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The "French paradox" and beyond: neuroprotective effects of polyphenols(1,2).
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Living On previous occassion we were the first website to disseminate information reviews on wine and health research to our customers. In an attempt to re-invent this tradition we are continuing a monthly literature review. It is our intent to keep winemakers up to date on the latest developments in health. Specifically, we wish to provide a down to earth iteration of medical research abstracts and corroborate news headlines in relation to wine and health. This section is written and maintained by Dr. Oliver Trochta who practices in Hamilton, Grimsby and Thorold Ontario. Moderate Alcohol Consumption Has Beneficial Glycemic Effects Kroenke CH, Chu NF, Rifai N, Spiegelman D, Hankinson SE, Manson JE, Rimm EB. Diabetes Care 2003; July; 26:1971-1978. OBJECTIVE: Little research has explored associations of drinking patterns with glycemic control, especially among women. Our objective was to determine the relationship of patterns of alcohol consumption-including average daily consumption, weekly frequency of consumption, drinking with meals, and beverage type-with biologic markers of insulin resistance in young women. RESEARCH DESIGN AND METHODS: This study was cross-sectional in design. The subjects consisted of a stratified random subpopulation of 459 U.S. normal-weight and overweight female nurses, 33-50 years of age, drawn from the Nurses' Health Study II and sampled for distinct drinking patterns. Women provided blood samples and detailed information on dietary and lifestyle factors between 1995 and 1999. The main outcome measures were fasting insulin, C-peptide, and HbA(1c). RESULTS: Adjusting for age, smoking, physical activity, television watching, BMI, and several dietary factors, average alcohol intake was inversely associated with HbA(1c) (units in percentage of HbA(1c)): 0 g/day (reference = 5.36%), 0.1 to <5.0 g/day (-0.04%), 5.0 to <15.0 g/day (-0.09%), 15.0 to <25.0 g/day (-0.10%), and > or =25.0 g/day (-0.17%) (P value, test for trend <0.001). We found an inverse association of alcohol intake and insulin, but only for women with a BMI > or =25 kg/m(2). Specifically, insulin levels were lowest for episodic drinkers consuming > or =2 drinks per day on 0-3 days per week. Consumption with meals and type of alcoholic beverage did not further influence these results. CONCLUSIONS: Moderate alcohol consumption of 1-2 drinks per day on a few to several days of the week may have a beneficial glycemic effect, particularly among overweight women. What this means Molecular evidence for the cardioprotective effects of wine are mounting. The researchers in this study have found in vivo evidence that in human female subjects there is a positive effect on human insulin levels. Through the use of detailed questionnaires, the researchers were able to assess several factors that play a role in blood sugar levels and their control. The authors found that even in the presence of obesity, there was a relationship that indicated that more than one drink per day decreased insuling levels in women with a body mass index (BMI) greater than 25. In short they go on to state that 1-2 drinks per day may help over-weight women with blood sugar control. Although this is a fascinating study in humans with a large number of participants and a relatively good design it is not meant to take the place of advice from your doctor. Be sure to check with your primary care provider before trying to modulate your blood sugar with alcohol if you are currently taking insulin or medication to control diabetes. Microbial aromatic acid metabolites formed in the gut account for a major fraction of the polyphenols excreted in urine of rats fed red wine polyphenols. Gonthier MP, Cheynier V, Donovan JL, Manach C, Morand C, Mila I, Lapierre C, Remesy C, Scalbert A. J Nutr 2003 Feb;133(2):461-7 The health effects of dietary polyphenols might be explained by both intact compounds and their metabolites formed either in the tissues or in the colon by the microflora. The quantitative importance and biological activities of the microbial metabolites have seldom been examined in vivo. We measured the microbial metabolites formed in four groups of rats (n = 8) fed for 8 d a diet supplemented with 0.12 g/100 g catechin, 0.25 or 0.50 g/100 g red wine powder containing proanthocyanidins, phenolic acids, flavanols, anthocyanins and flavonols or an unsupplemented diet. Fourteen aromatic acid metabolites were assayed in urine collected for 24 h by an HPLC-electrospray ionization (ESI)-mass spectrometry (MS)-MS method. The three main metabolites formed from the catechin diet were 3-hydroxyphenylpropionic acid, 3-hydroxybenzoic acid and 3-hydroxyhippuric acid. Their total urinary excretion accounted for 4.7 g/100 g of the catechin ingested and that of intact catechins for 45.3 g/100 g. For wine polyphenols, the same microbial metabolites as observed for the catechin diet were identified in urine along with hippuric, p-coumaric, vanillic, 4-hydroxybenzoic and 3-hydroxyphenylacetic acids. All together, these aromatic acids accounted for 9.2 g/100 g of the total wine polyphenols ingested and intact catechins for only 1.2 g/100 g. The higher excretion of aromatic acids by rats fed wine polyphenols is likely due to their poor absorption in the proximal part of the gut. Some of the microbial metabolites still bear a reducing phenolic group and should also prevent oxidative