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Flavonóides da Dieta vs Mortalidade por DAC (n=805 h) Zutphen Elderly Study-seguim.

: 5 anos
1 0,9 0,8
Risco Relativo

0,7 0,6 0,5 0,4 0,3 0,2 0,1 0
0 - 19

p < 0,003

19,1 - 29,9

> 29,9

Ingestão de Flavonóides (mg/dia) RR ajustado para idade, dieta e FR
Hertog MCL et al. Lancet 1993;342:1007-11

Zutphen Elderly Study
805 homens; seguimento: 5 a.

• Flavonóides:resveratrol, quercetina, Kempferol, apigenina, luteolina e mirecitina • Fontes: Chá Cebola Maçã

61% 13% 10%
Hertog MCL et al. Lancet 1993;342:1007-11

Wine Consumption and CHD
1000
Finland

CHD = -4.99W + 652.4 r = -0.580

800
Ireland

U.S.

Mortality rate

U.K. Canada 600 Norway Denmark Sweden

Australia New Zealand

400

W. Germany

Netherlands Belgium

Austria Italy France

200
Japan

Switzerland

0

20

40

60

80

100

Wine, liter/capita-year
Hegsted DM, Ausman LM. J Nutr. 1988;118:1184-1189.

Alcohol and Stroke Risk OR LOG 7.5 1.0 0 1 2 3 4 5 6 7 Drinks per Day O’Keefe JH et al.6 1.0 0.0 1.4 2.6 0.0 . JACC 2007.4 4.5 2.0 0.0.7 1.50:1009-14 .5 -1.5 0.

UVA E ATEROSCLEROSE: PERSPECTIVAS Dr.2009 VINHO TINTO.HC.FRUTIVAR. INCOR. Protásio L. da Luz Professor de Cardiologia.FMUSP Não há conflitos de interesse .

K.Wine. platelets.339:1523-26 .73 p < 0.001 800 1000 Dairy fat (Calories) (1980-85) Renaud S and Lorgeril M. Lancet 1992. alcohol. and the French paradox for coronary heart disease 300 CHD Mortality (1987) (men + women) U. Denmark Finland Ireland Sweden 200 Norway Australia Germany Austria Netherlands Yugoslavia Belgium Switzerland Italy Spain FRANCE 100 Portugal 0 0 200 400 600 r = 0.

87 p < 0. platelets.0001 200 300 0 0 200 145 + 0.Wine. Lancet 1992.138 dairy fat -0.917 wine Renaud S and Lorgeril M. and the French paradox for coronary heart disease 300 CHD Mortality (1987) (men + women) U. Australia Finland Ireland Denmark Sweden 200 Austria Germany Norway Switzerland Italy 100 Portugal Spain Yugoslavia FRANCE Netherlands Belgium r = 0. alcohol.K.339:1523-26 .

Meta-Analysis of Wine Intake and Vascular Risk
Kozararevic, 1980 (17) Friedman, 1986 (18) Rimm, 1991 (19) Klatsky, 1990 (20) Wannamethee, 1999 (21)

Prospective studies
Rosenberg, 1981 (22) Kaufman, 1985 (23) Marques-Vidal, 1996 (28) Sacco, 1999 (24) Gaziano, 1999 (25) Triff, 1999 (26) Cleophas, 1996 (29) Brenner, 2001 (27)

Case-Control studies Overall
0.3 0.4 0.5 0.6 0.7 0.8 Prospective effect 0.9 1.0 1.1 Risk effect

Di Castelnuovo A et al. Circulation 2002;105:2836-2844

Alcohol and All-Cause Mortality
1.4 Relative Risk of Total Mortality 1.3 1.2 1.1 1.0 0.9 0.8 0.7 0.6 0 1 2 3 4 5 6 7 Men Women Confidence Intervals

Drinks per Day Alcohol Consumption

O’Keefe JH et al. JACC 2007;50:1009-14

The Effect of Red Wine on Experimental Atherosclerosis: Lipid-Independent Protection

Protásio L. da Luz, Carlos V. Serrano Jr., Ana P. Chacra et al.
Exp Mol Pathology 1999;65:150-159

The Effect of Red Wine on Experimental Atherosclerosis: Lipid-Independent Protection.1999. Da Luz P et al.65:150-9 .

BJMBR . por 14 dias) P < 0.01 HR NT 10 0 Basal Vinho Tinto Basal Vinho Tinto Coimbra S. Da Luz PL.Avaliação da reatividade vascular endotélio dependente e independente com vinho tinto ( 250 ml/dia.01 % Dilatação da artéria braquial 20 P < 0.

BJMBR .Avaliação da reatividade vascular endotélio dependente e independente com suco de uva ( 500 ml/dia. por 14 dias) % Dilatação da artéria braquial 20 P < 0. Da Luz PL.01 P = ns HR NT 10 0 Basal Suco de Uva Basal Suco de Uva Coimbra S.

Grape Juice and Coronary Artery Disease 15.1050-5 . Circulation 1999:100.0 Baseline Grape Juice Stein JH et al.0 0.0 -5.0 10.0 % FMD 5.

0002 40 1 2 3 4 5 Year Lorgeril M et al.Mediterranean Diet and Coronary Heart Disease 100 90 Percent without event 80 Experimental 70 60 Control 50 p = 0. Circulation 1999.99:779-785 .

Redução de Mortalidade por Aumento de Dois pontos no Escore de Dieta Mediterrânea EPIC . N Eng J Med 2003. seguimento 44 meses Hazard Ratio ajustado 1.75 0.001 Trichopolou et al.8 0.Grécia N= 22. 348: 2599-608 .043 adultos.6 Geral DAC Câncer 0.76 P<0.67 0.0 0.

00% 10.00% 16.50% 20. Frutas/noz Vegetais Carne alta alta alta alta baixa Ingestão de Alimentos Álcool moderada Trichopoulou et al.00% 0.20% 10.338:b2337 .70% 5.00% Legumes Mono/Sat.00% 9.00% 23. BMJ 2009.Contribuição dos Alimentos na Redução de Morte Estudo EPIC 25.60% 15.20% 16.60% 11.

