Grapes and Grape Extracts

Our assessments of evidence for each medical benefit fall into one of these categories:

• Strong evidence: consistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analysesa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results
• Good evidence: significant effects in one large or several mid-sized and well-designed clinical studies ( randomized controlled trialsa study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects with an appropriate placebo or other strong comparison control or observational studies that control for confounds)
• Modest evidence: significant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies), or several small studies aggregated into a meta-analysis
• Preliminary evidence: significant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect
• Weak evidence: one or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects
• Insufficient evidence: preclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example)

Learn more about how we research and rate therapies and practices in How We Rate Therapies ›

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on prostate-specific antigen doubling time among men with biochemically recurrent prostate cancer treated with either 500 mg or 4000 mg MuscadinePlus in a mid-sized study

• No evidence of an effect on prostate-specific antigen doubling time among men with biochemically recurrent prostate cancer wishing to defer androgen deprivation therapy treated with either 500 mg or 4000 mg MuscadinePlus (pulverized muscadine grape skin containing ellagic acid, quercetin, epicatechin, and trans-resveratrol) daily compared to controls in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹Paller CJ, Zhou XC et al. Muscadine grape skin extract (MPX) in men with biochemically recurrent prostate cancer: a randomized, multicenter, placebo-controlled clinical trial. Clinical Cancer Research. 2018 Jan 15;24(2):306-315.

MB-6, a combination of fermented soybean extract, green tea extract, Antrodia camphorata mycelia, spirulina, grape seed extract, and curcumin extract: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of lower disease progression rate but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on best overall response rate after treatment with leucovorin, 5-fluorouracil, and oxaliplatin among people with metastatic colorectal cancer treated with MB-6

• Lower disease progression rate but no evidence of an effect on best overall response rate after treatment with leucovorin, 5-fluorouracil, and oxaliplatin among people with metastatic colorectal cancer treated with MB-6 for 16 weeks compared to chemotherapy alone in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²Chen WT, Yang TS et al. Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil-based chemotherapy in colorectal cancer. Nutrition Research. 2014 Jul;34(7):585-94.

A juice blend containing acai (Euterpe oleracea) extract, white grape juice concentrate, cranberry apple syrup, concord grape juice concentrate, pear juice concentrate, passion fruit juice concentrate, cranberry juice concentrate, dark sweet cherry juice concentrate, coffee (Coffea arabica) berry extract, and concentrated fruit extracts/powders of wild blueberries, grapes, grape seeds, raspberries, raspberry seeds, cranberries, prunes, cherries, strawberries, and wild bilberries (VitaBerry Plus high-ORAC fruit blend); green tea (Camellia sinensis) leaf extract, Camellia sinensis (white tea) leaf extract, Aloe barbadensis leaf extract; pomegranate (Punica granatum) extract, ascorbic acid, and potassium: weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of longer time for prostate-specific antigen to double (PSA doubling time) among 71% of people with biochemically recurrent prostate cancer with a rising PSA drinking a juice blend containing grapes and grape seeds along with many other fruits and natural products

• Longer PSA doubling time among 71% of people with biochemically recurrent prostate cancer with a rising prostate-specific antigen (PSA) of at least 0.2 ng/ml drinking 2 oz of a juice blend containing acai (Euterpe oleracea) extract, white grape juice concentrate, cranberry apple syrup, concord grape juice concentrate, pear juice concentrate, passion fruit juice concentrate, cranberry juice concentrate, dark sweet cherry juice concentrate, coffee (Coffea arabica) berry extract, and concentrated fruit extracts/powders of wild blueberries, grapes, grape seeds, raspberries, raspberry seeds, cranberries, prunes, cherries, strawberries, and wild bilberries (VitaBerry Plus high-ORAC fruit blend); green tea (Camellia sinensis) leaf extract, Camellia sinensis (white tea) leaf extract, Aloe barbadensis leaf extract; pomegranate (Punica granatum) extract, ascorbic acid, and potassium twice a day for 36 weeks compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design³Kessler ER, Su LJ et al. Phase II trial of acai juice product in biochemically recurrent prostate cancer. Integrative Cancer Therapies. 2018 Dec;17(4):1103-1108.

Purple grape juice: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of less platelet clumping among healthy people drinking purple grape juice

• Lower whole blood platelet aggregation response among healthy people drinking 5 to 7.5 ml purple grape juice per kilogram per day for 7 to 10 days compared to orange juice or grapefruit juice in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁴Keevil JG, Osman HE, Reed JD, Folts JD. Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation. Journal of Nutrition. 2000 Jan;130(1):53-6.
• Less platelet aggregation among healthy people drinking 7 ml purple grape juice per kilogram per day for 14 days compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁵Freedman JE, Parker C 3rd et al. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001 Jun 12;103(23):2792-8.
• Lower platelet aggregation and higher platelet-derived nitric oxide production among healthy people drinking 7 ml purple grape juice per kilogram per day for 14 days compared to baseline in a small uncontrolled trial⁶Freedman JE, Parker C 3rd et al. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001 Jun 12;103(23):2792-8.

Grape-red wine extracts: no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on platelet function among mildly hypertensive people treated with grape-red wine extracts in a small trial

• No evidence of an effect on platelet function among mildly hypertensive people treated with grape-red wine extracts for 4 weeks compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCT⁷Draijer R, de Graaf Y, Slettenaar M, de Groot E, Wright CI. Consumption of a polyphenol-rich grape-wine extract lowers ambulatory blood pressure in mildly hypertensive subjects. Nutrients. 2015 Apr 30;7(5):3138-53.

Grape seed extract: preliminary evidence of lower platelet reactivity among smokers treated with a flavanol-rich grape seed extract

• Lower platelet reactivity at 1, 2, and 6 hours after intake among smokers treated with a flavanol-rich grape seed extract compared to placebo in a small RCT⁸Polagruto JA, Gross HB et al. Platelet reactivity in male smokers following the acute consumption of a flavanol-rich grapeseed extract. Journal of Medicinal Foods. 2007 Dec;10(4):725-30.

Red wine: modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of lower risk of an abnormally large waist circumference among people with symptoms of metabolic syndrome drinking moderate amounts of red wine, with stronger effects among females, participants aged less than 70 years, and former or current smokers

• Lower risk of an abnormal waist circumference among people with symptoms of metabolic syndrome drinking moderate amounts of red wine compared to no red wine, with stronger effects among females, participants aged less than 70 years, and former or current smokers in a large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁹Tresserra-Rimbau A, Medina-Remón A et al; PREDIMED Study Investigators. Moderate red wine consumption is associated with a lower prevalence of the metabolic syndrome in the PREDIMED population. British Journal of Nutrition. 2015 Apr;113 Suppl 2:S121-30.

Grape seed extract

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on body weight or body mass index among people treated with grape seed extract in combined analyses of studies

• No evidence of an effect on body weight (7 studies) or body mass index (5 studies) among people treated with grape seed extract compared to controls in meta-analysesstatistical analyses that combine the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of RCTsrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁰Asbaghi O, Nazarian B et al. The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: a systematic review and meta-analysis of randomized controlled trials. Phytotherapy Research. 2020 Feb;34(2):239-253.

