Metabolic Flexibility and Female Hormones

In recent years, a new concept has been sweeping the world of diet and nutrition—metabolic flexibility, or the ability for the body to use different types of fuels to make energy1. Cells use energy made by mitochondria from dietary carbohydrates, stored carbohydrates (called glycogen), dietary fat, or stored fat (adipose tissue). Different organs and tissues typically favor either carbohydrates (glucose) or fats.

However, this is not entirely what metabolic flexibility is about. Metabolic flexibility is when fuel usage in the body can smoothly switch from carbohydrates to stored fats. Metabolic flexibility is an abbreviated way to describe the interplay between body composition, diet, exercise, and hormones to sustain cellular energy production.

Metabolic flexibility declines with age, but this is not inevitable. Women often note many symptoms of poor metabolic flexibility when perimenopause or menopause are evident2. Symptoms include weight gain, food cravings, low energy, poor sleep, and poor focus. Let’s walk through the key metabolic flexibility components and how aging and hormones impact metabolic flexibility in women.

Metabolic Flexibility in Action 

Under healthy conditions, the body prefers to use glucose from dietary and stored carbohydrates for energy. Glucose circulates in the blood and is stored as glycogen in muscles and the liver as a ready energy source. Fat is burned when glycogen and glucose are used up. This is metabolic flexibility 1.

The most common condition that is associated with metabolic inflexibility is insulin resistance3,4. Insulin resistance is a reduced ability to bring glucose into cells for energy. This is commonly caused by eating too many simple carbohydrates, likely from processed foods, although genetics and hormones may play a significant role. A surplus of glucose causes cells to reduce cellular glucose uptake. Excess glucose gets stored as fat.

Due to reduced glucose uptake people with insulin resistance can quickly feel depleted and eat more simple carbohydrates and reduce activity, perpetuating insulin resistance.

Another common cause of metabolic inflexibility is loss of muscle mass5. All tissue requires energy to maintain itself, but muscle tissue burns through more energy than fat tissue. As muscle mass declines, energy expenditure declines. If food consumption remains the same, the loss of muscle tips the balance toward insulin resistance and fat storage leaving the person with high energy storage but low available energy.

The body’s energy use is due to body composition (muscle and fat), hormones, diet, and activity levels. These four areas are interconnected and can be optimized to match the changing terrain.

Menopause and Metabolic Flexibility 

Hormone changes precede menopause by 10 or more years. With these changes come changes in body composition and insulin sensitivity, setting women up for the most common complaint of menopause—weight gain. Improving or maintaining metabolic flexibility can stabilize energy and weight and reduce the impact of aging5.

After age 35, women often develop estrogen dominance. Ovulation frequency and consistency decline leading to a decline in progesterone over time6. For some women, progesterone production is lower even with ovulation, for some, it is simply absent when ovulation is occasionally skipped. Estrogen (when in balance with progesterone) promotes weight maintenance. Estrogen dominance can increase fat storage and make it more difficult to lose weight. As women approach menopause, estrogen dominance becomes more severe and weight gain is common.

With the onset of menopause comes a dramatic decline in estrogen. Estrogen supports insulin sensitivity and muscle mass6,7. Although a causal relationship has not been established, menopause is associated with increased diabetes risk. The resulting decline in muscle mass, insulin sensitivity, and sex hormones with age leads to lowered metabolic flexibility, and further weight gain2,5,6,8.

At the same time, adrenal DHEA production declines. Adrenal DHEA is the main androgen source for women (9, 10). Maintaining muscle mass without increasing weight resistance exercise is unlikely. Although androgen levels do not appear to be directly affected by menopause, many women have low androgens when menopause hits, leaving them with low estrogen and low androgens.

Cortisol may increase with menopause, especially at night11. Cortisol’s main job is to increase circulating glucose. It does this by promoting insulin resistance and by converting protein (muscle) into glucose via “gluconeogenesis”. Even women with low stress can have higher cortisol levels during menopause.

As a result, women as young as 35 begin to decline in muscle mass, increase fat mass and insulin levels, and low estrogens with menopause make this worse. The result is reduced metabolic flexibility, low energy, and weight gain.

Listen to our interview with esther blum about finding comfort during menopause

How to Improve Metabolic Flexibility 

Age-related decline in muscle mass can be prevented by weight resistance exercise2,5,6. Weightlifting and aerobic exercise use up the body’s available glycogen and carbohydrate storage, and the resulting need to mobilize fat energy stores helps maintain the body’s ability to switch between fuel sources. They also build muscle, leading to increased fuel burning at rest. Intermittent fasting, or avoiding frequent snacking has a similar impact on fuel switching12,13,14. Exercise in the morning before eating breakfast or exercising three to four hours after a meal, with no snack in between may amplify these effects.

Reducing carb intake is a common approach to lowering insulin. Keep in mind that complex carbs found in whole foods are healthy in moderation. These carbs absorb slowly into the body allowing insulin to stay within a narrow range while providing glucose fuel for muscles and energy. Adequate protein intake is key to maintaining or increasing muscle mass.

For metabolic balance in females, research supports 25-40 grams of protein with each meal.

Hormone changes with menopause are a natural part of life. Some may find that hormone replacement therapy is crucial to fuel-switching, others may not6. Menopausal hormone therapy has not been proven to prevent insulin resistance, although some studies have found it may prevent weight gain15.

The most likely target for hormone balance and weight management in menopause is adrenal health. Optimal sleep and keeping cortisol within a healthy range are essential. Although this isn’t always easy! Some find adaptogen herbs like rhodiola, Siberian ginseng, maca, or ashwagandha can be helpful. Unfortunately, when DHEA declines with aging, stress support doesn’t always bring DHEA production back up. Some consider DHEA supplements helpful, and some studies have shown benefit to muscle mass if DHEA is taken along with a weight resistance training program.

Learn more about monitoring adrenal health using the DUTCH Plus

Health Benefits of Metabolic Flexibility 

Metabolic flexibility is the ability to switch between fuel sources. It impacts stamina, focus, energy, and weight management, so it’s not surprising that it has become a hot topic in recent years. Metabolic flexibility is affected by hormones, diet, exercise, and body composition1,2,3,6,12. Improving metabolic flexibility includes the ability to consume and use complex carbohydrates for energy, but simple carbohydrates found in processed foods only contribute to insulin resistance. Eating a whole-foods diet, weightlifting and aerobic exercise, practicing intermittent fasting, and managing stress are all key to promoting metabolic health. When a person has metabolic flexibility, they have sustained energy and metabolism even when energy needs are higher than normal. People who want to lose body fat benefit from being metabolically flexible because their body is ready to use up stored energy (fat) whenever there is an energy deficit.

The DUTCH Test comprehensively measures hormones as women age to identify the key areas of concern for each individual, and target treatment plans to optimize success! Hormone support during menopause may improve metabolic flexibility and help patients navigate this part of aging.