PQQ: Benefits, Forms, Dosing, and Side Effects

Pyrroloquinoline quinone (PQQ) is a redox-active, water-soluble quinone compound with the chemical structure 4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid [1][2]. It is a reddish-brown antioxidant compound that functions primarily as a cofactor for bacterial dehydrogenases and exhibits potent antioxidant properties in mammalian systems. PQQ was first discovered in the late 1960s as a novel cofactor in bacterial enzymes like glucose and alcohol dehydrogenases, with researchers Christopher Anthony and Leslie Zatman characterizing its unusual properties [2][14]. Its full chemical structure was elucidated in the 1970s, and the total chemical synthesis was achieved in 1981 by E. J. Corey and A. Tramontano through a 10-step route [2].

PQQ is classified as a vitamin-like accessory factor due to its involvement in essential biological processes such as mitochondrial biogenesis, growth, reproduction, and cellular energy production, though it is not officially recognized as a vitamin by major health authorities including the FDA and WHO as of 2025 [1][2]. The question of whether PQQ qualifies as the "14th vitamin" has been debated since the mid-1990s when studies by Robert B. Rucker's group demonstrated that PQQ-deficient diets impaired growth, reproduction, and immune responses in mice [2][3]. However, no PQQ-dependent enzyme has been identified in mammals, and the compound is considered an exogenous factor rather than a true vitamin [2].

Unlike vitamins that humans can synthesize to some degree, PQQ is not produced by cells in our bodies and must be obtained through dietary sources [1]. Despite marketing claims that may suggest otherwise, PQQ is not an essential nutrient and there is no established daily requirement for it [1]. It is present in extremely small amounts in plant-based foods — potatoes, green peppers, spinach, and green tea contain between 10 and 30 nanograms (0.000001 to 0.000003 mg) per gram [1][4]. This is vastly lower than the 10-20 mg doses used in clinical trials, which are produced industrially through chemical synthesis or bacterial fermentation [1].

In biological systems, PQQ supports redox balance by directly scavenging reactive oxygen species (ROS), enhances NAD+-dependent sirtuin activity, promotes mitochondrial function and ATP synthesis via pathways including PGC-1alpha and CREB, influences lipid metabolism, reduces inflammation, and protects against oxidative stress-related conditions [2][5]. Laboratory studies have shown that PQQ stimulates the growth of new mitochondria, the production of nerve growth factor, and inhibits the growth of cancer cells and the synthesis of amyloid proteins associated with Alzheimer's disease [5][6][7].

Only a few small and relatively short human studies have investigated PQQ supplementation. Most have been placebo-controlled, and most have been funded at least in part by manufacturers of PQQ ingredients — particularly Mitsubishi Gas Chemical Company, Inc. (maker of BioPQQ) and Ryusendo Co. (maker of mnemoPQQ) [1]. This is important context for interpreting the evidence: the clinical data is limited in both quantity and independence.

Table of Contents

• Overview
• Forms and Bioavailability
• Evidence for Benefits
• Recommended Dosing
• Safety and Side Effects
• Drug Interactions
• Dietary Sources
• References

Overview

Pyrroloquinoline quinone (PQQ) is a redox-active, water-soluble quinone compound with the molecular formula C14H6N2O8 and a molecular weight of 330.21 g/mol [2]. It is an aromatic, tricyclic ortho-quinone characterized by a pyrrolo ring fused to a quinoline ring system, featuring three carboxylic acid moieties and an ortho-quinone functionality that enables redox cycling [2]. This redox cycling capacity — the ability to undergo repeated oxidation-reduction cycles — underlies its potent antioxidant activity.

PQQ was first reported in the 1960s as the prosthetic group of bacterial dehydrogenases. Researchers Christopher Anthony and Leslie J. Zatman purified the unknown cofactor and characterized its unusual properties [2][14]. In 1979, Salisbury and colleagues determined the structure via X-ray crystallography, revealing a tricyclic o-quinone scaffold. The total chemical synthesis was achieved in 1981 by E. J. Corey and A. Tramontano through a 10-step route [2]. In the early 1980s, the compound was formally named pyrroloquinoline quinone based on its pyrrole-quinoline core.

