Grape Science Center

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Grape Research Overview

Concord and Niagara grapes provide an important mix of plant nutrients – polyphenols – that can help fuel healthy, vibrant lives. For more than a decade, researchers have been exploring the polyphenols found in Concord grapes and the effects they have on the body, including possible benefits in supporting cardiovascular health. In addition, emerging research is being conducted to determine whether Concord grapes play a role in supporting a healthy mind and immune system.

Please note that the following research summaries are only intended as brief overviews. Please refer to actual publications in each section for full details and to determine if this information may relate to you.

POLYPHENOL POWER – Polyphenols, which give Concord grapes their vibrant color, are plant nutrients that naturally function as antioxidants and help promote overall health.1-4

Polyphenols’ health benefits are often attributed to their antioxidant function. 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.1,2 The polyphenols found in Concord grapes contribute to the antioxidant power of 100% grape juice, as measured by in vitro ORAC lab tests.5

  • Research published in the American Journal of Clinical Nutrition by O’Byrne et al. in 2002 on antioxidant consumption in healthy adults found that those who consumed α-tocopherol (vitamin E), as well as those who drank Concord grape juice, experienced increases in serum antioxidant capacity and decreases in oxidation of LDL cholesterol rate after drinking Concord grape juice every day for two weeks.1
  • In a study by Albers et al. in 2004 on adults with coronary artery disease (CAD), drinking Concord grape juice daily for two weeks decreased free radical production and markers of inflammation.6 Similar research published in Circulation in 2001 on healthy adults found that daily Concord grape juice consumption for two weeks decreased the production of free radicals.7

CARDIOVASCULAR HEALTH – In addition to a produce-rich diet and active lifestyle, Concord grapes may be one important ingredient for maintaining a healthy cardiovascular system. Research suggests that polyphenols, like those found in Concord grapes, can contribute to heart health in certain populations by promoting healthy arteries.7-13

A literature review outlining nearly 20 years of research shows that grapes and grape products promote heart health. The findings from this review highlight strong evidence for the heart-health benefits of grapes in low-density (LDL) oxidation, oxidative stress, and vascular function.14

Concord grapes may help support flexible arteries to promote healthy blood flow.7-11
When the lining of arterial walls is not functioning properly, this can be an early sign of atherosclerosis (hardening of the arteries).18 Studies report that drinking Concord grape juice appears to help relax and dilate arteries in people with coronary artery disease.9,11 Relaxed and dilated arteries may support healthier blood flow throughout the body.

  • Concord grape juice consumption appears to help widen arteries when necessary, specifically in individuals with CAD. In 1999, Stein et al. studied 15 participants with CAD who consumed Concord grape juice for two weeks and saw significant increases in flow mediated dilation of the brachial artery.10 Chou and colleagues performed a similar study over a longer time period. These researchers found that in two groups of 11 adults with CAD, given different levels of Concord grape juice, there were equivalent and significant increases in brachial artery dilation after 28 days.9
  • A study completed and presented by Dorsey et al. suggests that drinking moderate amounts of Concord grape juice regularly supports healthy circulation in healthy overweight, older adults. This randomized, cross over, double blind, placebo-controlled study monitored 51 overweight men and women that were 50 years or older. Each group consumed 12 ounces (1½ cups) of Concord grape juice or a grape-flavored, sugar-sweetened drink daily during two continuous four-week periods. Researchers found that drinking Concord grape juice daily significantly improved flow mediated dilation versus placebo, demonstrating a benefit to vascular function and blood vessel health.15
  • In a study with young adult smokers who were otherwise considered healthy, Siasos et al. found that consumption of Concord grape juice increased flow mediated dilation (FMD) versus placebo. The 26 participants, average age 26 ± 5 years, consumed 7 mL/kg/d of Concord grape juice for two weeks and a placebo for two weeks with a four week washout period in-between. The researchers also found that chronic consumption of Concord grape juice prevented an immediate smoking-induced decrease in FMD.16
  • When compared to nearly 50 other fruit juices, Welch’s 100% Grape Juice grape juice made with Concord grapes made with Concord grapes, alongside blackcurrant juice and a red juice blend, had the most potent positive effect on blood vessel health. This laboratory research suggests that not only is it the polyphenol concentration, but also the type of polyphenols present in the grape juice, that supports blood vessel relaxation and healthy circulation.17
  • In a study published in Cardiovascular Research in 2007, researchers found that Concord grape juice was shown to stimulate the production of nitric oxide in cells that line the arteries, promoting arterial relaxation.8 Additional research has also illustrated that Concord grape juice produces this relaxation effect by stimulating the same reactions in the arteries that are activated by red wine. This research complements previous work by Freedman and colleagues, which showed increased production of nitric oxide from blood platelets in healthy adults drinking Concord grape juice,6 and may explain why coronary artery disease patients drinking Concord grape juice have shown improved arterial flexibility in some studies.9,11