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of lower measures of body weight during a calorie-restricted diet among obese or overweight people treated with grape seed extract

• Larger reductions in body weight, body mass index, waist circumference, and waist-to-hip ratio during a calorie-restricted diet among obese or overweight people treated with 300 mg grape seed extract per day for 12 weeks compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCT¹¹Parandoosh M, Yousefi R et al. The effects of grape seed extract (Vitis vinifera) supplement on inflammatory markers, neuropeptide Y, anthropometric measures, and appetite in obese or overweight individuals: a randomized clinical trial. Phytotherapy Research. 2020 Feb;34(2):379-387.
• Lower visceral adiposity index—a score based on waist circumference, body mass index, triglycerides, and HDL cholesterol—during a restricted-calorie diet among obese or overweight people treated with 300 mg grape seed extract per day compared to placebo in a small RCT¹²Yousefi R, Parandoosh M et al. Grape seed extract supplementation along with a restricted-calorie diet improves cardiovascular risk factors in obese or overweight adult individuals: a randomized, placebo-controlled trial. Phytotherapy Research. 2021 Feb;35(2):987-995.

Flour made from wine grape pomace: no evidence of an effect on waist circumference among males with at least one component of metabolic syndrome eating flour made from wine grape pomace in a small study

• No evidence of an effect on waist circumference among 30–65-year-old males with at least one component of metabolic syndrome eating 20 g of wine grape pomace flour at lunch per day for 16 weeks compared to controls in a small RCT¹³Urquiaga I, D’Acuña S et al. Wine grape pomace flour improves blood pressure, fasting glucose and protein damage in humans: a randomized controlled trial. Biological Research. 2015 Sep 4;48(1):49.

Grapes: no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on fasting blood glucose among people with high cholesterol eating either red or white grapes

• No evidence of an effect on fasting blood glucose among people with high cholesterol (hypercholesterolemia) eating 500 g of either Condori red grapes or Shahroodi white grapes daily for 8 weeks compared to controls in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁴Rahbar AR, Mahmoudabadi MM, Islam MS. Comparative effects of red and white grapes on oxidative markers and lipidemic parameters in adult hypercholesterolemic humans. Food & Function. 2015 Jun;6(6):1992-8.

Red wine: modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of better blood sugar control among people with metabolic disorders (metabolic syndromea cluster of conditions that occur together, including increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels or type 2 diabetes) drinking moderate amounts of red wine or nonalcoholic muscadine grape wine

• Lower risk of high blood sugar (fasting plasma glucose) among people meeting the criteria of metabolic syndrome drinking moderate amounts of red wine compared to no red wine, with stronger effects among females, participants aged less than 70 years, and former or current smokers in a large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹⁵Tresserra-Rimbau A, Medina-Remón A et al; PREDIMED Study Investigators. Moderate red wine consumption is associated with a lower prevalence of the metabolic syndrome in the PREDIMED population. British Journal of Nutrition. 2015 Apr;113 Suppl 2:S121-30.
• Better markers of glycemic control (lower levels blood glucose, glycated hemoglobin, and insulin) among people with type 2 diabetes drinking 150 ml muscadine grape wine or dealcoholized muscadine grape wine with meals for 28 days compared to muscadine grape juice in a small RCT¹⁶Banini AE, Boyd LC, Allen JC, Allen HG, Sauls DL. Muscadine grape products intake, diet and blood constituents of non-diabetic and type 2 diabetic subjects. Nutrition. 2006 Nov-Dec;22(11-12):1137-45.

Drink supplemented with grape polyphenols: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of lower markers of insulin and higher insulin sensitivity among healthy people drinking a beverage rich in polyphenols from red grape pomace

• Lower markers of insulin (insulin incremental area and insulin secretion index) and higher insulin sensitivity 5 hours after a standard meal among 20–40-year-old healthy people drinking a beverage rich in polyphenols from red grape pomace after an overnight fast and 3 hours before eating compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCT¹⁷Costabile G, Vitale M et al. Grape pomace polyphenols improve insulin response to a standard meal in healthy individuals: a pilot study. Clinical Nutrition. 2019 Dec;38(6):2727-2734.

Flour made from wine grape pomace: preliminary evidence of better blood sugar control among people with at least one component of metabolic syndrome eating food supplemented with flour made from wine grape pomace

• Lower blood sugar (glycemia) and a lower marker of insulin resistancea condition in which cells in your muscles, fat, and liver don’t respond well to insulin and can’t efficiently take up glucose from your blood for energy (homeostatic model assessment) among males with some components of metabolic syndrome eating a beef burger supplemented with 7% wine grape pomace flour containing 3.5% fiber and 1.2 mg gallic equivalents of polyphenols a day for a month compared to no burgers or unsupplemented burgers in a small RCT¹⁸Urquiaga I, Troncoso D et al. The consumption of beef burgers prepared with wine grape pomace flour improves fasting glucose, plasma antioxidant levels, and oxidative damage markers in humans: a controlled trial. Nutrients. 2018 Oct 1;10(10):1388.
• Lower fasting glucose levels among 30–65-year-old males with at least one component of metabolic syndrome eating 20 g of wine grape pomace flour at lunch per day for 16 weeks compared to controls in a small RCT¹⁹Urquiaga I, D’Acuña S et al. Wine grape pomace flour improves blood pressure, fasting glucose and protein damage in humans: a randomized controlled trial. Biological Research. 2015 Sep 4;48(1):49.

Grape seed extract

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of lower fasting plasma glucose but no evidence of an effect on HbA1ca form of hemoglobin, a protein in red blood cells, that is bound to sugar (glycated hemoglobin). Levels of HbA1c in the blood indicate the average level of blood sugar during the prior two to three months. among people treated with grape seed extract

• Lower fasting plasma glucose (8 studies) but no evidence of an effect on HbA1c (4 studies) among people treated with grape seed extract compared to controls in meta-analysesstatistical analyses that combine the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of RCTs²⁰Asbaghi O, Nazarian B et al. The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: a systematic review and meta-analysis of randomized controlled trials. Phytotherapy Research. 2020 Feb;34(2):239-253.

Preliminary evidence of lower insulin resistance and insulin during a weight-loss diet among adolescents with metabolic syndrome treated with grape seed extract

• Lower markers of insulin resistance (HOMA-IR) and insulin during a weight-loss diet among adolescents with metabolic syndrome treated with 100 mg grape seed extract per day for 8 weeks compared to placebo in a small RCT²¹Mohammad A, Shahnaz T, Sorayya K. Effect of 8 weeks’ supplementation grape seed extract on insulin resistance in Iranian adolescents with metabolic syndrome: a randomized controlled trial. Diabetes & Metabolic Syndrome. 2021 Jan-Feb;15(1):197-203.

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of better fasting insulin and insulin sensitivity but no evidence of an effect on blood sugar among people with prehypertension drinking juice supplemented with grape seed extract

• Weak trendsan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward better fasting insulin and insulin sensitivity but no evidence of an effect on blood sugar (glucose) among people with prehypertension drinking juice with 150 mg grape seed extract twice a day for 6 weeks compared to placebo in a small RCT²²Park E, Edirisinghe I, Choy YY, Waterhouse A, Burton-Freeman B. Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: a randomised, double-blinded, two-arm, parallel, placebo-controlled trial. British Journal of Nutrition. 2016 Jan 28;115(2):226-38.

