Supplements

PQQ

PQQ, short for pyrroloquinoline quinone (an older name is methoxatin), is a small redox molecule first found as a cofactor of bacterial enzymes. It occurs in trace amounts in many foods and is sold as a supplement, usually as PQQ disodium salt (brand name BioPQQ). It is marketed for “mitochondrial biogenesis” (the making of new mitochondria, the energy-producing parts of cells), memory and energy, often alongside CoQ10.

The most important fact: the mitochondrial story comes mainly from cell-culture and rodent studies. The human evidence is a handful of small, mostly manufacturer-linked trials of about 20 mg/day. They report changes in memory test scores, inflammation markers and cholesterol, and a 6-week exercise trial found no gain in aerobic performance. PQQ is not a recognized vitamin, despite a widely reported 2003 claim that it was one.

This page summarizes what the clinical trials, laboratory studies and food regulators (EFSA, FDA) report. It is for education only and is not medical advice.

Property Detail
Class Bacterial redox cofactor (an aromatic orthoquinone); dietary supplement
Other names Pyrroloquinoline quinone, methoxatin; supplement form is PQQ disodium salt (BioPQQ, mnemoPQQ)
Formula / weight C₁₄H₆N₂O₈, 330.21 g/mol (free acid); disodium salt C₁₄H₄N₂Na₂O₈, 374.17 Da
Route Oral
Doses in trials Usually 20 mg/day (21.5 mg/day in one trial); safety data cover 10–100 mg/day for up to 24 weeks
Half-life Not established in humans; after one oral dose, blood levels peaked at about 2 h
Intake from food Typically 1–30 ng/g of food; EFSA’s conservative estimate is ≈0.08 mg/day
US status Sold as a dietary supplement; FDA had “no questions” about several GRAS notices for use in beverages
EU status Authorized novel food since 2018: food supplements for adults (not pregnant or breastfeeding women), up to 20 mg/day
WADA status Not named on the 2026 Prohibited List

What it is

PQQ was identified in 1979 as a new coenzyme in the alcohol-oxidizing enzymes of bacteria (Salisbury et al., Nature 1979). Methanol-using bacteria such as Hyphomicrobium build it from the amino acids tyrosine and glutamic acid. No pathway for making PQQ is known in mammals, so the traces found in human tissue are thought to come from food (EFSA NDA Panel, 2017).

The free acid has the formula C₁₄H₆N₂O₈ and a molecular weight of 330.21 g/mol (PubChem). Commercial PQQ is the disodium salt, a reddish-brown powder. The ingredient EFSA assessed is made by bacterial fermentation with Hyphomicrobium denitrificans and purified to at least 99.0% (EFSA NDA Panel, 2017).

PQQ is found in small amounts in plant foods (potato, spinach, parsley, green pepper), fermented soy foods (natto, tofu, miso), milk and eggs. EFSA reported typical free PQQ levels of 1–30 ng/g in foods. A 20 mg supplement is at least 250 times the estimated intake from food.

The vitamin claim

The idea that PQQ is a vitamin has a specific history, and the claim remains disputed:

  • 1989, mice. Mice fed a chemically defined diet with no PQQ grew poorly, failed to reproduce, and had fragile skin and connective-tissue defects. The authors suggested PQQ might act “as a growth factor or vitamin” (Killgore et al., Science 1989).
  • 2003, the “new vitamin” paper. Kasahara and Kato reported in Nature that a mouse enzyme thought to work in lysine breakdown was a PQQ-dependent dehydrogenase. On that basis they called PQQ “a new redox-cofactor vitamin for mammals” (Kasahara & Kato, Nature 2003).
  • 2005, two rebuttals in Nature. One group showed that the claim rested on a sequence analysis that wrongly labeled a common protein fold (a beta-propeller) as a PQQ-binding motif. They concluded there was “nothing to indicate” the enzyme was PQQ-dependent (Felton & Anthony, Nature 2005). A second group tried to reproduce the finding in PQQ-deprived rodents and found that markers of lysine breakdown were not affected by PQQ intake (Rucker et al., Nature 2005).

