ReviewWine and oxidative stress: Up-to-date evidence of the effects of moderate wine consumption on oxidative damage in humans
Introduction
Wine and alcohol consumption has been considered to be protective against coronary heart disease development, an oxidative stress associated disease [for review see [1]]. Wine is a complex matrix and may be considered as a phyto-complex to which ethanol has been added following natural fermentation [2]. Lifestyle habits in European Mediterranean countries have suffered changes in recent decades. However, wine remains the preferential pattern of alcohol consumption in these countries [3]. This pattern could also have a role, within the frame of the Mediterranean Diet, to explain the low incidence rates of coronary heart disease (CHD) in the Southern European countries in comparison with those observed in the Northern ones, Canada, or the USA [4]. In this way, Spanish regional diversity in wine consumption has been pointed out as one of the explanatory factors for the differences in myocardial infarction incidence rates observed among Spanish areas in ecological analyses [3].
Moderate amounts of alcohol markedly reduce the risk of CHD [for review see [1]]. The plausible mechanisms are first, the increase in high-density lipoprotein (HDL) cholesterol due to alcohol, and second, alcohol consumption also favourably affects the clotting and thrombolytic processes [1]. Data on the in vivo oxidative damage linked to moderate alcohol consumption are controversial. In a cross-sectional study, alcohol consumption was in a direct relationship with the plasma concentration of in vivo oxidized low-density lipoproteins (LDL) [5], but the levels of the DNA oxidation marker 8-oxo-deoxyguanosine have been reported to decrease with the amount of alcohol consumed [6]. In intervention studies a change in daily beer alcohol consumption from a moderate-heavy intake to a light one lowered the plasma F2-isoprostanes in healthy non-smoking men [7]. In other human intervention studies, consumption of beer or spirits at daily moderate doses of 30 g/day [8] or 40 g/day [9], but not at doses of 15 g/day [8], promoted only a marginal increase in urinary F2-isoprostanes. Ethanol metabolism can produce free radicals and reduce the levels of glutathione, the major cellular protection against oxidative stress [10]. In addition to alcohol wine contains polyphenols with antioxidant properties which could confer it with beneficial properties for health versus other types of alcohol consumption [1], [2]. Thus, the key questions are: (1) could polyphenols present in wine counteract an oxidative effect of alcohol?, and (2) could polyphenols present in wine provide additional benefits on oxidative stress and oxidative damage other than to counteract the possible oxidative effect of alcohol?
A large number of studies, both in experimental models and in humans, have been performed to ascertain the antioxidant properties of wine. A general consensus exists concerning the benefits of wine consumption, particularly red wine, on oxidative damage. However, the precepts of the Evidence-Based Medicine require high level scientific evidence to be provided before recommendations or statements for the general public can be formulated. The scientific evidence required is only provided by human, randomized, placebo-controlled, double-blind, clinical trials (Level I of Evidence) and, to some extent, by large cohort studies (Level II of Evidence) [11]. Of course, the level of evidence of a particular study depends not only on its type of design, but also on the quality of the study (external and internal validity, homogeneity of the sample, and statistical power). Finally, evidence is built by the agreement of the results of several similar studies [11]. Here, we summarize the state of the art of the body of knowledge and the extent to which we possess evidence of the antioxidant benefits of wine consumption in humans.
Section snippets
Wine components and oxidative damage
Mechanisms by which wine components, namely ethanol and polyphenols, could interact with reactive oxygen species (ROS) and oxidative damage are shown in Fig. 1. ROS oxidize lipids, proteins, and DNA. Oxidation of LDL lipoproteins is a hallmark for atherosclerosis and CHD development [12], and mutagenesis from DNA oxidative damage is considered to be a crucial step in human carcinogenesis [13]. Somatic DNA mutations, promoted by DNA oxidation, are considered to be involved in the atherosclerotic
Phenolic compounds in wine
The level of phenolic compounds in a wine is highly variable due to differences in variety and grape sources as well as processing. Red wine contains a higher concentration (around 10-fold) of polyphenols than white wine because during the wine making process, unlike white wine, red wine is macerated for weeks with the skin and seeds and these contain most of the phenolic compounds [24]. Concentrations of phenolic compounds in red wine range from around 1.2 to 3.0 g/L. The major phenolic
Bioavailability and disposition of phenolic compounds from wine in humans
It has been suggested that non-absorbable phenolic compounds may display local antioxidant activities in the gastrointestinal tract [26]. However, one of the prerequisites for assessing the physiological significance of phenolic compounds from wine is to determine their bioavailability and disposition in humans.
Phenolic compounds such as caffeic and gallic acids, quercetin, catechin, kaempherol, malvidin-3-glucoside, and resveratrol have been detected and quantified in human biological fluids
Human studies on the effect of wine consumption on oxidative stress
We searched MEDLINE for clinical studies assessing the effect either of acute (single dose) or sustained wine consumption on oxidative stress markers. Cohort studies aimed at assessing the relationship of wine consumption and oxidative stress markers were also looked for, but none was obtained. The following Medical Subject Heading Terms: wine, oxidative stress, oxidation, oxidative damage, LDL oxidation, lipid peroxidation, DNA oxidation, plasma antioxidant capacity, human, healthy, volunteers
Summary of findings
There are extensive differences in the methods and markers used among the studies reviewed. Few of them have been performed with sensitive biomarkers of in vivo oxidative damage or with markers which have been shown to be predictors for oxidative stress associated diseases. Despite a general consensus attributing antioxidant benefits in healthy volunteers to sustained wine consumption, there is no evidence, at present, that sustained wine consumption provides antioxidant benefits other than to
Acknowledgement
The CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of the Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
References (70)
Wine, research and cardiovascular disease: instructions for use
Atherosclerosis
(2007)- et al.
Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10 year results from 37 WHO MONICA project populations. Monitoring trends and determinants in cardiovascular disease
Lancet
(1999) - et al.
Alcohol consumption is directly associated with circulating oxidized low-density lipoprotein
Free Rad Biol Med
(2006) - et al.
A reduction in alcohol consumption is associated with reduced plasma F2-isoprostanes and urinary 20-HETE excretion in men
Free Rad Biol Med
(2007) - et al.
Moderate alcohol consumption and lipoprotein-associated phospholipase A2 activity
Nutr Met Cardiovasc Dis
(2008) - et al.
Assessing the clinical effectiveness of preventive manoeuvres: analytic principals and systematic methods in reviewing evidence and developing clinical practice recommendations. A report by the Canadian Task Force on the Periodic Health Examination
J Clin Epidemiol
(1990) - et al.
The increase in human plasma antioxidant capacity after red wine consumption is due to both plasma urate and wine polyphenols
Atherosclerosis
(2008) - et al.
High-density lipoprotein function. Recent advances
J Am Coll Cardiol
(2005) - et al.
Oxidative breakage of cellular DNA by plant polyphenols: a putative mechanism for anticancer properties
Semin Cancer Biol
(2007) - et al.
Postprandial plasma lipid hydroperoxides: a possible link between diet and atherosclerosis
Free Radic Biol Med
(1998)