A. Venketeshwer Rao

Nibbling versus Gorging: Metabolic Advantages of Increased Meal Frequency

We studied the effect of increasing the frequency of meals on serum lipid concentrations and carbohydrate tolerance in normal subjects. Seven men were assigned in random order to two metabolically identical diets. One diet consisted of 17 snacks per day (the nibbling diet), and the other of three meals per day (the three-meal diet); each diet was followed for two weeks. As compared with the three-meal diet, the nibbling diet reduced fasting serum concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B by a mean (+/- SE) of 8.5 +/- 2.5 percent (P less than 0.02), 13.5 +/- 3.4 percent (P less than 0.01), and 15.1 +/- 5.7 percent (P less than 0.05), respectively. Although the mean blood glucose level and serum concentrations of free fatty acids, 3-hydroxybutyrate, and triglyceride were similar during both diets, during the nibbling diet the mean serum insulin level decreased by 27.9 +/- 6.3 percent (P less than 0.01) and the mean 24-hour urinary C-peptide output decreased by 20.2 +/- 5.6 percent (P less than 0.02). In addition, the mean 24-hour urinary cortisol excretion was lower by 17.3 +/- 5.9 percent (P less than 0.05) at the end of the nibbling diet than at the end of the three-meal diet. The blood glucose, serum insulin, and C-peptide responses to a standardized breakfast and the results of an intravenous glucose-tolerance test conducted at the end of each diet were similar. We conclude that in addition to the amount and type of food eaten, the frequency of meals may be an important determinant of fasting serum lipid levels, possibly in relation to changes in insulin secretion.

Effect of soya bean saponins on azoxymethane‐induced preneoplastic lesions in the colon of mice

The effect of saponins isolated from soya bean flour on the incidence of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in the colonic wall of CF1 mice was investigated. Four weekly injections of AOM, a known colon carcinogen, were administered to mice. One week after the last injection, mice were placed on an AIN-76 diet supplemented with 3% soya bean saponins or continued on the basal AIN-76 diet. Another group of mice was placed on the saponin diet without AOM initiation to observe the effect of saponins on the growth characteristics of mice. Dietary intake of soya saponins significantly reduced the incidence of ACF at the end of 14 weeks (postinitiation). Noninitiated mice maintained on a similar soya bean saponin-supplemented diet did not show any adverse effects on the growth and overall health of the animals. These findings suggest that soya bean saponins can play an important role in inhibiting the incidence of ACF in the colon of mice.

The effect of dietary lycopene on bioavailability, tissue distribution, in vivo antioxidant properties and colonic preneoplasia in rats

Recent studies have suggested a protective role for lycopene, an antioxidant carotenoid, in the prevention of chronic diseases including cancer and coronary heart disease. Tomatoes and tomato products are the major dietary source of lycopene. The aim of this study was to investigate the bioavailability, tissue distribution, and the in vivo antioxidant properties of lycopene and its role in colon carcinogenesis. Male Fischer 344 rats were used in this study. Lycopene in the form of 6% oleoresin was incorporated into an AIN93M diet at a concentration of 10 ppm lycopene. Azoxymethane (AOM) was used as the colon specific chemical carcinogen. Serum and tissue lycopene levels were measured as estimates of lycopene uptake and tissue distribution. Serum TBARS and thiols were measured as indicators of lipid and protein oxidation. Incidence and size of aberrant crypt foci (ACF) were measured as preneoplastic markers. Dietary lycopene was absorbed and distributed to various tissues. An increase in serum thiols and a decrease in serum TBARS was observed in rats fed the lycopene diet. Incidence of ACF in lycopene fed rats showed a trend towards reduced numbers and size. Effects were more pronounced when lycopene was fed during the promotion stage than during the initiation stage. Based on these results it is concluded that dietary lycopene is absorbed by rats and distributed to various tissues. It acts as an antioxidant in reducing oxidation and thereby may protect against AOM induced ACF incidence. Dietary lycopene may play an important role in protecting against oxidative stress and colon carcinogenesis.

