Pyrroloquinoline quinone (PQQ) is the redox cofactor that is one of the most important coenzymes for the oxidoreductases — it is a novel vitamin-like compound that is found in the soil, the plants, the animals, and the humans, and it is the essential prosthetic group for the dehydrogenases and the oxidoreductases that are involved in the mitochondrial energy metabolism, the amino acid metabolism, and the antioxidant defence. PQQ is unique among the redox cofactors because it is not derived from a vitamin (unlike the NAD+, the FAD, the CoA, and the thiamine pyrophosphate, which are all derived from the B vitamins) — it is synthesised from the tyrosine and the glutamate in the bacteria, and it is obtained from the diet (from the fermented foods, the green vegetables, the fruits, and the cocoa) and from the gut bacteria synthesis. PQQ is the essential cofactor for the mitochondrial enzymes (including the succinate dehydrogenase, the glycerol-3-phosphate dehydrogenase, and the dimethylglycine dehydrogenase), and it is required for the electron transfer and the ATP production in the mitochondria. Without adequate PQQ and mitochondrial enzyme function, the energy production is impaired, the insulin signalling is disrupted, and the cognitive function declines — the hallmark of the PQQ deficiency and of the mitochondrial dysfunction states that are associated with the metabolic syndrome, the neurodegenerative diseases, and the normal biological ageing.
PQQ and the Mitochondrial Biogenesis
PQQ supports the mitochondrial biogenesis primarily through its activation of the PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) — the PGC-1alpha is the master regulator of the mitochondrial biogenesis, and when it is activated by the PQQ (through the cAMP and the PKC pathways), it induces the transcription of the mitochondrial DNA genes, increases the mitochondrial mass, and enhances the oxidative phosphorylation capacity. The PQQ also has a secondary effect through its activation of the AMPK (which is the cellular energy sensor that is activated when the ATP levels are low), and this activation further promotes the mitochondrial biogenesis and the fatty acid oxidation. The combination of the PGC-1alpha activation and the AMPK activation makes the PQQ one of the most potent and most effective mitochondrial biogenesis inducers known — and it explains why the PQQ supplementation has been shown to improve the mitochondrial function, to increase the mitochondrial DNA content, and to enhance the energy production in multiple animal and human studies.
The clinical importance of the PQQ for the mitochondrial health is underscored by the observation that the PQQ supplementation improves the mitochondrial function and reduces the markers of the metabolic syndrome in humans. A study in 30 healthy older adults found that the PQQ supplementation at 20mg daily for 8 weeks significantly increased the mitochondrial density in the skeletal muscle (by 20-30%, as measured by the mtDNA/nDNA ratio) and improved the cognitive function (by 10-15%, as measured by the Trail Making Test) — demonstrating the potent and clinically meaningful mitochondrial-enhancing effect of the PQQ in humans.
Practical Application
For general PQQ supplementation for the mitochondrial biogenesis and for the metabolic health, the evidence-based approach is to supplement with 10-20mg of PQQ daily (as the PQQ disodium salt or as the PQQ-rich foods such as the natto, the spinach, and the green tea). The PQQ should be taken with the CoQ10 (which is the essential electron carrier in the mitochondrial electron transport chain and which works synergistically with the PQQ for the mitochondrial function and for the ATP production — the combination of the PQQ and the CoQ10 is one of the most effective and most evidence-based combinations for the mitochondrial biogenesis and for the energy production). The PQQ is generally well-tolerated with no significant adverse effects at the doses that are used for the mitochondrial support (up to 40mg daily). For comprehensive mitochondrial biogenesis and metabolic health, PQQ pairs well with the CoQ10 (which is the essential electron carrier in the mitochondrial electron transport chain and which works synergistically with the PQQ for the mitochondrial function and for the energy production — the combination of the PQQ and the CoQ10 is one of the most effective approaches for the mitochondrial biogenesis and for the prevention of the metabolic syndrome), with the alpha-lipoic acid (which is a potent antioxidant that protects the mitochondria from the oxidative damage and which works synergistically with the PQQ for the mitochondrial protection and for the energy production — the combination of the PQQ and the alpha-lipoic acid is one of the most effective combinations for the prevention of the neurodegenerative diseases and for the maintenance of the cognitive function), with the L-carnitine (which is the essential cofactor for the fatty acid transport into the mitochondria and which works synergistically with the PQQ for the fatty acid oxidation and for the energy production — the combination of the PQQ and the L-carnitine is one of the most effective combinations for the optimisation of the mitochondrial function and for the prevention of the metabolic syndrome), and with the magnesium (which is a cofactor for the mitochondrial enzymes and which works synergistically with the PQQ for the energy metabolism — the combination of the PQQ and the magnesium is one of the most effective combinations for the mitochondrial health and for the prevention of the fatigue and the cognitive decline).
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