Is PQQ the Next Nutrient Superstar?

Introduction

Pyrroloquinoline quinone (PQQ) is a novel vitamin-like compound found in plant foods that is showing a wide range of benefits to brain and body function based upon preclinical studies and initial clinical evaluation.1 Although PQQ is not currently viewed as a vitamin, it is likely to be considered an essential nutrient in the future.

What exactly does PQQ do?

PQQ stimulates growth and serves as a cofactor for a special class of enzymes involved in cellular function including cellular growth, development, differentiation, and survival.1
PQQ is also as an extremely powerful antioxidant capable of catalyzing continuous cycling (the ability to perform repeated oxidation and reduction reactions) to a much greater degree compared to other antioxidants. For example, PQQ is able to carry out 20,000 catalytic conversions compared to only 4 for vitamin C.1,2

Are there any food sources of PQQ?
PQQ has been found in all plant foods analyzed to date.1 PQQ-rich foods include parsley, green peppers, kiwi fruit, papaya and tofu.3 These foods contain about 2-3 mcg per 100 grams. Green tea provides about the same amount per 4 oz serving.

Is PQQ an essential nutrient?

Based upon the current research there is no question that it plays a critical role in human nutrition.1,4When PQQ is omitted from chemically defined diets in mammals it leads to growth impairment, compromised immune status, and abnormal reproductive function.5 The nutritional requirements of PQQ are probably in line with folic acid and biotin in terms of micrograms per day versus milligrams per day. Like essential nutrients, the immune system seems particularly sensitive to low levels of PQQ. With PQQ deprivation there are multiple defects in immune function and loss of white blood cells to respond properly.1

What is the most important function of PQQ?
One key action of PQQ involves a direct action on key enzymes involved in the energy producing compartments in our cells – the mitochondria. As a result PQQ improves energy production.1,6 In addition to PQQ’s powerful antioxidant effect protects against mitochondrial damage. But, PQQ not only protects mitochondria from oxidative stress—it also promotes the spontaneous generation of new mitochondria within aging cells, a process known as mitochondrial biogenesis or mitochondriogenesis.1,7,8 This effect is a “fountain of youth” for mitochondrial function.

What are the clinical uses of PQQ?
Given the nutritional importance and tremendous span of physiological effects of PQQ, there are considerable benefits in conditions that revolve around low mitochondrial function including in aging, many brain and neurological disease (e.g., Alzheimer’s and Parkinson’s disease), and many other chronic degenerative disease. Current research has primarily focused on its ability to protect memory and cognition in both aging animals and humans. Here are some of the effects noted in the animal studies:
PQQ reverses cognitive impairment caused by chronic oxidative stress and improve performance on memory tests in animal models.1,9
PQQ supplementation stimulates the production and release of nerve growth factor.1,1
PQQ protects against the self-oxidation of the DJ-1 gene, an early step in the onset of Parkinson’s disease.1,11
PQQ protects brain cells against oxidative damage in models of strokes.1,12
PQQ blocks the formation of inducible nitric oxide synthase (iNOS), a major source of reactive nitrogen species (RNS) that are so damaging to brain cells.1,13
PQQ protects against the likelihood of severe stroke in an experimental animal model for stroke.1,14
PQQ protects the brain against neurotoxicity induced by other powerful toxins, including mercury, glutamate, and oxidopamine (a potent neurotoxin used by scientists to induce Parkinsonism in laboratory animals).1,15,16
PQQ prevents development of alpha-synuclein, a protein associated with Parkinson’s disease.1,17
PQQ also protects nerve cells from the damaging effects of the beta-amyloid-protein linked with Alzheimer’s disease.1,18

Has PQQ been studied in human clinical trials?
Yes, preliminary clinical studies are extremely encouraging and several larger clinical trials are currently either completed waiting publication or are in process.
In regards to improving brain function, while PQQ is somewhat effective on its own, when it is combined with a related compound well-known to all – coenzyme Q10 – even better results have been shown. This synergistic effect was first seen in animal studies and further demonstrated in a human double-blind, placebo-controlled clinical trial conducted in Japan in 2007.19 In this study of 71 middle-aged and elderly people aged between 40-70, supplementation with 20 mg per day of PQQ resulted in improvements on tests of higher cognitive function compared to the placebo group, but in the group receiving 20 mg of PQQ along with 300 mg of CoQ10 the results were even more dramatic. PQQ and CoQ10 are both involved in mitochondrial energy production, so these results are not that surprising.

Does PQQ have to be used with CoQ10 to see results?
No, it is active on its own. In fact, in most people under 50 there may not be a need for simultaneous use of PQQ and CoQ10 unless the person is taking a drug like cholesterol-lowering statins that interfere with CoQ10 manufacture.
One human study used PQQ in 10 subjects (5 females, 5 males) the ages of 21–34 years. The subjects were given PQQ in a single dose (0.2 mg PQQ/kg) after which multiple measurements of plasma and urine PQQ levels and changes in antioxidant potential over a 48-hour period.20 Results indicated a significant increase in antioxidant potential even after this only one dosage. The same subjects were also given a daily dose of 0.3 mg PQQ/kg and had their blood measured for markers of inflammation (plasma C-reactive protein and interleukin (IL)-6 levels) and urinary metabolites related to energy metabolism before PQQ administration and 72 hours later.
PQQ supplementation resulted in significant decreases in the levels of the inflammatory markers of plasma C-reactive protein and IL-6. Furthermore, the 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.

