Perform Better: Nitric Oxide, Mitochondria and the Science of Sports Performance

By Jeff Butterworth N.D — Specialist Naturopath

Every athlete I have worked with, from weekend golfers to competitive cyclists, eventually asks the same question: how do I get more out of the body I already have? After 30 years in practice, my answer starts in the same place every time. Performance is not mainly a willpower problem or a training-volume problem. It is a delivery and conversion problem.

To perform, your muscles need oxygen and fuel delivered on demand, and they need to turn that oxygen and fuel into energy efficiently. Two systems govern those two jobs. Nitric oxide runs the delivery. Your mitochondria run the conversion. Get both working well and training feels easier, recovery comes faster, and you have more in reserve when it matters.

This article sets out the science behind that principle, what the research honestly shows, and where nutrients such as CoQ10, cocoa flavanols and trace minerals fit in.

Nitric oxide: the delivery system

Nitric oxide (NO) is the signal that tells the smooth muscle in your blood vessel walls to relax. When vessels relax and widen, more oxygen-rich blood reaches working muscle. During exercise, blood flow to a working leg can rise many times over, and nitric oxide is one of the main signals that makes that possible.

It does more than open vessels. Nitric oxide also helps match blood flow to the fibres that need it most, supports glucose uptake into muscle, and influences how muscle contracts and fatigues. In simple terms, it decides how well the supply lines keep up with the demand.

Why it matters more as we age

Nitric oxide production declines with age. By around 40, most adults make roughly half the nitric oxide they did at 20. That is one reason the same session feels harder at 45 than it did at 25, and why recovery stretches out. The engine has not necessarily changed. The fuel lines have narrowed.

Two ways your body makes it

1. The classic pathway. The enzyme eNOS converts the amino acid arginine into nitric oxide. L-citrulline is the better way to feed it, because it is absorbed well and converted to arginine in the kidneys, raising arginine levels more reliably than arginine itself.
2. The nitrate pathway. Nitrates from vegetables such as beetroot, rocket (arugula) and spinach are converted by bacteria on your tongue into nitrite, then into nitric oxide. This pathway works best in exactly the conditions athletes create: low oxygen and high acidity in hard-working muscle.

Having both pathways working is the foundation of the approach. When one is limited, by age, by training stress or by antibacterial mouthwash wiping out the oral bacteria, the other keeps supply flowing.

Mitochondria: the conversion system

Once oxygen and fuel arrive, your mitochondria turn them into ATP, the energy currency every muscle contraction spends. How much work you can do, and for how long, comes down to how many mitochondria you have and how efficiently they run.

This is where nitric oxide becomes far more than a blood-flow molecule. It talks directly to the mitochondria in three ways.

• It makes them more efficient. In a landmark 2011 study in Cell Metabolism, Larsen and colleagues gave healthy people dietary nitrate for three days. Their mitochondria produced more ATP for each unit of oxygen used. Earlier work from Bailey's group showed the same effect at the whole-body level: a lower oxygen cost for the same exercise, and longer tolerance of high-intensity work.
• It helps build new ones. Nitric oxide is one of the signals that switches on mitochondrial biogenesis, the creation of new mitochondria (Nisoli, Science, 2003). Training sends this signal too. The two reinforce each other.
• It fine-tunes oxygen use. In very small amounts, nitric oxide modulates the final step of the mitochondrial energy chain. This helps spread oxygen more evenly through working tissue rather than letting the first fibres it reaches use it all.

Put simply: nitric oxide gets more oxygen to the muscle, and helps the muscle do more with the oxygen it gets. That is the core of the performance principle.

What the research shows

Raising nitric oxide is one of the most thoroughly researched nutrition strategies in sports science. More than 100 placebo-controlled trials have now tested it, and the benefits show up across endurance, high-intensity, team-sport and muscle-power performance.

Endurance: going further before fatigue

• A 2017 meta-analysis in Sports Medicine pooled 47 studies and found nitrate significantly improved time to exhaustion, the most sensitive measure of endurance capacity (McMahon et al.).
• A larger 2021 meta-analysis of 73 randomised controlled trials and 1,061 participants found nitrate increased power output, extended time to exhaustion and lowered the oxygen needed for the same work (Gao et al., JISSN).
• A 2020 meta-analysis of 80 trials confirmed an overall performance benefit (Senefeld et al., Medicine & Science in Sports & Exercise).
• In individual studies, improvements in time to exhaustion have ranged from 4 to 25 per cent, with the clearest gains in efforts lasting around 10 to 17 minutes (Macuh and Knap, Nutrients, 2021).

High-intensity and team sport

Nitric oxide is not just for endurance athletes. In recreational team-sport players, a week of beetroot juice increased distance covered in the Yo-Yo intermittent recovery test by 4.2 per cent, a test that mimics the repeated sprints of football and rugby (Wylie et al., 2013). Similar improvements have been reported in footballers, along with faster reaction times after a week of nitrate.

