Background: Ascorbate and glutathione play central roles in the defense against free radicals and oxidants that are implicated in chronic diseases.
Objective: The objective was to determine the ability of vitamin C supplements to modulate the concentration of glutathione in human lymphocytes.
Design: The effect of vitamin C supplements was determined in a sequential study with time points before supplementation, after 13 wk of vitamin C supplements (500 or 1000 mg/d), and after 13 wk of matching placebo. The supplementation group was selected on the basis of low plasma ascorbate (<33 mmol/L) and consisted of 48 healthy men and women, smokers and nonsmokers, aged 25–64 y. Ascorbate and glutathione were measured in purified lymphocytes.
Results: At baseline, the mean (±SD) concentration of plasma ascorbate was 19.5 ± 7.2 µmol/L, 22.5 µmol/L below the median of normal distribution. The ascorbate concentration in plasma was linearly associated with that in lymphocytes (r = 0.53, P < 0.001). On supplementation with vitamin C, lymphocyte ascorbate increased by 51% (from 16.7 ± 4.9 to 25.3 ± 6.9 nmol/mg protein; P < 0.001) and was accompanied by an increase of lymphocyte glutathione by 18% (from 22.5 ± 4.5 to 26.6 ± 6.5 nmol/mg protein; P < 0.001). After placebo, the ascorbate and glutathione concentrations fell to near baseline concentrations (17.1 ± 5.4 and 23.5 ± 6.4 nmol/mg protein, respectively). No significant interaction was observed for sex and smoking status. Finally, the changes in lymphocyte ascorbate after supplementation were strongly associated with changes in lymphocyte glutathione (r = 0.71, P < 0.001). The association suggests that every 1-mol change in ascorbate is accompanied by a change of 
0.5 mol in glutathione.
Conclusion: Vitamin C supplements increase glutathione in human lymphocytes.