PQQ
PQQ disodium salt has food-ingredient authorizations and several small human trials. Selected cognitive tests and one lower-limb-strength trial favored PQQ, while total MoCA, exercise performance, and broad metabolic outcomes included null results. No human lifespan study exists.
Pyrroloquinoline quinone disodium salt evidence
- Four modern PQQ-alone cognition RCTs lasted 12 weeks; outcomes varied and study teams had product-company links.
- The 40-person trial found total MoCA change null, with one positive language subdomain among seven.
- A 2024 trial randomized 64 and analyzed 62 for strength and walking outcomes, but the abstract does not report the complete numerical results.
- A 23-man endurance-training study increased muscle PGC-1alpha protein without improving aerobic performance or body composition.
- The 2026 SAMP8 mouse paper found overall survival null despite a highlighted 75th-percentile result.
- No human dementia-prevention, lifespan or validated PQQ-deficiency result was found.
Which form was tested, and is PQQ a human vitamin?
Human trials and food decisions mainly cover PQQ disodium salt. Free-acid PQQ, reduced PQQH2 and the glycine adduct IPQ are different molecules. PQQ is a bacterial redox cofactor, but no human deficiency syndrome, dietary reference intake or PQQ-dependent mammalian enzyme has been established. A 2016 paper states that PQQ does not act as a mammalian lactate-dehydrogenase cofactor.
| Form or claim | Evidence |
|---|---|
| PQQ disodium salt | Best-defined trial and regulatory ingredient |
| Free PQQ, PQQH2 and IPQ | Different chemistry; cell and mouse results cannot be assigned to the disodium product |
| Human vitamin status | No validated deficiency syndrome, reference intake or replacement trial |
| Mammalian LDH cofactor | Direct mechanistic paper says PQQ is not the cofactor |
PubChem CID 3078772 · disodium identity
Government chemical database
National Center for Biotechnology Information. PubChem Compound Summary for CID 3078772, Pyrroloquinoline quinone disodium salt. National Library of Medicine.
The record identifies PQQ disodium salt as C14H4N2Na2O8, molecular weight 374.17 g/mol, CAS 122628-50-6.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Not applicable
- Study design
- Primary source record
Free acid, disodium salt, reduced PQQH2, and combination products may differ.
Read the original sourceEFSA safety opinion · novel food, not medicine
EU food-safety assessment
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Turck D et al. Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC) No 258/97. EFSA Journal. 2017;15(11):5058. doi:10.2903/j.efsa.2017.5058.
EFSA concluded PQQ disodium salt was safe under the proposed supplement conditions for healthy adults, excluding pregnant and lactating women. The panel emphasized limited ADME data and small, short human studies; rat renal findings informed the safety margin.
- Participants / model
- Healthy adults as the proposed food-supplement population; not pregnant or lactating
- Treatment
- PQQ disodium salt as a novel food ingredient
- Follow-up
- Safety assessment based on submitted studies
- Study design
- Regulatory food-safety opinion
A novel-food safety conclusion is not medicine approval and does not establish cognition or longevity efficacy.
Read the original source2016 mechanism · PQQ is not the mammalian LDH cofactor
Biochemical and cell study
PMID 27230956; PMCID PMC4882622.
PQQ bound LDH, redox-cycled NADH and NAD+, and altered ATP or lactate in fibroblasts.
- Participants / model
- Mouse fibroblasts and rabbit-muscle lactate dehydrogenase
- Treatment
- PQQ in vitro
- Follow-up
- Cell and biochemical experiments
- Study design
- Mechanistic study
The paper states that PQQ does not serve as a mammalian LDH cofactor. It does not establish human vitamin status.
Read the original sourceWhat do EU, Chinese and US food records mean?
EU novel-food authorization, Chinese new-food-raw-material actions and FDA GRAS Notice 694 apply to specified PQQ disodium preparations and food uses. They do not approve PQQ for memory, disease treatment or anti-aging. The EU excludes pregnant and lactating people; China also excludes infants.
| Record | Scope |
|---|---|
| EU 2018/1122 | Specified adult food-supplement use; pregnancy and lactation excluded |
| China 2022/2023 actions | Specified synthetic or fermentation-derived raw material; infants, pregnancy and lactation excluded |
| FDA GRN 694 | No-questions response for the notifier's specified beverage uses |
EU novel-food authorization
EU regulation
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.
The regulation authorizes PQQ disodium salt for adult food supplements under specified conditions and excludes pregnant and lactating women from the target population.
- Participants / model
- Adults using food supplements in the EU, excluding pregnant and lactating women
- Treatment
- PQQ disodium salt
- Follow-up
- Current novel-food authorization
- Study design
- EU implementing regulation
This is a food-ingredient authorization, not a medicinal indication or efficacy judgment.
Read the original sourceChina NHC · fermented PQQ disodium new-food approval
Chinese food-safety regulatory interpretation
National Health Commission of the People's Republic of China. Interpretation of the Announcement on 15 'Three New Foods' including peach gum (Announcement No. 8 of 2023). October 2023.
China's NHC states that synthetic PQQ disodium salt had been approved as a new food raw material in 2022 and that a fermentation-produced form passed safety review in 2023, with a recommended intake ceiling and exclusions for infants, pregnant women, and lactating women.
- Participants / model
- Food consumers under the authorization, excluding specified groups
- Treatment
- Specified synthetic or fermentation-produced PQQ disodium salt raw material
- Follow-up
- 2022 and 2023 food-ingredient actions
- Study design
- Chinese food-safety regulatory record
This is food-ingredient safety authorization, not approval to prevent cognitive decline or aging.
Read the original sourceFDA GRAS response · intended beverage uses
FDA food-ingredient record
U.S. Food and Drug Administration. GRAS Notice No. 694, Pyrroloquinoline quinone disodium salt. Response letter dated September 28, 2017.
FDA closed the notice with 'no questions' regarding the notifier's GRAS conclusion for specified beverage uses at the proposed levels.
- Participants / model
- Consumers of specified conventional beverage uses
- Treatment
- PQQ disodium salt as a food ingredient
- Follow-up
- GRAS notice and response
- Study design
- FDA GRAS notice record
A 'no questions' GRAS letter is not drug approval, supplement efficacy review, or a general safety finding for every product and exposure.
Read the original sourceEFSA safety opinion · novel food, not medicine
EU food-safety assessment
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Turck D et al. Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC) No 258/97. EFSA Journal. 2017;15(11):5058. doi:10.2903/j.efsa.2017.5058.
EFSA concluded PQQ disodium salt was safe under the proposed supplement conditions for healthy adults, excluding pregnant and lactating women. The panel emphasized limited ADME data and small, short human studies; rat renal findings informed the safety margin.
- Participants / model
- Healthy adults as the proposed food-supplement population; not pregnant or lactating
- Treatment
- PQQ disodium salt as a novel food ingredient
- Follow-up
- Safety assessment based on submitted studies
- Study design
- Regulatory food-safety opinion
A novel-food safety conclusion is not medicine approval and does not establish cognition or longevity efficacy.
Read the original sourceWhat do the four modern PQQ-alone cognition trials show?
