IngredientesVanadium (chemical symbol: V; atomic number: 23) is a transition metal element. It is a steel-grey, corrosion-resistant metal that exists in oxidation states ranging from −1 to +5. Metallic vanadium does not occur in nature, and the most common valence states are +3, +4, and +5. The pentavalent form (VO₃⁻) predominates in extracellular body fluids, whereas the quadrivalent form (VO²⁺) is the most common intracellular form.
In the context of nutritional and supplemental use, vanadium exists most importantly in two ionic forms: vanadate (the pentavalent V⁵⁺ form, VO₄³⁻) and vanadyl (the tetravalent V⁴⁺ form, VO²⁺). In vitro, vanadium in the form of vanadate regulates hormone, glucose, and lipid metabolism; however, vanadium most probably exists in the vanadyl form in vivo. It is found in compounds at valences of 2, 3, 4, or 5, with the tetravalent and pentavalent forms being the most common.
The chemical structure of vanadium is similar to that of phosphorus — the vanadium-oxygen bond is about 0.1 nm longer than the phosphorus-oxygen bond. This may explain in part the profound effects of vanadate on phosphorylation reactions.
Vanadium is marketed in dietary supplements primarily in the following chemical forms:
Vanadium may be found in various commercial nutritional supplements and multivitamins in amounts ranging from 0.0004 to 12.5 mg, depending on the serving size recommended by the manufacturer.
Small amounts of vanadium are found naturally in soil and water. Higher amounts of environmental vanadium are usually caused by contaminations, namely mining, fossil fuel and coal combustion, and use of fertilizers and pesticides, so its amount can vary from area to area. Vanadium occurs naturally in soil, water, and air; natural sources of atmospheric vanadium include continental dust, marine aerosol, and volcanic emissions.
Vanadium enters the food chain through the plants grown in the soil. Foods that contain relatively high amounts of vanadium include mushrooms, parsley, spinach, and oysters. Skim milk, lobster, vegetable oils, many vegetables, grains, and cereals are rich sources of vanadium (>1 ppm). Fruits, meats, fish, butter, cheese, and beverages are relatively poor sources of vanadium. Seafood generally contains higher concentrations of vanadium than meat from land animals.
Dietary intake of vanadium in the general population has been reported at 6–18 μg/day. The daily dietary intake in humans has been estimated to vary from 10 μg to 2 mg of elemental vanadium, depending on the environmental sources of this mineral in the air, water, and food of the particular region tested. Average vanadium concentrations in tap water are approximately 0.001 mg/L; assuming a daily intake of approximately 2 L of water, a daily intake of approximately 0.002 mg of vanadium from tap water can be estimated for adults.
Analysis of body fluids (including milk, blood, and excreta) and organs and tissues provided an estimate for the total body pool of vanadium in man of about 100 μg. Highest concentrations of vanadium are found in the liver, kidney, and bone.
Vanadium as a pure element was first identified in the early 19th century. Vanadium was discovered in 1801 by the Spanish mineralogist Andrés Manuel del Río, who named it erythronium but eventually came to believe it was merely impure chromium.
The medicinal interest in vanadium predates modern pharmacology. Before the discovery of insulin by Banting and Best in 1921 and its clinical trial for treating diabetes mellitus, findings in 1899 in which orally administered sodium vanadate (NaVO₃) was reported to improve human diabetes mellitus gave researchers the idea to use vanadium to treat diabetes. This 19th-century observation — predating the isolation of insulin by more than two decades — represents the earliest documented use of vanadium as a medicinal agent.
During the 20th century, several metabolic actions of vanadium were documented, including prevention of dental caries, treatment of infection, and partial control of diabetes.
In the second part of the 1980s, and in the 1990s, a number of investigators demonstrated — mainly in streptozotocin-induced (STZ) diabetic rats — that the vanadate and vanadyl forms of vanadium possessed a number of insulin-like effects in various cells. It was hypothesized that oral vanadium could be an alternative treatment to parenteral insulin in the therapy of diabetes mellitus.
Through the 1990s and 2000s, vanadium also gained popularity as a supplement among bodybuilders and athletes based on its postulated anabolic, insulin-mimetic properties. Vanadium is claimed to be anabolic and is used as a mineral supplement in bodybuilding. Up to 60 mg/day of vanadyl sulfate, equivalent to 18.6 mg of elemental vanadium per day, is reported to be used by weight-training athletes.
The essentiality of vanadium was first suggested in 1971 in three research studies. There has been a growing awareness that vanadium is an essential nutrient for certain plants, animals, and microorganisms. No dietary requirement for human beings has been estimated.
