Progress 10/01/03 to 09/30/06
Outputs Dietary polyphenols have been shown to possess cardioprotective effects. For example, the most noted role of grape polyphenols is in the French Paradox, where a diet high in saturated fat accompanied by regular consumption of red wine is associated with low coronary heart disease (CHD) risk. We conducted a study with post-menopausal and premenopausal women with elevated baseline levels of triglycerides and high concentrations of inflammatory cytokines. Women were given either a placebo or a grape preparation rich in polyphenols and after 3 weeks, they were crossed over to the alternate treatment. Significant reductions in plasma triglycerides, tumor necrosis factor alpha, apolipoporotein B concentrations and urinary isoprostanes was reported following the grape treatment. This study provides evidence of the cardioprotective effects of grape polyphenols.
Impacts Elevated levels of plasma triglycerides and apo B are important markers of coronary heart disease. Whole body oxidation is a marker of chronic disease. Grapes have been proven to reduce all these parameters indicating their key role in reducing coronary heart disease and other chronic disease.
Publications
- Wood, R.J., Volek, J.S., Davis, S.R., DellOva, C., Fernandez, M.L. 2006. Carbohydrate restriction favorably affects plasma markers for cardiovascular disease. Nutr. & Met. 3:19
- Ruano, G., Windemuth, A., Kocherla, M., Holford, T., Fernandez, M.L., Forsythe, C.E., Wood, R.J., Kraemer, W.J., Volek, J.S. 2006. Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction. Nutr. & Met. 3:20
- Fernandez, M.L., Volek, J.S. 2006. Guinea pigs: A Suitable Animal Model to study Lipoprotein Metabolism, Atherosclerosis and Inflammation. Nutr. Metab. 3:17
- Herron, K.L., McGrane, M.M., Lofgren, I.E., Waters, D., Clark, R.M., Ordovas, J.M., Fernandez, M.L. 2006. ABCG5 polymorphism contributes to the individual response to dietary cholesterol and to carotenoids present in eggs. J. Nutr. 136:1161-1165
- Aggarwal, D., Fernandez, M.L., Soliman, G.A. 2006. Rapamycin, an mTOR inhibitor disrupts triglyceride metabolism in guinea pigs. Met. Clin. Exp. 55:794-802
- Fernandez, M.L., Wood, R., Volek, J.S. 2006. Carbohydrate restricted diets alter the size, distribution and concentration of lipoprotein subclases in men following a weight reduction program. http//www.athero.org/commentaries/
- Greene, C.M., Fernandez, M.L. 2007. The role of nutrition in the prevention of cardiovascular disease in women of the developed world. Asian Pacific J. Clin. Nutr. 16:1-9
- Wood, R.J., Fernandez, M.L., Sharman, M.J., Silvestre, R., Greene, C.M., Zern, T.L., Shrestha, S., Judelson, D.A., Gomez, A.L., Kramer, W., Volek, J.S. 2007. Effects of a carbohydrate restricted diet with and without supplemental soluble fiber on plasma LDL-cholesterol and other clinical markers of cardiovascular risk. Metabolism 56:58-67
- Aggarwal, D., Soliman, G., Freake, H.C., Dutta, A., Fernandez, M.L. 2006. Validation of Using Gene Expression In Mononuclear Cells As A Marker For Hepatic Cholesterol Metabolism. Lipids Health Dis. 5:22
- Shrestha, S., Volek, J.S., Udani, J., Wood, R., Greene, C., Aggarwal, D., Contois, J.H., Kavoussi, B., Fernandez, M.L. 2006. A combination therapy including psyllium and plant sterol lowers LDL cholesterol by modifying lipoprotein metabolism in hypercholesterolemic individuals. J. Nutr. 136:2492-2497
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Progress 01/01/05 to 12/31/05
Outputs Dietary polyphenols have been shown to possess cardioprotective effects. For example, the most noted role of grape polyphenols is in the French Paradox, where a diet high in saturated fat accompanied by regular consumption of red wine is associated with low coronary heart disease risk. Initially, the Paradox was thought to be driven by the postulated major action of grape polyphenols in inhibiting LDL oxidation. While many studies have shown inhibitory effects on LDL oxidation, there have been an equal number of studies, which have shown a null effect on this parameter. In our study where we did an intervention with grape polyphenols in pre- and postmenopausal women, we found that there was a signficant decrease in plasma triglycerides, apo B and apo E following the consumption of grape polyphenol. Most importantly we found a decrease in the cytokine TNF-alpha and a decrease in urinary isoprostanes, a marker of whole body oxidative stress. Through alterations in
lipoprotein metabolism, oxidative stress and inflammatory markers, grape polyphenols beneficially affected key risk factors in coronary heart disease in both pre- and post-menopausal women.