Four small Japanese randomized trials report selected cognitive-test changes over 12 weeks. They do not converge on one replicated primary outcome. The 40-person trial found total MoCA change null and only the language subdomain positive. The other studies tested many domains, visits, age groups or subgroups, and all had product-company involvement.
| Study | Positive result | Nulls and limits |
|---|---|---|
| 2020: 40 healthy adults, age 50 to 71 | Language-domain change: placebo 0.15 vs PQQ 0.65 | Total MoCA change placebo 0.60 vs PQQ 1.25, p=0.118; six other domains null; no stated multiplicity correction |
| 2016: 41 older adults | Stroop interference favored PQQ | Visual-spatial result restricted to a lower-baseline subgroup; small product-linked trial |
| 2021: 64 randomized; 58 completed | Several Cognitrax, MMSE-J and DECO outcomes favored PQQ | 31 placebo vs 27 PQQ completers; many outcomes; product-linked team |
| 2023: 70 randomized; 62 in main tables | Composite memory p=0.003 and verbal memory p=0.001 at week 12 | Many domains, visits and age strata; no stated multiplicity correction; same-data classifier accuracy 0.57 and 0.67 |
40-person RCT · total MoCA null, language positive
Randomized double-blind placebo-controlled human substudy
PMID 32021931; PMCID PMC6994848.
Total MoCA change was placebo 0.60±0.31 versus PQQ 1.25±0.35, p=0.118. Language-domain change was 0.15±0.13 versus 0.65±0.13, p<0.05.
- Participants / model
- 40 healthy Japanese adults aged 50-71
- Treatment
- PQQ disodium 20 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled parallel trial
- Funding
- Japan Science and Technology Agency Matching Planner
Six other MoCA domains were null; no multiplicity correction stated. Two Mitsubishi employees authored and Mitsubishi commissioned testing, despite a no-conflict declaration.
Read the original sourceOlder Japanese trial · 41 randomized
Randomized controlled trial
Itoh Y, Hine K, Miura H, Uetake T, Nakano M, Takemura N, Sakatani K. Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQ) on Cognitive Functions. Advances in Experimental Medicine and Biology. 2016;876:319-325. doi:10.1007/978-1-4939-3023-4_40. PMID 26782228.
Forty-one healthy older participants received PQQ disodium salt or placebo for 12 weeks. Stroop interference favored PQQ, while the tablet-based visual-spatial finding was confined to a lower-baseline subgroup.
- Participants / model
- 41 healthy older adults
- Treatment
- Oral PQQ disodium salt 20 mg/day or placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- BioPQQ/product-linked program
Small sample, selective/subgroup findings, and no dementia, independence, or long-term outcome.
Read the original sourceHealthy Japanese trial · 64 randomized, 58 completed
Randomized controlled trial
Shiojima Y, Takahashi M, Takahashi R, Moriyama H, Bagchi D, Bagchi M, Akanuma M. Effect of Dietary Pyrroloquinoline Quinone Disodium Salt on Cognitive Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study. Journal of the American Nutrition Association. 2022;41(8):796-809. doi:10.1080/07315724.2021.1962770. PMID 34415830.
Sixty-four healthy Japanese adults aged 40 to under 80 who reported forgetfulness were randomized; 58 completed (31 placebo, 27 PQQ). After 12 weeks, multiple Cognitrax domains plus MMSE-J and DECO scores favored PQQ disodium salt.
- Participants / model
- 64 randomized healthy Japanese adults aged 40 to <80 with subjective forgetfulness; 58 completed
- Treatment
- Oral PQQ disodium salt 21.5 mg/day or placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled parallel trial
- Funding
- Ryusendo/product-linked authors
Small completer set, attrition, numerous endpoints, product-linked investigators, and no durable functional or disease outcome.
Read the original sourceJapanese RCT · 70 randomized, main analysis n=62
Randomized double-blind placebo-controlled trial
Tamakoshi M, Suzuki T, Nishihara E, Nakamura S, Ikemoto K. Pyrroloquinoline quinone disodium salt improves brain function in both younger and older adults. Food & Function. 2023;14(5):2496-2501. doi:10.1039/D2FO01515C. PMID 36807425.
At week 12, composite memory (p=0.003) and verbal memory (p=0.001) favored PQQ. Age-stratified differences appeared at different visits and domains; a same-dataset logistic model classified treatment with accuracy 0.57 at week 8 and 0.67 at week 12.
- Participants / model
- 70 healthy Japanese adults aged 20-65 randomized; 66 completed; main result tables analyzed 62 (31 per group)
- Treatment
- Oral BioPQQ disodium salt 20 mg/day or placebo after breakfast
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled parallel trial
- Funding
- Mitsubishi Gas Chemical; company employees authored the paper
The paper does not clearly reconcile the four completers absent from the 62-person table analysis. It tested 15 Cognitrax domains at multiple visits and subgroups without a stated multiplicity correction; the classifier used the same small dataset.
Read the original sourceOlder multi-arm reports · manufacturer summaries
Publisher bibliographic record
Nakano et al. 2009; Koikeda et al. 2011, Medical Consultation & New Remedies 48:519-527.
Manufacturer secondary summaries describe selected early, low-baseline or combination-arm memory findings.
- Participants / model
- Healthy middle-aged and older Japanese adults
- Treatment
- PQQ alone or PQQ plus CoQ10 versus placebo
- Follow-up
- Weeks to months
- Study design
- Reported controlled multi-arm studies
- Funding
- Manufacturer-linked program
The cited manufacturer summaries do not report complete primary tables, exact denominators, or adverse-event accounting. Combination effects cannot be assigned to PQQ.
Read the original sourceDoes PQQ improve strength, exercise performance or lifespan?
A 2024 Japanese trial reports a lower-limb-strength difference after 12 weeks, but the abstract does not provide a numerical effect estimate. The direct six-week endurance-training study found no aerobic-performance or body-composition benefit. No human lifespan outcome exists; the 2026 mouse study found overall survival null despite a positive 75th-percentile comparison.
| Study | Result | Limit |
|---|---|---|
| 2024 function RCT: 64 randomized, 62 analyzed | Registry and abstract report lower-limb-extensor-strength and walking differences | Numerical effects, confidence intervals, and multiplicity plan not reported; Ryusendo funded and led; registry disclosure followed trial completion |
| Endurance training: 23 untrained men | Muscle PGC-1alpha protein increased | Aerobic performance and body composition null; same-cohort Complex I, IV, citrate synthase and protein carbonyl interactions null |
| Beijing acute trial: 60 men | One Body Listening interaction, p=0.016 | No overall interoception advantage; one session and retrospective registration |
| SAMP8 mice, lifelong diet | 75th survival percentile 269 to 466 days | Overall survival null: median 455 vs 513 days; log-rank p=0.6570, Gehan p=0.1559; grip null |
64 randomized, 62 analyzed · strength signal without a reported effect size
Randomized double-blind placebo-controlled trial
Journal of Functional Foods. 2024. DOI 10.1016/j.jff.2024.106012; UMIN000048641.
The abstract and UMIN record report a lower-limb-extensor-strength difference and improvements in walking/function tests.
- Participants / model
- 64 randomized Japanese adults aged 20 to <75; 62 analyzed, 31 per arm; selected against sarcopenia and regular exercise
- Treatment
- PQQ disodium 21.5 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Ryusendo
The abstract does not report numerical effects, confidence intervals, multiplicity handling, or the two dropout reasons. The registry was entered before the trial and publicly disclosed after follow-up; the principal investigator was the company president and CEO.
