IngredientsPyrroloquinoline quinone (abbreviated PQQ) is the accepted common name for the compound with the systematic IUPAC designation 4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid. It is an aromatic, water-soluble quinone whose chemical properties have been described as analogous to combining the chemical features of ascorbic acid, riboflavin, and pyridoxal-5-phosphate into one molecule. PQQ is also known by the trivial name methoxatin, and its supplemental form is commonly sold as pyrroloquinoline quinone disodium salt.
PQQ is an aromatic tricyclic o-quinone that serves as a redox cofactor of a number of prokaryotic dehydrogenases, such as alcohol and sugar dehydrogenases. PQQ is now appreciated as part of a family of quinone cofactors, classified as quinoproteins, that are utilized by dehydrogenases and oxidases. The other quinoprotein cofactors include topaquinone (TPQ), lysine tyrosylquinone (LTQ), cysteine tryptophylquinone (CTQ), and tryptophan tylquinone (TTQ).
Both the oxidized (PQQox) and reduced (PQQH2) forms of PQQ carry out redox cycling. PQQ is naturally found in some foods and is available as a dietary supplement in its disodium crystal form.
With its unique pyrroloquinoline ring system, PQQ occurs naturally in various food sources including fermented foods, vegetables, and human breast milk. PQQ content is comparatively high in foods such as parsley, papaya, kiwi, green tea, natto (fermented beans), tofu, and green peppers. Human milk has a very high concentration of PQQ (140–180 ng/mL), which is approximately 4 to 5 times higher than that in cow milk. The concentration of PQQ in food sources ranges from nanograms (ng) to micrograms (µg) per kilogram.
PQQ is not biosynthesized in eukaryotic organisms, including mammals. However, trace amounts of PQQ can be detected in human and rat organs or tissues because of its presence in daily foods, such as vegetables and meats, at pM to nM levels.
PQQ is derived from the two amino acids glutamate and tyrosine encoded in the precursor peptide PqqA. Five reactions are necessary to form this quinone cofactor, and at least six genes in Klebsiella pneumoniae (PqqA–F) are required, all of which are located in the PQQ-operon. A novel aspect of PQQ is its biosynthesis in bacteria from a ribosomally translated precursor peptide, PqqA. A glutamic acid and a tyrosine in PqqA are cross-linked by the radical SAM enzyme PqqE with the help of PqqD in the first step of PqqA modification. A protease then liberates the Glu–Tyr molecule from the peptide backbone. PqqB oxidizes the 2 and 3 positions on the tyrosine ring, forming a quinone, and PqqC then forms the final pyrrole ring.
PQQ has no traditional use in any culture's medicinal or dietary practice in the way that botanical herbs do; it was not recognized as a distinct compound until the modern era of biochemistry. Pyrroloquinoline quinone (PQQ) was discovered in 1964. Its chemical structure was subsequently identified from experiments with bacterial methanol dehydrogenase in 1979.
PQQ was discovered as a bacterial coenzyme for dehydrogenase (Hauge, 1964), and its structure was later determined by derivatized crystallography (Salisbury et al., 1979). PQQ was first reported as a cofactor for bacterial dehydrogenases in the late 1960s. PQQ's recognition as a cofactor was important because, at the time, only nicotinamide cofactors and flavins were considered cofactors for bacterial dehydrogenases.
The discovery not only led to subsequent studies on the physiological significance of PQQ but also initiated investigations on other enzymes where the presence of PQQ was expected, resulting in the discovery of three other quinone cofactors — TPQ, TTQ, and LTQ — which differ from PQQ as they are part of the protein chain of the enzyme to which they belong.
A pivotal and still-debated moment in PQQ's research history occurred in 2003. The scientific journal Nature published a 2003 paper by Kasahara and Kato stating that PQQ was a new vitamin, a cofactor required for the activity of an enzyme believed to be involved in lysine metabolism (U26). In 2005, an article by Anthony and Felton stated that the 2003 Kasahara–Kato paper drew incorrect and unsubstantiated conclusions, specifically that the databases used inappropriately labeled β-propeller sequences as PQQ-binding motifs. More recently, an article by Bruce Ames in the Proceedings of the National Academy of Sciences in 2018 identified pyrroloquinoline quinone as a "longevity vitamin" — not essential for immediate survival, but necessary for long-term health.
Though PQQ was first recognized as a bacterial cofactor in 1964, it was not until the mid-1990s that researchers really began exploring its chemical and biological properties. Pyrroloquinoline quinone disodium salt (PQQ) was approved as a new food ingredient by the FDA in 2008. The product is also approved for consumption in Japan and the EU.