An Estimated Average Requirement (EAR) or Adequate Intake (AI) was not set for vanadium. Although there is some evidence to suggest that vanadium is an essential nutrient, a functional role for vanadium in humans has not been established; increases in abortion rates and decreased milk production have been observed in vanadium-deprived goats. The trace element vanadium has been studied by the nutrition community for four decades, yet has not achieved essential status for human beings.
The absorption of ingested vanadium is less than 5 percent, and therefore most ingested vanadium is found in the feces. Absorbed vanadate is converted to the vanadyl cation, which can complex with ferritin and transferrin in plasma and body fluids. Pharmacokinetic evaluation indicates a pattern of biodistribution consistent with fairly rapid dissociation and uptake, binding to serum transferrin for systemic circulation and transport to tissues, with preferential uptake in bone.
Plasma vanadium contents decline in three phases: the first phase is a rapid decline with a half-life (t½) of 1 hour, followed by a second intermediate decline (t½ ≈ 26 hours) and a third slow decline with t½ ≈ 10 days. Vanadium contents in blood are thus reduced to about 30% within the first 24 hours.
The primary proposed mechanism of vanadium's insulin-mimetic action involves the inhibition of protein tyrosine phosphatases. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin-signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins.
PTP1B acts as a negative regulator of insulin signaling by blocking the active site where phosphate hydrolysis of the insulin receptor takes place. Among the hitherto known PTPs, protein tyrosine phosphatase 1B (PTP1B) has received much attention due to its role as a negative regulator of insulin signaling. PTP1B is often considered to be a major contributor to the observed insulin-enhancing effects of vanadium compounds, and the inhibition of solely PTP1B would cause a very specific phenotype.
In mechanistic terms, now that PTP1B has been deactivated, the enzyme is kept in the phosphorylated state, thereby maintaining alive the signal transduction cascade and glucose continues entering the cells as if more insulin was working through the insulin receptors. This is the clinically observed insulin-mimetic or enhancing effect.
Documented downstream effects of vanadium include an increase of glucose transport in adipocytes, enhancement of insulin receptor-mediated tyrosine phosphorylation of insulin receptor substrate (IRS)-1, and induction of insulin receptor kinase (IRK) phosphorylation by inhibiting IRK-associated PTPases. The insulin-mimetic downstream effect is thought to be mainly originated by the inhibition of PTPases that are involved in dephosphorylating the insulin receptor, resulting in a prolonged insulin signal.
In human beings, pharmacologic amounts of vanadium (i.e., 10 to 100 times normal intake) affect cholesterol and triglyceride metabolism, influence the shape of erythrocytes, and stimulate glucose oxidation and glycogen synthesis in the liver. Vanadium's primary mode of action is as a cofactor that enhances or inhibits enzymes.
Both the bis(maltolato)oxovanadium(IV) and peroxovanadium complexes extend the insulin-mimetic action of vanadate in reducing cellular environments, probably by increased lifetimes under physiological conditions and/or by decomposing to other insulin-mimetic compounds.
Regarding anticancer mechanisms at the cellular level, studies on various cell lines reveal that vanadium exerts its antitumor effects through inhibition of cellular tyrosine phosphatases and/or activation of tyrosine phosphorylases. Both effects activate signal transduction pathways leading either to apoptosis and/or to activation of tumor suppressor genes. Furthermore, vanadium compounds may induce cell-cycle arrest and/or cytotoxic effects through DNA cleavage and fragmentation and plasma membrane lipoperoxidation. Reactive oxygen species generated by Fenton-like reactions and/or during the intracellular reduction of V(V) to V(IV) participate in the majority of the vanadium-induced intracellular events.
Preclinical evidence (animal studies): In vitro, vanadium salts mimic most effects of insulin on the main target tissues of the hormone, and in vivo they induce a sustained fall in blood glucose levels in insulin-deficient diabetic rats, and improve glucose homeostasis in obese, insulin-resistant diabetic rodents. Compounds of the trace element vanadium exert various insulin-like effects in in vitro and in vivo systems, including their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. This body of preclinical evidence is well-established and consistent across multiple laboratories.
Early human studies (inorganic vanadium salts): The first study on the effects of vanadium in non-insulin-dependent diabetes mellitus (NIDDM) patients was carried out by Cohen et al. (1995), at the Department of Medicine and Diabetes Research Center, Albert Einstein College of Medicine, New York, who examined in six NIDDM subjects the metabolic effects of vanadyl sulfate. In addition to animal studies, several reports documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies compared with animal work.
