Urinary tract infections (UTIs) are today the most common outpatient infections in the US.
It is estimated that they cause about 10.5 million doctor’s office visits each year, with a cost estimated at $3.5 billion per year.¹ Studies show that this number increases significantly every year.² As people age, the severity escalates.
As most UTI cases are caused by bacteria, they are treated with lengthy or repeated antibiotic cycles adding to the growing problem of antibiotic resistance and other negative outcomes from long-term antibiotic use.³ Because of this, effective scientifically supported approaches to urinary tract health (UTH) from natural or non-antibiotic sources are of growing value.
Historical use and early scientific progress with cranberry fruits
Today, there is a lot of focus on the scientific developments of cranberry extraction, concentration, testing methods, and resulting therapeutic benefits. However, the therapeutic use of cranberries dates back centuries, primarily among indigenous peoples in North America. Native American tribes, such as the Algonquin and Wampanoag, used cranberries for both food and medicinal purposes.⁴
Cranberries quickly became popular with settlers from Europe, and in 1672, in one of the earliest records of medicinal use, John Josselyn described cranberries as being an ‘excellent’ protection against scurvy on long sea voyages.⁵ By 1789 the fruit was so in demand that the New Jersey legislature restricted the harvesting of berries.
It was in the early 1900s that research began on the benefits of cranberry in support of UTH. The first papers on this subject were published in 1914, and they noted that cranberry increased the excretion of hippuric acid in urine.⁶ It was therefore assumed that the observed benefits of cranberry were due to hippuric acid (a bacteriostatic agent).
The active ingredients cranberry that result in anti-adhesion activity
It took another 60 years of research however to finally establish that the benefits of cranberry were not due to high acidity levels: in 1984 the first study was published establishing that cranberry’s activity in supporting UTH was due its ability to inhibit bacterial adherence to the urinary tract.⁷
Instead of killing the bacteria outright, cranberries were found to interfere with their ability to stick to the urinary tract lining, reducing the likelihood of infection. This explanation made sense to practitioners and consumers, establishing cranberry as a natural approach to urinary tract health.
As useful as this information was, cranberry still was not well-understood so the search for the active constituents in cranberry continued. A breakthrough was made in 1998 when Amy Howell et al published a study in the NEJM identifying proanthocyanidins (PACs) as being the compounds responsible for the process of bacterial anti-adhesion activity (AAA).⁸
PACs are a very large group of compounds that are present in almost all dark colored fruits and berries. A key question remained however: Why do the PACs from cranberry result in AAA when those from other berries don’t have this action?
Two other studies, authored by Amy Howell and LY Foo, resolved this question. They showed that cranberry is unique in that it contains A-type PACs (not found in other berries or fruits), and that these specific compounds are responsible for their anti-adhesion activity.⁹⁻¹⁰
Development of DMAC test method and dosage requirements for AAA
In the early 2000’s the DMAC method was developed as a sensitive, specific assay for quantifying A-type proanthocyanidins (PACs) in high-grade cranberry extracts.¹¹
DMAC is now the method endorsed by a number of labs and associations including United States Department of Agriculture (USDA), The Cranberry Institute, American Herbal Pharmacopoeia (AHP), European Food Safety Authority (EFSA), and Rutgers University.
Other methods that measure total PACs may give higher results, but these don’t identify the percentage of the active A-type PACs that are the source of AAA, and therefore the desired benefits.
Further progress was made in establishing effective dosage levels for optimal AAA. A key published study confirmed that dosage levels at 72mg A-type PACs (by DMAC method) provided effective AAA over a 24-hour period.¹¹
Another multicentric, randomized, double blind clinical trial conducted by Amy Howell at Rutgers University in 2017 using Cranberex brand cranberry extract from Ethical Naturals Inc. (ENI). The results clearly affirmed a bacterial anti-adhesion effect in urine based upon a 36mg dosage of cranberry A-type PAC (tested by DMAC method). It also found that effectiveness was dose-dependent, prolonged up to 24 hours with 72mg of PAC.¹²
The nature and science behind Cranberex
A-type PACs are found primarily in the skin of cranberry fruit, at very low percentages of total weight. Published data from American Herbal Pharmacopoeia (AHP) showed A-type PACs from different cranberry growing areas as: Oregon (70mg/100g), Massachusetts (42mg/100g) and Wisconsin (37mg/100g).¹³ Content in the juice and pulp of the fruit is even lower.
To achieve a therapeutic dosage of up to 15% A-type PACs requires a high-level of concentration (up to 200 times). These levels of concentration, plus the complex test method required to assure real percentage of A-type PACs, are why so many cranberry products fail to achieve effective levels and impart the benefits the consumer expects.
Many of these products are based upon simple concentrations, powdered juices or other methods that do not guarantee content of A-type PACs.
From field to finished product: The journey of Cranberex
The journey for the premium Cranberex extract begins every fall on the Oregon Coast, where family farms produce some of the highest-grade cranberries in the world.
The fruit then goes through a complex extraction process designed to maximize levels of A-type PACs, verified by DMAC testing. Cranberex is the culmination of the quest to identify and confirm the material that delivers the health benefits consumers are seeking and will rely upon.
The final extract is supplied to the US, EU and Asia-Pacific markets through ENI’s world-class NSF certified manufacturing and distribution facility in Redwood City, California: Cranberex - The Power of Oregon Cranberry.
References
- Medina, M.; et al. An introduction to the epidemiology and burden of urinary tract infections. Ther Adv Urol. 2019 May 2;11:1756287219832172.
- Simmering, J.E.; et al. The Increase in Hospitalizations for Urinary Tract Infections and the Associated Costs in the United States, 1998-2011. Open Forum Infect Dis. 2017 Feb 24;4(1):ofw281.
- Mareș, C.; et al. Update on Urinary Tract Infection Antibiotic Resistance-A Retrospective Study in Females in Conjunction with Clinical Data. Life (Basel). 2024 Jan 9;14(1):106.
- National Geographic. Cranberries, a Thanksgiving Staple, Were a Native American Superfood.
- Roy, Upton.; et al. Cranberry Fruit Vaccinium macrocarpon Aiton. American Herbal Pharmacopoeia and Therapeutic Compendium. 2016.
- Blatherwick, N.R. The Specific role of foods in relation to the composition of the urine. Arch Intern Med (Chic). 1914;XIV(3):409–450.
- Sobota, A.E. Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. J Urol. 1984 May;131(5):1013-6.
- Howell, A.B.; et al. Inhibition of the Adherence of P-Fimbriated Escherichia coli to Uroepithelial-Cell Surfaces by Proanthocyanidin Extracts from Cranberries. New Engl J Med 1998 Oct 8;339(15):1085-6.
- Foo, L.Y.; et al. The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated Escherichia coli in vitro. Journal of Natural Products. 2000, 63, 9, 1185-7.
- Howell, A.B.; et al. A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity. Phytochemistry. 2005 Sep;66(18):2281-91.
- Prior, R.L.; et al. Multi-laboratory validation of a standard method for quantifying proanthocyanidins in cranberry powders. J Sci Food Agric. 2010 Jul;90(9):1473-8.
- Howell, A.B.; Bacterial Anti-Adhesion Activity of Human Urine: Cranberex® (Ethical Naturals). Rutgers University. Feb 2017.
- American Herbal Pharmacopoeia and Therapeutic Compendium (2016). Cranberry Fruit, Vaccinium macrocarpon Aiton, Revision. Page 15.
