Cranberries are widely used in the treatment and prevention of urinary tract infections (UTIs) and for those at risk of such infections. With the growing resistance to antibiotics, cranberries can be viewed as a useful non-pharmaceutical remedy (Lavender, 2000). The initial studies that looked at the effects of cranberries on urine showed that the excretion of hippuric acid from the berries helped the urine to remain acidic, which could explain why they could be used to treat and prevent infection (Harkin, 2000). Recent studies argue that cranberries prevent Escherichia coli (E.coli) from adhering to uroepithelial cells in the bladder (Howell and Foxman, 2002). Cranberries contain a group of compounds, called proanthocyanidins, which are condensed tannins (Gray, 2002; Lowe and Fagelman, 2001; Kuzminski, 1996). These are thought to be the key factors in inhibiting E. coli adherence.

Systematic review of the literature

Cranberries are becoming increasingly popular as a form of prevention and treatment for UTIs (Stothers, 2002). Because it is important that recommendations remain evidence-based (Livesley, 2004), a systematic review of available evidence was undertaken to determine reliability and validity in corroborating the efficacy of cranberries in the prevention of UTIs.

Because most of the literature on the subject was anecdotal and not evidence-based, and to ensure the systematic review was non-biased, randomised controlled trials from 1979 to the present day were looked at. Hek et al (2000) maintain that randomised controlled trials are the optimum form of studies as they are less susceptible to bias than other forms of trials, and provide reliable outcomes.

Articles not in the English language may be included in a trial if they are relevant to the study and if translators are available (Keegan, 2003). As a translation service was not available at the time of review, non-English literature was excluded. Exclusion criteria also applied to literature that included trials on chronic urinary tract conditions, such as interstitial cystitis. This is a chronic inflammation of the bladder wall that is not thought to be caused by bacteria and that does not respond to antibiotics (Dolman, 2003).

Framework for critical appraisal

Six studies were chosen for critical appraisal based on a framework used by Brink and Wood (1994). This particular framework was used because it encourages evaluation of the literature by questioning the study methods, data analysis and validity.

Evidence for using cranberries

Early studies to evaluate the effectiveness of cranberries concentrated on theories that the berries reduced the pH of the urine (Kinney and Blount, 1979). However, in 1983, a study carried out on mice and humans, based on an experimental design, looked at whether cranberries prevented bacteria adhering to the uroepithelium (Sobota, 1984). Comparison was made between mice that were given cranberry juice and those that were given water. The results favoured the suggestion that cranberry juice prevents adherence of bacteria to the uroepithelial cells, but no mention was made of the amount of cranberry juice used.

Following the analysis of this part of the study, samples of urine were collected from 22 human volunteers after ingestion of 15oz of cranberry juice. Their urine was analysed using a controlled experiment for which Sobota compared the use of three different preparations of cranberry juice. However, once again there was no mention of the concentration of the cranberry juices and it was unclear which preparation was given to each of the volunteers. Such a method leaves the study open to bias (Burns and Grove, 2003).

The results of the part of the study using mice showed that their ingestion of cranberry juice over a period of time inhibited the adherence of bacteria to the uroepithelial cells by 80 per cent. The results of the part of the study using the 22 human participants showed that in 15 cases bacteria did not adhere to the uroepithelium. This was not a longitudinal study and was based on a single sample range. For studies to be reliable and valid they should be undertaken over a long period of time to take into consideration variances such as illness and infections (Jepson et al, 2004).

A similar study undertaken by Howell and Foxman (2002) looked at a sample group of 39 women with diagnosed UTI. Twenty-four of these infections involved bacteria that were resistant to antibiotics. A quasi-experimental approach was adopted in order to research the variables. It was concluded that there was evidence that ingestion of a cranberry cocktail could prevent infection. However, the data analysis was limited owing to the size of the sample group and to the time span of the study.

Cranberry juice and bacteriuria

The first randomised, double-blind placebo trial was undertaken by Avorn et al (1994), who looked at the effect cranberry juice had on bacteriuria and pyuria (the presence of pus in urine that gives it a cloudy appearance). The target population was older women living in long-term care facilities. Avorn et al were able to support their decision to use this group by referring to other literature (Avorn et al, 1994). The women were randomly assigned to drink 300ml of cranberry juice or a placebo. Baseline urine samples, followed by monthly ones, were taken over the six months of the study.

The results showed that bacteriuria and pyuria occurred in 28 per cent of the placebo group, whereas only 15 per cent of women in the cranberry juice group were affected. The researchers noted that the women chosen randomly to drink the cranberry juice had a lower percentage of previous urinary infections at baseline than those in the placebo group. The study did not state clearly whether baseline urine samples were included in the data analysis. Whether they were or not could have had a bearing on the results and findings.

Cranberry-lingonberry juice and Lactobacillus GG drink

Kontiokari et al (2001) carried out an open randomised controlled trial of 150 women over 12 months comparing the daily ingestion of 50ml of cranberry-lingonberry juice or 100ml of Lactobacillus GG drink taken over five days against no intervention (Kontiokari et al, 2001). (Lingonberries are a wild relative of the blueberry and cranberry and are sometimes confused with cranberries; Lactobacillus GG is a probiotic drink.)

