Effect of Concord Grape Juice on Chemotherapy-Induced Nausea and Vomiting: Results of a Pilot Study

Gail L. Ingersoll

Amy Wasilewski

Michele Haller

Kishan Pandya

John Bennett

Hua He

Claire Hoffmire

Cynthia Berry

nausea, nausea/vomiting, diet
ONF 2010, 37(2), 213-221. DOI: 10.1188/10.ONF.213-221

Purpose/Objectives: To determine the feasibility of administering a flavonoid-rich adjunctive treatment (Concord grape juice) for the management of chemotherapy-induced nausea and vomiting (CINV); to evaluate the usefulness of existing measures for assessing CINV frequency and severity, quality of life, control over life events, and psychological state; to identify any actual or potential adverse events associated with frequent grape juice intake; and to provide preliminary data concerning the effect of Concord grape juice on CINV, quality of life, perceived control over life events, and psychological state.

Design: Double-blind, randomized clinical trial.

Setting: A cancer center in an academic health science center in the northeastern United States.

Sample: 77 adult patients with cancer receiving moderately or highly emetogenic chemotherapy agents.

Methods: Participants drank 4 oz. of grape juice or placebo prior to meals for one week following each of four chemotherapy treatment cycles. They recorded frequency, duration, and distress of nausea, vomiting, and retching daily, beginning the evening of chemotherapy administration and continuing for seven days. Data were analyzed with generalized estimating equations methodology to model differences between groups over time.

Main Research Variables: Nausea and vomiting frequency, duration, and distress; quality of life; control over decision making; and psychological state.

Findings: Nausea and vomiting frequency, duration, and distress were lower for experimental group members, although a high attrition rate (50%) resulted in insufficient power to detect statistically significant differences over time. Greater levels of anxiety, depression, and hostility at baseline were related to nausea and vomiting, quality of life, and perceived control over decision making.

Conclusions: The effect of grape juice flavonoids on CINV should be investigated further with a larger sample to determine whether preliminary findings are supported. Alterations to the study protocol will be necessary to decrease attrition.

Implications for Nursing: Flavonoid-rich fruits and vegetables may provide additional protection against CINV. If the compounds work, they would offer a low-cost, readily available adjunctive treatment for the management of CINV.