Concord grapes may help promote healthy, clear arteries.1,11,19-21
Concord grape juice helps manage the effects of LDL or “bad” cholesterol to help keep arteries free and clear of excess plaque build-up in certain populations.1,11,19-21 If LDL cholesterol is oxidized while in the artery wall, it can initiate a cascade of events that can eventually lead to arterial blockage.22

  • A study conducted by O’Byrne and colleagues of healthy adults who either consumed Concord grape juice or a vitamin E supplement for two weeks found that the Concord grape juice drinkers experienced a similar increase in antioxidant capacity and decrease in LDL oxidation rate as those who were given the vitamin E supplement.1 Positive results on LDL-oxidation were also seen in Stein et al.’s study on adults with CAD.11 It’s important to note that while these findings are promising, Chou and colleagues found that consuming Concord grape juice had no beneficial effect on LDL oxidation rate in CAD patients studied over a 28-day period.9

Concord grapes have been shown to have an anti-clotting effect7,19,23 similar to red wine.24

  • Red wine has been shown to have an anti-clotting effect through its ability to inhibit platelet aggregation,24 and in two studies on humans, drinking Concord grape juice daily resulted in anti-clotting effects7,23 similar to red wine.
  • Platelet aggregation makes blood “sticky” and can lead to clots within the artery. A crossover study by Keevil et al. compared the effects of consuming either purple grape juice, orange juice or grapefruit juice in healthy adults.23 Only grape juice showed an ability to inhibit platelet aggregation. Freedman et al. published similar benefits of Concord grape juice in a study of 20 healthy adults.7 Both authors attribute the anti- clotting effects to the proanthocyanins and other flavonoid polyphenols found in high concentrations in Concord grape juice. Note that these outcomes were not replicated by Albers and colleagues in their study on Concord grape juice and platelet aggregation in individuals on aspirin therapy.6
  • An animal study by Shanmuganayagam et al. published in Atherosclerosis in 2007 found that, after feeding all subjects a high-cholesterol diet, the group who received Concord grape juice for 48 days experienced a reduction in clotting and cholesterol levels versus the group receiving a placebo-matched drink of sugar water.19

In certain populations, Concord grapes may play a role in healthy blood pressure.25-27
By promoting arterial relaxation, Concord grape juice may contribute to a healthy blood pressure for people with hypertension.25,26

  • Two studies on adult males with hypertension found those who consumed Concord grape juice daily for eight weeks25 or 12 weeks26 experienced decreases in both systolic and diastolic blood pressure.
  • It's healthy and normal for blood pressure to drop at night, giving the heart a rest. People who don’t experience these nighttime dips may, over time, be at increased risk for heart-related health issues.28,29 One study conducted by Dohadwala, Vita, and colleagues supports the role of Concord grape juice to benefit blood pressure, specifically nocturnal blood pressure. In this study, participants drank 100% Concord grape juice and a placebo-matched drink for eight weeks each, with a four-week rest period in between. Nocturnal blood pressure and blood glucose levels appeared to dip when subjects consumed Concord grape juice; however, it’s important to note that ambulatory blood pressure remained unchanged.27

COGNITIVE HEALTH – Researchers have begun investigating the role of Concord grapes in cognitive health.12,30-34

As we age, the effect of a lifetime of oxidative stress caused by free radicals in the body can have a damaging effect on the brain.35,36 Polyphenols can help neutralize free radicals, which may help to combat the effects of oxidative stress.

While more research is needed, specifically in humans, recent studies indicate that Concord grape juice may help slow the progression of age-related cognitive decline.

