The Power of the Grape: Research on Concord grapes,

grape polyphenols, and heart-health, plus emerging areas of study

Learning Objectives

• Identify the role of plant nutrients in heart health, particularly polyphenols found in grapes/grape products.

• Review growing scientific research on the role grapes/grape products play in promoting heart health.

• Recognize emerging areas of study on Concord grapes and health, such as cognition and immune health.

• Be aware of the role of Concord grapes and 100% juice as part of a healthy diet.

• Boost the heart-healthfulness of clients' diets, focusing on recipes and tips to enhance meals with vibrantly colored fruit.

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Heart Health and Concord Grapes: The Science

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Cardiovascular Health

• Genetics are a strong determinant of heart health.

• Modifiable factors such as diet and lifestyle affect risk:

– Eating heart-healthy foods, including fruits and vegetables

– Limiting total calories and saturated fat consumption

– Maintaining ideal weight

– Not smoking

– Being physically active

• 81 million Americans are afflicted with cardiovascular disease.1

– 37% of population

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Power of the Grape

• A large body of research supports the idea that consumption of Concord grape juice, as part of a produce-rich diet, can positively impact health.

• Mostly attributed to polyphenols – natural source of nutrients that support health:

– Found in skins and seeds of Concord grapes

– Give grapes their color

– Naturally function as antioxidants to protect against too many free radicals

– Have other important health-promoting effects

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Polyphenols: • Sub-group of phytonutrients.

• Found in foods like onions, tea, red wine, grapes, grape juice, blueberries and certain nuts.

• Plant biologists suggest that polyphenols protect plants against pathogens, parasites and predators, and often contribute to the flavor and color of produce. Flavonoids: • Largest and most studied sub-group of polyphenols.

• There are thousands of different flavonoids in fruits, vegetables and plant-derived beverages (e.g. teas, wines, and juices).

Phytonutrients = Plant Nutrients

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In Concord grapes, flavonoids are particularly found in the skins and seeds. The skin has a high concentration of a class of flavonoids called anthocyanins, while the seeds contain flavanols, including proanthocyanidins.

Researchers have been actively investigating the effects of flavonoids on cardiovascular health.

Phytonutrients = Plant Nutrients

Polyphenols as Antioxidants

Studies have shown:

• Concord grape juice has a greater polyphenol concentration than many other juices.2

– In 2008, scientists measuring the polyphenol content and antioxidant potential of a variety of beverages found that the total polyphenol content of Concord grape juice was higher than many other juices, including blueberry, cranberry, orange, and apple juices. Their study also showed that grape juice has the ability to scavenge free radicals and protect LDL cholesterol against free radical-induced damage.

• Antioxidant potential of Concord grape juice vs. red wine is about the same.3

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Polyphenols as Antioxidants

Studies have shown:

• Concord grape juice helps manage the effects of LDL cholesterol.4,5

– Published in 2002, O’Byrne and colleagues asked 15 healthy adults to drink grape juice (10 mL/kg/d) each day for two weeks. They measured the susceptibility of LDL to oxidative damage by isolating it from blood and adding a pro-oxidant. They found that the rate of LDL oxidation was significantly reduced after grape juice consumption. The effect was similar to the effect produced by the antioxidant vitamin E in another arm of the same study.

– Positive results on LDL oxidation were also seen by Stein and colleagues, where patients with coronary artery disease drinking Concord grape juice (8 mL/kg/d) experienced slowed LDL oxidation time versus baseline,5 although the same group saw no effect of grape juice on LDL oxidation in another study.6

– While the above studies showed that Concord grape juice can positively impact the rate of LDL oxidation, which benefits cardiovascular health, they did not demonstrate a decrease in LDL cholesterol levels.

