Article

Creatine and Creatinine Metabolism

F. Hoffmann-La Roche, Vitamins and Fine Chemicals Division, Basel, Switzerland.
Physiological Reviews (Impact Factor: 27.32). 08/2000; 80(3):1107-213.
Source: PubMed

ABSTRACT

The goal of this review is to present a comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the pathways and regulation of Cr biosynthesis and degradation, species and tissue distribution of the enzymes and metabolites involved, and of the inherent implications for physiology and human pathology. Very recently, a series of new discoveries have been made that are bound to have distinguished implications for bioenergetics, physiology, human pathology, and clinical diagnosis and that suggest that deregulation of the creatine kinase (CK) system is associated with a variety of diseases. Disturbances of the CK system have been observed in muscle, brain, cardiac, and renal diseases as well as in cancer. On the other hand, Cr and Cr analogs such as cyclocreatine were found to have antitumor, antiviral, and antidiabetic effects and to protect tissues from hypoxic, ischemic, neurodegenerative, or muscle damage. Oral Cr ingestion is used in sports as an ergogenic aid, and some data suggest that Cr and creatinine may be precursors of food mutagens and uremic toxins. These findings are discussed in depth, the interrelationships are outlined, and all is put into a broader context to provide a more detailed understanding of the biological functions of Cr and of the CK system.

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    ABSTRACT: A variety of dietary interventions has been used in the management of chronic fatigue syndrome (CFS), yet no therapeutic modality has demonstrated conclusive positive results in terms of effectiveness. The main aim of this study was to evaluate the effects of orally administered guanidinoacetic acid (GAA) on multidimensional fatigue inventory (MFI), musculoskeletal soreness, health-related quality of life, exercise performance, screening laboratory studies, and the occurrence of adverse events in women with CFS. Twenty-one women (age 39.3 ± 8.8 years, weight 62.8 ± 8.5 kg, height 169.5 ± 5.8 cm) who fulfilled the 1994 Centers for Disease Control and Prevention criteria for CFS were randomized in a double-blind, cross-over design, from 1 September 2014 through 31 May 2015, to receive either GAA (2.4 grams per day) or placebo (cellulose) by oral administration for three months, with a two-month wash-out period. No effects of intervention were found for the primary efficacy outcome (MFI score for general fatigue), and musculoskeletal pain at rest and during activity. After three months of intervention, participants receiving GAA significantly increased muscular creatine levels compared with the placebo group (36.3% vs. 2.4%; p < 0.01). Furthermore, changes from baseline in muscular strength and aerobic power were significantly greater in the GAA group compared with placebo (p < 0.05). Results from this study indicated that supplemental GAA can positively affect creatine metabolism and work capacity in women with CFS, yet GAA had no effect on main clinical outcomes, such as general fatigue and musculoskeletal soreness.
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    • "In relevance to this, the decrease in lipid metabolism exhibited by CA extract observed in our study could also be affected by the same mechanism. Creatinine, a degradation product of creatine, is biosynthesized from arginine and glycine in the muscles (Walker, 1961; Wyss and Kaddurah-Daouk, 2000; Brosnan and Brosnan, 2010). In this study, the urine and serum creatinine levels in diabetic rats were lower in comparison to normal rats. "
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    • "Creatine has also been shown to play a role in the growth of dendrites and axons , and migration of growth cones ( Wallimann et al . , 1992 ; Wyss and Kaddurah - Daouk , 2000 ) . The presence of SLC6A8 and GAMT mRNA in neuronal processes such as axons and dendrites might allow for the transport of these transcripts away from the cell body , for protein translation at sites of developmental growth that require creatine as an energy source ( Braissant et al . "
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