NW Spine - Library

© 2000

In recent years, several sports nutrition strategies and dietary supplements have proven their worth by enhancing performance and/or the physique. As optimistic as I am about emerging sports nutrition supplements, I was admittedly surprised following the publication of some late-breaking scientific research. An exciting possibility that has come to light is that certain dietary supplements may potentially help you to reach your genetic potential more rapidly, overcome plateaus, and even surpass your genetic limits.

I suspect that many readers are aware of or have even experienced the solemn fact that muscular development has an upper limit beyond which even the best training and nutrition fail to yield further improvement. There are several genes (portions of DNA that code for proteins), hormones (chemical messengers), and other influences that partly determine just how herculean one can become (Vierck, et al., in press). For this article, I’m going to focus on another restraint of muscle cell size: size itself. Now that I’ve confused you, read on.

The size of a cell is self-limiting for at least two reasons. The first limiting factor is referred to as surface area-to-volume ratio. When cells grow, the volume of the cell increases more quickly than does the surface area of the cell membrane that surrounds the cell. This is just a simple fact of geometry. Any substance that wants exchanged into or out of a cell, such as nutrients or anabolic (growth-promoting) hormones, must deal with the cell membrane. In addition, the goods must be transported from the cell membrane to the cell’s interior or vice versa. So, as a cell gets bigger and bigger, as with proper resistance exercise, the surface area of the cell cannot keep pace with the demands of the cell’s interior. It is thought that muscle cells may split (not by true cell division) in an attempt to increase the amount of cell membrane relative to the volume. To my knowledge, there’s no way for a hard-working fitness enthusiast to impact this problem, but it’s a nifty, elegantly simple explanation for why muscle cells (and all others with a possible exception of fat cells) have an upper limit to growth.

A second, similar problem in a big ol’ honkin’ cell is that messages can no longer efficiently get to and from the brain of the cell (the nucleus), whose job is to direct protein synthesis. I refer to this dilemma as outgrowing your genes. This limitation is described by another ratio sometimes called the nucleus-to-volume ratio (aka DNA unit or nuclear domain), which recognizes that a nucleus can reliably sustain only so much cell (Kadi, Eriksson, Holmner, & Thornell, 1999). How do we restore the ability to communicate between a nucleus and the rest of the cell? Answer: a cell phone. Actually, a solution to this problem is simply the addition of more nuclei, which occurs in skeletal muscle cells through the enlistment of nearby satellite cells that are developmentally leftover muscle precursors. With resistance exercise (i.e., weight training), our little satellite cells divide through mitosis and supply nuclei that fuse to our muscle cells (MacDougall, 1992; Bischoff, 1994). It’s a beautiful process! Wouldn’t it be great if there were a way to provide a little extra motivation to those little satellite cells? More satellite cell activity would mean more fusion of nuclei with muscle cells, the end result of which would be more nuclei to direct protein synthesis and to maintain a more favorable nucleus-to-volume ratio (Kadi, Eriksson, Holmner, & Thornell, 1999). Well, there may just be a way to get satellite cells more involved.

For quite a while there was debate as to whether anabolic steroids helped increase muscle mass in people who lift weights. Duh... Then the question became exactly how anabolic steroids exert their growth-promoting effect. New evidence sheds light on one mechanism of muscle growth enhancement from anabolic steroid use.

Previous research has shown regulatory effects of anabolic steroids on satellite cells in isolation (in vitro) (Vierck, et al., in press). To determine the mechanism of muscle growth from high doses of anabolic steroids, Kadi and colleagues (1999) studied muscle samples from competitive power lifters, some of whom had no drug history while others practiced recreational pharmacology using high doses of anabolic steroids for an average of nine years. Not surprisingly, the steroid users had significantly larger muscle cells. But, here’s the neat part. The steroid users’ cells displayed significantly more nuclei. And, the more nuclei, the larger the muscle cell because of more protein synthesis. How do you suppose those extra nuclei got there? Yep, they were generously donated by satellite cells.

