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One way to distinguish science-based medicine from alternative medicine is to observe how each deals with negative or contradictory evidence. Given sufficient evidence, the practice of medicine will change. Yes, the process can take too long. But good science does change medicine, and the practice of medicine is constantly changing as a result. The exact opposite can be observed in alternative, complementary and “integrative” medicine, which are largely impervious to new evidence, and where few therapies are ever discarded as ineffective or harmful. No matter how much evidence exists to show practices like homeopathy, acupuncture or reiki/therapeutic touch are clinically useless, nothing really changes. The willingness to stick with a practice, no matter the evidence, must give practitioners a certain clarity. Perhaps it’s comforting to base your own reality on perceptions, or what “feels” right, rather than scientific fact. Those of us in the reality-based, science-based community welcome new evidence and changing practices. For example, most of the therapeutics I learned in university is now irrelevant or outdated. HIV used to be a death sentence, and my 4th year textbook only mentioned three drugs, all of which were terrible. Today, HIV is managed much like a chronic disease, with drugs that didn’t even exist in 1993. Life expectancy has soared.

Cranberries and urinary tract infections

If there was a folk remedies course offered back in the 1990s, it probably would have mentioned the use of cranberries and cranberry juice to prevent or treat urinary tract infections. While there’s been interest in cranberries (juice or capsules) to treat or prevent urinary tract infection for decades, the science has been suggestively promising, but convincing evidence has been lacking. Now there’s a new, well-conducted trial which should put any questions about cranberry and urinary tract infections to rest. We have convincing evidence that cranberry (as capsules) is ineffective. As a companion editorial states, it is time to move on. Here’s why.

Why cranberry?

Cranberry seems to come up as a post topic every few years. In alternative medicine, it’s commonly used as a supplement (as juice, extract, or capsules) to prevent or treat urinary tract infections (“acute cystitis”). A scientific reason why cranberry might prevent or treat urinary tract infections is still lacking despite over five decades of study. Is it because the berries are so bitter, that they must be medicinal? An early hypothesis may have been the ability of cranberry to lower urinary pH, which was thought to help treat UTI. Later, an ingredient in cranberry, proanthocyanidins, was thought to block some variants of E. coli bacteria from adhering to bladder cells, which might reduce the risk of infection. But these “fimbriated” bacteria are uncommon in species isolated from urinary tract infections. So even if the theoretical mechanism of action is correct (which remains unproven), the real-world effect, based on this assumption, should be minimal. And that’s largely what the evidence shows, when you account for the poor research quality. So after decades of studies, there is still no valid rationale why cranberries might prevent or treat UTIs. But we don’t need to know how it works, if there is convincing evidence it actually does work. Sadly, no such evidence exists. Mark Crislip blogged about a randomized, placebo-controlled trial of cranberry juice back in 2011 and found the evidence was unconvincing. A 2012 Cochrane review concluded that there was no good evidence to suggest cranberries offer any meaningful benefits:

Cranberries (usually as cranberry juice) have been used to prevent urinary tract infections (UTIs). Cranberries contain a substance that can prevent bacteria from sticking on the walls of the bladder. This may help prevent bladder and other UTIs. This review identified 24 studies (4473 participants) comparing cranberry products with control or alternative treatments. There was a small trend towards fewer UTIs in people taking cranberry product compared to placebo or no treatment but this was not a significant finding. Many people in the studies stopped drinking the juice, suggesting it may not be an acceptable intervention. Cranberry juice does not appear to have a significant benefit in preventing UTIs and may be unacceptable to consume in the long term. Cranberry products (such as tablets or capsules) were also ineffective (although had the same effect as taking antibiotics), possibly due to lack of potency of the ‘active ingredient’.

The evidence base of trials that make up the meta-analysis is filled with problems, including:

Small numbers of patients

Vague inclusion criteria

Insufficient duration

Patient drop-outs

Poor follow-up

Unclear diagnostic criteria: Lack of confirmation of an actual infection

Inappropriate endpoints

Unstandardized products (unclear amounts of active ingredients)

There’s another significant issue with cranberry juice as a preventative of treatment: The calorie load. Unsweetened cranberry juice is unpalatable, so it’s usually sweetened. You’d need to consume about 500mL of cranberry cocktail to obtain the studied amount of the pure juice. Two cups supplies 52 grams of added sugars per day. Over a year, that’s 41 pounds of added sugar you’re putting in your diet in the hope of avoiding a urinary tract infection. So even if this is an effective treatment, the benefits and harms need to be weighed against drug products.

All of this background leads to the basis for what should be (but will probably not be) the last study of cranberry for preventing urinary tract infections.

The definitive trial on cranberries?

The latest trial is from Manisha Juthani-Mehta and colleagues. Published in the Journal of the American Medical Association in October 2016, it’s entitled “Effect of Cranberry Capsules on Bacteriuria Plus Pyuria Among Older Women in Nursing Homes.” The researchers have no conflicts of interest and all appear to be affiliated with the Yale School of Medicine.

This was a well-designed, well-conducted trial. It was a randomized, double-blind, placebo controlled study of 185 women over the age of 65 who were living in nursing homes. Patients were randomized to two oral capsules of cranberry, containing a (standardized) total of 72 mg of proanthocyanidins (equivalent to 20 ounces (or one (Imperial) pint) of cranberry juice. The cranberry capsules and placebos were manufactured by a herbal product manufacturer. The primary endpoint was the presence of bacteria and pus in the urine, measured every two months over a one-year period. Any single positive finding was deemed to satisfy the primary outcome. Secondary outcomes measured included urinary tract infections with symptoms, all cause death, all cause hospitalization, all multi-drug resistant organisms, antibiotics administered, and total administration of antimicrobials.

The mean age of participants was 86.4 years, mainly white, with 31.4% having bacteria and pus in the urine at baseline. 147 completed the study, with an overall adherence to therapy of 80.1%, which is excellent. Over the one year period, there were no significant differences in the presence of bacteria in the urine. Nor was there any difference in the rates of UTIs with symptoms, rates of death, hospitalizations, all multi-drug organisms identified, or antibiotics administered. In short, there were no meaningful differences between the groups. I won’t show you the graphs and charts, because there’s nothing interesting to observe.

It is time to abandon cranberry

This study adds convincing evidence to the scientific case against cranberries. There is no persuasive evidence that cranberries can prevent urinary tract infections. Given the lack of benefit, cranberry capsules should not be promoted to prevent or treat urinary tract infections. In 2013 I concluded my post on cranberries hoping that post was the last word, but fearing a zombie resurgence. I won’t make the same prediction this year. This should be the trial that shifts the focus of preventing urinary tract infections to other strategies. But I don’t think the cranberry myth can be killed. Evidence didn’t lead us to use cranberry to prevent UTI, and evidence probably won’t end its use, either.

Images courtesy flickr users Khuroshvili Ilya and Summer Bradshaw used under a CC licence.

Full disclosure: The author refuses to eat roast turkey unless it is accompanied by cranberries.