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A double-blinded, placebo-controlled, randomized trial of the neuropsychologic efficacy of cranberry juice in a sample of cognitively intact older adults: pilot study findings

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Authors
Crews WD Jr, Harrison DW, Griffin ML, Addison K, Yount AM, Giovenco MA and Hazell J.
Journal
J Altern Complement Med 11(2):305-9
Abstract

OBJECTIVES: The aim of this research was to conduct the first known clinical trial of the short-term (i.e., 6 weeks) efficacy of cranberry juice on the neuropsychologic functioning of cognitively intact older adults.PARTICIPANTS: Fifty (50) community-dwelling, cognitively intact volunteers, > or = 60 years old, who reported no history of dementia or significant neurocognitive impairments, participated in this study.DESIGN: A 6-week, double-blind, placebo-controlled, randomized, parallel-group, clinical trial was utilized. Participants were randomly assigned to receive either 32 ounces/day of a beverage containing 27% cranberry juice per volume (n = 25) or placebo (n = 25) for 6 weeks, and administered a series of neuropsychologic tests at both pretreatment baseline and again after 6 weeks of either cranberry juice or placebo treatment to assess treatment-related changes.OUTCOME MEASURES: Efficacy measures consisted of participants' raw scores on the following standardized neuropsychologic tests: Selective Reminding Test, Wechsler Memory Scale-III Faces I and Faces II subtests, Trail Making Test (Parts A and B), Stroop Color and Word Test, and the Wechsler Adult Intelligence Scale- III Digit Symbol-Coding subtest. A subjective Follow-up Self-report Questionnaire was also administered to participants at the conclusion of the end-of-treatment phase assessments.RESULTS: Two-factor, mixed analyses of variance (ANOVA) revealed no significant group (cranberry juice and placebo) by trial (pretreatment baseline and end-of-treatment assessments) interactions across all of the neuropsychologic tests and measures utilized in this study when a Bonferroni corrected alpha level was used to correct for multiple comparisons (i.e., .05/17 group by trial comparisons = .003). Pearson Chi-Square analyses of the groups' self-reported changes over the 6-week treatment phase in their abilities to remember, thinking processes, moods, energy levels, and overall health on the Follow-up Self-report Questionnaire revealed no significant relationships. However, a nonsignificant trend (X2(1) = 2.373, p = 0.123) was noted for participants' self-reported overall abilities to remember from pretreatment baseline to the end-of-treatment assessment. Specifically, more than twice as many participants in the cranberry group (n = 9, 37.5%) rated their overall abilities to remember by treatment end as "improved" as compared to placebo controls (n = 4, 17.4%).CONCLUSIONS: Taken together, no significant interactions were found between the cranberry and placebo groups and their pretreatment baseline and end-of-treatment phase (after 6 weeks) standardized neuropsychologic assessments. A nonsignificant trend was noted, however, on a subjective, self-report questionnaire where twice as many participants in the cranberry group rated their overall abilities to remember by treatment end as "improved" compared to placebo controls.

Comparison of urinary cytokines after ingestion of cranberry juice cocktail in pregnant subjects: a pilot study.

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Authors
Wing DA, Rumney PJ, Leu SY, Zaldivar F
Journal
Am J Perinatol 27(2):137-42
Abstract

Our objective was to evaluate urinary cytokine excretion after daily cranberry or placebo exposure in pregnant women. Four-hour urine samples were collected from 27 pregnant women subjects who were randomized to cranberry juice cocktail or placebo in three treatment arms: A: Cranberry (C) two times daily (C, C; n = 10 pregnant); B: cranberry in the AM, then placebo (P) in the PM (C, P; n = 9 pregnant); and C: placebo two times daily (P, P; n = 8 pregnant). Urinary cytokines were measured using commercially available kits. There was a statistically significant difference in interleukin (IL)-6 of the urinary cytokines between the multiple daily cranberry dosing group (group A [C, C]): median, 3.16 (range, 0.01 to 7.34) and the placebo group (group C [P, P]): 9.32 (0.53 to 29.61 pg/mL; p = 0.038, Kruskal-Wallis test). We concluded that a difference in IL-6 was found in the multiple daily cranberry dosing groups compared with placebo. Lack of differences based on treatment allocation in the other cytokines may be due to beta error. Further studies are planned to evaluate these assays for the assessment of clinical effect.

