Stimulating production & efficiency of mitochondria

Pyrroloquinoline quinone (PQQ)

Research from the University of California has shown that the vitamin-like compound PQQ activates genes that promote mitochondrial reproduction (1).

The implications for health and longevity have been described as significant, and several studies have already demonstrated that PQQ protects against damage and ageing in heart, brain and other tissues (2-5).

1.     Chowanadisai W1, Bauerly KA, Tchaparian E, et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem. 2010 Jan 1; 285(1): 142-52.

2.     Tao R1, Karliner JS, Simonis U, et al. Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes. Biochem Biophys Res Commun. 2007 Nov 16; 363(2): 257-62.

3.     Zhang JJ1, Zhang RF, Meng XK. Protective effect of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. Neurosci Lett. 2009 Oct 30;464(3):165-9. doi: 10,1016/j.neulet.2009.08.037.

4.     Ohwada K, Takeda H, Yamazaki M, et al. Pyrroloquinoline quinone (PQQ) prevents cognitive deficit caused by oxidative stress in rats. J Clin Biochem Nutr. 2008 Jan; 42:29-34.

5.      Nunome K, Miyazaki S, Nakano M, Iguchi-Ariga S, Ariga H. Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative

Some background

Mitochondria are the powerhouses of the cell. Younger people have in excess of 2,000 per cell, but as we get older they:

  • diminish in number, and
  • those that remain are less efficient.
  • All cells in our bodies are powered by energy
  • Mitochondria are responsible for creating more than 90 percent of cellular energy. Brain, liver and muscle cells are examples of cell types that need plenty of energy to function normally.
  • The energy generated is in the form of ATP, often referred to as the energy currency of the cell
  • The inherent chemical energy in ATP is then used to fuel virtually all biological processes in our cells
  • More and more scientific data show that degenerative diseases and ageing are intimately linked to mitochondrial dysfunction…

…and this is where PQQ makes a difference:

  • via PQQ’s dual property of:
  • protecting mitochondrial DNA from the oxidative damage caused by free radicals, and
  • promotion of the biogenesis of new mitochondria.

Studies suggest that PQQ delivers a wide range of benefits, from cardiovascular health to mental function.

PQQ is well-tolerated!

So what about the tolerability profile of PQQ (pyrroloquinoline quinone), one of the key components of Go3+? PQQ as a dietary supplement was approved by the US health authorities in 2009, and to the best of our knowledge no adverse effects have been reported! Furthermore, PQQ shows no genotoxicity. This profile of tolerability is encouraging in that it enables a broad approach of in the overall improvement of health.

 

Molecular structure of PQQ

Molecular structure of PQQ

Extrapolations from animal studies suggest that 20 mg of PQQ is an optimal daily dosage. There are several dietary supplements on the market containing PQQ in the range 10-20 mg. However, none of them have the unique Go 3+ approach.

 

Here are but some of the quotes from leading scientific journals:

Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases

”Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. Mitochondria are critical regulators of cell death, a key feature of neurodegeneration. Mutations in mitochondrial DNA and oxidative stress both contribute to ageing, which is the greatest risk factor for neurodegenerative diseases. In all major examples of these diseases there is strong evidence that mitochondrial dysfunction occurs early and acts causally in disease pathogenesis. Moreover, an impressive number of disease-specific proteins interact with mitochondria. Thus, therapies targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria, hold great promise.” 

Nature 443, 787-795 (19 October 2006) | doi:10.1038/nature05292; Published online 18 October 2006

Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects

”…dietary PQQ exposure (Study 1) resulted in apparent changes in antioxidant potential based on malonaldehyde-related TBAR assessments. In Study 2, PQQ supplementation resulted in significant decreases in the levels of plasma C-reactive protein, IL-6 and urinary methylated amines such as trimethylamine N-oxide, and changes in urinary metabolites consistent with enhanced mitochondria-related functions. The data are among the first to link systemic effects of PQQ in animals to corresponding effects in humans.”

J Nutr Biochem. 2013 Dec;24(12):2076-84. doi: 10.1016/j.jnutbio.2013.07.008.

