PQQ is a small quinone made by bacteria and found in trace amounts in foods such as natto, parsley and green tea. It builds new mitochondria in cultured cells. In humans the evidence is thin: a handful of small trials, most of them industry funded. In Great Britain it is a regulated novel food capped at 20 mg a day.
What is PQQ?
Pyrroloquinoline quinone is a compact, water soluble molecule with three fused rings and three carboxylic acid groups. It was identified in the 1960s as the redox cofactor of certain bacterial dehydrogenases, enzymes that let bacteria run their metabolism on methanol or glucose. In those organisms its job is unambiguous: it sits in the active site of a protein and carries electrons.
The interesting property is how well it does that. PQQ can cycle through thousands of oxidation and reduction turns without falling apart, which is unusual and is the origin of the claim that it is a uniquely stable antioxidant, a word that has had a hard two decades in randomised trials. That much is chemistry, and it is not in dispute.
PQQ turns up in small amounts across many foods, presumably because bacteria are everywhere in the food chain. Fermented soybeans, in the form of natto, are the richest measured source. Parsley, green tea, green peppers, kiwi fruit and human breast milk all contain it. Dietary intake in a normal diet is measured in micrograms a day, not milligrams, which is the single most useful number to keep in mind for the rest of this article.
Is PQQ a vitamin? The claim, and what happened to it
You will see PQQ described as the first new vitamin discovered since 1948, or as a vitamin like compound. Those two phrases are not the same thing, and the gap between them is a real scientific dispute rather than a marketing nuance.
HOW PQQ BECAME A VITAMIN, AND STOPPED BEING ONE
2003, the claim
Kasahara and Kato report in Nature that PQQ is a new redox cofactor vitamin for mammals. Their evidence is a mouse enzyme in lysine metabolism, which they predict to be a PQQ dependent dehydrogenase.
2005, the objection
Felton and Anthony reply in Nature. The prediction rested on sequence databases that label beta propeller structures as PQQ binding motifs. The enzyme has a seven bladed beta propeller and nothing indicates it uses PQQ at all.
Since then, the position
No PQQ dependent enzyme has been identified in mammals. Without one, PQQ cannot meet the definition of a vitamin, which requires an essential function that its absence disrupts.
What is left, and it is not nothing
Animals fed diets deliberately stripped of PQQ show reduced growth, impaired reproduction and lower mitochondrial content. Something is happening. It is described as vitamin like precisely because nobody can name the enzyme.
How PQQ is supposed to work
The mechanism everyone cites comes from Chowanadisai and colleagues in 2010. It is worth being precise about what they did, because the precision is usually lost. They exposed mouse Hepa1-6 liver cells, a cultured cell line, to 10 to 30 micromolar PQQ for 24 to 48 hours. Mitochondrial DNA content, citrate synthase activity, cytochrome c oxidase activity and cellular oxygen consumption all rose.
They then traced the route. PQQ triggered phosphorylation of CREB at serine 133, activated the PGC-1 alpha promoter, and raised PGC-1 alpha messenger RNA and protein. When either PGC-1 alpha or CREB was knocked down with interfering RNA, the effect disappeared. That is a well built experiment with a clean causal chain.
Rucker and his group has since argued the case more broadly. In a 2021 review they set out PQQ as an accessory factor rather than a classical cofactor, and propose a second route: by modulating lactate dehydrogenase and related enzymes, PQQ may raise NAD+ dependent sirtuin activity, which in turn drives PGC-1 alpha, NRF-1, NRF-2 and TFAM. They also note that removing PQQ from the diet of young animals produces something that looks like a vitamin deficiency, and that restoring it reverses the picture in a dose dependent way. It is a coherent argument built almost entirely on animal and cell data, written by the researchers who have spent thirty years on the molecule.
It is also a cell line in a dish. The concentrations used, 10 to 30 micromolar, are not obviously reachable in a human liver by swallowing a capsule. Nobody has shown that a person taking PQQ builds measurably more mitochondria in any tissue, in the way that lutein measurably raises the pigment density of the retina and the size of that rise tracks the change in vision. When a label says PQQ promotes mitochondrial biogenesis, this experiment is what it is pointing at.
What has been measured in humans
Two studies carry most of the human evidence, and neither is large.