Cranberry juice and adhesion of antibiotic-resistant uropathogens

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Authors
Howell AB and Foxman B
Journal
JAMA 287(23):3082-3
Abstract

No abstract - Introduction: Urinary tract infections (UTIs) account for more than 11 million physician visits annually in the United States and have become increasingly resistant to first-line antibiotic therapy. Recent evidence suggests that consumption of cranberry juice beverages is effective at preventing UTIs, although further studies are needed to validate potential treatment effects. While early research focused on a mechanism of urinary acidification, the largest clinical trial to date found no evidence to support this. Recent studies suggest that cranberry proanthocyanidins (condensed tannins) may inhibit P-fimbriated Escherichia coli from adhering to uroepithelial cells, the initial step in development of UTI. The effectiveness of cranberry proanthocyanidins and cranberry beverages against antibiotic-resistant E coli, however, has not been previously tested. We assessed whether consumption of cranberry juice cocktail prevents adhesion of antibiotic-resistant uropathogenic P-fimbriated E coli to the uroepithelium.

Cranberry juice and bacterial colonization in children--a placebo-controlled randomized trial

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Authors
Kontiokari T, Salo J, Eerola E and Uhari M
Journal
Clin Nutr 24(6):1065-72
Abstract

BACKGROUND: The cranberry produces antimicrobial compounds such as proanthocyanidines in response to microbial invasion. In vitro it is able to prevent growth, adhesion or biofilm formation of a large number of bacteria, while clinically, cranberry juice has been shown to prevent urinary tract infections (UTI) in women. However, the effect of cranberry on bacterial colonization more widely has not been evaluated. We were interested in studying cranberry juice in children since many children with recurrent UTI need long-term antimicrobial prophylaxis and would benefit from an alternative.

OBJECTIVE: To evaluate the effect of cranberry juice on nasopharyngeal and colonic bacterial flora, to evaluate how well cranberry juice is accepted by children and to evaluate its effect on infectious diseases and related symptoms.

DESIGN: Children (mean age 4.3 years) in day care centers were randomized to receive either cranberry juice (n=171) or a placebo (n=170) for 3 months. Bacterial samples were collected before and after the intervention and analyzed for both respiratory bacterial pathogens and enteric fatty acid composition, reflecting changes in the colonic bacterial flora. Infectious diseases and their symptoms were monitored using symptom diaries. Compliance was evaluated as the number of drop-outs during the trial and by counting the numbers of doses taken.

RESULTS: The carriage of respiratory bacteria did not change significantly during the intervention, while fecal fatty acid composition changed significantly with time (P0.001) but did not differ between the groups (P>0.05). Cranberry juice had no effect on common infectious diseases or their symptoms. The cranberry juice was well accepted: the number of drop-outs in 3 months was 18 (11%) in the cranberry group and 11 (7%) in the placebo group, and most of the doses were taken as instructed, 145 (88%) and 129 (77%) children, respectively, taking at least 90% of the doses.

CONCLUSIONS: Cranberry juice was well accepted by the children, but led to no change in either the bacterial flora in the nasopharynx or the bacterial fatty acid composition of stools. Thus cranberries seem to have beneficial effect on urinary health only and this is not compromised by other unexpected antimicrobial effects.

Cranberry juice induces nitric oxide-dependent vasodilation in vitro and its infusion transiently reduces blood pressure in anesthetized rats

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Authors
Maher MA, Mataczynski H, Stefaniak HM and Wilson T
Journal
J Med Food 3(3):141-7
Abstract

