EXPERIMENTAL AND CLINICAL-STUDIES ON THE REDUCTION OF ERYTHROCYTE SORBITOL-GLUCOSE RATIOS BY ASCORBIC-ACID IN DIABETES-MELLITUS

In order to confirm the effect of ascorbic acid (AA) on human erythroc yte sorbitol accumulation and explore its mechanism of action, the eff ects of ascorbic acid in vitro on the sorbitol (S) and glucose (EG) co ntent of human erythrocytes and in particular on the S/EG ratio as a m arker of aldose reductase (AR) activity were carefully observed. The r esults showed that both the accumulation of erythrocyte sorbitol and t he S/EG ratio were strongly reduced by the addition of AA. The sorbito l content in the erythrocyte and the S/EG ratio were reduced by a maxi mum of 87.3% and 83.4% and 93.8% and 63.9% when the medium's AA concen tration was at its peak with 5.6 mmol/l and 28 mmol/l glucose in the m edium, respectively. The contents of erythrocyte glucose measured coin cidentally revealed a positive correlation with the ascorbic acid conc entration in the medium during incubation in 5.6 mmol/l glucose while at a higher glucose level (28 mmol/l) in the medium the correlation be came negative. These results suggested that the polyol pathway could b e inhibited effectively by AA through its direct action on AR. The res ults of a double-blind cross-over trial using AA tablets or inositol t ablets in eight diabetic patients showed that the supplementation of 1 000 mg AA/day for 2 weeks resulted in reductions of 12.2% and 21.8% in erythrocyte sorbitol and red cell sorbitol/plasma glucose (S/PG) rati o, respectively (P < 0.05), whereas the fasting plasma glucose levels measured coincidentally revealed no changes (P > 0.05). This suggested that supplementation with moderate amounts of AA (1000 mg/day) might serve as a simple, safe and effective measure for prevention and ameli oration of the chronic complications of diabetes.