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Effects of a Novel
Zinc-Magnesium Formulation on Hormones and Strength
L.R. BRILLA1 AND
VICTOR CONTE2
1Exercise and Sports Science Laboratory, Western Washington University,
Bellingham, WA 98225-9067 and
2BALCO Laboratories, 1520 Gilbreth Road, Burlingame, CA 94010, Tel:
800-777-7122
L.R. BRILLA AND VICTOR CONTE. Effects of a Novel Zinc-Magnesium
Formulation on Hormones and Strength. JEPonline, 3(4): 26-36, 2000.
Muscle attributes and selected blood hormones of football players were
assessed in response to a nightly supplementation regimen during spring
football, over an 8-week period, with pre-post measures. A double-blind
randomized study was conducted with ZMA (30 mg zinc monomethionine
aspartate, 450 mg magnesium aspartate, and 10.5 mg of vitamin B-6) and
placebo (P), n=12 and n=15, respectively. Plasma zinc and magnesium
levels were ZMA (0.80 to 1.04 g/ml; 19.43 to 20.63 mcg/ml ) and P (0.84
to 0.80 g/ml ; 19.68 to 18.04 g/ml), respectively (P<0.001). Free
testosterone increased with ZMA (132.1 to 176.3 pg/mL), compared to P
(141.0 to 126.6 pg/mL) (P<0.001); IGF-I increased in the ZMA group
(424.2 to 439.3 ng/mL) and decreased in P (437.3 to 343.3 ng/mL)
(P<0.001). Muscle strength via torque measurements and functional power
were assessed with a Biodex dynamometer. Differences were noted between
the groups (P<0.001): ZMA (189.9 to 211 Nm at 180º/s and 316.5 to 373.7
Nm at 300º/s) and P (204.2 to 209.1 Nm at 180º/s and 369.5 to 404.3 Nm
at 300º/s). The results demonstrate the efficacy of a Zn-Mg preparation
(ZMA) on muscle attributes and selected hormones in strength-trained,
competitive athletes.
Key Words: vitamin B6, anabolic hormones, testosterone, IGF-I, muscle
INTRODUCTION
Zinc (Zn) and magnesium (Mg) may enhance levels of Insulin-like Growth
Factor-I (IGF-I)(1); and zinc, in particular, may contribute to
elevating serum testosterone (2). Both IGF-I and testosterone are
anabolic factors that enhance muscle function and physical performance.
Testosterone's role in physical performance enhancement has been studied
for a number of years. The IGF-I response to intense muscular activity
has not been well defined, relatively. Training may lead to a short-term
catabolic state hormonally expressed by reductions in IGF-I. Baseline
serum concentrations of testosterone, GH, and IGF-I were unaffected by
16-wk resistive training program which elicited an approximate 40%
increase in muscular strength in men, 60 4 yr. It was intimated that
training-induced increases in IGF-I could occur in muscle without
altering serum IGF-I concentration (3).
A condition named somatopause due to decreased IGF-I and GH has been
identified with aging. To countermeasure somatopause, 33 moderately
obese women (67.1 5.2 yr), self-injected IGF-I. Weight loss with muscle
strength increases were greater in IGF-I group due to training (12-wk:
walk 3 days, strength trained 2 days) (4). IGF-I may mediate the action
of GH on skeletal muscle as a paracrine agent. In male rats, larger mean
muscle weight and fiber cross-sectional area occurred when functional
overload was combined with GH/IGF-I administration, and myonuclear
number increased concomitantly with fiber volume. Increases in
myonuclear numbers in rats may be a prerequisite for prolonged and
substantial skeletal muscle fiber hypertrophy (5). IGF-I plus exercise
resulted in an increase in the size of each predominant fiber type (I,
IIa).
In contrast, the nutrients, Zn and Mg, may not be at optimal status in
physically active individuals to facilitate function of these anabolic
factors. Zn losses may be exacerbated through exercise (6), both long
duration and high intensity, sweating (7), and inadequate intake (8).
