CONFERENCE REPORT

The health properties of cranberry juice

E. GardnerLondon, UK

Royal Society of Medicine, London,3 December 2013

This report summarises the presentations and discussionat a meeting entitled ‘The Health Properties of Cran-berry Juice’ held at the Royal Society of Medicine on 3December 2013. The aim of the meeting was to gainconsensus on the health-giving properties of cranberryjuice, focusing primarily on urinary tract infections(UTIs). The meeting covered ‘Antibiotic resistance andurinary tract infections’, ‘The role of proanthocyanidins(PACs) and cranberries in urinary tract health’,‘Polyphenols, cranberries and health’ and ‘The potentialhealth benefits of cranberries in the context of a healthydiet and lifestyle’.

The meeting was chaired by Professor Stuart Stanton,President of the British Society of Urogynaecology, whointroduced the session by rhetorically questioning thedifferent roles of cranberry juice as a prophylactic. Newdevelopments and the future of cranberry juice withinthe health arena were suggested as potential topics fordiscussion after the presentations.

Summary of presentations

Cranberries and urinary tract infections

Dr Sarah Brewer (Medical Nutritionist and HealthWriter) examined the evidence and the links betweencranberries and UTIs. UTIs are a public health challengefor the UK accounting for 1–3% of all general practi-tioner consultations. Between April 2012 and March2013, there were 281 296 finished consultant episodesof UTI admission to UK hospitals (NICE 2013). In theUK, 1 in 3 women have at least one UTI by age 24 years,1 in 2 women are treated for at least one UTI duringtheir life and after an initial UTI, 20–30% of womenexperience a recurrence. This must be viewed alongsidethe fact that antibiotic resistance is a growing problem.

Ninety percent of UTIs are due to Escherichia coli (E.coli) infection, with the most common pathway beingtransferred from the rectum. The female urethra is 4 cmlong (as opposed to the male urethra of 20 cm), soaccess for E. coli in the urinary tract is easier in women.Sexual activity can multiply a woman’s risk of UTI by14 times.

Ninety-five percent of uropathogenic E. coli expresselongated type 1 fimbriae (pilae), which are longfilamentation appendages that greatly enhance the bact-eria’s ability to attach to the host and cause disease.E. coli may have as many as 100–400 fimbriae, someextending hundreds of nanometers in length. Thefimbriae contain subunits of glycan-binding proteins(lectins) that interact with glycoproteins on host cells.Bacterial lectins play a role in cell recognition and are aprerequisite for bacterial colonisation and infection, soare often also called adhesins. Bacteria are initiallyattracted to the bladder wall by weak, non-specific forcesand an initial low-affinity attachment occurs between theadhesion protein on the fimbrial tip (FimH) and the hostreceptor (mannose). Initial interactions are reinforced byadditional receptor pairing and when the body tries toshift the E. coli they are locked on tightly by a shear forceenhanced, catch-bond mechanism that leads to a high-affinity binding. This results in the micro-organism beingdifficult to flush from the cells lining the urinary tract.

An anti-adhesion mechanism to prevent the bindingprocess of micro-organisms is the blocking of adhesinswith soluble molecules; one potential molecule is theunique A-type proanthocyanidin, a polyphenol found incranberries. This differs from B-type proanthocyanidins(found in dark chocolate, green tea, apple or grape juice)due to differences in the bonding structure that influencetheir biological properties. Type A proanthocyanidinshave an ether-type bond, whereas B-type proan-thocyanidins have a single bond. Because of this differ-ence in structure, A-type proanthocyanidins showgreater inhibition of in vitro adhesion of E. coli fimbriaeand block E. coli adhesins by inhibiting bacterial surfaceattachment. They inhibit swarming motility and aggre-gation into biofilms, and so the blocked bacteria areeventually ‘flushed’ from the urinary tract. Consuming

Correspondence: Elaine Gardner, Dietitian, London, UK.E-mail: Elaine@RDejg-nutrition.org

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cranberry juice (240 ml) with A-type proanthocyanidinsinhibits bacterial adhesion, with activity peaking at 4–6hours and persisting for at least 8 hours. No effect is seenwith B-type proanthocyanidins, suggesting either thatthey do not have bacterial anti-adhesion activity or thecompounds they contain are not bioavailable (Howellet al. 2005).

