High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance

1 Diabetes Unit, National Center for Complementary and Alternative Medicine; 2 Cardiology Branch, National Heart, Lung, and Blood Institute; 3 Molecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland Submitted 19 July 2005 ; accepted in final form 23 August 2005 Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress. Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal. Thus endothelial dysfunction may worsen insulin resistance. Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes. In the present study, we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes. Plasma vitamin C levels in 109 diabetic subjects were lower than healthy (36 ± 2 µM) levels. Thirty-two diabetic subjects with low plasma vitamin C (80 µM). No significant changes in fasting glucose (156 ± 11 mg/dl), insulin (14 ± 2 µU/ml), SI Clamp [2.71 ± 0.46 x 10 –4 dl·kg –1 ·min –1 /(µU/ml)], or forearm blood flow in response to ACh, SNP, or insulin were observed after vitamin C treatment. We conclude that high-dose oral vitamin C therapy, resulting in incomplete replenishment of vitamin C levels, is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes. hypertension; hyperglycemia; hypercholesterolemia; insulin sensitivity; sodium nitroprusside Address for reprint requests and other correspondence: M. J. Quon, Diabetes Unit, NCCAM, NIH, Bldg. 10, Rm. 6C-205, 10 Center Dr. MSC 1632,