Grapes and their derivatives in modulation of cognitive decline: a critical review of epidemiological and randomized-controlled trials in humans.

With an increase in life expectancy, the incidence of chronic degenerative pathologies such as dementia has progressively risen. Cognitive impairment leads to the gradual loss of skills, which results in substantial personal and financial cost at the individual and societal levels. Grapes and wines are rich in healthy compounds, which may help to maintain homeostasis and reduce the risk of several chronic illnesses, including dementia. This review analyzed papers that were systematically searched in PubMed, MEDLINE, Embase, and CAB-Abstract, using the association between grapes (or their derivatives) and their effects on cognitive functions in humans. Analysis was restricted to epidemiological and randomized-controlled studies. Consumption of grape juice (200-500 mL/day) and/or light-to-moderate wine (one to four glasses/day) was generally associated with improved cognitive performance, while the results for other alcoholic beverages were controversial and inconclusive. Bioactive molecules contained in grapes and wine were also considered, with particular attention paid to resveratrol. Due to the relatively high doses required (150-1000 mg/day) for bioactivity coupled with its low bioavailability, resveratrol is only one of the possible grape-derived compounds that may partly underpin the beneficial effects of grapes on the central nervous system.

Resveratrol, human health and winemaking perspectives.

Resveratrol, (3, 5, 4'-trihydroxystilbene) is a non-flavonoid polyphenol stilbene synthesized by plants when damaged by infectious diseases or ionizing radiation. Although present in more than seventy plant species, grapes and wine are the major dietary contributors of resveratrol, responsible for 98% of the daily intake. In 1992, Renaud and De Lorgeril first linked wine polyphenols, including resveratrol, to the potential health benefits ascribed to regular and moderate wine consumption (the so called "French Paradox"). Since then, resveratrol has received increasing scientific interest, leading to research on its biological actions, and to a large number of published papers, which have been collected and discussed in this review. The relatively low amounts of resveratrol measured in wine following moderate consumption, however, may be insufficient to mitigate biological damage, such as that due to oxidative stress. On this basis, the authors also highlight the importance of viticulture and the winemaking process to enhance resveratrol concentrations in wine in order to bolster potential health benefits.

The Case for Anthocyanin Consumption to Promote Human Health: A Review.

Anthocyanins belong to the flavonoid group of polyphenolic compounds, which are responsible for the red and blue colors of plant organs such as fruits, flowers, and leaves. Due to their frequent presence in plants, particularly berry fruits, vegetables, and grapes, they are key components of the human diet. Interest in anthocyanins has increased widely during the past decade. Numerous studies have suggested that anthocyanins have a wide range of health-promoting properties. These compounds are therefore considered to be a functional food factor, which may have important implications in the prevention of chronic diseases. The aim of this body of work is to investigate and review the current literature on anthocyanins, and particularly their pharmacokinetics and any health-promoting properties, in order to summarize existing knowledge and highlight any aspects that require further study and analysis.

Is it merely a myth that alcoholic beverages such as red wine can be cardioprotective?

It has been suggested that although the negative impact of alcohol consumption varies from person to person, on a global level the adverse effect of alcohol on cardiovascular disease outweighs any protective effect by between two- and three-fold. This is inaccurate. There is a proven positive relationship between alcohol consumption and cardiovascular disease that is acknowledged by the World Health Organization. For example, moderate alcohol consumption reduces the risk of cardiovascular disease by approximately 25%, such that alcohol consumption per se accounts for -4.7% of the total cardiovascular disease burden in Australia. Correspondingly, cardiovascular disease accounted for 34% of the total number of deaths in Australia in 2008, and 18% of the overall burden of disease in Australia in 2003, with coronary heart disease and stroke contributing over 80% of this burden. Australia is not substantially different from other developed countries having similar demographics to, and the same leading causes of burden as, other high-income developed countries. This article examines the suggestions and evidence surrounding the relationship between light-to-moderate alcohol consumption and benefits to human health.

Polyphenols and Human Health: The Role of Bioavailability.

