Cranberry extract, vitamin D3 and D-mannose are among the ingredients showing promise in dietary supplements targeted for urinary tract health.

Maja Orešnik, Science and research director

March 5, 2021

4 Min Read
Formulating supplements that sway urologists.jpg

Supplements targeted toward urinary tract wellness are undergoing exciting development as they are increasingly being recognized by urologists and gynecologists as an alternative to or support for conventional approaches. Our sales data and client feedback show that in regions as different as CIS [Commonwealth of Independent States], Western Europe and the Middle East, supplements are making headway in the urinary tract arena through promotion to doctors and pharmacists.

A partner of PharmaLinea in the CIS region launched a sachet-form supplement supporting urinary tract wellness, promoting the launch solely through medical detailing and key opinion leaders. The company hit in excess of 10,000 units sold per week in its second month after product launch. Another partner in Western Europe also focused promotion on urologists and experienced stable growth—38% in its second year and 22% in its third year post-launch.

Acceptance by health care professionals and high consumer awareness of ingredients such as cranberry are fueling demand. The pandemic may also exert its effect, because in many regions of the world, accessing doctors is still very difficult—the focus on natural alternatives may grow in 2020 and beyond. For example, Google searches for the term “cranberry supplement” grew by 24% in year-to-date 2020 compared to the same period in 2019.

When developing a product for a promotion channel such as medical detailing, the pressure increases for the formulation to be scientifically sound, and either the specific ingredients used or (preferably) the finished product to be clinically supported. So how does one go about composing a successful urinary tract support supplement to convince health care professionals? In our view, three key ingredients can form a sound basis.

The first ingredient that comes to mind both for consumers and professionals is cranberry extract. It is one of the most successful and recognized ingredients for urinary tract health. Cranberry (Vaccinium macrocarpon) has a long history of traditional use to help manage urinary tract issues. Cranberry compounds, mainly proanthocyanidins (PACs), inhibit bacterial biofilm formation by E. coli in the urinary epithelium.1 PACs attach to the bacteria’s surface and prevent them from adhering to epithelial cells in the mucosal lining.2 Consequently, the bacteria are washed out of the body with urine. Effectiveness of cranberry extracts can, however, be compromised by the degradation of bioactive components of the cranberry in the acidic environment of the stomach. When selecting a cranberry ingredient, sources that improve digestive tract survival of anthocyanins—and thus bioavailability—should be considered.

The second ingredient is D-mannose—a molecule, naturally present in human metabolism, with a role in glycosylation of certain glycoproteins. Scientific data supports its antimicrobial properties in prevention of urinary tract infections (UTIs), as D-mannose acts as a competitive inhibitor, binding to adhesins on bacterial surface and blocking bacterial colonization.3 Several studies report that D-mannose supplementation significantly reduces the risk of recurrent UTIs.4,5,6

Lastly, recurrent UTIs have been associated with vitamin D3 deficiency.7,8 As the urinary tract is often exposed to bacterial infections, fast natural defense mechanisms are needed. Bladder epithelial cells secrete an antimicrobial peptide, which protects the urinary tract from pathogens, and vitamin D3 has shown to help increase the expression of this peptide.7,8 Thus, vitamin D3 is suggested to be a great complement for UTI management.

Whatever ingredients used, it is prudent to consider standardized and studied sources of them. The market is quite saturated with products, but space exists for differentiation. Products most often lack stability data and quality analyses, and most claims about their efficacy are based on nonvalidated bibliographical data.

Cranberry products are among the most popular herbal dietary supplements, but an eye must be kept on sourcing, as the American Botanical Council (ABC) reported adulterated cranberry raw materials are appearing in the marketplace.

Among the numerous juices and extracts in the market, products can differentiate themselves from the competition through high quality and clinical substantiation.

Maja Orešnik is the science and research director at PharmaLinea Ltd.


1 Al-Badr A, Al-Shaikh G. “Recurrent Urinary Tract Infections Management in Women.” Sultan Qaboos Univ Med J. 2013;13(3):359-367.

2 Beerepoot MA et al. “Cranberries vs Antibiotics to Prevent Urinary Tract Infections, A Randomized Double-blind Noninferiority Trial in Premenopausal Women.” Arch Intern Med. 2011;171(14):1270-1278.

3 Michaels EK et al. “Effect of D-mannose and D-glucose on Escherichia coli bacteriuria in rats.” Urol Res. 1983;11(2):97-102.

4 Altarac S, Papeš D. “Use of d-mannose in prophylaxis of recurrent urinary tract infections (UTIs) in women.” BJU Int. 2014;113:9-10.

5 Kranjcec B et al. “D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial.” World J Urol. 2014;32:79-84.

6 Porru D et al. “Oral D-mannose in recurrent urinary tract infections in women: A pilot study.” J Clin Urol. 2014;7(3):208-213.

7 Hertting O et al. “Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder.” PLoS One. 2012;5(12):e15580.

8 Georgieva V et al. “Association between vitamin D, antimicrobial peptides and urinary tract infection in infants and young children.” Acta Paediatr. 2018;108(3):551-556.

About the Author(s)

Maja Orešnik

Science and research director, PharmaLinea Ltd.

Maja Orešnik is the science and research director at PharmaLinea Ltd.

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