Read the original source23-man RCT · PGC-1alpha positive, performance null
Randomized placebo-controlled training trial
PMID 31860387; DOI 10.1080/07315724.2019.1705203.
Skeletal-muscle PGC-1alpha protein increased versus placebo.
- Participants / model
- 23 healthy untrained men; 12 PQQ and 11 placebo
- Treatment
- PQQ 20 mg/day versus placebo during supervised endurance training
- Follow-up
- Six weeks
- Study design
- Randomized placebo-controlled trial
- Funding
- Nascent Health Sciences
Aerobic performance and body composition did not differ by group.
Read the original sourceSame 23-man cohort · mitochondrial-marker interactions null
Same-cohort conference report
PMCID PMC9310654.
No supplement-by-time interactions occurred for Complex I, Complex IV, citrate synthase or protein carbonyls.
- Participants / model
- Same 23 men as the endurance-training trial
- Treatment
- PQQ 20 mg/day versus placebo
- Follow-up
- Six weeks
- Study design
- Secondary same-cohort biomarker report
- Funding
- Nascent Health Sciences
This is a follow-up of the same cohort, not an independent trial.
Read the original sourceBeijing RCT · 60 students, single exposure
Randomized double-blind placebo-controlled trial
Zhao C, Wu B, Sui H, Kuan G, Wei G, Yan Y. The effects of pyrroloquinoline quinone and nicotinamide mononucleotide supplementation on interoception following acute exhaustive exercise: a randomised, double-blind, placebo-controlled study. Scientific Reports. 2026;16:5408. doi:10.1038/s41598-025-34191-0. PMID 41651893.
There was no overall between-group advantage for interoception after exhaustive exercise. One MAIA Body Listening interaction was significant (p=0.016), driven by a within-PQQ change; the remaining effects were selective rather than a broad supplement benefit.
- Participants / model
- 60 male physical-education students in Beijing, mean age about 19; 15 per arm
- Treatment
- Single pre-exercise exposure: placebo, PQQ 20 mg, NMN 300 mg, or both
- Follow-up
- One acute exhaustive-exercise session
- Study design
- Randomized double-blind placebo-controlled four-arm trial; retrospectively registered
- Funding
- Fundamental Research Funds for the Central Universities
This was an acute exercise/interoception study in young men, not a cognition or aging trial. Adverse events were not reported.
Read the original source2026 mouse study · overall survival null
Controlled animal lifespan study
PMID 42132809; DOI 10.1039/d6fo00788k.
The 75th survival percentile was 269 days in control and 466 days with PQQ; selected truncated-interval tests were positive.
- Participants / model
- Male senescence-accelerated SAMP8 mice; lifelong control n=15, PQQ n=16, IPQ n=15
- Treatment
- 0.02% dietary PQQ, about 25 mg/kg/day in young adults
- Follow-up
- Lifelong and separate 16-week midlife experiments
- Study design
- Controlled animal lifespan study
- Funding
- Mitsubishi Gas Chemical
Overall survival was null: median 455 versus 513 days, log-rank p=0.6570 and Gehan p=0.1559. Grip and several muscle outcomes were null. Special male mouse strain and high exposure.
Read the original sourceWhat do the ovarian, lipid, skin and sleep studies show?
The other human studies are mostly null or uncontrolled. AMH did not change overall in a 2026 open-label ovarian study. A lipid RCT found marginal overall cholesterol results and a tiny post hoc subgroup. A dry-skin trial had one selected forearm result with broad null skin measures. The sleep/stress study had no control group.
| Study | Finding | Limit |
|---|---|---|
| Healthy women: 50 entered, 35 analyzed | AMH 1.561 to 1.439 ng/mL, p=0.182 | No control; small subgroups moved inconsistently |
| Lipids: 32 randomized, 29 analyzed | High-LDL subgroup signal at week 6 | Overall LDL p=0.052, total cholesterol p=0.087; triglycerides, body fat and BMI null; three outliers removed post hoc |
| Dry skin: 22 randomized; final 11 vs 8 | One forearm water-loss change and selected self-ratings | Cheek loss, conductance, viscoelasticity and raw forearm values null; asymmetric dropout |
| Sleep/stress: 17 office workers | Several pre-post questionnaires improved | Open-label, no placebo or blinding; cannot separate expectancy or regression to mean |
Healthy women · no overall AMH change
Single-arm prospective clinical study
Tsuji S, Takiuchi T, Handa M, Miura N, Aoyagi H, Uematsu Y, Shidomi M, Fukada K, Ogura C, Kimura T, Kodama M. Serum anti-Müllerian hormone response to pyrroloquinoline quinone supplementation in healthy women: no overall change and exploratory subgroup findings. Frontiers in Endocrinology. 2026;17:1831604. doi:10.3389/fendo.2026.1831604. PMID 42500134.
Fifty healthy women aged 25-42 entered; the per-protocol analysis included 35. After about 90 days, serum AMH did not change overall (1.561 to 1.439 ng/mL; p=0.182). Small exploratory age-by-baseline-AMH subgroups moved in inconsistent directions.
- Participants / model
- 50 healthy Japanese women aged 25-42 with regular cycles and baseline AMH 0.5 to <3.0 ng/mL; 35 in per-protocol analysis
- Treatment
- Oral PQQ 20 mg/day
- Follow-up
- 90 ± 10 days
- Study design
- Prospective single-arm open-label study
- Funding
- ROHTO Pharmaceutical employees among authors; product support disclosed
No control group, 30% excluded from the per-protocol analysis, hormonal surrogate primary endpoint, and small post hoc-style subgroups. It does not establish fertility, ovarian anti-aging, cognition, or longevity efficacy.
Read the original sourceChinese mouse ovarian-injury study
Animal preclinical study
Dai X, Yi X, Wang Y, Xia W, Tao J, Wu J, Miao D, Chen L. PQQ Dietary Supplementation Prevents Alkylating Agent-Induced Ovarian Dysfunction in Mice. Frontiers in Endocrinology. 2022;13:781404. doi:10.3389/fendo.2022.781404. PMID 35340329.
Sixty female C57BL/6-background mice were randomized to control, alkylating-agent injury, or injury plus PQQ feed. PQQ partially protected ovarian and fertility measures after busulfan/cyclophosphamide injury; pregnancy was 7/7 in control and PQQ groups versus 3/7 in injury controls, while litter size and several ovarian measures remained below uninjured controls.
- Participants / model
- 60 eight-week-old female C57BL/6-background mice across three groups; endpoint-specific subsamples included six per group for estrous monitoring and seven per group for mating
- Treatment
- Feed containing PQQ disodium salt 5 mg/kg, started one week before busulfan/cyclophosphamide injury and continued to sacrifice
- Follow-up
- One month to estrous monitoring; three months to mating or tissue collection; mating followed for two months
- Study design
- Randomized three-group mouse injury-model experiment
This is prevention in a severe chemotherapy-injury mouse model, not natural ovarian aging, a human fertility trial, or cognition/longevity evidence.
Read the original source32 randomized, 29 analyzed · overall lipid results weak
Randomized double-blind placebo-controlled trial
DOI 10.3177/jnsv.61.233.
A high-baseline-LDL subgroup of six versus five differed at week 6; week 12 was marginal.
