Cranberry pills myth (Adobe Photos)

I have long had issues with Fox News, mostly on reporting in the political arena. But I just came across a most apolitical subject, cranberries, and it gave me my customary Fox heartburn. To be fair and balanced, I have the same beef with science reporting in many other media, with the possible exception of the BBC and NPR, The Washington Post, and the New York Times. So, here is the first paragraph in the Fox News article:

“Taking cranberry supplements has long been recommended to prevent urinary tract infections (UTI), but it’s important to choose the right products, researchers say. Tests of seven popular cranberry-pill brands in the U.S. showed that most contained too little of the key bacteria-fighting ingredient to have any effect.”


What’s wrong with this picture?

It starts out by stating that “it has long been recommended.” Really? By whom? The subject of cranberries as a preventative or even cure for urinary tract infection (UTI) has been controversial to say the least, with a preponderance of researchers and clinicians either deeply skeptical or finding it totally useless. According to the Fox report, efficacy is not an issue at all, it is “choosing the right product” that is important.

The article goes on to describe the results of testing the content of seven brands of cranberry pills and finding that only one contained enough cranberry material to be effective. Effective for what? Nowhere in the article is there a mention that the studies were done in vitro (in a laboratory dish) and have very little relationship to efficacy in animals and humans. The amounts of the test material added to bacterial culture bear no resemblance to the amounts taken by people. They are hundreds of times higher on a mg/kg body weight basis. Taken at such concentrations, they could be even toxic, not beneficial.

There is something else. A petri dish is not a living organism. It has no metabolism. Don’t get me wrong: In drug development, such studies are valuable; if they are ineffective in vitro, there is no point in proceeding with the more laborious and expensive animal studies. But if they are effective, and at concentrations that are equivalent to physiological or therapeutic concentrations, it only means that animal studies are worth doing.

And finally, humans are not mice and rats. Our physiology is different and many times more complex. To illustrate: The vast majority of compounds showing efficacy in killing cancer cells in the petri dish fail when administered to experimental animals. Furthermore, the majority of compounds that cured mice and rats of cancer, do just that. But they are totally useless in humans. So, when you read a report on a compound that kills bacteria (such as E.coli) or cancer cells in a laboratory dish, be skeptical.


Why the controversy?

Although most of the studies of cranberry treatment showed no benefit in either prevention or therapy of UTI, some have claimed effectiveness in certain groups. For instance, a paper in the Journal of the American Geriatric Society reported a benefit for older women (n=401) and men (n=115) in long-term care facilities who were judged to be at high risk of UTI. The problem with this result is the non-precise definition for symptomatic infection that was applied. The primary diagnostic criteria for symptomatic UTI is bacteriuria (bacteria in the urine) and pyuria (white cells in the urine). The most important secondary criterion is localizing symptoms to the genitourinary tract. These criteria for diagnosis of UTI are important because, in a long-term facility, many of the residents have bacteria in the urine without any evidence of symptomatic infection. Many of the studies which showed benefit for cranberry capsules did not use these criteria, but rather symptoms such as increased confusion, fatigue, or falls in patients who had had bacteriuria (but no white cells in the urine, hence no infection). Indeed, when the more restrictive (and correct) criteria of UTI were applied to the above study, there was no difference between the group receiving cranberry capsules and the placebo group. Most of the other “positive” studies suffer from similar methodological problems.


A careful study

Manisha Juthani-Mehta and her collaborators from the the University of Manitoba conducted a randomized, double-blind clinical trial (n=185) with elderly women in nursing homes. Ninety-two women received cranberry capsules (72 mg total, equivalent to 20 ounces of cranberry juice) and 93 women received a placebo. The strength of this study is that it adhered to the strict definition of UTI of bacteriuria with pyuria (bacteria and white cells in the urine). Using these criteria, there was no difference between the treatment and placebo groups. Even secondary criteria, such as symptomatic UTI, mortality, hospitalization, or any other clinically meaningful outcome, showed no difference between the groups.

This paper is as close to a definitive rejection of the cranberry myth as possible. In a commentary on the implications of these findings, Prof. Lindsay E. Nicolle of the University of Manitoba states that

“The continuing promotion of cranberry use to prevent recurrent UTI in the popular press or online advice seems inconsistent with the reality of repeated negative studies or positive studies compromised by methodological shortcomings. Any continued promotion of the use of cranberry products seems to go beyond available scientific evidence and rational reasoning.”

She concludes (definitively):

“…clinicians should not be promoting cranberry use by suggesting that there is proven, or even possible, benefit. Clinicians who encourage such use are doing their patients a disservice.”

I couldn’t have said it better.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.


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