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Concord Grapes & Healthy Hearts

• Concord grapes may be one important ingredient for maintaining a healthy cardiovascular system; studies indicate Concord grapes may:

– Help support flexible arteries to promote healthy blood flow

– Have an anti-clotting effect similar to red wine

– Play a role in maintaining healthy blood pressure in certain populations

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Concord Grapes & Healthy Blood Flow

• The heart and arteries function to carry blood (and with the blood, oxygen and nutrients) to all cells in the body. An important regulator of the flow of blood is the vascular endothelium, which is the inner lining of cells inside all vessels.

• Normally, arteries dilate (open wider) in response to a demand for increased blood flow to a particular part of the body.

• People with risk factors for heart health issues have impaired dilation, and may have increased stiffness of their arteries.

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Concord Grapes & Healthy Blood Flow

• Concord grapes may help support flexible arteries.5-9

– Concord grape juice consumption has been shown to enhance flow-mediated dilation of the brachial artery.

• In one study, 15 patients with coronary artery disease drank grape juice (8 mL/kg/d) for two weeks. Researchers observed that flow-mediated dilation of the brachial artery (the large artery in the arm) was impaired in these patients at baseline and was improved after drinking the juice.5

• A second study from this same group showed significant increases in brachial artery dilation compared to baseline after coronary artery disease patients drank grape juice for 28 days.6

– Grape juice polyphenols have been shown to stimulate the production of nitric oxide,7,8 which can promote arterial relaxation.

• Nitric oxide is an important vasodilator produced by the endothelium; it acts to prevent inflammation and to inhibit platelet aggregation.

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Concord Grapes & Anti-Clotting Effects

• Concord grapes may have an anti-clotting effect7,10 similar to red wine.11

– In a study by Keevil et al, researchers compared the effects of grape juice, orange juice and grapefruit juice (~450 mL/d) in 10 healthy adults in a crossover study. Only grape juice showed an ability to inhibit platelet aggregation.10

– Similar results were seen in a study by Freedman et al on Concord grape juice consumption (7 mL/kg/d for 2 weeks) in 20 healthy adults.7

• Anti-platelet effects were attributed to the proanthocyanidins and other flavonoids found in Concord grape juice.

– Positive results were not seen in subjects on aspirin therapy, which also inhibits platelet aggregation.12

– An animal study has also shown reduced clotting and cholesterol levels.13

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Concord Grapes & Blood Pressure

• Concord grape juice and blood pressure is an emerging area of research.

• Concord grape juice may play a role in healthy blood pressure for men with hypertension.14,15

– Two studies on adult hypertensive males found those who drank Concord grape juice daily for 8 weeks (5.5 mL/kg/d)14 or 12 weeks (12 oz./d average)15 saw a decrease in systolic and diastolic blood pressure.

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Concord Grapes & Blood Pressure

• Nocturnal blood pressure is an indicator of healthy blood pressure regulation.

• Normally, blood pressure drops at night. Studies have shown

that people who do not show a drop or “dip” in blood pressure at night are more likely to develop heart-health related issues.

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Concord Grapes & Blood Pressure

• A recent study by Dohadwala et al. showed that the nocturnal dip was greater after subjects drank grape juice compared to after placebo.16

• Study details:

– Crossover study of 64 adult men and women with prehypertension or stage 1 hypertension.

– Participants drank 100% Concord grape juice (7 mL/kg/d) and a placebo drink for 8 wks each.

– Concord grape juice helped lower nocturnal blood pressure.

– Blood glucose levels were lower after Concord grape juice consumption and higher after placebo consumption.

– No significant decrease in ambulatory blood pressure.

• While preliminary, these results suggest a favorable effect of Concord grape juice and indicate that more research is warranted.

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Grapes & Nutrition Research

Epidemiological evidence on grape consumption and heart health, including the “French Paradox” is outlined in a 2009 Journal of Nutrition article.17

This review article supports the beneficial effects of grapes and grape polyphenols on cardiovascular health, including antioxidant effects, and effects on endothelial function, platelets, and blood pressure.

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Grapes & Nutrition Research

While many studies have focused on cardiovascular health, there are other potential benefits of grape consumption.

