Scope: Methods to verify cranberry juice consumption are lacking. Predictive multivariate models built upon validated biomarkers may help to verify human consumption of a food using a nutrimetabolomics approach. Methods: A 21-day double-blinded, randomized, placebo-controlled, cross-over study was conducted among healthy young women aged 1829. Plasma was collected at baseline and after 3-day and 21-day consumption of cranberry or placebo juice. Plasma metabolome was analyzed using UHPLC coupled with high resolution mass spectrometry. Results: 18 discriminant metabolites in positive mode and 18 discriminant metabolites in negative mode from a previous 3-day open-label study were re-discovered in the present blinded study. Predictive orthogonal partial least squares discriminant analysis (OPLS-DA) models were able to identify cranberry juice consumers over a placebo juice group with 96.9% correction rates after 3-day consumption in both positive and negative mode. This present study revealed 84 and 109 additional discriminant metabolites in positive and negative mode, respectively. Twelve of them were tentatively identified. Conclusion: Cranberry juice consumers were classified with high correction rates using predictive OPLS-DA models built upon validated plasma biomarkers. Additional biomarkers were tentatively identified. These OPLS-DA models and biomarkers provided an objective approach to verify participant compliance in future clinical trials..

The objectives of this research were to investigate urinary metabolome modifications and discover potential intake biomarkers in young women after cranberry juice consumption. Fifteen female college students were given either cranberry juice or apple juice for three days using a cross-over design. Urine samples were collected before and after juice consumption. The metabolome in the urine was analyzed using UHPLC-Q-orbitrap-HRMS-based metabolomics followed by orthogonal partial least squares-discriminant analyses (OPLS-DA). An S-plot was used to identify discriminant metabolites. Validated OPLS-DA analyses showed that cranberry juice consumption significantly altered the urinary metabolome. Compared to the baseline urine or urine after apple juice consumption, cranberry juice consumption increased urinary excretion of both exogenous and endogenous metabolites. The tentatively identified exogenous metabolites included quinic acid, coumaric acid, 4-hydroxy-5-(hydroxyphenyl)-valeric acid-O-sulphate, 5-(dihydroxyphenyl)-P-valerolactone sulfate, diphenol glucuronide, 3,4-dihydroxyphenyl propionic acid, 3-(hydroxyphenyl) propionic acid, 4-O-methylgallic acid, trihydroxybenzoic acid and 1,3,5-trimethoxybenzene. Modifications of endogenous metabolites after cranberry juice consumption included the increases in homocitric acid, hippuric acid, 3-hydroxy-3-carboxymethyl-adipic acid, (2)3-isopropylmalate, pimelic acid and N-acetyl-L-glutamate 5-semialdehyde. These metabolites may serve as urinary biomarkers of cranberry juice consumption and contribute to the bioactivities of cranberries against urinary tract infection.

The worrying rise in antibiotic resistances emphasizes the need to seek new approaches for treating and preventing periodontal diseases. The purpose of this study was to evaluate the antibacterial and anti-biofilm activity of cranberry in a validated in vitro biofilm model. After chemical characterization of a selected phenolic-rich cranberry extract, its values for minimum inhibitory concentration and minimum bactericidal concentration were calculated for the six bacteria forming the biofilm (Streptococcus oralis, Actinomyces naeslundii, Veillonella parvula, Fusobacterium nucleatum, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans). Antibacterial activity of the cranberry extract in the formed biofilm was evaluated by assessing the reduction in bacteria viability, using quantitative polymerase chain reaction (qPCR) combined with propidium monoazide (PMA), and by confocal laser scanning microscopy (CLSM), and anti-biofilm activity by studying the inhibition of the incorporation of different bacteria species in biofilms formed in the presence of the cranberry extract, using qPCR and CLSM. In planktonic state, bacteria viability was significantly reduced by cranberry (p < 0.05). When growing in biofilms, a significant effect was observed against initial and early colonizers (S. oralis (p 0.017), A. naeslundii (p = 0.006) and V. parvula (p = 0.010)) after 30 or 60 s of exposure, while no significant effects were detected against periodontal pathogens (F. nucleatum, P. gingivalis or A. actinomycetemcomitans (p > 0.05)). Conversely, cranberry significantly (p < 0.001 in all cases) interfered with the incorporation of five of the six bacteria species during the development of 6 h-biofilms, including P. gingivalis, A. actinomycetemcomitans, and F. nucleatum. It was concluded that cranberry had a moderate antibacterial effect against periodontal pathogens in biofilms, but relevant anti-biofilm properties, by affecting bacteria adhesion in the first 6 h of development of biofilms

