Scientific Name(s): Vaccinium macrocarpon Aiton
Common Name(s): American cranberry, Arandano Americano, Arandano rtepador, Cranberry, Grosse moosbeere, Kranbeere, Tsuru-kokemomo, Vaccinium
The cranberry plant is native to eastern North America. Some research on the plant can be found under its former name, Oxycoccus macrocarpus (Aiton) Pursh. A number of related cranberry species can be found in areas ranging from damp bogs to mountain forests. The plants grow from Alaska to Tennessee as small, trailing, evergreen shrubs. Their flowers vary from pink to purple and bloom from May to August depending on the species. Small, red berries start forming between June and July and are harvested in September to October.
The genus Vaccinium also includes the blueberry (Vaccinium angustifolium Ait.), deerberry (Vaccinium stamineum L.), bilberry (Vaccinium myrtillus), Caucasian whortleberry (Vaccinium arctostaphylos) and cowberry (Vaccinium vitis-idaea L.). The cranberry plant should not be confused with another plant sometimes known as highbush cranberry, Viburnum opulus L., which is in a different family known as Caprifoliaceae).1, 2, 3
The cranberry was primarily used as a traditional medicine for the treatment of bladder and kidney ailments among American Indians. The berries were also used as a fabric and food dye, and as a poultice to treat wounds and blood poisoning. Sailors used the berries to prevent scurvy. Despite a general lack of scientific evidence for their use as effective urinary acidifiers, interest in the medicinal use of cranberries persists among the public. Cranberries are used in Eastern European cultures because of their folkloric role in the treatment of cancers and reduction of fever.4
Cranberries contain about 88% water and are a rich source of phytochemicals, such as organic acids (including benzoic, cinnamic, sinapic, caffeic, ferulic and other acids) and flavonoids (including quercetin, myericetin, cyanidin, catechin, and epicatechin). Cranberries also contain iridoid glycosides and anthocyanins, triterpenoids, and other alkaloids and constituents. They also contain small amounts of protein, fiber, sodium, potassium, selenium, and vitamins A, C, and E (2 to 10 mg). Cranberries are also a dietary source of resveratrol.66 Dried berries contain little sodium or fat. Extensive reviews of the chemical composition of cranberries have been published.3, 4, 5
Uses and Pharmacology
Trials investigating the efficacy of cranberry in Helicobacter pylori eradication have been of varying methodological quality.26, 27 In vitro studies evaluated the effect of cranberry on GI bacteria as well as on nasopharyngeal bacteria.28, 29
Cranberry phytochemicals, especially proanthocyanins, quercetin, and ellagic and ursolic acids, have been investigated for a role in cancer treatment. Induction of apoptosis and inhibition of tumor proliferation via inhibition of cell invasion and migration have been suggested as mechanisms. In vitro studies have shown cranberry extracts to inhibit growth of human cancer cell lines, including oral, colon, prostate, breast, liver, lung, and leukemia.2, 5, 6
Limited animal studies have been conducted. Reductions in the incidence of induced tumors and decreased tumor size have been demonstrated.6
There are no clinical data regarding the use of cranberry for cancer treatment. The effect of cranberries on markers for cancer has been investigated in healthy adults.7
Reviews suggest that the high polyphenolic content of cranberry may contribute to a reduction in the risk of cardiovascular disease. Suggested mechanisms, based mainly on animal studies, include increased resistance of low-density lipoprotein to oxidation, inhibition of platelet aggregation, and reduced blood pressure.7, 30, 31 However, clinical trials have failed to consistently demonstrate clinically relevant effects of cranberry on blood pressure, lipid profile, or glycemic response, even at high daily intake of anthocyanins.32, 33, 34, 35 A small, 60-day study in patients with metabolic syndrome found that cranberry juice significantly increased adiponectin and folic acid levels, and reduced homocysteine and measures of oxidation. There was no significant change in pro-inflammatory cytokines.36 Variations in cranberry preparations used in the studies as well as interpersonal variations may have contributed to the equivocal findings in these studies.37
Urinary tract infections
A review of the suggested mechanisms by which cranberry may act against pathogens of the urinary tract has been published. Studies included in the review were largely conducted in vitro; however, a limited number of clinical studies were included.3 Cranberry does not appear to exert any direct bacteriostatic or bactericidal effects, nor does it change urine pH; however, it does inhibit the adherence of bacteria (primarily P-fimbriated Escherichia coli) to surfaces, including the inhibition of bacterial biofilm formation. Cranberry may also decrease UTI symptoms by suppressing inflammatory processes in response to bacteria.3, 8, 9
