Health Care Professional Information

Scientific Name
Vaccinium macrocarpon
Common Name

Mossberry, Sassamanash, bounceberry

Clinical Summary

Cranberry is an evergreen shrub that is grown in North America and in Europe. The processed fruit and juice, which are rich in vitamin C, are widely consumed as food. The juice extract is marketed as a dietary supplement for urinary tract health. Cranberry is thought to have antibacterial, anti-inflammatory, and antioxidant activities. It is used for oral and gastrointestinal infections, cardiovascular diseases, and against cancer. The proanthocyanidins in cranberries inhibit the adherence of E. coli fimbriae to uroepithelial cells (1) in vitro. Clinical studies demonstrate that cranberry extracts can help prevent urinary tract infections (UTI) in adults (2) (3), in children (4) and in prostate cancer patients undergoing radiation therapy (5). However, regular consumption of cranberry juice did not confer protection against UTIs (6). While cranberry is not as effective as trimethoprim-sulfamethoxazole in preventing UTI, patients using cranberry are also less likely to develop antibiotic resistant bacteria (7) (8). But conclusions from a meta-analysis indicate that there is not enough evidence to recommend cranberry juice for the prevention of UTIs (9).
In studies of cancer prevention and treatment, cranberry extracts demonstrated anti-proliferative effects against prostate (10) (11) (12), liver (13), breast (14), ovarian (15), colon (12,16), and oral (12) cancer cell lines in vitro. However, cranberry juice consumption did not lower oxidative status in humans suggesting lack of protective effect against cancer or heart disease (17).
Cranberry juice also inhibited the adhesion of H. pylori to human gastric mucosa (18). Regular consumption of cranberry juice can suppress H. pylori infection (19) (20), a major factor in peptic ulcer disease and gastric cancer. When used with standard treatment, cranberry juice helps to eradicate H. pylori in women (21).
Cranberry juice has also been shown to prevent plaque formation and the development of gum disease due to its anti-colonizing and anti-adhesion properties (22) (23).
Cranberry products may interact with prescription drugs and may increase risk of kidney stone formation.

Food Sources

Cranberry can be consumed as juice, sauce, or dried fruit.

Purported Uses
  • Urinary Tract Infections
  • Cancer Prevention and Treatment
  • Antiaging
  • Ulcers
  • Atherosclerosis
  • Gum disease
Constituents

Flavonols, anthocyanins (Quercetin, myricetin, cyanidin and peonidin), and proanthocyanidins, Catechins, phenolic acids, triterpenoids (ursolic acid) (24).

Mechanism of Action

Proanthocyanidins found in cranberries inhibit P-fimbriated E. coli from adhering to the uroepithelial cells, thus preventing the development of infections (25) (26) (27) (28). Research suggests that the high number of A-type linkage proanthocyanidins found in cranberries may enhance in vitro and urinary bacterial anti-adhesion activities that prevent UTIs (27). A constituent of cranberry juice inhibits adhesion of H. pylori to immobilized human mucus, human erythrocytes, and cultured gastric epithelial cells, suggesting that cranberry juice may also prevent stomach ulcers caused by H. pylori via preventing the adhesion of bacteria to the stomach lining (18) (29). Cranberry juice was also shown to decrease adherence of oral streptococci strains to saliva-coated hydroxyapatite (23), glucan-coated hydroxyapatite, and impaired biofilm formation (22) (30) indicating that cranberry juice may slow the development of dental plaque and offer protection from plaque-related diseases. A proanthocyanidin from cranberry has been shown to arrest ovarian cancer cell growth by inhibiting vascular endothelial growth factor and by generating reactive oxygen species (15). Cranberry extract inhibits prostate cancer cell growth by decreasing the expression of cyclin-dependant kinase and cyclins (10). It also decreases matrix metalloproteinase activity (31).

Contraindications

Warfarin: Data are conflicting on cranberry's ability to enhance the potential of warfarin (34) (35).

Adverse Reactions

Case Reports
Several cases of increased INR (36) (37)and/or bleeding due to suspected interactions involving warfarin and cranberry juice have been reported. Two patients suffered internal hemorrhage following concurrent use of warfarin and cranberry juice that resulted in their deaths (38,39).

