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Cranberry

Plant Part Used

Berry

Active Constituents

Proanthocyanidins, quinic acid.(1),(18)

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Cranberry is used for urinary tract health. Cranberry fruit juice is recommended by both grandmothers and health care professionals for individuals with urinary tract infections, with research supporting folk uses.(2),(3),(4),(5) Cranberry is a close relative of the American blueberry and European bilberry. It has been used for centuries in cooking and as a garnish.

In the United States, urinary tract infections (occurring with dysuria, frequency, and urgency) account for a significant number of the bacterial infections that are reported each year. Only strep throat accounts for more prescriptions written annually for infections in adults. By some estimates, more than 50 million cases of urinary tract infections (UTI) are treated annually. One of every five women in the U.S. will suffer from a UTI at some time in her life. The infection is usually caused by the bacteria E. coli (in more than 90 percent of the cases), with the bacteria adhering to the wall of the bladder and causing inflammation, pain, and fever. Although these infections are not usually life threatening or even a significant health risk for most individuals, there is increasing concern over bacterial resistance.

Proanthocyanidins found in Cranberry have been reported in laboratory studies to inhibit P-fimbriae synthesis and induce a bacterial deformation, on both antibiotic-susceptible and antibiotic-resistant uropathogenic Escherichia coli.(19) Cranberry may prevent bacteria from adhering to the uroepithelium of the bladder, thereby blocking the ability of E. coli to infect the urinary mucosa.

Interactions and Depletions

Interactions
  • warfarin ;although one small clinical study found no effect on coagulation vs. placebo.(20)

Drugs metabolized by CYP3A substrate. Cranberry has been reported in laboratory studies to affect drugs metabolized by CYP3A, including nifedipine (Procardia) and midazolam (Versed).(21),(22)

Dosage Info

Dosage Range

300-400mg (standardized extract), 2 times a day.

Juice (Unsweetened):5-20 ounces daily.

Most Common Dosage

300mg (standardized extract), 2 times a day.

Dosage of Cranberry juice in preventing and treating urinary tract infections (UTI) in individuals has ranged from 5-20oz administered daily (6oz juice = 90gm fresh fruit), with one study having results with 4-6oz of juice daily for 7 weeks.(6) An active UTI requires more juice than the prevention dose. Also, Cranberry juice concentrate capsules are available and have been used in the management of UTI. One 300mg capsule twice daily, either 1 hour before meals or 2 hours after a meal, is recommended. Drink plenty of filtered or bottled water throughout the day. Most studies focus on using Cranberry juice cocktail in treating UTI. However, Cranberry juice cocktails contain added sugar and may be diluted by other juices. While Cranberry juice cocktail is effective in reducing the frequency and severity of UTI, the use of 100% unsweetened Cranberry juice is recommended.(23)

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 11-12% quinic acid per dose; one can also use freeze dried berries or juice concentrate.

Uses

Frequently Reported Uses

  • Urinary Tract Health
Other Reported Uses
  • Antioxidant
  • Antiinflammatory
  • H. pylori inhibition; gastroprotective
  • Cardiovascular health
  • Oral health
  • Anticancer

Toxicities & Precautions

General

This dietary supplement is considered safe when used in accordance with proper dosing guidelines.

Health Conditions

Cranberry juice may contain varying amounts of oxalate, a common component of kidney stones. Use with caution in individuals prone to nephrolithiasis. Do not use in individuals currently with nephrolithiasis.(7)

Side Effects

Large doses of cranberry juice may cause mild diarrhea and gastric upset. (8)

Pregnancy/ Breast Feeding

Studies report Cranberry is safe to use during pregnancy and breastfeeding, but consult a physician first.(24)

