Deminice · European journal of nutrition 2014 · double-blind randomized controlled trial · n=23

Short-term creatine supplementation does not reduce increased homocysteine concentration induced by acute exercise in humans.

Cited 20 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial

PubMed 24318038 · doi:10.1007/s00394-013-0636-1 · record verified 2026-08-29

What was done

Twenty-three young under-20 soccer players were randomized in a double-blind controlled trial to receive either creatine (0.3 g/kg/day) or placebo tablets for 7 days. Before and after the 7-day period, athletes performed an acute sprint exercise protocol consisting of two consecutive running-based anaerobic sprint tests (six 35-meter sprints with 10 seconds rest). Blood samples were collected before and after the 7 days of supplementation, as well as at 0 and 1 hour post-exercise to measure plasma homocysteine, creatine, guanidinoacetic acid, B vitamins, and red blood cell methylation markers.

What was found

Acute exercise significantly increased plasma homocysteine by 18% at 1 hour post-exercise (P < 0.05) and reduced red blood cell S-adenosylmethionine (SAM) by 30% with no change in the SAM/SAH ratio. Seven days of creatine supplementation increased plasma creatine (placebo 130.1 ± 21.7 vs creatine 1,557.2 ± 220.3 μmol/L, P < 0.05) and reduced plasma guanidinoacetic acid by 33% (P < 0.05). However, creatine did not alter plasma homocysteine levels after 7 days of rest (placebo 6.9 ± 0.2 vs creatine 7.2 ± 0.2 μmol/L) or after acute exercise (placebo 8.2 ± 0.3 vs creatine 8.4 ± 0.3 μmol/L). No changes were observed in plasma vitamin B12, folate, cysteine, or methionine.

Why it matters

Endogenous creatine synthesis utilizes substantial methyl groups from the methionine cycle, leading to the hypothesis that creatine loading could spare methyl groups and lower exercise-induced homocysteine spikes. These findings show that despite suppressing endogenous synthesis, short-term creatine loading does not prevent acute exercise-induced increases in homocysteine.

Limits

The study had a small sample size (n = 23) consisting solely of young male soccer players, limiting generalizability to females, older populations, or non-athletes. The intervention lasted only 7 days, leaving the effects of chronic or lower-dose supplementation unaddressed.

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