J Am Geriatr Soc 1998.Alcohol and Age-related Macular Degeneration 10 9 AMD Percent with AMD (%) 8 7 6 5 4 3 2 1 0 No alcohol Beer Wine Liquor Types of alcohol Obisesan TO el al.46:1-7 .

Diabetes Mellitus 4. Neurology 2002.57:53-60 . Proc Natl Acad Sci USA 1997. Diabetes Care 2000.153:185-92 Truelsen T e col. Epidemiology 1997. Diabetes Research and Clinical Practice 2002.AÇÕES NÃO CARDIACAS DO VINHO .16:1-7 6 7 Ghem BD e col.12:1300-11 Wei M e col. Am J Epidemiol 1999:149:106-15 JM e col.Demência 3 .Hiperplasia Prostática Benigna 8 1 Obsisesan 2 Orgajazo 3 4 5 TO e col.Doença de Alzheimer 2 . J Am Geriatr Soc 1998.8:420-4 EA e col.94:1438-43 Aldoorl WH e col.Úlcera Duodenal 7 .5 .Degeneração macular senil 1 .Estrógeno 6 . Rev Neurol 1997.23:18-22 8 Paltz De Vegt F e col.

935 mortes Dieta Alcool moderado Atividade Fisica Abstinencia Fumo Todos 0 Hazard ratio (%) -10 -20 -30 -40 -50 -60 -70 Knoops et al.Redução de Mortalidade Total Estudos HALE. 292: 1433-9 . segui: 1988-2000. JAMA 2004. 832 M. SENECA e FINE 1507 H. 70-90 a.

nationalgeographicbr.br .com.www.

EH Moriguchi Instituto de Geriatria .PUCRS . J Siviero. M Taufer. G Flores. C Frentzel. A Manica. N Bruscato.Análise de Prevalência de Fatores de Risco Cardiovascular em Idoso do Projeto Veranópolis Ivana da Cruz. R Ehlers.

(1996) .3 y.100 > 80 y.o.Age: 84.last 5 years: 1 AMI death among > 80 • Study Sample: . RS: .4 ± 3.203 > 80 y. . . .16.o.910 hab.66 female: 34 male BRAZIL * Veranópolis (Italian Immigration) .SUBJECTS • Veranópolis.

Smoking Among Very Elderly Smoking Among Very Elderly 100% 80% 60% 40% 20% 0% * * * Never Former Smoker Male Female p<0.000 .000 p<0.

Distribution of Plasma Distribution of Plasma Lipid/Lipoproteins Lipid/Lipoproteins 250 200 * * Male Female mg/dl 150 100 50 0 *p<0.01 CT CT TG TG LDL-c LDL-c HDL-c HDL-c .

Como Eles Conseguem Viver Tanto SARDOS Bebem vinho tinto (com moderação) Compartilham com o cônjuge o trabalho Comem queijo pecorino (e outros alimentos ricos em ômega-3) ADVENTISTAS Comem nozes e feijões Guardam o sábado Têm fé TODOS Não fumam Priorizam a família Fazem atividades físicas Têm vida social Comem frutas.nationalgeographicbr. verduras e grâos integrais OKINAWANOS Mantêm amigos para toda a vida Comem porções pequenas Encontram sentido na vida www.com.br .

ULTRA-LEAN DIET This handsome fellow has lower glucose and insulin levels-and looks younger. . show effects of two regimens. NORMAL FARE This monkey has higher triglycerides and more oxidative damage to his cells. both 24. too.A Tale of Two Monkeys Rhesus Monkeys at Wisconsin Primate Research Center.

Pereira AC.PROJETO SOBREVIDA Efeito do tratamento crônico com resveratrol na sobrevida e em biomarcadores de envelhecimento em ratos idosos da Luz PL. Myakawa AA. Krieger JK. Tanaka LY. Brum PC .

Nature. 2003 .Restrição calórica PNC1 Resveratrol Sir/SIRT atividade deacetilase NAD+ nicotinamida + Ο-acetil-ADP-ribose -estabilidade do DNA -reparo no DNA -silenciamento transcricional -regulação da p53 sobrevida Howitz KT et al.

p16 .inibidoras de cdk (cdki) .encurtamento do telômero Tratamento com resveratrol Modulação de mecanismos envolvidos na senescência .atividade da telomerase .n=20/grupo -controle: ração e água controle -vinho tinto (25%) na água de beber -resveratrol (ração): 0.Protocolo Sobrevida Da Luz et al. 2008 -ratos Wistar .p21 .estresse oxidativo -sobrevida Análise funcional -tolerância ao esforço físico -consumo máximo de oxigênio -função endotelial .p53 (supressora de tumor).0015g/kg e 4g/kg .

Projeto Confrarias • Pergunta : bebedores habituais de vinho tinto são biologicamente mais jovens que abstêmios ? Têm menos aterosclerose ? • População : • 100 indíviduos “sadios”. pelo menos 4. que bebam pelo menos 1 taça de vinho tinto/dia. e do sexo masculino • O n= 200 foi calculado baseado no escore de cálcio coronário da Luz et al-2008 . abstêmios • Comparáveis em idade.5 vezes/ semana. nos últimos 5 anos • 100 controles “sadios”.

3 dias Função endotelial braquial e EIM carotídea por US Tomografia Computadorizada MD (64 ) coronária para escore de cálcio e lesões Perfil lipídico e PCRus Índices de envelhecimento em leucócitos circulantes: comprimento de telômero.Projeto Confrarias • • • • • • – Métodos Avaliação clínica : FR. p16. bgalactosidase da Luz et al-2008 . p21. telomerase. p53. dados antropométricos Registro alimentar .

Miocardiopatias • Diabetes descompensada • Doenças hepáticas • Alcoolismo • Adolescentes • Hipertrigliceridemia .Contra-Indicações ao uso de Vinho e/ou Bebidas Alcoólicas • Arritmias cardíacas • Disfunção ventricular .ICC.

