By Maya Shetty, BS and Felicia Song, BS
Midlife marks a significant life transition, bringing hormonal shifts that can reshape a woman’s body and well-being. As women navigate this period, their bodies undergo physiological changes that can impact muscle mass, bone density, metabolism, and overall well-being. Lifestyle factors play a fundamental role in healthy aging, but strategic supplementation can further support women in optimizing their health through midlife and beyond.
Nutrition and exercise researcher at Stanford Lifestyle Medicine Rachele Pojednic, PhD shares evidence-based strategies to help women maintain strength, vitality, and resilience as they age.
Different Supplements for Different Stages of Life
As women age, there are distinct shifts in body composition, and as a result, our nutritional needs change. For example, in our thirties, the focus should be on building and maintaining muscle mass, as bone formation peaks in the late teens and 20s. This foundation is critical because it helps offset the decline in estrogen during perimenopause, which reduces the body’s ability to preserve muscle and bone.
“Research shows that women begin losing skeletal muscle around age 30, with declines ranging from three to five percent per decade, and in some cases, up to 10 percent during the first postmenopausal decade,” states Dr. Pojednic.
After menopause, estrogen and other hormones stabilize at lower levels, making it more difficult for the body to build bone and muscle. Therefore, strength training, a nutrient-dense diet, and intentional supplementation become essential tools not just to mitigate loss of bone density and muscle mass, but to support long-term health.
Also, estrogen has anti-inflammatory properties throughout the body. When estrogen levels begin to decrease during perimenopause, systemic inflammation increases, contributing to a range of health concerns including changes in cognitive function, mood, and sleep. To help counter these effects, strategic supplementation can play a key role in supporting overall health, reducing inflammation, and maintaining balance.
Top 6 Supplements for Perimenopause and Menopause
1) Creatine
Creatine is a tripeptide that is naturally produced by the body and found in animal products. It plays a critical role in energy production and is crucial for maintaining muscle, bone, and brain health. In the body, creatine is stored in the muscles as phosphocreatine, which acts as a fast-acting energy reserve by donating a phosphate group to regenerate ATP, the primary energy currency of cells. This makes muscles more efficient, allowing for improved muscle function and greater overall strength.
“Creatine is one of the most extensively studied supplements in the world, and for good reason,” states Dr. Pojednic. “Recent research has shown considerable benefits in muscle, bone, and brain health.”
Why Creatine Matters for Women 40+
As women age, creatine levels naturally decline. In fact, women tend to have 70 to 80 percent lower creatine stores than men, and this difference becomes even more pronounced with age. This decline can contribute to age-related muscle loss, bone density reduction, and changes in cognitive and emotional health.
Benefits of Creatine Supplementation
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Muscle and Bone Health
Research suggests that creatine supplementation can help improve muscle function, increase muscle size, and enhance bone density in peri- and postmenopausal women, particularly when combined with resistance training.
“By enhancing ATP regeneration, creatine allows women to push their muscles a little harder during exercise, promoting more robust muscle mass and bone strength,” states Dr. Pojednic.
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Cognitive Health
The brain relies heavily on phosphocreatine for energy, and low levels can contribute to brain fog and mood changes. Studies have shown that creatine may enhance short-term memory and overall cognitive performance in adults aged 45 to 64.
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Mood Stability
Emerging research suggests that creatine supplementation may help offset mood changes associated with perimenopause, including anxiety, depression, and sympathetic overdrive. A recent study found that adding creatine to therapy for depression led to greater symptom improvement compared to therapy alone, highlighting its potential role in brain health as women age.
“Topping off creatine stores may help reduce brain fog, moodiness, and other cognitive side effects often experienced during perimenopause,” states Dr. Pojednic.
How to Supplement with Creatine
Dr. Pojednic recommends that women supplement with three-to-five grams of creatine per day. Timing doesn’t matter, so it can be taken at any time of the day that’s convenient. When choosing a supplement, look for one that uses a water-based wash rather than an acid-based wash, as the latter may cause gastrointestinal side effects.