Cranberry is a well-known functional food, but the compounds directly responsible for many of its reported health benefits remain unidentified. Complex carbohydrates, specifically xyloglucan and pectic oligosaccharides, are the newest recognized class of biologically active compounds identified in cranberry materials. Cranberry oligosaccharides have shown similar biological properties as other dietary oligosaccharides, including effects on bacterial adhesion, biofilm formation, and microbial growth. Immunomodulatory and anti-inflammatory activity has also been observed. Oligosaccharides may therefore be significant contributors to many of the health benefits associated with cranberry products. Soluble oligosaccharides are present at relatively high concentrations (~20% w/w or greater) in many cranberry materials, and yet their possible contributions to biological activity have remained unrecognized. This is partly due to the inherent difficulty of detecting these compounds without intentionally seeking them. Inconsistencies in product descriptions and terminology have led to additional confusion regarding cranberry product composition and the possible presence of oligosaccharides. This review will present our current understanding of cranberry oligosaccharides and will discuss their occurrence, structures, ADME, biological properties, and possible prebiotic effects for both gut and urinary tract microbiota. Our hope is that future investigators will consider these compounds as possible significant contributors to the observed biological effects of cranberry

This review summarizes the mechanistic and clinical research on the use of cranberry as an alternative management strategy for H. pylori bacteria in populations at high risk for infection-induced peptic ulcers and gastric cancer. The multiple mechanisms of action of cranberry polyphenols and how they may be applied in relation to what is known about the pathogenicity of H. pylori offers opportunity for utilizing this fruit to potentially help lower the incidence of ulcers and concomitant gastric cancer

The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran R). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran R were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran TM Phytosome TM, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone was found effective thus confirming the ex-vivo results.

INTRODUCTION: Ecological approaches to dental caries prevention play a key role in attaining long-term control over the disease and maintaining a symbiotic oral microbiome. OBJECTIVES: This study aimed to investigate the microbial ecological effects of 2 interventional dentifrices: a casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) dentifrice and the same dentifrice supplemented with a polyphenol-rich cranberry extract. METHODS: The interventional toothpastes were compared with each other and with an active control fluoride dentifrice in a double-blinded randomized controlled trial. Real-time quantitative polymerase chain reaction (qPCR) analysis was used to determine changes in the bacterial loads of 14 key bacterial species (8 caries associated and 6 health associated) in the dental plaque of trial participants after they used the dentifrices for 5 to 6 wk. RESULTS: From the baseline to the recall visit, significant differences were observed between the treatment groups in the bacterial loads of 2 caries-associated bacterial species (Streptococcus mutans [P < 0.001] and Veillonella parvula [P < 0.001]) and 3 health-associated bacterial species (Corynebacterium durum [P = 0.008], Neisseria flavescens [P = 0.005], and Streptococcus sanguinis [P < 0.001]). Compared to the fluoride control dentifrice, the CPP-ACP dentifrice demonstrated significant differences for S. mutans (P = 0.032), C. durum (P = 0.007), and S. sanguinis (P < 0.001), while combination CPP-ACP-cranberry dentifrice showed significant differences for S. mutans (P < 0.001), V. parvula (P < 0.001), N. flavescens (P = 0.003), and S. sanguinis (P < 0.001). However, no significant differences were observed in the bacterial load comparisons between the CPP-ACP and combination dentifrices for any of the targeted bacterial species (P > 0.05). CONCLUSIONS: Overall, the results indicate that dentifrices containing CPP-ACP and polyphenol-rich cranberry extracts can influence a species-level shift in the ecology of the oral microbiome, resulting in a microbial community less associated with dental caries (Australian New Zealand Clinical Trial Registry ANZCTR 12618000095268). KNOWLEDGE TRANSFER STATEMENT: The results of this randomized controlled trial indicate that dentifrices containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and polyphenol-rich cranberry extracts were able to beneficially modulate the microbial ecology of dental plaque in a group of high caries-risk patients. This could contribute toward lowering the risk of developing new caries lesions, an important goal sought by patients, clinicians, and policy makers.

