Mitochondria: The Missing Key in Chronic IllnessExploring mitochondrial dysfunction as the hidden architecture of modern chronic illness
“Without the midi‑chlorians, life could not exist, and we would have no knowledge of the Force. They continually speak to us, telling us the will of the Force. When you learn to quiet your mind, you’ll hear them speaking to you.”
Star Wars: Episode I – The Phantom Menace, Qui‑Gon Jinn to Anakin Skywalker
Fire Alarms: Treating Symptoms While Ignoring the Cause
When a fire alarm blares, our instinct is to silence it as quickly as possible. But turning off the alarm without investigating the underlying issue is dangerous. If nothing obvious triggered it, you would check for smoke, locate your children and pets, and determine whether evacuation was necessary.
Symptoms—such as a stuffy nose, rash, stomachache, fatigue, low mood, or anxiety—are not random annoyances — they are your body reporting a system under threat. They are danger signals — early alarm codes from inside the system itself. Treating symptoms without exploring their causes is like disabling a fire alarm while the house burns. Dr. Casey Means (2024) describes our approximately 37 trillion cells as infants who cannot communicate with words and instead cry for our attention through symptoms.
One major—but often overlooked—source of these alarms is mitochondrial dysfunction.
Mitochondria
Mitochondria, often referred to as the "powerhouses of the cell," generate the energy required for nearly all physiological processes (Raffelock, 2021). The mitochondrial genome, first fully sequenced in the early 1980s, is descended from ancient bacteria—explaining why mitochondria have their own DNA and operate semi-independently within our cells (Know, 2018). They are inherited strictly through the maternal line.
Research in the mid-1990s revealed that mitochondria govern apoptosis—programmed cell death, a critical process responsible for eliminating mutated or damaged cells (Know, 2018). When apoptosis fails, malfunctioning cells replicate unchecked, increasing the risk of cancer. Mitochondria are also central to stem cell maintenance and the body’s capacity for self-renewal.
Through the energetic combustion of oxygen, mitochondria convert carbohydrates, fats, and proteins into water, heat, carbon dioxide, and adenosine triphosphate (ATP), the cell’s energy currency (Medicosis Perfectionalis, 2018). Most human cells contain roughly 2,500 mitochondria on average, though energy-demanding cells contain many more (Know, 2018). In total, the human body holds over a quadrillion mitochondria.
ATP is produced through two pathways: anaerobic glycolysis and aerobic metabolism. Glycolysis yields only two ATP molecules per glucose molecule — comparable to trying to fuel a roaring fire with a handful of twigs (Raffelock, 2021). Aerobic metabolism, by contrast, produces approximately thirty‑six ATP and powers 90% of the body's energy needs through the Krebs cycle and electron transport chain (Know, 2018). The ETC functions like a rapid relay, passing electrons through protein complexes until ATP is synthesized.
Nutrient deficiencies—including oxygen deficiency—are significant contributors to mitochondrial disruption, which can initiate or maintain conditions such as diabetes, cardiovascular disease, and cognitive decline (Marrs, 2018). There is growing evidence, echoed by Means (2024), that mitochondrial dysfunction underlies rising rates of depression, anxiety, chronic fatigue, and other modern disorders. Know (2018) compiles extensive lists of symptoms and diseases associated with impaired mitochondrial function.
Healthy mitochondria are essential for the brain and heart—both exceptionally energy-intensive organs. When mitochondria malfunction, they can create profound energy deficits, physiological depression, and system-wide dysfunction.
Compounding the problem, many pharmaceutical agents are known to damage mitochondria (Vuda & Kamath, 2016). Yet assessment of mitochondrial toxicity is not required for regulatory approval by the FDA or Health Canada. Know (2018) argues that mitochondrial injury may account for a significant portion of medication side effects. Instead of addressing root causes, patients are often given additional medications, perpetuating a cycle of dysfunction.
