Mitochondrial health: how to build more cellular energy

Mitochondria are the structures inside your cells that turn food and oxygen into ATP, the molecule that powers almost everything your body does. "Building more cellular energy" really means building more and better mitochondria, a process called mitochondrial biogenesis. One lever dominates all others: regular exercise, especially harder efforts and high training volume, is by a wide margin the most reliable way to increase mitochondrial content and function in humans. Cold, heat and the popular supplements have far weaker evidence, and most claims around them outrun the data.

What mitochondria actually do

Mitochondria are tiny double-membraned compartments inside almost every cell. Their headline job is energy conversion: they feed the breakdown products of carbohydrate, fat and protein through the citric acid cycle, then use the resulting electrons to drive the electron transport chain on the inner membrane. That chain pumps protons to create a gradient, and the enzyme ATP synthase lets the protons flow back through, spinning like a turbine to make ATP, the cell's universal energy currency. This process, oxidative phosphorylation, produces around 90% of the ATP a typical cell uses.¹

The scale is easy to underestimate: the MRC Mitochondrial Biology Unit in Cambridge notes that your cells collectively generate roughly your own body weight in ATP every day.¹ Mitochondria also buffer calcium and help decide when a damaged cell should die. Tissues with high energy demand, such as heart, muscle and brain, are packed with them, which is why mitochondrial problems often show up first as fatigue and exercise intolerance.

Mitochondrial biogenesis and the PGC-1-alpha pathway

You do not have a fixed number of mitochondria. Cells continually build new ones and recycle worn-out ones; the building process is mitochondrial biogenesis. Its central conductor is a protein with an unwieldy name, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, mercifully shortened to PGC-1-alpha.²

The trigger is energy stress. When a cell burns through ATP faster than it can replace it, AMP and calcium rise and oxygen demand climbs. These signals activate sensors such as AMPK and the calcium-dependent enzyme CaMK, which switch on PGC-1-alpha. Activated PGC-1-alpha then moves into the nucleus and co-ordinates downstream factors, including NRF1 and TFAM, that turn on the genes for building new mitochondrial machinery.² The practical point is simple: PGC-1-alpha responds to demand. Repeatedly ask your muscles for more energy than they can comfortably supply, and they build more capacity. This is why no shortcut bypasses the work, and why the interventions that reliably raise PGC-1-alpha are the ones that genuinely stress your energy systems.

Exercise: the strongest lever by far

If you only do one thing for your mitochondria, train. A 2025 systematic review and meta-analysis of randomised trials confirmed that exercise significantly raises PGC-1-alpha in skeletal muscle, with a large pooled effect size (Hedges' g of about 1.2), and that both interval and continuous endurance training produce large effects.³ A single hard interval session can spike PGC-1-alpha messenger RNA several-fold within hours.⁵ Repeat that stimulus for weeks and you get structural change: training studies typically report increases of roughly 20 to 50% in mitochondrial content markers such as citrate synthase activity.⁴

Zone 2 versus high intensity

Two flavours dominate the conversation. Zone 2 is steady, conversational-pace aerobic work: hard enough to breathe deeply, easy enough to talk. High-intensity work means intervals or sustained hard efforts near your limit. Both build mitochondria, and the influential reviews by Granata, Bishop and colleagues explain the division of labour: training volume mainly drives mitochondrial content, while relative intensity mainly drives respiratory function. Crucially, those adaptations reverse quickly when you cut training volume.⁴

For time-limited people, intensity is efficient: a meta-analysis in overweight and obese adults found high-intensity interval training significantly improved the activity of mitochondrial enzymes including citrate synthase and electron transport chain complexes.⁶ Reviewers also note that very low intensities, below roughly 60% of maximum effort, are less reliable at raising mitochondrial density, which tempers the popular idea that easy Zone 2 alone is optimal.⁴ Zone 2 is not useless, it plainly works and is sustainable, but if your time is limited, adding genuinely hard efforts gives more adaptation per hour. Most endurance scientists land on a blend: a base of aerobic volume plus a smaller dose of high-intensity work. Our wider health library takes the same evidence-first line.

