The Red Wine Diet
The protective effect of red wine, which appears to be much greater than the protection by other alcoholic beverages (127), may also be mediated through KCa channels. Red wine has been shown to increase cGMP levels and decrease the tone in human coronary arteries and rat aorta. This increase was endothelium dependent and likely involves the release of NO from endothelium (128). All wines did not produce this effect, but it was observed only after the administration of certain red wines produced ''en barrique,'' possibly due to their high content of phenolic substances (128).
For example, resveratrol, a polyphenolic molecule found in red wine, has received much attention as a possible antiaging drug and CR mimetic based on this type of approach. The link between resveratrol and aging came out of a screen for small molecules that activate SirT1, a human protein orthologous to yeast Sir2 (Howitz et al., 2003). Sir2-family proteins (Sirtuins) have been reported to increase life span in yeast (Kaeberlein et al., 1999), worms (Tissenbaum and Guarente, 2001), and flies (Rogina and Helfand, 2004) when overexpressed, suggesting that Sirtuin activators might also slow aging.
Paradoxically, a recent report indicates that the antioxidant resveratrol, a component of red wine and an activator of sirtuin deacetylases, can attenuate polyQ-mediated neuronal death. Resveratrol treatment was effective in both a C. elegans HD model, which expressed an N-terminal htt fragment
The dependence of a mutagenic effect in recombinant test systems is usually demonstrated by conducting control experiments in the parental bacterial strain or cell line lacking the specific enzyme. As an alternative, an appropriate agent, such as pentachlorophenol with SULT1A1, can inhibit the heterologous enzyme. The test system can be used to study defined chemicals or complex samples for chemopre-ventive activity. For example, dealcoholized red wine completely suppressed the mutagenicity of N-OH-PhlP (7 Figure 13.9) and 1-hydroxymethylpyrene (1 Glatt, 2000b) to a TA1538-derived S. typhimurium strain expressing human SULT1A1. In this case, the effect was due to inhibition of the enzyme. It would be important to know whether this chemoprotection would also occur in vivo in the human. This situation is typically characterized by a low exposure to procarcinogens, a high total enzyme capacity, and limited (rather than total) inhibition by food-borne factors. With the limitation that...
Henry thought for a couple of seconds and replied, ''Complete faith in God, a good attitude toward life, a never-ending quest for learning, and an occasional glass of red wine.'' He smiled as the crowd broke into laughter. ''I've tried to live a simple life. All I've ever needed was a clever accountant, a forgiving minister, and a passionate wife.'' Henry added. Henry had outlived each of his three wives, and rumor had it that he was courting a possible fourth.
Many other plant natural products occur as glycosides. These glycosides do not demonstrate mutagenicity when tested in the Salmonella test however, upon hydrolysis of the glucosidic linkages they become mutagenic. There have been several studies showing mixed fecal cultures or fecal isolates of Streptococcus faecium can convert non-mutagenic rutin to quercetin (59). Quercetin has been shown to be mutagenic in the Ames salmonella assay. Red wine and tea contain glycosides of quercetin.
Machinery including RGC-1, and as a consequence PGC-1 transcriptionally activates the necessary gluconeogenic enzymes and precursors required for glucose production under starvation conditions. Remarkably, SIRT1 was shown to deacetylate PGC-1 and enhance its transcriptional ability under fasting conditions. These results support the idea that the Sir2 class of proteins can participate in nutritional responses and regulate whole-body metabolism and glucose homeostasis. The ability of this class of proteins to utilize NAD+ as a cofactor allows a fine-tuned response to nutritional conditions. Since energy status could potentially be a factor that dictates the ageing process, SIRT1 could represent a link to ageing in higher organisms (Rodgers et al., 2005 Nemoto et al., 2005). In light of this fact, there has been an effort to identify pharmacological tools that can activate the Sir2 class of proteins in order to harness their potential health benefits. In a search for Sir2 activators, it...
