How Midlife Metabolic Changes in Women Can Impact Brain Health

January 16, 2024

As women transition into midlife, they often encounter a myriad of health considerations, and in the spotlight is metabolic health, which extends a long reach into cardiovascular and cognitive health.  Midlife is a dance between hormones and metabolism that can set-up women for long-term health or tip the scales into health risks, leading to conditions such as insulin resistance, weight fluctuations, and altered energy regulation.1  These negative metabolic shifts, when left unaddressed, weave a web that lead to very specific consequences to the brain. 

Midlife Metabolic Changes and Challenges 

In midlife, hormonal fluctuations and physiological changes occur, which can impact numerous systems in the body.  You may have heard of a “poor metabolism” or increasing abdominal fat happening during midlife, especially in women entering menopause, but there are underlying metabolic changes taking place that contribute to the challenges we often face at this phase of life.2  

One common metabolic change is the increase in insulin resistance, a process in which the body does not respond normally to insulin, a hormone critically involved in regulating blood sugar levels.1  This leads to a rise in blood sugar levels, which can ultimately lead to type 2 diabetes over time.  

Weight fluctuations are another occurrence in midlife, with weight gain being especially common in women during menopause.  Weight gain is often specifically localized to the abdominal region, associated with increased amounts of visceral fat.  Visceral fat is located deeper inside the body around vital organs, especially around the abdomen.  It’s not the soft kind of fat near the surface; it is underneath the abdominal wall.  Importantly, researchers have discovered that visceral fat is not just a fat storage location, but also it can be classified as an endocrine organ, releasing inflammatory chemicals (called cytokines) and other chemicals that can increase blood pressure.3  It is no surprise that visceral fat is significantly associated with increased risk of cardiovascular disease.4 

Women often experiences changes in energy regulation during midlife as well, with people frequently reporting feeling fatigued or having reduced energy.  Insulin resistance reduces the movement of glucose (a sugar) from the blood into cells to be used to produce energy, resulting in lower energy production.5   

Imagine a car not being able to pump gasoline into the engine, or an electric car not wired to its battery.  Insulin resistance is a disconnect with our main energy source. 

The Elevated Risk of Metabolic Syndrome and Its Relationship to Menopause 

These changes are often associated with an increased risk of metabolic syndrome, which further increases risk of cardiovascular disease, stroke, and type 2 diabetes.  Metabolic syndrome is characterized by 3 or more of the below metabolic health conditions:6 

  • Abdominal obesity 
  • Elevated blood triglycerides 
  • Reduced HDL cholesterol 
  • Elevated blood pressure 
  • Elevated blood sugar levels 

To learn more about metabolic syndrome and the specific thresholds for which to beware, as well as how it can impact your brain health, visit here. 

In fact, women who enter menopause are more prone to having metabolic syndrome.2  (FYI:  menopause is defined by 12 months without a menstrual period and associated with a rapid drop in the hormone estradiol, or estrogen.  For more information about menopause, check out our previous article here.) 

The hormonal changes that women experience during menopause alter several systems in the body, which may contribute to metabolic syndrome.  For example, visceral fat cells are more sensitive to other hormones called androgens, which are predominant following the decrease in estrogen.  This may be responsible for why women see an increase in abdominal fat.2 

Also, while metabolic syndrome is more common in men than premenopausal women of the same age, during menopause, women have a higher prevalence of metabolic syndrome than men.2  In fact, one study found a 24% increase in risk of metabolic syndrome after menopause compared to before.7 

Health Risks for Women with Metabolic Syndrome  

  • Type 2 Diabetes: Several studies have shown that metabolic syndrome is highly associated with new onset of type 2 diabetes.  In particular, changes (increase) in fasting glucose have the strongest correlation with type 2 diabetes.8 
  • Cardiovascular Disease: The risk for cardiovascular disease also increases with metabolic syndrome.  Some key factors which may be responsible for the elevated risk of heart disease include increased total cholesterol and LDL cholesterol, which have been shown to increase the most just before and after the final menstrual period.  Additionally, blood pressure has been shown to increase 1 year after menopause.9 
  • Sleep and Sleep Apnea: Sleep is another area that often sees changes during midlife, and it can relate to metabolic health in several ways.  Menopause is often accompanied by sleep disturbances, which can in turn impact eating behavior and impulse control, leading to further metabolic changes.  Vasomotor symptoms such as hot flashes and night sweats are common with menopause and can significantly impact sleep.10  Metabolic syndrome has also been associated with obstructive sleep apnea, a sleep disorder characterized by frequent starting and stopping of breathing.11  (For more about the importance of sleep and sleep disorders, check out this article.) 

