The supplement aisle just got a lot more interesting for women over 40.
For decades, creatine has been filed away in our minds under “bodybuilder supplement” or “gym bro essential.” But emerging research is flipping that narrative on its head. Science now shows that creatine monohydrate—the most researched supplement on the planet—may be one of the most powerful tools for protecting and enhancing brain function as we age, especially for women navigating perimenopause, menopause, and beyond.
If you’re experiencing brain fog, struggling with word recall, or noticing your mental stamina isn’t what it used to be, this isn’t just “getting older.” Your brain is facing real energy challenges—and creatine might be exactly what it needs.
What Is Creatine, Really?
Creatine is an organic compound your body naturally produces from three amino acids: arginine, glycine, and methionine. About half of your body’s creatine comes from internal production, while the other half comes from dietary sources—primarily meat and fish. Creatine is stored mainly in your muscles (and brain), where it plays a critical role in energy production by replenishing ATP (adenosine triphosphate), the cellular currency your body uses for quick bursts of energy (Bonilla et al., 2021).
Here’s what most people don’t realize: your brain is an energy hog. Despite making up only 2% of your body weight, your brain consumes about 20% of your total energy. When brain energy production falters—due to aging, hormonal changes, stress, or sleep deprivation—cognitive function takes a hit. That’s where creatine supplementation comes in.
The Brain Energy Crisis: Why Women Over 40 Are Particularly Vulnerable
As women enter their 40s and transition through perimenopause and menopause, several physiological shifts create the perfect storm for declining brain energy:
1. Estrogen Decline Affects Brain Metabolism
Estrogen isn’t just a reproductive hormone—it’s a powerful neuroprotective agent that supports energy production in the brain, particularly in the hippocampus (the memory and learning center). As estrogen levels fluctuate and decline during perimenopause, the brain loses access to this critical fuel source, which helps explain the brain fog and memory lapses so many women experience in midlife (Forbes et al., 2023).
2. Women Have Lower Brain Creatine Levels Than Men
Research shows that women naturally have lower creatine concentrations in the brain, especially in the frontal cortex—the area responsible for mood regulation, attention, memory, and executive function (Smith-Ryan et al., 2021). This gender difference makes supplementation potentially even more beneficial for women.
3. Hormonal Changes Affect Creatine Production
The fluctuations in estrogen, progesterone, and testosterone during perimenopause and menopause can affect how much creatine your body produces, utilizes, and needs to function optimally (Cabre et al., 2025). This makes the 40s and 50s prime time for creatine supplementation.
The Science: What Recent Research Reveals About Creatine and Cognitive Function
Memory, Attention, and Processing Speed Improvements
A comprehensive 2024 systematic review and meta-analysis examined 16 randomized controlled trials involving 492 adults aged 20–76 years. The results were striking:
- Memory improved significantly (effect size: 0.30)
- Attention time improved (faster reaction times)
- Processing speed increased by 51% (Xu et al., 2024)
The researchers found that creatine supplementation was particularly beneficial for individuals aged 18–60 years, people with existing health conditions, and notably, for women.
Cognitive Function Under Stress
One of creatine’s most impressive benefits is its ability to protect cognitive function during periods of stress or sleep deprivation. A 2024 study published in Scientific Reports found that a single high dose of creatine improved cognitive performance and induced measurable changes in brain energy phosphates during sleep deprivation (Gordji-Nejad et al., 2024). While most people require weeks of supplementation for brain benefits, this research suggests creatine’s protective effects can be profound.
Brain Energy and Neuroprotection
Creatine works by supporting the brain’s energy systems at a cellular level. It helps regenerate ATP, the molecule that powers every thought, memory formation, and neural signal. This is particularly important during aging when mitochondrial function (your cells’ power plants) naturally declines. By boosting brain creatine stores, supplementation may help maintain cognitive resilience and protect against age-related cognitive decline (Ribeiro et al., 2025).
Emerging Research in Alzheimer’s Disease
Exciting preliminary research from 2025 shows promise for creatine in neurodegenerative conditions. A pilot study at the University of Kansas Alzheimer’s Disease Research Center found that 8 weeks of creatine monohydrate supplementation (20g/day) increased brain creatine levels and was associated with improvements in cognitive function in patients with Alzheimer’s disease (Smith et al., 2025). While more research is needed, these findings suggest creatine’s neuroprotective potential extends beyond healthy aging.
Beyond Cognition: The Mood and Mental Health Connection
Depression rates are twice as high in women compared to men, and this disparity is directly linked to hormonal milestones—puberty, the menstrual cycle, postpartum, and perimenopause (Smith-Ryan et al., 2021). Several factors make creatine particularly relevant for mood support:
Lower Brain Creatine = Higher Depression Risk
Research shows that women have lower levels of creatine in the brain’s frontal cortex, which governs mood, cognition, memory, and emotion. Studies have found an inverse relationship between dietary creatine intake and the incidence of depression—meaning higher creatine levels are associated with lower depression rates (Forbes et al., 2023).