Red wine polyphenols: no evidence of an effect on markers of insulin sensitivity among obese people treated with red wine polyphenols in a small study

• No evidence of an effect on markers of insulin sensitivity (hyperinsulinaemic-euglycaemic clamp, Matsuda index or HOMA-IR) among obese people (body mass index higher than 30) treated with 600 mg red wine polyphenols per day for 8 weeks compared to placebo in a small RCT²³Woerdeman J, Del Rio D et al. Red wine polyphenols do not improve obesity-associated insulin resistance: A randomized controlled trial. Diabetes, Obesity & Metabolism. 2018 Jan;20(1):206-210.

Red wine: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of higher levels of free testosterone and luteinizing hormone and lower levels of sex hormone binding globulin but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on follicle stimulating hormone among premenopausal women drinking red wine

• Higher levels of free testosterone and luteinizing hormone and lower levels of sex hormone binding globulin but no evidence of an effect on follicle stimulating hormone among premenopausal women drinking 8 ounces (237 ml) of red wine a day for 1 month compared to white wine in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²⁴Shufelt C, Merz CN et al. Red versus white wine as a nutritional aromatase inhibitor in premenopausal women: a pilot study. Journal of Women’s Health (Larchmt). 2012 Mar;21(3):281-4.

Grape seed extracts: no evidence of an effect on plasma levels of estrogen conjugates or androgen precursors among postmenopausal women treated with grape seed extract

• No evidence of an effect on plasma levels of estrogen conjugates or androgen precursors among postmenopausal women treated with 200, 400, 600, or 800 mg grape seed extract for 12 weeks compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCT²⁵Wahner-Roedler DL, Bauer BA et al. The effect of grape seed extract on estrogen levels of postmenopausal women: a pilot study. Journal of Dietary Supplements. 2014 Jun;11(2):184-97.

Grape juice: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of immune activation among people drinking Concord grape juice

• A higher marker of immune activation (levels of γδ T-cells) among people drinking 100% grape juice made from Concord grapes every day for 9 weeks compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²⁶Rowe CA, Nantz MP, Nieves C Jr, West RL, Percival SS. Regular consumption of concord grape juice benefits human immunity. Journal of Medicinal Food. 2011 Jan-Feb;14(1-2):69-78.

Polyphenols from red grape seeds: preliminary evidence of immune activation among people with allergic contact dermatitis treated with polyphenols extracted from red grape seeds

• Lower release of proinflammatory cytokines and nitric oxide (NO) and higher levels of interleukin (IL)-10, an anti-inflammatory cytokine, among people with allergic contact dermatitis to nickel treated with 300 mg polyphenols extracted from red grape seeds (NATUR-OX®) for 3 months compared to no changes among people treated with placebo in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial²⁷Magrone T, Jirillo E et al. Red grape polyphenol oral administration improves immune response in women affected by nickel-mediated allergic contact dermatitis. Endocrine, Metabolic & Immune Disorders Drug Targets. 2021;21(2):374-384.

Grape juice

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on inflammation among childhood cancer survivors drinking 6 ounces of purple grape juice

• No evidence of an effect on inflammation (C-reactive protein) among childhood cancer survivors drinking 6 ounces of purple grape juice twice a day compared to clear apple juice in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²⁸Blair CK, Kelly AS et al. Feasibility and preliminary efficacy of the effects of flavanoid-rich purple grape juice on the vascular health of childhood cancer survivors: a randomized, controlled crossover trial. Pediatric Blood & Cancer. 2014 Dec;61(12):2290-6.

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of a lower marker of inflammation among people undergoing hemodialysis drinking red grape juice

• A lower marker of inflammation (plasma monocyte chemoattractant protein 1) among people undergoing hemodialysis drinking 100 ml red grape juice per day for 3 weeks compared to controls in a small, poorly designed controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial²⁹Castilla P, Echarri R. Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinflammatory effects in both hemodialysis patients and healthy subjects. American Journal of Clinical Nutrition. 2006 Jul;84(1):252-62.

Red wine: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of a lower marker of inflammation among healthy males drinking either red wine or the equivalent amount of nonalcoholic red wine

• A lower marker of inflammation (C-reactive protein) among healthy males drinking either red wine or the equivalent amount of de-alcoholized red wine for 20 days compared to gin in a small RCT³⁰Queipo-Ortuño MI, Boto-Ordóñez M et al. Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers. American Journal of Clinical Nutrition. 2012 Jun;95(6):1323-34.

Grape seed extract: preliminary (conflicting) evidence of lower levels of markers of inflammation among people treated with grape seed extract

• A lower marker of inflammation (C-reactive protein) among people treated with grape seed extract compared to controls in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 6 RCTs³¹Asbaghi O, Nazarian B et al. The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: a systematic review and meta-analysis of randomized controlled trials. Phytotherapy Research. 2020 Feb;34(2):239-253.
• No evidence of an effect on a marker of inflammation (C-reactive protein) among people treated with grape seed extract in a meta-analysis of 9 RCTs³²Feringa HH, Laskey DA, Dickson JE, Coleman CI. The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials. Journal of the American Dietetic Association. 2011 Aug;111(8):1173-81.
• Lower levels of markers of inflammation (tumor necrosis factor alpha [TNF-α] and high-sensitivity C-reactive protein) among children with β-thalassemia major treated with 100 mg grape seed extract per day for 4 weeks compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCT³³Mottaghi S, Abbaszadeh H. Grape seed extract in combination with deferasirox ameliorates iron overload, oxidative stress, inflammation, and liver dysfunction in beta thalassemia children. Complementary Therapies in Clinical Practice. 2023 Nov;53:101804.
• Lower markers of inflammation (tumor necrosis factor alpha, and high sensitivity C-reactive protein) during a calorie-restricted diet among obese or overweight people treated with 300 mg grape seed extract per day for 12 weeks compared to placebo in a small RCT³⁴Parandoosh M, Yousefi R et al. The effects of grape seed extract (Vitis vinifera) supplement on inflammatory markers, neuropeptide Y, anthropometric measures, and appetite in obese or overweight individuals: a randomized clinical trial. Phytotherapy Research. 2020 Feb;34(2):379-387.

Grapes: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of a higher marker of control of oxidative stress (total antioxidant capacity) among people with high cholesterol eating red or white grapes

• Higher total antioxidant capacity among people with high cholesterol (hypercholesterolemia) eating 500 g of either Condori red grapes or Shahroodi white grapes daily for 8 weeks compared to controls in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects³⁵Rahbar AR, Mahmoudabadi MM, Islam MS. Comparative effects of red and white grapes on oxidative markers and lipidemic parameters in adult hypercholesterolemic humans. Food & Function. 2015 Jun;6(6):1992-8.

Purple grape juice

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on oxidative stress among childhood cancer survivors drinking purple grape juice

• No evidence of an effect on oxidative stress (myeloperoxidase) among childhood cancer survivors drinking 6 ounces of purple grape juice twice a day compared to clear apple juice in a small RCT³⁶Blair CK, Kelly AS et al. Feasibility and preliminary efficacy of the effects of flavanoid-rich purple grape juice on the vascular health of childhood cancer survivors: a randomized, controlled crossover trial. Pediatric Blood & Cancer. 2014 Dec;61(12):2290-6.