Polyphenols are a group of phytochemicals with potential health-promoting effects. They are classified as flavonoid (flavonols, flavanols, flavones, flavanones, isoflavones, and anthocyanins) and non-flavonoid molecules (phenolic acids, hydroxycinnamic acids, lignans, stilbenes, and tannins). Although an increasing number of trials have shown a correlation among polyphenol consumption and a reduction in risk factors for chronic diseases, discrepancies in explaining their positive effects have been found in terms of the bioavailability. In fact, polyphenols show a low bioavailability due to several factors: interaction with the food matrix, the metabolic processes mediated by the liver (phase I and II metabolism), intestine and microbiota. On the other hand, the biological activities of phenol compounds may be mediated by their metabolites, which are produced in vivo, and recent studies have confirmed that these molecules may have antioxidant and anti-phlogistic properties. This review discusses the studies performed in vivo, which consider the polyphenol bioavailability and their different food sources. Factors influencing the biological effects of the main classes of polyphenols are also considered.

Is it scientifically justifiable to exclude wine and/or unfermented grape derivatives from the diet of consumers with or at risk of developing type-2 diabetes?

The abuse of alcoholic beverages has been associated with an increased risk of chronic-degenerative diseases, including diabetes mellitus, so that there is a general diffidence towards the low/moderate consumption of wine by individuals with type-2 diabetes (T2D) or at risk of developing it. This narrative review investigates by critical revision of the scientific literature whether wine/grape derivatives must be excluded or if their low/moderate consumption could be part of the daily diet of T2D individuals. Although further intervention studies on the consumption of alcoholic beverages and the development or control of T2D are needed, the burden of evidence suggests that low/moderate wine consumption could have beneficial effects.

Specific and sensitive enzyme-linked immunosorbent assays for analysis of residual allergenic food proteins in commercial bottled wine fined with egg white, milk, and nongrape-derived tannins.

Regulations introduced by the Food Standards Australia New Zealand in December 2002 require all wine and wine product labels in Australia to identify the presence of a processing aid, additive or other ingredient, which is known to be a potential allergen. The objective of this study was to establish sensitive assays to detect and measure allergenic proteins from commonly used processing aids in final bottled wine. Sensitive and specific enzyme-linked immunosorbent assays (ELISA) were developed and established for the proteins casein, ovalbumin, and peanut. Lower limits of detection of these proteins were 8, 1, and 8 ng/mL, respectively. A panel of 153 commercially available bottled Australian wines were tested by these ELISA, and except for two red wines known to contain added whole eggs, residuals of these food allergens were not detected in any wine. These findings are consistent with a lack of residual potentially allergenic egg-, milk-, or nut-derived processing aids in final bottled wine produced in Australia according to good manufacturing practice at a concentration that could cause an adverse reaction in egg, milk, or peanut/tree-nut allergic adult consumers.

Potential food allergens in wine: double-blind, placebo-controlled trial and basophil activation analysis.

OBJECTIVE: Recent Australian and international legislation requires labeling of wines made by using the potentially allergenic food proteins casein, milk, egg white, or isinglass (fish-derived) where "there is a detectable residual processing aid." We investigated whether wines fined using these proteins or non-grape-derived tannins (tree-nut derived) can provoke significant clinical allergic reactions (anaphylaxis) in patients with confirmed immunoglobulin E-mediated relevant food allergy. METHODS: A double-blind, placebo-controlled trial was performed to determine whether allergic reactions followed consumption of Australian commercial wines fined using one or more of the legislation-targeted food proteins. In addition, allergenicity of a larger panel of these wines was evaluated by blood basophil activation. RESULTS: No anaphylaxis was induced by wine consumption. Three mild clinical reactions to protein-fined wine and two mild reactions to unfined wine occurred, but there was no statistically significant difference in reaction parameters between subject groups or between processing aids. No pattern of basophil activation correlated with wine type, processing aid, or subject group. CONCLUSION: Wines fined with egg white, isinglass, or non-grape-derived tannins present an extremely low risk of anaphylaxis to fish-, egg-, or peanut-allergic consumers. Although consumption of milk protein-fined wine did not induce anaphylaxis, there were insufficient subjects to determine statistically whether wines fined with milk proteins present a risk to the very rare milk-allergic consumers. In summary, the observed lack of anaphylaxis and basophil activation induced by wines made using the legislation-targeted food proteins according to good manufacturing practice suggests negligible residual food allergens in these wines.

The Relationship between Alcohol Consumption and other Risk Factors Assessed Using An Ongoing Population-based Surveillance System.

The aim of this study was to determine the relationship of alcohol consumption (reported in four different ways) with other specific disease-related risk factors (that is, smoking, high body mass index, low physical activity and insufficient fruit and vegetables). Data were collected from 2003 to 2015 in South Australia using an on-going monthly chronic disease and risk factor telephone survey of randomly selected persons (18+ years). The proportion of alcohol drinkers and, for those who drank alcohol, the proportion drinking more than one day per week, the proportion drinking on six or more days per week, and the mean alcohol drinks per day were assessed. Logistic regression and linear regression modelling were used on age and sex adjusted data. In total, over 71,000 respondents aged 18 years and older were interviewed (48.8% male). Overall prevalence of alcohol consumption was 81.3%. Trends in the direction promoted by current policies and preventative authorities were apparent with appropriate changes for all four measures for overall and for those underweight, undertaking sufficient activity, consuming <2 serves of fruit per day, consuming <5 serves of vegetables per day and with 3+ total risk factors. This research has provided evidence on the trends in alcohol consumption in relation to a range of other specific modifiable disease-related risk factors. The trends analysis has shown different patterns for each risk factor, and highlights the interplay between the respective modifiable or preventive risk factors.

Drinking pattern of wine and effects on human health: why should we drink moderately and with meals?

Conclusions of epidemiological studies examining the effects of alcoholic beverages on human health may be unclear and limited if they do not take into account drinking pattern parameters such as beverage type, regular moderate versus binge drinking and drinking with or without meals. This review considers different aspects of drinking patterns and effects on human health with special attention to wine. We particularly discuss the potential underlying mechanisms for epidemiological evidence that the beneficial effects of wine are more evident if consumed with food. In this context, we address the effects of food on blood alcohol concentration and acetaldehyde production in the gastrointestinal tract, the role of wine components and uric acid in counteracting the detrimental effects of postprandial oxidative stress, as well as wine's antimicrobial properties and its potential to act as a digestive aid. In addition to its biological correlates, drinking patterns with regard to different socio-cultural circumstances in different populations are also considered. In order to avoid confusion and misconceptions in the general population because of the hormetic associations of wine with human health, it is important that all medical and scientific information concerning the effect of wine consumption on human health are evidence-based and communicated in a competent, credible and unbiased manner. In conclusion, we propose several practical recommendations concerning wine consumption and consumer information to minimize the risks of alcohol-related harm and to encourage individual responsibility and a healthy lifestyle.

An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels.

Friedreich ataxia (FRDA) is due to a triplet repeat expansion in FXN, resulting in deficiency of the mitochondrial protein frataxin. Resveratrol is a naturally occurring polyphenol, identified to increase frataxin expression in cellular and mouse models of FRDA and has anti-oxidant properties. This open-label, non-randomized trial evaluated the effect of two different doses of resveratrol on peripheral blood mononuclear cell (PBMC) frataxin levels over a 12-week period in individuals with FRDA. Secondary outcome measures included PMBC FXN mRNA, oxidative stress markers, and clinical measures of disease severity. Safety and tolerability were studied. Twenty-four participants completed the study; 12 received low-dose resveratrol (1 g daily) and 12 high-dose resveratrol (5 g daily). PBMC frataxin levels did not change in either dosage group [low-dose group change: 0.08 pg/µg protein (95% CI -0.05, 0.21, p = 0.21); high-dose group change: 0.03 pg/µg protein (95% CI -0.10, 0.15, p = 0.62)]. Improvement in neurologic function was evident in the high-dose group [change in Friedreich Ataxia Rating Scale -3.4 points, 95% CI (-6.6, -0.3), p = 0.036], but not the low-dose group. Significant improvements in audiologic and speech measures, and in the oxidative stress marker plasma F2-isoprostane were demonstrated in the high-dose group only. There were no improvements in cardiac measures or patient-reported outcome measures. No serious adverse events were recorded. Gastrointestinal side-effects were a common, dose-related adverse event. This open-label study shows no effect of resveratrol on frataxin levels in FRDA, but suggests that independent positive clinical and biologic effects of high-dose resveratrol may exist. Further assessment of efficacy is warranted in a randomized placebo-controlled trial.

Immunochemical investigation of allergenic residues in experimental and commercially-available wines fined with egg white proteins.