- Participants / model
- 32 adults aged 40-60 with triglycerides 110-300 mg/dL; 29 analyzed
- Treatment
- PQQ 20 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Mitsubishi-linked program
Three triglyceride outliers were excluded post hoc. Overall LDL p=0.052, total cholesterol p=0.087; triglycerides, body fat and BMI null; HDL change favored placebo at week 6.
Read the original source22 randomized, final 11 vs 8 · selected forearm result
Randomized double-blind placebo-controlled trial
DOI 10.3177/jnsv.61.241.
One forearm water-loss change at week 4 and selected wrinkle/pigmentation self-ratings favored PQQ.
- Participants / model
- 22 healthy women with mild dry skin; final 11 PQQ and 8 placebo
- Treatment
- PQQ 20 mg/day versus placebo
- Follow-up
- Eight weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Mitsubishi-linked program
Raw forearm measures, cheek water loss, conductance and all viscoelasticity outcomes were null; three placebo dropouts and many comparisons.
Read the original source17-person open-label study · uncontrolled pre-post changes
Open-label uncontrolled study
DOI 10.31989/ffhd.v2i8.81.
Several mood, quality-of-life and sleep questionnaires improved from baseline; one cortisol-awakening correlation was r=-0.55.
- Participants / model
- 17 office workers with fatigue or sleep complaints
- Treatment
- PQQ 20 mg/day
- Follow-up
- Eight weeks
- Study design
- Open-label uncontrolled pre-post study
- Funding
- Mitsubishi-linked program
No placebo, blinding or fixed primary hierarchy; expectancy and regression to mean cannot be separated.
Read the original sourceWhat do mitochondrial markers and human exposure prove?
PQQ changes redox and mitochondrial markers in cell systems, and a ten-person study detected serum free PQQ after oral exposure. Mouse liver-cell CREB and PGC-1alpha findings do not establish human-brain mitochondrial biogenesis. In the endurance trial, muscle PGC-1alpha changed without better performance or consistent mitochondrial-abundance markers.
| Evidence | Finding | Boundary |
|---|---|---|
| Ten healthy adults | Serum free PQQ peaked about two hours after 0.2 mg/kg; exploratory inflammatory/metabolomic changes | Too small for universal PK, brain penetration or clinical benefit |
| Mouse Hepa1-6 liver cells | CREB, PGC-1alpha, mitochondrial DNA, citrate synthase and respiration changed | Mouse liver cells at micromolar exposure, not human brain |
| Twenty healthy older adults | Resting prefrontal NIRS measures changed | Tiny surrogate study without cognitive benefit |
| Human neuroblastoma/liver-cancer cells and injected mice | PQQ, PQQH2 and IPQ changed selected cellular or memory measures | Transformed cells and intraperitoneal 5 mg/kg mouse exposure do not model oral human dosing |
Exploratory human study · n=10
Small human crossover/metabolic study
Harris CB, Chowanadisai W, Mishchuk DO, Satre MA, Slupsky CM, Rucker RB. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. Journal of Nutritional Biochemistry. 2013;24(12):2076-2084. doi:10.1016/j.jnutbio.2013.07.008. PMID 24231099.
Ten adults completed single- and short repeated-exposure phases. Exploratory inflammatory and metabolomic measures changed; serum free PQQ peaked at about two hours after a single exposure.
- Participants / model
- 10 healthy adults, five women and five men
- Treatment
- Oral PQQ in single and repeated short exposures
- Follow-up
- Single exposure over 48 hours and repeated exposure over 76 hours
- Study design
- Exploratory human metabolic study
Tiny sample, short duration, multiple exploratory biomarkers, and no clinical cognition or longevity endpoint. The approximate two-hour peak is not a validated universal product Tmax.
Read the original sourceMouse liver-cell mechanism study
Cell preclinical study
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. Journal of Biological Chemistry. 2010;285(1):142-152. doi:10.1074/jbc.M109.030130. PMID 19861415.
In mouse Hepa1-6 liver cells, 15-30 micromolar PQQ increased CREB phosphorylation, PGC-1alpha expression, mitochondrial DNA, and citrate synthase activity; PGC-1alpha siRNA blocked the mitochondrial-biogenesis response.
- Participants / model
- Mouse Hepa1-6 liver cells
- Treatment
- PQQ in vitro
- Follow-up
- Cell-culture experiment
- Study design
- Preclinical cell study
The experiment used mouse liver cells, not a human brain or treated participants; in-vitro concentrations do not define a human exposure.
Read the original source20-person surrogate study · no clinical endpoint
Randomized placebo-controlled trial
PMID 27526146; DOI 10.1007/978-3-319-38810-6_29.
Resting right-prefrontal oxygenated and total hemoglobin increased; oxygen saturation decreased more.
- Participants / model
- 20 healthy adults aged 50-70; 10 per arm
- Treatment
- PQQ 20 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized placebo-controlled study
- Funding
- Mitsubishi-linked program
Tiny hemodynamic-surrogate study with no demonstrated cognition or functional benefit.
Read the original source40-person RCT · total MoCA null, language positive
Randomized double-blind placebo-controlled human substudy
PMID 32021931; PMCID PMC6994848.
Total MoCA change was placebo 0.60±0.31 versus PQQ 1.25±0.35, p=0.118. Language-domain change was 0.15±0.13 versus 0.65±0.13, p<0.05.
- Participants / model
- 40 healthy Japanese adults aged 50-71
- Treatment
- PQQ disodium 20 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled parallel trial
- Funding
- Japan Science and Technology Agency Matching Planner
Six other MoCA domains were null; no multiplicity correction stated. Two Mitsubishi employees authored and Mitsubishi commissioned testing, despite a no-conflict declaration.
Read the original source2016 mechanism · PQQ is not the mammalian LDH cofactor
Biochemical and cell study
PMID 27230956; PMCID PMC4882622.
PQQ bound LDH, redox-cycled NADH and NAD+, and altered ATP or lactate in fibroblasts.
- Participants / model
- Mouse fibroblasts and rabbit-muscle lactate dehydrogenase
- Treatment
- PQQ in vitro
- Follow-up
- Cell and biochemical experiments
- Study design
- Mechanistic study
The paper states that PQQ does not serve as a mammalian LDH cofactor. It does not establish human vitamin status.
Read the original sourceWhat limits the safety data?
EFSA found no safety concern for a specified at least 99% PQQ disodium ingredient at up to 20 mg/day in adults, excluding pregnancy and lactation. Human studies were small and lasted days to 24 weeks. Rat renal toxicity and urinary findings at high doses informed the safety margin. Chronic, pregnancy, interaction and rare-event safety remain unresolved.
| Evidence | Result |
|---|---|
| Human trials | Common short-term events generally reassuring in small selected samples |
| EFSA scope | Specified ingredient, up to 20 mg/day, adults excluding pregnancy/lactation |
| Rat studies | Renal toxicity at 768 mg/kg/day for 14 days; urinary crystals/protein at 200 mg/kg/day or more over 28 days |
| Unanswered | Multi-year use, kidney disease, children, pregnancy, interactions, rare events and variable commercial products |
EFSA safety opinion · novel food, not medicine
EU food-safety assessment
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Turck D et al. Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC) No 258/97. EFSA Journal. 2017;15(11):5058. doi:10.2903/j.efsa.2017.5058.
EFSA concluded PQQ disodium salt was safe under the proposed supplement conditions for healthy adults, excluding pregnant and lactating women. The panel emphasized limited ADME data and small, short human studies; rat renal findings informed the safety margin.
