V – Vanadium is found in igneous rocks at 135 ppm; shale at 130 ppm; sandstone at 20 ppm; limestone at 20 ppm; fresh water at 0.001 ppm; sea water at 0.002 ppm; soils at 100 ppm (V is absorbed by humus especially in alkaline soils); marine plants at 2 ppm; land plants at 1.6 ppm (accumulated by the fungus Arnanita muscaria); marine animals at 0. 14 to 2 ppm; land animals at 0. 15 ppm.
Metallic vanadium (vanadyl sulfate) is absorbed from the intestinal tract very poorly at only 0. 1 to 1.0 %; vanadium chelates at 40 % and plant derived colloidals at up to 98 %.
Vanadium was proven to be an essential trace mineral in 1971. Vanadium stimulates glucose (blood sugar) oxidation and transport in fat cells and glycogen (animal starch) synthesis in liver and muscle, and inhibits liver gluconeogenisis (production of glucose from fat) and absorption of glucose from the gut. Vanadium enhances the stimulating effect of insulin on DNA synthesis. Despite low serum insulin, the blood glucose levels of diabetic rats fed vanadium was the same as normal controls.
Vanadium appears to function like insulin by altering cell membrane function for ion transport processes, therefore vanadium has a very beneficial effect for humans with glucose tolerance problems (i.e. – hypoglycemia, hyperinsulinemia and diabetes) by making the cell membrane insulin receptors more sensitive to insulin. Several cultures including American Indians, Hispanics and Hawaiians have an increased rate of diabetes when they cease to eat their ethnic foods and consume canned, processed and fast foods. Vanadium supplementation can have a major positive economic impact by reducing or even eliminating most cases of adult onset diabetes – diabetes alone costs American taxpayers a minimum of $105 billion each year.
Vanadium inhibits cholesterol synthesis in animals and humans; this is followed by decreased plasma levels of cholesterol and reduced aortic cholesterol.
Vanadium initiates an increase in the contractile force of heart muscle known as the Inotropic effect.”
Vanadium has known anticarcinogenic properties. Induction of mouse mammary tumor growth was blocked by feeding 25 mcg of vanadium per gram of diet. The vanadium supplement reduced tumor incidence, average tumor count per animal and prolonged median cancer free time without inhibiting overall growth or health of the animals (sure beats chemotherapy and radiation!).
Clinical diseases associated with Vanadium deficiency include:
- Slow growth
- Increased infant mortality
- Infertility
- Elevated cholesterol
- Elevated triglycerides
- Hypoglycemia
- Hyperinsulinemia
- Diabetes
- Cardiovascular disease
- Obesity
Vanadium is a trace mineral required by animals for normal growth and development. Deprivation of this element causes slowed growth, reproductive problems and blood abnormalities in rats and chicks. Vanadium in the form of vanadate and vanadyl sulfate improves the effect of insulin in diabetic animals; and artificially induced diabetes in rats can be reversed by vanadate. Large doses also affect serum fat and cholesterol levels, though more research in this area is needed.
There is no Recommended Dietary Allowance for vanadium, and the amounts required for optimal health are unknown. Levels present in food would likely meet nutritional requirements. Black pepper and dill seeds are the richest sources. Whole grains, seafood, milk products and meat are fair sources, while beverages, vegetables and fruits contain the lowest amounts. The average daily intake in the United State is about 20 mcg, quite low in comparison to known essential trace elements. Elevated vanadium (in the inorganic form) is associated with manic-depression, and high levels of vanadium may be toxic.
Biochemical function
Recently, in a number of reviews, the possibility has been considered that vanadium might play a role in the regulation of Na+/K+-exchanging ATPase, phosphoryl-transfer enzymes, adenylate cyclase and protein kinases. The possible role of the vanadyl ion as an enzyme cofactor and its roles in hormone, glucose, lipid, bone and tooth metabolism have also been discussed. No specific biochemical function has yet been identified for vanadium in higher animals. However, the recent discovery in lower forms of life of vanadium-activated enzymes lends credence to the view that vanadium has similar roles in higher animals. Vanadium-dependent enzymes in lower organisms include nitrogenase in bacteria, which reduces molecular nitrogen to ammonia, and iodoperoxidase and bromoperoxidase in algae and lichens, which catalyse the oxidation of halide ions by hydrogen peroxide, thus facilitating the formation of a carbon-halogen bond. Haloperoxidases, such as thyroid peroxidase, play essential roles in higher animals, and it was recently shown that vanadium deprivation in rats affected the response of thyroid peroxidase to changing dietary iodine.
