These E. coli fimbriae facilitate infection by adhering to bladder wall
In October, I wrote about SuperMannan, a dietary supplement that is supposed to cure bladder infections. The “evidence” for that claim was a single study of 9 women who were family members and friends of the researchers. The research design was laughable; there was no control group, and there were many other flaws. Oh, and they vouched for SuperMannan’s safety because they had fed it to the family dog and the dog seemed OK! The research design was a recipe for disaster.
Now Facebook’s algorithm apparently thinks I want to buy supplements for UTIs (urinary tract infections), because my Facebook feed keeps sending me “sponsored” posts about Ellura, another dietary supplement for UTIs. I was expecting it to be just another over-hyped product with shoddy science behind it, but I was pleasantly surprised. The evidence indicates that Ellura is probably a safe and effective way to reduce the frequency of infections in patients with recurrent UTIs. Finally! A supplement that has been shown by science to really work.
The problem
Women are more susceptible to bladder infections than men. 40-60% of women will have a UTI during their lifetime, and most of those are bladder infections. In 25-30% of cases, the UTI will recur during the next 6 months, and sometimes recurrent infections are so frequent that daily antibiotics are prescribed for prevention. Antibiotics reliably prevent recurrent UTIs, but they may be expensive, may cause adverse reactions, and using them may contribute to the development of antibiotic resistance.
The ad
The ad starts with quotations from two urologists:
Ellura is an opportunity for my patients to use a product that is natural and is going to prevent a UTI without the use of antibiotics and all the side effects and expense that goes along with them.
Our patients are experiencing fewer UTIs, calling our office less and asking us for antibiotics less!
It goes on to say “85% of women report fewer UTIs.” And it links to a page on the Ellura website where you can buy a 3-month supply for $120. The website claims that Ellura “supports a clean urinary tract” and says “stop UTIs before they start” and “avoid antibiotic overuse.” Since it is marketed as a dietary supplement, they have the required disclaimer that the statements have not been evaluated by the FDA and the product is not intended to diagnose, treat, cure, or prevent any disease.” But they are clearly marketing it for prevention.
Patient comments
There are plenty of comments online from purchasers of Ellura. There are some negative ones (“didn’t work for me”) but many more positive ones (“changed my life”). One comment said the writer was hedging her bets by taking mannose along with Ellura. It’s apparent that some customers misunderstood the claims and took it to treat UTIs, which doesn’t work. The company clearly states Ellura should not be used to treat established infections. They advise patients to double up on the dose if they feel like a UTI might be coming on, and they advise that a urine culture is a must for diagnosing an infection.
What’s in Ellura?
Ellura is a cranberry derivative, but with a difference. To cause an infection, the bacteria must adhere to the cells lining the bladder. Cranberries contain A-type proanthocyanidins (PACs) that interfere with this adhesion. P fimbriae are appendages on the surface of E. coli bacteria that mediate adherence. Ellura does not protect against bacteria that don’t exhibit P-fimbriae, but it covers the bacteria that cause over 90% of UTIs. When adhesion is prevented, the bacteria get flushed out with urination, which is probably what the ads mean by the claim “supports a clean urinary tract”. If untreated, bladder infections can spread to the kidneys and lead to pyelonephritis, sepsis, kidney failure, and possibly even death.
Cranberry juice has long been recommended to prevent UTIs, but it doesn’t work. A Cochrane review concluded that cranberry products could not be recommended. And when our own Scott Gavura evaluated the evidence, he concluded:
Even taking the analysis at face value, cranberry is only modestly effective, expensive, and may come at a high dietary cost. And, it’s substantially less effective than conventional treatments.
Ellura is different. Each capsule contains 36 mg of type-A PAC derived from concentrated North American cranberry juice through a proprietary extraction process.
The research
The company’s website has a page for “Studies and clinical papers” that conveniently describes the research that has been done:
- In a small uncontrolled trial of 36 mg PACs in 22 patients with indwelling catheters, no symptomatic UTIs occurred, and antibiotic resistances decreased by 28%.
- In a randomized double-blind placebo-controlled study of 32 volunteers, 2 capsules of Ellura (72mg PACs) reduced bacterial adhesion in urine samples.
- A review published in 2007 documented the beneficial effects of PACs for prevention of infections in vitro and in vivo.
- A pilot study of Ellura in 15 bladder surgery patients found that it reduced asymptomatic bacteriuria by an estimated 93%.
- A 2012 Cochrane review found that cranberry products had no significant effect, but said more research was needed with quantification of the active ingredient.
- A syrup formulation of Ellura was tested in a study of 192 pediatric patients with recurrent UTIs in Spain. It was found to be noninferior to prophylaxis with the antibiotic trimethoprim for preventing recurrent UTIs in children.
The Ellura website says a dose of 36mg of PACs has been proven effective, but one study suggests that a dose of 72mg of PACs is preferable.
We still don’t have a gold standard randomized placebo-controlled study in women with recurrent UTIs who are currently taking antibiotics for prophylaxis and would be candidates for switching to Ellura. But the existing studies are very promising. In my opinion, the evidence is sufficient to warrant trying Ellura as a replacement for antibiotic prophylaxis in patients with recurrent UTIs, as long as proper precautions are taken. Patients who develop UTI-like symptoms while taking Ellura should be tested with urine cultures, and verified infections should be treated with an appropriate course of antibiotics.
Conclusion: the evidence is promising
We need to reduce the development of antibiotic-resistant bacteria. If Ellura can replace daily antibiotic prophylaxis for recurrent UTIs, that’s a good thing. Apparently, some urologists are already recommending it. If definitive studies showed it was safe and effective, it could be submitted to the FDA for approval as a drug. But we’re not likely to get the definitive studies we need, because they can continue to sell it as a dietary supplement. In the absence of more compelling evidence, I think it is reasonable to try it. Significant side effects have not been reported, so we can assume it is probably safe to try it; and if an infection occurs, patients can be treated. I don’t see any obvious downside other than the out-of-pocket expense, but antibiotics are often considerably more expensive.
It’s refreshing to see a dietary supplement with a good science-based rationale that can present evidence from studies that used the actual product rather than just a different preparation of an active ingredient, or a mixture of ingredients. After some of the supplements I’ve looked at, Ellura is a breath of fresh air. I didn’t notice any pseudoscience or mumbo-jumbo on their website.
A personal note: I have had recurrent UTIs but never often enough to warrant prophylaxis. I did finally persuade my doctor to give me a prescription for an antibiotic I could keep on hand to start taking the next time my symptoms recurred. That cured me 🙂 – the pill bottle sits untouched on a shelf in my medicine cabinet. No, I’m not going to give a testimonial that an unopened pill bottle is curative. But that does show how important it is to have a control group before concluding that a treatment has worked.