Is PQQ a vitamin? No authority lists it as one, and there is no recommended intake. The 2003 paper has not been retracted; PubMed lists the two 2005 rebuttals as comments on it. Researchers who favor PQQ now describe it as a “vitamin-like” factor and acknowledge that it is not accepted as a vitamin (Jonscher et al., Biomolecules 2021). Supplement labels that call PQQ a “new vitamin” are repeating the disputed 2003 claim.

How it works in the body

Human pharmacokinetic data are sparse. EFSA concluded that information on the absorption, distribution, metabolism and excretion of PQQ “is limited” in both animals and humans (EFSA NDA Panel, 2017).

Finding Study Result
Absorption Mice, single oral dose of radiolabeled PQQ At least 62% absorbed within 24 h (range 19–89%); ≈81% of the absorbed dose excreted in urine
Peak blood level 10 healthy adults, single dose of 0.2 mg/kg (≈14 mg) Peaked at 2 h at about 9 nM (≈3.4 ng/mL)
Steady intake Same volunteers, up to 0.3 mg/kg/day Serum free PQQ rose to about 14 nM
Urinary recovery Same volunteers About 0.1% of the dose recovered as free PQQ
Metabolism Lab studies Reacts with amino acids to form imidazole derivatives; metabolic fate in people not studied

Data are from EFSA’s review of the evidence, which draws on the mouse study and on Harris et al., J Nutr Biochem 2013. No human elimination half-life has been published.

Regulatory status

United States

PQQ is sold as a dietary supplement. FDA does not approve dietary supplements for safety or effectiveness before sale.

Separately, several companies have notified FDA that PQQ disodium salt is “generally recognized as safe” (GRAS) for adding to beverages. FDA’s inventory lists these responses (FDA GRAS Notice Inventory, GRN 625):

GRN Notifier Intended use FDA response
590 Nascent Health Sciences Drinks and bars, 0.008–0.05% Ceased to evaluate at notifier’s request (2016)
625 Nascent Health Sciences Energy, sport and meal-replacement drinks, waters; 8 mg per serving No questions (August 18, 2016)
641 Zhejiang Hisun Pharmaceutical Sport and electrolyte drinks, waters; up to 5–20 mg per serving No questions (October 14, 2016)
694 Fuzhou Contay Beverages, up to 0.083% No questions (September 28, 2017)
701 Nutraland USA Drinks and waters, 8–20 mg per serving No questions (September 8, 2017)
709 Shandong Jincheng Bio-Pharmaceutical Drinks and waters, 8–20 mg per serving No questions (March 6, 2018)
1118 Zhejiang Medicine Waters up to 20 mg, energy drinks up to 12 mg, other drinks up to 8 mg per serving No questions (July 31, 2023)

A “no questions” letter means FDA did not object to the company’s own GRAS conclusion for that use. It is not an FDA approval and says nothing about health effects.

European Union

EFSA’s nutrition panel assessed BioPQQ in 2017 for use in food supplements by healthy adults, excluding pregnant and breastfeeding women, at up to 20 mg/day. It concluded the ingredient was safe under those conditions (EFSA NDA Panel, 2017). The European Commission authorized PQQ disodium salt as a novel food from September 2, 2018 (Commission Implementing Regulation (EU) 2018/1122). The authorization covers:

  • food supplements for adults only, excluding pregnant and breastfeeding women;
  • a maximum of 20 mg/day;
  • a required label statement that the supplement is for adults only, excluding pregnant and breastfeeding women.

EFSA assessed safety only. It did not evaluate whether PQQ has any health benefit.

Sport

PQQ is not named on the WADA 2026 Prohibited List.

What the research shows

Who funded the research

Most human PQQ trials were run or funded by ingredient makers. Mitsubishi Gas Chemical, which makes BioPQQ, employed authors on the cognition, cholesterol and sleep studies below (Itoh et al., 2016; Nakano et al., 2015; Tamakoshi et al., 2023). The mnemoPQQ trial was run by researchers at the supplement company Ryusendo (Shiojima et al., 2022). No independent replication of these trials has been published, and there is no systematic review or meta-analysis of PQQ in humans.

