While the vast majority of research involving creatine supplementation has focused on skeletal muscle, there is a small body of accumulating research that has focused on creatine and the brain. Preliminary studies indicate that creatine supplementation (and guanidinoacetic acid; GAA) has the ability to increase brain creatine content in humans. Furthermore, creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression but its effect on neurodegenerative diseases appears to be lacking. The purpose of this narrative review is to summarize the current body of research pertaining to creatine supplementation on total creatine and phophorylcreatine (PCr) content, explore GAA as an alternative or adjunct to creatine supplementation on brain creatine uptake, assess the impact of creatine on cognition with a focus on sleep deprivation, discuss the effects of creatine supplementation on a variety of neurological and mental health conditions, and outline recent advances on creatine supplementation as a neuroprotective supplement following traumatic brain injury or concussion.

Sarcopenia, defined as the age-related decrease in muscle mass, strength and physical performance, is associated with reduced bone mass and elevated low-grade inflammation. From a healthy aging perspective, interventions which overcome sarcopenia are clinically relevant. Accumulating evidence suggests that exogenous creatine supplementation has the potential to increase aging muscle mass, muscle performance, and decrease the risk of falls and possibly attenuate inflammation and loss of bone mineral. Therefore, the purpose of this review is to: (1) summarize the effects of creatine supplementation, with and without resistance training, in aging adults and discuss possible mechanisms of action, (2) examine the effects of creatine on bone biology and risk of falls, (3) evaluate the potential anti-inflammatory effects of creatine and (4) determine the safety of creatine supplementation in aging adults.

The purpose of this paper was to carry out a systematic review with a meta-analysis of randomized controlled trials that examined the combined effects of resistance training (RT) and creatine supplementation on regional changes in muscle mass, with direct imaging measures of hypertrophy. Moreover, we performed regression analyses to determine the potential influence of covariates. We included trials that had a duration of at least 6 weeks and examined the combined effects of creatine supplementation and RT on site-specific direct measures of hypertrophy (magnetic resonance imaging (MRI), computed tomography (CT), or ultrasound) in healthy adults. A total of 44 outcomes were analyzed across 10 studies that met the inclusion criteria. A univariate analysis of all the standardized outcomes showed a pooled mean estimate of 0.11 (95% Credible Interval (CrI): −0.02 to 0.25), providing evidence for a very small effect favoring creatine supplementation when combined with RT compared to RT and a placebo. Multivariate analyses found similar small benefits for the combination of creatine supplementation and RT on changes in the upper and lower body muscle thickness (0.10–0.16 cm). Analyses of the moderating effects indicated a small superior benefit for creatine supplementation in younger compared to older adults (0.17 (95%CrI: −0.09 to 0.45)). In conclusion, the results suggest that creatine supplementation combined with RT promotes a small increase in the direct measures of skeletal muscle hypertrophy in both the upper and lower body.

Creatine supplementation in conjunction with resistance training (RT) augments gains in lean tissue mass and strength in aging adults; however, there is a large amount of heterogeneity between individual studies that may be related to creatine ingestion strategies. Therefore, the purpose of this review was to (1) perform updated meta-analyses comparing creatine vs. placebo (independent of dosage and frequency of ingestion) during a resistance training program on measures of lean tissue mass and strength, (2) perform meta-analyses examining the effects of different creatine dosing strategies (lower: ≤5 g/day and higher: >5 g/day), with and without a creatine-loading phase (≥20 g/day for 5–7 days), and (3) perform meta-analyses determining whether creatine supplementation only on resistance training days influences measures of lean tissue mass and strength. Overall, creatine (independent of dosing strategy) augments lean tissue mass and strength increase from RT vs. placebo. Subanalyses showed that creatine-loading followed by lower-dose creatine (≤5 g/day) increased chest press strength vs. placebo. Higher-dose creatine (>5 g/day), with and without a creatine-loading phase, produced significant gains in leg press strength vs. placebo. However, when studies involving a creatine-loading phase were excluded from the analyses, creatine had no greater effect on chest press or leg press strength vs. placebo. Finally, creatine supplementation only on resistance training days significantly increased measures of lean tissue mass and strength vs. placebo.

Sarcopenia negatively affects skeletal muscle mass and function in older adults. Omega-3 (ω-3) fatty acid supplementation, with or without resistance exercise training (RET), is suggested to play a role as a therapeutic component to prevent or treat the negative effects of sarcopenia. A systematic review and meta-analysis were conducted on the impact of ω-3 fatty acid supplementation with or without RET on measures of muscle mass and function in older adults (≥55 y). The data sources included SPORTDiscus, PubMed, and Medline. All the study types involving ω-3 fatty acid supplementation on measures of muscle mass and function in older adults (without disease) were included. The mean differences (MDs) or standardized mean differences (SMDs) with 95% confidence intervals were calculated and pooled effects assessed. Sixteen studies (1660 females, 778 males) met our inclusion criteria and were included in the meta-analysis. ω-3 fatty acid supplementation did not impact lean tissue mass (SMD 0.09 [−0.10, 0.28]). Benefits were observed for lower body strength (SMD 0.54 [0.33, 0.75]), timed-up-and-go (MD 0.29 [0.23, 0.35]s), and 30-s sit-to-stand performance (MD 1.93 [1.59, 2.26] repetitions) but not walking performance (SMD −0.01 [−0.10, 0.07]) or upper body strength (SMD 0.05 [−0.04, 0.13]). Supplementing with ω-3 fatty acids may improve the lower-body strength and functionality in older adults.

From an energy perspective, the brain is very metabolically demanding. It is well documented that creatine plays a key role in brain bioenergetics. There is some evidence that creatine supplementation can augment brain creatine stores, which could increase memory. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effects of creatine supplementation on memory performance in healthy humans. The literature was searched through the PubMed, Web of Science, Cochrane Library, and Scopus databases from inception until September 2021. Twenty-three eligible RCTs were initially identified. Ten RCTs examining the effect of creatine supplementation compared with placebo on measures of memory in healthy individuals met the inclusion criteria for systematic review, 8 of which were included in the meta-analysis. Overall, creatine supplementation improved measures of memory compared with placebo (standard mean difference [SMD] = 0.29, 95%CI, 0.04–0.53; I² = 66%; P = 0.02). Subgroup analyses revealed a significant improvement in memory in older adults (66–76 years) (SMD = 0.88; 95%CI, 0.22–1.55; I² = 83%; P = 0.009) compared with their younger counterparts (11–31 years) (SMD = 0.03; 95%CI, −0.14 to 0.20; I² = 0%; P = 0.72). Creatine dose (≈ 2.2–20 g/d), duration of intervention (5 days to 24 weeks), sex, or geographical origin did not influence the findings. Creatine supplementation enhanced measures of memory performance in healthy individuals, especially in older adults (66–76 years). PROSPERO registration no. 42021281027.