Anticholinergics are often deployed as the second-line therapeutic option for the management of overactive bladder (OAB) following behavioral and lifestyle modifications. Recently a large pool of data has associated anticholinergic medications with the increased risk of dementia. A nested case-control study of 58,769 patients with a diagnosis of dementia and 225,574 matched controls revealed a statistically significant association of dementia risk with exposure to anticholinergic drugs including common OAB medications after adjusting for confounding variables.¹ Considering such risks, patients and providers may be turned away from the use of anticholinergics in the management of OAB. Patient may find themselves turning to alternative over-the-counter supplements for therapeutic options. It is estimated that about 1 in 6 Americans purchase supplements online without any prescription and the number of Americans ordering online will likely continue to increase.² As a growing population looks to the Internet for these supplements, providers should be aware of the products available on popular online platforms.

We recently reviewed one of the largest online retailers, Amazon.com, to appreciate the variety of products marketed to relieve OAB symptoms. At the time of our review, the Amazon marketplace revealed 147 products, of which there were 65 distinct supplements. Products were filtered for those claiming to relieve “OAB,” “urinary frequency,” and/or “urinary urgency.” Product descriptions were assessed to gather the active ingredients used in the supplements and the top 10 active ingredients were investigated (see Table).

The most reported ingredient was pumpkin seed extract (Figure 1), which was an active ingredient in over 50% of the available products. Pumpkin seed extract contains high concentrations of free fatty acids (oleic, linoleic, palmitic, and stearic), which play a role in maintaining healthy brain function and are thought to help improve OAB symptoms. Specifically, consumption of pumpkin extracts has been shown to help with the sensation of residual urine volume and improve frequent urination and nocturia.³ While the exact mechanism in the use of OAB is unknown, it has historically been used in holistic practices to relieve urinary symptoms. Some theorize pumpkin seed oil increases production of nitric oxide due to high concentration of arginine facilitating relaxation of the bladder.⁴

Figure 1. Pumpkin seed.

Nishimura et al performed an open-label trial to investigate the effects of oil from Cucurbita maxima, the main species of pumpkin in Japan, on OAB symptoms in humans. They evaluated 45 volunteers taking 10 g of pumpkin seed oil per day administered for 12 weeks. The OABSS (Overactive Bladder Symptom Score) was compared at 6 and 12 weeks and showed significant improvements across all domains.⁵ This study was limited by a small sample size and nonrandomized design.

Often coupled with pumpkin seed extract, soy germ extract (Figure 2) was the next most reported active ingredient in OAB supplements. Soy germ extract contains large amounts of isoflavones with similar structures and hormonal effects of human estrogen. Estrogen replacement therapy has shown improvement in irritative voiding symptoms in postmenopausal women, bringing interest to soy isoflavones.⁶ In rat models, ovariectomized (estrogen deficient) rats had higher expression of the gap junction protein connexin-43 in the bladder, which induces detrusor overactivity. Soy isoflavone replacement altered connexin-43 expression pattern in the rats’ urinary bladders, suggesting it may play a role in improving the abnormal signaling system of intercellular communication through gap junctions caused by estrogen deficiency.⁷

Figure 2. Soybean germ.

Shim et al performed the first randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of Cucuflavone (containing extracts of pumpkin seed and soy germ) in 120 subjects suffering from OAB. They showed that after 12 weeks, those taking Cucuflavone showed improvements in urinary frequency, urgency, incontinence, and in OABSS as compared to placebo. Some improvement in both the Cucuflavone and placebo groups is hypothesized to be partly psychological from the feeling of “being helped” than the actual effects of the active ingredients. Similar placebo effects have been observed in several studies involving OAB supplements.⁸

Finally, cranberry (Vaccinium) extract (Figure 3) was the third most reported active ingredient in the online marketplace for OAB relief. Often cited as an alternative for urinary tract infection prevention, cranberry supplements have gained significant traction in the female urological health market.

Figure 3. Cranberry.

In a single-center, randomized, double-blind placebo-controlled study, researchers investigated the effects 500 g of dried cranberry powder daily during a 24-week period in women with OAB and found participants reported daily micturition decreased by 16.4% and urgency episodes by 57.3%.⁹ The authors were not able to explain the exact mechanism of cranberry supplements for the relief of OAB symptoms.

The Amazon marketplace is constantly evolving and represents only 1 of many online direct-to-consumer platforms without the need for a prescription or discussion with a provider. Pumpkin seed extract appears to be the most popular ingredient being marketed to OAB patients. While limited studies have shown minimal side effects for most OAB supplements, currently there is no conclusive level 1 evidence to support their use. Patients should be counseled appropriately of the large number of OAB symptom relief products on the market and balance their limited evidence with the risks of currently approved anticholinergic medications.