There is a long-standing concern that
creatine supplementation could be associated with
cancer, possibly by facilitating the formation of carcinogenic heterocyclic
amines (HCAs). This study provides compelling evidence that both low and high doses of
creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation. HCAs detection was unrelated to
creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo (n = 6) or
creatine supplementation (n = 3). These results directly challenge the recently suggested
biological plausibility for the association between
creatine use and risk of testicular
germ cell cancer.
Creatine supplementation has been associated with increased
cancer risk. In fact, there is evidence indicating that
creatine and/or
creatinine are important precursors of carcinogenic heterocyclic
amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose
creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-
b]pyridine (
PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]
quinoxaline (8-MeIQx), 2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-
b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]
quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose
creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs
PhIP, 8-MeIQx, IFP and
4,8-DiMeIQx were assessed through a newly developed HPLC-MS/MS method. Dietary HCA intake and blood and urinary
creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from
creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2;
PhIP: n = 4). Individual analyses revealed that diet rather than
creatine supplementation was the main responsible factor for HCA formation in these cases. This study provides compelling evidence that both low and high doses of
creatine supplementation, given either acutely or chronically, did not cause increases in the carcinogenic HCAs
PhIP, 8-MeIQx, IFP and
4,8-DiMeIQx in healthy subjects. These findings challenge the long-existing notion that
creatine supplementation could potentially increase the risk of
cancer by stimulating the formation of these
mutagens.