Highly Active Cranberry's Polyphenolic Fraction: New Advances in Processing and Clinical Applications.

Cranberry is a fruit originally from New England and currently growing throughout the east and northeast parts of the USA and Canada. The supplementation of cranberry extracts as nutraceuticals showed to contribute to the prevention of urinary tract infections, and most likely it may help to prevent cardiovascular and gastroenteric diseases, as highlighted by several clinical trials. However, aiming to validate the efficacy and safety of clinical applications as long-term randomized clinical trials (RCTs), further investigations of the mechanisms of action are required. In addition, a real challenge for next years is the standardization of cranberry's polyphenolic fractions. In this context, the optimization of the extraction process and downstream processing represent a key point for a reliable active principle for the formulation of a food supplement. For this reason, new non-conventional extraction methods have been developed to improve the quality of the extracts and reduce the overall costs. The aim of this survey is to describe both technologies and processes for highly active cranberry extracts as well as the effects observed in clinical studies and the respective tolerability notes.

Effects of cranberry beverages on oxidative stress and gut microbiota in subjects with Helicobacter pylori infection: a randomized, double-blind, placebo-controlled trial.

Helicobacter pylori-induced oxidative stress plays an important role in gastric diseases. H. pylori disturbs gut microbiota. The objective is to investigate the effects of cranberry beverages on oxidative stress biomarkers and gut microbiota in H. pylori positive subjects. 171 H. pylori positive participants were randomly assigned to one of the three groups: high-dose (HCb; 480 mL cranberry beverage), low-dose (LCb; 240 mL cranberry beverage plus 240 mL placebo) and placebo (480 mL). Subjects consumed the beverages daily for 4 weeks. Fasting blood samples were analyzed for oxidative stress biomarkers. The intestinal microbiome was analyzed by 16S rRNA sequencing. Compared with the placebo, HCb resulted in a significantly higher increase of total antioxidant capacity (mean ± SD: 1.39 ± 1.69 IU mL-1vs. 0.34 ± 1.73 IU mL-1; p < 0.001) and a higher decrease of the lipid peroxidation product malondialdehyde (-7.29 ± 10.83 nmol mg-1vs. -0.84 ± 15.66 nmol mg-1; p = 0.025). A significant dose-dependent effect on the elevation of superoxide dismutase was observed (p < 0.001). Microbiome data showed that consuming HCb and LCb led to a significant reduction of Pseudomonas (p < 0.05). In conclusion, the current research showed that consuming cranberry beverages significantly improved the antioxidant status in H. pylori positive subjects, which may be related to the reshaping of gut microbiota.

Suppression of Helicobacter pylori infection by daily cranberry intake: A double-blind, randomized, placebo-controlled trial.

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. TRIAL REGISTRATION: ChiCTR1800017522, per WHO ICTRP.

Regulatory Effects of Black Rice Extract on Helicobacter pylori Infection-Induced Apoptosis.

SCOPE: Black rice extract (BRE) contains cyanidin 3-O-glucoside (C3G), an anthocyanin, as the major component. In this study, we found that BRE inhibits the mRNA and protein expression of genes encoding cytotoxin-associated protein A (cagA) and vacuolating protein A (vacA) in Helicobacter pylori 60190 strain. METHODS AND RESULTS: We performed RT-PCR and western blotting to show that BRE inhibits the mRNA and protein expression of SecA. Because SecA is involved in VacA export in bacteria, our result suggests a positive correlation between BRE-induced inhibition of secA expression and VacA secretion. Further, we perform MTT assay and flow cytometry to show that BRE decreases the apoptosis of H. pylori-infected KATO III cells. Finally, we perform western blotting to show that the cell-protective effect of BRE is associated with decreased levels of active proapoptotic proteins caspases and PARP and increased levels of antiapoptotic proteins survivin and XIAP in H. pylori-infected cells. CONCLUSION: Thus, our results indicate that BRE acts as a potent inhibitor of the biogenesis of H. pylori virulence proteins and decreases the apoptosis of H. pylori-infected cells. Moreover, our results suggest that BRE can be used to exert beneficial effects in patients with gastroduodenal diseases caused by H. pylori.

Can Diet Modulate Helicobacter pylori-associated Gastric Pathogenesis? An Evidence-Based Analysis.

