Tuesday, June 12, 2012

19x Increase in Growth Hormone 60min After Ingestion of 1g of Glycerophosphocholine (GPC) in Young Male Subjects

Image 1: Don't worry one thing is sure - GPC won't give you a gut like that ;-)
A couple of days ago, I have written about the exorbitant choline consumption of some of bodybuilding legends, Randy Roach writes about in his Muscle Smoke & Mirrors Vol. II  and to be honest, I was quite surprised that among the many responses I got, none broached the issue of the latest and greatest supplemental choline spin-off: Glycerophosphocholine, or short GPC - a supposedly superior, because fat-bound (hence "glycero" as in "glycerol) and highly bioavailable bean-derived form of choline. Whatever the reasons may be, I suppose you still won't mind to hear that a recent experiment that was conducted at the Faculty of Sport and Health Science of Ritsumeikan University in Shiga, Japan, yielded quite interesting results with respect to the endocrine and metabolic short-term effects of 1,000mg of GPC in 8 healthy male (25+/1y) subjects (Kawamura. 2012).

19x more growth hormone 60 min after the ingestion of 1,000 mg GPC, ...

And no, the subheading above does not contain a typo, at least not in the number, which is "nineteen" as in +1800%, which was, as the data in figure 1 shows, the average increase in serum growth hormone concentration exactly 60 minutes the lean subjects (11% body fat) experienced after ingestion of the GPC caps compared to placebo (the study was double-blinded and randomized, there was a period of two weeks in-between the testing days).
Figure 1: Fatty acid metabolism (left), choline levels (middle) and growth hormone levels (right)  6min0 and 120 min after the ingestion of placebo pills or 1,000mg glycerophosphocholine (Kawamura. 2012)
It is unquestionable the data in figure 1  looks pretty impressive. Yet not all changes are in fact statistical significant (I marked them by adding the relative differences between active and placebo arm) and as exciting a growth hormone spike of +1800% may sound, the subsequent drop to levels below the placebo arm should remind you, a seasoned SuppVersity veteran of the futility of supplemental "growth hormone secretagogues", such as arginine, leucine, a combination of both etc.; they all share a fundamental weakness - after each spike there is a huge trough.

...but just  6.88x more GH production over 2h

And therefore it should not really surprise you that we have the 2-h AUC, i.e. the area under growth hormone curve, a measure for the total amount of growth hormone that is released in the course of the timespan for which the AUC was measured, was "only" 6.88x larger after the ingestion of the glycerophasphatecholine supplement, than after placebo(cf. figure 2).
Figure 2: 2h AUC for free choline, free fatty acid, 3-hydroxbutyrate (ketones) and growth hormone after the ingestion of 1,000mg GPC; data expressed relative to placebo control (Kawamura. 2012)
Still, even this obviously transient increase in growth hormone in the fasted that occured in response to the +38-51% increase in circulating plasma choline went hand in hand with profound increases in free fatty acids (due to the lipolytic effects of GH; cf. Marcus. 1994) and ketone bodies, which is a sign of increased fatty acid metabolism must be a good thing,... right? It would appear so, but without answering the following two fundamental questions "How does it work?" and "What does that mean", we will be having a hard time to justify this conclusion. After all, the ingestion of 4mg/kg caffeine have been shown to illicit a >500% increase in free fatty acids (FFA) after only 40min in trained subjects (LeBlanc. 1985) and still none of the caffeine laden "fat burners" with other ingredients, which further augment the lipolytic effects of caffeine will actively burn body fat.

So what's the mechanism of action? And what does it tell us about the real world implications?