2) Protein
Protein is a vital macronutrient made up of 20 amino acids, nine of which are essential, meaning they must come from food since the body cannot produce them. These essential amino acids—histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine—are crucial for muscle growth, maintenance, recovery, and overall health.
Why Protein Matters for Women 40+
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Increased Protein Needs
As women age, their ability to absorb and utilize protein efficiently declines, making adequate protein intake even more critical. Aging leads to anabolic resistance, meaning the body requires more protein and a greater resistance training stimulus to maintain and build muscle. Without sufficient protein, women may struggle to preserve lean mass, recover from exercise, and maintain metabolic health.
“Most women at all stages of life are not consuming enough protein, and this becomes more of a problem with age. While many women consume only 40 to 60 grams per day, research suggests that a more optimal range is 80 to 100 grams per day for muscle maintenance and growth,” states Dr. Pojednic.
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Muscle and Metabolic Health
Protein is necessary for preserving lean mass, which helps maintain strength, independence, and metabolic function. It also supports post-exercise recovery and reduces the risk of sarcopenia (age-related muscle loss).
How to Get Enough Protein
High-quality animal proteins like meat, dairy, and eggs naturally provide all nine essential amino acids needed for muscle maintenance. Plant-based options such as soy and pea protein can also be effective, but it’s important to ensure they offer a complete amino acid profile. Consuming protein after workouts is particularly beneficial for muscle recovery and growth. Dr. Pojednic recommends women aim for 1.2 to 1.6 grams of protein per kilogram of body weight per day, which translates to a more practical target of 80 to 100 grams.
While a food-first approach is ideal, strategic use of protein powders can help women meet their daily protein needs to support strength, metabolism, and longevity. When choosing a protein powder, look for one that contains all nine essential amino acids and has minimal additives, which can cause bloating or gut irritation. “I opt for unsweetened protein powders to limit additives and sweeten them with ingredients I prefer,” states Dr. Pojednic.
What About Collagen Protein?
While collagen supplements are often marketed for skin, hair, and nail health, collagen is an incomplete protein and does not contain all essential amino acids. It should not be relied upon as a primary protein source over complete protein supplements or whole foods.
3) Vitamin D3
Vitamin D3, in conjunction with calcium (next section), plays a critical role in maintaining bone density, muscle function, and overall health. While commonly associated with osteoporosis and osteopenia prevention, vitamin D is essential for many tissues beyond bone, including the muscles, immune system, cardiovascular health, and cognitive function.
“As women age, they experience a decline in skeletal muscle starting around age 30 and bone mass loss after 40, with both reducing at an accelerated rate during and after menopause,” states Dr. Pojednic. “Supplementation with Vitamin D3 can offer support with both muscle and bone health.”
Why Vitamin D3 Matters for Women 40+
Vitamin D3 is vital for calcium and phosphate regulation, ensuring that bones stay strong and muscles function properly. Additionally, estrogen and vitamin D interact to affect bone health, as estrogen regulates vitamin D metabolism. During perimenopause, declining estrogen levels reduce vitamin D’s effectiveness, making adequate intake even more important.
Key Benefits of Vitamin D3
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Bone and Muscle Health
Vitamin D plays a critical role in skeletal muscle function and bone maintenance. Deficiency in vitamin D (<50 nmol/L) is strongly associated with age-related muscle weakness and muscle mass loss. Inadequate vitamin D levels (<29 ng/ml) have been linked to poor lower body function, particularly in women, increasing the risk of falls and fractures. Studies have shown that supplementation with vitamin D3 improves muscle strength and function, particularly in postmenopausal women with insufficient levels.
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Iron Absorption and Recovery
Vitamin D plays a key role in iron regulation by reducing hepcidin levels, which helps improve iron absorption—particularly important for post-exercise recovery. Since training increases hepcidin, which inhibits iron absorption, taking vitamin D after exercise may counteract this effect, reducing the risk of low iron and anemia in active women.
