Herbal #2: Cranberry
Team Members Assigned: Mary and Jaimini
1. History:
The American cranberry (Vaccinium macrocarpon Ait) is an evergreen bush that is native to North America. Cranberry has been used for hundreds of years by both Native Americans and early European travelers as a source of medicine, food, and trade. Records show that the Native Americans used cranberries in wound care and to treat sepsis. The leaves from the cranberry bush were dried and given for what is now known to be diabetes, diarrhea and urinary tract infections. The Native Americans were also aware that cranberries could be used to prevent scurvy. The Indians passed along this information to the new European settlers; this passing of knowledge is celebrated each year with the presence of cranberry at Thanksgiving dinners across the nation. In later years, cranberries’ high Vitamin C content was utilized to keep American soldiers in the Revolutionary War from getting scurvy.
- Irvin, Suzanne. “The Cranberry: Therapeutic Properties” 2005 November 1 Clinical Excellence for Nurse Practitioners. 9: 37-40.
- Schenker, Sarah. “Facts Behind the Headlines: Cranberries” 2001. British Nutrition Foundation: 26, 115-116.
2. Medicinal and non-medicinal use:
Cranberries have long been used to make foodstuff such as juices, relishes and jams. Besides its dietary uses, cranberry has been used for hundreds of years as a medicinal product, said to be an effective remedy for diabetes, burns and cuts, gout, arthritis, scurvy and urinary and genital infections in women. Over the years, cranberry has been proven ineffective in the treatment of some of these ailments but still is used in the United States and many other countries as a treatment for and as a preventative measure against urinary tract infections. The Gale Encyclopedia of Alternative Medicine also reports somewhat effective results of using cranberry to prevent the development of kidney stones and prevent colds. On the other hand, the Encyclopedia also lists a variety of other ailments and diseases that cranberry has been used for but in all cases, scientific evidence in favor of its use is insufficient or nonexistent. These other uses of cranberry include: acting as a digestive enzyme, treating diarrhea, acne, dermatitis, psoriasis and battling the formation of gingivitis.
- Irvin, Suzanne. “The Cranberry: Therapeutic Properties” 2005 November 1 Clinical Excellence for Nurse Practitioners. 9: 37-40.
3. Major component(s) hypothesized to be the active ingredient(s). Include chemical entities if applicable:
Cranberries products contain cranberry as a sole active ingredient. Cranberry’s constituents are as follows:
- Acids
- Citric, malic, quinic and benzoic acids are present
- Carbohydrates
- Fructose and oligosaccharides
- Phenolics
- Dietary flavonoids:
- Anthocyanins-made up of peonidin and 3-galactosides
- Proanthocyanidins
Proanthocyanidins are found within the berry of the cranberry. The molecular structure of a proanthocyanidin is shown below. This compound is what is the hypothesized component of cranberry giving it its medicinal properties.
- Schenker, Sarah. “Facts Behind the Headlines: Cranberries” 2001. British Nutrition Foundation: 26, 115-116.
4. Theorized mechanism of action:
As mentioned previously, cranberry was found to contain proanthocyanidins, mainly epicatechin. Studies have found that this particular component of cranberry is responsible for its medicinal properties. Epicatechin is an antioxidant and a radical scavenger. This component of cranberry is most likely responsible for cranberry blocking E. Coli, and potentially other Gram negative bacteria, from adhering to the walls of the bladder, kidneys, and urethra. It is suspected that cranberry interferes with the surface component of E. Coli’s microbial structure that is responsible for adhering to mucosal surfaces, such as the uroepithelial cells.
- Schenker, Sarah. “Facts Behind the Headlines: Cranberries” 2001. British Nutrition Foundation: 26, 115-116.
5. Clinical issues; DDIs, suggested dose, adverse effects, pharmacokinetics, overdose, use in special population (pregnant women, elderly...etc.)
- Suggested dose:
- UTI Prophylaxis Oral capsules or tablets: 100 -500 mg standardized cranberry extract TID-QID
- UTI Prophylaxis Cranberry Juice: 300 ml daily, or 250 ml TID of of unsweetened or saccharin sweetened cranberry juice.
- DDIs:
- Interaction with Warfarin
- Several case reports have shown that consuming large quantities of cranberry may lead to increased INR and bleeding events.
- Cranberry is possibly a CYP2C9 Inhibitor, which can lead to increased levels of circulating warfarin
- H2RAs
- May antagonize its effects
- PPIs
- Cranberry juice significantly reduces gastric pH
- Avoid regular use of cranberry juice.
- No known interactions with food or other herbs and supplements
- Adverse Effects:
- Nephrolithiasis - renal colic, hematuria (Blood in urine), renal stones. This is due to the compound oxalate.
- Cranberries contain salicylic acid - don’t consume if have ASA allergy
- PK: No date available.