General functions & actions: growth & development, antihyperglycemic, (mimics insulin actions by increasing glucose uptake it’s metabolism by fat cells), increases glucose metabolism, activates glycogen synthesis, increased
storage glycogen in muscles, lowers high blood pressure (antihypertensive), may reduce development of breast cancer, may reduce risk of developing diabetes, and increased muscle size & strength (anabolic).
Traditional uses: atherosclerosis, diabetes mellitus, fatigue, hypercholesterolemia, hyperglycemia, hypertension, infertility, poor growth, weakness, infertility, kidney disease, and cardiovascular disease.
Deficiency and toxicity
Most of the deficiency signs reported for vanadium are questionable. However, Anke and coworkers recently reported some reasonably well substantiated deficiency signs in goats which, when fed only 10 ng of vanadium per gram of diet, as opposed to 2 mcg of vanadium per gm of diet, exhibited a higher abortion rate and produced less milk during the first 56 days of lactation. There was a high mortality among kids from vanadium-deprived goats. Serum creatinine and beta-lipoprotein were elevated and serum glucose was depressed in these goats. In addition, skeletal deformations were seen in the forelegs, and forefoot tarsal joints were thickened.
Uthus & Nielsen reported that, when compared with 1 mcg of vanadium per g of diet, vanadium deprivation (2 ng vanadium/g of diet) increased both the thyroid weight and thyroid weight/body weight ratio of rats, and tended to decrease growth.
The only epidemiological study in which an association between vanadium intake and a human disorder is reported is that of Masironi, in which an association between low intakes and cardiovascular disease was found.
Requirement and tolerable intakes
Average basal and normative requirements for vanadium cannot be set because the data required to do so are not available, nor can a safe range of population mean intakes for vanadium be proposed. However, the diets used in animal deprivation studies contained only 2-25 ng of vanadium/g and there was often no significant clinical effect. Vanadium deficiency has not been identified in humans although many diets supply less than 30 mcg daily and most about 15 mcg daily. This suggests that a dietary intake of 10 mcg daily probably meets any postulated basal vanadium requirement. A daily intake of 10 mg of vanadium produced signs of overt vanadium toxicity in humans. Much smaller amounts of vanadium (10-100 times the amount normally present in the diet) were found to have pharmacological effects on animals and humans. The threshold toxicity level may be much lower than 10 mg of vanadium/day.
Vanadium compound may be used for diabetics
C & E N Journal. May, 1992
A vanadium compound that may find use as a diabetes treatment has been discovered by John H. McNeill, V. G. Yuen, H. R Hoveyda, and Chris Orvig of the University of British Columbia U. Med. Chein., 35,1489 (1992)]. Diabetes is a potentially life-threatening illness in which blood glucose levels are abnormally high. Insulin is often used to control the disease. However, insulin is not orally active (it’s broken down by the digestive system), and thus must be taken by injection. Because injection is difficult, researchers have been trying to find orally active insulin mimics. Although the focus has been on vanadyl and vanadate salts, known to be effective insulin mimics, such compounds are poorly absorbed from the gastrointestinal tract and are toxic. Now, McNeill and coworkers find that bis- (maltolato)oxovanadium(IV) appears to exhibit higher uptake, and hence lower toxicity, than previously tested vanadium compounds. Tests of the compound on diabetic rats show reductions in plasma glucose levels to near-normal levels, in addition to other signs of improvement, such as reduced body weight gain (likely the result of decreased food intake) and normalized fluid consumption. The compound, or an analog, has potential as an insulin mimic or appetite suppressant.