Additionally, exogenous testosterone administration results in
significant reductions of Zn (9). Also, Mg has a putative effect on
muscle strength in clinical applications and previously untrained
individuals (10). Mg may be reduced due to intense and/or long-term
exercise (10). These diminutions in Zn and Mg may lead to a situation of
latent fatigue with decreased endurance (7,10,11). A special aspect of
the zinc-magnesium supplement used in this study was the inclusion of
vitamin B6 to enhance the absorption of Zn and Mg (12,13), in addition
to the known properties of vitamin B6 in protein metabolism.
Both of these minerals have been reported by the USDA to be low in
typical diets: 68% of diets have less than two-thirds of the RDA for Zn
and 39% contain less than two-thirds of the RDA for Mg. Some dietary
surveys of athletes have demonstrated that these nutrients may meet the
RDAs (2,14). It may be necessary for athletes to supplement these
nutrients in order to get dietary adequacy through meeting the RDA, or
beyond, for physical performance effects. The purpose of this study was
to assess the effect of a novel Zn, Mg, and vitamin B-6 formulation
(ZMA) on anabolic hormones and muscle function in varsity football
players during their spring football practice season.
METHODS
After approval of the project by the Western Washington University (WWU)
Human Subjects Committee, the study commenced with the recruitment of
subjects from the WWU football team, NCAA, Division II. Varsity football
players were solicited for a randomized, double blind supplementation
study. Fifty-seven players were involved in the initial testing which
included anthropometric data, a 3-day diet analysis with Nutritionist IV
software to determine dietary intake of nutrients of interest, a
venipuncture blood draw, and muscle isokinetic torque and power
assessments. All investigators were appropriately trained in the various
aspects of the testing protocols. Anthropometric data collection was
supervised by an individual trained in kinathropometric troika
methodology. A Certified Nutrition Specialist conducted the nutrition
analysis. The blood draws were completed by trained phlebotomists. The
isokinetic data was collected by trained and experienced testers, one
with 15 years experience. Twenty-seven players completed the
supplementation regimen and testing so their data were included in the
analysis. Activity consisted of supervised spring football practice.
All tests were performed pre-post the spring practice season, for a
total supplementation period of seven weeks. The first week was
familiarization with the practice routine and the assessments were made
at the first and eighth weeks. No intervening samples were taken because
of the variability of such elements as zinc and magnesium for tissue
saturation or steady state to be reached, approximately 3-5 weeks
depending on baseline status. All subjects were tested between 0700 and
1030, with the isokinetic testing held between 1030 and 1330. Since the
study was randomized, double-blinded, the tests were not controlled by
group although it was attempted to test each subject at the same time of
day, pre-post. Subjects reported to the lab, in the vicinity of the
weight room, weekly to pick up their supplements. Subjects had been
randomly assigned to one of two groups: control who took a placebo and
treatment who took the supplement, ZMA (SNAC System, Inc., Burlingame,
CA), the equivalent of 30 mg zinc monomethionine aspartate, 450 mg
magnesium aspartate, and 10.5 mg vitamin B-6. All subjects took three
capsules nightly between dinner and bedtime. Failure to comply with the
supplementation regimen resulted in subjects being dropped from the
study. The players were asked to not take any other nutrient supplements
during the course of the study. This request was monitored by-weekly
questioning when they picked up their supplement/placebo. A 10-hour
fasting blood sample was obtained early-morning via venipuncture before
any physical activity was undertaken. Blood samples were prepared for
analysis of plasma zinc and magnesium, and serum insulin-like growth
factor-1 (IGF-I), total testosterone, free testosterone, and percent
testosterone.