A comprehensive literature review published in 2010 supports the role of grapes and grape products in cardiovascular health, and discusses promising emerging research in cognitive and immune health.18

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Concord Grapes and Nutrition Research:

Emerging Areas of Study

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Concord Grapes and Cognitive Health

The research in this area is very preliminary, yet emerging science suggests that Concord grapes may offer certain cognitive health benefits.18-21

• Science indicates that the polyphenols in Concord grapes help support flexible arteries5-9 which, in turn, may help promote healthy blood flow to the brain.

• A diet rich in antioxidants, such as those found in fruits, vegetables, and their juices, can help slow and possibly even reverse age-related cognitive decline.22

• One pilot human study of older adults with early memory impairment found that daily Concord grape juice consumption resulted in improved memory measures. 19

• Most research has taken place in a laboratory setting – more clinical research needs to be conducted to truly understand if Concord grapes can impact cognitive health in humans.

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Concord Grapes and Immune Health

• Emerging research conducted in laboratory settings suggests that Concord grape polyphenols may play a role in supporting healthy immune function.23-26

• While more research is needed, a recent human study suggests that daily consumption of 100% grape juice made with Concord grapes and added vitamin C may play a role in adults’ immune system health.27

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Concord Grapes and Immune Health • Concord grape juice and immunity study (cont):27

– 85 adults ages 50-75 years consumed either 12 oz. 100% grape juice made with Concord grapes and added vitamin C or a placebo, grape-flavored drink every day for 9 weeks.

– Subjects who consumed the 100% grape juice showed significantly higher numbers and increased proliferation of gamma delta T-cells (a specific type of immune system cell) compared to the placebo group.

– The grape juice drinkers also had significantly higher levels of serum vitamin C, (which acts an antioxidant to support a healthy immune system), and significantly lower induced DNA strand breaks versus the placebo, suggesting antioxidant protection against oxidative stressors that can damage healthy cells.

– The observed positive effects could be the result of the vitamin C, the polyphenols, or both working together.

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Heart Health & Concord Grapes: Dietary Recommendations

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2010 Dietary Guidelines for Americans

• A healthy eating plan serves as the foundation for heart-healthy living. Eating within one’s calorie needs, getting essential nutrients and being active are all important for heart health.

• The 2010 Dietary Guidelines for Americans encourage:28

– Increased intake of nutrient-dense foods, such as produce, lean meats and low-fat dairy, whole grains and legumes

– Consumption of nutrients under-consumed by certain populations such as calcium, fiber, potassium and vitamin D

– Limited intake of foods and beverages with added sugars

– Increased fruit and vegetable consumption – colorful options

• Eating and drinking a broad array of colorful fruits and vegetables helps to ensure intake of a healthy mix of beneficial plant nutrients (polyphenols), as well as essential vitamins and minerals.

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Heart-Healthy Grocery List

Foods for a heart-healthy diet include:

– Whole grains

– Fat-free or low-fat milk/dairy

– Lean meats, poultry, fish, beans, eggs, nuts

– Foods low in saturated fats, trans fats, cholesterol, salt, and added sugars

– Vibrantly-colored fruits and vegetables

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About Vibrant, Blue/Purple Produce

• Darker-colored fruits typically offer more phytonutrients than lighter

options.

– Dark-skinned blue and purple fruits also have unique plant nutrients not found in many other colors of fruits and vegetables.

• Blue and purple fruits and vegetables account for about 3% of total produce intake,29 despite blue and purple fruits and vegetables being associated with healthier diets in children and adults.30

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About Vibrant, Blue/Purple Produce

The most popular blue/purple fruits and vegetables, accounting for almost 60% of blue/purple eating occasions, are:30

• Grapes

• 100% Grape Juice

• Raisins

Other sources include:

• Blackberries

• Blueberries

• Plums

• Dried plums/prunes

• Eggplant

• Purple cabbage

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Vibrant Heart-Healthy Fruits: Concord Grapes

• Concord grapes are a wholesome, nutrient-dense plant food and a great purple food option.

