in Weight-Training Athletes - Tahoma Clinic · perform the bench press, subjects were required to lower the weight to the chest (observed by spotters for their safety) and return

International Journal of Sport Nutrition, 1996, 6,382-390 O 1996 Human Kinetics Publishers, Inc.

The Effect of Oral Vanadyl Sulfate on Body Composition and Performance

in Weight-Training Athletes

J. Paul Fa wcett, Stephen J. Farquhar, Robert J. Walker, Thearoth Thou, Graham Lowe, and Ailsa Goulding

The effects of oral vanadyl sulfate (VOSO,) (0.5 mgkglday) on anthropometry, body composition, and performance were investigated in a 12-week, double- blind, placebo-controlled trial involving weight-training volunteers. Perfor- mance was assessed in the treatment (VS) and placebo (P) groups using 1 and 10 repetitions maximum (RM) for the bench press and leg extension. Thirty- one subjects completed the trial, with 2 VS subjects withdrawing because of apparent side effects. There were no significant treatment effects for anthropo- metric 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 RM leg extension @ = .002), which could have arisen because the VS group had a lower performance at baseline in this test. It was concluded that oral vanadyl sulfate was ineffective in changing body composition in weight-training athletes, and any modest performance-enhancing effect requires further investigation.

Key Words: anthropometry, dual energy x-ray absorptiometry, bench press, leg extension, sport nutrition

Approximately 23 years prior to the discovery of insulin, Lyonnet et al. observed that orally administered sodium vanadate improved glycosuria in diabetic patients (1 3). The insulin-mimetic activity of vanadium compounds was rediscov- ered in 1980, when it was shown that the oxovanadium ion (V02+) stimulates glucose oxidation in rat adipocytes (23). Subsequent work by McNeill and co- workers revealed that oral administration of oxovanadium sulfate (VOSO,, vanadyl sulfate) also lowers blood glucose and blood lipids in rats with streptozotocin- induced diabetes and prevents secondary complications of diabetes such as retin- opathy and cardiac dysfunction (2,11,19). Evidence now suggests that vanadate is converted to vanadyl intracellularly and that the vanadyl ion is the active insulin- mimetic species (20,21).

J.P. Fawcett, S.J. Farquhar, and T. Thou are with the School of Pharmacy, G. Lowe is with the School of Physical Education, and R.J. Walker and A. Goulding are with Otago Medical School, University of Otago, P.O. Box 913, Dunedin, New Zealand.

Vanadyl Sulfate / 383

The metabolic effect of insulin is to promote an anabolic state whereby total body stores of carbohydrate, protein, and fat are increased (6). The anabolic effects of vanadium compounds are unclear since evidence for stimulation of amino acid uptake and improved protein synthesis is limited to in vitro studies of rat skeletal muscle cells (17). Despite uncertainty about the effects and potential toxicity of vanadium compounds in healthy individuals, claims have emerged that VOSO, is a useful supplement for weight-training athletes as an anabolic and ergogenic agent (7). Anecdotal evidence from athletes taking up to 60 mg vanadyl sulfate daily as a nonsteroidal anabolic agent suggests that it may be effective when taken orally for 2 to 3 months at a time. For comparison, the daily dietary intake of vanadium is estimated as 10-60 yg, and no naturally occurring vanadium deficiency disease has been described in humans (18).

There are limited data on oral dosing with vanadium compounds in controlled studies or therapeutic trials. A trial of diarnmonium oxytartratovanadate (75-125 mglday) for 5 months as a potential cholesterol-lowering agent produced clear evidence of gastrointestinal toxicity in 6 out of 12 patients (24). More recent studies of insulin-dependent and non-insulin-dependent diabetics have shown that vanadyl sulfate (100 mglday) for 3 weeks (4) and sodium vanadate (1 25 mglday) for 2 weeks (9) were well tolerated except for some mild gastrointestinal upset. Vanadyl compounds appear to be less toxic than vanadate (1,22), and tests in rats have shown that chronic administration of vanadyl sulfate for 1 year in drinking water does not alter cardiovascular or hematological indices (5). Since vanadyl sulfate is freely available in anumber of countries and is being actively promoted for use by normal, healthy, nondiabetic athletes in doses of up to 60 mg daily for up to 3 months, we undertook a study of the effects of oral vanadyl sulfate in weight-training athletes.

