Why your markers matter — and what they're actually telling you.

The link between oxidative stress, adaptation, and performance

Cambridge, MA, 2025

At the end of day one at the MetFix Training Development Conference, I found myself at dinner with Bob Kaplan, Tomás Duraj, and Derek Lee. Thomás and Derek work for Dr. Thomas Seyfried's world renowned cancer research lab at Boston College. Bob is Head of Research at MetFix. Earlier, Tomás and Derek had presented on mitochondrial dysfunction in cancer, connecting the dots between reactive oxygen species (ROS), mitochondrial damage, and cancer progression. It was heavy science—but what stayed with me wasn't just the lecture. It was the conversation over dinner that really caught my attention.

Bob had said something earlier in the day that I needed clarified. He'd suggested ROS could be beneficial, even necessary. I asked him to explain. Bob described ROS as part of fuel signaling and insulin sensitivity. Thomás and Derek jumped in: moderate ROS is essential—it signals adaptation. Too much, too long, and it's destructive. We were all aligned: ROS wasn't just about damage. It was about balance.

Somewhere in that conversation, I had a realization: ROS might be the cellular version of intensity. Just like in the gym, there's a red line. Push too little, nothing changes. Push too hard, you break. Find the edge? That's where adaptation lives.

Reactive oxygen species are small, unstable molecules your body makes every day—superoxide, hydrogen peroxide, hydroxyl radicals. They're the exhaust from your metabolic engine. They appear when you burn fuel, contract muscles, or fight infection. At controlled levels, they're signals: telling cells to grow stronger, mitochondria to multiply, immune systems to sharpen. At uncontrolled levels, they're wrecking balls: oxidizing LDL, tearing DNA, inflaming neurons, damaging cells. This dual nature of oxidative stress actually caused the person who coined the term to divide it into two separate terms: (1) oxidative eustress (physiological and essential) and (2) oxidative distress (excessive and toxic).

Unchecked ROS drives disease through direct molecular damage. In heart disease, ROS tip the redox balance toward dysfunction. They damage the endothelium, disrupt normal signaling, and accelerate the processes that harden and clog arteries. Over time, this oxidative stress becomes a driver of atherosclerosis and vascular disease. In Alzheimer's disease, glucose metabolism is dramatically decreased, due in part to oxidative damage to enzymes involved in energy production. In cancer, elevated ROS levels are linked to various proliferative processes while even higher levels are mutagenic and can damage lipids, proteins, and nucleic acids. Radiation and most chemotherapies kill cancer cells through increasing ROS levels.

There's another side to this equation. Moderate, controlled ROS is the signal of adaptation. In humans, exercise raises oxidative markers, sparks antioxidant defenses, and induces adaptive responses. Fasting shows the same pattern. Endurance exercise and prolonged fasting share a reliance on fat for fuel produced in the mitochondria. Fueling with fat intrinsically generates more ROS in the mitochondria, and this serves as a signal for mitochondrial biogenesis—more mitochondria, more capacity. Want to stick a wrench in this process? Supplement training with antioxidants.

As Bob Kaplan discussed, emerging research suggests that stress alone doesn't explain the whole picture—fuel quality influences signaling and satiety. Seed oils disrupt the natural ROS signal that tells the brain we've eaten enough, leading to overconsumption and metabolic miscommunication. When it comes to exercise, the ROS signal is a direct response to intensity.

You can't walk into a diagnostic lab and get a neat ROS readout like you can with blood sugar. They're too reactive, too fleeting. But you can see their shadow in the outcomes: improved work capacity, blood pressure improves, triglycerides drop, A1C normalizes, bones grow stronger, recovery speeds up.

Relative intensity is not a new idea. We coach mechanics to protect clients and deliver a dose of training that drives adaptation without undue injury. Scaling isn't just about protecting joints or egos. It's protecting the cell. It's keeping ROS in the adaptive zone.

What clicked for me in Cambridge is this: intensity has a fingerprint. ROS are that fingerprint. They whisper, or scream, from the mitochondria, dictate adaptation or breakdown, and sit at the crossroads of performance, resilience, and chronic disease.

ROS is the exhaust signal of human performance—the unseen byproduct that hints at whether the levers of food and training were pulled correctly. A coach who understands ROS can read the signs of fatigue, aches, or bonks and know whether the dose of nutrition, scaling, and intensity is right.

Author note

Hollis Molloy is a career coach and Certified CrossFit Level 4 Trainer who served on the CrossFit HQ Seminar Staff from 2007 to 2025 and has owned CrossFit Santa Cruz since 2008. He continues his work at CrossFit Santa Cruz while expanding into MetFix Santa Cruz and serves as a member of the MetFix Academy Staff, teaching and developing education for coaches on metabolic health and performance.

The engine behind human performance

I've seen it, and so have you. We coach the same workout all day. Some athletes thrive on the challenge, and others don't look as good. We second-guess ourselves: "Did I scale them right?" "Was that the right workout today?" But sometimes the answer is simpler. It's not the workout that needs a closer look, it's the athlete who is struggling. This is where mitochondria enter the conversation.

That is why at MetFix we claim, "We are the only commercial entity concerned with the care and feeding of mitochondria."

Capacity lives or dies inside the mitochondria. What we call fitness is really mitochondrial function expressed on the floor.

Nearly every cell in your body is built around these engines. Mature red blood cells are the exception. They carry oxygen, but they do not have mitochondria. Most tissues do, and those mitochondria are where training turns into capacity.

Each mitochondrion fires like a cylinder, turning the fuel you eat into ATP, the cell's universal energy currency. Nutrition sets the fuel mix, and training controls how hard the engine has to work.

Everything (fat, carbohydrate, and protein) gets broken down into acetyl-CoA, the molecule they burn to produce ATP. In metabolic terms, fat is the long, clean burn; carbohydrate is the fast, hot flame.

Metabolic flexibility is the capacity to burn the right fuel at the right time. When mitochondria are efficient, fat supports the easy gears and glucose is reserved for speed. When they're limited, the engine runs too hot, too soon.

What we see as poor performance is often early metabolic disease. Long before fasting insulin climbs above 5 µIU/mL or the triglyceride-to-HDL ratio rises past 2.0, coaches can see the engine struggling on the gym floor.

Adaptation is a fuel problem long before it's a fitness problem. This is the care and feeding of mitochondria. They're trainable. Give them a consistent signal and they expand. Remove the signal and they retract.

Coach the mitochondria, and you coach both performance and health.