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The Effects of 8-Week Creatine Hydrochloride and Creatine Ethyl Ester Supplementation on Cognition, Clinical Outcomes, and Brain Creatine Levels in Perimenopausal and Menopausal Women (CONCRET-MENOPA): A Randomized Controlled Trial

Darinka Korovljev, Jelena Ostojic, Jovana Panic, Marijana Ranisavljev, Nikola Todorovic, David Nedeljkovic, Jovan Kuzmanovic, Milan Vranes, Valdemar Stajer, Sergej M Ostojic
J Am Nutr Assoc 2026 45(3):199-210

Bibliography

PubMed
PMID 40854087
DOI
10.1080/27697061.2025.2551184
Funding
Partially funded by the Provincial Secretariat for Higher Education and Scientific Research and Vireo Systems. Vireo Systems supplied the intervention products at no cost.
Competing interests
Sergej M. Ostojic disclosed AlzChem scientific-advisory-board service, creatine-related patents/patent applications, recent creatine research support from public and commercial sources including AlzChem and ThermoLife, and co-founding KRE-ALL, a company developing creatine-enriched foods. The article states no potential conflict was reported by the other authors.

Study snapshot

DesignParallel-group randomized placebo-controlled double-blind trial
ModelHuman
Sample36 apparently healthy perimenopausal and menopausal women; four study arms
InterventionCreatine hydrochloride 750 mg/day, creatine hydrochloride 1,500 mg/day, creatine hydrochloride plus creatine ethyl ester 800 mg/day (400 mg each), or placebo
Duration8 weeks
EndpointsReaction time and cognition; Frontal brain creatine by spectroscopy; Menopause-related symptoms; Serum lipid profile; Biochemical markers; Adverse effects

What the study showed, in plain terms

Small randomized trial testing low-dose creatine hydrochloride and a creatine-HCl/ethyl-ester combination in perimenopausal and menopausal women.

Key findings

The 1,500 mg/day creatine-HCl arm showed greater change than placebo in reaction time and frontal brain creatine and favorable lipid changes. The study did not test creatine monohydrate and did not establish HCl superiority to monohydrate.

What this study can and cannot tell us

Only 36 participants were divided among four arms, limiting precision. The trial tested creatine HCl and creatine ethyl ester rather than monohydrate, so findings cannot be transferred directly to standard creatine-monohydrate dosing. The study was partially funded by Vireo Systems, which also supplied the intervention products, and the senior author disclosed multiple creatine-related commercial interests.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction