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...
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.

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.
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.
References:

• 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.
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• 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.
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