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The Polyphenol

One Powerful Ingredient for Health

The Polyphenol: One Powerful Ingredient for Health

Fruits and vegetables, including Concord and Niagara grapes, are abundant in polyphenols, and juice made with Concord grapes contains many different types of polyphenols shown to help promote health.1

Polyphenols and Antioxidant Power

Polyphenols are concentrated in the seeds and skin of both Concord and Niagara grapes and they act as antioxidants to help neutralize damaging free radicals, which are unstable molecules that can harm healthy cells.2,3 The polyphenols found in Concord grapes contribute to the antioxidant power of 100% grape juice, as measured by in vitro ORAC lab tests.1 Like its cousin the purple Concord grape, the white Niagara grape contains a unique mix of polyphenols.

  • In the Journal of Agriculture and Food Chemistry, Seeram et al., (2008) reported that the polyphenol concentration in Concord grape juice exceeded that of many other juices, including blueberry, açaí, cranberry, orange, and apple juices.4 Although this study found a slightly higher polyphenol content in the red wines than grape juice, there were mixed results on in vitro measures of antioxidant power depending on the assay. Other in vitro research suggests little difference in antioxidant potential between the two beverages, on average.5
  • In 2009, Dr. Holt and colleagues (Journal of American Dietetic Association) conducted a cross-sectional study and determined that higher fruit and vegetable consumption in adolescents was associated with lower levels of inflammation and oxidative stress. Different foods high in polyphenols were associated with anti-inflammatory and antioxidant effects. For example, consumption of fruits and vegetables as a whole, vitamin C, beta-carotene and specific flavonoids (a sub-group of polyphenols) were found to be associated with a decrease in markers of oxidative stress.6 Concord and Niagara grapes were not examined within this study.
  • Specific to grapes, Zern et al., (Journal of Nutrition) documented reductions of urinary measures of oxidative stress and plasma concentrations of inflammatory cytokines following daily consumption of grape powder mixed with water. This study involved 24 pre- and 20 postmenopausal women who were randomly assigned to consume either 36 grams of a grape powder or a placebo for 4 weeks. The authors suggested that the decreases in oxidative stress resulted, at least in part, from the grape polyphenols acting as free radical scavengers. Consumption of grape powder caused a significant reduction in the concentration of LDL-cholesterol, but LDL oxidation lag time did not change.7

    While this work did not use a Concord-based grape powder, other researchers examined consumption of Concord grape juice for 2 weeks and saw no change in the same urinary oxidative stress marker. However, they did note a significant increase in LDL oxidation lag time and plasma antioxidant capacity.2
  • Esmaillzadeh and collaborators investigated the relationship between fruit and vegetable consumption and the prevalence of metabolic syndrome in middle-aged females living in Iran. This cross-sectional research, published in 2006 in the American Journal of Clinical Nutrition, found an inverse relationship between fruit and vegetable intakes and markers of inflammation, specifically C-reactive protein (CRP). This study also found that higher intakes of fruit and vegetables were associated with a lower risk of metabolic syndrome. In other words, those consuming the most fruits and vegetables were more likely to have reduced inflammation, and about a 30% reduced risk of metabolic syndrome as compared to those eating the least amount.8 While fruits and vegetables are known to be abundant in polyphenols, it’s important to note that this research did not look specifically at the effect of grapes or grape polyphenols on inflammation or metabolic syndrome. In studies specifically examining Concord grapes, there was no observed effect on decreasing CRP.9,10

Polyphenols and Cell-to-Cell Communications

Beyond the polyphenol’s antioxidant effects, these phytonutrients may impact health in other ways, including via cell signaling.

  • Laboratory studies have demonstrated the biological activity of flavonoids via cell signaling, or signal transduction pathways.11 Signaling is a complex, highly regulated means of communication between and within cells that controls all cellular activities, including development, protection, maintenance, and death. Errors in signaling are thought to be related to health issues. Researchers theorize that flavonoids and their metabolites may bind to and interact with certain “regulators” that ultimately alter gene expression, which could potentially result in protective health benefits to humans.11,12

Polyphenols and Heart, Mind and Immune System Health

Many of the polyphenols in Concord grapes are the same as those found in red wine and may be associated with heart-health benefits.13,14 More than a decade’s worth of research suggests that drinking Concord grape juice may benefit the heart by helping to maintain healthy, clear and flexible arteries to promote healthy blood flow.14-18

Other prospective cohort studies have investigated the relationship between flavonoid (a polyphenol) intake and cardiovascular disease (CVD).19,20

