Wine Polyphenols and Health
Critique 031. Wine polyphenols have a variety of beneficial effects on health
30 January 2011
Reference: Rodrigo R, Miranda A, Vergara L. Modulation of endogenous antioxidant system by wine polyphenols in human disease. Clin Chim Acta 2011;412:410-424.
Much of the protection against cardiovascular disease attributed to wine intake may relate not only to the alcohol in wine, but to its polyphenolic constituents. This review article summarizes research into the chemistry, bioavailability, metabolism and excretion of polyphenols as well as mechanisms of their action. As stated by the authors, “These protective effects could be due to one or many components of the complex mixture of bioavailable and bioactive compounds present in red wine including ethanol, resveratrol, flavonols, flavan-3-ols, anthocyanins, phenolic acids as well as their metabolites formed either in the tissues or in the colon by the microflora.” The authors describe their cardioprotective effects, effects on vascular function and atherosclerosis, anti-platelet effects, effects on myocardial ischemia, and anti cancer and anti-diabetic effects.
The authors conclude that “Polyphenols are the most abundant antioxidants in the diet and are widespread constituents of wine, fruits and vegetables.” Their review provides an extensive scientific literature on polyphenols in wine; it suggests multiple mechanisms by which such substances may have beneficial effects on health.
Critique 030. Young rats given red wine polyphenols show less deterioration in endothelial function with ageing. 30 January 2011
Reference: Dal-Ros S, Zoll J, Lang AL, Auger C, Keller N, Bronner C, Geny B, Schini-Kerth VB. Chronic intake of red wine polyphenols by young rats prevents aging-induced endothelial dysfunction and decline in physical performance: Role of NADPH oxidase. Biochem Biophys Res Commun 2011;404:743-749.
The gradual decrease in endothelial function over time is a key factor in the development of diseases associated with ageing, especially cardiovascular disease (CVD). Many epidemiologic studies suggest greater protection against CVD from wine than from other beverages containing alcohol, with at least one factor being the polyphenols in red wine (RWPs).
The present study in rats found that the administration of red wine polyphenols protected against ageing-induced endothelial dysfunction. As stated by the authors: “The present findings indicate that regular intake of RWPs in the drinking water starting at young age (16 week-old) prevented the aging-related endothelial dysfunction most likely by reducing the excessive oxidative stress in the arterial wall.” They further suggest an important role of NADPH oxidase and possibly also the angiotensin system in the abnormal vascular response in aging. Their study showed that, “RWPs intake had also a physiological beneficial effect since it improved the physical exercise capacity of old rats.”
Forum members thought that this was an excellent paper, as it begins to delve into mechanisms by which polyphenols improve health. A mechanism is addressed and results are consistent with the working hypothesis of a specific interaction between polyphenols and peculiar enzymes. There is a satisfying agreement between basic mechanisms and pathophysiology. Some scientists believe that interventions to improve endothelial function (such as the consumption of red wine or other sources of polyphenols) should begin earlier in life to slow down the endothelial dysfunction that occurs with ageing. This study in rats tends to support such a belief.
Critique 027. Effects of resveratrol and quercetin on inflammation and insulin resistance 20 December 2010
Reference: Chuang C-C, Martinez K, Xie G, Kennedy A, Bumrungpert A, Overman A, Jia W, McIntosh MK. Quercetin is equally or more effective than resveratrol in attenuating tumor necrosis factor-a–mediated inflammation and insulin resistance in primary human adipocytes. Am J Clin Nutr 2010;92:1511–1521.
A study was carried out to examine the extent to which quercetin and trans-resveratrol (RSV) prevented inflammation or insulin resistance in primary cultures of human adipocytes treated with tumor necrosis factor-a (TNF-a)—an inflammatory cytokine elevated in the plasma and adipose tissue of obese, diabetic individuals. Cultures of human adipocytes were pretreated with quercetin and trans-RSV followed by treatment with TNF-a. Subsequently, gene and protein markers of inflammation and insulin resistance were measured. The authors report that quercetin, and to a lesser extent trans-RSV, attenuated the TNF-a–induced expression of inflammatory genes such as interleukin (IL)-6, IL-1b, IL-8, and monocyte chemoattractant protein-1 (MCP-1) and the secretion of IL-6, IL-8, and MCP-1.
Forum members were concerned about certain aspects of the study, especially the extrapolation of in vitro results to in vivo situations. The in vitro conditions the authors describe are minimally representative of an in vivo condition. In vivo, after consumption of quercetin or resveratrol, these compounds undergo extensive metabolism, leading to glucuronidated, sulphated or methylated compounds. In a previous study, quercetin 3-glucoside was transformed to 3,4-dihydroxyphenylacetic acid, acetate and butyrate in cells from human gut; only 3′-methylquercetin has been detected in human plasma, present at a concentration of 0.1 to 0.2 µM after 3 h. The authors of the current paper are using concentrations up to 60 µM, concentrations which have not been found in vivo.
