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Interesting compound. Just ordered Jarrow Ubiquinol 100 mg, w/Pyrroloquinoline 10 mg
Pyrroloquinoline quinone (PQQ) was discovered by J.G. Hauge as the third redox cofactor after nicotinamide and flavin in bacteria (although he hypothesised that it was naphthoquinone).[1] Anthony and Zatman also found the unknown redox cofactor in alcohol dehydrogenase and named it methoxatin.[2] In 1979, Salisbury and colleagues[3] as well as Duine and colleagues[4] extracted this prosthetic group from methanol dehydrogenase of methylotrophs and identified its molecular structure. Adachi and colleagues identified that PQQ was also found in Acetobacter.[5]
These enzymes containing PQQ are called quinoproteins. Glucose dehydrogenase, one of the quinoproteins, is used as a glucose sensor. Subsequently, PQQ was found to stimulate growth in bacteria.[6] In addition, antioxidant and neuro-protective effects were also found.[7]
1 Mitochondrial biogenesis
1.1 Activation of signaling molecules
1.2 Neuroprotection
1.3 Cognition
1.4 Cardioprotection
1.5 Supplement dosage
2.0 References
Mitochondrial biogenesis
In 2010, researchers at the University of California at Davis released a peer-reviewed publication showing 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.
Most significantly, the study demonstrated that PQQ not only protects mitochondria from oxidative stress—it promotes the spontaneous generation of new mitochondria within aging cells, a process known as mitochondrial biogenesis.[8] The implications of this discovery for human health and longevity are significant because the only other known methods proven to stimulate mitochondiral biogenesis in aging humans are intense aerobic exercise,[9] strict caloric restriction,[10] and certain medications such as thiazolidinediones[11] and the diabetes drug metformin.[12]
Activation of signaling molecules
The team of researchers at the University of California analyzed PQQ’s influence over cell signaling pathways involved in the generation of new mitochondria and found that there are three signaling molecules activated by PQQ that cause cells to undergo spontaneous mitochondrial biogenesis:[8]
PQQ activates expression of PCG-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), a “master regulator” that mobilizes cells’ response to various external triggers. It directly stimulates genes that promote mitochondrial and cellular respiration, growth, and proliferation. Its capacity to upregulate cellular metabolism at the genetic level favorably affects blood pressure, cholesterol and triglyceride breakdown, and the onset of obesity.[13]
PQQ triggers the CREB signaling protein (cAMP-response element-binding protein), which plays a pivotal role in embryonic development and growth. It also beneficially interacts with histones, proteins involved in the packaging and nuclear organization of cell DNA.[14] CREB also stimulates the growth of new mitochondria.
PQQ regulates a recently discovered cell signaling protein called DJ-1. As with PCG-1α and CREB, DJ-1 is involved in cell function and survival, has been shown to prevent cell death by combating intensive oxidative stress,[15][16] and is likely important to brain health and function. DJ-1 mutations have been conclusively linked to the onset of rare inherited forms of Parkinson’s disease and other neurological disorders.
Neuroprotection:
PQQ is a neuroprotective compound that has been shown in a small number of preliminary studies to protect memory and cognition in aging animals and humans.[17][18] It has been shown to reverse cognitive impairment caused by chronic oxidative stress in animal models and improve performance on memory tests.[19] PQQ supplementation stimulates the production and release of nerve growth factors in cells that support neurons in the brain,[20] a possible mechanism for the improvement of memory function it appears to produce in aging humans and rats.