Because most individuals visiting this web site are likely not interested in using anabolic steroids due to legal, moral, or health issues, readers may desire an alternative means of enhancing testosterone levels. Probably the most obvious dietary strategy to increase testosterone production is via the use of the highly touted prohormones that have gained so much attention in the past few years. Prohormones are inactive substances that, once introduced into the body, are thought to be converted into active hormones, such as testosterone. Less kind terms for prohormones include steroid-like compounds, nonprescription steroids, and prodrugs. I am unaware of any studies that have studied the effects of prohormones on satellite cell activity. Nevertheless, the clinical research on prohormones has failed to demonstrate their efficacy on a number of measures such as body composition, muscle mass, and strength. Frankly, the prohormone research results have been extremely disappointing.

Although a slight divergence from our main topic, I’d like to summarize the results of the prohormone studies in a nutshell because much of the information is brand new and may be of interest to many readers. The prohormones primarily used in research trials so far include dehydroepiandrosterone (DHEA), androstenedione ("andro"), and androstenediol. The underlying premise is that these hormones are converted to testosterone in the body (Schnirring, 1998).

Increases in free (unbound, active) testosterone concentration following supplementation have been nonsignificant in some studies using androstenedione (King et al., 1999; Quindry et al., 2000) or androstenediol (Earnest, Olson, Beckham, Broeder, & Bruel, 1999; Quindry et al.). In contrast, some studies report significant increases in free testosterone following androstenedione ingestion (Antonio & Sanders, 1999; Earnest et al.). Unfortunately, it appears that an individual’s own testosterone secretion may be decreased within one month of regularly using androstenedione (Quindry et al.). Say goodbye to those testicles!

Limited data exist to show augmented strength and lean body mass with androstenedione supplementation (Van Gammeren et al., 2000). Much more research exists that has found no performance-enhancing benefits to supplementation with androstenedione (King et al., 1999; Thomson et al., 2000; Wallace, Lim, Cutler, & Bucci, 1999; Ziegenfuss, Berardi, & Lowery, 2000), androstenediol (Thomson et al.), or DHEA (Wallace et al.). Likewise, most studies have found no positive effect of prohormones on lean body mass (Antonio & Sanders, 1999; Dominick et al., 2000; King et al., Wallace et al). One study indicates that androstenedione does not enhance muscle growth and may even promote muscle breakdown (Rasmussen, Volpi, Gore, & Wolfe, 2000). Some studies have even reported an increase in body fat following supplementation with androstenedione (Antonio & Sanders; Dominick et.al.) or assorted prohormones (Van Gammeren et al.) despite resistance exercise. An increase in body fat is perhaps due to the fact that most (Brown, Kohut, Franke, Jackson, Vukovich, & King, 2000; King et al.; Leder, Longcope, Catlin, Ahrens, Schoenfeld, & Finkelstein, 2000; Quindry et al.; Rasmussen et al.) but not all (Ziegenfuss et al.) studies have demonstrated an increase in female hormone levels with supplementation of these prohormones. This conversion to female hormones is also supported by anecdotal evidence from two personal male acquaintances who are exercise physiologists that experienced tender breasts during androstenedione supplementation. Additionally, a decrease in good cholesterol (HDL) has been observed in some longer studies using androstenedione (Brown et al.; King et al.) and androstenediol (Brown et al.), while others using androstenedione (Antonio & Sanders) or DHEA (Wallace et al.) have not documented a decrease in HDL.

