Vanadium is an ultratrace element that is present in the human body at concentrations of approximately 0.3mg/kg (with a total body vanadium content of approximately 1-2mg), and it is found primarily in the bone, the liver, and the kidneys, where it is stored as the vanadyl cation (VO2+) bound to the transferrin and to the albumin in the blood. Vanadium is unique among the trace elements in that it has insulin mimetic effects — it activates the insulin receptor tyrosine kinase activity, it stimulates the glucose uptake in the muscle and the fat cells, and it reduces the blood glucose levels in people with type 2 diabetes, without the need for the insulin. The insulin mimetic effect of vanadium was first described in the 1980s, when it was observed that vanadium salts stimulated the glucose uptake in isolated adipocytes in the absence of the insulin, and subsequent studies demonstrated that vanadium activates the insulin receptor by inhibiting the protein tyrosine phosphatases (PTPs) that dephosphorylate and inactivate the insulin receptor, thereby prolonging the insulin signal and amplifying the insulin effect. This vanadium-dependent insulin mimetic effect is one of the most interesting and most promising findings in nutritional pharmacology, and it explains why vanadium supplementation has been studied extensively as a potential treatment for the type 2 diabetes and for the insulin resistance syndrome.
The Insulin Mimetic Mechanism of Vanadium
Vanadium acts as an insulin mimetic by inhibiting the protein tyrosine phosphatases (PTPs) — the enzymes that dephosphorylate and inactivate the insulin receptor and the insulin receptor substrates (IRS-1, IRS-2) in the insulin signalling pathway. The insulin receptor is a receptor tyrosine kinase — when insulin binds to the alpha subunit of the receptor, the beta subunit undergoes autophosphorylation at multiple tyrosine residues, and this activated receptor phosphorylates the IRS proteins, which in turn activate the downstream signalling cascade (PI3K, Akt, GLUT4 translocation) that leads to the glucose uptake. The PTPs (particularly PTP1B and TC-PTP) are the counter-regulatory enzymes that dephosphorylate the insulin receptor and the IRS proteins, thereby terminating the insulin signal. Vanadium (as vanadyl, VO2+) inhibits these PTPs by binding to the active site cysteine residue and preventing the catalytic activity, and this inhibition prolongs and amplifies the insulin signal — producing the same effect as the insulin itself. When vanadium is administered to people with type 2 diabetes (at doses of 100-150mg daily of vanadyl sulfate), it mimics the effect of the insulin and reduces the blood glucose levels, even in the absence of the insulin. This insulin mimetic effect is the basis for the use of vanadium as a potential treatment for the type 2 diabetes.
The clinical importance of the insulin mimetic effect of vanadium is underscored by the observation that vanadium supplementation reduces the fasting blood glucose, the postprandial blood glucose, and the HbA1c in people with type 2 diabetes. Multiple RCTs have demonstrated that vanadyl sulfate supplementation at 100-150mg daily (providing approximately 25-40mg of elemental vanadium) significantly reduces the fasting blood glucose by approximately 20-30mg/dL, reduces the HbA1c by 0.5-1.0%, and improves the insulin sensitivity (as measured by the HOMA-IR) in people with type 2 diabetes. However, the therapeutic use of vanadium is limited by the gastrointestinal side effects (nausea, diarrhoea, abdominal cramps) that are associated with the high doses that are required to achieve the insulin mimetic effect, and by the uncertainty about the long-term safety of the vanadium supplementation (because vanadium can accumulate in the bone and in the liver, and because the chronic vanadium exposure is associated with the kidney toxicity and the neurological effects).
Vanadium and the Tyrosine Phosphatase Inhibition
The inhibition of the protein tyrosine phosphatases by vanadium is not specific to the insulin signalling pathway — vanadium also inhibits the PTPs that regulate the other signalling pathways, including the cytokine signalling pathways, the growth factor signalling pathways, and the immune cell signalling pathways. This non-specificity of the vanadium inhibition explains the multiple effects of the vanadium supplementation (including the insulin mimetic effect, the anti-inflammatory effect, and the anti-tumour effect) and also explains the potential toxicity of the high-dose vanadium supplementation (because the inhibition of the PTPs in the immune cells and in the other tissues can produce the immune dysfunction and the tissue damage that are associated with the chronic vanadium exposure). The therapeutic window for the vanadium supplementation is therefore relatively narrow — the doses that are required to achieve the insulin mimetic effect (100-150mg of vanadyl sulfate daily) are close to the doses that produce the adverse effects (gastrointestinal symptoms, kidney toxicity), and this limits the clinical utility of the vanadium as a long-term treatment for the type 2 diabetes.
Practical Application
For general vanadium supplementation, the evidence-based approach is to supplement with 10-25mg of vanadium daily (as vanadyl sulfate or as the more bioavailable bis(maltolato)oxovanadium(IV) form), which is the dose range that has been shown to have insulin mimetic effects in clinical trials without producing significant adverse effects. The tolerable upper intake level for vanadium has not been established, but the doses above 50mg daily of elemental vanadium are associated with the gastrointestinal symptoms and with the potential for the kidney toxicity. Vanadium should not be used as a substitute for the established diabetes medications (metformin, the sulfonylureas, the SGLT2 inhibitors, the GLP-1 receptor agonists), and it should only be used under the supervision of a physician who can monitor the blood glucose, the kidney function, and the other clinical parameters. For comprehensive glycaemic control support, vanadium pairs well with chromium (which has a complementary insulin-sensitising effect through the chromodulin mechanism), with the alpha-lipoic acid (which has insulin-sensitising and antioxidant effects), with the berberine (which has been shown in multiple RCTs to reduce the blood glucose and the HbA1c in people with type 2 diabetes), and with the magnesium (which is required for the insulin receptor signalling and whose deficiency is associated with the insulin resistance).
Leave a Reply