- Overdose: Symptoms include stomach pain and diarrhea
- Use in Special Population:
- Pregnant Women: Cranberries and cranberry juice is safe, however, avoid supplements because their effects are unknown. Unknown whether cranberry passes into breast milk, so women should speak with their doctors during lactation.
- Children: Pediatric dosing is unavailable
6. Efficacy vs. safety
Cranberry has been used for hundreds of year for urinary tract infection prophylaxis and clinical trials have demonstrated the benefits of utilizing cranberry as a prophylactic therapy. However, patients are at higher risk for developing kidney stones due to the buildup of oxalate. It has also been suggested that cranberry may be useful in malodor due to urinary incontinence, however, the data are inconclusive. The major safety concern is renal stones, stomach upset and diarrhea.
7. Information about the standard of the various preparations available
Cranberry can be used simply by eating the fruit, drinking cranberry juice, either concentrated or cocktail, and can be administered in capsules. Cranberry capsule supplements can have doses from 400 mg of cranberry1 , 1000mg5 and up to 25,000mg of cranberry powder (500mg of a 50:1 concentrate = 25,000mg of cranberry fruit).2 Cranberry juices come in 100% concentrate3, but can also be sold as cocktail juices, such as Ocean Spray, which is a blend of 4 juices.4 Judging from the variation in doses, there does not seem to be a standard in doses for each dosage form. The dose depends on the brand, however, since the supplement products (excluding Ocean Spray Juice) are not regulated by the FDA, we cannot be certain that the supplements contain the stated amount of cranberry extract.
8. Cost (compare to prescription medication):
There are numerous antibiotics used to treat UTIs, most commonly ciprofloxacin, cephalexin and numerous other quinolones and cephalosporins. Most of the antibiotics used to treat uncomplicated UTIs are relatively inexpensive-ranging from $10 to $50 for a 10 day regimen. Cranberry is typically sold in capsule form and are sold in a variety of package sizes but in almost all cases cost 6 to 15 cents per capsule. Azo Cranberry is a well known brand in the United States and slightly more expensive than some of the other commercially sold cranberry capsules. Azo Cranberry retails at $10.89 for 50 capsules.
- http://www.amazon.com/s/ref=nb_sb_noss_1?url=search-alias%3Daps&field-keywords=azo+cranberry&rh=i%3Aaps%2Ck%3Aazo+cranberry
9. Prevalence of use:
In 2005, it was estimated that urinary tract infections constituted more than 11 million doctors visits in the United States. Due to the increase in antibiotic resistance, it would be of great societal benefit if cranberry would indeed serve as a viable alternative to antibiotic therapy or if it could act as a preventative measure from getting a urinary tract infection. Although cranberry is readily available to buy, we could not find any figure expressing the amount of Americans using it as a herbal supplement.
- Irvin, Suzanne. “The Cranberry: Therapeutic Properties” 2005 November 1 Clinical Excellence for Nurse Practitioners. 9: 37-40.
10. Evidence-based studies
Several studies have examined the effects of cranberry use, especially in the prevention of urinary tract infection. A study conducted by Marielle A. J. Beerepoot, MD, analyzed the efficacy of cranberry versus trimethoprim-sulfamethoxazole in the prevention of UTIs in premenopausal women. The women were randomized to either trimethoprim-sulfamethoxazole (TMP-SMX) 480 mg daily or cranberry capsules, 500 mg twice daily. The primary endpoint for this study included mean symptomatic UTI over 12 months, the proportion of patients with at least 1 symptomatic UTI, the median time to first UTI and the development of resistance by E. coli.Results showed that trimethoprim-sulfamethoxazole prevented UTIs better than cranberry, even with emerging resistance. The mean number of patients with at least 1 symptomatic UTI was 4 patients in the cranberry group as opposed to 1.8 in the TMP-SMX group. Additionally 78.1% of patients had at least 1 symptomatic UTI in the cranberry group versus 71.1% of patients in the TMP -SMX group. Lastly, the median time to firsts UTI was 4 months in the cranberry group versus 8 months in the TMP-SMX group. The results demonstrate that the antibiotic is still more effective than cranberry at preventing UTI. 1 Another meta-analysis analyzed studies that compared cranberry to placebo in the prevention of UTI. The results showed that consumption of cranberry products significantly reduced the incidence of UTIs after 12 month (RR 0.65, 95% CI 0.46 to 0.90). 2
- [Beerepoot MJ, ter Riet G, Nys S, 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. doi:10.1001/archinternmed.2011.306.]
- Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD001321. DOI: 10.1002/14651858.CD001321.pub4.
11. Comparable prescription or nonprescription medications
Although there are many antibiotics currently used to treat UTIs clinically, the antimicrobial effects of cranberry have not been proven, thus there is no way to compare cranberry’s effectiveness to that of presently used antibiotics.
12. Any regulatory issues
- Cranberry supplements are not regulated by the FDA, thus patients should be cautioned when using supplements.
- GRAS inventory mentions that the notice provided to the FDA does not provide a basis for GRAS determination.