Creatine as Adjunctive Therapy
Multiple studies have explored creatine as an adjunctive treatment alongside antidepressants. A 2024 pilot study found that creatine monohydrate supplementation enhanced the effectiveness of cognitive behavioral therapy (CBT) in treating depression (Sherpa et al., 2025). While creatine isn’t a standalone treatment for depression, it may support brain energy homeostasis in ways that improve mood and resilience.
The Menopause Connection: Why Creatine Matters Even More in Midlife
For women in perimenopause and menopause, creatine offers a unique constellation of benefits that address multiple aspects of health simultaneously:
1. Muscle Mass Preservation
Women can expect to lose 3–5% of their muscle mass per decade starting in their 30s, with accelerated loss after menopause. Since muscle is metabolically active, this loss often results in slower metabolism, weight gain, and insulin resistance. Creatine supplementation, especially when combined with resistance training, helps preserve and build lean muscle mass (Candow et al., 2024).
2. Bone Density Protection
A groundbreaking 2015 study assigned 47 postmenopausal women to resistance training plus either creatine or placebo for 12 months. The creatine group lost only 1.2% of bone mineral density at the femoral neck (a common site for osteoporotic fractures) compared to nearly 4% loss in the placebo group (Candow et al., 2015). This protective effect on bone health is particularly significant given the rapid bone loss women experience post-menopause.
3. Reduced Fatigue
Fatigue is one of the most common complaints in perimenopause. Creatine helps reduce fatigue by increasing cellular energy availability—particularly beneficial during hormonal fluctuations. It also supports greater workout intensity, recovery quality, and may improve sleep duration following resistance training (Cabre et al., 2025).
4. Metabolic Support
Creatine may help improve glucose metabolism and insulin sensitivity, which becomes increasingly important as the risk of metabolic syndrome rises during and after menopause (Forbes et al., 2023).
Dosing: How Much Creatine Should You Take?
Based on current research, here are evidence-based dosing recommendations:
Standard Protocol
- Daily dose: 3–5 grams per day of creatine monohydrate
- This simple approach gradually saturates muscle and brain creatine stores over 3–4 weeks (Kreider et al., 2017)
Loading Protocol (Optional)
- Loading phase: 20 grams per day (split into 4 doses of 5g) for 5–7 days
- Maintenance: 3–5 grams per day thereafter
- Loading achieves saturation faster but is not necessary (Antonio et al., 2021)
For Brain-Specific Benefits
- Some researchers suggest higher doses (15–20g/day for 3–7 days, followed by 5–10g/day) may be warranted for brain saturation due to the blood-brain barrier limiting uptake (Smith-Ryan et al., 2021)
Timing
- Creatine can be taken any time of day
- Taking it with a meal containing carbohydrates may slightly enhance uptake due to insulin’s role in creatine transport
- Consistency matters more than timing
Form Matters
Creatine monohydrate is the gold standard. It’s the most researched, most effective, and most affordable form. Other forms (ethyl ester, HCl, buffered) have not demonstrated superior benefits and often cost significantly more (Kreider et al., 2017).
Safety: Is Creatine Safe for Women Over 40?
After more than 25 years of research, creatine monohydrate is one of the most thoroughly studied supplements available. Here’s what the science says:
Well-Established Safety Profile
- Multiple long-term studies (up to 5 years) show no adverse effects on kidney or liver function in healthy adults at recommended doses (Antonio et al., 2021)
- A comprehensive 2025 safety analysis examined prevalence of side effects across clinical trials and found no significant difference between placebo and creatine groups (Forbes et al., 2025)
- The International Society of Sports Nutrition concludes that creatine monohydrate is safe for long-term use when taken at recommended doses (Kreider et al., 2017)
Common Concerns (Debunked)
“Will it damage my kidneys?” No. Extensive research shows creatine does not harm kidney function in healthy individuals. While rare case reports exist, these involve individuals with pre-existing kidney disease or concurrent use of nephrotoxic medications (Kreider et al., 2017).
“Will it make me gain weight?” Creatine may cause 1–3 pounds of water retention in the first week as it pulls water into muscle cells. This is temporary and not fat gain. Long-term, any weight gain is typically lean muscle mass when combined with resistance training.
“Is it only for men?” Absolutely not. In fact, women may benefit even more due to lower baseline creatine levels. A 2021 comprehensive review specifically on creatine in women’s health found it safe and beneficial across the lifespan (Smith-Ryan et al., 2021).
When to Exercise Caution
- If you have pre-existing kidney disease, consult your physician before supplementation
- Avoid during pregnancy and breastfeeding (insufficient safety data)
- Choose reputable brands that undergo third-party testing (look for NSF Certified for Sport or Informed Choice certifications)
Who Should Consider Creatine Supplementation?