Effect of nibbling versus gorging on cardiovascular risk factors: Serum uric acid and blood lipids

Nibbling has been reported to decrease serum cholesterol under fasting conditions, as well as the incidence of cardiovascular disease. It has been suggested that these effects are partly attributable to reduced concentrations of serum insulin, which are also observed. However, data on the effects of nibbling on serum lipids throughout the day are not available, nor is it known how nibbling affects serum uric acid as a further insulin-related risk factor for cardiovascular disease. We have attempted to address these issues. Seven healthy men consumed identical diets in a randomized crossover design either as three meals daily (control) or as 17 meals daily (nibbling) for 2 weeks. On day 13, serum lipid levels were measured over the course of the day (12 hours) together with the 24-hour urinary excretion of mevalonic acid as an indicator of hepatic cholesterol synthesis. Concentrations of uric acid in serum and 24-hour urinary excretion of uric acid were also determined. Mean (+/- SE) percent treatment differences in day-long total, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B were significant, with lower values on the nibbling diet as compared with the control diet (8.1% +/- 1.6%, P = .002; 12.2% +/- 2.6%, P = .005; 10.1% +/- 1.6%, P < .001; and 9.9% +/- 2.6%, P = .008, respectively). No significant difference was seen in the total to HDL cholesterol ratio or in urinary mevalonic acid excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of soybean saponins and gypsophilla saponin on growth and viability of colon carcinoma cells in culture

The effects of soybean saponins (SS) and gypsophilla saponin (GS) on the growth and viability of colon tumor (HCT-15) cells in culture were investigated. Cells were incubated in various concentrations of saponins for 1 hour (short term) or 48 hours (long term). Cell growth and viability were monitored at 24 and 48 hours. SS and GS inhibited cell growth and reduced cell viability in a dose-dependent manner in long-term treatment. The viability of cells was also reduced by short-term treatment with GS. The saponins differed in their effects on cell surface morphology: GS induced a rough and granular cell surface, whereas SS-treated cells displayed only minor morphological alterations. Changes in membrane permeability were assessed by measuring leakage of the cytoplasmic enzyme lactate dehydrogenase from cells. GS showed a concentration-dependent increase in lactate dehydrogenase leakage, whereas SS did not exhibit this effect. These results suggest that SS and GS have a significant growth-inhibitory effect on colon tumor cells in culture. However, it would appear that they are acting through different mechanisms.

Equol status and blood lipid profile in hyperlipidemia after consumption of diets containing soy foods

BACKGROUND Recent analyses have challenged the effectiveness of soy foods as part of a cardiovascular risk reduction diet. OBJECTIVE The objective of the study was to show whether equol status determines the effectiveness of soy foods to lower LDL cholesterol and to raise HDL cholesterol. DESIGN Eighty-five hypercholesterolemic men and postmenopausal women (42 men, 43 women) participated in 1 of 3 studies that represented a range of soy interventions and that followed the same general protocol at a Canadian university hospital research center. Soy foods were provided for 1 mo at doses of 30-52 g/d for the 3 studies as follows: 1) soy foods with either high-normal (73 mg/d) or low (10 mg/d) isoflavones, 2) soy foods with or without a prebiotic to enhance colonic fermentation (10 g polyfructans/d), or 3) soy foods with a low-carbohydrate diet (26% carbohydrate). Studies 1 and 2 were randomized controlled crossover trials, and study 3 was a parallel study. RESULTS The separation of the group into equol producers (n = 30) and nonproducers (n = 55) showed similar reductions from baseline in LDL cholesterol (-9.3 ± 2.5% and -11.1 ± 1.6%, respectively; P = 0.834), with preservation of HDL cholesterol and apolipoprotein A-I only in equol producers compared with reductions in nonproducers (HDL cholesterol: +0.9 ± 2.7% compared with -4.3 ± 1.1%, P = 0.006; apolipoprotein A-I: -1.0 ± 1.1% compared with -4.7 ± 1.0%; P = 0.011). The amount of urinary equol excreted did not relate to the changes in blood lipids. CONCLUSIONS Soy foods reduced serum LDL cholesterol equally in both equol producers and nonproducers. However, in equol producers, ~35% of our study population, soy consumption had the added cardiovascular benefit of maintaining higher HDL-cholesterol concentrations than those seen in equol nonproducers. This trial was registered at clinicaltrials.gov as NCT00877825 (study 1), NCT00516594 (study 2), and NCT00256516 (study 3).

Colonic bacterial activity and serum lipid risk factors for cardiovascular disease.

