PQQ

What PQQ is

Pyrroloquinoline quinone was discovered as a coenzyme of bacterial enzymes. It can accept and donate electrons, that is, switch between an oxidized and a reduced form, and do so very many times in a row. That is why it is considered a particularly stable redox molecule.

In foods, free PQQ occurs only in traces; one analysis found 3.7 to 61 ng per gram. Supplements deliver orders of magnitude more: EFSA estimates that 20 mg per day is at least 250 times the usual dietary intake. It is usually sold as PQQ disodium salt, which is produced by fermentation with bacteria. The EU authorization goes back to an application by the Japanese manufacturer Mitsubishi Gas Chemical, which obtains the material using the bacterium Hyphomicrobium denitrificans.

How it is supposed to work

The mitochondria narrative has a solid origin. In mouse liver cells, PQQ increased the number of mitochondria, respiration and the content of mitochondrial DNA. The pathway ran via the activation of CREB and PGC-1α, the central switch for the formation of new mitochondria. Without these two factors, the effect did not occur.

In humans there is a matching indication. In a study with 23 untrained men, PGC-1α protein content rose more with 20 mg PQQ and 6 weeks of endurance training than with placebo. In a small crossover study with 10 people, the inflammatory markers CRP and IL-6 fell after a few days, and urinary metabolites shifted toward a more active mitochondrial metabolism. The picture is not uniform, however: in human skin cells, PQQ did not increase mitochondrial formation. For the brain, the study authors refer to rat experiments in which animals given PQQ in their feed learned better, and to increased production of nerve growth factor.

Memory and attention

Most human studies concern cognitive performance. In a study with 64 healthy people aged 40 to 80, 21.5 mg daily over 12 weeks improved several areas of a computer-based test, including verbal memory, reaction time and attention. A second study with 41 healthy older people found a more stable Stroop test result with 20 mg, that is, better selective attention.

A third study examined adults aged 20 to 65. After 12 weeks, composite and verbal memory had improved. The split by age is interesting: in the younger participants, improvements in flexibility and processing speed appeared after just 8 weeks; in the older ones, they concerned memory and appeared after 12 weeks.

User reports

A documented voice of users comes from a skin study: women with dry skin took 20 mg daily for 8 weeks. Reduced water loss through the skin was measured, and in the questionnaires the participants described a positive impression of their skin. Such self-reports are reports, not proof of efficacy, but they show what users are interested in.

What the studies show

64 healthy people, 12 weeks

Randomized, double-blind, placebo-controlled, participants aged 40 to under 80, 21.5 mg daily. 58 people completed the study. The primary endpoint, a computer-based cognitive test, improved in several areas compared with placebo, as did a forgetfulness questionnaire and the Mini-Mental State Examination. No side effects were observed.

Training and mitochondria

23 untrained men took 20 mg PQQ or placebo and did endurance training for 6 weeks. Both groups became fitter; there was no difference in aerobic performance between the groups. The marker PGC-1α rose significantly only with PQQ. A biological signal without a measurable performance advantage.

Metabolic signals after a few days

In a crossover study with 10 people, 5 women and 5 men, participants first received a single dose of 0.2 mg per kilogram of body weight and later 0.3 mg per kilogram daily. After 76 hours of daily intake, CRP, IL-6 and trimethylamine N-oxide had fallen, while routine laboratory values remained unchanged. The authors see this as a first bridge between the animal data and humans. With 10 people and a few days, this is a pilot finding that deserves a larger study.

Mild cognitive impairment

34 older people, mean age 71.9 years, received a mixture of hydrogen-generating minerals and PQQ or placebo for 6 weeks. The primary endpoint BDNF rose within the group, but the comparison with placebo was not significant (p = 0.14). Orientation in the ADAS-Cog improved (p = 0.03), as did oxygen saturation in the brain, from 48.4 to 52.8 %. Because it is a combination product, the contribution of PQQ cannot be isolated.

Where the data stop

All human studies are small and run for 12 weeks at most. Two of the three cognition studies have authors from the manufacturer of the raw material; an independent replication and a meta-analysis are lacking. The improvements concern individual test areas; real-life endpoints were barely assessed.

The formation of new mitochondria is well demonstrated in cell culture and animals, but in humans only through the rise of a protein marker, without a performance gain. For blood lipids, a study with 29 adults found unchanged triglycerides and only a borderline significant decrease in LDL cholesterol from 136.1 to 127.0 mg/dL. A study without a control group in 50 women found no effect on anti-Müllerian hormone as a marker of ovarian reserve. According to EFSA, how PQQ is absorbed and metabolized in humans has been studied only to a limited extent.

Status, approval and legal

PQQ disodium salt has been authorized in the EU as a novel food since September 2, 2018, but only for food supplements for adults, excluding pregnant and breastfeeding women. The maximum amount is 20 mg per day, and the label must refer to the target group. There is no authorized health claim. Relevance to doping is not described in the literature reviewed.

Safety

In the human studies of up to 12 weeks, no adverse events occurred, and blood and urine values remained unremarkable. EFSA considers 20 mg per day safe for healthy adults, with a margin of safety of 344 relative to the NOAEL from animal studies. Pregnant and breastfeeding women are excluded from the authorization. Long-term data in humans are lacking, and interactions with medicines are not described in the literature reviewed.

Sources

• Shiojima et al., J Am Nutr Assoc 2022
• Itoh et al., Adv Exp Med Biol 2016
• Tamakoshi et al., Food Funct 2023
• Hwang et al., J Am Coll Nutr 2020
• Baltic et al., J Nutr Health Aging 2024
• Harris et al., J Nutr Biochem 2013
• Chowanadisai et al., J Biol Chem 2010
• EFSA NDA Panel, EFSA Journal 2017
• Commission Implementing Regulation (EU) 2018/1122