Clinical trials pose challenges to achieving convincingresults and require high numbers to demonstrate statis-tical significance with consistent, definable endpoints.Among other factors, sufficient duration to show aresponse is needed, alongside the use of a suitableplacebo for gold-standard randomised controlled trials(RCTs). Because of its acidity and unique taste, a goodplacebo is difficult to find for cranberry. Furthermore,consideration of the logistics associated with transport-ing cartons of liquid and collecting and analysing urinesamples is needed, as well as a way in which to assesscompliance. Therefore, taking the aforementioned intoconsideration, it is not surprising that results from clini-cal trials differ greatly.

Looking at the clinical evidence available regardingthe use of cranberries in the prevention of UTIs, a meta-analysis from 2004 established that recurrence ratesover 1 year were reduced by approximately 35% inyoung to middle-aged women who consumed 250 ml ofcranberry juice daily (or equivalent in concentrates ortablet forms) (Guay 2009). In a Cochrane review(Jepson & Craig 2008), studies on the consumption ofcranberry products demonstrated a decrease in thenumber of symptomatic UTIs over a 12-month period,particularly for women with recurrent UTIs. However,when this was updated and a further 14 studies wereadded to the meta-analysis, the effectiveness of cran-berry was not significantly different to antibiotics forwomen [relative risk (RR) 1.31, 95% confidence inter-val (CI) 0.85, 2.02] (Jepson et al. 2012). A systematicreview including 13 trials (n = 1494) compared preven-tion of UTIs in users of cranberry-containing productsvs. placebo or non-placebo controls (Wang et al. 2012).The findings showed that cranberry-containing prod-ucts were associated with a protective effect againstUTIs especially among women with recurrent UTIs (RR0.53; 95% CI, 0.33–0.83) (I2 = 0%) and those whoused cranberry-containing products more than twice aday (RR, 0.58; 95% CI, 0.40–0.84) (I2 = 18%). The I2

statistic looks at levels of heterogeneity, with I2 = <25%indicating small heterogeneity in both these associa-tions. One of the main criticisms, however, within boththe Cochrane reviews and the Wang et al. (2012)review was the ‘substantial heterogeneity acrosstrials’. Overall, trial results were conflicting due to

poor quality design, insufficient study numbers (so thechance of showing a statistical difference is low), insuf-ficient time for follow-up, limited information on studymethodology and a lack of defined endpoints such assymptomatic UTI or defined thresholds for asympto-matic bacteriuria.

In paediatric trials, Afshar et al. (2012) gave 40 chil-dren cranberry juice or a placebo and found a 65%reduction in the incidence of UTIs. Ferrara et al. (2009)gave 84 girls cranberry juice for 6 months, resulting in alower UTI incidence (18.5%) compared with controls(48.1%). In a study of 263 children treated for UTIs,cranberry juice or placebo was given for 6 months.Results showed a lower incidence (27 vs. 47 episodes) ofrecurrent UTIs and a reduced number of days in whichantibiotics were required (12 vs. 18 days) (Salo et al.2012).

Antibiotic resistance and urinary tract infections

A review of antibiotic resistance and UTIs was deliveredby Dr Ann Pallett (Lead Clinical Infection Specialist,University Hospital Southampton Trust) who focusedon antibiotic-resistant coliform bacteria and uncompli-cated (simple) UTIs, as well as the issue of fewer routineantibiotics being appropriate to treat UTIs.

Extended spectrum beta-lactases (ESBLs) are enzymesproduced by gram-negative bacteria, including E. coliand Klebsiella species that can inactivate common anti-biotics such as cephalosporins. Their plasmids alsocontain resistance genes to the antibiotics ciprofloxacinand trimethoprim. Following the discovery of ESBLs in1983, they began to spread worldwide. For example, inSouthampton in 2004, there was an outbreak of ESBL-producing E. coli infection, predominately affectingelderly catheterised patients or those with urinary tractpathology. Among those affected, there was prior use ofantibiotics and recent hospitalisation (including innursing homes) or recent travel to India (where 60% ofE. coli infections are ESBLs). A high proportion of theinfections resulted in bacteraemia (bacteria present inthe blood) with resultant mortality.

