Review Finds No Creatine Evidence in Psychiatric Supplements

Key Takeaways

• This review included 122 studies in psychiatric disorders, but creatine was not among the nutraceuticals analysed.
• Vitamin D3 and N-acetylcysteine were the most studied supplements, yet results were still heterogeneous.
• The authors found overall high risk of bias and generally low methodological quality across the literature.
• Many included studies were not randomised controlled trials, which weakens confidence in reported benefits.
• For creatine users, this is mainly a reminder not to assume mitochondrial theory equals proven psychiatric benefit.
• Creatine monohydrate remains well supported for exercise performance, but this review does not add psychiatric evidence for it.

What the review actually found

The main news here is as much about what wasn't found as what was. In a systematic review of 122 studies on nutraceuticals aimed at mitochondrial function in psychiatric disorders, the authors listed interventions such as vitamin D3, N-acetylcysteine, acetyl-L-carnitine, coenzyme Q10, alpha-lipoic acid, magnesium and several vitamins. Creatine was not among the included nutraceuticals.

That matters because creatine is often discussed as a mitochondrial or cellular-energy supplement. Some readers may reasonably expect it to appear in a review framed around mitochondrial support and mental health. Based on the abstract supplied, it did not. So this paper does not provide new clinical evidence that creatine improves psychiatric outcomes, nor does it show that creatine is ineffective. It simply was not part of the included evidence base.

Among the supplements that were studied, vitamin D3 accounted for 27.05% of included studies and N-acetylcysteine for 15.6%. Vitamin D3 was also the most extensively investigated in randomised controlled trials and had the highest number of trials reporting clinical improvements, but the findings were heterogeneous. In other words, there were some positive signals, but not a clean, consistent story.

For people browsing creatine guides and wondering whether creatine has established psychiatric uses, this review should be read carefully: it is a broad mitochondrial-nutraceutical review, not a positive creatine paper.

How the review was designed and why that matters

This was a systematic review conducted according to PRISMA methods, with database searches in PubMed, Embase and Scopus covering 1 January 2007 to 30 April 2024. The authors identified 2061 records and included 122 studies evaluating nutraceutical supplementation in psychiatric disorders or related conditions. They also performed a risk-of-bias assessment for studies compatible with the RoB2 tool.

On paper, that is a solid starting framework. Systematic reviews can be useful because they gather scattered evidence into one place, making it easier to see overall patterns. But the strength of a review depends heavily on the quality of the studies it includes. Here, that was the central problem.

The authors report that a substantial proportion of included studies were not randomised controlled trials. Many were open-label single-arm trials or case reports. There was also significant heterogeneity in:

• the nutraceutical ingredients used
• treatment duration
• psychiatric conditions studied
• outcomes measured
• whether supplements were used alone or in combinations

Notably, 14.8% of studies evaluated combinations of three or more nutraceuticals. That makes it difficult to know which ingredient, if any, was responsible for any reported effect. For readers trying to translate evidence into practical supplementation decisions, this kind of heterogeneity sharply limits confidence.

If you are comparing evidence quality across products in our creatine product catalog or creatine brand reviews, this review is a good reminder that broad supplement categories often sound stronger than the underlying data really are.

Why creatine users should care even though creatine was not included

Creatine users should care because this review highlights a common evidence trap: a plausible mechanism is not the same as proven clinical benefit. Creatine plays a recognised role in cellular energy metabolism, and that has led to interest in areas beyond sport, including brain health. But this particular paper does not move the needle on psychiatric uses of creatine because it did not include creatine studies.

That distinction is important. It would be inaccurate to use this review to claim that creatine helps depression, schizophrenia, bipolar disorder, ADHD or autism spectrum disorder. It would be just as inaccurate to claim the review disproves creatine for those uses. The correct interpretation is narrower: this review found a messy, low-quality evidence base for several mitochondrial-focused nutraceuticals, and creatine was not one of the analysed interventions.

For most consumers, the practical takeaway is straightforward:

• If you take creatine for strength, power, lean mass or training capacity, this review does not change the mainstream case for creatine monohydrate.
• If you are considering creatine specifically for a psychiatric condition, this paper is not evidence to rely on.
• If you want to dial in sport-focused use, a creatine dosage calculator can help with everyday dosing rather than disease-focused experimentation.