Metabolic Impact on Women’s Cognitive Health, Alzheimer's, and Related Dementias 

So, how do these metabolic conditions relate to the brain?  Similar to the old saying “all roads lead to Rome” we like to remember that “all metabolic roads lead to brain health.”  As such, the insulin resistance and diabetes, cardiovascular health, and sleep topics discussed above all contribute to brain health. 

Overall, metabolic syndrome is associated with an increased risk of cognitive impairment in older women.12  As we’ve mentioned previously, there are several factors that contribute to metabolic syndrome, and many of these components, including diabetes, obesity, and cardiovascular risk factors, are also separately associated with dementia risk.13 

So what’s happening in the brain?  There are several metabolic changes that occur directly in the brain, which may explain the higher risk of cognitive decline.  Insulin has physiological effects on the brain, and when insulin resistance occurs, it can impact glucose metabolism.  Glucose metabolism is critical to produce energy for the brain to function, especially since the brain is the most energy-demanding organ, using about half of all sugar in the body.14  The challenge is that glucose metabolism in the brain decreases in midlife during menopause.13,15 

Similarly, obesity and diabetes trigger an inflammatory response in the body, often resulting in chronic inflammation, which has many harmful effects on brain function.  That is, a decrease in estrogen and changes in glucose metabolism can activate an immune response that extends to the brain, causing neuroinflammation, a key contributor to Alzheimer’s disease.13  

In midlife women, we see both chronological aging and endocrine aging effects in the brain.  Endocrine aging is defined by the hormonal changes that occur and is more closely associated with a decrease in glucose metabolism and increase in inflammation.15  These changes can have drastic impacts on cognitive function, as one study found for every additional metabolic syndrome factor (out of the five), there was a 23% greater risk of cognitive impairment.12 

Strategies to Manage Metabolic and Brain Health in Menopausal Women 

In menopausal women, the combination of decreasing brain glucose metabolism, increasing neuroinflammation, as well as a higher risk for metabolic syndrome, highlight the importance of combating these through lifestyle.  

Here’s our metabolic health action plan to best support metabolic and brain health in midlife: 

  • Physical Activity:  Exercise has been shown to improve metabolic health, particularly in women after menopause.  Physical activity has been associated with reduced visceral fat, and helps the body compensate for some of the benefits of estrogen that are lost during menopause.16  Aim for 30 minutes daily of moderate exercise as a beginning step, like brisk walking.  Although you may not feel immediate effects (like weight loss), it will chip away at the deep visceral fat stores.  
  • Stop Smoking and Reduce Alcohol Intake:  It is well-known and recommended for people to quit smoking and limit alcohol use to reduce cardiovascular risk, since they contribute to poor metabolic health and increase inflammation.9 
  • Reduce Stress:  The stress response contributes to insulin resistance, and thus, metabolic syndrome, through the release of cortisol and epinephrine, so it’s important to reduce stress to best support optimal metabolic health.17  Some common stress management practices include deep breathing or meditation, exercise, keeping a gratitude journal, spending time with loved ones, and practicing self-care. 
  • Eat a Healthy Diet:  The Mediterranean diet is well-recognized for its many health benefits, and metabolic health is no exception.  It is characterized by the consumption of colorful fruits, vegetables, whole grains, legumes, nuts and seeds, fish, and generous helpings of olive oil.  The Mediterranean diet has been associated with better metabolic health in postmenopausal women.18  In fact, the Mediterranean diet itself is comparable to medications in its effectiveness to reduce risk of obesity and cardiovascular events.19 
  • Another factor to consider is hormone therapy (or hormone replacement therapy, HRT), since the underlying biology and growing evidence work in its favor.  While much has been written about the pros and cons of hormone therapy, it’s important to consult with your physician, since the timing of the therapy in relation to the onset of menopause appears to be a very important factor in its effectiveness.17 

As women enter midlife, special attention should be paid to their metabolic health with aims to manage metabolic health conditions in order to maintain overall health, and ultimately reduce any harmful impacts on brain health. 

For assistance with nutrition and helping yourself receive essential nutrients from the Mediterranean diet, consider RELEVATE.  RELEVATE contains 17 research-based nutrients to support both healthy metabolism and long-term brain health.  Its dosages are based on those consumed in brain-healthy diets like the Mediterranean and MIND diets.  RELEVATE is built on evidence from long-term studies of these brain strengthening diets that are linked to significantly reduced risk of age-related neurodegenerative disease (over 50% reduced risk of Alzheimer’s).20  Learn more about RELEVATE by visiting here.  You may want to consider a supplement like this if you want to close important gaps and reinforce your metabolic and cognitive health with neuroprotective nutrition.  

To learn more about metabolic health, check out our article on the “Four Horsemen” of disease and how they are connected to metabolism.21

For additional guidance on managing your metabolic health, with helpful guides, recipes, and more, download our FREE E-Guide “Metabolic Health Reset” by visiting here.  

