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Clinical and epidemiological studies

Nutritional epidemiology is an independent scientific discipline which main objective is to evaluate the effects of diet on the risk of certain diseases in specific population groups.

PREDIMED STUDY

Our group currently is actively involved in the PREDIMED study (PREvención con DIeta MEDiterránea), which is a thematic network of centers of the Ministry of Health began in October 2003 and includes 16 groups of researchers in eight regions of Spain.

The PREDIMED study is a large, parallel-group, multicenter, randomized, controlled clinical trial of 5-year duration aimed at assessing the effects of the Mediterranean diet on the primary prevention of cardiovascular disease (www.predimed.org; ISRCTN35739639).

Participants are assigned randomly into three equal-sized groups interventions:

1. Mediterranean-style diet supplemented with virgin olive oil.

2. Mediterranean-style diet supplemented with nuts.

3. Low-fat diet in accordance with guidelines from the American Heart Association.

Under the PREDIMED study, we also assesses the relationship between tomato consumption in its different forms (fresh, gazpacho and tomato sauce) and the excretion of total polyphenols in urine, as well as how affects the consumption of each foods on blood pressure values, and the prevalence of hypertension. We also studied the effect of certain genetic polymorphisms on blood pressure, and other phenotypes of cardiovascular risk and its modulation by consumption patterns associated with tomatoes.

The EPIC-Spain study

In addition, we are working with another observational epidemiological study: EPIC Study (European Prospective Investigation into Cancer; www.iarc.fr/epic). This is a cohort study, prospective, multicenter, coordinated by the International Agency for Research on Cancer (IARC, International Agency for Research on Cancer) from the World Health Organization (WHO).

The Spanish cohort (www.epic-spain.com) consists of 40.885 volunteers (61.7% women) enrolled in five geographic areas (Asturias, Granada, Guipúzcoa, Murcia y Navarra). This study was created to integrate epidemiology with the research laboratory, genetic and metabolic factors, and deepen the scientific knowledge of nutrition and cancer.

CLINICAL STUDIES

Our group evaluate the effect of consumption of polyphenols through clinical studies in animals and humans. In addition, we analyzed the effect of the matrix  and/or the dose on the absorption of different phenolic compounds.

TOMATO

The first study of tomato was carried out in collaboration with the National Research Center in Egypt with the aim of measuring the normal distribution of total polyphenols excreted in urine in 49 Egyptian children between 7 and 14 also were studied changes obtained in the excretion of polyphenols after an intervention with tomato juice.

Currently, in 60 patients at high cardiovascular risk, we measure the effect of a chronic consumption of tomato juice on blood pressure and endothelial function. We also studies the effect of different daily (servings) of tomato juice on the parameters of oxidation and inflammation associated with atherosclerosis. We are analyzing changes in the gene expression of the intervention with different doses of tomato to identify differentially expressed genes.

Finally, in order to understand the pathogenesis of the effects of tomatoes on blood pressure, we correlate changes in blood pressure, changes in plasma levels of lycopene and polyphenols in urine, with changes in expression of those candidate genes.

WINE

The aim of this study was to propose and evaluate the amount of resveratrol metabolites in urine as potential biomarkers of wine consumption in humans, after moderate consumption of sparkling wine, red or white wine, as representatives drinks with different content of resveratrol. To conduct the study were carried out  two prospective, randomized, crossover, controlled and single blind trials, which were conducted jointly with the Hospital Clinic of Barcelona.

COCOA

The first clinical study on cocoa, in collaboration with the Hospital Clinic of Barcelona, ​​aimed to determine epicatechin metabolites excreted in urine after ingestion of a standard serving of a shake of cocoa and the effect of these metabolites in total antioxidant capacity of urine. Thus, we wanted to know if all the conjugations that cocoa flavanoids suffer during their metabolism affect their bioactivity and, therefore, their possible beneficial health effects.

Another objective of this work was to study the possible effect of milk on the excretion of metabolites of cocoa epicatechin in healthy volunteers and observe if there is interference of the components of milk in the phase II metabolism of polyphenols.

