Following an application from Ocean Spray International Services Limited (UK) submitted pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of the United Kingdom, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to Ocean Spray cranberry products® containing typically 80 mg cranberry proanthocyanidins (PAC) per serving and urinary tract infection in women.
The scope of the application was proposed to fall under a health claim referring to disease risk reduction.
The foods that are the subject of the health claim are Ocean Spray cranberry products® (juice drinks and sweetened dried berries Craisins®) containing typically 80 mg cranberry proanthocyanidins (PAC) per serving. Only the fruit of the North American cranberry plant, Vaccinium macrocarpon Aiton is used as a source for these products. The PAC fraction isolated from cranberries is a mixture of epicatechin oligomers of various molecular weights, with activity associated with A-type linkages. The Panel considers that the foods that are the subject of the health claim are sufficiently characterised.
The claimed effect is “helps reduce the risk of urinary tract infection in women by inhibiting the adhesion of certain bacteria in the urinary tract”. The target population is healthy women from the age of 16 years. Urinary tract infection (UTI) refers to the presence of bacteria in the urinary tract. Symptomatic UTI are usually accompanied by bacteriuria at levels of ≥ 105 cfu/mL urine. Uropathogenic strains of E. coli bacteria cause up to 95 % of UTIs. Bacterial adherence to mucosal surfaces is generally considered to be an important prerequisite for colonisation and infection with bacteriuria. The Panel notes that bacterial adherence precedes an infection and therefore inhibition of bacterial adhesion might result in a reduction for the risk of symptomatic UTI with bacteriuria ≥105 cfu/mL. The Panel considers that the claimed effect “helps reduce the risk of urinary tract infection in women by inhibiting the adhesion of certain bacteria in the urinary tract” is beneficial to human health.
The applicant provided a considerable number of ex vivo / in vitro studies in which an in vitro inhibitory effect on bacterial adhesion to mucosal cells was demonstrated by urine obtained from healthy volunteers after the consumption of cranberry products, including the cranberry juice of the applicant. The Panel considers that these studies demonstrate an in vitro anti-adherence effect of urine on uropathogenic E. coli strains following consumption of cranberry products.
Six of a total of 12 human intervention studies claimed pertinent by the applicant, were carried out on patients suffering from neurogenic bladder, some of them children, or on patients with spinal cord injury. In another study the daily dose (1000 mg PAC) consumed was approximately 6 times higher than the use levels proposed by the applicant for the present claim (160 mg PAC/day). The Panel considers that these 7 studies are of limited relevance for the claim targeted to healthy women from the age of 16 at the proposed levels of use.
The Panel considered the other 5 human intervention studies to be pertinent to the claimed effect. Two of the 5 pertinent studies are claimed proprietary by the applicant and were designed to evaluate the effect of Ocean Spray Cranberry Juice in a randomised, double-blind, placebo-controlled study design. One of these two studies investigated the effects of 300 mL undiluted Ocean Spray cranberry juice (with estimated 100 mg PAC/day) daily consumed over 18 days in 376 elderly men and women. A total of 5.6 % of the participants developed a symptomatic UTI (primary outcome), 14 of the 189 in the placebo group and 7 from the 187 in the cranberry juice group. As the actual infection rate was lower than anticipated, the study had less than 50 % power to detect a significant difference between the intervention and control group. The short duration and lack of statistical power of this study considerably limit its value as a source of evidence to support the claimed effect.
The second randomised, placebo-controlled trial evaluating the effect of daily consumed 300 mL cranberry juice drink provided by Ocean Spray Inc. (with estimated 100 mg PAC/day) was carried out in a nursing home population of women with a mean age of 78.5 years over a period of 6 months. Bacteriuria with pyuria was found in 28 % of urine samples of the placebo group versus 15 % of the cranberry juice group. The data on the baseline measurements of the study participants, in particular on the history of previous urinary tract infections, show that the incidence of previous UTI in the 6 and 12 months prior to the intervention was 25 and 33 % in the placebo group, but only 7 and 17 % for the cranberry juice group. The lack of adequate randomisation and the high drop out rates in this study considerably limit its value as a source of evidence to support the claimed effect.
The Panel noted that in the other 3 pertinent human studies there were significant limitations, including use of different cranberry formulations from that in the application, poor study design e.g. small numbers of subjects, the lack of a control group, short duration of study, as well as high drop-out rate in some of the studies, that considerably limit their value as a source of evidence to substantiate the claimed effect.
The Panel considers that the provided studies do not establish that the anti-adherence effects of cranberry products in urine shown in vitro are predictive of the occurrence of a clinically relevant bacterial anti-adherence effect within the urinary tract under the conditions of use proposed for the claim.
The Panel concludes that the evidence provided is not sufficient to establish a cause and effect relationship between the consumption of Ocean Spray cranberry products® and the reduction of the risk of UTI in women by inhibiting the adhesion of certain bacteria in the urinary tract.