The specimen-preparation method used for plasma zinc and magnesium
analysis was a 50/50 nitric/perchloric acid digestion. The
instrumentation used in the analysis was an inductively coupled plasma
atomic emission spectrometer (ICP/AES) (Applied Research Laboratories,
Dearborn, MI; model 34000 simultaneous ICP). The detection limits of the
ICP-AES for Zn and Mg are 0.009 and 0.014 parts per million (ppm),
respectively. The ICP-AES inter-assay precision was determined from 20
assays on human plasma pools. The standard deviation and coefficient of
variation (%CV) were 0.05 ppm and 5.9% for Zn and 1.0 ppm and 4.4% for
Mg. Following organic extraction, a competitive radioimmunoassay (RIA)
which uses the I125 isotope as the competing antigen was the method used
in the analysis of total and free testosterone. The instrumentation used
was a dialysis beta counter. The precision for the quality control
samples ranged from a high of 335 ng/dL with a standard deviation (SD)
of 27 and %CV of 8.0% to low sample of 13.8 ng/dL with SD 1.26 and %CV
of 9.2%. IGF-I analysis was done through a combination of equilibrium
dialysis, extraction, chromatography, and radioimmunoassay (RIA) with
use of a gamma counter. The sample reproducibility for this methodology
ranges from high pool of 688 22.6 ng/mL and %CV of 3.3%, to a low pool
ng/mL SD of 10.1 and %CV of 8.3%. These quality control values meet the
acceptable criterion of coefficient of variation of less than 15.0%.
Torque and power measurements were preformed with the lower extremity on
a BIODEX isokinetic dynamometer. The set-up was adjusted for each
subject, and the same subject positions were recorded to use pre and
post. Three trials were given at two separate settings: 180 /s and 300
/s. Torque and power data were recorded from the best trial.
Means and standard deviations were calculated. A MANOVA was used to
assess the mineral and hormone data sets. ANCOVA was used to test for
muscle attributes of torque and power. P was set at <0.05. For
significant interactions, multiple pairwise comparisons with a
Bonferroni adjustment were used.
RESULTS
Data sets were completed on 27 subjects with resultant group sample
sizes of ZMA: 12, P: 15. The attrition may be accounted for through
inability to comply with supplementation regimen, injuries, and aversion
to testing such as phlebotomy. Any injuries were documented with the
athletic training staff. Other factors were self-report. Body weights
were 99.1 kg and 99.0 kg, pre-post in the ZMA group, and 95.9 kg and
95.6 kg, pre-post in placebo subjects. Diet records (3-day) showed that
mean values of selected nutrients exceeded the RDA for Zn (17.0 7.4 mg),
Mg (539 272 mg), and vitamin B-6 (3.6 1.6 mg). There was a significant
treatment by group interaction effect (P<0.001) for plasma values of
zinc, magnesium, and the serum anabolic hormone profile, except percent
testosterone. Subject characteristics plus mineral and hormone data are
presented in Table 1. Graphical display of the specific variables is
provided in Figure 1. Statistical comparisons of the significant
interactions of the mineral and hormone data are presented in Table 2.
Overall, control values dropped and ZMA supplemented values increased
for within groups comparisons, pre-post changes (P<0.0125, Bonferroni
adjustment). For the between groups analysis, no pre test comparisons
were significant. These findings demonstrate that the groups were
comparable at the commencement of the study for the plasma measures.
However, the post analysis showed significant differences in all
comparisons, except for a trend towards significance for IGF-I
(P=0.0195) with the Bonferroni adjustment. These findings indicate that
ZMA reverses the drops in these nutrients and anabolic hormones seen
with an intensive 8-week training program such as spring football
practice.
DISCUSSION
Varsity football players were solicited for a randomized, double blind
supplementation study. Of 57 subjects who initially volunteered for the
study, 27 successfully followed the nightly supplement regimen over the
course of the study and completed the testing sessions. The attrition
was due to the need for compliance not only with the supplement and
placebo regimen, but also with subsequent blood sampling. There were
also some injuries that occurred that prohibited some players from
participating fully in practices and/or follow-up muscle function
testing. The resultant groups were 15 players on the placebo and 12 with
the supplement treatment. The supplement was ZMA, a novel preparation of
30 mg zinc monomethionine aspartate, 450 mg magnesium aspartate, and
10.5 mg vitamin B-6.