stress in inner tissues. More attention should be given in the future to these microbial metabolites and their biological properties to help explain the health effects of polyphenols that are not easily absorbed through the gut barrier. What this means Molecular evidence for the cardioprotective effects of wine are mounting. The researchers in this study have found in vivo evidence that in the animal model, not all polyphenolic compounds are easily absorbed by the small intestine. In fact previous work done has shown that gut microflora, (bacterial species present in our digestive tract), may aid in improving wine's protective effects on the human body. The authors fed rats a specific diet to assess the total urinary output of phenolic compounds. The researchers found that metabolites from the rat's gut microflora may protect the rat from further oxidative stress. In conclusion, it may not only be the alcohol and anthocyanins (color components of the wine) that are carried into the blood stream directly that protect consumers it may also be metabolites produced in the gut that aid the body fight damage from day to day stress. Cardioprotection with Alcohol Role of Both Alcohol and Polyphenolic Antioxidants MOTOAKI SATO, NILANJANA MAULIK and DIPAK K. DAS Annals of the New York Academy of Sciences 957:122-135 (2002) Both epidemiological and experimental studies indicate that mild-to-moderate alcohol consumption is associated with a reduced incidence of mortality and morbidity from coronary heart disease. The consumption of wine, particularly red wine, imparts a greater benefit in the prevention of coronary heart disease than the consumption of other alcoholic beverages. The cardioprotective effects of red wine have been attributed to several polyphenolic antioxidants including resveratrol and proanthocyanidins. The results of our study documented that the polyphenolic antioxidants present in red wine, for example, resveratrol and proanthocyanidins, provide cardioprotection by their ability to function as in vivo antioxidants while its alcoholic component or alcohol by itself imparts cardioprotection by adapting the hearts to oxidative stress. Moderate alcohol consumption induced significant amount of oxidative stress to the hearts which was then translated into the induction of the expression of several cardioprotective oxidative stress-inducible proteins including heat shock protein (HSP) 70. Feeding the rats with red wine extract or its polyphenolic antioxidants as well as alcohol resulted in the improvement of postischemic ventricular function. Additionally, both wine and alcohol triggered a signal transduction cascade by reducing proapoptotic transcription factors and genes such as JNK-1 and c-Jun thereby potentiating an anti-death signal. This resulted in the reduction of myocardial infarct size and cardiomyocyte apoptosis. The results, thus, indicate that although both wine and alcohol alone reduce myocardial ischemic reperfusion injury, the mechanisms of cardioprotection differ from each other. What this means Molecular evidence for the cardioprotective effects of wine are mounting. The researchers in this study have found in vivo evidence that it is the synergy of the alcohol and antioxident molecules in red wine that help protect the heart. By measuring certain biomarkers of heart disease and heart damage they could see fewer cells dying in vitro (in the cell culture dish). The researchers also determined that alcohol and the antioxidant molecules worked in different ways. Health: Endothelin-1 synthesis reduced by red wine ROGER CORDER, JULIE A. DOUTHWAITE, DELPHINE M. LEES, NOORAFZA Q. KHAN, ANA CAROLINA VISEU DOS SANTOS, ELIZABETH G. WOOD & MARTIN J. CARRIER Nature 2001 Dec 20/27;414:863-864 Statistical evidence of reduced coronary heart disease in areas of high wine consumption has led to the widespread belief that wine affords a protective effect. Although moderate drinking of any alcohol helps to reduce the incidence of coronary heart disease, there is no clear evidence that red wine confers an additional benefit. Here we show that red wines strongly inhibit the synthesis of endothelin-1, a vasoactive peptide that is crucial in the development of coronary atherosclerosis. Our findings indicate that components specific to red wine may help to prevent coronary heart disease. What this means UK researchers have zeroed in on compounds in red wine that battle a protein linked to heart disease -- a finding that provides clues to why the French have relatively low rates of heart disease despite a national diet rich in creamy cheese and buttery desserts. The investigators found that polyphenols -- compounds in grape skins and present in red wine -- decrease the production of a protein that causes blood vessels to constrict and reduces the flow of oxygen to the heart. The protein, endothelin-1 (ET-1), is believed to play a key role in the development of heart disease. Their findings support the results of earlier studies showing that a moderate intake of red wine may lower the risk of heart disease. But while these studies focused on the antioxidant properties of polyphenols -- their ability to quench disease-causing free radicals in the body -- the results of the new study suggest a new mechanism by which red wine might bring benefits. Red wine polyphenols inhibit protein tyrosine kinases, a group of enzymes that play a key role in cell regulation. Compounds that inhibit these enzymes have been shown to suppress endothelin production. The effects that are described are completely unrelated