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J Am Coll Nutr. 2003 Jun;22(3):208-16.

Effect of five-year supplementation of vitamin C on serum vitamin C concentration and consumption of vegetables and fruits in middle-aged Japanese: a randomized controlled trial.

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Epidemiology & Biostatistics Division, National Cancer Center Research Institute East, Chiba, Japan.



This study was aimed at evaluating the effect of long-term vitamin C supplementation on serum and dietary vitamin C and identifying the factors associated with change in serum concentration.


A total of 439 subjects with atrophic gastritis initially participated in a randomized clinical trial using vitamin C and beta-carotene to prevent gastric cancer. We originally randomized the participants into four treatment groups using a 2x2 factorial design, whereby 0 or 15 mg/day beta-carotene and 50 or 500 mg/day vitamin C were administered in a double-blind manner. The beta-carotene component was terminated early after a mean treatment duration of four months. Before and upon early termination of beta-carotene supplementation, 134 subjects dropped out this trial, while 120 and 124 subjects took the vitamin C supplement at either 50 mg or 500 mg daily for five years.


Changes in serum vitamin C were significantly higher in the high-dose group (38.5% increase, 95% CI = 27.0-49.9) than in the low-dose group (13.0% increase, 5.1-20.9) or in the dropout group (3.3% increase, -2.1-8.6) after five-year supplementation. The serum vitamin C at baseline was negatively associated with changes in serum vitamin C (p < 0.0001), while high-dose (p < 0.0001) and low-dose (p < 0.05) supplementation and female gender (p < 0.001) were positively associated. Dietary intake of vitamin C in the supplementation group was almost identical before and after five-year supplementation of vitamin C (2.31 mg/day decrease, 95% CI = -15.3-10.7), while a 17.7 mg/day decrease (95% CI = -44.2-8.86) was observed in the drop-out group.


Five-year vitamin C supplementation induces a remarkable increase in serum vitamin C concentration, and our intervention program appears to have no effect on dietary vitamin C intake.

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