PQQ and Mitochondrial Function – That’s why you’re always tired

If you happen to wake up tired, to sleep without being able to recover, if your mind begins to lose blows with the memory that it tentennas and words arrive with slight delay, perhaps it is the case not to justify the thing giving guilt at age. It’s not just age. It is often thecellular energy that drops. And when energy falls, the first suspect has a precise name: mitochondria.
The problem could be solved with vitamin PQQ or "Vitamin B14" (which 99% of you, surely, never heard!).
In recent years Pirrolochinolina Chinone (PQQ) has become the subject of increasing scientific interest for its possible role in cellular energy regulation and oxidative stress. It is not a vitamin in the strict sense, but a molecule with biologically relevant redox activity, initially identified in the bacteria and subsequently detected also in animal and human tissues. Its importance derives above all from the interaction with mitochondria, organelles fundamental for the production of ATP and the intracellular oxidative balance.

Mytochondrial function tends to decrease with age and under chronic metabolic stress conditions. Less efficient mitochondria produce less energy and more reactive oxygen species (ROS), contributing to oxidative stress, a phenomenon involved in cell aging and numerous chronic diseases, including cardiovascular and neurodegenerative diseases. In this context, the PQ drew attention to a dual mechanism of action: on the one hand it carries out direct antioxidant activities, on the other it seems to influence the mitochondrial biogenesis.

A study published in 2009 by Chowanadisai and collaborators showed that PQQ stimulates the expression of PGC-1α, a key regulator of mitochondrial biogenesis, increasing the content of mitochondrial DNA and the activity of enzymes involved in cell breathing in animal models. This data suggests that PQQ is not limited to protecting existing mitochondria, but can contribute to the formation of new functional units, improving cell energy capacity. Further in vitro studies have confirmed that PQQ reduces ROS production and preserves mitochondrial integrity in cells under oxidative stress.

On the clinical level, evidence is still limited but interesting. A 2012 Japanese study gave 20 mg of PQQ per day for eight weeks to subjects with fatigue and sleeping disorders, observing a significant improvement in the scores related to the quality of rest and the perception of fatigue. In another randomized study conducted on untrained men subjected to aerobic exercise program, the intake of 20 mg/days of PQQ for six weeks has been associated with an increase of the markers of mitochondrial bigenesis compared to the control group. Although these studies are of limited dimensions, the results are consistent with the biological mechanisms observed in the experimental field.

Particularly relevant is the possible connection between mitochondrial function and oxidation of LDL. Atherosclerosis does not only depend on plasma levels of cholesterol, but is closely linked to inflammatory and oxidative processes. Oxidated LDLs (oxLDL) are more aterogeneous than native LDLs, as they are internalized by macrophages and contribute to the formation of foam cells and atherosclerotic plaque. Since dysfunctional mitochondria are an important source of ROS, improving their efficiency can theoretically reduce the pro-oxidant environment that promotes oxidation of lipoproteins. Although there is still no conclusive clinical trial that shows a direct reduction of oxLDL with PQQ, experimental data suggests a possible indirect effect through modulation of systemic oxidative stress.

PQQ is present in small amounts in foods such as natto, kiwi, parsley, green peppers and green tea, but food concentrations are modest compared to dosages used in clinical studies, generally between 10 and 20 mg daily. The most widely used form in supplements is disodium PQQ. With regard to safety, toxicity studies and short-term clinical trials indicate a good tolerability profile at commonly used doses. The reported side effects are rare and generally mild, such as insomnia if taken in the evening hours, headaches or gastrointestinal disorders. However, it remains prudent to consult a doctor in the presence of chronic diseases, complex pharmacological therapies, pregnancy or breastfeeding.

In summary, PQQ represents a biologically active molecule with a solid physiological rationale, in particular with regard to the regulation of mitochondrial function and oxidative stress. The evidence available, although preliminary, outlines a coherent framework that deserves further clinical insights. It does not replace the fundamental pillars of health – balanced nutrition, physical activity, quality of sleep and metabolic control – but it could fit, in selected contexts, as a support to cellular energy physiology. Research in this area is evolving and the next few years will clarify the real role of this molecule in clinical practice.

Disclaimer
This article has solely informative purposes and does not replace the advice of the doctor. The information contained does not constitute diagnosis or therapeutic indications. Before taking supplements or changing therapies, you must always consult a qualified healthcare professional.

Bibliography

1. Chowanadisai W, Bauerly KA, Tchaparian E, Wong A, Cortopassi GA, Rucker RB. Chinone pirrolochinoline stimulates mitochondrial biogenesis through CREB phosphorylation and increased PGC-1α expression (Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1α expression). J Biol Chem. 2009;284(6):3441–3449.
2. Rucker RB, Chowanadisai W, Nakano M. Possible physiological importance of pyrroloquinone (Potential physiological importance of pyrroloquinoline quinone). Altern Med Rev. 2009;14(3):268–277.
3. Harris CB, Chowanadisai W, Mishchuk DO, Satre MA, Slupsky CM, Rucker RB. Pirrolochinoline chinone in diet modifies indicators of inflammation and mitochondrial metabolism in man (Dietary pyrroloquinoline quinone alters indicators of inflammation and mitochondrial-related metabolism in human subjects). J Nutr Biochem. 2013;24(12):2076–2084.
4. Nakano M, Ubukata K, Yamamoto T. Effects of disodium chinone pyroloquin on fatigue and sleep in healthy adults: randomized study, double blind, placebo controlled (Effect of pyrroloquinoline quinone disodium jump on fatigue and sleep in healthy adults). Funct Foods Health Dis. 2012;2(8):307–324.
5. Ouchi A, Nakano M, Nagaoka S, Mukai K. Plasmatic cynthetics of pyroloquinone and its effects on mitochondrial biogenesis in man (Kinetics of plasma pyrroloquinoline quinone and its effect on mitochondrial biogenesis in humans). Nutrients. 2019;11(1):28.
6. Tao R, Karliner JS, Simonis U, Zheng J, Zhang J, Honbo N, Alano CC. Chinone pirrolochinoline preserves mitochondrial function and prevents oxidative damage in neuronal cells (Pyrroloquinoline quinone preserves mitochondrial function and preventives oxidative injury in neuronal cells). J Biol Chem. 2015;290(9):5569–5580.
7. Zhang Y, Feustel PJ, Kimelberg HK. Neuroprotective effects of pyroloquinone chinone in oxidative stress models (Neuroprotective effects of pyrroloquinoline quinone in oxidative stress models). Oxid Med Cell Longev. 2020;2020:1–12.
8. Nakano M, Matsui T, Sato H, et al. Safety assessment of disodium chinone pyroloquinone (BioPQTM): 4 week toxicity study in man (Safety evaluation of pyrroloquinoline quinone disodium salt). Food Chem Toxicol. 2014;67:185–190.