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of less oxidative stress and/or higher antioxidant capacity among people drinking purple or red grape juice

• Lower DNA damage after a simulated volleyball match among male athletes drinking 400 ml purple grape juice per day for 14 days compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCT³⁷Martins NC, Dorneles GP et al. Effects of grape juice consumption on oxidative stress and inflammation in male volleyball players: a randomized, double-blind, placebo-controlled clinical trial. Complementary Therapies in Medicine. 2020 Nov;54:102570.
• Higher serum antioxidant activity among people drinking 100% grape juice made from Concord grapes every day for 9 weeks compared to placebo in a small RCT³⁸Rowe CA, Nantz MP, Nieves C Jr, West RL, Percival SS. Regular consumption of concord grape juice benefits human immunity. Journal of Medicinal Food. 2011 Jan-Feb;14(1-2):69-78.
• Higher antioxidant capacity of plasma among people, including some undergoing hemodialysis, drinking 100 ml red grape juice per day for 14 days compared to controls in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial³⁹Castilla P, Echarri R. Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinflammatory effects in both hemodialysis patients and healthy subjects. American Journal of Clinical Nutrition. 2006 Jul;84(1):252-62.
• A lower marker of oxidative stress (superoxide production) among healthy people drinking 7 ml purple grape juice per kilogram per day for 14 days compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁴⁰Freedman JE, Parker C 3rd et al. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001 Jun 12;103(23):2792-8.
• A lower marker of oxidative stress (plasma protein-independent antioxidant activity) among healthy people drinking 7 ml purple grape juice per kilogram per day for 14 days compared to baseline in a small uncontrolled trial⁴¹Freedman JE, Parker C 3rd et al. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001 Jun 12;103(23):2792-8.

Grape seed extract

Preliminary evidence of lower oxidative stress among obese people with type 2 diabetes treated with grape seed extracts

• A lower marker of oxidative stress (glutathione) but no evidence of an effect on total antioxidant status among obese people with type 2 diabetes treated with 600 mg grape seed extracts per day for 4 weeks compared to placebo in a small RCT⁴²Kar P, Laight D, Rooprai HK, Shaw KM, Cummings M. Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity. Diabetic Medicine. 2009 May;26(5):526-31.

Preliminary evidence of higher a higher marker of control of oxidative stress (total antioxidant capacity) among people with high cholesterol eating red or white grapes and a lower marker of oxidative stress but no evidence of an effect on other markers during coronary artery bypass surgery among people treated with oral grape seed extract

• Higher total antioxidant capacity and a lower marker of oxidative stress (malondialdehyde) but no evidence of an effect on other markers (superoxide dismutase and glutathione peroxidase) during coronary artery bypass surgery among people treated with 100 mg oral grape seed extract every 6 hours for 24 hours before surgery compared to placebo in a small RCT⁴³Safaei N, Babaei H et al. Comparative effect of grape seed extract (Vitis vinifera) and ascorbic acid in oxidative stress induced by on-pump coronary artery bypass surgery. Annals of Cardiac Anaesthesia. 2017 Jan-Mar;20(1):45-51.

Preliminary evidence of lower oxidative stress among children with β-thalassemia major treated with grape seed extract

• Lower levels of some markers of oxidative stress (malondialdehyde and glutathione) but no evidence of an effect on another (superoxide dismutase) among children with β-thalassemia major treated with 100 mg grape seed extract per day for 4 weeks compared to placebo in a small RCT⁴⁴Mottaghi S, Abbaszadeh H. Grape seed extract in combination with deferasirox ameliorates iron overload, oxidative stress, inflammation, and liver dysfunction in beta thalassemia children. Complementary Therapies in Clinical Practice. 2023 Nov;53:101804.

No evidence of an effect on plasma antioxidant capacity among smokers treated with a single dose of flavanol-rich grape seed extract

• No evidence of an effect on plasma antioxidant capacity among smokers treated with a single dose of flavanol-rich grape seed extract compared to placebo in a small RCT⁴⁵Polagruto JA, Gross HB et al. Platelet reactivity in male smokers following the acute consumption of a flavanol-rich grapeseed extract. Journal of Medicinal Foods. 2007 Dec;10(4):725-30.

Flour made from wine grape pomace: preliminary evidence of some lower markers of oxidative damage among males with some components of metabolic syndromea cluster of conditions that occur together, including increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels eating a beef burger supplemented with flour made from wine grape pomace

• Some lower markers of oxidative damage (advanced oxidation protein products (AOPPs) and oxidized low-density lipoproteins) but no evidence of an effect on malondialdehyde among males with some components of metabolic syndrome eating a beef burger supplemented with 7% wine grape pomace flour containing 3.5% of fiber and 1.2 mg gallic equivalents of polyphenols a day for a month compared to either unsupplemented burgers or no burgers in a small RCT⁴⁶Urquiaga I, Troncoso D et al. The consumption of beef burgers prepared with wine grape pomace flour improves fasting glucose, plasma antioxidant levels, and oxidative damage markers in humans: a controlled trial. Nutrients. 2018 Oct 1;10(10):1388.

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of higher concentrations of several groups of microbes among healthy males drinking either red wine or the equivalent amount of nonalcoholic red wine

• Higher concentrations of Enterococcus, Prevotella, Bacteroides, Bifidobacterium, Bacteroides uniformis, Eggerthella lenta, and Blautia coccoides-Eubacterium rectale groups of microbes among healthy males drinking either red wine or the equivalent amount of de-alcoholized red wine for 20 days compared to gin in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁴⁷Queipo-Ortuño MI, Boto-Ordóñez M et al. Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers. American Journal of Clinical Nutrition. 2012 Jun;95(6):1323-34.

For some guidance interpreting what these changes may mean regarding cancer risk or outcomes, see the spreadsheet in Your Microbiome: Are you a health professional? ›

Vitamin C levels

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of higher vitamin C levels among people drinking Concord grape juice or nonalcoholic muscadine grape wine

• Higher serum vitamin C levels among people drinking 100% grape juice made from Concord grapes every day for 9 weeks compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁴⁸Rowe CA, Nantz MP, Nieves C Jr, West RL, Percival SS. Regular consumption of concord grape juice benefits human immunity. Journal of Medicinal Food. 2011 Jan-Feb;14(1-2):69-78.
• Higher vitamin C levels among people with type 2 diabetes drinking 150 ml dealcoholized muscadine grape wine with meals for 28 days compared to muscadine grape juice in a small RCT⁴⁹Banini AE, Boyd LC, Allen JC, Allen HG, Sauls DL. Muscadine grape products intake, diet and blood constituents of non-diabetic and type 2 diabetic subjects. Nutrition. 2006 Nov-Dec;22(11-12):1137-45.

Insufficient evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of an effect on vitamin C levels among males with some components of metabolic syndrome eating food supplemented with flour made from wine grape pomace

• Higher plasma vitamin C levels among males with some components of metabolic syndrome eating a beef burger supplemented with 7% wine grape pomace flour containing 3.5% of fiber and 1.2 mg gallic equivalents of polyphenols a day for a month compared to unsupplemented burgers in a small RCT⁵⁰Urquiaga I, Troncoso D et al. The consumption of beef burgers prepared with wine grape pomace flour improves fasting glucose, plasma antioxidant levels, and oxidative damage markers in humans: a controlled trial. Nutrients. 2018 Oct 1;10(10):1388.
• No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on vitamin C levels among 30–65-year-old males with at least one component of metabolic syndrome eating 20 g of wine grape pomace flour at lunch per day for 16 weeks compared to controls in a small RCT⁵¹Urquiaga I, D’Acuña S et al. Wine grape pomace flour improves blood pressure, fasting glucose and protein damage in humans: a randomized controlled trial. Biological Research. 2015 Sep 4;48(1):49.