Pyrroloquinoline-quinone and its versatile roles in biological processes

”Pyrroloquinoline-quinine (PQQ) was initially characterized as a redox cofactor for membrane-bound dehydrogenases in the bacterial system. Subsequently, PQQ was shown to be an antioxidant protecting the living cells from oxidative damage in vivo and the biomolecules from artificially produced reaction oxygen species in vitro. The presence of PQQ has been documented from different biological samples. It functions as a nutrient and vitamin for supporting the growth and protection of living cells under stress. Recently, the role of PQQ has also been shown as a bio-control agent for plant fungal pathogens, an inducer for proteins kinases involved in cellular differentiation of mammalian cells and as a redox sensor leading to development of biosensor. Recent reviews published on PQQ and enzymes requiring this cofactor have brought forth the case specific roles of PQQ. This review covers the comprehensive information on various aspects of PQQ known till date. These include the roles of PQQ in the regulation of cellular growth and differentiation in mammalian system, as a nutrient and vitamin in stress tolerance, in crop productivity through increasing the availability of insoluble phosphate and as a bio-control agent, and as a redox agent leading to the biosensor development. Most recent findings correlating the exceptionally high redox recycling ability of PQQ to its potential as anti-neurodegenerative, anticancer and pharmacological agents, and as a signalling molecule have been distinctly brought out. This review discusses different findings suggesting the versatility in PQQ functions and provides the most plausible intellectual basis to the ubiquitous roles of this compound in a large number of biological processes, as a nutrient and a perspective vitamin.”

Journal of Biosciences. 2012 Jun;37(2):313-25

Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes

”Our results provide direct evidence that PQQ reduces oxidative stress, mitochondrial dysfunction, and cell death in isolated adult rat cardiomyocytes. These findings provide new insight into the mechanisms of PQQ action in the heart.”

Biochem Biophys Res Commun. 2007 Nov 16;363(2):257-62. Epub 2007 Aug 14.

Pyrroloquinoline quinone stimulates epithelial cell proliferation by activating epidermal growth factor receptor through redox cycling

”Our data suggest that PQQ may stimulate epithelial cell proliferation by activating EGFR by oxidation and subsequent inactivation of PTP1B via its redox cycling. Our results provide novel insight into the mechanisms by which PQQ may function as a growth factor to contribute to mammalian growth.”

Free Radic Biol Med. 2012 Sep 15;53(6):1239-51. Epub 2012 Jul 21.

Pyrroloquinoline quinone (PQQ) producing Escherichia coli Nissle 1917 (EcN) alleviates age associated oxidative stress and hyperlipidemia, and improves mitochondrial function in ageing rats.

”Ageing involves oxidative stress mediated by Reactive Oxygen Species (ROS) and mitochondrial dysfunction. The present work demonstrates the protective effect of PQQ producing EcN against rotenone induced mitochondrial oxidative stress and consequence of mitochondrial and cellular dysfunction in naturally ageing rat model. PQQ is a potent antioxidant molecule also known to stimulate mitochondrial biogenesis and function in mammals.

These results suggest that genetically modified EcN-5 can be used as a nutritional supplement which can reduce age related oxidative stress and hyperlipidemia. Furthermore, it also rejuvenates healthy mitochondria by stimulating mitochondrial biogenesis and metabolism.”

Experimental Gerontology. 2015 Jun;66:1-9

Protective Effect of Pyrroloquinoline Quinone (PQQ) in Rat Model of Intracerebral Hemorrhage

”Pyrroloquinoline quinone (PQQ) has invoked considerable interest because of its presence in foods, antioxidant properties, cofactor of dehydrogenase, and amine oxidase. Protective roles of PQQ in central nervous system diseases, such as experimental stroke and spinal cord injury models have been emerged. However, it is unclear whether intracerebral hemorrhage (ICH), as an acute devastating disease, can also benefit from PQQ in experimental conditions. Herein, we examined the possible effect of PQQ on neuronal functions following ICH in the adult rats. The results showed that rats pretreated with PQQ at 10 mg/kg effectively improved the locomotor functions, alleviated the hematoma volumes, and reduced the expansion of brain edema after ICH. Also, pretreated rats with PQQ obviously reduced the production of reactive oxygen species after ICH, probably due to its antioxidant properties. Further, we found that, Bcl-2/Bax, the important indicator of oxidative stress insult in mitochondria after ICH, exhibited increasing ratio in PQQ-pretreated groups. Moreover, activated caspase-3, the apoptotic executor, showed coincident alleviation in PQQ groups after ICH. Collectively, we speculated that PQQ might be an effective and potential neuroprotectant in clinical therapy for ICH.”

Cellular and Molecular Neurobiology. Volume 35, Issue 7, pp 921-930

Boost your energy and promote anti-ageing!

Kurt 61, Leipzig Germany
Both Isabelle and I would like to add that over-and-above an overall energy boost, our love life has also benefited. Hope it’s OK to mention this “positive side effect”! (05/15)