  • Hirvonen and colleagues (Epidemiology) examined data from a 6-year primary prevention trial of middle-aged smoking males and found those with a higher intake of flavonoids (specifically flavonols and flavones) had a lower risk of non-fatal heart attacks and a lower risk of coronary death, when compared to those with the lowest intake of these phytonutrients. The men with higher intake of flavonoids also ate more fruits, berries, and vegetables.19
  • Similarly, in 2007, Mink et al., (American Journal of Clinical Nutrition) reported inverse associations between flavonoid intake (including anthocyanins) and cardiovascular disease (CVD) in post-menopausal females followed for 16 years as part of the Iowa Women’s Health Study.20

Researchers have also begun investigating the role of Concord grapes in cognitive function. The science in this area is very preliminary, with more human trials needed before any conclusions can be drawn. However, emerging science suggests that, thanks to the polyphenols, Concord grapes may offer certain health benefits for the mind. Specifically, these preliminary results suggest that polyphenols help keep arteries flexible2,14-18 – which, in turn, can help promote healthy blood flow to the mind.21,22 Early research also proposes that a diet rich in antioxidants, like those found in fruits and vegetables, can help slow and possibly even reverse age-related cognitive decline.23,24 Also, a recent review supports that, while additional research is necessary, fruit-derived phytonutrients, like polyphenols, may play a role in supporting memory, learning and overall mental performance.22

Additional studies suggest that a diet rich in polyphenols can help support cognitive performance.25

  • In 2007, The Journal of American Epidemiology published a prospective cohort study, by Letenneur et al., of healthy subjects aged 65 and older. The decade-long study found that there was an association between the highest flavonoid intake and better cognitive performance as compared to those with the lowest flavonoid intake, after adjusting for potential confounders such as age, education, smoking status, and gender.25

Promising early research is also underway in the area of immune health.26-30

For more information on the research behind Concord grapes and health,
visit Concord Grapes and Health.

Bottom Line

Early research suggests that phytonutrients, including polyphenols found in Concord and Niagara grapes, may have health benefits. These natural compounds are being actively investigated in the scientific community, and more research is needed before any conclusions can be drawn. Specifically, it’s important to note that much of the research to date has been conducted in laboratory settings and in select populations who, in some cases, had pre-existing health conditions. With that said, a diet high in phytonutrient-containing fruits and vegetables appears to support overall health by helping to positively impact inflammation and oxidative stress, among other possible benefits for overall health.


  1. Mullen W, Marks SC and Crozier C. Evaluation of Phenolic Compounds in Commercial Fruit Juices and Fruit Drinks. J. Agric. Food Chem. 2007. 55(8:3148–3157.
  2. O'Byrne DJ, Devaraj S, Grundy SM and 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.
  3. Castilla P, Echarri R, Davalos A, Cerrato F, Ortega H, Teruel JL, Lucas MF, Gomez-Coronado D, Ortuno J and Lasuncion MA. Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinflammatory effects in both hemodialysis patients and healthy subjects. Am J Clin Nutr. 2006. 84(1):252-262.
  4. 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.
  5. 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.
  6. Holt EM, Steffen LM, Moran A, Basu S, Steinberger J, Ross JA, Hong CP, Sinaiko AR. Fruit and vegetable consumption and its relation to markers of inflammation and oxidative stress in adolescents. J Am Diet Assoc. 2009. 109(3):414-421.
  7. Zern TL, Wood RJ, Greene C, 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. 135(8):1911-1917.
  8. Esmaillzadeh A, Kimiagar M, Mehrabi Y, Azadbakht L, Hu FB and Willett WC. Fruit and vegetable intakes, C-reactive protein, and the metabolic syndrome. Am J Clin Nutr. 2006. 84(6):1489-1497.
  9. 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(11):e179-180.
  10. 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. 92(5):1052-1059.
  11. Williams RJ, Spencer JP and Rice-Evans C. Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med. 2004. 36(7):838-849.
  12. Spencer JP, Rice-Evans C, Williams RJ. Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability. J Biol Chem. Sep 12 2003;278(37):34783-34793.
  13. Folts JD. Antithrombotic potential of grape juice and red wine for preventing heart attacks. Pharmaceutical Biology. 1998. 36(Supplement 1):21-27.
  14. 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.
  15. Fitzpatrick DF, Bing B, Maggi DA, Fleming RC and O'Malley RM. Vasodilating procyanidins derived from grape seeds. Ann N Y Acad Sci. 2002. 957:78-89.
  16. Freedman JE, Parker C, 3rd, Li L, et al. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001. 103(23):2792-2798.
  17. 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.
  18. 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.
  19. Hirvonen T, Pietinen P, Virtanen M, Ovaskainen ML, Häkkinen S, Albanes D, Virtamo J. Intake of flavonols and flavones and risk of coronary heart disease in male smokers. Epidemiology. 2001. 12(1):62-67.
  20. Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong CP, Nettleton JA, Jacobs DR Jr. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr. 2007. 85(3):895-909.
  21. Nash, DT and Fillit H. Cardiovascular disease risk factors and cognitive impairment. Am. J. Cardiol. 2006. 97(8):1262-1265.
  22. Spencer JP. Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance. Proc Nutr Society. 2008. 67(2):238-252.
  23. 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(suppl):313S-316S.
  24. 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.
  25. Letenneur L, Proust-Lima C, Le Gouge A, Dartigues JF and Barberger-Gateau P. Flavonoid intake and cognitive decline over a 10-year period. Am J Epidemiol. 2007. 165(12):1364-1371.
  26. 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.
  27. Percival SS. Grape consumption supports immunity in animals and humans. J Nutr. 2009. 139(9):1801S-1805S.
  28. 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.
  29. 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.
  30. 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.
Eating a balanced diet rich in a variety of fruits and vegetables is important for maintaining overall health. Delicious Concord grapes and 100% grape juice are part of a nutritious diet, but they should not be used to treat health problems. If you are worried about your health or are faced with a medical concern, be sure to consult with your doctor.

