The health effects of moderate wine consumption

Transcription

1 The health effects of moderate wine consumption Sabina Passamonti Department of Life Sciences 1

2 The problem with wine drinking Wine contains a drug named alcohol (12%) This drug causes first pleasure, then harm Pleasure causes psychological and physical dependence ALCOLISM Pleasure is sought at any cost: excess drinking 2

3 The problem with wine drinking According to the World Health Organization, ALCOL KILLS approximately 2.5 million people each year worldwide, causing 4% of all deaths - more than violence, AIDS, or tuberculosis. 3

4 The problem with wine drinking Wine is freely accessible and consumed a good business PUBLIC HEALTH CONCERN What advice should be given? Should the wine economy be closed and replaced? Is there any hidden effect on health due to habitual wine drinking? 4

5 The problem with wine drinking PUBLIC HEALTH CONCERN addressed by PUBLIC FUNDED RESEARCH WORLDWIDE 5

6 The problem with wine drinking THE POISON Economic cost > $ 234 billions/yr in USA The harmful use of alcohol is the world s leading risk factor for death among males (15-59 years), mainly due to: accidents, injuries, violence, cardiovascular diseases, cirrhosis, seizures, stroke, poisonings, many cancers. THE REMEDY Economic gain (to be calculated) Light to moderate drinking ensures substantial reductions of: cardiovascular disease, diabetes mellitus, stroke, and total mortality. 6

7 Alcohol as a poison, though there are exceptions check below 7

8 The unexpect effect of alcohol drinks on mortality A remedy only if A Drink A Day Tikves Expert Conference "Value of Wine" 8 1 drink = 14 g of ethanol 360 ml beer 150 ml wine 45 ml spirit Copyright 2014 Mayo Foundation for Medical Education and Research Terms and Conditions Mayo Clinic Proceedings , DOI: ( /j.mayocp )

9 Lower risk of mortality is due in part to less cardiovascular diseases G. Corrao et al. / Preventive Medicine 38 (2004) block of coronary arteries myocardial infarction Coronary heart disease is decreased by 2 small glasses of wine (20 g ethanol) every day. This beneficial effect is lost by 5-6 small glasses of wine (72-89 g) 9

10 Figure 4 Less risk of myocardial infarction by 1-2 drinks a day 10 Mayo Clinic Proceedings , DOI: ( /j.mayocp ) Copyright 2014 Mayo Foundation for Medical Education and Research Terms and Conditions

11 Figure 7 Less risk of ischemic stroke by 2-4 drinks a day block of brain arteries stroke Stroke is decreased by 2-3 drinks of wine every day. This beneficial effect is lost by doubling the daily drinks. Mayo Clinic Proceedings , DOI: ( /j.mayocp ) Copyright 2014 Mayo Foundation for Medical Education and Research Terms and Conditions 11

12 Figure 6 Less risk of hypertension by 1 drink a day Stifness of arteries hypertension arterial injury coronary disease heart attack, stroke, etc. Hypertension is decreased by 1 small glasses of RED wine every day. This beneficial effect is not seen with WHITE wine. Mayo Clinic Proceedings , DOI: ( /j.mayocp ) Copyright 2014 Mayo Foundation for Medical Education and Research Terms and Conditions 12

13 What is the magic in wine? Alcohol or not alcohol? From epidemiological studies to experimental studies From observations to explanations My work within my network 13

14 In isolated aortic rings, anthocyanins cause relaxation, thus more blood is delivered Red Wine Polyphenols Mix of pure anthocyanins Single pure anthocyanin Work done at the University of Strasbourg (France) and Ljubljana (Slovenia) Relaxation is reduced if polyphenols/anthocyanins cannot enter into the cells lining the inner aortic ring (vascular endothelial cells) Special reagent provided by my lab 14

15 Is cyanidin 3-glucoside cardioprotective? Test in the isolated, ischemic rat heart 1. explantation 2. adaptation out of the body, perfusion with oxygen 3. ischemia (no oxygen) 4. reperfusion with oxygen This simulates a heart attack / myocardial infarction Let s see if a wine pigment protects the heart Ziberna L, Tramer F, Moze S, Vrhovsek U, Mattivi F, Passamonti S. Transport and bioactivity of cyanidin 3-glucoside into the vascular endothelium. Free Radic Biol Med May 1;52(9):