Harris and colleagues ran a crossover study in 2013 with ten subjects, five women and five men. In the first arm they gave a single dose of 0.2 mg PQQ per kilogram of body weight and followed plasma and urine for 48 hours. In the second they gave 0.3 mg per kilogram daily and measured at 76 hours. Standard clinical indices, cholesterol, glucose, triglycerides and the rest, were normal and unchanged. What did move was inflammation: plasma C reactive protein and interleukin 6 both fell significantly, alongside changes in urinary methylated amines. Ten people, three days. It is a signal, not a result.
Shiojima and colleagues published a randomised, double blind, placebo controlled trial in 2021. Sixty four healthy Japanese adults were assigned to 21.5 mg a day of PQQ disodium salt or placebo for twelve weeks, and 58 completed it. The composite memory domain of the Cognitrax battery improved significantly against placebo. Two things are worth saying alongside that finding: the trial tested a branded ingredient and several authors are associated with the supplier, and a single twelve week trial in 58 people is where a question starts rather than where it ends.
WHERE THE PQQ EVIDENCE ACTUALLY SITS
Is PQQ the same thing as CoQ10?
No, and the two are often sold together on the assumption that they are complementary. They belong to different chemical families and sit in different parts of the cell.
| PQQ | CoQ10 | |
|---|---|---|
| Chemistry | Small water soluble quinone, three rings | Large fat soluble quinone with a long isoprenoid tail |
| Where it sits | Cytosol and extracellular fluid | Inner mitochondrial membrane |
| Made by the body | No, bacterial origin | Yes, synthesised in every cell |
| Established role in humans | None identified | Electron carrier in the respiratory chain |
| Depleted by common drugs | Not described | Yes, statins reduce circulating levels |
| GB regulatory status | Authorised novel food, 20 mg a day maximum | Long standing food supplement ingredient |
The honest summary is that CoQ10 has a defined job in human mitochondria and a known reason to run low. PQQ has neither. Whether taking them together does anything a person can feel has not been tested properly.
How far a capsule is from a plate
This is the number that reframes the whole subject, and it comes from the European Food Safety Authority assessment that underpins the authorisation. The maximum level of 20 mg a day is, in the panel’s own words, at least 250 times higher than the estimated background intake of PQQ occurring naturally in foods.
Form matters here too, and the labels are inconsistent. What is authorised in Great Britain is the disodium salt, produced by fermentation with the bacterium Hyphomicrobium denitrificans and purified to at least 99 per cent. The branded ingredients you will see named on packs, BioPQQ and mnemoPQQ among them, are that same salt. A product listing PQQ as a free acid is not the material the authorisation covers, and it is not the material the human trials used.
So a PQQ supplement is not topping up a dietary shortfall. It is delivering a pharmacological quantity of a compound your diet supplies in trace amounts, with no established requirement and no deficiency state to correct. That may still turn out to be useful. It is simply a different proposition from taking vitamin D through a British winter, and the two get discussed in the same tone of voice.
The same question is worth asking of any concentrated plant compound you take. What matters is not the milligram figure on the front but how much of it reaches the tissue, which is the whole argument for a biodisponible turmeric formulation over ground spice, and the reason that argument has to be made with absorption data rather than with dose.
What the law allows in Great Britain
PQQ disodium salt is a regulated novel food, not an ordinary supplement ingredient. It was authorised on 2 September 2018 and it appears on the Great Britain novel foods register maintained by the Food Standards Agency, having carried over from the EU authorisation before the registers separated at the start of 2021. The conditions attached to it are specific.
20 MG A DAY
The maximum permitted level in a food supplement. Anything on sale here above that figure is outside the authorisation.
ADULTS ONLY
Pregnant and lactating women are explicitly excluded from the authorised population. The safety dossier did not cover them.
A MANDATORY STATEMENT
The label must carry the words that the supplement should be consumed by adults only, excluding pregnant and lactating women.
The safety margin behind that ceiling is public. The EFSA panel took a no observed adverse effect level of 100 mg per kilogram of body weight per day from a 90 day repeated dose oral toxicity study, compared it with the proposed 20 mg a day, which works out at 0.29 mg per kilogram for a 70 kg adult, and calculated a margin of exposure of 344. The panel judged that sufficient and noted at the same time that information on absorption, distribution, metabolism and excretion in humans is limited.
One practical consequence. The five year data protection that reserved the market to a single Japanese supplier expired on 2 September 2023, which is why more brands appeared afterwards. It changed who may sell it. It did not change the dose ceiling or the excluded groups.
Side effects, and who should leave it alone
Reported side effects in the small human trials are mild and uncommon: headache, drowsiness or its opposite, and some digestive upset. Nothing serious has been documented at the authorised level. That statement carries less weight than it sounds, because the total number of people studied for twelve weeks or more is in the dozens rather than the thousands.