The Scottish Intercollegiate Guidelines Network Management of suspected bacterial urinary tract infection in adults (2012) recommended that women with recurrent UTI consider using cranberry products to reduce the frequency of recurrence based on placebo-controlled data. There are no trials about the effectiveness of antibiotics or cranberry products for preventing recurrent UTI in men. In addition, the guidelines recommend that cranberry products be avoided in patients taking warfarin.10 The Society of Obstetricians and Gynaecologists of Canada (SOGC) guidelines on recurrent UTI (2010) strongly recommend cranberry products as effective in reducing recurrent UTIs based on controlled data.11 The American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin (2008) for the treatment of UTIs in nonpregnant women notes that there is some data to suggest that the use of cranberry products may decrease recurrent UTIs; there are insufficient data to determine the length of therapy and the concentration required to prevent recurrence long term. No recommendation regarding the use of cranberry juice is provided.12 The Infectious Diseases Society of America guidelines regarding catheter-associated UTI in adults (2010) recommend that cranberry products not be used routinely to reduce catheter-associated bacteriuria or catheter-associated UTIs in patients with neurogenic bladders managed with intermittent or indwelling catheterization. The guidelines further state that data are insufficient to make a recommendation on the use of cranberry products to reduce catheter-associated bacteriuria or catheter-associated UTI in other groups of catheterized patients.13
Clinical data (prevention)
The most recent Cochrane Systematic Review of cranberry for UTI prevention pooled data from 24 studies (n = 3412) and concluded that cranberry products did not significantly reduce the incidence of symptomatic UTI compared with placebo, water, or no treatment (relative risk [RR] 0.74; 95% confidence interval [CI], 0.42 to 1.31). Cranberry also failed to demonstrate significant benefit for UTI prevention in specific populations including the elderly (RR 0.75; 95% CI, 0.39 to 1.44); pregnant women (RR 1.04; 95% CI, 0.97 to 1.17); pediatric recurrent UTI (RR 0.48; 95% CI, 0.19 to 1.22); oncology (RR 1.15; 95% CI, 0.75 to 1.77); or neurogenic bladder/spinal cord injury (RR 0.95; 95% CI, 0.75 to 1.20). Cranberry was not significantly better than antibiotics in females with UTI (RR 1.31; 95% CI, 0.85 to 2.02), or children (RR 0.69; 95% CI, 0.32 to 1.51).14 A 24-week, placebo–controlled trial published after the Cochrane review found no overall benefit of cranberry juice compared with placebo for prevention of UTI recurrence in women with a history of frequent UTIs, but women older than 50 (n = 118) had a significantly lower incidence with cranberry.15 However, a double-blind, randomized, placebo-controlled trial reported a statistically significant reduction in the occurrence of UTIs in 160 catheterized women (23 to 88 years of age) who took cranberry capsules subsequent to elective gynecological surgery. The treatment group received 2 cranberry capsules (cranberry extract 360 mg; proanthocyanidins [PACs] 36 mg) twice daily for 6 weeks after surgery. Incidence of UTI was reduced by 50% with cranberry versus placebo (19% vs 38%, P = 0.008); culture confirmed incidence was also significantly reduced (15% vs 29%, P = 0.037) and the median time to UTI was longer (18 days vs 8.5 days, P = 0.0005).60 Similar results were found in a small controlled pilot study in 36 adolescents with recurrent UTIs in which a standardized extract (120 mg cranberry with 36 mg PACs/day × 60 days) added to standard treatment produced significantly fewer UTIs compared to baseline (P=0.0001) and standard treatment alone (P=0.0001). The number of patients experiencing zero symptoms during the 60 days was also significantly lower with cranberry versus control (63.1% vs 23.5%, respectively, P<0.05).64 However, a 1-year double-blind, randomized, placebo-controlled trial in 185 elderly women residing in nursing homes found no significant difference in bacteriuria plus pyuria between oral cranberry supplementation compared to control. Cranberry 72 mg or control was administered daily for 360 days to women whose mean age was 86.4 years. Surrogate consent had to be obtained for the majority of participants (93.5%). Protocol dictated clean catch urine specimens 6 times over 12 months to assess for bacteriuria plus pyuria; secondary outcomes included symptomatic UTI, antibiotics for suspected UTI, and total antimicrobial prescriptions, all-cause death, and all-cause hospitalization.62 In a randomized, controlled trial (n=67), consumption of 120 mL cranberry juice daily for 6 months was observed to significantly reduce recurrence of UTIs in uncircumcised boys (6 to 18 years of age) compared to placebo in both circumcised and uncircumcised boys.65
Trials comparing cranberry with trimethoprim 100 mg/day (for 6 months) or trimethoprim-sulfamethoxazole (TMP-SMX) 480 mg/day yielded results favoring antibiotic therapy for reducing the risk of UTI recurrence17, 61; however, antibiotic resistance measured in 1 trial was over the 12-month trial period,16 and adverse effects were higher for trimethoprim in the other trial.17 Cost-effectiveness did not favor cranberry (1 g/day) compared with TMP-SMX (480 mg/day) over a 12-month period in premenopausal women with recurrent UTIs.61
