By: Jeff Feliciano
“Effects of a Novel Zinc-Magnesium Formulation on Hormones and Strength” is the title of a remarkable study by L.R. Brilla and Victor Conte published in Journal of Exercise Physiologyonline, 2000, 3(4):26-36. This study launched ZMA® into elite Sports Nutrition due to the quality of ZMA® ingredients, the timing of dosing, and the quality of the Brilla study.
In the Brilla study, ZMA® is given to NCAA football players during Spring training, and endogenous hormone levels and strength were tracked over an 8-week period. If you have ever competed at that level, you understand the training is no cake walk, and that fully repleting water as well as macronutrients and micronutrients is a function of your eating habits or training table.
Repletion of macronutrients, water, and lost vitamins is a major task in and of itself for athletes; however, while repleting the micronutrients like zinc and magnesium may not be specific targets of training tables, or your diet, they should be given far greater consideration. Zinc and magnesium deficiencies are common during high intensity training, resulting in lower testosterone levels and other anabolic factors as well as reduced muscle strength.
Consequently, the Brilla study found that these two micronutrients, zinc and magnesium, can be normalized independently of deficient diets or generalized training tables. This is a big deal although it is only part of the story surrounding zinc and magnesium supplements designed to help maintain testosterone levels and other anabolic markers in addition to measures of strength.
The recommendations for using ZMA®, such as the nighttime formulary instructions provided by Conte are critically important when companies utilize the ZMA® ingredients in their own brand of products. The superior quality of the zinc and magnesium components are also important to achieve the highest rate of absorption, which is no easy feat considering the facts of gastrointestinal physiology.
Although we won’t go into to the GI tract details in this essay, suffice to say that it is not straight forward, and there are many factors that must be considered with any effective ZMA® product design. In particular, the specific amino acid chelates used to deliver biologically active zinc and magnesium. Jim Stoppani, Ph.D. and formulator of ZMA® JYM states in his product offering:
“ZMA® JYM is not just zinc, magnesium, and vitamin B6 thrown into a bottle. ZMA® JYM contains specific forms of these minerals that enhance their uptake and utilization by the body. ZMA® JYM specifically uses zinc mono-L-methionine, and aspartate and magnesium aspartate. This is critical because there are two forms of zinc monomethionine: zinc mono-L-methionine and zinc mono-D-methionine. Only the "L" form is readily absorbed and used by the body. The human body is not able to use the "D" form. Some bogus products use a combo of both the "L" and "D" form. The D form actually inhibits the absorption of the L form and undermines zinc uptake. If a product does not specifically list zinc mono-L-methionine, and instead lists zinc monomethionine, don’t bother with it. An easy way to ensure that a product uses real ZMA® is to look for the SNAC System trademark listed on the bottle, ZMA®. Anything else is an imposter."
Furthermore, the use of these high quality chelates, zinc mono-L-methionine, zinc-aspartate, and magnesium aspartate are crucial to the bioavailability in the gastrointestinal tract for both zinc and magnesium. It is important to understand that all zinc and magnesium chelates are not created the same.
Not only are there transporter details to consider, but also dosing time since consuming ZMA® on an empty stomach sometime shortly before bed is crucial. There are many foods, supplements, and plant anti-nutritive factors that can inhibit zinc and magnesium uptake.
An example of research combining zinc and magnesium along with other ingredients that inhibit the absorption of these two minerals is not quality research that supports the efficacy of using ZMA® in a similar context to the Brilla research.
In a 2004 study entitled, “Effects of Zinc Magnesium Aspartate, (ZMA) Supplementation on Training Adaptations and Markers of Anabolism and Catabolism,” from Dr. Richard Kreider’s lab at Baylor University, (Wilburn CD, et al., 2004) describes an analysis of Z-Mass PM, (Cytodyne Technologies, Lakewood, NJ). The Z-Mass PM label indicates that the supplement is to be consumed on an empty stomach 30-60 minutes prior to bed. This study was performed over 8 weeks on resistant-trained subjects. The product label indicates it contains 11 mg of Vitamin B-6 (pyridoxine HCl), 450 mg of magnesium (as magnesium aspartate), 30 mg of zinc (as monomethionine and aspartate), 10 mg of potassium (as potassium aspartate), and 706 mg of a proprietary blend of Mucuna pruriens (seeds) standardized for 50 mg of L-Dopa, and Polypodium vulgare/Suma root (herb) standardized for 30 mg of 20-hydroxyecdysone.
These additional ingredients make some sense considering L-Dopa is believed to enhance anabolic markers, such as serum testosterone and growth hormone release, and 20-hydroxyecdysone, a plant sterol, believed to reduce catabolism.
However, the Wilburn et al., 2004, results indicated a non-significant rise in serum zinc of 12%-17% (P=0.12), remaining within the normal range. Serum magnesium levels were also within the normal range and were not significantly affected by Z-Mass PM supplementation. No significant differences were observed in anabolic or catabolic hormone status between the control and Z-Mass PM groups.
