Optimizing Growth Hormone as an Athletic Ergogenic Aid

Media and image today shape our mindset and expectation. Flashy pictures of sports hero’s and Hollywood stars filter down to all of us setting in motion behaviors that are often based on myth not fact. The notion that others are getting ahead with the use of ergogenic aids such as growth hormone brings us to question if we “need” these elements in order to compete in the modern age. My goal is to present a different mentality that simply suggests that athletic competition is a great arena to expand who we are and express our competitive spirit. But these endeavors should serve to promote our health, not compromise it.

I reject the notion that we need to cheat in order to get ahead. In fact many of the products athletes pursue in an effort to gain a competitive advantage are actually holding them back. When we review the science behind growth hormone and it’s application in athletic pursuits we find an amazing body of well-designed literature that tells a surprising story. Many athletes are applying 1970’s dogma to their training regimens and damaging their own chance of success as well as health. I propose we examine the truth and redefine our training table to promote not only better athletic results but better health in the process.

Lastly I want to offer the view that this impacts our youth in dramatic fashion. Like it or not our sports stars are idolized and emulated by student athletes. A study by Eisenberg[1] of 20 different urban middle and high schools revealed that 5.9% of students had experimented with steroid use.

So what is it that makes growth hormone so attractive in athletics? Growth hormone has many beneficial effects in our normal physiology[2]:

• Stimulate lipolysis

• Increases release of IGF-1 causing protein synthesis and increased muscle mass

• Stimulates gluconeogenesis in liver

• Stimulates the immune system

• Mineralizes bone

• Supports healthy metabolic rate

  So in keeping with the American philosophy that “if a little is good then more is better”, we find athletes abusing growth hormone in an effort to gain a competitive advantage. But what are the consequences? Lets explore three questions:

  1. Is the use of growth hormone safe?
  2. Does growth hormone supplementation improve athletic performance?
  3. Is there a natural way tos upport proper growth hormone function?

In a study by Bartke[3] they examined the effect of growth hormone (GH) deficiency versus excess on mice. The results will surprise you:

• Low GH is consistent with greater longevity

• Low GH leads to low IGF-1 and therefore lower cancer incidence

• Reduced activity of mTOR, reduced protein synthesis, therefore reduced muscle mass

• Low insulin levels enhance longevity

• Reduced levels of ROS and increased anti-oxidant enzymes: catalase, superoxide dismutase, glutathione

  The mice that had lower growth hormone (GH) levels possessed greater resistance to stress by virtue of higher anti-oxidant enzymes. They showed greater adiponectin levels and had greater insulin sensitivity therefore were much leaner and unlikely to become diabetic. So from a health perspective there were distinct advantages to having low levels of growth hormone. Certainly athletes would not accept the lower muscle mass associated with this state but we have to recognize that excess growth hormone is not a ticket to immortality, in fact it is quite the opposite. But what about GH in human trials?

  A review by Westly[4] discusses the link between excess IGF-1, a product of growth hormone and the link to diabetes and cancer rates in humans. Growth hormone deficient children, when treated with appropriate doses of growth hormone, experience a high rate of diabetes. So if its appropriate use in a deficient physiology results in diabetes, what are we to expect when it is inappropriately used in excess? Growth hormone has clearly been shown to be diabetagenic in multiple studies. Conversely when we explore diabetic patients we consistently find that growth hormone levels are higher than normal.[5,6] So clearly, artificially manipulating growth hormone will result in elevated insulin and abnormal glucose function which we all agree has catastrophic cardiovascular consequences. This is not a healthy pursuit and so in answer to question #1, it does not appear to be safe.[7]

  So, what if I am a million dollar athlete and I don't care about safety I just demand results? Lets simply explore its athletic benefit. In a systematic review of growth hormone on athletic performance, Liu[8] looked at over 7000 titles to find 44 articles representing 27 study samples that met their inclusion criteria. Participants were young (mean age, 27 years), lean and physically fit. Growth hormone (GH) dosage used varied by study but the mean dose was significant at 36 ug/kg per day with a treatment duration of (mean) 20 days. The results showed a lean body mass increase of 4.6 pounds on average but this did not confer any improvement in strength or exercise capacity. Lactate levels were higher in growth hormone users and they frequently experienced soft tissue edema and fatigue. Soft tissue edema occurred in 44% of GH users while only 1% in non-users. Fatigue was reported in 35% of GH users and 0% in non-users. Growth hormone treated participants also experienced arthralgia’s and carpal tunnel syndrome more often.