Mitochondrial biogenesis (cell and animal data)

The main mechanism claim is that PQQ makes cells build more mitochondria. The evidence for this is almost entirely preclinical:

  • In cell culture. Mouse liver cells (Hepa1-6) exposed to 10–30 µM PQQ for 24–48 h had more mitochondrial DNA, more mitochondrial enzyme activity and higher oxygen use. The effect ran through CREB and PGC-1α, a master regulator of mitochondrial biogenesis, and disappeared when either gene was knocked down (Chowanadisai et al., J Biol Chem 2010).
  • In mice. Weanling mice fed a PQQ-free diet had 20–30% fewer liver mitochondria and poorer mitochondrial respiration than mice given PQQ at 2 mg/kg of diet. In mice switched to the PQQ-free diet only at weaning, higher blood glucose and amino acid levels seen at 4 weeks (with only a non-significant trend toward less mitochondrial DNA) were gone by 8 weeks (Stites et al., J Nutr 2006).

These concentrations matter. The cell study used 10–30 µM (10,000–30,000 nM). In people taking about 20 mg/day, serum PQQ reached only about 14 nM, far below the cell-culture levels (EFSA NDA Panel, 2017). The mouse findings also come from PQQ-deficient diets, which do not occur in people eating ordinary food.

Exercise and mitochondrial markers in people

The only controlled human test of the mitochondrial claim with performance outcomes randomized 23 untrained men to 20 mg/day PQQ or placebo during a supervised 6-week endurance training program (Hwang et al., J Am Coll Nutr 2020):

Outcome Result
Peak oxygen uptake (VO₂peak) and test duration Improved with training in both groups; no difference between PQQ and placebo
Body composition (DEXA) No effect of PQQ
PGC-1α protein Rose from baseline in the PQQ group and was higher than placebo after 6 weeks

The authors concluded that PQQ did not improve aerobic performance or body composition, even though a molecular marker of mitochondrial biogenesis moved.

Cognition

Three randomized, double-blind, placebo-controlled trials of 12 weeks each have tested PQQ alone on memory and attention:

Trial Participants Dose Main reported findings
Itoh et al., 2016 41 healthy older adults BioPQQ 20 mg/day Smaller change in Stroop interference ratio (an attention measure) than placebo; a spatial-memory gain only in a subgroup with low starting scores
Shiojima et al., 2022 64 randomized, 58 completed; aged 40 to under 80 (completers averaged ≈71 y) who felt more forgetful mnemoPQQ 21.5 mg/day Better composite and verbal memory, reaction time, attention and other domains on a computerized test (Cognitrax) vs placebo; better MMSE-J and forgetfulness questionnaire scores; no adverse events
Tamakoshi et al., 2023 Adults aged 20–65 (sample size not stated in the abstract) BioPQQ 20 mg/day Better composite and verbal memory at 12 weeks; in an age-split analysis, faster cognitive-flexibility and speed gains in 20–40-year-olds at 8 weeks

Several limits apply to these trials:

  • They were small and each used a different test battery.
  • Several findings came from subgroup analyses, which can produce chance results.
  • None measured long-term outcomes such as dementia.

A manufacturer-authored review also describes trials combining PQQ 20 mg/day with CoQ10 300 mg/day. It reports that the combination improved word recall at 12 weeks, while PQQ alone “tended to improve memory, but not significantly.” In the 24-week study, the combination’s short-term memory gain at 8 weeks did not persist to 24 weeks (Ikemoto et al., J Med Invest 2024).

Sleep, fatigue and mood

The sleep evidence is a single open-label study with no placebo group. Seventeen adults took 20 mg/day PQQ for 8 weeks (Nakano et al., Funct Foods Health Dis 2012). Questionnaire scores for the following improved compared with their own baseline:

  • mood (all six scales of the Profile of Mood States, including fatigue and vigor);
  • sleep onset, sleep maintenance, sleep duration and sleepiness on waking (Oguri-Shirakawa-Azumi inventory and Pittsburgh Sleep Quality Index);
  • appetite and quality of life.

The change in sleep scores correlated with the change in the morning cortisol rise (R = −0.55). Without a placebo group, these changes cannot be separated from placebo effects, expectation or regression to the mean.