- Pregnant and breastfeeding women. Excluded from the authorisation. This is not caution on the part of a writer, it is the condition of sale.
- Anyone under 18. The authorised population is adults.
- Anyone on prescribed medication. Interaction data barely exists. Ask a pharmacist before adding it.
- Anyone taking it for a diagnosed condition. PQQ carries no authorised health claim in Great Britain, which means no claim about treating or preventing anything is lawful on a label.
If what brought you here is fatigue, brain fog or a tendon that will not settle, the sequence matters. Persistent fatigue deserves a GP appointment and a blood test before it deserves a capsule, because thyroid disease, iron deficiency and sleep apnoea all present that way. A stubborn tendon responds to graded loading, and a supplement formulated for tendon pain works alongside that rehabilitation rather than in place of it.
Frequently asked questions
What is PQQ used for?
It is sold for energy, mental clarity, sleep and mitochondrial support. None of those uses carries an authorised health claim in Great Britain. The underlying research is mostly in cultured cells and rodents, with two small human trials on inflammatory markers and on memory.
Is PQQ the same thing as CoQ10?
No. CoQ10 is a large fat soluble quinone that your body makes and that carries electrons inside the mitochondrial membrane. PQQ is a small water soluble quinone of bacterial origin with no identified enzyme partner in humans. They are chemically related as quinones and unrelated in function.
What are the side effects of taking PQQ?
Headache, sleepiness or restlessness and mild digestive upset have been reported. No serious adverse effect has been documented at the 20 mg a day ceiling authorised in Great Britain. The evidence base is small, so absence of reports is not the same as evidence of safety over years.
Does PQQ deplete glutathione?
No human study has shown that. The idea comes from the chemistry: PQQ is an efficient redox cycler, and a compound that cycles can in principle consume reducing equivalents such as glutathione in a test tube. That has not been demonstrated in people at dietary or supplement levels.
Is PQQ a vitamin?
Not on the accepted definition. A 2003 paper in Nature proposed it as one, and a 2005 reply in the same journal showed the supporting enzyme identification was an artefact of sequence annotation. No PQQ dependent enzyme has been found in mammals since. Vitamin like is the accurate phrase.
Which foods contain PQQ?
Natto, the Japanese fermented soybean, is the richest measured source. Parsley, green tea, green peppers, kiwi fruit, papaya and human breast milk all contain small amounts. Ordinary dietary intake is in the microgram range, several hundred times below a supplement dose.
How much PQQ is allowed in a UK supplement?
Twenty milligrams a day is the maximum permitted level on the Great Britain novel foods register, in food supplements only, for adults excluding pregnant and lactating women, with that exclusion printed on the label. This is a legal ceiling set by the safety assessment, not a recommended intake.
Sources
Kasahara T., Kato T. A new redox-cofactor vitamin for mammals. Nature, 2003. DOI: 10.1038/422832a
Felton L.M., Anthony C. Role of PQQ as a mammalian enzyme cofactor? Nature, 2005. DOI: 10.1038/nature03322
Chowanadisai W., Bauerly K.A., Tchaparian E., Wong A., Cortopassi G.A., Rucker R.B. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. Journal of Biological Chemistry, 2010. DOI: 10.1074/jbc.M109.030130
Harris C.B., Chowanadisai W., Mishchuk D.O., Satre M.A., Slupsky C.M., Rucker R.B. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. Journal of Nutritional Biochemistry, 2013. DOI: 10.1016/j.jnutbio.2013.07.008
EFSA Panel on Dietetic Products, Nutrition and Allergies. Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC) No 258/97. EFSA Journal, 2017. DOI: 10.2903/j.efsa.2017.5058
Shiojima Y., Takahashi M., Takahashi R., et al. Effect of dietary pyrroloquinoline quinone disodium salt on cognitive function in healthy volunteers: a randomized, double-blind, placebo-controlled, parallel-group study. Journal of the American Nutrition Association, 2021. DOI: 10.1080/07315724.2021.1962770
Jonscher K.R., Chowanadisai W., Rucker R.B. Pyrroloquinoline-quinone is more than an antioxidant: a vitamin-like accessory factor important in health and disease prevention. Biomolecules, 2021. DOI: 10.3390/biom11101441
This article is general information, not medical advice. PQQ carries no authorised health claim in Great Britain. Speak to a pharmacist or your GP before starting a supplement, particularly if you take prescribed medication.
