Gastrointestinal Disease

Improving H. pylori Eradication Rates Naturally

Abstract & Commentary

By Donald Brown, ND, Director, Natural Product Research Consultants, Seattle, WA. Dr. Brown is a consultant to the supplement industry. He reports no financial relationships relevant to this field of study.

Synopsis: Results from this small open-label trial out of Turkey suggest that vitamins C and E decrease Helicobacter pylori (H. pylori) intensity and possibly local inflammation in patients with H. pylori-positive non-ulcer dyspepsia. The results provide added support to results from an earlier clinical trial by the investigators that found adjunctive use of vitamins C and E improved eradication rates of conventional triple therapy for H. pylori infection.

Source: Sezikli M, et al. Effects of alpha tocopherol and ascorbic acid on Helicobacter pylori colonization and severity of gastric inflammation. Helicobacter 2012;17:127-132.

Helicobacter pylori (H. pylori) creates a microenvironment through the formation of biofilms to protect itself from gastric acid and host defense systems, and increases oxidative stress in the area it colonizes.1 It has been found that reactive oxygen species (ROS) are increased in patients infected with H. pylori and are decreased following H. pylori eradication.2 Eradication rates using standard triple-therapy (clarithromycin, amoxicillin or metronidazole, and a proton pump inhibitor [metrionidazole is sometimes substituted for amoxicillin in allergic individuals]) typically do not exceed 80% and vary in degree between geographic locations.3 Gastrointestinal (GI) side effects often reduce treatment tolerability and may cause treatment discontinuation and failure to eradicate H. pylori. Additionally, antibiotic resistance is becoming an important factor.

In the current trial, patients with H. pylori-positive non-ulcer dyspepsia were admitted to Haydarpasa Numune Education and Research Hospital's Gastroenterology Outpatient Clinic for potential participation in this open-label study. Patients who complained of dyspepsia and were infected with H. pylori as diagnosed by 14C-urea breath test underwent upper GI endoscopy. Of those, 30 patients with a diagnosis of H. pylori-positive non-ulcer dyspepsia were included in the study. Twenty-two of the participants were women and the mean age was 35.4 + 8.96 years.

The patients were given vitamin C 500 mg bid and vitamin E 200 IU (the form of vitamin E was not specified) bid orally for 4 weeks. Patients were not allowed to take any bismuth salts, non-steroidal anti-inflammatory drugs, proton-pump inhibitors, H2-receptor blockers, antibiotics, or probiotics during the study.

In addition to the screening endoscopy, all participants underwent an additional upper endoscopy. Tissue samples were taken from the lesser and greater curvature in both the prepyloric antrum and corpus for histopathologic examination of the tissue and measurement of vitamins C and E concentration. Two independent pathologists carried out histopathologic examination of all tissue samples. Concentrations of gastric tissue vitamin C and E were measured with high-pressure liquid chromatography. Blood samples were also obtained prior to and following vitamin C and E intervention and were used to measure total antioxidant capacity (TAC).

Compared to baseline, H. pylori intensity (term representing the combination of gastritis, metaplasia, and the presence of the bacteria in the mucin layer) in the antrum decreased significantly by the end of therapy according to both pathologists (P = 0.007 and P = 0.039, respectively). Although H. pylori intensity in the corpus decreased following treatment, the change did not reach statistical significance. Neutrophilic activity in the antrum decreased significantly following therapy (P = 0.000* and P = 0.025, respectively) but not in the corpus (the authors note that H. pylori colonizes predominately in the antrum). Compared to baseline, mean concentrations of vitamins C and E were significantly increased (P = 0.000* and P = 0.006, respectively). There were no significant changes in TAC following treatment.

*Editor's Note: The authors use P = 0.000 twice in the paper to report statistical significance. Dr. Brown has been unable to obtain clarification from them.

Commentary

The findings from this study provide information on how vitamins C and E affect H. pylori and possibly inflammation in patients with H. pylori-positive non-ulcer dyspepsia. More importantly, they provide support for an earlier clinical trial by the same investigators that found the addition of vitamins C and E to standard triple therapy significantly improved eradication of H. pylori in patients with H. pylori-positive non-ulcer dyspepsia.4

In that study, 160 patients infected with H. pylori were all treated with lansoprazole (30 mg bid), amoxicillin (1000 mg bid), clarithromycin (500 mg bid), and bismuth subcitrate (300 mg qid) for 14 days. Half the patients additionally received vitamin C (500 mg bid) and vitamin E (200 IU bid) during the 14-day treatment period. In persons receiving additional vitamin C and E therapy, H. pylori eradication was achieved in 73 (91.25%) of the 80 patients in the intention-to-treat (ITT) analysis and 73 (93.5%) of the 78 patients included in the per-protocol (PP) analysis. In the group receiving only standard therapy, the eradication rates were 48 (60%) of the 80 patients included in the ITT analysis and 48 (64%) of the 75 patients in the PP analysis. The difference in eradication rates between the two groups was significant for both those in the ITT analysis and PP analysis (P < 0.05).

Previous studies adding either vitamin C alone or vitamins C and E have had mixed results. One study added 500 mg/day of vitamin C to standard triple therapy for 1 week and found that eradication rates were 78% in those taking vitamin C compared to 48.8% for those receiving only standard therapy.5 However, another study using the same dose of vitamin C found no improvement in eradication rates when taken with triple therapy.6 Finally, a study looking at the effects of vitamin C (250 mg/day) and vitamin E (200 IU/day) found no additional eradication effect when taken with amoxicillin, metronidazole, and lansoprazole.7 The authors of the current study suggest that the amount of vitamins C and E may have been too low in this trial.

