Tuesday, October 15, 2013

Creatine, DHT, Hair Loss & Prostate Cancer - Bro-Scientific Old Wives' Tales or Possible Side Effect? Plus: (Non-)Sense Creatine Loading, Exercise Induced 5-α Reduction & More

Poor guy! Must have taken too much creatine and treated his hair for muscle ;-) Ok, seriously, creatine may have helped a little that he was able to build this impressive physique, but the hair? Come on, seriously!?
If you have been around the bulletin boards of the fitness and bodybuilding community, I am pretty sure you will have heard about creatine induced increases in dehydrotestosterone (DHT). Probably you will also have had someone chime in who claimed that his hair started to fall out, when he started to use creatine supplements - right? Well, I guess in that case you will probably also remember how another guy chimed in and said: "Hold on does that mean that creatine will cause prostate cancer?"

Never heard something like that? I suggest you trust my word, then; and in case you want "scientific evidence" head over to www.pubmed.com and type in "creatine D" it will offer you "creatine DHT" as one of the typical search phrases people are looking for.

Cock-and-bull - right?

It is true that there is a study that supports the concept of increased DHT levels in athletes (20 collegiate rugby players to be precise) in response to 21 days of creatine supplementation. The athletes who participated in the said trial came from a Rugby Institute situated near Stellenbosch University in South Africa. None of the subjects had taken any supplements with their normal diet for 6 weeks before the trial in the course of which all had been randomized to one of the following groups:
  • creatine: 25g creatine + 25g glucose for 7 days; 5g crea + 25g glucose for 14 days
  • placebo: 50g glucose for 7 days; 30g glucose for 14 days
The subjects underwent standardized training, albeit for different player positions, during the whole study period. All subjects were residents at the institute and the ate the same food at the cafeteria. Moreover, all 20 were just coming back from a winter break and were "in similar condition as the start of the study and not fatigued from consecutive weeks of match play" (van der Merwe. 2009).
Instead of simply taking more you may rather want to "Super Charge Creatine W/ Baking Soda" | learn more
Creatine loading is neither necessary nor useful for the majority of athletes. Unless you have a meet close ahead there is no need to gobble down 25g+ doses of creatine - specifically not in one sitting. While the typical creatine supplementation protocol consists of a loading phase of 20 g creatine/d or 0.3 g creatine/kg/d that's followed by a 3-5 g/day (or 0.03g/kg) maintenance phase (Buford. 2007), it is also possible to use daily doses of ~3–6 g or between 0.03 to 0.1 g/kg per day (Willoughby. 2001; Hickner. 2010).
All subjects were lean (13-14% body fat and muscular 75kg muscle of 86-87kg total body weight) and thus way more representative of the average creatine guzzling gymrat than untrained average Joes whose beer bellies may well have messed up their endocrine system to an extend that could explain the DHT increases from 0.98 nmol/L to 1.53 nmol/L. The fact that the DHT levels in the control group did not change significantly in the course of the 7-day loading phase (in fact they dropped, but due to the high standard deviation the drop from 1.26 nmol/L to 1.09 nmol/L was non-significant), lends further support that the changes, the researchers observed must have been the result of the 25g of creatine the 10 subjects in the active arm of the trial had to swallow on during the first seven days of the study period.
Figure 1: Serum DHT levels total (left) and expressed relative to baseline levels in control group (right); data calculated based on van der Merwe et al. 2009
As you will probably already have read in-between the lines, I am not exactly impressed - let alone scared - by these results. Why? Well, the initial 56% increase in DHT was not only followed by a -10% decline during the maintenance phase, but this decline brought the DHT levels of the young men in the creatine group pretty close to where they had been in the placebo group at T0 (1.38nmol/L vs. 1.26 nmol/L for creatine vs. placebo, respectively).

