Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 26311810 · doi:10.3945/jn.115.216739
What was done
A double-blind, randomized, placebo-controlled trial in Bangladeshi adults evaluated the effects of 12 weeks of supplementation across 4 parallel arms: placebo (n = 101), 3 g/day creatine (Cr; n = 101), 400 μg/day folic acid (FA; n = 153), or 3 g/day creatine plus 400 μg/day folic acid (Cr+FA; n = 103). Primary outcomes included plasma guanidinoacetate and total homocysteine (tHcys), alongside whole blood SAM and SAH, measured at baseline and week 12 by HPLC.
What was found
Plasma guanidinoacetate declined by 10.6% (95% CI: 4.9, 15.9) in the Cr group compared to a 3.7% increase (95% CI: -0.8, 8.5) in the placebo group (P = 0.0002). In the Cr+FA group, guanidinoacetate fell by 9.0% (95% CI: 3.4, 14.2) versus a 7.0% increase (95% CI: 2.0, 12.2) in the FA group (P < 0.0001). Creatine alone did not significantly change plasma tHcys compared to placebo (P = 0.35). Plasma tHcys declined by 23.4% (95% CI: 19.5, 27.1) in the FA group and 21.0% (95% CI: 16.4, 25.2) in the Cr+FA group (between-group P = 0.41). A decrease in guanidinoacetate over time was associated with a decrease in tHcys in the Cr+FA group (β = 0.30; 95% CI: 0.17, 0.43; P < 0.0001). Numerical results for blood SAM and SAH were not reported in the abstract.
Why it matters
Although creatine supplementation downregulates endogenous synthesis by lowering guanidinoacetate, this metabolic effect does not reliably translate into a reduction in plasma homocysteine in humans.
Limits
The trial was limited to Bangladeshi adults, which may restrict generalizability to other populations. Specific numerical findings for whole blood SAM and SAH were omitted from the abstract, and only a single dose of creatine (3 g/day) over 12 weeks was tested.
Cited by
- supports The majority of studies evaluating creatine supplementation show it does not decrease homocysteine levels.