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Unlocking the Benefits of Creatine: The Under-Appreciated Nutrient for Women's Health & Performance

Creatine is naturally found in our muscles and stored as phosphocreatine. It is also found in smaller amounts in our brains, liver, and kidneys. Our diet can obtain some creatine, particularly from animal products like meat and fish.


When cells need energy for activities like muscle contractions, creatine kinase breaks down phosphocreatine (a stored form of creatine) to produce ATP (adenosine triphosphate), which is the primary energy currency of cells. This process is known as the creatine kinase reaction, and it is essential for providing energy to cells during high-intensity activities like weightlifting or sprinting.


Women have 70-80% fewer stores of creatine than men. Like many areas of research, the evidence of use in women is understudied. However, the current body of literature that evaluated the effects of creatine supplementation in women has shown some promise. Most studies indicate numerous metabolic, hormonal and neurological benefits.



Due to hormonal changes that occur during different stages of female reproduction, the body's ability to produce and utilise creatine changes. This affects the way creatine is made and transported, as well as how it is used in the body. These changes suggest that taking creatine supplements could be beneficial for females at different stages of their reproductive lives.


Copyright: Abbey E Smyth-Ryan et al.


Creatine in premenopausal women

Blood levels of creatine kinase are higher in menstruating versus non-menstruating years. Their levels decrease with age and during pregnancy. Sex hormones, predominantly estrogen and progesterone, have been shown to affect creatine kinase activities and the expression of key enzymes for the endogenous synthesis of creatine. More research is needed regarding creatine supplementation around the menstrual cycle as this may have important implications for women who have low estrogen concentrations, suffer amenorrhea, during pregnancy and transition into menopause. During a normal menstrual cycle, high levels of estrogen (in the luteal phase), increase protein breakdown and reduces carbohydrate storage and creatine supplementation may be effective in mitigating some of these effects.

Many women may be reluctant to supplement with creatine due to the weight-gaining effects, which are temporary during the loading phase and reflect cellular hydration as opposed to fat gain. You can read more about these kinds of myths and pitfalls that often confuse women when it comes to their body composition. The commonly recommended loading doses for creatine do not apply to women.


Creatine in strength and performance

There is a significant body of evidence suggesting that creatine can serve as a useful ergogenic aid for enhancing strength, power, and overall athletic performance in females, all without causing noticeable fluctuations in body weight. Instead of a loading dose of 1g/kg/day, women benefit from 0.3g/kg/day divided into 4 doses for 5 days.

Eg. 58kg women will need a total of 17.4g per day. This is around 4-5g per dose 4 times per day (or every 4 hrs) for 5 days.

Thereafter, a maintenance dose of 3-5g/ day is recommended.

The most optimal use of creatine supplementation is for activities that involve short, high-intensity bursts or repeated bouts of such exercise with minimal rest periods - such as resistance training, jumping, and sprinting. This is because the heightened levels of phosphocreatine (PCr) brought about by creatine supplementation can more swiftly re-synthesize ATP through the creatine kinase reaction. Furthermore, PCr can serve as a buffer for hydrogen ions (H+) that accrue during high-intensity exercise, potentially delaying the onset of fatigue. Essentially, an increase in intramuscular PCr stores due to creatine supplementation can help promote greater physiological adaptations, leading to improvements in muscle mass, strength, and muscle fibre hypertrophy as a result of more intense and effective training. A 10-week study in young healthy sedentary women (ages 19-22) combined creatine supplementation with resistance training demonstrated a 20-25% increase in 1RM for leg press, leg extension and squat compared to placebo. There was no significant change in body fat % or body weight and fat-free mass increased in the creatine group.

In trained women or athletes, most studies demonstrate an improvement in strength performance. However, there were some non-responders and this may be due to an inadequate loading dose, training volume and response may have been better in individuals who have lower endogenous creatine levels.

While research on the impact of creatine on endurance exercise performance is not as extensive, some evidence suggests that it may offer some ergogenic benefits. One study, for example, found that a 7-day creatine loading period resulted in lower oxygen consumption (VO2) during submaximal workloads and a reduction in the workload borne by the cardiovascular system during a graded exercise test (GXT). Specifically, the study demonstrated that total test time was significantly increased with creatine (from 20.3 ± 4 min to 21.5 ± 3.5 min) compared to a placebo (from 17.3 ± 3 min to 17.4 min ± 3 min), and that VO2 and heart rate were notably lower for the creatine group during the first five stages of the GXT, while there was no change for the placebo group.


Creatine during pregnancy

The increased metabolic demands of growth and development during pregnancy, particularly from the placenta, have been observed to lead to a decrease in the available creatine pool. Recent human studies have shown that pregnancy can result in a significant shift in creatine homeostasis, with lower creatine stores during pregnancy linked to low birth weight and pre-term birth.