Unlike multi-constituent botanical extracts, PQQ is a single, well-characterized small molecule. Its bioactivities arise from its unique redox chemistry and its interactions with cellular signaling pathways.
From a physiological perspective, the chemical properties of PQQ are analogous to combining some of the best chemical features of nicotinamide derivatives (hydride transfers), ascorbic acid (reducing and antioxidant potential), riboflavin (single electron transfer reactions), and pyridoxal (carbonyl reactivity, carbinolamine adduct formation) into one molecule. On a molar basis, PQQ is at least 100 times more efficient than ascorbic acid, menadione, and all isoflavonoids and polyphenolic compounds tested to date in assays that assess redox cycling potential.
PQQ is an effective scavenger of superoxide and hydroxyl radicals, major contributors to mitochondrial dysfunction, and has been shown to counteract various forms of oxidative stress-induced cellular damage, such as reoxygenation cardiac injury, murine hepatitis virus strain 3-induced liver injury, chronic heart failure, and hydrogen peroxide-induced apoptotic effects in nucleus pulposus cells.
PQQ serves as a catalytic accessory factor for lactate and other dehydrogenases in the oxidation of NADH to NAD⁺. PQQ enhances NAD⁺-dependent sirtuin activity and the expression of sirtuin targets, such as PGC-1α, NRF-1 and NRF-2, and TFAM.
PQQ plays a role in the process of NAD⁺ production by enhancing the expression of nicotinamide phosphoribosyltransferase (Nampt). Increasing Nampt activity increases NAD⁺ cellular levels. NAD⁺ performs two principal functions: first, as a cofactor for dehydrogenases and reductases such as lactic acid dehydrogenase (LDH); and second, as a co-substrate for sirtuin-catalyzed protein deacetylations. PQQ is also a catalytic cofactor for LDH and facilitates the conversion of lactate to pyruvate.
Degradation of the essential amino acid lysine depends on PQQ. Lysine is oxidized to 2-aminoadipic 6-semialdehyde (AAS), catalyzed by AAS synthetase (AASS), and then oxidized further to 2-aminoadipic acid by AAS dehydrogenase (AASDH). PQQ acts as a redox cofactor for AASDH in this reaction. PQQ binds all PQQ-dependent enzymes (quinoproteins) in a non-covalent binding form.
Studies have shown that mice and rats fed diets lacking in pyrroloquinoline quinone (PQQ) have reduced mitochondrial content. Exposure of mouse Hepa1-6 cells to 10–30 µM PQQ for 24–48 h resulted in increased citrate synthase and cytochrome c oxidase activity, Mitotracker staining, mitochondrial DNA content, and cellular oxygen respiration. The induction of this process occurred through the activation of cAMP response element-binding protein (CREB) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α), a pathway known to regulate mitochondrial biogenesis.
PQQ exposure stimulated phosphorylation of CREB at serine 133, activated the promoter of PGC-1α, and increased PGC-1α mRNA and protein expression. PQQ did not stimulate mitochondrial biogenesis after small interfering RNA-mediated reduction in either PGC-1α or CREB expression. Consistent with activation of the PGC-1α pathway, PQQ increased nuclear respiratory factor activation (NRF-1 and NRF-2) and Tfam, TFB1M, and TFB2M mRNA expression.
PQQ has been reported to promote mitochondrial biogenesis primarily through activation of the PGC-1α/SIRT1 signaling pathway.
PQQ's anti-inflammatory properties are mediated by a decrease in the release of inflammatory factors and an attenuation of the activation of nuclear (NF)-κB phosphorylation, thus attenuating inflammatory diseases. PQQ influences mitochondrial biogenesis and fat metabolism (by regulating PGC-1α, PPAR-α, and PPAR-γ), cell regulation (by regulating MAPK and JAK pathways), and inflammation (through the modulation of NF-κB).
PQQ is associated with biological processes such as mitochondriogenesis, reproduction, growth, and aging. In addition, PQQ attenuates clinically relevant dysfunctions such as those associated with ischemia, inflammation, and lipotoxicity. PQQ is novel among biofactors not currently accepted as vitamins or conditional vitamins. For example, the absence of PQQ in diets produces a response like a vitamin-related deficiency, with recovery upon PQQ repletion in a dose-dependent manner.
Cognitive function is the area with the greatest volume of human clinical data for PQQ supplementation, though the trials conducted to date are generally small and often of short duration.