PQQ is classified as a vitamin-like accessory factor due to its involvement in mitochondrial biogenesis, growth, reproduction, and cellular energy production, though it is not officially recognized as a vitamin by the FDA or WHO as of 2025 [1][2]. The debate over whether PQQ qualifies as the "14th vitamin" began in the mid-1990s when Robert B. Rucker's group demonstrated that PQQ-deficient diets impaired growth, reproduction, and immune responses in mice [2][3]. These mouse models showed reduced mitochondrial function and altered connective tissue integrity. However, no PQQ-dependent enzyme has been identified in mammals, distinguishing PQQ's roles from prokaryotic systems where it acts as a redox cofactor in quinoprotein enzymes [2].

In mammals, PQQ is not produced endogenously and must be obtained through dietary sources. Typical dietary intake is estimated at 0.1-1.0 mg/day from foods [2], which is vastly lower than the 10-20 mg doses used in clinical trials. PQQ is found at trace levels in plant-based foods — potatoes, green peppers, spinach, and green tea contain between 10 and 30 nanograms per gram [1][4]. Trace amounts are also detected in mammalian tissues (e.g., 10-20 pg/g in human liver), likely derived from dietary intake rather than endogenous production [2][13].

PQQ's primary biological effects in mammals operate through non-cofactor signaling pathways. It supports redox balance by directly scavenging reactive oxygen species (particularly superoxide radicals), enhances NAD+-dependent sirtuin activity, promotes mitochondrial biogenesis via CREB phosphorylation and PGC-1alpha upregulation, influences lipid metabolism, and reduces inflammation [2][5]. Laboratory studies have demonstrated that PQQ stimulates the growth of new mitochondria, the production of nerve growth factor, inhibits cancer cell growth, and inhibits amyloid protein synthesis associated with Alzheimer's disease [5][6][7].

Forms and Bioavailability

PQQ Disodium Salt

All commercially available PQQ supplements contain PQQ as PQQ disodium salt [1]. This is the form used in clinical trials and the form filed as a new dietary ingredient (NDI) with the FDA. PQQ disodium salt exhibits solubility of approximately 3 g/L at 25 degrees Celsius in water, while the free acid form has lower solubility and is not used in supplements [2][8].

Chemical Properties

PQQ demonstrates good stability in acidic conditions but is sensitive to alkali (decomposing at pH values above 8) and to light exposure under certain conditions [2][14]. It is thermally stable with a melting point exceeding 300 degrees Celsius [2][8]. The pKa values of its three carboxylic acid groups are approximately 1.2 (C7-COOH), 1.4 (C9-COOH), and 3.4 (C2-COOH) [2]. As a redox-active orthoquinone, PQQ undergoes a two-electron reduction to its quinol form (PQQH2), with a standard reduction potential of about +0.09 V vs. NHE at pH 7 [2][14].

Branded Ingredients

Several branded PQQ ingredients are available on the market [1]:

• BioPQQ — Manufactured by Mitsubishi Gas Chemical Company through bacterial fermentation. Mitsubishi was the first to introduce PQQ to the U.S. market in 2008 when it filed PQQ disodium salt as an NDI with the FDA and received no objection [1]. BioPQQ is the most commonly used ingredient in clinical trials.
• PureQQ — Manufactured by Nascent Health Sciences through chemical synthesis. In 2016, the FDA did not object to a GRAS notice for PureQQ in dietary supplements at a maximum of 8 mg per serving [1][8]. This is currently the only GRAS notice specifically covering dietary supplements.
• mnemoPQQ — Manufactured by Ryusendo Co. Used in several recent Japanese clinical trials examining cognitive and physical performance benefits [9][10].
• Other manufacturers — Additional GRAS notifications from Hisun (2016), Nutraland (2017), Fuzou Contay (2017), and JinCheng (2018) for bacterial fermentation PQQ at 5-20 mg per serving in drinks and beverages [1].

