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Creatine Supplementation in Women’s Health

Dietary supplementation with creatine is increasingly frequent, and this data among women has its growth proportional to the degree of education and age. It is known that the ergogenic potential of creatine can be attributed to several mechanisms, in addition to being possible to present different effects in men and women.

Briefly, creatine is an essential substrate for the creatine kinase reaction, which catalyzes the production of adenosine triphosphate (ATP) from creatine and phosphocreatine. It also serves as an endogenous metabolic buffer aiding in the maintenance of pH, both mechanisms of which can sustain energy availability during exercise. In addition, creatine concentrations in the central nervous system also suggest the role of neural participation in exercise adaptations.

However, the characteristics of creatine vary between men and women, since females have endogenous creatine reserves 70-80% lower than males. Not to mention that Women also consume significantly lower amounts of creatine in the diet, which strengthens the hypothesis that women may benefit from creatine supplementation as a strategy to increase their endogenous stores.

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Creatine and Life Stages

Due to hormonal changes over various stages of female reproduction, the endogenous synthesis, transport, bioavailability, and kinetics of creatine kinase and creatine are altered according to the stages of a woman’s life. That is, creatine supplementation can be of particular importance during menstruation, pregnancy, postpartum, pre- and post-menopause.

Thus, the literature demonstrates that the menstrual cycle is able to influence the homeostasis of creatine due to the cyclical nature of the regulation of sex hormones, which is proven by studies that have demonstrated the expression of arginine-glycine aminotransferase (AGAT), the limiting stage of creatine synthesis, being influenced by estrogen and testosterone levels. Thus, sex hormones, predominantly estrogen and progesterone, affect creatine kinase activities and the expression of key enzymes for endogenous creatine synthesis, as well as metabolic capacity for protein and carbohydrate oxidation.

Creatine and Menstruation

The serum creatine kinase levels are significantly elevated during menstruation and decreased in the years without menstruation (adolescent premenarche or amenorrhea), early pregnancy (20 weeks or less), and in the transition to menopause due to low estrogen concentrations of the follicular phase. This is because, possibly, creatine metabolism increases and decreases in a synchronized way with estrogen levels. Suggesting that during the luteal phase, when estrogen levels are at peak, muscle damage may be reduced after exercise due to the preservation of creatine kinase.

Thus, when we consider that estrogen is a regulator of bioenergetics, we have its highest levels occurring during the luteal phase, which begins shortly after ovulation and goes until the end of the menstrual cycle. At this time, catabolism and protein oxidation were shown to be high, while carbohydrate storage was reduced. Therefore, due to increased protein turnover and challenges with glycogen saturation, creatine supplementation may be even more effective in the high luteal/estrogen phase.

Creatine in Premenopause

The Creatine supplementation for premenopausal women is even more effective when it comes to high-intensity, short-duration activities or repeated high-intensity exercise with short rest periods., such as jumping, running, and resistance training, since it induces increased levels of phosphocreatine (PCr) that can rephosphorylate adenosine diphosphate (ADP) into adenosine triphosphate (ATP) through the creatine kinase reaction.

In addition, PCr acts as a buffer of hydrogen ions (H+) that accumulate during high-intensity exercise, delaying the onset of fatigue.. In practice, the increase in intramuscular stores of PCr through supplementation allows greater stimulation to training, which results in physiological adaptations that induce increased muscle mass, strength and hypertrophy of muscle fibers.

Creatine and Pregnancy

At this stage of life, there is an increase in metabolic demand for the development of the fetus to occur during pregnancy., particularly from the placenta, which has been linked to reduced creatine levels. It is possible to find recent human data suggesting the association between reduction in creatine stores during pregnancy with the occurrence of low birth weight and premature birth.

Thus, in practice we have that creatine supplementation during pregnancy increases the absorption of creatine by neuronal cells and supports the mitochondrial integrity of the fetus, thus reducing brain injury. Also consisting of a safe and low-cost nutritional strategy to reduce intra- and postpartum complications associated with cellular energy depletion.

Creatine in the Postmenopausal

Menopause-related estrogen decrease is the main contributing factor to age-related loss in muscle, bone mass, and strength. There is also an association between low estrogen levels and increased inflammation and oxidative stress, which may contribute to the reduction of muscle protein.

However, it is worth paying attention to the indication of resistance training for this public, since the muscle contractions induced by this type of physical exercise lead to a greater uptake of intramuscular creatine from supplementation.

In this context, creatine supplementation acts as a possible countermeasure to such losses and, in addition to reducing inflammation and oxidative stress, it is possible to observe a reduction in serum markers of bone resorption, as well as simultaneously an increase in the activity of osteoblastic cells.

Clinical practice

Supplementation can be performed using two strategies, both of which result in similar increases in intramuscular phosphocreatine levels, i.e., through daily doses of 5g for three to four weeks or doses of 20g for 5 to 7 days.. Also pay attention to offer the patient creatine monohydrate, since it has an extremely high bioavailability.

However, the absorption of creatine by skeletal muscle may also be influenced by insulin availability., which can increase creatine retention. Meanwhile, due to the menstrual cycle, the lower carbohydrate oxidation in the follicular phase may suggest that macronutrients added to increase creatine retention are not needed. Being an interesting strategy, recommend its intake associated with a usual meal or add it to a protein shake due to the insulin properties of amino acids.

Bibliographic references

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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