by Chris D. Meletis, ND and Jeffrey Reinhardt, MSc
Resveratrol is the best known health promoting molecule in red wine1 and has been studied by scientists investigating its effects on genes as well as the heart, breast, prostate, uterus, and immune system. In addition, recent studies show that resveratrol sustains healthy nerves and important brain functions including cognitive processes.2-4
In various epidemiological studies and clinical trials, consumption of resveratrol, quercetin and other red wine components have been associated with a reduced risk of heart disease and improved cardiovascular health. In vitro and animal studies also have shown that red wine components can influence various factors associated with breast, prostate and lung health, and can reduce the free radical damage that occurs during influenza virus infection. In fact, quercetin, red wine polyphenols and resveratrol provide important synergistic benefits for the heart.
Heart Health
Resveratrol is a plant protective phytoalexin produced by grapes, mulberries, peanuts and soy beans, and is found in honeybee hives, red wines such as Pinot Noir, Itadori tea and various medicinal herbs such as Japanese Knotweed (Polygonum cuspidatum). This compound occurs in two conformational forms – cis and trans-resveratrol. Trans-resveratrol is the preferred functional form. The most effective trans-resveratrol is one that is exceptionally high quality, extracted from Polygonum cuspidatum in a process that results in very low levels (1 percent or less) of undesirable cis- isomers. It is further enzymatically hydrolyzed to remove the glycosides (naturally-occurring sugar molecules), since the aglycone (sugar-free) form of trans-resveratrol is more efficiently absorbed. Accelerated stability studies performed with our trans-resveratrol demonstrate excellent stability over its projected two-year shelf life.
Trans-resveratrol is thought to improve heart health in a number of ways. Laboratory experiments in vitro and studies in animals have shown that trans-resveratrol can stop blood platelets from sticking together (platelet aggregation). In one study, scientists investigated the effects of resveratrol and red wine on aggregation of platelets isolated from healthy male volunteers.
The researchers induced platelet aggregation in blood from healthy subjects and determined that trans-resveratrol significantly inhibited the sticking together of blood platelets. Researchers also induced platelet aggregation in rabbits with high cholesterol and found that when trans-resveratrol was given to the rabbits, the platelets did not stick together.5 Since sticky platelets are tied to increased risk of heart attack, stroke and blood clots throughout the body, this is a significant finding in regards to life-threatening risk factors.
According to the researchers, “These results suggest that trans-resveratrol can inhibit platelet aggregation both in vitro and in vivo, which conceivably could be one of the mechanisms by which this red wine polyphenol exerts its cardioprotective effects.”
Another of trans-resveratrol’s interesting cardiovascular implications is its ability to enhance angiogenesis, the development of new blood vessels, in order to help feed the heart during periods of oxygen deprivation (ischemia). The formation of new blood vessels caused by trans-resveratrol restores the blood supply to the ischemic area, preventing heart cell death and abnormal changes to the heart.6
In a study of 24 pre- and 20 postmenopausal women, researchers randomly assigned the subjects to receive either a placebo or grape powder rich in trans-resveratrol, quercetin and other polyphenols for four weeks. After a 3-week washout period, the subjects given the grape powder were switched to a placebo and the subjects receiving the placebo then received the grape powder. In both the pre-and postmenopausal women, concentrations of plasma triglycerides, another cardiac risk factor, dropped by 15 and 6 percent respectively after supplementation with the grape polyphenols. In addition, plasma LDL cholesterol and apolipoproteins B and E levels were lower after supplementation with the grape powder. In addition, whole-body oxidative stress was significantly reduced after supplementation with the grape powder. When subjects were taking the grape powder, the levels of plasma tumor necrosis factor-alpha, which plays a major role in the inflammation process, were lower.7 These results led the researchers to conclude that grape polyphenols, through alterations in lipoprotein metabolism, oxidative stress, and inflammatory markers, “beneficially affected key risk factors for coronary heart disease in both pre- and postmenopausal women.”
In another study, red grape polyphenol extract containing quercetin, trans-resveratrol and other polyphenols improved blood flow in the arteries of male patients with coronary heart disease.8
Anti-Inflammatory Actions
Not only are trans-resveratrol, quercetin and other red wine polyphenols powerful antioxidants, they also exert a strong anti-inflammatory effect. They appear to accomplish this by inhibiting nuclear factor-kappa beta (NF-kappaB), a protein with a pivotal role in controlling cell signaling in the body under certain physiological and pathological conditions. Among other functions, NF-kappaB controls the expression of genes encoding the pro-inflammatory cytokines (proteins produced by white blood cells), chemokines (cytokines that assist in destroying invading micro-organisms) and immune receptors, all of which play critical roles in controlling most inflammatory processes. NF-kappaB is so important in controlling inflammation that over the last decade researchers have spent a great deal of time identifying compounds that interfere with the NF-kappaB pathway in the hopes of finding agents useful in inflammatory diseases such as arthritis, asthma and autoimmune conditions. Recently, researchers have discovered that trans-resveratrol, quercetin and other polyphenols found in red wine may inhibit the NF-kappaB pathway.9
These same red wine compounds inhibit expression of another important marker of inflammation and a risk factor for heart disease—C-reactive protein (CRP). Recent research has found that quercetin and trans-resveratrol can, in a dose-dependent manner, suppress the expression of CRP that occurs after the activation of inflammatory cytokines.10
Conclusion
Trans-resveratrol is a multifunctional modulator of numerous, complex cellular signaling pathways, which regulate vital cellular processes such as cell growth, apoptosis or programmed cell death, ischemic heart disease and thrombosis, insulin resistance and diet-induced obesity, improved mitochondrial functions plus the activation of the Sirtuin family of longevity genes (see sidebar). In addition to being a powerful antioxidant, trans-resveratrol acts like a molecular master key, “opening” or up regulating important genes and functionally related sequences of DNA or “families” of genes that directly control both the lifespan and metabolic efficiency. Trans-resveratrol also stimulates the production of ATP in the mitochondria of muscles.9
As a key regulatory molecule, trans-resveratrol improves cellular energy production and up regulates the expression of many different genes, leading to metabolic homeostasis as a prerequisite for a long and healthy life.
Dr. Chris D. Meletis, Executive Director, The Institute for Healthy Aging, article reprint via an educational grant from Complementary Prescriptions
References
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- Zhuang H., Kim YS, Koehler RC, Dore S., Potential mechanism by which resveratrol, a red wine constituent, protects neurons. Ann NY Acad Sci. 2003 May; 993: 276-86; discussion 287-88.
- Wang Z, Huang Y, Zou J, Cao K, Xu Y, Wu JM. Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. Int J Mol Med. 2002 Jan;9(1):77-9.
- Maulik N. Reactive oxygen species drives myocardial angiogenesis? Antioxid Redox Signal. 2006 Nov-Dec;8(11-12):2161-8.
- Zern TL, Wood RJ, Greene C, West KL, Liu Y, Aggarwal D, Shachter NS, Fernandez ML. Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress. J Nutr. 2005 Aug;135(8):1911-7.
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- Nam NH. Naturally occurring NF-kappaB inhibitors. Mini Rev Med Chem. 2006 Aug;6(8):945-51.
- Kaur G, Rao LV, Agrawal A, Pendurthi UR. Effect of wine phenolics on cytokine-induced C-reactive protein expression. J Thromb Haemost. 2007 Jun;5(6):1309-17.