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Urinary Tract Health

Cranberry has been used to prevent kidney stones, as well as to remove unwanted toxins from the body.(9) As early as the 1840's, German researchers were examining the connection between using the Cranberry and the incidence of UTI. Researchers thought that Cranberry worked for UTI by acidifying the urine, preventing the bacteria from growing. In 1984, a researcher reported that Cranberry does not acidify the urine sufficiently to produce an antibacterial effect in the bladder.(10) Instead, Cranberry prevented E. coli from adhering to the cells lining the bladder wall, thus preventing infection.(25),(26) Research has reported that this property may be due to a glycoprotein found in the Cranberry fruit. Further research reported that Cranberry was a potent inhibitor of the most virulent strains of E. coli from attaching to the bladder wall.(11),(12) Studies also report that other members of the Vaccinium genus have similar properties, including bilberry and blueberry.(12) The anti-adhesive qualities of Cranberry may prevent E. coli from colonizing in the gut as well.(12)  In vitro studies have also reported some antibacterial activity of Cranberry juice.(27)

A randomized controlled study in older women found that Cranberry’s activity against UTI was as effective as trimethoprim.(28) A small, placebo controlled study in 188 pregnant women found there is a protective effect of Cranberry ingestion against asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy.(29) The findings of the Cochrane Collaboration support the potential use of Cranberry products in the prophylaxis of recurrent UTIs in young and middle-aged women.(30) Also, a small, randomized, double blind, placebo-controlled trial in 47 individuals with spinal cord injury found that Cranberry tablets reduced the incidence of UTI in those with neurogenic bladder.(31)

Other Uses

Cranberry was also reported to inhibit the adhesion of H. pylori to human gastric mucus and to human erythrocytes.(13) A recent human study reported that Cranberry juice is an effective antioxidant. The authors suggested that the antioxidant activity may be in part due to the relatively high vitamin C content.(14) Other laboratory studies support the antioxidant capabilities of the flavonoid constituents in cranberry.(15),(16),(32)

A number of studies, both laboratory and clinical, support the use of polyphenols, including those found in cranberries, in reducing the risk of cardiovascular disease (CVD) by increasing the resistance of LDL to oxidation, inhibiting platelet aggregation, reducing blood pressure, and via other anti-thrombotic and anti-inflammatory mechanisms.(33) Cranberry juice may increase plasma antioxidant levels reducing the risk of heart disease.(17) A small study in Type 2 diabetics taking oral glucose-lowering agents found Cranberry supplements to be effective in reducing atherosclerotic cholesterol profiles, including LDL cholesterol (although oxidized LDL was not affected) and total cholesterol levels, as well as total HDL/ cholesterol ratio.(34) The study also reported a neutral effect on glycaemic control. Another clinical study found that Cranberry did decrease oxidized LDL and intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin concentrations in men.(35)

A small clinical study in children found that use of Cranberry juice and Lactobacillus sp. was effective in reducing the number of H. pylori bacteria in the gut.(36) Another clinical study found that Cranberry in conjunction with PPIs and antibiotics helped eradicate H. pylori from the gut more effectively than the drugs alone.(37)

Matrix metalloproteinases (MMPs) play a major role in periodontal tissue destruction. An in vitro study found Cranberry proanthocyanidins inhibit the production of MMPs in a concentration-dependent manner.(38) Other laboratory studies have found Cranberry components to inhibit acid production, attachment, and biofilm formation by Streptococcus mutans.

Glucan-binding proteins, extracellular enzymes, carbohydrate production, and bacterial hydrophobicity, are all affected by Cranberry components. Regarding periodontal diseases, the same Cranberry fraction inhibits host inflammatory responses, production, and activity of enzymes that cause the destruction of the extracellular matrix, biofilm formation, and adherence of Porphyromonas gingivalis, and proteolytic activities and coaggregation of periodontopathogens. The above-listed effects suggest that Cranberry components, especially those with high molecular weight, could serve as bioactive molecules for the prevention and/or treatment of oral diseases.

Cranberry extracts have also been reported in laboratory studies to be effective against various cancer cell lines, including paraplatin-resistant ovarian cancer, breast, colon, prostate, and lung cancer cell lines.(39),(40)

