Cranberry Article April 2010 News


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Cranberry products, including juice and supplements, decrease the incidence of certain bacterial infections. There is an abundance of clinical evidence that supports this concept in the case of urinary tract infections in some people. Further study should be able to establish a precise and systematic approach to using cranberry products in the prevention of urinary tract infections and decreasing the overall incidence of this problem in the population. In addition, cranberry products may decrease the extent of infections by Helicobacter pylori, the bacterial species that causes gastric ulcers, as well as bacterial infections associated with plaque formation on teeth. Finally, preliminary observations suggest that cranberry may have cardio-protective and anticancer properties.

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Cranberry Article April 2010 News

  1. 1. NMR News: Volume 3, Issue 4, April 2010 THE NEW AGE OF CRANBERRIES: Extraordinary condition-specific benefits in a centuries-old fruit By: Charles Spielholz, Ph.D. T he cranberry fruit comes from a fruit is generally processed into juice, sauce plant that is an evergreen dwarf or dried fruit; only a small amount of the shrub or trailing vine. Cranberries cranberry crop is sold as fresh fruit. Almost are related to the bilberry (see the March all processed cranberry products contain 2010 article on bilberry), blueberry and added sugar or another fruit juice product huckleberry. Represented by several species because cranberry is generally considered to of Vaccinium, the cranberry grows in the be too “sharp” or “tart” for the palate. cooler climates of the Northern Hemisphere. Therefore, cranberry juice is generally Cranberries are cultivated both in the available as a cocktail mixed with another, United States and Canada. The cultivated 1
  2. 2. NMR News: Volume 3, Issue 4, April 2010 sweeter juice in order to cover the “sharp” magnesium, sodium, phosphorus, or “tart” taste of cranberry. potassium, flavonoids (including anthocyanin, peonidin, and quercetin) and Cranberry products have been tannins. However cranberries are not associated with a variety of health benefits. considered palatable by most individuals In addition to nutritional benefits, cranberry and are not generally eaten as a fruit. has been associated with a decrease in Processed cranberries are often mixed with urinary tract infections, ulcers, and dental sugar; added sugar decreases the nutritional plaques. In addition, significance of processed there are some cranberry products for many suggestions that people. cranberry may have benefits related to There have been kidney stones and multiple observations showing cardiovascular health as that cranberry (generally the well as possible species Vaccinium macrocarpon) anticancer properties. either as a juice or as a Each of these claims is reviewed. supplement, decreases the incidence of urinary tract infections in women under Nutritionally, cranberry contains certain conditions. Thus far, the best vitamin A (including related molecules evidence supports the idea that cranberry carotene, leutein, and zeaxanthin), vitamin juice or supplements help prevent urinary C and K, dietary fiber, manganese, calcium, 2
  3. 3. NMR News: Volume 3, Issue 4, April 2010 tract infections in otherwise healthy women cranberry decreases the ability of certain (1-13). However, there is little evidence that types of bacteria and yeast to adhere to cranberry is useful for the treatment of uroepithelial cells. In the case of bacteria, it urinary tract infections. This means that appears that cranberry causes changes in cranberry products might be a good, non- bacterial fimbriae. Cranberry also appears to pharmaceutical method of decreasing the contain polyphenols and tannins that play chances of urinary tract infections and may an antibacterial role. Mechanism evidence of be particularly useful for people who are this type further supports the clinical prone to such infections. Please note that observations that cranberry products are individuals must seek the advice of a useful for the prevention of urinary tract physician for the treatment of a urinary tract infections. infection: The data shows that cranberry Although the evidence that cranberry products can be useful as a preventative of is helpful in preventing urinary tract urinary tract infections, not a treatment for infections is strong, this evidence needs to an active infection. be refined. Clinical trials are needed to Efficacy of cranberry products in the determine the best dose, duration, frequency prevention of urinary tract infections has of use, mode of administration, and patient been supported by data indicating a base. Cranberry does not appear to be mechanism of action of cranberry against associated with significant adverse effects bacteria (1, 6, 7, 9, 14-17). Experimental data (discussed below). The patient best suited and clinical observations indicate that for using cranberry products to prevent 3
