Cranberry for the Treatment and Prevention of Urinary Tract Infections

Editor’s Note:

Urinary tract infections (UTIs) are among the most common infections in women: one in three will have an infection in their lifetime. Many seek medical advice. And recurrent UTIs, while rarely serious, can be troublesome. Their ubiquity costs the health care system millions of dollars per year. Cranberries and cranberry juice have been touted as a preventative and treatment option of UTIs for decades. Today’s guest post is from a pharmacist who blogs under the pseudonym Avicenna, who looks at the evidence supporting the use of cranberries for urinary tract infections (UTIs).

In my short career in pharmacy, I’ve been approached many times by patients about the merits of cranberry supplements. Adolescent, adult and elderly women who have a soft spot for alternative therapies are generally curious about cranberry. Since their sources are usually anecdotal, like friends, family, and alternative health magazines, I’m happy to summarize the evidence for them.

My questions starts with the symptoms they’re having, and why they want to try cranberry in the first place. Some describe symptoms that sound like a bladder infection – I redirect these cases immediately, as bladder infections require assessment and evaluation by a physician. Some are hesitant to see a physician or state concerns about antibiotics. When I explain the benefits of treatment, and the risks of self-treatment, most put the cranberries back on the shelf.

But occasionally, a patient asks about cranberries to prevent infections. In some cases, their physician has recommended the supplement. But what’s the evidence to support this approach? This article examines the benefits and safety issues in cranberry products in prevention of bladder infections.

Urinary Tract Infections: Prevalence and Risk Factors

When bacteria infect the bladder, we call this a urinary tract infection, or UTI. UTI affect 50 times more women than men: one in three women will have a UTI in their lifetime. They’re responsible for approximately eight million office visits in the US, one million US hospital admissions, and are estimated to cost the American health care system about $1 billion per year.

Women have more UTIs than men because of anatomy – the urethra is more exposed to fecal matter. Bacteria enter after a bowel movement and can progress through the urethra to the bladder. Other risk factors include sexual activity, a history of prior UTIs, some birth control products, and underlying medical conditions.

Not all urinary infections involve the bladder. Some microbes affect only the urethra (e.g., gonorrhoea or chlamydia) while some nasty strains tends to cause kidney infections or recurrent bladder infections (RUTIs).

Left untreated, bladder infections can progress up to the kidneys, and ultimately the blood where more serious problems can arise. While this is rare in people without underlying medical conditions, UTIs do require medical attention and treatment.

Diagnosis and Symptoms

The most common microbes causing bladder infections are Escherichia coli (around 65% of cases) and Staphylococcus saprophyticus (5-20%), with others being much less common. Common symptoms of an infection include abdominal pain, pain while urinating, the urge to urinate, low back pain, and fever.

Sometimes a urine sample is collected to measure the bacteria species, its levels, and presence of white blood cells in the urine – but this is uncommon, and a diagnosis usually based on symptoms. Typical infections are called “uncomplicated”; a “complicated” UTI means there are other factors present, such as young age, male gender, catheterization, kidney involvement , abnormal urinary tract anatomy, etc.

Three UTIs in a year or two in six months earns the diagnosis of “recurrent” UTIs. About 20% of women experience recurrent UTIs. For the sake of this review, further mention of urinary infections will refer to uncomplicated UTIs, unless noted otherwise.

Mechanism of Action

Cranberries were first examined scientifically in the 1960s and 1970s. The hypothesis centered around an ingredient called quinic acid. Quinic acid was thought to cause hippuric acid to be excreted in the urine, which acted as an antibiotic. This hypothesis was discarded because it was found there was little difference in urine levels, or the effect was short-lived.

More recent studies have put forth another hypothesis. Mostly based on in vitro or laboratory evidence, this new theory proposes the ingredients proanthocyanidin (PAC) and fructose (fruit sugar) can act to prevent bacteria in urine from sticking to the bladder’s lining by “wrapping” around the bacteria. This reduces the risk of an infection getting started.

However, this theory seems implausible, as nearly all known effective antibiotics act by killing bacteria or preventing them from multiplying. PAC is not well understood, and questions remain regarding how cranberries might actually work. But we can set this aside for now, and focus on the relevant evidence.

The Evidence

A systematic review, part of the Cochrane Collaboration, was published online by Jepson et al in 2008. It examined the effectiveness of cranberry juice in preventing complicated and uncomplicated UTIs. Ten trials met the group’s quality standards.

It was difficult to evaluate the effectiveness of cranberries in preventing UTIs, since they combined different population samples (i.e., elderly, adult women, patients with catheters) and various cranberry products. Trials used different doses of cranberry juice, concentrates, cranberry-lingonberry juice or cranberry pills given for at least a month. Most studies were of short duration (3 to 6 months). Most trials counted the number of confirmed UTIs as their primary endpoint. Some measured how many patients stayed on therapy.

Out of the 10 trials included, 8 compared cranberries (as juice, extract or tablets) to placebo (fake cranberry juice), while the two other trials had two intervention groups (they added a probiotic juice as treatment, or had both cranberry juice and tablets) compared to placebo. Only 4 of the 10 studies were properly randomized, though 7 of 10 trials were double-blinded. Most striking, one study was so poorly done that the baseline characteristics showed that placebo group had two to three times the rate of UTI than in cranberry group, effectively making this trial rigged from the start.