GROUP PUBLICATIONS

PREDIMED:

  • Sala-Vila A, Harris WS, Cofán M, Pérez-Heras AM, Pintó X, Lamuela-Raventós RM, Covas MI, Estruch R, Ros E. Determinants of the omega-3 index in a Mediterranean population at increased risk for CHD. Br J Nutr. 2011 Mar 30:1-7. PubMed.
  • Medina-Remón A, Zamora-Ros R, Rotchés-Ribalta M, Andres-Lacueva C, Martínez-González MA, Covas MI, Corella D, Salas-Salvadó J, Gómez-Gracia E, Ruiz-Gutiérrez V, García de la Corte FJ, Fiol M, Pena MA, Saez GT, Ros E, Serra-Majem L, Pinto X, Warnberg J, Estruch R, Lamuela-Raventos RM; on behalf of the PREDIMED Study Investigators. Total polyphenol excretion and blood pressure in subjects at high cardiovascular risk. Nutrition, Metabolism, and Cardiovascular Diseases. 2011, 21(5):323-31. PubMed
  • Martínez-González MA, Corella D, Salas-Salvadó J, Ros E, Covas MI, Fiol M, Wärnberg J, Aros F, Ruíz-Gutiérrez V, Lamuela-Raventós RM, Lapetra J, Muñoz MA, Martínez JA, Sáez G, Serra-Majem L, Pintó X, Mitjavila MT, Tur JA, Portillo MD, Estruch R; for the PREDIMED Study Investigators. Cohort Profile: design and methods of the PREDIMED study. Int J Epidemiol. 2010 Dec 20. PubMed.
  • Llorente-Cortés V, Estruch R, Mena MP, Ros E, González MA, Fitó M, Lamuela-Raventós RM, Badimon L. Effect of Mediterranean diet on the expression of pro-atherogenic genes in a population at high cardiovascular risk Atherosclerosis. 2010 Feb;208(2):442-50. PubMed.
  • Fandos M, Corella D, Guillén M, Portolés O, Carrasco P, Iradi A, Martínez-González MA, Estruch R, Covas MI, Lamuela-Raventós RM, Michavilla MT, Cerdá C, Torregrosa R, Redón J, Chaves FF, Tormos MC, Ocete D, Sáez GT. Impact of cardiovascular risk factors on oxidative stress and DNA damage in a high risk Mediterranean population. Free Radic Res. 2009 Dec;43(12):1179-86. PubMed
  • Medina-Remón A, Barrionuevo-González A, Zamora-Ros R, Andres-Lacueva C, Estruch R, Martínez-González MA, Diez-Espino J, Lamuela-Raventos RM. Rapid Folin-Ciocalteu method using microtiter 96-well plate cartridges for solid phase extraction to assess urinary total phenolic compounds, as a biomarker of total polyphenols intake. Anal Chim Acta. 2009 Feb 16;634(1):54-60. PubMed.
  • Mena MP, Sacanella E, Vazquez-Agell M, Morales M, Fitó M, Escoda R, Serrano-Martínez M, Salas-Salvadó J, Benages N, Casas R, Lamuela-Raventós RM, Masanes F, Ros E, Estruch R. Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet. Am J Clin Nutr. 2009 Jan;89(1):248-56. PubMed.
  • Zazpe I, Sanchez-Tainta A, Estruch R, Lamuela-Raventos RM, Schröder H, Salas-Salvado J, Corella D, Fiol M, Gomez-Gracia E, Aros F, Ros E, Ruíz-Gutierrez V, Iglesias P, Conde-Herrera M, Martinez-Gonzalez MA. A large randomized individual and group intervention conducted by registered dietitians increased adherence to Mediterranean-type diets: the PREDIMED study. J Am Diet Assoc. 2008 Jul;108(7):1134-44; discussion 1145. PubMed.
  • Toledo E, Delgado-Rodríguez M, Estruch R, Salas-Salvadó J, Corella D, Gomez-Gracia E, Fiol M, Lamuela-Raventós RM, Schröder H, Arós F, Ros E, Ruíz-Gutiérrez V, Lapetra J, Conde-Herrera M, Sáez G, Vinyoles E, Martínez-González MA. Low-fat dairy products and blood pressure: follow-up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study. Br J Nutr. 2009 Jan;101(1):59-67. PubMed.
  • Zamora-Ros R, Urpí-Sardà M, Lamuela-Raventós RM, Estruch R, Martínez-González MA, Bulló M, Arós F, Cherubini A, Andres-Lacueva C. Resveratrol metabolites in urine as a biomarker of wine intake in free-living subjects: The PREDIMED Study. Free Radical & Biology Medicine. 2009;46(12):1562-1566. PubMed

