The study, co-authored by cranberry expert Dr. Amy Howell,ย โused a combination of in vitroย โbioassays and ex vivoย โurine analyses to compare the anti-adhesion activity of the two supplements in the same group of 20 participants.
โFollowing daily intake for a week, the cranberry fruit juice dry extract product with 36 mg PAC (proanthocyanidin) provided significantly greater urinary bacterial anti-adhesion activity over each 24-hour period than the D-mannose product against both P-type and Type 1ย E. coliโย strains that cause UTIs,โ Dr. Howell told NutraIngredients-USA.ย
The researchers used a 206 mg Gikacran (Vaccinium macrocarpon Ait.)โย cranberry juice concentrate extract manufactured as Ellura by Solv Wellness (serving size one capsule) and a 500 mg D-mannose capsule from NOW Foods (serving size three capsules), both purchased online.
Prophylactic power: Cranberry vs. D-mannoseโ
According toย a large-scale meta-analysisโย published inย The Cochrane Database of Systematic Reviewsโย in 2023, consumption of highly-standardized cranberry juice extract products can prevent and reduce the risk of recurrent UTIs in women, children and other at-risk individuals.
Dr. Howell highlighted that not all cranberry supplements are created equal when it comes to maintaining urinary tract health, with research to date supporting cranberry juice-based supplements standardized to 36 mg of PAC content as most effective. ย ย
โMany lower cost supplements contain the pomace fiber material left over after the juice is removed and are not as effective at preventing bacterial adhesion,โ she explained. โThe whole berry supplements have some juice, but higher intake would be needed compared to a pure juice-based product.โ
The anti-adhesion activity of cranberry juice wasย discovered in 1984 by A.E. Sobotaโ, disproving the theory that the acidity of cranberry was responsible for killing off the UTI-triggering bacteria. By the late 1990s, researchers had tied the PAC content to theย in vitroโ activity, which then correlated with ex vivoโ activity in the urine following cranberry intake and against P-type uropathogenicย E. coliโ.
โSince then, [the anti-adhesion activity] of cranberry has been detected against Type 1ย E. coliโย expressing fimbriae with FimH adhesins that bind to mannose-like receptors causing the majority of lower UTI bladder infections, implicating PACs, flavonols and oligosaccharides as potential actives,โ the study noted.
Regarding the efficacy of the monosaccharide bioactive found in D-Mannose,ย a 2022 Cochrane reviewโย (without meta-analysis due to lack of comparable dose and treatment) concluded that โthere is currently little to no evidence to support or refute the use of D-mannose to prevent or treat UTIs in all populations.โย
The reviewers reported that many of the D-Mannose studies had design flaws in terms of completeness and applicability of evidence, however, a double-blind randomized placebo-controlled trial published inย JAMA Internal Medicineย โin April 2024โย found that daily D-mannose supplementation in 598 women for six months did not significantly reduce UTI recurrence.
โOur current study supports these findings from a mechanistic perspective in that daily D-mannose intake had only a small and questionable effect on Type 1 uropathogenicย E. coliโย bacterial adhesion in urine (ex vivoโ level) and did not significantly prevent P-type adhesion,โ Dr. Howell said.
She noted that other studies have found that ingesting D-mannoseโa simple sugar that occurs naturally in the human body and in some plantsโmay not be appropriate for routine use by diabetics and could have other potential side effects.
โThe latest findings do not support the use of D-mannose supplements, however there could be benefit from more complex pharmaceutical-based engineered mannosides in the future that are showing positive outcomes against Type 1ย E. coliโ,โ she added.
Surprises and questionsโ
Dr. Howell was most surprised to find that the majority of urinary bacterial anti-adhesion activity against Type 1ย E. coliโย after D-mannose intake was not as high as the in vitroโ results.ย
โThe urinary activity that was detected may not be due to D-mannose itself but to an adhesion inhibitor (Tamm-Horsfall protein) produced naturally by the body and found in background urine samples,โ she said.ย
Also unexpected was the significant effect of cranberry PACs against Type 1ย E.coliโ, considering that these PACS have historically been considered to be more active against P-type bacteria.
Questions raised for future study included how cranberry PACS induce the bacterial anti-adhesion activity against Type 1ย E. coliโย bacteria and whether PACs induce the kidneys to produce the bacterial adhesion inhibitor Tamm-Horsfall protein or physically aggregate the bacteria and inhibit their ability to bind to the uroepithelium. ย ย
โMore research is needed on the details of how the anti-adhesion activity is induced in the urine following consumption of cranberry products and how compliance in clinical trials can accurately be measured following intake,โ Dr. Howell said.
ย
Source:ย Journal of Dietary Supplementsโ
โDifferences in P-Type and Type 1 Uropathogenicย Escherichia coliโย Urinary Anti-Adhesion Activity of Cranberry Fruit Juice Dry Extract Product and D-Mannose Dietary Supplementโ
doi:ย 10.1080/19390211.2024.2356592โ
Authors: Amy B. Howell et al.