PQQ has also been shown to safeguard against the self-oxidation of the DJ-1 protein, an early step in the onset of some forms of Parkinson’s disease.[21]
PQQ protects brain cells against oxidative damage following ischemia-reperfusion injury—the inflammation and oxidative damage that result from the sudden return of blood and nutrients to tissues deprived of them by stroke.[22] Reactive nitrogen species (RNS) arise spontaneously following stroke and spinal cord injuries and impose severe stresses on damaged neurons, contributing to subsequent long-term neurological damage.[23] PQQ suppresses RNS in experimentally induced strokes,[24] and provides additional protection following spinal cord injury by blocking inducible nitric oxide synthase (iNOS), a major source of RNS.[25]
In animal models, administration of PQQ immediately prior to induction of stroke significantly reduces the size of the damaged brain area.[26] These observations have been compounded by the observation in vivo that PQQ protects against the likelihood of severe stroke in an experimental animal model for stroke and brain hypoxia.[22]
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.,[27][28] and so reducing excitotoxicity—the damaging consequence of long-term overstimulation of neurons that is associated with many neurodegenerative diseases and seizures.[29][30][31][32]
PQQ also protects the brain against neurotoxicity induced by other powerful toxins, including mercury[33](a suspected factor in the development of Alzheimer’s disease[34]) and oxidopamine[35] (a potent neurotoxin used by scientists to induce Parkinsonism in laboratory animals by destroying dopaminergic and noradrenergic neurons.[36])
PQQ prevents aggregation of alpha-synuclein, a protein associated with Parkinson’s disease.[37] PQQ also protects nerve cells from the toxic effects of the amyloid-beta protein linked with Alzheimer’s disease,[38] and reduces the formation of new amyloid beta aggregates.[39]
Cognition:
PQQ has been shown to promote memory, attention, and cognition in laboratory animals.[17]
In humans, in one double-blind, placebo-controlled clinical trial conducted in Japan in 2007, supplementation with 20 mg per day of PQQ resulted in improvements on tests of higher cognitive function in a group of 71 middle-aged and elderly people aged between 40-70, who outperformed the placebo group by more than twofold in their standardized memory tests.[18] Interestingly, co-administration of the unrelated compound coenzyme Q10 (CoQ10) further improved performance on standardized memory tests when subjects also took 300 mg per day of CoQ10. No adverse effects were linked to the supplementation, and the results suggested that PQQ, especially when combined with CoQ10, can be used to improve mental status and quality of life in older patients, and help slow or prevent age-related cognitive decline in middle-age patients.
However, the study was not peer-reviewed and was published in a non-academic journal. No proper scientific study of PQQ effects on memory or cognition in humans has been conducted, as of 2013.
Cardioprotection:
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 heart attack (myocardial infarction). Significantly, this occurs irrespective of whether the chemical is given before or after the ischemic event itself, suggesting that administration within the first hours of medical response may offer benefits to heart attack victims.[40]
Researches at the University of California at San Francisco investigated this potential, comparing PQQ with the beta blocker metoprolol—a standard post-MI clinical treatment. Independently, 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. These results led the researches to conclude that “PQQ is superior to metoprolol in protecting mitochondria from ischemia/reperfusion oxidative damage.” [41]]
Subsequent research has also demonstrated that PQQ helps heart muscle cells resist acute oxidative stress by preserving and enhancing mitochondrial function.[42]
Supplement dosage:
Despite its proposed classification as an essential nutrient,[24] no recommended daily intake of PQQ has been established.
Animal studies suggest PQQ supports healthy mitochondrial function at human equivalent doses (H.E.D.) as low as 1.44 milligrams per day,[43] but 3 milligrams per kilogram have been shown to protect rat hearts from ischemic injury.[44] The majority of human studies have used higher doses, of 10–20 mg or more. Consequently, nearly all PQQ sold as supplements in the United States range from 10–20 mg.[45][unreliable source?]
Controversy:
Although Nature Magazine published the 2003 paper by Kasahara and Kato which essentially stated that PQQ was a new vitamin, they also subsequently published, in 2005, an article by Chris Anthony and his colleague L.M. Fenton of the University of Southhampton which states that the 2003 Kasahara and Kato paper drew incorrect and unsubstantiated conclusions.[46] On his website,[47] Anthony discusses the Nature Magazine publications:
When I pointed out to the journal Nature that their high reputation was being used to justify investments of millions of dollars in the development of PQQ as a vitamin, they investigated the original paper, agreed with our objections and published our argument against it (Felton & Anthony, Nature Vol. 433, 2005). They also published (alongside ours) a paper by Rucker disagreeing with the conclusions of Kasahara and Kato on nutritional grounds, concluding “that insufficient information is available so far to state that PQQ uniquely performs an essential vitamin function in animals”.
Anthony further states on his website that "No mammalian PQQ-containing enzyme (quinoprotein) has been described" and that PQQ therefore cannot be called a "vitamin".
References:
^ Hauge JG (1964). "Glucose dehydrogenase of bacterium anitratum: an enzyme with a novel prosthetic group". J Biol Chem 239: 3630–9. PMID 14257587.
^ Anthony C, Zatman LJ (1967). "The microbial oxidation of methanol. The prosthetic group of the alcohol dehydrogenase of Pseudomonas sp. M27: a new oxidoreductase prosthetic group". Biochem J 104 (3): 960–9. PMC 1271238. PMID 6049934.