Post blood samples and muscle function measures were obtained for
comparison to the baseline testing. The results of ZMA supplementation
on anabolic hormone profile in football players pre-post spring football
practice indicates an amelioration of the anabolic hormones so that the
ZMA group had increased concentrations of total testosterone, free
testosterone, and IGF-I compared to plateaus or drops in the placebo
group. Free testosterone levels have been positively correlated with IGF-I
levels (15) and muscle mass (16). Previous research has demonstrated
that testosterone responds to intense muscular activity through a
decline over time (17) or no significant change (18). Elevated levels of
testosterone may be accounted for by exercise-induced changes in plasma
volume, therefore no significant differences are demonstrated when
hemoconcentration is considered. The subjects in this study were well
hydrated in a temperate environment, and tested at least 24 hours after
the last strenuous workout of spring football practice.
The preliminary evidence from the results of the present study indicates
that simple nutritional supplementation with ZMA may improve the
anabolic hormone profile of athletes engaging in intense physical
activity. Zinc plays an essential role in androgen metabolism and
interaction with steroid receptors (19). Zinc deficiency in male rats
reduced circulating luteinizing hormone and testosterone concentrations,
by 34% and 68%, respectively. The livers of zinc-deficient rats
exhibited a higher aromatization of testosterone to estradiol than did
those of controls (19). Concentration of hepatic estrogen receptors in
the liver cytosol was significantly higher in zinc deficiency. Zinc
deficiency has deleterious effects similar to those of alcohol or
castration on hepatic androgen metabolism and aromatization of
androgens. Zinc deficiency caused a 41% reduction in the number of
androgen binding sites and a 57% increase in the number of estrogen
receptors. Zinc maintains the structural integrity of DNA and plays an
important role in synthesis of nucleic acid and protein (2). In the
present study, the reverse action of deficiency, Zn supplementation, was
used to determine effects on anabolic hormones, with positive effects
demonstrated on testosterone. Direct muscle function studies with
manipulation of zinc status over a short time interval of 3 weeks
demonstrated that zinc status positively alters the total work capacity
of skeletal muscle in humans (20). The present study results contribute
to those findings, although the preparation used in this study was more
complex including magnesium and vitamin B-6 as well as zinc.
Exquisite sensitivity of circulating IGF-I to nutrients has been
observed. Nutrition is one of the main regulators of circulating IGF-I,
which is lowered by energy and/ or protein deprivation (21). Enhanced
nitrogen balance is demonstrated in caloric restriction with IGF-I
administration. IGF is putatively strongly linked to diet, specifically
carbohydrate content in caloric restriction. Although most research
attention has been on the energy and macronutrient content of the diet,
there have been studies that evaluated specific nutrients on IGF-I
levels. When purported growth hormone enhancers, arginine and lysine,
were administered together with a strength training program, there was
no change in resting levels of IGF-I (22). The strongest associations
may be between IGF-I and micronutrient levels. Increase in growth
velocity in growth-retarded children resulted from zinc supplementation
associated with a 70% increase in plasma IGF-I concentration (23). Zinc
and magnesium deficiencies lead to marked growth retardation. In a study
using rats, dietary zinc and magnesium were manipulated to assess
effects on IGF- I (1). When animals were deprived of magnesium, serum
magnesium was reduced 76% and serum IGF-I decreased 60% from baseline.