J of Adv in Med. Vol. 9, No. 2, Summer 1996
The Insulin-Like Effects of Vanadium
R. J. Shamherger. PhD.
Introduction to Abstract
When insulin was introduced in the 1920s it became an effective treatment for diabetes mellitus, which is one of the leading causes of illness and death in North America. Daily injections of insulin are inconvenient and complications are a significant problem. A search for an alternative therapy has shown that vanadium has insulin-like effects and is currently under consideration as an oral therapy. In addition to its insulin-like activity, vanadium also reduces gluconeogenesis, increases glycogen deposition and has an anorectic action. In general, vanadium compounds are poorly absorbed. Searches are underway for vanadium derivatives that are better absorbed. In this way, total vanadium intake can be reduced, thus decreasing the possibility of toxicity. Even though it is known to be an essential element in rats, chicks, and goats, its essentiality in humans has not been established.
Occurrence
Vanadium is a transition metal occurring in the relative abundance of 0.02% in nature. The average concentration in the earth’s crust is about 150 mg/Kg, and it is the 21st most abundant element. Although it is mainly used in manufacturing alloy steel in industry, it has very complex chemistry, becoming either anionic or cationic according to its oxidation state.
In the +5 oxidation state, under physiological conditions, it mainly exists as metavanadate (H2V04). Both the metavanadate and the orthovanadate resemble phosphate. The chemical structure of vanadium is similar to that of phosphorus and vanadate has an effect on many phosphorylation reactions. When it exists in the +4 oxidation state, it is in its cationic form as vanadyl (V02+) and resembles Mg2+. In biological systems, vanadium is present in extracellular fluid mainly in the +5 redox state (vanadate). It is reduced to vanadyl, the +4 redox state (vanadyl), intracellularly and forms complexes with several biologically important compounds.
Essentiality
Vanadium is present as an ultratrace element in mammals and there is evidence for its essentiality in chicks, rats, and goats. The earliest experiments suggested that its deficiency reduced growth of wing and tail feathers in chicks. Rats show reduced growth. Vanadium deficient goats show irreversible bone deformities in their front legs. Human essentiality is not determined.
Dietary intake ranges from 10 to 60 mcg a day, resulting in plasma concentration of 20 nmols and a total body pool between 100 and 200 mg. The first evidence that vanadium could influence a biological system was observed in 1977 when it was demonstrated that it inhibited Na+/K + transport ATPase in vitro. Vanadium salts have subsequently been shown to inhibit other transport ATPases, but there is no evidence that it is a physiological regulator of these ion pumps.
Food Content of Vanadium
Foods that are considered to be rich sources of the element include black pepper, dill, parsley, mushrooms, and shellfish. Fresh fruits, vegetables, fats, and oils contain low concentrations.
Glucose Metabolism
Net glucose concentration in the blood depends upon the balance between liver glucose production and its metabolism by the peripheral tissues, which is highly regulated by several hormones. Only insulin, however, possesses glucose lowering properties. Type I diabetes brings about insulin-dependency and hyperglycemia results mainly from severe insulin deficiency due to destruction of the pancreatic beta-cells. Insulin injections are necessary for treatment. In contrast, Type II diabetes is noninsulin dependent (NIDDM) and hyperglycemia occurs in spite of elevated plasma insulin levels. Seventy percent of patients are obese. Insulin has decreased effectiveness due to resistance at the cell-receptor sites and the pancreatic beta-cells are unable to secrete enough insulin to overcome this resistance.
The main treatment for NIDDM is through diet, exercise and stimulation of insulin secretion, mainly by oral sulphonylureas. These drugs are not completely satisfactory in a large proportion of patients and new therapeutic strategies are being explored, particularly to find compounds that might correct insulin resistance. Some compounds such as thiazolidinediones increase the effectiveness of insulin. Others, like vanadium salts, mimic its action. The objective of this review is to outline the insulin-like properties of vanadium salts and their potential future in treatment of diabetes.
Insulin-like Effects of Vanadium in Vitro
Early research showed that vanadium compounds had insulin-like effects by increasing glucose transport as well as oxidation in adipocytes. Vanadium compounds also stimulated glycogen deposition in liver and diaphragm and inhibit gluconeogenesis in hepatocytes. Its insulin-like effects have been dissociated from its ability to inhibit the Na/K ATPase.