Diseases Associated with Mitochondrial Dysfunction
Mitochondrial dysfunction has been identified in individuals diagnosed with depression, bipolar disorder, and schizophrenia, with an average thirteen-year delay between symptom onset and confirmed mitochondrial disease (Mass, 2018). Know (2018) highlights mitochondrial involvement in cardiovascular disease, neurodegenerative conditions, infertility, hearing loss, and age-related changes such as skin wrinkling.
Cellular survival depends on mitochondrial energy production; without efficient ATP synthesis, cells die (Know, 2018). Many patients receive medications that may further compromise mitochondrial integrity, exacerbating disease progression.
“The mitochondria strike again” has become a recurring theme as research increasingly links mitochondrial dysfunction to metabolic disorders, autoimmune disease, cancer, diabetes, Alzheimer’s disease, ADHD, and more. Environmental toxins—including glyphosate, aluminium, pesticides, fluoride, and EMF radiation—may further impair mitochondrial health.
With the scope of mitochondrial influence established, the next step is understanding how to protect and restore mitochondrial function.
How to Support Mitochondrial Health
Know (2018) emphasizes that mitochondrial healing rarely results from a single intervention. The most effective approach combines lifestyle medicine, targeted nutrients, and consistent exercise.
Exercise
Exercise is arguably the single most potent therapy we have — because it builds mitochondrial capacity directly. It improves nearly every disease outcome and strengthens mitochondrial function through two primary mechanisms:
Increased energy demand, which signals the body to make more mitochondria.
Upregulation of antioxidant molecules, counteracting free radicals that contribute to cancer, autoimmune disease, cardiovascular disease, and neurodegeneration (Means, 2024).
Just six weeks of aerobic exercise — three to four sessions per week, 15–20 minutes each at about 50% of your VO₂ max — can increase mitochondrial density in muscle cells by up to 50% (Know, 2018). VO₂ max refers to your maximal oxygen uptake capacity — essentially your "ceiling" for aerobic energy generation. In simple terms, it reflects how efficiently your body can extract oxygen from air and deliver it to your tissues to make ATP. It is one of the most powerful biomarkers we have of metabolic fitness and long‑term disease risk.
A one-year aerobic intervention in older adults increased hippocampal volume by 1%, improved memory, and elevated brain-derived neurotrophic factor (BDNF) — a molecule that drives neuroplasticity in the brain (Erickson et al., 2011). The hippocampus is deeply involved in memory formation, stress regulation, and emotional processing. Even small increases in hippocampal volume translate into improved cognition, resilience, learning capacity, and better overall brain health.
Sleep
Sleep is when mitochondria repair and recover. Deep sleep increases mitochondrial fusion, autophagy, and cellular clean‑up. In contrast, poor sleep — or irregular sleep timing — elevates cortisol, destabilises glucose, and directly impairs mitochondrial efficiency (Means, 2024).
One of the fastest ways to improve mitochondrial function is to stabilise circadian rhythm — which means going to bed and waking up at consistent times.
Practical leverage: prioritise a dark bedroom (no blue light), stop screens 60–90 minutes before bed, and keep a consistent wake time. These are simple interventions — yet they create measurable improvements in mitochondrial behaviour.
Stress and Mitochondria
Stress is not just a feeling — it is a metabolic event. And not all stress is harmful. Mild stressors — challenge, novelty, activity, learning — can actually improve mitochondrial efficiency. This is called hormesis.
Where we get into danger is chronic, unresolved stress.
When stress becomes continuous — when there is no recovery between hits — mitochondria shift from energy production into defence mode. ATP output drops, inflammatory signalling increases, and mitochondria begin operating as if the organism is in danger — even when the threat is psychological, historical, or abstract.
This shift is not a malfunction — it is evolutionary design. Acute stress was meant to be brief. Our ancestors mobilized energy to survive a real threat — then returned to baseline.
But the modern world is full of never‑ending low‑grade threats — where the stress is real, but the threat is not typically life or death. The amygdala (the brain’s threat detection centre) still tags these inputs as danger, and the nervous system stays activated even when no actual survival threat is present. The amygdala doesn’t differentiate threat intensity — it only detects that a threat exists.
