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Biomedical subjects

Cyril W C Kendall

Publications and source records attributed to Cyril W C Kendall.

At least 19 recordsLinked to original sources

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.

Adult↗

Almonds decrease postprandial glycemia, insulinemia, and oxidative damage in healthy individuals.

Strategies that decrease postprandial glucose excursions, including digestive enzyme inhibition, and low glycemic index diets result in lower diabetes incidence and coronary heart disease (CHD) risk, possibly through lower postprandial oxidative damage to lipids and proteins. We therefore assessed the effect of decreasing postprandial glucose excursions on measures of oxidative damage. Fifteen healthy subjects ate 2 bread control meals and 3 test meals: almonds and bread; parboiled rice; and instant mashed potatoes, balanced in carbohydrate, fat, and protein, using butter and cheese. We obtained blood samples at baseline and for 4 h postprandially. Glycemic indices for the rice (38 +/- 6) and almond meals (55 +/- 7) were less than for the potato meal (94 +/- 11) (P < 0.003), as were the postprandial areas under the insulin concentration time curve (P < 0.001). No postmeal treatment differences were seen in total antioxidant capacity. However, the serum protein thiol concentration increased following the almond meal (15 +/- 14 mmol/L), indicating less oxidative protein damage, and decreased after the control bread, rice, and potato meals (-10 +/- 8 mmol/L), when data from these 3 meals were pooled (P = 0.021). The change in protein thiols was also negatively related to the postprandial incremental peak glucose (r = -0.29, n = 60 observations, P = 0.026) and peak insulin responses (r = -0.26, n = 60 observations, P = 0.046). Therefore, lowering postprandial glucose excursions may decrease the risk of oxidative damage to proteins. Almonds are likely to lower this risk by decreasing the glycemic excursion and by providing antioxidants. These actions may relate to mechanisms by which nuts are associated with a decreased risk of CHD.

Adult↗

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.

Carbohydrate Metabolism↗

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.

Blood Glucose↗

Effects of a diet high in plant sterols, vegetable proteins, and viscous fibers (dietary portfolio) on circulating sterol levels and red cell fragility in hypercholesterolemic subjects.

Plant sterols, soy proteins, viscous fibers, and nuts are advised for cholesterol reduction, but their combined effect on plant sterol absorption has never been tested. We assessed their combined action on serum sterols in hyperlipidemic subjects who were following low-saturated fat diets before starting the study and who returned to these diets post-test. The 1-mon test (combination) diet was high in plant sterols (1 g/1,000 kcal), soy protein (23 g/1,000 kcal), viscous fiber (9 g/1,000 kcal), and almonds (14 g/1000 kcal). Fasting blood was obtained for serum lipids and sterols, and erythrocytes were obtained for fragility prior to and at 2-wk intervals during the study. The combination diet raised serum campesterol concentrations by 50% and beta-sitosterol by 27%, although these changes were not significant after Bonferroni correction; near-maximal rises were found by the end of the first week, but no change was found in red cell fragility despite a 29% reduction in the LDL cholesterol level. No significant associations were observed between changes in red cell fragility and blood lipids or sterols. We conclude that plant sterols had a minimal impact on serum sterol concentrations or red cell fragility in hyperlipidemic subjects on diets that greatly reduced their serum lipids.

Adult↗

Effect of antibiotics as cholesterol-lowering agents.

