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Creatine in Health and Disease
Richard B. Kreider and Jeffery R. Stout
Abstract
Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported. This is because creatine plays a critical role in cellular metabolism, particularly during metabolically stressed states, and limitations in the ability to transport and/or store creatine can impair metabolism. Moreover, increasing availability of creatine in tissue may enhance cellular metabolism and thereby lessen the severity of injury and/or disease conditions, particularly when oxygen availability is compromised. This systematic review assesses the peer-reviewed scientific and medical evidence related to creatine’s role in promoting general health as we age and how creatine supplementation has been used as a nutritional strategy to help individuals recover from injury and/or manage chronic disease. Additionally, it provides reasonable conclusions about the role of creatine on health and disease based on current scientific evidence. Based on this analysis, it can be concluded that creatine supplementation has several health and therapeutic benefits throughout the lifespan.
Keywords: ergogenic aids; cellular metabolism; phosphagens; sarcopenia; cognition; diabetes; creatine synthesis deficiencies; concussion; traumatic brain injury; spinal cord injury; muscle atrophy; rehabilitation; pregnancy; immunity; anti-inflammatory; antioxidant; anticancer
Kreider, R.B.; Stout, J.R. Creatine in Health and Disease. Nutrients 2021, 13, 447.
Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review
Diego A. Bonilla, Richard B. Kreider, Jeffrey R. Stout, Diego A. Forero, Chad M. Kerksick, Michael D. Roberts and Eric S. Rawson
Abstract
Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl−-dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg2+:ATP4−]2− and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3−]−. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states.
Keywords: creatine kinase; energy metabolism; cell survival; bioinformatics; systems biology; cellular allostasis; dynamic biosensor
Bonilla, D.A.; Kreider, R.B.; Stout, J.R.; Forero, D.A.; Kerksick, C.M.; Roberts, M.D.; Rawson, E.S. Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review. Nutrients 2021, 13, 1238.
Creatine Metabolism in Female Reproduction, Pregnancy and Newborn Health
Anna Maria Muccini, Nhi T. Tran, Deborah L. de Guingand, Mamatha Philip, Paul A. Della Gatta, Robert Galinsky, Larry S. Sherman, Meredith A. Kelleher, Kirsten R. Palmer, Mary J. Berry, David W. Walker, Rod J. Snow and Stacey J. Ellery
Abstract
Creatine metabolism is an important component of cellular energy homeostasis. Via the creatine kinase circuit, creatine derived from our diet or synthesized endogenously provides spatial and temporal maintenance of intracellular adenosine triphosphate (ATP) production; this is particularly important for cells with high or fluctuating energy demands. The use of this circuit by tissues within the female reproductive system, as well as the placenta and the developing fetus during pregnancy is apparent throughout the literature, with some studies linking perturbations in creatine metabolism to reduced fertility and poor pregnancy outcomes. Maternal dietary creatine supplementation during pregnancy as a safeguard against hypoxia-induced perinatal injury, particularly that of the brain, has also been widely studied in pre-clinical in vitro and small animal models. However, there is still no consensus on whether creatine is essential for successful reproduction. This review consolidates the available literature on creatine metabolism in female reproduction, pregnancy and the early neonatal period. Creatine metabolism is discussed in relation to cellular bioenergetics and de novo synthesis, as well as the potential to use dietary creatine in a reproductive setting. We highlight the apparent knowledge gaps and the research “road forward” to understand, and then utilize, creatine to improve reproductive health and perinatal outcomes.
Keywords: creatine; nutritional supplements; fertility; pregnancy; newborn; development; brain injury
Muccini, A.M.; Tran, N.T.; de Guingand, D.L.; Philip, M.; Della Gatta, P.A.; Galinsky, R.; Sherman, L.S.; Kelleher, M.A.; Palmer, K.R.; Berry, M.J.; Walker, D.W.; Snow, R.J.; Ellery, S.J. Creatine Metabolism in Female Reproduction, Pregnancy and Newborn Health. Nutrients 2021, 13, 490.
