Tuesday, January 7, 2014

Study Says: Prohormone "1-Andro" Works, But It's Bad for You! Plus: What About Other Prohormones or Steroids Such As Androstenedione, DHEA, Testosterone & DECA?

If you ask your doctor about prohormones, he will tell you that they don't work and make you sick... don't argue with him, 'cause that's his job and believing in this half-truth is certainly good for your health.
Published ahead of print in the Journal of Applied Physiology is a paper on the ergogenic and healht effects of 3b-hydroxy-5a-androst-1-en-17-one aka 1-ANDRO. According to Jorge Granadosm, Trevor L. Gillum, Kevin M. Christmas, and Matthew R. Kuennen, the authors of the said paper, this is the first official evaluation of the viability of prohormone supplements ever since the Anabolic Steroid Control Act was amended in 2004 (Granadosm. 2013b) - a statement of which you as a SuppVersity reader know that it is true only if we are talking about the experiments, noto about the papers, though. The one at hand, is after all paper #2 Granados et al. are publishing.

"I knew I know this study!"

Yes, you heard me right. The researchers from the West Texas A&M University, the California Baptist University and the University of Texas at Austin have actually published a paper with the main results of this experiment  in the International Journal of Exercise Science earlier in 2013 (Granados. 2013a) and I guess some of you may even remember that they've read about it here at the SuppVersity.

Figure 1: Relative changes in muscle mass (total change above the bars) and kidney, "liver" and lipoprotein metabolism after four weeks on a 1-AD clone; note SGOT is the old name for AST (Granados. 2013a)
I mean, don't you recognize Figure 1? No? That's fine, because it means, you did not realize that I simply copied it from a short-new item I published on March 09, 2013 (go back). This has obviously little to do with plagiarism, or laziness ;-) I simply thought it may be worth taking a loser look at the study. A look that goes beyond the short-news item from March and, as the headline already announced, even beyond the effects of "1-Andro".

Evidence from previous trials using other (pro-)hormone: The study at hand is not just the first since the amendment of the Anabolic Steroid Control Act it is also one of the few studies that which evaluate the effects of (pro)hormones on the outcomes of resistance training regimen in young men, anyway. Aside from the information on 1-AD my cursory search of the databases revealed the following information about "alternative" agents:
androsterone (100mg/day for 4 weeks), normal young man: no increase in strength or size gains, no difference in effects on body com, no increase in testosterone, increase in estradiol and estrone, reduced HDL levels that remained low for one months after the supplementation (King. 1999)
DHEA (150mg/day for 8 weeks), normal young men: While it does work in older men & women (Villarea. 2006), it has no effect on total testosterone, estrone, estradiol, estriol, lipids, and liver transaminases, identical strength and size gains as in placebo (Brown. 1999)
nandrolone (600mg weekly for 12 weeks), young men with HIV: significant increase in total body weight, 5.2kg lean mass in 12 weeks, significant increases in muscle size, 14.4–53.0% strength gains, no changes in fasting serum total cholesterol and triglycerides (LDL and HDL not measured; cf. Sattler. 1999)
testosterone (600 mg of testosterone enanthate (TE) or placebo weekly for 10 weeks), normal young men: Increases in fat-free mass (6.1±0.6 kg) and muscle size (triceps area, 501±104 mm²; quadriceps area, 1174±91 mm²), increases in muscle strength (bench-press strength, 22±2 kg; squatting-exercise capacity, 38±4 kg), neither mood nor behavior was altered in any group, increase in serum creatinine concentration (1.0 mg/dl to 1.1mg/dl),  no change in plasma concentrations of total and LDL cholesterol and triglycerides, HDL  cholesterol  decreased  significantly, but less in the TE + resistance training (-10%) vs. resistance training only groups (-12%; cf. Bhasin. 1996)
What strikes me as odd is the fact that the HDL decrease with in the Basin study occurred only when the participants worked out. In the sedentary participants who received the same dosage of testosterone enanthate, such effects were not observed.
Here is the elevator pitch on the study design

The scientists recruited 17 resistance-trained males (23±1yrs; 13.1±1.5% body fat) and randomly assigned them to ingest either 330mg/day 3b-hydroxy-5a-androst-1-en-17-one (PH; n=9) that were "enhanced" with 50mg of 6,7,-dihydrobergamottin, a grapefruit flavenol member of the furanocoumarin family that inhibits cytochrome P450-34A (Edwards. 1996), or 330mg/day plain maltodextrin (PLA; n=8). During the following 4 weeks, the subjects participated in a 16 session of structured resistance-training.

