Effects of Antioxidant Supplements (BioPQQ™) on Cerebral Blood Flow and Oxygen Metabolism in the Prefrontal Cortex

  • Masahiko Nakano
  • Yuta Murayama
  • Lizhen Hu
  • Kazuto Ikemoto
  • Tatsuo Uetake
  • Kaoru SakataniEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 923)


Pyrroloquinoline quinone (PQQ) is a quinone compound originally identified in methanol-utilizing bacteria and is a cofactor for redox enzymes. At the Meeting of the International Society on Oxygen Transport to Tissue (ISOTT) 2014, we reported that PQQ disodium salt (BioPQQ™) improved cognitive function in humans, as assessed by the Stroop test. However, the physiological mechanism of PQQ remains unclear. In the present study, we measured regional cerebral blood flow (rCBF) and oxygen metabolism in prefrontal cortex (PFC), before and after administration of PQQ, using time-resolved near-infrared spectroscopy (tNIRS). A total of 20 healthy subjects between 50 and 70 years of age were administered BioPQQ™ (20 mg) or placebo orally once daily for 12 weeks. Hemoglobin (Hb) concentration and absolute tissue oxygen saturation (SO2) in the bilateral PFC were evaluated under resting conditions using tNIRS. We found that baseline concentrations of hemoglobin and total hemoglobin in the right PFC significantly increased after administration of PQQ (p < 0.05). In addition, decreases in SO2 level in the PFC were more pronounced in the PQQ group than in the placebo group (p < 0.05). These results suggest that PQQ causes increased activity in the right PFC associated with increases in rCBF and oxygen metabolism, resulting in enhanced cognitive function.


NIRS Prefrontal cortex Pyrroloquinoline quinone Stroop test Working memory 



This research was supported in part by the Strategic Research Foundation Grant-aided Project for Private Universities (S1411017) and a Grant-in-Aid for Exploratory Research (25560356) from the Ministry of Education, Culture, Sports, Sciences, and Technology of Japan. Furthermore, this research was supported through grants from Iing Co., Ltd. (Tokyo, Japan), Alpha Electron Co., Ltd. (Fukushima, Japan), NJI Co., Ltd. (Fukushima, Japan), and Southern Tohoku General Hospital (Fukushima, Japan).


  1. 1.
    Salisbury SA, Forrest HS, Cruse WBT et al (1979) A novel coenzyme from bacterial primary alcohol dehydrogenase. Nature 280:843–844CrossRefPubMedGoogle Scholar
  2. 2.
    Duine JA, Frank J, Van Zeeland JK (1979) Glucose dehydrogenase from Acinetobacter calcoaceticus: a quinoprotein. FEBS Lett 108:443–446CrossRefPubMedGoogle Scholar
  3. 3.
    Kumazawa T, Sato K, Seno H et al (1995) Levels of pyrroloquinoline quinone in various foods. Biochem J 307:331–333CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Kumazawa T, Seno H, Urakami T et al (1992) Trace levels of pyrroloquinoline quinone in human and rat samples detected by gas chromatography/mass spectrometry. Biochem Biophys Acta 1156:62–66CrossRefPubMedGoogle Scholar
  5. 5.
    Mitchell AE, Johnes AD, Mercer RS et al (1999) Characterization of pyrroloquinoline quinone amino acid derivatives by electrospray ionization mass spectrometry and detection in human milk. Anal Biochem 269:317–325CrossRefPubMedGoogle Scholar
  6. 6.
    Harris CB, Chowanadisai W, Mishchuk DO et al (2013) Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem 24:2076–2084CrossRefPubMedGoogle Scholar
  7. 7.
    Rucker R, Chowanadisai W, Nakano M (2009) Potential physiological importance of pyrroloquinoline quinone. Altern Med Rev 14:268–277PubMedGoogle Scholar
  8. 8.
    Mukai K, Ouchi A, Nakano M (2011) Kinetic study of the quenching reaction of singlet oxygen by pyrroloquinolinequinol (PQQH2, a reduced form of pyrroloquinolinequinone) in micellar solution. J Agric Food Chem 59:1705–1712CrossRefPubMedGoogle Scholar
  9. 9.
    Nunome K, Miyazaki S, Nakano M et al (2008) Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative status of DJ-1. Biol Pharma Bull 31:1321–1326CrossRefGoogle Scholar
  10. 10.
    Yamaguchi K, Sasano A, Urakami T et al (1993) Stimulation of nerve growth factor production by pyrroloquinoline quinone and its derivatives in vitro and in vivo. Biosci Biotech Biochem 57:1231–1233CrossRefGoogle Scholar
  11. 11.
    Ohwada K, Takeda H, Yamazaki M et al (2008) Pyrroloquinoline quinone (PQQ) prevents cognitive deficit caused by oxidative stress in rats. J Clin Biochem Nutr 42:29–34CrossRefPubMedGoogle Scholar
  12. 12.
    Itoh Y, Hine K, Miura H et al (in press) Effect of the antioxidant supplement pyrroloquinoline quinone disodium salt (BioPQQTM) on cognitive functions. Adv Exp Med Biol 876:319–326Google Scholar
  13. 13.
    Tanida M, Sakatani K, Tsujii T (2012) Relation between working memory performance and evoked cerebral blood oxygenation changes in the prefrontal cortex evaluated by quantitative time-resolved near-infrared spectroscopy. Neurol Res 34:114–119PubMedGoogle Scholar
  14. 14.
    Ishikawa W, Sato M, Fukuda Y et al (2014) Correlation between asymmetry of spontaneous oscillation of hemodynamic changes in the prefrontal cortex and anxiety levels: a near-infrared spectroscopy study. J Biomed Optics 19:027005CrossRefGoogle Scholar
  15. 15.
    Hoshi Y, Kobayashi N, Tamura M (2001) Interpretation of near-infrared spectroscopy signals: a study with a newly developed perfused rat brain model. J Appl Physiol 90:1657–1662PubMedGoogle Scholar
  16. 16.
    Nakano M, Yamamoto T, Okumura H et al (2012) Effects of oral supplementation with pyrroloquinoline quinone on stress, fatigue, and sleep. Funct Foods Health Dis 2:307–324Google Scholar
  17. 17.
    Sakatani K, Tanida M, Hirano N, Takemura N (2014) Ginkgo biloba extract improves working memory performance in middle-aged women: role of asymmetry of prefrontal cortex activity during a working memory task. Adv Exp Med Biol 12:295–301CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Masahiko Nakano
    • 1
  • Yuta Murayama
    • 2
  • Lizhen Hu
    • 2
  • Kazuto Ikemoto
    • 1
  • Tatsuo Uetake
    • 3
  • Kaoru Sakatani
    • 2
    • 4
    Email author
  1. 1.Niigata Research LaboratoryMitsubishi Gas Chemical Co., Inc.TokyoJapan
  2. 2.Department of Electrical and Electronic EngineeringNEWCAT Research Institute, College of Engineering, Nihon UniversityKoriyamaJapan
  3. 3.CX Medical Japan Co., Inc.TokyoJapan
  4. 4.Department of Neurological SurgerySchool of Medicine, Nihon UniversityTokyoJapan

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