Cranberry products can increase urine oxalate excretion and may promote the formation of kidney stones (32) (33) (40).

Herb-Drug Interactions
  • Warfarin: Cranberry juice may potentiate warfarin-induced anticoagulation, but data are conflicting (34) (41).
  • Cyclosporin: A randomized controlled trial has shown that 240 mL of cranberry juice had no clinically significant effect on the disposition of a 200 mg dose of cyclosporin (42).
  • UGT (Uridine 5'-diphospho-glucuronosyltransferase) substrates: Cranberry modulates UGT enzymes in vitro and can increase risk of side effects of drugs metabolized by them (35).
  • Cytochrome P450 substrates: Cranberry inhibits enteric CYP3A activities and may interfere with the absorption of substrate drugs (43). Cranberry inhibits CYP2C9 in in vitro studies, but this activity was not observed in humans (44).
Herb Lab Interactions

Urinary pH has been shown to decrease after drinking cranberry juice (32) (33).

Literature Summary and Critique

Beerepoot MAJ, Riet GT, Nys S, et al. Cranberries vs Antibiotics to Prevent Urinary Tract Infections. A Randomized Double-blind Noninferiority Trial in Premenopausal Women. Arch Intern Med. 2011;171(14):1270-1278.
In this study, 221 premenopausal women with recurrent urinary tract infections (UTIs) were randomized to receive trimethoprim-sulfamethoxazole (TMP-SMX), 480 mg once daily, or cranberry capsules, 500mg twice daily for one year. The primary end points were the mean number of symptomatic UTIs, the proportion of patients with at least 1 symptomatic UTI, the median time to first UTI, and development of antibiotic resistance in indigenous Escherichia coli. Researchers observed the mean number and proportion of patients with at least 1 symptomatic UTI to be higher in the cranberry group. The median time to first symptomatic UTI was 4 and 8 months for the cranberry and TMP-SMX groups respectively. However, increased resistance was observed for TMP-SMX, trimethoprim, amoxicillin, and ciprofloxacin in the E.coli isolates in the TMP-SMX group. No such increases were seen in women who took cranberry.
TMP-SMX is more effective than cranberry capsules in preventing recurrent UTIs but antibiotic resistance is a major concern.

Barbosa-Cesnik C, Brown MB, Buxton M, et al. Cranberry juice fails to prevent recurrent urinary tract infection: results from a randomized placebo-controlled trial. Clin Infect Dis. 2011 Jan;52(1):23-30.
In this double-blind, placebo-controlled trial 319 college-aged women with acute urinary tract infection (UTI) were randomized to receive 8 ounces of 27% cranberry juice twice daily or placebo for six months. The subjects were followed up for 6 months or until the occurrence of a second UTI. Researchers failed to find any significant differences in urinary symptoms between the treatment and placebo groups at follow-up. Although small studies have reported the benefits of cranberry juice for prevention of UTIs, large randomized studies are lacking. Further research is needed to determine the usefulness of cranberry juice.

Zhang L, Ma J, Pan K, Go VL, Chen J, You WC. Efficacy of cranberry juice on Helicobacter pylori infection: a double-blind, randomized placebo-controlled trial. Helicobacter 2005;10(2):139-45.
This randomized, double-blind, placebo-controlled trial was conducted to test the effectiveness of cranberry juice in the suppression of H. pylori in an endemically infected population. One hundred and eighty seven adults with H. pylori infection were randomly assigned to receive cranberry juice or a placebo for 90 days. The extent of H. pylori infection was determined using the 13C-urea breath test. The study concluded that significantly more subjects in the cranberry juice group (14.43%) than the placebo group (5.44%) yielded negative test results, suggesting that regular consumption of cranberry juice can suppress H. pylori infection in endemically infected populations.