Fermentation vs. Chemical Synthesis

PQQ is produced commercially by two methods [1]:

Bacterial fermentation — Used by BioPQQ and others. PQQ is biosynthesized in certain prokaryotes (such as Methylobacterium extorquens and Klebsiella pneumoniae) through a multi-enzymatic pathway encoded by the pqq operon (pqqA through pqqE genes) [2]. The pathway assembles PQQ from L-glutamic acid and L-tyrosine precursors through a series of radical-mediated coupling, proteolytic processing, hydroxylation, and oxidation steps [2].

Chemical synthesis — Used by PureQQ. First achieved in 1981 by Corey and Tramontano through a 10-step route [2].

It is not clear if either production method yields a clinically superior product. In 2013, Mitsubishi claimed testing of competing PQQ products detected high levels of impurities, but these results do not appear to have been published in peer-reviewed literature [1].

Absorption and Pharmacokinetics

Upon ingestion, PQQ is rapidly absorbed in the small intestine with approximately 60% bioavailability in animal models [2][11]. Key pharmacokinetic parameters:

• Peak serum concentrations: Reached within 2-3 hours after oral ingestion [2][11]
• Distribution: Accumulates preferentially in kidney and skin, with up to 20% retention after 24 hours [2][11][12]
• Excretion: Approximately 80% excreted unchanged in urine within 24 hours [2][11]
• Plasma half-life: 3-5 hours in humans [2][11]
• Water solubility: PQQ is water-soluble and does not require food for absorption [1]

The intestinal microbiota may contribute minimally to PQQ availability — diet remains the dominant source [2][11].

Evidence for Benefits

Memory and Cognition

Small, company-funded studies suggest PQQ may have a modest benefit on certain aspects of cognition among healthy adults, but PQQ does not appear to be helpful among people with mild cognitive impairment (MCI) [1].

Healthy adults with subjective forgetfulness (best available evidence): The most promising study involved 58 healthy adults in Japan ages 40 to under 80 who felt they had become more forgetful. About half the group received 21.5 mg daily of PQQ disodium salt (mnemoPQQ, by Ryusendo Co.) while the other half received placebo. After 12 weeks, the PQQ group had small improvements in 7 out of 11 aspects of cognitive function — including memory, attention, judgment, and cognitive flexibility — compared to placebo. However, the placebo group improved more than the PQQ group on complex attention. Approximately 10% of participants reported stomach discomfort. The study was funded by Ryusendo Co. (Shiojima et al., J Am Coll Nutr, 2021) [9].

Middle-aged adults — PQQ alone and with CoQ10: A 2009 study reportedly found that 20 mg of PQQ daily for 12 weeks improved word recall and memory tasks compared to placebo, and that 20 mg PQQ plus 300 mg of CoQ10 produced greater cognitive improvements than PQQ alone. However, this study (published by Nakano in Food Style in 2009) does not appear to be available online, severely limiting evaluation of its methodology [1].

Older adults — modest attention improvement: A trial among 41 older men and women (average age 58) reported very modest improvement in attention with 20 mg of BioPQQ daily for three months compared to placebo. However, this was only after the researchers excluded some participants' data and performed a second analysis — the original primary analysis did not show significant benefit (Itoh et al., Adv Exp Med Biol, 2016) [15].

Elderly with mild cognitive impairment — no benefit: A study among 34 older men and women (average age 72) with MCI found that taking 20 mg of PQQ plus 80 mg of magnesium (Alpha Hope, by CalerieLife) twice daily for six weeks did not improve overall cognition based on the MMSE and ADAS-cog, except for a slight improvement in orientation — just one of 12 categories measured. One author is a CalerieLife employee (Baltic et al., J Nutr Health Aging, 2024) [16].

Preclinical neuroprotective evidence: Laboratory studies suggest PQQ inhibits amyloid protein synthesis associated with Alzheimer's disease, enhances brain-derived neurotrophic factor (BDNF) expression, reduces amyloid-beta toxicity, and protects dopaminergic neurons via the PI3K/Akt signaling pathway [2][7]. Recent 2023 studies demonstrate PQQ's benefits in folate deficiency-induced neurodamage, restoring blood-brain barrier integrity in rodent models [2][17]. However, most neuroprotective evidence remains preclinical and has not translated to human cognitive benefits.