Guide to Navigating Research Studies

The definition of scientific research is performing a methodical study in order to prove a theory or answer a question. The following is a brief overview of different types of research used in health and nutrition exploration 1:

Case-Control Study
Clinical Study
Cohort Study
Cross-Sectional Study
Observational Study
Pilot Study
Preclinical or Laboratory Studies
Randomized Controlled Trials


1. Hulley SB, Cummings SR, Browner WS, Grady D, Hearst N, Newman TB. Designing Clinical Research: An Epidemiologic Approach. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007.

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An observational study, usually a retrospective study (a study that looks backward in time) that compares two groups of people: 1) those with the specific condition (e.g., disease) being studied (cases) and, 2) a similar group of people without that condition (controls). Researchers compare these two groups of people and important characteristics, such as certain lifestyle choices, to determine what factors may be associated with the condition under investigation.

A type of study that often includes patients with specific health conditions who could benefit from receiving a new treatment. These studies can also be performed in healthy subjects. The end goal of a clinical study (also called clinical research or clinical trial) is to determine effectiveness and safety of a health intervention in humans.

An observational study, usually prospective (looking forward), that follows a group of similar people over time. The goal is to determine which factors and exposures affect the development of a specific outcome or health condition (e.g., disease) during the study’s time period.

A type of observational study, often given as a survey, that examines a group of subjects during a single occasion, or over a very short period of time. This type of study aims to describe the relationship between health-related conditions (e.g., metabolic syndrome, hypertension) and other factors that exist in the general population (e.g., dietary intake, physical activity levels), during a particular time period.

A type of study in which researchers simply observe subjects and measure the associations between certain characteristics (e.g., fruit/vegetable intake) and specific outcomes (e.g., obesity). Examples of observational studies include case-control studies, cross-sectional studies, and cohort studies. While these studies gather important information, they cannot prove that a specific treatment or factor affects health.

A small scale, preliminary study that is conducted to determine the potential for a larger study.

A stage of research that often occurs prior to trials involving humans. This type of research can help determine mechanisms of action of a treatment, or how the treatment is causing the effect, as well as help ensure the safety of treatment in subsequent human trials.

In vitro
Testing performed in a controlled environment, such as a test tube or a Petri dish, instead of living organisms. In vitro literally means "within the glass" in Latin.

Ex vivo
These experiments are performed on tissue (e.g., animal or human cells) taking place outside of the organism, such as in a laboratory setting. In Latin, this means "out of the living."

In vivo
These tests are done on whole, living organisms. Technically, animal and human testing are two forms of in vivo research, which means "within the living." These experiments may be performed outside of a laboratory setting.

A study designed to provide the most credible information about the cause and effects of treatment. These types of studies are recognized as unbiased because they involve the random assignment of treatments to subjects being studied.

The tendency throughout any stage of research to generate findings that may not reflect "true values." In clinical trials, researchers try to avoid many kinds of bias, including selection by randomizing subjects, measurement by creating placebos and performing blind trials, and confounding by carefully designing the study and analyzing the findings.

Study in which subjects do not know whether they receive the treatment or the placebo, which assists in prevention of bias. Double-blinded studies are a higher level of scientific rigor because neither the participants nor the investigators know who is receiving the treatment or the placebo. A double-blind crossover study means each participant undergoes both the treatment and control scenario, typically with a wash-out period in between.

Study that allows researchers to isolate the effect size of the treatment by comparing a group given a simulated treatment (e.g., grape flavored drink) to those with the real treatment (e.g., Concord grape juice), which reduces measurement bias. The placebo should match as closely as possible to the treatment without containing the active ingredients.

Study involving participants who are randomly assigned to either the treatment or the placebo group, reducing selection bias.