健康と病気におけるクレアチン

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Learn more: PMC Disclaimer | PMC Copyright Notice Nutrients . 2021 Jan 29;13(2):447. doi: 10.3390/nu13020447 Creatine in Health and Disease Richard B Kreider Richard B Kreider 1 Human Clinical Research Facility, Exercise & Sport Nutrition Lab, Department of Health & Kinesiology, Texas A&M University, College Station, TX 77843, USA Find articles by Richard B Kreider 1, * , Jeffery R Stout Jeffery R Stout 2 Physiology of Work and Exercise Response (POWER) Laboratory, Institute of Exercise Physiology and Rehabilitation Science, School of Kinesiology and Physical Therapy, University of Central Florida, 12494 University Blvd., Orlando, FL 32816, USA; [email protected] Find articles by Jeffery R Stout 2 Editor: Iacone Roberto Author information Article notes Copyright and License information 1 Human Clinical Research Facility, Exercise & Sport Nutrition Lab, Department of Health & Kinesiology, Texas A&M University, College Station, TX 77843, USA 2 Physiology of Work and Exercise Response (POWER) Laboratory, Institute of Exercise Physiology and Rehabilitation Science, School of Kinesiology and Physical Therapy, University of Central Florida, 12494 University Blvd., Orlando, FL 32816, USA; [email protected] * Correspondence: [email protected] Roles Iacone Roberto : Academic Editor Received 2020 Dec 8; Accepted 2021 Jan 27; Collection date 2021 Feb. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/ ). PMC Copyright notice PMCID: PMC7910963 PMID: 33572884 Abstract Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported. This is because creatine plays a critical role in cellular metabolism, particularly during metabolically stressed states, and limitations in the ability to transport and/or store creatine can impair metabolism. Moreover, increasing availability of creatine in tissue may enhance cellular metabolism and thereby lessen the severity of injury and/or disease conditions, particularly when oxygen availability is compromised. This systematic review assesses the peer-reviewed scientific and medical evidence related to creatine’s role in promoting general health as we age and how creatine supplementation has been used as a nutritional strategy to help individuals recover from injury and/or manage chronic disease. Additionally, it provides reasonable conclusions about the role of creatine on health and disease based on current scientific evidence. Based on this analysis, it can be concluded that creatine supplementation has several health and therapeutic benefits throughout the lifespan. Keywords: ergogenic aids, cellular metabolism, phosphagens, sarcopenia, cognition, diabetes, creatine synthesis deficiencies, concussion, traumatic brain injury, spinal cord injury, muscle atrophy, rehabilitation, pregnancy, immunity, anti-inflammatory, antioxidant, anticancer 1. Introduction Creatine supplementation is one of the most studied and effective ergogenic aids for athletes [ 1 ]. The multifaceted mechanisms by which creatine exerts its beneficial effect include increasing anaerobic energy capacity, decreasing protein breakdown, leading to increased muscle mass and physical performance [ 1 ]. While these well-recognized creatine effects benefit the athlete, creatine may also serve as a potential clinical and therapeutic supplementary treatment to conventional medical interventions [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. In this regard, over recent years, researchers have been investigating the potential therapeutic role of creatine supplementation on health-related conditions such as diabetes [ 11 ], sarcopenia [ 4 , 6 , 12 , 13 ], osteoporosis [ 2 , 14 ], cancer [ 10 , 15 , 16 , 17 , 18 ], rehabilitation [ 4 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ], cognition [ 3 , 27 , 28 , 29 ], and cardiovascular health [ 5 , 6 , 8 , 30 , 31 , 32 ], among others. This work has increased interest in creatine use as a nutritional strategy to help maintain functional and mental capacity and, as we age, reduce risk to chronic disease, and/or serve as an adjunctive intervention to help manage disease and/or promote recovery. This special issue aims to provide comprehensive reviews of the role of creatine in health and clinical disease. To do so, we have invited a number of top creatine scholars to contribute comprehensive reviews as well as encouraged colleagues to submit meta-analyses and original research to this special issue. As an introduction about creatine’s potential role in health and disease, the following