Three creatine reviews in one month: solid on strength, shaky on mood

Creatine has spent the last two years migrating out of the gym and into general wellness marketing, where it is increasingly sold for mood, cognition and healthy ageing rather than for lifting. Three systematic reviews published within a month of one another offer an unusually clean look at where the evidence sits for each of those claims. The short version: the strength claim holds up, the mood claim is weak and possibly biased, and the long-standing kidney worry does not survive the data.

This article describes published research. It is not advice about whether to take a supplement, and anyone with kidney disease or taking prescribed medication should raise that question with a clinician rather than an article.

The mood claim

A systematic review in the British Journal of Nutrition searched four databases up to February 2025 for trials comparing creatine with placebo in people with or without depression, assessing risk of bias with RoB 2 and certainty of evidence with GRADE [s1].

Eleven trials with 1,093 participants were pooled [s1]. The standardised mean difference was −0.34 (95% CI −0.68 to 0.00), which the authors translate to 2.2 points on the seventeen-item Hamilton Depression Rating Scale — below the minimal important difference of 3.0 points [s1]. The confidence interval touches zero, so the result includes the possibility of no effect at all, and heterogeneity was substantial at I² = 71.3% [s1].

The certainty rating is the most informative number in the paper: GRADE very low [s1]. Effects appeared larger in clinically depressed populations, but subgroup analyses and trim-and-fill adjustment indicated substantial bias favouring creatine — that is, the pattern of results across trials looks like what you see when unfavourable studies are missing from the literature [s1].

Secondary endpoints split. Remission, across three trials, showed an odds ratio of 3.60 (95% CI 1.76 to 7.56); treatment response, across two trials, did not (OR 0.72, 95% CI 0.28 to 1.88) [s1]. Two- and three-trial subsets are not a basis for confidence in either direction.

The authors' own conclusion is that creatine may offer a small-to-moderate benefit in depression but that average effects were not clinically important and the true effect may be trivial or null, with larger and more rigorous trials required [s1].

The kidney question

The most persistent safety concern about creatine is that it raises serum creatinine, the standard blood marker used to estimate kidney function. A meta-analysis in BMC Nephrology searched PubMed, Scopus, Web of Science and Google Scholar for studies published between January 2000 and March 2025, with serum creatinine and glomerular filtration rate as primary outcomes [s2].

Twenty-one studies entered the systematic review and 12 the meta-analysis of serum creatinine, covering 177 participants in creatine groups and 263 controls [s2]. Creatine supplementation was associated with a small but statistically significant increase in serum creatinine (mean difference 0.07 µmol/L, 95% CI 0.01 to 0.12; p = 0.03) [s2]. Subgroup analysis by follow-up duration found the effect significant in studies of one week or less (MD 0.12, 95% CI 0.03 to 0.21), not significant between one and twelve weeks (MD 0.04, 95% CI −0.09 to 0.17), and significant again beyond twelve weeks [s2].

The outcome that matters clinically showed nothing: the meta-analysis found no statistically significant difference in glomerular filtration rate between creatine and control [s2]. The authors interpret the creatinine rise as reflecting metabolic turnover rather than renal impairment, and conclude kidney function was preserved [s2].

The participant numbers are small — 440 people across the creatinine meta-analysis [s2] — and the included populations are largely healthy. This is not evidence about people with existing kidney disease, and the review does not claim to be.

The strength claim

The third review, in PeerJ, pooled trials of creatine and muscle strength using both conventional and robust variance estimation models, prospectively registered on PROSPERO [s3]. Baseline strength did not differ between creatine and control groups; after intervention, the creatine group showed significant strength gains [s3].

The subgroup pattern is the useful part. Untrained individuals improved more than trained ones; low-to-moderate doses outperformed high doses; and high-intensity training produced larger effect sizes than low-intensity training [s3]. No definitive conclusion was reached on whether middle-aged and older adults respond differently from younger ones, which the authors attribute to needing larger samples [s3].

That untrained people gain more is the ordinary shape of any training-adjacent intervention — there is more room to move. That low-to-moderate doses beat high doses is the finding most at odds with how the supplement is sold.

Reading the three together

The pattern across all three is that creatine's best-evidenced effect is the one it has been studied for longest, in the population it was studied in, on the outcome it was designed to affect. The newer claims are supported by smaller literatures with weaker methods, and in the case of depression by a literature that shows signs of selective reporting [s1].

None of these reviews is a trial, and a meta-analysis inherits the flaws of its inputs. The depression review's GRADE rating of very low is an explicit statement that further research is likely to change the estimate [s1]. The kidney review's reassurance rests on 440 participants, mostly healthy, over short follow-ups [s2].

What to watch

For the mood claim, the thing that would settle it is a large, adequately powered, pre-registered trial in a clinically depressed population — precisely what the review says does not yet exist [s1]. For safety, longer follow-up in populations with reduced baseline kidney function. For strength, the dose-response question the PeerJ review raises: whether the standard loading protocols sold to consumers are above the range where benefit is maximised [s3].

Sources

• Creatine supplementation for treating symptoms of depression: a systematic review and meta-analysis — British Journal of Nutrition, 2025-11-05
• Effect of creatine supplementation on kidney function: a systematic review and meta-analysis — BMC Nephrology, 2025-11-06
• Effects of creatine supplementation on muscle strength gains—a meta-analysis and systematic review — PeerJ, 2025-11-27