Although limited in number, select studies have demonstrated that creatine supplementation is an effective nutritional strategy to promote increases in the phosphocreatine content and energy status of the cell among pediatric populations [
9,
10]; however, some evidence suggests this is potentially so, but to a lesser extent when compared to what is commonly reported in adult populations [
1]. Depending on baseline levels of creatine content, which tend to be heavily influenced by exogenous creatine intake [
11], increases of 10–40% in creatine or phosphocreatine content within skeletal muscle tissue are routinely reported following periods of creatine supplementation in adult populations [
1]. Interestingly, preliminary evidence suggests that an age-dependent effect of creatine supplementation may exist regarding intramuscular creatine uptake, thereby indicating that the development of age-specific supplementation strategies may be warranted [
9,
10]. Further, research in adult populations [
3,
12,
13] has indicated a moderate degree of variability in tissue uptake response to creatine supplementation protocols. It is currently unknown if similar variabilities (i.e., responder vs. nonresponder effects) are also present among children and adolescents. Due to age and ethical considerations, the majority of research in pediatric populations has relied on magnetic resonance imaging or laboratory markers as indirect measures of creatine and phosphocreatine content rather than through muscle biopsies, which is a common technique used for measuring intramuscular creatine content in adult populations. Additionally, lower doses of creatine are sometimes used among pediatric populations, which is also likely to influence the magnitude of changes observed in creatine content following a supplementation period. Therefore, it is difficult to directly compare the efficacy of creatine supplementation strategies between age groups when different techniques are used to quantify creatine content and different dosing strategies may be employed. However, a study by Solis et al. [
10] was able to examine changes in brain and muscle phosphocreatine content across three age groups (children,
n = 15, adult omnivores,
n = 17, adult vegetarians,
n = 14, and elderly adults,
n = 18) using
31P-magnetic resonance spectroscopy, following a standard creatine loading protocol (0.3 g/kg/day for 7 days). Results indicated intramuscular phosphocreatine content significantly increased by 13.9% while brain phosphocreatine levels only increased by 2.1% among the group of children [
10]. Comparatively, following the same creatine dosing regimen, larger increases in muscle phosphocreatine content were observed in the elderly (22.7%) but not adult omnivores (10.3%) when compared to the children. It is also worth noting that lower baseline levels of muscle phosphocreatine content were observed in the children compared to the adult groups. Using a lower dose (5 g/day), but over an 8-week period, Banerjee et al. [
9] reported significantly greater increases in the mean phosphocreatine/inorganic phosphate ratio following creatine supplementation compared to placebo (Creatine: 4.7; 95% CI: 3.9–5.6 vs. Placebo 3.3; 95% CI 2.5–4.2;
p = 0.03) in patients with Duchenne Muscular Dystrophy. Alternatively, contradictory reports to these outcomes regarding the efficacy of creatine supplementation have indicated little to no impact on intramuscular phosphocreatine content; however the relative dose used in these studies may have been too low (0.1 g/kg/day for 12 weeks) to elicit any meaningful changes in creatine content [
12,
13]. Additionally, it is also worth noting these studies were conducted in patients with childhood-onset systemic lupus erythematosus and juvenile dermatomyositis, which may have influenced the efficacy of creatine supplementation in its ability to increase phosphocreatine content. Preliminary evidence among specialized clinical populations with inborn errors of metabolism, such as creatine deficiencies, has also indicated that creatine supplementation can positively influence brain creatine content with a subsequent influence on cognition, natural development, and quality of life [
14,
15,
16]. However, as highlighted previously by Solis et al. [
10], it was reported that a standard creatine loading regimen (0.3 g/kg/day for 7 days) in prepubescent children, omnivore adults, vegetarian adults, and elderly adults was not able to elicit significant changes in brain phosphocreatine content [
10]. Similar findings have also been observed in healthy young children between the ages of 10 to 12 years of age [
17], which failed to observe significant increases in brain creatine content following creatine supplementation. However, a review by Dolan et al. [
18] highlighted multiple studies in adult populations, all of which utilized varying creatine supplementation strategies (2–20 g per day from 5 days to 8 weeks), that were able to demonstrate significant increases in brain creatine and phosphocreatine content following supplementation. It is possible that higher doses of creatine over longer periods of time may be required for meaningful increases in brain creatine content to occur among healthy populations as has been previously suggested [
18]. The potential increase in brain creatine content following supplementation may also be age-dependent. Nevertheless, more research is needed to identify the extent to which creatine supplementation can impact brain creatine levels and whether or not modified creatine supplementation strategies for this purpose are warranted.