Brain health nutrients including PQQ and polyphenols

Dr Paul Clayton’s Health Newsletter October 2014

The latest nutrient craze is a supposedly new vitamin called pyrroloquinoline quinone. As the name of this compound doesn’t exactly roll off the tongue, we are fortunate indeed that it is routinely abbreviated to PQQ. PQQ is being boosted on a number of websites, where companies are selling it (under related names such as BioPQQ) as not only a new B vitamin but also the key to brain health. It is claimed to be an antioxidant (whatever that is), a booster of nerve growth factor and a mitochondrial support, and as such the answer to brain fog, brain ageing and even brain disease.

Is it really all these things? Let us look at these claims in more detail.

? PQQ is a new vitamin ?
Well, in 2003 a Japanese research group (Kasahara et al ’03) published an interesting paper in the august journal Nature in which they made a case that PQQ might indeed be a vitamin, citing evidence based on some rather esoteric molecular modelling. In 2005, however, that same journal published a paper by a US team (Felton & Anthony ’05) which pointed out key mistakes in the earlier work. Bottom line – PQQ is a fascinating molecule with a number of valuable functions in the body, but it is probably not a vitamin.

? PQQ acts as a nerve growth factor (NGF) ?
Maybe. There are some ex vivo data showing that PQQ can help rat nerves to grow in silicon (Liu et al ‘05), and increases NGF synthesis (Zhang et al ’12) but doubt remains as to whether PQQ supplements can increase or mimic nerve growth factor in human brains. If it does so, this could be a useful anti-ageing tool. I tend to believe that PQQ does indeed have this effect but the jury is still out.

? PQQ triggers growth of new mitochondria ?
in a process sometimes termed mitochondrial neogenesis. Ahah! Here is a potentially important claim, as mitochondrial ageing is a deep and strategic component of ageing and anything that enhances or renews mitochondrial function (and therefore the cells’ ability to produce usable energy) would have many therapeutic effects. And here the case is clearer; the balance of the available evidence suggests that PQQ can both protect mitochondria against oxidative and other stresses (Xu et al ’14) and, under favourable circumstances, trigger the growth of new mitochondria (Chowanidisai et al ’10). Moreover, broadly analogous effects have been shown in human subjects (Harris et al ’13), where PQQ supplements of 30 to 40 mg resulted in improved mitochondrial function and related anti-inflammatory benefits.

So, should we all start adding PQQ to our already onerous list of nutrients? Not so fast …
There are many antioxidant compounds in our foods and in our bodies, and quite a few that have the ability to get inside the mitochondria and protect them from oxidative stress. These include the well known melatonin (Guo et al ’14) and Q10 (ie Noh et al ’13), the latter compound being essential to mitochondrial function.

But there are many other nutrients that both protect mitochondria and trigger mitochondrial neogenesis, including dozens and perhaps hundreds of polyphenols (Laurent et al ’12) ranging from the resveratrol in red wine (Davinelli et al ’13, Kim et al ’14) to the equol derived from soy (Davinelli et al ’13), the more widely occurring catechins in tea and cocoa (Moreno-Ulloa et al ’14), the ubiquitous quercitin (Davis et al ’09), and the truly fascinating olive polyphenols (Zhu et al ’10).

The polyphenols have multiple beneficial effects in the body which are broadly tissue protective and anti-inflammatory, but their regulatory status – despite a large body of evidence indicating that the polyphenols are, collectively, a vitamin – remains unclear. This regulatory omission is causing us enormous harm.

Just as a reminder, polyphenols are a large group of structurally related compounds that occur widely in plants, and in all but the most processed plant-derived foods. Unfortunately it is the latter, highly processed food that have been thrust down our collective throats by an out-of-control food industry, working with regulatory regimes (EU-EFSA and USA-FDA) which have been captured and corrupted by the industries they nominally oversee (Light et al ’13). These regulators have allowed the creation of a food universe which is grossly unhealthy.

