Improving the success rate of Helicobacter pylori eradication therapy

August 23, 2018

In the past few decades, it has become apparent that recurrences of peptic ulcers can be prevented by eradicating Helicobacter pylori, a bacterial infection that occurs commonly in the stomach of ulcer patients. Treatment with a combination of antibiotics, acid blockers (proton pump inhibitors) and sometimes bismuth is often effective for eradicating this infection, but in a substantial minority of patients the infection persists despite treatment. New research has shown that certain dietary modifications and nutritional supplements can increase the success rate of conventional H. pylori eradication therapy. Interventions that have been reported to be successful include a low-nickel diet, supplementation with N-acetylcysteine, and administration of probiotics.

Low-nickel diet

H. pylori contains a nickel-dependent urease enzyme. This enzyme catalyzes the hydrolysis of urea in gastric juice to form ammonia, an alkaline compound that protects H. pylori against gastric acidity. NiFe-hydrogenase is another nickel-dependent enzyme produced by H. pylori that helps the organism survive the acid environment of the stomach. In a randomized controlled trial, consumption of a low-nickel diet significantly increased the success rate in patients receiving conventional H. pylori eradication therapy.

Fifty-two patients with newly diagnosed H. pylori infection were randomly assigned to consume a standard diet or a diet in which all foods high in nickel content were prohibited. Starting on day 15 of the diet, all patients were treated with 15 mg of lansoprazole, 500 mg of clarithromycin, and 1,000 mg of amoxicillin, each twice a day for 7 days. H. pylori eradication was assessed by the urea breath test 4 weeks after the end of treatment. The eradication rate was significantly higher with the low-nickel diet than with the standard diet (84.6% vs. 46.2%; p < 0.01). Information on how to follow a low-nickel diet is available on the Internet.

N-Acetylcysteine

H. pylori produces a protective matrix known as a biofilm. Biofilms are thought to promote antibiotic resistance by several different mechanisms, one of which is to block the penetration of antibiotics. N-Acetylcysteine (NAC) has been found to prevent biofilm formation in vitro and to promote the degradation of existing biofilm. In clinical trials, supplementation with NAC markedly increased the success rate of conventional eradication therapy, both in patients who had previously had multiple unsuccessful attempts to eradicate H. pylori and in those undergoing their first course of treatment.

Forty patients who had had at least 4 unsuccessful attempts to eradicate H. pylori were randomly assigned to receive NAC (600 mg once a day) or no NAC (controls) for 1 week, followed by a culture-guided eradication regimen that included 2 antibiotics and a proton pump inhibitor. The eradication rate was significantly higher in the NAC group than in the control group (65% vs. 20%; p < 0.01). Biofilm disappeared in all patients in whom eradication was successful, but persisted in patients in whom eradication was unsuccessful.

Seventy patients with H. pylori infection were randomly assigned to receive 500 mg of clarithromycin and 30 mg of lansoprazole, each twice a day, plus 10 ml (400 mg) of NAC liquid 3 times per day for 10 days, or clarithromycin and lansoprazole without NAC (control group). Eradication of H. pylori was assessed 1 month after the completion of treatment by performing a rapid urease test on gastric biopsy samples. The eradication rate was significantly higher in the NAC group than in the control group (50% vs. 23%; p = 0.034).

Based on these findings, adjunctive treatment with NAC should be considered for all patients undergoing H. pylori eradication therapy.

Probiotics

Administration of various probiotic agents has been reported to reduce the incidence of antibiotic-induced gastrointestinal side effects in patients with H. pylori infection. In addition a meta-analysis of 10 controlled trials found a significant increase in eradication rates when probiotics were added to conventional therapy. This beneficial effect may be due in large part to a decrease in antibiotic side effects, which would increase the proportion of patients who complete the full course of treatment. In addition, some probiotic organisms have demonstrated antibacterial activity against H. pylori. For example, L. acidophilus inhibited in vitro the growth of H. pylori isolated from gastric biopsy samples of patients with “acid-peptic disease.” Administration of L. salivarius also prevented gastric colonization of H. pylori in mice. While probiotics may decrease the side effects and enhance the efficacy of conventional treatment, there is no evidence that probiotic therapy by itself would be an effective treatment for H. pylori infection.

References

  1. Campanale M, et al. Nickel free-diet enhances the Helicobacter pylori eradication rate: a pilot study. Dig Dis Sci. 2014;59:1851-1855.
  2. Penn State Hershey. Milton S. Hershey Medical Center. Low nickel diet. http://www.pennstatehershey.org/c/document_library/get_file?uuid=0888ec6e-3d2f-4766-833e-b38bd920ffcd&groupId=102184. Accessed April 8, 2017.
  3. Dinicola S, et al. N-acetylcysteine as powerful molecule to destroy bacterial biofilms. A systematic review. Eur Rev Med Pharmacol Sci. 2014;18:2942-2948.
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Reprinted with permission from the Townsend Letter.

Alan Gaby

Alan Gaby MD

Dr. Gaby received his undergraduate degree from Yale University, his M.S. in biochemistry from Emory University, and his M.D. from the University of Maryland. He was in private practice for 19 years, specializing in nutritional medicine.

He is past-president of the American Holistic Medical Association who has given expert testimony to the White House Commission on Complementary and Alternative Medicine on the cost-effectiveness of nutritional supplements. He is the author of Preventing and Reversing Osteoporosis (Prima, 1994), The Doctor’s Guide to Vitamin B6 (Rodale Press, 1984), the co-author of The Patient’s Book of Natural Healing (Prima, 1999). Dr. Gaby has written numerous scientific papers in the field of nutritional medicine. He has been the contributing medical editor for the Townsend Letter for Doctors since 1985, and was contributing editor for Alternative Medicine Review from 1996 to 2010.

Over the past 36 years, Dr. Gaby has developed a computerized database of more than 28,000 individually chosen medical journal articles related to the field of natural medicine. He was professor of nutrition and a member of the clinical faculty at Bastyr University in Kenmore, WA, from 1995 to 2002. He is Chief Science Editor for Aisle 7 (formerly Healthnotes, Inc.) and has appeared on the CBS Evening News and the Donahue Show. In 2010, Dr. Gaby completed a 30-year project: the textbook Nutritional Medicine. Over the past 6 years, he has worked on completing the updated second edition of Nutritional Medicine.