Materials and Methods

Subjects

Forty healthy individuals (30 males, 10 females) using weight training as part of their fitness programs volunteered to participate in the study. Four individuals were involved in power lifting. The study was approved by the Southern Regional Health Authority Ethics Committee (Otago), and all participants gave their written in- formed consent. All subjects were between 19 and 39 years of age and 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 individuals were given a medical examination and were subject to the following exclusion criteria: diabetes mellitus, psychiatric illness, use of anabolic steroids or other anabolic agents, pregnancy, chronic illness, orparticipa- tion in other drug trials. Subjects were asked to continue their current training programs, diets, and other daily activities throughout the trial and were given diaries 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 (VS) or the placebo (PI group.

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Procedures

A double-blind protocol was used. Vanadyl sulfate tablets (VOSO4.3H,O, 7.5 mg) and placebo tablets were supplied by the manufacturer (SportPharma USA, Con- cord, CA). In order to ensure blinding, powdered tablets were encapsulated in opaque capsules in an amount equivalent to 1 tabletkapsule. Each subject received either vanadyl sulfate capsules or placebo capsules sufficient for 1 month at a time, at a dosage of 0.5 mgkglday for 12 weeks. This is the dosage recommended by the manufacturer to "maximize muscle hardness, strength, and lean muscle mass." The dosage regimen involved taking two capsules at a time with meals for the 12-week period. Compliance was monitored by a capsule count at the end of each month when subjects received their next bottle of capsules.

Subjects also completed 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, dizzi- ness, changes in mood or libido, sweating, increased aggression, or disturbed sleep patterns. As part of the same questionnaire they were asked whether they had perceived changes in any of the following training-related parameters: muscle fullness or size, strength, fatigue during or after training, hunger or thirst during or after training, and desire to train longer or harder. The questionnaire was scored out of 18 for side effects andfrom-14 to +14 for adverse or positive effects on training.

The measurements taken at baseline and after 4,8, and 12 weeks of treatment included body weight, six skinfold measurements, three body circumference measurements, and the 1 and 10 repetitions maximum (I RM and 10 RM) tests for bench press and leg extension. Whole-body lean and fat tissue was measured at the beginning and end of the trial by dual energy x-ray absorptiometry (DEXA scan). At each visit, fasting blood samples were collected for hematology, urea and electrolytes, glucose, creatinine, insulin, and liver function tests. Midstream urine samples (single void) were collected at 0,2,4,8, and 12 weeks and frozen at 80 "C until analyzed for vanadium at the completion of the trial.

Anthropometric Measures

One investigator (GL) performed all body weight, skinfold, and circumference measurements at each testing session. Body weight was measured with subjects wearing minimal clothing. Circumferences (muscle girths) of the upper arm, chest (after inspiration and expiration), and thigh were measured on standing subjects using a nonelastic tape measure under consistent tension without compressing the skin. Chest circumference was measured at the nipple level for men and at the axillary level for women. Upper arm (bicepsitriceps) circumference was measured on the peak of the maximally contracted biceps of the subject's dominant arm, and dominant thigh circumference (quadriceps) was measured with the tape positioned distal to the gluteal furrow and with the thigh muscle maximally contracted.

For the skinfold measurements, six sites (triceps, subscapular, suprailiac, abdomen, thigh, andmedial calf) were chosen on the right-hand side for all subjects and were measured in the same order each time. A double skinfold was raised 1 cm proximal to the site, and the skinfold calipers were positioned perpendicular to the fold. Measurements were repeated until two sequential measurements at a given site were within 0.5 mm of each other. The six values were combined to give a sum of six skinfolds.