Short-term clinical trials with vanadium salts also seem promising in type II (non-insulin-dependent) diabetic patients, in whom liver and peripheral insulin resistance was attenuated, indicating the therapeutic potential of vanadium salts, pending demonstration of their long-term safety.
Vanadium in the forms of vanadyl sulfate (100 mg/day) and sodium metavanadate (125 mg/day) has been used as a supplement. There is some evidence that high doses of vanadyl sulfate (100 mg daily, providing 31 mg elemental vanadium) might improve the way people with type 2 diabetes use insulin. The study suggested that high-dose vanadium might lower blood sugar in people with type 2 diabetes.
Although insulin requirements were decreased in patients with Type 1 diabetes, the doses of vanadium used in the supplements were about 100 times the usual intakes, and they greatly exceed the Tolerable Upper Intake Level (UL) for vanadium.
Systematic review evidence: A systematic review of oral vanadium supplementation for glycemic control in type 2 diabetes mellitus (published in PubMed, 2008) reached a sobering conclusion: there is no rigorous evidence that oral vanadium supplementation improves glycaemic control in type 2 diabetes. The routine use of vanadium for this purpose cannot be recommended. A large-scale randomized controlled trial is needed to address this clinical question.
Organic vanadium complexes (BMOV and BEOV): Maltol and ethyl maltol have proven especially suitable as ligands for vanadyl ions in potential insulin-enhancing agents for diabetes mellitus. Both BMOV and BEOV have the desired intermediate stability for pro-drug use and have undergone extensive pre-clinical testing for safety and efficacy.
Phase I and Phase IIa human clinical trials have been completed with the ethyl analogue of BMOV (i.e., BEOV). BEOV at much lower doses (20–40 mg/day of the compound versus 100 mg vanadyl sulfate) achieved comparable glucose lowering in a phase IIa trial in 16 type 2 diabetic patients, with acceptable safety. However, Phases I and II of the clinical trials of BEOV have been completed, but the tests were interrupted due to renal problems experienced by several patients, the financial problems of the company which performed the tests (Akesis Pharmaceuticals), and patent expiration.
A Phase I pharmacokinetic trial of BEOV found encouraging early safety signals: there were no adverse health effects in any of the volunteers; gastrointestinal, liver and kidney function, blood parameters such as hemoglobin and bilirubin levels, all remained within their normal limits throughout the study. Overall bioavailability of vanadium from BEOV was three times that of VOSO₄.
Overall evidence strength for diabetes: The evidence from animal models of both Type 1 and Type 2 diabetes is robust and consistent. Human evidence, while suggestive of modest insulin-sensitizing effects, is limited to small, short-duration trials. A systematic review found no rigorous human evidence supporting routine supplemental use. Large-scale randomized controlled trials have not been completed. Evidence is therefore characterized as preliminary and insufficient to support a clinical recommendation.
Fawcett et al. (1996; 1997) studied the effects of oral vanadyl sulfate (0.5 mg/kg/day for 12 weeks in 31 weight-training athletes) in a double-blind, placebo-controlled trial. They did not find any vanadyl-related effects on body weight, blood pressure, hematological indices, blood viscosity, or on biochemical parameters relating to liver and kidney function or lipid metabolism.
A separate 12-week double-blind, placebo-controlled study investigated the effects of vanadyl sulfate (VOSO₄) at 0.5 mg/kg/day on anthropometry, body composition, and performance in weight-training volunteers. The effects of oral vanadyl sulfate (0.5 mg/kg/day) on anthropometry, body composition, and performance were investigated in a 12-week, double-blind, placebo-controlled trial involving weight-training volunteers, with performance assessed in the treatment and placebo groups.
Overall evidence strength for athletic performance: Evidence from the available controlled trials does not support ergogenic benefits of vanadyl sulfate supplementation in healthy athletes. The evidence is weak and negative based on published controlled trials.
Some experimental animal studies reported that vanadium had beneficial effects on blood total cholesterol (TC) and triglyceride (TG). However, the relationship between vanadium exposure and lipid and lipoprotein profiles in human subjects remains uncertain.
A cross-sectional population study examined lipid profiles in vanadium-exposed versus non-exposed workers: this cross-sectional study recruited 533 vanadium-exposed workers and 241 non-exposed workers from a steel and iron group in Sichuan, China; demographic characteristics, occupational information, and serum lipid and lipoprotein levels were measured for all participants. This type of observational, occupational-exposure design cannot establish causation and is confounded by multiple environmental variables.
Decreased plasma cholesterol levels after both acute and long-term administration of vanadium have been reported. However, human evidence is observational and limited in quality.