Vitamin E levels

Preliminary evidence of higher vitamin E levels among people with type 2 diabetes drinking 150 ml dealcoholized muscadine grape wine

• Higher vitamin E levels among people with type 2 diabetes drinking 150 ml dealcoholized muscadine grape wine with meals for 28 days compared to muscadine grape juice in a small RCT⁵²Banini AE, Boyd LC, Allen JC, Allen HG, Sauls DL. Muscadine grape products intake, diet and blood constituents of non-diabetic and type 2 diabetic subjects. Nutrition. 2006 Nov-Dec;22(11-12):1137-45.

Leucoselect Phytosome, a standardized grape seed extract formulated with soy phospholipids

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of higher serum total antioxidant activity among young people treated with Leucoselect

• Higher serum total antioxidant activity among young people treated with 2 capsules Leucoselect Phytosome containing 300 mg grape procyanidin extracts for 5 days compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁵³Nuttall SL, Kendall MJ, Bombardelli E, Morazzoni P. An evaluation of the antioxidant activity of a standardized grape seed extract, Leucoselect. Journal of Clinical Pharmacy and Therapeutics. 1998 Oct;23(5):385-9.

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of higher levels of omega-3 fatty acids (EPA and DHA) and an EPA metabolite with anticancer properties among heavy active and former smokers treated with Leucoselect Phytosome

• Higher levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) after 1 month, and higher serum prostaglandin (PG) E3, a metabolite of EPA with anti-inflammatory and anticancer (antineoplastic) properties, after 3 months of treatment among heavy active and former smokers treated with Leucoselect Phytosome compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁵⁴Mao JT, Xue B et al. Leucoselect phytosome modulates serum eicosapentaenoic acid, docosahexaenoic acid, and prostaglandin e3 in a phase I lung cancer chemoprevention study. Cancer Prevention Research (Philadelphia). 2021 Jun;14(6):619-626.

Grape seed extract with a special diet: preliminary evidence of lower oxidative stress among people with stage 3B–4 breast cancer treated with 15 ml grape seed extract, 15 ml balsamic vinegar from apples and honey, with seabuckthorn berry rich in carotenoids, rosemary, sage, and basil extracts, and  150 g whole-wheat bread with 2.5% of the nutraceutic mixture VITAPANper day

• A lower marker of oxidative stress (free oxygen radical test) among people with stage 3B–4 breast cancer treated with a diet including 15 ml grape seed extracts, 15 ml balsamic vinegar from apples and honey, with seabuckthorn berry rich in carotenoids, rosemary, sage, and basil extracts per day, and 150 g whole-wheat bread with 2.5% of the nutraceutic mixture VITAPAN per day per day for 3 months compared to controls in a small RCT⁵⁵Drăgan S, Nicola T et al. Role of multi-component functional foods in the complex treatment of patients with advanced breast cancer. Revista Medico-Chirurgicala a Societatii de Medici si Naturalisti din Iasi. 2007 Oct-Dec;111(4):877-84.

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on endothelial function among childhood cancer survivors drinking 6 ounces of purple grape juice in a small study

• No evidence of an effect on endothelial function among childhood cancer survivors drinking 6 ounces of purple grape juice twice a day compared to clear apple juice in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁵⁶Blair CK, Kelly AS et al. Feasibility and preliminary efficacy of the effects of flavanoid-rich purple grape juice on the vascular health of childhood cancer survivors: a randomized, controlled crossover trial. Pediatric Blood & Cancer. 2014 Dec;61(12):2290-6.

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of higher self-reported physical well-being among people with metastatic or unresectable cancers who were progressing on standard therapies treated with grape seed extract

• Higher self-reported physical well-being among people with metastatic or unresectable cancers who were progressing on standard therapies treated with grape seed extract with 320 to 1600 mg total phenolics per day for 8 weeks compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁵⁷Bitting RL, Tooze JA et al. Phase I study of muscadine grape extract for patients with advanced cancer. American Journal of Clinical Oncology. 2021 Jun 1;44(6):239-246.

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on breast hardness, pain, or tenderness among people with moderate or marked breast thickening and hardening from prior radiotherapy for early breast cancer treated with grape seed proanthocyanidin extract in a small study

• No evidence of an effect on breast hardness, pain, or tenderness among people with moderate or marked breast induration from prior radiotherapy for early breast cancer treated with 100 mg oral IH636 grape seed proanthocyanidin extract 3 times a day for 6 months compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁵⁸Brooker S, Martin S et al. Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration. Radiotherapy and Oncology. 2006 Apr;79(1):45-51.

Anxiety or depression: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of lower anxiety or depression scores among women with at least one menopausal symptom treated with grape seed extract

• Lower anxiety or depression scores among women with at least one menopausal symptom treated with grape seed extract tablets containing 200 mg proanthocyanidin per day for 8 weeks compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁵⁹Terauchi M, Horiguchi N et al. Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled pilot study. Menopause. 2014 Sep;21(9):990-6.

Body composition: preliminary evidence of higher muscle mass among women with at least one menopausal symptom treated with grape seed extract tablets

• Higher muscle mass among women with at least one menopausal symptom treated with grape seed extract tablets containing either 100 or 200 mg proanthocyanidin per day for 8 weeks compared to placebo in a small RCT⁶⁰Terauchi M, Horiguchi N et al. Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled pilot study. Menopause. 2014 Sep;21(9):990-6.

Cardiovascular symptoms

Red wine: modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of lower blood pressure among people drinking either red wine or the equivalent amount of nonalcoholic red wine

• Lower risk of high blood pressure among people with symptoms of metabolic syndrome drinking moderate amounts of red wine compared to no red wine, with stronger effects among females, participants aged less than 70 years, and former or current smokers in a large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁶¹Tresserra-Rimbau A, Medina-Remón A et al; PREDIMED Study Investigators. Moderate red wine consumption is associated with a lower prevalence of the metabolic syndrome in the PREDIMED population. British Journal of Nutrition. 2015 Apr;113 Suppl 2:S121-30.
• Lower systolic and diastolic blood pressures among healthy males drinking either red wine or the equivalent amount of de-alcoholized red wine for 20 days compared to gin in a small RCT⁶²Queipo-Ortuño MI, Boto-Ordóñez M et al. Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers. American Journal of Clinical Nutrition. 2012 Jun;95(6):1323-34.

Flour made from wine grape pomace: preliminary evidence of lower systolic and diastolic blood pressure among 30–65-year-old males with at least one component of metabolic syndromea cluster of conditions that occur together, including increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels eating flour made from wine grape pomace

• Lower systolic and diastolic blood pressure among 30–65-year-old males with at least one component of metabolic syndrome eating 20 g of wine grape pomace flour at lunch per day  for 16 weeks compared to controls in a small RCT⁶³Urquiaga I, D’Acuña S et al. Wine grape pomace flour improves blood pressure, fasting glucose and protein damage in humans: a randomized controlled trial. Biological Research. 2015 Sep 4;48(1):49.