ABSTRACT Red wine vasodilates rat aortae, an effect attributed to polyphenolic compounds. Cranberry juice (CBJ) is also rich in polyphenols. We determined that CBJ has vasorelaxing properties similar to those of red wine. Rat aortic rings cleaned in Krebs buffer, pH 7.4, bubbled with 95% O(2) and 5% CO(2) were recovered for 30 minutes at 37 degrees C under 2.0 g tension. After phenylephrine (PE, 100 mumol/L) contraction, acetylcholine (3 mumol/L)-induced relaxation of intact vessel was significantly higher than in denuded vessels (59.1 +/- 0.27% versus 10.1 +/- 0.09% of the maximal PE contraction; P .003). After a second PE contraction, a 1:100 dilution of CBJ was added. Intact rings were vasodilated by CBJ with 56.7 +/- 0.26% relaxation, compared to denuded rings with 8.9 +/- 0.06% relaxation (P .002). Addition of L-NAME reversed CBJ-induced vasorelaxation in intact vessels with 0.54 +/- 0.34 g compared to 0.04 +/- 0.04 g in denuded vessels (P .007). Subsequent addition of L-arginine resulted in a return of vasodilation in intact vessels. Additionally, CBJ infusion at a 1:100 dilution of estimated blood volume resulted in a 16% reduction of mean arterial blood pressure in anesthetized rats. This study suggests that, like red wine, CBJ has the capacity to exert in vitro and in vivo vasodilatory effects.

Does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? A double-blind, placebo-controlled trial.

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Authors
McMurdo ME, Bissett LY, Price RJ, Phillips G and Crombie IK
Journal
Age Aging 34(3):256-61
Abstract

Background: cranberry juice is often given to older people in hospital to prevent urinary tract infection (UTI), although
there is little evidence to support its use.
Objective: to assess whether cranberry juice ingestion is effective in reducing UTIs in older people in hospital.
Design: randomised, placebo-controlled, double-blind trial.
Setting: Medicine for the Elderly assessment and rehabilitation hospital wards.
Subjects: 376 older patients in hospital.
Methods: participants were randomised to daily ingestion of 300 ml of cranberry juice or matching placebo beverage. The primary outcome was time to onset of first UTI. Secondary outcomes were adherence to beverage drinking, courses of antibiotics prescribed, and organisms responsible for UTIs.
Results: a total of 21/376 (5.6%) participants developed a symptomatic UTI: 14/189 in the placebo group and 7/187 in the cranberry juice group. These between-group differences were not significant, relative risk (RR) 0.51 [95% CI 0.21–1.22, P = 0.122). Although there were significantly fewer infections with Escherichia coli in the cranberry group (13 versus 4) RR 0.31 [95% CI 0.10–0.94, P =0.027], this should be interpreted with caution as it was a secondary outcome.
Conclusion: despite having the largest sample size of any clinical trial yet to have examined the effect of cranberry juice ingestion, the actual infection rate observed was lower than anticipated, making the study underpowered. This study has confirmed the acceptability of cranberry juice to older people. Larger trials are now required to determine whether it is effective in reducing UTIs in older hospital patients.

Inhibitory effect of cranberry polyphenol on cariogenic bacteria

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Authors
Yamanaka-Okada A, Sato E, Kouchi T, Kimizuka R, Kato T, Okuda K
Journal
Bull Tokyo Dent Coll 49(3):107-12
Abstract

The purpose of this study was to investigate the effect of cranberry polyphenol fraction on mutans streptococci. Hydrophobicity is an important factor in the adherence of bacteria to the tooth surface. We found that cranberry polyphenol fraction significantly decreased the hydrophobicity of Streptococcus sobrinus 6715, Streptococcus mutans MT8148R and JC2 in a dose-dependent manner (p0.05). Biofilm formation by S. sobrinus 6715 and S. mutans MT8148R was inhibited by 100 microg/ml cranberry polyphenol fraction (p0.01). When dosage was increased to 500 microg/ml, biofilm formation by S. mutans JC2 was significantly inhibited (p0.05). Addition of 500 microg/ml cranberry polyphenol fraction to medium inhibited growth of S. mutans MT8148R compared with the control (p0.05).

