Mitochondrial Dysfunction and Chronic Disease: Why Energy Is at the Root of So Many Symptoms
When people are struggling with chronic fatigue, pain, brain fog, or long-term illness, the focus almost always turns to diagnosis. What is this? What do I have? There's a natural human need to name things, to have a label that explains the suffering.
But one of the most important shifts in perspective, and one that Dr. Sarah Myhill, a British physician who has spent decades specialising in chronic fatigue syndrome and ecological medicine, returns to again and again, is that the label is rarely where the answer lies. Chronic fatigue syndrome is a clinical picture, not a diagnosis. So is fibromyalgia. So, she argues, is dementia. They describe what we can observe. They don't explain why it's happening.
And it's the ‘why’, in Dr. Myhill's view, that changes everything.
Most chronic western illness, she believes, is driven by two things working in tandem: poor energy delivery mechanisms and inflammation. These aren't separate problems; they feed each other, often for years before symptoms become impossible to ignore. At the centre of both sits the mitochondria, and understanding what happens when mitochondrial function begins to decline goes a long way toward explaining why so many people feel so persistently unwell.
This blog was inspired by our Healing With Confidence Podcast Episode with Dr. Sarah Myhill, click the image below to watch it.
What Do Mitochondria Actually Do?
Mitochondria are the organelle inside your cells responsible for producing energy, every bit of energy your body uses for everything it does. Thinking, moving, digesting, repairing tissue, regulating the immune system: all of it depends on cellular energy production carried out by mitochondria. They are present in every living cell, and without them, life simply isn't possible.
The currency they produce is ATP, adenosine triphosphate. Dr. Myhill describes it as money: with ATP, the body can purchase whatever it needs to do. Synthesise a hormone. Fire a nerve impulse. Power the immune system. Keep the heart contracting. The moment ATP supply starts falling short of demand, the effects ripple outward, quietly at first, then harder to ignore.
What makes the scale of this process so striking is the sheer volume involved. The total weight of ATP generated in the body each day is somewhere around 70 to 80 kilograms, recycled continuously from a standing store of just 80 grams. A single molecule can complete the cycle from mitochondria into the cell and back again every 10 seconds. It is, by any measure, an extraordinary feat of biological engineering.
The tissues with the highest energy demands naturally contain the most mitochondria. A single heart cell may hold two to three thousand. The liver is densely packed with them, because the liver is never really off duty, detoxifying, maintaining homeostasis, and processing the constant flow of material arriving from the gut. Brain mitochondria are equally vital: without sufficient mitochondrial energy, nerve impulses can't fire properly, proteins can't be synthesised, and clear thinking becomes genuinely difficult.
When everything is working well, this system gives the body an extraordinary capacity to heal, adapt, and self-regulate. When it starts to falter, symptoms tend to accumulate, often across more than one system at a time.
Why Does Mitochondrial Dysfunction Drive So Much Chronic Disease?
It was once considered a niche concern, largely relevant only to rare inherited conditions. But the picture has shifted considerably. Mitochondria are now understood to be involved in virtually every major category of chronic disease, including cardiovascular diseases, metabolic conditions, neurodegenerative diseases, cancer, and the fatigue syndromes that have long defied easy explanation. Researchers at the National Institutes of Health and institutions worldwide increasingly recognise mitochondrial health as central, not peripheral, to the development of chronic disease.
Dr. Myhill published three papers specifically examining mitochondrial function in patients with chronic fatigue syndrome, and what those papers reflected, alongside decades of clinical experience, was that dysfunctional mitochondria are far from rare. They are, in her view, one of the most consistently overlooked factors in chronic illness.
Mitochondrial damage rarely arrives suddenly or from a single source. It tends to develop gradually, as the body absorbs sustained pressure from multiple directions:
Poor nutrition and micronutrient deficiencies
Chronic inflammation
A disrupted gut
Environmental toxins and pesticides
Blood sugar instability
The molecular mechanisms are multifactorial, and defective mitochondria are usually the result of a system that has been quietly struggling for some time before symptoms make it obvious.
Why Does Fatigue Run So Deep?
Fatigue, real bone-deep fatigue of the kind that doesn't respond to rest, is one of the most misunderstood symptoms in medicine. It tends to be treated as a diagnosis in itself, when it is much more usefully understood as a signal. Specifically, it is what happens when the gap between energy supply and energy demand becomes too wide to bridge.
When mitochondrial output drops, the body responds logically: it conserves. The effects tend to creep in gradually:
Activities that were once effortless start to require real effort
Concentration becomes harder to sustain
Sleep stops feeling restorative
Small tasks leave people disproportionately drained
The cumulative effect is a person who is functioning, but only just, and often at significant cost.