The working principle Kawamura et al. suggest is actually quite straight forward: With increasing serum choline levels, the influx of choline into the brain will increase as well. This will augment the synthesis of acetylcholine, which, in turn, has been found to decrease the concentration of somatotropin release-inhibiting factors right at the hypothalamic level and thus disinhibit the production of growth hormone (Blusztajn. 1983). Put simply: Somewhere down the line the increase in serum choline will pull the breaks that keep your body from producing growth hormone.
A note to all the stim-junkies out there: I guess, you will be intrigued (or shocked?) to hear that blocking the catecholamine induced stimulation of the a2-adrenergic receptor with yohimbine has been shown to negate the aforementioned growth hormone promoting cascade. And that irrespective of whether you try to augment it by supplements or just want to keep your natural rhythm intact (Minamitani. 1989). The first real-world implication would thus be "don't take your GPC alongside alpha-2 antagonists such as yohimbine" (better not take those at all ;-)!
Now this raises the question does that matter? With arginine and lysine, we already know that it doesn't, but maybe we just have a larger effect size here? To answer the last question first - the spike is in fact spectacular and way above the average response to the long-touted GH boosters arginine, lysine or glutamine, which ranges from "no effect at all" (Carlson. 1989) over 4.5x (Welbourne. 1995) to the whopping 13x increase in response to an intravenous injection of  0.5 g arginine/kg (Tanaka. 1991). If do yet take another look figure 2 you will notice that I inserted a quote from Kawamura et al.'s discussion of the results into the graph - a quote that is of paramount importance to quantify the real world significance of these ostensibly HUGE increase in GH (which you will certainly see referenced by respective supplement manufacturers in their glossy marketing material, very soon):
"The GPC-induced increases in GH levels observed in this study were of a comparable degree to the increase induced by moderate-intensity exercise"
I guess, you don't need me to tell you how "effective" popping a couple of those pills is thus going to be compared to training and diet alone in furthering your muscle gains and fat loss. And in terms of overall and cardiovascular health, you should already know from my previous blogpost, "Old School Supplements: Choline  Faster, Stronger, Leaner & more Muscular" that regular dietary choline as in eggs, meats, fish, leafy greens, etc. will do just as fine.
How much choline do you need? According to Coates et al. plasma choline concentrations can double after a 2-egg meal (~225mg choline) by up to two-fold (Coates. 2005). That would effectively be more than what we see as peak increase in the study at hand. And certainly puts the "need" for supplemental choline into perspective. The LD50, i.e. the purportedly fatal dosis, after the ingestion of which 50% of the subjects would die, is "of the order of 200-400g" (Gilman. 1980) - an amount of choline your tummy probably would not hold o to long enough to be absorbed, anyway ;-)
And in the unfortunate case that you do believe that you are running short of choline, because you don't eat all the good choline containing foods out of ethical or whatever other reasons, and thus insist on supplementing, I suggest you yourself a 500g container of choline bitartrate powder (don't let that become wet, though! It will stink like rotten fish ;-). Those 500g of choline bitartrate (40% choline, 60% tartate) will cost you about as much as 60x300mg caps of the overpriced GPC and has been "scientifically proven" (not in supplement company terms, but in SuppVersity terms) to safely increase circulating and brain choline levels and its metabolites after oral ingestion, as well (Stoll. 1996; Babb. 2004). And let's be honest, even if the effects on growth hormone were GPC specific - even on the boards, people have meanwhile realized none of those arginine + lysine GH boosters does make a difference and not because they would not produce transient increases in GH, but simply because those are physiologically meaningless and mostly compensated for in the course of 24h.

References:
  1. Babb SM, Ke Y, Lange N, Kaufman MJ, Renshaw PF, Cohen BM. Oral choline increases choline metabolites in human brain. Psychiatry Res. 2004 Jan 15;130(1):1-9.
  2. Blusztajn JK, Wurtman RJ. Choline and cholinergic neurons. Science 1983;221:614–20.
  3. Coates, P.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., White, J.D. (Ed), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, NY. 2005. p. 108. . 
  4. Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co. Inc. 1980. p. 1575. 
  5. Carlson HE, Miglietta JT, Roginsky MS, Stegnik LD. Stimulation of pituitary hormone secretion by neurotransmitter amino acids in humans. Metabolism 1989;38:1179
  6. Kawamura T, Okubo T, Sato K, Fujita S, Goto K, Hamaoka T, Iemitsu M. Glycerophosphocholine enhances growth hormone secretion and fat oxidation in young adults. Nutrition. 2012 Jun 5. 
  7. LeBlanc J, Jobin M, Côté J, Samson P, Labrie A. Enhanced metabolic response to caffeine in exercise-trained human subjects. J Appl Physiol. 1985 Sep;59(3):832-7.  
  8. Liu H, Bravata DM, Olkin I, Friedlander A, Liu V, Roberts B, Bendavid E, Saynina O, Salpeter SR, Garber AM, Hoffman AR. Systematic review: the effects of growth hormone on athletic performance. Ann Intern Med. 2008 May 20;148(10):747-58. Epub 2008 Mar 17.
  9. Marcus C, Bolme P, Micha-Johansson G, Margery V, Brönnegård M. Growth hormone increases the lipolytic sensitivity for catecholamines in adipocytes from healthy adults. Life Sci.1994;54(18):1335-41.
  10. Minamitani N, Chihara K, Kaji H, Kodama H, Kita T, Fujita T. Alpha 2-adrenergic control of growth hormone (GH) secretion in conscious male rabbits: involvement of endogenous GH-releasing factor and somatostatin. Endocrinology 1989;125:2839–45.
  11. Stoll AL, Renshaw PF, De Micheli E, Wurtman R, Pillay SS, Cohen BM. Choline ingestion increases the resonance of choline-containing compounds in human brain: an in vivo proton magnetic resonance study. Biol Psychiatry. 1995 Feb 1;37(3):170-4. 
  12. Welbourne TC. Increased plasma bicarbonate and growth hormone after an oral glutamine load. Am J Clin Nutr 1995;61:1058