  • A study from the University of Cincinnati, College of Medicine was one of the first placebo-controlled human studies to investigate whether regular consumption of a polyphenol-rich food or beverage could have beneficial effects against age-related cognitive decline. Of the 12 older adults participating in this pilot study, five who drank the Concord grape juice had significant improvement in list learning and trended toward improved verbal recall and spatial memory compared to controls.30
  • Building on this earlier research, Krikorian and colleagues demonstrated that Concord grape juice can increase blood flow to certain regions of the brain, as well as improve memory function compared to those consuming a grape-flavored placebo. In this study, 21older adults (average age = 77) were given either Concord grape juice or the placebo daily for 16 weeks, and were tested in various areas related to long-term memory. Those who drank Concord grape juice were less susceptible to distraction when asked to remember what they had previously learned. Test scores in other areas like learning and retention did not improve with the juice.33
  • A hallmark of Alzheimer’s disease is the accumulation of amyloid-beta peptides and their formation into plaques in the brain. Researchers at Mount Sinai School of Medicine presented by Ho and colleagues at Experimental Biology in 2010 found that select polyphenol extracts from red wine and Concord grape juice may have the ability to inhibit the production and accumulation of amyloid-beta peptides in experimental models of Alzheimer’s disease.32
  • In a study conducted by the USDA-ARS Human Nutrition Research Center on Aging at Tufts University, older animals were tested for short-term memory and neuro-motor skills. Scientific lead, Dr. James Joseph, noted improved cognitive performance and enhanced motor function in the Concord grape juice-treated groups compared to those receiving the placebo drink.31

IMMUNE HEALTH – Emerging research suggests that micronutrients and polyphenols, like those found in Concord and Niagara grapes, have the potential to play a role in immune system health.37-43

  • To date, most research suggesting that polyphenols may impact immune function has been done in a laboratory setting;40-42,44-46 however, in one study conducted by the University of Florida, healthy adults who drank 100% grape juice made with Concord grapes and added vitamin C showed a significant increase in a type of immune cell – the gamma delta T cell – which signals to the immune system to attack when a pathogen is present.43 Subjects who received a placebo drink experienced no beneficial impact on immunity. Researchers are uncertain if this effect was due to the polyphenols, the micronutrient vitamin C in the beverage, or both; more research on humans is needed before any conclusions can be drawn.
  • Based on the animal studies, researchers suggest the polyphenols in grapes may block or neutralize certain viruses, preventing them from entering the cell and replicating.39,42 A great deal more research is needed before it can be determined if grape juice will protect humans against viruses in real-life conditions.
  • In a study presented at the 2009 American Society for Microbiology conference in Philadelphia, researchers demonstrated that in a laboratory model, natural compounds found in Concord grape juice protected cells from a rotavirus infection.40 Grape juice was shown to have a protective effect when added to the cells either before the virus was introduced or after the cells were infected by the virus, suggesting that consumption of grape juice could have a protective effect in one’s digestive system prior to or soon after virus infection. Similar results were seen in a study conducted by Leon and colleagues presented at The American Society for Microbiology in 2010.41

References:
1O'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.

2Castilla 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.

3Scalbert A, Manach C, Morand C, Rémésy C and Jiménez L. Dietary Polyphenols and the Prevention of Diseases. Crit Rev Food Sci Nutr. 2005. 45(4):287-306.

4Samieri C, Sun Q, Townsend MK, Rimm EB and Grodstein F. Dietary flavonoid intake at midlife and healthy aging in women. Am J Clin Nutr. 2014. 100(6):1489-1497.

5Mullen W, Marks SC, and Crozier A. Evaluation of Phenolic Compounds in Commercial Fruit Juices and Fruit Drinks. J Agric Food Chem. 2007. 55(8):3148–3157.

6Albers 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.

7Freedman 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.

8Anselm 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.

9Chou 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.

10Fitzpatrick 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.

11Stein 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.

12Vislocky LM and Fernandez MLF. Biomedical Effects of Grape Products. Nutrition Reviews. 2010. 68(11): 656-670.

13Vislocky LM, and Fernandez ML. Grapes and Grape Products: Their Role in Health. Nutr Today. 2013. 48(1):47-51.

14Wightman JD and Heuberger RA. Effect of grape and other berries on cardiovascular health. J Sci Food Agric. 2015. 95(8):1584-1597. www.ncbi.nlm.nih.gov/pubmed/25171728

15Dorsey PG, Holbrook M, Carey M, Leleiko RM, Rodrigues I, Aasen J, Eberhardt RT, and Vita JA. Concord Grape Juice Improves Endothelial Function in Overweight, Older Adults. Presented at the 55th Annual Conference of American College of Nutrition. San Antonio, TX. October 15-18, 2014.

16Siasos G, Tousoulis D, Kokkou E, Oikonomou E, Kollia ME, Verveniotis A, Gouliopoulos N, Zisimos K, Plastiras A, Maniatis K and Stefanadis C. Favorable effects of Concord grape juice on endothelial function and arterial stiffness in healthy smokers. Am J Hypertens. 2014. 27(1):38-45.