Grape seed extract

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of lower blood pressure among people treated with grape seed extract

• Lower systolic and diastolic blood pressure among people treated with grape seed extract in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 9 RCTs⁶⁴Feringa HH, Laskey DA, Dickson JE, Coleman CI. The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials. Journal of the American Dietetic Association. 2011 Aug;111(8):1173-81.
• Lower mean arterial pressure at rest and at 40% and 60% workloads and less aortic stiffness at rest among obese and overweight males treated with grape seed extract for 7 days compared to placebo in a small RCT⁶⁵Dillon K, Shariffi B et al. Effects of chronic dietary grape seed extract supplementation on aortic stiffness and hemodynamic responses in obese/overweight males during submaximal exercise. European Journal of Sport Science. 2022 Jul;22(7):1057-1064.
• Lower blood pressure among healthy men but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. among postmenopausal women with mild hypertension treated with 150 mg grape seed extract (Enovita) twice a day for 8 weeks or longer compared to placebo in a small RCT⁶⁶Schön C, Allegrini P, Engelhart-Jentzsch K, Riva A, Petrangolini G. Grape seed extract positively modulates blood pressure and perceived stress: a randomized, double-blind, placebo-controlled study in healthy volunteers. Nutrients. 2021 Feb 17;13(2):654.
• Lower systolic blood pressure and mean arterial pressure among men of either normal or elevated body weight, and lower cardiac output only among obese men, 2 hours after being treated with grape seed extract compared to placebo in a small RCT⁶⁷Dillon KN, Shariffi B, Thompson B, Steele R, Kim JK. Effects of acute grape seed extract supplementation on hemodynamics in normal body weight and obese males. Journal of Nutritional Science and Vitaminology (Tokyo). 2020;66(5):427-431.
• Lower systolic blood pressure and other markers of cardiovascular health among people with prehypertension treated with 400 mg grape seed proanthocyanidin extract (but not 200 mg) per day for 12 weeks compared to placebo in a small RCT⁶⁸Odai T, Terauchi M, Kato K, Hirose A, Miyasaka N. Effects of grape seed proanthocyanidin extract on vascular endothelial function in participants with prehypertension: a randomized, double-blind, placebo-controlled study. Nutrients. 2019 Nov 20;11(12):2844.
• Lower mean arterial pressure during dynamic exercise among prehypertensive males 2 hours after being treated with 300 mg grape seed extract compared to placebo in a small RCT⁶⁹Kim JK, Kim KA, Choi HM, Park SK, Stebbins CL. Grape seed extract supplementation attenuates the blood pressure response to exercise in prehypertensive men. Journal of Medicinal Food. 2018 May;21(5):445-453.
• Lower systolic and diastolic blood pressure among women with at least one menopausal symptom treated with grape seed extract tablets containing either 100 or 200 mg proanthocyanidin per day for 4 weeks compared to placebo in a small RCT⁷⁰Terauchi M, Horiguchi N et al. Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled pilot study. Menopause. 2014 Sep;21(9):990-6.
• Lower systolic and a weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward lower diastolic blood pressure, with stronger effects among people with higher blood pressure at baseline, among people with prehypertension drinking juice with 150 mg grape seed extract in it twice a day for 6 weeks compared to placebo in a small RCT⁷¹Park E, Edirisinghe I, Choy YY, Waterhouse A, Burton-Freeman B. Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: a randomised, double-blinded, two-arm, parallel, placebo-controlled trial. British Journal of Nutrition. 2016 Jan 28;115(2):226-38.

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on a marker of blood pressure among people with prehypertension treated with grape seed proanthocyanidin extract in a small study

• No evidence of an effect a marker of blood pressure (brachial flow-mediated dilation) among people with prehypertension treated with 200 mg or 400 mg grape seed proanthocyanidin extract per day for 12 weeks compared to placebo in a small RCT⁷²Odai T, Terauchi M, Kato K, Hirose A, Miyasaka N. Effects of grape seed proanthocyanidin extract on vascular endothelial function in participants with prehypertension: a randomized, double-blind, placebo-controlled study. Nutrients. 2019 Nov 20;11(12):2844.

Insufficient evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of an effect on endothelial dysfunction among people with mild hypertension or type 2 diabetes treated with grape seed extract in small studies

• No evidence of an effect on endothelial dysfunction among healthy men and postmenopausal women with mild hypertension treated with 150 mg grape seed extract (Enovita) twice a day for 8 weeks or longer compared to placebo in a small RCT⁷³Schön C, Allegrini P, Engelhart-Jentzsch K, Riva A, Petrangolini G. Grape seed extract positively modulates blood pressure and perceived stress: a randomized, double-blind, placebo-controlled study in healthy volunteers. Nutrients. 2021 Feb 17;13(2):654.
• Lower cardiac output and total vascular conductance, and greater endothelial function (flow-mediated dilation) during dynamic exercise among prehypertensive males 2 hours after being treated with 300 mg grape seed extract compared to placebo in a small RCT⁷⁴Kim JK, Kim KA, Choi HM, Park SK, Stebbins CL. Grape seed extract supplementation attenuates the blood pressure response to exercise in prehypertensive men. Journal of Medicinal Food. 2018 May;21(5):445-453.
• No evidence of an effect on endothelial dysfunction among obese people with type 2 diabetes treated with 600 mg grape seed extracts per day for 4 weeks compared to placebo in a small RCT⁷⁵Kar P, Laight D, Rooprai HK, Shaw KM, Cummings M. Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity. Diabetic Medicine. 2009 May;26(5):526-31.

Red grape cell powder: preliminary evidence of better dilation of arteries in response to blood flow among people with prehypertension or mild hypertension eating red grape cell powder

• Better flow-mediated dilation among people with prehypertension or mild hypertension eating 200 or 400 mg red grape cell powder daily for 12 weeks, and lower diastolic blood pressure only among people consuming 200 mg, compared to or placebo in a small RCT⁷⁶Vaisman N, Niv E. Daily consumption of red grape cell powder in a dietary dose improves cardiovascular parameters: a double blind, placebo-controlled, randomized study. International Journal of Food Sciences and Nutrition. 2015 May;66(3):342-9.

Grape-red wine extracts

Preliminary evidence of lower blood pressure among mildly hypertensive people treated with grape-red wine extracts

• Lower 24-hour ambulatory systolic/diastolic blood pressure among mildly hypertensive people treated with grape-red wine extracts for 4 weeks compared to placebo in a small RCT⁷⁷Draijer R, de Graaf Y, Slettenaar M, de Groot E, Wright CI. Consumption of a polyphenol-rich grape-wine extract lowers ambulatory blood pressure in mildly hypertensive subjects. Nutrients. 2015 Apr 30;7(5):3138-53.

Preliminary evidence of higher dilation of brachial arteries in response to blood flow among males with coronary heart disease treated with red grape polyphenolcompounds found naturally in many plants and plant foods that have antioxidant properties extract

• Higher brachial artery flow-mediated dilation after 60 minutes among males with coronary heart disease treated with 600 mg red grape polyphenol extract dissolved in 20 ml of water compared to placebo in a small RCT⁷⁸Lekakis J, Rallidis LS et al. Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. European Journal of Cardiovascular Prevention and Rehabilitation. 2005 Dec;12(6):596-600.