Helicobacter pylori is involved in the pathogenesis of gastritis, peptic ulcer, and gastric cancer. The infection is prevalent in more than half of the world's population. Although the infection may lead to detrimental consequences, still the majority of the infected individuals only develop mild gastritis. Several factors are behind this paradoxical outcome including virulence of the infecting H. pylori strains, genetic background of the host, and factors related to lifestyle such as dietary habits. Among these, lifestyle including dietary factors was not in the limelight, until recently, as one of the important factors that could modulate H. pylori-linked gastric diseases. This review is directed to gather and elucidate the role of dietary components in augmenting or attenuating pathological processes initiated by H. pylori. Available evidence strongly supports the notion that the diet may play a critical role in defining the final outcome of H. pylori infection particularly if certain dietary components are taken on a regular basis for a long time. Despite a recent surge in research related to the role of dietary ingredients, further studies involving large-scale clinical trials are required to gain a better understanding of the precise role played by the dietary ingredients in H. pylori-associated pathogenesis.

Recent advances in complementary and replacement therapy with nutraceuticals in combating gastrointestinal illnesses.

The digestive system provides nourishment to the whole body. Disorders in this system would result in many associated illnesses as the body is deprived of essential nutrients. Gastrointestinal diseases, in particular, gastric ulceration, inflammatory bowel diseases and colorectal cancer have become more prevalent in all population age groups. While this can be attributed to diet and lifestyle changes, the measures to combat these illnesses with conventional drugs is losing popularity owing to the harsh side effects, drug resistance and lack of patient compliance. The focus of this review is to endorse promising nutraceutical dietary components such as phytosterols, polyphenols, anthocyanins and polyunsaturated fatty acids and their synergistic value, in combination with conventional management of key gastrointestinal diseases. As most of these nutraceuticals are labile compounds, the need for protection and delivery using a carrier system is stressed and the methods for targeting to specific parts of the gastrointestinal tract are discussed. A section has also been devoted to perspectives on co-encapsulation methods of drugs and nutraceuticals using different particle systems. Multilayered carrier systems like double layered and core shell particles have been proposed as an exemplary system to co-encapsulate both drugs and nutrients while keeping them segregated.

Efficacy of probiotics as an adjuvant agent in eradication of Helicobacter pylori infection and associated side effects.

The intestinal tract is a host to various types of bacteria that are essential to health. Interactions between intestinal bacteria, i.e. the normal microbiota of the host's intestine, have been a subject of intensive research, as they may influence disease cycles. Recent studies of selected probiotic species and their therapeutic benefits have suggested a potential efficacy in treatment of several gastrointestinal illnesses, including Helicobacter pylori infection. The increasing evidence from these clinical studies supports the promising role of probiotics in improving the treatment of H. pylori by increasing eradication rates as well as decreasing the adverse effects of current medication therapy. However, many unsolved questions remain which require high quality trials on specific probiotic strains in the future. The main part of this review will focus on the effects of supplementary probiotic products during standard triple H. pylori therapy.

Probiotic supplementation does not improve eradication rate of Helicobacter pylori infection compared to placebo based on standard therapy: a meta-analysis.

This meta-analysis included eligible randomized controlled trials (RCTs) with the aim of determining whether probiotic supplementation can improve H. pylori eradication rates. PUBMED, EBSCO, Web of Science, and Ovid databases were searched. We included RCTs that investigated the effect of combining probiotics, with or without a placebo, with standard therapy. A total of 21 RCTs that reported standard therapy plus probiotics were included. Compared to the placebo group, the probiotics group was 1.21(OR 1.21, 95% CI: 0.86, 1.69) and 1.28 (OR 1.28, 95% CI: 0.88, 1.86) times more likely to achieve eradication of H. pylori infection in intent-to-treat (ITT) analysis and per protocol (PP) analysis, respectively. Probiotics with triple therapy plus a 14-day course of treatment did not improve the eradication of H. pylori infection (OR 1.44, 95% CI: 0.87, 2.39) compared to the placebo. Moreover, the placebo plus standard therapy did not improve eradication rates compared to standard therapy alone (P = 0.816). However, probiotics did improve the adverse effects of diarrhea and nausea. These pooled data suggest that the use of probiotics plus standard therapy does not improve the eradication rate of H. pylori infection compared to the placebo.