Overall evidence strength for lipid effects: Animal evidence suggests some favorable lipid effects, but human evidence is insufficient and inconsistent. No controlled clinical trials specifically targeting lipid outcomes with dietary vanadium supplementation have demonstrated definitive benefit in humans.
Multiple biochemical and molecular actions of vanadium have been implicated in its inhibitory effects on various tumor cells of human origin. Successful in vitro studies over the past few decades have advanced the anticancer research on vanadium into the preclinical stage. Vanadium in several animal cancer models provides protection against all stages of carcinogenesis — initiation, promotion, and progression.
Vanadium compounds may induce cell-cycle arrest and/or cytotoxic effects through DNA cleavage and fragmentation and plasma membrane lipoperoxidation. Reactive oxygen species generated by Fenton-like reactions and/or during the intracellular reduction of V(V) to V(IV) by NADPH participate in the majority of vanadium-induced intracellular events. Vanadium may also exert inhibitory effects on cancer cell metastatic potential through modulation of cellular adhesive molecules, and reverse antineoplastic drug resistance.
Overall evidence strength for anticancer effects: Evidence is strictly preclinical (in vitro and animal models). No published randomized controlled trials in humans have demonstrated anticancer efficacy of vanadium supplementation. This area remains investigational.
The potential role of vanadium in human health is described as a building material of bones and teeth. Higher levels of vanadium have been detected in hair, bone, and teeth. Animal models of vanadium deficiency (particularly goats) have demonstrated skeletal damage, suggesting a potential role in bone development, but this has not been formally translated into human clinical evidence. Evidence strength: Preliminary; animal and mechanistic data only.
Vanadium deprivation in rats affects the response of thyroid peroxidase to changing dietary iodine concentrations, suggesting a possible interaction between vanadium and thyroid function. This area has not been clinically characterized in humans. Evidence strength: Animal/mechanistic only.
Based on published research, vanadium has been associated with the following physiological systems:
The following dosages have been specifically reported in published scientific literature and clinical contexts:
The National Institute of Medicine has set the Tolerable Upper Intake Level (UL) of vanadium at 1.8 mg per day of elemental vanadium for adults. No UL has been set for infants, children, and pregnant or breast-feeding women. In these groups, vanadium intake should be limited to food or infant formula. It should be noted that therapeutic doses used in diabetes research significantly exceed this UL.
The limited data available for assessing gastrointestinal effects suggest that exposure to vanadium may cause mild gastrointestinal irritation. Symptoms of gastrointestinal irritation (diarrhea, cramps, nausea) have been observed in humans following bolus administration of sodium metavanadate, vanadyl sulfate, ammonium vanadyl tartrate, or diammonium vanado-tartrate as a treatment in non-insulin-dependent diabetics or patients with ischemic heart disease. The gastrointestinal effects occurred following ingestion of ≥14 mg vanadium; no effects were observed in subjects ingesting capsules containing 7.8 mg vanadium.
Undesirable effects of very high oral doses (>10 mg/day) include gastrointestinal discomfort and green coloring of the tongue.
There are limited data on the renal toxicity of vanadium compounds. Narrowing of the lumen of the proximal tubules was observed in rats exposed to 4.7 or 12 mg vanadium/kg/day as sodium metavanadate in drinking water for 7 months. In human clinical trials, renal problems were a documented reason for the halting of the BEOV Phase II clinical trial program. There is developing evidence that vanadium might harm the kidneys.
Slowed growth, renal failure, respiratory and cardiovascular distress might occur at very high doses. Toxic effects due to high concentrations of vanadium have been documented in the cardiovascular, reproductive, digestive, hematopoietic, hepatic, neurological, renal, and respiratory systems, as well as on genes and mitochondria.
Occupational exposure has led to contact dermatitis; asthma; headache; dry mouth; green discoloration of the tongue, fingers, scrotum, and legs; excessive tearing; red edematous nasal mucosa; wheezing; dyspnea; and productive cough that resolved when exposure was stopped.
Long-term and/or chronic administration of vanadium compounds should also mean tissue vanadium accumulation and risks of toxicity. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long-term therapy. Therefore, new organo-vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes.
The no-effect level has been set to a daily intake of 10 mg V per kg body mass. The respective limit values for intravenous application are 7 mg/kg, and for breathing air 35 mg/m³.
Antidiabetic medications: Vanadium seems to decrease blood sugar in people with type 2 diabetes. Diabetes medications are also used to lower blood sugar. Taking vanadium along with diabetes medications might cause blood sugar to go too low. Some medications for which this interaction is relevant include glimepiride (Amaryl), glyburide (DiaBeta), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), tolbutamide (Orinase), and others.
