SCIENCE  |  SUPPLEMENTS

Pyrroloquinoline Quinone (PQQ)

Pyrroloquinoline quinone (PQQ) is a redox cofactor and antioxidant that supports mitochondrial function and energy production. It is found in various foods and has been linked to improved cognitive function and protection against oxidative stress. PQQ may also enhance cellular growth and longevity.

PQQ

Mechanisms of PQQ in Extending Lifespan

  1. Enhancement of Mitochondrial Function
    • SIRT1/PGC-1α Signaling: PQQ enhances SIRT1/PGC-1α signaling, promoting mitochondrial fusion and improving mitochondrial respiratory capacity. This mechanism helps maintain mitochondrial function and protect against cellular aging. (NPJ Aging. 2022 Apr 19;8(1):3)
    • Mitochondrial Biogenesis: PQQ increases mitochondrial biogenesis marker PGC-1α, which supports the production of new mitochondria, enhancing cellular energy metabolism. (J Am Coll Nutr. 2020 Aug;39(6):547-556)
  2. Reduction of Oxidative Stress
    • Antioxidant Properties: PQQ reduces oxidative stress by decreasing reactive oxygen species (ROS) levels, which protects cells from oxidative damage and supports overall cellular health. (Front Aging. 2024 Feb 29;5:1351860)
  3. Regulation of Inflammatory Responses
    • Anti-Inflammaging: PQQ delays TNF-α-induced cellular senescence in an inflammaging model by reducing the expression of p16, p21, and Jagged1. This anti-inflammatory action helps mitigate age-related inflammation and cellular aging. (Clin Exp Pharmacol Physiol. 2020 Jan;47(1):102-110)
  4. Modulation of Lipid Metabolism
    • Lipid Profile Adjustment: PQQ modifies lipid profiles by activating both fatty acid oxidation and lipid synthesis in palmitic acid-treated myotubes. This dual action helps regulate lipid metabolism under stress conditions. (Int J Mol Sci. 2020 Nov 8;21(21):8382)
  5. Stimulation of Autophagy
    • Insulin/IGF1 Signaling Pathway: PQQ activates autophagy through the insulin/IGF1 signaling pathway, which contributes to improved longevity, stress resistance, and reduced fat accumulation and ROS levels. (Food Funct. 2021 Nov 15;12(22):11319-11330)
  6. Bone Health and Osteogenesis
    • MCM3-Keap1-Nrf2 Axis: PQQ stimulates bone formation and inhibits bone resorption through the MCM3-Keap1-Nrf2 axis and upregulation of Fbn1, preventing age-related osteoporosis. (Aging Cell. 2023 Sep;22(9):e13912)
  7. Cognitive Enhancement
    • Brain Function: PQQ improves cognitive function by enhancing cerebral blood flow and oxygen metabolism in the prefrontal cortex. This supports better brain activity and cognitive performance. (Adv Exp Med Biol. 2016;923:215-222)
  8. Cardiovascular Protection
    • Mitochondrial Regulation in Heart Cells: PQQ prevents chronic heart failure by improving mitochondrial function, regulating ROS levels, and preventing [Ca2+]m overload, thus reducing cardiac damage in pressure overload models. (Cardiovasc Diagn Ther. 2020 Jun;10(3):453-469)
  9. Metabolic Benefits
    • Cholesterol Management: PQQ intake reduces serum LDL-cholesterol levels, indicating its role in managing cholesterol and reducing the risk of lifestyle-related diseases. (J Nutr Sci Vitaminol (Tokyo). 2015;61(3):233-40)
  10. Exercise Performance and Fatigue Reduction
    • Enhanced Mitochondrial Function: PQQ protects against exercise-induced fatigue and oxidative damage by enhancing mitochondrial function, reducing ROS production, and improving antioxidant enzyme activity, which supports better exercise performance and recovery. (FASEB J. 2021 Apr;35(4):e21394)

