In almost every cell of your body, a multitude of tiny power plants are at work – mitochondria. They were once independent bacteria that settled in primitive cells billions of years ago and stayed. To this day they have their own DNA, which you inherit from your mother. They produce ATP, the universal energy currency of the cell, but they are not just batteries. They sense nutrients, oxygen and stress and decide accordingly whether the cell will grow, defend itself or die. Your fitness largely mirrors the fitness of your mitochondria.
How to read the numbers: Fact = a finding from research or biology
mitochondrial dysfunction is one of them
to activate brown fat
with CoQ10 and with placebo
How mitochondria produce energy
Sugars and fats from food are turned in the cell into intermediates that the mitochondrion processes in the so-called respiratory chain on its inner membrane. Electrons travel through a series of protein complexes, at the end they combine with the oxygen you breathe, and the energy released drives the production of ATP. This process also generates a small amount of free radicals. In small amounts they are important signals; in excess they damage membranes, proteins and mitochondrial DNA itself.
Why mitochondria weaken with age
A review published in Cell in 2023 lists mitochondrial dysfunction among the twelve basic hallmarks of ageing, alongside chronic inflammation, impaired autophagy and epigenetic changes. With age, damaged mitochondria accumulate, their output declines and the cell renews them less well. This shows up as fatigue, lower endurance, muscle loss and poorer insulin sensitivity. It is a vicious circle: weakened mitochondria produce more radicals and inflammatory signals, which damage them further.
The body has two tools to defend itself. Mitophagy is the targeted removal of damaged mitochondria, a special form of autophagy – cellular housekeeping. Biogenesis is the creation of new mitochondria. A healthy cell needs both: throw out the old and build new, better ones.
Cold, fasting and exercise have one thing in common: they briefly “create a problem” for the cell. Mild, temporary stress signals to the mitochondria that more capacity is needed. The body therefore rewards it with more and better power plants.
Biogenesis: exercise, cold and fasting
Exercise has the strongest evidence. In a study in Cell Metabolism, twelve weeks of high-intensity interval training improved muscle mitochondrial respiration in both young and older adults and, in older adults, reversed many age-related changes in mitochondrial proteins. Resistance training improved insulin sensitivity and muscle mass, but only interval and combined training increased mitochondrial capacity. A sensible foundation is therefore a combination: easy-paced endurance, occasional intense intervals and strength.
Cold activates brown fat – tissue packed with mitochondria that produces heat instead of storing energy. In a Dutch study, ten days of regular exposure to mild cold were enough to increase brown fat activity and non-shivering heat production in adults, and people tolerated the cold better.
Fasting and periods without food activate pathways that trigger autophagy and mitophagy and support the formation of mitochondria. Most of this evidence, however, comes from cells and animals; in humans we know that fasting improves metabolic markers, but direct measurements of mitochondria are still scarce.
Three to four hours of easy-paced activity at which you can still talk. One or two short interval sessions. Two strength sessions. Regular mild cold, for example a cold finish to your usual shower. An early evening meal, so that twelve or more hours pass between dinner and breakfast. And enough sleep, without which regeneration does not happen.
Supplements: what is backed and what is not
Coenzyme Q10 is part of the respiratory chain and also an antioxidant. The strongest evidence comes from the Q-SYMBIO trial in 420 people with moderate to severe heart failure: after two years of 300 mg a day (split into three doses) alongside standard treatment, 15 % of patients had a major cardiovascular event versus 26 % in the placebo group. These were sick people, however; in healthy people evidence of benefit is lacking. If you have heart disease, always discuss its use with your cardiologist.
Creatine helps the cell regenerate ATP quickly. According to the position stand of the International Society of Sports Nutrition (ISSN), it improves performance in short, intense exercise and supports training adaptations, and long-term use is safe in healthy people. A review of six studies in 281 healthy people also suggested improvements in short-term memory and reasoning, especially in vegetarians. Usually 3 – 5 grams of creatine monohydrate a day is enough; a loading phase is not necessary.
Urolithin A is formed in the gut from compounds in pomegranate, nuts and raspberries, but only some people can convert them, depending on their microbiome. In the first human study it was safe at doses of 500 and 1,000 mg and changed mitochondrial markers in muscle. In a randomised trial in 66 people aged 65 – 90, it improved muscle endurance after four months, but the main outcomes – walking distance and maximal ATP production – did not improve significantly. Promising, but not yet convincing.
PQQ (pyrroloquinoline quinone) supports mitochondrial formation in the laboratory and in animals. Human studies are small and short, so we do not yet know whether it has a measurable benefit in healthy people.
Methylene blue: a medicine, not a toy
Methylene blue is popular in the biohacking community because it can carry electrons in the respiratory chain. Above all, however, it is a prescription medicine that hospitals give, for example, for methaemoglobinaemia, and it belongs only in the hands of a doctor, with no self-dosing. The US FDA warns that methylene blue is a potent reversible inhibitor of the enzyme MAO-A, which breaks down serotonin. Combined with SSRI and SNRI antidepressants (for example sertraline, escitalopram, fluoxetine, venlafaxine or duloxetine), it can trigger serotonin syndrome – a condition with confusion, fever, muscle twitching, seizures and even coma.
- If you take antidepressants or other drugs affecting serotonin, do not take methylene blue. With fluoxetine the risk persists for weeks after stopping.
- Never stop antidepressants on your own in order to try a supplement.
- Technical and aquarium products are not intended for humans and may contain impurities.
- In pregnancy, kidney disease or G6PD enzyme deficiency methylene blue is even riskier.
- Strong evidence Regular exercise, especially endurance and interval training, improves mitochondrial function at any age; creatine is safe and improves performance in intense exercise; methylene blue with SSRI and SNRI antidepressants risks serotonin syndrome.
- Moderate evidence CoQ10 in heart failure; cold activates brown fat; creatine and short-term memory.
- Weak evidence Urolithin A for muscle endurance in older people, PQQ, direct effects of fasting on mitochondria in humans.
- No evidence Methylene blue as a safe daily “nootropic” supplement for healthy people, or CoQ10 as rejuvenation for the healthy.
Conclusion
Mitochondria do not need an expensive miracle; they need a reason to grow. You give them that reason with exercise, cold, sensible gaps between meals and good sleep. Supplements such as creatine or coenzyme Q10 can have their place; urolithin A and PQQ are still more promise than proof. And treat methylene blue as a medicine, not as just another capsule in your morning routine.