In contrast, the Brilla study indicated there were significant ZMA® treatment effects (P=0.001) for zinc and magnesium plasma values, and the serum anabolic hormone profile, except percent testosterone between the control group and the ZMA® treated group. Free-testosterone, and total testosterone increased in the ZMA® group, as well as a trend towards significance for IGF-1 (P=0.0195) with the Bonferroni adjustment compared to the control group, indicating that ZMA® reverses the drops in these nutrients and anabolic hormones seen over an intensive 8-week training program such as NCAA spring football practice.
However, this is not a contest between two different research groups. Both these studies are important to the understanding of zinc and magnesium supplementation and the expected results. Maybe a formulation difference can explain why Z-Mass PM did not affect increases in serum zinc and magnesium levels enough to increase anabolic hormone levels compared to ZMA®. Also included in Z-Mass PM is Mucuna pruriens and Polypodium vulgare, which as stated before makes some sense, considering ultimately, the goal is to positively affect anabolic markers while diminishing catabolic metabolism. The inclusion of measures of cortisol, an indicator of catabolism although not included in the Brilla study was recommended by Brilla for future zinc and magnesium studies. In fact, independent studies of zinc and magnesium supplementation have shown that both minerals can lower the levels of the catabolic hormone, cortisol.
The formulation issue with herbal and seed extracts when also delivering zinc and magnesium is that these plant products also contain phytic acid or phytates, which inhibit the absorption of both minerals. This effect is well documented using various plant materials, including Mucuna Pruriens and many other sources utilized as active ingredients in the world of dietary supplements.
Furthermore, there are other popular zinc and magnesium-based products sold as “testosterone boosters” that also contain the seed extract fenugreek. Fenugreek contains phytic acid or phytates, which also inhibit the absorption of both of these minerals.
In an article published in the December 5, 2012 issue on Nutraceuticaworld.com, Dr. Douglas Kalman, Ph.D. outlines the issue of phytates contained in products such as Z-Mass PM that work to defeat the overall purpose of zinc and magnesium delivery adequate to duplicate the serum zinc and magnesium increases and anabolic effects of ZMA® found in the Brilla study:
“Now, let’s consider why this second study (Z-Mass PM) seemed to fail to result in any positive findings. I mentioned previously the importance of vetting out any potential interactions. The study that tested Z-Mass PM included the botanical ingredients Mucuna pruriens (seeds), and Polypodium vulgare/suma root (herb). The researchers of the second study failed to realize or consider that the product they were testing contained “anti-nutritional” factors.
Zinc and magnesium are principal ingredients in ZMA®. Both of these minerals are easily affected in terms of how well they are absorbed in the body. The researchers failed to note that the Mucuna pruriens ingredient (also in the formula they tested) is rich in phytic acids (phytate).
Phytates are well known to interfere with the absorption of zinc. Thus, the formula itself was poorly designed if the intent was to showcase potential benefits of ZMA®. Mucuna pruriens contains about 5.68 mg of phytates per gram of product. The Z-Mass PM product contained roughly 4.0 mg of phytic acid. A dose of as little as 4.0mg phytic acid is known to reduce zinc absorption by at least 20%. Research shows that with almost every gram of phytates/phytic acid ingested, zinc requirements nearly double. In addition, Mucuna pruriens is known to have other components that interfere with nutrient absorption.
It appears the product formulator for Z-Mass PM did not know, or was unaware of, the negative nutrient-nutrient interaction of the individual ingredients chosen. The researchers did not seem to know either, as they did not write about this in the study publication. If they had then there would be a better understanding of why their study failed to find any benefit of the multi-ingredient formula as compared to the study that used ZMA® without other added ingredients.”
The point is that novel products supported by clinical research are created to assure the formulation and the clinical study address real world applications. This process often entails an understanding of how to reach the goals outlined on the product label supported by their rationale and structure/function claims.
The method of product design is not an easy process. It requires meticulous due diligence on the label owner’s behalf, particularly, when discussing a product like the registered trademark ZMA®.
In the same article quoted above by Dr. Kalman, Ph.D., he discusses aspects of clinical trials/research studies and concerns with regard to choosing ingredients similar to trademark product like ZMA®:
“When choosing the ingredient or supplement—whether a single ingredient or a multi-ingredient product—as the interventional agent being studied, it is also imperative to understand the product well. That is to say, one must be aware of how each ingredient undergoes “ADME” (absorption, digestion, metabolism and excretion); potentially more important is how each ingredient may interact with other ingredients in the product, in cases of multi-ingredient formulas. One should not minimize the potential for nutrient-nutrient interactions, as some nutrients may enhance or inhibit others in ADME. It is also important to know if there are any benefits or restrictions for the product to be taken with or without food, much like prescription drugs.”
Once again, as Dr. Stoppani mentions in his product information for ZMA® JYM, “an easy way to ensure that a product uses real ZMA® is to look for the SNAC System trademark listed on the bottle, ZMA®. Anything else is an imposter."