to any antioxidant properties of polyphenols. Of supreme interest to our readers is the fact that in this study, Valpolicella (Corvina and Molinara only) and Sangiovese based wines had a very low IC50 values 5.3 and 2.7 respectively, which is the concentration of each wine or juice extract causing a 50% reduction in basal ET-1 synthesis over 6h. Simple put these wines were found to protect the heart better! Bonum vinum laetificat cor hominum. Stoclet JC. Med Sci Monit 2001 Jul-Aug;7(4):842-7 Beneficial effects of wine consumption on health have been suspected since the antiquity. Recent epidemiological studies show that coronary heart disease mortality markedly decreases from northern to southern Europe and is lower in Mediterranean than in other developed countries. Because wine is a component of the Mediterranean diet, it has been suggested that moderate wine especially red wine consumption may produce additional beneficial effects on cardiovascular morbidity and mortality compared to consuming the same quantitiy of alcohol in other beverages. Polyphenols are good candidates to explain the putative cardiovascular protective effect of wine, because they are abundant in wine especially red wine, and possess antioxidant and superoxide ion scavenging properties. Because it is readily accessible from blood and produces cardioprotective agents like nitric oxide (NO) the endothelial cell may be a privileged target for wine polyphenols. Polyphenols from red wine can prevent oxidation of low density lipoproteins (LDL). As oxidized LDL inhibit agonist-activated NO release from endothelial cells and subsequent endothelium-dependent relaxation of arteries, wine polyphenols might prevent LDL-induced alterations of endothelial function. Furthermore some wine polyphenols contained in oligomeric condensed tannins- and anthocyaninsD enriched fractions can act directly on endothelial cells to cause calcium-dependent release of NO. The latter effect is independent from superoxide scavenging and antioxidant properties of the polyphenols, and it is produced by compounds with specific structures only. Thus, decreased oxidation of LDL and enhanced release of NO from endothelium caused by polyphenols from red wine may result in cardiovascular protection. However further studies are required to demonstrate whether or not these effects are involved in the putative protective effect of wine on cardiovascular morbidity and mortality. What this means This article explores the putative molecular mechanisms related to the beneficial effects that wine has on the cardiovascular system. The author has found a somewhat compelling amount of evidence that suggests that endothelial cells (those cells that line the arterial blood vessels) may actually be the target of some of the polyphenolic compounds (biologically active organic chemical agents). The article draws our attention to gaps in our understanding of related health mechanisms. The author postulates that low density lipoprotein (LDL), oxidation of endothelial cells may be prevented by cardioprotective components in wine, chiefly the polyphenolics. Interestingly enough this study comes from the University of Louis Pasteur of Strasbourg France. The "French paradox" and beyond: neuroprotective effects of polyphenols(1,2). Sun AY, Simonyi A, Sun GY. Free Radic Biol Med 2002 Feb 15;32(4):314-8 Chronic ethanol ingestion is known to cause oxidative damage to a number of organs including the brain. This is partly due to the ability of ethanol to enhance oxygen free radical production and lipid peroxidation. Increase in oxidative stress has been regarded as an important underlying factor for a number of human health problems including cardiovascular diseases, aging, as well as many age-related neurodegenerative diseases. The strikingly low incidences of coronary heart diseases (CHD) in France, despite intake of a high-fat diet, have been attributed to the consumption of red wine containing high levels of polyphenolic compounds. In recent years, understanding the "French Paradox" has stimulated new research interest to investigate whether polyphenolic antioxidants may offer protective effects beyond the cardiovascular system, and whether polyphenols from other botanical sources may similarly offer beneficial effects to human health. Our studies with animal models have provided information clearly indicating the ability of grape polyphenols to ameliorate neuronal damages due to chronic ethanol consumption. Studies with resveratrol, an important component of grape polyphenols, also show protective effects on neuron cell death induced by ethanol and other oxidative agents. These studies demonstrate an urgent need to extend research beyond the "French Paradox" towards better understanding molecular mechanisms of action of polyphenolic compounds and their application to human health. What this means This study attempted to characterize the exact mechanism of the antioxidant constituents in wine, protecting brain and central nervous system cells from damage by ethanol. Theses constituents are found to be the usual suspects which include trans-resveratrol (a favourite molecule here at Kamil Juices), and anthocyanides. Evidence in the paper demonstrates that the antioxidant molecules not only protect brain cells from the damage of everyday agents but the ethanol that is present in wine. This may indicate why only wine is being promoted as being protective for a number of chronic health conditions rather than the ethanol itself. |
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