“O whisky é o melhor amigo do homem. O whisky é o cachorro engarrafado” Vinícius de Moraes .

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Who was at greater risk for the development of heart disease? Jim Fixx . author dead at 53 of a heart attack Sir Winston Churchill – broke every tenet of “healthy life style” – dead at age 91 JAMES MUELLER . exercise advocate.marathon runner.

Obrigado! .

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338:b2337 .Contribuição dos Alimentos na Redução de Morte Estudo EPIC 25.00% 0.50% 20.70% 5.20% 15.60% 16. Legumes alta alta alta Ingestão de Alimentos Trichopoulou et al.00% 16.60% 10.20% 10.00% 23.00% 11.00% 9.00% Álcool moderada Carne baixa Vegetais alta Frutas/noz Mono/Sat. BMJ 2009.

vinho resv.05 vs. CTR .Projeto Sobrevida. dados preliminares ctr p53 p16 β -actina Western Blotting em homogenato de aorta Da Luz et al. alto baixo resv. Relaxamento máximo à ACh 65 Relaxamento máximo ao NPS % Relaxamento % relaxamento * 60 55 * 100 75 50 CTR baixo resv vinho alto resv 50 CTR baixo resv vinho alto resv *p<0.

2004 59% . 2003 18% -Viswanathan M et al. 2005 16 . Curr. 2006 ? .Wood JG et al. Nature.Resveratrol e sobrevida em diferentes espécies 70% . Nature.20% . Dev Cell.Valenzano DR et al. Biol.Wood LG et al.

Restrição calórica PNC1 Resveratrol Sir/SIRT atividade deacetilase NAD+ nicotinamida + Ο-acetil-ADP-ribose -estabilidade do DNA -reparo no DNA -silenciamento transcricional -regulação da p53 sobrevida Howitz KT et al. Nature. 2003 .

resveratrol 1mg/kg/dia .Cemib/Unicamp .n=20 .8 meses idade .água . biomarcadores de envelhecimento. METODOLOGIA ratos Wistar machos .veículo (etanol) .n=20 Sobrevida: curva de Kaplan-Meier. .OBJETIVOS Analisar os efeitos do tratamento crônico com resveratrol sobre: a sobrevida de ratos normais.n=20 .

. plasma e leucócito) coração. aorta. Atividade da telomerase: TeloTAGGG Telomerase PCR ELISA (Roche). rim. pulmão e orelha SA-ß-Galactosidase: detecção histoquímica após incubação overnight c/ solução X-Gal. Comprimento do telômero: Telo TTAGGG Telomere Length (Roche): ddhibridização com probe do telômero e detecção por reação luminescente GSH/GSSG: detecção eletroquímica em HPLC. p53 (Santa Cruz) e p21 (Calbiochem).Biomarcadores de envelhecimento (n=5) Tecidos coletados: sangue (eritrócito. fígado. Western Blot: p16 (Santa Cruz) . Arf (Upstate).

Resveratrol improves health and survival of mice on a highcalorie diet 100 Proporção sobreviventes (%) 80 60 40 20 Dieta padrão Dieta hipercalórica Dieta hipercalórica + Resveratrol 0 50 60 70 80 90 100 Tempo sobrevivência (semanas) 110 Baur et al. Nature 2006. 404: 337.42 .

Alcohol and Coronary Calcium Odds ratio For Severe Coronary Calcification 1.2 1.2 0 Non-drinkers 1 Drink/d 2 Drinks/d > 2 Drinks/d O’Keefe JH et al.4 0. JACC 2007.4 1.6 0.0 0.8 0.50:1009-14 .

0 1.0 Multivariate Relative Risk of Cognitive Impairment TICS = denotes the Telephone Interview for Cognitive Status Stampfer MJ et al.30.6 1.0 .6 0.0 0.2 0.352:245-53 .4 0.8 1. NEJM 2005.0 .14.0 g of alcohol/day 1.9 g of alcohol/day Worst 10% for verbal memory score Worst 10% for global cognitive score 0.8 2.Effects of Moderate Alcohol Consumption on Cognitive Function in Women TICS score < 31 15.4 1.2 1.

00 0.76 (0.00 0.58-1.00 0.74-0.98) 1.03) 0.9 g/day 15.Relative Risk of a Substantial Decline in Cognitive Function over a Two-Year Period.89 (0.670 1. Who Completed Test None** Alcohol Intake 1.0-30.102 1. According to Alcohol Intake Measure of Substantial Cognitive Decline* No.0-14.97) 0.54-1.83 (0.0 g/day relative risk (95 percent confidence interval) TICS score for worst 10% of distribution of decline Multivariate-adjusted Verbal memory score for worst 10% of distribution of decline Multivariate-adjusted Global cognitive score for worst 10% of distribution of decline Multivariate-adjusted 11.16) * TICS denotes the Telephne Interview for Cognitive Status ** Nondrinkers (51%) served as the reference group Stampfer MJ et al.352:245-53 .77-1.72-0.85 (0.82 (0.09) 9.77-1.661 1. NEJM 2005.41) 9.04 (0.

Chev.eNOS Induction by Red Wine nt 450 *** p<0. 10% TNGM 100 EtOH-Co L. 10% Wallerath T et al. J Am Coll Cardiol 2003.001 *** eNOS mRNA level (% of control) 417 400 350 300 250 200 150 100 50 0 eNOS 311 249 200 151 140 118 GAPDH EtOH-Co L.Chev.41:471-8 .

J Am Coll Cardiol 2003.Bonnet L.05 *** p<0.Chevaliers Wallerath T et al.41:471-8 .001 200 *** ** *** 150 100 0 EtOHCo 1% 3% 10% 1% 3% 10% 1% 3% 10% Dornfelder Ch.eNOS Induction by Red Wine eNOS mRNA level (% of control) 250 ** p<0.

