Saturday, May 27, 2017

Real Growth Hormone for Athletes - Lean Mass ↗, Fat Mass ↓, Water ↑, but Limited Evidence of Performance Increases

Physique athletes > sprinters > endurance athletes - That's probably the ranking of those athletes who benefit most from GH (ab-)use. Why? Well, its effects on body composition are attractive for BBs & Co, its potential ability to boost anaerobic performance for sprinters and its lack of effect on VO2max limits their use in marathoners to accelerated recovery.
If you believe in the claims of the supplement industry, you probably expect extreme gains, significant fat loss and huge performance increases from a boost in natural GH production. Well, guess what: that's another of the lies the industry is based on. There's no "natural GH booster" that will increase the total amount of growth hormone your body produces on a daily basis (early studies also suggest that the effect wears off over time, even if you use the products only every 10 days | Isidori 1981).

As reported previously in articles about combinations of various amino acids, some may - if taken in really high doses and on an empty stomach - in fact, enforce the production of growth hormone. Unfortunately, the temporary "natural" spike in GH levels is followed by a reduced GH production later in the day. It is thus not surprising that there's no scientific backup for any of the unwarranted (Chromiak 2002) claims you will find on the average mix of arginine and lysine.
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Things look differently for "real" growth hormone (and probably some of the secretagogues on which we don't have enough evidence, though, to tell for sure). According to the latest review of the effects of growth hormone (ab-)use in athletes from the Aarhus University Hospital in Denmark, there are yet only 54 potentially relevant articles investigating the effect of GH administration on body composition, substrate metabolism, and athletic performance in healthy, young subjects.

Of these 54 studies, the scientists identified in the English-language based databases PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched, and eligible articles were reviewed in accordance with the PRISMA guidelines, only 11 were included in this analysis comprising 254 subjects, though, because not all fulfilled the scientists' inclusion criteria:
Figure 1: Flowchart of study selection (Hermansen 2017) - most of the studies the scientists found didn't meet their inclusion criteria.
"All randomized, double-blind, placebo-controlled trials of GH administration were included if they provided at least one of the following outcome measures: body composition (e.g. weight, lean body mass, extracellular water, body cell mass, or fat mass), strength (e.g. biceps strength, quadriceps strength, or isometric deadlift strength), indices of lipolysis (e.g. circulating levels of glycerol and/or free fatty acids, or respiratory exchange ratio) or exercise capacity (e.g. lactate levels, bicycling speed, or maximum oxygen uptake). Restriction was applied on participants' age and health status. All participants should be healthy without evidence of pituitary disease. Moreover, studies specifically targeting children, adolescents (< 18 years of age), or older adults (> 45 years of age) were excluded" (Hermansen 2017).
With the subjects being predominantly male (72%) and young (mean age of 26.7 years [SD: 1.9] ranging between 18 and 40 years across trials) and relatively muscular and fit, it should be obvious that these 11 studies are not representative of the effects on everyone. The average SuppVersity reader is yet probably decently captured by the sum of all 11 studies.
Figure 2: Graphical summary of the most important study results (based on Hermansen 2017).
Accordingly, the same should go for the effects on body composition, lipolysis, i.e. the release of fatty acids from body fat stores, and, at least in some, athletic performance.
What do we know about the "GH gut" & co? From a science perspective, the answer to this question is 'very little' - unfortunately. There are the well-known immediate side effects, such as. Potential adverse events include suppression of the hypothalamic-pituitary GH/IGF-1 axis, water retention, edema, increased intracranial pressure, or joint and muscle aches (Hoffman 2009). Most of what we actually "know" about the long-term effects, however, is based on inference from studies in people with acromegaly (excessive GH production) and/or long-term high-dose GH treatment for medical conditions that are characterized by suboptimal GH levels. Whether GH abusers will see similarly increased mortality rates (+100%) and increasing mortality risk with each month on supraphysiological HGH levels as patients with acromegaly will yet have to be investigated in future studies. The same goes for the significant adverse cardiovascular effects, including cardiomyopathy, hypertension, valve dysfunction, and arrhythmia, as well as the increased risk of diabetes mellitus or impaired respiratory function that have been observed in response to super-physiological levels of GH in the blood, with the GH gut being a possible consequence of metabolic derangements that lead to an increased storage and formation of visceral (=organ) fat - with all its highly detrimental health effects (Tchernof 2013).
While I've compiled an overview of the most important findings in Figure 2, I am aware that SuppVersity Readers aren't only young (or feel young ;-) and athletic, but also interested in details, let's take a look at what exactly the scientists found in their meta-analysis of the effects of GH administration on athletic performance (Hermansen 2017):
  • treatment regimen: the mode of GH intervention varied considerably among the included studies. Two studies evaluated the acute effect of a single GH injection. The other studies provided longer treatment duration ranging from 2 to 12 weeks with a mean of 5.2 weeks [SD: 3.3]. The daily dose of GH ranged from 25 to 67 μg/kg with a mean of 36.5 μg/kg [SD: 12.7] among the included studies. All the included studies provided subcutaneous GH injections.
  • effects on body composition: compared to placebo, the average study registered a weight increase of 1.62 kg [95% CI, 0.79 to 2.45 kg] with a probability of less than 1% that this was a random observation (p < 0.01); luckily, this increase in weight was exclusively due to increases in lean body mass (LBM | weighted mean difference: 2.86 kg [95% CI, 2.22 to 3.50 kg], p < 0.01);
    Figure 3: Mean changes in body composition according to the meta-analysis (Hermansen 2017).
    unfortunately, a significant part of the "extra mass" came from extracellular water (weighted mean difference: 1.77 kg [95% CI, 1.01 to 2.53 kg], p < 0.01) - an observation that confirms reports of GH users on the various pertinent forums on the internet; only 0.90 kg [95% CI, − 0.09 to 1.89 kg] and thus ~31% of the alleged gains materialized in for of actual increases in cell mass (p = 0.07); with a concomitant loss of (on average) -1.22 kg [95% CI, − 1.71 to − 0.74 kg] of body fat (p < 0.01), however, the results are yet likewise in line with the commonly heard claim that GH would, despite with the water bloat, significantly improve its users physiques
  • increased lipolysis: the actual rate of appearance of glycerol and free fatty acids during exercise was measured by only three studies; the scientists' calculation reveal a weighted mean difference of 146 μmol/l [95% CI, 34 to 258 μmol/l], and 281 μmol/l [95% CI, 134 to 428 μmol/l] for glycerol (p = 0.01) and free fatty acids (p < 0.01), respectively; however, no significant decrease was observed in exercising respiratory exchange ratio (weighted mean difference: − 0.03 [95% CI, − 0.10 to 0.03], p = 0.30) - in other words: there was no significant shift in substrate use during exercise from glucose to fat
  • muscle strength: despite the small, but significant increase in lean mass, the four studies that actually investigated the effects on the subjects' strength found no statistically significant increase in the amount of weight the study participants lifted - in fact, the average relative change in muscle strength was − 0.02 [95% CI, − 0.05 to 0.02, p = 0.36] and thus quite certainly not just statistically non-significant, but non-existent
  • exercise capacity: the average study found no effect of GH on exercise capacity; in that, we have to distinguish, though, between "exercise capacity" as measured by changes in by maximum oxygen uptake, which didn't occur and improvements in anaerobic exercise capacity, which were tested and observed in only one study, though (in said study the subjects' performance during a Wingate test increased significantly)
Eccentric Training Keeps You Gainin' and T & GH Up When, in Weeks 5-10, Traditional Training Stops Yielding Results | more
So, what's the verdict, then? If you look at the overall result of the meta-analysis, it turns out that subcutaneous GH injections are neither powerful muscle-builders, nor performance enhancers. Compared to a handful of other drugs from the arsenal of the world of doping GH is thus of relatively little value to the average cheater.

The meta-analysis at hand does yet also show that it does exactly what it's used for by those who think of it rather as a lifestyle drug: it yields significant improvement in body composition that may, however, be hidden under the significant increase in extracellular water.

Moreover, the overall effect size is everything but mindboggling (let's be honest, you can easily shed <2kg of body fat while gaining <1kg of actual lean mass by diet and exercise in no time). Accordingly, it would seem that the benefits of the administration of moderate amounts of GH (BBs have reported using ~20 units of HGH (that's >80µg/kg), almost always in conjunction with 50–75 µg/day of IGF-I to turn the mediocre into real gains | Brennan 2011), in fit, lean young men are almost as exaggerated as those of their initially alluded to, simply non-effective natural counterparts. For older individuals who have been shown to gain impressive 6% of lean mass while losing -15% of their total fat mass within 6 months on only 30µg/d (Rudman 1991), however, things may look differently, though. | Comment on Facebook!
  • Brennan, Brian P., et al. "Human growth hormone abuse in male weightlifters." The American journal on addictions 20.1 (2011): 9-13.
  • Chromiak, Joseph A., and Jose Antonio. "Use of amino acids as growth hormone-releasing agents by athletes." Nutrition 18.7 (2002): 657-661.
  • Hermansen, Kasper, et al. "Impact of GH administration on athletic performance in healthy young adults: A systematic review and meta-analysis of placebo-controlled trials." Growth Hormone & IGF Research (2017).
  • Hoffman, Jay R., et al. "Position stand on androgen and human growth hormone use." The Journal of Strength & Conditioning Research 23 (2009): S1-S59.
  • Isidori, A., A. Lo Monaco, and Marco Cappa. "A study of growth hormone release in man after oral administration of amino acids." Current medical research and opinion 7.7 (1981): 475-481.
  • Rudman, Daniel, et al. "Effects of human growth hormone on body composition in elderly men." Hormone Research in Paediatrics 36.Suppl. 1 (1991): 73-81.
  • Tchernof, André, and Jean-Pierre Després. "Pathophysiology of human visceral obesity: an update." Physiological Reviews 93.1 (2013): 359-404.