How to Supplement with Vitamin D3
Vitamin D is difficult to obtain from diet alone, as it is naturally found in few foods, including fatty fish, liver, beef, and fortified foods like cereals, dairy, and juice. The body’s main source of vitamin D comes from sun exposure, but in many regions, the sun’s UVB rays are not strong enough to support vitamin D synthesis between October and April.
To ensure adequate levels, supplementation is often necessary. The recommended dose ranges from 800 to 4,000 IU per day, though higher doses can be detrimental to bone health.
“Finding the ‘sweet spot’ is key, as excessive intake of vitamin D offers diminishing returns. Blood testing can help determine individual needs, ensuring levels are sufficient without exceeding optimal ranges,” states Dr. Pojednic.
For best absorption, look for Vitamin D3 (cholecalciferol), the most bioavailable form. Additionally, taking a Vitamin D3 supplement with fat, such as an omega-3 supplement (keep reading for more on this) will enhance its absorption.
4) Calcium
Calcium is a key mineral required for bone rigidity, stability, and muscle contraction, yet many people—especially women—fail to consume enough from their diets. While green leafy vegetables and dairy are excellent sources, many people don’t eat enough of them, and dairy alternatives are often not fortified with calcium. Without sufficient intake, the body pulls calcium from bones, increasing the risk of osteopenia and osteoporosis with age.
“While calcium is crucial for bones, it also plays a role in nerve function, blood clotting, and muscle contractions—making it essential for heart health and overall mobility,” says Dr. Pojednic.
How Much Calcium Do You Need?
The recommended daily intake for women in their 40s is 1,000 mg of calcium per day. “However, balance is key—too little calcium weakens bones, but excessive calcium without proper nutrient pairing may lead to arterial calcification instead of proper bone mineralization,” warns Dr. Pojednic.
5) Omega-3 Fatty Acids (Fish Oil)
Omega-3 fatty acids are essential nutrients because the body cannot produce them, meaning they must come from food or supplements. These powerful antioxidants help scavenge free radicals, reducing tissue damage and supporting cell membrane integrity in every organ. Omega-3s are particularly important for vascular health, keeping blood vessels flexible and reducing the risk of cardiovascular disease and dementia. They also play a key role in brain function, supporting neurons, maintaining myelin, and helping to keep chronic inflammation low.
Why Omega-3s Matter for Women 40+
Estrogen has natural anti-inflammatory properties, offering protection against chronic inflammation throughout life. However, perimenopausal women lose some of this protective effect, increasing the need for anti-inflammatory support through other mechanisms.
Key Benefits of Omega-3s
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Cognitive Health
Omega-3s may help reduce the risk of Alzheimer’s disease by lowering brain inflammation and supporting nitric oxide production, which promotes blood flow to the brain.
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Muscle Health
Research shows that omega-3s enhance muscle protein synthesis and mitochondrial function, helping to counteract sarcopenia. Their anti-inflammatory properties may also aid recovery and improve performance in athletes.
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Inflammation Reduction
Omega-3s help regulate inflammatory cytokines like IL-1 and IL-6, which may support joint health and post-exercise recovery.
How to Supplement with Omega-3s
For optimal benefits, choose high-quality, purified fish oil supplements to avoid contaminants. If possible, prioritize whole food sources such as fatty fish (salmon, sardines, mackerel), which provide a naturally balanced omega-3 profile. While omega-3s have well-documented benefits, most research has been conducted in men, so more studies are needed to fully understand their effects in female athletes and aging women.
6) Fiber
Rather than a supplement, fiber should primarily be consumed in our diet. The current dietary guideline for fiber is 25 grams daily through fruits, vegetables, whole grains, legumes, beans, nuts, and seeds. Fiber is crucial for our gut health, helps to maintain our blood glucose levels and improve insulin sensitivity, and helps to lower LDL (the bad) cholesterol.
“If fiber is not sufficient through diet, I recommend a fiber supplement, such as psyllium husk, inulin, or methylcellulose daily to help you meet the fiber requirements,” says Gray Shimko, RD, leading dietician at the Stanford Menopause and Healthy Aging program.
