BACKGROUND: Latent tissue scurvy in clinical and experimental ascorbic acid (AA) deficiency resembles diabetic microangiopathy as reflected in capillary hyperperfusion and increased transcapillary escape rate (TER), von Willebrand factor (vWf), and capillary fragility (CF). We aimed to investigate the possible clinical impact of the low plasma AA level observed in type 1 diabetes mellitus. METHODS: Twenty normoalbuminuric patients with retinopathy were included in a randomized, double-blinded, placebo-controlled 6-month study with AA (6 g/day; n=10, mean age+/-S.D. 35.3+/-8.5 years, diabetes duration 17.2+/-3.3 years) or placebo (n=10; mean age 37.8+/-6.6 years, diabetes duration 18.4+/-1.7 years). RESULTS: An inverse correlation between log plasma AA (HPLC method) and TER of (125)I-labelled albumin was found (r=-0.66, p=0.002). TER decreased in the AA-treated group from 6.8+/-1.0 to 5.4+/-1.5%/h compared to the unchanged placebo group (from 5.6+/-1.5 to 5.9+/-1.1%/h; p=0.031). The CF (capillary resistance test) decreased in the AA group compared to the placebo group (p=0.028), while vWf, fibrinogen and fibronectin levels, and glomerular filtration rate (clearance of (125)I-iothalamate) remained unchanged. CONCLUSIONS: The results suggest that a low plasma AA level might be associated (pathogenetic?) with development of microangiopathy in type 1 diabetes mellitus and points to a possible treatment modality.