  4. 4. NMR News: Volume 3, Issue 4, April 2010 urinary tract infections also needs to be Use of cranberry juice in firmly established. Currently, available data clinical trials for urinary indicates that women in reasonably good tract infection have suffered from large health with a history of recurrent urinary patient drop-out rates; this large drop-out tract infections or whose lifestyle puts them rate may be due to the caloric content of the at risk for urinary tract infections appear to cranberry product or the "sharp" or "tart" be the best candidates for using cranberry as taste in unsweetened cranberry products. a preventive measure. Data for use of Research also indicates that cranberry cranberry in the prevention of urinary tract may be effective at inhibiting the adhesion infections in women with health issues, of Helicobacter pylori to gastric mucus and men, and children are much more epithelial cells and may suppress this preliminary and require more investigation. bacterial species in the human digestive Cranberry, as a well known food product, is tract (18-22). In a randomized, double-blind, generally recognized as safe; adverse effects placebo controlled, clinical trial, cranberry are not expected to be a major issue (see juice was shown to significantly decrease discussion below). Finally, since most the extent of Helicobacter pylori in patients cranberry products contain added sugar in with such infections (19). This result order to make the product palatable, it may indicates that drinking cranberry juice may be best to use cranberry as a concentrated be helpful to people with such infections. supplement without added sugar. Indeed, it Furthermore, it can be proposed that use of may be possible to gain greater patient cranberry products may be able to decrease compliance with a cranberry supplement. 4
  5. 5. NMR News: Volume 3, Issue 4, April 2010 the incidence of gastric ulcers. Of course, the the sugar content. If successful, research answer to this hypothesis can only be along these lines will center either on determined by a clinical trial in which the cranberry supplements that do not contain incidence of gastric ulcers of users of sugar or on active chemical constituents cranberry products is directly tested. found in cranberry. Since cranberry is active against There have been at least two reports certain types of bacteria, preliminary in the medical literature suggesting that research into the effects of cranberry on consumption of cranberry juice may be bacteria that cause dental plaque have been useful for decreasing the incidence of performed. Preliminary research indicates kidney stone formation (26, 27). Results that cranberry juice or cranberry from these two reports indicated that constituents inhibit the attachment of oral consumption of cranberry juice increased bacterial species to model dental surfaces the acidity of urine, decreased the excretion used in the laboratory (21-25). One of the of oxalate and phosphate, and increased the studies also showed that dental caries were excretion of citrate. The authors of these two reduced in laboratory rats treated with reports considered these changes to indicate flavonoids found in cranberry (25). This a role for the consumption of cranberry juice work has not yet been extended to humans. in the management of urolithiasis (kidney Cranberry juice itself as well as other stones). However, these two reports must be commercial cranberry products will not balanced against a report that indicates that make useful dental health aids because of cranberry concentrate tablets (as opposed to 5
  6. 6. NMR News: Volume 3, Issue 4, April 2010 cranberry juice) increases the risk of For the case of cardio-protective nephrolitiasis (the condition of having effects, it is hypothesized that the kidney stones) because of the oxalate phytochemical composition of cranberries content of cranberry (28). Clearly, no can help decrease atherosclerosis, inhibit the recommendation can be made with regard oxidation of low density lipoprotein (LDL), to cranberry products and kidney stones inhibit platelet aggregation and adhesion, until additional research is performed. decrease total and LDL-cholesterol, decrease blood pressure and decrease inflammation Cranberry products have also been (30-32). However, no recommendations can associated with cardio-protective effects and be made regarding the use of cranberries in anticancer properties (29-39). These cardiovascular health at this time since there potential attributes are believed to be due to is not enough evidence to support such a the phytochemical content of cranberries, in view; this work is too preliminary at this particular the content of flavonoids, which point. appear to be high in antioxidant activity, and hydroxycinnamic Anticancer properties of cranberries acid. Two classes of are associated with phytochemicals that flavonoids of particular appear to reduce cell and tissue damage interest are the from oxidative stress (32, 34). However, the anthocynanins and only experiments performed thus far have proanthocyanidins. been in cultured tumor cell lines (35-39). Proposed mechanisms of action for these 6