The Importance of Exercise When Taking Supplements
While supplements like creatine, protein, vitamin D3, calcium, omega-3s, and fiber provide the body with essential nutrients for muscle, bone, and brain health, they cannot replace the need for exercise. Strength training serves as the necessary trigger for muscle growth and adaptation. While protein and creatine supply the raw materials for muscle repair, it is the physical act of contracting muscles through exercise that signals the body to build and strengthen them.
“To effectively build and maintain muscle as we age, women must actively engage in resistance training, as muscle follows a ‘use it or lose it’ principle,” states Dr. Pojednic. “Engaging in resistance training at least two-to-three times per week—whether through weightlifting, resistance bands, or bodyweight exercises—helps maintain muscle mass, improve bone density, and support metabolic health.”
Exercise also improves how the body absorbs and utilizes nutrients, making supplementation more effective. For example, creatine supplementation enhances strength and performance, but its full benefits are only realized when paired with resistance training. Similarly, omega-3s can reduce inflammation and support muscle recovery, but their impact is greatest when muscles are actively engaged in movement.
By combining strategic supplementation with regular strength training, women 40 plus can maximize muscle retention, protect bone health, and maintain cognitive function, ensuring long-term strength, mobility, and independence as they age.
Foundational Nutrition Before Supplementation
Lastly, when choosing supplements, quality and transparency are key. Look for third-party tested products to ensure two critical factors: first, that the ingredients listed on the bottle are actually present and in the correct doses. Second, third-party testing verifies that there are no undisclosed or harmful substances, such as heavy metals or adulterants. While supplements should complement–not replace–a nutrient-rich diet, the 40s decade is a pivotal transition, making it especially important to identify and address any dietary gaps.
“Think of supplementation as the icing on the cake—helpful for optimizing health, but most effective when approached with prudence and balance,” says Dr. Pojednic. “Supplements should be viewed as tools for marginal gains, not miracle solutions. Foundational nutrition—getting enough protein, fiber, and healthy fats from our food—remains crucial.”
In recent years, a groundbreaking field known as Metabolic Psychiatry has emerged at the intersection of metabolic and brain health. Spearheaded by Shebani Sethi, MD, a Clinical Associate Professor in the Department of Psychiatry and Behavioral Sciences at Stanford University, this innovative field sheds light on the powerful connection between our metabolic health and mental well-being.
As rates of mental illnesses like Alzheimer’s, bipolar disorder, and schizophrenia rise alongside metabolic conditions such as obesity, diabetes, and cardiovascular disease, researchers are uncovering how these seemingly distinct issues may be intertwined. A Stanford study found that developing a metabolic disorder like insulin resistance can double your risk of depression, even if you’ve never experienced mental illness before. As such, emotional and metabolic disorders often occur together, with over forty percent of individuals with severe mental illnesses also experiencing metabolic syndrome.
It’s easy to see how mental illness could lead to conditions such as obesity or diabetes because someone struggling emotionally might be unable to eat well or exercise. However, it’s becoming increasingly apparent that metabolic disorders have a distinct role in the onset and progression of mental illnesses.
“Many psychiatric diseases have underpinnings in metabolic dysfunction,” explains Dr. Sethi. “We are seeing insulin and glucose handling differences in the brain in patients with psychiatric conditions.”
These metabolic issues in the brain are present even at the early stages of disease detection and progression. Dr. Sethi explains that patients diagnosed with a first episode of schizophrenia—before any treatment with medications—already show disrupted energy metabolism in the brain. Similarly, Alzheimer’s disease has been referred to as type III diabetes due to its strong link to disrupted insulin signaling in the brain.
Dr. Sethi has been a trailblazer in this area since 2015, founding the first academic Metabolic Psychiatry Clinic focused on treating patients with both mental health and metabolic disorders. Metabolic Psychiatry examines how improving metabolic health through nutritional interventions can significantly enhance brain health and mitigate the symptoms of severe psychiatric conditions.