Dosage (Inside MSKCC Only)
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References
  1. Gupta K, Chou MY, Howell A, et al. Cranberry products inhibit adherence of p-fimbriated Escherichia coli to primary cultured bladder and vaginal epithelial cells. The Journal of urology. Jun 2007;177(6):2357-2360.
  2. Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. The Canadian journal of urology. Jun 2002;9(3):1558-1562.
  3. Kontiokari T, Sundqvist K, Nuutinen M, et al. Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. Bmj. Jun 30 2001;322(7302):1571.
  4. Ferrara P, Romaniello L, Vitelli O, et al. Cranberry juice for the prevention of recurrent urinary tract infections: a randomized controlled trial in children. Scandinavian journal of urology and nephrology. 2009;43(5):369-372.
  5. Bonetta A, Di Pierro F. Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary symptoms during radiotherapy for prostate carcinoma. Cancer management and research. 2012;4:281-286.
  6. Barbosa-Cesnik C, Brown MB, Buxton M, et al. Cranberry juice fails to prevent recurrent urinary tract infection: results from a randomized placebo-controlled trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. Jan 1 2011;52(1):23-30.
  7. Howell AB, Botto H, Combescure C, et al. Dosage effect on uropathogenic Escherichia coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study. BMC infectious diseases. 2010;10:94.
  8. Beerepoot MA, ter Riet G, Nys S, et al. Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women. Archives of internal medicine. Jul 25 2011;171(14):1270-1278.
  9. Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane database of systematic reviews. 2012;10:CD001321.
  10. Deziel B, MacPhee J, Patel K, et al. American cranberry (Vaccinium macrocarpon) extract affects human prostate cancer cell growth via cell cycle arrest by modulating expression of cell cycle regulators. Food & function. May 2012;3(5):556-564.
  11. Ferguson PJ, Kurowska E, Freeman DJ, et al. A flavonoid fraction from cranberry extract inhibits proliferation of human tumor cell lines. The Journal of nutrition. Jun 2004;134(6):1529-1535.
  12. Seeram NP, Adams LS, Hardy ML, et al. Total cranberry extract versus its phytochemical constituents: antiproliferative and synergistic effects against human tumor cell lines. Journal of agricultural and food chemistry. May 5 2004;52(9):2512-2517.
  13. Sun J, Chu YF, Wu X, et al. Antioxidant and antiproliferative activities of common fruits. Journal of agricultural and food chemistry. Dec 4 2002;50(25):7449-7454.
  14. Sun J, Hai Liu R. Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells. Cancer letters. Sep 8 2006;241(1):124-134.
  15. Kim KK, Singh AP, Singh RK, et al. Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells. International journal of oncology. Jan 2012;40(1):227-235.
  16. Parry J, Su L, Moore J, et al. Chemical compositions, antioxidant capacities, and antiproliferative activities of selected fruit seed flours. Journal of agricultural and food chemistry. May 31 2006;54(11):3773-3778.
  17. Duthie SJ, Jenkinson AM, Crozier A, et al. The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers. European journal of nutrition. Mar 2006;45(2):113-122.
  18. Burger O, Ofek I, Tabak M, et al. A high molecular mass constituent of cranberry juice inhibits helicobacter pylori adhesion to human gastric mucus. FEMS immunology and medical microbiology. Dec 2000;29(4):295-301.
  19. Zhang L, Ma J, Pan K, et al. Efficacy of cranberry juice on Helicobacter pylori infection: a double-blind, randomized placebo-controlled trial. Helicobacter. Apr 2005;10(2):139-145.
  20. Gotteland M, Andrews M, Toledo M, et al. Modulation of Helicobacter pylori colonization with cranberry juice and Lactobacillus johnsonii La1 in children. Nutrition (Burbank, Los Angeles County, Calif). May 2008;24(5):421-426.
  21. Shmuely H, Yahav J, Samra Z, et al. Effect of cranberry juice on eradication of Helicobacter pylori in patients treated with antibiotics and a proton pump inhibitor. Molecular nutrition & food research. Jun 2007;51(6):746-751.