Anticoagulants: Evidence from pharmacological studies indicates that vanadate may exhibit anticoagulant activity, which represents a potential interaction with anticoagulant medications, though formal drug interaction studies have not been systematically performed in humans.
Information regarding use of supplemental vanadium in pregnancy and lactation is lacking. Taking vanadium as a supplement during pregnancy is possibly unsafe. Having higher levels of vanadium in the body while pregnant might slow the growth of the fetus and cause other serious side effects.
Vanadium is not recognized as an essential nutrient for humans by major regulatory bodies, including the Institute of Medicine and the World Health Organization. Clinical data do not support the effectiveness of vanadium for any specific therapeutic purpose. Vanadium is sold as a dietary supplement in the United States under the Dietary Supplement Health and Education Act (DSHEA) framework, without FDA approval for treating any disease.
The most advanced clinical research on vanadium — the BEOV Phase IIa program — was discontinued. Further investigation of BEOV as an oral antidiabetic agent had to be relinquished due to reported problems. Research into next-generation vanadium complexes with improved pharmacological profiles and safety margins continues in the academic literature, but no vanadium compound has received regulatory approval as a pharmaceutical agent in any major jurisdiction as of the available literature.
The potential of vanadium complexes to treat diabetes is still an open field. Insulin-mimetic vanadium compounds are considered mostly as oral drugs for the potential treatment of type 2 (non-insulin-dependent) diabetes. Robust large-scale randomized controlled trials remain necessary to establish any clinical application.
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In animal models, vanadyl sulfate and BMOV have consistently lowered blood pressure in spontaneously hypertensive and hyperinsulinemic rats. The proposed mechanism links blood pressure reduction to improved insulin sensitivity. The single human study examining blood pressure found no significant change at supplemental doses, though the evidence base is very limited.
Multiple short-term human clinical trials demonstrate that vanadyl sulfate and other vanadium salts reduce fasting blood glucose in type 1 and type 2 diabetes patients. Mechanistically, vanadium acts as an insulin mimetic by inhibiting protein tyrosine phosphatase 1B (PTP1B) and activating downstream insulin signaling. Effects are modest compared to animal models and no long-term human safety data exists.
Preclinical studies show vanadium accumulates in bone and stimulates osteoblast differentiation while inhibiting osteoclast activity, with in vitro evidence of bone cell proliferation. Animal studies involving vanadium-deficient goats showed skeletal deformations. No human RCT evidence demonstrates that vanadium supplementation increases bone mineral density.
Several human clinical trials in diabetic patients have documented reductions in total cholesterol and LDL-cholesterol following vanadium supplementation. A long-term (30-month) study in type 1 diabetics showed decreased plasma total cholesterol with vanadyl sulfate. Animal studies consistently show cholesterol-lowering effects; human data are supportive but based on small, short trials.
Vanadium compounds have demonstrated cardioprotective effects in animal and preclinical models of myocardial ischemia/reperfusion injury, cardiac hypertrophy, and hypertension. The mechanism involves Akt signaling activation via PTP inhibition. No controlled human clinical trials specifically targeting heart disease outcomes have been completed.
Vanadium salts act as insulin mimetics and produce glucose-lowering effects in animal models and human diabetic subjects. NIH-documented evidence shows supplementation (25–100 mg elemental vanadium/day) partially normalizes glucose metabolism in type 2 diabetes. A 2023 network meta-analysis of 170 RCTs confirmed glycemic modulating activity for vanadium.
Vanadyl sulfate has been shown in several small human trials to improve both hepatic and peripheral insulin sensitivity in type 2 diabetes. The mechanism involves PTP1B inhibition and activation of serine/threonine kinases downstream of the insulin receptor. Results across studies are inconsistent and effect sizes are modest.
Vanadyl sulfate has been investigated in animal models of metabolic syndrome (fructose-induced obesity), normalizing blood glucose, triglycerides, and insulin levels. Human clinical trial data show improvements in multiple metabolic syndrome components—HbA1c, LDL-C, triglycerides, and BMI—in T2DM patients, which overlap substantially with metabolic syndrome criteria.
Human clinical trials including a 12-week trial in 60 T2DM patients on sodium metavanadate showed reductions in triglyceride levels alongside HbA1c and LDL-cholesterol. Animal studies consistently confirm triglyceride-lowering effects. However, one human study found vanadyl sulfate actually increased triglycerides in obese patients, indicating inconsistent human findings.
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