Vitamin B-6 restriction tends to reduce the red blood cell glutathione synthesis rate without affecting red blood cell or plasma glutathione concentrations in healthy men and women.

Background: Glutathione plays various protective roles in the human body. Vitamin B-6 as pyridoxal-5'-phosphate (PLP) is required as the coenzyme in the formation of glutathione precursors. Despite this obligatory role of PLP, previous studies from this laboratory showed that vitamin B-6 deficiency caused elevated glutathione concentrations in rat liver and human plasma.

Objective: Our aim was to determine the effect of marginal vitamin B-6 deficiency (plasma PLP 20-30 nmol/L) on the rate of red blood cell (RBC) glutathione synthesis.

Design: We measured plasma and RBC glutathione concentrations and the fractional and absolute synthesis rates of RBC glutathione using the stable-isotope-labeled glutathione precursor [1,2-(13)C(2)]glycine in 13 healthy volunteers aged 21-39 y.

Results: Dietary vitamin B-6 restriction did not significantly affect the glutathione concentration in plasma (6.9 +/- 1.9 compared with 6.7 +/- 1.1 micromol/L) or RBCs (2068 +/- 50 compared with 2117 +/- 48 micromol/L). For RBC glutathione, the mean fractional synthesis rates were 54 +/- 5%/d and 43 +/- 4%/d (P = 0.10), and the absolute synthesis rates were 1116 +/- 100 and 916 +/- 92 micromol . L(-1) . d(-1) (P = 0.14) before and after vitamin B-6 restriction, respectively.

Conclusions: Marginal vitamin B-6 deficiency tended to decrease mean RBC glutathione synthesis with no effect on RBC glutathione concentration, but the responses varied widely among individuals. Because the cysteine concentration in plasma and RBC did not change during vitamin B-6 restriction, we conclude that the effects of marginal vitamin B-6 deficiency on glutathione synthesis are not caused by altered precursor concentrations.