AmpC beta-lactamases [enzymes that hydrolysebroad and extended-spectrum cephalosporin (antibiot-ics) but are not inhibited by beta-lactamase inhibitorssuch as clavulanic acid] are typically encoded on thechromosome of gram-negative bacteria includingEnterobacter species. Their production is triggered byexposure to beta-lactam antibiotics, leading to cephalo-sporin, co-amoxiclav (and amoxicillin) (antibiotic)resistance. They may also be resistant to the antibioticstrimethoprim and ciprofloxacin.

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Carbapenems are a powerful group of broad-spectrum antibiotics which currently, in many cases, areour last effective defence against multi-resistant bacte-rial infections. What is of concern, however, is thatresistance is beginning to emerge towards carbapenemsin the form of New Delhi metallo beta-lactamase(NDM-1), an enzyme that inactivates carbapenem anti-biotics. Bacteria with NDM-1 are most widespread inthe Indian subcontinent but have spread to variouscountries around the world, including the UK, whichdetected its first case in 2008 and reported 32 cases in2009 (Kumarasamy et al. 2010).

The level of carbapenem-resistant Enterobacteriaceae(CRE) infections in the US has been documentedrecently (CDC 2013). In 140 000 health care-associatedEnterobacteriaceae infections each year, approximately9300 are caused by CRE. Each year, about 600 deathsresult from infections caused by the two most commontypes: carbapenem-resistant Klebsiella species (520deaths) and carbapenem-resistant E. coli (90 deaths).Centers for Disease Control and Prevention labora-tories in the US have confirmed at least one type of CREin healthcare facilities in 44 states and 4% of US short-stay hospitals (18% of long-term acute care hospitals)had at least one patient with a serious CRE infectionduring the first half of 2012 (CDC 2013). One issue inthe UK has been problems with sensitivity testing,and resistance figures have been misleading due tomethodologies.

Asymptomatic bacteriuria (the presence of bacteriain urine) occurs in 1% of schoolgirls, 20% of healthywomen and at much higher levels in the elderly, eventhose living in the community (as opposed to carefacilities). As stated, it is associated with sexual activ-ity, whereas it is also more common in people withdiabetes. It is rare in young men, but increases over theage of 60 to 6–15% for those living in the community.Between 25% and 50% of elderly women and15–40% of elderly men in care facilities have bacte-riuria, and patients with catheters acquire bacteriuriaat the rate of 2–7% per day (Nicolle et al. 2005).Diagnosis of symptomatic UTIs can be difficult, espe-cially in the confused elderly patient because of non-specificity and misleading symptoms and signs; manyactually present with signs of a chest infection (Rao &Patel 2009). Diagnosis of a UTI is often based on urineexamination but it is difficult to collect an uncontami-nated urine specimen and in a catheterised patient,urine culture is frequently positive. Furthermore, posi-tive leukocyte esterase (a urine test for the presence ofinfection) and nitrite tests are less reliable in this groupwith a <50% positive predictive value.

An uncomplicated or simple UTI is defined in womenas the absence of fever, flank pain or other suspicion ofpyelonephritis (kidney infection). They should not bepregnant or immunocompromised, and they shouldhave no anatomical abnormalities. The Infectious Dis-eases Society of America (IDSA) Guidelines provide anapproach to choosing an optimal antimicrobial agentfor the treatment of acute uncomplicated UTIs and notethat women who are post-menopausal or have well-controlled diabetes without urological sequelae mayhave an uncomplicated UTI, and thus a short course ofantibiotics can be used in this group (Gupta et al. 2011).Symptoms are required before treatment, not just thepresence of micro-organisms in the urine. Older womenover 65 years with uncomplicated UTIs do not need alonger course of antibiotics and should be treated assimple UTIs, unless they belong to a group with anincreased risk of complications (Jepson et al. 2012).

