Dechent · The American journal of physiology 1999 · uncontrolled before-after study · n=6

Increase of total creatine in human brain after oral supplementation of creatine-monohydrate.

Cited 223 times in the scientific literature.

Level 4 - case-series / case-control

Small prospective uncontrolled before-after interventional study in healthy volunteers

PubMed 10484486 · doi:10.1152/ajpregu.1999.277.3.R698 · record verified 2026-08-26

What was done

Brain metabolite concentrations in gray matter, white matter, cerebellum, and thalamus were measured in 6 healthy young volunteers using quantitative localized proton magnetic resonance spectroscopy (1H-MRS at 2.0 T). Participants took oral creatine-monohydrate (4 × 5 g/day) for 4 weeks, with follow-up control measurements taken at least 3 months after cessation.

What was found

Oral creatine consumption significantly increased mean total creatine (tCr) across brain regions and subjects by 8.7% (0.6 mM, P < 0.001), with individual increases ranging from 3.5% to 13.3%. Regionally, tCr increased significantly in gray matter (4.7%), white matter (11.5%), cerebellum (5.4%), and thalamus (14.6% or 1.0 mM). Significant decreases were observed for N-acetyl-containing compounds in the cerebellum and thalamus, and for choline-containing compounds in the thalamus. All metabolic changes were reversible after at least 3 months.

Why it matters

It demonstrates in vivo that dietary creatine monohydrate can cross the human blood-brain barrier to elevate brain creatine concentrations in a reversible, region-dependent manner.

Limits

The sample size is extremely small (n = 6), and the study lacked a control or placebo group. Cognitive, functional, or clinical correlates were not evaluated.

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