TLDR: Fatigue that sleep doesn’t fix. Brain fog. Always cold. Muscle heaviness. Crashing after a workout. These aren’t personality traits or “just aging”; they’re often signs that your mitochondria, the tiny power plants inside every cell, aren’t running the way they should. In this episode, I walk through:
What mitochondria actually do (in plain English)
The 6 physical warning signs your body sends when they’re struggling
The 5 lab markers that reveal mitochondrial stress — most of which your standard panel isn’t interpreting correctly
Why your body’s pH and proton gradient might be the most underrated marker you’ve never heard of
8 ways to start rebuilding mitochondrial function this week, starting today
This is a very rudimentary explanation…
Every one of your roughly 37 trillion cells contains tiny structures called mitochondria. Their job is to take the food you eat and the oxygen you breathe and convert them into a usable form of energy called ATP (adenosine triphosphate).
Think of it like currency exchange. Food is your paycheck. But you can’t pay your bills with a paycheck directly. You have to convert it into cash first. That’s what mitochondria do. Your heart, brain, and liver cells are packed with hundreds to thousands of them, because those organs demand the most energy.
So the real question is: what happens when those mitochondria get damaged?
In 1931, German biochemist Otto Warburg won the Nobel Prize in Physiology or Medicine for his work on cellular respiration. Part of what made him famous was an earlier observation: many cancer cells generate energy primarily through fermentation (a process called aerobic glycolysis) rather than through the oxygen-based process healthy cells typically rely on - even when plenty of oxygen is available. Warburg’s Nobel Prize was officially awarded for his discovery of the respiratory enzyme, and part of what he demonstrated along the way was that cancerous cells can live and develop even in the absence of oxygen. This pattern is now known as the Warburg effect.
Here’s where I want to be careful, because this is the kind of claim that’s easy to oversimplify. It’s tempting to say “damaged mitochondria cause cancer,” full stop. The real picture is messier and still debated. Researchers have gone back and forth for decades on whether this metabolic shift is a cause of cancer or a consequence of it, and more importantly, later research found that in most cancers, the mitochondria aren’t actually broken. Subsequent research has shown that mitochondrial function is not impaired in most cancer cells, even though those cells still preferentially ferment glucose. The “why” behind that switch remains one of the more actively studied questions in cancer metabolism.
So what does this mean for you, a person who almost certainly doesn’t have cancer but does feel exhausted all the time? It means the fermentation-under-stress pattern Warburg first described is a real, well-documented phenomenon in cell biology, but I’m not going to tell you that your fatigue is “pre-cancer” or that a milder version of the Warburg effect is definitively what’s causing your brain fog. What the broader mitochondrial dysfunction research does support is more modest and, frankly, more useful: when mitochondria are chronically stressed by poor diet, chronic stress, poor sleep, toxin exposure, or simply aging, cells generate less usable energy and more oxidative byproducts, and that shows up in the body long before it shows up on a standard lab panel.
I hear a version of this sentence constantly: “My doctor ran labs and everything came back normal.” I believe them - the numbers usually do fall within standard reference ranges. But standard panels weren’t built to catch mitochondrial strain. The body, on the other hand, tends to tell you well before a lab does. As you read this list, take honest mental inventory:
Brain fog and poor concentration. Your brain uses roughly 20% of your total energy output despite being about 2% of your body weight, so when brain-cell mitochondria underperform, mental clarity is often the first thing to go.
Fatigue that sleep doesn’t fix. Not “I’m tired,” but “I slept eight hours, and I’m still exhausted.” This is one of the most common complaints I hear in practice.
Always feeling cold, or a low body temperature. Body heat is a byproduct of mitochondrial activity, so a consistently low waking temperature (roughly below 97.8°F) can point to a slower metabolic rate.
Muscle weakness or heaviness without a clear cause. Muscle cells are mitochondria-dense and need constant energy for contraction.
Exercise intolerance. You work out, and instead of feeling good afterward, you’re wiped out for days without properly recovering.
Sensitivity to light or sound. Sensory processing is energy-expensive, and when cellular energy runs low, the nervous system loses some of its buffering capacity.
None of these symptoms are proof of mitochondrial dysfunction on their own; fatigue and brain fog have a long list of possible causes, from thyroid issues to iron deficiency to depression to sleep apnea, and a thorough workup should rule those out first. But if several of these are chronic and unexplained, mitochondrial strain deserves a place on the list.
These are markers you can request from a standard blood draw, though a few need to be ordered specifically. I want to flag something important up front: the “optimal” ranges I use in my own practice are tighter than the standard reference range most labs will flag as normal. That’s intentional. A value can sit inside the reference range and still not be where I’d want to see it for someone chasing energy and longevity, rather than just ruling out overt disease. That distinction matters, and it’s worth discussing with your own physician rather than self-diagnosing off a lab printout.
Fasting insulin. Most labs allow up to 25 µIU/mL as “normal.” I typically look for something closer to 2–5. Insulin creeping up into the high single digits or beyond can be an early sign that cells are struggling to use glucose efficiently.