^ Salisbury SA, Forrest HS, Cruse WB, Kennard O (1979). "A novel coenzyme from bacterial primary alcohol dehydrogenases". Nature 280 (5725): 843–4. doi:10.1038/280843a0. PMID 471057.
^ Westerling J, Frank J, Duine JA (1979). "The prosthetic group of methanol dehydrogenase from Hyphomicrobium X: electron spin resonance evidence for a quinone structure". Biochem Biophys Res Commun 87 (3): 719–24. doi:10.1016/0006-291X(79)92018-7. PMID 222269.
^ Ameyama M, Matsushita K, Ohno Y, Shinagawa E, Adachi O (1981). "Existence of a novel prosthetic group, PQQ, in membrane-bound, electron transport chain-linked, primary dehydrogenases of oxidative bacteria". FEBS Lett 130 (2): 179–83. doi:10.1016/0014-5793(81)81114-3. PMID 6793395.
^ Ameyama M, Matsushita K, Shinagawa E, Hayashi M, Adachi O (1988). "Pyrroloquinoline quinone: excretion by methylotrophs and growth stimulation for microorganisms". BioFactors 1 (1): 51–3. PMID 2855583.
^ Rucker R, Chowanadisai W, Nakano M. (2009). "Potential physiological importance of pyrroloquinoline quinone". Altern Med Rev. 14 (3): 179–83.
^ a b Chowanadisai, W; Bauerly, KA; Tchaparian, E; Wong, A; Cortopassi, GA; Rucker, RB (2010 Jan). "Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression". Journal of Biological Chemistry 285 (1): 142–52. doi:10.1074/jbc.M109.030130. PMC 2804159. PMID 19861415. edit
^ Lanza, IR; Sreekumaran Nair, K (2010 Aug). "Regulation of skeletal muscle mitochondrial function: genes to proteins". Acta Physiologica 199 (4): 529–47. doi:10.1111/j.1748-1716.2010.02124.x. PMID 20345409. edit
^ Spindler, SR (2010 Jul). "Caloric restriction: from soup to nuts". Ageing Research Reviews 9 (3): 324–53. doi:10.1016/j.arr.2009.10.003. PMID 19853062. edit
^ Fujisawa, K.; Nishikawa, T.; Kukidome, D.; Imoto, K.; Yamashiro, T.; Motoshima, H.; Matsumura, T.; Araki, E. (2009). "TZDs reduce mitochondrial ROS production and enhance mitochondrial biogenesis". Biochemical and Biophysical Research Communications 379 (1): 43–48. doi:10.1016/j.bbrc.2008.11.141. PMID 19084501. edit
^ Suwa, M; Egashira, T; Nakano, H; Sasaki, H; Kumagai, S (2006 Dec). "Metformin increases the PGC-1alpha protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo". Journal of Applied Physiology 101 (6): 1685–92. doi:10.1152/japplphysiol.00255.2006. PMID 16902066. edit
^ "Entrez Gene: PPARGC1A peroxisome proliferator-activated receptor gamma, coactivator 1 alpha [ Homo sapiens ] GeneID: 10891".
^ "Entrez Gene: CREBBP CREB binding protein [ Homo sapiens ] GeneID: 1387".
^ Mitsumoto, A; Nakagawa, Y (2001). "DJ-1 is an indicator for endogenous reactive oxygen species elicited by endotoxin". Free radical research 35 (6): 885–93. PMID 11811539. edit
^ Taira, T; Saito, Y; Niki, T; Iguchi-Ariga, SMM; Takahashi, K; Ariga, H (2004 Feb). "DJ-1 has a role in antioxidative stress to prevent cell death". EMBO Reports 5 (2): 213–8. doi:10.1038/sj.embor.7400074. PMC 1298985. PMID 14749723. edit
^ a b Takatsu, H; Owada, K; Abe, K; Nakano, M; Urano, S (2009). "Effect of vitamin E on learning and memory deficit in aged rats". Journal of nutritional science and vitaminology 55 (5): 389–93. PMID 19926923. edit
^ a b "Effect of pyrroloquinoline quinone (PQQ) on mental status of middle-aged and elderly persons". Food Style 21 13 (7): 50–52. 2009.
