El resveratrol és un component del vi, el qual té uns potencials efectes beneficiosos en malalties relacionades amb l'envelliment com poden ser el càncer, la malaltia cardiovascular, la diabetis i ...les malalties neurodegeneratives, augmentant l'esperança de vida d'organismes simples i mamífers actuant com a mimetic de la restricció calòrica. Els biomarcadors nutricionals poden ser una millor mesura de l'exposició dietètica que les dades estimades mitjançant enquestes alimentàries, perquè tenen tres grans avantatges envers les enquestes : a) els biomarcadors nutricionals són més precisos; b) les dades dietètiques són normalment més inadequades degut a les limitacions en les dades de composició dels aliments; c) l'anàlisi del biomarcador proporciona una mesura més pròxima del nutrient específic que les dades dietètiques perquè és una mesura integrada del metabolisme del component. Un biomarcador ideal ha de ser quantitativament robust, específic, sensible als canvis en la ingesta del component dietètic, i un període de vida mig adequat. La hipòtesis d'aquesta tesi doctoral ha estat la de determinar els metabòlits urinaris del resveratrol (URM) com a biomarcadors útils de la consumició del vi.Es van realitzar dos estudis clínics aleatoritzats, creuats, prospectius. En el primer estudi 10 homes sans van consumir 30g d'etanol/dia en forma de cava o ginebra durant 28 dies. En el segon assaig, 10 dones sanes van consumir 20g d'etanol/dia en forma de vi blanc o negre durant 28 dies. A més a més es van analitzar 1000 participants free-living en un estudi per avaluar efectes d'una dieta mediterrània en la prevenció primària de la malaltia cardiovascular (estudi de PREDIMED). Les anàlisis de URM foren realitzades mitjançant LC-MS/MS després d'una extracció en fase sòlida. Es van utilitzar els valors predictius i la corba ROC per determinar l'exactitud de la prova diagnòstica.S'utilitza una metodologia robusta LC-MS/MS per determinar el URM en humans. La dosis diària de consumició de vi va ser correlacionada positivament amb els URM (r = 0.895, p< 0.001). En l'anàlisi estadístic mitjançant corba ROC es van obtenir els valors òptims de sensibilitat, la especificitat i els valors predictius.També es van estimar ingesta dietètica del resveratrol i del piceid (R&P) en la població adulta espanyola. Per aquest propòsit es va compilar una completa base de dades de composició d'aliments de R&P en aliments d'origen espanyol. L'estudi on es va aplicar va ser la cohort espanyola de l'estudi European Prospective Investigation into Cancer and nutrition (EPIC), on participen 40685 voluntaris. La mediana estimada i la mitjana de R&P van ser 100 i 933 microgr./d respectivament. La font més important de R&P van ser els vins (98.4%).Per tant, els URM se poden utilitzar com a una mesura objectiva i útil del consum de vi en estudios clínics i garns estudis epidemiològics free-living.
Resveratrol, a constituent of wine, has been shown to have beneficial effects on diseases of ageing including cancer, cardiovascular disease, diabetes and neurodegeneration, as well as increase stress resistance and extent the lifespan of organisms and mammals as caloric restriction mimetic. Nutritional biomarkers may be a better measure of dietary exposure than self-reported dietary data, because they have three distinct advantages over dietary data: a) biochemical markers of some nutrient intake are more precise than dietary assessment; b) dietary data are often inadequate because of limitation in food composition data; c) biomarker analysis provides a more proximal measure of specific nutrient intake than dietary data because it is useful as an integrated measure of the metabolism of the component. An ideal biomarker should be quantitatively robust, specific, sensitive to changes in intake of the dietary component, and have an adequate half-life. The hypothesis of this thesis was to assess urinary resveratrol metabolites (URM) as useful biomarkers of wine consumption.We performed two randomized, crossover trials and a cohort study. In the first study 10 healthy men consumed 30 g ethanol/day as sparkling wine or gin for 28 days. In the second trial, 10 healthy women consumed 20 g ethanol/day as white or red wine for 28 days. Furthermore 1000 free living participants in a study on the effects of a Mediterranean diet on primary prevention of cardiovascular disease (PREDIMED study) were also evaluated. Analyses of URM were carried out by LC-MS/MS after a solid phase extraction. We used predictive values and ROC curve analyses to assess the diagnostic accuracy.A robust methodology using LC-MS/MS analysis was applied to determinate the URM in humans. The reported daily dose of wine consumption was correlated positively with URM (r = 0.895, p<0.001). With the ROC curve analysis, optimal values of sensitivity, specifity and predictive values were obtained.We also estimated the dietary intake of resveratrol and piceid (R&P) in the Spanish adult population. For this purpose, a food composition data base (FCDB) of R&P in Spanish foods was compiled. The study included 40685 subjects a who were included in the European Prospective Investigation into Cancer and nutrition (EPIC)-Spain cohort. The estimated median and mean of R&P intake were 100 and 933 microgr./d respectively. The most important source of R&P were wines (98·4%).URM can be used as an objective an useful measure of wine consumption in clinical and large free-living epidemiologic studies.
Atherosclerosis is considered a low-grade inflammatory disease. Polyphenol-rich alcoholic beverages (red wine) have shown a more pronounced antiinflammatory effect than polyphenol-free alcoholic ...beverages (gin). However, no studies to our knowledge have evaluated the antiinflammatory effects of alcoholic beverages with medium-level polyphenol content such as cava (sparkling wine). We enrolled 20 healthy men (aged 34 ± 9 y) in a randomized crossover study to receive 30 g ethanol/d as cava or gin for 28 d. Before both interventions, subjects abstained from alcohol for 2 wk. Inflammatory biomarkers of atherosclerosis and expression of adhesion molecules on peripheral leukocytes were measured before and after each intervention. Likewise, dietary intake and exercise were also evaluated. Expression of lymphocyte function-associated antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), Sialyl-Lewisx (SLex), and CD40 on monocytes decreased after cava intake (all P < 0.05), whereas only SLex was reduced after gin intake (P = 0.036). Circulating markers of atherosclerosis including vascular cell adhesion molecule-1, E-selectin, and P-selectin decreased after both interventions (all P < 0.05). High-sensitivity C-reactive protein, intercellular adhesion molecule-1 (ICAM-1), IL-6, monocyte chemoattractant protein-1 (MCP-1), and CD40L were diminished only after cava intake (all P < 0.05). The effects of cava on circulating CD40L, ICAM-1, and MCP-1, and monocyte surface expression of CD40, LFA-1, and VLA-4 were greater than those of gin (all P < 0.05). In conclusion, both cava and gin showed antiinflammatory properties; however, cava had a greater protective effect, probably due its polyphenol content.
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