Mol.65:150- * p = NS *p<0.01: Diet vs Wine and NAPW .65:150-9 Exp. 1999. Pathol.MACROSCOPIC PLANIMETRY OF AORTAS Atherosclerotic Area/Total Area Ratio Stained Area/Total Area (%) 80 60 40 20 0 Diet (n=10) Wine (n=11) NAPW (n=10) Da Luz PL et al. 1999. Exp. Pathol.

AORTA HISTOLOGIC EVALUATION Intima/Media Thickness Ratio Intima/Media Ratio (%) 80 60 40 20 0 Diet (n=9) Wine (n=8) NAPW (n=9) Da Luz PL et al.01: Diet vs Wine and NAPW Tukey’s Studentized Range (HSD) Test .65:150-9 Exp.65:150- * p = NS *p<0. Mol. Pathol. Exp. 1999. Pathol. 1999.

J Am Coll Cardiol 2003.M .001 ng art Wallerath T et al.C he fel ou ell on ab are -C sh ur va eg de ier ss o ne eim gu lie ch rav r ea t es nd rs au er u e er de Ro se *** p<0.41:471-8 en Co .C Sp Ch Ch Ch OH ieg ätb .eNOS Induction by Red Wine 500 eNOS mRNA level (% of control) German red wines Bordeaux Rhone Burgundy French red wines *** *** *** *** 450 400 350 300 250 200 150 100 50 0 *** *** Kr Et Do Ch Ch L.B .R rn .B .

Chevaliers eNOS β-Tub.eNOS Induction by Red Wine Ch. J Am Coll Cardiol 2003. Bonnet L. EtOHCo 1% 3% 10% EtOHCo 1% 3% 10% Wallerath T et al.41:471-8 .

Bonnet L. J Am Coll Cardiol 2003.eNOS Induction by Red Wine 450 * * p < 0.05 ** p < 0.01 ** * ** NO production (% of control) 400 350 300 250 200 150 100 50 0 EtOHCo 1% 3% 10% 1% 3% 10% Ch.41:471-8 . Chevaliers Wallerath T et al.

001 *** *** *** ** EtOHCo 1% 3% 10% 1% 3% 10% Ch. Chevaliers Wallerath T et al.41:471-8 .01 *** p < 0. J Am Coll Cardiol 2003.eNOS Induction by Red Wine eNOS promoter activity (% of control) 400 350 300 250 200 150 100 50 0 ** p < 0. Bonnet L.

41:471-8 . Chevaliers 10% Wallerath T et al. J Am Coll Cardiol 2003.eNOS Induction by Red Wine eNOS promoter activity (% of each control) 0 50 100 150 200 250 300 350 pGI3basic Luc -1600 +1 Luc -1111 +1 Luc -633 +1 Luc -326 +1 EtOH-Co L.

eNOS Induction by Red Wine 120 *** ** eNOS mRNA level (% of control) 100 ** p < 0. J Am Coll Cardiol 2003. Bonnet 10% EtOH-Co 20 0 0 12 24 36 Time (h) after actinomycin D treatment Wallerath T et al.01 *** p < 0.41:471-8 .001 80 *** 60 40 Ch.

910-6 . British J Pharmcol 2002:135.Flavonoid-rich Diets and Nitric Oxide in Rat Aorta 0 -20 Relaxation (%) -40 -60 -80 -100 Control Dealcoholated red wine -9 -8 -7 -6 -5 -4 -3 Ach (-log M) Benito S et al.

910-6 .Flavonoid-rich Diets and Nitric Oxide in Rat Aorta 1200 [NOS activity] (pmol citrulline (mg protein h)-1 150 * P<0.01 [-NO] (intensity units mg tissue) 200 ** ** * * * P<0.05 ** P<0.01 * * 800 100 400 50 0 0 Diet Control Dealcoholated red wine Quercetin Catechin Diet Benito S et al. British J Pharmcol 2002:135.

25:1593-1598 . Stroke 1994.Alcohol Consumption and Carotid Atherosclerosis: Evidence of DoseDependent Atherogenic Effects Results From the Bruneck Study Kiechl S et al.

0 1.a Current Alcohol Consumption 6.0 0.25:1593-1598 1994.0 Wine Other sources 2.0 age adjusted multivariate continuous alcohol variable b Type of Beverage Odds ratio ↑ 3. Stroke 1994.25:1593- .5 0 1-50 51-99 51- 100100- Alcohol consumption g/day g/day → 0 1-50 51-99 51- 100100- Alcohol consumption g/day g/day → Kiechl S et al.0 Odds ratio ↑ 3.0 1.0 2.5 0.

0 2.25:1593- .a Current Alcohol Consumption 6.0 age adjusted multivariate continuous alcohol variable b Type of Beverage Odds ratio ↑ 3.5 0 1-50 51-99 51- 100100- Alcohol consumption g/day g/day → 0 1-50 51-99 51- 100100- Alcohol consumption g/day g/day → Kiechl S et al. Stroke 1994.0 1.0 Odds ratio ↑ 3.5 0.0 Wine Other sources 2.25:1593-1598 1994.0 0.0 1.

0 1.c Current Alcohol Consumption Ex-Drinkers Excluded Odds ratio ↑ 3.0 age adjusted multivariate 2.25:1593-1598 1994.0 0.0 1.25:1593- .5 0 1-50 51-99 51100100g/day g/day → 0.0 2.5 -20 21-25 21- 26-30 26- 3131- Alcohol consumption Gamma-glutamyl transferase Gamma- U/L → Kiechl S et al. Stroke 1994.0 age adjusted multivariate d Gamma-Glutamyl Transferase Odds ratio ↑ 3.

Increases FMD . Increases eNOS production Benito et al Brit J Pharmacol 135:910-6.Flavonoid rich diet increases NO production in rat aorta . 2002 .

