Role of Creatine in the Heart: Health and Disease

Abstract

Creatine is a key player in heart contraction and energy metabolism. Creatine supplementation (throughout the paper, only supplementation with creatine monohydrate will be reviewed, as this is by far the most used and best-known way of supplementing creatine) increases creatine content even in the normal heart, and it is generally safe. In heart failure, creatine and phosphocreatine decrease because of decreased expression of the creatine transporter, and because phosphocreatine degrades to prevent adenosine triphosphate (ATP) exhaustion. This causes decreased contractility reserve of the myocardium and correlates with left ventricular ejection fraction, and it is a predictor of mortality. Thus, there is a strong rationale to supplement with creatine the failing heart. Pending additional trials, creatine supplementation in heart failure may be useful given data showing its effectiveness (1) against specific parameters of heart failure, and (2) against the decrease in muscle strength and endurance of heart failure patients. In heart ischemia, the majority of trials used phosphocreatine, whose mechanism of action is mostly unrelated to changes in the ergogenic creatine-phosphocreatine system. Nevertheless, preliminary data with creatine supplementation are encouraging, and warrant additional studies. Prevention of cardiac toxicity of the chemotherapy compounds anthracyclines is a novel field where creatine supplementation may also be useful. Creatine effectiveness in this case may be because anthracyclines reduce expression of the creatine transporter, and because of the pleiotropic antioxidant properties of creatine. Moreover, creatine may also reduce concomitant muscle damage by anthracyclines.

Sex- and tissue-dependent creatine uptake in response to different creatine monohydrate doses in male and female Sprague–Dawley rats

“…This novel finding may be clinically relevant, as throughout the progression of heart failure TCr concentrations and CK activity in heart are decreased resulting in a lowered energy reserve within cardiac tissue (Zervou et al, 2015). Decreased TCr concentrations have been previously observed during the course of heart failure using multiple in vivo models and it has been suggested that this may be in part due to down-regualation of the creatine transporter, a decrease in CK activity, and excessive consumption of PCr to delay ATP exhaustion (Balestrino, 2021). Some studies have demonstrated that CM supplemention in humans experiencing heart failure has led to favourable outcomes; including an increase in the rate of oxygen consumption and global functional improvement, although it is not clear whether these outcomes were due to improvements related to heart failure or skeletal muscle performance (Balestrino, 2021).…”

“…Decreased TCr concentrations have been previously observed during the course of heart failure using multiple in vivo models and it has been suggested that this may be in part due to down-regualation of the creatine transporter, a decrease in CK activity, and excessive consumption of PCr to delay ATP exhaustion (Balestrino, 2021). Some studies have demonstrated that CM supplemention in humans experiencing heart failure has led to favourable outcomes; including an increase in the rate of oxygen consumption and global functional improvement, although it is not clear whether these outcomes were due to improvements related to heart failure or skeletal muscle performance (Balestrino, 2021). It is possible that our observed differences between male and female TCr content within HRT could partly explain why females appear to be less prone to the development of heart failure and display better survival rates in relation to heart failure compared to males (Regitz-Zagrosek et al, 2010), however this is speculative and clearly more work is needed to determine if CM supplementation could lead to meaningful improvement of cardiac health, and whether it would be more efficacious in males or females.…”

“…The purpose of this pilot experiment was to investigate in vivo differences in TCr concentrations between males and females in response to increasing doses of CM supplementation in extensor digitorum longus (EDL), soleus (SOL), red-(RGAS) and whitefiber (WGAS) gastrocnemius muscle, cardiac muscle (HRT), and brain (BR). While multiple Cr analogues may be used for supplementation purposes, CM was selected as it has no major safety concerns and has been used extensively in past literature (Balestrino, 2021). It was hypothesized that increasing doses of CM would lead to greater increases in TCr in all tissues examined and that the increases would be relatively greater in females as compared to males.…”

Creatine Enhances the Effects of Cluster-Set Resistance Training on Lower-Limb Body Composition and Strength in Resistance-Trained Men: A Pilot Study

“…Hence, the CK/PCr system might be considered as a crucial spatio-temporal energy and metabolic buffer during high-intensity short-duration physical exercise [ 8 ]. Optimization of the CK/PCr system can be attained by supplementation with creatine monohydrate (CrM), which is not only the most studied, safe, and effective nutritional ergogenic aid [ 12 , 13 , 14 , 15 ] but also has several potential health/therapeutic benefits [ 16 , 17 , 18 , 19 , 20 , 21 ].…”

A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation

“…The CK/PCr system can be enhanced through supplementation with creatine monohydrate (CrM), which is the most studied, safe, and effective nutritional supplement to optimize physical performance [ 5 , 6 , 7 , 8 ], with potential benefits in health and disease [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. It seems that the elevation of intracellular PCr concentration causes a greater capacity for phosphagens to contribute to energy metabolism, while working to reduce the accumulation of Pi and H + and improving Ca 2+ handling as important mediators of fatigability in young and older adults [ 20 , 21 , 22 , 23 ].…”