Grapes activate genes that prevent heart failure.

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Grapes reduce heart failure associated with chronic (hypertension) by increasing the activity of several genes responsible for antioxidant defense in . Grapes are a known of antioxidants and other polyphenols.

The research was published in the Journal of Nutritional Biochemistry and researchers discovered a natural way that grapes exert on the heart which researchers believe to be responsible for the observed with grape consumption, influencing gene activities and that improve the levels of glutathione, the most abundant cellular antioxidant in the heart.

Hypertension affects approximately 1 billion people worldwide, which increases the risk of heart failure by 2 to 3-fold. Heart failure resulting from can result in an enlarged that becomes thick and rigid (), and unable to fill with blood properly (diastolic dysfunction) or pump blood effectively. Oxidative stress is strongly correlated with heart failure, and deficiency of glutathione is regularly observed in both human and of heart failure. Antioxidant-rich diets, containing lots of , consistently correlate with reduced hypertension.

“Our earlier studies showed that grapes could protect against the of hypertensive heart failure, but just how that was accomplished – the mechanism – was not yet known,” said lead investigator E. Mitchell Seymour, Ph.D. “The insights gained from our NIH study, including the ability of grapes to influence several genetic pathways related to antioxidant defense, provide further evidence that grapes work on multiple levels to deliver their .”

Seymour noted that the next phase of the NIH study, which will continue into 2014, will allow his team to further define the mechanisms of grape action, and also look at the impact of whole grape intake compared to individual grape phytonutrients on hypertension-associated heart failure.

“Our hypothesis is that whole grapes will be superior to any individual grape component, in each of the areas being investigated,” said Dr. Seymour. “The whole fruit contains hundreds of individual components, which we suspect likely work together to provide a synergistic beneficial effect.”

The insights gained from this research will further the knowledge on grapes and heart health, but will also provide translational information on the value of dietary (whole foods) and dietary supplement approaches for prevention of heart disease stemming from .

“The NIH grant is allowing the team at the University of Michigan Medical System to expand its work in this important area and further highlight the multi-faceted role of grapes in supporting heart health,” said Kathleen Nave, president of the California Table Grape Commission. “This work will also provide key insights into the role of whole fruit versus individual components of a fruit, using grapes as the benchmark.”

Previous studies have shown the correlation effects of grape consumption and improving antioxidant capacity, oxidative stress, and blood vessel function. In one study regular intake of grapes twice a day for 21 days had a significant effect.

A laboratory study showed that adding grapes to the diet of rats helped prevent the accumulation of harmful oxidized cholesterol and inhibited the development of atherosclerotic lesions. Specifically, the grape-enriched diet helped reduce oxidative stress, increase serum antioxidant capacity, reduce cell uptake of oxidized cholesterol and decrease the oxidation of LDL cholesterol. These processes can help reduce the accumulation of cholesterol in the cells and inhibit atherosclerosis.

In a series of laboratory studies, a grape-enriched diet helped protect against and the development of heart failure commonly associated with a high-salt diet. One study examined the impact of adding grapes to the diet of lab rats consuming either a high- or low-salt diet and also those receiving a mild dose of a common blood pressure drug, hydrazine. Those consuming a grape-enriched diet had lower blood pressure, better heart function, reduced inflammation throughout their bodies, and fewer signs of damage than those consuming the same diet but without grapes. The group receiving the blood pressure medicine but no grapes saw a reduction in blood pressure, but their hearts were not protected from damage as they were in the grape-fed group. Two additional studies, using a similar rat model and feeding a grape- enriched diet, also demonstrated these types of protective effects.

Source

E. Mitchell Seymour, Maurice R. Bennink, Steven F. Bolling. Diet-relevant phytochemical intake affects the cardiac AhR and nrf2 transcriptome and reduces heart failure in hypertensive rats. The Journal of Nutritional Biochemistry, 2013; DOI: 10.1016/j.jnutbio.2013.01.008

Chaves AA et al. Vasoprotective endothelial effects of a standardized grape product in humans. Vascular Pharmacology.50 2009: 20-26.

Zern TL, Fernandez ML. Grape polyphenols exert a cardioprotective effect in pre- and post-menopausal women by lowering plasma lipids and reducing oxidative stress. J Nutr. 2005,135:1911.

Fuhrman B, et al. Grape Powder Polyphenols Attenuate Atherosclerosis Development in Apolipoprotein E Deficient Mice and Reduce Macrophage Atherogenicity. J Nutr. May 2005, 135:722-728.

Seymour EM. Chronic intake of phytochemical-enriched diet reduced cardiac and diastolic dysfunction caused by prolonged salt-sensitive hypertension. J Gerontol Biolog Sci. 2008, Vol. 63A , No. 10; 1034-1042.

Seymour EM, et al. Grape Intake Reduces Heart Failure Pathogenesis in Rats. Acta Hortic. 2009, 841:207-213.

Seymour EM et. al. Whole Grape Intake Impacts Cardiac Peroxisome Proliferator-Activated Receptor and Nuclear Factor κβ Activity and Cytokine Expression in Rats With Diastolic Dysfunction. Hypertension. May 2010, Vol.55, No. 5.

Chaves AA et al. Vasoprotective endothelial effects of a standardized grape product in humans. Vascular Pharmacology.50 2009: 20-26.

Prior RL, et al. Plasma antioxidant capacity changes following a meal as a measure of the ability of a food to alter in vivo antioxidant status. J. Am Coll Nutr. 2007, 26, No.2:170-181.

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