Vanadium, oxalate complexes

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

other: human data

Adequacy of study:

supporting study

Study period:

not specified

Reliability:

other: not rated acc. to Klimisch

Rationale for reliability incl. deficiencies:

other: Any kind of reliability rating is not considered to be applicable, since human studies/reports are not conducted/reported according to standardised guidelines.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

The effect of oral vanadyl sulfate on body composition and performance in weight-training athletes

Author:

Fawcett, J.P. et al.

Year:

1996

Bibliographic source:

International Journal of Sport Nutrition 6: 382 - 390.

Reference 2

Reference Type:

publication

Title:

Oral vanadyl sulphate does not affect blood cells, viscosity or biochemistry in humans

Author:

Fawcett, J.P. et al.

Year:

1997

Bibliographic source:

Pharmacology & Toxicology 80: 202 - 206.

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

repeated dose toxicity: oral

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

This study investigated the effects of oral administration of vanadyl sulfate (VOSO4 * 3H2O) in weight-training athletes. Thirty healthy males and ten healthy females (19 to 39 years old) participated in this experiment. All subjects had been weight training for at least 1 year and four individuals were involved in power lifting. Using a double-blind protocol, each subject received either vanadyl sulfate capsules (dosage: 0.5 mg/kg/day) or placebo capsules for 12 weeks. The dosing regimen involved taking two capsules at a time with meals during the treatment period. The following parameters were measured/recorded: clinical signs, training-related parameters (muscle fullness, muscle strength, fatigue, hunger, thirst, desire to train), anthropometric measurements (body weight, skinfold measurements, body circumference measurements), performance measurements (1 and 10 repetitions maximum tests for bench press and leg extension), whole body lean and fat tissue, haematology (red blood cell, white blood cell, platelet counts, red cell mean cell volume and haemoglobin level), clinical chemistry (lipids and indices of liver and kidney function), blood viscosity (haematocrit, plasma visocity and blood viscosity at 10/s and 100/s shear rate), and urine analysis (determination of vanadium content).

GLP compliance:

not specified

Remarks:

not specified in the publication

Test material

Test material information

Constituent 1

Reference substance name:

Vanadium oxide sulphate

EC Number:

248-652-7

EC Name:

Vanadium oxide sulphate

Cas Number:

27774-13-6

Molecular formula:

VOSO4

IUPAC Name:

oxovanadium(2+) sulfate

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): Vanadyl sulfate tablets (VOSO4 * 3H2O)(manufacturer: SportPharma USA, Concord, CA, USA)

Specific details on test material used for the study:

not applicable

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 40 healthy individuals
- Sex: 30 males / 10 females
- Age: 19 to 39 years old

Participating individuals used weight training as part of their fitness programs. Four individuals were involved in power lifting and all subjects had been weight training for at least 1 year when the study began. Inclusion in the study was dependent upon their training programs being constant (i.e., no buildup for competitions) and balanced in terms of upper and lower body and aerobic and anaerobic components.

The individualy were given a medical examination and were subject to the following exclusion criteria: diabetes mellitus, psychiatric illness, use of anabolic steriods or other anabolic agents, pregnancy, chronic illness, or paticipation in other drug trials. Subjects were asked to continue their current training programs, diets, and other daily activities throughout the trial and were asked to record their daily training routines. Volunteers were matched in pairs on the basis of sex, age, weight, height, and training program, and one member of each pair was randomly allocated to either the treatment or the placebo group.

Ethical approval:

confirmed and informed consent free of coercion received

Route of exposure:

oral

Reason of exposure:

intentional

Exposure assessment:

estimated

Details on exposure:

Prior to administration, vanadyl sulfate tablets (7.5 mg) and placebo tablets were powdered and encapsulated in opaque capsules in an amount equivalent to 1 tablet/capsule. Using a double-blind protocol, each subject received either vanadyl sulfate capsules at a dosage of 0.5 mg/kg/day or placebo capsules for 12 weeks. The dosing regimen involved taking two capsules at a time with meals for the 12 week period. The daily dose as vanadium was 9 mg (range 5 - 14 mg).

