James W. Anderson

Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol

BACKGROUND Although it is generally accepted that lowering elevated serum levels of low-density lipoprotein (LDL) cholesterol in patients with coronary heart disease is beneficial, there are few data to guide decisions about therapy for patients whose primary lipid abnormality is a low level of high-density lipoprotein (HDL) cholesterol. METHODS We conducted a double-blind trial comparing gemfibrozil (1200 mg per day) with placebo in 2531 men with coronary heart disease, an HDL cholesterol level of 40 mg per deciliter (1.0 mmol per liter) or less, and an LDL cholesterol level of 140 mg per deciliter (3.6 mmol per liter) or less. The primary study outcome was nonfatal myocardial infarction or death from coronary causes. RESULTS The median follow-up was 5.1 years. At one year, the mean HDL cholesterol level was 6 percent higher, the mean triglyceride level was 31 percent lower, and the mean total cholesterol level was 4 percent lower in the gemfibrozil group than in the placebo group. LDL cholesterol levels did not differ significantly between the groups. A primary event occurred in 275 of the 1267 patients assigned to placebo (21.7 percent) and in 219 of the 1264 patients assigned to gemfibrozil (17.3 percent). The overall reduction in the risk of an event was 4.4 percentage points, and the reduction in relative risk was 22 percent (95 percent confidence interval, 7 to 35 percent; P=0.006). We observed a 24 percent reduction in the combined outcome of death from coronary heart disease, nonfatal myocardial infarction, and stroke (P< 0.001). There were no significant differences in the rates of coronary revascularization, hospitalization for unstable angina, death from any cause, and cancer. CONCLUSIONS Gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level. The findings suggest that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels.

Meta-Analysis of the Effects of Soy Protein Intake on Serum Lipids

BACKGROUND In laboratory animals, the consumption of soy protein, rather than animal protein, decreases serum cholesterol concentrations, but studies in humans have been inconclusive. In this meta-analysis of 38 controlled clinical trials, we examined the relation between soy protein consumption and serum lipid concentrations in humans. METHODS We used a random-effects model to quantify the average effects of soy protein intake on serum lipids in the studies we examined and used hierarchical mixed-effects regression models to predict variation as a function of the characteristics of the studies. RESULTS In most of the studies, the intake of energy, fat, saturated fat, and cholesterol was similar when the subjects ingested control and soy-containing diets; soy protein intake averaged 47 g per day. Ingestion of soy protein was associated with the following net changes in serum lipid concentrations from the concentrations reached with the control diet: total cholesterol, a decrease of 23.2 mg per deciliter (0.60 mmol per liter); 95 percent confidence interval, 13.5 to 32.9 mg per deciliter [0.35 to 0.85 mmol per liter]), or 9.3 percent; low-density lipoprotein (LDL) cholesterol, a decrease of 21.7 mg per deciliter (0.56 mmol per liter); 95 percent confidence interval, 11.2 to 31.7 mg per deciliter [0.30 to 0.82 mmol per liter]), or 12.9 percent; and triglycerides, a decrease of 13.3 mg per deciliter (0.15 mmol per liter; 95 percent confidence interval, 0.3 to 25.7 mg per deciliter [0.003 to 0.29 mmol per liter]), or 10.5 percent. The changes in serum cholesterol and LDL cholesterol concentrations were directly related to the initial serum cholesterol concentration (P < 0.001). The ingestion of soy protein was associated with a nonsignificant 2.4 percent increase in serum concentrations of high-density lipoprotein (HDL) cholesterol. CONCLUSIONS In this meta-analysis we found that the consumption of soy protein rather than animal protein significantly decreased serum concentrations of total cholesterol, LDL cholesterol, and triglycerides without significantly affecting serum HDL cholesterol concentrations.