Synthesis: The cognitive evidence for PQQ in humans is weak. The best study showed only modest improvements in some cognitive domains, sample sizes are small (34-58 participants), study durations are short (6-12 weeks), and nearly all research is industry-funded. PQQ does not appear to help people with mild cognitive impairment.

Energy, Mood, and Sleep Quality

One study found that 20 mg of PQQ daily for 8 weeks significantly improved measures of mood, fatigue, and sleep quality in adults ages 20 to 60 (Nakano et al., Functional Foods in Health and Disease, 2012) [18]. However, this study was not placebo-controlled, meaning it is impossible to distinguish genuine PQQ effects from placebo response, which is substantial for subjective outcomes like mood and fatigue.

The mechanistic rationale for energy enhancement is plausible: PQQ promotes mitochondrial biogenesis by activating CREB and PGC-1alpha, leading to elevated mitochondrial DNA copy number and higher respiratory chain protein levels [2][5][19]. In cell culture studies, PQQ treatment at 10-30 micromolar concentrations significantly increased PGC-1alpha expression through CREB phosphorylation [2][5]. However, the leap from enhanced mitochondrial biogenesis in cell cultures to subjective energy improvements in humans has not been established in controlled trials.

Inflammation

A small study in 10 young adults (ages 21 to 34) found that approximately 20 mg of PQQ daily for three days significantly reduced C-reactive protein (CRP) and interleukin-6 (IL-6) (Harris et al., J Nutr Biochem, 2013) [20]. There was no placebo control and only 10 participants, making this extremely preliminary evidence.

At the cellular level, PQQ functions as a potent antioxidant through multiple mechanisms: direct ROS scavenging (IC50 of approximately 1-6 x 10^-8 M), inhibition of mitochondrial ROS production, support for regeneration of other antioxidants such as vitamins C and E, and activation of the Nrf2 pathway upregulating antioxidant gene expression [2][21]. These mechanisms provide biological plausibility for anti-inflammatory effects, but the human evidence is insufficient.

Muscle Strength, Exercise Endurance, and Body Composition

Older adults — modest strength improvements: A study among 62 healthy men and women (average age 54) found that 21.5 mg of PQQ disodium salt (mnemoPQQ) daily for three months modestly increased leg extension strength compared to placebo, with slight improvements in hand grip strength and exercise tolerability. Notably, there were more adverse events in the PQQ group than placebo (23 vs 14), including headache, sore throat, fatigue, diarrhea, heartburn, and swollen gums. Funded by Ryusendo Co. (Shiojima et al., J Funct Foods, 2024) [10].

Young adults during exercise training — no benefit: A study among 23 healthy young men (average age 19) who participated in six weeks of endurance exercise training found that 20 mg of PQQ daily did not improve aerobic exercise performance or body composition compared to placebo. Funded by Nascent Health Sciences (Hwang et al., J Am Coll Nutr, 2019) [22].

Preclinical evidence on muscle aging: Animal studies show PQQ attenuates age-related muscle atrophy by improving mitochondrial biogenesis and reducing oxidative stress in aged mice [2][23]. Long-term PQQ supplementation has been shown to reprogram the single-cell landscape in aging tissues, lowering inflammatory markers and extending physiological healthspan in rodent models [2][24]. These animal findings have not been confirmed in human trials.

Cholesterol-Lowering

One study conducted in Japan among 29 men and women (average age 49) found that 10 mg of BioPQQ taken twice daily (20 mg total) for three months lowered LDL cholesterol compared to placebo — a decrease of 9 mg/dL with BioPQQ versus an increase of 3.7 mg/dL with placebo (Nakano et al., J Nutr Sci Vitaminol, 2015) [25].