In conditions like chronic fatigue syndrome and fibromyalgia, this energy shortfall pushes muscles into anaerobic metabolism, a backup pathway the body uses when the mitochondria can't keep up. The problem is that anaerobic metabolism is extraordinarily inefficient. Where healthy mitochondrial metabolism yields 36 molecules of ATP from a single acetate molecule, anaerobic metabolism produces just two. It also generates lactic acid as a by-product, and converting that lactic acid back into usable energy requires six ATP molecules. The net result is a deficit that deepens with exertion, leaving patients in a cycle of pain and exhaustion that can persist long after the triggering activity has passed.
This is the biochemical reality behind the post-exertional malaise that defines chronic fatigue syndrome or even Long-COVID. It isn't psychological. It is a predictable consequence of what happens when mitochondria begin to fail under demand. Pacing, managing activity carefully to stay within the limits of what the mitochondria can actually support, isn't a passive resignation. It's a clinical necessity, and ignoring it tends to make everything considerably worse.
What Does Mitochondrial Dysfunction Have to Do With Brain Fog and Dementia?
The brain is one of the most energy-hungry organs in the body, and brain mitochondria work constantly to meet that demand. When mitochondrial energy is compromised, the brain is often among the first places to show it. The cognitive fog, slowed thinking, and emotional dysregulation that so many people with fatigue-related conditions experience aren't imagined or exaggerated. They are the brain running on insufficient fuel.
But the implications extend well beyond symptoms of fatigue. Both Alzheimer's disease and Parkinson's disease have now been linked to mitochondrial damage and dysfunction. Research using a mouse model of Alzheimer's disease has demonstrated that mitochondrial dysfunction may actually precede the characteristic pathology of the disease, suggesting it plays a role in development, not just progression. Brain mitochondria are highly active and, it turns out, highly vulnerable. Their decline may be a pivotal factor in conditions we have long assumed were simply inevitable consequences of ageing.
Dr. Myhill's position is that these diagnoses should always prompt the question why, because if the answer involves energy delivery to the brain, then energy is also where treatment should begin.
The Ketogenic Diet and Mitochondrial Energy Metabolism
Of all the recommendations Dr. Myhill makes, the most foundational, and the one she returns to most insistently, is dietary. Specifically, the paleo ketogenic diet. Not as one tool among many, but as the non-negotiable starting point from which everything else follows.
Mitochondria are capable of burning both glucose and ketones, but ketones are their preferred fuel. Healthy fats from quality animal sources provide the ketone groups that mitochondria use most efficiently, producing more stable energy output and fewer inflammatory by-products than glucose metabolism. The ketogenic diet works, in mitochondrial terms, because it shifts the body's fuel source to the substrate the engines are actually designed to run on.
There's a second reason it matters so much. Sugars, refined carbohydrates, and processed foods are, in Dr. Myhill's words, “the most pro-inflammatory things a person can consume.” Ketones, by contrast, actively suppress inflammation. Since inflammation is the second of the two core drivers of chronic disease, the dietary shift isn't just addressing energy; it's addressing both problems at once.
The paleo ketogenic diet is built around meat, fish, eggs, vegetables, berries, nuts, and seeds. It excludes grains, dairy with the exception of butter, and all processed foods. It comes before supplements, before testing, before any more targeted intervention, because without the right fuel, the engine cannot function properly, and nothing added on top of a dysfunctional foundation will work as it should.
What Nutrients Do Mitochondria Actually Need?
Once the dietary foundation is in place and the gut is absorbing properly, targeted nutritional support can make a meaningful difference to mitochondrial function. The key word, as Dr. Myhill frames it, is friction. These nutrients don't force the mitochondria to work harder, they remove the obstacles that are slowing them down.
Her core mitochondrial support package:
Coenzyme Q10 (100mg) — essential for the electron transport chain and ATP production
Niacinamide / Vitamin B3 (1,500mg) — critically important for mitochondrial function and almost universally deficient; in Dr. Myhill's clinical experience, B3 deficiency is close to the norm, not the exception
Magnesium (minimum 200mg) — vital for mitochondrial processes, and dependent on vitamin D for proper absorption
Acetyl-L-carnitine (1g) — plays an established role in shuttling ketone groups into mitochondria to be used as fuel
D-ribose — the raw material the body uses to synthesise new ATP; particularly helpful in severe fatigue
Vitamin D (10,000 IU) — supports magnesium absorption and carries significant anti-inflammatory effects in its own right
Quality Daily Multivitamin and minerals— supports enzyme production and supplies minerals which our soils and food are deficient in due to monocrop agriculture
Alongside this, vitamin C at 5 grams each morning in warm water and Lugol's iodine at 3 drops each night form part of her foundational daily protocol, essential not only for immune function but for maintaining gut health, which in turn determines how well all other nutrients are absorbed. Benfotiamine, a fat-soluble form of vitamin B1, is another useful addition, particularly for patients dealing with blood sugar dysregulation or neuropathy, where it improves insulin sensitivity and supports mitochondrial function simultaneously.