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Vanadyl Sulfate / 385

DEXA Scan

DEXA measurements were made with a total-body scanner (Model DPX-L, Lunar Radiation Corp., Madison, WI) in the Nuclear Medicine Department of Dunedin Hospital. Subjects were scanned using a constant potential x-ray source at 12.5 fJ and a K-edge filter (cerium) to achieve a congruent beam of stable dual-energy radiation of 38 and 70 keV. A series of transverse scans were made from head to toe at 1-cm intervals. The scan area was approximately 60 X 200 cm.

Data were collected for approximately 120 pixel elements on each transverse scan, each pixel being approximately 5 X 10 mrn. Of the 20,000-22,000 pixels in a typical scan, the projection of the body involves 10,000-12,000 pixels; 4045% of these contain bone and soft tissue and 55-60% contain soft tissue alone. Scans were performed with a transverse scan speed of either 16 or 8 cm . s-', giving scan times of 10-60 min for the total body determination depending on the subject's size. The radiation doses, measured by thermoluminescent density with lithium fluoride chips, were 0.05 and 0.1 pGy, respectively (14).

Performance Measures

For practical and safety reasons, RM testing was chosen as the most appropriate method for measuring changes in strength (8). Jackson et al. suggested that the best assessment measures of lower and upper body strength are the leg press and the bench press, respectively (12). However, most weight-training machinery employs the isokinetic leg extension as the major exercise to test leg strength because it is easy to learn and effectively isolates the muscles contributing to extension at the knee (15). Although our subjects had well-balanced training programs that included the bench press, most had not included either the leg press or the leg extension in their training. The leg extension was chosen to test strength in the lower body, but subjects were asked not to alter the components of their current training programs.

The bench press was performed using an Olympic@ 20-kg bar with a bench and the leg extension on a category 11 1 cam-assisted Polaris@ leg extension machine. After warm-ups with light weights, subjects performed the bench press before the leg extension and the 10 RM prior to the 1 RM for each exercise. To perform the bench press, subjects were required to lower the weight to the chest (observed by spotters for their safety) and return it to the straight-arm position while keeping the buttocks and feet on the bench. Subjects had to control the bar at all times and maintain continuity of movement with no bounce off the chest.

In the leg extension, controlled and continuous movement was again required with the subject sitting upright pushing the weight upward and extending the leg(s) to the locked position. Both legs were used in the 10 RM, but males used the dominant leg only in the 1 RM due to a limitation of weight (100 kg) available on the leg extensionmachine. The weights for the 10 RM exercises were selected based on what the subjects considered they could perform with good technique. The 10 RM test was limited to a single set. The first attempt for the 1 RM was a weight within 80% of subjects' self-reported 1 RM, and subsequent lifts were increased until the subject either failed to complete the lift or indicated a maximum had been reached. At each subsequent gym assessment, subjects were encouraged to attempt heavier weights.

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Blood and Urine Assays

Full blood count (Coulter counter) and plasma biochemistry were carried out by laboratory staff of Dunedin Hospital using standard laboratory procedures. Insulin was measured by ELISA using the Enzymun-Test Insulin@ (Boehringer Mannheim). Vanadium in urine was analyzed by carbon furnace atomic absorption spectros- copy. Determinations were performed on a Varian Spectra AA 40 at 3 18.4 nm using a pyrolytically coated graphite partition furnace and Zeeman background correc- tion. Urine samples were acidified with 10% H,SO, and treated with 5% cupferron before extracting vanadium into methyl isobutyl ketone. To correct for variations in urine output, creatinine in urine was also determined allowing vanadium concentrations to be quoted in yglg creatinine.

Data Analysis

Data are presented as mean + SD. All criterion measures were analyzed by SPSS on a PC-based system (Release 5.0, SPSS Inc., Chicago). A 2 X 2 X 4 factorial ANOVA for treatment, gender, and time with repeated measures over time was used to analyze the data for all parameters except DEXA scan, where a 2 X 2 X 2 factorial ANOVA was used. For post hoc analysis, if required, we compared means at each test point using the Bonferroni inequality for multiple comparisons. The level of significance was set at p < .05.