Examinations:

- Clinical signs: subjects complete a questionnaire at the conclusion of every physical assessment regarding whether they had experienced any of the following side effects in the previous month: gastrointestinal symptoms, muscle cramps, dizziness, change in mood or libido, sweating, increased aggression, or disturbed sleep patterns.

- Training-related parameters: subject completed a questionnaire at the conclusion of every physical assessment regarding whether they had experienced any of the following changes in training-related parameters: muscle fullness or size, strength, fatigue during or after training, hunger or thrist during or after training, and desire to train longer or harder.

- Anthropometric measurements: body weight, six skinfold measurements (sites: triceps, subscapular, suprailiac, abdomen, thigh, and medial calf), and three body circumference measurements (muscle girths of upper arm, chest (after inspiration and expiration), and thigh) were recorded at baseline and after 4, 8, and 12 weeks of treatment.

- Performance measurements: 1 and 10 repetitions maximum (1 RM and 10 RM) tests for bench press (Olympic® 20-kg bar with a bench) and leg extension (category 111 cam-assisted Polaris® leg extension maschine) were recorded at baseline and after 4, 8, and 12 weeks of treatment.

- Dual energy x-ray absorptiometry (DEXA scan): whole body lean and fat tissue was measured with a total-body scanner (Model DPX-L) at the beginning and end of the trial. A series of transverse scans were made from head to toe at 1-cm intervals.

- Haematology: at each visit, fasting blood samples were collected in the morning at 0 and 12 weeks for measurement of haematological indices (erythrocyte count, haemoglobin, mean cell volume, mean cell haemoglobin, platelet count, leukocyte count, and leukocyte differential counts (neutrophil, lymphocyte, monocyte, eosinophil, basophil)).

- Clinical chemistry: at 0 and 12 weeks, fasting blood samples were collected for urea, electrolytes, glucose, creatinine, insulin, albumin, protein, total bilirubin, direct bilirubin, alkaline phosphatase, alanine aminotransferase, cholesterol, high density lipoprotein, triglyceride, and serum lipids.

- Blood viscosity: at each visit, fasting blood samples were collected in the morning at 0, 2, 4, 8, and 12 weeks for viscosity measurements (whole blood viscosity in centipoise together with haematocrit, plasma viscosity, and relative blood viscosity).

- Urine analysis: midstream urine samples (single void) were collected at 0, 2, 4, 8, and 12 weeks and analysed for vanadium by carbon furnace atomic absorption spectroscopy. To correct for variations in urine output, creatinine in urine was also determined allowing vanadium concentrations to be quoted in µg/g creatinine.

Medical treatment:

not applicable

Results and discussion

Clinical signs:

Two male subjects in the treatment group withdrew within the first 6 weeks as a result of apparent side effects: excessive tiredness during training in one case and excessive tiredness and mood changes involving feelings of aggression and being short-tempered in the other case. No abnormal haemtological findings or clinical chemistry findings could be found.

With regard to the subjective assessment of side effects, vanadyl sulfate appeared to be well tolerated.. Between 7 and 9 participants in each group reported one or more side effects at every time point, but the range of side effects was similar for the two groups.

In general, the participants remained positive about training, except for the treatment group after 8 weeks. This was mainly due to two males, who complained of general fatigue.

Results of examinations:

31 of the forty subjects (23 males / 8 females; mean age 28.0 years, range 19 - 39 years) completed the trial of oral administration of vanadyl sulfate. Two male subjects of the treatment group withdrew from the study as a result of apparent side effects. Seven subjects (treatment: 3 subjects; placebo: 4 subjects) either did not attend the baseline physical assessment or withdrew for personal reasons not related to the study. The remaining subjects were equally divided between treatment group (11 males / 4 females; mean age 29.0 ± 6.8 years) and placebo group (12 males / 4 females; mean age 27.1 ± 5.9 years) and groups were homogenous for sex, age, height and body weight. Power lifter and those with previous experience with the leg extension were also equally divided among groups. All subjects maintained consistency of training throughout the trial.

