Wednesday, May 10, 2017

Dubious Effects of Creatine on Markers of CNS Adaptation and Heart Health in "Bodybuilders" - Reason to Be Afraid?

Bodybuilding and creatine ain't mentioned in one breath without a reason - Crea simply works! Dozens of studies have shown that... not one, however, tested the effects on the CNS.
Based on the extreme excitement I observed in response my recent Facebook News item on creatine's ability to reduce the sleep requirements in a rodent trial [(re-)read it], I assume that you'd like to learn about more or less every study on everyone's favorite ergogenic - correct?

Not every study? Oh, yes, obviously, study #103 showing that creatine yields strength and size increases on your average hypertrophy workout would indeed no longer be news-worthy. Much in contrast, however, to a study that claims that creatine may blunt the beneficial effects of resistance training on heart health? Ok, I see that's getting you excited. So let's take a closer look at how the authors come up with claim...
You can learn more about creatine at the SuppVersity

Creatine Doubles 'Ur GainZ!

Creatine Loading = Unnecessary

Creatine Pre or After Workouts?

1st Benefits of Creatine-HCL

The Real Bioavai-lability of Crea

Anti-Cre GAA Better Than Cre?
As the Turkish authors of the corresponding peer-reviewed paper that's about to be published in Pacing and Clinical Electrophysiology (Mert 2017) point out, 'bodybuilding' is not just an increasingly "popular sport among adolescents", it is also a sport that involves exercises capable of "increas[ing] stroke volume and cardiac output to a greater degree than [selected other sports]" (Mert 2017 base this statement on Ahlgrim 2009). As a gymrat, you will not be surprised to hear that bodybuilding type workouts have also been found to affect heart rate variability (HRV | learn what it's got to do with overtraining), of which you, as a SuppVersity Reader, know that it can be used (comparing intra-individual values, not as in the study at hand for intra-individual comparisons) to decently predict/measure overtraining - or, more precisely, the way in which your training impacts your autonomic nervous system (ANS). Now that, in turn, will affect your heart health, because...
  • sympathetic stimulation increases the heart rate, contractility, and conduction velocity, whereas parasympathetic stimulation has the opposite effects;
  • there's a significant relationship between ANS imbalance and cardiovascular mortality, including sudden cardiac death;
  • the effects of exercise on cardiovascular mortality and sudden cardiac death may be mediated by its effects on ANS or, more specifically, the way it modifies the autonomic balance.
As of now, studies have not assessed, if this generally positive effect of bodybuilding (in the absence of overtraining) is augmented or impaired by creatine supplementation. In fact, Mert et al. rightly point out that "there is no study regarding the assessment of HRV especially in bodybuilders so far," anyway. In their latest study, the scientists thus "aimed to investigate HRV parameters of cardiac autonomic functions in bodybuilders compared to healthy control subjects and evaluate effects of creatine supplementation on HRV parameters" (Mert 2017).

Hey, bros: Let me measure your HRV!

For their observational study, the Turkish scientists recruited 32 male "competitive" bodybuilders - 16 of these sportsmen, who were no pro-bodybuilders, but had at least 5 years of training experience (10–12h/week), had been taking creatine for at least 4 weeks (7.5 mg/day | range 3.5-15.0mg) the other 16 sportsmen didn't.
Please note: This is an observational, not an experimental study!  As previously highlighted (underlined), the study at hand is not a randomized controlled trial. It is an observational study. An observational study that didn't reliably test the subjects for current or prior steroid use and took for granted that all "bodybuilders" consumed protein supplements - if the subjects were actually clean, how much protein they consumed and, more importantly, how that differed from one group to the other, however, is not clear... with obvious consequences for the practical significance and reliability of the results.
Table 1: Overview of selected subject characteristics in the control, and the subjects in the two training groups of Mert et al.'s observational study.
Sixteen sex-, age- and body mass index (BMI) matched healthy volunteers were also enrolled as control group. In all subjects, a detailed cardiovascular and systemic examination was performed at the beginning of the study with demographic data and anthropometric measures including weight, height, and BMI. 12-lead electrocardiography at 25 mm/s (paper speed), and at resting day 24h ambulatory ECG monitorization was performed in each participant. In addition, fasting blood glucose, total cholesterol, LDL, HDL, triglyceride, blood urea nitrogen (BUN), serum creatinine, serum sodium, serum potassium and a full blood count were obtained from all subjects.

The scientists found no significant inter-group difference in the trained study subjects; even though there were fewer smokers in the creatine compared to the 'no creatine' group. As you can see in Table 1 that's different for the comparison of the two training groups to the untrained control subjects.

To be precise, a significant difference was observed for the resting heart rate between the 'no creatine' and the control, yet not the creatine and the control group - a significant difference between the two training groups, however, didn't exist. Additionally, the subjects in the creatine group had significantly higher BUN and - quite obviously - creatinine levels.
My criticism of the scientists use of HRV in the study at hand does not contradict the previously discussed usefulness of HRV as a marker of overtraining | more
Does this mean that HRV can no longer be used to diagnose overtraining? The answer is complicated. For one, HRV may be one of the best indicators we have that someone is overtraining. Taken on its own, however, it is not enough to "diagnose" overtraining. Moreover, inter-athlete comparisons as they were done in the study at hand are of little use here - changes with the athlete's baseline levels as a reference, which are obviously not available in the study at hand, are necessary to make a decently reliable statement about overtraining. Practically speaking, this means that you have to get a baseline reading after a deloading period to be able to reliabley predict where you're at (learn more).