5 0 Morte Cardíaca IAM não Fatal 0. colesterol*. 99: 779 .37 0.5 1 0. Lipidios* 34% (12% saturados e 6% polinsaturados). proteínas .54 Morte não Cardíaca Logeril et al. fibras*. álcool . colesterol*.16 g 3 Eventos/ 100 pacientes-ano 2.36 0.312 mg.6 g.19 g.7 2.5 2 1. Circulation 1999. proteínas . Lipidios* 30% ( 8% saturados e 5% polinsaturados).17 g Calorias* 1947. fibras* .203 mg.Dieta Mediterrânea e Doença Isquêmica do Coração Lyon Diet Heart Study 5 anos Calorias* 2088.41 1. álcool .83 Controles n = 303 Experimental n = 302 0.6 g.16 g.

Circulation 1999. 99: 779 .5 anos Controles n = 303 Nível sangüíneo (mg/dl) 250 200 150 100 50 0 238.6 74.5 49.9 67.Lyon Diet Heart Study Perfil Lipídico .6 239.4 49.3 Experimental n = 302 175.5 174.9 Col Tot HDL LDL TG Logeril et al.

343:1454-1459 . Lancet 1994.Mortalily in Relation to Consumption of Alcohol: 13 Years’ Observations on Male British Doctors De Lorgeril M et al.

0-30.77-1.0 g/day relative risk (95 percent confidence interval) TICS score for worst 10% of distribution of decline Multivariate-adjusted Verbal memory score for worst 10% of distribution of decline Multivariate-adjusted Global cognitive score for worst 10% of distribution of decline Multivariate-adjusted 11.82 (0.00 0.661 1.89 (0.16) * TICS denotes the Telephne Interview for Cognitive Status ** Nondrinkers (51%) served as the reference group Stampfer MJ et al.83 (0.58-1.54-1.85 (0. According to Alcohol Intake Measure of Substantial Cognitive Decline* No.97) 0.72-0. NEJM 2005.Relative Risk of a Substantial Decline in Cognitive Function over a Two-Year Period.04 (0.98) 1.670 1.77-1.0-14. Who Completed Test None** Alcohol Intake 1.9 g/day 15.00 0.76 (0.09) 9.102 1.00 0.74-0.352:245-53 .03) 0.41) 9.

The Cardiovascular Health Study.32:1939-46 “↓ de anormalidade da substância ↓ branca e infartos cerebrais em bebedores moderados vs abstêmios” • Mukamal et al. idosos Mecanismos • Mukamal et al. Stroke 2001.289:1405-13 “pronunciada redução de demência vascular e Alzheimer entre pessoas que consumiam 1 a 6 drinks/semana” . JAMA 2003.Proteção da Função Cognitiva em Bebedores Moderados.

Effects of Red Wine upon SNS and Endothelial Function in Humans • 7 normal controls • 9 hypertensives • 10 hypercholesterolemics • Methods : Brachial artery reactivity by US.Thesis.Consolim-Colombo F.Krieger EM. 2006 . Sympathetic activity in the peroneal nerve Magalhães A. Da Luz PL.

PRE RW 27 burst/min 36 burst/min 27 burst/min POST RW 49 burst/min 63 burst/min 34 burst/min .Basal Ice test A HYPERTENSIVE man. 46 y. 40 y. PRE RW Muscular contraction 29 burst/min POST RW 46 burst/min 26 burst/min 43 burst/min 60 burst/min 37 burst/min B HYPERCHOLESTEROLEMIC man.

0 10. Krieger EM.Consolim-Colombo F.0 12. Da Luz PL.Thesis.0 6.0 Pre RW Post RW •BP was not altered Magalhães A.RED WINE & VASCULAR REACTIVITY IN HUMANS Brachial Artery FMD 20.0 18.0 16.0 10.05 * % Dilation 35.0 0. 2006 Dyslipidemia (10) Arterial Hypertension (9) Controls (7) .0 15.0 14.0 4.0 5.0 20.0 Flow Independent Dilation P=NS * P<0.0 2.0 25.0 8.0 % Dilation Pre RW Post RW 0.0 30.

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Republic of Korea .WCC 2006 6 Sep 2006 Green Tea Catechin Improves Endothelial Dysfunction by Increases Circulation Endothelial Progenitor Cells in Chronic Smokers W Kim. Gwangju Veterans Hospital. T Murohara. SH Cho. BS. MD Heart Center. MD. T Kondo. Chonnam National University Hospital Cardiovascular Department. MD. YK Ahn. BS. MH Jeong. Gwangju. MD. JH Yun. MD.

S. Sano et al. et al.68:665-70 . Duffy. et al. Heart 2004. • Short.104:151-156 • Green tea reverses endothelial dysfunction in healty smokers.and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. J. Nagaya.90:1485-6 • Green tea consumption was associated with low incidence of coronary artery disease in Japanese patients. Circulation 2001. 2004.Tea Green Tea Consumption improves FMD • Green tea is a free radical scavenger and has abundant catechin which exerts powerful antioxidant action. Circ J.

0001 9.34±2.25±2.4(%) 9.FMD Change Before and After Tx P<0.25± 7.34± 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 7.8(%) FMD Before T x After Tx .

3 .7 baseline to 169.2±35.The Effect of EPCs Count of Green Tea a Dil AcylLDL/FITC lectin double positive attaching cells(mean/10 field) b P<0.001 200 150 100 50 0 A B Before After C Before D After After two weeks consumption. EPCs number (Dil AcLDL/FITC-lectin double positive attaching cells) was significantly increased from 118.1±53.

Quantification of EPCs by FACS a a Before CD45lowCD34+VEGFR2+ cells(/200ul) After b b 200 150 100 50 0 c P<0.001 c Before After Dil-AcLDL/FITC-lectin double positive cells derived from CD45lowCD34+VEGFR2+ cells .

ICC .Miocardiopatias • Diabetes • Doenças hepáticas • Alcoolismo .Contra-Indicações ao uso de Vinho e/ou Bebidas Alcoólicas • Arritmias cardíacas • Disfunção ventricular .

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7 ger 29.4 ger 29. Nature 2003.3 ger Howitz et al.9 ger 21 ger 35.8 ger 39.Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan 19 ger 37. 425: 191-6 .