However, this finding has important limitations: only 29 participants, a single unreplicated study, and the muscle strength study by Shiojima et al. (2024) using a similar dosage of a different PQQ brand did not replicate this cholesterol-lowering finding [10]. A 12-week study in adults with elevated triglycerides showed LDL reductions among those with baseline levels at or above 140 mg/dL [2], suggesting the effect may be limited to those with already-elevated cholesterol.

Metabolic and Insulin-Sensitizing Effects

Animal studies demonstrate significant metabolic effects. In diet-induced obesity models, PQQ improved insulin sensitivity and reduced hepatic fat accumulation by suppressing lipogenesis and promoting fatty acid beta-oxidation [2][26][27]. High-fat diet-fed mice and rats receiving PQQ at 0.2-2 mg/kg diet for 6-16 weeks showed decreased body weight gain, visceral fat mass, and fasting blood glucose [2][3][26]. Recent 2023-2024 investigations highlight PQQ's potential to mitigate insulin resistance through improved mitochondrial function [2][26].

Clinical trials as of 2025 are evaluating PQQ for metabolic disorders including obesity [2][28]. However, no published human clinical trial has demonstrated that PQQ supplementation improves insulin sensitivity, blood glucose, or body weight in people.

Liver Protection (Preclinical Only)

In several animal studies, PQQ demonstrated hepatoprotective effects. PQQ protected against liver injury in mouse models (Huang et al., Exp Ther Med, 2015) [29], showed persistent long-term protective effects on hepatic lipotoxicity and inflammation in obese mice (Jonscher et al., FASEB J, 2017) [30], and protected against non-alcoholic fatty liver disease progression (Friedman et al., Hepatol Commun, 2018) [31]. However, there are no studies investigating PQQ's effects on liver disease in people [1].

Statin-Related Side Effects

While there is evidence that CoQ10 may help reduce statin-related side effects (muscle pain, weakness, etc.), there do not appear to be any studies on PQQ supplementation for statin-related side effects [1].

Neuroprotection and Stroke (Preclinical Only)

Rodent models of stroke show that PQQ administration at 10 mg/kg intravenously reduces cerebral infarct size by approximately 40% in reversible middle cerebral artery occlusion, preserving neurological function 72 hours post-ischemia (Zhang et al., Exp Neurol, 2006) [32]. Similar effects occur in traumatic brain injury models [2]. PQQ prevents neuronal apoptosis by suppressing caspase activation and ROS-mediated pathways, and enhances BDNF expression promoting synaptic plasticity [2]. These are exclusively preclinical findings — no human trials have evaluated PQQ for stroke.

Mitochondrial Biogenesis

PQQ's most well-characterized mechanism is the stimulation of mitochondrial biogenesis — the growth and division of new mitochondria within cells [5][2]. The seminal study by Chowanadisai et al. (J Biol Chem, 2010) demonstrated this through a defined signaling cascade [5]:

• PQQ activates CREB by phosphorylation at serine 133
• Phosphorylated CREB upregulates PGC-1alpha gene expression
• PGC-1alpha activates nuclear respiratory factors (NRF-1 and NRF-2)
• This leads to increased mitochondrial DNA copy number and respiratory chain protein expression [2][5][19]

Animal deficiency studies confirm PQQ's importance: mice fed PQQ-deprived diets (<0.3 ng/g) show reduced mitochondrial content, reduced fertility, impaired immune responses, and growth retardation — all reversed by supplementation at 0.3-2 micrograms/g diet [2][3][19][33]. Saihara et al. (Biochemistry, 2017) confirmed that PQQ also stimulates mitochondrial biogenesis through the SIRT1/PGC-1alpha pathway [21].

Importantly, PQQ does not directly participate in the mammalian electron transport chain. No PQQ-dependent enzymes have been identified in mammals [2]. Instead, PQQ exerts non-cofactor effects through CREB/PGC-1alpha activation and Nrf2 pathway modulation [2][21].

Potential Synergy with CoQ10 and NAD+ Precursors

The 2009 Nakano study suggested that 20 mg PQQ plus 300 mg CoQ10 produced greater cognitive improvements than PQQ alone [1]. Since both compounds support mitochondrial function through different mechanisms — PQQ stimulates biogenesis of new mitochondria while CoQ10 supports electron transport within existing mitochondria — a synergistic effect is biologically plausible but unconfirmed.