Instead of a literal physical predator, we now face unfinished emotional processing, unresolved trauma, relentless digital stimulation, financial uncertainty, work inflation, and isolation.
So the stress physiology stays on.
This is why chronic stress feels like exhaustion — mitochondria are literally stuck prioritizing defence over energy creation.
Your ability to shift your state — down‑regulate stress, recover, ground, repair — is mitochondrial therapy. The calmer your system, the more your mitochondria can return to energy creation rather than defence.
Trauma and Mitochondria
Trauma is not just stored in memory — it is stored in metabolism. Traumatic stress leaves an energetic signature inside the cell. It creates a chronic readiness for threat — which keeps mitochondria in defence mode long after the event has passed. Bessel van der Kolk describes trauma as “the body keeping the score.” On the mitochondrial level, that score is written in impaired oxidative phosphorylation, elevated inflammation, and reduced ATP.
Polyvagal theory extends this. When the nervous system is stuck in sympathetic survival physiology or dorsal shutdown, mitochondria must choose survival over cellular expansion. They conserve, suppress, and tighten down energy output.
This is why trauma healing isn’t only psychological — it is biological. When trauma resolves — mitochondria can finally shift out of defence into repair.
Connection and Belonging
Human connection is not optional for cellular health — it is a requirement. Loneliness is interpreted by the brain as danger. Social isolation elevates inflammatory signalling and shifts mitochondria toward defence physiology. In contrast, connection — eye contact, shared presence, co-regulation — releases endogenous opioids and oxytocin, which restore parasympathetic safety cues and allow mitochondria to return to growth mode.
Belonging is a metabolic intervention.
This means that time with people you feel safe with — even brief, authentic moments — is mitochondrial therapy in real time.
Meaning and Purpose
Purpose shapes cellular behaviour — not metaphorically, but biologically. When people have a sense of meaning — direction, contribution, a future they feel connected to — the body literally shifts the set-point away from chronic inflammation. Mitochondria begin acting like there is a future to build, not simply danger to survive.
Hopelessness suppresses metabolism. Purpose expands it — because purpose signals that growth is both possible and worth investing energy into.
Meaning is not abstract — it is biologically integrated into how energy is allocated at the cellular level.
Sunlight (and why it is mitochondrial medicine)
Means (2024) describes sunlight as a primary life source carrying photonic information — literal packets of energy that interface with the human body. We do not simply “get a tan” from the sun; sunlight interacts with the mitochondria directly. Near‑infrared wavelengths penetrate deeply into tissues and stimulate mitochondrial cytochrome c oxidase — increasing ATP production.
Sunlight is one of the only free, immediate, evolutionarily consistent mitochondrial enhancers available to humans.
Time spent outdoors also reduces the risk of obesity and chronic disease (Means, 2024; Roberts et al., 2015). Spending time outside is mitochondrial medicine. Morning light acts as a biological “time stamp.” It syncs your circadian rhythm, regulates cortisol, balances melatonin production, and coordinates downstream hormones through the suprachiasmatic nucleus. Get outside within the first 60 minutes after waking — even 3–7 minutes makes a hormonal difference. This circadian anchoring is a metabolic stabiliser.
Sunlight also synthesises vitamin D3 in the skin — which functions as a steroid hormone involved in immune regulation, gene transcription, calcium metabolism, and neuro‑immune signalling (Holick, 2004).
Humans evolved to co‑regulate metabolism, immune defence, and brain function with environmental light.
Inadequate direct sunlight — especially morning sunlight received without sunglasses (because tinted lenses block specific wavelengths that must reach the retina to inform your circadian system) — is now recognised as a major disruptor of healthy metabolism, not a harmless inconvenience.
Note: light exposure through glass does not count — windows block the exact wavelengths required to anchor circadian rhythm.
Action step: aim for direct natural light into your eyes (no sunglasses, no glass window in between) for a few minutes early in the day — it delivers the “daytime signal” your mitochondria use to set the metabolic clock.