Flavonols are the most ubiquitous flavonoids in plants, with the main representatives being quercetin, kaempferol, myricetin, and isohamnetin, which are predominantly present as glycosides bound to a variety of sugar moieties. The richest sources are onions, curly kale, leeks, broccoli, and blueberries and are present at levels of approximately 30 mg kg fresh weight although in certain circumstances can reach in excess of 1.2 g kg fresh weight. Red wine and tea are also rich sources.
The red to purple colored anthocyanidins are responsible for a good portion of color in fruits and flowers. They are only present as glycosides or anthocyanins and their color is pH dependent. In the human diet, anthocyanidins are present in red wine, certain varieties of cereals, certain leafy and root vegetables (e.g., aubergines, cabbage, beans, onions, and radishes) and most abundantly in fruit. The content is generally proportional to the color intensity and may reach values of 2-4 g kg fresh weight in blackberries and black currants. They are found mainly in the skin, except where the flesh is also colored.
A few plant polyphenols, including quercetin, piceatoannol, and resver-atrol activate some Sir2 enzymes (43). Demonstrating the best activation of the compounds tested, resveratrol lowers the Km for NAD+ and for acetylated substrate but does not affect the turnover rate of the enzyme. Life span extension and increased cell survival upon DNA damage were observed in the presence of resveratrol (43), making this polyphenol found in red wine an excellent tool for future studies on Sir2 regulation. Recent studies have shown that the previously observed resveratrol activation, in vitro, was dependent on the use of fluorophore-containing peptides as substrates (43a,b). Peptide substrates lacking the fluorophore exhibited no activation. Activation was also largely specific to SIRT1. Therefore, unclear at this point is the mechanism of resveratrol-mediated Sir2 activation in vivo. Resveratrol has known antioxidant properties, and it is not clear whether the observed Sir2 activation is due to...
World consumption of natural health products, nutraceuticals, and functional foods is estimated to be between 140 and 250 billion and growing at an annual rate of about 10 . Nutraceuticals, also referred to as functional foods, are ordinary foods that have components or ingredients incorporated into them to give them a specific medical or physiological benefit, other than a purely nutritional effect. A good example comes from the so-called French paradox Epidemiological data prove that France has a low morbidity through cardiovascular coronaries (infarctus) despite the fact the diet is rich in lipids and risk factors in arteriosclerosis (think of the French cheeses and cigarettes). Polyphenols in red wine are now thought to play a role in the prevention of heart disease. Polyphenols inhibit the production of a peptide by blood vessel cells, a small protein called endothelin-1.
Flavonoids are widely distributed plant pigments and tannins occurring in barks, roots, leaves, flowers, and fruits. Their roles in plants include photoprotection and contributing to the plant color. Consequently, our diet contains flavonoids which can be found in a variety of foods from green vegetables to red wine 49 .
Animal experiments indicate that doses of quercetin equivalent to 1-2 glasses of red wine exerts a cardioprotective effect following ischaemia-reperfusion by improving the function of mitochondria, which play a critical role in myocardial recovery (Brookes et al 2002) and may also prevent the development of atherosclerosis through several indirect mechanisms (Auger et al 2005). In humans quercetin inhibits platelet aggregation and signalling and thrombus formation at doses of 1 50 mg or 300 mg quercetin-4'-0-beta-D-glucoside (Hubbard etal 2004). This effect, however, may not occur with clinically relevant doses.
Neuropsychological impairment may be detected in nearly half of individuals who drink excessive alcohol daily. Women and the elderly are particularly susceptible (Cummings & Benson, 1983). The prevalence of overt dementia is lower but may approach 25 in elderly alcoholics (Finlayson, Hurt, Davis, & Morse, 1988). Pellagra as a cause of dementia in alcoholics has diminished greatly since the institution of grain products fortified with niacin. Degeneration of the corpus callosum, Marchiafava-Bignami disease, is a rare complication of chronic alcohol consumption. It was first described in red wine-drinking Italian men, but has since been reported with many other forms of alcohol and in multiple locations worldwide. Hy-pothyroidism and vitamin B12 deficiency are both common in the elderly, but B12 deficiency is much rarer as a cause of dementia.
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