Effects of creatine supplementation on the formation of heterocyclic aromatic amines in humans

• Grant number: 13/00632-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2013
• End date: March 31, 2015
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Bruno Gualano
• Grantee: Renato Tavares dos Santos Pereira
• Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Creatine has been considered as an effective dietary supplement able to not only improve muscle mass and exercise performance in healthy subjects, but also alleviate symptoms in diseases mainly characterized by muscle atrophy. However, it has been speculated that creatine could shown carcinogenic effects. The food cocking is associated with the formation of mutagenic substances that are known chemically as amino-imidazoazaarenes (so-called heterocyclic aromatic amines, or just HCA). The most important HCA are 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), Imidazol- pyridine (IFP), and 2-amino-3,8dimethylimidazo[4,5-f]quinoxaline (DiMeIQx). The formation of HCA is a result of the conjugation of creatine/creatinine, aminoacids and hexoxes. Given the imminent role of HCA in carcinogenesis, as well as its underlying mechanisms of formation, it is important to investigate the possible influence of creatine supplementation upon HCA formation. The aim of the project is to investigate the role of creatine supplementation on the formation of HCA and its metabolites. To that end, it will be performed a prospective, cross-over, single-blind trial, in which 15 healthy subjects will be given glucose (placebo, 4 x 5g/d for 7 d) and afterwards creatine (4 x 5g/d for 7 d). At baseline and after each intervention (i.e., placebo and creatine), it will be assessed urinary HCA concentration (i.e., MeIQx, 4,8-DiMeIQx, PhIP, and IFP) by high performance liquid chromatograph (HPLC) attached to a mass spectrometer (LC-MS/MS). Food ingestion will be evaluated by 3 d 24-h food records at baseline and after each intervention to ensure the HCA formation is not a consequence of changes in food ingestion. Data will be presented as individual data, mean, standard deviation, estimated difference between means, and confidence interval. Possible differences between means will be tested by Mixed Model (SAS) for repeated measures and, when pertinent, Tukey's post-hoc for multiple comparisons. Significance level was previously set at p < 0.05.