^ Ohwada, K; Takeda, H; Yamazaki, M; Isogai, H; Nakano, M; Shimomura, M; Fukui, K; Urano, S (2008 Jan). "Pyrroloquinoline quinone (PQQ) prevents cognitive deficit caused by oxidative stress in rats". Journal of Clinical Biochemistry and Nutrition 42: 29–34. doi:10.3164/jcbn.2008005. PMC 2212345. PMID 18231627. edit
^ Murase, K; Hattori, A; Kohno, M; Hayashi, K (1993). "Stimulation of nerve growth factor synthesis/secretion in mouse astroglial cells by coenzymes". Biochemistry and molecular biology international 30 (4): 615–21. PMID 8401318. edit
^ Nunome, K; Miyazaki, S; Nakano, M; Iguchi-Ariga, S; Ariga, H (2008). "Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative status of DJ-1". Biological & Pharmaceutical Bulletin 31 (7): 1321–6. PMID 18591768. edit
^ a b Jensen, FE; Gardner, GJ; Williams, AP; Gallop, PM; Aizenman, E; Rosenberg, PA (1994). "The putative essential nutrient pyrroloquinoline quinone is neuroprotective in a rodent model of hypoxic/ischemic brain injury". Neuroscience 62 (2): 399–406. doi:10.1016/0306-4522(94)90375-1. PMID 7830887. edit
^ Ono, K; Suzuki, H; Sawada, M (2010 Apr 5). "Delayed neural damage is induced by iNOS-expressing microglia in a brain injury model". Neuroscience Letters 473 (2): 146–150. doi:10.1016/j.neulet.2010.02.041. PMID 20178828. edit
^ a b Zhang, Y; Rosenberg, PA (2002). "The essential nutrient pyrroloquinoline quinone may act as a neuroprotectant by suppressing peroxynitrite formation". The European Journal of Neuroscience 16 (6): 1015–24. PMID 12383230. edit
^ Hirakawa, A; Shimizu, K; Fukumitsu, H; Furukawa, S (2009 Jan 9). "Pyrroloquinoline quinone attenuates iNOS gene expression in the injured spinal cord". Biochemical and Biophysical Research Communications 378 (2): 308–12. doi:10.1016/j.bbrc.2008.11.045. PMID 19026989. edit
^ Zhang, Y; Feustel, P; Kimelberg, H (2006 Jun 13). "Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in the adult rat". Brain Research 1094 (1): 200–6. doi:10.1016/j.brainres.2006.03.111. PMID 16709402. edit
^ Aizenman, E; Hartnett, KA; Zhong, C; Gallop, PM; Rosenberg, PA (1992). "Interaction of the putative essential nutrient pyrroloquinoline quinone with the N-methyl-D-aspartate receptor redox modulatory site". Journal of Neuroscience 12 (6): 2362–9. PMID 1318959. edit
^ Aizenman, E; Jensen, FE; Gallop, PM; Rosenberg, PA; Tang, LH (1994). "Further evidence that pyrroloquinoline quinone interacts with the N-methyl-D-aspartate receptor redox site in rat cortical neurons in vitro". Neuroscience letters 168 (1-2): 189–92. doi:10.1016/0304-3940(94)90447-2. PMID 7518062. edit
^ Scanlon, JM; Aizenman, E; Reynolds, IJ (1997). "Effects of pyrroloquinoline quinone on glutamate-induced production of reactive oxygen species in neurons". European Journal of Pharmacology 326 (1): 67–74. doi:10.1016/S0014-2999(97)00137-4. PMID 9178657. edit
^ Hossain, MA (2005 Sep). "Molecular mediators of hypoxic-ischemic injury and implications for epilepsy in the developing brain". Epilepsy & Behavior 7 (2): 204–213. doi:10.1016/j.yebeh.2005.05.015. PMID 16054439. edit
^ Dong, XX; Wang, Y; Qin, ZH (2009 Apr). "Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases". Acta Pharmacologica Sinica 30 (4): 379–87. doi:10.1038/aps.2009.24. PMID 19343058. edit
^ Foran, E; Trotti, D (2009 Jul). "Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis". Antioxidants & Redox Signaling 11 (7): 1587–602. doi:10.1089/ars.2009.2444. PMID 19413484. edit