Fasting glucose. Optimal is generally lower than most people assume, closer to 72–85 mg/dL rather than the upper 90s that many labs will still call normal.
High-sensitivity CRP (hs-CRP). This measures systemic inflammation. Levels of CRP less than 1 mg/L are generally considered low cardiovascular risk, 1 to 3 mg/L moderate risk, and above 3 mg/L elevated risk. Damaged mitochondria leak more free radicals, and that oxidative debris is one of several things that can trigger this kind of low-grade inflammatory signal.
CO2 (bicarbonate). Part of a standard basic metabolic panel, usually reported somewhere in the low-to-high 20s (mEq/L). When it trends toward the lower end, it can be a signal of mild metabolic acidosis; worth flagging and discussing with your doctor rather than a red-alert finding on its own.
Lactate-to-pyruvate ratio. This is a more advanced, specialist-ordered marker. Normally pyruvate flows into the mitochondria and gets converted into usable energy; when mitochondrial function is impaired, pyruvate backs up and converts to lactate instead. It’s worth being precise here about what the actual research supports: a lactate-to-pyruvate ratio above 20 has been shown to distinguish patients with primary mitochondrial disease from those with other conditions in clinical studies, and this marker’s best-documented use is in diagnosing rare inherited mitochondrial disorders or evaluating critically ill patients not as a general screening tool for everyday fatigue. If you’re curious about your own ratio, this is a conversation to have with a clinician who can interpret it in the context of your full picture, not something to self-order and self-interpret.
Here’s a mental picture that helped this concept click for me: imagine Niagara Falls. Water crashes from a height, and that force turns a turbine that generates electricity at the base. Mitochondria do something similar, except instead of water, they’re moving protons (hydrogen ions) across a membrane, building up a pressure gradient. When those protons flow back through a molecular structure called ATP synthase, that “turbine” spins and produces ATP.
Now imagine you lower the height of the falls. Less force, less electricity. That’s roughly what happens when your body’s internal environment shifts toward acidity; the proton gradient shrinks, and energy production slows with it.
Blood pH is tightly regulated and normally stays between 7.35 and 7.45, it doesn’t swing wildly, and if you ever see it trend outside that narrow range on a lab, that’s a signal your body’s buffering systems are genuinely taxed, not a subtle wellness finding. Because blood pH is so tightly controlled and hard to use as an early, everyday signal, a more practical (though far less precise) proxy some practitioners use is first-morning urine pH, tested with an inexpensive strip. Consistently low first-morning urine pH is sometimes used as a rough indicator that the body is buffering more acid overnight than ideal; though it’s a screening tool at best, not a diagnostic one, and it can be influenced by diet, hydration, and other unrelated factors.
A quick, honest aside on “structured water.” You may hear claims - including sometimes in wellness spaces I respect - that water inside your cells exists in a special “fourth phase” or “exclusion zone” structure that’s central to mitochondrial function, an idea popularized by bioengineer Gerald Pollack. I want to be straight with you about where this stands scientifically: it’s a genuinely contested hypothesis, not a fact. Independent researchers have proposed alternative physical explanations for the phenomena Pollack describes, and some of his specific claims - like light-driven charge separation in water - are considered difficult to reconcile with basic physical chemistry. The underlying biology of cellular hydration and mitochondrial function is real and important; the specific “structured water” framework is an interesting but unproven idea layered on top of it, and I don’t want to present it to you as settled science.
The good news is that mitochondria aren’t fixed in number or function. Your body can build new ones; a process researchers call mitochondrial biogenesis. Here are eight inputs that support it, roughly in the order I’d actually prioritize them with a patient. Notice that supplements are last, not first.
Morning sunlight. Getting outside within about 30 minutes of waking supports circadian alignment, which in turn supports metabolic function.
Zone 2 cardio. This is exercise intensity where you can still hold a conversation roughly 3–4 sessions per week, 30–45 minutes. It’s popularly described as uniquely effective for mitochondrial biogenesis through a signaling pathway called PGC-1α. I want to add a fair caveat here: while Zone 2 has been widely positioned in popular media as the optimal intensity for improving mitochondrial and fatty-acid oxidative capacity, a 2025 narrative review found the evidence for that specific claim is more mixed than commonly portrayed, and some research suggests higher-intensity training activates these same pathways just as strongly, if not more so. Zone 2 is still a well-supported, low-risk, sustainable way to build an aerobic base; I just don’t want to oversell it as the only path to mitochondrial adaptation.
Cold exposure. This is a stressor, so I don’t recommend starting here if you haven’t built a foundation first. In animal studies, chronic cold exposure increases expression of mitochondrial proteins and the master regulator of mitochondrial biogenesis, PGC-1α, in brown adipose tissue - human data on the same mechanism is still developing. However, functional brown fat has been confirmed to exist and activate with cold exposure in adult humans. If you’re adapted to it, starting with 30–60 seconds at the end of a shower is a reasonable entry point.