Omega-3 Polyunsaturated Fatty Acids Intake to Regulate Helicobacter pylori-Associated Gastric Diseases as Nonantimicrobial Dietary Approach.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), commonly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been acknowledged as essential long-chain fatty acids imposing either optimal health promotion or the rescuing from chronic inflammatory diseases such as atherosclerosis, fatty liver, and various inflammatory gastrointestinal diseases. Recent studies dealing with EPA and DHA have sparked highest interests because detailed molecular mechanisms had been documented with the identification of its receptor, G protein coupled receptor, and GPR120. In this review article, we have described clear evidences showing that n-3 PUFAs could reduce various Helicobacter pylori- (H. pylori-) associated gastric diseases and extended to play even cancer preventive outcomes including H. pylori-associated gastric cancer by influencing multiple targets, including proliferation, survival, angiogenesis, inflammation, and metastasis. Since our previous studies strongly concluded that nonantimicrobial dietary approach for reducing inflammation, for instance, application of phytoceuticals, probiotics, natural products including Korean red ginseng, and walnut plentiful of n-3 PUFAs, might be prerequisite step for preventing H. pylori-associated gastric cancer as well as facilitating the rejuvenation of precancerous atrophic gastritis, these beneficial lipids can restore or modify inflammation-associated lipid distortion and correction of altered lipid rafts to send right signaling to maintain healthy stomach even after chronic H. pylori infection.

Dietary amelioration of Helicobacter infection.

We review herein the basis for using dietary components to treat and/or prevent Helicobacter pylori infection, with emphasis on (a) work reported in the last decade, (b) dietary components for which there is mechanism-based plausibility, and (c) components for which clinical results on H pylori amelioration are available. There is evidence that a diet-based treatment may reduce the levels and/or the virulence of H pylori colonization without completely eradicating the organism in treated individuals. This concept was endorsed a decade ago by the participants in a small international consensus conference held in Honolulu, Hawaii, USA, and interest in such a diet-based approach has increased dramatically since then. This approach is attractive in terms of cost, treatment, tolerability, and cultural acceptability. This review, therefore, highlights specific foods, food components, and food products, grouped as follows: bee products (eg, honey and propolis); probiotics; dairy products; vegetables; fruits; oils; essential oils; and herbs, spices, and other plants. A discussion of the small number of clinical studies that are available is supplemented by supportive in vitro and animal studies. This very large body of in vitro and preclinical evidence must now be followed up with rationally designed, unambiguous human trials.

Nickel free-diet enhances the Helicobacter pylori eradication rate: a pilot study.

BACKGROUND: The Helicobacter pylori eradication rate with standard triple therapy is very low. H. pylori is known to require the nickel-containing metalloenzymes urease and NiFe-hydrogenase to survive at the low pH environment in the stomach. AIM: To compare the H. pylori eradication rate of a nickel free-diet associated with standard triple therapy and standard triple therapy alone as the first-line regimen. METHODS: Fifty-two sex- and age-matched patients at the first diagnosis of H. pylori infection were randomized 1:1 into two different therapeutic schemes: (1) standard LCA (26 patients): lansoprazole 15 mg bid, clarithromycin 500 mg bid and amoxicillin 1,000 mg bid for 7 days with a common diet; (2) standard LCA plus a nickel free-diet (NFD-LCA) (26 patients). Patients followed 30 days of a nickel-free diet plus a week of lansoprazole 15 mg bid, clarithromycin 500 mg bid and amoxicillin 1,000 mg bid starting from day 15 of the diet. RESULTS: All patients completed the study. A significantly higher eradication rate was observed in the NFD-LCA group (22/26) versus LCA group (12/26) (p < 0.01). Only a few patients (9 of 52) reported the occurrence of mild therapy-related side effects, without any significant differences between the two groups. CONCLUSIONS: The addition of a nickel-free diet to standard triple therapy significantly increases the H. pylori eradication rate. The reduction of H. pylori urease activity due to the nickel-free diet could expose the bacterium to gastric acid and increase H. pylori's susceptibility to amoxicillin. Further studies are necessary to confirm this preliminary result.

Genomic and phenotypic evidence for probiotic influences of Lactobacillus gasseri on human health.