In the field of cognitive function, double-blind, placebo-controlled trials have been conducted. Various improvements have been reported regarding general memory, verbal memory, working memory, and attention. Furthermore, a stratified analysis of a population with a wide range of ages revealed unique effects in young people (20–40 years old) that were not observed in older adults (41–65 years old). Specifically, cognitive flexibility and executive speed improved more rapidly in young people at 8 weeks.
Co-administration of PQQ and coenzyme Q10 further enhanced these effects. In an open-label trial, PQQ was shown to improve sleep and mood. Additionally, PQQ was found to suppress skin moisture loss and increase PGC-1α expression.
A 2024 randomized controlled trial examined the use of a dihydrogen-PQQ combination in elderly individuals with mild cognitive impairment. The study employed a parallel-group, randomized, placebo-controlled, double-blind experimental design. Thirty-four elderly individuals with mild cognitive impairment (mean age 71.9 ± 3.8 years; 28 females) voluntarily provided written consent to participate. The dihydrogen-PQQ intervention resulted in a significant elevation in serum brain-derived neurotrophic factor (BDNF) levels at the six-week follow-up (P = 0.01); conversely, no changes in BDNF levels were observed in the placebo group throughout the study duration (P = 0.27). It should be noted that this was a combination product with molecular hydrogen, making it difficult to attribute effects to PQQ alone.
Evidence strength: Preliminary to moderate. Human double-blind, placebo-controlled trials exist but are generally small in sample size. Most trials involve Japanese populations and study durations of 8–12 weeks. Larger, independently replicated RCTs are needed before strong conclusions can be drawn.
A key early human trial was conducted at the University of California, Davis. Using a crossover study design, 10 subjects (5 females, 5 males) ingested PQQ added to a fruit-flavored drink in two separate studies. In Study 1, PQQ was given in a single dose (0.2 mg PQQ/kg). In Study 2, PQQ was administered as a daily dose (0.3 mg PQQ/kg). After 76 h, measurements included indices of inflammation (plasma C-reactive protein and interleukin (IL)-6 levels) as well as standard clinical indices including cholesterol, glucose, HDL, LDL, and triglycerides.
The standard clinical indices were normal and not altered by PQQ supplementation. However, dietary PQQ exposure in Study 1 resulted in apparent changes in antioxidant potential based on malonaldehyde-related TBAR assessments. In Study 2, PQQ supplementation resulted in significant decreases in the levels of plasma C-reactive protein, IL-6, and urinary methylated amines such as trimethylamine N-oxide, and changes in urinary metabolites consistent with enhanced mitochondria-related functions. The data are among the first to link systemic effects of PQQ in animals to corresponding effects in humans.
Evidence strength: Preliminary. The crossover trial by Harris et al. (2013) is an important proof-of-concept study but included only 10 subjects and a short exposure duration. Replication in larger controlled trials is required.
PQQ, which is a cofactor of microbial quinoprotein enzymes, was found to be a potent enhancer of nerve growth factor (NGF) production in vitro. PQQ exerts its effects through several key molecular mechanisms, including the activation of antioxidant pathways via Nrf2/ARE signaling, enhancement of mitochondrial biogenesis and function through AMPK/PGC-1α, and the regulation of inflammatory processes through NF-κB inhibition.
In animal models of cerebral ischemia, PQQ has demonstrated measurable protective effects. PQQ at 10 mg/kg infused at the initiation, or 3 h after the initiation, of reversible middle cerebral artery occlusion (rMCAo) was effective in reducing cerebral infarct volumes measured 72 h later. At 3 h after ischemia, a dose of 3 mg/kg significantly reduced infarct volume compared to vehicle-treated animals, but 1 mg/kg was ineffective. Neurobehavioral scores were also significantly better in the PQQ-treated group compared to vehicle controls when PQQ was given at 10 and 3 mg/kg, but not at 1 mg/kg. Thus, PQQ was neuroprotective when given as a single administration at least 3 h after initiation of rMCAo.
The ability of PQQ to protect against neurodegeneration may go beyond mitochondriogenesis, given that PQQ can reduce α-synuclein fibril formation. PQQ has garnered significant interest for its potential therapeutic role in neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD).
Evidence strength: Preclinical only. Neuroprotective effects are well-documented in cell culture and animal models, including models of ischemia, Parkinson's-related toxicity (rotenone/6-OHDA models), and Alzheimer's-related amyloid pathology. As of the literature reviewed, direct human clinical evidence for these specific neurological disease applications is lacking.
PQQ is associated with biological processes such as mitochondriogenesis, reproduction, growth, and aging. PQQ has been demonstrated to enhance energy metabolism in humans. When a single dose (0.2 mg/kg) or daily for 3 days (0.3 mg/kg) of PQQ was administered to 10 young participants, the levels of trimethylamine N-oxide, a marker of perturbed energy metabolism, decreased following PQQ intake. The ratio of blood lactate to pyruvate and the profile of urinary metabolites were consistent with enhanced mitochondrial oxidation.
