Designer Anabolic/ Anti-catabolic Agents

1. Designer Anabolic/ Anti-catabolic Agents Lecture 21

3. What works? • We know that: • Anabolic steroids (testosterone) increase FFM and muscular strength. They also have an anti-catabolic effect. • Schedule III drug available legally with a prescription • Prohormones (androstenedione and androstenediol) have some (maybe) effect increasing FFM or strength performance. • Sale of androstenedione and androstenediol (but not DHEA) restricted by U.S. govt. in late 2005

4. What works? • We know that: • Anabolic steroids (testosterone) increase FFM and muscular strength. They also have an anti-catabolic effect. • Prohormones (androstenedione and androstenediol) have no apparent effect on increasing FFM or strength performance. • Creatine - will be talking about creatine on Wednesday)

5. Are there other products that work to increase FFM, strength and power? • Anabolic (growth hormone secretagogues) • Anti-catabolic (inhibitors of protein degradation)

6. Popular “Body Building” Supplements Anabolic: • Growth Hormone secretagogues • Zinc/Magnesium Aspartate (ZMA) • Arginine alpha-ketoglutarate (AAKG) Anti-catabolics: • Beta-hydroxy beta-methylbutyrate (HMB)

7. Growth hormone (somatotropin) • Stimulates bone and cartilage growth • Facilitates protein synthesis • Increasing amino acid transport into muscle • Stimulating RNA formation • Facilitating protein synthesis • Also slows CHO breakdown and mobilizes fat as an energy source. Exercise stimulates an increase in circulating GH and preserves plasma glucose for the CNS.

9. Growth Hormone: Ergogenic Aid • Use medically, children who suffer from GH deficiencies or kidney failure • Reduced GH: low FFM and high fat mass • Increased GH in youth: gigantism • Acromegaly – enlarged hands, feet and facial features. • Synthetic growth hormone (recombinant DNA production) is used by athletes and bodybuilders to increase strength performance.

10. Growth Hormone: Performance • Appealing to strength and power athletes because at physiological levels: • Stimulates amino acid uptake and protein synthesis • Enhances fat breakdown • Conserves glycogen reserves Also GH does not suppress the body's hypothalamic-pituitary-gonadal axis like anabolic steroids. Use can be continuous.

11. One study found that 6 weeks of resistance training with GH decreased body fat and increased FFM significantly (but second study found no effect). GH is illegal and very expensive. The hormone can only be obtained on the black market and can cost $500-4000/month. GH is usually stacked with anabolic steroids and is typically used with insulin to get maximum results. Body-builders use the combination to achieve the desired muscle size, vascularity and appearance of paper thin skin “sucked to muscle”. **** Growth hormone use can lead to diabetes

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14. Growth hormone secretagogues • Use of amino acids to stimulate GH secretion. • Arginine • Lysine • Ornithine Exercise increases GH concentrations so these amino acids are often taken before a workout to further accentuate the exercise-induced GH release.

15. Amino acid ingestion and GH • Combination of arginine and lysine together seems to be more potent than either alone. • Trained individuals have a blunted response (especially if they are strength trained eating a high protein diet) • Women show a greater response than men • Amino acid ingestion, GH and exercise • Ingestion of amino acids before exercise does not increase GH more than exercise alone. • Consuming a protein supplement before exercise and immediately after exercise had no effect on maintaining elevated GH concentrations.

16. May be a dosage or timing issue, further studies necessary... There are no well-designed studies using specific amino acids as GH secretagogues in conjunction with strength training. • Alternatively, peptide and non-peptide compounds can also stimulate GH release. • Ex: synthetic hexapeptide (GHRP-6) These secretagogues do increase circulating GH and IGF- 1, there are no published studies indicating how use would affect athletic performance.

17. Zinc/Magnesium Aspartate (ZMA) • Popular supplement to promote anabolism at night. • Zinc/magnesium deficiencies may reduce the production of testosterone and IGF-1 (regulates the action of GH) • Shown that athletes in training may be zinc deficient. Zinc participates in metabolism and protection against free radical damage. • Magnesium supplementation showed a decrease in cortisol (theoretically magnesium would be anti-catabolic).

18. Studies: • Brilla and Conte reported ZMA supplementation in football players during off-season resistance training promoted increases in testosterone, IGF-1 and muscular strength. • Wilborn et al. (2004) double blind study design • n=42 resistance trained males • matched according to FFM • Took either ZMA or placebo prior to going to sleep during 8 weeks of strength training Results: no significant differences between groups in hormone status, body comp, 1 RM bench press and leg press, muscular endurance or anaerobic capacity. - population was resistance trained.

19. Arginine alpha-ketoglutarate (AAKG) • Anabolic and anti-catabolic Arginine: • stimulates GH release • Raises nitric oxide (NO) synthesis • NO acts as a vasodilator. Hypothesized that NO supplementation would enhance blood flow, oxygen delivery and glucose uptake by working muscles. α-ketoglutarate: • Intermediate in the TCA cycle and is a precursor for the synthesis of glutamine and arginine. • Limited data on athletic performance; however, there is some data that suggests an anti-catabolic role. (similar to glutamine under conditions over severe stress, ex: surgery)

20. Campbell et al. (2006) • Randomized, double-blind, controlled study design • 12g daily (4g, 3X per day) over 8 weeks of resistance training (4X per week) • Measures were taken at 0, 4, 8 weeks in blood markers, 1 RM max strength, aerobic power, anaerobic endurance, total body water and body composition.

23. Beta-hydroxy beta-methylbutyrate (HMB) • HMB is a metabolite of the amino acid leucine. • Found naturally in small quantities in catfish, citrus fruits and breast milk. • Leucine is an essential amino acid that has the highest oxidation rate of all amino acids during exercise. HMB derived from leucine is converted to HMG-CoA in some tissues and serves as a key carbon source for cholesterol synthesis in various cell types. - saturating the cell with HMG-CoA would allow the cell to undergo the maximum growth response (athletes, muscle hypertrophy in response to resistance training)

24. Supplementing with 1.5-3g/d of calcium HMB has demonstrated increases in muscle mass and strength (especially in untrained individuals initiating a training program) • Gains are typically 0.5 to 1kg greater than controls during 3-6 weeks of training. • Also evidence that HMB is anti-catabolic. HMB in conjunction with creatine may have an additive effect but results are unclear. • Large variability among athletes, more research is necessary.

25. Please check the website for a reading on tetrahydrogestrinone (THG), the designer anabolic steroid that BALCO constructed in 2002-2003.