Pyrroloquinoline Quinone
Evidence Fact Sheet
PQQ
Pyrroloquinoline quinone (PQQ) is a redox-active quinone cofactor studied as a dietary supplement (typically the disodium salt, 10-20 mg/day) for cognition, mitochondrial biogenesis and antioxidant signaling. Small human RCTs report cognitive and PGC-1α signals; aerobic-performance benefit was null. US GRAS, EU/CN Novel Food.
Also known as: PQQ · Pyrroloquinoline Quinone · PQQ disodium salt (PQQ·2Na) · Methoxatin · BioPQQ® (Mitsubishi Gas Chemical branded grade)
Overview
Pyrroloquinoline quinone (PQQ) is a redox-active quinone compound used in supplements almost exclusively as the disodium salt (PQQ·2Na, e.g. BioPQQ). Mechanistically it acts as a high-turnover radical-scavenging cofactor and, in cell and animal models, engages PGC-1α/NRF1/TFAM signaling linked to mitochondrial biogenesis plus NRF2 antioxidant pathways; direct human mechanistic data are limited. Cognition is the only direction with multiple human RCTs, generally dosed at 20 mg/day; sleep, fatigue, cardiovascular and mitochondrial-biogenesis claims rest largely on mechanistic or animal data. Typical research doses are 10-20 mg/day PQQ disodium salt, matching regulatory caps. Regulatory status: US FDA GRAS (no-questions notices, max 20 mg/day) and DSHEA structure/function claims; EU and China authorize PQQ disodium salt as a Novel Food at ≤20 mg/day for adults; no authorized health claim in any market; Brazil ANVISA has no compliant route.
Mechanism of Action
Redox cofactor / radical scavenging (high-turnover quinone, ~20,000 cycles in vitro) · PGC-1α / NRF1 / TFAM signaling → mitochondrial biogenesis (in vitro + animal; limited direct human data) · NRF2 antioxidant pathway activation · Autophagy / mitophagy modulation
Body systems: Mitochondrial & Cellular Energy · Neurological & Cognitive · Cardiovascular · Cellular Renewal · Sleep-Wake System
Evidence-Based Benefits
Each benefit below is anchored to a specific PubMed-indexed study. Effect sizes, sample sizes, and p-values are reported as published; no values are inferred. Honest negatives and null results are kept alongside the positive findings, and disease-research populations are described as such — Pyrroloquinoline Quinone is not characterized as a treatment for any disease.
Cognition / Memory
RCT supported- 20 mg/dayPQQ disodium · 12 wk
- 20-65 yrage range studied
In a double-blind placebo-controlled RCT of adults aged 20-65 taking 20 mg/day PQQ disodium salt for 12 weeks, the supplemented group showed improvements in composite and verbal memory, with age-stratified gains (younger adults in cognitive flexibility/processing/execution speed by 8 weeks; older adults in complex and verbal memory by 12 weeks). The abstract describes direction of effect but reports no effect-size numbers.
Effect size: this study reports the direction of the finding but does not state a specific numeric effect size, so none is given here rather than estimated.
“After 12 weeks, the participants showed improvements in composite memory and verbal memory. In younger adults (aged 20-40 years), PQQ improved cognitive function (cognitive flexibility, processing speed, and execution speed) after 8 weeks. Only older adults (aged 41-65 years) showed improvements in complex and verbal memory after 12 weeks.”
Source: PMID 36807425 · Tamakoshi 2023 · Food Funct
Cognition (Cognitive Battery)
RCT supportedA separate randomized, double-blind, placebo-controlled parallel-group RCT in 58 healthy completers given 21.5 mg/day PQQ disodium salt for 12 weeks reported significant improvements versus placebo across several Cognitrax domains (composite memory, verbal memory, reaction time, complex attention, cognitive flexibility, executive function, motor speed), with no adverse events. The abstract states significance but provides no numeric effect sizes.
Effect size: this study reports the direction of the finding but does not state a specific numeric effect size, so none is given here rather than estimated.
“Significant improvements were observed on the Cognitrax's cognitive function domain score on 'composite memory', 'verbal memory', 'reaction time', 'complex attention', 'cognitive flexibility', 'executive function', and 'motor speed' in the mnemoPQQ® group as compared to the placebo group.”
Source: PMID 34415830 · Shiojima 2022 · J Am Nutr Assoc
Mitochondrial Biogenesis (PGC-1α) vs. Aerobic Performance (Honest Negative)
Null / no benefit RCT supported- p < 0.05PGC-1α rise vs placebo
- p > 0.05aerobic performance · no diff
In an RCT of untrained men combining PQQ with endurance training, PQQ raised PGC-1α protein (a mitochondrial-biogenesis marker) versus placebo, but there was no between-group difference in aerobic exercise performance — VO2peak and exercise duration improved with training regardless of PQQ. This is an honest negative for performance despite a positive molecular signal.
Reported effect: No significant between-group difference in aerobic performance (p > 0.05); PQQ group significant increase in PGC-1α protein vs placebo (p < 0.05)
“There were no significant differences between groups in aerobic performance after endurance-training (p > 0.05). However, there were significant improvements in peak oxygen consumption (VO₂peak) and total exercise test duration after endurance-training, irrespective of group (p < 0.05). The PQQ group had a significant increase in PGC-1α protein levels from baseline to post endurance training compared to PLC (p < 0.05).”
Source: PMID 31860387 · Hwang 2020 · J Am Coll Nutr
Cerebral Blood Flow / Oxygen Metabolism
RCT supported- p < 0.05right-PFC hemoglobin rise
- p < 0.05PFC SO2 decrease vs placebo
An RCT using near-infrared measurement of the prefrontal cortex (PFC) reported that PQQ significantly increased baseline hemoglobin and total hemoglobin in the right PFC and produced more pronounced decreases in oxygen saturation (SO2) than placebo, interpreted as increased oxygen utilization/blood flow. Numbers beyond significance thresholds are not given in the abstract.