  22. Weiss EI, Lev-Dor R, Kashamn Y, et al. Inhibiting interspecies coaggregation of plaque bacteria with a cranberry juice constituent [published erratam appear in J Am Dent Assoc 1999 Jan;130(1):36 and 1999 Mar;130(3):332]. Journal of the American Dental Association. Dec 1998;129(12):1719-1723.
  23. Yamanaka A, Kimizuka R, Kato T, et al. Inhibitory effects of cranberry juice on attachment of oral streptococci and biofilm formation. Oral microbiology and immunology. Jun 2004;19(3):150-154.
  24. Neto CC. Cranberry and its phytochemicals: a review of in vitro anticancer studies. The Journal of nutrition. Jan 2007;137(1 Suppl):186S-193S.
  25. Foo LY, Lu Y, Howell AB, et al. A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli. Journal of natural products. Sep 2000;63(9):1225-1228.
  26. Foo LY, Lu Y, Howell AB, et al. The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated Escherichia coli in vitro. Phytochemistry. May 2000;54(2):173-181.
  27. Howell AB, Reed JD, Krueger CG, et al. A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity. Phytochemistry. Sep 2005;66(18):2281-2291.
  28. Howell AB, Vorsa N, Der Marderosian A, et al. Inhibition of the adherence of P-fimbriated Escherichia coli to uroepithelial-cell surfaces by proanthocyanidin extracts from cranberries. The New England journal of medicine. Oct 8 1998;339(15):1085-1086.
  29. Burger O, Weiss E, Sharon N, et al. Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high-molecular-weight constituent of cranberry juice. Critical reviews in food science and nutrition. 2002;42(3 Suppl):279-284.
  30. Koo H, Nino de Guzman P, Schobel BD, et al. Influence of cranberry juice on glucan-mediated processes involved in Streptococcus mutans biofilm development. Caries research. 2006;40(1):20-27.
  31. Deziel BA, Patel K, Neto C, et al. Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways. Journal of cellular biochemistry. Oct 15 2010;111(3):742-754.
  32. Gettman MT, Ogan K, Brinkley LJ, et al. Effect of cranberry juice consumption on urinary stone risk factors. The Journal of urology. Aug 2005;174(2):590-594; quiz 801.
  33. Kessler T, Jansen B, Hesse A. Effect of blackcurrant-, cranberry- and plum juice consumption on risk factors associated with kidney stone formation. European journal of clinical nutrition. Oct 2002;56(10):1020-1023.
  34. Greenblatt DJ, von Moltke LL, Perloff ES, et al. Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. Clinical pharmacology and therapeutics. Jan 2006;79(1):125-133.
  35. Mohamed ME, Frye RF. Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta medica. Mar 2011;77(4):311-321.
  36. Hamann GL, Campbell JD, George CM. Warfarin-cranberry juice interaction. The Annals of pharmacotherapy. Mar 2011;45(3):e17.
  37. Roberts D, Flanagan P. Case report: Cranberry juice and warfarin. Home healthcare nurse. Feb 2011;29(2):92-97.
  38. Griffiths AP, Beddall A, Pegler S. Fatal haemopericardium and gastrointestinal haemorrhage due to possible interaction of cranberry juice with warfarin. The journal of the Royal Society for the Promotion of Health. Nov 2008;128(6):324-326.
  39. Suvarna R, Pirmohamed M, Henderson L. Possible interaction between warfarin and cranberry juice. Bmj. Dec 20 2003;327(7429):1454.
  40. Terris MK, Issa MM, Tacker JR. Dietary supplementation with cranberry concentrate tablets may increase the risk of nephrolithiasis. Urology. Jan 2001;57(1):26-29.
  41. Mohammed Abdul MI, Jiang X, Williams KM, et al. Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects. British journal of pharmacology. Aug 2008;154(8):1691-1700.
  42. Grenier J, Fradette C, Morelli G, et al. Pomelo juice, but not cranberry juice, affects the pharmacokinetics of cyclosporine in humans. Clinical pharmacology and therapeutics. Mar 2006;79(3):255-262.
  43. Kim E, Sy-Cordero A, Graf TN, et al. Isolation and identification of intestinal CYP3A inhibitors from cranberry (Vaccinium macrocarpon) using human intestinal microsomes. Planta medica. Feb 2011;77(3):265-270.
  44. Ushijima K, Tsuruoka S, Tsuda H, et al. Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects. British journal of clinical pharmacology. Aug 2009;68(2):194-200.

