Latin name Vaccinium macrocarpon
Cranberries, blueberries, and Concord grapes are the only 3 fruits that are native to the United States and Canada. Most commercial farms today are located in northern United States, Massachusetts, and New Jersey and the Canadian provinces of Quebec and British Columbia. Commercial harvests occur in September and October. Cranberries contain >80% water and 10% carbohydrates. Among other constituents are flavonoids, anthocyanins, catechin, triterpenoids, organic acids-citric, malic, and quinic acids, with small amounts of benzoic and glucuronic acids. Anthocyanin pigments obtained from cranberry pulp are used for coloring applications. Cranberries can be processed into fresh fruit, concentrate, sauce products, and juice drinks. The single-strength juice is very acidic and unpalatable.
Native Americans were the first to use cranberries for their medicinal properties (1). Cranberries were used for a variety of complaints, including blood disorders, stomach ailments, liver problems, and fever. During the 1880s, German physicians observed that urinary excretion of hippuric acid increased after ingestion of cranberries. In 1914, Blatherwick (2) published an article showing that cranberries are rich in benzoic acid, which is then excreted in urine as hippuric acid. Hence the usefulness of cranberry juice was thought to be based on the urinary excretion of hippuric acid, which is a bacteriostatic
agent and has the potential to acidify urine (3). Today, it is known that the low amount of benzoic acid present in the fruit, coupled with maximum tolerated amounts of cranberry juice (∼4 L/d), rarely results in enough hippuric acid excretion necessary to achieve bacteriostatic urinary concentrations (4). Ingestion of large amounts of cranberry juice is required to slightly reduce pH of urine and modestly increase hippuric acid excretion, changes that do not confer significant antibacterial activity to urine, therefore another mechanism must be involved.
In 1984, Sobota (5) was first to suggest that “reported benefits derived from the use of cranberry juice may be related to its ability to inhibit bacterial adherence”. Sobota found that cranberry juice cocktail reduced adherence by 175% in 160% of 77 clinical isolates of E. coli recovered from patients with UTI. Fifteen of 22 subjects showed significant antiadherence activity in their urine.
Urinary Tract Infections
In a study by Kontiokari et al. (6), which was an open, randomized, controlled trial, 150 women were divided into 3 groups: one group drank 50 mL a day of cranberry-lingonberry juice concentrate, another group drank 100 mL of a lactobacillus drink; and a third group received no intervention. After 6 months’ treatment, 16% of the cranberry group, 39% of the lactobacillus group, and 36% of the control group had experienced >1 recurrence of UTI. This translates to a 20% reduction in absolute risk for the cranberry group. Interestingly, the percentage of women who experienced recurrence at 12 months was still significantly lower in the cranberry group, implying a residual effect supporting the hypothesis that cranberry selects for less adherent bacterial strains.
Stothers (7) performed a randomized, placebo-controlled, double-blind study. A total of 150 women with previous UTI
were divided into 3 groups: persons who received placebo juice and placebo tablets, persons who received cranberry juice and placebo tablets, and persons who received placebo juice and cranberry tablets. After 1 year, results showed that 32% of placebo recipients had experienced >1 UTI during the year, compared with 20% in the cranberry juice group and 18% in the cranberry tablet group. The absolute risk reduction for cranberry products was 12%–14%, similar to the findings of Kontiokari et al.
A smaller study by Walker et al (8) adds further support to the above findings. In this study, which followed a doubleblind crossover design, 19 women with recurrent UTI were provided either cranberry capsule (with 400 mg cranberry solids) or a placebo capsule for 3 months. Patients then switched to an alternative therapy for the next 3 months. Overall, these 3 studies show that use of cranberry is effective, at least statistically, for prophylaxis of UTI in adult women with recurrent UTI.
