Dose-escalation study with supplemental creatine-guanidinoacetate in healthy adults
Keywords:
creatine, guanidinoacetate, homocysteine, dose-escalatingAbstract
Background and aim: A co-administration of creatine and guanidinoacetate (GAA) emerges as a promising dietary intervention yet limited information is currently available regarding its safety for dose-escalating studies. In this open-label pilot study, we assessed the impact of escalating doses of supplemental creatine-GAA on total homocysteine levels (T-Hcy) in the plasma of healthy adults
Methods:Eight young, physically active volunteers (age 22.5 ± 2.2 years, weight 64.1 ± 10.8 kg, height 165.4 ± 7.1; six females) provided informed consent to receive three escalating doses of the mixture, each administered for four weeks.
Results:One-way ANOVA analysis revealed no significant differences in mean T-Hcy levels across the study (P = 0.76). Moreover, no cases of hyperhomocysteinemia (T-Hcy > 15 µmol/L) were observed during the study period.
Conclusions: These findings suggest that the mixture is generally well-tolerated when administered up to three grams each of creatine and GAA over a three-month dose-escalating protocol in healthy adults, with no significant increase in homocysteine levels.
References
Ostojic SM. Co-administration of creatine and guanidinoacetic acid for augmented tissue bioenergetics: A novel approach? Biomed Pharmacother. 2017;91:238-240. doi: 10.1016/j.biopha.2017.04.075.
Semeredi S, Stajer V, Ostojic J, Vranes M, Ostojic SM. Guanidinoacetic acid with creatine compared with creatine alone for tissue creatine content, hyperhomocysteinemia, and exercise performance: A randomized, double-blind superiority trial. Nutrition. 2019;57:162-166. doi: 10.1016/j.nut.2018.04.009.
Seper V, Korovljev D, Todorovic N, Stajer V, Ostojic J, Nesic N, Ostojic SM. Guanidinoacetate-creatine supplementation improves functional performance and muscle and brain bioenergetics in the elderly: a pilot study. Ann Nutr Metab. 2021;77(4):244-247. doi: 10.1159/000518499.
Ostojic SM, Ostojic J, Zanini D, Jezdimirovic T, Stajer V. Guanidinoacetate-creatine in secondary progressive multiple sclerosis: a case report. J Int Med Res. 2022;50(1):3000605211073305. doi: 10.1177/03000605211073305.
Veeranna V, Zalawadiya SK, Niraj A, Pradhan J, Ference B, Burack RC, Jacob S, Afonso L. Homocysteine and reclassification of cardiovascular disease risk. J Am Coll Cardiol. 2011;58(10):1025-33. doi: 10.1016/j.jacc.2011.05.028.
Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015;14:6. doi: 10.1186/1475-2891-14-6.
Chrysant SG, Chrysant GS. The current status of homocysteine as a risk factor for cardiovascular disease: a mini review. Expert Rev Cardiovasc Ther. 2018;16(8):559-565. doi: 10.1080/14779072.2018.1497974.
Ostojic SM. Safety of dietary guanidinoacetic acid: a villain of a good guy? Nutrients. 2021;14(1):75. doi: 10.3390/nu14010075.
Ostojic SM, Todorovic N, Stajer V. Effect of Creatine and guanidinoacetate supplementation on plasma homocysteine in metabolically healthy men and women. Ann Nutr Metab. 2021;77(5):307-308. doi: 10.1159/000518126.
Deminice R, Portari GV, Vannucchi H, Jordao AA. Effects of creatine supplementation on homocysteine levels and lipid peroxidation in rats. Br J Nutr. 2009;102(1):110-6. doi: 10.1017/S0007114508162985.
Peters BA, Hall MN, Liu X, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Ilievski V, Graziano JH, Gamble MV. Low-dose creatine supplementation lowers plasma guanidinoacetate, but not plasma homocysteine, in a double-blind, randomized, placebo-controlled trial. J Nutr. 2015;145(10):2245-52. doi: 10.3945/jn.115.216739.
Van Bavel D, de Moraes R, Tibirica E. Effects of dietary supplementation with creatine on homocysteinemia and systemic microvascular endothelial function in individuals adhering to vegan diets. Fundam Clin Pharmacol. 2019;33(4):428-440. doi: 10.1111/fcp.12442.
Blom HJ, Smulders Y. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis. 2011;34(1):75-81. doi: 10.1007/s10545-010-9177-4.
Froese DS, Fowler B, Baumgartner MR. Vitamin B12 , folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation. J Inherit Metab Dis. 2019;42(4):673-685. doi: 10.1002/jimd.12009.
Gerrard A, Dawson C. Homocystinuria diagnosis and management: it is not all classical. J Clin Pathol. 2022:jclinpath-2021-208029. doi: 10.1136/jcp-2021-208029.
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