The Upper Fermenting Gut: A Hidden Bottleneck
There is a concept central to Dr. Myhill's clinical approach that doesn't get nearly enough attention: the upper fermenting gut. And it matters because without addressing it, everything else - the diet, the supplements, the carefully chosen nutrients - may simply not reach the cells that need them.
When the upper digestive tract becomes colonised by fermenting microbes, typically as a result of a diet high in sugars, refined carbohydrates, and processed foods, the consequences extend well beyond digestive discomfort:
Fermentation produces gas and bloating
It contributes to intestinal permeability (leaky gut)
It impairs protein and mineral absorption
Critically, it means nutrients consumed or supplemented may be feeding the microbes rather than reaching the mitochondria, commonly seen in anemia
The supply chain breaks down before it reaches its destination.
Vitamin C taken in the morning and Lugol's iodine taken at night contact-kill the full range of gut pathogens, helping to restore and maintain the near-sterility the upper gut requires. It is step two, immediately after diet, and until it is properly addressed, the body's capacity to benefit from everything else is significantly reduced.
What Does the Thyroid Have to Do With Energy?
Mitochondria don't operate independently. They are governed by control systems, and the thyroid, in Dr. Myhill's analogy, is the accelerator pedal. The speed at which mitochondria run is largely determined by thyroid hormone levels, which is why an underactive thyroid can produce such pervasive fatigue even when everything else appears to be in order.
The difficulty is that conventional thyroid testing frequently misses the problem. A result that sits within the "normal" reference range may still represent significant underfunction for a given individual, particularly where conversion of T4 to the active T3 is poor, or where thyroid hormone receptor resistance is a factor. The body responds to insufficient thyroid output by mobilising adrenaline to compensate, a short-term fix that creates blood sugar instability, energy crashes, and the kind of metabolic disruption that makes recovery harder to sustain.
This is why Dr. Myhill is so specific about the order of interventions:
Diet — the foundation; without the right fuel nothing else works
Gut health — ensures nutrients actually reach the cells
Mitochondrial nutritional support — removes the biochemical bottlenecks
Thyroid evaluation — only once the engine is properly resourced
Pressing the accelerator harder on an engine that lacks adequate fuel achieves nothing. The conditions for each intervention to work have to be in place before the intervention itself can be useful.
Inflammation, Damaged Mitochondria, and the Feedback Loop
Inflammation is frequently positioned as the primary villain in chronic disease, and it is certainly implicated in a great deal of suffering. But from a mitochondrial perspective, it is more accurately understood as one part of the healing cycle. The part that can get stuck once established and if sustained, wreaks havoc.
When mitochondrial energy output drops, immune regulation becomes less precise, and inflammation can transition from an acute, purposeful response to a chronic, low-grade state. That persistent inflammation then damages mitochondria further, producing defective mitochondria that generate excess free radicals, driving more oxidative stress, and accelerating the original dysfunction. The loop tightens.
Melatonin is among the most important antioxidants operating within mitochondria, neutralising the free radicals that are an inevitable by-product of energy production. Its decline with age may partly account for both the increase in mitochondrial dysfunction seen in older people and the growing difficulty of mitochondrial biogenesis, the creation of new mitochondria, as the years pass. Breaking the inflammatory cycle requires addressing what's driving it, not simply dampening the signal. Suppressing inflammation without improving the energy deficit that sustains it tends to buy time rather than resolution.
Can Targeting Mitochondria Actually Reverse Chronic Illness?
What makes the mitochondrial framework so useful clinically is that it offers a single, coherent explanation for why so many different systems can be affected at once, and a logical sequence for addressing them. Rather than chasing individual symptoms with interventions that add friction to an already struggling system, the goal becomes reducing that friction: restoring the conditions under which mitochondria can function as they are designed to.
The therapeutic potential of this approach spans an impressive range of conditions. From chronic fatigue and fibromyalgia to cardiovascular diseases, cancer treatment support, and neurodegenerative conditions including Parkinson's disease and Alzheimer's disease, mitochondrial dysfunction is increasingly understood to play a role in the development and progression of disease that goes well beyond the primary mitochondrial disorders where it was first formally recognised.
A Different Way to Think About Recovery
Chronic fatigue and the conditions that so often accompany it are rarely straightforward. But approaching them through the lens of mitochondrial health shifts the question from “what diagnosis do I have?” to “what does my body need?”, and that shift in framing tends to open up possibilities that symptom management alone cannot reach.
Energy, in this context, means something more fundamental than how alert or motivated a person feels on a given morning. It is the substrate of every biological process, the resource the body draws on to heal, regulate, and recover. When mitochondria are producing adequate ATP, resilience returns. The body's capacity to manage inflammation, repair tissue, and respond to stress improves, not because anything has been forced, but because the underlying conditions for normal function have been restored.
The order matters, and patience with that order matters too. Diet first, then gut health, then mitochondrial nutritional support, then the broader control mechanisms. It is not always fast. But it is, in Dr. Myhill's experience across thousands of patients, where meaningful and lasting change tends to begin.