In plain terms: PQQ (Pyrroloquinoline Quinone) shows early signals in human research but the evidence is limited -- small trials, surrogate endpoints, or not yet independently replicated. It is an emerging area, not yet a proven one.
PQQ (Pyrroloquinoline Quinone)
The evidence as the record states it
Three small randomized placebo-controlled trials measured cognition, all with a branded PQQ disodium salt and all 12 weeks. Itoh et al. (Adv Exp Med Biol, 2016; PMID 26782228): 41 healthy older adults, BioPQQ 20 mg/day; Stroop interference improved against placebo, and a visual-spatial test improved only in the half with lower baseline scores. Shiojima et al. (J Am Nutr Assoc, 2022; PMID 34415830): 64 healthy adults aged 40 to 80, mnemoPQQ 21.5 mg/day; Cognitrax was the primary outcome and several domains improved against placebo. Tamakoshi et al. (Food Funct, 2023; PMID 36807425): adults aged 20 to 65, PQQ 20 mg/day; composite and verbal memory improved at 12 weeks. Two further trials measured no cognition: Nakano et al. (Adv Exp Med Biol, 2016; PMID 27526146) measured prefrontal blood flow by near-infrared spectroscopy, and Harris et al. (J Nutr Biochem, 2013; PMID 24231099) measured blood inflammatory markers in 10 young adults with no placebo arm. Grade C: small manufacturer-linked trials on cognitive test scores, none independently replicated; nothing here speaks to dementia prevention or longevity.
Why Grade C and not Grade B
Grade C reflects early or limited human evidence -- small trials, surrogate endpoints, or preliminary findings not yet independently replicated. The evidence points in a promising direction but does not yet meet the standard for Grade B. A single well-powered, independently replicated trial with a meaningful endpoint would move this to Grade B or higher.
What would move this grade
A well-powered randomized trial with an objective, clinically meaningful primary endpoint and at least one independent replication would support Grade B or higher.