Sezikli M, Çetinkaya ZA, Güzelbulut F, et al. Effects of alpha tocopherol and ascorbic acid on Helicobacter pylori colonization and severity of gastric inflammation. Helicobacter. 2012;17:127-132.
A 4-week open-label, intervention study
Thirty patients with a diagnosis of Helicobacter pylori (H. pylori)–positive non-ulcer dyspepsia. Twenty-two of the participants were women, and the mean age was 35.4 years.
The patients were given vitamin C (500 mg bid) and vitamin E (200 IU bid) orally for 4 weeks. Patients were not allowed to take any bismuth salts, nonsteroidal anti-inflammatory drugs, proton-pump inhibitors, H2-receptor blockers, antibiotics, or probiotics during the study.
Before and after vitamin C and E intervention, all participants underwent an upper gastrointestinal tract endoscopy. During the procedure, tissue samples were taken from the lesser and greater curvature in both 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. Histopathologic examination included the presence of H. pylori in the mucin layer. The intensity of the bacteria was also graded. Concentrations of gastric tissue vitamin C and E were measured with high-pressure liquid chromatography. Blood samples were also obtained before and after vitamin C and E intervention and were used to measure total antioxidant capacity (TAC).
Compared to baseline, H. pylori intensity in the antrum decreased significantly at the end of therapy for both pathologists (P=0.007 and P=0.039, respectively). Although H. pylori intensity in the corpus decreased after treatment, it did not reach statistical significance. Neutrophilic activity in the antrum decreased significantly after 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 after treatment.
*Note: The authors use P=0.000 twice in the paper to report statistical significance. I have been unable to obtain clarification from them.
H. pylori creates a microenvironment (typically through the formation of biofilms) to protect itself from gastric acid and host defense systems, and it 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 after H. pylori eradication.2 Eradication rates using standard triple-therapy (clarithromycin, amoxicillin, and a proton pump inhibitor [metronidazole is sometimes substituted for amoxicillin in allergic individuals]) typically do not exceed 80% and vary in degree between geographic locations.3 Gastrointestinal 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 as well.
The findings from this study provide specific information on how vitamins C and E affect H. pylori and possibly inflammation in patients with H. pylori-positive non-ulcer dyspepsia. More importantly, it provides 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 (1,000 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 people 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 2 groups was significant for both those in the ITT analysis and PP analysis (P<0.05).
The findings from this study provide specific information on how vitamins C and E affect H. pylori and possibly inflammation in patients with H. pylori-positive non-ulcer dyspepsia.
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 vitamins C (250 mg/day) and vitamin E (200 IU/day found no additional eradication effect for when taken with amoxicillin, metronidazole, and lansoprazole.7
Considering other adjunctive therapies for the treatment of H. pylori, the largest body of clinical data to date is on probiotics. Three meta-analyses have looked at the use of probiotics both to reduce side effects associated with standard therapy and also to improve eradication rates and have slightly different conclusions. A 2007 meta-analysis (14 studies)8 and a 2009 meta-analysis (8 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 (4 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. NAC appears to disrupt biofilms created by H. pylori, and pretreatment with 600 mg/day of NAC improved outcomes of triple therapy in a small pilot study.12 In addition to activity against uropathogenic E. coli, cranberry has also been shown to inhibit adhesion of H. pylori.13,14 The addition of 500 ml/day of cranberry juice during triple therapy and for 2 weeks following 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 the treatment outcomes for patients receiving standard triple therapy. It will be interesting to see if ongoing use the combination of vitamins C and E, probiotics, and cranberry may also prevent recurrence of H. pylori infection. A natural triple therapy?
- Naito Y, Yoshikawa T. Molecular and cellular mechanism involved in H. pylori-induced inflammation and oxidative stress. Free Radic Biol Med. 2002;33:323-326.
- Mashimo M, Nishikara M, Higuchi K, et al. Production of reactive oxygen species in peripheral blood is increase in individuals with Helicobacter pylori infection and decreased after its eradication. Helicobacter. 2006;11:217-224.
- Vilaichone RK, Mahachai V, Graham DY. Helicobacter pylori diagnosis and management. Gastroenterol Clin Norht Amer. 2006;35:229-247.
- Sezikli M, Çetinkaya ZA, Sezikli H, et al. Oxidative stress in Helicobacter pylori infection: Does supplementation with vitamin C and E increase the eradication rate? Helicobacter. 2009;14:280-285.
- Chuang CH, Sheu BS, Kao AW, et al. Adjuvant effect of vitamin C on omeprazole-amoxicillin-clarithromycin triple therapy for Helicobacter pylori eradication. Hepatogastroenterol. 2007;54:320-324.
- Kaboli SA, Zojaji H, Mirasattari D, 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.
- Chuang CH, Sheu BS, Huan AH, 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.
- Tong JL, Ran ZH, Shen J, 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. 25:155-168.
- Zou J, Dong J, Yu X. Meta-analysis: Lactobacillus containing quadruple therapy versus standard triple first-line therapy for Helicobacter pylori eradication. Helicobacter. 2009;14:449-59.
- Wilhelm SM, Johnson JL, Kale-Pradhan PB. Treating bugs with bugs: the role of probiotics as adjunctive therapy for Helicobacter pylori. Ann Pharmacother 2011;45:960-966.
- Chenoli E, Cassinos B, Bataller E, et al. Novel probiotic Bifidobacterium bifidum CECT 7366 strain active against the pathogenic bacterium Helicobacter pylori. Appl Environ Microbiol. 2011;77:1335-1343.
- Cammarota G, Brnaca G, Ardito F, et al. Biofilm demolition and antibiotic treatment to eradicate resistant Helicobacter pylori: a clinical trial. Clin Gastroenterol Hepatol. 2010;8:817-820.
- Shmuely H, Burger O, Neeman I, 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.
- Burger O, Weiss E, Sharon N, et al. Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high-molecular-weight constituent of cranberry. Crit Rev Food Sci Nutr. 2002;42(Suppl 3):279-284.
- Shmuley H, Yahav J, Samra Z, 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.