Jump to a section


    Baker, P. D., Morzorati, S. L., & Ellett, M. L. (2005). The pathophysiology of chemotherapy-induced nausea and vomiting. Gastroenterology Nursing, 28, 469-480.
    Ballatori, E., & Roila, F. (2003). Impact of nausea and vomiting on quality of life in cancer patients during chemotherapy. Health and Quality of Life Outcomes, 1. Retrieved from
    Bhat, K. P. L., & Pezzuto, J. M. (2002). Cancer chemopreventive activity of resveratrol. Annals of the New York Academy of Sciences, 957, 210-229. doi: 10.1111/j.1749-6632.2002.tb02918.x
    Bloechl-Daum, B., Deuson, R. R., Mavros, P., Hansen, M., & Herrstedt, J. (2006). Delayed nausea and vomiting continue to reduce patients' quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. Journal of Clinical Oncology, 24, 4472-4478. doi: 10.1200/JCO.2006.05.6382
    Boulton, D. W., Walle, U. K., & Walle, T. (1997). Extensive binding of the bioflavonoid quercetin to human plasma proteins. Journal of Pharmacy and Pharmacology, 50, 243-249.
    Carelle, N., Piotto, E., Bellanger, A., Germanaud, J., Thuillier, A., & Khayat, D. (2002). Changing patient perceptions of the side effects of cancer chemotherapy. Cancer, 95, 155-163.
    Chou, F. H., Lin, L. L., Cooney, A. T., Walker, L. O., & Riggs, M. W. (2003). Psychosocial factors related to nausea, vomiting, and fatigue in early pregnancy. Journal of Nursing Scholarship, 35, 119-125. doi: 10.1111/j.1547-5069.2003.00119.x
    Cohen, L., de Moor, C. A., Eisenberg, P., Ming, E. E., & Hu, H. (2007). Chemotherapy-induced nausea and vomiting: Incidence and impact on patient quality of life at community oncology settings. Supportive Care in Cancer, 15, 497-503. doi: 10.1007/s00520-006-0173-z
    Cohen, S. R., Hassan, S. A., Lapointe, B. J., & Mount, B. M. (1996). Quality of life in HIV disease as measured by the McGill Quality of Life Questionnaire. AIDS, 10, 1421-1427.
    Cohen, S. R., Mount, B. M., Bruera, E., Provost, M., Rowe, J., & Tong, K. (1997). Validity of the McGill Quality of Life Questionnaire in the palliative care setting: A multi-centre Canadian study demonstrating the importance of the existential domain. Palliative Medicine, 11, 3-20.
    Cohen, S. R., Mount, B. M., Tomas, J. J. N., & Mount, L. F. (1996). Existential well-being is an important determinant of quality of life. Evidence from the McGill Quality of Life Questionnaire. Cancer, 77, 576-586.
    Colagiuri, B., Roscoe, J. A., Morrow, G. R., Atkins, J. N., Giguere, J. K., & Colman, L. K. (2008). How do patient expectancies, quality of life, and postchemotherapy nausea relate? Cancer, 113, 654-661. doi: 10.1002/cncr.23594
    Dando, T. M., & Perry, C. M. (2004). Aprepitant. A review of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs, 64, 777-794.
    Dibble, S. L., Israel, J., Nussey, B., Casey, K., & Luce, J. (2003). Delayed chemotherapy-induced nausea in women treated for breast cancer [Online exclusive]. Oncology Nursing Forum, 30, E40-E47. doi: 10.1188/03.ONF.E40-E47
    Erazo Valle, A., Wisniewski, T., Figueroa Vadillo, J. I., Burke, T. A., & Martinez Corona, R. (2006). Incidence of chemotherapy-induced nausea and vomiting in Mexico: Healthcare provider predictions versus observed. Current Medical Research and Opinion, 22, 2403-2410. doi: 10.1185/030079906X154033
    Ezzo, J., Richardson, M. A., Vickers, A., Allen, C., Dibble, S., Issell, B. F., … Zhang, G. (2006). Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting. Cochrane Database of Systematic Reviews, 2, CD002285. doi: 10.1002/14651858.CD002285.pub2
    Fetzer, S. J., Hand, M. C., Bouchard, P. A., Smith, H., & Jenkins, M. B. (2004). Evaluation of the Rhodes Index of Nausea and Vomiting for ambulatory surgery patients. Journal of Advanced Nursing, 47, 74-80. doi: 10.1111/j.1365-2648.2004.03067.x
    Folkman, S., & Moskowitz, J. T. (2000). Positive affect and the other side of coping. American Psychologist, 55, 647-654. doi: 10.1037/0003-066X.55.6.647
