Crananidin: Cranberry Extract for Urinary Tract Infections in Dogs and Cats?

The question of whether cranberries, in some form, have value in treating or preventing urinary tract infections (UTIs) is a pretty old one. Mark Crislip at Science-Based Medicine has written a nice summary of the topic, and he has found over 100 references dating back to 1962. Like most herbal remedies, it has traditionally been thought helpful for a wide variety of unrelated disorders, but it is now pretty firmly established in most people’s minds as useful for UTIs.

Unfortunately, as usual the subject is more complicated than is generally realized. The theoretical justification for using cranberry to treat UTIs used to be that it acidified urine and made it less hospitable for bacteria, however that is no longer believed to be true. The current theory is that chemicals called proanthocyanidins interfere with the attachment of bacteria to the bladder wall, making it easier for the body to eliminate these bacteria and harder for infections to get started.

This is certainly a plausible mechanism established  by in vitro studies. The trouble is that the proanthocyanidins inhibit attachment only for E.coli with little hairs called fimbriae on them. There are many other bacteria that can cause UTIs, and there isn’t yet any evidence that proanthocyanidins affect these. And in humans fewer than 20% of E.coli in bladder infections have fimbriae, so theoretically, these chemicals should be only be useful in preventing recurrent infection in a small minority of cases. (Interestingly, the vast majority of E.coli from kidney infections are fimbriated, so cranberry could possibly be more useful in these cases). There is also the problem that no one has actually proven that oral cranberry leads to proanthocyanidins getting into the urine, or being biologically active when they get there.

As Dr. Crislip points out, though, the theoretical mechanisms are not so important if the remedy doesn’t actually work in clinical trials. So does it? Well, there is still no consensus, since some trials show and effect and others don’t. The best that can be said as of now is that cranberry probably isn’t useful for treating UTIS and it may or may not be useful for preventing them.

Despite this uncertainty, the popular belief that cranberry products are useful for urinary tract infections in humans makes it inevitable that such products will be marketed to pet owners for UTIs in dogs and cats. As in humans, many UTIs are caused by bacteria other than E.coli, and I am not aware of any research on the proportion of fimbriated E.coli in canine and feline UTIs, so the theoretical rationale for this remedy is even weaker than in humans. But a quick Google search shows plenty of veterinary versions on the market anyway, often with pretty confident claims.

I recently came across some marketing materials for one of these, Crananidin from Nutramax. They are careful to avoid any treatment or prevention claims, since that would violate the Dietary Supplement Health and Education Act (DSHEA). However, they try pretty hard to suggest a benefit and even superiority over their competitors despite the absence of any clinical trial evidence.

The Nutramax literature has a nifty little graph of bioactivity in the dog purporting to show that “by 7 days the average bioactivity is over 78% at inhibiting E.coli.” They cite two articles to support this statement. One is an NMR study of the molecular structure of proanthocyanidin, and the only bioactivity data is from mixing fimbriated E.coli with human red blood cells and some cell-surface-receptor coated plastic beads in vitro (interestingly, this study was funded by Ocean Spray). There is no testing or discussion of clinical effects, and no data concerning dog urine. There really seems no way to interpret this citation other than being deliberately misleading.

The other reference is “Data on file, Nutramax Laboratories,” so I presume it is an unpublished in-house experiment. Unpublished data from a company selling a product that “proves” the product works, and is better than the competition, ought to be viewed somewhat skeptically, needless to say.

The marketing literature also has a little chart showing their product “passing” a test of bioactivity and all the competing products failing it. The references for this are the same, and since the published article has nothing to do with this issue, apparently the only evidence for this claim is unpublished in-house data from Nutramax. I’m not aware of any published clinical trials investigating this or any other cranberry product for use in UTIs in dogs or cats.

There also isn’t any evidence concerning the safety of cranberry products in dogs and cats. In humans, one concern is that cranberry juice has a lot of salicylic acid, so people with aspirin allergies or on anti-coagulant medications aren’t supposed to take a lot of it. But those are pretty rare issues in veterinary medicine. And some studies have shown it increases oxalate in the urine by up to 43%, so I wouldn’t recommend it for patients with a history of oxalate urinary tract stones (even though, again, this data is for people, and there are no studies I can find in dogs or cats).

Bottom Line
There is weak theoretical justification for using cranberry products for UTIs, though none of the supporting preclinical evidence involves dogs or cats. There is conflicting clinical trial evidence in humans, and no clinical studies in dogs and cats. There are weak theoretical safety concerns. And, of course, there is abundant marketing making bold statements unsupported by the little evidence that exists. You pays your money and you takes your chances. Fortunately (for Nutramax, if not for our pets), anecdotes claiming a benefit are easy to find, so there should be little trouble selling the products even without convincing evidence of safety or efficacy.

