Metabolic Flexibility Part 2: When Life Forces You Off Course

Finding Your Way Back from Metabolic Exile

In Part 1, we discussed that metabolic flexibility isn’t about perfection or rigid rules. It’s about restoring your body’s natural ability to use whatever fuel serves you best in each moment, not which fuel is better. We discussed the role of proteins, and how your body shifts between burning carbohydrates and fats.

Remember March 2020? One day you were commuting to work, hitting the gym, walking to lunch meetings, and grabbing coffee with colleagues. Then without warning, you found yourself hunched over a laptop at your kitchen table, fumbling through Zoom calls while your sofa became both office and lunch spot. Nobody chose this dramatic shift – it simply happened, turning our daily rhythms upside down overnight.

Within weeks, millions of people experienced something they’d never considered: rapid physical deconditioning. Not from illness or injury, but from a sudden, enforced stillness.

If you felt mysteriously exhausted after just a few weeks of lockdown life, you weren’t imagining things. And no, it wasn’t just stress or anxiety weighing you down. Your body had adapted—with ruthless efficiency—to your new reality.

A lockdown isn’t required—life has a way of throwing speed bumps at us.

Photo: Beckett Zapp

When Odysseus Lost His Way: Understanding Metabolic Deconditioning

Imagine Odysseus, the mighty warrior of Troy, trapped for seven years on Calypso’s island. Every comfort provided, no battles to fight, no ships to sail. When he finally escaped and made his way home to Ithaca after twenty years of wandering, nobody recognized the once-powerful king. His own people saw only a weathered stranger.

The true test came when he tried to string his own bow—a feat he’d once performed effortlessly. Now, his muscles trembled with the effort. His body had adapted so thoroughly to years of reduced demands that reclaiming his former strength became its own heroic quest.

This is exactly what happened to millions during the 2020 lockdowns. Like Odysseus, we found ourselves in unexpected exile from our normal lives, and our bodies adapted with remarkable efficiency to these new circumstances.

Your body is remarkably intelligent about energy conservation. Physical deconditioning can occur after only a few days of inactivity, with muscle strength decreasing at a rate of one to three percent per day, and noticeable strength loss occurring after about two and a half to three weeks. Research shows that significant muscle fiber atrophy and decreased oxidative capacity occur within just five days of reduced activity.

This isn’t just about muscles getting smaller. During inactivity, the body starts shifting energy and resources away from areas not being used, affecting muscle strength, stamina, coordination, and even mental health. Your cardiovascular system reduces its capacity when not challenged regularly. Your mitochondria—those cellular powerhouses—literally decrease in number and efficiency when energy demands drop. Even your glucose metabolism changes as muscles lose their ability to efficiently uptake and store carbohydrates.

The Lotus-Eaters’ Trap: Mind-Body Accommodation

Remember when Odysseus’s crew ate the lotus flowers? They lost all desire to return home, content to remain in pleasant lethargy, forgetting their purpose and their strength. This mythological amnesia perfectly captures what happens during deconditioning.

Here’s where it gets psychologically complex: as your physical capacity changes, your mind accommodates these changes. Without conscious decision, you begin gravitating toward activities that match your body’s current state. Physical challenges become less appealing. Extended periods of sitting feel natural. You start avoiding the stairs. Your preferences, interests, and daily rhythms all shift to align with what your deconditioned body can comfortably sustain.

This isn’t laziness—it’s intelligent biological adaptation. The problem arises when this protective accommodation becomes a trap that prevents you from rebuilding capacity even when circumstances change for the better.

Many people find themselves caught between knowing that movement would help their energy and feeling genuinely too tired to move. It’s not a willpower problem; it’s a physiological reality that requires a different approach than simply “pushing through.”

The Hydration Foundation Nobody Talks About

Before Odysseus could reclaim his strength, he needed the basics—food, water, rest. Before addressing any metabolic inflexibility, we need to acknowledge the foundation that supports all cellular function: hydration. Every aspect of energy production, nutrient transport, and waste elimination depends on adequate water. Yet chronic mild dehydration is so common that people accept fatigue, brain fog, and sluggish metabolism as normal.

When you’re dehydrated, your blood becomes more viscous, making your heart work harder to circulate nutrients and oxygen. It affects blood pressure by causing it to both drop and rise, depending on the body’s response, while it negatively impacts digestion by leading to constipation. Your kidneys struggle to eliminate waste products that can interfere with cellular function. Even your appetite regulation becomes confused as your body sends mixed signals about what it needs.

Nothing you do with diet, exercise, herbs or supplements works optimally when your body is running on insufficient water. This becomes even more critical during periods of metabolic stress or when rebuilding from deconditioning.

When Disease Changes the Metabolic Game

Some health conditions fundamentally alter how your body processes fuel, requiring temporary or long-term modifications to the metabolic flexibility approach we discussed in Part 1.

Cancer cells, for instance, become heavily dependent on glucose through a process called the Warburg effect. Unlike healthy cells that can efficiently switch between glucose and fat burning, cancer cells reprogram themselves to consume glucose rapidly and wastefully (200 times more than healthy cells), even when oxygen is available for more efficient energy production.

This metabolic inflexibility in cancer cells has led some practitioners to explore therapeutic ketogenic approaches—the idea being to limit the fuel source that cancer cells depend on while supporting healthy cells that retain metabolic flexibility. However, this approach requires careful medical supervision and isn’t appropriate for everyone. The research is evolving, individual responses vary, and the metabolic demands of cancer treatment itself must be considered.

Autoimmune conditions present a different challenge. Chronic inflammation can interfere with insulin sensitivity and cellular energy production, creating a state where the body struggles to efficiently use any fuel source. Some people with autoimmune conditions find that reducing glucose intake helps manage inflammatory responses, while others need adequate carbohydrates to support their immune system during active treatment phase.

The key insight is that these conditions may temporarily require moving away from metabolic flexibility toward more therapeutic approaches—but always under professional guidance and with regular monitoring.

The Return to Ithaca: Understanding the Deconditioning Journey

Like Odysseus’s decade-long journey home, the path from deconditioning to restored metabolic flexibility rarely follows a straight line. Far more common than serious illness is the gradual loss of metabolic flexibility through life changes that reduce physical activity:

• Career transitions that shift from active to sedentary work.

• Aging that naturally reduces muscle mass and mitochondrial function.

• Injury recovery that requires extended periods of reduced activity.

• Caregiving responsibilities that leave little time for personal health maintenance.

• Major life stress that disrupts sleep, exercise, and eating patterns.

The 2020 lockdowns provided a massive real-world experiment in rapid deconditioning. People who were reasonably active found themselves struggling with tasks that previously felt effortless. A flight of stairs left them winded. Their usual walking routes felt surprisingly challenging.

This wasn’t just “being out of shape”—it was comprehensive metabolic deconditioning affecting energy production at the cellular level. Metabolic flexibility relies on cellular and organelle processes, particularly in the mitochondria, which regulate the ability to switch between glucose and fatty acid oxidation (breaking carbs and fats down to be used as fuel.)

Stringing the Bow: The Gentle Path Back

Odysseus didn’t immediately transform back into the warrior he’d been. First, he had to accept his current state, then work strategically to reclaim his strength. Rebuilding metabolic flexibility after deconditioning requires this same patient, strategic approach—working with your body’s current capacity rather than forcing it to perform at previous levels.

The recovery process can take three times longer than the period of inactivity—if someone rests for one week, it may take two to three weeks of activity to fully recover their strength. This reality check helps set appropriate expectations.

• Start with micro-movements. Ten to fifteen minutes of walking might be genuinely challenging if you’ve been sedentary for months. Don’t consider this a failure—it’s information about your current starting point (a benchmark), whatever it may be. Give yourself complete permission to stop when your body signals it’s had enough. You may be surprised at how quickly your body can regain strength and stamina.

• Prioritize consistency over intensity. Exercise training promotes enhanced metabolic flexibility by increasing mitochondrial biogenesis, content, and function, improving both insulin sensitivity and the capacity for fatty acid oxidation. Your mitochondria rebuild through regular, gentle stimulation rather than occasional heroic efforts. A daily 10-minute walk does more for long-term metabolic health than one 60-minute workout followed by a week of inactivity.

• Support the rebuilding process nutritionally. Deconditioning affects your body’s ability to utilize nutrients efficiently. Whole foods become even more important, as your compromised system needs easily absorbed nutrition to fuel the rebuilding process.

  • Nettle, rich in bioavailable minerals and B vitamins, can provide foundational support for cellular energy production. Rhodiola may help your body adapt to the gentle stress of rebuilding activity tolerance. But remember—herbs support the process; they don’t replace the fundamental work of gradually reactivating dormant systems.

• Hydrate intentionally. As you begin moving more, your hydration needs increase not just from perspiration but from the increased metabolic activity of rebuilding cellular function. Spread your water intake throughout the day rather than trying to catch up with large amounts at once.

When Professional Guidance Becomes Essential

While healthy individuals can often rebuild metabolic flexibility through gradual lifestyle changes, certain circumstances require professional support:

• Chronic health conditions that affect metabolism

• Medications that interfere with energy production or appetite regulation

• Severe deconditioning that makes even gentle movement challenging

• Eating disorders or disordered relationships with food and exercise

• Multiple failed attempts at rebuilding activity tolerance

Healthcare providers familiar with metabolic medicine can assess whether underlying issues are interfering with your body’s ability to rebuild flexibility. They can also monitor biomarkers to ensure that your approach is supporting rather than stressing your system.

The Patience of Penelope

Perhaps the most challenging aspect of rebuilding metabolic flexibility is accepting that it may take time—often much longer than the deconditioning process itself. Penelope waited twenty years for Odysseus to return, weaving and unweaving her tapestry, maintaining faith in eventual restoration.

Research shows that losses in muscle strength and volume can exceed 10% within the first two weeks after surgery or inactivity, with older adults at greater risk due to reduced regenerative capacity. Rebuilding this capacity happens gradually over a similar or longer timeframe. However, the point to remember is that you will see improvement with consistent effort.

This patience becomes even more critical when health challenges are involved. Someone recovering from illness or managing a chronic condition may need to rebuild flexibility in stages, with setbacks and plateaus along the way.

The goal isn’t to return to some idealized previous state but to optimize function within your current circumstances. A 70-year-old rebuilding from deconditioning has different capacities than a 30-year-old, and that’s normal and appropriate. The good news is that muscles don’t age.

Recognizing Your Own Patterns

Many people don’t realize they’ve lost metabolic flexibility until they try to change something. You might notice:

• Feeling exhausted after activities that used to be routine.

• Needing frequent snacks to maintain energy.

• Weight changes despite eating similarly to before.

• Difficulty recovering from minor illnesses.

• Sleep that doesn’t feel restorative.

• Mood changes related to meal timing.

• Lack of motivation to engage in activities that require mild physical effort.

Don’t automatically assume these are due to failure or signs of aging that must be accepted. They’re often indicators that your metabolic flexibility has decreased and can potentially be improved through appropriate interventions.

The Bigger Picture

Metabolic inflexibility rarely exists in isolation. Like Odysseus’s journey, which involved not just physical challenges but storms, enchantments, and divine interventions, your metabolic health interweaves with other factors—disrupted sleep, increased stress, social isolation, or reduced exposure to natural light and fresh air.

Metabolic flexibility emerges as a critical determinant of perioperative resilience (ability to cope and recover), with targeted exercise and nutritional strategies enhancing mitochondrial function, improving nutrient-sensing pathways, and increasing substrate oxidation (process by which the body converts fuel sources like carbohydrates and fats into usable energy). This same principle applies to daily life—addressing flexibility requires considering these broader lifestyle factors rather than focusing solely on diet and exercise.

The lockdown taught us that our metabolic health is more fragile than we realized, but it also demonstrated our capacity for adaptation. The same biological intelligence that efficiently adapted to reduced activity can, with appropriate support, rebuild capacity.