What is the proper dosage?
One question regarding PQQ is what is an effective dosage? Specifically, if the nutritional requirement of PQQ is likely less than 500 mcg daily why is the recommended dosage 10 to 20 mg? In order to get a measured response in mitochondrial function in adult animals there is the need to feed higher amounts of PQQ much like why only 8 to 15 mg of vitamin C might protect against the overt signs of scurvy, the recommended dietary allowance currently stands at 75 to 90 milligram per day (for adults, excluding pregnant and lactating women) for optimal function, and even higher amounts are required for clinical applications.

The current recommendation of 10 to 20 mg of PQQ daily is based upon the equivalent dose in animals has consistently improved various mitochondrial functions. There are also some clinical and observational studies that justify the dosage, especially the 20 mg dosage for enhancing memory.21

Key References:
1.Rucker R, Chowanadisai W, Nakano M. Potential physiological importance of pyrroloquinoline quinone. Altern Med Rev. 2009 Sep;14(3):268-77.
2.Paz MA, Martin P, Fluckiger R, et al. The catalysis of redox cycling by pyrroloquinoline quinone (PQQ), PQQ derivatives, and isomers and the specificity of inhibitors. Anal Biochem 1996;238:145-149.
3.Kumazawa T, Sato K, Seno H, et al. Levels of pyrroloquinoline quinone in various foods. Biochem J 1995;307:331-333.
4.Kasahara T, Kato T. Nutritional biochemistry: a new redox-cofactor vitamin for mammals. Nature 2003;422:832.
5.Steinberg F, Stites TE, Anderson P, et al. Pyrroloquinoline quinone improves growth and reproductive performance in mice fed chemically defined diets. Exp Biol Med (Maywood) 2003;228:160-166.
6.Chowanadisai W, Bauerly KA, Tchaparian E, et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. Journal of Biological Chemistry 2010;285(1): 142–52
7.Stites T, Storms D, Bauerly K, et al. Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice. J Nutr 2006;136:390-396.
8.Chowanadisai W, Bauerly K, Tchaparian E, Rucker RB. Pyrroloquinoline quinone (PQQ) stimulates mitochondrial biogenesis. FASEB J 2007;21:854.
9.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;42:29-34.
10.Yamaguchi K, Sasano A, Urakami T, Tsuji T, Kondo K. Stimulation of nerve growth factor production by pyrroloquinoline quinone and its derivatives in vitro and in vivo. Biosci Biotechnol Biochem. 1993 Jul;57(7):1231-3.
11.Nunome K, Miyazaki S, Nakano M, Iguchi-Ariga S, Ariga H. Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative status of DJ-1. Biol Pharm Bull. 2008 Jul;31(7):1321-6.
12.Zhang Y, Feustel PJ, Kimelberg HK. Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in the adult rat. Brain Res 2006;1094:200-206.
13.Hirakawa A, Shimizu K, Fukumitsu H, Furukawa S. Pyrroloquinoline quinone attenuates iNOS gene expression in the injured spinal cord. Biochem Biophys Res Commun 2009;378:308-312.
14.Jensen FE, Gardner GJ, Williams AP, et al. The putative essential nutrient pyrroloquinoline quinone is neuroprotective in a rodent model of hypoxic/ ischemic brain injury. Neuroscience 1994;62:399-406.
15.Zhang P, Xu Y, Sun J, et al. Protection of pyrroloquinoline quinone against methylmercury- induced neurotoxicity via reducing oxidative stress. Free Radic Res 2009;43:224-233.
16.Zhang Q, Shen M, Ding M, Shen D, Ding F. The neuroprotective action of pyrroloquinoline quinone against glutamate-induced apoptosis in hippocampal neurons is mediated through the activation of PI3K/Akt pathway. Toxicol Appl Pharmacol. 2011 Apr 1;252(1):62-72.
17.Kim J, Harada R, Kobayashi M, Kobayashi N, Sode K. The inhibitory effect of pyrroloquinoline quinone on the amyloid formation and cytotoxicity of truncated alpha-synuclein. Mol Neurodegener. 2010 May 20;5:20
18.Kim J, Kobayashi M, Fukuda M, et al. Pyrroloquinoline quinone inhibits the fibrillation of amyloid proteins. Prion. 2010 Jan;4(1):26-31.
19.Nakano M, Ubukata K, Yamamoto T, Yamaguchi H. Effect of pyrroloquinoline quinone (PQQ) on mental status of middle-aged and elderly persons. FOOD Style. 2009;21:13(7):50-3.
20.Harris CB1, Chowanadisai W, Mishchuk DO, et al. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. 2013 Dec;24(12):2076-84.
21.http://pyrroloquinoline-quinone.com/pqq-info/ accessed 2/28/2014.

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