The effect of 5‐year vitamin C supplementation on serum pepsinogen level and Helicobacter pylori infection (original) (raw)

Abstract

We conducted a population‐based, double‐blind, randomized controlled trial to examine the effect of vitamin C supplementation on serum pepsinogen (PG) level, Helicobacter pylori (H. pylori) infection, and cytotoxin‐associated gene A (Cag A) status. Subjects aged 40 to 69 years living in one village in Akita prefecture, a high‐risk area for gastric cancer in Japan, were recruited through annual health check‐up programs. Among 635 subjects diagnosed as having chronic gastritis on the basis of serum PG levels, after excluding ineligible cases, 439 subjects were assigned to one of four groups using a 2×2 factorial design (0 or 15 mg/day β‐carotene and 50 or 500 mg/day vitamin C). However, based on the results from two β‐carotene trials in the United States, we discontinued β‐carotene (vitamin C supplementation was continued). Finally, 120 subjects in the low‐dose group (vitamin C 50 mg), and 124 subjects in the high‐dose group (vitamin C 500 mg) completed the 5‐year supplementation. The difference in the change of PGI/II ratio between baseline and after 5‐year follow up was statistically significant between the intervention groups among those who completed the supplementation: ‐0.25 for the low‐dose group and ‐0.13 for the high‐dose group (_P_=0.046). To conclude, vitamin C supplementation may protect against progression of gastric mucosal atrophy. (Cancer Sci 2003; 94: 378–382)

References

• 1.Correa P, Malcom G, Schmidt B, Fontham E, Ruiz B, Bravo JC, Bravo LE, Zarama G, Realpe JL. Review article: antioxidant micronutrients and gastric cancer. Aliment Pharmacol Ther 1998; 12 Suppl 1: 73–82. [DOI] [PubMed] [Google Scholar]
• 2.Tannenbaum SR, Wishnok JS, Leaf CD. Inhibition of nitrosamine formation by ascorbic acid. Am. J Clin Nutr 1991; 53: 247S–50S. [DOI] [PubMed] [Google Scholar]
• 3.Block G. Vitamin C and cancer prevention: the epidemiologic evidence. Am J Clin Nutr 1991; 53: 270S–82S. [DOI] [PubMed] [Google Scholar]
• 4.Zhang HM, Wakisaka N, Maeda O, Yamamoto T. Vitamin C inhibits the growth of a bacterial risk factor for gastric carcinoma: Helicobacter pylori. Cancer 1997; 80: 1897–903. [PubMed] [Google Scholar]
• 5.Jarosz M, Dzieniszewski J, Ufniarz ED, Wartanowicz M, Ziemlanski S, Reed PI. Effects of high dose vitamin C treatment on Helicobacter pylori infection and total vitamin C concentration in gastric juice. Eur J Cancer Prev 1998; 7: 449–54. [DOI] [PubMed] [Google Scholar]
• 6.Miki K, Ichinose M, Shimizu A, Huang SC, Oka H, Furihata C, Matsushima T, Takahashi K. Serum pepsinogens as a screening test of extensive chronic gastritis. Gastroenterol Jpn 1987; 22: 133–41. [DOI] [PubMed] [Google Scholar]
• 7.Tsubono Y, Okubo S, Hayashi M, Kakizoe T, Tsugane S. A randomized controlled trial for chemoprevention of gastric cancer in high‐risk Japanese population; study design, feasibility and protocol modification. Jpn J Cancer Res 1997; 88: 344–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 8.Anonymous . Beta carotene and vitamin A halted in lung cancer prevention trial. National Cancer Institute Press Release, Jan. 18, 1996. [Google Scholar]
• 9.Recommended dietary allowance for Japanese. 5th ed. Tokyo : Daiichi Shuppan; 1994. (in Japanese). [Google Scholar]
• 10.Levine M, Conry‐Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc NatlAcad Sci USA 1996; 93: 3704–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 11.Correa P, Haenszel W, Cuello C, Zavala D, Fontham E, Zarama G, Tannenbaum S, Collazos T, Ruiz B. Gastric precancerous process in a high risk population: cross‐sectional studies. Cancer Res 1990; 50: 4731–6. [PubMed] [Google Scholar]
• 12.Miki K. The clinical application of serum pepsinogen measurement. Naika 1990; 66: 618–20 (in Japanese). [Google Scholar]
• 13.Bodger K, Wyatt JI, Heatley RV. Variation in serum pepsinogen with severity and topography of Helicobacter pylori‐associated chronic gastritis in dyspeptic patients referred for endoscopy. Helicobacter 2001; 6: 216–24. [DOI] [PubMed] [Google Scholar]
• 14.El‐omar EM, Oien K, El‐nujumi A, Gillen D, Wirz A, Dahill S, Williams C, Ardill JES, Mccoll KEL. Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology 1997; 113: 15–24. [DOI] [PubMed] [Google Scholar]
• 15.Helicobacter and Cancer Collaborative Group . Gastric cancer and Helicobacter pylori: a combined analysis of 12 cases control studies nested within prospective studies. Gut 2001; 49: 347–53. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 16.Webb PM, Bates CJ, Palli D, Forman D, the Eurogast Study Group. Gastric cancer, gastritis and plasma vitamin C: results from an international correlation and cross‐sectional study. Int J Cancer 1997; 73: 684–9. [DOI] [PubMed] [Google Scholar]
• 17.Sobala GM, Schorah CJ, Sanderson M, Dixon MF, Tompkins DS, Godwin P, Axon ATR. Ascorbic acid in the human stomach. Gastroenterology 1989; 97: 357–63. [DOI] [PubMed] [Google Scholar]
• 18.Sobala GM, Crabtree JE, Dixon MF, Schorah CJ, Taylor JD, Rathbone BJ, Heatley RV, Axon ATR. Acute Helicobacter pylori infection: clinical features, local and systemic immune response, gastric mucosal histology, and gastric juice ascorbic acid concentrations. Gut 1991; 34: 1415–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 19.Banerjee S, Hawksby C, Miller S, Dahill S, Beattie AD, McColl KEL. Effect of H. pylori and its eradication on gastric juice ascorbic acid. Gut 1994; 35: 317–22. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 20.Crabtree JE, Covacci A, Farmery SM, Xiang Z, Tompkins DS, Perry S, Lindley IJ, Rappuoli R. Helicobacter pylori induced interleukin‐8 expression in gastric epithelial cells is associated with CagA positive phenotype. J Clin Pathol 1995; 48: 41–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 21.Cover TL, Glupczynski Y, Lage AP, Burette A, Tummuru MK, Perez‐Perez GI, Blaser MJ. Serologic detection of infection with CagA+Helicobacter pylori strains. J Clin Microbiol 1995; 33: 1496–500. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 22.Blaser MJ. Intrastrain differences in Helicobacter pylori: a key question in mucosal damage? Ann Med 1995; 27: 559–63. [DOI] [PubMed] [Google Scholar]
• 23.Kuipers EJ, Perez‐Perez GI, Meuwissen SG, Blaser MJ. Helicobacter pylori and atrophic gastritis: importance of the CagA status. J Natl Cancer Inst 1995; 87: 1777–80. [DOI] [PubMed] [Google Scholar]
• 24.Blaser MJ, Perez‐Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, Stemmermann GN, Nomura A. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 1995; 55: 2111–5. [PubMed] [Google Scholar]
• 25.Correa P. Human gastric carcinogenesis: a multistep and multifactorial process–first American Cancer Society award lecture on cancer epidemiology and prevention. Cancer Res 1992; 52: 6735–40. [PubMed] [Google Scholar]