^ Zhang, P; Xu, Y; Sun, J; Li, X; Wang, L; Jin, L (2009 Mar). "Protection of pyrroloquinoline quinone against methylmercury-induced neurotoxicity via reducing oxidative stress". Free Radical Research 43 (3): 224–33. doi:10.1080/10715760802677348. PMID 19191107. edit
^ Mutter J, C. A. (2010). "Does inorganic mercury play a role in Alzheimer's disease? A systematic review and an integrated molecular mechanism". Journal of Alzheimer's Disease 22 (2): 357–374. doi:10.3233/JAD-2010-100705. PMID 20847438. edit
^ Hara, H; Hiramatsu, H; Adachi, T (2007 Mar). "Pyrroloquinoline quinone is a potent neuroprotective nutrient against 6-hydroxydopamine-induced neurotoxicity". Neurochemical Research 32 (3): 489–95. doi:10.1007/s11064-006-9257-x. PMID 17268846. edit
^ Breese, GR; Knapp, DJ; Criswell, HE; Moy, SS; Papadeas, ST; Blake, BL (2005 Feb). "The neonate-6-hydroxydopamine-lesioned rat: a model for clinical neuroscience and neurobiological principles". Brain Research Reviews 48 (1): 57–73. doi:10.1016/j.brainresrev.2004.08.004. PMID 15708628. edit
^ Kobayashi, M; Kim, J; Kobayashi, N; Han, S; Nakamura, C; Ikebukuro, K; Sode, K (2006 Oct 27). "Pyrroloquinoline quinone (PQQ) prevents fibril formation of alpha-synuclein". Biochemical and Biophysical Research Communications 349 (3): 1139–44. doi:10.1016/j.bbrc.2006.08.144. PMID 16962995. edit
^ Zhang JJ; Zhang RF; Meng XK (2009 Oct 30). "Protective effect of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells". Neuroscience Letters 464 (3): 165–9. doi:10.1016/j.neulet.2009.08.037. PMID 19699263. edit
^ Kim, J; Kobayashi, M; Fukuda, M; Ogasawara, D; Kobayashi, N; Han, S; Nakamura, C; Inada, M et al. (2010). "Pyrroloquinoline quinone inhibits the fibrillation of amyloid proteins". Prion 4 (1): 26–31. PMC 2850417. PMID 20083898. edit
^ Zhu BQ, Zhou HZ, Teerlink JR, Karliner JS (2004 Nov). "Pyrroloquinoline quinone (PQQ) decreases myocardial infarct size and improves cardiac function in rat models of ischemia and ischemia/reperfusion". Cardiovascular Drugs and Therapy 18 (6): 421–31. doi:10.1007/s10557-004-6219-x. PMID 15770429. edit
^ Zhu BQ; Simonis U; Cecchini G; Zhou HZ; Li L; Teerlink JR; Karliner JS (2006 Jun). "Comparison of pyrroloquinoline quinone and/or metoprolol on myocardial infarct size and mitochondrial damage in a rat model of ischemia/reperfusion injury". Journal of Cardiovascular Pharmacology and Therapeutics 11 (2): 119–28. doi:10.1177/1074248406288757. PMID 16891289. edit
^ Tao, R; Karliner, J; Simonis, U; Zheng, J; Zhang, J; Honbo, N; Alano, C (2007). "Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes". Biochemical and Biophysical Research Communications 363 (2): 257–62. doi:10.1016/j.bbrc.2007.08.041. PMC 2844438. PMID 17880922. edit
^ Stites, T; Storms, D; Bauerly, K; Mah, J; Harris, C; Fascetti, A; Rogers, Q; Tchaparian, E et al. (2006). "Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice". The Journal of nutrition 136 (2): 390–6. PMID 16424117. edit
^ Zhu BQ, Simonis U, Cecchini G, Zhou HZ, Li L, Teerlink JR, Karliner JS (2006). "Comparison of pyrroloquinoline quinone and/or metoprolol on myocardial infarct size and mitochondrial damage in a rat model of ischemia/reperfusion injury". JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS 11 (2): 119–128. doi:10.1177/1074248406288757. PMID 16891289.
^ "PQQ Dosage; What size pyrroloquinoline quinone pills should I take?". PQQ.
^ Felton LM, Anthony C (2005). "Biochemistry: role of PQQ as a mammalian enzyme cofactor?". Nature 433 (7025): E10; discussion E11–2. doi:10.1038/nature03322. PMID 15689995.
^ Anthony C. "Chris Anthony/My Research". Retrieved 2012-04-22.