References

  1. Leung A, et al. Encyclopedia of Common Natural Ingredients Used in Foods, Drugs, and Cosmetcs. New York: Wiley-Interscience Publication; 1996:50-53.
  2. Leaver RB. Cranberry Juice. Prof Nurse. 1996;11(8):525-26.
  3. View Abstract: Nazarko L. Infection Control. The Therapeutic Uses of Cranberry Juice. Nurs Stand. 1995;9(34):33-35.
  4. View Abstract: Lynch DM. Cranberry for prevention of urinary tract infections. Am Fam Physician. 2004 Dec 1;70(11):2175-7.
  5. View Abstract: Jepson RG. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2004;(2):CD001321.
  6. Gibson L, Pike L, et al. Effectiveness of Cranberry Juice in Preventing Urinary Tract Infections in Long-term Care Facility Patients. J Naturopathic Med. 1991;2:45-47.
  7. View Abstract: Terris MK, Issa MM, Tacker JR. Dietary supplementation with cranberry concentrate tablets may increase the risk of nephrolithiasis. Urology. Jan2001;57(1):26-9.
  8. Behrman: Nelson Textbook of Pediatrics, 16th ed. W B Saunders Company; 2000:2304.
  9. View Abstract: Schmidt DR, et al. An Examination of the Anti-adherence Activity of Cranberry Juice on Urinary and Nonurinary Bacterial Isolates. Microbios. 1988;55(224-225):173-81.
  10. View Abstract: Zafriri D, et al. Inhibitory Activity of Cranberry Juice on Adherence of Type 1 and Type P Fimbriated Escherichia coli to Eucaryotic Cells. Antimicrob Agents Chemother. 1989;33(1):92-98.
  11. View Abstract: 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. May2000;54(2):173-81.
  12. Ofek I, et al. Anti-Escherichia coli Adhesion Activity of Cranberry and Blueberry Juices. Adv Exp Med Biol. 1996;408:179-83.
  13. View Abstract: Burger O, Ofek I, Tabak M, Weiss EI, Sharon N, Neeman I. A high molecular mass constituent of cranberry juice inhibits helicobacter pylori adhesion to human gastric mucus. FEMS Immunol Med Microbiol. Dec2000;29(4):295-301.
  14. View Abstract: Pedersen CB, et al. Effects of blueberry and cranberry juice consumption on the plasma antioxidant capacity of healthy female volunteers. Eur J Clin Nutr. May2000;54(5):405-8.
  15. View Abstract: Wang SY, Jiao H. Scavenging Capacity of Berry Crops on Superoxide Radicals, Hydrogen Peroxide, Hydroxyl Radicals, and Singlet Oxygen. J Agric Food Chem. Nov2000;48(11):5677-5684.
  16. View Abstract: Yan X, Murphy BT, Hammond GB, Vinson JA, Neto CC. Antioxidant activities and antitumor screening of extracts from cranberry fruit (Vaccinium macrocarpon). J Agric Food Chem. Oct2002;50(21):5844-9.
  17. View Abstract: Vinson, JA, Kharrat HA, Samman N. Single-dose and supplementation studies with cranberry juice relevant to its role in heart disease as an antioxidant. American Chemical Society, New Orleans. Mar2003
  18. He X, Liu RH. Cranberry phytochemicals: Isolation, structure elucidation, and their antiproliferative and antioxidant activities. J Agric Food Chem. 20 Sep 2006;54(19):7069-7074.
  19. Pérez-López FR, Haya J, Chedraui P. Vaccinium macrocarpon: an interesting option for women with recurrent urinary tract infections and other health benefits. J Obstet Gynaecol Res. Aug 2009;35(4):630-639. Review.
  20. Ansell J, McDonough M, Zhao Y, Harmatz JS, Greenblatt DJ. The absence of an interaction between warfarin and Cranberry juice: a randomized, double-blind trial. J Clin Pharmacol. Jul 2009;49(7):824-830.
  21. Ngo N, Yan Z, Graf TN, Carrizosa DR, Kashuba AD, Dees EC, Oberlies NH, Paine MF. Identification of a Cranberry juice product that inhibits enteric CYP3A-mediated first-pass metabolism in humans. Drug Metab Dispos. Mar 2009;37(3):514-522. Epub 2008 Dec 29.