Recurrent UTIs (defined in women as two or moreinfections in 6 months or three or more in 1 year) shouldhave a urine culture sent at recurrence (if within 2weeks) and at relapse, and be treated as for a simpleUTI, alongside advice not to use a diaphragm and sper-micides (Gupta & Trautner 2013). In these circum-stances patient-initiated therapy is recommended (this iswhen a patient is given a prescription and asked to waitand see whether they still require the antibiotics as thesymptoms of some UTIs self-resolve). Prophylaxistreatment can be a low-dose antibiotic (such asnitrofurantoin or trimethoprim) post coital or threetimes per week or daily at night for about 6 months.This reduces the risk of adverse effects and the develop-ment of antibiotic resistance. Asymptomatic bacteriuriashould NOT be treated with antibiotics (except in preg-nancy as it can lead to pyelonephritis, a potential causeof miscarriage) as they can damage bowel flora, mayincrease the risk of cystitis and can lead to a selection ofresistant organisms. Cranberry products should also beconsidered; however, the potential benefit of cranberrywith regard to product type (solid vs. liquid), dosing andoptimal patient population remains to be elucidated. ACochrane review (Jepson et al. 2012) concluded that theeffect of daily cranberry products (juice or tablets)decreases the frequency of recurrent infection in womenwith recurrent UTIs by about 30–40%, but theoptimum dosage or method of administration is notclear. Beerepoot et al. (2011) showed that cranberrycapsules are less effective than low-dose antibiotics inthe prevention of recurrent UTIs in pre-menopausalwomen. However, in contrast to low-dose antibiotics,cranberries do not result in an increase in resistantmicro-organisms in the commensal flora.

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Polyphenols, cranberries and health

Gaynor Bussell (Dietitian and Registered Nutritionist)provided a summary of the polyphenol components incranberries and their potential links with health. Cran-berries are among the fruits with the highest polyphenolcontent, with a level of 373 mg of total phenolsper serving (pear = 317 mg per serving; straw-berries = 195 mg per serving; green grapes = 155 mg perserving) (Bhagwat et al. 2013).

Although some of the research on polyphenols, par-ticularly regarding mechanisms, comes from in vitrostudies, and as such cannot be directly transferred toeffects on the human body there are an increasingnumber of studies in vivo that are looking at the poten-tial effects of polyphenols. Many of these are short termhowever, and longer term effects of polyphenols cannotyet be attributed. In vitro, polyphenols have been shownto exhibit a wide range of biological and pharmacologi-cal activities such as anti-allergenic, anti-microbial (anti-bacterial, anti-fungal and anti-viral), anti-cancer, anti-diarrheal and anti-platelet activity. Caution needs to beexercised before extrapolating these findings further (i.e.in vitro), as the majority of work in this domain is beingundertaken in vivo. The European Food Safety Author-ity (EFSA) has now allowed some health claims for thepolyphenols found in olive oil and cocoa through Article14 of the health claims regulation, but as yet no healthclaims directly related to cranberries have beenapproved. However, studies are currently ongoing witha view to resubmitting a potential proposal for a healthclaim in 2014.

Polyphenols include flavonoids (or bioflavonoids), themost common group of polyphenolic compounds in thehuman diet, which are found ubiquitously in plants andmay have anti-inflammatory potential (Ruel &Couillard 2007; Hooper & Frazier 2012). Flavanols(further subdivided into flavan-3-ols and includingproanthocyanidins) and flavonols (such as quercetin)are both distinct forms of flavonoids and both arefound in cranberries. Cranberry has the highestproanthocyanidin content among similar fruits, con-taining 418.8 mg/100 g (blueberry = 331.9 mg/100 g;strawberry = 145 mg/100 g) (Gu et al. 2004) with51–91% of total proanthocyanidins found as the A-typeproanthocyanidin structure.

With regard to heart health, Basu et al. (2010)reviewed 20 human intervention studies using berries(including eight studies involving cranberries) or puri-fied anthocyanin extracts. In two RCTs involving cran-berries (a total of 21 healthy volunteers), cranberryconsumption was shown to significantly reduce post-

prandial oxidative stress, especially lipid peroxidation(Pederson et al. 2000; Jensen et al. 2008). Basu et al.(2010) suggest that consumption of berries, includingthe different varieties included in the other ten studies,may counteract post-prandial metabolic and oxidativestresses associated with coronary artery disease. In astudy by Ruel et al. (2008) (n = 30) consumption ofincreasing levels of cranberry juice (125, 250 and500 ml/day) in successive 4-week phases showed adecrease in systolic blood pressure (P < 0.05). Basu et al.(2010) propose that further studies are needed to look atthe potential of berry supplementation for the manage-ment of hypertension. Underlying mechanisms thoughtto influence these effects include up-regulation ofendothelial nitric oxide synthase, decreased oxidativestress, as well as inhibition of inflammatory gene expres-sion and foam cell formation (Basu et al. 2010).