Muscle power, especially as we age

This is the finding I find most exciting for my clients. In healthy adults with an average age of 71, a single dose of nitrate increased maximal leg-extension speed by 10.9 per cent and muscle power by 4.4 per cent within two hours (Coggan et al., Journals of Gerontology, 2020). Muscle power is one of the first things we lose with age, and one of the strongest predictors of staying active and independent.

Strength and recovery

The citrulline pathway adds to this. A 2019 meta-analysis of 12 studies found citrulline significantly improved high-intensity strength and power performance (Trexler et al., Sports Medicine). A second meta-analysis of 13 trials found it made exercise feel easier and reduced muscle soreness at 24 and 48 hours (Rhim et al., Journal of Sport and Health Science, 2020).

Who benefits most

The research is consistent on this point: the biggest gains are in recreational athletes and active adults rather than elite endurance athletes (Campos et al., British Journal of Nutrition, 2018). Elite athletes have spent years training their nitric oxide and mitochondrial systems close to the ceiling, so there is less room to improve. For anyone over 40, whose own production has already fallen, the opportunity is far greater.

How to use it

The research points to around 300 to 560 mg of nitrate, taken two to three hours before exercise. Benefits also build with daily intake over days to weeks, so a daily foundation and a pre-session top-up work together rather than as alternatives.

BOOST: supporting the mitochondria directly

If a nitric oxide formula looks after delivery, BOOST is built around the cell's resilience and energy output. I formulated it for my own training and recovery long before it became a product.

The standout for performance is cordyceps. Small human trials have reported improvements in VO2 max and time to exhaustion after three to six weeks of daily use, in both older adults and active people. The proposed mechanism is better oxygen use and support for cellular energy production. The evidence is promising rather than settled, and I present it that way.

Around cordyceps, BOOST adds beetroot as a further nitrate source, greens such as spirulina and chlorella for antioxidant and mineral support, and adaptogenic mushrooms such as reishi to support the stress response that heavy training places on the body. Training is a stress. Recovery is where the adaptation happens. BOOST is designed for that side of the equation.

Optional supports: CoQ10, cocoa flavanols and trace minerals

These three are not the foundation. They are options worth considering once the foundation is in place, depending on your age, training load and diet.

CoQ10: the mitochondrial spark plug

Coenzyme Q10 sits inside the mitochondrial energy chain, carrying electrons so ATP can be made. It also acts as an antioxidant inside the membrane. Levels fall with age, and statin medication lowers them further.

The most cited athletic trial gave 18 elite kendo athletes 300 mg a day for 20 days during intense training. Markers of muscle damage (creatine kinase and myoglobin) and oxidative stress rose significantly less than with placebo (Kon et al., British Journal of Nutrition, 2008). A 2013 trial in German Olympic athletes reported improved peak power after six weeks of ubiquinol. Direct effects on endurance are mixed, so I see CoQ10 mainly as a recovery and resilience support, most useful for those over 40, heavy trainers and anyone on a statin.

Cocoa flavanols: a second route to nitric oxide

Cocoa flavanols, especially epicatechin, support eNOS activity and help protect nitric oxide from being broken down. In one study, 40 g of dark chocolate a day improved the gas-exchange threshold and two-minute time-trial performance in moderately trained men compared with white chocolate (Patel et al., 2015). In well-trained cyclists, a single large dose of about 900 mg of flavanols made little difference to performance, although it did raise antioxidant capacity (Decroix et al., 2017).

The pattern mirrors nitrate: a regular habit, with the clearest gains in non-elite athletes. A few squares of high-cocoa dark chocolate (85 per cent or more) or unsweetened cocoa is a simple way to include it.

Trace minerals: the cofactors the system runs on

Every step described above depends on minerals. Magnesium is bound to ATP and needed for energy production and muscle relaxation. Iron carries oxygen in blood and muscle. Zinc and selenium support the antioxidant enzymes that protect nitric oxide and mitochondria. Athletes lose minerals in sweat and use more of them, so low levels are common.

The research is clear on one point: correcting a deficiency improves performance, while extra minerals in someone already replete adds little (Heffernan et al., Nutrients, 2019). That makes trace minerals a test-and-correct strategy. Check ferritin, magnesium and zinc with your practitioner, particularly if you are a woman, train heavily or eat a plant-based diet.

Train smart: hormesis, HRV and daily testing

Fitness is not built during training. It is built while you recover from training. Knowing when to push and when to hold back is where most of the gains are won or lost.

Hormesis: the right stress at the right time

Hormesis is the principle that a small, well-timed stress makes the body adapt and come back stronger. Hard exercise is a classic hormetic stress. It briefly raises free radicals and drains cellular energy, and those signals switch on PGC-1α, the master regulator of new mitochondria, along with your own antioxidant defences and nitric oxide production.

