Harris · Clinical science (London, England : 1979) 1992 · controlled clinical trial · n=17

Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation.

Cited 1134 times in the scientific literature.

Level 3 - non-randomized controlled study

Non-randomized controlled clinical experimental trial in healthy human volunteers.

PubMed 1327657 · doi:10.1042/cs0830367 · record verified 2026-08-26

What was done

Researchers evaluated the absorption and muscle uptake of oral creatine monohydrate supplementation in healthy volunteers. Plasma concentrations were evaluated after single low doses (<=1 g) and 5 g doses in 3 subjects (76–87 kg), as well as repeated 5 g doses every 2 hours. Muscle total creatine, phosphocreatine, and ATP contents were measured in the quadriceps femoris of 17 subjects receiving 5 g doses 4 or 6 times daily for 2 or more days, alongside measurements of urinary renal excretion.

What was found

A single 5 g dose produced a mean peak plasma creatine concentration of 795 (SD 104) µmol/L after 1 hour, and repeated 5 g doses every 2 hours sustained levels around 1000 µmol/L. Supplementation of 20–30 g/day for >=2 days significantly increased total quadriceps creatine content across 17 subjects, increasing up to 50% in subjects with low baseline levels. Muscle uptake peaked during the first 2 days (32% of administered dose retained in 3 subjects on 30 g/day), while renal excretion rose to 40%, 61%, and 68% across days 1, 2, and 3. At least 20% of retained creatine was stored as phosphocreatine, with no observed changes in resting muscle ATP.

Why it matters

This landmark study provided direct physiological proof that high-dose oral creatine monohydrate is absorbed, retained, and substantially expands total creatine and phosphocreatine pools in human skeletal muscle.

Limits

The abstract describes a small overall cohort (n = 17 total, with subset analyses in only 3 subjects), lacks a randomized placebo control group, and the abstract text is truncated at 250 words, omitting full details on the exercise protocol and long-term retention.

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