gpetrecca

Final paper

=The Health Benefits of Wine=

By: Grace Petrecca
Wine has been seen throughout history and has played an important role in human culture. It is an alcoholic beverage made from fermented grapes. Extra sugars, acids, water, enzymes, or other nutrients are not added to the fermenting grapes because the grapes do not require them [1]. Different varieties of grapes will produce a different type, or style, of wine. The differences in the style and flavors of the wine not only come from the type of grape used, but the region and surroundings it’s grown in.

Gamay, Merlot, Pinot Noir, Chardonnay, and Cabernet Sauvignon are the most popular varieties of European grapes used to make wine. Wines can either be made from one variety or be “blended” with a mixture of species of grapes. In France, and other wine-making areas, the region the wine is produced in can dictate its grape make-up. For example, a Beaujolais wine is made from 100% Gamay grape. There are twelve appellations of the Beaujolais, each of them containing their own villages for production [2]. Each appellation and village vary in terroir and climate, affecting the conditions the grapes are grown in. This, therefore, makes each village unique in not only flavor but in the concentrations of the different components of the grape, itself.

Figure 1: Gamay grape

Resveratrol is a non-flavenoid polyphenol, phytoalexin that is produced in the skin of grapes and other plants in response to fungal attack. Resveratrol has both cis and trans isomers but the trans isomer is formed in greater concentration. Trans-resveratrol has been found to contribute to the antioxidant potential of the wine and help prevent cardiovascular diseases [3]. It has been shown that resveratrol has been a major contributor for what is called the “French paradox.” The “French paradox” is the observation that French people, although having a high-fat diet, have relatiely low insidances of coronary heart disease [4].

Because of the fact that it is produced in the skin of the grapes and not the flesh, trans-resveratrol is present in higher concentrations in red wine than it is in white or rose. The concentrations in red wine tipically range from 0.1 to 15 mg/L [5].

Trans-resveratrol is metabolized in the intestine and then convertred to sulphated and glucuronidated forms in the liver and transproted to their target organs. After employing their effects, they are then eliminated through urine and stools [6]. Resveratrol has also been shown to have anticancer properties, as well as anti-inflammatory activity and estrogenic activity. Trans-resveratrol also inhibits lipid peroxidation and platlet aggregation. Resveratrol also chelates copper and scavenges free radicals in the body.

Figure 2: Trans-Resveratrol

A recent study shows that trans-resveratrol has an antiproliferative effect in vitro and prevents the formation of mammary tumors [7]. It has been described as a chemopreventive agent. Based on those in vitro studies, trans-resveratrol downregulates the expression of DNA methyltransferases and the cancer-promoting prostaglandin (PG)E₂ [8]. Trans-resveratrol is efficiently absorbed after oral administration and rapidly metabolized by the liver. In the blood, trans-resveratrol binds to albumin and low density lipoproteins. This helps it get to the epithelial cell surface and uptake the cell membrane [8].

In addition to mammary toumors, trans-resveratrol has been shown to help prevent against prostate cancer in men. Preclinical studies have indicated beneficial results of resveratrol in preventing and treating cancer, with few associated side effects. A ten year epidemiologic study showed a greater than 50% reduction in breast cancer risk in women who ingested resveratrol by consuming grapes. A recent study showed that resveratrol reduces the viability and invasiveness of PC-3M-MM2 cells, prostate carcinoma cells, in “culture and tumor growth in xenograft mouse model by inhibiting miR-21 expression” [8].

Figure 3. Resveratrol reduces PC-3M-MM2 cell viability by increasing apoptosis. [8].

In addition to anticancer and antitoumor properties, resveratrol has also been shown, by a study in 2003, that resveratrol increased the cell survival of budding yeast Saccharomyces cerevisiae by stimulating SIRT1-dependent deacetylation of, the tumor protein, p53, an effect independent of its antioxidant activity [9, 10]. Resveratrol has also been shown to mimic the effect of a lower calorie intake (calorie restriction) on extending the lifespan in the yeast previously tested by up to 70%. Another study has shown a relationship between quercetin and resveratrol in the inhibition of fat cell production, thereby exerting potential anti-obesity effects [11]. The region and the climate that the grapes are grown in effects the concentration of resveratrol produced by the grapes. Warmer climates tend to produce lower in vitro antioxidant capabilities. However, they tend to have the same bioavailability as those grown in cooler climates [12]. The results of an additional study showed the highest concentration of resveratrol was found in wines from Cordoba; which had the highest average amount of precipitation [13].