How Metabolic Health Impacts Brain Health
Many psychiatric diseases are characterized by metabolic dysfunctions, which impair the brain’s ability to function properly. These dysfunctions occur when chemical processes are disrupted, hindering the body’s ability to produce and utilize energy efficiently.
A well-known example is insulin resistance, where the body’s cells don’t respond appropriately to insulin—the hormone that allows glucose to enter cells and be metabolized for energy. The brain, one of the most metabolically active organs, requires large amounts of energy to function. It is highly dependent on glucose due to its limited flexibility to use other energy sources. This dependence makes metabolic conditions like insulin resistance particularly harmful, as any disruption in glucose supply puts the brain at risk for cognitive decline and neuronal degeneration.
“If you don’t have optimal metabolic functioning in the brain, then you won’t process and create energy as efficiently as a healthy brain,” states Dr. Sethi. “The brain will have all this glucose around it, but you can’t actually use it properly. This is called cerebral glucose hypometabolism, and it’s very common in psychiatric and neurodegenerative diseases.”
Other metabolic abnormalities commonly seen in psychiatric conditions include oxidative stress, mitochondrial dysfunction, and neurotransmitter imbalances, which all have downstream effects on synapse connection and neuronal excitability.
“We don’t know for sure what the primary drivers for these metabolic dysfunctions are, but it is likely a combination of factors influencing one another,” says Dr. Sethi. “For example, insulin resistance is correlated with higher inflammation levels and oxidative stress in the brain, which in turn exacerbates mitochondrial and neurotransmitter dysfunction.”
Chronic inflammation disrupts brain activity and undermines the integrity of the brain’s protective mechanisms. The blood-brain barrier (BBB), a critical structure that protects the brain from harmful substances in the blood, becomes compromised. This “leaky” BBB allows inflammatory molecules, pathogens, and toxins to enter the brain from the bloodstream, exacerbating the inflammatory response within the brain and creating a self-perpetuating cycle of neuroinflammation. “We see significantly more inflammation in the brains of people with mental illness, especially in treatment-resistant patients, than in healthy people,” states Dr. Sethi.
How Nutrition Can Improve Brain Health
Dr. Sethi’s metabolic approach to brain health not only enhances our understanding of psychiatric conditions but also opens up new avenues for treatment, such as nutritional interventions. Studies have shown that nutritional interventions can impact the balance of neurotransmitters in the brain, which is crucial for regulating mood and behavior.
By targeting metabolic dysfunctions such as insulin resistance, oxidative stress, and improper energy utilization, nutritional interventions can help restore brain function and reduce inflammation. This comprehensive approach addresses the symptoms of psychiatric conditions while tackling their underlying causes, offering a more effective and holistic treatment strategy.
The Stanford Metabolic Psychiatry group, led by Dr. Sethi, is investigating whether dietary changes, such as adopting a ketogenic diet, can stabilize brain health. The ketogenic diet, which is high in fat and low in carbohydrates, encourages the brain to use fat and ketone bodies as primary fuels instead of glucose. This metabolic shift helps counteract issues related to glucose metabolism and insulin resistance. The diet adopted in the study focuses on consuming whole, unprocessed foods, including protein and non-starchy vegetables, without restricting fats.
“The ketogenic diet is a strong, powerful metabolic intervention. It can improve neurological and psychiatric conditions by making changes in the brain through these pathways,” says Dr. Sethi. “By providing ketones as an alternative energy source, the ketogenic diet reduces glucose dependency, which is beneficial in counteracting glucose hypometabolism.”
In Dr. Sethi’s study among participants with schizophrenia consuming a ketogenic diet, there was a 32 percent reduction in Brief Psychiatric Rating Scale scores. There was also increased life satisfaction and enhanced sleep quality among participants.
