Every year, World Health Month prompts the same conversation… We talk about prevention. We talk about lifestyle. We talk about the growing burden of chronic disease and the need to intervene earlier, more effectively, and more sustainably. All important, all priorities. Yet, despite all of this, the trajectory hasn’t shifted in the way we might have hoped, which suggests that something more fundamental may still be missing.
Not for lack of data, and certainly not for lack of technology. If anything, we are measuring more than ever; from glucose, insulin, and HbA1c, to full lipid panels and inflammatory markers, to ECG parameters and coronary artery calcium scores, to body composition, blood pressure, and continuous glucose monitoring, each offering a highly detailed, increasingly sophisticated snapshot of health at a single point in time. But increasingly, these feel like downstream markers. Important, yes… but perhaps not where the story actually begins.
Because underneath all of them sits something we rarely measure directly, and yet may explain far more about how a person feels, functions, and fares over time.
The capacity to produce energy and to do so adaptively.
That underlying feature is known as metabolic flexibility.
At its core, metabolic flexibility refers to the body’s ability to switch between fuel sources (primarily fat and glucose) depending on what it’s required to do. In a healthy system, fat oxidation predominates at rest and during lower-intensity activity, providing a stable and efficient source of energy. As demand increases, there is a coordinated shift toward carbohydrate utilisation to support higher rates of ATP production. This is not a preference for one fuel over another; it is a dynamic system designed for adaptability.
The problem is that, for many individuals, this adaptability is lost.
What is increasingly being seen, across chronic disease, post-viral syndromes, and even in otherwise “healthy” populations, is a form of metabolic rigidity. The system becomes heavily reliant on glucose, even at workloads where fat should be the dominant fuel. The shift happens earlier than it should, and once it happens, it comes at a cost. Lactate accumulates sooner, energy production becomes less efficient, and the perception of effort increases. Patients describe this in very practical terms: fatigue that arrives too early, recovery that takes too long, and a sense that their body is simply not keeping up.
And here’s where it becomes difficult to ignore.
The human body is not short of energy. While glycogen stores are relatively limited, fat stores represent a substantial and readily available energy reserve. From a physiological perspective, the ability to access fat efficiently is not a niche advantage; it is central to sustained energy production and metabolic stability. When fat oxidation is impaired, the system is forced into an earlier and more sustained reliance on glycolysis, increasing metabolic strain and reducing efficiency over time.
Mitochondrial function sits at the centre of this process. When functioning well, mitochondria support oxidative metabolism with relatively low levels of metabolic by-products, allowing for sustained energy production. When compromised, there is a shift toward less efficient pathways, with greater lactate production and reduced energetic stability. This is particularly evident in emerging data from post-COVID populations, where individuals demonstrate reduced rates of fat oxidation and elevated lactate levels at comparatively low workloads. In practical terms, the system transitions too early from fat to glucose metabolism: a hallmark of impaired metabolic flexibility.
What is striking, though perhaps not entirely surprising, is that this pattern is not unique to post-COVID syndromes. Similar metabolic signatures are observed in type 2 diabetes, obesity, cardiovascular disease, and in sedentary populations. The common thread is not simply the presence of disease, but the reduced capacity of the system to adapt its energy production appropriately. In that sense, metabolic inflexibility may be less of a consequence and more of a contributor, something that develops quietly and then begins to shape outcomes in ways we only recognise later. Emerging evidence suggests that this underlying metabolic dysfunction may play a more central role in disease progression than is currently appreciated. Maybe it is this that is the real silent driver.
For a long time, this has been difficult to measure in a way that is both practical and clinically meaningful. What has been missing is not more data, but a way of understanding how the system behaves under physiological stress, how the body actually produces and regulates energy when it is required to perform. This is where cardiopulmonary exercise testing (CPET) changes the conversation.
Rather than relying on static measurements, CPET provides an integrated, real-time assessment of how the cardiovascular, pulmonary, and muscular systems work together under load. It allows us to observe oxygen utilisation, substrate use, and metabolic transitions as they happen, offering direct and holistic insight into how efficiently energy is being produced. Within this, markers such as Fatmax (the point of maximal fat oxidation) and the timing of the shift toward carbohydrate reliance provide a practical way of assessing metabolic flexibility in action.
These are not abstract concepts. They are measurable, trackable, and clinically meaningful indicators of how the system is functioning. And once you start measuring them, a slightly uncomfortable pattern emerges.
Metabolic inflexibility is not the exception. It is increasingly the rule.
Which raises a more fundamental question: if this is the system that underpins energy production, functional capacity, and recovery, why are we not targeting it more directly? Perhaps because it sits just outside the endpoints we have become used to focusing on. It does not fit neatly into a single lab value or diagnostic category. It requires a different lens, one that considers the body as an integrated system, rather than a collection of isolated markers.
But once you adopt that lens, things begin to align.
Fatigue starts to make sense. Exercise intolerance is no longer vague or unexplained. Even the variability in how patients respond to treatment becomes easier to interpret when viewed through the capacity of their metabolism to adapt.
And importantly, it becomes actionable.
If metabolic flexibility can be measured, it can also be improved. Through targeted exercise interventions, nutritional strategies that support fat oxidation, and approaches that restore mitochondrial efficiency, it is possible to shift the system back toward a more adaptable state. Not overnight, and not without effort, but meaningfully.
This perspective aims to frame an emerging clinical approach to understanding and targeting metabolic health through integrated physiological assessment.
Over the coming weeks, we will be sharing a series of real-world case studies from our work with VO2, where these principles are not theoretical. Different individuals, different clinical pictures, but a consistent underlying theme.
When the system becomes more flexible, outcomes begin to shift. And perhaps that’s the point we’ve been circling all along… not that metabolism is one part of the story, but that it might, in fact, be the story we should have started with.