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Redução Mortalidade Estudos HALE, SENECA e FINE
Dieta Alcool Atividade Fisica Abs. Fumo

DAC

DCV

Cancer

Outras causas

Hazard ratio (%)

0 -10 -20 -30 -40 -50 -60
Knoops et al. JAMA 2004; 292: 1433-9

modulção gênica Aumento do tempo de vida outras intervenções (caloric restriction)

Bartke A et al. Nature, 2001

Satyanarayana e Rudolph - J Clin Invest, 2004

gramas 420 440 460 480 500 520 540 ve íc in i cia l ve íc fin al 1 m g/ kg in ici al 1 m g/ kg fin g 15 al g/ k in m Progressão do peso após 35 dias 15 m ici g/ k al g f in al .

Hidroperóxidos lipídicos no plasma 80 pmol/mg prot 60 40 20 0 veículo veic * * 1 mg/kg 1 mg/kg grupos 15 mg/kg mg/kg *p<0. veículo .05 15 mg/kg vs.

Grape Juice and Coronary Artery Disease 140 120 Mean Lag Time (min) 100 80 60 40 20 0 Baseline Grape Juice Stein JH et al.1050-5 . Circulation 1999:100.

15 mg/kg vs.GSH/GSSG 30 25 20 15 10 5 0 veículo 1 mg/kg grupos *p=0.03 .15 mg/kg vs.02 . 1 mg/kg * 15 mg/kg . Veículo *p=0.

343:1454-1459 .Mortalily in Relation to Consumption of Alcohol: 13 Years’ Observations on Male British Doctors De Lorgeril M et al. Lancet 1994.

102:1020-1026 6 . Circulation 2000.Red Wine Intake Prevents NF-κB Activation κ 350 300 250 * * % vs Basal 200 150 100 50 * * * No Wine Low Dose Full Dose Vodka 0 ho ur s ho ur s ho ur s ho ur s 9 0 3 Blanco-Colio LM et al.

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0 4.0 Flow Independent Dilation P=NS * P<0.Thesis. 2006 Dyslipidemia (10) Arterial Hypertension (9) Controls (7) .0 8.0 16.05 * % Dilation 35.0 % Dilation Pre RW Post RW 0.0 15.0 25.0 18.0 Pre RW Post RW •BP was not altered Magalhães A.0 12.0 10.0 10.0 20.0 5.Consolim-Colombo F.0 2.0 30.RED WINE & VASCULAR REACTIVITY IN HUMANS Brachial Artery FMD 20.0 0.0 6. Da Luz PL. Krieger EM.0 14.

Diabetes Care 2000.57:53-60 . Am J Epidemiol 1999:149:106-15 JM e col.Hiperplasia Prostática Benigna 8 1 Obsisesan 2 Orgajazo 3 4 5 TO e col.Estrógeno 6 .Diabetes Mellitus 4.153:185-92 Truelsen T e col.12:1300-11 Wei M e col. Rev Neurol 1997.8:420-4 EA e col.23:18-22 8 Paltz De Vegt F e col. J Am Geriatr Soc 1998.5 .Úlcera Duodenal 7 . Neurology 2002.16:1-7 6 7 Ghem BD e col. Diabetes Research and Clinical Practice 2002. Proc Natl Acad Sci USA 1997.Demência 3 .94:1438-43 Aldoorl WH e col.Doença de Alzheimer 2 . Epidemiology 1997.AÇÕES NÃO CARDIACAS DO VINHO .Degeneração macular senil 1 .

03) 0.76 (0.00 0.54-1.89 (0.97) 0. NEJM 2005.77-1.04 (0.670 1. Who Completed Test None** Alcohol Intake 1.102 1.00 0.98) 1.09) 9.0-30. According to Alcohol Intake Measure of Substantial Cognitive Decline* No.0-14.352:245-53 .74-0.77-1.Relative Risk of a Substantial Decline in Cognitive Function over a Two-Year Period.9 g/day 15.72-0.16) * TICS denotes the Telephne Interview for Cognitive Status ** Nondrinkers (51%) served as the reference group Stampfer MJ et al.661 1.41) 9.83 (0.58-1.85 (0.00 0.0 g/day relative risk (95 percent confidence interval) TICS score for worst 10% of distribution of decline Multivariate-adjusted Verbal memory score for worst 10% of distribution of decline Multivariate-adjusted Global cognitive score for worst 10% of distribution of decline Multivariate-adjusted 11.82 (0.

0 1.0 0.0 .9 g of alcohol/day Worst 10% for verbal memory score Worst 10% for global cognitive score 0.6 1.4 1.0 Multivariate Relative Risk of Cognitive Impairment TICS = denotes the Telephone Interview for Cognitive Status Stampfer MJ et al. NEJM 2005.352:245-53 .2 1.0 .0 g of alcohol/day 1.8 1.6 0.8 2.2 0.Effects of Moderate Alcohol Consumption on Cognitive Function in Women TICS score < 31 15.14.30.4 0.

289:1405-13 “pronunciada redução de demência vascular e Alzheimer entre pessoas que consumiam 1 a 6 drinks/semana” . idosos Mecanismos • Mukamal et al.Proteção da Função Cognitiva em Bebedores Moderados.32:1939-46 “↓ de anormalidade da substância ↓ branca e infartos cerebrais em bebedores moderados vs abstêmios” • Mukamal et al. Stroke 2001. The Cardiovascular Health Study. JAMA 2003.

32:1939-46. ↑ ↓ fibrinogênio e outros fatores trombóticos) • preservação da vasculatura cerebral • ↓ AVCs subclínicos (Mukamal et al.289:1405-13) .Proteção da Função Cognitiva em Bebedores Moderados. Mukamal et al. JAMA 2003. Idosos Mecanismos • ↓ eventos cardiovasculares (↑ HDL. The Cardiovascular Health Study. Stroke 2001.