PQQ protected cells from mitochondrial inhibition by rotenone, 3-nitropropionic acid, antimycin A, and sodium azide. The ability of PQQ to stimulate mitochondrial biogenesis accounts in part for the action of this compound and suggests that PQQ may be beneficial in diseases associated with mitochondrial dysfunction.
Evidence strength: Preliminary in humans; well-established in cell and animal models. The mechanistic pathway (CREB/PGC-1α activation) is well characterized in preclinical studies. Human data on mitochondrial biogenesis markers are limited to very small trials.
PQQ is a potent natural antioxidant with anti-diabetic, neuroprotective, and cardioprotective properties, known to promote mitochondrial biogenesis. Preclinical studies have examined its effects on myocardial health. Treatment of a transverse aortic constriction model of myocardial hypertrophy with PQQ significantly suppressed myocardial hypertrophy and fibrosis, in addition to inhibiting the ferroptotic death of hypertrophic myocardial cells in vivo. In vitro analyses revealed that treatment with PQQ was sufficient to significantly alleviate phenylephrine-induced hypertrophic activity and to prevent ferroptotic induction in primary murine cardiomyocytes.
PQQ pre-treatment significantly inhibited the expression of cardiac hypertrophy marker proteins, such as atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain in cell culture models of cardiac injury.
Evidence strength: Preclinical only. Cardiovascular evidence for PQQ rests on in vitro and animal experiments. No large-scale human RCTs on cardiovascular endpoints have been identified in the reviewed literature.
In high-fat and high-sucrose diet-induced obesity models, PQQ supplementation improves insulin sensitivity, glucose tolerance, and lipid profile while reducing oxidative stress. PQQ has been reported to promote lipid metabolism by stimulating lipolysis and fatty acid oxidation within the mitochondria, contributing to energy balance and body weight regulation in animal models. Furthermore, PQQ has been reported to regulate lipid biosynthesis and contribute to metabolic homeostasis by modulating gene expression.
Evidence strength: Preclinical. Metabolic benefits have been documented in animal models of diet-induced obesity, but human intervention data on these specific metabolic outcomes are limited.
Seventeen adult male and female subjects participated in a clinical trial using an open-label design to evaluate the effectiveness of PQQ on stress, fatigue, quality of life, and sleep. They ingested 20 mg of PQQ daily for 8 weeks. Changes in stress, fatigue, quality of life measures, and sleep were evaluated using various inventories and questionnaires. The open-label, uncontrolled design of this study represents a significant limitation, as placebo effects cannot be excluded.
Evidence strength: Very preliminary. Results come from a single small open-label (uncontrolled) trial. Placebo-controlled replication is needed.
A 2025 preclinical study investigated PQQ's potential as a senomorphic (senescence-modulating) agent. In preclinical trials, PQQ alleviates pathological symptoms by preventing organ degeneration in naturally aged mice while reserving senescent cells in the tissue microenvironment. The study supports the feasibility of exploiting a redox-active quinone molecule with senomorphic capacity to achieve geroprotective effects by modulating the senescence-associated secretory phenotype (SASP). Prospective efforts are warranted to determine long-term outcomes and the potential of PQQ for the intervention of geriatric syndromes in clinical settings.
Evidence strength: Preclinical. Anti-aging and senomorphic effects are emerging areas of investigation with no human clinical evidence yet available.
The applicant for EU novel food approval intended to market PQQ for use in food supplements for healthy adults, except pregnant and lactating women, at a maximum proposed level of consumption of 20 mg/day (corresponding to 0.29 mg/kg bw per day for a 70-kg person).
The proposed level of consumption (20 mg/day) is at least 250 times higher than the estimated background intake of PQQ occurring naturally in foods.
Dosages used across the major human clinical studies include:
PQQ primarily accumulates in urine (81%), with smaller amounts found in kidneys (10.7%), liver (1.5%), skin (1.3%), blood (1.2%), and other tissues. Serum concentrations reached up to 9 nM or about 3.4 ng/mL within a few hours after dosing, peaking at around 2–3 hours post-administration.
Regarding commercially available supplement forms, PQQ is most commonly supplied as:
PQQ meets all the USA-FDA "generally regarded as safe" (GRAS) requirements. The EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) concluded that the novel food, pyrroloquinoline quinone disodium salt (BioPQQ™), is safe under the intended conditions of use as specified by the applicant.