Some proponents of prohormones may speculate that persons with lower testosterone levels than the relatively young, male subjects used in most of the studies above would benefit more so from testosterone precursors. Persons with lower testosterone include older individuals, women, and patients with certain hormonal deficiencies. However, data are even more lacking in these groups. While there are other forms of prohormones with slight molecular differences that may show more promise, such as 19-norandrostenedione, there simply are no data to recommend their use at this time. In addition, even if small, sustained elevations in testosterone production could be achieved with prohormones, we can’t be certain that it will have the meaningful impact on satellite cell activity as observed with the high doses of anabolic steroids by the subjects in Kadi and colleagues’ study. Finally, effective doses of prohormones would likely carry a similar risk of side effects as that associated with anabolic steroids (Schnirring, 1998). The possibility that these prohormones could increase satellite cell activity is intriguing, but does not appear to have practical application at this time.

Many in the scientific and athletic communities have developed a love affair with creatine because its worth has been demonstrated under a variety of circumstances. I have no financial interest in creatine (boy, I wish I did!) and try to remain unbiased in my assessment of its effects, but I would be lying if I said I wasn’t impressed with its many applications. Nevertheless, I was surprised at a recent report detailing a previously undocumented effect of creatine supplementation.

Dangott, Schultz, and Mozdziak (2000) tested the effects of oral creatine supplementation in rats. All vermin had two out of three calf muscles removed on one side to functionally overload the remaining calf muscle on that side. Rats were then assigned to receive a normal diet or a diet including creatine supplementation. Thus, there were four groups (2 different legs X 2 different diets = 4) that described the calf muscles: nonoverloaded, overloaded, nonoverloaded + creatine, and overloaded + creatine. After four weeks of supplementation and/or overload, the critters met their maker so the remaining calf muscles could be examined. The creatine supplementation did not enhance muscle weight or muscle cell diameter in any of the groups, and the authors explain that rats tend not to increase bodyweight with creatine supplementation. They further elaborate that muscle cell diameter was unaffected by creatine due to the possibility that the particular kind of chronic overload used in the study may have desensitized the muscle cells to creatine. The truly interesting finding deals with satellite cell mitotic activity. Satellite cell activity was significantly higher in the overloaded + creatine group when compared to the other groups. Very pertinent to our discussion of nucleus-to-volume ratio is the authors’ comment that "An increased satellite cell labeling index is consistent with the idea that satellite cell mitotic activity is necessary to maintain a constant volume of cytoplasm surrounding each myonucleus during compensatory increase in muscle size." Simply put, the creatine enhanced the ability of the muscle cells to maintain a favorable nucleus-to-volume ratio during growth. The authors also conclude, "...creatine supplementation, only in combination with increased functional activity, increased satellite cell mitotic activity, while creatine supplementation alone does not appear to affect satellite cell mitotic activity in growing muscles." So, creatine plus exercise is what may allow you to jump start your satellite cells. And for those of us who resistance train, the authors speculate, "It is possible that a more intense intermittent overload, such as occurs with conventional weightlifting exercise, may illicit an even greater satellite cell mitotic response in combination with creatine supplementation."

Tweaking satellite cell division to increase the number of nuclei in our muscle cells seems like a plausible means for enhancing muscle growth. However, prohormone supplementation has a long ways to go before we can ever hope that it will stimulate satellite cell activity as does anabolic steroid use. In contrast, creatine may be the first oral nutritional compound demonstrated to enhance satellite cell activation. More research is needed to substantiate the role of creatine in satellite cell stimulation, but the data thus far present an exciting possibility for those interested in maximizing their muscular development, perhaps even beyond what nature would have allowed.

Back to Library Main Page

Dr. Greg Bradley-Popovich holds dual master's degrees in Exercise Physiology and Human Nutrition from West Virginia University as well as a doctorate in Physical Therapy from Creighton University. He is the Director of Clinical Research at Northwest Spine Management, Rehabilitation, and Sports Conditioning in Portland, Oregon.

Antonio, J. & Sanders, M. (1999). Effects of self-administered androstenedione on a young male body builder: A single-subject study. Current Therapeutic Research, 60, 486-491.

Bischoff, R. The satellite cell and muscle regeneration. In: A.G. Engel & C. Franzini-Armstrong (Eds.), Myology (2nd ed., 97-118). New York, NY: McGraw-Hill.

