Ingredient Reference
PQQ (Pyrroloquinoline Quinone): Chemistry, Forms, Studied Amounts and Safety
A reference page on PQQ chemistry, the disodium salt used in supplements, food amounts, each human trial and its daily amount, safety data, and regulatory status in the US and EU.
Pre-order Brain Energy CapsulesPQQ on the Label
What our planned label lists, per serving.
Planned formula. Pre-order, no payment taken now. The product page reads: "Pre-order to join the launch list. No payment is taken now." How this compares with research amounts: 20 mg a day is the amount most PQQ trials below used, and the top amount EFSA assessed for food supplements. Use as directed on the label once it ships.
PQQ at a Glance
| Item | Details |
|---|---|
| Names | Pyrroloquinoline quinone, PQQ, methoxatin. Supplements use PQQ disodium salt. |
| Chemistry | Free acid C14H6N2O8, 330.2 g/mol (CAS 72909-34-3). Disodium salt C14H4N2Na2O8, 374.17 Da (CAS 122628-50-6). |
| In food | Free PQQ at 3.7 to 61 ng per gram across the foods surveyed; about 0.08 mg a day from diet (EFSA estimate). |
| Amounts in human trials | Mostly 20 to 21.5 mg a day for 6 to 12 weeks. |
| Main cautions | Not assessed for pregnancy, breastfeeding or children; kidney changes in rats at high doses. |
| Regulatory | EU novel food since 2018, up to 20 mg a day in supplements. Two FDA GRAS notices for beverages, 2016. |
Here for benefits or timing? What PQQ does, how to take it and how it compares with CoQ10 are covered in PQQ Benefits: What It Does, Dosage, Side Effects and PQQ vs CoQ10. This page sticks to reference facts.
Chemistry, Names and Natural Sources
PQQ is an ortho-quinone built on three fused rings, a pyrrole joined to a quinoline, carrying three carboxylic acid groups. EFSA's chemical name for the salt, disodium 9-carboxy-4,5-dioxo-1H-pyrrolo[5,4-f]quinoline-2,7-dicarboxylate, spells this out: two oxo (quinone) groups and three carboxyl groups, two of them as sodium salts.
A bacterial cofactor first
PQQ was first described as a cofactor for bacterial dehydrogenases, beginning with work on glucose dehydrogenase in 1964, and its structure was settled over the next fifteen years. It belongs to the quinoprotein family and also serves bacterial alcohol dehydrogenases. In lab assays it cycles between oxidized and reduced states 100 to 1,000 times more efficiently, mole for mole, than enediols such as vitamin C. It is not classed as a vitamin.
How much is in food
A 1995 survey found free PQQ in every food and drink sampled, at 3.7 to 61 ng per gram or millilitre, and levels in human tissues 5 to 10 times lower than in foods. EFSA lists potato, spinach, parsley, green pepper, natto, tofu, miso, milk and egg among sources, mostly at 1 to 30 ng per gram and up to 61 ng per gram in natto. Its cautious estimate of intake from food was 0.08 mg a day, so 20 mg is 250 or more times that amount. Human milk holds about 20 to 30 micrograms of PQQ per litre, or 140 to 180 micrograms counting related compounds.
Forms and How to Read a Label
| Form | What it is | What to know |
|---|---|---|
| PQQ disodium salt, fermented | Made with the bacterium Hyphomicrobium denitrificans CK-275, then purified (sold as BioPQQ). | The form EFSA assessed: at least 99.0% pure, reddish brown powder. |
| PQQ disodium salt, synthetic | Made by chemical synthesis; one supplier describes it as identical to the fermented form. | Ask for the purity and contaminant specification. |
| PQQ free acid | The parent molecule without sodium. | Not interchangeable with the salt gram for gram. |
Salt weight versus PQQ weight
Labels usually give the weight of the salt. Because sodium adds mass, 20 mg of PQQ disodium salt holds about 17.6 mg of PQQ (330.2 divided by 374.17 is about 0.88). The trials below report amounts of the disodium salt.
What to look for
- The form named: PQQ disodium salt or PQQ.
- Milligrams per serving, not only a blend total.
- Source: fermentation or synthesis, with a purity figure.
- Ingredient testing for heavy metals and microbes.