• Just one 4-oz. glass of 100% grape juice made with Concord grapes counts as one serving (or ½ cup) of purple fruit.

• Fresh, frozen and canned fruit, as well as 100% juice, each count towards fruits needs to help fill ½ the plate with fruits and vegetables

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Heart-Healthy Recipes with Concord Grapes

• Incorporating 100% grape juice made with Concord grapes into heart-healthy recipes is another way to increase intake of purple produce as part of a healthy diet.

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Nutrition Resources: for Health Professionals

and Their Clients

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Resources for Health Professionals

• Grape Science Center at

grapescience.com; includes

information on:

– Grapes & Health

– Grape Research Library

– Grape Chemistry

– Grape Nutrition Resources

– Grape Glossary

– Grapes in the News

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References

1. Heart Disease and Stroke Statistics 2010 Update: A Report From the American Heart Association. Circulation. 2010, 121;e46-e215.

2. Seeram NP, Aviram M, Zhang Y, Henning SM, Feng L, Dreher M, Heber D. Comparison of antioxidant potency of commonly consumed polyphenol-rich beverages in the United States. J Agric Food Chem. 2008. 56(4):1415-1422.

3. Durak I, Avci A, Kacmaz M, Büyükkoçak S, Cimen MY, Elgün S, Oztürk HS. Comparison of antioxidant potentials of red wine, white wine, grape juice and alcohol. Curr Med Res Opin. 1999. 15(4):316-320.

4. O’Byrne DJ, Devaraj S, Grundy SM, Jialal I. Comparison of the antioxidant effects of Concord grape juice flavonoids alpha-tocopherol on markers of oxidative stress in healthy adults. Am J Clin Nutr. 2002. 76(6):1367-1374.

5. Stein JH, Keevil JG, Wiebe DA, Aeschlimann S and Folts JD. Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation. 1999. 100(10):1050-1055.

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References

6. Chou EJ, Keevil JG, Aeschlimann S, Wiebe DA, Folts JD and Stein JH. Effect of ingestion of purple grape juice on endothelial function in patients with coronary heart disease. Am J Cardiol. 2001.88(5):553-555.

7. Freedman JE, Parker C, 3rd, Li L, Perlman JA, Frei B, Ivanov V, Deak LR, Iafrati MD and Folts JD. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001. 103(23):2792-2798.

8. Anselm E, Chataigneau M, Ndiaye M, Chataigneau T and Schini-Kerth VB. Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS. Cardiovasc Res. 2007. 73(2):404-413.

9. Fitzpatrick DF, Hirschfield SL and Coffey RG. Endothelium-dependent vasorelaxing activity of wine and other grape products. Am J Physiol Heart Circ Physiol. 1993. 265(34):H774-H778.

10. Keevil JG, Osman HE, Reed JD and Folts JD. Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation. J Nutr. 2000. 130(1):53-56.

11. Folts JD. Antithromboic potential of grape juice and red wine for preventing heart attacks. Pharmaceutical Biology. 1998. 36(Supplement 1):21-27.

12. Albers AR, Varghese S, Vitseva O, Vita JA and Freedman JE. The antiinflammatory effects of purple grape juice consumption in subjects with stable coronary artery disease. Arterioscler Thromb Vasc Biol. 2004. 24(Nov):e179-e180.

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References 13. Shanmuganayagam D, Warner TF, Krueger CG, Reed JD, Folts JD. Concord grape juice

attenuates platelet aggregation, serum cholesterol and development of atheroma in hypercholesterolemic rabbits. Atherosclerosis. 2007. 190(1):135-142.

14. Park YK, Kim JS and Kang MH. Concord grape juice supplementation reduces blood pressure in Korean hypertensive men: double-blind, placebo controlled intervention trial. Biofactors. 2004. 22(1-4):145-147.

15. Mark D and Maki K. Concord grape juice reduces blood pressure in men with high systolic blood pressure. Experimental Biology. San Diego, CA. April 11-15, 2003.

