Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review
Abstract
:1. Introduction
2. Methods
3. Creatine’s Ergogenic Role in Mitochondrial Dysfunction
3.1. Acute, Traumatic Mitochondrial Dysfunction
3.2. Chronic, Atraumatic Mitochondrial Dysfunction
4. Noncommunicable Chronic Diseases (NCD)
5. Cardiovascular Disease and Ischemic Heart Failure
6. Traumatic and Ischemic Central Nervous System Injuries
7. Neurodegenerative Disorders
8. Psychological Disorders
9. Chronic Fatigue Syndrome, Post Viral Fatigue Syndrome, and Long COVID
10. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study | Disease | Subject | Treatment | Randomized | Subjects | Efficacy | Effect Role |
---|---|---|---|---|---|---|---|
Sakellaris et al. [71] | Traumatic brain injury | Human | 0.4 g/kg per day for 6 months | Yes | 39 | Improved self-care, cognition, behavior functions and communication | Direct effect on disease |
Sakellaris et al. [72] | Traumatic brain injury | Human | 0.4 g/kg per day for 6 months | Yes | 39 | Reduced fatigue, headache and dizziness | Direct effect on disease |
Study | Disease | Subject | Treatment | Randomized | Subjects | Efficacy | Effect Role |
---|---|---|---|---|---|---|---|
Guimarães-Ferreira et al. [128] | - | Animal/vitro | 5 g/kg per day for 6 days | no | 39 | Decrease in ROS in muscle tissue | Anima model |
Kato et al. [124] | Bipolar disorder | Humans | None | No | 25 (disease) vs. 21 (control) | Abnormal energy phosphate metabolism in bipolar disorder | No intervention, only descriptive, observational findings |
Study | Disease | Subject | Treatment | Randomized | Subjects | Efficacy | Effect Role |
---|---|---|---|---|---|---|---|
Rider et al. [151] | Obesity | Human | None | None | 64 | Deranged cardiac energetics and diastolic dysfunction in obesity group | Observational, disease related changes in metabolism |
Scheuermann-Freestone et al. [150] | Diabetes Type 2 | Human | None | None | 36 | Impaired myocardial and skeletal muscle metabolism (reduced PCR/ATP ratio) | Observational disease related changes in metabolism |
Lamb et al. [152] | Hypertension | Human | None | None | 24 | Altered high-energy phosphate metabolism in hypertension. Cardiac dysfunction correlates with metabolic alterations | Observational, disease related changes in metabolism |
Gualano et al. [164] | Diabetes Type 2 | Human | 5 g creatine for 12 weeks + physical activity program | Yes | 25 | Improved glycemic control in supplementation group (by GLUT-4 recruitment) | Direct effect on disease related metabolic effects |
Earnest et al. [165] | Hyper-cholester-inaemia | Human | 4 × 5 g creatine for 5 days and afterwards 2 times per day for 51 days (orally) | Yes | 34 | Minor reduction of total cholesterol during supplementation. Reduction of triacylglycerol’s and very-low-density-lipoprotein c 4 weeks after finishing supplementation | Direct effect of supplementation on metabolism. |
Deminice et al. [166] | Fatty liver | Animal | Control vs. 0.25% choline diet vs. 0.25% choline + 2% creatine diet | None | 24 | Prevention of fat liver accumulation and hepatic events in creatine-fed group | Animal model |
Study | Disease | Subject | Treatment | Randomized | Subjects | Efficacy | Effect Role |
---|---|---|---|---|---|---|---|
Elgebaly et al. [187] | - | Animal/vitro | 500 mg/kg BW | no | 6 | Better aortic flow, coronary flow, cardiac output, stroke volume, and stroke work | Animal model |
Cisowski et al. [188] | Cardiac surgery | Humans | 6 g 3 days pre-surgery, intra-surgical and two days post- surgery i.v. | yes | 40 | Reduced arrhythmic events, reduced need of ionotropic medication | Direct effect on surgical procedure |
Ruda et al. [189] | Ischemic myocardial infarct | human | 2 g bolus + 4 g/h over 2 h | Yes | 60 | Reduced arrhythmic events | Direct effect on short term outcome |
Chida et al. [192] | Dilated Cardio-myopathy | Human | None | None | 13 | Plasma BNP level was correlated negatively with the myocardial phosphocreatine/adenosine triphosphate | Observational finding |
Roberts et al. [191]. | None | Animal | Oral creatine-feeding | None | Not clear | Higher cellular ATP during ischemia in creatine-fed rat hearts | Animal model |
Study | Disease | Subject | Treatment | Randomized | Subjects | Efficacy | Effect Role |
---|---|---|---|---|---|---|---|