Dose and timing decide the outcome. Too little stress sends no signal. Too much, too often, or on a body that has not recovered, and the stress outruns repair. That is the road to stalled performance, frequent illness and overtraining.

One practical lesson follows. Several studies found that high-dose antioxidant pills (1,000 mg of vitamin C with vitamin E) taken around training blunted the mitochondrial and metabolic gains from that training. The signal needs to be heard. Antioxidants from food and moderate doses still support the system, but keep megadose antioxidant pills away from your key sessions.

HRV: your daily readiness score

Heart rate variability (HRV) is the small variation in time between heartbeats. It reflects the tone of your vagus nerve, the brake pedal of the nervous system. When HRV sits at or above your own baseline, you have recovered and can absorb hard training. When it drops below baseline, your body is still dealing with stress, whether from training, poor sleep, illness, alcohol or life.

Measure it every morning under the same conditions: on waking, lying still, before coffee, with a chest strap or a validated wearable. Compare each reading with your own seven-day average, never with someone else's number.

The research supports training this way. In HRV-guided studies, athletes who trained hard only when HRV was at or above baseline matched or improved on fixed training plans, often while doing fewer hard sessions (Kiviniemi et al., 2007; Vesterinen et al., 2016). Nitric oxide and HRV are also linked, because healthy nitric oxide supports vagal tone. I cover this in Nitric Oxide, HRV and the Vagus Nerve.

Daily nitric oxide testing

I encourage testing your nitric oxide every morning, not just once. Daily readings show two things. First, the trend: whether your levels are climbing toward the optimal range as the foundation builds. Second, how you are recovering.

In my clinical experience, a level that falls after a hard training block or a run of poor sleep, and stays low, often goes with under-recovery. Heavy training and oxidative stress use up nitric oxide faster than it is replaced. One low reading means little. A downward trend over several days, alongside falling HRV, is a signal to back off.

Putting it together: a daily readiness check

Push when you are ready, recover when you are not. That is hormesis in practice: the right stress, at the right time, on a body ready to respond.

The Butterworth performance protocol

This is how I put the principle into practice with active clients. It follows the same rule as everything I do: test, support, retest.

1. Test daily. Use a saliva strip every morning, before food or brushing. It takes 15 seconds. The optimal range is roughly 220 to 435 mg/L, with a practical target near 350. Record your morning HRV at the same time, so you can see both your starting point and how you are recovering.
2. Build the daily foundation. Take Ultimate 4 once a day. It feeds both pathways: L-citrulline for the eNOS pathway, beetroot and rocket nitrates for the nitrate pathway, and vitamin C, glycine, taurine, hibiscus and magnesium taurate to help protect nitric oxide once it is made.
3. Support the mitochondria. Add BOOST daily for cordyceps, greens and adaptogenic mushrooms. Together these make up the Heart & Energy pairing.
4. Let your readings decide when to push. Use the daily readiness check above. Save your hardest sessions for the days you are ready to push. Before those sessions or a race, take your nitric oxide support two to three hours ahead and add a nitrate-rich meal such as beetroot or a large rocket salad.
5. Add the optional layers if they fit you. CoQ10 if you are over 40, train heavily or take a statin. Cocoa flavanols as a daily habit. Trace minerals once blood tests show a gap.
6. Protect the system. Avoid antibacterial mouthwash, which kills the oral bacteria the nitrate pathway depends on. Breathe through your nose in easy sessions, since the nasal sinuses produce nitric oxide. Prioritise sleep, when most adaptation happens.
7. Review the trend after four weeks. Look at your nitric oxide trend alongside HRV, resting heart rate and how training feels. If your levels have not moved, look at mouthwash, diet and gut health before adding more. If both are falling, the answer is usually more recovery, not more training.

A note on safety. If you take blood pressure medication, any nitrate medication or erectile-function medication, speak to your doctor before starting nitric oxide support.

The takeaway

Performance rests on two systems: nitric oxide to deliver oxygen and fuel, and mitochondria to turn them into energy. Both decline with age, and both respond to training and nutrition. Support nitric oxide through both pathways, give your mitochondria what they need, and correct the minerals they run on. Then measure it daily, and let your nitric oxide and HRV tell you when to push and when to recover.

No supplement replaces training, sleep and good food. But for the active adult whose body is not responding the way it used to, this is often the missing piece. Perform better, at any age.

This article is for general education. Butterworth Health products are complementary health supplements and are not intended to diagnose, treat, cure or prevent any disease. Individual results may vary. Always read the label and follow the directions for use. Consult a qualified healthcare professional before starting any supplement, particularly if you take prescription medication or have a pre-existing condition. Competitive athletes should check products against their sport's anti-doping rules.

References

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