Table 1.
Pleiotropic effects of creatine for cell function and cell protection
| Energy-related effects of creatine | |
| Cr improves cellular energy state (PCr/ATP ratio) and muscle performance | (Harris et al. 1992; Greenhaff et al. 1993) |
| Cr facilitates intracellular energy transport (PCr circuit or shuttle) | (Wallimann 1975; Saks et al. 1978, 2006b; Bessman and Geiger 1981; Wallimann and Eppenberger 1985; Bessman 1986; Wallimann et al. 1992, 1998; Kaasik et al. 2003; Wallimann et al. 2007) |
| Cr improves the efficiency of cellular energy utilization (e.g. for Ca2+-handling) | (Rossi et al. 1990; Steeghs et al. 1997; Pulido et al. 1998; van Leemputte et al. 1999) |
| Cr stimulates mitochondrial respiration (improved energy provision) | (Kay et al. 2000; Meyer et al. 2006) |
| Cr stabilizes mitochondrial PTP complex and thus acts as mitochondrial protectant (anti-apoptotic) | (O’Gorman et al. 1997a; Dolder et al. 2003; Hatano et al. 2004) |
| Anti-oxidant and anti-apoptotic effects of creatine | |
| Cr acts as a mild direct anti-oxidant (free radical scavenger) | (Lawler et al. 2002) |
| Cr acts as a strong indirect anti-oxidant in mitochondria (where ROS production is lowered by tight coupling of respiration/ATP production to ATP export) | (Meyer et al. 2006; Sestili et al. 2006) |
| Cr reduces oxidative damage to DNA, specifically to mtDNA | (Guidi et al. 2008) |
| Cr up-regulates enzymes for oxidative stress defence | (Young et al. 2010) |
| Cr strongly protects in vivo from mitochondrial toxins (Rotenone & Paraquat) | (Hosamani et al. 2010) |
| Cr stabilizes mitochondrial PTP complex and thus acts as mitochondrial protectant (anti-apoptotic) | (O’Gorman et al. 1997a; Dolder et al. 2003; Hatano et al. 2004) |
| Other effects of creatine | |
| Cr induces differential expression of transcription factors and other genes | (Hespel et al. 2001; Louis et al. 2004; Deldicque et al. 2008; Safdar et al. 2008) |
| Cr reduces the appearance of inflammation markers during endurance exercise | (Santos et al. 2004; Bassit et al. 2008) |
| Cr activates cell signalling and enhances muscle cell differentiation | (Ceddia and Sweeney 2004; Louis et al. 2004; Deldicque et al. 2007, 2008) |
| Cr lowers homocysteine levels and lipid peroxidation (heart risk factors) | (Deminice et al. 2009) |
| Cr acts as an osmolyte, protecting cells against hypertonic stress | (Alfieri et al. 2006) |
| PCr binds to cell membranes and stabilizes and protects erythrocyte cell membranes | (Saks et al. 1996; Tokarska-Schlattner et al. 2003, 2005a) |