Handbook of Vitamin C Research

Vitamin C: Dietary Requirements, Dietary Sources, and Adverse Effects 135concentration is now regarded as an important contributing factor for increased oxidativestress and endothelial dysfunction [125].In the study by Tousoulis et al., patients with type 2 diabetes and coronary artery disease(CAD) were treated with or without vitamin C supplement (2g/day) for 4 weeks. Forearmblood flow and vasodilatory response were measured. The results revealed that acute highdose vitamin C improved vasodilatory response to reactive hyperemia and decreased thelevels of tissue plasminogen activator and von Willebrand factor [126] . A recent studyshowed that supplementary vitamin C 1000 mg/day can reduce diabetes-associatedcomplications. Patients with diabetes were randomized into two groups. Participants in onegroup received vitamin C 500 mg/day for 6 weeks, and those in the other group received adose of 1000 mg/day for 6 weeks. The results revealed that the concentrations of fastingblood sugar, triglyceride, low-density lipoprotein cholesterol, hemoglobulin A1C, and seruminsulin were significantly lower in the high-dose group than in the low-dose group. Theresearchers postulated that the reduction in laboratory values was due to the antioxidantcapacity of vitamin C [127].Andrea Natali and her colleagues measured the effect of vitamin C on acetylcholine(ACh)-induced vasodilatation and on forearm glucose uptake during systemichyperinsulinemia. In their study, a high dose of vitamin C (12 mg per min) was infused intothe brachial artery in patients with essential hypertension [128]. The contralateral forearmwas used as the control for comparison. In response to insulin, tested blood flow increasedafter vitamin C infusion. The rate of insulin-stimulated whole-body glucose disposal,considered a marker of insulin resistance, decreased after vitamin C infusion, but notsignificantly. Forearm O 2 uptake was similar in the forearms with or without vitamin Cinfusion. They conclude that in the deep forearm tissues of patients with essentialhypertension and insulin resistance, an acute improvement in endothelial function, obtainedwith pharmacological doses of vitamin C, restores insulin-mediated vasodilatation but doesnot improve insulin-mediated glucose uptake. According to their results, endothelialdysfunction in patients with essential hypertension is unlikely to be responsible for metabolicinsulin resistance.Rather than infusing vitamin C, Chen et al. investigated the effects of orally administeredhigh-dose vitamin C on attenuation of endothelial dysfunction and insulin resistance inpatients with Type 2 diabetes. They found that plasma vitamin C levels were lower in 109diabetic subjects than in healthy controls. The researchers then recruited 32 of the 109diabetic subjects with low plasma vitamin C levels to participate in a randomized, doubleblind,placebo controlled study of vitamin C (800 mg/day for 4 weeks). Insulin sensitivity(determined by glucose clamp) and forearm blood flow in response to ACh, sodiumnitroprusside (SNP), or insulin (determined by plethysmography) were determined before andafter 4 weeks of treatment. In the vitamin C group, basal plasma vitamin C increased aftertreatment, but the level was significantly lower than expected for healthy subjects. Nosignificant changes in fasting glucose, SIClamp, or forearm blood flow in response to ACh,SNP, or insulin were observed after vitamin C supplements. They conclude that high-doseoral vitamin C therapy, resulting in incomplete replenishment of vitamin C levels, does notimprove endothelial dysfunction and insulin resistance in type 2 diabetes [129].