Alcohol, itself, is also believed to be a cardioprotective substance when consumed moderately. The cardiovascular effects of both red wine and vodka in a swine model of endothelial dysfunction were measured to give a comparison to the overall effects of both ethanol and polyphenols (resveratrol) in wine. The study showed that “supplementation with both red wine and vodka decreased oxidative stress by several measures, implicating the effects of ethanol in reducing oxidative stress in the myocardium. However, it was only in the red wine–supplemented group that an improvement in microvessel function was observed. This suggests that a component of red wine, independent of ethanol, possibly a polyphenol such as resveratrol, may confer cardioprotection by normalizing endothelial dysfunction induced by an atherogenic diet.” [14]

The alcohol matrix of the wine was determined to not influence the bioavailability of the resveratrol in the wine. In one study, red wine and dealcoholized red wine were given to volunteers for four weeks of moderate consumption. The 24-hour excretion values for the volunteers were compared and no differences were found, for any resveratrol metabolite, for the sum of the resveratrol phase II metabolites, resveratrol glucosides, and for gut microbial metabolites, between those who drank the alcoholic red wine and those who drank the dealcoholized red wine [15].

A pharmacokinetic study of the metabolic profile of resveratrol has been performed in healthy men after moderate red wine consumption. Since the bioavailability of resveratrol is highly influenced by several factors, such as the food matrix, this study has been compared with a pilot study in which men ingested grape extract tablets as a nutraceutical, containing similar total amounts of resveratrol than red wine. When both treatments were compared, statistically significant differences for some metabolites were obtained. This could potentially be due to the different composition of resveratrol and piceid in both sources. However, grape extract formulation seems to delay resveratrol absorption, which makes it stay longer in the gut where could be metabolized to a greater degree. This means that supplement intake could also be a sufficient way to bring resveratrol benefits to human health [16].

Figure 4: Graphical Analysis of the Comparison of Red Wine vs. Grape Extract Intake [16].

A functional food is considered a food that is intended to be consumed as a part of the normal diet and that contains biologically active components that offer the potential of enhanced health or reduced risk of disease. Studies have started to show that functional foods may be beneficial in helping to prevent, or lessen the effects of, certain age-related diseases [17]. This poses the question: should wine be considered a functional food? As previously established, red wine helps prevent cardiovascular disease, and has antitumor, anticancer, and anti-inflammatory properties. It has also been shown to help prevent certain types of cancer and slow the progression of Alzheimer’s disease [16]. Resveratrol also scavenges free radicals that constantly attack and damage human cells [3,17]. The human body produces antioxidants to protect itself from free radicals. This means that adding additional antioxidants, like resveratrol, to one’s diet would help the body protect itself from free radicals, delaying, and potentially halting, various diseases [17]. The use of resveratrol would help prevent cell damage and can help repair damaged cells, to some extent [17,18]. A study giving rats a daily dose of 28 milligrams of resveratrol per kilogram of their body weight over a 28-day period concluded that due to the lack of harmful effects from giving high doses of trans-resveratrol, trans-resveratrol has a large safety margin [17,19].

In recent years, resveratrol has become widely available as a botanical dietary supplement in the United States [20]. They can be purchased at local drug stores, such as Wallgreens or CVS, or online. Since resveratrol is only present in small amounts in grapes, wine, and peanuts, (0.2-3.8 mg/L) multiple methods of extraction have been developed [20]. As previously stated, resveratrol has anticancer, anti-inflammatory and antitumor propertied. It also inhibits platelet aggregation and prevents low-density lip- oprotein (LDL) oxidation, which provides cardioprotective effects. It is consumed orally and metabolized in the liver. Trans resveratrol is a beneficial substance in the human diet.

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