Accurate analysis, that's at least what a recent from Italy suggests, this may require more than a simple heart-rate monitor and a software that analyzes the frequency. Ideally, an ECG should be recorded at respiratory rates above 10 breath/min to get 100% reliable data (Lucini 2007). 
More importantly, however, the time-domain and frequency domain analysis of data of the 24 hours holter recordings of all participants showed that the athletes who supplemented with creatine did neither have significantly elevated higher SDNN, SDNN index, RMSDD, pNN50, high (HF) and low frequency (LF) components, nor a lowered LF/HF ratio compared to the control group. Ha? Well, here's what the individual parameters have been linked to:
  • SDNN - estimate of overall HRV; A decrease in SDNN has been associated with sudden cardiac death
  • SDANN - reflects circadian rhythmicity of autonomic function
  • pNN50 - is virtually independent of circadian rhythms; reflects alterations in autonomic function that are primarily vagally mediated
  • RMSDD - estimate of the short-term components of HRV, provides Vagal Index.
To understand what the LF/HF ratio is, one has to know that the low frequency (LF) domain has traditionally been associated with sympathetic nervous system activity, while the high frequency (HF) domain is generally considered to represent the parasympathetic activity (it is, therefore, also seen as a marker of vagal activity). A lower LF/HF ratio is thus indicative of an improved "sympathovagal balance" - and that's basically why the authors of the study at hand say that their study would show that creatine supplementation is associated with a reduced beneficial effect of resistance training (bodybuilding-style) on the sympathetic nervous system and downstream heart-health.
Creatine: 17-20g for Loading is Bogus, 5-7g May Be More Than Necessary to Maintain, Study in Gymrats Suggests | That's Good News: Less Bloating, Better Effect, Lower Risk of Side Effects - Including CNS-Sides | more.
The scientists' conclusion is based on unreliable data and false assumptions: Now, there are two important problems with this conclusion: (a) we're not dealing with experimental data, but relatively unreliable observations, where dozens of unassessed or insufficiently assessed parameters (e.g. training volume, intensity, frequency, caffeine intake etc.) could be the actual reason(s) for the observed differences; and (b) it is based on the meanwhile highly questioned assumption that the LF/HF ratio would, in fact, be an accurate measure of cardiac sympathovagal balance. In view of the latest evidence that suggests influences of both parasympathetic and sympathetic activity on the LF component and the way it is confounded by the mechanical effects of respiration and prevailing heart rate, it is yet "impossible to delineate the physiological basis for LF/HF with any degree of certainty".

So, the study data is close to anecdotal, the interpretation is questionable... ergo, no reason to be scared by a supplement the safety of which has been proven time and again (Juhn 1998; Kreider 1998; Schilling 2001; Bizzarine 2004; Buford 2007; Jäger 2011; Kim 2011) - I have to admit, though, that its CNS effects are 'understudied'; it is yet up to future experimental research to determine whether and what kind of effects everyone's favorite ergogenic will have on your central nervous system and its ability to adapt to resistance training | Comment on Facebook!
  • Ahlgrim, Christoph, and Maya Guglin. "Anabolics and cardiomyopathy in a bodybuilder: case report and literature review." Journal of cardiac failure 15.6 (2009): 496-500.
  • Akselrod, Solange, et al. "Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control." science 213.4504 (1981): 220-222.
  • Appel, Marvin L., et al. "Beat to beat variability in cardiovascular variables: noise or music?." Journal of the American College of Cardiology 14.5 (1989): 1139-1148.
  • Billman, George E. "The LF/HF ratio does not accurately measure cardiac sympathovagal balance." Heart Rate Variability: Clinical Applications and Interaction between HRV and Heart Rate (2007): 54.
  • Bizzarini, E., and L. De Angelis. "Is the use of oral creatine supplementation safe?." Journal of Sports Medicine and Physical Fitness 44.4 (2004): 411.
  • Buford, Thomas W., et al. "International Society of Sports Nutrition position stand: creatine supplementation and exercise." Journal of the International Society of Sports Nutrition 4.1 (2007): 6.
  • Houle, Melanie S., and George E. Billman. "Low-frequency component of the heart rate variability spectrum: a poor marker of sympathetic activity." American Journal of Physiology-Heart and Circulatory Physiology 276.1 (1999): H215-H223.
  • Jäger, Ralf, et al. "Analysis of the efficacy, safety, and regulatory status of novel forms of creatine." Amino acids 40.5 (2011): 1369-1383.
  • Juhn, Mark S., and Mark Tarnopolsky. "Potential side effects of oral creatine supplementation: a critical review." Clinical Journal of Sport Medicine 8.4 (1998): 298-304.
  • Kim, Hyo Jeong, et al. "Studies on the safety of creatine supplementation." Amino acids 40.5 (2011): 1409-1418.
  • Kreider, Richard B. "Creatine supplementation: analysis of ergogenic value, medical safety, and concerns." J Exerc Physiol Online 1.1 (1998).
  • Lucini, Daniela, et al. "Heart rate variability to monitor performance in elite athletes: Criticalities and avoidable pitfalls." International Journal of Cardiology (2017).
  • Mert, Kadir Uğur, et al. "Effects of creatine supplementation on cardiac autonomic functions in bodybuilders." Pacing and Clinical Electrophysiology (2017).
  • Schilling, Brian K., et al. "Creatine supplementation and health variables: a retrospective study." Medicine and science in sports and exercise 33.2 (2001): 183-188.