Cranberry

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For Patients & Caregivers

How It Works

Cranberry juice or extracts have not been shown to treat or prevent cancer. It may be helpful for urinary tract infections (UTIs) in limited populations, but there is not enough evidence to recommend it for UTI prevention.

Cranberries contain compounds known as proanthocyanidins that have been shown to prevent bacteria from attaching to the bladder wall, which could cause UTIs. Human studies suggest it may be helpful for this purpose in some limited populations, including prostate cancer patients, but overall evidence is conflicting. Cranberry may also prevent bacteria from attaching to the stomach lining and areas in the mouth. Although lab studies suggest activity with several types of cancer cells, this has yet to be confirmed in human studies.

In patients who are prone to kidney stones, regular use of cranberry should be limited as it contains oxalates, a compound found in the most common form of kidney stones.

Purported Uses

Prevention and treatment of urinary tract infections (UTIs)
The evidence for this claim is mixed.
Anticancer effects
Lab studies show that cranberry juice extract and isolated compounds can inhibit various types of cancer cells, but this has not been confirmed by clinical trials.
Prevention of stomach ulcers
Cranberry juice may help to prevent or suppress H. pylori infection.
Prevention of atherosclerosis
Although one study in healthy volunteers does not suggest benefit, another study in diabetic men suggests cranberry juice may help to reduce heart disease risk factors.
Prevention of gum disease/cavities
In the lab, cranberry juice prevents bacteria from attaching to one another thereby slowing down plaque formation.

Do Not Take If

You are taking warfarin: Because data is mixed on whether cranberry juice may increase bleeding, usage of cranberry juice should be monitored by a healthcare professional, if not avoided. Case reports of bleeding and death in 2 elderly patients who used cranberry juice and warfarin have occurred.
You are taking CYP450 substrate drugs: Cranberry may increase blood levels of these drugs or their adverse effects.
You are taking UGT substrate drugs: Cranberry may increase the risk of side effects for these drugs.
You have a history of kidney stones: Cranberry contains high concentrations of oxalate, a component common to kidney stones.
You are taking Tacrolimus: The serum levels of tacrolimus dropped when taken along with cranberry extract. The levels returned to desired range after stopping cranberry intake.

Side Effects

Nausea, vomiting and diarrhea have occurred with large amounts of cranberry juice (3 cups daily).

Case reports

Increased International Normalized Ratio (INR) and/or bleeding: Several cases were due to suspected interactions between cranberry juice and warfarin.
Internal hemorrhage resulting in death: In 2 patients, following concurrent use of warfarin and cranberry juice.

For Healthcare Professionals

Scientific Name

Vaccinium macrocarpon

Clinical Summary

Cranberry is an evergreen shrub that is grown in North America and Europe. The processed fruit and juice, both rich in vitamin C, are widely consumed as food. The juice extract is marketed as a dietary supplement for urinary tract health and to prevent urinary tract infections (UTIs). It has also been used for oral and gastrointestinal infections, cardiovascular diseases, and against cancer. In preclinical studies, cranberry juice extracts and constituents exhibited antibacterial ⁽¹⁾, antimicrobial ⁽⁴⁵⁾, antifungal ⁽⁴⁶⁾, anti-inflammatory ⁽⁴⁷⁾, antioxidant ⁽⁴⁸⁾, and antiadherence ⁽⁴⁹⁾ properties.