Human Research, Study by Study
Each trial gave PQQ by mouth. Amounts are as the authors reported them.
| Study | Who | Amount a day | Length | Measured | Result |
|---|---|---|---|---|---|
| Harris 2013, J Nutr Biochem | 10 adults (5 women, 5 men) | 0.2 mg/kg once; then 0.3 mg/kg daily | 48 hours; 76 hours | Plasma and urine PQQ, antioxidant potential, CRP, IL-6, clinical blood panel, urine metabolites | CRP and IL-6 fell; urine metabolites shifted in a pattern consistent with mitochondrial activity; blood panel unchanged and in range |
| Nakano 2012, Funct Foods Health Dis | 17 adults, open label (no placebo group) | 20 mg | 8 weeks | Mood (POMS), sleep questionnaires, quality of life, cortisol awakening response | Mood, quality of life and sleep scores improved from baseline; changes tracked the cortisol response |
| Itoh 2016, Adv Exp Med Biol | 41 healthy older adults, placebo controlled | 20 mg | 12 weeks | Stroop tests, Touch M test, prefrontal blood flow, blood, urine and exams | Smaller change in Stroop interference than placebo; Touch M gains in lower scorers; no abnormal findings |
| Shiojima 2022, J Am Nutr Assoc | 58 healthy adults reporting age related forgetfulness, placebo controlled | 21.5 mg | 12 weeks | Computerized cognitive battery | Placebo comparison favored PQQ on reaction time, complex attention, cognitive flexibility, and composite and verbal memory; no adverse events |
| Hwang 2020, J Am Coll Nutr | 23 untrained men, placebo controlled, all doing endurance training | 20 mg | 6 weeks | VO2peak, exercise time, body composition, muscle PGC-1alpha | VO2peak and exercise time rose in both groups; PGC-1alpha, a marker of new mitochondria, rose more with PQQ |
| Tamakoshi 2023, Food Funct | Adults aged 20 to 65, placebo controlled | 20 mg | 12 weeks | Cognitive battery, by age group | Composite and verbal memory improved at 12 weeks; flexibility and processing speed improved by 8 weeks in ages 20 to 40 |
Amounts Used in Human Studies
Study amounts, not directions. Follow your product's label.
| Setting | Amount |
|---|---|
| Cognitive trials | 20 to 21.5 mg a day for 12 weeks |
| Exercise trial | 20 mg a day for 6 weeks |
| Short metabolic study (Harris 2013) | 0.075 to 0.3 mg per kg a day, about 5 to 21 mg |
| 12 human studies EFSA reviewed | 10 to 100 mg a day, for 3 days to 24 weeks |
| EU maximum for food supplements | 20 mg a day, healthy adults |
| Typical diet (EFSA estimate) | About 0.08 mg a day |
Safety, Side Effects and Interactions
None of the trials above recorded adverse events at 20 to 21.5 mg a day for up to 12 weeks, and Itoh 2016 found no abnormal blood, urine or physical exam results.
What the animal data show
EFSA set a no observed adverse effect level of 100 mg per kg of body weight a day from a 90 day rat study. Kidney findings at 200 mg per kg in a 28 day rat study were the critical effect. For a 70 kg adult taking 20 mg a day, that leaves a margin of 344, which EFSA called sufficient. EFSA also noted that the human studies were not designed to assess kidney function.
Genotoxicity
A bacterial mutation (Ames) test and a mouse micronucleus test up to 2,000 mg per kg were negative. One lab chromosome test showed some effect that a repeat test and a human lymphocyte test did not reproduce. EFSA saw no genotoxicity concern.
Who should ask a clinician first
EFSA's assessment covered healthy adults and excluded pregnant and breastfeeding women, and EFSA states that PQQ supplements are not intended for children. Ask a clinician first if you have a kidney condition, take prescription medicine, or combine several supplements. The trials and the EFSA opinion cited here did not include drug interaction studies.
Regulatory Status in the US and EU
United States
PQQ is sold as a dietary supplement under the Dietary Supplement Health and Education Act of 1994. FDA does not approve supplements before sale; the maker is responsible for safety and labeling. Mitsubishi Gas Chemical filed a new dietary ingredient notification for its fermented BioPQQ, which its attorney described in 2014 as successful. For conventional foods, FDA responded to two GRAS notices for PQQ disodium salt with no questions: GRN 625 from Nascent Health Sciences (August 18, 2016), for sport, energy and enhanced water drinks at up to 8 mg per serving, and GRN 641 from Zhejiang Hisun Pharmaceutical (October 14, 2016), for sport and energy drinks at up to 5 mg per serving and fortified water at up to 20 mg. A no questions letter is not FDA's own GRAS determination.