  7. 7. NMR News: Volume 3, Issue 4, April 2010 phytochemicals include an increased rate of literature indicates that cranberries are safe programmed cell death (apoptosis) of tumor even for pregnant and nursing women (40). cells maintained in laboratory culture (35, There was one report linking the use of 36), decreases in the activity of enzymes cranberry juice with a death in a person required by the cultured tumor cells for taking the blood thinner warfarin (41). That cellular functions (35), anti-inflammatory report concluded that people taking properties (36, 37), decreases in the activity warfarin should exercise caution with the of proteins associated with the development use of cranberry products. However, the and progression of tumor cells (35, 36) as results of a randomized clinical trial well as decreases in angiogenesis (39). indicated that cranberry juice did not However, it is important to note that these interfere with the pharmacokinetics of laboratory studies and proposed warfarin (42). Individuals using mechanisms of action have not been pharmaceuticals should speak with a health correlated with clinical or epidemiological care provider before using a supplement studies. Therefore, no recommendations can form of cranberries. be made regarding cranberries and a role in Evidence shows that cranberry cancer prevention at this time. products, including juice and supplements, Cranberries are not associated with provide a means of preventing urinary tract any significant adverse effects. Since they infections in certain individuals. Additional are a food item, cranberries are accepted as clinical trials will establish the exact being generally safe. In fact, a review of the conditions of using these products 7
  8. 8. NMR News: Volume 3, Issue 4, April 2010 effectively. For some people, the use of 7) Jepson RG, Craig JC. 2007. A systematic review of the evidence for cranberries and blueberries in UTI prevention. cranberry products as a preventative Mol Nutr Food Res.51:738-745. measure could decrease the incidence of 8) Santillo VM, Lowe FC. 2007. Cranberry juice for the prevention and treatment of urinary tract infections. Drugs urinary tract infections and avoid the need Today (Barc). 43:47-54. of antibiotics required for treatment. 9) Nowack R. 2007. Cranberry juice-- a well-characterized folk-remedy against bacterial urinary tract infection. Wien References Med Wochenschr. 157:325-330. 1) Zafriri D, Ofek I, Adar R, Pocino M, Sharon N. 1989. 10) Jepson RG, Craig JC. 2008. Cranberries for preventing Inhibitory activity of cranberry juice on adherence of type 1 urinary tract infections. Cochrane Database Syst Rev. 2008 and type P fimbriated Escherichia coli to eucaryotic cells. Jan 23;(1):CD001321. Antimicrob Agents Chemother. 33:92-98. 11) Perez-Lopez FR, Haya J, Chedraui P. 2009. Vaccinium 2) Avorn J, Monane M, Gurwitz JH, Glynn RJ, macrocarpon: an interesting option for women with Choodnovskiy I, Lipsitz LA. 1994. Reduction of bacteriuria recurrent urinary tract infections and other health benefits. and pyuria after ingestion of cranberry juice. JAMA. 1994. J Obstet Gynaecol Res. 35:630-639. 271:751-754. 12) Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, 3) High KP. 2001. Nutritional strategies to boost immunity Koskela M, Uhari M. 2001. Randomised trial of cranberry- and prevent infection in elderly individuals. Clin Infect Dis. lingonberry juice and Lactobacillus GG drink for the 2001. 33:1892-1900. prevention of urinary tract infections in women. BMJ. 322:1571. 4) Dwyer PL, O'Reilly M. 2002. Recurrent urinary tract infection in the female. Curr Opin Obstet Gynecol. 14:537- 13) Stothers L. 2002. A randomized trial to evaluate 543. effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract 5) Stothers L. 2002. A randomized trial to evaluate infection in women. Can J Urol. 9:1558-1562.12) Di Martino effectiveness and cost effectiveness of naturopathic P, Agniel R, David K, Templer C, Gaillard JL, Denys P, cranberry products as prophylaxis against urinary tract Botto H. 2006. Escherichia coli adherence to uroepithelial infection in women. Can J Urol. 9:1558-1562. bladder cells after consumption of cranberry juice: a double-blind randomized placebo-controlled cross-over 6) Cimolai N, Cimolai T. 2007. The cranberry and the trial. World J Urol. 24:21-27. urinary tract. Eur J Clin Microbiol Infect Dis. 26:767-776. 14) Di Martino P, Agniel R, David K, Templer C, Gaillard JL, Denys P, Botto H. 2006. Reduction of Escherichia coli adherence to uroepithelial bladder cells after consumption 8