BACKGROUND AND AIM: Dietary strategies that contribute to reducing incidence of Helicobacter pylori infection without negative side effects are highly desirable owing to worldwide bacterial prevalence and carcinogenesis potential. The aim of this study was to determine dosage effect of daily cranberry consumption on H. pylori suppression over time in infected adults to assess the potential of this complementary management strategy in a region with high gastric cancer risk and high prevalence of H. pylori infection. METHODS: This double-blind, randomized, placebo-controlled trial on 522 H. pylori-positive adults evaluated dose-response effects of proanthocyanidin-standardized cranberry juice, cranberry powder, or their placebos on suppression of H. pylori at 2 and 8 weeks by 13 C-urea breath testing and eradication at 45 days post-intervention. RESULTS: H. pylori-negative rates in placebo, low-proanthocyanidin, medium-proanthocyanidin, and high-proanthocyanidin cranberry juice groups at week 2 were 13.24%, 7.58%, 1.49%, and 13.85% and at week 8 were 7.35%, 7.58%, 4.48%, and 20.00%, respectively. Consumption of high-proanthocyanidin juice twice daily (44 mg proanthocyanidin/240-mL serving) for 8 weeks resulted in decreased H. pylori infection rate by 20% as compared with other dosages and placebo (P < 0.05). Percentage of H. pylori-negative participants increased from 2 to 8 weeks in subjects who consumed 44 mg proanthocyanidin/day juice once or twice daily, showing a statistically significant positive trend over time. Encapsulated cranberry powder doses were not significantly effective at either time point. Overall trial compliance was 94.25%. Cranberry juice and powder were well-tolerated. CONCLUSIONS: Twice-daily consumption of proanthocyanidin-standardized cranberry juice may help potentiate suppression of H. pylori infection.

Lipid metabolism and inflammation contribute to CVD development. This study investigated whether the consumption of cranberries (CR; Vaccinium macrocarpon) can alter HDL metabolism and prevent inflammation in mice expressing human apo A-I transgene (hApoAITg), which have similar HDL profiles to those of humans. Male hApoAITg mice were fed a modified American Institute of Nutrition-93M high-fat/high-cholesterol diet (16 % fat, 0.25 % cholesterol, w/w; n 15) or the high-fat/high-cholesterol diet containing CR (5 % dried CR powder, w/w, n 16) for 8 weeks. There were no significant differences in body weight between the groups. Serum total cholesterol, non-HDL-cholesterol and TAG concentrations were significantly lower in the control than CR group with no significant differences in serum HDL-cholesterol and apoA-I. Mice fed CR showed significantly lower serum lecithin-cholesterol acyltransferase activity than the control. Liver weight and steatosis were not significantly different between the groups, but hepatic expression of genes involved in cholesterol metabolism was significantly lower in the CR group. In the epididymal white adipose tissue (eWAT), the CR group showed higher weights with decreased expression of genes for lipogenesis and fatty acid oxidation. The mRNA abundance of F4/80, a macrophage marker and the numbers of crown-like structures were less in the CR group. In the soleus muscle, the CR group also demonstrated higher expression of genes for fatty acid beta-oxidation and mitochondrial biogenesis than those of the control. In conclusion, although CR consumption elicited minor effects on HDL metabolism, it prevented obesity-induced inflammation in eWAT with concomitant alterations in soleus muscle energy metabolism.

Background & aims: The impetus for the current study was to evaluate the efficacy of cranberry supplementation on cardiovascular disease metabolic risk factors in adult populations. Methods: A systematic review was conducted on PubMed, Scopus, Web of Science and Google Scholar up to June 2018, to identify randomized controlled trials investigating the effect of cranberry supplementation on cardiovascular metabolic risk factors. Results: The results of the pooled effect size indicated that cranberry administration significantly reduced systolic blood pressure and body mass index. No statistically significant change was observed in triacylglycerol, total cholesterol, low-density lipoprotein, high-density lipoprotein, fasting plasma glucose, fasting insulin, homeostasis model assessment of insulin resistance, diastolic blood pressure, waist circumference, C-reactive protein, and intercellular adhesion molecule. Stratified analysis showed that SBP reduction was more pronounced in studies with 50 mean age participants. Also, subgroup analysis suggested a significant increase in high-density lipoprotein concentrations in subgroups with subjects <50 mean age, and triacylglycerol levels in subsets with cranberry administered in juice form. Conclusions: This systematic review and meta-analysis suggests cranberry supplementation may be effective in managing systolic blood pressure, body mass index and high-density lipoprotein in younger adults. Further high-quality studies are needed to confirm these results