There were also concerns with the work on cell uptake of quercetin and resveratrol. Primary adipocytes were incubated with the polyphenols, but it is not clear whether or not the concentrations used were subtoxic. Our current knowledge is limited about local concentration of the molecules we are studying in subcellular compartments, their interaction with alternative targets, and eventually their transformation into products that could be more or less active on a given specific pathway. The real difficult and important issue is the identification of a reasonable convergence — if not agreement — between data originating from extremely distant approaches. In this case, the notion that metabolic diseases are related to a homeostatic imbalance in adipose tissue, linked to a different redox status, linked to activation of specific pathways, and that different redox sensitive polyphenols do have a protective effect, encompasses the evidence produced by extremely distant approaches.
From a clinical point of view, the role of phytochemicals acting as antioxidants and anti-inflammatory agents could be extremely important in inflammation-associated chronic conditions such as cardiovascular disease, diabetes, and cancer. Quercetin and resveratrol may indeed play an important role in this regard, and need to be investigated further to establish the clinical importance of natural dietary compounds in the prevention of chronic degenerative conditions.
Critique 023. Evidence that PPAR-gamma is a mechanism for the effects of wine polyphenolics on cardiovascular risk. 27 November 2010
Reference: Zoechling A, Liebner F, Jungbauer A. Red wine: A source of potent ligands for peroxisome proliferator-activated receptor γ. Food & Function, Journal of the Royal Society of Chemistry, in press. DOI: 10.1039/c0fo00086h.
It is important that biological mechanisms are identified for the observed inverse relation between the moderate consumption of wine and cardiovascular disease shown in most epidemiologic studies. A paper by Zoechling et al is an elegant example of the needed effort to provide a biochemical mechanism for the biological effects of wine. Data on binding of different wine component were produced and this result is interpreted in light of epidemiological evidence.
It would have been appropriate to provide evidence also for the actual shift of gene expression primed by the same wine component in a cell or animal model. In this respect, results must be rated appropriate but still as preliminary; a ligand could have different effects. Further, biological evidence is not provided to support the contention that these polyphenols act through the PPAR-gamma receptor. The sort of evidence that should have been provided is a comparison with rosiglitazone in a cell population known to respond to PPAR-gamma agonists (e.g. adipocytes).
Further, the analytical data does not describe the amounts of any of the “active” substances. So while there is a lot of discussion of the active components, it is not possible to compare any wine’s “activity” with the amount of the key substances. Lacking such a comparison, it is very hard to conclude that these substances are in fact the responsible factors in the observed activity. Nevertheless, this paper provides important data on potential mechanisms by which the constituents of wine and certain other beverages may act to reduce the risk of cardiovascular disease.
Critique 014. Moderate drinking, especially of wine, is associated with better cognitive function 13 August 2010
Reference: Arntzen KA, Schirmer H, Wilsgaard T, Mathiesen EB. Moderate wine consumption is associated with better cognitive test results: a 7 year follow up of 5033 subjects in the Tromsø Study. Acta Neurol Scandd 2010; Suppl 190:23-29.
A large prospective study of men and women in northern Norway reported that moderate wine consumption was independently associated with better performance on cognitive tests after 7 years of follow up. There was no consistent association between consumption of beer or spirits and cognitive test results. The authors also reported that abstinence was associated with significantly lower cognitive performance in women. As noted by the authors, in any observational study there is the possibility of residual confounding by other lifestyle habits affecting cognitive function, and the present study was not able to adjust for certain ones (e.g., diet, income, or profession) but did adjust for age, education, body mass index, depression, and cardiovascular disease and its major risk factors.
The results of this study support findings from a number of observational, prospective studies that have shown that the moderate consumption of alcohol, especially of wine, may have favorable effects on cognitive function. Such effects could relate to the presence in wine of a number of polyphenols and other substances that reduce the risk of cognitive decline with ageing. Mechanisms that have been suggested for such protection against cognitive dysfunction include effects on atherosclerosis, coagulation, inflammation, as well as direct neuroprotective effects.
Critique 002. Red wine, but not other types of alcohol, improve endothelial function in a randomized trial 26 April 2010
Reference: Huang PH, Chen YH, Tsai HY, Chen JS, Wu TC, Lin FY, Sata M, Chen JW, Lin SJ. Intake of red wine increases the number and functional capacity of circulating endothelial progenitor cells by enhancing nitric oxide bioavailability. Arteriosclerosis Thrombosis and Vascular Biology 2010;30:869-877.
The healthy state of cells that form the lining of arteries, assessed by indices of endothelial function, is a key factor associated with preventing the development and progression of atherosclerosis and coronary heart disease. In a randomized trial among healthy young adults, the daily consumption of about 3 ounces of red wine for three weeks led to significant improvement in endothelial function. Such improvements were not seen with the consumption of water, or of beer or vodka containing similar amounts of alcohol.
Further, in a series of in-vitro studies, the authors showed very similar effects from red wine and from a high concentration of resveratrol (but not from beer or ethanol) on factors associated with improved endothelial function. The study supports many epidemiologic and animal experiments suggesting that certain non-alcoholic constituents of red wine have additional beneficial effects on cardiovascular risk over those of just the alcohol itself.