- Participants / model
- Healthy adults as the proposed food-supplement population; not pregnant or lactating
- Treatment
- PQQ disodium salt as a novel food ingredient
- Follow-up
- Safety assessment based on submitted studies
- Study design
- Regulatory food-safety opinion
A novel-food safety conclusion is not medicine approval and does not establish cognition or longevity efficacy.
Read the original sourceEU novel-food authorization
EU regulation
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.
The regulation authorizes PQQ disodium salt for adult food supplements under specified conditions and excludes pregnant and lactating women from the target population.
- Participants / model
- Adults using food supplements in the EU, excluding pregnant and lactating women
- Treatment
- PQQ disodium salt
- Follow-up
- Current novel-food authorization
- Study design
- EU implementing regulation
This is a food-ingredient authorization, not a medicinal indication or efficacy judgment.
Read the original sourceChina NHC · fermented PQQ disodium new-food approval
Chinese food-safety regulatory interpretation
National Health Commission of the People's Republic of China. Interpretation of the Announcement on 15 'Three New Foods' including peach gum (Announcement No. 8 of 2023). October 2023.
China's NHC states that synthetic PQQ disodium salt had been approved as a new food raw material in 2022 and that a fermentation-produced form passed safety review in 2023, with a recommended intake ceiling and exclusions for infants, pregnant women, and lactating women.
- Participants / model
- Food consumers under the authorization, excluding specified groups
- Treatment
- Specified synthetic or fermentation-produced PQQ disodium salt raw material
- Follow-up
- 2022 and 2023 food-ingredient actions
- Study design
- Chinese food-safety regulatory record
This is food-ingredient safety authorization, not approval to prevent cognitive decline or aging.
Read the original source64 randomized, 62 analyzed · strength signal without a reported effect size
Randomized double-blind placebo-controlled trial
Journal of Functional Foods. 2024. DOI 10.1016/j.jff.2024.106012; UMIN000048641.
The abstract and UMIN record report a lower-limb-extensor-strength difference and improvements in walking/function tests.
- Participants / model
- 64 randomized Japanese adults aged 20 to <75; 62 analyzed, 31 per arm; selected against sarcopenia and regular exercise
- Treatment
- PQQ disodium 21.5 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Ryusendo
The abstract does not report numerical effects, confidence intervals, multiplicity handling, or the two dropout reasons. The registry was entered before the trial and publicly disclosed after follow-up; the principal investigator was the company president and CEO.
Read the original sourceWhat does C tier mean for PQQ?
C tier reflects small controlled studies with uncertain effect size and reproducibility. Some cognition and function measures improved, while total cognition, exercise performance, broad metabolic outcomes and overall mouse survival include clear nulls. No human dementia-prevention, disease or lifespan outcome has been shown.
| Claim | Judgment |
|---|---|
| Short-term selected cognition tests | Possible effect; four small product-linked trials use different outcomes |
| Strength and function | One positive 62-person randomized result without a reported numerical effect |
| Aerobic performance and training adaptation | Direct trial null for performance and body composition |
| Sleep, lipids, skin or ovarian aging | Uncontrolled, post hoc, selected or overall null evidence |
| Dementia prevention and human longevity | No evidence |
| Long-term safety | Unknown beyond specified ingredient and short studies |
40-person RCT · total MoCA null, language positive
Randomized double-blind placebo-controlled human substudy
PMID 32021931; PMCID PMC6994848.
Total MoCA change was placebo 0.60±0.31 versus PQQ 1.25±0.35, p=0.118. Language-domain change was 0.15±0.13 versus 0.65±0.13, p<0.05.
- Participants / model
- 40 healthy Japanese adults aged 50-71
- Treatment
- PQQ disodium 20 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled parallel trial
- Funding
- Japan Science and Technology Agency Matching Planner
Six other MoCA domains were null; no multiplicity correction stated. Two Mitsubishi employees authored and Mitsubishi commissioned testing, despite a no-conflict declaration.
Read the original sourceJapanese RCT · 70 randomized, main analysis n=62
Randomized double-blind placebo-controlled trial
Tamakoshi M, Suzuki T, Nishihara E, Nakamura S, Ikemoto K. Pyrroloquinoline quinone disodium salt improves brain function in both younger and older adults. Food & Function. 2023;14(5):2496-2501. doi:10.1039/D2FO01515C. PMID 36807425.
At week 12, composite memory (p=0.003) and verbal memory (p=0.001) favored PQQ. Age-stratified differences appeared at different visits and domains; a same-dataset logistic model classified treatment with accuracy 0.57 at week 8 and 0.67 at week 12.
- Participants / model
- 70 healthy Japanese adults aged 20-65 randomized; 66 completed; main result tables analyzed 62 (31 per group)
- Treatment
- Oral BioPQQ disodium salt 20 mg/day or placebo after breakfast
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled parallel trial
- Funding
- Mitsubishi Gas Chemical; company employees authored the paper
The paper does not clearly reconcile the four completers absent from the 62-person table analysis. It tested 15 Cognitrax domains at multiple visits and subgroups without a stated multiplicity correction; the classifier used the same small dataset.
Read the original source64 randomized, 62 analyzed · strength signal without a reported effect size
Randomized double-blind placebo-controlled trial
Journal of Functional Foods. 2024. DOI 10.1016/j.jff.2024.106012; UMIN000048641.
The abstract and UMIN record report a lower-limb-extensor-strength difference and improvements in walking/function tests.
- Participants / model
- 64 randomized Japanese adults aged 20 to <75; 62 analyzed, 31 per arm; selected against sarcopenia and regular exercise
- Treatment
- PQQ disodium 21.5 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Ryusendo
The abstract does not report numerical effects, confidence intervals, multiplicity handling, or the two dropout reasons. The registry was entered before the trial and publicly disclosed after follow-up; the principal investigator was the company president and CEO.
Read the original source23-man RCT · PGC-1alpha positive, performance null
Randomized placebo-controlled training trial
PMID 31860387; DOI 10.1080/07315724.2019.1705203.
Skeletal-muscle PGC-1alpha protein increased versus placebo.
- Participants / model
- 23 healthy untrained men; 12 PQQ and 11 placebo
- Treatment
- PQQ 20 mg/day versus placebo during supervised endurance training
- Follow-up
- Six weeks
- Study design
- Randomized placebo-controlled trial
- Funding
- Nascent Health Sciences
Aerobic performance and body composition did not differ by group.
Read the original source2026 mouse study · overall survival null
Controlled animal lifespan study
PMID 42132809; DOI 10.1039/d6fo00788k.
The 75th survival percentile was 269 days in control and 466 days with PQQ; selected truncated-interval tests were positive.
- Participants / model
- Male senescence-accelerated SAMP8 mice; lifelong control n=15, PQQ n=16, IPQ n=15
- Treatment
- 0.02% dietary PQQ, about 25 mg/kg/day in young adults
- Follow-up
- Lifelong and separate 16-week midlife experiments
- Study design
- Controlled animal lifespan study
- Funding
- Mitsubishi Gas Chemical
Overall survival was null: median 455 versus 513 days, log-rank p=0.6570 and Gehan p=0.1559. Grip and several muscle outcomes were null. Special male mouse strain and high exposure.
Read the original sourceEFSA safety opinion · novel food, not medicine
EU food-safety assessment
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Turck D et al. Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC) No 258/97. EFSA Journal. 2017;15(11):5058. doi:10.2903/j.efsa.2017.5058.