Reported effect: Right-PFC hemoglobin and total hemoglobin significantly increased (p < 0.05); PFC SO2 decrease more pronounced in PQQ than placebo (p < 0.05)
“We found that baseline concentrations of hemoglobin and total hemoglobin in the right PFC significantly increased after administration of PQQ (p < 0.05). decreases in SO2 level in the PFC were more pronounced in the PQQ group than in the placebo group (p < 0.05).”
Source: PMID 27526146 · Nakano 2016 · Adv Exp Med Biol
Antioxidant / Inflammation
Emerging / indexedAntioxidant and anti-inflammatory effects of PQQ (e.g. on CRP, IL-6, urinary 8-OHdG) are described mainly in narrative reviews and animal/cell models rather than human monotherapy RCTs; no PQQ-monotherapy meta-analysis or systematic review exists. The closest human signal comes from a cognition RCT in 41 elderly subjects on 20 mg/day where Stroop-interference change favored PQQ — supportive but qualitative, not a direct antioxidant-marker outcome.
Effect size: this study reports the direction of the finding but does not state a specific numeric effect size, so none is given here rather than estimated.
“In the Stroop test, the change of Stroop interference ratios (SIs) for the PQQ group was significantly smaller than for the placebo group.”
Source: PMID 26782228
Dosage (research context · not a recommendation)
10-20 mg/day PQQ disodium salt (cognition RCTs 20 mg/day; market regulatory caps ≤20 mg/day in CN/EU). Japanese MGC safety tolerance ≤60 mg/day × 4 wk. CoQ10 co-administration studied at PQQ 20 mg + CoQ10 300 mg/day.
Regulatory Status · 4 Markets
- US · FDA
- FDA GRAS · no-questions notices exist for PQQ disodium salt (e.g. GRN 641, 701, 709), max 20 mg/day. DSHEA dietary supplement; structure/function claims permitted with mandatory FDA disclaimer. No authorized health claim or qualified health claim. each GRAS notice covers a specific manufacturer grade — generic PQQ not auto-covered.
- EU · EFSA
- Authorized Novel Food · Commission Implementing Regulation (EU) 2018/1122 (PQQ disodium salt, generic authorisation), food supplements ≤20 mg/day adults ≥18. EFSA has authorized NO PQQ health claim (Art 13 / 13.5 / 14 all empty). Mandatory label: not for under-18s / pregnant / breastfeeding women.
- CN · China
- China: PQQ disodium salt approved as a novel food (NHC Novel Food Announcement 2022 No.6) for general-food use within limits; not a health-food raw material, no blue-hat approval, no authorized functional claim.
- BR · ANVISA
- Not on approved supplement-ingredient lists (not in IN 28/2018); no domestic compliant route. Would require RDC 839/2023 new-ingredient evaluation (est. 12-24 months). No ANVISA-authorized functional claim.
Safety
Generally well tolerated at studied doses (20 mg/day); rare reports of headache or mild GI discomfort. BioPQQ® disodium salt completed acute (rat oral LD50 >1000 mg/kg), genotoxicity (Ames negative), and 90-day repeat-dose (rat NOAEL 100 mg/kg/d) assessments. NOT recommended in pregnancy/lactation or under-18s (insufficient data; EU 2018/1122 mandates "not for pregnant/breastfeeding women or under-18s" labeling). Generic non-disodium-salt PQQ grades cannot inherit BioPQQ® safety data. Caution with immunosuppressants; CoQ10 co-use carries theoretical warfarin interaction.
Related
Goals: cognitive-support · longevity-stack
Lifestyles: senior-60-plus
References
PubMed-indexed citations anchoring the benefit findings above. Effect sizes are reported as published.
- PMID 36807425 · Tamakoshi 2023 · Food Funct — Cognition / Memory
- PMID 34415830 · Shiojima 2022 · J Am Nutr Assoc — Cognition (Cognitive Battery)
- PMID 31860387 · Hwang 2020 · J Am Coll Nutr — Mitochondrial Biogenesis (PGC-1α) vs. Aerobic Performance (Honest Negative)
- PMID 27526146 · Nakano 2016 · Adv Exp Med Biol — Cerebral Blood Flow / Oxygen Metabolism
- PMID 26782228 — Antioxidant / Inflammation
Frequently Asked Questions
1. What form and dose of PQQ is used in studies?
Human studies use PQQ disodium salt (PQQ·2Na, e.g. BioPQQ), not free-acid PQQ. Cognition RCTs dosed around 20 mg/day (one used 21.5 mg/day) for 12 weeks, which matches the EU/China/US regulatory caps of ≤20 mg/day for adults.
2. Does PQQ actually improve memory?
Two double-blind placebo-controlled RCTs report cognitive improvements: Tamakoshi 2023 (PMID 36807425) found gains in composite and verbal memory over 12 weeks, and Shiojima 2022 (PMID 34415830) found significant improvements across several Cognitrax domains in 58 completers. Both abstracts state significance qualitatively without publishing effect-size numbers, so the size of the benefit is not quantifiable from these reports.
3. Does PQQ boost exercise performance or mitochondria?
In an RCT of untrained men (Hwang 2020, PMID 31860387), PQQ raised the mitochondrial-biogenesis marker PGC-1α versus placebo (p < 0.05), but there was no between-group difference in aerobic performance (p > 0.05) — VO2peak and exercise duration improved from training alone. So the molecular signal did not translate into a measured performance gain in that trial.
Last evidence review: 2026-06-13