Animal models have provided increasing evidence that creatine supplementation during pregnancy can enhance neuronal cell uptake of creatine and promote mitochondrial integrity in offspring, thereby reducing brain injury caused by intrapartum asphyxia. While human studies have yet to evaluate the effects of creatine supplementation during pregnancy, this nutritional strategy could serve as a safe and affordable means of mitigating intra- and post-partum complications related to cellular energy depletion.


Creatine for post-menopausal women

The decline in estrogen levels associated with menopause is a major contributing factor to the age-related loss of muscle and bone mass and strength, also known as dynapenia. While the exact mechanisms linking estrogen levels to muscle mass and strength are not yet fully understood, research suggests that low estrogen levels may be linked to heightened inflammation and oxidative stress. This, in turn, could lead to a diminished response of muscle protein synthesis and satellite cell activation to anabolic stimuli such as resistance training.

Research suggests that creatine supplementation may serve as a potential solution to the decline in muscle, bone, and strength associated with menopause. This is due in part to creatine's ability to reduce inflammation, oxidative stress, and serum markers of bone resorption, while also increasing the activity of osteoblast cells, which contribute to bone formation. Creatine has also been shown to promote muscle integrity by boosting satellite cell activity, growth factors (such as IGF-1), protein kinases downstream in the mammalian target of the rapamycin pathway, and myogenic transcription factors. These effects have been studied in females, often in combination with resistance training. Given the cyclical and long-term changes in estrogen throughout a woman's life, creatine supplementation may be an intriguing therapeutic strategy for post-menopausal women.


Creatine for depression and mood

Females experience depression at a rate twice as high as males. This higher prevalence of depression in women has been linked directly to hormonal milestones, with major depression rates increasing during puberty, the luteal phase (when estrogen levels are high), following pregnancy, and during perimenopause. However, research suggests that this pattern is not solely determined by the levels of estrogen and progesterone in the body, but rather by how sensitive the brain is to these hormones.

Early investigations into the role of dysfunctional creatine metabolism in the neurochemical underpinnings of depression in adults found a positive correlation between levels of cerebral spinal fluid creatine and dopamine and serotonin metabolites. These findings suggest that efficient neurotransmission of mood-altering metabolites relies on the proper functioning of the creatine-phosphocreatine system. Furthermore, the severity of a depressive episode is inversely linked to concentrations of creatine and phosphocreatine in the white matter within the brain, suggesting a relationship between depression and brain creatine metabolism. Such patterns are beneficial for anti-depressant treatment, indicating that dietary creatine supplementation may offer a pro-energetic effect on brain chemistry by facilitating the efficient regeneration of high-energy phosphates within cells in females.

Both clinical and pre-clinical studies have shown that creatine supplementation can have a positive impact on mood by restoring brain energy levels and homeostasis. Alterations in brain bioenergetics and mitochondrial dysfunction have been linked to depression, specifically to creatine kinase (CK), ATP, and inorganic phosphate. In terms of energy usage, in vivo measurements of the brains of adult females with major depressive disorder demonstrate a distinct pattern of energy-related metabolites, including a decrease in beta-nucleoside triphosphate and an increase in phosphocreatine level that results from increased use of ATP.

Research has indicated that females tend to have lower levels of creatine in the brain, particularly in the frontal lobe - the region that controls important functions such as mood, cognition, memory, and emotion. Due to these sex-based differences in brain creatine concentrations, creatine supplementation may prove even more effective for females in promoting a pro-energetic environment within the brain. When combined with regular antidepressant use, an 8-week regimen of creatine supplementation was found to reduce depressive symptoms in female adolescents and adults with major depression. In healthy adolescent females taking antidepressant medication, the mean score on the Children's Depression Rating Scale-Revised (CDRS-R) fell from 69 to 30.6 - a 56% decrease - in those who consumed 4 grams of creatine daily for 8 weeks. Similar results were seen in healthy adult females taking antidepressant medication, with significantly greater improvements in Hamilton Depression Rating Scale (HAM-D) scores observed after just 2 weeks in those consuming 5 grams of creatine per day for 8 weeks.

Studies have shown that there is an inverse relationship between dietary creatine intake and the occurrence of depression, with a 31% higher incidence of depression in adults who consume the lowest quartile of creatine. Increasing the concentration of creatine in the brain through increased consumption of animal protein, or more effectively through creatine supplementation, has shown strong evidence for its ability to improve mood and alleviate depression, particularly in females. This has important implications across various stages of a woman's life, as cyclical hormonal changes during puberty, post-partum, and menopause are associated with increased rates of depression.



Creatine for sleep and cognition

Studies of creatine supplementation in humans have consistently shown improvements in cognitive performance, brain function, and reduced mental fatigue during stressful mental tasks, particularly in healthy adults. Individuals with cognitive impairments have also reported greater cognitive improvements following creatine supplementation. Vegetarians, who tend to have lower brain creatine concentrations, have also shown improved cognitive function with creatine supplementation. As females process stress differently from males, often engaging in frequent multitasking and being more susceptible to sleep deprivation due to pregnancy, post-partum demands, and menopausal sleep disturbances, creatine supplementation is particularly beneficial in supporting these scenarios by enhancing mental capacity even under conditions of sleep deprivation.