Antidiabetic Effects of Vanadium in Vivo
Because of the in vitro effects of vanadium, Heylinger et al. were the first to demonstrate its effectiveness in vivo. Their experiments started numerous studies in animal models of both Type I and 11 diabetes. One of the most widely used rat experimental systems is that caused by streptozotocin injection which destroys pancreatic betacells and is considered to be a model of Type 1. Vanadium has marked protective effects and oral administration of vanadate or vanadyl markedly decreases blood glucose levels in 2-5 days. The improvement from this treatment is inversely related to the severity of the disease and the improvement may last up to one year. Circulating insulin levels remain low and cannot be responsible for reducing levels of blood sugar. Another possibility, which may be an explanation, would be increased renal excretion, but glucosuria is decreased with vanadium administration. Reduction in blood glucose is probably not due to decreased intestinal glucose absorption because similar effects of vanadium are observed during both intravenous and oral glucose tolerance tests, and in the fasting state.
Human Studies
At the end of the last century, sodium metavanadate was thought to be the “panacee universelle” and was used to treat diabetes and a variety of debilitating diseases. Two out of three diabetic patients had a decrease in glucosuria. In the early 1960s, some, but not all, studies showed decreases in plasma cholesterol during 6 to 26 week treatments with vanadium.
Clinical studies were encouraged by the results from both in vitro and animal studies. Two groups of diabetic patients were given either 100 mg/day of vanadyl sulfate, or 125 mg/day of sodium metavanadate. Beneficial effects were observed with both, even though the doses were 100-fold less than those used in the majority of animal studies.
In Type I diabetic patients, there were no consistent effects on glucose control from vanadium, but requirements of daily insulin decreased by 14%. In Type 11 patients, however, vanadium treatment increased insulin sensitivity. This enhanced sensitivity resulted in less glycogenolysis and improved glycogen storage. Consistent with animal studies, most of these metabolic, effects were sustained for up to two weeks following the end of treatment.
Anorectic Effect of Vanadium
Insulin action also has an anabolic effect, but with vanadium there is usually a decrease in body weight as well. This decrease appears to be mainly attributed to hypophagia (decreased appetite) caused by a major effect on the appetite center. At first sight the hypoglycemic effect of vanadate might be attributed to its anorectic effect, but the experimental evidence disagrees with this possibility, since it is seen in both the fasting and satiated states, and after oral or intravenous glucose tolerance tests.
Oral vanadate in low doses, given to mildly diabetic rats, improved their glucose status without reductions in food intake and weight gain. In addition, according to these authors, several experiments with insulin-deficient and insulin-resistant animals have shown that neither plasma glucose concentrations nor hepatic and peripheral glucose metabolism were improved by caloric restriction. Similarly the beneficial effects of vanadium supplementation in humans did not result from body weight changes or caloric consumption. Its anorectic effect does not seem to explain its anti-hyperglycemic effects. It seems to be due to a genuine action of the element in liver and other tissues.
Vanadium Toxicity
In general, vanadium is non toxic after oral administration because of its poor absorption from the gastrointestinal tract, but it may become toxic after parenteral administration. In diabetic animals treated regularly with oral vanadium, its serum concentration averages 20 mmols, which is nearly 1000 times greater than in controls. In organs in which vanadium concentrates, such as bone and kidney, even higher levels can be found. The most obvious side effect of its administration to animals in doses of 25 mg/Kg is failure to gain weight, and diarrhea. This improves when the dosage is lowered.
Vanadium Use by Athletes
Athletes are being exposed to ill-advised and potentially hazardous nutrients and/or drugs for enhanced performance. Gerrard et al. reported the case of a student taking an over-the-counter preparation which was purported to exert a “natural” anabolic effect. A teacher discovered that one tablet contained 7.5 mg of vanadyl sulfate and the recommended dose was 4 tablets a day. The anabolic effect of vanadyl sulfate is similar to that of insulin because it increases stores of liver and muscle glycogen. Until long term toxicity studies prove that vanadium compounds are clinically safe, athletes should be aware of the possible risks when using them as performance-enhancing aids.