Interesting compound. Just ordered Jarrow Ubiquinol 100 mg, w/Pyrroloquinoline 10 mg
Pyrroloquinoline quinone (PQQ) was discovered by J.G. Hauge as the third redox cofactor after nicotinamide and flavin in bacteria (although he hypothesised that it was naphthoquinone).[1] Anthony and Zatman also found the unknown redox cofactor in alcohol dehydrogenase and named it methoxatin.[2] In 1979, Salisbury and colleagues[3] as well as Duine and colleagues[4] extracted this prosthetic group from methanol dehydrogenase of methylotrophs and identified its molecular structure. Adachi and colleagues identified that PQQ was also found in Acetobacter.[5]
These enzymes containing PQQ are called quinoproteins. Glucose dehydrogenase, one of the quinoproteins, is used as a glucose sensor. Subsequently, PQQ was found to stimulate growth in bacteria.[6] In addition, antioxidant and neuro-protective effects were also found.[7]
1 Mitochondrial biogenesis
1.1 Activation of signaling molecules
1.2 Neuroprotection
1.3 Cognition
1.4 Cardioprotection
1.5 Supplement dosage
2.0 References
Mitochondrial biogenesis
In 2010, researchers at the University of California at Davis released a peer-reviewed publication showing 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.
Most significantly, the study demonstrated that PQQ not only protects mitochondria from oxidative stress—it promotes the spontaneous generation of new mitochondria within aging cells, a process known as mitochondrial biogenesis.[8] The implications of this discovery for human health and longevity are significant because the only other known methods proven to stimulate mitochondiral biogenesis in aging humans are intense aerobic exercise,[9] strict caloric restriction,[10] and certain medications such as thiazolidinediones[11] and the diabetes drug metformin.[12]
Activation of signaling molecules
The team of researchers at the University of California analyzed PQQ’s influence over cell signaling pathways involved in the generation of new mitochondria and found that there are three signaling molecules activated by PQQ that cause cells to undergo spontaneous mitochondrial biogenesis:[8]
PQQ activates expression of PCG-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), a “master regulator” that mobilizes cells’ response to various external triggers. It directly stimulates genes that promote mitochondrial and cellular respiration, growth, and proliferation. Its capacity to upregulate cellular metabolism at the genetic level favorably affects blood pressure, cholesterol and triglyceride breakdown, and the onset of obesity.[13]
PQQ triggers the CREB signaling protein (cAMP-response element-binding protein), which plays a pivotal role in embryonic development and growth. It also beneficially interacts with histones, proteins involved in the packaging and nuclear organization of cell DNA.[14] CREB also stimulates the growth of new mitochondria.
PQQ regulates a recently discovered cell signaling protein called DJ-1. As with PCG-1α and CREB, DJ-1 is involved in cell function and survival, has been shown to prevent cell death by combating intensive oxidative stress,[15][16] and is likely important to brain health and function. DJ-1 mutations have been conclusively linked to the onset of rare inherited forms of Parkinson’s disease and other neurological disorders.
Neuroprotection:
PQQ is a neuroprotective compound that has been shown in a small number of preliminary studies to protect memory and cognition in aging animals and humans.[17][18] It has been shown to reverse cognitive impairment caused by chronic oxidative stress in animal models and improve performance on memory tests.[19] PQQ supplementation stimulates the production and release of nerve growth factors in cells that support neurons in the brain,[20] a possible mechanism for the improvement of memory function it appears to produce in aging humans and rats.