    Grunberg, S. M., Deuson, R. R., Mavros, P., Geling, O., Hansen, M., Cruciani, G., … Daugaard, G. (2004). Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer, 100, 2261-2268. doi: 10.1002/cncr.20230
    Han, Y. (2007). Synergic effect of grape seed extract with amphotericin B against disseminated candidiasis due to Candida albicans. Phytomedicine, 14, 733-738. doi: 10.1016/j.phymed.2007.08.004
    Havsteen, B. (1983). Flavonoids, a class of natural products of high pharmacological potency. Biochemical Pharmacology, 32, 1141-1148.
    Hesketh, P. J. (2008). Chemotherapy-induced nausea and vomiting. New England Journal of Medicine, 358, 2482-2494.
    Hesketh, P. J., Grunberg, S. M., Gralla, R. J., Warr, D. G., Roila, F., de Wit, R., … Aprepitant Protocol 052 Study Group. (2003). The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: A multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin. Journal of Clinical Oncology, 21, 4112-4119. doi: 10.1200/JCO.2003.01.095
    Hogan, C. M., & Grant, M. (1997). Physiologic mechanisms of nausea and vomiting in patients with cancer. Oncology Nursing Forum, 24(7, Suppl.), 8-12.
    Hollman, P. C., de Vries, J. H., van Leeuwen, S. D., Mengelers, M. J., & Katan, M. B. (1995). Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. American Journal of Clinical Nutrition, 62, 1276-1282.
    Hollman, P. C. H., & Katan, M. B. (1998). Bioavailability and health effects of dietary flavonols in man. Archives of Toxicology Supplement, 20, 237-248.
    Jayaprakasha, G. K., Selvi, T., & Sakariah, K. K. (2003). Antibacterial and antioxidant activities of grape (vitis vinifera) seed extracts. Food Research International, 36, 117-122. doi: 10.1016/S0963-9969(02)00116-3
    Korkina, L. G., & Afanas'ev, I. B. (1997). Antioxidants and chelating properties of flavonoids. In H. Sies (Ed.), Advances in pharmacology (vol. 38, pp. 151-163). New York, NY: Academic Press.
    Kris, M. G., Hesketh, P. J., Somerfield, M. R., Feyer, P., Clark-Snow, R., Koeller, J. M., … Grunberg, S. M. (2006). American Society of Clinical Oncology guideline for antiemetics in oncology: Update 2006. Journal of Clinical Oncology, 24, 2932-2947. doi: 10.1200/JCO.2006.06.9591
    Littlefield, V. M., Chang, A., & Adams, B. N. (1990). Participation in alternative care: Relationship to anxiety, depression, and hostility. Research in Nursing and Health, 13, 17-25.
    Mitsunaga, Y., Takanaga, H., Matsuo, H., Naito, M., Tsuruo, T., Ohtani, H., & Sawada, Y. (2000). Effect of bioflavonoids on vincristine transport across blood-brain barrier. European Journal of Pharmacology, 395, 193-201.
    Nunnally, J. C. (1978). Psychometric theory (2nd ed.). New York, NY: McGraw-Hill.
    Oncology Nursing Society. (2008). ONS Putting Evidence Into Practice: Nausea and vomiting. Evidence table. Retrieved from
    Pearlin, L. I., & Schooler C. (1978). The structure of coping. Journal of Health and Social Behavior, 19, 2-21.
    Pennington, J. A. T. (1998). Food values of portions commonly used (17th ed.). Philadelphia, PA: Lippincott.
    Perman, J. A. (1996). Digestion and absorption of fruit juice carbohydrates. Journal of the American College of Nutrition, 15(5, Suppl.), 12S-17S.
    Pietta, P. G. (2000). Flavonoids as antioxidants. Journal of Natural Products, 63, 1035-1042. doi: 10.1021/np9904509
    Prior, R. L., & Cao, G. (2000). Antioxidant phytochemicals in fruits and vegetables: Diet and health implications. Horticultural Science, 35, 588-592.
    Radwin, L. (2000). Oncology patients' perceptions of quality nursing care. Research in Nursing and Health, 23, 179-190. doi: 10.1002/1098-240X(200006)23:3179::AID-NUR2>3.0.CO;2-T
    Rhodes, V. A., & McDaniel, R. W. (1999). The Index of Nausea, Vomiting, and Retching: A new format of the Index of Nausea and Vomiting. Oncology Nursing Forum, 26, 889-894.
    Rhodes, V. A., Watson, P. M., & Johnson, M. H. (1984). Development of reliable and valid measures of nausea and vomiting. Cancer Nursing, 7, 33-41.
