Metabolic Flexibility: The Science of Optimizing Your Metabolism

By Olga Afonsky, CNS

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Our bodies evolved to handle fluctuations in food availability and energy demand. In ancient times, we faced cycles of feast and famine, so our metabolism learned to adapt. We can store nutrients during times of plenty and use them efficiently during scarcity. Our metabolism adjusts to energy demands and nutrient availability and can switch between burning different energy sources. We call this metabolic flexibility.

But the modern lifestyle, with its constant access to calorie-dense, processed foods and less physical activity, often disrupts this balance. Many people now struggle with metabolic inflexibility, which can lead to conditions like obesity, type 2 diabetes, and other metabolic disorders. Let’s explore metabolic flexibility, its importance, how it’s regulated, and how to improve it.

What Is Metabolism and Metabolic Flexibility?

Metabolism is the sum of chemical reactions that occur in the body within each cell and provide the body with energy. Our metabolism is in constant flux and has to adapt to the availability of nutrients and energy requirements, as well as nutrient storage and utilization.

This adaptability, which keeps our energy levels stable, is known as metabolic flexibility. For example, our body switches between energy sources several times a day depending on whether we just ate or haven’t eaten for several hours.

- After a meal, your body prefers to burn glucose for energy.

- During fasting or prolonged exercise, it shifts to burning stored fat for fuel.

In addition, your body has a fantastic way of adapting to changes in food intake. Whether you’re fasting for long periods, cutting calories, or eating too much, your body uses a mix of clever mechanisms to keep you going. Here are some examples of your metabolism complexity.

What Happens When You Fast?

When you don’t eat for a long time, your body has to find alternative fuel sources to keep your organs running, especially your brain. Typically, your brain uses glucose for energy but switches to ketone bodies during fasting. These are energy molecules made in your liver from fat.

Ketones are an excellent energy source and produce more energy than glucose, gram for gram. This shift happens because, during fasting, insulin levels drop. Low insulin allows fat stores to break down, releasing fatty acids that your liver converts into ketones.

Besides providing fuel, ketones have some exciting potential uses. Scientists are exploring their role in boosting exercise performance and helping with certain metabolic disorders.

How Does Calorie Restriction Work?

Calorie restriction means eating fewer calories than you need. If you do it right, you can still get all your essential vitamins and nutrients. When you restrict calories for a long time, your body activates a survival mode. It starts recycling its own materials, a process called autophagy, which can be thought of as a ‘clean-up’ process where the body breaks down and recycles damaged or unnecessary cellular components to stay efficient.

Cellular sensors manage this process, helping conserve energy and repair damage. At the same time, factors that promote growth when food is plentiful are turned off. This shift allows your body to focus on maintenance and internal clean-up, which may explain how caloric restriction can improve health and prolong life.

What Happens When You Overeat?

Overeating overwhelms your body’s metabolic processes. When there’s an excess of food—especially fats and sugars—your mitochondria (the energy factories in your cells) struggle to keep up. This can cause a ‘metabolic gridlock,’ a situation where your body’s metabolic processes can’t use all the fuel efficiently, leading to potential health issues.

Over time, this can lead to problems like fat buildup in tissues where it doesn’t belong, increased oxidative stress, insulin resistance, and cell damage, leading to obesity, diabetes, and heart disease.

Exercise and Metabolic Flexibility

Exercise is one of the best ways to improve your body’s ability to switch between fuel sources and maintain metabolic flexibility. Different types of muscle fibers in your body prefer different fuels. For example:

- During low-intensity prolonged exercise, your muscles mostly burn fat.

- During intense exercise, they switch to using glucose.

Regular exercise is a powerful tool to improve your body’s ability to switch between fuel sources and maintain metabolic flexibility. It helps burn fuel more efficiently and boosts insulin sensitivity, mitochondrial function, and energy production.

Cold Exposure and Sleep Patterns

Your body’s metabolic flexibility isn’t just influenced by food and exercise. Cold exposure can activate special fat cells called brown fat, which burn calories to produce heat. This process might improve metabolic health and insulin sensitivity.

Similarly, your circadian rhythm (your internal clock) plays a significant role in how your body uses energy. Disruptions like eating late at night or working night shifts can reduce your metabolism.

