Subcell Biochem. 2007;46:275-89.
Safety of creatine supplementation.
Persky AM, Rawson ES.
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
The literature on creatine supplementation supporting its efficacy has grown rapidly and has included studies in both healthy volunteers and patient populations. However, the first rule in the development of therapeutic agents is safety. Creatine is well-tolerated in most individuals in short-term studies. However, isolated reports suggest creatine may be associated with various side effects affecting several organ systems including skeletal muscle, the kidney and the gastrointestinal tract. The majority of clinical studies fail to find an increased incidence of side effects with creatine supplementation. To date, studies have not found clinically significant deviations from normal values in renal, hepatic, cardiac or muscle function. Few data are available on the long-term consequences of creatine supplementation.
Subcell Biochem. 2007;46:261-73.
Pharmacokinetics of creatine.
McCall W, Persky AM.
Division of pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
Research has demonstrated that creatine supplementation has some therapeutic benefit with respect to muscle function and more recently neurological function. Despite the growing body of literature on the pharmacologic effect of creatine, very little is known about the disposition of creatine after supraphysiologic doses. The movement of creatine throughout the body is governed by transport processes which impact the absorption of creatine from the intestine, clearance of creatine from the kidney, and access of creatine to target tissues. With repeated doses of creatine, it appears that the clearance of creatine decreases mainly due to the saturation of skeletal muscle stores. Insulin and insulin-stimulating foods appear to enhance muscle uptake of creatine but at the same time, high carbohydrate meals may slow the absorption of creatine from the intestine. Little is known about creatine disposition in special populations including the elderly and patients with neuromuscular disease. Knowledge of creatine disposition in these clinically relevant populations can help remove some of the guess work of dose selection during clinical trials.
Subcell Biochem. 2007;46:205-43.
The neuroprotective role of creatine.
Klein AM, Ferrante RJ.
Neurology Department, Brigham and Womens Hospital, Boston, MA 02115, USA; and Harvard Medical School, Boston, MA 02115, USA.
Significant progress has been made in identifying neuroprotective agents and their translation to patients with neurological disorders. While the direct causative pathways of neurodegeneration remain unclear, they are under great clinical and experimental investigation. There are a number of interrelated pathogenic mechanisms triggering molecular events that lead to neuronal death. One putative mechanism reported to play a prominent role in the pathogenesis of neurological diseases is impaired energy metabolism. If reduced energy stores play a role in neuronal loss, then therapeutic strategies that buffer intracellular energy levels may prevent or impede the neurodegenerative process. Recent studies suggest that impaired energy production promotes neurological disease onset and progression. Sustained ATP levels are critical to cellular homeostasis and may have both direct and indirect influence on pathogenic mechanisms associated with neurological disorders. Creatine is a critical component in maintaining cellular energy homeostasis, and its administration has been reported to be neuroprotective in a wide number of both acute and chronic experimental models of neurological disease. In the context of this chapter, we will review the experimental evidence for creatine supplementation as a neurotherapeutic strategy in patients with neurological disorders, including Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease, as well as in ischemic stroke, brain and spinal cord trauma, and epilepsy.
Med Sci Sports Exerc. 2008 Aug 5. [Epub ahead of print]
Low-Dose Creatine Combined with Protein during Resistance Training in Older Men.
Candow DG, Little JP, Chilibeck PD, Abeysekara S, Zello GA, Kazachkov M, Cornish SM, Yu PH.
1Faculty of Kinesiology and Health Studies, University of Regina, Regina, Saskatchewan, CANADA; and 2College of Kinesiology,3College of Pharmacy and Nutrition, and 4Department of Psychiatry, Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, Saskatchewan, CANADA.
PURPOSE: To determine whether low-dose creatine and protein supplementation during resistance training (RT; 3 d.wk; 10 wk) in older men (59-77 yr) is effective for improving strength and muscle mass without producing potentially cytotoxic metabolites (formaldehyde). METHODS:: Older men were randomized (double-blind) to receive 0.1 g.kg creatine + 0.3 g.kg protein (CP; n = 10), creatine (C; n = 13), or placebo (PLA; n = 12) on training days. Measurements before and after RT included lean tissue mass (air-displacement plethysmography), muscle thickness (ultrasound) of elbow, knee, and ankle flexors and extensors, leg andbench press strength, and urinary indicators of cytotoxicity (formaldehyde), myofibrillar protein degradation [3-methylhistidine (3-MH)],and bone resorption [cross-linked N-telopeptides of type I collagen (NTx)]. RESULTS:: Subjects in C and CP groups combined experienced greater increases in body mass and total muscle thickness than PLA (P < 0.05). Subjects who received CP increased lean tissue mass (+5.6%) more than C (+2.2%) or PLA (+1.0%; P < 0.05) and increased bench press strength (+25%) to a greater extent than C and PLA combined (+12.5%; P < 0.05). CP and C did not differ from PLA for changes in formaldehyde production (+24% each). Subjects receiving creatine (C and CP) experienced a decrease in 3-MH by 40% compared with an increase of 29% for PLA (P < 0.05) and a reduction in NTx (-27%) versus PLA (+13%; P = 0.05). CONCLUSIONS:: Low-dose creatine combined with protein supplementation increases lean tissue mass and results in a greater relative increase in bench press but not leg press strength. Low-dose creatine reduces muscle protein degradation and bone resorption without increasing formaldehyde production.
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