PQQ may also offer synergistic benefits with nicotinamide mononucleotide (NMN), an NAD+ precursor [2]. PQQ and NMN target complementary aspects of mitochondrial health, with potential convergence on SIRT1/PGC-1alpha signaling. No known adverse interactions exist, but comprehensive human trials on combined efficacy have not been conducted [2].

Animal Deficiency Evidence

Studies in mice fed PQQ-deprived diets have demonstrated [2][3][33]:

• Growth: PQQ deprivation causes growth retardation reversed by supplementation
• Reproduction: Reduced fertility (fewer pups per litter, lower conception rates)
• Immune function: Decreased T-cell proliferation and impaired immune responses
• Skin and connective tissue: Altered connective tissue integrity (friable skin)
• Mitochondrial function: Reduced mitochondrial content, lower respiratory chain protein expression

These deficiency effects occur at dietary PQQ levels below 0.3 ng/g and are dose-dependently reversed by supplementation [2][3]. While these findings support PQQ's physiological importance, the absence of a confirmed mammalian apo-enzyme form means PQQ does not meet the classical definition of a vitamin [2].

Recommended Dosing

Clinical Trial Doses

The typical dose of PQQ used in clinical studies is 20 mg per day, taken either as 10 mg twice daily or 20 mg once daily [1]. One research group used 21.5 mg per day [9][10]. The range across published studies is 10-21.5 mg per day, with one study using 40 mg per day (20 mg twice daily) [16].

Study	Daily Dose	Duration	Form	Outcome
Shiojima et al., 2021 (cognition) [9]	21.5 mg	12 weeks	mnemoPQQ	Modest cognitive improvements
Shiojima et al., 2024 (muscle) [10]	21.5 mg	12 weeks	mnemoPQQ	Modest strength improvement
Nakano et al., 2012 (mood/sleep) [18]	20 mg	8 weeks	BioPQQ	Improved mood/sleep (no placebo)
Nakano et al., 2015 (cholesterol) [25]	20 mg (10 mg x2)	12 weeks	BioPQQ	LDL reduction (-9 mg/dL)
Itoh et al., 2016 (cognition) [15]	20 mg	12 weeks	BioPQQ	Modest attention improvement
Hwang et al., 2019 (exercise) [22]	20 mg	6 weeks	PureQQ	No benefit
Harris et al., 2013 (inflammation) [20]	~20 mg	3 days	PQQ in drink	Reduced CRP and IL-6
Baltic et al., 2024 (MCI) [16]	40 mg (20 mg x2)	6 weeks	Alpha Hope	No benefit in MCI
Nakano, 2009 (cognition) [1]	20 mg	12 weeks	Not specified	Improved recall (unavailable)

How to Take

Suggested usage instructions on supplement labels are conflicting — some brands suggest taking PQQ with water while others suggest taking it with food [1]. Key considerations:

• Absorption: PQQ is water-soluble and does not require food for absorption [1]
• GI tolerance: Approximately 10% of PQQ users reported stomach discomfort [9], so taking with food may help
• Timing in trials: PQQ was typically taken within 30 minutes after breakfast [9][10], or split into two daily doses [16]
• Peak levels: PQQ reaches peak serum concentrations within 2-3 hours [2][11]
• Half-life: Plasma half-life is 3-5 hours [2][11], suggesting twice-daily dosing may maintain more consistent levels

GRAS Status and Regulatory Position

Multiple GRAS notifications have been filed with the FDA [1][8]:

• Mitsubishi Gas Chemical (BioPQQ), 2008: Filed PQQ disodium salt as an NDI. FDA did not object.
• Nascent Health Sciences (PureQQ), 2016: FDA did not object to GRAS for dietary supplements at max 8 mg per serving. Currently the only GRAS notice for dietary supplements.
• Hisun, Nutraland, Fuzou Contay, JinCheng (2016-2018): GRAS for fermented PQQ at 5-20 mg per serving in beverages.