In a 91-day subchronic oral toxicity study in rats, no mortality or toxicologically significant changes in clinical signs, body weight, food consumption, necropsy findings, or organ weights were observed. Differences between treated and control groups in some hematological and serum biochemical examinations and histopathological examination were not considered treatment-related. The no-observed-adverse-effect-level (NOAEL) of PQQ disodium salt in rats was considered to be 400 mg/kg bw/day for both sexes — the highest dose tested.
Acute toxicity studies of mnemoPQQ® in Wistar rats revealed that its LD50 was 1825 and 1410 mg/kg body weight in male and female rats, respectively, whereas its acute dermal LD50 was >2000 mg/kg bw. An Ames bacterial reverse mutation assay and an in vitro mammalian cell gene mutation test exhibited its non-mutagenic potential. In a mammalian in vivo erythrocyte micronucleus test, mnemoPQQ® was classified as non-clastogenic and non-mutagenic.
The EFSA assessment identified a specific consideration regarding the kidney. The Panel noted that the twelve clinical studies reviewed were not designed to assess renal function and are of limited value for the safety assessment. A 14-day dose-range finding study, a 90-day repeated-dose toxicity study, and a 28-day renal toxicity study were conducted in rats using BioPQQ™. The Panel considered the findings of crystal and protein in urine at 200 mg/kg bw in the 28-day toxicity study as a critical effect, based on the fact that renal toxicity was observed at a concentration of 768 mg/kg bw in the 14-day study.
Considering the NOAEL of 100 mg/kg bw per day from a 90-day repeated dose oral toxicity study with BioPQQ™, and the maximum proposed level of consumption (20 mg/day), the EFSA Panel concluded that the margin of exposure (of 344) is sufficient, and the novel food is safe under the intended conditions of use.
The NOAEL was determined to be 400 mg/kg bw/day in a subchronic toxicity study in rats. After applying a safety margin of 100, it can be concluded that doses up to 4 mg/kg bw/day or 240 mg/person/day would be safe in adults weighing 60 kg.
An in vitro bacterial reverse mutation assay, three in vitro chromosomal aberration tests, and one in vivo micronucleus test were conducted with PQQ. Based on these studies, the EFSA Panel concluded that there is no concern with regard to the potential genotoxicity of PQQ.
Information on the absorption, distribution, metabolism, and excretion of PQQ in animals and humans is limited. Information on the absorption, distribution, metabolism, and excretion of PQQ in animals and humans is limited — a fact noted by EFSA as a gap in the evidence base at the time of their assessment.
The EU novel food approval was intended for use in food supplements for healthy adults, except pregnant and lactating women, reflecting uncertainty regarding safety in these populations due to insufficient specific data.
As of the reviewed literature, no formally characterized pharmacokinetic drug–drug interactions with PQQ have been reported in peer-reviewed clinical studies. Given PQQ's effects on NAD⁺ metabolism, sirtuin pathways, NF-κB signaling, and mitochondrial function, theoretical interactions with agents that modulate these same pathways (e.g., other NAD⁺ precursors, anti-inflammatory drugs) exist but have not been characterized in human studies.
Health conditions that Pyrroloquinoline quinone may help support.
Pyrroloquinoline quinone (PQQ) is a redox-active quinone that promotes mitochondrial biogenesis (creation of new mitochondria) and protects existing mitochondria from oxidative damage, thereby supporting cellular energy capacity. Human and animal studies confirm effects on energy metabolism and antifatigue outcomes.
Pyrroloquinoline quinone (PQQ) is a mitochondrial biogenesis cofactor with anti-inflammatory and antioxidant properties studied in glaucoma neuroprotection. A 2024–2025 PubMed-based review identifies PQQ among emerging neuroprotective agents for glaucoma, showing reduced systemic inflammation and enhanced mitochondrial metabolites relevant to RGC survival.
Pyrroloquinoline quinone (PQQ) is a redox cofactor with neuroprotective and mitochondrial biogenesis-promoting properties. Double-blind, placebo-controlled trials demonstrate improvements in attention, working memory, and cognitive flexibility, particularly in younger adults.
Pyrroloquinoline quinone (PQQ) is one of the few dietary compounds with evidence for stimulating mitochondrial biogenesis via the PGC-1α/NRF-1/TFAM pathway. Dietary PQQ deficiency reduces mitochondrial content in mammals, and supplementation has been studied in human trials for mitochondrial density and aerobic performance. It modulates NAD⁺-dependent sirtuin activity relevant to mitochondrial regulation.
Body systems that Pyrroloquinoline quinone may help support.
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