Circadian alignment. Consistent sleep/wake timing supports the same systems that morning light and cold exposure influence.
Structured hydration. Beyond simply drinking more water, this includes grounding and infrared light exposure - inputs that (independent of the more speculative “structured water” claims above) are reasonably tied to circadian and metabolic health.
Metabolic flexibility. This is your body’s ability to switch between burning glucose and burning fat for fuel. Time-restricted eating is one of the more accessible tools for improving this, but it’s a second-phase intervention, not a starting point, especially if your body isn’t metabolically ready for it yet.
Red and near-infrared light therapy. Red to near-infrared light is absorbed by cytochrome c oxidase, an enzyme in the mitochondrial electron transport chain, and this interaction is associated with increased ATP synthesis by mitochondria. Most of the research uses roughly 10–20 minutes of targeted exposure, often over the head and torso.
Mitochondrial cofactors. This is where most people want to start and where I’d ask you to start last. CoQ10, magnesium, and B vitamins (especially B1, B2, B3) function as electron carriers within the Krebs cycle, and alpha-lipoic acid is a mitochondria-specific antioxidant. On top of these, I use Nion to support the body’s pH and hydration balance, and Protandim NrF2 to help address the oxidative load that builds up when mitochondria are already under stress, but these work best layered on top of the lifestyle inputs above, not as a substitute for them.
These "optimal" figures reflect the ranges I personally use with patients pursuing proactive metabolic health, not universal diagnostic cutoffs. Always interpret your own labs with a clinician who has your full history.
Three simple steps, none of which should cost much or take more than a few minutes a day:
Tomorrow morning: get outside within 30 minutes of waking for a few minutes of natural light.
Pick up pH test strips (inexpensive, available almost anywhere) and test your first-morning urine for three consecutive days. Write the numbers down.
Pull your last basic metabolic panel and find your CO2/bicarbonate value. If you don’t have a recent one, get one drawn.
If you recognized yourself in several of the symptoms above, the first move isn’t panic - it’s data. We walk through exactly this kind of cellular assessment with patients every week inside the Thrive 120 framework. If you want a professional to look at your labs and symptom picture and tell you the top three things to address first:
Disclaimer: this article is educational, not medical advice. Talk to your doctor before making changes to your diet, exercise routine, or supplement regimen, especially if you’re pregnant, nursing, on blood thinners, or managing a chronic condition — including cancer. Some links below are affiliate links — if you buy through them, I may earn a commission at no extra cost to you. These statements have not been evaluated by the FDA, and none of these products are intended to diagnose, treat, cure, or prevent any disease.)
Nobel Prize in Physiology or Medicine 1931 — Otto Warburg, biographical: https://www.nobelprize.org/prizes/medicine/1931/warburg/biographical/
Warburg effect(s) — a biographical sketch of Otto Warburg and his impacts on tumor metabolism — PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784299/
Warburg Effect — a Consequence or the Cause of Carcinogenesis? — J Cancer: https://www.jcancer.org/v07p0817.htm
Genome-Scale Metabolic Modeling: mitochondrial function is not impaired in most cancer cells — PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053319/
C-Reactive Protein and cardiovascular risk categories — Circulation (AHA): https://www.ahajournals.org/doi/10.1161/01.cir.0000093381.57779.67
Clinical usefulness of hs-CRP across Framingham risk scores — Circulation (AHA): https://www.ahajournals.org/doi/10.1161/01.cir.0000125690.80303.a8
Diagnostic values of lactate-to-pyruvate ratio in mitochondrial disease — PMC: https://pmc.ncbi.nlm.nih.gov/articles/PMC9334250/
Lactate and lactate:pyruvate ratio in pediatric acute liver failure — PMC: https://pmc.ncbi.nlm.nih.gov/articles/PMC5328928/
Mitochondrial dysfunction and ischemia in critical illness (lactate:pyruvate ratio) — PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470667/
Much Ado About Zone 2: A Narrative Review — PubMed: https://pubmed.ncbi.nlm.nih.gov/40560504/
Chronic cold exposure induces mitochondrial biogenesis in brown adipose tissue — iScience: https://www.cell.com/iscience/fulltext/S2589-0042(21)00402-8
Effect of habitual cold exposure on brown adipose tissue activity — systematic review: https://www.tandfonline.com/doi/full/10.1080/22423982.2025.2545059
Photobiomodulation of cytochrome c oxidase by chronic transcranial laser — PMC: https://pmc.ncbi.nlm.nih.gov/articles/PMC8971717/
Brain Photobiomodulation Therapy: A Narrative Review — PMC: https://pmc.ncbi.nlm.nih.gov/articles/PMC6041198/
Exclusion Zone Phenomena in Water — A Critical Review of Experimental Findings and Theories: https://arxiv.org/pdf/1909.06822
Links mentioned:
Metabolic Blueprint Session: https://calendly.com/tripleplaydoc/complimentary-consult
Protandim NrF2: https://tripleplaydoc.lifevantage.com/us-en/shop/protandim-nrf2
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