GRAS status is based on filings to which the FDA has not objected but does not represent formal FDA confirmation of safety [1]. The FDA has indicated PQQ is safe at up to 0.3 mg/kg body weight daily (approximately 21 mg/day for a 70 kg adult) [2][8].

Practical Dosing Summary

• General supplementation: 10-20 mg per day
• No established RDA: PQQ is not an essential nutrient and has no recommended daily allowance
• No UL established: No tolerable upper intake level has been set for PQQ
• Timing: Can be taken with or without food; taking with breakfast may reduce GI side effects
• Duration: Clinical trials lasted 3 days to 12 weeks; long-term safety data beyond 3 months is not available

Safety and Side Effects

Reported Adverse Effects

Mild adverse effects reported with PQQ supplementation include headache, dizziness, nausea, heartburn, diarrhea, sore throat, fatigue, and swollen gums [1][10]. In the Shiojima et al. (2024) muscle study, there were notably more adverse events in the PQQ group than placebo (23 vs 14 events) [10]. In the Shiojima et al. (2021) cognition study, approximately 10% reported stomach discomfort [9].

Severe Adverse Effects

Severe adverse effects have not been reported in clinical trials [1]. However, only short-term studies have been conducted — lasting several weeks to three months — typically at about 20 mg per day [1]. The absence of severe adverse effects in a small number of short trials does not establish long-term safety.

Long-Term Safety

The safety of PQQ supplementation at higher dosages or long-term has not been evaluated in clinical trials [1]. All published human data comes from studies lasting 3 days to 12 weeks. There are no data on PQQ safety when taken for months or years.

Toxicology Data

PQQ is classified as non-toxic at dietary levels, with no significant genotoxicity observed in vivo [2]. Animal deficiency studies demonstrate that PQQ deprivation causes reversible harm including reduced fertility, impaired immune responses, and growth retardation [2][3][33]. PQQ is naturally present in human breast milk at approximately 20-30 micrograms per liter [2][3], indicating it is a normal component of human nutrition at trace levels.

Special Populations

Pregnancy and lactation: No supplementation data available. PQQ is naturally in breast milk [2][3], but this does not establish safety of supplemental doses (10,000-20,000 micrograms/day).

Children: No data on PQQ supplementation in children or adolescents.

Kidney disease: Given that approximately 80% of PQQ is excreted unchanged in urine [2][11], impaired kidney function could theoretically lead to accumulation. No studies exist in renal-impaired patients.

Drug Interactions

There are no well-documented drug interactions with PQQ in the published literature. The limited number of human studies and short durations mean meaningful interactions may not yet have been identified.

Theoretical Considerations

Anticoagulants and antiplatelet agents: PQQ has antioxidant effects and may influence inflammatory pathways [20]. No interaction documented, but individuals on blood thinners should exercise caution.

Chemotherapy agents: PQQ inhibits cancer cell growth in laboratory studies [6]. Whether it could interfere with or enhance chemotherapy is unknown. Consult an oncologist before use.

Cholesterol-lowering medications: PQQ may modestly lower LDL cholesterol [25], which could theoretically be additive with statin effects. No interaction studies have been conducted.

CoQ10 and NAD+ precursors: No reported adverse interactions. One study suggested enhanced cognitive benefits when combined with CoQ10 [1]. These combinations are used in supplement formulations without documented safety concerns [2].

Immunosuppressive medications: PQQ may modulate immune function based on animal studies [2][3]. Whether supplemental PQQ could interfere with immunosuppressive therapy is unknown but theoretically possible.

The standard recommendation is to inform your healthcare provider about PQQ supplementation, particularly if taking prescription medications, and to separate PQQ from medications by at least 2 hours as a general precaution.

Dietary Sources

PQQ is found in extremely small amounts in various foods. Concentrations are orders of magnitude lower than supplemental doses — food sources are measured in nanograms per gram while supplement doses are in milligrams, approximately a 1,000-fold difference [1][2][4].

