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.