For many decades cranberry juice has been thought to reduce bacterial infections of the bladder. Studies in recent years have shown that cranberry juice inhibits adherence of E. coli cells to cells lining the bladder. Two different constituents have been implicated, one being fructose and the other a large polymeric compound of unknown structure. Fructose is present in all fruits, but the large polymeric compound is found only in cranberry and blueberry juices, and not those of grapefruit, orange, guava, mango and pineapple.
How big is the problem?
Bacteriuria is common among elderly women both in and out of institutions. While it is often asymptomatic, and does not require treatment, a large proportion of women over 65 years will experience at least one urinary tract infection each year. Recurrent urinary tract infection is common in patients who are incontinent: 73% of catheterised patients may receive treatment for bacteriuria, as well as 40% of patients managed by incontinence pads [1]. Young women with symptomatic cystitis also represent a large group.
How to organise a study
The well-conducted randomised, double-blind, placebo controlled trial performed in Boston and published in JAMA [2] is a superb example of how studies should be conducted.
The authors studied 153 elderly women (mean age 79 years) in whom bacteriuria with pyuria was likely to have a high incidence (above 30%). The women were both inside (44) and outside (109) long-term care institutions, and were asked to consume 300 mL of a cranberry juice cocktail every day for six months. Urine samples were collected each month, and the main outcome measure was the presence of bacteriuria (defined as more than 100,000 organisms per mL) with pyuria.
The study went to great lengths to ensure that there was true double blinding - a cranberry juice manufacturer made a placebo beverage containing no juice, but flavoured and coloured to simulate the appearance and taste of commercially available cranberry juice cocktail. To prevent the possibility that subjects in the institutional setting who were randomised to placebo might inadvertently drink standard cranberry juice elsewhere in the institution, all such beverages were converted to placebo throughout the institution for the duration of the study.
Patients were interviewed by a research nurse each month to help ensure compliance and to collect used bottle caps. The nurses also ensured that the urine samples were collected regularly and taken immediately to the bacteriology laboratory.
The results
A total of 818 urine specimens were collected from the study subjects after baseline. About one third produced growths above 100,000 organisms per mL, one third no bacterial growth and one third intermediate growths. E. coli was the most prevalent organism (43%), with Klebsiella the second most common (7%). About 45% of all urines had microscopic or chemical evidence of the presence of white cells, and symptoms relating to the urinary tract were noted on 22% of interviews. Consumption of study beverages exceeded 80% of assigned quantities.
Bacteriuria was noted in 28% of urines in the placebo group and in 15% of the cranberry group. The difference was not apparent in the first month, but appeared between months one and two and remained fairly stable thereafter.
The study demonstrated that the odds ratio of bacteriuria with pyuria in the cranberry group compared with placebo was 0.42 (95% confidence interval 0.23 to 0.76, p = 0.004).
Antibiotic use for treatment of urinary tract infection occurred on 16 occasions in the placebo group compared with eight in the cranberry group; this is a rate of 3.2 per 100 patient months compared with 1.7 per 100 patient months in the cranberry group.
Prevention or cure?
Cranberry juice could have been working by curing existing infections, by preventing new infections, or by a combination of these mechanisms.
The average one-month probability of change from infection to non-infection was 0.54 in the cranberry group, compared with 0.28 with placebo. The average one-month probability of changing from non-infection to infection was 0.09 in the cranberry group and 0.12 with placebo. The implication here is that cranberry juice actually cures existing infection. Indeed, the odds ratio for monthly intervals beginning with a bacteriuric-pyuric infection ending with a bacteriuric-pyuric infection was only 0.27 in the cranberry group compared with placebo, indicating that cranberry drinkers were only a quarter as likely as placebo to continue to have bacteriuric-pyuric urine samples.
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