Antibiotics are being proposed for the treatment of cardiovascular disease. In the past, antibiotics were advocated for the control of hypercholesterolemia. We have therefore investigated the relation between colonic bacterial activity and serum lipids. In a four-phase randomized crossover study, we fed a different starch supplement during each 2-week phase to 24 healthy subjects. In two phases, supplements containing resistant starches were fed that reach the colon and are largely fermented by colonic bacteria. Fecal starch recovery therefore reflects the metabolic activity of colonic microflora. The control treatments were conventional starches. Blood lipid levels were obtained at the start and 4-day fecal collections at the end of each phase. Resistant starch supplements increased fecal starch excretion by 3.8 +/- 1.2 g/d more than conventional starches (P = .006). Mean starch excretion was related positively to pretreatment serum high-density lipoprotein (HDL) cholesterol (r = -.57, P = .003) and negatively to low-density lipoprotein (LDL) cholesterol (r = -.57, P = .004), apolipoprotein B:AI (r = -.56, P = .005), and fecal output of fusobacteria (r = -.73, P = .003) and bacteroides (r = -.72, P = .003). The ratio of fusobacteria to total anaerobes was also related to pretreatment LDL cholesterol (r = .56, P = .037). Differences in starch excretion between healthy subjects, as a measure of bacterial activity, accounted for 32% of the variation in pretreatment LDL cholesterol. The activity of colonic microflora therefore appears to influence serum lipid levels. Alterations of bacterial number and activity may provide an additional strategy to control serum lipid risk factors for cardiovascular disease.

Supplemental Barley Protein and Casein Similarly Affect Serum Lipids in Hypercholesterolemic Women and Men

High-protein diets have been advocated for weight loss and the treatment of diabetes. Yet animal protein sources are often high in saturated fat and cholesterol. Vegetable protein sources, by contrast, are low in saturated fat and without associated cholesterol. We have therefore assessed the effect on serum lipids of raising the protein intake by 5% using a cereal protein, barley protein, as part of a standard therapeutic diet. Twenty-three hypercholesterolemic men and postmenopausal women completed a randomized crossover study comparing a bread enriched with either barley protein or calcium caseinate [30 g protein, 8374 kJ (2000 kcal)] taken separately as two 1-mo treatment phases with a minimum 2-wk washout. Body weight and diet history were collected weekly during each treatment. Fasting blood samples were obtained at wk 0, 2, and 4. Palatability, satiety, and compliance were similar for both the barley protein- and casein-enriched breads, with no differences between the treatments in effects on serum LDL cholesterol or C-reactive protein, measures of oxidative stress, or blood pressure. Nevertheless, because no adverse effects were observed on cardiovascular risk factors, barley protein remains an additional option for raising the protein content of the diet.

Interrelationships between age, total dietary fiber intake and breath methane in humans.

Abstract In western populations the prevalence of methane producers (MP) is 30–50%. Studies related to dietary intakes of MP are lacking. The aim of this study was to compare dietary intakes in MP and methane nonproducers (MNP). In 122 healthy subjects, breath gases were analysed and 3-day food records were collected to assess the nutrient intakes. The 63 MP were significantly older than the 59 MNP (48.9±2.0 vs 38.3±2.2 y: P

The Glycemic Index: Blood Glucose Response to Foods

Much of the current interest in the blood glucose responses to food evolved as a natural consequence of earlier dietary fiber studies. Considerable impetus has also come from the need to find sustained release or lente carbohydrate foods that would fit the requirements for the diabetic diet, where an increase in carbohydrate intake has been recommended [Committee of the American Diabetes Association on Food and Nutrition, 1979; Special Report Committee, 1981 (Canadian Diabetes Association); Nutrition Sub-Committee of the British Diabetic Association’s Medical Advisory Committee, 1982)]. Such studies, therefore, have focused attention on the differences among the foods and on those factors, including fiber, that were responsible for these differences. Investigation of the physiological effect of foods has proceeded in a similar fashion to what was applied to the screening of dietary fibers. Foods have been tested to determine whether there were in fact differences in digestibiity and whether the rate of nutrient release from the gastrointestinal tract might be a factor in determining the glycemic response (Jenkins et al., 1982, 1984c; 0’Dea et al., 1981). In turn, the glycemic responses to a range of foods have been studied in both normal and diabetic individuals and the foods analyzed for fiber, macronutrients, and selected antinutrients to assess whether these could account for the observed differences.