Proteinaceous egg whites are widely used as a fining agent during the production of red wines. Residues of egg white in the final wine could present a risk for individuals allergic to eggs. This study investigated the presence of allergenic residues in both red and white wines fined with egg whites. Experimental and commercially available wines fined with egg whites, with or without subsequent bentonite fining, were studied. Unfined wines were used as negative controls. The physicochemical characteristics of each wine were determined to assess their possible role in enhancing or hindering the elimination of allergenic residues from wine. The amount of egg white protein residues was investigated both by a specifically developed/validated ELISA test and by immunoblotting. Both immunochemical tests used the same anti-total egg white protein antibody and were highly sensitive to the allergen. No egg white protein was detected in the wines studied in either immunochemical test, irrespective of the physicochemical characteristics of the wine, the type and dosage of the fining agent and the oenological process used. The risk of adverse reactions in egg-allergic individuals should therefore be considered negligible, but the exemption from labelling should be allowed only when the absence of residues is confirmed by analytical controls.

Effects of red wine on established markers of arterial structure and function in human studies: current knowledge and future research directions.

Evidence from observational studies suggests that mild-to-moderate consumption of red wine is associated with reduced cardiovascular morbidity and mortality. Various individual chemical components of red wine also show salutary effects on vascular homeostasis, that is, enhanced endothelial function and arterial distensibility, both in vitro and in animal studies. However, testing the beneficial potential of red wine in primary and secondary cardiovascular prevention on established surrogate cardiovascular markers requires further study with longer term intervention trials. This report reviews and critically appraises the published evidence for the effects of red wine on endothelium-dependent vasodilation, arterial stiffness and arterial wave reflections in healthy subjects and in patients with cardiovascular disease. Suggestions for future research directions are also provided.

Bioavailability of wine-derived phenolic compounds in humans: a review.

Phenolic compounds are produced in the seeds and skins of grapes, and are transferred into wine during the fermentation process. Phenolic compounds can also be imparted into wine from maturation and storage in oak wood barrels after fermentation. The consumption of wine, an alcoholic beverage, has been observed in epidemiological studies to reduce the risk of cardiovascular disease and certain cancers, as well as diabetes and dementia, in a J-shaped relationship between amount consumed and level of risk. The bioactivity of wine primarily observed in vitro and ex vivo, may result from wine's relatively high content of phenolic compounds, which is similar to that observed in fruits and vegetables; a Mediterranean fruit and vegetable rich-diet is also associated with a reduced risk of cardiovascular disease and cancers. If the wine-derived phenolic compounds or their active metabolites are not absorbed in sufficient amounts and in a readily available form for cells, however, then they are less likely to have any significant in vivo activity. This review considers and discusses the available data to date on the bioavailability of the different wine-derived phenolic compounds in humans.

Moderation in Australia-policy and achievements.

Alcohol has been consumed in Australia since European settlement in 1788. In 1998, approximately 60% of Australians consumed an alcoholic beverage at least once per week. The effects of alcohol on the human body are dose dependent, where the harmful effects of alcohol are generally observed only when alcohol consumption exceeds moderate consumption levels of 30 to 40 g of alcohol per day. The discovery that a J-shaped curve described the relationship between level of alcohol consumption and risk of cardiovascular disease was, however, only made in 1990-cardiovascular disease is the leading cause of death in the western world. Thus prior to 1990, Australian public health policy focused primarily on the harmful effects of alcohol consumption and the health benefits of a moderate level of alcohol consumption have only recently been recognized in public policy. This paper chronicles changes in Australian Federal government policy on alcohol since the initial draft National health policy on alcohol in Australia was presented to the Ministerial Council on Drug Strategy in 1987 to the National Drug Strategic plan for action 2001 to 2003-2004 which was launched in July last year.

Moderation in Australia-Policy and achievements

Alcohol has been consumed in Australia since European settlement in 1788. In 1998, approximately 60 % of Australians consumed an alcoholic beverage at least once per week. The effects of alcohol on the human body are dose dependent, where the harmful effects of alcohol are generally observed only when alcohol consumption exceeds moderate consumption levels of 30 to 40 g of alcohol per day. The discovery that a J-shaped curve described the relationship between level of alcohol consumption and risk of cardiovascular disease was, however, only made in 1990_cardiovascular disease is the leading cause of death in the western world. Thus prior to 1990, Australian public health policy focused primarily on the harmful effects of alcohol consumption and the health benefits of a moderate level of alcohol consumption have only recently been recognized in public policy. This paper chronicles changes in Australian Federal government policy on alcohol since the initial draft National health policy on alcohol in Australia was presented to the Ministerial Council on Drug Strategy in 1987 to the National Drug Strategic plan for action 2001 to 2003-2004 which was launched in July last year.