The ketogenic diet can also have a positive influence on brain aging for everyone and has been experientially understood to help normalize the brain for centuries. Dating back to roughly 500 BC, fasting (which mimics the ketogenic diet) was used to treat epilepsy. Current research shows that the destabilization of brain networks might indicate early signs of reduced metabolism, which is linked to dementia. By increasing the use of ketones for energy, dietary interventions like the ketogenic diet can provide more energy to the brain and potentially protect against aging-related cognitive decline.
Dr. Sethi warns, however, that “the ketogenic diet is very specific and may not be suitable for everyone. It can be incredibly beneficial for people with insulin resistance, obesity, or diabetes, but it may not be feasible or appropriate for all individuals.”
Future studies will reveal further dietary interventions that benefit brain health. For example, Dr. Sethi and her team plan to conduct a randomized controlled trial with the ketogenic diet versus the Mediterranean diet in cases of serious mental illness. Whichever diet one chooses, Dr. Sethi recommends the reduction of sugar, ultra-processed foods, and refined carbohydrates to promote both metabolic and brain health.
“Our diet provides the precursors for neurotransmitters and other vital cellular structures in the brain, while also impacting inflammation levels. If we have deficiencies in our diet, we’re not going to be able to create the components and environment we need for optimal brain function and regulation of mood,” states Dr. Sethi.
By Mary Grace Descourouez, MS, NBC-HWC
The human gastrointestinal tract is home to trillions of microorganisms that create the gut microbiome. The gut is where the body digests and absorbs nutrients from our food and, therefore, where we get our energy to perform daily human functions. Microbiota are microorganisms in the gut microbiome that help the body harvest energy, fight pathogens, and regulate immunity. Having a high diversity of microbiota helps us to process food effectively, providing the substrates and nutrients needed to keep us going throughout the day. Therefore, it is crucial to make lifestyle choices that promote a healthy and diverse microbiome.
Many people know that a nutrient-rich diet contributes to a healthy microbiome, however, research shows that movement and exercise may also have a positive effect, and, inversely, a healthy microbiome may improve athletic performance.
“It is a relatively new field, but available studies suggest a bidirectional relationship between performance and the health of the microbiome,” says Anne Friedlander, PhD, Exercise Physiologist and Assistant Director of Stanford Lifestyle Medicine. “People who are more active have a healthier and more diverse microbiome, and that, in turn, provides the person with the nutrients required to enhance physical and cognitive performance. It is a mutually beneficial relationship.”
How Exercise Improves the Microbiome
Movement and exercise have many benefits on our overall health, including positive effects on the microbiome. Studies show that athletes have a more diverse microbiome composition than non-athletes. Microbiome diversity is important because it helps make our food’s nutrients more bioavailable for optimal functioning of the body.
Another study found that active women were associated with high microbiome diversity compared to sedentary women. Specifically, researchers found that consistent physical activity increased the amount of 11 genera of “good” bacteria, including Bifidobacterium spp, Roseburia hominis, Akkermansia muciniphila, and Faecalibacterium prausnitzii.
How the Microbiome Improves Athletic Performance
Just as exercise positively impacts the microbiome, emerging research shows that microbiome health may also play a part in enhancing exercise performance.
For example, a 2019 study showed that a specific gut microbiota in marathon runners may have enhanced their athletic performance on race day. In this study, researchers collected fecal samples from the runners before and after the marathon and compared them to microbiota of non-runners. The “good” bacteria Veillonella emerged as the most common in the runners, especially post marathon. Veillonella is a bacterial strain that converts exercise-induced lactate into propionate, which is a natural enzymatic process known to enhance athletic performance.
Researchers then put the Veillonella bacteria from the marathon runners into lab mice who underwent a treadmill exertion test to investigate the hypothesis that this bacterial strain enhances athletic performance. The results showed the mice improved performance by 13 percent after inoculation. This study is one of the first to infer that a healthy microbiome could enhance athletic performance.
“We have a long way to go to fully understand the complex system that involves the microbiome and athletic performance, but the early data look promising regarding gut health and exercise,” says Dr. Friedlander. “Exercise, along with eating fermented foods and fiber, is a great place to start if you want to improve your gut health and overall health.”