EPIC-Spain:

  • Zamora-Ros R, Andres-Lacueva C, Lamuela-Raventós RM, Berenguer T, Jakszyn P, Barricarte A, Ardanaz E, Amiano P, Dorronsoro M, Larrañaga N, Martínez C, Sánchez MJ, Navarro C, Chirlaque MD, Tormo MJ, Quirós JR, González CA. Estimation of dietary sources and flavonoid intake in a Spanish adult population (EPIC-Spain). Journal of American Dietetic Association. 2010;110(3):390-398. PubMed
  • Zamora-Ros R, Andres-Lacueva C, Lamuela-Raventós RM, Berenguer T, Jakszyn P, Martínez C, Sánchez MJ, Navarro C, Chirlaque MD, Tormo MJ, Quirós JR, Amiano P, Dorronsoro M, Larrañaga N, Barricarte A, Ardanaz E, González CA. Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. British Journal of Nutrition. 2008;100(1):188-196. PubMed

Tomato Study:

  • Hussein L, Medina A, Barrionnevo A, Lamuela-Raventos RM, Andres-Lacueva C. Normal distribution of urinary polyphenol excretion among Egyptian males 7-14 years old and changes following nutritional intervention with tomato juice (Lycopersicon esculentum). Int J Food Sci Nutr. 2009;60(4):302-11.
  • Hussein L, Medina A, Barrionuevo A, Lamuela-Raventós RM, Andrés-Lacueva C. Normal distribution of urinary polyphenol excretion among male adolescents and changes associated with nutritional intervention with tomato juice (Lycopersicon esculentum). Ann Nutr Metab. 2007;51(Suppl 1):70.

Wine Study:

  • Chiva-Blanch G, Urpi-Sarda M, Rotchés-Ribalta M, Zamora-Ros R, Llorach R, Lamuela-Raventós RM, Estruch R, Andrés-Lacueva C. Determination of resveratrol and piceid in beer matrices by solid-phase extraction and liquid chromatography-tandem mass spectrometry. Journal of Chromatography. A. 2011;1218(5):698-705. PubMed
  • Estruch R, Sacanella E, Mota F, Chiva-Blanch G, Antúneza E, Casals E, Deulofeu R, Rotilio D, Andres-Lacueva C, Lamuela-Raventos RM, de Gaetano G, Urbano-Marquez A. Moderate consumption of red wine, but not gin, decreases erythrocyte superoxide dismutase activity: A randomised cross-over trial. Nutrition Metabolism and Cardiovascular Diseases. 2011;21(1):46-53. PubMed
  • Ortuno J, Covas MI, Farre M, Pujadas M, Fito M, Khymenets O, Andres-Lacueva C, Roset P, Joglar J, Lamuela-Raventos RM, de la Torre R. Matrix effects on the bioavailability of resveratrol in humans. Food Chemistry. 2010;120(4):1123-1130. ScienceDirect
  • Zamora-Ros R, Andres-Lacueva C, Lamuela-Raventós RM, Berenguer T, Jakszyn P, Barricarte A, Ardanaz E, Amiano P, Dorronsoro M, Larrañaga N, Martínez C, Sánchez MJ, Navarro C, Chirlaque MD, Tormo MJ, Quirós JR, González CA. Estimation of dietary sources and flavonoid intake in a Spanish adult population (EPIC-Spain). Journal of American Dietetic Association. 2010;110(3):390-398. PubMed
  • Monagas M, Khan N, Andrés-Lacueva C, Urpí-Sardá M, Vázquez-Agell M, Lamuela-Raventós RM, Estruch R. Dihydroxylated phenolic acids derived from microbial metabolism reduce lipopolysaccharide-stimulated cytokine secretion by human peripheral blood mononuclear cells. British Journal of Nutrition. 2009;102(2):201-206. PubMed
  • Zamora-Ros R, Urpí-Sardà M, Lamuela-Raventós RM, Estruch R, Martínez-González MA, Bulló M, Arós F, Cherubini A, Andres-Lacueva C. Resveratrol metabolites in urine as a biomarker of wine intake in free-living subjects: The PREDIMED Study. Free Radical Biology & Medicine. 2009;46(12):1562-1566. PubMed
  • Zamora-Ros R, Lamuela-Raventós RM, Estruch R, Andres-Lacueva C. Resveratrol, a new biomarker of moderate wine intake? British Journal of Nutrition. 2009;101(1):148. PubMed
  • Zamora-Ros R, Andres-Lacueva C, Lamuela-Raventós RM, Berenguer T, Jakszyn P, Martínez C, Sánchez MJ, Navarro C, Chirlaque MD, Tormo MJ, Quirós JR, Amiano P, Dorronsoro M, Larrañaga N, Barricarte A, Ardanaz E, González CA. Concentrations of resveratrol and derivates in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. British Journal of Nutrition. 2008;100(1):188-196. PubMed
  • Darias-Martin JJ, Andres-Lacueva C, Diaz-Romero C, Lamuela-Raventos RM. Phenolic profile in varietal white wines made in the Canary Islands. European Food Research & Technology. 2008;226(4):871-876. Abstract
  • de Andrés-de Prado R, Yuste-Rojas M, Sort X, Andrés-Lacueva C, Torres M, Lamuela-Raventós RM. Effect of soil type on wines produced from Vitis vinifera L. cv. Grenache in commercial vineyards. Journal of Agricultural and Food Chemistry. 2007;55(3): 779-786.
  • Vázquez-Agell M, Sacanella E, Tobias E, Monagas M, Antúnez E, Zamora-Ros R, Andrés-Lacueva C, Lamuela-Raventós RM, Fernández-Solá J, Nicolás JM, Estruch R. Inflammatory markers of atherosclerosis are decreased after moderate consumption of cava (sparkling wine) in men with low cardiovascular risk. Journal of Nutrition. 2007;137(10):2279-2284. PubMed
  • Urpi-Sarda M, Zamora-Ros R, Lamuela-Raventos R, Cherubini A, Jauregui O, de la Torre R, Covas MI, Estruch R, Jaeger W, Andres-Lacueva C. HPLC-tandem mass spectrometric method to characterize resveratrol metabolism in humans. Clinical Chemistry. 2007;53(2):292-299. PubMed
  • Zamora-Ros R, Urpí-Sardà M, Lamuela-Raventós RM, Estruch R, Vázquez-Agell M, Serrano-Martínez M, Jaeger W, Andres-Lacueva C. Diagnostic performance of urinary resveratrol metabolites as a biomarker of moderate wine consumption. Clinical Chemistry. 2006;52(7):1373-1380. PubMed
  • Urpí-Sardà M, Jáuregui O, Lamuela-Raventós RM, Jaeger W, Miksits M, Covas MI, Andres-Lacueva C. Uptake of diet resveratrol into the human low-density lipoprotein. Identification and quantification of resveratrol metabolites by liquid chromatography coupled with tandem mass spectrometry. Analytical Chemistry. 2005;77(10):3149-3155. PubMed

Cocoa study: 