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102:1020-1026 . Circulation 2000.Red Wine Intake Prevents NF-κB Activation in κ Peripheral Blood Mononuclear Cells of Healthy Volunteers During Postprandial Lipemia • 16 voluntários normais • Café da manhã enriquecido com gordura: 602 kcal/m².8% como gordura) • 140 kcal/m² de vinho (dose moderada) • 84 kcal/m² de vinho (dose baixa) Blanco-Colio LM et al. com 342 kcal/m² (56.

102:1020-1026 .Red Wine Intake Prevents NF-κB Activation κ Blanco-Colio LM et al. Circulation 2000.

J Am Coll Cardiol 2003.05 ** p<0.001 100 0 12 24 36 48 60 10 d Incubation time (h) Wallerath T et al.01 *** p<0.41:471-8 . *** *** *** ** eNOS mRNA level (% of control) 180 1% 160 *** ** * * * * * 140 120 * P<0. Bonnet Ch.eNOS Induction by Red Wine 200 10% 3% Ch.

2 0 -0.8 0.6 0. JACC 2007.2 -60 0 60 120 180 240 300 360 ∆ glucose (mmol/L) wine Drinks per Day O’Keefe JH et al.Wine With Meal Reduced Postprandial Glucose 0.50:1009-14 .4 0.

00 2. JACC 2007.00 All Subjects 0.50:1009-14 .3/mo 1-4/wk 5-7/wk >2/d Numbers of Drinks O’Keefe JH et al.00 1. mg/L 2.5 0.50 CRP.0 Primary Prevention Secondary Prevention No alcohol/ < 1/mo 1.Alcohol and CRP Levels 3.50 1.

J Biochem.143:179-186 .VINHO TINTO E RESVERATROL CÉLULAS PROGENITORAS ENDOTELIAIS Balestrieri et al. 2008.

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.

Cell 2008.133:387-91 .Xenohormesis: Sensing the Chemical Cues of Other Species Howitz KT and Sinclair DA.

Cell 2008.133:387-91 .Direct Modulation of Key Mammalian Enzymes by Plant Metabolites Howitz KT and Sinclair DA.

2008.VINHO TINTO E RESVERATROL CÉLULAS PROGENITORAS ENDOTELIAIS Balestrieri et al. J Biochem.143:179-186 .

CRP and Fibrinogen * P = 0.001 Sierksma A et al. European J Clin Nutr 2002.02 * P ≤ 0.56:1130-6 .Alcohol Consumption.

FMUSP ⇒* Não há conflitos de interesse ( não sou abstêmio. nem alcoólatra !) .63°Congresso Brasileiro de Cardiologia Curitiba.2008 Controvérsia.9. 9. Divisão de Cardiologia Clínica INCOR. da Luz Diretor.HC.Agonista USO MODERADO DE VINHO TINTO É BENÉFICO NA PREVENÇÃO DA ATEROSCLEROSE Dr. Protásio L.

Contra-Indicações ao uso de Vinho e/ou Bebidas Alcoólicas • Arritmias cardíacas • Disfunção ventricular . Miocardiopatias • Diabetes descompensada • Doenças hepáticas • Alcoolismo • Adolescentes • Hipertrigliceridemia .ICC.

5 0.4 4.6 0.6 1.0.0 0.0 1.5 -1.5 1.Alcohol and Stroke Risk OR LOG 7.50:1009-14 .7 1.0 .0 0 1 2 3 4 5 6 7 Drinks per Day O’Keefe JH et al. JACC 2007.5 2.0 0.4 2.

2 0 Non-drinkers 1 Drink/d 2 Drinks/d > 2 Drinks/d O’Keefe JH et al.4 1.0 0.50:1009-14 .Alcohol and Coronary Calcium Odds ratio For Severe Coronary Calcification 1.6 0.4 0.2 1.8 0. JACC 2007.

Mecanismos de Ação do Vinho Tinto • • • • • • • • ↑ HDL ↓ agregação plaquetária ↓ expressão de NF-κB e síntese de ET1 κ ↑ vasodilatação art.: flavonóides (quercetina. apigenina. endotélio dependente (↑eNOS) ↑ anti-oxidante (?!) anti-inflamatório ↑ cels. resveratrol e outros) parecem ser os elementos químicos fundamentais . progenitoras endoteliais ↑ sensibilidade à insulina Obs.

Neurology 2002.153:185-92 Truelsen T e col. Am J Epidemiol 1999:149:106-15 JM e col. Proc Natl Acad Sci USA 1997.Demência 3 .16:1-7 6 7 Ghem BD e col.Doença de Alzheimer 2 .57:53-60 .5 . Diabetes Care 2000.Estrógeno 6 .94:1438-43 Aldoorl WH e col. J Am Geriatr Soc 1998.AÇÕES NÃO CARDIACAS DO VINHO .Degeneração macular senil 1 .8:420-4 EA e col.Diabetes Mellitus 4.12:1300-11 Wei M e col. Epidemiology 1997. Diabetes Research and Clinical Practice 2002.23:18-22 8 Paltz De Vegt F e col.Úlcera Duodenal 7 . Rev Neurol 1997.Hiperplasia Prostática Benigna 8 1 Obsisesan 2 Orgajazo 3 4 5 TO e col.

72-0.0 g/day relative risk (95 percent confidence interval) TICS score for worst 10% of distribution of decline Multivariate-adjusted Verbal memory score for worst 10% of distribution of decline Multivariate-adjusted Global cognitive score for worst 10% of distribution of decline Multivariate-adjusted 11.9 g/day 15.54-1.77-1.00 0.98) 1.77-1.102 1.00 0.661 1. NEJM 2005.97) 0.76 (0.04 (0.83 (0.41) 9.85 (0.16) * TICS denotes the Telephne Interview for Cognitive Status ** Nondrinkers (51%) served as the reference group Stampfer MJ et al.03) 0. According to Alcohol Intake Measure of Substantial Cognitive Decline* No. Who Completed Test None** Alcohol Intake 1.89 (0.09) 9.0-14.58-1.352:245-53 .82 (0.Relative Risk of a Substantial Decline in Cognitive Function over a Two-Year Period.0-30.00 0.74-0.670 1.