Food
Food profoundly shapes mitochondrial health. The molecules you eat become signalling molecules — they literally instruct your genes which proteins to make and which pathways to activate. We consume approximately seventy metric tons of food in a lifetime, and its molecular structure influences gene expression, emotional regulation, DNA folding, and membrane integrity (Means, 2024). The gut microbiome produces postbiotic chemicals that directly affect mitochondrial function and overall vitality. A thriving microbiome is intimately linked to metabolic health, mood, and longevity.
Practically speaking — this means you can feed mitochondria directly.
Foods that contain polyphenols, phytonutrients, omega‑3 fats, minerals, and antioxidants literally become substrates and signalling molecules that increase ATP production and reduce oxidative stress.
Whole foods grown in soil and raised in sunlight contain the chemical “intelligence” mitochondria read. Ultra‑processed foods do the opposite — they dysregulate glucose, increase free radical formation, impair the microbiome, and drain energy from the system.
This is not about perfection — it is about leverage.
Every whole food meal is a dose — a therapeutic input — that pushes the system toward repair, resilience, and mitochondrial efficiency.
Here is the simplest way to feel this in your real life: after a whole food meal (especially protein+fibre+colour), most people experience more stable mood, sustained energy, and clearer thinking. After an ultra-processed meal (especially sugar+refined seed oils), most people feel wired/tired, foggy, irritable, and fatigued. That shift isn’t psychological — that is your mitochondria immediately reporting back on the quality of the inputs.
When you grasp this, something shifts: food stops being about “discipline” and becomes about metabolic communication. You are choosing what kind of message you send to the cellular engines that run you. The mitochondria hear everything.
Specific Mealtime Strategies
· Front-load protein early in the day → stabilises blood sugar and supports mitochondrial protein synthesis.
· Eat colour (polyphenols) at every meal → berries, herbs, leafy greens, beets, peppers. Polyphenols are mitochondrial signalling molecules.
· Cook in stable fats (butter, olive oil, avocado oil, coconut) → seed oils oxidize easily and increase free radicals.
· Finish eating at least 2–3 hours before bed → mitochondria repair and autophagy happens much more efficiently in a fasted state overnight.
· Pair carbs with fibre and fat → prevents glucose spikes that overwhelm mitochondria.
These are small, ordinary choices — but cumulatively they create a very different metabolic trajectory.
Vitamins and Supplementation
The following compounds and mechanisms are synthesised from the work of Know (2018), Means (2024), and primary mitochondrial therapeutics literature.
Supplements are not meant to replace foundational behaviours (sleep, light, movement, food), but they can accelerate mitochondrial recovery — especially when the system is already under strain.
Think of them as targeted tools.
Some substances directly participate in ATP production. Some act as cofactors. Others reduce oxidative stress so mitochondria can actually do their job.
Three categories matter most clinically:
1. cofactors → they make the machinery run
2. antioxidants → they reduce oxidative burden
3. biogenesis stimulators → they help make more mitochondria
With this in mind, the following compounds are considered the most classical, evidence-supported mitochondrial therapeutics:
Means (2024) identifies selenium, magnesium, zinc, B vitamins, and short-chain fatty acids as essential micronutrients. Know (2018) adds CoQ10, D-ribose, PQQ, L-carnitine, creatine, iron, resveratrol, and cannabis.
CoQ10
CoQ10 is like the spark plug inside the electron transport chain — it shuttles electrons where they need to go. Levels drop dramatically with age — and statin medications further reduce them by blocking the same pathway that makes cholesterol. This is why low CoQ10 often shows up as low mood, fatigue, muscle weakness, and brain fog.
How to use it: 100–200 mg/day (liposomal or ubiquinol form is best).
D-ribose
D-ribose is a natural five‑carbon sugar essential for metabolic processes such as energy synthesis. It is the structural backbone of ATP — and also makes up part of DNA and RNA. Supplementation of D‑ribose has been shown to accelerate the recovery of cardiac cellular energy by replenishing purine pools and restoring ATP after depletion. Know (2018) describes a 1991 study where administration of D‑ribose to patients with ischemia and hypoxia “woke up” dormant tissue thought to be permanently damaged.
