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Clinical Science (2005) 108, (507–513) (Printed in Great Britain)
Effect of ascorbic acid on microcirculation in patients with Type II diabetes: a randomized placebo-controlled cross-over study
Qing LU*, Ingemar BJÖRKHEM*, Bengt WRETLIND†, Ulf DICZFALUSY*, Peter HENRIKSSON‡ and Anna FREYSCHUSS§
*Division of Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm SE-141 86, Sweden, †Division of Bacteriology, Karolinska University Hospital, Huddinge, Stockholm SE-141 86, Sweden, ‡Department of Medicine, Karolinska Institutet at Danderyd Hospital, SE-182 88 Stockholm, Sweden, and §Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Key words: ascorbic acid, microcirculation, oxidative stress, Type II diabetes, vascular disease.

Abbreviations: ACE, angiotensin-converting enzyme; AT1, angiotensin type 1 receptor; HbA1c, glycated haemoglobin; HDL, high-density lipoprotein; hs-CRP, high-sensitivity C-reactive protein; IL-1ra, interleukin-1 receptor antagonist; IL-6, interleukin-6; ox-LDL, oxidized low-density lipoprotein; PRH, post-occlusive reactive hyperaemia; TtP, time to peak.

Correspondence: Dr Anna Freyschuss (email anna.freyschuss@medhs.ki.se).


Manifestations of vascular disease, including microvascular changes, constitute the major part of the morbidity and mortality in diabetic patients. Oxidative stress has been suggested to play an important role in the vascular dysfunction of diabetic patients. Furthermore, epidemiological observations indicate a beneficial effect of an increased dietary intake of antioxidants. The present study tested the hypothesis that the antioxidant ascorbic acid influences microcirculatory function in patients with Type II diabetes. Patients with Type II diabetes were treated with 1 g of ascorbic acid three times a day for 2 weeks in a randomized placebo-controlled double-blind cross-over design. Microvascular reactivity was assessed by vital capillaroscopy and PRH (post-occlusive reactive hyperaemia). hs-CRP (high-sensitivity C-reactive protein), IL-6 (interleukin-6), IL-1ra (interleukin-1 receptor antagonist) and ox-LDL (oxidized low-density lipoprotein) were analysed. The results showed no significant change in microvascular reactivity assessed after 2 weeks of ascorbic acid treatment. TtP (time to peak) was 12.0±3.3 s before and 11.2±3.5 s after ascorbic acid (n=17). In comparison, TtP was 11.5±2.9 s before and 10.6±2.8 s after placebo (not significant). IL-1ra, IL-6, hs-CRP and ox-LDL did not change significantly after ascorbic acid, neither as absolute or relative values. In conclusion, in contrast with some studies reported previously, we could not demonstrate an effect of continuous oral treatment with ascorbic acid on microvascular reactivity assessed at the level of individual capillaries. Furthermore, we found no indication of an effect on inflammatory cytokines or ox-LDL.


Received 5 October 2004/14 January 2005; accepted 27 January 2005

Published as Immediate Publication 27 January 2005, DOI 10.1042/CS20040291


©2005 The Biochemical Society



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