Certain lactic acid bacteria (LAB) have the capacity to occupy mucosal niches of humans, including the oral cavity, gastrointestinal tract, and vagina. Among commensal, LAB are species of the acidophilus complex, which have proven to be a substantial reservoir for microorganisms with probiotic attributes. Specifically, Lactobacillus gasseri is an autochthonous microorganism which has been evaluated for probiotic activity based on the availability of genome sequence and species-specific adaptation to the human mucosa. Niche-related characteristics of L. gasseri contributing to indigenous colonization include tolerance of low pH environments, resistance to bile salts, and adhesion to the host epithelium. In humans, L. gasseri elicits various health benefits through its antimicrobial activity, bacteriocin production, and immunomodulation of the innate and adaptive systems. The genomic and empirical evidence supporting use of L. gasseri in probiotic applications is substantiated by clinical trial data displaying maintenance of vaginal homeostasis, mitigation of Helicobacter pylori infection, and amelioration of diarrhea.

Probiotics as an alternative strategy for prevention and treatment of human diseases: a review.

Probiotics are live microbial food supplements or their components, which have been shown to have beneficial effects on human health. Probiotics can be bacteria, molds, or yeasts, but most of them fall into the group known as lactic acid bacteria and are normally consumed in the form of yogurt, fermented milk, or other fermented foods. Data from clinical trials have shown contrasting effects and should be interpreted with caution. A large variety of potential beneficial effects have been reported including improvement of intestinal tract health, enhancing the immune system, reducing symptoms of lactose intolerance, decreasing the prevalence of allergy in susceptible individuals, reducing risk of certain cancers, treating colitis, lowering serum cholesterol concentrations, reducing blood pressure in hypertensives, and improving female urogenital infections and Helicobacter pylori infections. The aim of this article is to present a review of the current expanding knowledge of applications of utilizing probiotic microorganisms in the prevention and treatment of several diseases.

[Effectiveness and safety of probiotics in children on the basis of clinical trials]. / Skutecnosc i bezpieczenstwo stosowania proniotykow na podtawie badan klinicznych przeprowadzonych u dzieci.

Probiotics may be helpful if they are used according to current medical knowledge based on the results of properly designed and well-conducted clinical trials. Their effects depend on the specific strain and defined dose of the probiotic microorganism, and should not be extrapolated on other, even closely related strains. Meta-analyses of randomized clinical trials performed in children showed the greatest probiotic efficacy of Lactobacillus rhamnosus GG (LGG) and Saccharomyces boulardii strains in the treatment of acute viral infectious diarrhea and in prevention of non-difficile antibiotic associated-diarrhea (AAD). The clinical efficacy of probiotics in other indications in children has not been substantiated until now, however the results of some clinical trials (e.g. in necrotizing enterocolitis (NEC) or atopic dermatitis) are promising. When using probiotics, it is necessary to rely on the results of well-designed clinical trials, not on commercials. This paper provides information based on recent knowledge concerning the efficacy and safety of probiotics according to the results of clinical trials performed in children.

Cranberry components for the therapy of infectious disease.

Summary of the in vitro data support a beneficial effect of cranberry or its proanthocyanin constituents by blocking adhesion to and biofilm formation on target tissues of pathogens. In vivo data partially support these beneficial effects. Consumption of various cranberry products benefited young and elderly females in preventing urinary tract infections, and in conjunction with antibiotic treatment in eradicating Helicobacter pylori infections in women. Mouthwash supplemented with an isolated cranberry derivative reduced significantly the caryogenic mutans streptococci. None of the mice infected intranasal with lethal dose of influenza virus and treated with cranberry fraction died after two weeks. Further studies should focus on the active cranberry component as supplement for food and other products especially where whole juice or powder cannot be used.

Supplementing vitamins C and E to standard triple therapy for the eradication of Helicobacter pylori.