Health benefits of dietary fiber

Dietary fiber intake provides many health benefits. However, average fiber intakes for US children and adults are less than half of the recommended levels. Individuals with high intakes of dietary fiber appear to be at significantly lower risk for developing coronary heart disease, stroke, hypertension, diabetes, obesity, and certain gastrointestinal diseases. Increasing fiber intake lowers blood pressure and serum cholesterol levels. Increased intake of soluble fiber improves glycemia and insulin sensitivity in non-diabetic and diabetic individuals. Fiber supplementation in obese individuals significantly enhances weight loss. Increased fiber intake benefits a number of gastrointestinal disorders including the following: gastroesophageal reflux disease, duodenal ulcer, diverticulitis, constipation, and hemorrhoids. Prebiotic fibers appear to enhance immune function. Dietary fiber intake provides similar benefits for children as for adults. The recommended dietary fiber intakes for children and adults are 14 g/1000 kcal. More effective communication and consumer education is required to enhance fiber consumption from foods or supplements.

Importance of Weight Management in Type 2 Diabetes: Review with Meta-analysis of Clinical Studies

Obesity is a major risk factor for development of diabetes, and excessive energy intake is a major contributor to poor glycemic control in Type 2 diabetes. The impact of obesity on risk for diabetes as well as coronary heart disease (CHD) risk factors and the benefits of weight loss in decreasing risk for developing diabetes and improving glycemia and CHD risks were reviewed. A systematic review of the medical literature to assess the impact of obesity and weight gain on risk for diabetes and CHD was done. We performed a meta-analysis of the effects of weight loss for obese diabetic individuals. Controlled clinical trials assessing lifestyle changes on risk for developing diabetes and weight loss effects on glycemia and CHD risk factors were reviewed. Obesity and weight gain can increase risk for diabetes by greater than ninetyfold and CHD by about sixfold. Very-low-energy diets (VLED) decrease fasting plasma glucose values by ∼50% within two weeks and these changes are sustained with continued energy restriction. Twelve weeks of energy-restricted diets were associated with these significant decreases: body weight, 9.6%; fasting plasma glucose, 25.7%; serum cholesterol, 9.2%; serum triglycerides, 26.7%; systolic blood pressure, 8.1%; and diastolic blood pressure, 8.6%. Larger weight losses were associated with larger reductions in these values. The reviewed data suggest that US health care providers should endorse the American Heart Association’s and European diabetes associations’ recommendations that diabetic persons achieve and maintain a BMI of ≤25 kg/m2. Weight management may be the most important therapeutic task for most obese Type 2 diabetic individuals.

Propionate May Mediate the Hypocholesterolemic Effects of Certain Soluble Plant Fibers in Cholesterol-Fed Rats:

Abstract The effects of propionate on serum and liver lipid concentrations were studied in cholesterol-fed rats. Both serum and liver cholesterol levels were significantly lower in rats fed the cholesterol-propionate diet than in rats fed the cholesterol diet without propionate. Liver triglyceride levels were also significantly lower in the propionate-treated group. Serum triglyceride concentrations were not influenced by the propionate feeding. Propionate intake was not associated with histologic changes in liver tissue. This study indicates that 0.5% sodium propionate-sup-plemented diets slightly but significantly reduced cholesterol accumulation in both serum and liver of cholesterol-fed rats. Thus propionate, a metabolic product of fiber fermentation, may mediate some of the hypocholesterolemic effects of certain soluble plant fibers.

Cardiovascular and renal benefits of dry bean and soybean intake

Dry beans and soybeans are nutrient-dense, fiber-rich, and are high-quality sources of protein. Protective and therapeutic effects of both dry bean and soybean intake have been documented. Studies show that dry bean intake has the potential to decrease serum cholesterol concentrations, improve many aspects of the diabetic state, and provide metabolic benefits that aid in weight control. Soybeans are a unique source of the isoflavones genistein and diadzein, which have numerous biological functions. Soybeans and soyfoods potentially have multifaceted health-promoting effects, including cholesterol reduction, improved vascular health, preserved bone mineral density, and reduction of menopausal symptoms. Soy appears to have salutary effects on renal function, although these effects are not well understood. Whereas populations consuming high intakes of soy have lower prevalences of certain cancers, definitive experimental data are insufficient to clarify a protective role of soy. The availability of legume products and resources is increasing, incorporating dry beans and soyfoods into the diet can be practical and enjoyable. With the shift toward a more plant-based diet, dry beans and soy will be potent tools in the treatment and prevention of chronic disease.

