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Cranberry
The cranberry plant, Vaccinium macrocarpon, is native to North America. Other related plants in the Vaccinium genus Include blueberry and bilberry. The ripe fruit, which is extremely sour, is used both as food and as an herbal medicine.
Uses and Benefits:
Cranberry juice has a long tradition in American folklore of helping to treat or prevent urinary tract infections (UTls). Scientific studies have attempted to validate the empiric use of cranberry as a urologic antimicrobial agent and as a potential medicinal herb to help prevent UTls in susceptible individuals.
Pharmacology:
Cranberry juice was originally thought to inhibit urinary bacteria by acidifying the urine or by being excreted as tlippuric acid, an antibacterial chemical. More recent investigations have failed to validate these mechanisms. Instead, it is now known that specific proanthocyanidins, condensed tannins from the cranberry fruit (also found in blueberries), can inhibit the adherence of uropathogenic E. coli and other bacteria to epithelial cells in vitro and in vivo.A similar constituent has been found to inhibit the coadhesion of dental plaque bacteria. Cranberry juice has recently been found to have some in vitro bactericidal activity as well.
Clinical Trials:
Initial claims that cranberry juice was effective in treating or preventing UTls were based on case reports or small uncontrolled studies. Only three double-blind, placebo­controlled trials have adequately investigated cranberry's clinical effects; two of these trials found clinical benefits. All three studies were conducted in the U.S., but the two positive studies have methodologic weaknesses (e.g., unstated or quasi-randomization procedures, high drop-out rates, no intention-to-treat analysis) that reduce the reliability of the results. 8 Cranberry has not been studied for the treatment of acute symptomatic UTls.
In one randomized controlled trial (RCT), investigators gave 300 ml/day of cranberry juice cocktail or a placebo beverage to 192 elderly female nursing home residents over a 6-month period. ' ° Pyuria with bacteriuria was significantly reduced in the cranberry group (15%) as compared to the placebo group (28.1 %) (P = 0.004). Antibiotics for UTls were prescribed eight times in the cranberry group by subjects' own physicians, and 16 times in the placebo group. Criticisms of this study included im­portant differences in baseline characteristics of the treatment and placebo groups, and a 20% drop-out rate.
In a small RCT using a 6-month crossover-design, investiga­tors gave a daily cranberry extract capsule or placebo to sexually active women (median age 37) with recurrent UTls; only 10 subjects could be evaluated. incidents of UTls, 6 occurred while taking the cranberry product, and occurred while taking placebo, a statistically significant difference (P < 0.005).
Lastly, no benefits were found in a 6-month crossover study of 15 high-risk children with neurogenic bladder requiring clean in­termittent catheterization q.i.d. Subjects drank ounces daily of a cranberry concentrate juice (equivalent to 300 ml of cranberry cocktail) or a placebo, and weekly catheterized urine specimens were obtained at home visits. Cranberry juice, compared to placebo, failed to reduce the frequency of bacteriuria (75% in each group), isolation of E. coli (43% vs. 48%, respectively), or sympto­matic UTls (three in each group). No reduction in bacteriuria was found, but the power to detect a difference in the number of clini­cal UTls was small due to the low number of UTls in the children.
Adverse Effects:
There are no documented adverse effects with cranberry products.
Side Effects and Interactions:
There are no recognized drug interactions.
Cautions:
Cranberry juice contains moderately high levels of oxalate, which may increase the risk of kidney stones in susceptible individuals. One man with a distant history of calcium oxalate nephrolithiasis developed recurrent stones following self-administration of cranberry extract tablets for 6 months. A pilot study of an extract taken daily for 1 week in five healthy subjects confirmed an increase in urinary oxalate levels. However, substances known to both induce (e.g., sodium) and inhibit (e.g., magnesium, potassium) stone formation were also increased; the overall effect is still not clear. The large amounts of sugar in many beverage products may be relatively contraindicated for patients with diabetes. Individuals should not rely on cranberry preparations to cure an established, symptomatic UTI, and should not dday in obtaining necessary medical treatment.
Preparations & Doses:
Pure cranberry juice is very acidic ,and sour; the most commonly marketed drink, cranberry juice cocktail, is a mixture of cranberry juice (at least 25% by volume), sweeteners, and vitamin C.Preparations and doses used in the above clinical trials included 300 ml/day (10 oz) of a standard cranberry juice cocktail beverage or 2 oz of concentrate (both :,supplied by Ocean Spray Cranberries, Inc.) in single or divided doses. A daily dietary supplement capsule containing 400 mg of cranberry extract (Solaray, Inc.) was also used in one trial. There are many other cranberry foods and supplements on the market that would be expected to have similar active constituents, but the optimal preparation and dose is unknown.
Summary Evaluation:
Cranberry's anti-infective activity in the urinary tract is well docucmented. Primarily, it inhibits the adherence of bacteria to urinary pithelial cells. Limited controlled trials suggest that cranberry products may help prevent UTls in susceptible individuals; how­(~ver, the available evidence is conflicting, and the studies all have methodologic flaws. Because cranberry is a safe and well-toler­died herbal remedy, it is not unreasonable for individuals with re­current UTls to try cranberry products for chronic preventive therapy. However, the potential beneficial effects, if clinically significant, are likely to be small.