The trace element vanadium has not been established as an essential nutrient, and human deficiency has not been documented. Vanadium exists in several valence states, with vanadate (+4) and vanadyl (+5) forms most common in biological systems. Vanadyl sulfate and sodium metavanadate are the most common supplemental forms, but other organic vanadium compounds have been developed.
In animal models, vanadium has been shown to facilitate glucose uptake and metabolism, facilitate lipid and amino acid metabolism, improve thyroid function, enhance insulin sensitivity, and negatively affect bone and tooth development in high doses. In humans, pharmacological doses alter lipid and glucose metabolism by enhancing glucose oxidation, glycogen synthesis, and hepatic glucose output. Vanadium acts primarily as an insulinmimetic agent, although enhanced insulin activity and increased insulin sensitivity have also been noted. More recent research suggests that insulin may be required for its effects.
Vanadium is ubiquitous in the environment but is present in extremely small quantities. This makes it difficult to accurately measure status or to induce deficiencies. There are no accurate assays for clinical settings. There is also no RDA. The usual U.S. diet is estimated to provide 10–60 μg/day.
Vanadium is stored primarily in bone and transported in the bloodstream on transferrin. It is cleared primarily through the kidney.
Mechanism of action.
Vanadium’s chemical structure is similar to that of phosphorus, which appears to influence its biochemical actions. It may act as a phosphate analog and has been shown to alter the rate of activity of a number of adenosine triphosphatases, phosphatases, and phosphotransferases.
Vanadium appears to affect several points in the insulin signaling pathway and may lead to upregulation of the insulin receptor and subsequent intracellular signaling pathways. Suggested effects include insulin receptor autophosphorylation, increased protein tyrosine and serine threonine kinase activity, inhibition of phosphotyrosine phosphatase activity, increased adenylate cyclase activity, altered glucose-6-phosphatase activity, inhibition of hepatic gluconeogenesis, and increased glycogen synthesis.
Several small trials have evaluated the use of oral vanadium supplements in diabetes. Most focused on type 2 diabetes, although animal studies suggest that vanadium also has potential benefit in type 1 diabetes.
In subjects with type 2 diabetes, vanadium increased insulin sensitivity as assessed by euglycemic, hyperinsulinemic clamp studies in some, but not all, trials. Glucose oxidation and glycogen synthesis were increased, and hepatic glucose output was suppressed in two studies.
In type 1 diabetes, vanadium did not affect insulin sensitivity, although daily insulin doses declined. Supplementation decreased FBG, HbA1c, and cholesterol levels and stimulated kinase activity.
Pharmacological doses appear to have a mild effect on insulin sensitivity and glucose utilization in type 2 diabetes. Effects in animal models are stronger than in humans, and there is no information on the long-term effects in diabetes.
When evaluating these studies, one should pay particular attention to the form of vanadium utilized, specific animal model of diabetes used or type of diabetes in humans, doses, physiological relevance of the results, length of study, and the impact on food intake and weight caused by the anorexiant effects of vanadium. It is also important to look at study design, controls, washout period, and assay methods, especially in vitro phosphorylation assays, which are notoriously difficult to conduct well.