Creatine--its chemical synthesis, chemistry, and legal status.

Creatine, a small molecule present in muscular tissue of many vertebrates, evolves to one of the most widely used and successful dietary supplements of recent decades (Graham and Hatton, 1999). Importantly, in the industrial manufacturing process, a high quality standard must be maintained. Validated analytical methods capable of providing reliable and consistent analysis of the main substance, side products and potentially harmful impurities must be employed. The principles of those determinations and the nature of possible byproducts will be elucidated in this chapter. In addition, the pure creatine produced may be unstable under certain conditions, e.g. within special formulations or galenical forms. Some hints how to deal with this fact and how to avoid instability will also be discussed. Thus, this chapter will serve as a survey of the paths of chemical synthesis of creatine, its chemistry, properties, stability, analytical determination methods and legal status.

Standardization of p-creatinine assays and use of lean body mass allow improved prediction of calculated glomerular filtration rate in adults: a new equation.

OBJECTIVE: To evaluate the Cockcroft-Gault (CG) equation, using various body weight expressions, and the Sawyer equation in predicting glomerular filtration rate (GFR) using an enzymatic and zero-calibrated Jaffe plasma-creatinine assay, and to derive a new robust equation in adults. MATERIAL AND METHODS: The CG weight measures included total, ideal and adjusted body weight (ABW; lowest of total and ideal) and two lean body mass (LBM) expressions, while the Sawyer equation is based primarily on LBM. Iohexol clearance was used to measure GFR. One derivation set (n = 436; enzymatic assay) was used to evaluate and bias-adjust existing equations when indicated, and to derive a new equation based on plasma-creatinine, age, gender and the body weight measure yielding the best adjusted R2. All equations were then validated in a separate set (n = 414; Jaffe assay). RESULTS: The existing equations all performed similarly in both sets. Prediction errors of equations based on LBM showed no correlation with BMI. The CGABW and Sawyer equations performed best. The new equation with LBM yielded the highest adjusted R2. In the combined set (n = 850), its accuracy (86 %/98 % of estimates within 30 %/50 % of measured GFR) was significantly better than for the CGABW (79 %/95 %) and Sawyer equations (79 %/93 %) (p<0.001) for each 30 mL/min GFR subgroup within +/-30 % and +/-50 %, except within +/-30 % >120 mL/min. Prediction error did not correlate with BMI, age or gender. CONCLUSION: A new creatinine-based equation derived in a mainly Caucasian patient sample is a better predictor of GFR than CG-type equations irrespective of the body weight measure used or, if bias-adjusted, when using zero-calibrated creatinine assays.

Quantitative determination of guanidinoacetate and creatine in dried blood spot by flow injection analysis-electrospray tandem mass spectrometry.

BACKGROUND: Guanidinoacetate (GAA) and creatine (Cr) are reliable biochemical markers of primary creatine disorders. The aim of this study was to develop and validate a method for the determination of GAA and Cr in dried blood spot through the use of stable isotope dilution and flow injection analysis (FIA)-ESI-MS/MS. METHODS: Dried blood spots were extracted using methanol-water solution containing D3-Cr. After evaporation and formation of butyl esters, samples were analyzed using multiple reaction monitoring mode (m/z 174.2-->101.1 for GAA, 188.3-->90.1 for Cr and 191.3-->93.1 for D3-Cr). RESULTS: The analysis was very fast (1 min). The detection limits were 0.34 micromol/l of blood and 0.30 micromol/l of blood for Cr and GAA, respectively, and the response was linear over the range 0.25-12.5 micromol/l of blood for GAA and 3.57-624.7 micromol/l of blood for Cr. Recovery range was 93-101% for Cr and 94-105% for GAA and between-run CVs were 5.3% for GAA and 4.5% for Cr. Ion suppression effect was also studied. The method was applied to spots obtained from two patients affected by GAMT deficiency, four patients affected by AGAT deficiency (including a newborn) as well as 282 healthy subjects. CONCLUSIONS: The detection of GAA in dried blood spot by FIA-ESI-MS/MS is a highly reliable and high throughput method for the diagnosis of GAMT and AGAT deficiencies and a possible tool for newborn screening of both these tractable disorders.

Creatine and its application as an ergogenic aid.

Phosphocreatine (PCr) availability is likely to limit performance in brief, high-power exercise because the depletion of PCr results in an inability to maintain adenosine triphosphate (ATP) resynthesis at the rate required. It is now known that the daily ingestion of four 5-g doses of creatine for 5 days will significantly increase intramuscular creatine and PCr concentrations prior to exercise and will facilitate PCr resynthesis during recovery from exercise, particularly in those individuals with relatively low creatine concentrations prior to feeding. As a consequence of creatine ingestion, work output during repeated bouts of high-power exercise has been increased under a variety of experimental conditions. The reduced accumulation of ammonia and hypoxanthine in plasma and the attenuation of muscle ATP degradation after creatine feeding suggest that the ergogenic effect of creatine is achieved by better maintaining ATP turnover during contraction.