The training plans were hypertrophy specific and personalized. It is thus not really surprising that all subjects gained a significant amount of lean mass. What is surprising, though is how pronounced the inter-group differences were.

While the "1-Andro cycle" lead to significant increases in lean body mass 6.3±1.2%, decreased the total body fat mass by 24.6±7.1%, and increased the back squat 1-RM and average strength by 14.3±1.5% and 12.8±1.1%, respectively, the participants who were "on sugar" experienced only minor changes in body composition: 0.5±0.8% increases in lean mass and a 9.5±3.6% reduction in body fat. Needless to say that these changes, as well as the increased back squat 1-RM and average strength of 5.7±1.7% and 5.9±1.7% were also statistically different from the pronounced gains in the "1-Andro" group. In fact, they look pretty much like the almost frustatringly slow, but persistent gains you'd expect to see in already highly trained subjects within only 4 weeks (Note: The subjects in the placebo groups, i.e. the "low gainers", had 2 years less training (4.5y) experience than the high gainers in the "1-Andro group" with their 6.3y of resistance training history).

But that cannot be good for your health, can it?

If you want to be accepted as a scientists, and still do research into anabolic steroids or prohormones, you obviously must not refrain from pointing out that the previously described beneficial effects on body comp came at the expense of a 38.7±4.0% reduction in HDL (p<0.01), a 32.8±15.05% elevation in LDL (p<0.01), and elevations of 120.0±22.6% and 77.4±12.0% in LDL/HDL and C/HDL; respectively (both p<0.01), due to which the prohormone group got from a groovy 2.2:1 ratio for total cholesterol / HDL (everything < 3.5 : 1  is "optimal") up right to the edge of the 5:1 + danger zone (4.8 ± 0.6). In addition to that, the researchers observed
  • increases in serum creatinine (19.6±4.3%; p<0.01), a breakdown product of creatine phosphate in muscle,
  • elevated aspartate transaminase (AST or SGOT) levels (113.8±61.1%; p=0.05), which could be an indicator of liver strain (they are elevated by any form of strenous training, but the elevations in the control group were not significant),
  • significant reductions in serum albumin (5.1±1.9%; p=0.04), which could be a consequence of the strain on the liver or the kidneys, but are still much less pronounced than in patients with "real" liver disease or nephrotic syndrome,
  • increases in alkaline phosphatase (ALP; 16.4±4.7%; p=0.04), which could indicate a beginning obstruction of the bile ducts, and
  • elevated glomerular filtration rats (18.0±3.3%;p=0.04), which tell you that the kindeys are working overtime.
All the above are changes you will see in response to heavy resistance training, anyway, but in view of the fact that they are much less pronounced / non-existent in the control group, the scientists are probably right when the conclude that the improvements in body composition you can achieve with 300mg of 1-Andro per day come at the expense of "[c]ardiovascular health and liver function".

You want to know what the size of that expense is?

Well, I already said that the changes in ALT & Co are difficult to judge, I've seen much higher AST & ALT levels than those 41.4 IU/L and 49.4 IU/L (reference ranges are < 41 IU/L and <48 IU/L) after only one training sessions. In the recreationally trained men in Pettersson's study from 2008, for example (see figure 2) - against that background, I would not worry about the alleged liver enzymes first... they are after all also muscle enzymes and last time I checked, converting one amino acid into another - which is what "trans-aminases" do - was not per se a bad thing, per se ;-)

Figure 2: Changes in AST in response to a single 1h weight lifting sessions . an "NO!", the recreationally trained subjects didn't die from liver failure. Surprise? Not really!  (Pettersson. 2008)
The decline in HDL to a pathetic 27.3 mg/dl, on the other hand, is definitely something you should worry about.