The measured plasma free fatty acids were increased in GH users reflecting the increased lipolysis. The lack of improved muscle strength despite more lean muscle mass is explained by the tissue edema that commonly occurs. Muscles held more water but were not stronger. This edema is a problem as it takes more energy to move a heavier body and will be a disadvantage to endurance athletes. GH resulted in no change in VO2 max, power output or endurance.

A similar review by Birzniece[9] found no benefit to GH use by trained athletes. The effect of GH on aerobic exercise capacity revealed a lack of improvement. Only two studies have investigated effects of longer-term GH administration on VO2max in healthy adults. Studies by Berggren[10] and Meinhart[11] looked at 4 and 8 week courses of GH on healthy athletes but failed to show any significant effect on VO2max or on maximum achieved power output. For all its hype, growth hormone as an exogenous adjunct appears to offer no clear benefit.

There are very few placebo-controlled studies looking at GH effect in muscles strength. In three separate studies[11,12,13], growth hormone was administered over 6 to 12 weeks and results measured by a variety of tools including assessment of jump height, voluntary strength measure of bicep and quadriceps muscle, and dead lift dynamometer. All of these studies failed to show any improvement in strength with the use of GH.

So despite the broad abuse of this element in athletic circles and its repeated appearance in news stories, the science would say that exogenous administration of growth hormone is a foolish pursuit. But what about healthy levels produced by healthy athletes? Certainly we desire the healthy physiologic benefits that come from “normal” growth hormone production as it does support lean muscle mass, repair and lipolysis. What are we doing as athletes that promote or reduce natural levels of growth hormone?

Natural growth hormone production occurs in a pulsatile fashion[2]. The normal production of GH is about 400 mcg per day but is on a gradual decline through most of our life after peaking in our early 20’s. Once the hypothalamic-pituitary axis has produced a pulse of GH there is a refractory period where stimulation from other sources will not elicit a GH response. The half-life of GH is between 25 to 50 minutes and once it has cleared the body then another pulse may occur. This becomes important when we discuss exogenous elements such as arginine, which can be used to artificially spike GH but first lets understand what natural events occur that optimize GH.

The two most significant factors that influence GH production are exercise and sleep. The largest spike of GH on a daily basis occurs just after the first hour of sleep and is followed by subsequent spikes of GH during sleep. This comprises the bulk of our GH production. Consequently we can see how poor sleep patterns might destroy an athlete’s ability to repair following severe training efforts. Lack of sleep will also result in reduced levels of testosterone.[14]

The second most important influence of GH production is exercise but more specifically the “intensity” of exercise. There is a linear dose-response pattern to GH secretion with increasing intensity but not with volume of exercise.[15,16]  This response is even able to override the GH refractory auto-negative feedback mechanism. Intense exercise performed 4 hours apart can cause repetitive spikes in GH that would otherwise be refractory to stimulation.

Resistance training that employs rest periods less than 90 seconds between sets offers greater intensity and thus greater GH response. High intensity interval training is another great tool for generating GH response. Anything that exceeds lactate threshold will increase pulsatile GH production.[17,18]

Food has significant influence on GH response. The intake of sugar will suppress GH production while protein or amino acids will drive GH production. This has significant implication when we make recommendations for food pre and post workout. The 1970’s dogma that sugar is the best fuel for athletes has been disproven with current research.[19]  Taking on sugary sports drinks during and after workouts is problematic and will reduce growth hormone production limiting tissue repair and growth. The application of branched chain amino acids pre and post workout has been shown to greatly accelerate our athletic potential, support growth hormone production, extend glycogen stores for greater energy production and limit risk for the development of type 2 diabetes. Amino acids positively influence metabolic control of diabetes, which is a common issue with endurance athletes.[20,21]

Taken one step further, given that our greatest pulse of GH occurs after the first hour of sleep, what we eat right before bed can either help of hinder GH production. The dated concept of carb loading on heavy doses of pasta needs to be revised especially in light of the huge allergenic potential that occurs with todays genetically modified wheat products. A better option exists in providing a more balanced diet and consideration of amino acids or protein at bedtime to promote a healthy GH response.