Additional benefits include improved recovery after cardiac surgery, improved heart function in those with congestive heart failure, coronary artery disease, and angina — through improved cellular energetics — and restoration of energy to depleted skeletal muscles. D‑ribose also improves recovery following athletic performance by improving diastolic function and exercise tolerance (Know, 2018).
Because it is a natural substance, there are few known side effects, and it is generally well tolerated.
How to use it: many clinicians suggest beginning with small divided doses (for example 1–3 grams with meals) and adjusting based on individual response.
PQQ
PQQ stimulates mitochondrial biogenesis — the literal creation of new mitochondria. It also supports nerve growth, cognitive function, and immune regulation (Know, 2018). This makes PQQ particularly relevant for people wanting improved brain function and long‑term resilience.
How to use it: many clinicians use 10–20 mg/day.
L‑carnitine
L‑carnitine shuttles fatty acids into mitochondria so they can be burned for ATP. When L‑carnitine is low, fat oxidation drops — and people feel slow, foggy, and fatigued. This is one of the simplest leverage points for increasing mitochondrial fat‑burning capacity.
How to use it: 1,000–2,000 mg/day (often divided).
Creatine
Creatine helps recycle ATP during high energy demands. Beyond athletes, creatine improves cognition, mood, and brain energy metabolism. It stabilises brain ATP — which is why it is also used clinically in neurodegenerative disease research.
How to use it: approximately 3–5 grams/day.
Magnesium
Magnesium is required for ATP to be biologically active — ATP is “Mg‑ATP” inside cells. Nearly every mitochondrial enzyme depends on magnesium. Low magnesium = low metabolic efficiency.
How to use it: 200–400 mg/day (commonly as glycinate or threonate).
B‑vitamins
B1, B2, B3, B5, and B12 all act as mitochondrial cofactors — they plug directly into the Krebs cycle and electron transport chain. Without these vitamins, the machinery stalls.
How to use it: many clinicians use a full activated B‑complex daily (often in the range of 50–100 mg of B1/B2/B3 in the formula).
Alpha‑lipoic acid (ALA)
ALA is a potent mitochondrial antioxidant and improves insulin sensitivity. It also helps regenerate other antioxidants like glutathione — amplifying cellular resilience.
How to use it: 300–600 mg/day.
Omega‑3 fatty acids (EPA/DHA)
Omega‑3s stabilise mitochondrial membranes and reduce inflammatory signalling. They also support cell membrane fluidity — which improves signalling and energy transfer.
How to use it: many clinicians aim for 1-2 grams combined EPA+DHA/day.
Resveratrol
Resveratrol activates sirtuins — longevity pathways that improve mitochondrial resilience. This supports long‑term cellular repair and slows age‑associated mitochondrial decline.
How to use it: often 150–300 mg/day.
Conclusion
You now know something most people will never be told in a medical office:
Your symptoms are not betrayals of your body — they are communications from it.
Mitochondria are not passive batteries — they are intelligent sensors, constantly adjusting your metabolism based on what your environment, behaviours, relationships, and beliefs signal about the world you are living in.
That means this:
You are not powerless. Your biology is not broken.
Your mitochondria are always trying to keep you alive with the resources they have.
When you give them light, movement, nutrient‑dense food, safety cues, connection, and meaning — they respond. They adapt upward. They expand energy production. They heal. They regenerate.
This is the most hopeful truth in modern physiology:
healing isn’t magic — it’s metabolic.
And the levers that improve mitochondrial function are not fringe biohacks — they are ancient behaviours our species evolved under.
· morning light
· whole, minimally processed real food
· deep sleep
· healing of trauma
· connection and belonging
· purpose and meaning
· and movement that challenges you just enough to grow
Those inputs are not lifestyle bonuses — they are mitochondrial requirements.
If you change the inputs, you change the outputs.
If you support the cell, the cell supports you back.
And when enough cells heal — the organism heals.
References
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