Then, diets were replete with magnesium. The serum magnesium normalized,
then 2 weeks later, IGF-I reached control levels. When animals were
deprived of zinc, serum zinc was reduced 80% and serum IGF-I decreased
69% from baseline. With dietary zinc repletion, serum IGF-I improved
194%. The researchers concluded that decreased IGF-I was not attributed
to reduced energy intake, but seems to be a specific effect of
nutritional deficiency of magnesium and/or zinc. Growth retardation in
hypocaloric states may be due to magnesium or zinc deficiency mediated
through reduced serum IGF-I. Serum changes of magnesium and zinc might
be of importance as a mediator for regulating serum IGF-I levels. These
studies on specific nutrients, specifically zinc and magnesium, were
corroborated with the results of the present study. The element levels
were low at the start of the study and increased, but remained within
the normal laboratory ranges. Supplementation with ZMA, a novel
zinc-magnesium combination, resulted in increased plasma element
concentrations and concomitant stabilization of IGF-I levels compared to
the placebo group, which demonstrated significant reductions in IGF-I
mean values over the training period.
Both zinc and magnesium supplementation have been shown to significantly
decrease the levels of the catabolic "stress" hormone, cortisol. In a
double blind, randomized study of 23 triathletes, serum cortisol was
lower in the magnesium-supplemented group before and after competition
compared to controls (24). The authors concluded that the magnesium
supplementation resulted in a reduced stress response without affecting
competitive potential. In addition to increasing the football players
anabolic hormone levels, the ZMA may have had an anti-catabolic effect
as well. It would be beneficial to include cortisol measures in future
studies.
Related to the improved hormone profile were enhanced posttest values of
muscle measures with ZMA. There were relatively greater values with ZMA
than placebo in lower extremity isokinetic torque and functional power
(180 /s and 300 /s, except for torque at 300 /s) compared to baseline
measures as demonstrated in Figure 2.
There is extensive evidence that the anabolic hormones supported by the
nutriture of the ZMA supplementation are involved in muscle anabolism
and related force production changes (2, 10, 20, 21, 23, 24). Virtually
every tissue type is capable of autocrine production of the IGFs.
Elevated IGF-I may contribute to hypertrophy response, possibly via
mobilization of satellite cells to provide increases in muscle DNA,
maintaining some critical DNA-to-protein ratio (25). Increased IGF-I
production coincides with increases in muscle DNA and precedes
measurable increases in muscle protein. IGF-I may be acting to directly
stimulate processes such as protein synthesis and satellite cell
proliferation, which result in skeletal muscle hypertrophy. Purported
ability of IGF-I to stimulate both anabolic and myogenic effects in
vitro suggests it as a component of cellular-level signaling system in
skeletal muscle. After acute exercise, IGF-I receptor mRNA was elevated.
The main function of IGF-I is to regulate cellular growth and
metabolism; IGF-I stimulates DNA synthesis, cell proliferation, and
protein synthesis. The anabolic effects of testosterone are mediated
primarily through protein synthesis and retarding muscle catabolism, as
has been clearly defined over the years (26).
Related to the ZMA supplementation-induced enhanced blood profile of
zinc, magnesium, and anabolic hormones were significant increases in
isokinetic torque and power measurements. The ZMA group increases were
significantly different than the placebo group. On a relative scale, the
10%-range increases in quadriceps torque and 12.7% to 15.2% increases in
quadriceps power for ZMA supplementation were comparatively greater
compared to the -0.8% to 2.4% change in quadriceps torque and 8.6% to
10.8% change in quadriceps power for the placebo group. There was a
baseline difference in muscle torque and power as a result
randomization, which resulted in higher values for the placebo group
versus the treatment group at the outset. Further statistical analysis
was applied so that the significant differences between groups were
noted when analyzed with an ANCOVA. Both groups had overall increases in
the training and supplementation period, but the ZMA supplementation
resulted in greater increases compared to the placebo.
The results of the study are intriguing, since ZMA supplementation was
associated with improved anabolic hormone profile and muscle function in
already strength-trained varsity collegiate football players. Further
research on applications of the novel ZMA compound and related
contributing mechanisms would elucidate the effects demonstrated in this
preliminary study.
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