EFSA concluded PQQ disodium salt was safe under the proposed supplement conditions for healthy adults, excluding pregnant and lactating women. The panel emphasized limited ADME data and small, short human studies; rat renal findings informed the safety margin.
- Participants / model
- Healthy adults as the proposed food-supplement population; not pregnant or lactating
- Treatment
- PQQ disodium salt as a novel food ingredient
- Follow-up
- Safety assessment based on submitted studies
- Study design
- Regulatory food-safety opinion
A novel-food safety conclusion is not medicine approval and does not establish cognition or longevity efficacy.
Read the original source2019 Russian review · no local clinical cohort
Russian-language literature review
Использование пирролохинолин хинона как препарата нейропротекции. 2019.
The review summarizes foreign cell, animal and human PQQ literature.
- Participants / model
- Literature review; no participant cohort
- Treatment
- No intervention
- Follow-up
- Review
- Study design
- Russian-language literature review
This is a Russian-language synthesis, not a Russian-participant PQQ trial. The indexed record contains no domestic human intervention; unindexed records may exist.
Read the original sourceStudies and sources
PubChem CID 3078772 · disodium identity
Government chemical database
National Center for Biotechnology Information. PubChem Compound Summary for CID 3078772, Pyrroloquinoline quinone disodium salt. National Library of Medicine.
The record identifies PQQ disodium salt as C14H4N2Na2O8, molecular weight 374.17 g/mol, CAS 122628-50-6.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Not applicable
- Study design
- Primary source record
Free acid, disodium salt, reduced PQQH2, and combination products may differ.
Read the original sourceEFSA safety opinion · novel food, not medicine
EU food-safety assessment
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Turck D et al. Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC) No 258/97. EFSA Journal. 2017;15(11):5058. doi:10.2903/j.efsa.2017.5058.
EFSA concluded PQQ disodium salt was safe under the proposed supplement conditions for healthy adults, excluding pregnant and lactating women. The panel emphasized limited ADME data and small, short human studies; rat renal findings informed the safety margin.
- Participants / model
- Healthy adults as the proposed food-supplement population; not pregnant or lactating
- Treatment
- PQQ disodium salt as a novel food ingredient
- Follow-up
- Safety assessment based on submitted studies
- Study design
- Regulatory food-safety opinion
A novel-food safety conclusion is not medicine approval and does not establish cognition or longevity efficacy.
Read the original sourceChina NHC · fermented PQQ disodium new-food approval
Chinese food-safety regulatory interpretation
National Health Commission of the People's Republic of China. Interpretation of the Announcement on 15 'Three New Foods' including peach gum (Announcement No. 8 of 2023). October 2023.
China's NHC states that synthetic PQQ disodium salt had been approved as a new food raw material in 2022 and that a fermentation-produced form passed safety review in 2023, with a recommended intake ceiling and exclusions for infants, pregnant women, and lactating women.
- Participants / model
- Food consumers under the authorization, excluding specified groups
- Treatment
- Specified synthetic or fermentation-produced PQQ disodium salt raw material
- Follow-up
- 2022 and 2023 food-ingredient actions
- Study design
- Chinese food-safety regulatory record
This is food-ingredient safety authorization, not approval to prevent cognitive decline or aging.
Read the original sourceFDA GRAS response · intended beverage uses
FDA food-ingredient record
U.S. Food and Drug Administration. GRAS Notice No. 694, Pyrroloquinoline quinone disodium salt. Response letter dated September 28, 2017.
FDA closed the notice with 'no questions' regarding the notifier's GRAS conclusion for specified beverage uses at the proposed levels.
- Participants / model
- Consumers of specified conventional beverage uses
- Treatment
- PQQ disodium salt as a food ingredient
- Follow-up
- GRAS notice and response
- Study design
- FDA GRAS notice record
A 'no questions' GRAS letter is not drug approval, supplement efficacy review, or a general safety finding for every product and exposure.
Read the original sourceHealthy Japanese trial · 64 randomized, 58 completed
Randomized controlled trial
Shiojima Y, Takahashi M, Takahashi R, Moriyama H, Bagchi D, Bagchi M, Akanuma M. Effect of Dietary Pyrroloquinoline Quinone Disodium Salt on Cognitive Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study. Journal of the American Nutrition Association. 2022;41(8):796-809. doi:10.1080/07315724.2021.1962770. PMID 34415830.
Sixty-four healthy Japanese adults aged 40 to under 80 who reported forgetfulness were randomized; 58 completed (31 placebo, 27 PQQ). After 12 weeks, multiple Cognitrax domains plus MMSE-J and DECO scores favored PQQ disodium salt.
- Participants / model
- 64 randomized healthy Japanese adults aged 40 to <80 with subjective forgetfulness; 58 completed
- Treatment
- Oral PQQ disodium salt 21.5 mg/day or placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled parallel trial
- Funding
- Ryusendo/product-linked authors
Small completer set, attrition, numerous endpoints, product-linked investigators, and no durable functional or disease outcome.
Read the original sourceOlder Japanese trial · 41 randomized
Randomized controlled trial
Itoh Y, Hine K, Miura H, Uetake T, Nakano M, Takemura N, Sakatani K. Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQ) on Cognitive Functions. Advances in Experimental Medicine and Biology. 2016;876:319-325. doi:10.1007/978-1-4939-3023-4_40. PMID 26782228.
Forty-one healthy older participants received PQQ disodium salt or placebo for 12 weeks. Stroop interference favored PQQ, while the tablet-based visual-spatial finding was confined to a lower-baseline subgroup.
- Participants / model
- 41 healthy older adults
- Treatment
- Oral PQQ disodium salt 20 mg/day or placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- BioPQQ/product-linked program
Small sample, selective/subgroup findings, and no dementia, independence, or long-term outcome.
Read the original sourceExploratory human study · n=10
Small human crossover/metabolic study
Harris CB, Chowanadisai W, Mishchuk DO, Satre MA, Slupsky CM, Rucker RB. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. Journal of Nutritional Biochemistry. 2013;24(12):2076-2084. doi:10.1016/j.jnutbio.2013.07.008. PMID 24231099.
Ten adults completed single- and short repeated-exposure phases. Exploratory inflammatory and metabolomic measures changed; serum free PQQ peaked at about two hours after a single exposure.
- Participants / model
- 10 healthy adults, five women and five men
- Treatment
- Oral PQQ in single and repeated short exposures
- Follow-up
- Single exposure over 48 hours and repeated exposure over 76 hours
- Study design
- Exploratory human metabolic study
Tiny sample, short duration, multiple exploratory biomarkers, and no clinical cognition or longevity endpoint. The approximate two-hour peak is not a validated universal product Tmax.
Read the original sourceHealthy women · no overall AMH change
Single-arm prospective clinical study
Tsuji S, Takiuchi T, Handa M, Miura N, Aoyagi H, Uematsu Y, Shidomi M, Fukada K, Ogura C, Kimura T, Kodama M. Serum anti-Müllerian hormone response to pyrroloquinoline quinone supplementation in healthy women: no overall change and exploratory subgroup findings. Frontiers in Endocrinology. 2026;17:1831604. doi:10.3389/fendo.2026.1831604. PMID 42500134.
