Novel renal biomarkers show that creatine supplementation is safe: a double-blind, placebo-controlled randomized clinical trial.
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled trial
PubMed 32670557 · doi:10.1093/toxres/tfaa028
What was done
In a double-blind, placebo-controlled randomized trial, 36 healthy, active male university students were assigned to one of three groups for 35 days: placebo, 3 g/day creatine supplementation (G3), or 5 g/day creatine supplementation (G5). Renal function was evaluated pre- and post-intervention using standard markers (serum creatinine, eGFR, serum albumin, serum urea, proteinuria, albuminuria) and novel renal injury biomarkers (kidney injury molecule-1 [KIM-1] and monocyte chemoattractant protein-1 [MCP-1]).
What was found
After 35 days, there were no statistically significant differences (P > 0.05) between the groups in any measured parameters, including KIM-1, MCP-1, serum creatinine, and eGFR. Within-group paired analyses showed that both creatine groups (G3 and G5) experienced a statistically significant increase in serum creatinine and a decrease in eGFR (P < 0.05), though all values remained within normal clinical reference ranges. Exact numerical values and confidence intervals were not reported in the abstract.
Why it matters
Because creatine metabolizes into creatinine, supplementation often causes an isolated rise in serum creatinine that can mimic renal impairment on standard blood tests. Demonstrating that sensitive, direct injury biomarkers like KIM-1 and MCP-1 remain unchanged confirms that these serum creatinine changes reflect metabolic artifact rather than actual kidney damage.
Limits
The study sample was small (n = 36 across three arms) and limited strictly to young, active, healthy males over a short follow-up period of 35 days. The findings cannot be generalized to females, older populations, individuals with underlying renal impairment, or long-term/high-dose supplementation protocols.