Carbohydrate and fiber recommendations for individuals with diabetes: a quantitative assessment and meta-analysis of the evidence.

To review international nutrition recommendations with a special emphasis on carbohydrate and fiber, analyze clinical trial information, and provide an evidence-based recommendation for medical nutrition therapy for individuals with diabetes. Relevant articles were identified by a thorough review of the literature and the data tabulated. Fixed-effects meta-analyses techniques were used to obtain mean estimates of changes in outcome measures in response to diet interventions. Most international organizations recommend that diabetic individuals achieve and maintain a desirable body weight with a body mass index of ≤25 kg/m2. For diabetic subjects moderate carbohydrate, high fiber diets compared to moderate carbohydrate, low fiber diets are associated with significantly lower values for: postprandial plasma glucose, total and low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. High carbohydrate, high fiber diets compared to moderate carbohydrate, low fiber diets are associated with lower values for: fasting, postprandial and average plasma glucose; hemoglobin A1c; total, LDL-cholesterol, HDL-cholesterol and triglycerides. Low glycemic index diets compared to high glycemic index diets are associated with lower fasting plasma glucose values and lower glycated protein values. Based on these analyses we recommend that the diabetic individual should be encouraged to achieve and maintain a desirable body weight and that the diet should provide these percentages of nutrients: carbohydrate, ≥55%; protein, 12–16%; fat, <30%; and monounsaturated fat, 12–15%. The diet should provide 25–50 g/day of dietary fiber (15–25 g/1000 kcal). Glycemic index information should be incorporated into exchanges and teaching material.

Distribution of lipids in 8,500 men with coronary artery disease

In the present study we measured fasting lipid profiles in over 8,500 community-living men with coronary artery disease (CAD) to determine the distribution of lipid abnormalities in this population: 81% were white and 16% black; mean age 62.9 +/- 8 years; mean total cholesterol 214 +/- 41 mg/dl; low-density lipoprotein (LDL) cholesterol 140 +/- 37 mg/dl; high-density lipoprotein (HDL) cholesterol 39 +/- 11 mg/dl; and triglycerides 190 +/- 142 mg/dl. After adjusting for age, the only significant difference between blacks and whites was a higher HDL cholesterol in blacks (45 vs 38 mg/dl, p < 0.003). With use of cut points established by the National Cholesterol Education Program, 87% of subjects had high LDL cholesterol (> or = 100 mg/dl), 38% had low HDL cholesterol (< 35 mg/dl), and 33% had high triglycerides (> 200 mg/dl). We estimated that 42% of men with CAD would be definite candidates for cholesterol-lowering medication according to the National Cholesterol Education Program guidelines and that 41% of those in whom cholesterol-lowering medication would not be definitely indicated had low levels of HDL cholesterol. We conclude that (1) black men with CAD have substantially higher HDL cholesterol than white men, (2) almost 90% of male patients with CAD are candidates for dietary intervention and > 40% may need medications to lower LDL cholesterol, and (3) 40% of patients without a definite indication for cholesterol-lowering medications have low levels of HDL cholesterol.

Whole Grain Foods and Heart Disease Risk

Coronary heart disease (CHD) is the leading cause of death in most developed nations and is rapidly increasing in prevalence in developing countries. Death rates from cardiovascular disease exceed 1 million annually in the United States and account for the largest disease-related cost to health with total costs estimated to exceed

Rational design of a combination medication for the treatment of obesity.

120 billion per annum. Many dietary factors, including total and saturated fat consumption, fruit and vegetable intake and dietary fiber, have been shown to contribute to risk for CHD. We have systematically reviewed literature from the past 20 years evaluating an association between dietary fiber and CHD. Foods that are rich in dietary fiber, including fruits, vegetables, legumes and whole grain cereals, also tend to be a rich source of vitamins, minerals, phytochemicals, antioxidants and other micronutrients. Each of these factors may be independently contributing to the cardiovascular protective effects of fiber-rich foods.