This article is part of our May 2022 Healthy Aging special issue. Download the full issue here.
Dos Santos EEP, de Araújo RC, Candow DG, et al. Efficacy of creatine supplementation combined with resistance training on muscle strength and muscle mass in older females: a systematic review and meta-analysis. Nutrients. 2021;13(11):3757.
To determine the influence of creatine and resistance training on muscle strength and mass in older females through systemic review and meta-analysis
Creatine supplementation is a promising and safe intervention to aid resistance training in older females to reduce dynapenia.
Systematic review and meta-analysis
In the systematic review, investigators included 10 randomized controlled trials. Participant total was 211. Investigators initially identified a total of 543 studies and 2 additional studies from gray literature, but only 12 met eligibility criteria following screening.
Studies met the criteria if they compared creatine only (versus a combination of ingredients) and resistance training to placebo in older females (aged greater than 60 years) and used the outcome measures of muscle strength and/or muscle mass.
Studies that did not include a placebo control group were excluded, as was a trial that recruited patients with neurodegenerative disease. Two additional studies were not evaluated in the meta-analysis due to lack of access to the raw data.
Study Parameters Assessed
As far as quality of the evidence, investigators assigned a PEDro score to each study included in the analysis. Scores ranged from 6 to 9 with an average PEDro score of 7.7. PEDro scores refer to the Physiotherapy Evidence Database and are scored between 0 and 11, where 11 is the highest quality of evidence. Imprecision was determined to be high in the meta-analysis, and the quality of the evidence, according to GRADE (Grading of Recommendations, Assessment, Development and Evaluation), was low, indicating limited confidence in the effect size. Wide confidence intervals and sample sizes lower than 300 contributed to this quality rating.
Risk of bias was minimized as studies with low PEDro scores were not used, and publication bias due to using fewer than 10 studies was not seen in this analysis.
Overall, creatine significantly increased upper-body strength (7 studies with 142 participants [P=0.04]) but had no effect on lower-body strength or muscle mass of upper or lower body. However, when studies had a duration of greater than 24 weeks, both upper-body strength (P=0.05) and lower-body strength (P=0.03) increased in the creatine groups, again without any significant changes in muscle mass.
As disclosed by the authors: “D.G.C. has conducted industry sponsored research involving creatine supplementation, received creatine donation for scientific studies and travel support for presentations involving creatine supplementation at scientific conferences. In addition, D.G.C. serves on the Scientific Advisory Board for Alzchem (a company which manufactures creatine). S.C.F. has previously served as a Scientific Advisor for a company that sold creatine.”
Practice Implications & Limitations
Increased risks of disability, frailty, and falls are relevant to aging patients due, in part, to the physiologic and functional declines associated with sarcopenia, which includes the loss of muscle mass and strength.1 Dynapenia is specifically the loss of muscle strength.
Strength improvement and increasing muscle mass also have metabolic benefits, including countering insulin resistance. These 2 benefits alone support the recommendation of resistance training in aging patients.2 An additional promising benefit of resistance training is support of mitochondrial function within muscle cells, which also declines with age.3
Physical activity and exercise are well-established countermeasures against muscle aging and the sequalae of age-related decreases in muscle mass, strength, and regenerative capacity, as well as impairments in muscle metabolism.4 Maximizing this effect with additional diet, lifestyle, or supplemental support is often a strategy used by integrative medicine clinicians. Creatine (creatine monohydrate) is an intervention worthy of consideration.
In primary care as well as specialty settings, the use of creatine often arouses discussion of safety especially as it relates to renal and liver function. However, in a position statement from the International Society of Sports Nutrition, a review of the available evidence suggests that both short-term and long-term supplementation is safe and well-tolerated in healthy individuals.5 This review also concluded older adults tolerated creatine supplementation well.
Dynapenia is specifically the loss of muscle strength."
Most studies evaluating creatine supplementation report no adverse events, even when renal and liver function were assessed.6,7,8
A prior systemic review and meta-analysis concluded that postmenopausal females can safely use supplemental creatine.9 Being mindful of one’s responsibility to the individual patient, practitioners can corroborate confidence of safety by monitoring with liver function tests (ALT [alanine aminotransferase], AST [aspartate aminotransferase]) as well as renal function tests (BUN [blood urea nitrogen], creatinine). Individualization of patient management requires judgement of the practitioner.
For older females, recommending resistance exercise 2 to 3 times per week using compound or multijoint movements such as chest press, bench press, leg press, and hack squat is a relevant intervention. Statistical significance for strength was reached in this meta-analysis of creatine plus resistance training, but the effect size has limited confidence. Thus, it is somewhat challenging to help a patient understand how much the addition of creatine may help, and if it is worth the cost and effort of forming a new habit.
In the studies included in this review publication, the dosing of creatine ranged from 5 g daily (typical maintenance dose) to 20 g daily for 5 to 7 days, followed by 5 g daily, or a weight-based dosing of 0.1 g per kg daily (for a 150-pound individual, this equates to 6.8 g). Optimal or preferred dosing has not been determined.
From this review the greatest muscle strength benefit suggests exercise duration of more than 24 weeks, but some benefits in upper body strength may be achieved in only 12 weeks. Perhaps the most relevant clinical implication from this systematic review and meta-analysis is that monitoring progress of a resistance-training and creatine regimen in older females should focus on muscle strength rather than muscle mass. Upper-body strength improvements are likely noticed earlier than lower-body strength. Similarly executed reviews in older adults previously suggested improvements in both muscle strength and mass, but these reviews included both males and females.8 The addition of creatine to resistance-training recommendations in older females is promising but still largely based on preference of the patient and individualization of care.