Creatine and the Liver: Metabolism and Possible Interactions

Abstract

The process of creatine synthesis occurs in two steps, catalyzed by L-arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT), which take place mainly in kidney and liver, respectively. This molecule plays an important energy/pH buffer function in tissues, and to guarantee the maintenance of its total body pool, the lost creatine must be replaced from diet or de novo synthesis. Creatine administration is known to decrease the consumption of Sadenosyl methionine and also reduce the homocysteine production in liver, diminishing fat accumulation and resulting in beneficial effects in fatty liver and non-alcoholic liver disease. Different studies have shown that creatine supplementation could supply brain energy, presenting neuroprotective effects against the encephalopathy induced by hyperammonemia in acute liver failure. Creatine is also taken by many athletes for its ergogenic properties. However, little is known about the adverse effects of creatine supplementation, which are barely described in the literature, with reports of mainly hypothetical effects arising from a small number of scientific publications. Antioxidant effects have been found in several studies, although one of the theories regarding the potential for toxicity from creatine supplementation is that it can increase oxidative stress and potentially form carcinogenic compounds.

Identification of the Potential Metabolic Pathways Involved in the Hepatic Tumorigenesis of Rat Diethylnitrosamine-Induced Hepatocellular Carcinoma via 1H NMR-Based Metabolomic Analysis

“…Creatine is another metabolite participating in energy production, which mainly accumulate in the liver and can help to maintain the fluctuating energy demands [21]. In this study, significantly elevated content of creatine was detected in the DEN-treated liver at the 15 th weeks, but no difference was found at the 3 rd and 8 th week as compared to the level in the normal livers, suggesting that the increased level of creatine was associated with the malignant transformation of hepatocytes as that happening in HCC tissue.…”

Chenopodium Quinoa and Salvia Hispanica Provide Immunonutritional Agonists to Ameliorate Hepatocarcinoma Severity under a High-Fat Diet

“…Animals receiving PIs from C. quinoa displayed pattern changes in creatine levels consistent with an increased utilization of it, which was reflected in a significant reduction of the hepatic production of homocysteine (HCys) ( Figure 5 A). These changes could help explaining the diminished triglycerides accumulation [ 42 , 43 ] in the different groups of treatment ( Figure 3 A). The decreased concentrations of HCys are interpreted as positive effects reducing hepatocytes transformation via 4-epoxyeicosatrienoic acid production (i.e., CYP450 metabolism).…”

Dynamic Analysis of Metabolic Response in Gastric Ulcer (GU) Rats with Electroacupuncture Treatment Using 1H NMR-Based Metabolomics

“…In addition, succinate plays an important role in three carboxylic acid (TCA) cycle and participates in the synthesis of adenosine triphosphate (ATP) [30]. On the other hand, the main role of creatine is to promote the recycling of ATP by providing phosphoric acid groups to adenosine diphosphate (ADP) and transforming it into ATP [31]. In this study, the levels of glycerol and alanine in liver of GU rats were reversed to normal after electroacupuncture treatment for 1 day; the renal levels of glycerol, creatine, and alanine in GU rats reached the normal after electroacupuncture treatment for 4 days.…”