WHAT IS KNOWN AND OBJECTIVE: Helicobacter pylori eradication rates of currently accepted triple therapy regimens vary between geographic locations and do not exceed 70-80%. Eradication rates are much lower in locations where uncontrolled antibiotic use is common such as Turkey. In the present study, we aimed to test whether supplementing vitamins C and E to standard triple therapy, including a proton pump inhibitor plus amoxicillin plus clarithromycin, increased the H. pylori eradication rate. METHODS: Two hundred patients infected with H. pylori were randomized into two groups in an open-label trial. In group A, patients (n = 160) were given standard triple therapy, including lansoprazole 30 mg BID plus amoxicillin 1000 mg BID plus clarithromycin 500 mg BID for 14 days, plus vitamin C 500 mg BID plus vitamin E 200 IU BID for 30 days. In group B, patients (n = 40) were given standard triple therapy for 14 days. The success of H. pylori eradication was defined as a negative ¹4C-urea breath test result, 4-6 weeks after the completion of therapy. Comaprisons were by both intention-to-treat (ITT) and per-protocol (PP) analysis. RESULTS AND DISCUSSION: Two hundred patients (137 women, 63 men) were analysed using ITT analysis and 195 patients completed the study. In group A, H. pylori eradication was achieved in 132 of the 160 patients (82·5%) included in ITT analysis and 132 of the 157 patients (84%) included in PP analysis. In group B, H. pylori eradication was achieved in 18 of the 40 patients (45%) included in ITT analysis and 18 of the 38 patients (47·4%) included in PP analysis. Eradication rates were significantly higher in group A than in group B (P < 0·005). Eradication rates were not statistically significant between men and women in both groups. WHAT IS NEW AND CONCLUSION: Adding vitamins C and E to standard triple therapy increases the eradication rate of H. pylori. Vitamins C and E may increase the eradication rate via increasing the effectiveness of the antibiotics by decreasing oxidative stress in the gastric mucosa and strengthening the immune system.

Treating bugs with bugs: the role of probiotics as adjunctive therapy for Helicobacter pylori.

OBJECTIVE: To review the literature on the role of probiotics as adjunctive therapy in the treatment of Helicobacter pylori infections. DATA SOURCES: Literature was accessed through MEDLINE (1966-March 2011) using the terms H. pylori, probiotic, Lactobacillus, Bifidobacterium, Saccharomyces, Bacillus clausii, and Propionibacterium. Article references were hand-searched for additional relevant articles and abstracts. STUDY SELECTION AND DATA EXTRACTION: All English-language articles published in full were evaluated. Randomized, double-blind, placebo-controlled trials assessing the use of probiotics combined with standard eradication therapy of H. pylori infection in adults were included in the review. DATA SYNTHESIS: Various probiotics, including Lactobacillus spp., Saccharomyces spp., Bifidobacterium spp., and B. clausii, reduce adverse effects such as nausea, taste disturbance, diarrhea, and epigastric pain, and increase tolerability of H. pylori eradication therapy. Based on the studies reviewed, probiotics do not affect H. pylori eradication rates. CONCLUSIONS: Probiotics may be beneficial in reducing adverse effects and increasing tolerability of H. pylori eradication regimens. They may especially be helpful in patients with recurrent H. pylori infection and a history of gastrointestinal adverse effects with antibiotics. Pharmacists can play an important role in educating patients regarding probiotic use during H. pylori eradication therapy.

Efficacy of probiotics in Helicobacter pylori eradication therapy.

BACKGROUND/AIMS: Triple therapy with a proton pump inhibitor, amoxicillin and clarithromycin in Helicobacter pylori eradication is widely accepted, but this combination fails in a considerable number of cases. Our aim was to evaluate whether probiotic-containing yogurt affects the success of eradication. The second aim was to investigate the efficacy of probiotics in the prevention of the side effects related to eradication therapy. METHODS: A total of 76 histopathologically proven H. pylori-positive patients enrolled in this study were randomized into two groups. The following regimens were recommended: Group A: pantoprazole (40 mg, b.i.d.), amoxicillin (1000 mg b.i.d.), clarithromycin (500 mg b.i.d.), and 125 ml of probiotic-containing yogurt (Bifidobacterium DN-173 010-1010 cfu/g) before breakfast for 14 days; and Group B: pantoprazole (40 mg, b.i.d.), amoxicillin (1000 mg b.i.d.) and clarithromycin (500 mg b.i.d.) for 14 days. Subjects were asked to report any side effects of therapy during the treatment period. H. pylori status was rechecked four weeks after the completion of the eradication therapy by 13C-urea breath test. RESULTS: H. pylori eradication was achieved in 25 of the 38 patients in Group A (66%) and in 20 of the 38 patients (53%) in Group B. Although the success rate was higher in Group A than in Group B, the difference was not significant (p=0.350). The addition of probiotics to the triple therapy significantly lessened the frequency of stomatitis and constipation (p=0.037 and p=0.046, respectively). CONCLUSIONS: The addition of probiotic-containing yogurt to the triple therapy did not increase the H. pylori eradication rates for the evaluated dosage and model; however, it decreased the frequency of stomatitis and constipation.