Inflammation markers

One small human study looked at inflammation (Harris et al., J Nutr Biochem 2013). Ten healthy adults (5 women, 5 men) took PQQ in a fruit drink in two crossover experiments:

  • Single dose (0.2 mg/kg): a change in one antioxidant marker (TBAR, a lipid-oxidation assay) over 48 h.
  • Daily dosing (0.3 mg/kg/day, measured after 76 h): plasma C-reactive protein (CRP) and interleukin-6 (IL-6), two blood markers of inflammation, fell significantly, along with urinary trimethylamine N-oxide. Urinary metabolite patterns shifted in a way the authors read as consistent with more mitochondrial activity.

Standard clinical tests (cholesterol, glucose, HDL, LDL, triglycerides) were normal and unchanged. The study had 10 participants and lasted only days. It does not show a lasting anti-inflammatory effect.

Blood lipids

A randomized, double-blind, placebo-controlled trial gave 20 mg/day BioPQQ or placebo for 12 weeks to 29 healthy Japanese adults aged 40–57 with normal to moderately high triglycerides (110–300 mg/dL) (Nakano et al., J Nutr Sci Vitaminol 2015):

Measure Result in the PQQ group
Triglycerides (the primary target) No change
LDL cholesterol, whole group 136.1 → 127.0 mg/dL, described as “marginally significant”
LDL cholesterol, subgroup starting at 140 mg/dL or higher (11 of 29 people) Fell significantly vs placebo

The trial did not lower triglycerides, which it was designed to study. The LDL result in the whole group was borderline, and the clearer result came from a subgroup of 11 people.

Side effects and risks

What human studies report

No serious adverse effects have been attributed to PQQ in published human studies. EFSA reviewed 12 clinical studies submitted by the manufacturer, with doses of 10–100 mg/day for 3 days to 24 weeks and 10–71 participants each. None showed treatment effects on physical exams, blood tests, urinalysis or reported side effects (EFSA NDA Panel, 2017).

EFSA added an important caveat. The human studies “were not designed to assess renal function” and are of limited value for safety. No study measured kidney function in depth, and no long-term or chronic toxicity study exists.

Kidney findings in rats

The kidney is the organ of concern in animal studies. EFSA summarized these findings:

Study (rats) Dose Finding
14-day dose-range study 768 mg/kg/day Heavier kidneys and tubule damage in females
28-day kidney study 200 and 700 mg/kg/day Urinary crystals in 11/12 and 12/12 females; urinary protein in 5/12 and 6/12 vs 1/12 controls; crystals cleared after a 4-week recovery; protein persisted in 3 rats
90-day study Up to 100 mg/kg/day No adverse effect (the NOAEL, the highest dose with no observed harm)
Injection study (Watanabe 1989) 11.5 mg/kg/day into the abdomen for 4 days Swollen kidneys and tubule cell death; higher urea and creatinine

From the 100 mg/kg/day NOAEL, EFSA calculated a margin of exposure of 344 at 20 mg/day for a 70 kg adult and judged it sufficient. Injected doses are not comparable to oral intake, but these findings explain why the EU limit is 20 mg/day.

Pregnancy, children and pro-oxidant effects

  • Pregnancy and breastfeeding. EFSA’s assessment and the EU authorization exclude pregnant and breastfeeding women; no safety data cover these groups.
  • Children. The EU authorization is for adults only.
  • Pro-oxidant activity. At high concentrations (1 µM–1 mM) in test tubes, PQQ can act as a pro-oxidant (it can generate damaging oxygen species). EFSA did not consider this a concern at the nanomolar blood levels reached at 20 mg/day.
  • Drug interactions. No interaction studies have been published.

PQQ is often sold in “mitochondrial” or longevity combinations. These library pages cover the most common partners:

  • CoQ10, which carries electrons in the mitochondrial energy chain and has a larger evidence base, especially in heart failure.
  • NAD+ and its precursors NMN and nicotinamide riboside (NR), marketed to raise cellular NAD+ levels.
  • Urolithin A, a gut-bacteria metabolite studied for mitophagy (the clearing of damaged mitochondria).