Fifty healthy women aged 25-42 entered; the per-protocol analysis included 35. After about 90 days, serum AMH did not change overall (1.561 to 1.439 ng/mL; p=0.182). Small exploratory age-by-baseline-AMH subgroups moved in inconsistent directions.
- Participants / model
- 50 healthy Japanese women aged 25-42 with regular cycles and baseline AMH 0.5 to <3.0 ng/mL; 35 in per-protocol analysis
- Treatment
- Oral PQQ 20 mg/day
- Follow-up
- 90 ± 10 days
- Study design
- Prospective single-arm open-label study
- Funding
- ROHTO Pharmaceutical employees among authors; product support disclosed
No control group, 30% excluded from the per-protocol analysis, hormonal surrogate primary endpoint, and small post hoc-style subgroups. It does not establish fertility, ovarian anti-aging, cognition, or longevity efficacy.
Read the original sourceChinese mouse ovarian-injury study
Animal preclinical study
Dai X, Yi X, Wang Y, Xia W, Tao J, Wu J, Miao D, Chen L. PQQ Dietary Supplementation Prevents Alkylating Agent-Induced Ovarian Dysfunction in Mice. Frontiers in Endocrinology. 2022;13:781404. doi:10.3389/fendo.2022.781404. PMID 35340329.
Sixty female C57BL/6-background mice were randomized to control, alkylating-agent injury, or injury plus PQQ feed. PQQ partially protected ovarian and fertility measures after busulfan/cyclophosphamide injury; pregnancy was 7/7 in control and PQQ groups versus 3/7 in injury controls, while litter size and several ovarian measures remained below uninjured controls.
- Participants / model
- 60 eight-week-old female C57BL/6-background mice across three groups; endpoint-specific subsamples included six per group for estrous monitoring and seven per group for mating
- Treatment
- Feed containing PQQ disodium salt 5 mg/kg, started one week before busulfan/cyclophosphamide injury and continued to sacrifice
- Follow-up
- One month to estrous monitoring; three months to mating or tissue collection; mating followed for two months
- Study design
- Randomized three-group mouse injury-model experiment
This is prevention in a severe chemotherapy-injury mouse model, not natural ovarian aging, a human fertility trial, or cognition/longevity evidence.
Read the original sourceMouse liver-cell mechanism study
Cell preclinical study
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. Journal of Biological Chemistry. 2010;285(1):142-152. doi:10.1074/jbc.M109.030130. PMID 19861415.
In mouse Hepa1-6 liver cells, 15-30 micromolar PQQ increased CREB phosphorylation, PGC-1alpha expression, mitochondrial DNA, and citrate synthase activity; PGC-1alpha siRNA blocked the mitochondrial-biogenesis response.
- Participants / model
- Mouse Hepa1-6 liver cells
- Treatment
- PQQ in vitro
- Follow-up
- Cell-culture experiment
- Study design
- Preclinical cell study
The experiment used mouse liver cells, not a human brain or treated participants; in-vitro concentrations do not define a human exposure.
Read the original sourceJapanese RCT · 70 randomized, main analysis n=62
Randomized double-blind placebo-controlled trial
Tamakoshi M, Suzuki T, Nishihara E, Nakamura S, Ikemoto K. Pyrroloquinoline quinone disodium salt improves brain function in both younger and older adults. Food & Function. 2023;14(5):2496-2501. doi:10.1039/D2FO01515C. PMID 36807425.
At week 12, composite memory (p=0.003) and verbal memory (p=0.001) favored PQQ. Age-stratified differences appeared at different visits and domains; a same-dataset logistic model classified treatment with accuracy 0.57 at week 8 and 0.67 at week 12.
- Participants / model
- 70 healthy Japanese adults aged 20-65 randomized; 66 completed; main result tables analyzed 62 (31 per group)
- Treatment
- Oral BioPQQ disodium salt 20 mg/day or placebo after breakfast
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled parallel trial
- Funding
- Mitsubishi Gas Chemical; company employees authored the paper
The paper does not clearly reconcile the four completers absent from the 62-person table analysis. It tested 15 Cognitrax domains at multiple visits and subgroups without a stated multiplicity correction; the classifier used the same small dataset.
Read the original sourceBeijing RCT · 60 students, single exposure
Randomized double-blind placebo-controlled trial
Zhao C, Wu B, Sui H, Kuan G, Wei G, Yan Y. The effects of pyrroloquinoline quinone and nicotinamide mononucleotide supplementation on interoception following acute exhaustive exercise: a randomised, double-blind, placebo-controlled study. Scientific Reports. 2026;16:5408. doi:10.1038/s41598-025-34191-0. PMID 41651893.
There was no overall between-group advantage for interoception after exhaustive exercise. One MAIA Body Listening interaction was significant (p=0.016), driven by a within-PQQ change; the remaining effects were selective rather than a broad supplement benefit.
- Participants / model
- 60 male physical-education students in Beijing, mean age about 19; 15 per arm
- Treatment
- Single pre-exercise exposure: placebo, PQQ 20 mg, NMN 300 mg, or both
- Follow-up
- One acute exhaustive-exercise session
- Study design
- Randomized double-blind placebo-controlled four-arm trial; retrospectively registered
- Funding
- Fundamental Research Funds for the Central Universities
This was an acute exercise/interoception study in young men, not a cognition or aging trial. Adverse events were not reported.
Read the original sourceMCI mixture RCT · 34 participants
Randomized double-blind placebo-controlled combination trial
Baltic S, Nedeljkovic D, Todorovic N, Ranisavljev M, Korovljev D, Cvejic J, Ostojic J, LeBaron TW, Timmcke J, Stajer V, Ostojic SM. The impact of six-week dihydrogen-pyrroloquinoline quinone supplementation on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals with mild cognitive impairment: a randomized controlled trial. The Journal of Nutrition, Health & Aging. 2024;28(8):100287. doi:10.1016/j.jnha.2024.100287. PMID 38908296.
The primary BDNF time-by-treatment interaction was not significant (p=0.14), and total MMSE and ADAS-Cog interactions were not significant. Only the ADAS-Cog orientation domain favored the mixture (p=0.03); uncontrolled active-arm brain-oxygen and spectroscopy changes cannot establish comparative effects.
- Participants / model
- 34 adults with MCI in Serbia, mean age 71.9 years; 17 per arm
- Treatment
- Alpha Hope mixture containing PQQ 20 mg and hydrogen-producing elemental magnesium 80 mg versus non-hydrogen-producing magnesium placebo
- Follow-up
- Six weeks
- Study design
- Randomized double-blind placebo-controlled parallel combination trial
- Funding
- Product supplied by CalerieLife; author conflicts and hydrogen-product affiliations disclosed
The formulation combined PQQ with hydrogen-producing magnesium, so its result cannot be assigned to PQQ alone. The sample was tiny, baseline BDNF differed sharply, and many secondary measures were tested.
Read the original source2016 mechanism · PQQ is not the mammalian LDH cofactor
Biochemical and cell study
PMID 27230956; PMCID PMC4882622.
PQQ bound LDH, redox-cycled NADH and NAD+, and altered ATP or lactate in fibroblasts.
- Participants / model
- Mouse fibroblasts and rabbit-muscle lactate dehydrogenase
- Treatment
- PQQ in vitro
- Follow-up
- Cell and biochemical experiments
- Study design
- Mechanistic study
The paper states that PQQ does not serve as a mammalian LDH cofactor. It does not establish human vitamin status.