Clinical studies demonstrate that cranberry extracts can help prevent UTIs in adults ⁽²⁾ ⁽³⁾, children ⁽⁴⁾, in prostate cancer patients undergoing radiation therapy ⁽⁵⁾ ⁽⁵⁰⁾, and in patients following urostomy ⁽⁶⁸⁾. A large double-blind study of older adults with high-baseline UTI risk also showed benefit ⁽⁵¹⁾, but another similar study reported negative findings ⁽⁵²⁾. A subsequent analysis revealed increased costs with no meaningful reduction in UTI rates in a geriatric nursing home environment ⁽⁵³⁾. Studies of cranberry juice for recurrent UTIs have also been mixed, with one study finding no benefit among college-aged women ⁽⁶⁾, and another observing significant reductions in UTI relapse in women over age 50 ⁽⁵⁴⁾. Cranberry was not as effective or cost-effective as trimethoprim-sulfamethoxazole in preventing UTIs in premenopausal women, but patients were less likely to develop antibiotic-resistant bacteria ⁽⁸⁾ ⁽⁵⁵⁾. In volunteers from different regions, anti-adhesion activity with cranberry powder was found to be dose-dependent ⁽⁷⁾ . Overall, a systematic review determined that cranberry juice was more effective than capsules or tablets ^⁽⁵⁶⁾, but despite some support for recurrent UTI prophylaxis ⁽⁶⁹⁾, there is not enough evidence to recommend cranberry juice for UTI prevention ⁽⁹⁾ ⁽⁷⁰⁾.

In other studies, cranberry juice inhibited the adhesion of H. pylori to human gastric mucosa ⁽¹⁸⁾, and regular consumption may suppress H. pylori infection ⁽¹⁹⁾ ⁽²⁰⁾, a major factor in peptic ulcer disease and gastric cancer. When used with standard treatment, cranberry juice helped eradicate H. pylori ⁽²¹⁾. It was shown to prevent plaque formation and the development of gum disease as well due to its anticolonizing and antiadhesion properties ⁽²²⁾ ⁽²³⁾.

Cranberry extracts and proanthocyanidins also exhibited antiproliferative effects against prostate ⁽¹⁰⁾ ⁽¹¹⁾ ⁽¹²⁾, liver ⁽¹³⁾, lung ⁽⁵⁷⁾, neuroblastoma ⁽⁵⁸⁾, breast ⁽¹⁴⁾, ovarian ⁽¹⁵⁾, gastric ⁽⁵⁹⁾, colon ⁽¹²⁾ ⁽¹⁶⁾, esophageal ⁽⁶⁰⁾, and oral ⁽¹²⁾ cancer cells. Although cranberry juice consumption did not lower oxidative status in humans, suggesting lack of protective effect against cancer or heart disease ⁽¹⁷⁾, it did appear to improve cardiovascular disease (CVD) risk factors in diabetic men ⁽⁶¹⁾. However, cranberry juice has high concentrations of oxalate, a common component of kidney stones, and should be limited in patients with a history of nephrolithiasis ⁽⁴⁰⁾. Other data suggest it may be helpful in uncommon forms including struvite stones, which are associated with bladder infections ⁽³³⁾ ⁽⁶²⁾ ⁽⁶³⁾.

Food Sources

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

Purported Uses

Urinary tract infections
Cancer prevention and treatment
Ulcers
Atherosclerosis
Gum disease

Mechanism of Action

The A-type linkages in cranberry proanthocyanidins C-PACs may enhance urinary bacterial antiadhesion activities to prevent UTIs ⁽²⁵⁾ ⁽²⁶⁾ ⁽²⁷⁾ ⁽²⁸⁾ ⁽⁶⁴⁾. Similarly, the bioactivity against C. albicans biofilm formation is due to anti-adherence properties and/or iron chelation ⁽⁴⁶⁾. In susceptible populations, improved preventive effects with cranberry juice over capsules or tablets may be related to better hydration with liquid, and/or additive effects with additional compounds in juice not contained in supplements ⁽⁵⁶⁾. Anti-adhesion properties were also demonstrated in other microenvironments. Cranberry prevented H. pylori-induced stomach ulcers by inhibiting bacterial adhesions in the stomach lining ⁽¹⁸⁾ ⁽²⁹⁾, decreased adherence of oral streptococci strains to saliva-coated hydroxyapatite ⁽²³⁾ and glucan-coated hydroxyapatite, and impaired biofilm formation ⁽²²⁾ ⁽³⁰⁾ indicating it may slow development of dental plaque and protect against plaque-related diseases. Cranberry also regulated aggressive human periodontitis fibroblast inflammatory responses via nuclear factor-kappaB and matrix metalloproteinase-3 (MMP3) inhibition ⁽⁴⁷⁾.

