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A new study suggests that specific low-dose formulations of creatine, a popular dietary supplement, may improve some aspects of cognitive function and elevate the compound’s levels within the brain in women navigating the menopausal transition. The research, published in the Journal of the American Nutrition Association, found that an eight-week supplementation regimen was associated with faster reaction times, improved lipid profiles, and a potential reduction in mood swings for perimenopausal and menopausal women.
The transition to menopause is characterized by significant hormonal shifts, most notably a decline in estrogen. These changes can affect multiple systems in the body, including the brain. Because estrogen helps regulate brain blood flow, energy production within cells, and the health of neurons, its decline can contribute to cognitive symptoms often described as “brain fog,” which includes memory lapses and reduced attention. This period can also coincide with structural changes in the brain and a decrease in its ability to efficiently use glucose, its primary fuel.
Creatine is a naturally occurring compound that plays a fundamental part in cellular energy management. It helps recycle the body’s main energy molecule, especially in tissues with high energy demands like muscle and brain tissue. Researchers have theorized that supplementing with creatine could help counteract some of the brain-related energy deficits associated with menopause.
The new study was conducted by a team of researchers from the University of Novi Sad in Serbia, led by Sergej M. Ostojic, to investigate whether low-dose versions of creatine, specifically creatine hydrochloride and creatine ethyl ester, could offer benefits without the need for high-dose regimens. These forms are believed to have enhanced solubility, which might improve their absorption.
The investigation was designed as a randomized, double-blind, placebo-controlled trial, a structure considered a high standard in clinical research. This design means that neither the participants nor the researchers knew who was receiving the active supplement or an inactive placebo, reducing the potential for bias. A total of 36 healthy perimenopausal and menopausal women between the ages of 40 and 60 participated in the study for eight weeks.
Participants were randomly assigned to one of four groups. One group received a low dose of creatine hydrochloride (750 milligrams per day), a second received a medium dose (1,500 milligrams per day), and a third group took a combination of creatine hydrochloride and creatine ethyl ester (800 milligrams per day). The fourth group received a placebo made of non-starch polysaccharides.
Before and after the eight-week period, the researchers assessed participants using a variety of measures, including computerized tests of cognitive function, questionnaires about menopause symptoms and fatigue, and blood tests. A subset of 16 participants also underwent a specialized brain imaging technique to measure creatine concentrations in different brain regions.
After eight weeks, the groups taking creatine supplements showed improvements in several cognitive areas compared to their baseline measurements. Participants in the medium-dose creatine hydrochloride group exhibited a significant increase in reaction time. The low-dose group showed improvements in alertness, executive control, and performance on a test measuring information processing speed. The combination supplement was also associated with better alertness and faster reaction times.
One of the study’s key observations came from the brain imaging analysis. All three groups that received a creatine supplement showed a significant rise in total creatine levels within the brain. These increases were particularly evident in the frontal regions, areas associated with mood, cognition, and memory. In contrast, the placebo group experienced a slight decrease in brain creatine levels in some of these same regions over the eight-week period.
The study also evaluated clinical symptoms related to menopause. Women taking the medium-dose creatine hydrochloride supplement reported a significant reduction in general fatigue and concentration difficulties. This group also showed a trend toward a reduction in the severity of mood swings. The group taking the combination of creatine hydrochloride and creatine ethyl ester reported a significant decrease in anxiety.
Analysis of blood samples revealed no significant changes in hormone levels or markers of inflammation across any of the groups. However, the researchers did observe favorable changes in blood lipids. The group receiving the combination supplement showed a significant reduction in both low-density lipoprotein cholesterol, often called “bad” cholesterol, and triglyceride levels.
The interventions were reported to be safe and well tolerated, with only minor side effects like transient heartburn noted in a few participants. Importantly, no group experienced weight gain, a common concern associated with creatine supplementation.
The researchers acknowledge some limitations to their study. The sample size was relatively small, which means the findings should be considered preliminary and require confirmation in larger populations. The eight-week duration may also be too short to detect longer-term effects on brain health or bone density. The study did not separate the results for perimenopausal and postmenopausal women, which could obscure differences between these distinct phases.
Additionally, the study relied on participants’ self-reports for symptoms, which can be subjective, and did not monitor diet or physical activity levels, which could have influenced the outcomes. The lead author, Sergej M. Ostojic, has existing connections to the dietary supplement industry, including serving on an advisory board and co-owning patents related to creatine. The supplements for the trial were supplied at no cost by a commercial entity. Future research should involve larger and more diverse groups of women over longer periods, with objective monitoring of lifestyle factors, to build upon these initial findings.
The study, “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,” was authored by Darinka Korovljeva, Jelena Ostojic, Jovana Panic, Marijana Ranisavljev, Nikola Todorovic, David Nedeljkovic, Jovan Kuzmanovic, Milan Vranes, Valdemar Stajer, and Sergej M. Ostojic.
