How Metabolic Flexibility is Key to Your Health Resiliency

How Metabolic Flexibility is Key to Your Health Resiliency

by Dr. Charny August 21, 2021

During the pandemic, as we have continued to learn more about COVID-19 one constant thread has remained – how do we assess our risk factors and improve our system’s defenses? We know that patients with pre-existing conditions such as diabetes, heart disease, or obesity (to name a few) experience stronger and more severe reactions to the SARS-CoV-2 virus.

My goal in this blog isn’t to address COVID-19 so much as to examine what is the common denominator between degenerative diseases that lead to poorer COVID-19 outcomes? What it often comes down to is that these patients’ underlying conditions are byproducts of inflexible metabolisms, and therefore they are ill prepared to adapt efficiently and effectively to viral infections.

Biology 101 Recap

The three main purposes of metabolism include:

  1. Converting food into energy to run cellular processes. The chemical energy produced by the mitochondria (the powerhouse of the cell) are stored in small molecules called adenosine triphosphate (ATP).

  2. Converting food/fuel into building blocks for proteins, lipids, nucleic acids, and some carbohydrates. Mitochondria are responsible for processing fuel (food) into energy and keeping the lights on in our system.

  3. Eliminating metabolic wastes.

What is Metabolic Flexibility and Why Do We Need It?

Metabolic flexibility is defined by the mitochondrial ability to switch freely between fuel sources based on nutritional and physiological demands, interpreting energetic signals from the body to efficiently fine tune fuel source for optimal performance. Metabolic flexibility gives us more room for error, more ability to respond to the changing demands and stresses our systems encounter.

Metabolic (In)Flexibility

Metabolic inflexibility occurs when the cells and tissues lose the ability to adapt fuel utilization to fuel availability. People with poor metabolic flexibility have dysfunctional mitochondria that produce less energy than healthy mitochondria, making the switch between fuels that much more difficult. This is a hallmark of many age-related metabolic diseases such as diabetes, high blood pressure, and heart disease (to name a few). Higher blood glucose levels also may impact viral replication and the development of cytokine storm.

Some signs of Metabolic InFlexibility


  • Weak/tired before or after meals

  • Feeling sleepy after eating carbs

  • Tendency for excessive hunger

  • Needing to eat every 2-3 hrs

  • Weight gain


  • Poor cognitive function

  • Poor ability to focus / brain fog

  • Easily frustrated

  • Hard to finish tasks at hand

  • Poor sleep


  • Fatigue

  • Midday crash every day after lunch

  • Taking frequent coffee breaks for caffeine-induced energy

  • Shortness of breath

Causes of Metabolic InFlexibility

Insulin Insensitivity

Insulin signaling is pivotal for maintaining glucose and fatty acid metabolism balance. Insulin resistance forces our bodies to utilize compensatory mechanisms, which not only reduce energy efficiency but also drive metabolic disease.

Dietary Composition

Our diets should strive to be organic and pesticide-/chemical-free. But our dietary composition is just as important, and should take into account other factors such as total calories, the relative contribution of fat type to total calories, dietary antioxidants, and intake of fiber and carbohydrates.

Circadian Disruption (Poor Sleep)

Our circadian clock is closely tied to metabolic efficiency. Variations to this rhythm can influence metabolic flexibility.

Oxidative Stress

As our bodies metabolize and generate ATP we also produce signaling molecules called reactive oxygen species (ROS). Imbalances between ROS and antioxidant reducing agents are a culprit of many functional imbalances such as fatigue and brain fog, and chronic diseases such as diabetes.


Overproduction of ROS causes chronic/low grade inflammation, which may lead to metabolic dysfunction, functional imbalances and chronic diseases. Increased ROS production may also lead to inflammatory cytokines.

Sedentary Lifestyle

The power of movement cannot be overstated. Exercise acts as a stimulus for our genes, hormones, neurotransmitters, enzymes and transcription factors to maintain cellular metabolic functions.

Microbiome, Dysbiosis & Leaky Gut

Imbalance in the microbiome and dysbiosis lead to digestive system dysfunction and bacterial/fungal overgrowth. Leaky gut allows the byproducts of bad bacterial metabolism called LPS to enter the bloodstream and initiate local and systemic inflammation.

Some Biomarkers to Measure Metabolic Flexibility

  • Larger waist circumference

  • High blood pressure

  • Blood test biomarkers outside normal range, such as

    • Fatty acid membrane analysis

    • Glutathione

    • HbA1c

    • hs-CRP

    • Insulin sensitivity

    • Organic acids

    • Triglyceride and HDL levels

    • Vitamin D levels

What Increases Metabolic Flexibility?

There are several key factors to improve our metabolic flexibility: improving insulin sensitivity, blood glucose control, stimulating fasting physiology and providing antioxidant support.


Exercise improves insulin sensitivity through enhanced glucose uptake into skeletal muscles.

Caloric Restriction and Ketogenic Diet

The efficient production of ATP, blood sugar reduction, increase in fat oxidation, and mitochondrial efficiency improvement may be achieved through a ketogenic diet, intermittent fasting, and exercise. Any of these tools may increase NAD+ levels, an important factor in mitochondrial adaptation that aids metabolic fitness improvement.


Antioxidants offer defense against ROS production. As previously discussed, ROS production initiates inflammation and mitochondrial dysfunction.

Nrf2 activation

Nrf2 is a transcription factor, activating our own built-in antioxidant system to induce antioxidant enzymes, driving the synthesis of glutathione – the master defender against oxidative stress.

AMPK activation (in skeletal muscle, fat cells & liver)

AMPK is an enzyme which maintains cellular energy homeostasis. It regulates many physiological processes and is dysregulated in obesity, diabetes, inflammation and cancer.

Here's the bottom line...

We’ve covered some ground in this blog, but if there’s one clear takeaway it should be this – a responsive, flexible metabolism is imperative to our health. Inflexible metabolisms seem to be a common thread among severely adverse COVID-19 cases, and so taking steps to increase our ability to fight off viral infections has never been more timely. Through exercise, proper diet, and nutritional supplementation we can take steps to improve our metabolism and wellbeing.

Supplements Mentioned in this Post

Dr. Charny
Dr. Charny

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