Antibiotics were once proposed as hypercholesterolemic agents although the mechanism is unclear, despite broad implications, including providing an alternative approach to cholesterol reduction, with potential relevance for current trials of antibiotics to reduce cardiovascular disease, and possible confounding of routine diagnostic cholesterol measurements. The effect on serum lipids of antibiotics against aerobes and anaerobes, together with possible mechanisms, was therefore explored. Twenty-two men and women took antibiotics for 10 days (either ciprofloxacin for 13 subjects or metronidazole for 10 subjects), with 10 days control in random order separated by 2-week washout periods. Subjects maintained low-fat diets throughout the study. Blood samples and blood pressure were obtained on days 0 and 10 of each phase with 3-day fecal collections and 12-hour breath gas collections at the end of each phase. The results indicated that metronidazole markedly reduced low-density lipoprotein cholesterol (-14.0 +/- 4.0%, P = .006), oxidized low-density lipoprotein (-23.0 +/- 5.1%, P = .002), and the apolipoprotein B/A-I ratio (-18.0 +/- 2.8%, P < .001), whereas the reduction with ciprofloxacin was less pronounced (apolipoprotein B/A-I, -5.0 +/- 1.8%, P = .017). Neither antibiotic altered C-reactive protein or blood pressure. The low-density lipoprotein cholesterol reduction related to an increase in bifidobacteria (r = -0.46, P = .029), but not to markers of colonic fermentation. We conclude that antibiotics can reduce serum lipids acutely. These effects may confound diagnostic measurements but indicate possible links between colonic microflora and blood lipids and the need to study ways of altering colonic microflora by nonantibiotic means as a potential therapeutic option.

Aged↗

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.

Adult↗

A dietary portfolio: maximal reduction of low-density lipoprotein cholesterol with diet.

Over the past two decades, cholesterol-lowering drugs have proven to be effective and have been found to significantly reduce the risk of coronary heart disease (CHD). However, diet and lifestyle factors are still recognized as the first line of intervention for CHD risk reduction by the National Cholesterol Education Program and the American Heart Association, which now advocate use of viscous fibers and plant sterols, and soy protein and nuts, respectively. In a series of metabolically controlled studies, we have combined these four cholesterol-lowering dietary components in the same diet (ie, a dietary portfolio of cholesterol-lowering foods) in an attempt to maximize low-density lipoprotein cholesterol reduction. We have found that the portfolio diet reduced low-density lipoprotein cholesterol by approximately 30% and produced clinically significant reductions in CHD risk. These reductions were the same as found with a starting dose of a first-generation statin drug.

Cardiovascular Diseases↗

Combined effects of a dietary portfolio of plant sterols, vegetable protein, viscous fibre and almonds on LDL particle size.

Studies conducted in the last 20 years have led to the identification of small dense LDL as an important risk factor for CVD. Consumption of plant sterols, soyabean proteins, viscous fibre and nuts are known to modulate the risk of CVD favourably through their cholesterol (Chol)-lowering properties, both independently and more recently in combination. Nevertheless, their combined impact on the LDL particle size phenotype has never been tested. In the present study, we assessed the effect of incorporating concurrently plant sterols (1 g/4.2 MJ), soyabean protein (23 g/4.2 MJ), viscous fibre (9 g/4.2 MJ) and almonds (15 g/4.2 MJ) into a diet very low in saturated fat in twelve patients with mildly elevated plasma LDL-Chol levels. Fasting blood lipids were obtained at the start of the study and at 2-week intervals during the 4-week study. The diet-induced reduction in plasma LDL-Chol of 30.0 (se 3.0) % (P<0.0001) was attributed to concurrent reductions in the serum Chol concentrations of large (>26.0 nm-30 (se 8) %, P<0.001), medium (25.5-26.0 nm-29 (se 3) %, P<0.001) and small (<25.5 nm-21 (sd 6) %, P<0.01) LDL particles, with near maximal reductions seen by week 2. These results indicate that foods and dietary components advocated for their potential to reduce the risk of CVD are effective in reducing serum concentrations of all LDL fractions including small dense LDL, thus potentially further contributing to an overall lower risk of CVD.

Adult↗

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/m(2). 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 A(1c); 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.

Blood Glucose↗

Role of cell walls in the bioaccessibility of lipids in almond seeds.