Brown, G., Kohut, M., Franke, W., Jackson, D., Vukovich, M, & King, D. (2000). Serum hormonal and lipid responses to androgenic supplementation in 30-59 year old men. [Abstract]. Medicine and Science in Sports and Exercise, 32 (Suppl.), S122.

Dangott, B., Schultz, E., & Mozdziak, P. E. (2000). Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. International Journal of Sports Medicine, 21, 13-16.

Dominick, G., Quindry, J., Brittingham, K., Panton, J., Breuel, J., Earnest, C., Olson, M., & Broeder, C. (2000). The andro project: Androstenediol or androstenedione use on body composition in men [Abstract]. Medicine and Science in Sports and Exercise, 32 (Suppl.), S177.

Earnest, C., Olson, M., Beckham, S., Broeder, C., & Bruel, K. (1999). Oral 4-androstene-3,17-dione and 4-androstene-3,17-diol supplementation in young males [Abstract]. Journal of Parenteral and Enteral Nutrition, 23, S16.

Kadi, F., Eriksson, A., Holmner, S., & Thornell, L. (1999). Effects of anabolic steroids on the muscle cells of strength-trained athletes. Medicine and Science in Sports and Exercise, 31, 1528-1534.

King, D., Sharp, R., Vukovich, M., Brown, G., Reifenrath, T., Uhl, N., & Parsons, K. (1999). Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: A randomized controlled trial. Journal of the American Medical Association, 281, 2020-2028.

Leder, B., Longcope, C., Catlin, D., Ahrens, B., Schoenfeld, D., & Finkelstein, J. (2000). Oral androstenedione administration and serum testosterone concentrations in young men. Journal of the American Medical Association, 283, 779-782.

MacDougall, J. (1992). Hypertrophy or hyperplasia. In: P. Komi (Ed.), Strength and power in sport (pp. 230-238). Cambridge, MA: Blackwell Science.

Quindry, J., Brittingham, K., Panton, L., Breuel, J., Earnest, C., Olson, M., & Broeder, C. (2000). The andro project: Androstenediol or androstenedione use on sex-hormone profiles in men [Abstract]. Medicine and Science in Sports and Exercise, 32 (Suppl.), S122.

Rasmussen, B., Volpi, E., Gore, D., & Wolfe, R. (2000). Androstenedione does not stimulate muscle protein anabolism in young healthy men. Journal of Clinical Endocrinology and Metabolism, 85, 55-59.

Schnirring, L. Androstenedione et al: Nonprescription steroids. The Physician and Sports Medicine, 26 (11), 15-18.

Thomson, J., Quindry, J., Brittingham, K., Panton, L., Breuel, J., Earnest, C., Olson, M., & Broeder, C. (2000). The andro project: Effects of androstenediol or androstenedione use on strength in men [Abstract]. Medicine and Science in Sports and Exercise, 32 (Suppl.), S177.

Van Gammeren, D., Uelmen, J., Ehler, L., Raether, J., Sanders, M., Ziegenfuss, T., & Antonio, J. (2000). Effects of legal androgens on strength and body composition in bodybuilders [Abstract]. Medicine and Science in Sports and Exercise, 32 (Suppl.), S177.

Vierck, J., O’Reilly, B., Hossner, K., Antonio, J., Byrne, K., Bucci, L., Dodson, M. (in press). Satellite cell regulation following myotrauma caused by resistance exercise. Cell Biology International.

Wallace, M., Lim, J., Cutler, A., & Bucci, L. (1999). Effects of dehydroepiandrosterone vs androstenedione supplementation in men. Medicine and Science in Sports and Exercise, 31 , 1788-1792.

Ziegenfuss, T., Berardi, J., & Lowery, L. (2000). Effects of an androgen mixture on testosterone, estradiol, and anaerobic performance [Abstract]. Medicine and Science in Sports and Exercise, 32 (Suppl.), S122.

 

Back to Library Main Page