Impacts Inflammatory cytokines and whole body oxidative stress have been associated with atherosclerosis and heart disease. Foods that are high in polyphenols such as grapes can exert a cardioprotective effect not just by lowering plasma triglycerides but also by reducing inflammation and whole body oxidative stress.
Publications
- Greene, C.M., Waters, D., Clark, R.M., Contois, J.H. & Fernandez, M.L. 2006. Plasma LDL and HDL characteristics and carotenoid content are positively influenced by egg consumption in an elderly population. Nutr. Met. 3:6
- Wood, R.J., Volek, J.S., Liu, Y., Shachter, N.S., Contois, J.H. & Fernandez, M.L. 2005. Carbohydrate restriction alters lipoprotein metabolism by modifying VLDL, LDL and HDL subfraction distribution and size in overweight men. J. Nutr. 136:384-389
- Herron, K.L., Lofgren, I.E., Adiconis, X., Ordovas, J.M. & Fernandezm M.L. 2006. Associations between plasma lipid parameters and APOC3 and APOA4 genotypes in a healthy population are independent of dietary cholesterol intake. Atherosclerosis: Atherosclerosis 184:113-120
- Aggarwal, D., West, K.L., Zern, T.L., Shresthra, S., Vergara-Jimenez, M. & Fernandez, M.L. 2005. JTT-130, a microsomal transfer protein inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic triglycerides in the guinea pig. BMC Card. Dis. 5:30
- Lofgren, I.E., Herron, K.L., West, K.L., Zern, T.L., Brownhill, R., Ilich-Ernst, J., Koo, S.I. & Fernandez, M.L. 2005. A weight loss program favorably modifies anthropometrics and reverses the metabolic syndrome and insulin resistance in premenopausal women. Am. J. Coll. Nutr. 24:486-493
- Fernandez, M,L. 2005. Dietary cholesterol provided by eggs and plasma lipoproteins in healthy populations. Curr. Op. Med. Nutr. Met. Care 9:8-12
- Greene, C.M., Zern, T.L., Wood, R., Shrestha, S., Aggarwal, D., Sharman, M., Volek, J.S. & Fernandez, M.L. 2005. Maintenance of the LDL cholesterol: HDL cholesterol ration in an elderly population given a dietary cholesterol challenge. J. Nutr. 135:2793-2798
- Zern, T.L. & Fernandez, M.L. 2005. Cardioprotective effects of dietary polyphenols 2005. J. Nutr. 135:2291-2294
- West, K.L., McGrane, M.M., Odon, D., Kelley, B.L. & Fernandez, M.L. 2005. SC-435, an ileal apical sodium-codependent bile acid transporter (ASBT) inhibitor alters mRNA levels and enzyme activities of selected genes involved in hepatic cholesterol and lipoprotein metabolism in guinea pigs. J. Nutr. Biochem. 16:722-728
- Fernandez, M.L. & West, K.L. 2005. Mechanisms by which dietary fatty acids modulate plasma Lipids. J. Nutr. 135:2075-2078
- Zern, T.L., Wood, R., Greene, C.M., West, K.L., Liu, Y. Aggarwal, D., Shachter, N.S. & Fernandez, M.L. 2005. Grape polyphenols lower plasma lipids and apolipoproteins associated with increased risk for cardiovascular disease in pre and post-menopausal women. J. Nutr. 135:1911-1947
- Lofgren, I.E., Zern, T.L., Herron, K.L., West, K.L., Sharman, M., Volek, J.S., Schachter, N.S., Koo, S.I. & Fernandez, M.L. 2005. Weight loss reduces the atherogenicity of LDL in premenopausal women. Metabolism Clin. Exp. 54:1133-1141
- Fernandez, M.L. & Vega-Lopez, S. 2005. Efficacy and safety of beta-sitosterol in the management of blood cholesterol levels. Cardiovasc. Res. 23:73-86
- Fernandez, M.L. & Vergara-Jimenez, M. 2005. Associations between Carbohydrate Intake and Risk for Coronary Heart Disease, Insulin Resistance and the Metabolic Syndrome. In Focus on Dietary Carbohydrate Research. Nova Science Publishers, Inc. Chapter 3
- Lofgren, I.E., Herron, K.L., West, K.L., Zern, T.L., Patalay, M., Koo, S.I. & Fernandez, M.L. 2005. Carbohydrate intake is correlated with biomarkers for coronary heart disease in a population of overweight premenopausal women. J. Nutr. Biochem. 16:245-250