Read the original source40-person RCT · total MoCA null, language positive
Randomized double-blind placebo-controlled human substudy
PMID 32021931; PMCID PMC6994848.
Total MoCA change was placebo 0.60±0.31 versus PQQ 1.25±0.35, p=0.118. Language-domain change was 0.15±0.13 versus 0.65±0.13, p<0.05.
- Participants / model
- 40 healthy Japanese adults aged 50-71
- Treatment
- PQQ disodium 20 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled parallel trial
- Funding
- Japan Science and Technology Agency Matching Planner
Six other MoCA domains were null; no multiplicity correction stated. Two Mitsubishi employees authored and Mitsubishi commissioned testing, despite a no-conflict declaration.
Read the original sourceOlder multi-arm reports · manufacturer summaries
Publisher bibliographic record
Nakano et al. 2009; Koikeda et al. 2011, Medical Consultation & New Remedies 48:519-527.
Manufacturer secondary summaries describe selected early, low-baseline or combination-arm memory findings.
- Participants / model
- Healthy middle-aged and older Japanese adults
- Treatment
- PQQ alone or PQQ plus CoQ10 versus placebo
- Follow-up
- Weeks to months
- Study design
- Reported controlled multi-arm studies
- Funding
- Manufacturer-linked program
The cited manufacturer summaries do not report complete primary tables, exact denominators, or adverse-event accounting. Combination effects cannot be assigned to PQQ.
Read the original source64 randomized, 62 analyzed · strength signal without a reported effect size
Randomized double-blind placebo-controlled trial
Journal of Functional Foods. 2024. DOI 10.1016/j.jff.2024.106012; UMIN000048641.
The abstract and UMIN record report a lower-limb-extensor-strength difference and improvements in walking/function tests.
- Participants / model
- 64 randomized Japanese adults aged 20 to <75; 62 analyzed, 31 per arm; selected against sarcopenia and regular exercise
- Treatment
- PQQ disodium 21.5 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Ryusendo
The abstract does not report numerical effects, confidence intervals, multiplicity handling, or the two dropout reasons. The registry was entered before the trial and publicly disclosed after follow-up; the principal investigator was the company president and CEO.
Read the original source23-man RCT · PGC-1alpha positive, performance null
Randomized placebo-controlled training trial
PMID 31860387; DOI 10.1080/07315724.2019.1705203.
Skeletal-muscle PGC-1alpha protein increased versus placebo.
- Participants / model
- 23 healthy untrained men; 12 PQQ and 11 placebo
- Treatment
- PQQ 20 mg/day versus placebo during supervised endurance training
- Follow-up
- Six weeks
- Study design
- Randomized placebo-controlled trial
- Funding
- Nascent Health Sciences
Aerobic performance and body composition did not differ by group.
Read the original sourceSame 23-man cohort · mitochondrial-marker interactions null
Same-cohort conference report
PMCID PMC9310654.
No supplement-by-time interactions occurred for Complex I, Complex IV, citrate synthase or protein carbonyls.
- Participants / model
- Same 23 men as the endurance-training trial
- Treatment
- PQQ 20 mg/day versus placebo
- Follow-up
- Six weeks
- Study design
- Secondary same-cohort biomarker report
- Funding
- Nascent Health Sciences
This is a follow-up of the same cohort, not an independent trial.
Read the original source2026 mouse study · overall survival null
Controlled animal lifespan study
PMID 42132809; DOI 10.1039/d6fo00788k.
The 75th survival percentile was 269 days in control and 466 days with PQQ; selected truncated-interval tests were positive.
- Participants / model
- Male senescence-accelerated SAMP8 mice; lifelong control n=15, PQQ n=16, IPQ n=15
- Treatment
- 0.02% dietary PQQ, about 25 mg/kg/day in young adults
- Follow-up
- Lifelong and separate 16-week midlife experiments
- Study design
- Controlled animal lifespan study
- Funding
- Mitsubishi Gas Chemical
Overall survival was null: median 455 versus 513 days, log-rank p=0.6570 and Gehan p=0.1559. Grip and several muscle outcomes were null. Special male mouse strain and high exposure.
Read the original source32 randomized, 29 analyzed · overall lipid results weak
Randomized double-blind placebo-controlled trial
DOI 10.3177/jnsv.61.233.
A high-baseline-LDL subgroup of six versus five differed at week 6; week 12 was marginal.
- Participants / model
- 32 adults aged 40-60 with triglycerides 110-300 mg/dL; 29 analyzed
- Treatment
- PQQ 20 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Mitsubishi-linked program
Three triglyceride outliers were excluded post hoc. Overall LDL p=0.052, total cholesterol p=0.087; triglycerides, body fat and BMI null; HDL change favored placebo at week 6.
Read the original source22 randomized, final 11 vs 8 · selected forearm result
Randomized double-blind placebo-controlled trial
DOI 10.3177/jnsv.61.241.
One forearm water-loss change at week 4 and selected wrinkle/pigmentation self-ratings favored PQQ.
- Participants / model
- 22 healthy women with mild dry skin; final 11 PQQ and 8 placebo
- Treatment
- PQQ 20 mg/day versus placebo
- Follow-up
- Eight weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Mitsubishi-linked program
Raw forearm measures, cheek water loss, conductance and all viscoelasticity outcomes were null; three placebo dropouts and many comparisons.
Read the original source17-person open-label study · uncontrolled pre-post changes
Open-label uncontrolled study
DOI 10.31989/ffhd.v2i8.81.
Several mood, quality-of-life and sleep questionnaires improved from baseline; one cortisol-awakening correlation was r=-0.55.
- Participants / model
- 17 office workers with fatigue or sleep complaints
- Treatment
- PQQ 20 mg/day
- Follow-up
- Eight weeks
- Study design
- Open-label uncontrolled pre-post study
- Funding
- Mitsubishi-linked program
No placebo, blinding or fixed primary hierarchy; expectancy and regression to mean cannot be separated.
Read the original source20-person surrogate study · no clinical endpoint
Randomized placebo-controlled trial
PMID 27526146; DOI 10.1007/978-3-319-38810-6_29.
Resting right-prefrontal oxygenated and total hemoglobin increased; oxygen saturation decreased more.
- Participants / model
- 20 healthy adults aged 50-70; 10 per arm
- Treatment
- PQQ 20 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized placebo-controlled study
- Funding
- Mitsubishi-linked program
Tiny hemodynamic-surrogate study with no demonstrated cognition or functional benefit.
Read the original source2019 Russian review · no local clinical cohort
Russian-language literature review
Использование пирролохинолин хинона как препарата нейропротекции. 2019.
The review summarizes foreign cell, animal and human PQQ literature.
- Participants / model
- Literature review; no participant cohort
- Treatment
- No intervention
- Follow-up
- Review
- Study design
- Russian-language literature review
This is a Russian-language synthesis, not a Russian-participant PQQ trial. The indexed record contains no domestic human intervention; unindexed records may exist.
Read the original sourceWhy is PQQ in C tier?
Tier C: small controlled studies report selected cognition and physical-function changes, while total cognitive scores, direct exercise performance and broad metabolic outcomes include clear nulls. Trials are short, endpoint-heavy and often product-linked. No clinical disease, dementia-prevention or human-longevity outcome has been shown, and long-term safety remains limited.