENTIONS: Participants were randomly assigned to undergo 1 of 3 interventions on an outpatient basis for 1 month: a diet very low in saturated fat, based on milled whole-wheat cereals and low-fat dairy foods (n = 16; control); the same diet plus lovastatin, 20 mg/d (n = 14); or a diet high in plant sterols (1.0 g/1000 kcal), soy protein (21.4 g/1000 kcal), viscous fibers (9.8 g/1000 kcal), and almonds (14 g/1000 kcal) (n = 16; dietary portfolio). MAIN OUTCOME MEASURES: Lipid and C-reactive protein levels, obtained from fasting blood samples; blood pressure; and body weight; measured at weeks 0, 2, and 4 and compared among the 3 treatment groups. RESULTS: The control, statin, and dietary portfolio groups had mean (SE) decreases in low-density lipoprotein cholesterol of 8.0% (2.1%) (P =.002), 30.9% (3.6%) (P<.001), and 28.6% (3.2%) (P<.001), respectively. Respective reductions in C-reactive protein were 10.0% (8.6%) (P =.27), 33.3% (8.3%) (P =.002), and 28.2% (10.8%) (P =.02). The significant reductions in the statin and dietary portfolio groups were all significantly different from changes in the control group. There were no significant differences in efficacy between the statin and dietary portfolio treatments. CONCLUSION: In this study, diversifying cholesterol-lowering components in the same dietary portfolio increased the effectiveness of diet as a treatment of hypercholesterolemia.