Our food universe is not only depleted in polyphenols but also in omega 3 fatty acids and 1-3, 1-6 beta glucans. This has left us extra-ordinarily vulnerable to chronic inflammation, as shown by the current multiple pandemics of degenerative disease. In populations which consume far higher amounts of the anti-inflammatory polyphenols and/or omega 3s, inflammatory diseases such as heart disease, diabetes, stroke and cancer are around 10% of the levels in ‘civilised’ society (ie Bang et al ’80, Bayard et al ’07).

We urgently need to put this right. There are honest regulators and even (possibly) a few honest lawmakers, but they are stuck in the past. Their idea of nutrition is still influenced by early work on vitamins which set in stone the idea that specific nutrients have a key and unique role in the body, and are the only compounds that can do this. But this is far from the truth.

Many nutrients have multiple functions in the body, and many functions can be modulated by multiple nutrients. Metabolism is not linear but stochastic; there is an overwhelming complexity and a huge degree of redundancy. It was ‘designed’ thus by evolution so that life can continue even if one nutrient or handful of nutrients is temporarily unavailable, because others can fill in to a greater or lesser extent, at least for periods of time. We still have unique dependencies (a handful of vitamins, essential amino acids and essential fatty acids), but these represent a very small proportion indeed of the many tens of thousands of compounds that flow, merge together and separate in our bodies to enable the enormous complexity and dynamism of life.

Let’s loop back to where we started. Take PQQ if you like, but you will be better off, in my opinion, consuming large amounts and numbers of different polyphenols in foods and/or supplements.


Bang HO, Dyerberg J, Sinclair HM. The composition of the Eskimo food in north western Greenland. Am J Clin Nutr. 1980 Dec;33(12):2657-61.

Bayard V et al. Does flavanol intake influence mortality …? Panama Int J Med Sci. 2007 Jan 27;4(1):53-8.

Chowanadisai W et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis … J Biol Chem. 2010 Jan 1;285(1):142-52.

Davis JM et al. Quercetin increases … mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R1071-7.

Davinelli S et al. Enhancement of mitochondrial biogenesis with polyphenols … Immun Ageing. 2013 Jul 11;10(1):28

Felton LM, Anthony C. Biochemistry: role of PQQ as a mammalian enzyme cofactor? Naturre. 2005 Feb 3;433(7025):E10; discussion E11-2.

Guo P et al. Melatonin Improves Mitochondrial Function … In Vitro. Toxicol Sci. 2014 Aug 26. pii: kfu164. [Epub ahead of print]

Harris CB et al. Dietary PQQ alters indicators of inflammation and … metabolism in human subjects. J Nutr Biochem. 2013 Dec;24(12):2076-84.

Kasahara T, Kato T. Nutritional biochemistry: A new redox-cofactor vitamin for mammals. Nature. 2003 Apr 24;422(6934):832.

Kim SK et al. Resveratrol induces hepatic mitochondrial biogenesis … Antioxid Redox Signal. 2014 Jun 1;20(16):2589-605.

Laurent C et al. Polyphenols decreased liver NADPH oxidase activity … in aged rats. Free Radic Res. 2012 Sep;46(9):1140-9.

Light DW et al. Institutional Corruption of Pharmaceuticals and the Myth of Safe and Effective Drugs. J. Law, Medicine & Ethics 14(3). ‘13

Liu S et al. Enhanced rat sciatic nerve regeneration through … pyrroloquinoline quinone. Microsurgery. 2005;25(4):329-37.

Moreno-Ulloa A et al. Recovery of Indicators of … Aging With Epicatechin … J Gerontol A Biol Sci Med Sci. 2014 Aug 20. pii: glu131. [Epub before print]

Noh YH et al. Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass … Cell Death Dis. 2013 Oct 3;4:e820.

Xu F, Yu H, Liu J, Cheng L. Pyrroloquinoline quinone inhibits … apoptosis … Mol Cell Biochem. 2014 Jan;386(1-2):107-15.

Zhang Q et al. Pyrroloquinoline quinone rescues hippocampal neurons … Genet Mol Res. 2012 Aug 16;11(3):2652-64.

Zhu L et al. Hydroxytyrosol protects against oxidative damage … J Nutr Biochem. 2010 Nov;21(11):1089-98.