Pyrroloquinoline quinone

History

It was discovered by J.G. Hauge as the third redox cofactor after nicotinamide and flavin in bacteria (although he hypothesised that it was naphthoquinone). Anthony and Zatman also found the unknown redox cofactor in alcohol dehydrogenase. In 1979, Salisbury and colleagues as well as Duine and colleagues extracted this prosthetic group from methanol dehydrogenase of methylotrophs and identified its molecular structure. Adachi and colleagues discovered that PQQ was also found in Acetobacter.

Mitochondrial biogenesis in mice

A 2010 study revealed that PQQ’s critical role in growth and development stems from its unique ability to activate cell signaling pathways directly involved in cellular energy metabolism, development and function. The study demonstrated that PQQ protects mouse hepatocyte mitochondria from oxidative stress and promotes the spontaneous generation of new mitochondria within aging cells, a process known as mitochondrial biogenesis.

PQQ’s influence over cell signaling pathways is involved in the generation of new mitochondria. Three mouse proteins that are activated by PQQ cause cells to undergo spontaneous mitochondrial biogenesis: peroxisome proliferator-activated receptor gamma coactivator 1-alpha, cAMP response element-binding protein and the DJ-1 protein.

Cardioprotection in rat models

Damage from a heart attack, like a stroke, is inflicted via ischemic reperfusion injury. PQQ administration reduces the size of damaged areas in animal models of acute myocardial infarction (MI). Significantly, this occurs irrespective of whether the chemical is given before or after the ischemic event, suggesting that administration within the first hours of medical response may offer benefits to heart attack victims.

In a study comparing PQQ with the beta blocker metoprolol—a standard post-MI clinical treatment, both treatments reduced the size of the damaged areas and protected against heart muscle dysfunction. When given together, the left ventricle’s pumping pressure was enhanced. The combination of PQQ with metoprolol also increased mitochondrial energy-producing functions—but the effect was modest compared with PQQ alone. Only PQQ favorably reduced lipid peroxidation. The study concluded that “PQQ is superior to metoprolol in protecting mitochondria from ischemia/reperfusion oxidative damage.”

Subsequent research demonstrated that PQQ helps heart muscle cells resist acute oxidative stress by preserving and enhancing mitochondrial function.

Radiation poisoning in mice

In a study of gamma radiation poisoning in mice, 4mg/kg of PQQ improved 30-day survival from 2/20 to 12/20 at an 8 Gy dose.

Neuroprotection

PQQ is a neuroprotective compound that has been shown in preliminary studies to protect memory and cognition in animals and humans. PQQ can reverse cognitive impairment caused by chronic oxidative stress in animal models and improve performance on memory tests. PQQ supplementation stimulates the production and release of nerve growth factors in cells that support brain neurons. It offers a possible mechanism for the improvement of memory function it appears to produce in aging humans and rats.

PQQ can prevent the self-oxidation of the DJ-1 protein, an early step in the onset of some forms of Parkinson's disease.

PQQ protects brain cells against oxidative damage following ischemia-reperfusion injury—the inflammation and oxidative damage that results from the sudden return of blood and nutrients to tissues deprived of them by stroke. Reactive nitrogen species (RNS) arise spontaneously following stroke and spinal cord injuries and stress damaged neurons, contributing to subsequent long-term neurological damage. PQQ suppresses RNS in experimentally induced strokes and provides additional protection following spinal cord injury by blocking inducible nitric oxide synthase (iNOS), a major source of RNS.

In animal models, PQQ administration immediately prior to induction of stroke significantly reduces the size of the damaged brain area. In vivo PQQ protects against the likelihood of severe stroke in an animal model.

PQQ also affects some of the brain’s neurotransmitter systems. It protects neurons by modulating the properties of the N-methyl-D-aspartate (NMDA) receptor, and so reducing excitotoxicity—the damaging consequence of long-term overstimulation of neurons that is associated with many neurodegenerative diseases and seizures.

PQQ also protects the brain against neurotoxicity induced by other powerful toxins, including mercury(a suspected factor in the development of Alzheimer's disease) and oxidopamine (a potent neurotoxin used by scientists to induce Parkinsonism in laboratory animals by destroying dopaminergic and noradrenergic neurons.)

PQQ prevents aggregation of alpha-synuclein, a protein associated with Parkinson's disease. PQQ also protects nerve cells from the toxic effects of the amyloid-beta protein linked with Alzheimer's disease, and reduces the formation of new amyloid beta aggregates.

Nonalcoholic fatty liver disease in mice

A 2017 study found that PQQ had protective effect against nonalcoholic fatty liver disease (NAFLD) in a mouse model. PQQ was given to obese mouse mothers during pregnancy and lactation. Their offspring failed to develop liver fat and did not experience damage that could lead to liver disease in early adulthood.

Controversy regarding role as vitamin

The scientific journal Nature published the 2003 paper by Kasahara and Kato that essentially stated that PQQ was a new vitamin and in 2005, an article by Anthony and Fenton that stated that the 2003 Kasahara and Kato paper drew incorrect and unsubstantiated conclusions.