Aging and Metabolism

As we age, our metabolism slows, and our cells become less metabolically flexible. This decline is due, on the one hand, to reduced physical activity and, on the other hand, to changes in cellular processes. However, regular movement can help combat this decline, keeping your cells healthy and your metabolism flexible.

How Your Body Regulates Metabolic Flexibility

Your body’s ability to use energy efficiently—whether it’s burning fuel or storing it—depends on how well your metabolic systems work together. Energy production happens within each cell, but cells within an organ need to work in unison. Organs and tissues should coordinate with each other. This coordination involves enzymes, genes, mitochondria, and hormones, which are, in turn, influenced by environmental factors like diet, exercise, stress, etc.

Mitochondria: Your Cell’s Energy Factories

Mitochondria play a central role in your body’s metabolic flexibility. In healthy individuals, mitochondria can efficiently switch between fuel types. They take nutrients and convert them into a usable form of energy called ATP. This energy conversion involves complex chemical processes, using oxygen to power your body’s activities.

When mitochondria work efficiently, they adapt based on what you eat and how much energy your body needs. For example:

- Too much food can fragment mitochondria, reducing their efficiency, but it also helps to protect cells from the adverse effects of overeating.

- Calorie restriction or fasting helps mitochondria become more interconnected and efficient, producing energy with fewer resources.

However, poor mitochondrial function can make it harder for your body to switch between burning carbs or fats, negatively affecting your metabolic flexibility.

Hormones and Metabolic Flexibility

Hormones are key players in helping your body balance energy use and storage:

- Insulin and glucagon are key hormones that control nutrient storage and burning and how your body manages blood sugar, especially after eating or fasting.

- GLP-1 is released by your gut after meals; GLP-1 boosts insulin release and lowers sugar production in the liver.

- Bile acids not only help digest fats but also improve insulin sensitivity and energy use.

- Ghrelin, often called the “hunger hormone,” decreases after eating, reducing liver sugar production and encouraging muscles to take up glucose.

Together, these hormones help your body adjust fuel use depending on whether you’ve just eaten or haven’t eaten for a while.

Your muscles and fat tissue actively communicate with the rest of your body to regulate metabolism:

- Adiponectin (from fat cells) helps muscles burn fat and lowers sugar production in the liver.

- Leptin (from fat cells) signals your brain about your energy reserves and helps regulate appetite.

- Myokines (from muscles) are released during exercise and improve your body’s ability to burn fat, process sugar, and respond to insulin.

Epigenetics: Your Lifestyle Affects Your Genes

Your lifestyle—what you eat, how often you exercise, and even how much you sleep—can influence your genes through a process called epigenetics. Environmental factors can “switch on” or “switch off” specific genes, affecting your metabolic flexibility.

For example:

- Obesity and diabetes are associated with changes in DNA that disrupt energy use and mitochondrial function in muscles, fat, and the liver.

- Exercise and a healthy diet can positively influence these genetic markers, improving metabolic flexibility.

Metabolic Inflexibility in Simple Terms

When we can’t adequately respond to metabolic challenges, we lose our metabolic health and become “metabolically inflexible.” Our body struggles to switch between fuel sources for energy production, hormonal regulation is disrupted, and the balance between nutrient storage and burning is off. Impaired metabolic flexibility can cause diseases like obesity, metabolic syndrome, type 2 diabetes, cancer, and systemic inflammation.

Obesity

Obesity is a problem related to fat storage and breakdown. Usually, your body burns fat for energy when you fast and stops after you eat. In obesity, this process doesn’t work correctly. Excess fat spills over into areas it shouldn’t like your liver and muscles, causing inflammation and insulin resistance. Over time, the cycle of fat buildup and inflammation worsens metabolic flexibility, increasing the risk of metabolic diseases.

Metabolic Syndrome

Metabolic syndrome is a cluster of conditions that includes:

Increased waist circumference
High blood pressure
High blood sugar
High triglycerides
Low HDL (good cholesterol)

If you have three of the five conditions listed above, your doctor can diagnose you with Metabolic Syndrome, which increases your risk of diabetes and heart disease.

The clinical assessment of metabolic health is helpful, but it doesn’t give us a complete picture. If your measurements fall within a specific range, you believe you’re metabolically healthy. Even when you have a normal weight and most of your blood tests are within the ranges, your metabolic flexibility might be under stress. It takes a long time to get from metabolic health to metabolic disease.