PQQ has also been shown to safeguard against the self-oxidation of the DJ-1 protein, an early step in the onset of some forms of Parkinson’s disease.[21]
PQQ protects brain cells against oxidative damage following ischemia-reperfusion injury—the inflammation and oxidative damage that result from the sudden return of blood and nutrients to tissues deprived of them by stroke.[22] Reactive nitrogen species (RNS) arise spontaneously following stroke and spinal cord injuries and impose severe stresses on damaged neurons, contributing to subsequent long-term neurological damage.[23] PQQ suppresses RNS in experimentally induced strokes,[24] and provides additional protection following spinal cord injury by blocking inducible nitric oxide synthase (iNOS), a major source of RNS.[25]
In animal models, administration of PQQ immediately prior to induction of stroke significantly reduces the size of the damaged brain area.[26] These observations have been compounded by the observation in vivo that PQQ protects against the likelihood of severe stroke in an experimental animal model for stroke and brain hypoxia.[22]
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.,[27][28] and so reducing excitotoxicity—the damaging consequence of long-term overstimulation of neurons that is associated with many neurodegenerative diseases and seizures.[29][30][31][32]
PQQ also protects the brain against neurotoxicity induced by other powerful toxins, including mercury[33](a suspected factor in the development of Alzheimer’s disease[34]) and oxidopamine[35] (a potent neurotoxin used by scientists to induce Parkinsonism in laboratory animals by destroying dopaminergic and noradrenergic neurons.[36])
PQQ prevents aggregation of alpha-synuclein, a protein associated with Parkinson’s disease.[37] PQQ also protects nerve cells from the toxic effects of the amyloid-beta protein linked with Alzheimer’s disease,[38] and reduces the formation of new amyloid beta aggregates.[39]
Cognition:
PQQ has been shown to promote memory, attention, and cognition in laboratory animals.[17]
In humans, in one double-blind, placebo-controlled clinical trial conducted in Japan in 2007, supplementation with 20 mg per day of PQQ resulted in improvements on tests of higher cognitive function in a group of 71 middle-aged and elderly people aged between 40-70, who outperformed the placebo group by more than twofold in their standardized memory tests.[18] Interestingly, co-administration of the unrelated compound coenzyme Q10 (CoQ10) further improved performance on standardized memory tests when subjects also took 300 mg per day of CoQ10. No adverse effects were linked to the supplementation, and the results suggested that PQQ, especially when combined with CoQ10, can be used to improve mental status and quality of life in older patients, and help slow or prevent age-related cognitive decline in middle-age patients.
However, the study was not peer-reviewed and was published in a non-academic journal. No proper scientific study of PQQ effects on memory or cognition in humans has been conducted, as of 2013.
Cardioprotection:
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 heart attack (myocardial infarction). Significantly, this occurs irrespective of whether the chemical is given before or after the ischemic event itself, suggesting that administration within the first hours of medical response may offer benefits to heart attack victims.[40]
Researches at the University of California at San Francisco investigated this potential, comparing PQQ with the beta blocker metoprolol—a standard post-MI clinical treatment. Independently, 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. These results led the researches to conclude that “PQQ is superior to metoprolol in protecting mitochondria from ischemia/reperfusion oxidative damage.” [41]]
Subsequent research has also demonstrated that PQQ helps heart muscle cells resist acute oxidative stress by preserving and enhancing mitochondrial function.[42]
Supplement dosage:
Despite its proposed classification as an essential nutrient,[24] no recommended daily intake of PQQ has been established.
Animal studies suggest PQQ supports healthy mitochondrial function at human equivalent doses (H.E.D.) as low as 1.44 milligrams per day,[43] but 3 milligrams per kilogram have been shown to protect rat hearts from ischemic injury.[44] The majority of human studies have used higher doses, of 10–20 mg or more. Consequently, nearly all PQQ sold as supplements in the United States range from 10–20 mg.[45][unreliable source?]
Controversy:
Although Nature Magazine published the 2003 paper by Kasahara and Kato which essentially stated that PQQ was a new vitamin, they also subsequently published, in 2005, an article by Chris Anthony and his colleague L.M. Fenton of the University of Southhampton which states that the 2003 Kasahara and Kato paper drew incorrect and unsubstantiated conclusions.[46] On his website,[47] Anthony discusses the Nature Magazine publications:
When I pointed out to the journal Nature that their high reputation was being used to justify investments of millions of dollars in the development of PQQ as a vitamin, they investigated the original paper, agreed with our objections and published our argument against it (Felton & Anthony, Nature Vol. 433, 2005). They also published (alongside ours) a paper by Rucker disagreeing with the conclusions of Kasahara and Kato on nutritional grounds, concluding “that insufficient information is available so far to state that PQQ uniquely performs an essential vitamin function in animals”.
Anthony further states on his website that "No mammalian PQQ-containing enzyme (quinoprotein) has been described" and that PQQ therefore cannot be called a "vitamin".
References:
^ Hauge JG (1964). "Glucose dehydrogenase of bacterium anitratum: an enzyme with a novel prosthetic group". J Biol Chem 239: 3630–9. PMID 14257587.
^ Anthony C, Zatman LJ (1967). "The microbial oxidation of methanol. The prosthetic group of the alcohol dehydrogenase of Pseudomonas sp. M27: a new oxidoreductase prosthetic group". Biochem J 104 (3): 960–9. PMC 1271238. PMID 6049934.
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