Pyrroloquinoline quinone disodium salt improves brain function in both younger and older adults
Masanori Tamakoshi et al. Food Funct. 2023.
Abstract:
Brain function is important for a good quality of life. Pyrroloquinoline quinone disodium salt (PQQ) has been proven to improve brain function and cognition in older adults (above 45 years). In this double-blind, placebo-controlled study, we investigated the effects of PQQ on cognitive function in adults aged between 20 and 65 years. PQQ (20 mg per day) was administered for 12 weeks to the participants. After 12 weeks, the participants showed improvements in composite memory and verbal memory. A further age-stratified analysis was performed. In younger adults (aged 20-40 years), PQQ improved cognitive function (cognitive flexibility, processing speed, and execution speed) after 8 weeks. Only older adults (aged 41-65 years) showed improvements in complex and verbal memory after 12 weeks. In the logistic regression analysis that included the results of all cognitive tests, the changes due to PQQ intake were observed at 8 and 12 weeks in the young and old groups, respectively.
Interesting! @John_Hemming have you looked into this at all, given your interest in mitochondrial health?
Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects
This human clinical study does look interesting:
Results: A total of 58 subjects (placebo = 31; Age = 70.91 ± 3.06 Y; mnemoPQQÂź group = 27; Age = 72.10 ± 3.77 Y) completed the study over a period of 12 weeks of supplementation. Significant improvements were observed on the Cognitraxâs cognitive function domain score on âcomposite memoryâ, âverbal memoryâ, âreaction timeâ, âcomplex attentionâ, âcognitive flexibilityâ, âexecutive functionâ, and âmotor speedâ in the mnemoPQQÂź group as compared to the placebo group. The DECO and the MMSE-J scores were also significantly improved in the mnemoPQQÂź group. No adverse events were observed.
Conclusions: Study demonstrates that supplementation of PQQ disodium salt is useful in improving memory, attention, judgment, and cognitive function, in middle-aged to elderly population, who feel they have become more forgetful because of aging.
I took some PQQ and it completely freaked me out. It was the worst thing that happened this year. It seemed to drive up some bacterial response in my gut and I had an awful night. My CRP built up quite a bit although it later dropped down below the minimum measureable response.
I think one reason it caused an issue was that I also drank a lot and there is a combinatorial effect.
Hence although it remains on my list of interesting molecules it also has a big red flag. I am not tried it when not drinking, however.
A one or two-time negative reaction could just be a coincidence. I have taken PQQ on and off over the years and felt no subjective effects, good or bad.
Now that I am getting really old, by my standard, I think I will try it again with a larger dose, 40mg. daily for 90 days and then I will test my CRP to see if it has a negative or positive effect.
Very interesting new study. I probably took 20mg PQQ for about 5 years in a row but then eventually stopped because I wasnât sure how important it really was. I may have to order some again.
Iâm back on it for three days now and I have to say, my energy feels normal again. Itâs definitely not placebo but I also canât rule out a coincidence either. Letâs see if this continues.
I eat 100g natto every single day, but PQQ supplements contain far more than what is possible in the diet, so Iâm not entirely sure how much PQQ we would need to get for the mitochondrial biogenesis benefits.
Short answer: Yesâpyrroloquinoline-quinone (PQQ) reliably activates the PGC-1α pathway, but it does so indirectly. It boosts PGC-1α mRNA and protein abundance and keeps the co-activator in its de-acetylated, phosphorylated âonâ state via CREB-, SIRT1-, and AMPK-dependent signaling. No data support PQQ binding PGC-1α directly.
What the evidence shows
Experimental system
What PQQ does to PGC-1α
Upstream trigger(s)
Key read-outs
HepG2 & C2C12 cells (10â30 ”M)
â PGC-1α promoter activity, â mRNA & protein within 4 h
CREB-Ser133 phosphorylation (cAMP/PKA)
Loss of effect when CREB or PGC-1α is silenced; â NRF-1/2, TFAM, mitochondrial DNA content (PubMed, PMC)
SIRT1 de-acetylates PGC-1α, increasing its co-activator potency.
AMPK phosphorylates PGC-1α, further boosting activity and favoring oxidative metabolism.
Direct vs. indirect activation
Direct ligand? No binding pocket on PGC-1α has been shown for PQQ, and surface-plasmon/thermal-shift assays find no detectable affinity.
Functional activator? Because PQQ reproducibly raises PGC-1α abundance and converts it to its active de-acetylated state, most authors label it a PGC-1α activatorâjust an upstream one.
Practical implications
Dose window. Cell studies use 10â30 ”M; this corresponds to oral intakes of ~10â20 mg dayâ»Âč in humans, which yield low-micromolar peak plasma levels in small clinical pharmacokinetic studiesâenough to reach the CREB/SIRT1 thresholds.
Mitochondrial benefits (higher VOâmax, lower triglycerides, faster ÎČ-oxidation) observed in rodent and early human trials can be traced back to PGC-1α activation.
Stacking with other agents: nutrients that also raise NADâș (NR, NMN) or activate AMPK (metformin, AICAR) may work additively with PQQ because they converge on the same PGC-1α node.
Bottom line
PQQ does not latch onto PGC-1α like a small-molecule agonist would, but by turning on CREB, SIRT1, and AMPK it up-regulates and potentiates PGC-1α, making it a bona-fide indirect activator of the master regulator of mitochondrial biogenesis.