The high DHT levels observed in the study at hand, were only midrange

If that does not comfort you, maybe it will help, if I tell you that the reference range for adult men ranges from 0.8-3.4 nmol/L (NHS Pathology. 2013 - please note that these reference ranges vary from lab to lab, in ng/dL the upper limit usually is 85ng/dL, which is 2.93nmol/L). Accordingly, the total DHT level of the subjects in the van der Merwe study did not even scratch the 50% mark on the reference range, when they maxed out at the end of the 7-day loading phase.

With a meager 9% difference to the baseline levels in the control group and a total DHT level of 1.38nmol/L in the "low DHT" zone of the reference range, I wouldn't say it is necessary (from a mere safety perspective) to investigate, as Green suggested it in a 2010 letter to the editor, whether the creatine supplement that has been used in the study may have been contaminated with androgenic compounds (Green. 2010). To answer the question about the why, i.e. "Why did the DHT levels in the creatine group go up, while those in the control group remained the same?",  it would yet in fact be nice to know if we were dealing with the side effects of androgenic compounds in the creatine supplement or the physiological effects of exercise, which has repeatedly been shown to be able to increase both intra-muscular and systemic DHT levels in men and rodent models (see the bottom line for selected references).

Want to learn how to modulate your DHT levels naturally? Rice, safflower, sorghum & Co. can help! learn more
In view of the fact that these increases are intensity dependent, but limited by the androgen suppressive effects of overtraining, The increased DHT levels may eventually have been a secondary response to increased training loads and the ameliorative effect creatine exerts on the androgen suppressive effects of overreaching (Volek. 2004).

And while I cannot tell you if this actually was the reason for the increase in DHT, I can tell you that the scientists assertion that what they observed was a "large increase in DHT rather than a marginal (possibly physiologically insignificant)"  (van de Merwe. 2009) is (at best) warranted if we look at the intra-group effect. In view of the broad "normal" range and the low baseline DHT levels in the creatine group, this relevance of this relative increase is yet more than questionable.

And the increasing DHT:Testosterone ratio?

Even at the risk of sounding like a smart ass, I do not want to forgot to mention that the "oh so dangerous" increase in DHT/T levels the scientists emphasize in their conclusion was found to be associated with a reduced risk of hair loss (-35% risk reduction) in 315 male subjects who were stratified with regard to age, race, and case-control (Demark-Wahnefried. 1997).

This and similar observations which have been made by Nomura et al. (1988), Hsing (1993) Shaneyfelt (2000) with respect to the non-significant impact of high(er) serum DHT levels on the occurance of prostate cancer and, more importantly, the increased risk that comes with higher T:DHT ratios, I seriously doubt that you have to be concerned about either your superb head of hair or your hitherto still pain and cancer free prostate when you are downing your daily dose of 3-5g creatine monohydrate.
No! Physical activity does not cause prostate cancer. I guess you will be surprised that I even address this issue, but due to several major shortcomings in previous prospective and epidemiological studies, you will easily find studies such as the one by Cerhan et al. which claims that men with a high physical activity have a 90%(!) increased risk of prostate cancer. What the abstract does not tell you, though, is that the researchers "forgot" to conduct a time lagged analysis to overcome the "I started to exercise yesterday, so I exercise vigorously every day" effect and did thus fail to measure consistent physical activity. Edward et al. did just that over a 4 year period and observed a -53% risk reduction for men aged 65+ to develop advanced prostate cancer.
Take home message: Despite being statistically relevant the absolute changes in the DHT levels van der Merwe et al. observed in the study at hand were neither physiologically relevant (DHT remained well within the reference range), nor totally inexplicable. Being afraid of hair loss, let alone prostate cancer, in response to the consumption of (untainted) creatine supplements is thus totally unwarranted.

