Why do baseball players use hGH: Part II, The Science

An unlikely way hGH improves performance.

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Last time, I wrote about how and why players use PEDs.  Included in that post was highlighting how sometimes players are ahead of the science (arguably steroids) and at other times behind the science (i.e. urinating on your hands, rubbing your bats with ham bones, and arguably steroids).  Somewhat blind assumptions, halo effects, and mob mentality tend to shape an uninformed perspective more so than what experts say is likely or know to be true.  I forget where I saw this and cannot seem to find it, but a study that surprised me was a study that consisted of telling participants various surprising facts.  These facts were differentiated in that some were attributed to "experts" and others were just given.  Participants were more likely to accept surprising facts from non-expert sources.  So . . . maybe there is a fourth effect, which is perhaps a societal suspicion of scientific literature, which I think would be largely due to a misunderstanding of the scientific method.  People often want definitive answers and there are awfully few laws in science.  Anyway, this is going on a tangent.

However, with all that being said . . . that players are using something to give them a competitive edge is a great reason to investigate on the efficacy of the treatment.  Sometimes lacking a full comprehension of something does not prevent someone from discovering something new.  What many baseball players have become are alchemists.  Alchemy had its usefulness as it encouraged the works of many, such as Isaac Newton and Paracelsus.  It also fostered some silly beliefs such as all things could be turned into gold.  So, it may be that baseball players and others have actually hit gold on hGH.

In today's article, I'll be reviewing (or, more aptly, summarizing) several articles about hGH and its effect on athletic performance.

Where did the hGH craze begin?
In 1990, an article was released by Rudman et al (New England Journal of Medicine) in which twelve elderly men ranging in age between 61 and 81 years old were injected with hGH at a concentration similar to what would be found in young adult males for six months.  The twelve subjects were found to have about a ten pound increase in lean muscle, a seven pound decrease in fat, and denser bones.  The conclusion stated that these effects were like a ten to twenty year reversal of aging.  An eager medical and pharmacological community aware of the future elderly care scenarios with baby boomers embraced the possibilities suggested by this article.  It also resulted in a boom of pseudoscience and pseudomedical claims and clinics advertising assumed benefits of hGH.  Claims have included that hGH improves eyesight, removes scars, renews interest in sex, resurgence of hair growth, increase in muscle strength, increase in stamina, and deepening of one's voice.  These benefits extended well beyond the boundaries of the scientific data, claiming that hGH could inhibit processes that lead to aging.  However, these claims tend to ignore several follow up studies that dispute their proclamations.

A good summary of follow up studies was provided by Mary Lee Vance in the New England Journal of Medicine in 2003:

A recent double-blind, placebo-controlled study involving 27 women and 34 men, 68 to 88 years of age, who were given growth hormone or placebo for 6.5 months confirmed the effects of growth hormone on body composition; there was no change in muscle strength or maximal oxygen uptake during exercise in either group.3 This study corroborated the findings of a study by Papadakis et al. involving 52 healthy men, 70 to 85 years of age, who were given placebo or growth hormone for six months. Not mentioned on the “antiaging” Web sites is a study of 18 healthy men, 65 to 82 years of age, who underwent progressive strength training for 14 weeks, followed by an additional 10 weeks of strength training plus either growth hormone or placebo. In that study, resistance exercise training increased muscle strength significantly; the addition of growth hormone did not result in any further improvement. Going to the gym is beneficial and certainly cheaper than growth hormone.

 Ok, so it is fairly well shown that hGH does not seem to help the elderly increase functional strength, but we can probably agree that an elderly population may not be equal to a younger one.  After the jump, we'll review the literature highlighting studies on hGH use in athletes and young adults.  This short review will consist of an example of one of the many studies showing no difference, the only study showing a difference, a couple review papers, and expert testimony from the congressional hearing a couple years ago.  I could have written a far longer piece going over a couple dozen studies, but figured that excess would not convince anyone one way or the other more than the review papers do.  I also figure the review papers provide a stronger summary than I can at this moment.




Where there is a major review of literature, I did not write up individual studies and let the review speak for them.  However, there are a few studies I would like to highlight, some reviews, and some expert testimony.

Study 1: J Clinical Endrocrin and Mateb 90(6) 3268-3273, 2005
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.
Berggren et al.

In this study, groups of 15 men and 15 women were further split into high, low, and no dose groups.  This means 5 men received a placebo, 5 received a low dose (0.033 mg/kg.d, and 5 received a high dose (0.067 mg/kg.d).  These doses were administered over the course of four weeks.  Participants were assessed for their oxygen uptake while using a stationary bicycle, power output, blood pressure, heart rate, and ECG.  They found that while body weight increased, there was no statistically significant increase in performance (i.e. oxygen uptake, power output).

This is typical for a general study done on hGH.  The population size is rather small and the exposure duration is pretty limited.  That said, I do not know if baseball players cycle their hGH.  They might.  In that case, a four week exposure might make sense.  What gives this study a bit more power is that these results are continually found in every study done, except one.  And that study was released last year . . .

Study 2: Ann Intern Med 153(9) 2010
The effects of growth hormone on body composition and physical performance in recreational athletes.
Meinhardt et al (Ken Ho's research group in Sydney)

In this study, 63 men and 33 women with an age of 27.9 +/- 5.7 years old were included.  The participants were trained athletes with intense workout regimes for a year prior to the study.  The men were seperated in groups that included placebo, testosterone (250 mg/wk intramuscularly), growth hormone (2 mg/d subcutaneously), or testosterone and growth hormone.  The treatment phase lasted eight weeks with a six week depuration phase.  Metrics included body composition characteristics (i.e. fat mass, lean mass, extracellular water mass, and body cell mass) and performance (i.e. endurance, strength, jump height, and bicycle sprint capacity).  Growth hormone alone was found to decrease fat and increase lean body mass.  However, when administered alone this increase was explained by water retention, but with the addition of testosterone the increase was then explained by body cell mass.  At the end of the eight weeks, bicycle sprint capacity did significantly increase with administration of growth hormone and was not related to the testosterone injection.  This improvement quickly dissipated and was gone by the end of the six week depuration phase.  Endurance, strength, and jump height were not affected.  This research was funded by the World Anti-Doping Agency.

This is a fascinating study as it is the only one that has shown hGH having an effect. Ken Ho's group is one to pay attention to with respect to how hGH may be used.  It is also interesting in that a previous platform presentation of this work had shown an increase in jump height and nothing else.  At least, that was what I remember, but I cannot seem to find it.  I think that was released in 2007, so this probably a different study and this current one appears to have a much larger sample size.  All of this does not mean this current study is wrong, just that I think we need to tread carefully here as it might be a false positive.  What I also find confusing is this statement:

“We found the enhancement in sprint capacity would correlate to a 0.4 second improvement over 10 seconds in a 100- meter dash,” said Ken Ho, Garvan’s head of pituitary research and a co-author of the study, in a statement. “This improvement could turn the last-place finisher in the Olympic finals into a gold medal winner.”

These are the words of a researcher who does not know how to speak to the media or one who knows exactly how science writers just juicy stories.  Conditional words are used here and the sentences themselves are not problematic, but I think when lay people read that . . . it does not appear as conditional as it should appear.  Ho uses a bicycle sprint test called the Wingate test.  This is poorly related to sprinting from what I understand.  I'm not sure why he would make this statement.  It really colors the science a bit and that is unfortunate.  In a later article, Ho steps back a bit from those statements and writes:

...“we do not know how an improvement in Wingate test performance translates to performance in the sporting field,” our speculation of what this might mean in a sprint event is based on mechanistic and conceptual extrapolation.

Regardless, I think the difference seen in hGH effects for sprinting is something to note and register.  However, like any study, we need to verify this with future studies.  From what I remember of his past reports, this one had a different result than those and it may simply be the case of a false positive.  We also should not ignore it.  This could be the first piece of a larger group of evidence.  However, it does not appear strength or endurance is improved.

Review 1: Current Sports Med Rep 3(4) 229-233, 2004
Ergogenic aids: human growth hormone.
Stacy et al.

They note that no study prior to the publication of this journal article demonstrated that there was any connection between the administration of hGH and any athletic performance metric.  They highlight how patients with acromegaly have significantly greater muscle mass than normal individuals, but that this does not translate into an increase in strength.  In order words, muscle gained from high levels of hGH has not been shown to increase strength in these individuals.  This is similar to findings using trained athletes.  However, the authors do note that it is possible that in actual use that athletes take concentrations that would not be permissible in a research trial.  There would also be significant adverse risk from these dosages and is a reason why they are not typically allowed in research trials.

Review 2: Ann Intern Med 2008
Systematic review: The effect of growth hormone on athletic performance
Liu et al.

This review included all studies published until October 2007 from three comprehensive article databases.  The authors were able to find 27 unique studies on hGH dosing (36 +/- 21 g/kg per day) running from one day up to three months (20 +/- 18 days) that focused on young adults (27 +/- 3 years old).  Participants in these studies experienced an increase in lean body mass, but strength and exercise capacity did not appear to improve.  Fatique and soft tissue edemas appeared more frequent in those dosed with hGH.  The authors note that the claims of hGH improving athletic performance is not supported by the literature even though it appears it does affect body composition.  They also note that it should be recognized that the treatment regimes used in these study most likely do not reflect real world usage and that adds uncertainty.

Expert Testimony: From the last congressional hearing...

Four research doctors testified and all agreed that hGH does not appear to significantly improve athletic perfprmance, but that more research is needed on hGH.  Thomas Perls said to the committee, "There is no credible scientific evidence that growth hormone substantively increases muscle strength or aerobic exercise capacity in normal individuals."

Conclusion

As I wrote in the previous post about hGH and PEDs, it would be absurd to think either side has a definitive answer.  I think it is also fair to say that those who say that hGH has no discernible effect on performance have the weight of the evidence with them.  Several peer-reviewed articles back up that perspective with little mechanistically saying otherwise.  There is one study with human subjects that states otherwise.  It is a weak position at the moment for those who say hGH certainly improves performance.  I think we have also shown that just because a group does something does not mean it works.  We are all aware of groups of people doing things that have no bearing on future events.  Whether you are burning an ox at the alter, rubbing your bat with a ham bone, or urinating on your hands to prevent blisters . . . none of these are likely going to affect the future.  All of these have been devout beliefs of many.  Belief does not equal reality.  However, sometimes belief is nestled in with reality and beliefs should not be rejected out of hand.  As such, we should continue to look at hGH with an inquisitive mind, but we need to be more open and comfortable that the evidence is not there for us to truly label it as a performance enhancing drug.  This does not mean that it is not one, it means that there is not enough evidence to say it is.  One study and mob mentality has difficulty overturning the rest of the scientific literature out there.

Future studies definitively need to do a few things:

1. Further explore the Sydney group's findings on hGH affecting athletic performance.
2. Invest in larger sample size.
3. Invest in developing an exposure-response relationship.
4. Design experiments based on how athletes described their regimens while maintaining ethical consideration.

Hopefully, with a few more studies we can determine whether or not more credence needs to be given to the hGH as PED perspective.