PUBLICATIONS

  1. Dietary pyrroloquinoline quinone hinders aging progression in male mice and D-galactose-induced cells.
          • Front Aging. 2024 Feb 29;5:1351860.
          • Design: Naturally aged C57BL/6J male mice were fed a normal diet with or without PQQ (20 mg/kg/day) for 10 weeks.
          • Summary: PQQ supplementation improved metabolic function, muscle strength, and skin condition in aged mice. In cell models, PQQ enhanced mitochondrial function, reduced oxidative stress and senescence, and improved intestinal barrier function, suggesting its potential in healthy aging strategies.
  2. Pyrroloquinoline quinone alleviates natural aging-related osteoporosis via a novel MCM3-Keap1-Nrf2 axis-mediated stress response and Fbn1 upregulation.
          • Aging Cell. 2023 Sep;22(9):e13912.
          • Design: 6-month-old and 12-month-old wild-type mice were supplemented with PQQ for 12 and 6 months, respectively.
          • Summary: PQQ prevented age-related osteoporosis in mice by inhibiting bone resorption and stimulating bone formation through the MCM3-Keap1-Nrf2 axis and upregulation of Fbn1. The study suggests PQQ’s potential for preventing and treating natural aging-induced osteoporosis.
  3. Pyrroloquinoline quinone disodium salt improves brain function in both younger and older adults.
          • Food Funct. 2023 Mar 6;14(5):2496-2501.
          • Design: Double-blind, placebo-controlled study with PQQ (20 mg/day) administered for 12 weeks to adults aged 20-65 years.
          • Summary: PQQ disodium salt improved cognitive function in adults, with younger adults showing improved cognitive flexibility and processing speed, while older adults exhibited enhancements in complex and verbal memory. This suggests PQQ’s benefits for brain health across different age groups.
  4. Effect of Dietary Pyrroloquinoline Quinone Disodium Salt on Cognitive Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.
          • J Am Nutr Assoc. 2022 Nov-Dec;41(8):796-809.
          • Design: 64 healthy subjects randomly assigned to receive either PQQ disodium salt (21.5 mg/day) or placebo for 12 weeks.
          • Summary: PQQ supplementation significantly improved cognitive functions such as memory, attention, and executive function in middle-aged to elderly individuals. This study supports PQQ’s potential to enhance cognitive performance in an aging population.
  5. Pyrroloquinoline quinone (PQQ) protects mitochondrial function of HEI-OC1 cells under premature senescence.
          • NPJ Aging. 2022 Apr 19;8(1):3.
          • Design: Cells were treated with PQQ for 1 day before H2O2 (100 μM) exposure to establish a premature senescence model.
          • Summary: PQQ protected mitochondrial function in premature senescence models of auditory cells by enhancing SIRT1/PGC-1α signaling, promoting mitochondrial fusion, and improving mitochondrial respiratory capacity. This indicates PQQ’s protective effects against cellular aging.
  6. Pyrroloquinoline quinone extends Caenorhabditis elegans’ longevity through the insulin/IGF1 signaling pathway-mediated activation of autophagy.
          • Food Funct. 2021 Nov 15;12(22):11319-11330.
          • Design: PQQ at a concentration of 1 mM was used to treat Caenorhabditis elegans.
          • Summary: PQQ extended the lifespan of Caenorhabditis elegans by 33.1% through the insulin/IGF1 signaling pathway and activation of autophagy, improving locomotion, stress resistance, and reducing fat accumulation and ROS levels, highlighting its anti-aging properties.
  7. Pyrroloquinoline quinone protects against exercise-induced fatigue and oxidative damage via improving mitochondrial function in mice.
          • FASEB J. 2021 Apr;35(4):e21394.
          • Design: Models for exercise-induced fatigue were established in mice.
          • Summary: PQQ significantly protected mice from exercise-induced fatigue and oxidative damage by enhancing mitochondrial function, reducing ROS production, and improving antioxidant enzyme activity, suggesting its potential for reducing exercise-related stress.
  8. Pyrroloquinoline Quinone Modifies Lipid Profile, but Not Insulin Sensitivity, of Palmitic Acid-Treated L6 Myotubes.
          • Int J Mol Sci. 2020 Nov 8;21(21):8382.
          • Design: Muscle cells were subjected to short (2 h) and prolonged (24 h) incubation with PQQ.
          • Summary: PQQ modified lipid profiles in palmitic acid-treated myotubes, activating both fatty acid oxidation and lipid synthesis but did not improve insulin resistance, indicating its complex role in lipid metabolism under stress conditions.
  9. Effects of Pyrroloquinoline Quinone (PQQ) Supplementation on Aerobic Exercise Performance and Indices of Mitochondrial Biogenesis in Untrained Men.
          • J Am Coll Nutr. 2020 Aug;39(6):547-556.
          • Design: 23 males were randomized to consume 20 mg/day of PQQ or placebo for six weeks while following a supervised endurance exercise program.
          • Summary: PQQ supplementation during a six-week endurance exercise program increased mitochondrial biogenesis marker PGC-1α but did not significantly enhance aerobic performance or body composition in untrained men, suggesting its specific role in mitochondrial function.
  10. Pyrroloquinoline quinone can prevent chronic heart failure by regulating mitochondrial function.
          • Cardiovasc Diagn Ther. 2020 Jun;10(3):453-469.
          • Design: Sprague Dawley rats were administered PQQ intragastrically for 12 weeks after transaortic constriction.
          • Summary: PQQ improved mitochondrial function, regulated ROS levels, and prevented [Ca2+]m overload, thereby reducing cardiac damage and preventing chronic heart failure in pressure overload models. This highlights PQQ’s potential in cardiac health.
  11. Pyrroloquinoline quinone delays inflammaging induced by TNF-α through the p16/p21 and Jagged1 signalling pathways.
          • Clin Exp Pharmacol Physiol. 2020 Jan;47(1):102-110.
          • Design: Human embryonic lung fibroblasts were preincubated with PQQ prior to TNF-α treatment to establish an inflammaging model in vitro.
          • Summary: PQQ delayed TNF-α-induced cellular senescence in an inflammaging model by reducing the expression of p16, p21, and Jagged1, indicating its anti-inflammaging properties and potential to mitigate age-related inflammation.
  12. Effects of Antioxidant Supplements (BioPQQ™) on Cerebral Blood Flow and Oxygen Metabolism in the Prefrontal Cortex.
          • Adv Exp Med Biol. 2016;923:215-222.
          • Design: 20 healthy subjects aged 50-70 years were administered BioPQQ™ (20 mg) or placebo orally once daily for 12 weeks.
          • Summary: PQQ supplementation increased cerebral blood flow and oxygen metabolism in the prefrontal cortex of older adults, suggesting enhanced cognitive function through improved brain activity.
  13. Effects of Pyrroloquinoline Quinone Disodium Salt Intake on the Serum Cholesterol Levels of Healthy Japanese Adults.
          • J Nutr Sci Vitaminol (Tokyo). 2015;61(3):233-40.
          • Design: 29 healthy Japanese adults with normal to moderately high TG levels were treated with PQQ disodium salt (20 mg/day) for 12 weeks in a randomized, placebo-controlled, double-blinded trial.
          • Summary: PQQ intake significantly reduced serum LDL-cholesterol levels in individuals with high baseline LDL, indicating its potential in managing cholesterol and reducing the risk of lifestyle-related diseases.
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