Changes in appetite: preliminary evidence of slightly lower energy consumption among people with an energy requirement at or higher than the median but no evidence of an effect among other people treated with grape seed extract

• Slightly lower energy consumption among people with an energy requirement at or higher than the median of 7.5 MJ per day but no evidence of an effect among other people treated with grape seed extract 30 to 60 minutes before a standardized breakfast and unrestricted (ad libitum) lunch and dinner for 3 days compared to placebo in a small RCT⁷⁹Vogels N, Nijs IM, Westerterp-Plantenga MS. The effect of grape-seed extract on 24 h energy intake in humans. European Journal of Clinical Nutrition. 2004 Apr;58(4):667-73.

Cognitive difficulties

Purple grape juice: preliminary evidence of better reaction time on some measures of cognition but no evidence of an effects on memory measures among healthy young adults drinking purple grape juice

• Better reaction time on a composite attention measure and calm ratings but no evidence of an effects on memory measures among healthy young adults drinking 230 ml purple grape juice compared to a sugar-matched control in a small RCT⁸⁰Haskell-Ramsay CF, Stuart RC, Okello EJ, Watson AW. Cognitive and mood improvements following acute supplementation with purple grape juice in healthy young adults. European Journal of Nutrition. 2017 Dec;56(8):2621-2631.

Raisins: preliminary evidence of slightly better cognitive performance among healthy people over age 70 eating raisins

• Slightly better cognitive performance (orientation, visuospatial/executive capacity, language, immediate and delayed recall, auditory verbal learning) among healthy people over age 70 eating 50 g of raisins per day added to their usual diet for 6 months compared to usual diet alone in a small RCT⁸¹Rodrigo-Gonzalo MJ, González-Manzano S et al. Effects of a raisin supplement on cognitive performance, quality of life, and functional activities in healthy older adults-randomized clinical trial. Nutrients. 2023 Jun 20;15(12):2811.

Grape seed extract: preliminary evidence of some improvements in reaction time and psychomotor skills among healthy young adults treated with grape seed extract

• Some improvements in reaction time among healthy young adults at 2, 4 and 6 hours after being treated with 400 mg grape seed polyphenol extract compared to placebo in a small RCT⁸²Bell L, Whyte AR et al. Grape seed polyphenol extract and cognitive function in healthy young adults: a randomised, placebo-controlled, parallel-groups acute-on-chronic trial. Nutritional Neuroscience. 2022 Jan;25(1):54-63.
• Some improvements in psychomotor skill among healthy young adults treated with 400 mg grape seed polyphenol extract for 12 weeks compared to placebo in a small RCT⁸³Bell L, Whyte AR et al. Grape seed polyphenol extract and cognitive function in healthy young adults: a randomised, placebo-controlled, parallel-groups acute-on-chronic trial. Nutritional Neuroscience. 2022 Jan;25(1):54-63.

Gastrointestinal symptoms: preliminary evidence of lower levels of markers of liver dysfunction among children with β-thalassemia major treated with grape seed extract

• Lower levels of markers of liver dysfunction (alanine transaminase and aspartate aminotransferase) among children with β-thalassemia major treated with 100 mg grape seed extract per day for 4 weeks compared to placebo in a small RCT⁸⁴Mottaghi S, Abbaszadeh H. Grape seed extract in combination with deferasirox ameliorates iron overload, oxidative stress, inflammation, and liver dysfunction in beta thalassemia children. Complementary Therapies in Clinical Practice. 2023 Nov;53:101804.

Hot flashes: preliminary evidence of lower scores for hot flashes among women with at least one menopausal symptom treated with grape seed extract

• Lower scores for hot flashes among women with at least one menopausal symptom treated with grape seed extract tablets containing 200 mg proanthocyanidin per day for 8 weeks compared to placebo in a small RCT⁸⁵Terauchi M, Horiguchi N et al. Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled pilot study. Menopause. 2014 Sep;21(9):990-6.

Quality of life and physical function

Raisins: preliminary evidence of slightly better quality of life and greater autonomy in activities of daily living among healthy people over age 70 eating raisins

• Slightly better quality of life and greater autonomy in instrumental activities of daily living among healthy people over age 70 eating 50 g of raisins per day added to their usual diet for 6 months compared to usual diet alone in a small RCT⁸⁶Rodrigo-Gonzalo MJ, González-Manzano S et al. Effects of a raisin supplement on cognitive performance, quality of life, and functional activities in healthy older adults-randomized clinical trial. Nutrients. 2023 Jun 20;15(12):2811.

Grape seed extract: preliminary evidence of better physical symptoms among women with at least one menopausal symptom treated with grape seed extract

• Better physical symptoms (lower scores) among women with at least one menopausal symptom treated with grape seed extract tablets containing 200 mg proanthocyanidin per day for 8 weeks compared to placebo in a small RCT⁸⁷Terauchi M, Horiguchi N et al. Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled pilot study. Menopause. 2014 Sep;21(9):990-6.

Sleep disruption: preliminary evidence of less sleep disruption among women with at least one menopausal symptom treated with grape seed extract

• Lower scores for insomnia among women with at least one menopausal symptom treated with grape seed extract tablets containing 200 mg proanthocyanidin per day for 8 weeks compared to placebo in a small RCT⁸⁸Terauchi M, Horiguchi N et al. Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled pilot study. Menopause. 2014 Sep;21(9):990-6.

Stress: preliminary evidence of lower stress among healthy men and postmenopausal women with mild hypertension treated with grape seed extract

• Lower stress (worry scores) among healthy men and postmenopausal women with mild hypertension treated with 150 mg grape seed extract (Enovita) twice a day for 8 weeks or longer compared to placebo in a small RCT⁸⁹Schön C, Allegrini P, Engelhart-Jentzsch K, Riva A, Petrangolini G. Grape seed extract positively modulates blood pressure and perceived stress: a randomized, double-blind, placebo-controlled study in healthy volunteers. Nutrients. 2021 Feb 17;13(2):654.

Wound healing: modest evidence of better wound healing after surgery or excision among people treated with topical grape seed extract ointment or cream

• Better wound healing indices after cesarean section among women treated with topical 5% grape seed extract ointment for 6 or 14 days compared to placebo or 2.5% ointment in a mid-sized RCT⁹⁰Izadpanah A, Soorgi S, Geraminejad N, Hosseini M. Effect of grape seed extract ointment on cesarean section wound healing: a double-blind, randomized, controlled clinical trial. Complementary Therapies in Clinical Practice. 2019 May;35:323-328.
• More rapid wound healing after excision of skin lesions among people treated with topical 2% grape seed extract cream compared to placebo in a small RCT⁹¹Hemmati AA, Foroozan M et al. The topical effect of grape seed extract 2% cream on surgery wound healing. Global Journal of Health Science. 2014 Oct 29;7(3):52-8.

MB-6, a preparation of fermented soybean extract, green tea extract, Antrodia camphorata mycelia, spirulina, grape seed extract, and curcumin extract: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of lower occurrence of increased serum creatinine (an indicator of kidney toxicity) and lower incidence of adverse events of grade 4 or higher during chemotherapy among people with metastatic colorectal cancer treated with MB-6

• Lower incidence of side effects (adverse events, at least grade 4) and occurrence of increased serum creatinine (an indicator of kidney toxicity) during chemotherapy among people with metastatic colorectal cancer treated with MB-6 for 16 weeks compared to chemotherapy alone in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁹²Chen WT, Yang TS et al. Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil-based chemotherapy in colorectal cancer. Nutrition Research. 2014 Jul;34(7):585-94.

Grape seed extract with a special diet: 15 ml balsamic vinegar from apples and honey, with seabuckthorn berry rich in carotenoids, rosemary, sage, and basil extracts, 150 g whole-wheat bread with 2.5% of the nutraceutic mixture VITAPAN, and 15 ml grape seed extract per day: preliminary evidence of better physical and functional well-being scores but no evidence of an effect on social/family well-being and emotional well-being scores among people with stage 3B–4 breast cancer treated with a special diet and grape seed extract

• Better physical and functional well-being scores but no evidence of an effect on social/family well-being and emotional well-being scores among people with stage 3B–4 breast cancer treated with 15 ml grape seed extract per day plus a diet including 15 ml balsamic vinegar from apples and honey, with seabuckthorn berry rich in carotenoids, rosemary, sage, and basil extracts per day, and 150 g whole-wheat bread with 2.5% of the nutraceutic mixture VITAPAN per day for 3 months compared to controls in a small RCT⁹³Drăgan S, Nicola T et al. Role of multi-component functional foods in the complex treatment of patients with advanced breast cancer. Revista Medico-Chirurgicala a Societatii de Medici si Naturalisti din Iasi. 2007 Oct-Dec;111(4):877-84.

Gelsectan, a medical device with active components xyloglucan, pea protein, tannins from grape seed extract, and xylo-oligosaccharides: preliminary evidence of fewer symptoms of irritable bowel syndrome among symptomatic people with diarrhea-predominant irritable bowel syndrome treated with Gelsectan

• Fewer symptoms of irritable bowel syndrome among symptomatic people with diarrhea-predominant irritable bowel syndrome treated with Gelsectan for 28 days compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCT⁹⁴Trifan A, Burta O et al. Efficacy and safety of Gelsectan for diarrhoea-predominant irritable bowel syndrome: a randomised, crossover clinical trial. United European Gastroenterology Journal. 2019 Oct;7(8):1093-1101.

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of lower expression of a key signaling pathway involved in colon cancer initiation in normal colonic mucosa but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. in colon cancer tissue from people with suspected or documented colorectal cancer treated with grape powder

• Lower expression of a key signaling pathway involved in colon cancer initiation (Wnt target gene expression) in normal colonic mucosa but no evidence of an effect in colon cancer tissue from people with suspected or documented colorectal cancer treated with grape powder compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁹⁵Nguyen AV, Martinez M et al. Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer. Cancer Management and Research. 2009 Apr 3;1:25-37.

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of a marker of protection against redness from exposure to ultraviolet light—a risk factor for melanoma and other skin cancers—among healthy males drinking red wine with the highest polyphenol content

• A marker of protection against redness from exposure to ultraviolet light (higher minimal erythema dose) among healthy males drinking red wine with the highest polyphenol content but no evidence of an effect from wine with lower polyphenol content compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁹⁶Moehrle M, Dietrich H, Patz CD, Häfner HM. Sun protection by red wine? Journal der Deutschen Dermatologischen Gesellschaft. 2009 Jan;7(1):29-32, 29-33. English, German.

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of better symptom scores and morphology of oral mucosa lesions among people with erosive oral lichen planus—a risk factor for cancer—but no evidence of an effect with non-erosive oral lichen planus among people rinsing with anthocyanins extracted from grape skin

• Better symptom scores and morphology of oral mucosa lesions among people with erosive oral lichen planus but no evidence of an effect with non erosive oral lichen planus among people rinsing with 100 mg anthocyanins extracted from grape skin diluted in 5 ml water for 5 minutes and spit 3 times a day compared to clobetasol propionate-neomycin-nystatin cream in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial⁹⁷Rivarola de Gutierrez E, Di Fabio A, Salomón S, Lanfranchi H. Topical treatment of oral lichen planus with anthocyanins. Medicina Oral, Patología Oral, y Cirugía Bucal. 2014 Sep 1;19(5):e459-66.

Leucoselect Phytosome, a standardized grape seed extract formulated with soy phospholipids: weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of lower markers of rapid cell growth (proliferation) among heavy active and former smokers treated with Leucoselect Phytosome

• A lower marker of cell proliferation (Ki-67 labeling index) on the bronchial epithelium from heavy active and former smokers treated with Leucoselect Phytosome for 3 months compared to baseline and less proliferation of human lung cancer cell lines treated with their plasma in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁹⁸Mao JT, Xue B et al. Leucoselect phytosome modulates serum eicosapentaenoic acid, docosahexaenoic acid, and prostaglandin e3 in a phase I lung cancer chemoprevention study. Cancer Prevention Research (Philadelphia). 2021 Jun;14(6):619-626.
• A lower marker of cell proliferation (Ki-67 labeling index) in bronchial biopsy samples from heavy active and former smokers treated with Leucoselect Phytosome for 3 months compared to baseline in a small uncontrolled trial⁹⁹Mao JT, Lu QY et al. A pilot study of a grape seed procyanidin extract for lung cancer chemoprevention. Cancer Prevention Research (Philadelphia). 2019 Aug;12(8):557-566.

Cucumis melo extract, acerola extract, olive fruit, aloe vera gel, grape seed extract, and lycopene: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of fewer symptoms of photoaging of skin—a risk factor for skin cancer—among healthy people treated with oral Cucumis melo extract, acerola extract, olive fruit, aloe vera gel, grape seed extract, and lycopene

• Fewer symptoms of photoaging of skin among healthy people treated with oral Cucumis melo extract, acerola extract, olive fruit, aloe vera gel, grape seed extract, and lycopene for 12 weeks compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁰⁰Xie Y, Zhu G et al. A new product of multi-plant extracts improved skin photoaging: An oral intake in vivo study. Journal of Cosmetic Dermatology. 2022 Aug;21(8):3406-3415.

Antioxidant cocktail containing grape seed extract, vitamin E, ubiquinone, and vitamin C: preliminary evidence of a smaller increase in a marker of photoaging after exposure to infrared A radiation among healthy people treated with SPF 30 sunscreen supplemented with an antioxidant cocktail containing grape seed extract, vitamin E, ubiquinone, and vitamin C

• A smaller increase in a marker of photoaging (upregulated MMP-1 expression) after exposure to infrared A radiation among healthy people treated with SPF 30 sunscreen supplemented with an antioxidant cocktail containing grape seed extract, vitamin E, ubiquinone, and vitamin C applied before radiation exposure compared to the sunscreen alone in a small RCT¹⁰¹Grether-Beck S, Marini A, Jaenicke T, Krutmann J. Effective photoprotection of human skin against infrared A radiation by topically applied antioxidants: results from a vehicle controlled, double-blind, randomized study. Photochemistry and Photobiology. 2015 Jan-Feb;91(1):248-50.

Red wine and 12% alcohol: no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on redness from exposure to ultraviolet light—a risk factor for melanoma and other skin cancers—among healthy males treated topically with red wine as well as 12% alcohol

• No evidence of an effect on redness (erythema) from exposure to ultraviolet light among healthy males treated topically with 20 minutes of occlusive application of red wine as well as 12% alcohol to the back compared to baseline in a small uncontrolled trial¹⁰²Moehrle M, Dietrich H, Patz CD, Häfner HM. Sun protection by red wine? Journal der Deutschen Dermatologischen Gesellschaft. 2009 Jan;7(1):29-32, 29-33. English, German.