BACKGROUND: Certain nutrients and phytochemicals in almonds may confer protection against cardiovascular disease, but little is known about factors that influence their bioavailability. A crucial and relevant aspect is the amount of these dietary components available for absorption in the intestine, which is a concept referred to as bioaccessibility. OBJECTIVE: We investigated the role played by cell walls in influencing the bioaccessibility of intracellular lipid from almond seeds. DESIGN: Quantitative analyses of nonstarch polysaccharides (NSPs) and phenolic compounds of cell walls were performed by gas-liquid chromatography and HPLC, respectively. In a series of experiments, the effects of mechanical disruption, chewing, and digestion on almond seed microstructure and intracellular lipid release were determined. In the digestibility study, fecal samples were collected from healthy subjects who had consumed diets with or without almonds. Almond seeds and fecal samples were examined by microscopy to identify cell walls and intracellular lipid. RESULTS: Cell walls were found to be rich in NSPs, particularly arabinose-rich polysaccharides, with a high concentration of phenolic compounds detected in the seed coat cell wall. During disruption of almond tissue by mechanical methods or chewing, only the first layer of cells at the fractured surface was ruptured and able to release lipid. In fecal samples collected from subjects consuming the almond diet, we observed intact cotyledonary cells, in which the cell walls encapsulated intracellular lipid. This lipid appeared susceptible to colonic fermentation once the cotyledonary cell walls were breached by bacterial degradation. CONCLUSION: The cell walls of almond seeds reduce lipid bioaccessibility by hindering the release of lipid available for digestion.

Adult↗

Association between components of the insulin-like growth factor system and endometrial cancer risk.

OBJECTIVE: The insulin-like growth factor (IGF) system has been related to cell proliferation, obesity, diabetes, hyperinsulinemia and endometrial cancer risk. We used data from a case-control study conducted in Italy to provide additional information on the relation between the IGF system and endometrial cancer. METHODS: A case-control study was conducted between 1999 and 2002 in Italy, including a total of 73 women with incident, histologically confirmed endometrial cancer and 108 controls admitted to the same hospital network for acute, nonneoplastic diseases. All subjects were interviewed using a validated questionnaire. RESULTS: The odds ratios for endometrial cancer comparing the highest versus the lowest tertile of various IGF components were as follows: 0.5 [95% confidence interval (CI) 0.2-1.2] for free IGF-I, 1.1 (95% CI 0.5-2.6) for total IGF-I, 1.2 (95% CI 0.6-2.6) for total IGF-II, 2.4 (95% CI 1.0-5.9) for IGF binding protein (IGFBP)-1 and 0.8 (95% CI 0.4-2.0) for IGFBP-3. Further allowance for all IGF components in the model did not modify the results. The direct relation with IGFBP-1 was stronger and limited to heavier and older women. CONCLUSIONS: The present findings suggest a limited effect of the IGF system on endometrial cancer risk. Increasing IGFBP-1 levels seem to be associated with endometrial cancer risk in older women and in women with a higher body mass index.

Adult↗

Association between components of the insulin-like growth factor system and epithelial ovarian cancer risk.

BACKGROUND: Components of the insulin-like growth factor (IGF) system have been associated with several cancers, but very few studies are available for ovarian cancer. METHODS: A case-control study conducted between 1999 and 2003 in Italy, including a total of 59 women with incident, histologically confirmed ovarian cancer and 108 controls admitted to the same hospital network as cases, for acute non-neoplastic diseases. All subjects were interviewed using a validated questionnaire. RESULTS: After adjustment for potential confounders, the multivariate odds ratios for the highest versus the lowest tertile of various IGF components were 0.6 (95% confidence interval, CI: 0.2-1.4) for free IGF-I, 0.4 (CI: 0.1-1.5) for total IGF-I, 2.6 (CI: 0.9-6.9) for IGF-binding protein (IGFBP)-1, and 0.2 (CI: 0.0-0.6) for IGFBP-3. CONCLUSIONS: This study suggests a protective role of IGFBP-3 and a positive association of IGFBP-1 with ovarian cancer. The complex role of the IGF system in ovarian carcinogenesis deserves further clarification.

Adult↗

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.

Anticholesteremic Agents↗