Clinical data (treatment)
A systematic review found no well-designed trials assessing evidence for effect in the treatment of UTIs. Methodological issues included study design, measurement of outcomes and dosage, and duration of treatment. A dose-dependent effect on the inhibition of adherence by E. coli was demonstrated in 1 clinical study, and an optimal dose of proanthocyanins 72 mg/day was consequently suggested.8, 16 Another dose study suggests using 500 to 1,000 mg/day of a standardized preparation containing 1.5% proanthocyanidins (≈ 7.5 to 15 mg/day) based on elimination rates of E. coli in study participants.18 The use of cranberries for first-line treatment of UTIs remains unsupported.3, 19, 20, 21
Clinical data (special populations)
In elderly men with lower UTI symptom scores (including elevated prostate-specific antigen and chronic nonbacterial prostatitis) anthocyanins 1.65 mg/day for 6 months lowered irritative and obstructive symptomatic scores and improved measures of urination.22 Similarly, a double-blind, randomized, placebo-controlled trial evaluated 6-months of a commercial cranberry powder product (Flowens) on mild to moderate lower urinary tract symptoms (LUTS) in 124 men. LUTS was evaluated using the international prostate symptom score (IPSS); all participants had an IPSS of 8 or higher and a PSA less than 2.5 ng/mL. IPSS was significantly reduced in both the cranberry powder 250 mg and 500 mg groups (−3.1 and −4.1, respectively), whereas placebo yielded a −1.5 difference. Dose and baseline IPSS were significant covariates (P<0.0001 each). Voiding and storage symptoms were significantly improved at 6 months with 500 mg cranberry powder (P<0.001 and P=0.018, respectively). A significant dose-dependent reduction in post-voiding residual volume was observed.63 A 1-year controlled trial in elderly long-term care residents found significant improvements in the incidence of clinically-defined UTIs with cranberry (1,000 mg/day; 1.8% proanthocyanidins) in those at high-risk (ie, long-term catheterization, diabetes mellitus, previous UTI in last year) compared with placebo.59 A small, 1-year, pediatric study in toilet-trained children with a history of 2 UTIs in the previous year found that cranberry juice fortified with proanthocyanidins significantly reduced the incidence of UTI recurrence compared with placebo.23 A randomized, controlled study in 55 uncircumcised boys 6 to 18 years of age with uncomplicated UTI observed a significant reduction in rates of recurrent episodes in boys who consumed 120 mL cranberry juice (Ocean Spray) daily for 6 months compared to placebo (25% vs 37%, respectively, P<0.05). Additionally, the reduction in recurrence in the cranberry group was also significantly greater than the positive control of 12 circumcised boys who consumed the placebo juice (25% vs 33.3%, respectively, P<0.05).65 A retrospective evaluation of data on renal transplant patients found a lower incidence of UTI recurrence in patients who received cranberry or L-methionine compared with those receiving no prophylaxis.24 Activity against Candida in the urine was shown in a small study.25
Uptake of anthocyanins has been shown to be highly variable, which may have implications for interpreting trial data.37 Cranberry juice, juice concentrate, and dried extract have been studied in UTIs; however, consistency in dosage regimens is lacking.3 Doses of juice cocktail (25% pure cranberry juice) have ranged from 120 to 1,000 mL/day in divided doses. Concentrated cranberry extract in the form of tablets and capsules is available and 600 mg to more than 1,200 mg/day in divided doses has been used in studies in UTIs.3 For the prevention of UTIs following catheterization during elective gynecologic surgery, cranberry extract 360 mg (proanthocyanidins 36 mg) has been used twice daily for 6 weeks.60
Pregnancy / Lactation
No direct evidence of safety or harm to the mother or fetus has been found. Indirect evidence suggests minimal risk in pregnancy. There were insufficient data to evaluate risk during lactation. When ingested at normal food consumption amounts, cranberries are considered safe during pregnancy.40
The ingestion of more than 3 to 4 L per day of cranberry juice may result in diarrhea and other GI symptoms; however, clinical trials recorded few adverse reactions beyond this effect.3, 11, 14, 33 Use with caution in individuals with diabetes or glucose intolerance, due to risk of hyperglycemia. Some commercially available cranberry juice products contain large amounts of sugar. Sugar-free cranberry juice products are also available. Controversy exists over cranberry as a risk factor for the formation of calcium oxalate kidney stones, and the use of cranberry products in individuals with a history of nephrolithiasis probably should be avoided.3, 56, 57 Cranberry juice should not be used to clear enteral feeding tubes because water has been shown to be more effective and, due to the acidity of the juice, proteins in the tube could be denatured and contribute to further clogging.58
Information is lacking. An oral median lethal dose of more than 5g/kg body weight in rats has been suggested.2
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