An elevated blood sugar affects the hypothalamus reducing GHRH thereby reducing GH production. Hunger and ghrelin stimulate more GH release. The use of low glycemic carbs should be relied on to stimulate controlled insulin release to work with GH to drive AA’s into the cell. High glycemic foods offer no benefit to today’s athlete and certainly invite some risk. High sugar intake after workouts will reduce GH production.

Koopman[22] demonstrated that when ample protein is ingested post workout, that coingestion of carbohydrate offered no further stimulation of muscle protein synthesis. The protein itself resulted in adequate insulin release to fuel muscle recovery and the carbohydrate offered no advantage. Insulin appears to play merely a permissive role in stimulating muscle repair and that high levels of insulin are neither needed nor desired. Howarth[23] found that adding protein to recovery meals was needed to produce whole body net protein balance. The Glynn[24] study reinforces the need for protein post workout and that adding carbohydrate did not improve muscle protein anabolic response. So lets drop the tired notion that sugar post workout is necessary and acknowledge that it is in fact harmful and counter productive as it reduces growth hormone recovery.

This brings us to the study of arginine as an ergogenic element. Arginine when taken in doses beyond 2 grams[25,26] and ideally 7 grams[27], will result in elevation of growth hormone. Arginine works by suppressing somatostatin, a regulatory protein of the endocrine system that suppresses GH production. So on paper the use of arginine may appear desirable to enhance GH production. The problem arises when we look at how most athletes are currently using arginine. Many products in the market place are promoted as pre-workout aids that contain arginine to enhance blood flow to muscles. This gives the feel of enhanced “pump” during resistance training. A secondary gain that is advertised is a rise in growth hormone.

A typical workout of sufficient intensity to cause GH elevation will result in a 5 fold increase. But as Collier[27] demonstrated, when that workout is preempted by the intake of arginine, the rise in GH was reduced by 200%. This reflects the autonegative feedback on the somatotrope from the arginine ingestion. In other words the spike of growth hormone stimulated by the arginine is present but small in size. But this small response of GH is enough to lead to a refractory period that ultimately reduced the total amount of GH produced. Repeated GHRH administration leads to a progressively decreasing somatotrope response due to a receptor or post-receptor down-regulation.

Consequently if arginine is to be used it needs to be administered in doses of 5 to 9 grams and avoided just prior to exercise or bedtime when GH production is typically optimized. There is a significant cost both financially and physiologically to engaging in GH manipulation. Perhaps the best approach is to optimize nutrition and sleep to facilitate a “healthy” response. It is equally important to avoid adverse doses of sugar and bad habits that interfere with normal good function.

For hard training athletes the best recommendation to promote healthy levels of growth hormone and athletic development include:

1. The intake of BCAA at a dose of 2.5 grams during or immediately after exercise and again before bedtime to promote muscle recovery and growth hormone production.

2. Proper protein intake to facilitate muscle recovery:  recommendations start at 1.7 gms/Kg/day and go up from there depending on sport and need.

3. Unless you have a clearly documented deficiency, the exogenous use of growth hormone is dangerous and without benefit. Improper use may increases risk for diabetes and cancer.

4. Avoid high glycemic sugar intake in all forms. Seek out low glycemic whole foods such as beans or brown rice that offer good carbohydrate nutrition.

5. Facilitate proper sleep patterns devoid of interruptions and lasting more than 7 hours nightly. Nothing promotes greater natural growth hormone better than good deep sleep. 
    

REFERENCES

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3. Bartke,Andrzej.Growthhormone,insulinandaging:Thebenefitsof endocrine defects. Exper. Gerontology Vol.46, 2011.

4. Westly,andMay.Atwenty-firstcenturycancerepidemiccausedby obesity: The involvement of insulin, diabetes, and insulin-like growth factor. Intr. J. of Endocrinology 2013.

