As the American populace becomes more sedentary and thus more obese, diabetes
is steadily on the rise. Due to the mortality rate of this disease raising
almost as fast as the blood sugar, potentially new, less-invasive and
less-toxic modalities are always being researched. One particularly promising
agent is the trace element vanadium. Research conducted almost one hundred
years ago by French physician B. Lyonnet demonstrated that when a vanadium
salt was administered to diabetic subjects, the concentration of glucose in
urine dropped sharply. Within the past 20 years a resurgence of vanadium
research has taken place in areas such as pharmacodynamics and toxicity.
Various studies on vanadium, such as those performed on streptozocin-induced
diabeties in rats, resulted in a normalization in blood glucose levels.
Stimulation of glucose oxidation and adipocyte transport has been demonstrated
via vanadium by several experiments, as well as enhancement of glycogen
synthesis and inhibitaion of hepatic gluconeogenesis. Investigators also
believe vanadium to be responsible for the phosphorylation of the insulin
receptor, resulting in activation and glucose sensitivity.
It has been demonstrated that the inorganic vanadate 5+ salt forms have great
potential for toxicity (primarily manifesting as elevation of hepatic enzymes,
neuropathy and renal damage) in long term treatment. These negative aspects
were also observed with vanadyl sulfate, even at clinical doses. Other forms
of the element were studied for gut absorption, bioavailability, and
dose-to-efficacy toxicity.
BMOV: Preferred Bioavailability
The recent multitude of vanadium research regarding its potential role as a
therapy for diabetes has spawn a new era of vanadium technology. Organic
ligands have been developed due to the molecules structure benefiting gastric
absorption and overall increased bioavailability. Some of these experimential
models include: bis(cysteinamide-N-octyl) oxovandium,
bis(pyrrolidine-N-carbodithioato) oxovanadium, bis(clycinato)oxovanadium,
vanadyl-cysteine-methyl ester, and bis(maltolato) oxovanadium (BMOV). BMOV was
shown to have greater absorption and higher bioavailabiyl than other organic
forms of vanadium previously stated. BMOV did not demonstrate a potential for
toxicity at therapeutic doses, even when administered for a prolonged period.
This was due to increased absorption and a higher rate of clearance and
excretion than other forms of vanadium. The increased bioavailability of BMOV
thus resulted in a reduced requirement for the element to achieve glucose
stability and a reduction and/or elimination of toxicity potential.
BMOV is widely considered by scientific studies to be the preferred choice of
the element for long term therapy of various hyperglycemic conditions.
BMOV: Detailed Data
Bis(maltolato)oxovanadium (known as BMOV) was extensively investigated in rats
treated with streptozotocin (STZ) which subsequently developed diabetes
(1.,2,3,4,5,6,7) BMOV was proven effective in lowereing plasma glucose in STZ
diabetic rats, when administered in drinking water over a 25-week period.
Initially the effective dose of BMOV was calculated to be 0.45 mmol/kg,
compared with the .55 to .64 mmol/kg for vanadyl sulfate. The maintenance dose
of BMOV 0.18 mmol/kg/day was approximately 50% of that required for VS, i.e.
0.18 mmol/kg/day vs. 0.4 mmol/kg/day.
The BMOV treatment of STZ-rats was more effective and showed no toxicity as
compared to vanadyl sulfate treated animals (1.2.3). Comparison of the dose
response to intraperitoneal injection of BMOV versus vanadyl sulfate, showed
that BMOV administered at a dose of 0.13 mmol/kg produced a normalization of
plasma glucose among 100% of the animals treated, without any toxic effects.
Only 92% of the animals responded to the treatment of vanadyl sulfate at a
dose of 0.28 mmol/kg, with 21% mortality rate in treated animals The ED50 for
oral administration of BMOV was 0.5 mmol/kg, while for vanadyl sulfate the
estimated ED50 was 0.9 mmol/kg.
Comparison of pharmacokinetic action of BMOV vs. vanadyl sulfate in
STZ-diabetic rats suggest that BMOV had a more rapid onset of action and was
approximately 1.5 times potent than vanadyl sulfate at producing glucose
lowering effects. The superior efficacy of BMOV over vanadyl sulfate may in
part be explained by the better absorption of BMOV. Bone levels of vanadium
with BMOV administration were roughly two to four times those previously
reported with vanadyl sulfate treatments(3,5).
Treatment with BMOV resulted in normalization of plasma triglyceride and
cholesterol levels in diabetic animals(1), as was previously reported in
experimental therapy with vanadyl sulfate. Plasma triglycerides were
comparable to the control group and approximately 3 times lower than in the
untreated STZ-diabetic rats. Plasma cholesterol was also normalized and
approximately two times lower than in the diabetic animals.
