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To investigate the influence of iron deficiency and iron supplementation on nitric oxide (NO) production, we measured serum iron markers, serum nitrate and nitrite (NOx) concentrations, reticulocyte maturity index (RMI), and serum transferrin receptor (sTfR) levels in 369 females aged 14-19 years. RMI was analyzed by flow cytometry, sTfR concentrations were measured by enzyme immunoassay, and serum NOx levels were tested by the Griess reaction. NOx concentrations of the subjects in iron depletion phase were significantly higher than those of healthy controls. NOx concentrations increased gradually as iron deficiency progressed and were threefold higher than for the healthy controls, when the subjects attained a frank iron deficiency anemia. In particular, the NOx concentrations were 7.5-fold higher in the patients with severe iron deficiency anemia (Hb<80 g/l) than for the subjects with high hemoglobin value (Hb>or=140 g/l). The increased NOx concentrations (132.6+/-42.1 microM) observed in the group with severe anemia decreased significantly (46.3+/-15.8 microM) after hemoglobin levels were normalized by iron supplementation ( P<0.01). NOx concentrations correlated inversely with hemoglobin levels ( r(2)=0.202, P<0.01), but correlated positively with the sTfR concentrations ( r(2)=0.322, P<0.01) and the RMI ( r(2)=0.369, P<0.01). In conclusion, iron deficiency anemia increases NO production, and elevated NOx concentrations in iron deficiency anemia return to normal with iron supplementation.

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