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Progress 01/01/04 to 12/31/04
Outputs Grape polyphenols have been shown to have cardioprotective effects. Due to the increase in plasma cholesterol and triglycerides (TG) concentrations following menopause, grape supplementation may be beneficial in reducing key coronary heart disease (CHD) risk factors in post-menopausal women. We conducted these studies to evaluate the effects of lyophilized grape polyphenol preparation (LGP) on plasma lipids, lipoprotein metabolism, and LDL oxidation parameters in both pre-and post-menopausal women. Twenty four pre- and 20 post-menopausal women were randomly assigned to 36 g of either a freeze-dried grape powder or placebo for 4 wk. The LGP consisted of 92% carbohydrate and was rich in flavans, anthocyanins, quercetin, myricetin, kaempferol and resveratrol. Following a 3-wk washout period, subjects were allocated to the alternate treatment for an additional 4 wk. The placebo consisted of an equal ratio of fructose and dextrose and had a similar appearance and caloric
content (132 kcal) to that of the grape supplement. Plasma TG concentrations were reduced by 15 and 6 % in pre- and post-menopausal women (P < 0.01) following supplementation with the LGP. In addition, plasma LDL-cholesterol and apolipoproteins B and E were decreased due to LGP treatment (P < 0.05). Further, cholesterol ester transfer protein (CETP) activity was decreased by 15% with intake of LGP (P <0.05). In contrast to these beneficial effects on plasma lipids, the parameters of LDL oxidation were not modified by LGP treatment. Through alterations in lipoprotein metabolism, LGP intake beneficially affected key risk factors in CHD in both pre- and post-menopausal women.
Impacts Plasma triglycerides are a known biomarker for both the metabolic syndrome (insulin resistance) and coronary heart disease. Grapes contain polyphenols, which are potent anti-oxidants and also reduce plasma triglyceride concentrations. The correct selection of foods that may exert a cardioprotective effect becomes relevant in indidivuals who are at higher risk for chronic disease such as postmenopausal women.
Publications
- Patalay, M.K., Lofgren, I.E., Freake, H.C., Koo, S.I., Fernandez, M.L. 2004. The lowering of plasma lipids following a weight reduction program is related to increased expression of the LDL receptor and lipoprotein lipase. J. Nutr. (in press).
- Lofgren, I.E., Herron, K.L., West, K.L., Zern, T.L., Pataly, M., Koo, S.I., Fernandez, M.L. 2004. Carbohydrate intake is correlated with biomarkers for coronary heart disease in a population of overweight premenopausal women. J. Nutr. Biochem. (in press).
- Ballesteros, M.N., Cabrera, R.M., Saucedo, M.S., Aggarwal, D., Shachter, N.S., Fernandez, M.L. 2004, Identification of risk factors for chronic disease in a population of children from Northern Mexico. J. Nutr. 135:70-73.
- Fernandez, M.L., Metghalchim S., Vega-Lopez, S., Conde-Knape, K., Lohman, T.G. Cordero-MacIntyre, Z. 2004. Beneficial effects of weight loss on plasma apolipoproteins in postmenopausal women. J. Nutr. Biochem. 15:717-721.
- Ballesteros, M.N., Cabrera, R.M., Saucedo, M.S., Fernandez, M.L. 2004. Dietary cholesterol does not increase biomarkers for chronic disease in a pediatric population at risk from Northern Mexico. Am. J. Clin. Nutr. 80:855-861
- Lofgren, I.E., Herron, K.L., Zern, T.L., West, K.L., Patalay, M., Shachter, N.S., Koo, S.I., Fernandez, M.L. 2004. Waist circumference is a better predictor than body mass index of coronary heart disease risk in overweight premenopausal women J. Nutr. 134:1071-1076.
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