- anthropometric measurements, performance measurements, and dual energy x-ray absorptiometry:
Repeated-measures ANOVA revealed that sex was a main effect in the analysis of weight, muscle girths except thigh, total percentage fat and lean tissue (DEXA), and bench press. Regarding changes in anthropometry, time was a significant main effect for weight and sum of six skinfolds but not for muscle girths or DEXA parameters. Post hoc analysis of weight showed a significant within-group increase from baseline for the treatment group after 4 weeks. Sum of six skinfolds was significantly higher than baseline for the treatment group at 4, 8, and 12 weeks and for the placebo group at 12 weeks.
Body weight of the two groups remained stable during the trial (please refer to table 1 in the field "Any other information on results incl. tables" below).

Regarding changes in performance measures, time was a significant main effect in both bench press and leg extension, showing that both groups improved with training. There was a significant Treatment X Time interaction in the 1 repetitions maximum (RM) leg extension (p = 0.002), which post hoc analysis showed results from the treatment group improving more than the placebo group in the first 4 weeks. Although this interaction could arise due to a real effect, it is compromised by the fact that the treatment group started at a lower baseline than the placebo group. Nevertheless, the difference between the treatment group and placebo groups in performance at baseline was not statistically significant (p = 0.13, unparied Student's t test).

- Haematology: time was a significant main effect for some of the haematological indices (haemoglobin and mean cell haemoglobin, leukocyte count and eosinophil count) but there were no significant effects of treatment. Two males in the placebo group had elevated neutrophils at twelve weeks arising from minor infections but other wise all indices remained within their normal ranges.
Please also refer to table 2 in the field "Any other information on results incl. tables" below

- Clinical chemistry: no significant Treatment x Time interactions in biochemical parameters or liver function tests after 12 weeks were observed. All biochemical indices remained stable.
After 8 weeks the treatment group had significantly higher levels of glucose (5.2 ± 0.5 vs. 4.7 ± 0.4 mmol/L, p <0.01) and insulin (9.4 ± 3.2 vs. 6.7 ± 2.6 mIU/L, p<0.01), whereas increases in the placebo group were not significant (glucose 5.0 ± 0.5 vs. 4.6 ± 0.4 mmol/L; insulin 8.6 ± 1.6 vs. 7.1 ± 5.5 mIU/L).
Please also refer to table 3 in the field "Any other information on results incl. tables" below

- Blood viscosity: blood pressure of the two groups remained stable during the trial (please refer to table 1 in the field "Any other information on results incl. tables" below). Plasma viscosity was stable but time was a significant main effect for haematocrit, which increased by 3.3 - 3.6 % over 8 weeks before declining. Time was also a significant main effect for both blood viscosity and relative blood viscosity which increased steadily over the trial by 9 - 11 % at 100/s shear and 35 - 38 % at 10/s shear. There was no significant effects of treatment and no treatment x time interactions for an measure of blood viscosity.

- Urine analysis: vanadium concentration in urine of the treatment group was elevated after 2 weeks (51 ± 30 vs. 0.5 ± 0.5 µg/g creatinine at baseline) and remained at steady state for the remainder of the trial (41 ± 29, 52 ± 28, 39 ± 24 µg/g creatinine at 4, 8, and 12 weeks, respectively).

Effectivity of medical treatment:

not applicable

Outcome of incidence:

not applicable

Any other information on results incl. tables

Table 1: Body weight and blood pressure (BP) in weight training athletes at baseline (0) and after 4, 8 and 12 weeks of oral vanadyl sulphate or placebo

Variable	Vanadyl sulphate				Placebo
	0	4	8	12	0	4	8	12
weight (kg)	77.9	78.4	78.4	78.7	79.3	79.4	79.8	80.6
	(16.8)	(16.4)	(16.4)	(16.0)	(15.2)	(15.6)	(15.6)	(15.6)
systolic BP (mmHg)	129	126	125	122	124	127	127	125
	(13)	(8)	(8)	(8)	(10)	(13)	(9)	(13)
diastolic BP (mmHg)	76	79	77	74	77	80	77	75
	(9)	(12)	(12)	(8)	(7)	(6)	(8)	(5)