Zhu et al. [206] | None/induced ischemia | Animal | 2% creatine-supplemented diet for 4 weeks | None | 6 per group | Reduction in ischemia induced infarct size | Animal model |
Turner et al. [205] | None/induced hypoxia | Human | 7-ds oral creatine-supplementation | Yes | 15 | Less decrease in cognitive performance, attentional capacity, corticomotor excitability for creatine-group | Human brain metabolism |
Hausmann et al. [207] | None/induced spinal cord injury | Animal | 4 weeks oral creatine-supplementation | none | 20 | Better locomotor scores after 1 week for creatine-group. Less scar tissue for creatine-group after 2 weeks | Animal model |
Sullivan et al. [208] | None/induced traumatic brain injury | Animal | Mice: 0.1 mL/10 g/BW creatine monohydrate injection for 1, 3 or 5 days | none | 40 mice/24 rats | Reduction of brain tissue damage size by 36% mice and 50% rats | Animal model |
Rats: 1% creatine diet for 4 weeks. | |||||||
Prass et al. [209] | None/induced experimental stroke | Animal | Creatine-rich diet (0%, 0.5%, 1%, 2% for 3 weeks | None | Unclear | Reduction of infarct size by 40% in 2% creatine-fed group | Animal model |
Study | Disease | Subject | Treatment | Randomized | Subjects | Efficacy | Effect Role |
---|---|---|---|---|---|---|---|
Hammett et al. [234] | None | Human | 20 g/d creatine for 5 days + 5 g/d for 2-days | Yes | 22 | Reduction of stress related blood oxygen level dependent in fMRI in creatine-group | Human metabolic response |
Watanabe et al. [235] | None | Human | 8 g/d for 5-days | Yes | 24 | Reduction of mental fatigue and increased brain oxygen consumption in creatine-group | Human metabolic response |
McMorris et al. [236] | None | Human | 4 × 5 g/d | yes | 20 | Better in central complex executive tasks with creatine while sleep deprivation | Human metabolic response |
McMorris et al. [45] | None | Human | 4 × 5 g/d | Yes | 15 | random number generation, forward number and spatial recall, and long-term memory | Human metabolism |
Study | Disease | Subject | Treatment | Randomized | Subjects | Efficacy | Effect Role |
---|---|---|---|---|---|---|---|
Kondo et al. [250] | Adolescent major depressive disorder | Human | 4 g/d creatine for 8 weeks | None | 15 | Reduction in children-depression symptom scores. Significant increase in brain phosphocreatine level. | Direct effect on disease (no RCT) |
Roitman et al. [251] | Treatment resistant depression | Human | 3–5 g/d creatine for 4 weeks | None | 8 unipolar depressed patients and two bipolar patients | Development of hypomania/mania in bipolar patients. Improved Hamilton Depression Rating Scale, Hamilton Anxiety Scale, and Clinical Global Impression for 7 of 8 unipolar depressed patients | Direct effect on disease (no RCT) |
Toniolo et al. [252] | Depressive episode of Bipolar Type 1 and Type 2 | Human | 6 g/d creatine for 6 weeks | Yes | 35 | No significant difference in Montgomery-Åsberg Depression Rating Scale by intervention but higher remission rate in creatine supplemented group | Direct effect on disease |
Kondo et al. [255] | Adolescent with SSRI resistant major depressive disorder | Human | 0 g vs. 2 g vs. 4 g vs. 10 g creatine supplementation for 8 weeks | Yes | 34 | Clinical depression scores correlated inversely with brain phosphocreatine (PCR) levels. PCR level improved with higher dose. | Potential direct effect on disease |
Study | Disease | Subject | Treatment | Randomized | Subjects | Efficacy | Effect Role |
---|---|---|---|---|---|---|---|
Ostojic et al. [264] | Chronic Fatigue syndrome | Human | 2 g, 4 g oral Guanidinoacetic Acid for 3 months vs. placebo | Yes | 21 | Higher muscle creatine-phosphate level and better oxidative capacity. However, no significant improvement of fatigue symptoms | Direct effect on disease related metabolism |
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Marshall, R.P.; Droste, J.-N.; Giessing, J.; Kreider, R.B. Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review. Nutrients 2022, 14, 529. https://doi.org/10.3390/nu14030529
Marshall RP, Droste J-N, Giessing J, Kreider RB. Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review. Nutrients. 2022; 14(3):529. https://doi.org/10.3390/nu14030529
Chicago/Turabian StyleMarshall, Robert Percy, Jan-Niklas Droste, Jürgen Giessing, and Richard B. Kreider. 2022. "Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review" Nutrients 14, no. 3: 529. https://doi.org/10.3390/nu14030529