The effects of creatine, lithium, and co-supplementation on total creatine concentration in muscle from male and female rats

Abstract

Creatine (Cr) is an element necessary to maintain muscle function in tissues with high energy demand. This is because Cr and phosphocreatine (PCr) play a critical role in cellular energy provision and intracellular shuttling through the Cr-PCr immediate energy system. Cr can be synthesized endogenously, as well as consumed exogenously via diet or supplementation. Literature supports the potential for increased Cr uptake to augment several factors of human performance – most namely muscle function in sports related to strength, speed, and power. Moreover, recent research suggests potential for lithium (Li) to upregulate Cr uptake and Cr transport into cells. Therefore, the purpose of this research was to investigate the individual and combined effects of creatine monohydrate (CM) and lithium chloride (LiCl) supplementation on Cr content in rat cardiac and skeletal muscle in vivo. Potential sex-specific effects were also explored. 64 Sprague-Dawley rats (32 males, 32 females) were randomized into four experimental groups: control (CON), creatine (Cr), lithium (Li), and creatine-lithium (Cr-Li). CM (5 g/L) and LiCl (0.2 g/L) were provided to rats via drinking water. All groups were provided ad libitum access to their respective drinking water (all supplemented with 0.5% sucrose for palatability) and AIN- 93G rodent diet. When males and females were examined together, intramuscular total creatine concentration ([TCr]) was greater (p<0.01) with CM supplementation compared to LiCl supplementation and tended to be greater (p=0.0706) than CON in cardiac muscle. There were no significant main effects for treatment in any of the skeletal muscle outcomes examined. A main effect for sex revealed that male rats had greater [TCr] than female rats, in extensor digitorum longus (EDL) (p<0.01). In soleus (SOL) and EDL, female rats had greater total glycogen synthase 3 beta (GSK3β) protein expression compared to males (p<0.05), but there were no significant effects of treatment observed. Protein content of the creatine transporter (CrT) was greater in males than females in cardiac muscle (p<0.05). It was also greater in CON rats compared to Li (p<0.01) and CrLi (p<0.05) supplemented rats, in SOL. In conclusion, supplementation with CM, with or without LiCl, altered TCr concentrations in a tissue-dependent manner.