Modulation of Helicobacter pylori colonization with cranberry juice and Lactobacillus johnsonii La1 in children

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Authors
Gotteland M, Andrews M, Toledo M, Munoz L, Caceres P, Anziani A, Wittig E, Speisky H, Salazar G.
Journal
Nutrition 24(5):421-426
Abstract

OBJECTIVE: Probiotics and cranberry have been shown to inhibit Helicobacter pylori in vitro owing to bacteriocin production and high levels of proanthocyanidins, respectively. These effects have been confirmed in clinical trials with H. pylori-positive subjects. The aim of this study was to evaluate whether regular intake of cranberry juice and the probiotic Lactobacillus johnsonii La1 (La1) may result in an additive or synergistic inhibition of H. pylori in colonized children.METHODS: A multicentric, randomized, controlled, double-blind trial was carried out in 295 asymptomatic children (6-16 y of age) who tested positive for H. pylori by (13)C-urea breath test (UBT). Subjects were allocated in four groups: cranberry juice/La1 (CB/La1), placebo juice/La1 (La1), cranberry juice/heat-killed La1 (CB), and placebo juice/heat-killed La1 (control). Cranberry juice (200 mL) and La1 product (80 mL) were given daily for 3 wk, after which a second UBT was carried out. A third UBT was done after a 1-mo washout in those children who tested negative in the second UBT.RESULTS: Two hundred seventy-one children completed the treatment period (dropout 8.1%). Helicobacter pylori eradication rates significantly differed in the four groups: 1.5% in the control group compared with 14.9%, 16.9%, and 22.9% in the La1, CB, and CB/La1 groups, respectively (P 0.01); the latter group showed a slight but not significant increase when compared with the other treated groups. The third UBT was carried out only in 19 of the 38 children who tested negative in the second UBT and H. pylori was detected in 80% of them.CONCLUSION: These results suggest that regular intake of cranberry juice or La1 may be useful in the management of asymptomatic children colonized by H. pylori; however, no synergistic inhibitory effects on H. pylori colonization were observed when both foodstuffs were simultaneously consumed.

Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women

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Authors
Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M and Uhari M
Journal
BMJ 322(7302):1571
Abstract

OBJECTIVE: To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink. Design: Open, randomised controlled 12 month follow up trial.

SETTING: Health centres for university students and staff of university hospital.

PARTICIPANTS: 150 women with urinary tract infection caused by Escherichia coli randomly allocated into three groups. Interventions: 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention. Main outcome measure: First recurrence of symptomatic urinary tract infection, defined as bacterial growth >/=10(5 )colony forming units/ml in a clean voided midstream urine specimen.

RESULTS: The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34).

CONCLUSION: Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection.

Reduction of Escherichia coli adherence to uroepithelial bladder cells after consumption of cranberry juice: a double-blind randomized placebo-controlled cross-over trial

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Authors
Di Martino P, Agniel R, David K, Templer C, Gaillard JL, Denys P, Botto H
Journal
World J Urol 24(1):21-7
Abstract

To determine the efficacy of the consumption of cranberry juice versus placebo with regard to the presence of in vitro bacterial anti-adherence activity in the urine of healthy volunteers. Twenty healthy volunteers, 10 men and 10 women, were included. The study was a double-blind, randomized, placebo-controlled, and cross-over study. In addition to normal diet, each volunteer received at dinner a single dose of 750 ml of a total drink composed of: (1) 250 ml of the placebo and 500 ml of mineral water, or (2) 750 ml of the placebo, or (3) 250 ml of the cranberry juice and 500 ml of mineral water, or (4) 750 ml of the cranberry juice. Each volunteer took the four regimens successively in a randomly order, with a washout period of at least 6 days between every change in regimen. The first urine of the morning following cranberry or placebo consumption was collected and used to support bacterial growth. Six uropathogenic Escherichia coli strains (all expressing type 1 pili; three positive for the gene marker for P-fimbriae papC and three negative for papC), previously isolated from patients with symptomatic urinary tract infections, were grown in urine samples and tested for their ability to adhere to the T24 bladder cell line in vitro. There were no significant differences in the pH or specific gravity between the urine samples collected after cranberry or placebo consumption. We observed a dose dependent significant decrease in bacterial adherence associated with cranberry consumption. Adherence inhibition was observed independently from the presence of genes encoding type P pili and antibiotic resistance phenotypes. Cranberry juice consumption provides significant anti-adherence activity against different E. coli uropathogenic strains in the urine compared with placebo.