Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review

Abstract

Creatine monohydrate (CrM) is one of the most widely used nutritional supplements among active individuals and athletes to improve high-intensity exercise performance and training adaptations. However, research suggests that CrM supplementation may also serve as a therapeutic tool in the management of some chronic and traumatic diseases. Creatine supplementation has been reported to improve high-energy phosphate availability as well as have antioxidative, neuroprotective, anti-lactatic, and calcium-homoeostatic effects. These characteristics may have a direct impact on mitochondrion’s survival and health particularly during stressful conditions such as ischemia and injury. This narrative review discusses current scientific evidence for use or supplemental CrM as a therapeutic agent during conditions associated with mitochondrial dysfunction. Based on this analysis, it appears that CrM supplementation may have a role in improving cellular bioenergetics in several mitochondrial dysfunction-related diseases, ischemic conditions, and injury pathology and thereby could provide therapeutic benefit in the management of these conditions. However, larger clinical trials are needed to explore these potential therapeutic applications before definitive conclusions can be drawn.

Nutritional Strategies in the Rehabilitation of Musculoskeletal Injuries in Athletes: A Systematic Integrative Review

“…Potential effects of CrM consumption as a therapeutic nutritional agent in clinical conditions have been suggested for some chronic and traumatic diseases (acute injuries, spinal cord injury, postoperative orthopedic recovery, muscular dystrophy, immobility, and atrophy due to muscle disuse, among others) [ 90 ]. Furthermore, CrM supplementation could help in maintaining or improving clinical outcomes by improving physiological adaptations during rehabilitation processes in patients with substantially reduced skeletal muscle contractile capacity [ 91 ], as in the case of sports injuries.…”

Untargeted Metabolomics Analysis of Gingival Tissue in Patients with Severe Periodontitis

“…It can also be converted into phosphocreatine by creatine kinase, an important metabolite involved in ATP metabolism, supplying energy to muscles, nerve tissue, and other organs requiring significant energy . Furthermore, creatine supplementation can modulate acidosis, inflammation, and oxidative stress in cells . Increasingly, researchers have suggested that metabolites can manipulate cellular signaling by directly binding or covalently post-translationally modifying certain proteins to affect cell growth. , Although the direct target of creatine remains to be elucidated, creatine has been proven to modulate Smad2/3 signaling through activation of the monopolar spindle 1 .…”

Creatine maintains mitochondrial integrity and protects against dysfunction in molecular systems involved in early epileptiform activity and cognitive impairment in young rats submitted to traumatic brain injury

“…These experimental data suggest that stabilizing enzymes such as CKm, which play a central role in regulating the metabolic feedback of mitochondrial respiration, attenuate TBI-induced toxicity. This idea is based on the ability of this guanidine compound to stabilize the contact sites of the inner and outer mitochondrial membranes and prevent the opening of mitochondrial permeability pores and, consequently, the excess of oxygen free radicals [55][56][57].…”