16 LDH is a marker of myocardial cell death. It is released by the ischemic heart. However, cyanidin 3-glucoside prevents cell death. Co, control ( ); Ab ( ), pre-incubated bilitranslocase antibody C3G (1 µmol/l) + Ab ( ) C3G (1 µmol/l, ; 10 µmol/l, ) after explantation, adaptation phase reperfusion phase 16

17 Cyanidin 3-glucoside protects against ischemic arrythmia 17

18 Figure drinks/day reduces the risk of developing diabetes Mayo Clinic Proceedings , DOI: ( /j.mayocp ) Copyright 2014 Mayo Foundation for Medical Education and Research Terms and Conditions

19 In diabetic subjects, no grounds to discourage mild to moderate alcohol consumption. adjusted hazard ratio in diabetic subjects 1 0,8 0,6 0,4 0,83 0,85 0,87 0,2 0 cardiovascular events microvascular complications all-cause mortality Data from: Blomster et al. The Relationship Between Alcohol Consumption and Vascular Complications and Mortality in Individuals With Type 2 Diabetes. Diabetes Care 2014;37:

20 Health risk in late years Dementia confusion, loss of memory, troubles in carrying out normal tasks, 20

21 Percent of people with signs of dementia in OECD countries 21

22 Some cardiovascular drugs might cause dementia 22

23 WHAT DIET DOES PROTECT AGAINST SENILE DEMENTIA? Study on elderly in two provinces of South-East of France 23

24 Scores of cognitive tests decline with age, though less if diet is rich in fruits and vegetables 24

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26 Relative risk Does wine cause dementia? 1,2 1 0,8 0,6 Rischio demenza 0,4 Rischio morbo di Alzheimer 0,2 0 nessuno 1 o 2 3 o 4 più di 4 Wine drinks/day 26

27 Review of 143 studies that described the relationship between moderate drinking of alcohol and some aspect of cognition Light to moderate drinking: 1. Does not impair cognition in younger subject. 2. Reduce the risk of dementia and cognitive decline in older subjects. Moderate alcohol consumption and cognitive risk. Neafsey EJ, Collins MA. Neuropsychiatr Dis Treat. 2011;7:

28 Cognitive decline is reduced by other life-style factors Relative risk of cognitive decline - dementia 1 0,8 0,6 0,4 0,77 0,6 0,84 0,64 0,2 0 Moderate alcohol drinking Mediterranean diet Education, intellectual life Gardening Data found in: Moderate alcohol consumption and cognitive risk. Neafsey EJ, Collins MA. Neuropsychiatr Dis Treat. 2011;7: Thus, the effect is not strange 28

29 Wine and mind 1. Dorozynski, A. (1997) Wine may prevent dementia. BMJ 314, Larrieu, S., Letenneur, L., Helmer, C., Dartigues, J. F., and Barberger-Gateau, P. (2004) Nutritional factors and risk of incident dementia in the PAQUID longitudinal cohort. J. Nutr. Health Aging 8, Lindsay, J., Laurin, D., Verreault, R., Hebert, R., Helliwell, B., Hill, G. B., and McDowell, I. (2002) Risk factors for Alzheimer s disease: a prospective analysis from the Canadian Study of Health and Aging. Am. J. Epidemiol. 156, Luchsinger, J. A., Tang, M. X., Siddiqui, M., Shea, S., and Mayeux, R. (2004) Alcohol intake and risk of dementia. J. Am. Geriatr. Soc. 52, Orgogozo, J. M., Dartigues, J. F., Lafont, S., Letenneur, L., Commenges, D., Salamon, R., Renaud, S., and Breteler, M. B. (1997) Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev. Neurol. (Paris) 153, Truelsen, T., Thudium, D., and Gronbaek, M. (2002) Amount and type of alcohol and risk of dementia: the Copenhagen City Heart Study. Neurology 59, Wang, J., Ho, L., Zhao, Z., Seror, I., Humala, N., Dickstein, D. L., Thiyagarajan, M., Percival, S. S., Talcott, S. T., and Pasinetti, G. M. (2006) Moderate consumption of Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer s disease. FASEB J. 20, Pasinetti GM. Novel role of red wine-derived polyphenols in the prevention of Alzheimer's disease dementia and brain pathology: experimental approaches and clinical implications. Planta Med Oct;78(15): Tikves Expert Conference "Value of Wine" 29