16. Dohadwala MM, Hamburg NM, Holbrook M, Kim BH, Duess M, Levit A, Titas M, Chung WB, Vincent FB, Caiano T, Frame AA, Keaney Jr JF, and Vita JA. Effects of Concord grape juice on ambulatory blood pressure in prehypertension and stage 1 hypertension. Am J Clin Nutr. 2010. 91(5):1052-1059.

17. Dohadwala MM and Vita JA. Grapes and cardiovascular disease. J Nutr 2009. 139(9): 1788S-1793S.

18. Vislocky LM and Fernandez MLF. Biomedical Effects of Grape Products. Nutrition Reviews. 2010. 68(11): 656-670.

19. Krikorian R, Nash TA, Shidler MD, Shukitt-Hale B and Joseph JA. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2010. 103(5):730-734.

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References 20. Shukitt-Hale B, Carey A, Simon L, Mark DA and Joseph JA. Effects of Concord grape juice

on cognitive and motor deficits in aging. Nutrition. 2006. 22(3):295-302.

21. Ho L, Ferruzzi MG, Janle EM, Lobo J, Chen TY, Talcott ST, Simon J, Wu QL, Wang J, Cheng A, Weaver CM, Percival SS and Pasinetti GM. Bioavailability of grape-derived polyphenolics and implications in Alzheimer’s disease prevention and therapy. Presented at Experimental Biology 2010. Anaheim CA. April 24-28, 2010.

22. Joseph JA, Shukitt-Hale B and Casadesus G. Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr. 2005. 81(1 Suppl):313S-316S.

23. Lipson SM, Cohen P, Zhou J, Burdowski A and Stotzky G. Cranberry cocktail juice, cranberry concentrates, and proanthocyanidins reduce reovirus infectivity titers in African green monkey kidney epithelial cell cultures. Mol Nutr Food Res. 2007. 51(6):752-758.

24. Ferrari C, Monge L, Zaccheo A, Gordon R, Livingston R, Stotzky G, Burdowski A and Lipson SM. Effect of store-purchased and pure cranberry and grape juice drinks on the reduction of Reoviridae infectivity titers in cell culture and cell-free suspensions. Presented at The American Society for Microbiology 109th General Meeting. Philadelphia, PA. May 17-21, 2009.

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References 25. Leon MS, Kibrik P, Karthikeyan L, Gordon Ronald E and Lipson Steven M. Cranberry and

Grape Juices Reduce Rotavirus Infectivity in Cell-Free Suspension and Maintain Tight Junction Integrity of Infected Epithelial Cells in Monolayer Culture. Presented at The American Society for Microbiology 110th General Meeting. San Diego, CA. May 23-27, 2010.

26. Lipson SM, Gordon RE, Karthikeyan L, Singh M, Burdowski A, Roy M and Stotzky G. Cranberry and Grape Juice Drinks Affect Infectivity, Integrity, and Pathology of Enteric Viruses in an Animal Model. Ch. 11. In Flavor and Health Benefits of Small Fruits. Qian MC and Rimando AM, Eds. American Chemical Society: Washington, DC. 2010. 177-195.

27. Rowe CA, Nantz MP, Nieves C, West RL and Percival SS. Regular Consumption of Concord Grape Juice Benefits Human Immunity. J Med Food. 2011. 14(1-2):69-78.

28. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2010. 7th Edition, Washington, DC: U.S. Government Printing Office, December 2010.

29. Produce For Better Health Foundation. State of the Plate Study on America's Consumption of Fruits and Vegetables. Wilmington, Delaware. 2003.

30. McGill CR, Wightman JD, Fulgoni S and Fulgoni III VL. Consumption of Purple/Blue Produce is Associated with Increased Nutrient Intake and Reduced Risk for Metabolic Syndrome: Results From the National Health and Nutrition Examination Survey 1999-2002. Am J Lifestyle Med. 2011. 5(3):279-290.

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This continuing education opportunity was made possible through an educational grant from

Welch's and is intended for use with a health professional audience.

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