provides a general overview of creatine’s metabolic role, purported benefits throughout the lifespan, and potential therapeutic applications. Additionally, we provide reasonable conclusions about the state of the science on creatine supplementation. This overview will be accompanied by separate, more comprehensive, literature reviews on the metabolic basis of creatine in health and disease as well as the potential role of creatine in pregnancy; children and adolescents; exercise and performance; physical therapy and rehabilitation; women’s health; aging, sarcopenia, and osteoporosis; brain neuroprotection and function; immunity, cancer protection and management; heart and muscle health; and, chronic and post-viral fatigue. We hope that this review and special issue will help readers and medical practitioners better understand the safety and efficacy of creatine supplementation in a variety of populations and provide recommendations about future research needs. 2. Methods A systematic review of the scientific and medical literature was conducted to assess the state of the science related to creatine supplementation on metabolism, performance, health, and disease management. This was accomplished by doing keyword searches related to creatine supplementation on each topic summarized using the National Institutes for Health National Library of Medicine PubMed.gov search engine. A total of 1322 articles were reviewed with relevant research highlighted in this systematic review. 3. Metabolic Role Creatine ( N -aminoiminomethyl- N -methyl glycine) is a naturally occurring and nitrogen-containing compound comprised from amino acids that is classified within the family of guanidine phosphagens [ 1 , 33 ]. Creatine is synthesized endogenously from arginine and glycine by arginine glycine amidinotransferase (AGAT) to guanidinoacetate (GAA). The GAA is then methylated by the enzyme guanidinoacetate N-methyltransferase (GAMT) with S-adenosyl methionine (SAMe) to form creatine [ 34 ]. The kidney, pancreas, liver, and some regions in the brain contain AGAT with most GAA formed in the kidney and converted by GMAT to creatine in the liver [ 35 , 36 , 37 ]. Endogenous creatine synthesis provides about half of the daily need for creatine [ 35 ]. The remaining amount of creatine needed to maintain normal tissue levels of creatine is obtained in the diet primarily from red meat and fish [ 38 , 39 , 40 , 41 ] or dietary supplements [ 1 , 42 , 43 ]. About 95% of creatine is stored in muscle with the remaining amount found in other tissues, like the heart, brain, and testes [ 44 , 45 ]. Of this, about 2/3 of creatine is bound with inorganic phosphate (Pi) and stored as phosphocreatine (PCr) with the remainder stored as free creatine (Cr). The total creatine pool (Cr + PCr) is about 120 mmol/kg of dry muscle mass for a 70 kg individual who maintains a diet that includes red meat and fish. Vegetarians have been reported to have muscle creatine and PCr stores about 20–30% lower than non-vegetarians [ 46 , 47 ]. The body breaks down about 1–2% of creatine in the muscle per day into creatinine which is excreted in the urine [ 46 , 48 , 49 ]. Degradation of creatine to creatinine is greater in individuals with larger muscle mass and individuals with higher physical activity levels. Therefore, a normal-sized individual may need to consume 2–3 g/day of creatine to maintain normal creatine stores depending on diet, muscle mass, and physical activity levels. In fact, Wallimann and colleagues [ 50 ] noted that since creatine stores are not fully saturated on vegan or normal omnivore diets that generally provide 0 or 0.75–1.5 g/day of creatine, daily dietary creatine needs may be in the order of 2–4 g/person/day to promote general health [ 1 , 50 ]. The most effective and rapid way to increase muscle creatine stores is to ingest 5 g of creatine monohydrate four times daily for 5–7 days (i.e., 0.3 g/kg/day) [ 46 , 49 ]. However, some studies have shown that consuming 2–3 g/day of creatine for 30 days can also effectively increase muscle creatine stores [ 46 , 49 ]. Dietary supplementation of 20–30 g/day of creatine monohydrate for up to 5 years has also been studied in some clinical populations who need higher levels to increase brain concentrations of creatine, offset creatine synthesis deficiencies, or influence disease states [ 51 , 52 , 53 ]. Creatine and phosphagens play a critical role in providing energy through the creatine kinase (CK) and PCr system [ 50 , 54 , 55 ]. In this regard, the free energy yielded from the enzymat