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Cranberry

Scientific Name(s): Vaccinium macrocarpon Aiton
Common Name(s): American cranberry, Arandano Americano, Arandano rtepador, Cranberry, Grosse moosbeere, Kranbeere, Tsuru-kokemomo, Vaccinium

Medically reviewed by Drugs.com. Last updated on Dec 19, 2022.

Clinical Overview

Use

Some evidence exists for the use of cranberry in preventing, but not treating, urinary tract infections (UTIs). Other possible uses for cranberry, with limited evidence, include reduction of the risk of cardiovascular disease.

Dosing

Cranberry juice, juice concentrate, and dried extract have been studied in UTIs; however, consistency in dosage regimens is lacking. 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 have been used in studies in UTIs. 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.

Contraindications

Predisposition to or history of nephrolithiasis (kidney stones); known allergy to cranberry products.

Pregnancy/Lactation

Information is limited; however, when ingested at normal food consumption amounts, cranberry is considered relatively safe in pregnancy. Safety during lactation is unknown.

Interactions

See Drug Interactions section.

Adverse Reactions

The berries and juice have few adverse reactions associated with their consumption. Large daily doses may produce GI symptoms, such as diarrhea. Concentrated cranberry tablets may predispose patients to nephrolithiasis. Cranberry juice should not be used to clear enteral feeding tubes.

Toxicology

Information is lacking.

Scientific Family

Botany

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

History

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

Chemistry

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

Antibacterial

In vitro data

In vitro studies have shown effects of cranberry against Bacillus, Clostridium, Escherichia coli, Listeria monocytogenes, and Salmonella species as well as on nasopharyngeal bacteria.(28)

Clinical data

Trials investigating the efficacy of cranberry in Helicobacter pylori eradication have been industry-funded and of varying methodological quality. In one double-blind, randomized, placebo-controlled trial, no overall difference was found among patients who received 7-day triple antibiotic therapy alone (n=712) or with those who used adjunctive cranberry juice (n=89) or placebo (n=88) for 3 weeks. However, subgroup analysis showed a significant improvement in H. pylori eradication rate for females who used adjunctive cranberry compared to triple therapy alone (95.2% vs 80%, respectively; P=0.03). In another double-blind, randomized, placebo-controlled trial, data from 189 participants reflected higher rates of negative H. pylori tests at days 35 and 90 of cranberry juice consumption compared to placebo (14.43% vs 5.44%, respectively; P=0.04)(26, 27)

In healthy children attending day care centers, 3-month supplementation of cranberry juice (5 mL/kg, up to 300 mL/day) did not affect nasopharyngeal carriage of respiratory pathogenic bacteria, bacterial flora, number of infection episodes, or duration of symptoms compared to placebo. Infections that accounted for 71% of all diagnoses during the 3-month study were acute otitis media, upper respiratory infection, acute bronchitis, and acute conjunctivitis.(29) Based on data from 4,521 healthy participants enrolled in 20 randomized controlled trials (including 1 study with cranberry), meta-analyses demonstrated that flavonoid-containing supplements were safe and effective in preventing acute respiratory tract infections (ARTIs) compared to controls with a relative risk (RR) of 0.81 (95% conficence interval [CI], 0.74 to 0.89; P<0.001) and low heterogeneity. A reduction in mean ARTI sick days was also observed with the supplements; however, heterogeneity was significant (weighted mean difference [WMD] −0.56; 95% CI, −1.04 to −0.08; P=0.021). In subgroup analysis, significance in mean ARTI sick days was retained with flavonoid mixtures (as seen with cranberry products) but not with use of single flavonoids (ie, quercetin, catechin). Pooled results from 16 of the trials indicated that adverse reactions were not increased in the flavonoid supplement groups compared to controls.(77)

Cancer

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)

Animal data

Limited animal studies have been conducted. Reductions in the incidence of induced tumors and decreased tumor size have been demonstrated.(6)

Clinical data

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)

Cardiovascular

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)

Clinical data

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)

Memory

Clinical data

A double-blind, randomized, placebo-controlled trial assessed the impact of cranberry powder supplementation for 12 weeks on cognitive health in 60 healthy older adults (50 to 80 years of age) with no subjective memory complaints at baseline. The intervention group incorporated freeze-dried cranberry powder into food and drinks (4.5 g twice daily), which was equivalent to 100 g or 1 cup of fresh cranberries/day. At week 12, no significant difference was found between groups in any of the cognitive performance tests or brain MRIs, although the cranberry group experienced significant improvement from baseline in delayed memory recall and in perfusion of the right hemisphere whereas those in placebo did not.(74)

Overactive bladder

Clinical data

Supplementation with 500 mg/day of dried cranberry powder capsules for 24 weeks led to a statistically significant improvement in 3 of 12 measurements in adult women with dry overactive bladder (without incontinence). Data from the 60 women in the per-protocol population showed the number of mean daily micturitions, the daily grade-3 and -4 urgency episodes, and the patient perception of bladder condition subscore improved in favor of cranberry compared to placebo with mean differences of −1.91 (P=0.041), −2.81 (P=0.007), and −0.66 (P=0.026), respectively. The study was conducted as a double-blind, randomized, placebo-controlled trial.(70)

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 American Urological Association/Canadian Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction guideline on recurrent uncomplicated UTI infections in women (2022) conditionally recommended the use of cranberry for prophylactic use of recurrent UTIs (Grade C). No apparent net benefit or harm was evident. The high sugar content of fruit juices may limit their use in diabetic patients.(68, 75) The Scottish Intercollegiate Guidelines Network updated guideline on the management of suspected bacterial lower urinary tract infections (2020), which is now specific for adult women, indicated that based on high-quality, robust data, it is not possible to form a recommendation on use of cranberry products for the prevention of recurrent UTI due to equivocal data reported in meta-analyses with methodological inconsistencies.(SIGN 2020)(76) The Society of Obstetricians and Gynaecologists of Canada's (SOGC) guidelines on recurrent UTI (2017) recommend informing patients that cranberry products are effective in reducing recurrent UTIs (level I-A).(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)

A 2012 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 (RR 0.74; 95% 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) Failing to identify any studies that used cranberry supplementation to treat acute, uncomplicated UTI, a 2020 systematic review reported equivocal results from a total of 3 randomized controlled trials that assessed the role of cranberry juice and extract in prevention of recurrent UTIs. Methodology, follow-up duration, and cranberry dosage regimens were highly variable across the 3 studies.(69)

A 24-week, placebo–controlled trial 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) In contrast, 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)

In a more complicated clinical scenario, 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)

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 recurrence(17, 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) A subsequent systematic review also failed to identify any randomized controlled studies that investigated the effect of oral cranberry supplementation on treatment of acute, uncomplicated UTIs in women.(69)

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) 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)

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)

Dosing

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

Interactions

Vitamin K antagonists: Cranberry may enhance the anticoagulant effect of vitamin K antagonists. Monitor therapy.(41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 71, 72, 73)

Adverse Reactions

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. A small study observed that consumption of 1 L/day of cranberry juice significantly increases the relative saturation ratio of calcium oxalate compared to drinking water similarly for subjects with and without a medical history of calcium oxalate stone formation.3, 56, 57, 67 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

Toxicology

Information is lacking. An oral median lethal dose of more than 5g/kg body weight in rats has been suggested.2

Index Terms

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Frequently asked questions

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