5. Hansen,Aage.Abnormalserumgrowthhormoneresponsetoexercisein juvenile diabetes. The J of Clinical Invest. Vol.49, 1970.

6. Theodoridis,Chance,etal.Plasmainsulinandgrowthhormonelevelsin untreated diabetic children. Arch of Disease in Childhood, 1970.

7. Whitney,Bilkan,etal.Growthhormoneexacerbatesdiabeticrenal damage in male but not female rats. Biology of Sex Differences, 2013

8. Liu,Bravata,etal.Systematicreview:theeffectsofgrowthhormoneon athletic performance. Ann Internal Med. 2008

9. Birzniece,Nelson,andHo.Growthhormoneandphysicalperformance. Trends in Endocrin & Metab, Vol.22, 2011.

10. 10.Berggren, A. et al. Short-term administration of supraphysiological recombinant human growth hormone (GH) does not increase maximum endurance exercise capacity in healthy, active young men and women with normal GH-insulin-like growth factor I axes. J. Clin. Endocrinol. Metab. 90, 2005.

11. 11.Meinhardt, U. et al. The effects of growth hormone on body composition and physical performance in recreational athletes: a randomized placebo- controlled trial. Ann. Intern. Med. 152, 568–577, 2010.

12. 12.Yarasheski, K.E. et al. Effect of growth hormone and resistance exercise on muscle growth in young men. Am. J. Physiol. 262, E261– E267, 1992

13. 13.Deyssig, R. et al. Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. Acta Endocrinol. (Copenh.) 128, 313–318, 1993

14. 14.Leproult, Effect of 1 Week of Sleep Restriction on Testosterone Levels in Young Healthy Men, JAMA 2011

15. 15.Pritzlaff, Wideman, et al. Impact of acute exercise intensity on pulsatile growth hormone release in men. J. Appl Physiol 1999.

16. 16.Kanaley, Weltman, et al. Human growth hormone response to repeated bouts of aerobic exercise. J. Appl Physiol 1997

17. 17.Kraemer, Fleck, et al. Changes in hormonal concentrations after different heavy-resistance exercise protocols in women. J. Appl Physiol 1993

18. 18.Weltman, Weltman, et al. Endurance training amplifies the pulsatile release of growth hormone: effects of training intensity. J. Appl Physiol 1992

19. 19.Shiiya, Nakazato, et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin. J of Clin. Endocrin & Metab, 2002.

20. 20.Phillips, Van Loon. Dietary protein for athletes: from requirements to optimum adaptation. J. of Sports Sciences, 2011

21. 21.Solerte, Gazzaruso, et al. Nutritional Supplements with Oral Amino Acid Mixtures Increases Whole-Body Lean Mass and Insulin Sensitivity in Elderly Subjects with Sarcopenia. Am. J. Cardiology, 2008

22. 22.Koopman, Beelen, et al. Coingestion of carbohydrates with protein does not further augment post-exercise muscle protein synthesis. Am. J. Physiol. Endocr. Metab. 2007

23. 23.Howarth, Moreau, et al. Coingestion of protein with carbohydrate during recovery from endurance exercise stimulates muscle protein synthesis in humans. J. Appl. Physiol Vol.106, 2009

24. 24.Glynn, Fry, et al. Addition of carbohydrate or alanine to an essential amino acid mixture does not enhance human skeletal muscle protein anabolism. The J. of Nutrition, 2013

25. 25.T.J. Marcell, D.R. Taaffe, S.A. Hawkins, et al., Oral arginine does not stimulate basal or augment exercise-induced GH secretion in either young or old adults, J. Gerontol. A Biol. Sci. Med. Sci. 54 (1999) M395–399.

26. 26.Fogelholm GM, Naveri HK, Kiilavuori KT, Harkonen MH. Low-dose amino acid supplementation: no effects on serum human growth hormone and insulin in male weightlifters. Int J Sport Nutr 1993; 3: 290 ± 297

27. 27.Collier, Casey, Kanaley, et al. Growth hormone responses to varying doses of oral arginine. Growth Hormone & IGF Research, 2005