1717 Auger C, Pollet B, Arnold C, Marx C and Schini-Kerth VB. Great Heterogeneity of Commercial Fruit Juices to Induce Endothelium-Dependent Relaxation in Isolated Porcine Coronary Arteries: Role of Phenolic Content and Composition. J Med Food. 2015.18(1):128-136 www.ncbi.nlm.nih.gov/pubmed/25009961

18Mano T, Masuyama T, Yamamoto K, Naito J, Kondo H, Nagano R, Tanouchi J, Hori M, Inoue M and Kamada T. Endothelial dysfunction in the early stage of atherosclerosis precedes appearance of intimal lesions assessable with intravascular ultrasound. Am Heart J. 1996. 131(2):231-238.

19Shanmuganayagam 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.

20Vinson JA, Yang J, Proch J and Liang X. Grape juice, but not orange juice, has in vitro, ex vivo and in vivo antioxidant properties. Journal of Medicinal Food 2000 3(4):167-171.

21Vinson JA, Teufel K, Wu N. Red wine, dealcoholized red wine, and especially grape juice, inhibit atherosclerosis in a hamster model. Atherosclerosis. 2001. 156(1):67-72.

22Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA, Watson AD and Lusis AJ. Atherosclerosis: Basic Mechanisms Circulation. 1995.91(9):2488-2496.

23Keevil 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.

24Folts JD. Antithromboic potential of grape juice and red wine for preventing heart attacks. Pharmaceutical Biology. 1998. 36(Supplement 1):21-27.

25Park 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.

26Mark 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.

27Dohadwala 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.

28Ben-Dov IZ, Kark, JD, Ben Ishay D, Mekler J, Ben Arie L and Bursztyn M. Predictors of all-cause mortality in clinical ambulatory monitoring: unique aspects of blood pressure during sleep. Hypertension. 2007;49(6):1235-41.

29Sayk F, Becker, C, Teckentrup C, Fehm HL, Struk J, Wellhoener JP and Dodt C. To dip or not to dip: on the physiology of blood pressure decrease during nocturnal sleep in healthy humans. Hypertension. 2007;49(5):1070-6.

30Krikorian 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.

31Shukitt-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.

32Ho 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.

33Krikorian R, Boespflug EL, Fleck DE, Stein AL, Wightman JD, Shidler MD and Sadat-Hossieny S. Concord grape juice supplementation and neurocognitive function in human aging. J Agric Food Chem. 2012. 60(23):5736- 5742.

34Lamport DJ, Dye L, Wightman JD and Lawton CL. The effects of flavonoid and other polyphenol consumption on cognitive performance: A systematic research review of human experimental and epidemiological studies. Nutrition & Aging. 2012. 1(1):5-25.

35Nash DT and Fillit H. Cardiovascular disease risk factors and cognitive impairment. Am J Cardiol. 2006. 97(8):1262-1265.

36Floyd RA and Carney JM. Free radical damage to protein and DNA: Mechanisms involved and relevant observations on brain undergoing oxidative stress. Ann Neurol. 1992. 32(S1):S22-S27.

37Percival SS. Grape Consumption Supports Immunity in Animals and Humans. J Nutr. 2009. 139(9):1801S- 1805S.

38Zhang XY, Li WG, Wu YJ, Zheng TZ, Li W, Qu SY and Liu NF. Proanthocyanidin from grape seeds potentiates anti-tumor activity of doxorubicin via immunomodulatory mechanism. Int Immunopharmacol. 2005. 5(7- 8):1247-1257.

39Lipson 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. Molec Nutr Food Res. 2007. 51(6):752-758.

40Ferrari 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.

41Leon 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.

42Lipson 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.

43Rowe CA, Nantz MP, Nieves CJ, West RL and Percival SS. Regular Consumption of Concord Grape Juice Benefits Human Immunity. J Med Food. 2011. 14(1-2):69-78.

44Falchetti R, Fuggetta MP, Lanzilli G, Tricarico M and Ravagnan G. Effects of resveratrol on human immune cell function. Life Sci. 2001. 70(1):81-96.

45Evers DL, Wang X, Huong SM, Huang DY and Huang ES. 3,4',5-Trihydroxy-trans-stilbene (resveratrol) inhibits human cytomegalovirus replication and virus-induced cellular signaling. Antiviral Res. 2004. 63(2):85- 95.

46Berardi V, Ricci F, Castelli M, Galati G and Risuleo G. Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use. J Exp Clin Cancer Res. 2009. 28:96.

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

Reference:

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.

Bias
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.

Blind
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.

Placebo-controlled
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.

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