And just in case you still want to freak out, I suggest you keep sitting on your ass for the rest of your life and refrain from ever playing football or any other sport again... why? Well according to Lupo et al., your DHT levels will double during a single football match. This and similar observations by Hawkins in a middle aged men on a 12-months aerobic exercise program (14.5% increase with moderate intensity cardio 6x per week; cf. Hawkins. 2008), as well as the results from Aizawa et al. who were able to demonstrate "that acute exercise enhances the local bioactive androgen metabolism in the skeletal muscle of both sexes" and not just men, do as bro-logic dictates suggest that any kind of physical activity will make you hair fall out and your prostate grow... now tell me how realistic is that?
  • Aizawa K, Iemitsu M, Maeda S, Otsuki T, Sato K, Ushida T, Mesaki N, Akimoto T. Acute exercise activates local bioactive androgen metabolism in skeletal muscle. Steroids. 2010 Mar;75(3):219-23.
  • Buford T, Kreider R, Stout J, Greenwood M, Campbell B, Spano M, Ziegenfuss T, Lopez H, Landis J, Antonio J:International Society of Sports Nutrition position stand: creatine supplementation and exercise.J Int Soc Sports Nutr. 2007;4.
  • Cerhan JR, Torner JC, Lynch CF, Rubenstein LM, Lemke JH, Cohen MB, Lubaroff DM, Wallace RB. Association of smoking, body mass, and physical activity with risk of prostate cancer in the Iowa 65+ Rural Health Study (United States). Cancer Causes Control. 1997 Mar;8(2):229-38. 
  • Demark-Wahnefried W, Lesko SM, Conaway MR, Robertson CN, Clark RV, Lobaugh B,
    Mathias BJ, Strigo TS, Paulson DF. Serum androgens: associations with prostate
    cancer risk and hair patterning. J Androl. 1997 Sep-Oct;18(5):495-500. 
  • Giovannucci EL, Liu Y, Leitzmann MF, Stampfer MJ, Willett WC. A prospective study of physical activity and incident and fatal prostate cancer. Arch Intern Med. 2005 May 9;165(9):1005-10.
  • Hawkins VN, Foster-Schubert K, Chubak J, Sorensen B, Ulrich CM, Stancyzk FZ, Plymate S, Stanford J, White E, Potter JD, McTiernan A. Effect of exercise on serum sex hormones in men: a 12-month randomized clinical trial. Med Sci Sports Exerc. 2008 Feb;40(2):223-33
  • Hickner R, Dyck D, Sklar J, Hatley H, Byrd P:Effect of 28 days of creatine ingestion on muscle metabolism and performance of a simulated cycling road race.J Int Soc Sports Nutr 2010;7:26.
  • Hsing AW, Comstock GW. Serological precursors of cancer: serum hormones and risk of subsequent prostate cancer. Cancer Epidemiol Biomarkers Prev. 1993 Jan-Feb;2(1):27-32.
  • van der Merwe J, Brooks NE, Myburgh KH. Three weeks of creatine monohydrate supplementation affects dihydrotestosterone to testosterone ratio in college-aged rugby players. Clin J Sport Med. 2009 Sep;19(5):399-404.
  • Nomura A, Heilbrun LK, Stemmermann GN, Judd HL. Prediagnostic serum hormones and the risk of prostate cancer. Cancer Res. 1988 Jun 15;48(12):3515-7.
  • Shaneyfelt T, Husein R, Bubley G, Mantzoros CS. Hormonal predictors of prostate cancer: a meta-analysis. J Clin Oncol. 2000 Feb;18(4):847-53.
  • Van der Merwe J, Brooks NE, Myburgh KH. Three weeks of creatine monohydrate supplementation affects DHT to testosterone ratio in college-aged rugby players.Clin J Sports Med. 2009;19:399–404.
  • Volek JS, Ratamess NA, Rubin MR, Gómez AL, French DN, McGuigan MM, Scheett TP, Sharman MJ, Häkkinen K, Kraemer WJ. The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. Eur J Appl Physiol. 2004 May;91(5-6):628-37.
  • Willoughby DS, Rosene J:Effects of oral creatine and resistance training on myosin heavy chain expression.Med Sci Sports Exerc2001,33:1674–1681.