If you read the latest SuppVersity Facebook News about the role HDL plays not just in metabolic and heart health, but also in brain health (read more), you have at least three good reasons? And if you want a number on one of them, I can give you the estimated difference for the risk of a major cardiovascular event that corresponds to the -18.7 mg/dl decrease in HDL, the subjects in the 1-Andro study experienced. It's roughly 18% - at least if you put some faith into one of the most recent of the few prospective case–cohort studies with healthy subjects (Kappelle. 2011).

So I guess, if you want to worry about, this 18% increased risk, you better worry about the effects on your blood lipids, than about elevated transaminases, of which I am not even sure that you wouldn't have to blame them on side-effects / interactions of the added dihydrobergamottin in the prohormone formula.
So it's not worth it? Whether you personally would agree that "[g]iven these findings [...]the harm associated with this particular PS [prohormone supplement] outweighs any potential benefit" (Grandos. 2013b) is obviously a question of perspective; and I am not the one to tell you which perspective is right for you. Everyone picks his own poison! And having read this article, you are at least better informed than you'd be after studying the colorful advertisement banners on the Internet.
  • Bhasin, S., Storer, T. W., Berman, N., Callegari, C., Clevenger, B., Phillips, J., ... & Casaburi, R. (1996). The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. New England Journal of Medicine, 335(1), 1-7. 
  • Brown, G. A., Vukovich, M. D., Sharp, R. L., Reifenrath, T. A., Parsons, K. A., & King, D. S. (1999). Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men. Journal of Applied Physiology, 87(6), 2274-2283. 
  • Edwards, D. J., Bellevue, F. H., & Woster, P. M. (1996). Identification of 6', 7'-dihydroxybergamottin, a cytochrome P450 inhibitor, in grapefruit juice. Drug metabolism and disposition, 24(12), 1287-1290.
  • Granados J, Gillum T, Hodges C, Kuennen M. (2013a) 3-hydroxy-5alpha-androst-1-en-17-one Enhances Muscular Gains but Impairs the Cardio-metabolic Health of Resistance Trained Males. International Journal of Exercise Science. TACM.
  • Granados J, Gillum T, Hodges C, Kuennen M. (2013b) Prohormone supplement 3b-hydroxy-5a-androst-1-en-17-one enhances resistance training gains but impairs user health. Published online before print December 31, 2013. 
  • Kappelle, P. J. W. H., Gansevoort, R. T., Hillege, J. L., Wolffenbuttel, B. H. R., & Dullaart, R. P. F. (2011). Apolipoprotein B/A‐I and total cholesterol/high‐density lipoprotein cholesterol ratios both predict cardiovascular events in the general population independently of nonlipid risk factors, albuminuria and C‐reactive protein. Journal of internal medicine, 269(2), 232-242.
  • King, D. S., Sharp, R. L., Vukovich, M. D., Brown, G. A., Reifenrath, T. A., Uhl, N. L., & Parsons, K. A. (1999). Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men. JAMA: the journal of the American Medical Association, 281(21), 2020-2028. 
  • Pettersson, J., Hindorf, U., Persson, P., Bengtsson, T., Malmqvist, U., Werkström, V., & Ekelund, M. (2008). Muscular exercise can cause highly pathological liver function tests in healthy men. British journal of clinical pharmacology, 65(2), 253-259.
  • Sattler, F. R., Jaque, S. V., Schroeder, E. T., Olson, C., Dube, M. P., Martinez, C., ... & Azen, S. (1999). Effects of pharmacological doses of nandrolone decanoate and progressive resistance training in immunodeficient patients infected with human immunodeficiency virus. Journal of Clinical Endocrinology & Metabolism, 84(4), 1268-1276.
  • Villareal, D. T., & Holloszy, J. O. (2006). DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. American Journal of Physiology-Endocrinology And Metabolism, 291(5), E1003-E1008.