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Creatine in Women’s Mental Health

Rates of depression are twice as high among women compared to men; this is mainly due to the hormonal milestones present in a woman’s life since the literature already reports that rates of significant depression increase during puberty, the luteal phase, after pregnancy, and during perimenopause. Despite the hormonal pattern, evidence suggests that this trajectory depends not only on the amount of estrogen and progesterone but also on the brain’s sensitivity to these hormones.



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Creatine and Depression

In this context, the literature suggests that the efficient neurotransmission of metabolites that affect mood depends directly on the proper functioning of the creatine-phosphocreatine system, since a positive relationship between creatine and dopamine levels and serotonin metabolites in cerebrospinal fluid has been demonstrated. Thus, the severity of a depressive episode was inversely linked to white matter creatine and phosphocreatine concentrations in the brain, suggesting that there is a relationship between cerebral creatine metabolism and depression.

In addition, clinical and preclinical evidence has reported positive effects of creatine supplementation on mood, restoring brain energy levels and homeostasis. Altered brain bioenergetics and mitochondrial dysfunction, points that are improved with creatine supplementation, have also been linked to depression, particularly in creatine kinase, adenosine triphosphate (ATP), and inorganic phosphate. It is also important to point out that creatine supplementation also contributes to antidepressant treatment by being able to accelerate the mechanism of action of drugs.

Creatine, Cognition, and Sleep

Brain activity rapidly reduces phosphocreatine levels to maintain adenosine triphosphate (ATP) levels, so in periods of high mental stress, which require higher demand for phosphocreatine, ATP turnover can be impaired. In addition to the fact that it is well elucidated that creatine concentrations in the brain appear to be variable based on/depending on age, lifestyle choices, diet, and other factors. In this context, Creatine supplementation has been shown to support increased neural ATP resynthesis, which provides a cognitive advantage for tasks that depend on the frontal cortex, such as cognition, attention, and memory.

Moreover, in the same line of reasoning, similar results indicate a cognitive decline in disturbances associated with sleep, as well as a reduction in the quality of this for women during the follicular phase, characterized by low estrogen levels, which is also when creatine kinase levels appear to be lowest. Therefore, as a result of this promising research, Creatine supplementation throughout the menstrual cycle can help mitigate its adverse effects on cognition and sleep, and the benefits are even more helpful during periods of high stress and sleep deprivation.

Clinical practice

As a result of changes in creatine homeostasis throughout the life cycle, particularly estrogen, creatine supplementation seems to provide many potential benefits for women. Thus, to maximize brain uptake, a loading phase with 15 to 20 g/day or for 3 to 7 days followed by a consistent regular daily dose of 5 to 10 g is ideal for tissue saturation, and the peak creatine absorption from supplementation is optimized when ingested as a solution versus capsule, tablet, or solid meat. High “attack doses,” or routine daily doses of 5 g for four weeks, can be used regarding mood and cognition.

Bibliographic references

Watch the video on the Science Play platform – Women’s Nutrition and Health

Smith-Ryan AE, Cabre HE, Eckerson JM, Candow DG. Creatine Supplementation in Women’s Health: A Lifespan Perspective. Nutrients. 2021 Mar 8;13(3):877. doi: 10.3390/nu13030877. PMID: 33800439; PMCID: PMC7998865.

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