Results

A total of 3 1 subjects (23 males, 8 females; mean age 28.0 years, range 19-39 years) completed the trial of oral vanadyl sulfate. The subjects were equally divided between the VS group (1 1 males, 4 females) and P group (12 males, 4 females). Training histories revealed that the power lifters and those with previous experience with the leg extension were equally distributed between the two groups. 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. Examination by a physician was unremarkable, and hematology and blood biochemistry were within normal limits. Seven subjects either did not attend the baseline physical assessment or withdrew for personal reasons not related to the study. Examination of personal diaries revealed that all subjects maintained consistency of training throughout the trial. Compliance as assessed by capsules returned at 4, 8, and 12 weeks was satisfactory.

With regard to the subjective assessment of side effects, oral vanadyl sulfate appeared to be well tolerated, with mean side effect scores (SD) after 4, 8, and 12 weeks of 1.7 (1.8), 1.7 (2. I), and 1.3 (1.8) for the VS group and 1.3 (1.4), 1.1 (1.6), and 1.0 (1.4) for the P group, respectively (maximum score of 18). 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 VS group after 8 weeks. The scores for adverse or positive effects on training (-14 to +14) were 2.4 (2.6), -0.2 (4.9), and 1.1 (2.8) for VS and 2.3 (3.8), 1.4 (2.9), and 1.2 (3.3) for the P group. The negative score for VS at 8 weeks was mainly due to 2 males with scores of -9 and -10, who complained of general fatigue.

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The changes in mean weight, sum of six skinfolds, muscle girths, total percentage fat and lean tissue (DEXA), and performance measures for the VS and P groups during the trial are given in Table 1. 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. The absence of a sex effect in the leg extension is possibly due to males performing the test with one leg, whereas the females used both. 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 VS group after 4 weeks. Sum of six skinfolds was significantly higher than baseline for the VS group at 4,8, and 12 weeks and for the P group at 12 weeks.

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 RM leg extension ( p = .002), which post hoc analysis showed resulted from the VS group improving more than the P group in the first 4 weeks. Although this interaction could arise due to a real effect, it is compromised by the fact that the VS group started at a lower baseline than the P group. Nevertheless, the difference between the VS and P groups in performance at baseline was not statistically significant (p = .13, unpaired Student's t test).

There were no significant Treatment X Time interactions in hematological or biochemical parameters or liver function tests after 12 weeks, and all values remained within their normal ranges. After 8 weeks the VS group had significantly higher levels of glucose (5.2 f 0.5 vs. 4.7 + 0.4 mmol . L-',p <.01) and insulin (9.4 ? 3.2 vs. 6.7 +. 2.6 mIU . L-l, p < .01), whereas increases in the P group were not significant (glucose 5.0 f 0.5 vs. 4.6 ? 0.4; insulin 8.6 f 1.6 vs. 7.1 f 5.5 mIU . L-I). The vanadium concentration in urine of the VS group was elevated after 2 weeks (51 f 30 vs. 0.5 +. 0.5 pglg creatinine at baseline) and remained at steady state for the remainder of the trial (41 f 29,52 f 28,39 + 24 pglg creatinine at 4,8, and 12 weeks, respectively).

Discussion

Vanadyl sulfate has well-documented insulin-mimetic activity in non-insulin- dependent diabetes and experimental models of diabetes (1, 2). Animal studies which show that vanadyl sulfate increases transport of glucose and is incorporated into glycogen in muscle and liver (3, 10) suggest that it may also have anabolic and ergogenic effects. In the popular bodybuilding literature, there are many anecdotal reports that weight-training athletes taking oral vanadyl sulfate say their muscles feel more full or "pumped" after training than when the athletes do not take the supplement. However, we are unaware of any clinical studies investigating these putative anabolic and ergogenic effects.

The aim of this study was to use DEXA scan, anthropometry, and perfor- mance measures to determine the effects of oral vanadyl sulfate in a healthy population using weight training for fitness. The urinary excretion of vanadium in the treatment group reached steady state after 2 weeks, suggesting that plasma levels remained at steady state for most of the trial. Despite the increased intake of vanadyl ion, oral vanadyl sulfate did not significantly change body composition. The lack of change in anthropometric measures and lean tissue by DEXA scan shows there

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Table 1 Anthropometry, Body Composition (DEXA), and Performance of Subjects During the Clinical Trial of Oral Vanadyl Sulfate: Data are Mean (SD) at 0,4,8, and 12 Weeks

Vanadyl sulfate (n = 15) Placebo (n = 16)

Variable 0 4 8 12 0 4 8 12

Weight (kg)

Sum of six skinfolds (mm)

Muscle girths (cm) Chest (exp)

Chest (insp)

Upper arm

Thigh

Total % fat (DEXA) (kg)

Total % lean (DEXA) (kg)

Bench press (kg) 10 RM

Leg extension (kg) 10 RM

l RMt

*p < .05, **p < .01, Bonferroni inequality for comparison with 0 weeks. t p < .002 for Treatment X Time interaction on repeated-measures ANOVA.

was no increase in lean body mass. Thus, this study did not support claims that vanadyl sulfate is an anabolic agent.

Although major changes in body composition did not occur, both groups showed small increases in body weight, which anthropometry suggests are due to an increase in fat. The increase in weight and sum of six skinfolds was greater in the VS group after 4 weeks but similar in both groups after 12 weeks, suggesting that vanadyl sulfate may promote deposition of body fat over a short period. The small but significant increases in blood glucose and insulin observed in the VS group

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imply that vanadyl sulfate may diminish insulin action, but further investigation is required to substantiate this finding.

There were significant training effects in both measures of performance but particularly in the leg extension tests. This is consistent with the fact that at the start of the trial participants were familiar with the bench press but some were not as familiar with the leg extension exercise. Both groups approached a performance plateau in the leg extension tests toward the end of the trial, and improvements were not accompanied by concomitant increases in muscle girths. The Treatment X Time interaction in the 1 RM leg extension, suggesting that vanadyl sulfate accelerates performance improvement produced by training, clearly requires confirmation. It is interesting to note, however, that anecdotal evidence from athletes using the drug supports the idea of a limited period of efficacy of about 1 month.

It has been suggested that athletes should carefully weigh the possible benefits of vanadyl supplementation against the potential risks (16). The present investigation shows that oral vanadyl sulfate has no favorable or consistent effects on anthropometric measures after 12 weeks of use and may be associated with excessivetiredness during and after training in some 20% of individuals. Tiredness or fatigue as a result of exercise has not been previously recognized as a side effect of vanadium ingestion. If any ergogenic effect exists, it appears to occur within 4 weeks. Further placebo-controlled studies of oral vanadyl sulfate, using larger groups of weight trainers and bodybuilders carefully matched for performance, are required to confirm any ergogenic effect.

Oral vanadyl sulfate at a dose of 0.5 mg/kg/day for 12 weeks caused no gastrointestinal symptoms and no significant alterations in hematological or bio- chemical parameters in weight-training athletes except for small increases in fasting glucose and insulin. Vanadyl sulfate has no anabolic effect on lean muscle mass when taken for 12 weeks but may have a modest ergogenic effect during the first month. The possibility that vanadyl sulfate is associated with subjective feelings of excessive fatigue during and after training requires further investigation.

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Acknowledgments

We wouldliie to thank the Otago Medical Research Foundation for financial support and Sportpharma USA for kindly donating the vanadyl sulfate. We also thankh4r. Trevor Walmsley for vanadium assays, Ms. Elspeth Gold and Mr. David Boulton for technical assistance, Mr. Simon Davies for statistical expertise, and Ms. Liz Christie for typing the manuscript.

Manuscript received: October 30, 1995 Accepted for publication: August 5 , 1996

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