  • Vázquez-Agell M, Urpi-Sarda M, Sacanella E, Camino-López S, Chiva-Blanch G, Llorente-Cortés V, Tobias E, Roura E, Andres-Lacueva C, Lamuela-Raventós RM, Badimon L, Estruch R. Cocoa consumption reduces NF-κB activation in peripheral blood mononuclear cells in humans. Nutrition, Metabolism, and Cardiovascular Diseases [en prensa].
  • Khan N, Monagas M, Andrés-Lacueva C, Casas R, Urpí-Sardà M, Lamuela-Raventós RM, Estruch R. Regular consumption of cocoa powder with milk increases HDL cholesterol and reduces oxidized LDL levels in subjects at high-risk of cardiovascular disease. Nutrition, Metabolism, and Cardiovascular Diseases [en prensa].
  • Urpi-Sarda M, Llorach R, Khan N, Monagas M, Rotches-Ribalta M, Lamuela-Raventos R, Estruch R, Tinahones FJ, Andres-Lacueva C. Effect of milk on the urinary excretion of microbial phenolic acids after cocoa powder consumption in humans. Journal of Agricultural and Food Chemistry. 2010;58(8):4706-4711. PubMed
  • Urpi-Sarda M, Monagas M, Khan N, Llorach R, Lamuela-Raventós RM, Jáuregui O, Estruch R, Izquierdo-Pulido M, Andrés-Lacueva C. Targeted metabolic profiling of phenolics in urine and plasma after regular consumption of cocoa by liquid chromatography-tandem mass spectrometry. Journal of Chromatography A. 2009;1216(43):7258-7267. PubMed
  • Monagas M, Khan N, Andres-Lacueva C, Casas R, Urpí-Sardà M, Llorach R, Lamuela-Raventós RM, Estruch R. Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease. American Journal of Clinical Nutrition. 2009;90(5):1144-1150. PubMed
  • Urpi-Sarda M, Monagas M, Khan N, Lamuela-Raventos RM, Santos-Buelga C, Sacanella E, Castell M, Permanyer J, Andres-Lacueva C. Epicatechin, procyanidins, and phenolic microbial metabolites after cocoa intake in humans and rats. Analytical and Bioanalytical Chemistry. 2009;394(6):1545-1556. PubMed
  • Roura E, Andrés-Lacueva C, Estruch R, Mata-Bilbao ML, Izquierdo-Pulido M, Lamuela-Raventós RM. The effects of milk as a food matrix for polyphenols on the excretion profile of cocoa (-)-epicatechin metabolites in healthy human subjects. British Journal of Nutrition. 2008;100(4):846-851. PubMed
  • Andres-Lacueva C, Monagas M, Khan N, Izquierdo-Pulido M, Urpi-Sarda M, Permanyer J, Lamuela-Raventós RM. Flavanol and flavonol contents of cocoa powder products: influence of the manufacturing process. Journal of Agricultural and Food Chemistry. 2008;56(9):3111-3117. PubMed
  • Roura E, Andrés-Lacueva C, Estruch R, Mata-Bilbao ML, Izquierdo-Pulido M, Waterhouse AL, Lamuela-Raventós RM. Milk does not affect the bioavailability of cocoa powder flavonoid in healthy human. Annals of Nutrition & Metabolism. 2007;51(6):493-498. PubMed
  • Roura E, Almajano MP, Bilbao ML, Andrés-Lacueva C, Estruch R, Lamuela-Raventós RM. Human urine: epicatechin metabolites and antioxidant activity after cocoa beverage intake. Free Radical Research. 2007;41(8):943-949. PubMed
  • Lamuela-Raventós RM, Romero-Pérez AI, Andrés-Lacueva C, Tornero, A. Health Effects of Cocoa Flavonoids. Food Science and Technology International. 2005:11(3):159-176. Abstract
  • Roura E, Andrés-Lacueva C, Jáuregui O, Badia E, Estruch R, Izquierdo-Pulido M, Lamuela-Raventós RM. Rapid liquid chromatography tandem mass spectrometry assay to quantify plasma (-)-epicatechin metabolites after ingestion of a standard portion of cocoa beverage in humans. J Agricultural and Food Chemistry. 2005;53(16):6190-6194. PubMed
  • Roura E, Andrés-Lacueva C, Jáuregui O, Badia E, Estruch R, Izquierdo-Pulido M, Lamuela-Raventós RM. Rapid liquid chromatography tandem mass spectrometry assay to quantify plasma (-)-epicatechin metabolites after ingestion of a standard portion of cocoa beverage in humans. Journal of Agricultural and Food Chemistry. 2005; 53(16):6190-6194. PubMed
  • Sánchez-Rabaneda F, Jáuregui O, Casals I, Andrés-Lacueva C, Izquierdo-Pulido M, Lamuela-Raventós RM. Liquid chromatographic/electrospray ionization tandem mass spectrometric study of the phenolic composition of cocoa (Theobroma cacao). Journal of Mass Spectrometry. 2003;38(1):35-42. PubMed
  • Lamuela-Raventós RM, Andrés-Lacueva C, Permanyer J, Izquierdo-Pulido M. More antioxidants in cocoa. Journal of Nutrition. 2001;131(3):834-835. PubMed
  • Andres-Lacueva C, Lamuela-Raventós RM, Jauregui O, Casals I, Izquierdo-Pulido M, Permanyer J. An LC method for the analysis of cocoa phenolics. LC GC Europe. 2000;902-4.