Primary Research · 2011
Analysis of the efficacy, safety, and regulatory status of novel forms of creatine
Jäger et al. · Amino Acids, 2011
Key finding
Review of creatine forms. Concludes monohydrate remains the gold standard; novel forms have no demonstrated advantage.
Abstract
PubMed · PMID 21399917 →Doubtful allegations of adverse effects of creatine supplementation have been released through the press media and through scientific publications. In the present review we have tried to separate the wheat from the chaff by looking for the experimental evidence of any such claims. Anecdotal reports from athletes have appeared on muscle cramp and gastrointestinal complaints during creatine supplementation, but the incidence of these is limited and not necessarily linked to creatine itself. Despite several unproved allegations, liver (enzymes, urea) and kidneys (glomerular filtration urea and albumin excretion rates) show no change in functionality in healthy subjects supplemented with creatine, even during several months, in both young and older populations. The potential effects (production of heterocyclic amines) of mutagenicity and carcinogenicity induced by creatine supplementation have been claimed by a French Sanitary Agency (AFSSA), which might put consumers at risk. Even if there is a slight increase (within the normal range) of urinary methylamine and formaldehyde excretion after a heavy load of creatine (20 g/day) this is without effect on kidney function. The search for the excretion of heterocyclic amines remains a future task to definitively exclude the unproved allegation made by some national agencies. We advise that high-dose (>3-5 g/day) creatine supplementation should not be used by individuals with pre-existing renal disease or those with a potential risk for renal dysfunction (diabetes, hypertension, reduced glomerular filtration rate). A pre-supplementation investigation of kidney function might be considered for reasons of safety, but in normal healthy subjects appears unnecessary.
Abstract sourced from PubMed, a database of the U.S. National Library of Medicine. Displayed in the authors’ own words for context; our critique is in the sections below.
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How to read a study like this
The same questions worth asking about any research paper, not just this one. Worth a minute even if you trust the grade.
Who was studied, and do you resemble them?
Supplement effects often depend on baseline status. Vitamin D helps people who are deficient; iron helps people who are anemic. A result in people unlike you may not apply to you.
What was measured, and does it matter in daily life?
A study that shows a blood marker moved isn't the same as a study that shows people felt or functioned better. Ask what the outcome means in practice.
How large was the effect — not just whether it was significant.
'Statistically significant' only means the effect is unlikely to be zero. It doesn't tell you the effect is large enough to notice. Look for effect sizes, not just p-values.
Who paid for the trial, and what did they stand to gain?
Industry-funded trials are several times more likely to report positive results than independent ones. It's not usually fraud — it's subtle design and reporting choices. Weight accordingly.
Has anyone else replicated this?
Single positive trials are hypotheses. Replication by independent groups is what turns a hypothesis into reliable evidence. If the only positive trial is the one you're reading, wait.
Does the dose in the trial match what's being sold?
Supplement marketing routinely cites trials that used 5–10× the dose in the product. If the effective dose was 2 g/day and the capsule has 200 mg, expect roughly no effect.
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