Mental Health
Although the long-term effects of vanadium on mental health and glucose metabolism are unknown, there is evidence that sodium pump activity is reduced in manic-depressive illness, and vanadium may have a causative role. There is evidence that sodium pump activity is reduced in that illness, and vanadium may have a causative role. Patients with the condition may have a defect in this pump, thus making it vulnerable to vanadate. It has been suggested that vanadate may be binding competitively to the phosphate-binding sites on Na/K-ATPase, with high affinity. This would prevent further enzyme turnover due to a relatively slow dissociation of the vanadate enzyme complex. Elevated vanadium levels have been observed in the plasma of patients with the disease, and reduction of vanadium levels has been shown to be an effective treatment.
Mol Cell Biochem 1995 Dec 6-20;153(1-2):175-80
Increased potency of vanadium using organic ligands.
McNeill JH, Yuen VG, Dai S, Orvig C
Faculty of Pharmaceutical Sciences, Vancouver, B.C., Canada.
The in vivo glucose lowering effect of orally administered inorganic vanadium compounds in diabetes was first reported in our laboratory in 1985. While both vanadate and vanadyl forms of vanadium are orally active, they are still not well absorbed.
NOTE: We use a product in our office that is 100% absorbable. Metallic vanadium is converted into a gas (ionized) and then is dissolved in distilled, ozonated water. This Vanadium solution is totally 100% absorbable with no toxicity because it is water-soluble.
Biol Trace Elem Res 1995 Jun;48(3):275-285
Time course effects of vanadium supplement on cytosolic reduced glutathione level and glutathione S-transferase activity.
Bishayee A, Chatterjee M
Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.
The influence of vanadium, an important dietary micronutrient, was evaluated on the cytosolic reduced glutathione (GSH) content and glutathione S-transferase (GST) activity in several rat target tissues. Supplementation of drinking water with vanadium at the level of 0.2 or 0.5 ppm for 4, 8, or 12 wk was found to increase the GSH level with a concomitant elevation in GST activity in the liver followed by small intestine mucosa, large intestine mucosa, and kidney. The results were almost dose-dependent and mostly pronounced with 0.5 ppm vanadium after 12 wk of its continuous supplementation. Neither the GSH level nor GST activity was significantly altered in forestomach and lung following vanadium supplementation throughout the study. The levels of vanadium that were found to increase the content of GSH and activity of GST in the liver, intestine, and kidney did not exert any toxic manifestation as evidenced from water and food consumption as well as the growth responses of the experimental animals. Moreover, these doses of vanadium did not impair either hepatic or renal functions as they did not alter the serum activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), sorbitol dehydrogenase (SDH), as well as serum urea and creatinine level. All these results clearly indicate that vanadium under the doses employed in our study has a significant inducing role on GSH content with a concurrent elevation in GST activity in the liver and specific extrahepatic tissues without any apparent sign of cytotoxicity. This attribute of vanadium may have a greater importance in terms of biotransformation and detoxification of xenobiotics, including carcinogens. In addition, since the ability to afford an increment in the endogenous GSH-GST pool by anticarcinogenic natural substances has been found to correlate with their activity to inhibit neoplastic transformation, the trace element vanadium may be considered as a novel anticancer agent.
Acta Physiol Pharmacol Bulg 1993;19(3):83-89
Selective enhancement of glutathione S-transferase activity in liver and extrahepatic tissues of rat following oral administration of vanadate.
Bishayee A, Chatterjee M
Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.
The effect of oral administration of vanadate (100, 200 and 400 nM for 30 days) on the activity of the detoxifying enzyme system glutathione S-transferase (GST) in rat liver and in several extrahepatic tissues was examined. Vanadate showed a high activity as GST inducer in liver and in small intestine mucosa followed by large intestine mucosa and kidney in a dose-dependent manner. No significant alterations in GST activity were observed in forestomach and lung tissues after vanadate. Vanadate treatment that resulted in an enhancement of GST activity impaired neither hepatic nor renal function as evidenced by serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, sorbitol dehydrogenase, urea, and creatinine. Since the ability to induce an increase of detoxifying enzyme activity by anticarcinogenic agents was found to correlate with their activity in the inhibition of tumorigenesis, the trace element vanadium might be considered a potential cancer chemopreventive agent.
Mol Cell Biochem 1995 Apr 26;145(2):97-102
Vanadium derivatives act as growth factor–mimetic compounds upon differentiation and proliferation of osteoblast-like UMR106 cells.
Cortizo AM, Etcheverry SB
Catedra de Bioquimica Patologica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Argentina.
