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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. |
