Objective To evaluate the roles of folic acid and β-carotene in the chemoprevention of gastric and other gastrointestinal (GI) cancers. Methods In a randomized, double-blind, placebo-controlled trial, a total of 216 patients with atrophic gastritis were randomly assigned to one of the four groups: ①folate (FA, 20 mg per day plus vitamin B 12 1 mg, intramuscularly, per month for one year, then 20 mg two times a week plus 1 mg per three months for the next year); ②natural β-carotene (N-βC, 30 mg per day for first year, then 30mg two times a week for the next); ③synthetic β-carotene (S-βC, administered as in N-βC); and ④placebo. Follow-ups continued from 1994 to 2001. Results A total of 7 new cases of gastrointestinal cancers were diagnosed with 3 stomach, 1 colon and 1 esophageal cancers occurring in the placebo group; 1 stomach cancer in both of the N-βC and S-βC groups, and no cancer occurring in FA group. In terms of GI cancers, there was a significant reduction in the FA group, compared with the placebo group (P= 0.04). A similar trend was observed in both N-βC and S-βC groups (P=0.07-0.08). Taken together, the three intervention groups displayed a highly significant decrease in occurrence (P=0.004, vs placebo), and a lower risk for GI cancers (OR=0.12; 95% confidence interval, 0.03-0.51). For development of gastric cancer, any one of the three active-treated groups did not reach statistically significant reduction. The FA group showed obvious improvement of the gastric mucosal lesions with more patients displaying lesions reversed or stable atrophy and inflammation (P=0.04), reversed intestinal metaplasia (P=0.06) at the end of follow-up, and reversed displasia (P=0.017) at 12 months. Two cases of false jaundice were found in β-carotene groups with no influence on administration, and no side-effects were reported in FA group. Conclusions This trial revealed the interventional effect of folic acid on the development of GI cancers, a similar effect of β-carotene was also detected. Also, folic acid may be of use to treat atrophic gastritis by preventing or reversing the precancerous lesions. Objective To evaluate the roles of folic acid and β-carotene in the chemoprevention of gastric and other gastrointestinal (GI) cancers. Methods In a randomized, double-blind, placebo-controlled trial, a total of 216 patients with atrophic gastritis were randomly assigned (FA, 20 mg per day plus vitamin B 12 1 mg, intramuscularly, per month for one year, then 20 mg two times a week plus 1 mg per three months for the next year); ② natural β-carotene (N-βC, 30 mg per day for first year, then 30 mg two times a week for the next); ③synthetic β-carotene (S-βC, administered as N-βC); and ④placebo. Follow-ups continued from 1994 to 2001. Results A total of 7 new cases of gastrointestinal cancers were diagnosed with 3 stomach, 1 colon and 1 esophageal cancers occurring in the placebo group; 1 stomach cancer in both of the N-βC and S-βC groups, and no cancer occurring in FA group. In terms of GI cancers, there was a significant red The common phenomenon was observed in both N-βC and S-βC groups (P = 0.07-0.08). Taken together, the three intervention groups displayed a highly For development of gastric cancer, any one of the three active-treated groups (P = 0.004, vs placebo), and a lower risk for GI cancers (OR = 0.12; 95% confidence interval, 0.03-0.51) The FA group showed significantly improvement of the gastric mucosal lesions with more patients of the 19-year-old follow-up (P = 0.06) Two cases of false jaundice were found in β-carotene groups with no influence on administration, and no side-effects were reported in FA group. Conclusions This trial revealed the interventional effect of folic acid on the developme nt of GI cancers, asimilar effect of β-carotene was also detected. Also, folic acid may be of use to treat atrophic gastritis by preventing or reversing the precancerous lesions.