Previous reports with inorganic form of vanadium indicated that administration
to the diabetic animals reduced food and fluid intake, or polyphagia and
polydipsia the two characteristic symptoms of diabetes. A similar effect was
observed with BMOV therapy. However there was no incidence of the diarrhea
that had previously been attributed to the gastrointestinaly toxicity of
vanadium (as vanadly sulfate) therapy(1).
Previous studies with inorganic vanadium have also shown slower body weight
gain among healthy animals receiving vanadium, which was attributed to a
reduction in food and fluid intake. There also may be an additional factor
contributing to the slower weight gain and reduction in plasma insulin levels
in healthy animals receiving vanadium(1). Healthy rats receiving BMOV had
significantly lower plasma insulin levels as compared to the control animals,
61.7 uU/ml vs. 87.1 uU/ml.
This observation correlated positively with the significantly lower body
weight in animals receiving BMOV, 557 gm vs. 667 gm in the control group. The
lower levels of circulating insulin may account for its lower anabolic effect,
and a subsequent slowdown in weight gain. In the diabetic group of animals
BMOV did not lower but rather slightly increased the levels of circulating
insulin, thus demonstrating a possible homeostatic mechanism in regulating
insulin body levels.
The role vanadium as BMOV in preventing secondary complications of diabetes
such as cardiac dysfunction and eye cataracts was also studied(1,5). The
25-week administration of BMOV normalized heart function in STZ-diabetic rats
as measured by the left atrial filling pressure (5). This normalization might
be due to improved glucose homeostasis since treated rats had lower plasma
glucose and percent of glycosylated hemoglobin, and integrated measure of
blood glucose control. During this study, the 60% of untreated animals
developed cataracts as compared to 8% in the BMOV-treated group(1).
Vanadium in the form of BMOV appears in many ways to be superior to the
inorganic vanadate or vanadyl, and to organic complexes of vanadium currently
available, particularly since equal therapeutic effects are accomplished with
a significantly lower dose of the BMOV vanadium compound. Safety of vanadium
therapy should be of primary consideration, because , as was previously
mentioned, it is extensively used as a nutritional supplement and in
nutritional therapy in humans. Recent findings indicate that vanadium may be
of importance in human nutrition, and therefore overall guidelines as to its
use should be developed.
Mitch Chavez, B.SC., C.N. is a Certified Nutritionist with an
undergraduate in nutrition science with emphasis on nutritional biochemistry.
He is an independent technical consultant to the natural products industry and
Director of Education for Progressive Apothecary, a professional products
distributor exclusively for practioners of natural medicine.
In addition to his position with Progressive Apothecary, he is the Vice
President and Director of Research and Development of Nutraceutical Research
Laboratories and Chief Science Officer for Integrative Medical Research, Ltd.,
both makers/suppliers of cutting edge nutritionals for physicans specializing
in complementary and integrative medicine.
Mr. Chavez has had numerous articles published in both lay magazines and
peer reviewed journals regarding nutritional supplemention and product formula
rationale. He has also lectured internationally by invitation to medical
schools at a post-graduate level concerning nutritional biochemistry and
botanical medicine.
REFERENCES:
-
Yuen, V.G. et al. (1993) Glucose-lowering Effects of a New Organic Vanadium
Complex, Bis(maltolato)oxovanadium (IV). Can. J. Physiol. Pharmacol.,
71:263-269.
-
NcNeill, J.H., Yuen, V.G., Hoveya, H.R. and Orvig, C. (1992)
Bis(maltolato)oxovanadium (IV) is a Potent Insulin Mimic. J. Med. Chem.,
35:1489-1491
-
Yuen, V.G., Orvig, C. and McNeill, J.H. (1995) Comparision of the
Glucose-lowering Properties of Vanadyl sulfate and Bis(maltolato)oxovanadium
(IV) Following Acute and Chronic Administration. Can. J. Physiol. Pharmacol.,
73:55-64.
-
Yuen, V.G. et al. (1996) Effects of Low and High Dose Administration of
Bis(maltolato)oxovanadium (IV) on Fa/Fa/ Zuker Rats. Can. J. Physiol.
Pharmacol. 74:1001-1009.
-
Yuen, V.G. et al. (1993) Improvement in Cardiac Dysfunction in
Streptozotocin-induced Diabetic Rats Following Chronic Oral Administration of
Bis(maltolato)oxovanadium (IV). Can. J. Pharmacol., 71:270-276.
-
Yuen, V.G. et al. (1997) Effects of Bis(maltolato)oxovanadium (IV) are
Distinct From Food Restriction in STZ-diabetic Rats. Am. J. Physicol.,
272:E30-E35.
-
Bhanot, S. et al. (1994 Jul.) Bis(maltolato)oxovanadium (IV) Atteuates
Hyperinsulinemia and Hypertension in Spontaneously Hypertensive Rats.
Diabetes, 43(7):857-861.