In a randomised, double-blind, placebo-controlledtrial, Basu et al. (2011) demonstrated that cranberryjuice consumption (two cups per day) significantlydecreased oxidised low-density lipoprotein (oxLDL)(which can lead to the initiation of the inflammationprocess and development of plaque in arteries) andmalondialdehyde (MDA, a marker for oxidative stress)following 8 weeks of juice consumption comparedwith a placebo (−33% vs. −17% decrease in oxLDL;−50% decrease vs. +7% increase in MDA, P < 0.05).A. Basu (personal communication, 24 March 2014)stated that a non-significant increase in MDA in theplacebo group is common over a period of time suchas 8 weeks, and could be initiated by other serum anti-oxidants such as glutathione not measured in thestudy. The significant decrease of MDA, along withoxLDL, in the cranberry juice group as compared withthe placebo does show some of the benefits of cran-berry supplementation. However, this study did notcause any significant improvements in blood pressure,glucose and lipid profiles or measures of inflammation(Basu et al. 2011).

Arterial stiffness can predict cardiovascular eventsand incident hypertension; in a placebo-controlledcrossover trial (n = 44), Dohadwala et al. (2011)showed significantly decreased central aortic stiffness(measured by carotid–femoral pulse wave velocity) afterdaily consumption of cranberry juice (480 ml of 54%juice; 835 mg of total polyphenols per day) in patientswith coronary artery disease. Although this was notconfirmed in a further study with obese participants(500 ml of 27% juice; 400 mg of total polyphenols perday), this is most likely due to differences in the dose ofpolyphenols used, the study population and the meas-urement indicator used. For example, Ruel et al. (2013)

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used augmentation index, which, even though it is acommonly accepted measure for arterial stiffness, doesnot relate as strongly to cardiovascular events as pulsewave velocity; Blumberg et al. (2013) suggest that pulsewave velocity has greater clinical significance.

When considering type 2 diabetes, cranberry supple-ments were found to be effective in reducing atheroscle-rotic cholesterol profiles, including LDL cholesterol andtotal cholesterol levels, as well as total:HDL cholesterolratio, but had a neutral effect on glycaemic control insubjects taking oral glucose-lowering agents (Lee et al.2008). However, some studies have suggested thatpolyphenols may influence carbohydrate digestion andabsorption and thereby post-prandial glycaemia. In aRCT, following the consumption of a purée ofpolyphenol-rich berries including cranberry, plasmaglucose concentrations were significantly lower at 15and 30 minutes (P < 0.05, P < 0.01, respectively) andsignificantly higher at 150 minutes (P < 0.05) comparedwith the control meal. The peak glucose concentrationwas reached at 45 minutes after the berry meal and at 30minutes after the control meal (Törrönen et al. 2010).The peak increase from the baseline was 1.0 mmol/lsmaller (P = 0.002) after ingestion of the berry meal.There was no statistically significant difference in the3-hour area under the glucose response curve. Thedelayed and attenuated glycaemic response suggestsreduced digestion and/or absorption of sucrose from theberry meal, although the number of subjects in the studywas low (n = 12). Shidfar et al. (2012) found that onecup of cranberry juice per day taken for 12 weeks intype 2 diabetic male patients was effective in reducingserum glucose and apolipoprotein B (the main lipopro-tein fraction in LDL) and increasing apolipoprotein A-1and serum paraoxonase-1 activity (both components ofhigh-density lipoprotein) so may have beneficial effectson reducing CVD risk factors, but again study numberswere low.

It has been suggested that proanthocyanidins fromcranberry juice might inhibit formation of plaque byStreptococcus mutans (S. mutans) pathogens that causetooth decay. Bacterial coaggregation leads to plaqueformation and then biofilm development on surfaces ofthe oral cavity. A recent study (Babu et al. 2012) foundcranberry consumption could inhibit adhesion of bacte-ria and prevent bacterial coaggregation of bacterialpairs in vitro. This study used microtitre plates toexamine the metabolic activity of Streptococcusgordonii (S. gordonii) and biofilm formation, whenchallenged with cranberry extract and a control on avariety of dental surfaces, such as amalgam and dentalcomposite. Cranberry selectively inhibited metabolic

activity of S. gordonii without affecting bacterial viabil-ity at low concentrations of 0.05–0.1 mg/ml. Research-ers concluded that inhibiting the metabolic activity ofbacteria in biofilm may benefit the health of the oralcavity (Babu et al. 2012).