The effect of different vanadium compounds on proliferation and differentiation was examined in osteoblast-like UMR106 cells. Vanadate increased the cell growth in a biphasic manner, the higher doses inhibiting cell progression. Vanadyl stimulated cell proliferation in a dose-responsive manner. Similar to vanadate, pervanadate increased osteoblast-like cell proliferation in a biphasic manner but no inhibition of growth was observed. Vanadyl and pervanadate were stronger stimulators of cell growth than vanadate. Only vanadate was able to regulate the cell differentiation as measured by cell alkaline phosphatase activity. These results suggest those vanadium derivatives behave like growth factors on osteoblast-like cells and are potential pharmacological tools in the control of cell growth.
J Trace Elem Med Biol 1997 Jun;11(2):110-5
Maltol complexes of vanadium (IV) and (V) regulate in vitro alkaline phosphatase activity and osteoblast-like cell growth.
Barrio DA, Braziunas MD, Etcheverry SB, Cortizo AM
Catedra de Bioquimica Patologica, Universidad Nacional de la Plata, Argentina.
Vanadium compounds have been found to possess insulin and growth factor-mimetic effects. In consequence, these derivatives are potentially useful as effective oral therapeutic agents in diabetic patients. However, their use has been limited by various toxic side-effects and by the low solubility of different derivatives. Recently, vanadium complex with maltol, a sugar used as a common food additive, have been synthesized and investigated in animals, showing possible insulin-mimetic effects with low toxic side-effects. In the present study we have investigated the effect of bis(maltolato)oxovanadium (IV) (BMOV) and bis(maltolato)dioxovanadium (V) (BMV) on bone cells in culture as well as their direct effect on alkaline phosphatase in vitro. A comparison was also made with the action of vanadate and vanadyl cation. Vanadium compounds regulated cell proliferation in a biphasic manner with similar potencies. Osteoblast differentiation, assessed by alkaline phosphatase activity, was found to be dose-dependent, with the inhibitory effect being stronger for vanadate and BMOV than for vanadyl and BMV. All vanadium compounds directly inhibited bovine intestinal ALP with a similar potency. Thus, maltol vanadium derivatives behave in a similar way to vanadate and vanadyl in osteoblast-like UMR 106 cells in culture.
Magnes Trace Elem 1990;9(4):219-226
Effect of vanadium, iodine and their interaction on growth, blood variables, liver trace elements and thyroid status indices in rats.
Uthus EO, Nielsen FH
United States Department of Agriculture, Grand Forks Human Nutrition Research Center, N. D.
A two-factor, two-by-three factorially arranged experiment was performed to ascertain whether iodine affects the response of rats to vanadium deprivation. Male weanling Wistar-Kyoto rats were fed a 16% casein 68% acid-washed ground corn diet for 8 weeks. The variables were supplemental vanadium at 0 or 1 mcg/g and supplemental iodine at 0, 0.33 or 25 mcg/g. Vanadium deprivation increased thyroid weight and thyroid weight/body weight ratio and decreased the concentration of vanadium in liver. Vanadium and iodine interacted such that, as dietary iodine was increased, plasma glucose increased in the vanadium-deficient rats but decreased in the vanadium-supplemented rats. Also, as dietary iodine was increased, thyroid peroxidase activity decreased; the decrease was more marked in the vanadium-supplemented than the vanadium-deprived rats. The findings suggest that vanadium may have a physiological role affecting iodine metabolism and thyroid function.
The Effect of Vanadium, Iodine and Their Interaction on Thyroid Status Indices
E O Uthus and F H Nielsen
USDA, ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND USA 58202
An experiment was performed which demonstrated that vanadium deprivation, and a vanadium-iodine interaction affected rats. Vanadium deprivation Increased thyroid weight and thyroid weight/body weight ratio. Vanadium and iodine interacted such that, as dietary iodine increased, plasma glucose increased in the vanadium-deficient rats but decreased in the vanadium-supplemented rats. Also, as dietary iodine increased, thyroid peroxidase activity decreased with the decrease more marked in the vanadium-supplemented rats than in the vanadium-deprived rats. These findings suggest that vanadium may have a physiological role affecting iodine metabolism and thyroid function.