PQQ

PQQ is an aromatic tricyclic quinone, first identified as a redox cofactor for bacterial enzymes. Mammals cannot make it, but trace amounts turn up in human and rat tissues from food. In rodents, diets lacking PQQ cause growth, immune and reproductive problems, which is why it is sometimes discussed as a possible nutrient. It is not classified as a vitamin [1].

The human evidence is a small set of cognition trials using PQQ disodium salt. In a 12-week double-blind trial in 58 older adults who felt more forgetful, PQQ improved composite and verbal memory, reaction time, attention and executive function scores compared with placebo [4]. A second 12-week trial in adults aged 20 to 65 found memory gains. Younger participants improved on cognitive flexibility and processing speed by week 8, and older ones on memory by week 12 [5]. A six-week trial of a PQQ-containing blend in older adults with mild cognitive impairment reported better orientation scores, brain oxygenation and brain metabolite levels, from a small sample [6].

The mitochondrial story comes from cell studies. In mouse liver cells, PQQ increased mitochondrial DNA, respiration and markers of mitochondrial content. It did so by activating CREB and PGC-1α, the master switch for mitochondrial biogenesis, and the effect disappeared when either was knocked down [2]. In fibroblasts, low nanomolar PQQ raised NAD+ and activated SIRT1, which in turn switched on PGC-1α [3].

Whether oral doses reach tissues at concentrations that do this in people has not been shown in the trials cited here.

None of the cited trials reported adverse events from PQQ [4]. Reviews describe no reported toxicity or genotoxicity in the studies to date [7]. The human safety record is short-term, measured in weeks.