References

  1. Carr MC. The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab. 2003;88(6):2404-2411. doi:10.1210/jc.2003-030242
  2. Jeong HG, Park H. Metabolic Disorders in Menopause. Metabolites. 2022;12(10). doi:10.3390/metabo12100954
  3. Taking Aim at Belly Fat - Harvard Health Publishing - Harvard Health. (n.d.). Retrieved January 15, 2024, from https://www.health.harvard.edu/staying-healthy/taking-aim-at-belly-fat 
  4. Kapoor E, Collazo-Clavell ML, Faubion SS. Weight Gain in Women at Midlife: A Concise Review of the Pathophysiology and Strategies for Management. Mayo Clin Proc. 2017;92(10):1552-1558. doi:10.1016/j.mayocp.2017.08.004  
  1. Rahman MS, Hossain KS, Das S, et al. Role of insulin in health and disease: An update. Int J Mol Sci. 2021;22(12):1-19. doi:10.3390/ijms22126403
  2. Metabolic Syndrome - What Is Metabolic Syndrome? | NHLBI, NIH. https://www.nhlbi.nih.gov/health/metabolic-syndrome. Accessed January 2, 2024.
  3. Janssen I, Powell LH, Crawford S, Lasley B, Sutton-Tyrrell K. Menopause and the Metabolic Syndrome: The Study of Women’s Health Across the Nation. Arch Intern Med. 2008;168(14):1568-1575. doi:10.1001/archinte.168.14.1568
  4. Shin JA, Lee JH, Lim SY, et al. Metabolic syndrome as a predictor of type 2 diabetes, and its clinical interpretations and usefulness. J Diabetes Investig. 2013;4(4):334-343. doi:10.1111/jdi.12075
  5. El Khoudary SR, Nasr A. Cardiovascular disease in women: Does menopause matter? Curr Opin Endocr Metab Res. 2022;27:100419. doi:10.1016/j.coemr.2022.100419
  6. Kravitz HM, Kazlauskaite R, Joffe H. Sleep, Health, and Metabolism in Midlife Women and Menopause: Food for Thought. Obstet Gynecol Clin North Am. 2018;45(4):679-694. doi:10.1016/j.ogc.2018.07.008
  7. Kim DH, Kim B, Han K, Kim SW. The relationship between metabolic syndrome and obstructive sleep apnea syndrome: a nationwide population-based study. Sci Rep. 2021;11(1):1-8. doi:10.1038/s41598-021-88233-4
  8. Yaffe K, Weston AL, Blackwell T, Krueger KA. The Metabolic Syndrome and Development of Cognitive Impairment Among Older Women. Arch Neurol. 2009;66(3):324-328. doi:10.1001/archneurol.2008.566
  1. Christensen A, Pike CJ. Menopause, obesity and inflammation: Interactive risk factors for Alzheimer’s disease. Front Aging Neurosci. 2015;7(JUN):1-14. doi:10.3389/fnagi.2015.00130
  2. Sugar and the Brain | Harvard Medical School. (n.d.). Retrieved January 15, 2024, from https://hms.harvard.edu/news-events/publications-archive/brain/sugar-brain
  3. Brinton RD, Wang Y, Mishra A. Transitions in metabolic and immune systems from pre-menopause to post-menopause: Implications for age-associated neurodegenerative diseases. F1000Research. 2020;9. doi:10.12688/f1000research.21599.1
  4. Marsh ML, Oliveira MN, Vieira-Potter VJ. Adipocyte Metabolism and Health after the Menopause: The Role of Exercise. Nutrients. 2023;15(2). doi:10.3390/nu15020444
  5. Seematter G, Binnert C, Tappy L. Stress and metabolism. Metab Syndr Relat Disord. 2005;3(1):8-13. doi:10.1089/met.2005.3.8
  6. Leone A, De Amicis R, Battezzati A, Bertoli S. Adherence to the Mediterranean Diet and Risk of Metabolically Unhealthy Obesity in Women: A Cross-Sectional Study. Front Nutr. 2022;9(April):1-9. doi:10.3389/fnut.2022.858206
  7. Barrea L, Pugliese G, Laudisio D, Colao A, Savastano S, Muscogiuri G. Mediterranean diet as medical prescription in menopausal women with obesity: a practical guide for nutritionists. Crit Rev Food Sci Nutr. 2021;61(7):1201-1211. doi:10.1080/10408398.2020.1755220
  8. Morris, M. C., Tangney, C. C., Wang, Y., et al., MIND diet associated with reduced incidence of Alzheimer's disease. Alzheimer’s and Dement., 2015, 11, 1007–1014.
  9. Attia, P., & Gifford, B. (2023). Outlive:  The Science & Art of Longevity (First Edition). Harmony Books.
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