Vitamin C supplementation does not protect L ‐gulono‐γ‐lactone oxidase‐deficient mice from Helicobacter pylori ‐induced gastritis and gastric premalignancy

In human studies, low vitamin C intake has been associated with more severe Helicobacter pylori gastritis and a higher incidence of gastric cancer. However, vitamin C supplementation has not been definitively shown to protect against gastric cancer. Using vitamin C‐deficient B6.129P2‐Gulo tm1Umc /mmcd (gulo −/− ) mice lacking L ‐gulono‐γ‐lactone oxidase, we compared gastric lesions and Th1 immune responses in H. pylori ‐infected gulo −/− mice supplemented with low (33 mg/L) or high (3,300 mg/L) vitamin C in drinking water for 16 or 32 weeks. Vitamin C levels in plasma and gastric tissue correlated with the vitamin C supplementation levels in gulo −/− mice. H. pylori infection resulted in comparable gastritis and premalignant lesions in wildtype C57BL/6 and gulo −/− mice supplemented with high vitamin C, but lesions were less severe in gulo −/− mice supplemented with low vitamin C at 32 weeks post infection. The reduced gastric lesions in infected gulo −/− mice supplemented with low vitamin C correlated with reduced Th1‐associated IgG2c, gastric IFN‐γ and TNF‐α mRNA and higher H. pylori colonization levels. These results in the H. pylori ‐infected gulo −/− mouse model suggest that although supplementation with a high level of vitamin C achieved physiologically normal vitamin C levels in plasma and gastric tissue, this dose of vitamin C did not protect gulo −/− mice from H. pylori ‐induced premalignant gastric lesions. In addition, less severe gastric lesions in H.pylori infected gulo −/− mice supplemented with low vitamin C correlated with an attenuated Th1 inflammatory response. © 2007 Wiley‐Liss, Inc.