The flavonoids in cranberries have shown possibleactivity as anti-cancer agents in vitro, particularlyrelated to prostate, lung, ovarian and breast cancer(Seeram et al. 2006; Déziel et al. 2012). Research isongoing to examine the effect in vivo, and whole cran-berry extract has been found to affect the behaviour ofcancer cells, in particular affecting the cell cycle inthree different tumour cells (Ferguson et al. 2006).Katsargyris et al. (2012) states that current data provideevidence for several anti-cancer properties of eitherwhole cranberry and/or its extracts. Possible mecha-nisms are those that counteract oxidative stress,decrease inflammation and modulate macromolecularinteractions and expression of genes associated withdisease processes (Neto 2007).

In conjunction with antibiotic treatment, cranberriesmay be useful in eradicating Helicobacter pylori (H.pylori) infections, the bacteria responsible for 80–90%of stomach ulcers. The proposed mechanism is similarto the effect of cranberries in UTI infections and plaqueformation in the mouth, namely by blocking adhesionand aggregation to form a biofilm on target tissues ofpathogens (Shmuely et al. 2012).

The potential health benefits of cranberries in thecontext of a healthy diet and lifestyle

Geoff Woolford (Vice President, Research and Devel-opment and Corporate Quality, Ocean Spray) gave anoverview of some of the research associated with thepotential health benefits of cranberries. Cranberry juicehas been the subject of research for over 50 years,when the original hypothesis was that their acidity wastheir unique health-promoting element, but this theorywas refuted in 1959 in the first publication on UTI andcranberries. In the 1980s, research focused on the anti-adhesion activity of cranberry juice, quickly followedin the 1990s by the benefits of proanthocyanidinsas contained in cranberries. Research also widenedfurther than UTIs to look at the effects and benefits ofcranberry on oral health, on H. pylori and on cardio-vascular disease. Currently, there is a large multi-centreplacebo-controlled, double-blinded trial taking place at17 sites in the US and one in France, including 300women, looking at the effects of cranberry juice onthe occurrence of UTIs. This will be completed in2014.

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Beyond UTIs there is interest in the potential ‘healtheffects’ of cranberry (Blumberg et al. 2013). Theseinclude investigations into the potential benefits to oralhealth and tooth decay by reducing the level ofS. mutans, potential benefits to heart health throughreductions in blood pressure, the potential to increasethe effectiveness of the drug regime for H. pylori infec-tion and the potential to reduce the length of time spenton antibiotics for children with UTIs. Overall, Blumberget al. (2013) propose that cranberry juice may prove tobe an important nutritional approach to maintainurinary tract health.

There is little natural sugar in cranberry juice and ithas a low sugar to acid ratio of 3.8. This compares witha ratio of 1.6 for lemon juice, 10 for grapefruit juice, 15for orange juice, 24 for apple juice and 114 for grapejuice. As a result, cranberry juice needs to be sweetenedto make it palatable. This is achieved by adding sucrose,sweetener in the form of sucralose or by blending withother fruit juices containing sugars. These additionsresult in Cranberry Classic having a similar, or some-times lower, sugar content compared with other juiceswith natural sugars (Cranberry Classic = 11 g of sugars/100 ml; apple juice = 10.3 g of sugars/100 ml; grapejuice = 16.5 g of sugars/100 ml).

The addition of sugar as opposed to naturally occur-ring sugars, however, does mean that some cranberryjuice products are excluded from labelling in the UK5-A-DAY programme. This is despite the presence ofpolyphenols including proanthocyanidins in bioactiveform and their potential anti-adhesion properties.However, the 100% cranberry juice blend product isincluded as it contains no added sugars and is sweetenedwith grape juice, providing 13.9 g sugars/100 ml. Areport that looked specifically at cranberry juice con-sumers using the US National Health and NutritionExamination Survey database showed that they are lesslikely to be overweight and obese, suggesting that cran-berry juice can be part of a healthy, balanced diet(Duffey & Sutherland 2013).