Effectiveness and Side-Effects

Out of the original 10 studies included, authors of the review combined the four trials deemed most adequate, making a study population of 665. The relative reduction in risk of developing a UTI in this group was 34%. That is, the risk of a UTI in people taking cranberries was 2/3 that of a placebo – with the actual value ranging between a 47% and 92% reduction. In adult women specifically, two studies (N=241) found a 39% decreased risk in symptomatic women who took cranberry juice or capsules. Most of the positive effects were due to these two studies. Studies in catheter/neuropathic patients and of hospitalized elderly had negative results for cranberry treatment. No effect was seen in elderly men or women, patients who had neuropathic bladders, or needed catheterisation. No data exists at all in in pregnant women or patients with abnormal urinary tract.

Of the two positive trials, both were small in size (150 women in each) and lasted no more than a year. One was not blinded, so the investigators and patients knew they were receiving cranberry juice or not. One author estimated that 5 women need to drink cranberry juice for a year to prevent 1 UTI. Not that impressive.

Side effects were mild, and included heartburn, nausea, vomiting, high blood sugar (in a patient with diabetes). There were high drop out rates in most of these trials (20-55%), which may be due to side-effects, impracticality of drinking juice three times a day, or lack of benefit.

Of of the studies analysed  one looked at the cost of cranberry juice, and estimate a year of treatment costs between $650 and $1200, depending on whether juice or tablets were selected. The authors concluded:

“From the results of two well conducted RCTs there is some evidence to recommend cranberry juice for the prevention of UTIs in women with symptomatic UTIs. The evidence is inconclusive as to whether it is effective in older people (both men and women), and current evidence suggest that it is not effective in people with a neuropathic bladder. …cranberry juice may not be acceptable over long periods of time.”

Safety and Interactions

Long term consumption of moderate amounts of cranberry juice (less than 1 litre per day) appears safe in healthy people. However, it is not without risks. Most forms contain added sugar, which can be a dietary concern to some. It can also cause kidney stones, so those at risk should avoid it.

No adequate evidence is available for pregnant or breastfeeding women. Moderate amounts of cranberry juice is thought to be likely safe in children.

Cranberries, like many other fruits and vegetables, contain significant amounts of salicylic acid (SA), an anti-inflammatory which is similar to ASA (Aspirin). Drinking 1 cup (250 ml) of cranberry juice 3 times daily for 2 weeks does produce measurable blood levels of SA. Because of this, people with severe ASA allergies or sensitivities (e.g.m asthmatics) may want to avoid drinking large amounts of cranberry juice.

When it comes to interactions with drugs, there is contradictory evidence: Cranberry products may affect liver enzymes that are responsible for metabolizing or detoxifying drugs. It is not know if cranberry can affect protein carriers in the blood, which may also potentially lead to drug interactions. Cranberries may influence blood levels of warfarin (Coumadin). People who take warfarin should avoid taking cranberry and talk to their pharmacist or physician if they are taking both. Other drug interactions may exists, and should always be verified.

Commentary

The claim that cranberry juice can treat an active urinary tract infection is not supported by persuasive evidence. Using cranberry juice for this purpose is potentially dangerous, since it delays effective treatment. The science suggests that the only possibly useful therapeutic use of cranberry is in prevention of recurrent UTIs in those at high risk of infections. As clinical studies are of such low quality, many unanswered questions remain, and the effects may not be real. Given that 5 people need to be treated for one year to prevent one infection, it’s clear the beneficial effects, if any, are modest. Importantly, no effect was seen in the elderly, pregnant women, and patients with neurogenic bladders or catheters.

Many questions remain about cranberries. To say that cranberry is effective in preventing UTIs is somewhat misleading since only a small sub-population seems to moderately benefit from it. On top of it all, it’s unclear which type of cranberry product is most effective (juice, capsules, etc), what dose is appropriate, and whether it can impact on the effects of other drugs.

Given that prescription antibiotics for recurrent UTIs are more effective, better tolerated and less expensive, cranberry juice comes in well behind modern medicine. Although cranberry products may be safe to use in most adults, don’t expect it to have great results in preventing urinary tract infections.

When it comes to alternative medicine for urinary tract infections, there’s not much use in cranberry juice.

References

The Merck Manual, Online Medical Library accessed 29-09-09

Wong ES and Orenstein R, Urinary Tract Infections in Adults, American Family Physician, March 1999. accessed: 29-09-09

Mehnert-Kay SA, Diagnosis and Management of Uncomplicated Urinary Tract Infections, American Family Physician, August 2005, accessed: 29-09-09

Natural Medicines Comprehensive Database, accessed: 06-10-09

Possible interaction between warfarin and cranberry juice Suvarna et al. BMJ.2003; 327: 1454

Committee on the Safety of Medicines. Possible interaction between warfarin and cranberry juice. Current Problems in Pharmacovigilance 2003;29:8.

Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD001321. DOI: 10.1002/14651858.CD001321.pub4.

Jepson RG, Mihaljevic L, Craig JC. Cranberries for treating urinary tract infections. Cochrane Database of Systematic Reviews 1998, Issue 4. Art. No.: CD001322. DOI: 10.1002/14651858.CD001322.

Albert X, Huertas I, Pereiró II, Sanfélix J, Gosalbes V, Perrota C. Antibiotics for preventing recurrent urinary tract infection in non-pregnant women. Cochrane Database Syst Rev 2004;(4):CD001209.