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There have been a number of reports that natural foods such as garlic, honey, and capsaicin can inhibit Helicobacter pylori in vitro and each report has suggested the natural ingredient be used for treatment of the infection. We investigated whether garlic or capsaicin-containing peppers would actually inhibit H. pylori in vivo.We performed a prospective crossover study in healthy H. pylori-infected adults. We used the urea breath test to assess the status of the H. pylori infection. On separate days subjects received three test meals consisting of beef, tortillas, and salad with one of the following: fresh garlic (10 sliced cloves), capsaicin (six sliced fresh jalapeños), two tablets of bismuth subsalicylate (Pepto-Bismol, positive control), or nothing added (negative control). Breath testing was done before the first meal, the evening meal, and the following morning. At least 2 days elapsed between the test substances.Twelve subjects participated (seven men, five women), with an average age of 41.4 yr, range 27–51 yr. Ten subjects received garlic, six received jalapeños, and 11 received bismuth. Neither garlic nor capsaicin had any in vivo effect on H. pylori (median urease activity 28.5 vs 39.8 and 43.7 vs 46.6 before and after garlic and jalapeños, respectively) p > 0.8. Bismuth had a marked inhibitory effect (median 55.8 vs 14.3 before and after bismuth) p < 0.001, respectively.This study did not support a role for either garlic or jalapeños in the treatment of H. pylori infection. Caution must be used when attempting to extrapolate data from in vitro studies to the in vivo condition.