The frequency and amounts of juice given were based on the availability of the products from the suppliers. The success of any study depends on the extent of control the researcher has on variables being analysed (Brink and Wood, 1994). The study of Kontiokari et al is thus open to bias, and reliability and validity were jeopardised. Furthermore, the researchers did not clearly define what sample method they used to identify the target population.

The primary outcome variable was based on the first recurrent UTI during the study. However, recruitment had to be discontinued in the cranberry-lingonberry group after six months as the suppliers suspended manufacture of the juice.

The data collected showed that one or more infections occurred in eight of the cranberry-lingonberry group in comparison to the Lactobacillus group (18) and the non-intervention group (19). Although the results are significant, they remain inconclusive: there is no certainty as to whether or not further recruitment in the cranberry-lingonberry group would have altered the findings. The researchers could not confirm that the cranberry-lingonberry juice reduced the risk of infections, but they did suggest that it may help.

Clinical effectiveness

In 2002, a study was undertaken of 150 women to evaluate both the cost-effectiveness and clinical effectiveness of using cranberries as a means of preventing UTIs (Stothers, 2002). The women were randomised into one of three groups for one year: placebo, cranberry supplement or cranberry juice. Stothers hypothesised that there would be 50 per cent fewer UTIs among the patients receiving cranberry extract than those in the placebo group. This hypothesis, however, had not been substantiated by previous research or evidence.

The results showed a considerable reduction of UTIs in participants taking cranberry juice or cranberry tablets, with significant cost savings to patients. However, the calculation of the cost implications was based on participants experiencing more than two UTIs in 12 months and missing three days of work. These cost savings were based on conjecture rather than substantiated with data, and threatened the validity of the findings.

Cranberry extract and neurogenic bladder

In 2002, a six-month double-blind randomised placebo-controlled trial looked at patients with multiple sclerosis. Before this time, patients with neurogenic bladders had not been included in studies investigating the effect of cranberry extract on UTIs. A total of 135 participants were recruited and asked to take either 8,000mg of cranberry extract or a placebo (McGuinness et al, 2002).

The primary outcome variable was a diagnosed UTI. Information on common symptoms of a UTI, such as urgency, frequency, nocturia and pain, was given to the participants before they took part in the study. Participants suspected of having a UTI were asked to provide a sample of urine for analysis despite the authors noting that symptoms of a UTI are generally masked in patients with multiple sclerosis. No evidence was given to corroborate this statement and no alternative criteria for diagnosis were discussed. This raises the question of whether relevant data might have been overlooked.

In the final analysis, the study was unable to confirm that there was a relationship between the consumption of cranberry extract and the prevention of UTIs.

Discussion

This systematic review did show evidence that cranberries have clinical benefits in preventing UTIs (Avorn et al, 1994; Kontiokari et al, 2001; Stothers, 2002). Nonetheless there were limitations and inconsistencies in the studies. For example, sample groups in all of them were small, ranging from 22 to 150 participants. However, in none of the studies was a power analysis used to calculate whether an appropriate sample size had been found. A further limitation was the short duration of the studies. This limited data extraction and may have influenced the findings. Jepson et al (2004) maintain that studies should be longitudinal to take into consideration unforeseen variables that may affect the outcomes.

The amount of cranberry supplement or juice given to participants varied considerably in each study, which was a further limitation. However, no evidence or justification was found to suggest a recommended volume.

Cost implications for patients should be taken into account when considering a recommendation for long-term use of a product. Cost-effectiveness was looked at in one of the studies (Stothers, 2002), and this concluded that cranberry tablets are a more cost-effective option than juice, although the amount of cranberry extract needed to attain results remains unclear.

As the findings of the studies reviewed were not conclusive, further research is needed to confirm the relationship between taking cranberries and UTIs. If a relationship is proven, studies should identify when, how often and the quantity of cranberries that are needed for a therapeutic outcome.

In 2004, the National Center for Complimentary and Alternative Medicine in the United States, a branch of the National Institutes of Health, agreed to fund further research proposals designed to answer questions identified by previous studies on cranberry and urinary tract infections (Howell, 2004). The range of projects will include:

• Clinical intervention trials looking at cranberries as a preventive measure for UTIs;
• The mechanism of action;
• The interaction of cranberries with other medicines.

Cranberry products will be standardised in all the proposed studies to ensure that the participants in each receive the same level of concentration of cranberries. The studies are expected to be completed by 2008.

Conclusion

The systematic review identified that many studies citing evidence for the effectiveness of cranberries for treating UTIs were anecdotal rather than research-based. It also revealed the lack of high quality research in this field. Overall, the studies confirmed that, although cranberries may be effective at reducing the risk of UTIs, the findings remain inconclusive.

As health professionals, it is vital that we continue to work with evidence-based practice rather than hearsay. Nurses should be encouraged to understand the rationale for using cranberries to prevent UTIs and be able to explain this to patients, who can then make an informed decision.

IMPLICATIONS FOR PRACTICE

Many studies citing evidence of the effectiveness of cranberries for the treatment of urinary tract infections are anecdotal rather than research-based;

• Studies confirm that, although cranberries may be effective at reducing the risk of urinary tract infections, the findings remain inconclusive;
• Cranberry products are expensive and nurses need to understand the rationale for using cranberries to prevent urinary tract infections;
• Nurses need to be able to explain this rationale to patients.

© Janet Hutchinson, BSc, RGN, Dip Postreg Studies for Nursing; Nursing Times; (2005); 101; 47; 38.

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