Other considerations

Research has clarified the anti-coagulant effect of cran-berry. Ansell et al. (2009) randomised 30 patients onstable warfarin anti-coagulation [international normal-ised ratio (INR), range 1.7–3.3] to receive 240 ml ofcranberry juice or 240 ml of placebo beverage, oncedaily for 2 weeks. The normal INR ratings range from2.5 to 3.5 for people who are taking warfarin, but dodepend on the reason for taking it. The INR values andplasma levels of R- and S-warfarin (two different

isomers) were measured during the 2-week period andat 1-week follow-up. The cranberry juice and placebogroups (n = 14 and 16, respectively) did not differ sig-nificantly in mean plasma R- and S-warfarin concentra-tions. Ansell and colleagues concluded that a small,although statistically significant, pharmacodynamicenhancement of INR by cranberry juice at a single timepoint is unlikely to be clinically important and may be arandom change. The majority of studies have not founda significant anti-coagulation interaction between cran-berry and warfarin (Haber et al. 2012), and the refer-ence to avoiding cranberry juice in the patientprescribing leaflet has been removed (Bristol-MyersSquibb 2011). Current British National Formularyadvice, however, is that warfarin’s anti-coagulant effectis possibly enhanced by cranberry juice and thereforeconcomitant use should be avoided (BNF 2013).

The issue of antibiotic resistance was discussed by thespeakers and Dr Pallett pointed out that no new antibi-otics have been developed in the last 10 years. Publicperceptions and expectations require a behaviouralchange to avoid overprescription of antibiotics andthere may come a point where antibiotics are not anoption due to resistance. The precise dose of cranberryjuice for differing population groups needs to be definedand more studies are also needed in specific populationgroups such as the elderly, paediatrics and in pregnantwomen as these groups may be most vulnerable withregard to either the (re-)occurrence of UTIs or thosewhere alternatives to antibiotics may be most necessaryas resistance continues to increase.

Summary

UTIs are a public health challenge in the UK, which arebecoming increasingly difficult to treat due to bacteriabecoming more resistant to antibiotics. Consequently,few antibiotics are available to treat multi-resistant bac-terial infections, and now bacterial enzymes are beingproduced that have the potential to inactivate even theseremaining antibiotics. The IDSA Guidelines clearly statethat asymptomatic bacteriuria should not be treated,except in pregnancy (Gupta et al. 2011); that in thosewith recurrent UTIs, patient-initiated therapy is suit-able; and that cranberry products should also beconsidered.

Cranberry juice is successful in preventing the adhe-sion of E. coli to the bladder wall by binding withA-type proanthocyanidins, and the blocked bacteria arethen ‘flushed’ from the urinary tract. Although clinicalevidence for the use of cranberry products in UTIs hasbeen inconsistent, results from a recent meta-analysis

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(Wang et al. 2012) support the consumption ofcranberry-containing products to protect against UTIsin certain populations, such as women with recurrentUTIs. However, their potential benefit in terms ofproduct type, dosing and optimal patient populationremains to be elucidated.

Cranberries contain wide-ranging componentsincluding polyphenols, such as proanthocyanidins,anthocyanins in the skin and flesh, fibre in the form ofpectin, vitamin C and omega-3 fatty acids in the form ofalpha-linolenic acid in the seeds. There is interest in thepromising ‘health effects’ of cranberry including poten-tial benefits to oral health and tooth decay by reducingthe level of S. mutans; to heart health, through reduc-tions in blood pressure; and also possibly via increasingthe effectiveness of the drug regime for H. pylori, thebacteria responsible for 80–90% of stomach ulcers.

Because there is little natural sugar in cranberry juice,it needs to be sweetened to make it palatable. Thismeans that cranberry juice has a similar, or sometimeslower, sugar content compared with other juices withnatural sugars. The addition of sugar as opposed tonaturally occurring sugars does however excludesome cranberry juice products from labelling withinthe UK’s 5-A-DAY programme, despite the presenceof polyphenols, including proanthocyanidins, in thebioactive form.

Cranberry juice may have a role in the prevention ofUTIs, especially for those patients who would prefermore ‘natural’ treatments or are disinclined to use anti-biotics, but as yet this remains without a suitable healthclaim and as such more research is needed. With this ismind, Ocean Spray eventually plan to submit a healthclaim to EFSA regarding the benefits of cranberry juiceand UTIs in the future, and is also considering furtherclaims with regard to heart health and oral health afterfurther trials.

Conflict of interest

The meeting was sponsored by Ocean Spray and one ofthe speakers, Geoff Woolford, is an employee of OceanSpray. Views expressed are those of the speakers and notnecessarily those of Ocean Spray.

References

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