The broader lesson is to separate established sports nutrition evidence from emerging or speculative clinical applications. Those are not the same level of proof.

Where this fits in the wider creatine evidence

In the broader creatine literature, the clearest evidence still sits with exercise performance and training adaptations, especially for creatine monohydrate. Position stands and evidence summaries consistently support monohydrate as the most studied form, with typical maintenance intakes around 3 to 5 g per day and optional loading protocols of about 20 g per day split into four doses for 5 to 7 days. That consensus is well described in the ISSN position stand and in the review on common questions and misconceptions about creatine supplementation.

What is not established to the same standard is psychiatric treatment. There is scientific interest in brain energetics, mitochondrial function and creatine's role in ATP buffering, but readers should not confuse mechanistic plausibility with replicated clinical efficacy. This new review reinforces that caution indirectly: even across a large body of mitochondrial-oriented nutraceutical studies, the field was marked by small samples, short follow-up and poor standardisation.

For shoppers comparing forms and quality, the safest evidence-based default remains plain monohydrate rather than exotic positioning around brain or mood benefits. If you are looking for practical buying help, see our best creatine rankings. But whatever product you choose, be careful with marketing that jumps from mitochondrial language to strong mental-health claims without high-quality clinical trials behind it.

Practical implications for dosing, timing and who should be cautious

Because creatine was not an included intervention in this review, there is no psychiatric dosing protocol to pull from this paper. So the practical guidance for creatine remains the standard sports-nutrition approach rather than a mental-health protocol.

For healthy adults using creatine for performance or training support, mainstream evidence still points to:

• Maintenance: 3 to 5 g/day of creatine monohydrate
• Optional loading: about 20 g/day split into 4 doses for 5 to 7 days, followed by maintenance
• Timing: less important than daily consistency

This review gives no reason to change those basics. It also provides no evidence-based basis to increase dose in hopes of psychiatric benefits.

Who should be cautious? Anyone considering creatine as a self-directed treatment for a diagnosed psychiatric disorder should involve a clinician. That is not because creatine is uniquely alarming, but because psychiatric conditions are complex, symptoms fluctuate and supplement use can muddy medication management or delay evidence-based care. The review authors specifically call for robust RCTs with standardised protocols and validated biomarkers of efficacy before stronger clinical conclusions can be made.

So if your goal is gym performance, routine monohydrate use is still the evidence-led lane. If your goal is mental-health treatment, this paper argues for better research, not confident self-prescription. Our broader creatine guides can help distinguish proven use cases from emerging ones.

Bottom line

This systematic review does not provide new evidence for creatine in psychiatric disorders because creatine was not among the included nutraceuticals. What it does show is that the wider mitochondrial-supplement literature in psychiatry is promising in places but methodologically weak overall.

The strongest signals in the review came from heavily studied supplements such as vitamin D3 and N-acetylcysteine, yet even there the evidence was heterogeneous. Across the field, the authors found high risk of bias, low methodological quality, small samples, short follow-up and poor standardisation. That is a recipe for uncertainty, not confident treatment claims.

For creatine users, the practical conclusion is simple: keep this paper in its lane. It does not challenge the established sports-performance case for creatine monohydrate, and it does not support using creatine as a proven psychiatric intervention. If future trials test creatine directly in well-designed psychiatric RCTs, that could change the conversation. This review, however, is not that study.

In a supplement market that often turns mechanistic buzzwords into sweeping promises, that restraint matters. The evidence-based position today is still to treat creatine as a well-supported performance supplement first, while recognising that psychiatric applications remain an open research question rather than settled practice.

What this psychiatric supplement review showed

• 122 Studies included — Systematic review of nutraceuticals in psychiatric disorders
• 2061 Records identified — Screened across PubMed, Embase and Scopus
• 27.05% Vitamin D3 share — Most studied nutraceutical in the review
• 14.8% Multi-supplement studies — Evaluated combinations of 3 or more nutraceuticals

Frequently Asked Questions

Sources & Further Reading

• Kreider et al. (2017), ISSN Position Stand: Safety and Efficacy of Creatine — JISSN
• Antonio et al. (2021), Common questions and misconceptions about creatine supplementation — JISSN