  22. Lilja JJ, Backman JT, Neuvonen PJ. Effects of daily ingestion of Cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam--probes of CYP2C9, CYP1A2, and CYP3A4. Clin Pharmacol Ther. Jun 2007;81(6):833-839. Epub 2007 Mar 28.
  23. Wilson T, Singh AP, Vorsa N, Goettl CD, Kittleson KM, Roe CM, Kastello GM, Ragsdale FR. Human glycemic response and phenolic content of unsweetened Cranberry juice. J Med Food. Mar 2008;11(1):46-54.
  24. Dugoua JJ, Seely D, Perri D, Mills E, Koren G. Safety and efficacy of Cranberry (Vaccinium macrocarpon) during pregnancy and lactation. Can J Clin Pharmacol. 2008 Winter;15(1):e80-86. Epub 2008 Jan 18. Review.
  25. Guay DR. Cranberry and urinary tract infections. Drugs. 2009;69(7):775-807. DOI: 10.2165/00003495-200969070-00002. Review.
  26. Liu Y, Gallardo-Moreno AM, Pinzon-Arango PA, Reynolds Y, Rodriguez G, Camesano TA. Cranberry changes the physicochemical surface properties of E. coli and adhesion with uroepithelial cells. Colloids Surf B Biointerfaces. 1 Aug 2008;65(1):35-42. Epub 2008 Feb 26.
  27. Magariños HL, Sahr C, Selaive SD, Costa ME, Figuerola FE, Pizarro OA. In vitro inhibitory effect of Cranberry (Vaccinium macrocarpom Ait.) juice on pathogenic microorganisms. Prikl Biokhim Mikrobiol. May-Jun 2008;44(3):333-336.
  28. McMurdo ME, Argo I, Phillips G, Daly F, Davey P. Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women. J Antimicrob Chemother. Feb 2009;63(2):389-395. Epub 2008 Nov 28.
  29. Wing DA, Rumney PJ, Preslicka CW, Chung JH. Daily Cranberry juice for the prevention of asymptomatic bacteriuria in pregnancy: a randomized, controlled pilot study. J Urol. Oct2008;180(4):1367-1372. Epub 2008 Aug 15.
  30. Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. Jan 2008 23;(1):CD001321. Review.
  31. Hess MJ, Hess PE, Sullivan MR, Nee M, Yalla SV. Evaluation of Cranberry tablets for the prevention of urinary tract infections in spinal cord injured patients with neurogenic bladder. Spinal Cord. Sep 2008;46(9):622-626. Epub 2008 Apr 8.
  32. Vinson JA, Bose P, Proch J, Al Kharrat H, Samman N. Cranberries and Cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants. J Agric Food Chem. 23 Jul 2008 ;56(14):5884-5891. Epub 2008 Jun 18.
  33. McKay DL, Blumberg JB. Cranberries (Vaccinium macrocarpon) and cardiovascular disease risk factors. Nutr Rev. Nov 2007;65(11):490-502. Review.
  34. Lee IT, Chan YC, Lin CW, Lee WJ, Sheu WH. Effect of Cranberry extracts on lipid profiles in subjects with Type 2 diabetes. Diabet Med. Dec 2008;25(12):1473-1477.
  35. Ruel G, Pomerleau S, Couture P, Lemieux S, Lamarche B, Couillard C. Low-calorie Cranberry juice supplementation reduces plasma oxidized LDL and cell adhesion molecule concentrations in men. Br J Nutr. Feb 2008;99(2):352-359. Epub 2007 Aug 29.
  36. Gotteland M, Andrews M, Toledo M, Muñoz L, Caceres P, Anziani A, Wittig E, Speisky H, Salazar G. Modulation of Helicobacter pylori colonization with Cranberry juice and Lactobacillus johnsonii La1 in children. Nutrition. May 2008;24(5):421-426. Epub 2008 Mar 17.
  37. 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. Mol Nutr Food Res. Jun 2007;51(6):746-751.
  38. La VD, Howell AB, Grenier D. Cranberry proanthocyanidins inhibit MMP production and activity. J Dent Res. Jul 2009;88(7):627-632.
  39. Singh AP, Singh RK, Kim KK, Satyan KS, Nussbaum R, Torres M, Brard L, Vorsa N. Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin. Phytother Res. Aug 2009;23(8):1066-1074.
  40. Neto CC, Amoroso JW, Liberty AM. Anticancer activities of Cranberry phytochemicals: an update. Mol Nutr Food Res. Jun 2008;52 (Suppl 1):S18-27. Review.

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