Considering other adjunctive therapies for the treatment of H. pylori, the largest body of clinical data to date is for probiotics. Three meta-analyses have looked at the use of probiotics to both reduce side effects associated with standard therapy and also improve eradication rates and have slightly different conclusions. A 2007 meta-analysis (14 studies)8 and a 2009 meta-analysis (eight studies limited to just those using Lactobacilli strains)9 concluded that probiotics were effective in reducing side effects such as diarrhea, bloating, and taste disturbances and also improved eradication rates. A more recent 2011 meta-analysis (four studies) agreed with the reduction of side effects of triple therapy with adjunctive use of probiotics but did not find evidence that they improved eradication rates.10 Recently, Spanish researchers have isolated a Bifodobacterium bifidum strain (CECT 7366) that has shown potent anti-H. pylori activity in vitro and in mice.11

Preliminary research has also pointed to N-acetylcysteine (NAC) and cranberry as potentially promising adjunctive therapies to improve standard H. pylori eradication therapy. Increasing attention has been paid in the past several years to the role that biofilm formation plays in increasing the resistance to antibiotic therapy for pathogenic bacteria such as Escherichia coli and H. pylori. Following an in vitro study that found NAC disrupted biofilm formation by H. pylori, a small study looked at the ability of NAC to improve eradication therapy in patients who had previously failed to eradicate H. pylori.12 In an open-label study, 40 patients with a history of four failed attempts to eradicate H. pylori received either NAC (600 mg/day) or no additional treatment for 1 week prior to 1 week of triple therapy. At baseline, evidence of biofilms was found in all patients. Two months after the end of eradication therapy, H. pylori was eradicated in 13 (65%) patients who received NAC compared to four (20%) of 20 patients who did not receive NAC (P < 0.01). In all patients who had successful eradication, biofilms had disappeared.

In addition to activity against uropathogenic E. coli, cranberry also has been shown to inhibit adhesion of H. pylori.13,14 A double-blind, randomized trial in Israel studied the adjunctive effect of cranberry juice on eradication of H. pylori in subjects being treated with omeprazole, amoxicillin, and clarithromycin. One hundred seventy-seven patients with H. pylori infection were included in the study. The addition of 500 mL/day of cranberry juice during triple therapy and for 2 weeks following significantly improved eradication rates in female patients but not male patients.15

The ability of relatively inexpensive and safe adjunctive therapies to disrupt the microenvironment created by H. pylori appears to hold promise for improving treatment outcomes for patients receiving standard triple therapy. Of greater concern clinically would be the ability of these combinations to affect outcomes in patients with peptic ulcer disease. It will be interesting to see if ongoing use of the combination of vitamins C and E, probiotics, and cranberry may also prevent recurrence of H. pylori infection. Could this be a natural triple therapy?

References

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2. Mashimo M, et al. Production of reactive oxygen species in peripheral blood is increased in individuals with Helicobacter pylori infection and decreased after its eradication. Helicobacter 2006;11:217-224.

3. Vilaichone RK, et al. Helicobacter pylori diagnosis and management. Gastroenterol Clin North Amer 2006;35:229-247.

4. Sezikli M, et al. Oxidative stress in Helicobacter pylori infection: Does supplementation with vitamin C and E increase the eradication rate? Helicobacter 2009;14:280-285.

5. Chuang CH, et al. Adjuvant effect of vitamin C on omeprazole-amoxicillin-clarithromycin triple therapy for Helicobacter pylori eradication. Hepatogastroenterology 2007;54:320-324.

6. Kaboli SA, et al. Effect of addition of vitamin C to clarithromycin-amoxicillin-omeprazole triple regimen on for Helicobacter pylori eradication. Acta Gastroenterol Belg 2009;72:222-224.

7. Chuang CH, et al. Vitamin C and E supplements to lansoprazole-amoxicillin-metronidazole triple therapy may reduce eradication rate of metronidazole-susceptible for Helicobacter pylori infection. Helicobacter 2002;7:310-316.

8. Tong JL, et al. Meta-analysis: The effect of supplementation with probiotics on eradication rates and adverse events during for Helicobacter pylori eradication therapy. Aliment Pharmacol Ther 2007;25:155-168.

9. Zou J, et al. Meta-analysis: Lactobacillus containing quadruple therapy versus standard triple first-line therapy for Helicobacter pylori eradication. Helicobacter 2009;14:97-107.

10. Wilhelm SM, et al. Treating bugs with bugs: The role of probiotics as adjunctive therapy for Helicobacter pylori. Ann Pharmacother 2011;45:960-966.

11. Chenoll E, et al. Novel probiotic Bifidobacterium bifidum CECT 7366 strain active against the pathogenic bacterium Helicobacter pylori. Appl Environ Microbiol 2011;77:1335-1343.

12. Cammarota G, et al. Biofilm demolition and antibiotic treatment to eradicate resistant Helicobacter pylori: A clinical trial. Clin Gastroenterol Hepatol 2010;8:817-820.e3.

13. Shmuely H, et al. Susceptibility of Helicobacter pylori isolates to antiadhesion activity of a high-molecular-weight constituent of cranberry. Diagn Microbial Infect Dis 2004;50:231-235.

14. Burger O, et al. Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high-molecular-weight constituent of cranberry juice. Crit Rev Food Sci Nutr 2002;42(3 Suppl):279-284.

15. Shmuley H, et al. Effect of cranberry juice on eradication of Helicobacter pylori in patients treated with antibiotics and a proton pump inhibitor. Mol Nutr Food Res 2007;51:746-751.