Creatine may be particularly beneficial if you:
✓ Are experiencing brain fog, memory lapses, or difficulty concentrating during perimenopause/menopause
✓ Want to preserve muscle mass and metabolic health after 40
✓ Are concerned about bone density and fracture risk
✓ Follow a vegetarian or vegan diet (plant-based eaters have lower creatine stores)
✓ Experience mental fatigue or difficulty recovering from poor sleep
✓ Are doing resistance training and want to maximize results
✓ Have a family history of cognitive decline or are interested in neuroprotection
✓ Struggle with low mood or energy during hormonal transitions
The Bottom Line
Creatine isn’t just for bodybuilders anymore—it’s emerging as one of the most promising supplements for brain health, cognitive function, and healthy aging, especially for women over 40. The science is remarkably consistent: creatine monohydrate supplementation can improve memory, attention, processing speed, and mental resilience while also supporting muscle mass, bone density, and metabolic health during the critical transition through menopause.
At 3–5 grams per day, creatine is affordable (often less than $20/month), safe, and backed by more research than virtually any other supplement on the market. For women navigating the cognitive and physical changes of midlife, it represents a simple, evidence-based strategy to support both brain and body.
Your brain deserves the same attention as your muscles. And in an age where we’re redefining what 40, 50, 60, and beyond can look like, creatine might just be the cognitive edge you’ve been missing.
References
Antonio, J., Candow, D. G., Forbes, S. C., Gualano, B., Jagim, A. R., Kreider, R. B., Rawson, E. S., Smith-Ryan, A. E., VanDusseldorp, T. A., Willoughby, D. S., & Ziegenfuss, T. N. (2021). Common questions and misconceptions about creatine supplementation: What does the scientific evidence really show? Journal of the International Society of Sports Nutrition, 18(1), 13. https://doi.org/10.1186/s12970-021-00412-w
Bonilla, D. A., Kreider, R. B., Stout, J. R., Forero, D. A., Kerksick, C. M., Roberts, M. D., & Rawson, E. S. (2021). Metabolic basis of creatine in health and disease: A bioinformatics-assisted review. Nutrients, 13(4), 1238. https://doi.org/10.3390/nu13041238
Cabre, H. E., Moore, A. N., Poole, C. N., Olson, K., Davy, K. P., & Hulver, M. W. (2025). Creatine in women’s health: Bridging the gap from menstruation through pregnancy to menopause. Journal of the International Society of Sports Nutrition, 22(1), 2502094. https://doi.org/10.1080/15502783.2025.2502094
Candow, D. G., Chilibeck, P. D., Forbes, S. C., Fairman, C. M., Gualano, B., & Roschel, H. (2024). Creatine supplementation for older adults: Focus on sarcopenia, osteoporosis, frailty and Cachexia. Bone, 162, 116467. https://doi.org/10.1016/j.bone.2022.116467
Candow, D. G., Chilibeck, P. D., & Forbes, S. C. (2015). Effect of creatine supplementation and resistance training on muscle creatine stores and bone mineral content in postmenopausal women. Journal of Bone and Mineral Research, 30(Suppl 1), S151.
Forbes, S. C., Candow, D. G., Ostojic, S. M., Roberts, M. D., & Chilibeck, P. D. (2023). Creatine supplementation and muscle-brain axis. Nutrients, 15(2), 134. https://doi.org/10.3390/nu15020134
Forbes, S. C., Candow, D. G., Ferreira, L. H. B., & Souza-Junior, T. P. (2025). Safety of creatine supplementation: Analysis of the prevalence of reported side effects in clinical trials and adverse event reports. Nutrients, 17(5), 789. https://doi.org/10.3390/nu17050789
Gordji-Nejad, A., Matusch, A., Kleedörfer, S., Raimundo, A. M., Pierscianek, D., Chen, B., Drzezga, A., & Tarnopolsky, M. A. (2024). Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Scientific Reports, 14(1), 4937. https://doi.org/10.1038/s41598-024-54249-9
Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., Candow, D. G., Kleiner, S. M., Almada, A. L., & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14, 18. https://doi.org/10.1186/s12970-017-0173-z
Ribeiro, F., Forbes, S. C., Candow, D. G., Perim, P., Lira, F. S., Lancha, A. H., Jr., & Rosa Neto, J. C. (2025). Creatine supplementation and muscle-brain axis: A new possible mechanism? Frontiers in Nutrition, 12, 1579204. https://doi.org/10.3389/fnut.2025.1579204
Sherpa, N. N., De Giorgi, R., Ostinelli, E. G., Choudhury, A., Dolma, T., & Dorjee, S. (2025). Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area. European Neuropsychopharmacology, 90, 28–35. https://doi.org/10.1016/j.euroneuro.2024.10.004
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DISCLAIMER: This article is for educational and informational purposes only and is not intended as medical advice. Always consult with a qualified healthcare provider before starting any new supplement regimen, especially if you have pre-existing health conditions or are taking medications. The information provided is based on current scientific research but should not replace personalized medical guidance.
About Island Wellness: At Island Wellness, we believe in empowering you with evidence-based strategies for optimal health at every stage of life. Our approach combines cutting-edge research with personalized care to help you thrive through perimenopause, menopause, and beyond.