Key takeaways

  • A bacterial cofactor, not a vitamin. The 2003 “new vitamin” claim was disputed in Nature in 2005, and no authority lists PQQ as a vitamin or sets an intake.
  • Mitochondrial biogenesis is mainly a lab finding. It was shown in mouse cells at micromolar levels and in PQQ-deficient rodents. Human blood levels at 20 mg/day are in the low nanomolar range, far below those concentrations.
  • No performance benefit shown. In the one controlled training trial (23 men, 6 weeks), PQQ raised PGC-1α protein but did not improve VO₂peak or body composition.
  • Small, industry-linked human trials. Studies of 10–64 people report better memory test scores, a borderline LDL drop and lower CRP and IL-6, often in subgroups or without placebo control.
  • Regulators accept 20 mg/day as safe for adults. EFSA and the EU set 20 mg/day for adults, excluding pregnancy and breastfeeding. US GRAS notices cover beverage use at up to 20 mg per serving.
  • The kidney is the organ of concern in animals. Rats given high doses developed urinary crystals, protein in the urine and tubule damage. Human studies have not examined kidney function closely.

Sources

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  2. Killgore J, Smidt C, Duich L, et al. Nutritional importance of pyrroloquinoline quinone. Science. 1989;245(4920):850–852. PubMed.
  3. Kasahara T, Kato T. Nutritional biochemistry: a new redox-cofactor vitamin for mammals. Nature. 2003;422(6934):832. PubMed.
  4. Felton LM, Anthony C. Biochemistry: role of PQQ as a mammalian enzyme cofactor? Nature. 2005;433(7025):E10. PubMed.
  5. Rucker R, Storms D, Sheets A, et al. Biochemistry: is pyrroloquinoline quinone a vitamin? Nature. 2005;433(7025):E10–E11. PubMed.
  6. Jonscher KR, Chowanadisai W, Rucker RB. Pyrroloquinoline-quinone is more than an antioxidant: a vitamin-like accessory factor important in health and disease prevention. Biomolecules. 2021;11(10):1441. PubMed.
  7. Stites T, Storms D, Bauerly K, et al. Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice. J Nutr. 2006;136(2):390–396. PubMed.
  8. 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. J Biol Chem. 2010;285(1):142–152. PubMed.
  9. Harris CB, 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;24(12):2076–2084. PubMed.
  10. Nakano M, Kawasaki Y, Suzuki N, Takara T. Effects of pyrroloquinoline quinone disodium salt intake on the serum cholesterol levels of healthy Japanese adults. J Nutr Sci Vitaminol (Tokyo). 2015;61(3):233–240. PubMed.
  11. Itoh Y, Hine K, Miura H, et al. Effect of the antioxidant supplement pyrroloquinoline quinone disodium salt (BioPQQ) on cognitive functions. Adv Exp Med Biol. 2016;876:319–325. PubMed.
  12. Shiojima Y, Takahashi M, Takahashi R, et al. 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;41(8):796–809. PubMed.
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  15. Nakano M, Yamamoto T, Okamura H, et al. Effects of oral supplementation with pyrroloquinoline quinone on stress, fatigue, and sleep. Funct Foods Health Dis. 2012;2(8):307–324. DOI.
  16. Hwang PS, Machek SB, Cardaci TD, et al. Effects of pyrroloquinoline quinone (PQQ) supplementation on aerobic exercise performance and indices of mitochondrial biogenesis in untrained men. J Am Coll Nutr. 2020;39(6):547–556. PubMed.
  17. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), Turck D, Bresson JL, et al. Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC) No 258/97. EFSA J. 2017;15(11):e05058. PubMed.
  18. European Commission. Commission Implementing Regulation (EU) 2018/1122 of 10 August 2018 authorising the placing on the market of pyrroloquinoline quinone disodium salt as a novel food under Regulation (EU) 2015/2283 and amending Commission Implementing Regulation (EU) 2017/2470. legislation.gov.uk (as adopted).
  19. US Food and Drug Administration. GRAS Notice Inventory: GRN 625, pyrroloquinoline quinone disodium salt (also GRN 590, 641, 694, 701, 709 and 1118). FDA.
  20. National Center for Biotechnology Information. PubChem Compound Summary for CID 1024, pyrroloquinoline quinone. PubChem.
  21. World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.