30 Some wine polyphenols HO O + O O HO HO O O O HO O O O O O O Cyanidin 3-glucoside catechin gallate rutin 30

31 Anthocyanins are neuroprotective 1: Badshah H, Kim TH, Kim MO. Protective effects of anthocyanins against amyloid beta-induced neurotoxicity in vivo and in vitro. Neurochem Int Jan;80:51-9. doi: /j.neuint Epub 2014 Nov 10. PubMed PMID: : Shah SA, Yoon GH, Kim MO. Protection of the developing brain with anthocyanins against ethanol-induced oxidative stress and neurodegeneration. Mol Neurobiol. 2015;51(3): doi: /s Epub 2014 Jul 6. PubMed PMID: :Ullah I, Park HY, Kim MO. Anthocyanins protect against kainic acid-induced excitotoxicity and apoptosis via ROS-activated AMPK pathway in hippocampal neurons. CNS Neurosci Ther Apr;20(4): doi: /cns Epub 2014 Jan 7. PubMed PMID: and other 20 research papers (not listed here) 31

32 Do anthocyanins reach the brain? The brain is very protected 98% of compounds found in blood do not enter the brain 32

33 Wine polyphenols must pass the blood-brain barrier 33

34 Test in anaesthetised rats A mix of anthocynins is given in the stomach. 10 min later, anthocyanins are found in the brain of most animals Anthocyanins in plasma and brain Subject #10 #11 #13 #8 #12 #4 #6 #1 #5 #9 #2 #3 #7 #10 #11 #13 #8 #12 #4 #6 #1 #5 #9 #2 #3 #7 Subject Plasma anthocyanins (ng/ml) Brain anthocyanins (ng/g) Total anthocyanins Malvidin 3-glucoside Malvidin 3-(6-O-p-coumaroyl)-glucoside Passamonti, S., Vrhovsek, U., Vanzo, A. & Mattivi, F. Fast access of some grape pigments to the brain. J Agric Food Chem 53, , /jf050565k (2005). 34

35 Refined test Let s see how much of cyanidin 3-glucoside in the blood can cross the barrier and go to the brain Rapid distribution of C3G in the brain, with an apparently constant plasma/brain ratio in the physiologically relevant plasma concentration range ( nm). Fornasaro, S. et al. Determination of cyanidin 3-glucoside in rat brain, liver and kidneys by UPLC/MS-MS and its application to a short-term pharmacokinetic study. Sci. Rep. 6,

36 Most wine polyphenols are not absorbed in the intestine HO O + O HO O they stay in the colon and are cut in molecular fragments 36

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38 Some of these fragments can reach the brain Gasperotti, M. et al. Fate of Microbial Metabolites of Dietary Polyphenols in Rats: Is the Brain Their Target Destination? ACS chem Neurosci 6, and they help neurons grow better 38

39 CONCLUSIONS There is reasonable unanimity in beneficial effects of moderate wine consumption in cardiovascular disease, diabetes, osteoporosis, maybe neurological diseases, and longevity. Maturitas Jan;80(1):3-13. The idea of a total prohibition of alcohol consumption (including moderate consumption with meals) appears over dimensioned, poorly feasible and scientifically not sound. Nutrition, Metabolism & Cardiovascular Diseases (2014) 24, e2-e26 39

40 благодарение THANK YOU FOR YOUR ATTENTION 40

41 Thanks to all my co-authors and collaborators Agricultural Institute of Slovenia Andreja Vanzo, Klemen Lisjak Agricultural Institute of San Michele all Adige (Italy) Fulvio Mattivi, Urska Vrhovsek University of Ljubljana, Faculty of Medicine, Institute of Pharmacology Lovro Ziberna University of Trieste (Italy), Federica Tramer, Stefano Fornasaro, and many young researchers Trans2Care network ( Agrotur network ( 41