What’s Next

Understanding when and why circumstances might require temporary modifications to metabolic flexibility helps you navigate life’s inevitable changes without panic or self-judgment. Sometimes the most metabolically intelligent thing you can do is adapt your expectations to current realities while working gradually toward improved capacity.

Like Odysseus finally stringing his bow and reclaiming his throne, rebuilding metabolic flexibility is about patient, strategic effort aligned with your body’s current capacity. The journey home may be longer than expected, but every step forward matters and will make a difference.

For now, if you recognize yourself in the deconditioning pattern, start with self-compassion. Your body did exactly what it was designed to do—adapt to circumstances. Now it’s ready to adapt again, but only if you work with its current capacity rather than against it.

Remember: Metabolic flexibility isn’t just about healthy individuals optimizing their energy. It’s about understanding how your “whole” body and its fuel utilization changes with circumstances and knowing how to support those changes appropriately. Whether you’re dealing with health challenges, recovering from deconditioning, or simply navigating life’s unexpected speed bumps, the principles remain the same—work with your body’s intelligence, not against it.

In Part 3 of this series, we’ll explore practical applications—how to experiment with different approaches based on your individual circumstances, activity level, and health status. We’ll discuss meal timing strategies, movement patterns, and how to know whether your approach is working for your unique situation.

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Disclaimer: Educational Purposes Only. Always consult with your healthcare provider. Individual results may vary and statements have not been evaluated by the FDA.

References

Warburg, O. (1956). On the origin of cancer cells. Science, 123(3191), 309-314. PMID: 13298683

Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009). Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 324(5930), 1029-1033. PMID: 19460998

Weber, D. D., Aminzadeh-Gohari, S., Tulipan, J., Catalano, L., Feichtinger, R. G., & Kofler, B. (2020). Ketogenic diet in the treatment of cancer–Where do we stand? Molecular Metabolism, 33, 102-121. PMID: 31399389

Gaber, T., Strehl, C., & Buttgereit, F. (2017). Metabolic regulation of inflammation. Nature Reviews Rheumatology, 13(5), 267-279. PMID: 28331208

Arc-Chagnaud, C., Py, G., Fovet, T., Roumanille, R., Demangel, R., et al. (2021). Early Deconditioning of Human Skeletal Muscles and the Effects of a Thigh Cuff Countermeasure. International Journal of Molecular Sciences, 22(21), 12064. PMID: 34769492

Deconditioning syndrome: Symptoms and recovery. Medical News Today. (2024, December 3). Retrieved from medicalnewstoday.com

Deconditioning After Surgery. Radius Anesthesia of Ohio. (2025, January 28). Retrieved from radiusohio.com

Deconditioning. Elsevier Health. (2022, October 10). Retrieved from elsevier.health

Goodpaster, B. H., & Sparks, L. M. (2017). Metabolic Flexibility in Health and Disease. Cell Metabolism, 25(5), 1027-1036. PMID: 28467922

Meex, R. C., Schrauwen-Hinderling, V. B., Moonen-Kornips, E., et al. (2010). Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity. Diabetes, 59(3), 572-579. PMID: 20028948

Smith, R. L., Soeters, M. R., Wüst, R. C. I., & Houtkooper, R. H. (2018). Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease. Endocrine Reviews, 39(4), 489-517. PMID: 29697773

Goodpaster, B. H. (2022). Metabolic Flexibility and Its Impact on Health Outcomes. Mayo Clinic Proceedings, 97(4), 761-767. PMID: 35287951

Yang, W. H., & Park, H. (2022). Energetic Contributions Including Gender Differences and Metabolic Flexibility in the General Population and Athletes. International Journal of Environmental Research and Public Health, 19(20), 13643. PMID: 36295868

Charidemou, E., Tsiarli, M. A., Theocharidou, E., & O’Dowd, J. (2024). Prehabilitation: Do We Need Metabolic Flexibility? Annals of Nutrition and Metabolism, 80(4), 178-190. PMID: 40122036