Additional studies have shown that C-PACs may play a role in enhancing host innate immunity. In a worm model, a standardized cranberry extract mediated host immune response via p38 MAPK signaling, insulin/insulin-like growth factor 1 signaling, and heat shock factor 1 ⁽⁴⁵⁾. Antiatherogenic effects of cranberry juice occur via reductions in serum glucose and apoB, and increases in serum and apoA-1 and paraoxonase, associated with stabilizing HDL ⁽⁶¹⁾.

Mechanisms underlying the anticancer effects of cranberry extracts and C-PACs have also been investigated. A cranberry extract inhibited prostate cancer cell growth by decreasing cyclins, cyclin-dependant kinase expression ⁽¹⁰⁾ , and MMP activity ⁽³¹⁾. Dose-response inhibition of gastric cancer cells to cranberry is in part due to decreased proliferating cell nuclear antigen expression and apoptotic induction ⁽⁵⁹⁾. A proanthocyanidin isolate was shown to arrest ovarian cancer cell growth by inhibiting vascular endothelial growth factor and generating reactive oxygen species ⁽¹⁵⁾. C-PACs were also found to induce cell death in esophageal adenocarcinoma via microRNA modifications within cancer cells ⁽⁶⁰⁾, and in human lung cancer cells, they altered gene expression, induced apoptosis, and modulated cell-cycle processes ⁽⁵⁷⁾. In high-risk neuroblastoma cells, a purified C-PAC induced apoptosis and ROS generation, and encouraged cyclophosphamide retention with synergistic cytotoxic benefits ⁽⁵⁸⁾.

Cranberry juice increases the risk of uric acid stone formation because of its acidifying effect and slowing of urate synthesis, thereby decreasing urinary pH ⁽³²⁾ ⁽³³⁾.

Contraindications

• Cranberry products can increase urine oxalate excretion and may promote the formation of the most common type of kidney stones ⁽³²⁾ ⁽³³⁾ ⁽⁴⁰⁾. Its use should therefore be limited in patients with a history of nephrolithiasis ⁽⁴⁰⁾.

Adverse Reactions

Ingesting large amounts of cranberry juice (3 cups daily) has been associated with gastrointestinal upset including nausea, vomiting, and diarrhea ⁽⁶⁶⁾.

Case Reports

Recurrent stones: In a 47-year-old man with severe right renal colic and hematuria who took cranberry concentrate tablets twice daily over 6 months ⁽⁴⁰⁾.

Several cases of increased International Normalized Ratio (INR): Due to suspected interactions between warfarin and cranberry juice ⁽³⁶⁾ ⁽³⁷⁾.

Internal hemorrhage and subsequent death: In 2 patients with concurrent use of warfarin and cranberry juice ⁽³⁸⁾ ⁽³⁹⁾.

Herb-Drug Interactions

Warfarin: Cranberry juice may potentiate warfarin-induced anticoagulation, but data are conflicting ⁽³⁴⁾ ⁽⁴¹⁾ ⁽⁶⁵⁾. Although consumption of cranberry juice in large quantities (1–2 L daily or supplements for >3–4 weeks) may alter warfarin effects, monitoring intake rather than total avoidance of cranberry juice by warfarin users in other cases may be warranted ⁽⁶⁷⁾.

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 vitro, but this activity was not observed in humans ⁽⁴⁴⁾.

Tacrolimus: Concurrent use with cranberry extracts resulted in sub-therapeutic serum levels of tacrolimus in a renal transplant patient ⁽⁷¹⁾. The levels returned to desired range following cessation of cranberry.

Herb Lab Interactions

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

Dosage (OneMSK Only)

References

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Friday, October 26, 2018

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