  9. 9. NMR News: Volume 3, Issue 4, April 2010 of cranberry juice: a double-blind randomized placebo- 23) Yamanaka A, Kouchi T, Kasai K, Kato T, Ishihara K, controlled cross-over trial. World J Urol. 24:21-27. Okuda K. 2007. Inhibitory effect of cranberry polyphenol on biofilm formation and cysteine proteases of 15) Howell AB. 2007. Bioactive compounds in cranberries Porphyromonas gingivalis. J Periodontal Res. 42:589-592. and their role in prevention of urinary tract infections. Mol Nutr Food Res. 51:732-737. 24) Bodet C, Grenier D, Chandad F, Ofek I, Steinberg D, Weiss EI. 2008. Potential oral health benefits of cranberry. 16) Jass J, Reid G. Effect of cranberry drink on bacterial Crit Rev Food Sci Nutr. 48:672-680. adhesion in vitro and vaginal microbiota in healthy females. Can J Urol. 16:4901-4907. 25) Koo H, Duarte S, Murata RM, Scott-Anne K, Gregoire S, Watson GE, Singh AP, Vorsa N. 2010. Influence of 17) Pinzón-Arango PA, Liu Y, Camesano TA. 2009. Role of Cranberry Proanthocyanidins on Formation of Biofilms by cranberry on bacterial adhesion forces and implications for Streptococcus mutans on Saliva-Coated Apatitic Surface Escherichia coli-uroepithelial cell attachment. J Med Food. and on Dental Caries Development in vivo. Caries Res. 12:259-270. 44:116-126. 18) Burger O, Weiss E, Sharon N, Tabak M, Neeman I, Ofek 26) Kessler T, Jansen B, Hesse A. 2002. Effect of I. 2002. Inhibition of Helicobacter pylori adhesion to human blackcurrant-, cranberry- and plum juice consumption on gastric mucus by a high-molecular-weight constituent of risk factors associated with kidney stone formation. Eur J cranberry juice. Crit Rev Food Sci Nutr. 42:279-284. Clin Nutr. 56:1020-1023. 19) Zhang L, Ma J, Pan K, Go VL, Chen J, You WC. 2005. 27) McHarg T, Rodgers A, Charlton K. 2003. Influence of Efficacy of cranberry juice on Helicobacter pylori infection: cranberry juice on the urinary risk factors for calcium a double-blind, randomized placebo-controlled trial. oxalate kidney stone formation. BJU Int. 92:765-768. Helicobacter. 10:139-145. 28) Terris MK, Issa MM, Tacker JR. 2001. Dietary 20) Lin YT, Kwon YI, Labbe RG, Shetty K. 2005. Inhibition supplementation with cranberry concentrate tablets may of Helicobacter pylori and associated urease by oregano increase the risk of nephrolithiasis. Urology. 57:26-29. and cranberry phytochemical synergies. Appl Environ Microbiol. 71:8558-8564. 29) Ruel G, Couillard C. 2007. Evidences of the cardioprotective potential of fruits: the case of cranberries. 21) Steinberg D, Feldman M, Ofek I, Weiss EI. 2004. Effect Mol Nutr Food Res. 51:692-701. of a high-molecular-weight component of cranberry on constituents of dental biofilm. J Antimicrob Chemother. 30) Reed J. 2002. Cranberry flavonoids, atherosclerosis and 54:86-89. cardiovascular health. Crit Rev Food Sci Nutr. 42:301-316. 22) Yamanaka A, Kimizuka R, Kato T, Okuda K. 2004. 31) McKay DL, Blumberg JB. 2007. Cranberries (Vaccinium Inhibitory effects of cranberry juice on attachment of oral macrocarpon) and cardiovascular disease risk factors. Nutr streptococci and biofilm formation. Oral Microbiol Rev. 65:490-502. Immunol. 19:150-154. 9
  10. 10. NMR News: Volume 3, Issue 4, April 2010 32) Neto CC. 2007. Cranberry and blueberry: evidence for during pregnancy and lactation. Can J Clin Pharmacol. protective effects against cancer and vascular diseases. Mol 15:e80-6. Nutr Food Res. 51:652-664. 41) Suvarna R, Pirmohamed M, Henderson L. 2003. 33) Spormann TM, Albert FW, Rath T, Dietrich H, Will F, Possible interaction between warfarin and cranberry juice. Stockis JP, Eisenbrand G, Janzowski C. 2008. BMJ. 327:1454. Anthocyanin/polyphenolic-rich fruit juice reduces oxidative cell damage in an intervention study with 42) Greenblatt DJ, von Moltke LL, Perloff ES, Luo Y, patients on hemodialysis. Cancer Epidemiol Biomarkers Harmatz JS, Zinny MA. 2006 Interaction of flurbiprofen Prev. 2008 Dec;17(12):3372-3380. with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. Clin Pharmacol Ther. 79:125-133. 34) Nichenametla SN, Taruscio TG, Barney DL, Exon JH. 2006. A review of the effects and mechanisms of polyphenolics in cancer. Crit Rev Food Sci Nutr. 46:161-183. 35) Hafeez BB, Siddiqui IA, Asim M, Malik A, Afaq F, Adhami VM, Saleem M, Din M, Mukhtar H. 2008. A dietary anthocyanidin delphinidin induces apoptosis of human prostate cancer PC3 cells in vitro and in vivo: involvement of nuclear factor-kappaB signaling. Cancer Res. 68:8564-8572. 36) Neto CC. 2007. Cranberry and its phytochemicals: a review of in vitro anticancer studies. J Nutr. 137:186S-193S. 37) Neto CC, Amoroso JW, Liberty AM. 2008. Anticancer activities of cranberry phytochemicals: an update. Mol Nutr Food Res. 52:S18-27. 38) Wang LS, Stoner GD. 2008. Anthocyanins and their role in cancer prevention. Cancer Lett. 269:281-290. 39) Bagchi D, Sen CK, Bagchi M, Atalay M. 2004. Anti- angiogenic, antioxidant, and anti-carcinogenic properties of a novel anthocyanin-rich berry extract formula. Biochemistry (Mosc). 69:75-80. 40) Dugoua JJ, Seely D, Perri D, Mills E, Koren G. 2008. Safety and efficacy of cranberry (vaccinium macrocarpon) 10