European Union
In 2017 EFSA concluded that PQQ disodium salt, at intakes up to 20 mg daily in food supplements, is safe for healthy adults. Commission Implementing Regulation (EU) 2018/1122 of 10 August 2018 then authorised it as a novel food, in force from 2 September 2018.
PQQ FAQ
What is PQQ disodium salt?
It is PQQ with two of its three acid groups bound to sodium, a reddish brown powder with the formula C14H4N2Na2O8. It is the form EFSA assessed and the form used in the trials on this page.
How much actual PQQ is in 20 mg of PQQ disodium salt?
About 17.6 mg. The salt weighs 374.17 Da per molecule and the free acid 330.2, so roughly 88% of the salt's weight is PQQ itself.
Is supplement PQQ made by fermentation or by chemical synthesis?
Both exist. The ingredient EFSA assessed is made by fermenting the bacterium Hyphomicrobium denitrificans and purified to at least 99%. Other suppliers sell PQQ made by chemical synthesis.
How much PQQ does a normal diet provide?
Very little. Foods hold nanogram amounts per gram, and EFSA's cautious estimate of daily intake from food was about 0.08 mg.
What is the EU status of PQQ?
In 2017 EFSA judged PQQ disodium salt safe in food supplements at intakes up to 20 mg daily, for healthy adults excluding pregnant and breastfeeding women and children. The European Commission authorised it as a novel food in August 2018.
Has FDA reviewed PQQ?
FDA answered two GRAS notices for PQQ disodium salt in beverages in 2016 with no questions. FDA does not approve dietary supplements before sale.
How much PQQ is in Brain Energy Capsules?
The planned formula lists PQQ 20 mg per serving, alongside 500 mg citicoline and 25 mg L-ergothioneine. It is a pre-order, and no payment is taken now.
More on PQQ
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Guides
Sources
- Jonscher KR, et al. Pyrroloquinoline quinone is more than an antioxidant: a vitamin-like accessory factor important in health and disease prevention. Biomolecules, 2021. DOI 10.3390/biom11101441
- Kumazawa T, et al. Levels of pyrroloquinoline quinone in various foods. Biochemical Journal, 1995. PMC1136652
- EFSA NDA Panel. Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC) No 258/97. EFSA Journal, 2017;15(11):5058. efsa.europa.eu
- Commission Implementing Regulation (EU) 2018/1122 authorising pyrroloquinoline quinone disodium salt as a novel food. 10 August 2018. eur-lex.europa.eu
- Harris CB, et al. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. Journal of Nutritional Biochemistry, 2013. PubMed 24231099
- Nakano M, et al. Effects of oral supplementation with pyrroloquinoline quinone on stress, fatigue, and sleep. Functional Foods in Health and Disease, 2012. DOI 10.31989/ffhd.v2i8.81
- Itoh Y, et al. Effect of the antioxidant supplement pyrroloquinoline quinone disodium salt (BioPQQ) on cognitive functions. Advances in Experimental Medicine and Biology, 2016. PubMed 26782228
- Shiojima Y, et al. Effect of dietary pyrroloquinoline quinone disodium salt on cognitive function in healthy volunteers. Journal of the American Nutrition Association, 2022. PubMed 34415830
- Hwang PS, et al. Effects of pyrroloquinoline quinone (PQQ) supplementation on aerobic exercise performance and indices of mitochondrial biogenesis in untrained men. Journal of the American College of Nutrition, 2020. DOI 10.1080/07315724.2019.1705203
- Tamakoshi M, et al. Pyrroloquinoline quinone disodium salt improves brain function in both younger and older adults. Food and Function, 2023. pubs.rsc.org
- US Food and Drug Administration. Agency Response Letter, GRAS Notice No. GRN 000625. 2016. fda.gov
- US Food and Drug Administration. Agency Response Letter, GRAS Notice No. GRN 000641. 2016. fda.gov
- NutraIngredients. Nascent 100% confident in the quality and safety of its PQQ, despite FDA safety concerns. May 2014. nutraingredients.com
- US Food and Drug Administration. Questions and Answers on Dietary Supplements. fda.gov
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. If you are pregnant, breastfeeding, taking medication, managing a kidney condition or another health condition, talk with a qualified healthcare professional before use.