We can get insights into your metabolic health before you develop any of the five conditions mentioned above. Your HOMA score, insulin resistance score, and glucose fluctuations throughout the day, tracked via continuous glucose monitors, can provide the necessary information.

How do we lose Metabolic flexibility?

Modern lifestyles are the main culprit. Here’s how:

Constant eating: Frequent snacking meals prevent the body from switching to fat-burning mode and overexposes our cells to insulin.
Processed foods: High in sugars and unhealthy fats disrupt nutrient sensing.
Overeating: Overloads our mitochondria and reduces their efficiency. Fat accumulation around muscle and liver cells makes them insulin-resistant.
Sedentary behavior: Lack of movement reduces the body’s ability to adapt its fuel use.

Over time, these factors can lead to “metabolic insensitivity,” where the body becomes less responsive to insulin and struggles to balance energy.

Why Metabolic Flexibility Matters

When metabolically flexible, your body can easily switch between burning carbs, fats, or proteins for energy. This adaptability is essential for maintaining stable energy levels, managing blood sugar, and preventing chronic health conditions that plague our society. It also increases the likelihood of living longer and maintaining the quality of life that you enjoy, as well as reduces the chances of degenerative diseases of old age.

While we live longer than ever, the quality of our health is diminishing. Achieving metabolic health extends your health span, which is the duration of your life spent in good health, free from disease, pain, and suffering. Improving your health span makes it possible to enjoy the activities you love, even as you age. This approach leads to a fuller life and the energy to enjoy the activities you love. In contrast, poor metabolic health can drastically shorten both your health span and overall lifespan.

How to Improve Metabolic Flexibility

I wanted to impress you with the complexity and overarching importance of your metabolism. Lifestyle changes that influence many aspects of metabolism can improve metabolic flexibility. Because so many factors are involved, a pill can hardly be a solution, as it can only affect a sliver of the process.

Here are some suggestions on what you can do to make lasting changes to your metabolic health:

1. Eat Whole Foods:

Focus on nutrient-dense, unprocessed foods (grass-fed meat and dairy, fruits and vegetables in season) and avoid ultra-processed foods loaded with refined carbs and vegetable oils.

1. Balance Your Meals:

Combine protein and healthy fats with some carbs to prevent blood sugar spikes.

1. Reduce Frequency of Eating:

Eat 2-3 times a day and avoid snacking. Practice periodic fasting, which allows your body to switch to fat-burning mode and enhances your metabolic flexibility.

1. Exercise Regularly:

Physical activity, especially strength training and aerobic exercise, improves your muscles’ ability to effectively switch between glucose and fat for energy. It also improves the health and number of mitochondria in muscle cells, making your body more efficient at burning.

1. Get Enough Sleep:

Poor sleep can disrupt hormones that regulate metabolism.

1. Reduce Stress:

Chronic stress can affect insulin sensitivity and metabolic health.

Improving metabolic flexibility helps prevent diseases like diabetes and obesity, boosts energy, supports weight management, and enhances overall health. With consistent effort, your body can relearn how to adapt to different energy demands and regain metabolic flexibility.

Understanding and supporting your metabolism allows you to control your energy balance and set yourself up for long-term health. Small changes, such as better food choices, regular exercise, and adequate rest, can make a big difference.

In Summary

- Our metabolism is constantly changing, adapting to nutrient availability and energy requirements. We call this adaptability Metabolic Flexibility, whose job is to keep our energy stable.

- Metabolic flexibility is complex and involves all cells, organs, and tissues. Hormones and various factors within the body and in each cell regulate it.

- When we become “metabolically inflexible,” our body struggles to switch between fuel sources, hormonal regulation is disrupted, and nutrient storage and burning are out of balance. Our diet and lifestyle are the main culprits in losing metabolic flexibility.

- Clinical diagnosis of metabolic health includes three out of five conditions: large waist circumference, high fasting blood glucose, high systolic blood pressure, high triglycerides, and low HDL cholesterol.

- You shouldn’t wait for the diagnosis of metabolic syndrome; there are tools to catch earlier signs of metabolic inflexibility.

- Metabolic health prolongs lifespan and health span and lets you keep an enjoyable and healthy life in old age.

- Small, consistent changes in how you eat, move, and rest can significantly impact your metabolic health and are powerful tools to restore balance, improve energy use, and reduce the risk of long-term health problems like diabetes, heart disease, and degenerative diseases of old age.