Cold and heat: interesting, much weaker

Both temperature extremes can nudge the same signalling pathways as exercise, but the human evidence for using them to build mitochondria is far thinner, and in one case cautionary.

Heat. Hafen and colleagues (2018, Journal of Applied Physiology) applied deep-tissue heating to the thigh muscle of 20 adults, raising muscle temperature by about 3.9C, and after repeated sessions found rises in heat shock proteins and improved mitochondrial respiration.⁷ Heat stress does activate PGC-1-alpha. But these are small, short studies using localised lab heating, not proof that regular sauna use builds mitochondria the way training does.

Cold. Here the evidence flips. Roberts and colleagues (2015, The Journal of Physiology) found that regular post-exercise cold-water immersion attenuated the anabolic signalling and long-term muscle adaptations to strength training.⁸ Cold-water endurance studies are mixed: some show a transient boost in PGC-1-alpha signalling after one session but little effect on mitochondrial protein content after weeks. The caution is real: dunking in cold water straight after a workout may blunt the very response you trained for. Save cold for rest days.

Supplements: modest, specific, or unproven

Three supplements come up constantly. None is a substitute for training, and in the UK all are sold as food supplements rather than licensed medicines, so quality is not guaranteed.

CoQ10 (ubiquinone). CoQ10 is a genuine component of the electron transport chain, which is why it appeals. A 2022 systematic review and meta-analysis of 13 randomised trials (1,126 participants) found CoQ10 produced a statistically significant reduction in fatigue scores versus placebo.⁹ But evidence for CoQ10 in statin-related muscle symptoms is mixed, and NICE does not recommend it for cardiovascular prevention in the general population.¹⁰ It has a clearer role in specific clinical mitochondrial disorders, which is different from a healthy person chasing more energy.

Creatine. Creatine is one of the best-supported sports supplements for strength and power, working largely through the phosphocreatine system that rapidly regenerates ATP. Its direct effects on mitochondrial biogenesis in healthy people rest more on mechanistic and preclinical work than robust human trials.¹¹ It is reasonable and well-tolerated for performance, but framing it as a mitochondrial builder overstates the evidence.

Urolithin A. This gut-derived metabolite stimulates mitophagy, the clearance of damaged mitochondria, in animals. Human trials are early but real: a randomised trial in middle-aged adults (Singh and colleagues, 2022, Cell Reports Medicine) reported around a 12% improvement in muscle strength, and a trial in adults aged 65 to 90 (Liu and colleagues, 2022, JAMA Network Open) found improved muscle endurance with 1,000mg daily, though it missed its co-primary muscle endpoints.¹²¹³ Promising, mostly industry-funded, not yet settled. Before buying any of these, our stack builder can pressure-test whether the evidence justifies the cost.

Honest expectations

Two things are worth holding onto. First, the dominant lever is not exotic: it is exercise that genuinely stresses your energy systems, ideally a base of aerobic volume plus some hard intervals. Everything else is at best a minor add-on. Second, "more cellular energy" is not a switch you flip; it is a capacity you build over weeks and lose within weeks if you stop. Persistent low energy can also have ordinary medical causes such as anaemia, thyroid problems, sleep apnoea or low vitamin D, worth ruling out before reaching for supplements. Our start here page offers a structured starting point, and our insights archive covers specific compounds.

This article is educational and does not constitute medical advice, diagnosis, or a treatment recommendation. Medication uses described as “off-label” are not licensed for that purpose in the UK and should only be considered under qualified clinical supervision. Always speak to your GP, pharmacist, or a registered specialist before starting, stopping, or changing any treatment. If you have severe or alarm symptoms - unintentional weight loss, blood in your stool, difficulty swallowing, persistent vomiting, a fever, or severe pain - seek urgent medical care.