The Paradoxical Effect of Creatine Monohydrate on Muscle Damage Markers: A Systematic Review and Meta-Analysis
Authors: Doma Kenji , Ramachandran Akhilesh Kumar , Boullosa Daniel , Connor Jonathan 
Published: February 2022

Abstract
Background
Several studies have examined the effect of creatine monohydrate (CrM) on indirect muscle damage markers and muscle performance, although pooled data from several studies indicate that the benefits of CrM on recovery dynamics are limited.

Objective
This systematic review and meta-analysis determined whether the ergogenic effects of CrM ameliorated markers of muscle damage and performance following muscle-damaging exercises.

Methods
In total, 23 studies were included, consisting of 240 participants in the CrM group (age 23.9 ± 10.4 years, height 178 ± 5 cm, body mass 76.9 ± 7.6 kg, females 10.4%) and 229 participants in the placebo group (age 23.7 ± 8.5 years, height 177 ± 5 cm, body mass 77.0 ± 6.6 kg, females 10.0%). These studies were rated as fair to excellent following the PEDro scale. The outcome measures were compared between the CrM and placebo groups at 24–36 h and 48–90 h following muscle-damaging exercises, using standardised mean differences (SMDs) and associated p-values via forest plots. Furthermore, sub-group analyses were conducted by separating studies into those that examined the effects of CrM as an acute training response (i.e., after one muscle-damaging exercise bout) and those that examined the chronic training response (i.e., examining the acute response after the last training session following several weeks of training).

Results
According to the meta-analysis, the CrM group exhibited significantly lower indirect muscle damage markers (i.e., creatine kinase, lactate dehydrogenase, and/or myoglobin) at 48–90 h post-exercise for the acute training response (SMD − 1.09; p = 0.03). However, indirect muscle damage markers were significantly greater in the CrM group at 24 h post-exercise (SMD 0.95; p = 0.04) for the chronic training response. Although not significant, a large difference in indirect muscle damage markers was also found at 48 h post-exercise (SMD 1.24) for the chronic training response. The CrM group also showed lower inflammation for the acute training response at 24–36 h post-exercise and 48–90 h post-exercise with a large effect size (SMD − 1.38 ≤ d ≤  − 1.79). Similarly, the oxidative stress markers were lower for the acute training response in the CrM group at 24–36 h post-exercise and 90 h post-exercise, with a large effect size (SMD − 1.37 and − 1.36, respectively). For delayed-onset muscle soreness (DOMS), the measures were lower for the CrM group at 24 h post-exercise with a moderate effect size (SMD − 0.66) as an acute training response. However, the inter-group differences for inflammation, oxidative stress, and DOMS were not statistically significant (p > 0.05).

Conclusion
Overall, our meta-analysis demonstrated a paradoxical effect of CrM supplementation post-exercise, where CrM appears to minimise exercise-induced muscle damage as an acute training response, although this trend is reversed as a chronic training response. Thus, CrM may be effective in reducing the level of exercise-induced muscle damage following a single bout of strenuous exercises, although training-induced stress could be exacerbated following long-term supplementation of CrM. Although long-term usage of CrM is known to enhance training adaptations, whether the increased level of exercise-induced muscle damage as a chronic training response may provide potential mechanisms to enhance chronic training adaptations with CrM supplementation remains to be confirmed.