Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review, 2022, Marshall et al

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.

Open access, https://www.mdpi.com/2072-6643/14/3/529/htm

 

From the paper,

"9. Chronic Fatigue Syndrome, Post Viral Fatigue Syndrome, and Long COVID

Fatigue is the most characteristic symptom of an energy deficit. There does not, however, exist a proper definition of the fatigue syndrome [259]. Fibromyalgia is a similar pathological entity closely related to CFS. Initially thought to be purely a psychological problem, linking fatigue to depression or other psychiatric diseases, newer research has been able to prove a metabolic dysfunction causing the symptoms [99,260,261]. Linking this clinical state with mitochondrial dysfunction was first able when lowered mitochondrial ATP levels were shown using MRS on patients with fatigue syndrome [262]. Later muscle biopsies and serum biomarkers have been able to show reduced mitochondrial biomarkers [263,264]. These markers have been Carnitine and CoQ10 [265]. On a mitochondrial level fatty acid metabolism was altered, electron transport chain was disrupted, there was a greater need in glucose concentrations and higher levels of lactate were shown [266]. Higher creatinine excretion via urine was shown to correlate positively with fatigue and pain severity. Being the end product of creatine, this urine marker could imply a higher turnover and depletion of the body’s creatine storage [267]. More recent hypotheses state that these alterations have been caused by an activation of immune–inflammatory pathways due to viral infections (e.g., Epstein Barr, Q Fever, Ross River Infection) [268].

Long COVID is a persistent fatigue state after Sars-2-CoV-2 infection [269,270]. Interestingly, even asymptomatic patients exhibited raised biomarkers involved in inflammation and stress response [271]. Long COVID, Chronic Fatigue Syndrome, and Post Viral Fatigue Syndrome are believed to be the same entity [248,272]. Supplementation of guadinioacteic acid, a precursor of creatine, was able to attenuate several aspects of fatigue in fibromyalgia patients [273]. In combination of experimental findings as well as these first promising clinical outcomes, creatine might be an important key in the rehabilitation process of CFS and Long COVID patients [274]. Table 8 summarizes the available literature on the effects of the creatine precursor GAA on chronic fatigue and Post-COVID syndrome [274]."