Creatine Metabolism in Female Reproduction, Pregnancy and Newborn Health

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.

Relationship between Dietary Creatine and Growth Indicators in Children and Adolescents Aged 2–19 Years: A Cross-Sectional Study

“…Creatine is a pleiotropic nutraceutical that plays an essential role in several metabolic pathways, including tissue bioenergetics and cellular growth. Its contribution to early growth and development is apparent throughout the literature, with de novo and dietary creatine necessary to uphold optimal placental function, maintenance of pregnancy, as well as fetal growth and maturation [5]. Dietary creatine is also proving to effectively tackle creatine deficiency syndrome, a genetic malfunction of creatine biosynthetic enzymatic machinery characterized by developmental delay and neuromuscular manifestations, allowing neonates and youngest children with the condition to thrive [6].…”

Temporal trends in dietary creatine intake from 1999 to 2018: an ecological study with 89,161 participants

“…Our data also suggest that for each additional round of NHANES completed from 1999 to 2000 onwards, the expected amount of creatine consumed significantly decreased for 2.08 mg in infants, and for 3.22 mg in children and adolescents. Although this amount appears small, the trend might be of high clinical relevance owing to the fundamental role that dietary creatine plays in normal growth and health, with lower creatine availability appears to jeopardize young brain development in preclinical and clinical nutrition [ 7 ]. Whether dietary creatine shortfall affects children’s well-being currently remains unaddressed at the community-wide level.…”

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review

“…Special attention should be paid to the increased Cr demand during pregnancy due to the important role of the PCr/CK system in the uterus and placenta for the maintenance and termination of gestation [34,228,229].…”