Safety of GAA plus creatine
- Post by: Admin
- August 31, 2025
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Guanidinoacetic acid (GAA) is the precursor to creatine. Preliminary studies indicate that GAA supplementation (e.g. 2–3 g/d for 4 weeks) can increase brain creatine to a similar degree as higher amounts of CrM. However, more research is needed to assess the efficacy of long-term higher-dose CrM supplementation on cognitive function and whether GAA may provide similar or additive benefits. Additionally, since GAA is involved in homocysteine synthesis, more research is needed to evaluate whether GAA supplementation adversely affects homocysteine levels. This study examined whether CrM and/or GAA supplementation affects health markers. 66 healthy and recreationally active adults (40.6 ± 14 years, 78.5 ± 2.1 kg, 37 female) were administered in a double-blind and randomized manner either a placebo (PLA), CrM (2 × 5 g/d), GAA (2 × 1 g/d), or CrM + GAA for six weeks. Prior to and following supplementation, participants donated fasting blood samples. Blood samples were evaluated for clinical health markers as well as creatinine, homocysteine, estimated glomerular filtration rate (eGFR), and HbA1c. Data were analyzed using General Linear Model multivariate and univariate with repeated measures and mean changes from baseline with 95% confidence intervals with LSD and Bonferroni pairwise comparisons. Data are presented as mean percent changes from baseline with 95% CI (LL, UL). Analysis of blood data revealed significant group ×time interaction effects in creatinine (p = 0.041) and HbA1c (p = 0.011) while homocysteine levels tended to interact (p = 0.077). Creatinine levels increased in the CrM (0.083 mg/dL [0.02, 0.14), p = 0.006) and CrM + GAA groups (0.084 mg/dL [0.04, 0.13), p = 0.001), although the changes were small, remained low (mean 0.93 mg/dL [0.88, 0.99]), and were not significantly different among groups. Homocysteine significantly decreased with CrM (−1.3 µmol/L [−2.5, −0.10], p = 0.034) and tended to be lower than the CrM + GAA group (−1.76 µmol/L [−3.6, 0.11], p = 0.064), although values ranged between 8.3–10.1 µmol/L (mean 9.2 µmol/L [8.6, 9.8]) and were well below clinically significant levels (i.e. > 15 µmol/L). eGFR levels significantly decreased in the CrM + GAA group (−7.5 mL/min/1.73 m2 [−12.2, −2.7], p = 0.003), but no significant differences were observe among groups, all values were > 83 mL/min/1.73 m2 (mean 93.4 mL/min/1.73 m2 [88.5, 98.2]), values were well above clinically significant levels (i.e. < 60 mL/min/1.73 m2), and this may be misleading since creatine supplementation may increase creatinine levels. HbA1c was significantly decreased in the CrM group (−0.2% [−0.33, −0.064] p = 0.005), but these changes were small (mean 5.7% [4.5, 6.0]) and within normal ranges. Percent changes from baseline. There was some evidence that changes in creatinine (p = 0.077), homocysteine (p = 0.099), and HbA1c (p = 0.027) differed among groups. LSD pairwise comparison analysis revealed that changes in creatinine were greater in the CrM and CrM + GAA groups, while homocysteine and HbA1c concentrations decreased with CrM. However, only the reduction in HbA1c levels was significant when using the Bonferroni correction for pairwise comparisons (CrM −3.5% [−6.8, −0.3], p = 0.028 from PLA; −3.5% [−7.1, 0.06], p = 0.057) from CrM + GAA). No significant multivariate differences were observed among whole blood red and white cell counts (p = 0.913), markers of catabolism and liver function (p = 0.417), electrolytes (p = 0.565), or blood lipids (p = 0.024). No side effects were reported. CrM supplementation (10 g/d) with or without GAA (2 g/d) does not negatively affect homocysteine or clinical blood markers in healthy adults. These findings suggest that CrM and GAA can be safely used as a means of improving cognitive function for at least up to 6 weeks.