Effect of polyphenol compounds on eradication: a systematic review with meta-analysis.

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• This is the first meta-analysis of polyphenol efficacy and safety in eradicating H. pylori.
• The results suggest that polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) can improve eradication rates.
• Furthermore, polyphenol compounds combined with standard triple therapy for H.pylori infection can significantly improve eradication (p=0.03).
• No evidence for an increased rate of side effects could be found.
• Due to the low quality of the included studies, these results should be interpreted with caution.

Background

The authors highlight that Helicobacter pylori (H. pylori) has been classified as a group 1 carcinogen and H. pylori infection is considered the leading cause of gastric cancer. More than half the world’s population is infected with H. pylori and recurrence rates have increased over the past decade. Several studies indicate that polyphenol compounds positively affect H. pylori eradication. However, experimental and clinical studies have shown different results.

Methods

• This is the first meta-analysis to assess the efficacy and safety of polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) in eradicating H. pylori.
• A total of 12 RCTs with 1251 adult participants were finally included. Two studies evaluated the efficacy of curcumin, four studies evaluated the efficacy of cranberry, four studies assessed the efficacy of liquorice, one study evaluated the efficacy of garlic, and one study assessed the efficacy of broccoli.
• Subgroup analysis of different treatment schemes on the eradication rate of H.pylori infection included: three studies which compared the effects of polyphenols with placebo; six studies compared the effects of polyphenols along with triple therapy; two studies compared the effects of polyphenol plus triple therapy with bismuth triple therapy; one study compared the effects of polyphenols plus quadruple regimen with quadruple regimen plus placebo.

Results

• The results indicate that polyphenols are conducive to H. pylori eradication. The total eradication rate of H.pylori in the polyphenol compounds group was significantly higher than in the group without polyphenol compounds (RR 1.19, 95% CI 1.03 to 1.38, p=0.02).
• In subgroup analyses, eradication rate with polyphenol therapy was superior to that without polyphenol therapy in the polyphenols versus placebo subgroup (RR 4.23, 95% CI 1.38 to 12.95, p=0.01) and in the polyphenols plus triple therapy versus triple therapy subgroup (RR 1.11, 95% CI 1.01 to 1.22, p=0.03).
• No significant differences existed between the five different polyphenol compounds analysed.
• The most frequent adverse effects of polyphenol compounds included diarrhoea, headache and vomiting. However, there were no differences regarding side effects between the polyphenol compounds and control groups (RR 1.47, 95% CI 0.83 to 2.58, p=0.18).

Limitations:

• Only the eradication rate of H. pylori infection according to different treatment schemes and polyphenol compounds was analysed, with no analysis of polyphenol dose.
• Visual inspection of the funnel plot suggested that publication bias existed. Most studies ignored possible adverse reactions, and safety observations could be improved.
• The number of cases included in this meta-analysis is small and the methodological quality of the included trials was generally poor.
• The results of subgroup analyses on different treatment schemes and polyphenol compound species seem more inconclusive due to the small number of studies that could be included.
• The polyphenol contents of each food before and after the eradication period from each study could not be determined which might work as a confounding factor. This confounding factor may have an impact on the final result.

• Infection with H.pylori is a major pathogenic factor for many gastrointestinal conditions such as chronic atrophic gastric ulcers and has been linked with several extra-digestive diseases such as atherosclerosis, Alzheimer’s disease and rosacea.
• The efficacy of standard 1-week triple therapy containing clarithromycin and either metronidazole or amoxicillin combined with a PPI has decreased dramatically, with eradication rates as low as 50%–70%. Antibiotic resistance and patient compliance are the major causes of this decline.
• Concomitant, sequential and hybrid therapies are also recommended for treating H. pylori infection. However, there are currently few, if any, regimens which consistently achieve eradication rates exceeding 90%. In this analysis H. pylori eradication rates ranged from 54.4% to 91.7% in the polyphenol treatment groups.
• The results of this analysis indicate that polyphenol compounds can significantly improve H. pylori eradication rates and might be more effective during polyphenol treatment combined with standard triple therapy.
• No evidence for an increased rate of side effects could be found.
• Due to the low quality of the included studies, these results should be interpreted with caution.

• While a few included studies mention doses of these polyphenol compounds for eradicating H. pylori, it was not an outcome analysed in this meta-analysis and therefore future research on this would help to clarify appropriate dosages.
• Adverse reactions and safety observations warrant further study.
• More large-scale, high-quality clinical trials should be conducted to provide a stronger, evidence-based foundation for guiding clinical medication. In particular in relation to more studies on different treatment schemes and species.
• Finally, the polyphenol contents of each food before and after the eradication period from each manuscript included in the analysis could not be determined which could be a confounding factor. Future studies should address this.