Food	PQQ Content (ng/g)	Notes
Natto (fermented soybeans)	Up to 61	Highest known food source [2][13]
Parsley	34	Fresh parsley [2][13]
Kiwi fruit	27	[2][13]
Papaya	27	[2][13]
Tofu	24	[4]
Green tea	10-30	Brewed [1][4]
Green peppers	10-30	[1][4]
Spinach	10-30	[1][4]
Potatoes	10-30	[1][4]
Cocoa	3.7-30	Range depends on processing [2][13]
Celery	6	[4]

The typical dietary intake is estimated at 0.1-1.0 mg per day [2]. A clinical trial dose of 20 mg would require roughly 330 kg of natto or more than 660 kg of green peppers per day. Human breast milk contains approximately 20-30 micrograms per liter [2][3], substantially higher than most foods but far below supplemental doses.

PQQ is produced exclusively by certain bacteria, not by plants, animals, or fungi [2]. It enters the food chain through soil bacteria and rhizobacteria that synthesize PQQ via the pqq operon biosynthetic pathway [2]. PQQ-producing bacteria like Pseudomonas fluorescens B16 also function as plant growth promotion factors [2][34]. Fermented foods like natto have higher PQQ content because fermentation involves PQQ-producing bacteria [2][13].

References

1. ConsumerLab. "PQQ Supplements Review." Accessed 2025. https://www.consumerlab.com/reviews/pqq-review/pqq/

2. Grokipedia. "Pyrroloquinoline quinone." https://grokipedia.com/page/Pyrroloquinoline_quinone

3. Rucker R, Chowanadisai W, Nakano M. "Potential physiological importance of pyrroloquinoline quinone." Altern Med Rev. 2009;14(3):268-277. https://pubmed.ncbi.nlm.nih.gov/19803551/

4. Kumazawa T, Sato K, Seno H, Ishii A, Suzuki O. "Levels of pyrroloquinoline quinone in various foods." Biochem J. 1995;307(Pt 2):331-333. https://doi.org/10.1042/bj3070331

5. Chowanadisai W, Bauerly KA, Tchaparian E, Wong A, Cortopassi GA, Rucker RB. "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. https://doi.org/10.1074/jbc.M109.030130

6. Min Z, Wang L, Jin J, et al. "Pyrroloquinoline quinone induces cancer cell apoptosis via mitochondrial-dependent pathway and down-regulating cellular Bcl-2 protein expression." J Cancer. 2014;5(7):609-624. https://doi.org/10.7150/jca.9002

7. Misra HS, Rajpurohit YS, Khairnar NP. "Pyrroloquinoline-quinone and its versatile roles in biological processes." J Biosci. 2012;37(2):313-325. https://doi.org/10.1007/s12038-012-9195-5

8. U.S. Food and Drug Administration. GRAS Notice No. GRN 000709: Pyrroloquinoline quinone disodium salt. 2016. https://www.fda.gov/media/113888/download

9. Shiojima Y, Takahashi M, Takahashi R, et al. "Effect of dietary pyrroloquinoline quinone disodium salt on cognitive function in healthy volunteers." J Am Coll Nutr. 2021;41(8):796-809. https://doi.org/10.1080/07315724.2021.1962770

10. Shiojima Y, Takahashi M, Takahashi R, et al. "Effect of dietary pyrroloquinoline quinone disodium salt on muscle and physical function in healthy volunteers." J Funct Foods. 2024;112:105978. https://doi.org/10.1016/j.jff.2023.105978

11. Smidt CR, Unkefer CJ, Houck DR, Rucker RB. "Intestinal absorption and tissue distribution of [14C]pyrroloquinoline quinone in mice." Proc Soc Exp Biol Med. 1991;197(1):27-31. https://doi.org/10.3181/00379727-197-43219

12. 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. https://doi.org/10.1016/j.jnutbio.2013.07.008

13. Kumazawa T, Sato K, Seno H, Ishii A, Suzuki O. "Levels of pyrroloquinoline quinone in various foods." Biochem J. 1995;307(Pt 2):331-333. https://doi.org/10.1042/bj3070331

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