Table 2: Haematological indices in weight training athletes at baseline (0) and after 12 weeks of oral vanadyl sulphate or placebo

Variable	Vanadyl sulphate		Placebo
	0	12	0	12
Erythrocyte count (x10^6/mm^3)	4.77 ± 0.30	4.86 ± 0.33	4.81 ± 0.44	4.83 ± 0.43
Haemoglobin (g%)	14.3 ± 0.1	14.7 ± 0.1	14.5 ± 0.1	14.7 ± 0.1
Mean cell volume (fL)	87.2 ± 2.9	87.1 ± 3.1	88.8 ± 3.1	87.7 ± 1.9
Mean cell haemoglobin (pg)	29.9 ± 1.1	30.3 ± 1.1	30.2 ± 0.6	30.5 ± 0.8
Platelet count (x10^5/mm^3)	2.50 ± 0.34	2.57 ± 0.33	2.41 ± 0.54	2.58 ± 0.74
Leukocyte count (x10^3/mm^3)	5.13 ± 0.89	5.69 ± 1.39	5.47 ± 0.92	6.77 ± 2.31
Leukocyte differential counts (x10^3/mm^3)
Neutrophil	2.68 ± 0.66	3.03 ± 1.31	3.01 ± 0.88	4.01 ± 2.16
Lymphocyte	1.77 ± 0.47	1.86 ± 0.47	1.77 ± 0.38	1.94 ± 0.51
Monocyte	0.44 ± 0.08	0.52 ± 0.09	0.51 ± 0.14	0.57 ± 0.19
Eosinophil	0.21 ± 0.11	0.23 ± 0.11	0.15 ± 0.06	0.19 ± 0.10
Basophil	0.04 ± 0.02	0.05 ± 0.05	0.04 ± 0.02	0.5 ± 0.02

Table 3: Biochemical indices in weight training athletes at baseline (0) and after 12 weeks of oral vanadyl sulphate or placebo

Variable	Vanadyl sulphate		Placebo
	0	12	0	12
Albumin (g/l)	45.6 ± 2.0	49.5 ± 3.3	45.3 ± 3.4	47.1 ± 3.6
Protein (g/l)	69.2 ± 3.6	67.8 ± 3.4	68.3 ± 4.2	70.1 ± 4.2
Total bilirubin (µmol/l)	13.8 ± 6.2	12.1 ± 6.4	13.8 ± 5.4	11.1 ± 3.5
Direct bilirubin (µmol/l)	4.6 ± 2.7	4.4 ± 2.4	4.7 ± 1.6	4.2 ± 1.4
ALP (IU/l)	76 ± 21	76 ± 19	84 ± 29	81 ± 28
ALT(IU/l)	28 ± 11	26 ± 13	26 ± 10	25 ± 11
Cholesterol (mmol/l)	4.5 ± 0.6	4.7 ± 0.7	4.5 ± 0.9	4.9 ± 1.0
HDL (mmol/l)	1.10 ± 0.29	1.20 ± 0.37	1.21 ± 0.35	1.24 ± 0.36
Triglyceride (mmol/l)	0.80 ± 0.28	0.99 ± 0.52	1.01 ± 0.43	1.22 ± 0.60
Urea (mmol/l)	6.2 ± 1.9	6.3 ± 1.5	6.2 ± 1.6	5.8 ± 1.2
Creatinine (mmol/l)	100 ± 10	104 ± 9	99 ± 10	98 ± 10

Applicant's summary and conclusion

Conclusions:

According to the authors, vanadyl sulfate (VOSO4 * 3H2O; dosage: 0.5 mg/kg/day) had no significant treatment effects on anthropometric parameters and body composition during the trial. Both groups had significant improvements in performance but the only significant effect of treatment was a Treatment x Time interaction in the 1 repetitive measurement leg extension. Furthermore, the authors stated that the substance seems to have no effect on blood viscosity, body weight, and blood pressure in weight training athletes. Lastly, no significant changes were observed by the authors in haematological indices, biochemical parameters relating to liver and kidney function, or lipid metabolism after 12 weeks of administration of vanadyl sulfate.