Two studies have evaluated the use of cranberries in elderly women, but unlike the above 3 prospective studies, these trials chose bacteriuria as their primary parameter. Avorn et al (9) conducted a large randomized, double-blind study in which 153 asymptomatic elderly women received 300 mL per day of cranberry juice or placebo. Urine samples were obtained at baseline and at 1-month intervals for 6 months, and tested for bacteriuria and pyuria. At baseline, bacteriuria and pyuria were present in ∼20% of samples in both the cranberry group and the placebo group. At the 1-month mark, there was no difference in the percentage of urine samples with bacteriuria and pyuria in the 2 groups (∼25%). However, from the 2-month mark on, there was a statistically significant difference between groups favouring the cranberry group. At the end of the 6-month study, bacteriuria and pyuria were present in 28% of urine samples from the cranberry group. The chances of having bacteriuria with pyuria were 42% less in the cranberry group than in the control group. Haverkorn and Mandigers (10) also evaluated the use of cranberry by elderly patients, but they used a non-blinded crossover design. Men and women in a nursing department of a general hospital were provided 15 mL cranberry juice mixed with water twice daily or the same amount of water daily. There were fewer instances of bacteriuria during the cranberry period than during the control period, supporting a moderately preventive role for cranberry juice.
In a Danish trial (11), the incidence of UTI was compared in 2 geriatric departments. Patients were offered cranberry juice in one department and the usual mixed berry juice in the other. The results showed that cranberry juice did not influence incidence of UTI. In another study, 538 nursing home residents were provided either 220 mL of cranberry juice or 6 capsules containing cranberry extract daily (12). Compared with historical controls, the incidence of UTI was significantly reduced, from 27 cases a month to 20 cases a month.
Two studies have evaluated the potential of cranberry in paediatric patients with medical conditions predisposing them to UTI. These trials did not show any benefit of cranberry for prevention of UTI or bacteriuria (13,14).
Two additional studies were performed in adult patients, but neither study evaluated clinical outcomes. In 8 adult patients with multiple sclerosis randomized to receive 20 days’ therapy, cranberry increased acidity of urine, and in 15 patients with spinal cord injury, cranberry reduced bacterial biofilm load in the bladder (15,16).
Jepson et al (17) reviewed in the Cochrane Library all randomized or quasi-randomized controlled studies for the prevention of UTI with cranberry juice. Until 2000, only 5 trials met all the criteria adopted for evaluation. The conclusion of the review was that because of the small number and poor quality of trials, there is insufficient evidence to show the effectiveness of cranberry juice for prevention of UTI. However, the Cochrane reviewer did not include the latest 2 studies by Stothers and Kontiokari et al (6,7). Both studies were randomized and large, and they found that women with previous UTIs who took cranberry products as prophylaxis experienced fewer recurrent UTI. On the basis of these 2 trials, a recent evidence-based answer (18) suggested that a trial of cranberry juice (3 glasses daily) was reasonable for women with recurrent UTI who are being considered for antibiotic prophylaxis.
Evidence regarding the role of cranberries for treating, rather than preventing, UTI is almost nonexistent. The same Cochrane reviewer who evaluated UTI prevention also systematically reviewed the literature for trials that evaluated use of cranberries for treating UTI (19). Papas et al. (20) studied patients with bacteriuria, but this was not a randomized trial. Another nonrandomized study (21) found decreased leukocyte counts in urine samples obtained from handicapped children (most with indwelling catheters) who drank cranberry juice. This, too, was not a randomized trial.
The Cochrane reviewers concluded that randomized studies assessing effectiveness of cranberry juice for treatment of UTI have not yet been conducted. Therefore, at present, there is no evidence to suggest that cranberry juice or other cranberry products are effective for treatment of UTI.
The safety of cranberries is considered to be excellent. Some patients may experience a slight laxative effect, depending on
the amount ingested. Nevertheless, at least one author has warned that ingesting a large amount of cranberries
over a long duration may increase risk of some types of urinary stones in high-risk patients because of the increased urinary excretion of oxalate and slight urinary acidification.
There is currently no EMEA Monograph for cranberry
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