Effects of Moderate Alcohol Consumption on Cognitive Function in Women
TICS score < 31
15.0 - 30.0 g of alcohol/day 1.0 - 14.9 g of alcohol/day

Worst 10% for verbal memory score

Worst 10% for global cognitive score

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

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Multivariate Relative Risk of Cognitive Impairment
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Stampfer MJ et al. NEJM 2005;352:245-53

Proteção da Função Cognitiva em Bebedores Moderados, idosos Mecanismos
• Mukamal et al, The Cardiovascular Health
Study, Stroke 2001;32:1939-46

“↓ de anormalidade da substância ↓ branca e infartos cerebrais em bebedores moderados vs abstêmios” • Mukamal et al, JAMA 2003;289:1405-13 “pronunciada redução de demência vascular e Alzheimer entre pessoas que consumiam 1 a 6 drinks/semana”

Proteção da Função Cognitiva em Bebedores Moderados, Idosos Mecanismos
• ↓ eventos cardiovasculares (↑ HDL; ↑ ↓ fibrinogênio e outros fatores trombóticos) • preservação da vasculatura cerebral • ↓ AVCs subclínicos
(Mukamal et al. The Cardiovascular Health Study, Stroke 2001;32:1939-46. Mukamal et al, JAMA 2003;289:1405-13)

143:179-186 . J Biochem. 2008.VINHO TINTO E RESVERATROL CÉLULAS PROGENITORAS ENDOTELIAIS Balestrieri et al.

Mecanismos de Ação do Vinho Tinto • • • • • • • • ↑ HDL ↓ agregação plaquetária ↓ expressão de NF-κB e síntese de ET1 κ ↑ vasodilatação art. apigenina. progenitoras endoteliais ↑ sensibilidade à insulina Obs. endotélio dependente (↑eNOS) ↑ anti-oxidante (?!) anti-inflamatório ↑ cels. resveratrol e outros) parecem ser os elementos químicos fundamentais .: flavonóides (quercetina.

.

men • 1 drink / day . JACC 2007.50:1009-14 .Cardioprotective Alcohol Intake is: • 1-2 drinks / day .women • 1 drink = ± 15g alcohol O’Keefe JH et al.

www.nationalgeographicbr.com.br .

com.Como Eles Conseguem Viver Tanto SARDOS Bebem vinho tinto (com moderação) Compartilham com o cônjuge o trabalho Comem queijo pecorino (e outros alimentos ricos em ômega-3) ADVENTISTAS Comem nozes e feijões Guardam o sábado Têm fé TODOS Não fumam Priorizam a família Fazem atividades físicas Têm vida social Comem frutas. verduras e grâos integrais OKINAWANOS Mantêm amigos para toda a vida Comem porções pequenas Encontram sentido na vida www.br .nationalgeographicbr.

both 24.A Tale of Two Monkeys Rhesus Monkeys at Wisconsin Primate Research Center. show effects of two regimens. ULTRA-LEAN DIET This handsome fellow has lower glucose and insulin levels-and looks younger. NORMAL FARE This monkey has higher triglycerides and more oxidative damage to his cells. too. .

Nature. 2003 .Restrição calórica PNC1 Sir/SIRT Resveratrol atividade deacetilase NAD+ nicotinamida + Ο-acetil-ADP-ribose -estabilidade do DNA -reparo no DNA -silenciamento transcricional -regulação da p53 sobrevida Howitz KT et al.

Valenzano DR et al. 2006 . Curr. Dev Cell.20% .Wood LG et al. 2003 18% -Viswanathan M et al. Biol. 2005 16 . Nature.Resveratrol e sobrevida em diferentes espécies 70% . 2004 59% . 2006 Baur JA et al Nature.Wood JG et al. Nature.

Lancet 1994.343:1454-1459 .Mortalily in Relation to Consumption of Alcohol: 13 Years’ Observations on Male British Doctors De Lorgeril M et al.

HITLER ERA ABSTÊMIO ! .

102:1020-1026 . com 342 kcal/m² (56.8% como gordura) • 140 kcal/m² de vinho (dose moderada) • 84 kcal/m² de vinho (dose baixa) Blanco-Colio LM et al.Red Wine Intake Prevents NF-κB Activation in κ Peripheral Blood Mononuclear Cells of Healthy Volunteers During Postprandial Lipemia • 16 voluntários normais • Café da manhã enriquecido com gordura: 602 kcal/m². Circulation 2000.

102:1020-1026 .Red Wine Intake Prevents NF-κB Activation κ Blanco-Colio LM et al. Circulation 2000.

05 ** p<0. J Am Coll Cardiol 2003. Bonnet Ch. *** *** *** ** eNOS mRNA level (% of control) 180 1% 160 *** ** * * * * * 140 120 * P<0.41:471-8 .01 *** p<0.eNOS Induction by Red Wine 200 10% 3% Ch.001 100 0 12 24 36 48 60 10 d Incubation time (h) Wallerath T et al.

50:1009-14 . JACC 2007.6 0.2 0 -0.2 -60 0 60 120 180 240 300 360 ∆ glucose (mmol/L) wine Drinks per Day O’Keefe JH et al.4 0.Wine With Meal Reduced Postprandial Glucose 0.8 0.

5 0.50:1009-14 .00 2.00 All Subjects 0.50 1. JACC 2007.00 1.Alcohol and CRP Levels 3.50 CRP.0 Primary Prevention Secondary Prevention No alcohol/ < 1/mo 1.3/mo 1-4/wk 5-7/wk >2/d Numbers of Drinks O’Keefe JH et al. mg/L 2.

J Am Coll Cardiol 2003.Red Wine Increases the Expression of Human Endothelial Nitric Oxide Synthase A Mechanism That May Contribute to its Beneficial Cardiovascular Effects Wallerath T et al.41:471-8 .