 

 

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8 Responses to Crananidin: Cranberry Extract for Urinary Tract Infections in Dogs and Cats?

  1. Jenzia says:

    What do you think about D-Mannose for urinary health? I have been using it for my 18 year old who has CKD and he hasn’t been having urinary issues (infections) which he has had. And please, concerning this topic and the idea of being accurate, I wish vets could become more knowlegeable about urinary disorders in cats. Even vets with years of training, still commonly diagnose UTIs, when most cats (younger cats or cats without concurrent disease like CKD or diabetes which dilutes the urine, such as my cat) don’t have bacterial infections. Why do people and vets automatically assume UTI? I’m sick of these disorders being confused. I see it all the time on forums? “My cat has a UTI, Help…And then they go on to say he has been blocking or has “crystals”. Where did people get so confused about this. Why does any urinary problem = UTI? Shouldn’t most vets know that cystitis is the most common urinary disorder in cats? Annoying and scary.

  2. skeptvet says:

    Yes, it is frustrating to see UTI diagnosed without proper testing in cases where there is very unlikley to be an actual infection (such as young cats). Certainly, I agree that veterinarians should know when UTIs are likely and when they aren’t.

    I haven’t looked into the d-mannose question, but I’ll put it on my list and see what I can find. Thanks for the comment.

  3. Food for Thought says:

    “In this study, healthy dogs were administered Crananidin orally at approximately 1 mg/kg of body weight once daily for three weeks. Serial urine samples were collected at various time points throughout the day on days one, three, five, seven and 21, with routine blood work performed to assess product safety. Anti-adhesion activity was noted in urine of all dogs at day five and peaked at day seven with activity maintained throughout the day. Anti-adhesion activity was noted at day 21, again throughout the 24-hour time period, and was still seen three days after Crananidin administration was stopped. There were no clinically significant changes in blood work..”

  4. MjM says:

    Wondering why you didn’t cite the complete article, which is very short but opens with:

    “The study, performed at Rutgers University, Marucci Center for Blueberry Cranberry Research, showed that Crananidin inhibited adhesion of P-fimbriated E. coli in canine urine, according to the company. ”

    Nutramax does not mention any actual numbers in increased anti-adhesion, only that it was “noted” and “peaked”. To which I would ask, peaked at what? 10% higher? 20%? 1%?

    Indeed, the press-release “results” of this “study” only support exactly what skeptvet wrote; the possibility of limited success against one specific bacterium.

  5. Pingback: Is there benefit to feeding my cats cat food that incorporates fruits and vegetables? | CL-UAT

  6. caroline says:

    I had a beloved dog now passed on who was diabetic. He seemed to have recurring bladder infections- although a few times he tested negative for bladder infections.. Well it turned outto be bladder cancer. UGH. Well I learned a lot of things from my most beloved- and treating him to the best of my ability (and great vets of course!
    1) Diabetes is really quite manageable for dog and owner IF owner is willing to be consistent and learn about nutrition etc. Be patient and expect the best.
    2) Diabetes and cancer DO NOT MIX- do not bother with chemo if your dog is diabetic. It is just too much for the body . I would actually have tried that chemo on a non diabetic dog as I saw some results but boy it totally screwed up blood sugar that had been stable etc. boy what a mess. Anyway- and the main point for this-I also took my dog to a doctor of chinese medicine. She not only did acupuncture (which really did seem to help) but prescribed some herbs that I swear worked better than anything on his recurrent bladder infections. My poor dogs body was becoming more and mroe resistant to every antibiotic..so I tried the herbs and wow. really amazing results. IF I WERE TO DO the whole thing over- I would have NEVER have done the chemo- only done chinese med(plus any other vet medicine ) just not chemo on a diabetic dog. LESSON LEARNED.

  7. Sue D. says:

    Thank-you for these insights. Somebody asked in this thread about D-mannose and I came across this review of clinical trials *in humans*. I noticed there are several D-mannose containing supplements for dogs but could not find any clinical studies. Would be curious to know your opinion of it now, a few years after this post. Again, though, the main target would be e coli, not other infections. https://pubmed.ncbi.nlm.nih.gov/32497610/

  8. skeptvet says:

    I agree, no canine studies, so not much we can say either way. The human evidence is pretty limited as well, which is why the authors of the review concluded “Overall, our MA suggests that D-mannose is protective for recurrent UTI (versus placebo) with possibly similar effectiveness as antibiotics, but this should be interpreted in the setting of an overall small number of studies with varying study design and quality.” A big “Who knows?” at this point. 🙂

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