Research has shown that acute and chronic sleep deprivation can have a greater negative impact on females compared to males, resulting in lower alertness and increased risks of sleep-related issues. Sleep deprivation has also been linked to reduced cognition, as well as poorer sleep quality for females during the follicular phase (when estrogen levels are low), which also coincides with lower creatine kinase levels. Given this promising research, supplementing with creatine throughout the menstrual cycle may help mitigate the adverse effects of sleep deprivation on cognition and sleep. The cognitive and sleep benefits of creatine supplementation may be especially helpful during times of high stress and sleep deprivation.


Dosing strategies

Creatine can be taken as a loading dose according to the protocol previously discussed. This will increase creatine concentrations in muscles by 19%, comparable to men. Alternatively, a daily dose of 5g can be taken but this will require 3-4 weeks to achieve muscle creatine stores similar to the 5-day loading protocol.

Research indicates that after completing a loading phase, creatine levels remain elevated for approximately 30 days, regardless of whether the individual is male or female. Based on the available evidence, it appears that females can follow the same dosing strategy as males. However, there is individual variability in response to creatine supplementation, with some individuals being responders, quasi-responders, or non-responders. While this has not yet been explored in females, all individuals may likely respond differently to creatine supplementation.

Insulin availability can influence the uptake of creatine by skeletal muscle, potentially enhancing its retention. Consuming creatine with carbohydrates (~50 g) and protein (~50 g), or with 1 g∙kg−1 of glucose, may increase total muscle creatine concentrations compared to creatine supplementation alone. However, for females, the additional calories from carbohydrates and protein to enhance ingestion, particularly during a loading phase, may not be necessary. Women tend to burn fewer calories than men, and if additional calories are not needed to meet training requirements, the potential benefits of enhanced absorption do not justify the added caloric intake. Moreover, due to the menstrual cycle, lower carbohydrate oxidation during the follicular phase may suggest that additional macronutrients are not necessary. One strategy is to take creatine with a regular meal or add it to a protein shake due to the insulin properties of amino acids.

Studies have shown that brain concentrations of creatine and phosphocreatine can be increased through a daily intake of 0.13-0.80 g/kg for 14 days. To maximize brain uptake, a loading phase of 15-20 g per day for 3-7 days, followed by a consistent daily dose of 5-10 g, is recommended for tissue saturation. Ingesting creatine as a drink is the optimal method for peak absorption from supplementation, as opposed to taking it in a capsule, lozenge, or solid meat form.


Potential side effects and interactions

Oral creatine is generally well tolerated, with the most commonly reported adverse effects including dehydration, diarrhea, gastrointestinal discomfort, muscle cramps, and water retention.

There is a potential risk of serious adverse effects when combining caffeine, ephedra, and creatine. There have been reports of an athlete experiencing an ischemic stroke after consuming 6 grams of creatine monohydrate, 400-600 mg of caffeine, 40-60 mg of ephedra, and various other supplements daily for a period of 6 weeks. Additionally, preliminary clinical research suggests that caffeine may reduce the beneficial effects of creatine on athletic performance. Some experts believe that caffeine may inhibit the resynthesis of phosphocreatine.

It is important to exercise caution when using creatine with individuals diagnosed with bipolar disorder, as there have been reports of depression-to-mania switching.

Isolated case reports are suggesting that individuals with pre-existing kidney dysfunction may be at risk of experiencing worsened dysfunction with creatine supplementation. However, this risk has yet to be evaluated in prospective clinical trials.

Patients with Parkinson's disease should exercise caution when combining creatine and caffeine. Taking 10 grams of creatine daily along with a caffeine intake of over 300 mg per day may exacerbate the progression of Parkinson's disease.


Summary:

Due to the changes in creatine homeostasis that occur throughout a woman's life, particularly estrogen, creatine supplementation may offer numerous potential benefits for females. Research has consistently shown that creatine use increases muscle and brain PCr levels, leading to improvements in strength and exercise capacity. When combined with resistance training, creatine can further enhance body composition and bone mineral density, especially in post-menopausal women. Moreover, creatine supplementation has been found to improve mood and cognition.


For females, both a traditional loading dose (0.3 g∙day−1 for 5-7 days) and a routine daily dose (5 g for 4 weeks) are effective. To achieve brain saturation, higher doses of creatine (15-20 g∙day−1 for 3-7 days, followed by 5-10 g∙day−1) may be necessary. Further research is needed to evaluate the specific effects of creatine across the menstrual cycle and to better understand the potential benefits at different phases of the cycle, as well as the use of creatine across the lifespan. Always seek advice from your health professional before taking any supplements.


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