    Rhodes, V. A., Watson, P. M., Johnson, M. H., Madsen, R. W., & Beck, N. C. (1987). Patterns of nausea, vomiting, and distress in patients receiving antineoplastic drug protocols. Oncology Nursing Forum, 14(4), 35-44.
    Rimm, E. B., Katan, M. B., Ascherio, A., Stampfer, M. J., & Willett, W. C. (1996). Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Annals of Internal Medicine, 125, 384-389. Retrieved from
    Roila, F., Hesketh, P. J., Herrstedt, J., & the Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer. (2006). Prevention of chemotherapy- and radiotherapy-induced emesis: Results of the 2004 Perugia International Antiemetic Consensus Conference. Annals of Oncology, 17, 20-28. doi: 10.1093/annonc/mdj078
    Saito, M., Hosoyama, H., Ariga, T., Kataoka, S., & Yamaji, N. (1998). Antiulcer activity of grape seed extract and procyanidins. Journal of Agricultural and Food Chemistry, 46, 1460-1464. doi: 10.1021/jf9709156
    Saito, R., Takano, Y., & Kamiya, H. (2003). Roles of substance P and NK(1) receptor in the brainstem in the development of emesis. Journal of Pharmacological Sciences, 91, 87-94. doi: 10.1254/jphs.91.87
    Sanger, G. J., & Andrews, P. L. (2006). Treatment of nausea and vomiting: Gaps in our knowledge. Autonomic Neuroscience: Basic and Clinical, 129(1-2), 3-16. doi: 10.1016/j.autneu.2006.07.009
    Sharma, G., Tyagi, A. K., Singh, R. P., Chan, D. C., & Agarwal, R. (2004). Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells. Breast Cancer Research and Treatment, 85, 1-12. doi: 10.1023/B:BREA.0000020991.55659.59
    Shoskes, D. A., Jones, E. A., & Shahed, A. (2000). Synergy of mycophenolate mofetil and bioflavonoids in prevention of immune and ischemic injury. Transplantation Proceedings, 32, 798-799.
    Singh, R. P., Tyagi, A. K., Dhanalakshmi, S., Agarwal, R., & Agarwal, C. (2004). Grape seed extract inhibits advanced human prostate tumor growth and angiogenesis and upregulates insulin-like growth factor binding protein-3. International Journal of Cancer, 108, 733-740. doi: 10.1002/ijc.11620
    Sitzia, J., & Wood, N. (1999). Development and evaluation of a questionnaire to assess patient satisfaction with chemotherapy nursing care. European Journal of Oncology Nursing, 3, 126-140.
    Spencer, J. P., Chowrimootoo, G., Choudhury, R., Debnam, E. S., Srai, S. K., & Rice-Evans, C. (1999). The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Letters, 458, 224-230.
    Waqar, M. A., Chitneni, P., Williams, K., Goodgame, B. W., Gao, F., Govindan, R., & Baggstrom, M. Q. (2008). A prospective study on the incidence of delayed nausea and vomiting following administration of carboplatin containing regimens for treatment of cancer without prophylactic aprepitant [Abstract 20626]. Journal of Clinical Oncology, 26(Suppl. 15S). Retrieved from
    Ware, J. E., Snyder, M. K., Wright, R., & Davies, A. R. (1983). Defining and measuring patient satisfaction with medical care. Evaluation and Program Planning, 6, 247-263.
    Zautra, A. J., Reich, J. W., & Newsom, J. T. (1995). Autonomy and sense of control among older adults: An examination of their effects on mental health. In L. A. Bond, S. J. Cutler, & A. Grams (Eds.), Promoting successful and productive aging (pp. 153-170). Thousand Oaks, CA: Sage.
    Zheng, T., Boyle, P., Willett, W. C., Huanfang, H., Dan, J., Evstifeena, T. V., … MacMahon, B. (1993). A case-control study of oral cancer in Beijing, People's Republic of China. Associations with nutrient intake, foods and food groups. European Journal of Cancer: Part B Oral Oncology, 29B(1), 45-55.
    Zhou, Q., O'Brien, B., & Soeken, K. (2001). Rhodes Index of Nausea and Vomiting-Form 2 in pregnant women. A confirmatory factor analysis. Nursing Research, 50, 251-257.
    Zuckerman, M., & Lubin, B. (1985). Manual for the MAACL-R. The Multiple Affect Adjective Check List Revised. San Diego, CA: Educational and Industrial Testing Service.