Consumer Information

How It Works

Bottom Line: Cranberry juice has not been shown to treat or prevent cancer.

Cranberries contain compounds known as proanthocyanidins that have been shown to inhibit E. coli from attaching to the bladder wall, thus preventing the development of an infection. Cranberry juice has also been shown to inhibit the attachment of oral bacteria in the laboratory setting, suggesting that it may slow the development of dental plaque and offer some protection from plaque-related diseases.

 

Purported Uses
  • Prevention and treatment of urinary tract infections (UTIs)
    The evidence for this claim is mixed.
  • Anticancer effects
    Lab studies have shown that cranberry juice extract has anti-proliferative effects on cancer cells such as prostate, liver, breast, colon, and oral. But such effects have not been confirmed by clinical trials.
  • Anti aging
    There is no scientific evidence to support this use.
  • Prevention of stomach ulcers
    A study done in China has shown cranberry juice to be effective for the prevention of H. pylori infection.
  • Prevention of Atherosclerosis
    This use is not backed by clinical data.
  • Prevention of Gum Disease/Cavities
    Laboratory studies have shown that cranberry juice prevents bacteria from attaching to one another thereby slowing down plaque formation.
Research Evidence

Prevention of UTIs:
In this study, 221 premenopausal women with recurrent urinary tract infections (UTIs) were randomized to receive trimethoprim-sulfamethoxazole (TMP-SMX), 480 mg once daily, or cranberry capsules, 500mg twice daily for one year. The primary end points were the mean number of symptomatic UTIs, the proportion of patients with at least 1 symptomatic UTI, the median time to first UTI, and development of antibiotic resistance in indigenous Escherichia coli. Researchers observed the mean number and proportion of patients with at least 1 symptomatic UTI to be higher in the cranberry group. The median time to first symptomatic UTI was 4 and 8 months for the cranberry and TMP-SMX groups respectively. However, increased resistance was observed for TMP-SMX, trimethoprim, amoxicillin, and ciprofloxacin in the E.coli isolates in the TMP-SMX group. No such increases were seen in women who took cranberry.
TMP-SMX is more effective than cranberry capsules in preventing recurrent UTIs but antibiotic resistance is a major concern.

In a double-blind, placebo-controlled trial 319 college-aged women with acute urinary tract infection (UTI) received 8 ounces of 27% cranberry juice twice daily or placebo for six months. The subjects were followed up for 6 months or until the occurrence of a second UTI. Researchers failed to find any significant differences in urinary symptoms between the treatment and placebo groups at follow-up. Although small studies have reported the benefits of cranberry juice for prevention of UTIs, large randomized studies are lacking. Further research is needed to determine the usefulness of cranberry juice.

A study of 150 women with UTIs caused by E. coli were given 50ml of cranberry-lingonberry juice concentrate a day for six months, an intervention of 100ml of lactobacillus drink five days a week for one year, or no intervention. The study showed that the cranberry group had a 20% risk reduction of UTI recurrence, suggesting that regular drinking of cranberry juice may reduce the recurrence of UTIs. A study of 150 patients showed that cranberry juice and cranberry tablets both decreased the number of patients experiencing at least one UTI per year when compared to placebo. Tablets were taken twice a day and 250ml of juice was taken three times a day for the one year trial. The study also concluded that tablets provided a more cost effective prevention of UTI compared to cranberry juice.

Do Not Take If
  • You are taking warfarin (cranberry juice may increase bleeding).
  • • You are taking drugs that are substrates of CYP450 (cranberry may increase the blood level and the risk of adverse effects of these drugs).
  • You are taking drugs that are substrates of UGT (Uridine 5'-diphospho-glucuronosyltransferase) enzymes (cranberry may increase the risk of side effects of these drugs).
Side Effects
  • Several cases of increased INR and/or bleeding due to suspected interactions involving warfarin and cranberry juice have been reported.
  • Two patients suffered internal hemorrhage following concurrent use of warfarin and cranberry juice that resulted in their deaths.
E-mail your questions and comments to aboutherbs@mskcc.org.