Congestive Heart Failure

Patients with congestive heart failure (CHF) demonstrate systemic vasoconstriction and reduced peripheral perfusion. While an increased sympathetic tone and an activated renin-angiotensin system have been proposed to be involved in the reduced vasodilator capacity in heart failure, clinical studies have documented endothelial dysfunction of peripheral resistance arteries60 and an impaired flow-dependent, endothelium-mediated dilation of conduit arteries.61 An important functional consequence of endothelial dysfunction is the inability of a vessel to dilate in response to endothelium-derived NO after physiological stimuli.62,63 It has been hypothesized this is caused by reduced synthesis of NO possibly due to a reduced NO-synthase gene expression.64 However, other mechanisms such as reduced availability of L-arginine or enhanced inactivation of NO by free radicals may be involved as well.65

Vitamin C has been shown to improve CHF by increasing the availability of nitric oxide.66 This observation suggests endothelial dysfunction in patients with CHF may be due to accelerated degradation of nitric oxide by free radicals.

Vitamin C and Iron Deficiency Anemia

Iron deficiency is regarded as the major cause of nutritional anemia, but vitamins A, B12, C, E, folic acid, and riboflavin have also been linked to its development and control. Ascorbic acid has been reported to play a key role in the absorption of dietary non-heme iron.67,68,69

Diabetes Mellitus

The cellular uptake of vitamin C is promoted by insulin and is inhibited by hyperglycemia. In the absence of insulin, hyperglycemia produces “tissue scurvy.” The complications of diabetes mellitus (DM), in part, are believed to result from either the intracellular accumulation of sorbitol or the nonenzymatic glycoxidation of proteins or both. In type 1 diabetic patients, vitamin C supplementation may be necessary to prevent protein glycoxidation and to optimize aldose reductase inhibition.70 Ascorbic acid status depends on the interactions of dietary vitamin C intake, plasma insulin concentrations, and glycemia. Insulin promotes the active cellular uptake of vitamin C whereas hyperglycemia inhibits renal vitamin C reabsorption. In type 1 diabetes mellitus, an adequate dietary intake of vitamin C is often associated with an unexpectedly low ascorbic acid status.

The role of vitamin C as an aldose reductase inhibitor and a water soluble antioxidant in body fluids is an important adjunct to tight glycemic control. Hyperglycemia also appears to be a fundamental abnormality underlying the mechanisms that cause endothelial dysfunction in diabetic patients, which are impaired in both animal models and humans with type 1 or type 2 DM.71,72,73,74,75

Indeed, the administration of vitamin C has been shown to improve endothelium-dependent vasodilation in both experimental hyperglycemia in healthy, nondiabetic human subjects as well as in patients with either type 1 or type 2 DM.73,74,76,77,78