That's very interesting. I got brain fog and sluggishness from trials of ashwaganda as well... but I don't recall those being as profoundly unpleasant as PQQ. Have not tried Vinpocetine. ALA is a daily staple that I feel is required to keep my attention/energy levels up.
I wish I could say it way a scientific conclusion, but it's mostly just by correlating the results of PQQ ingestion with other substances I've taken that alter Glutathione/Glutamate functioning in the brain. For instance, vinpocetine antagonizes glutamatergic function, as does ashwaganda. When I tried both of these supplements, they effected me like PQQ did. I am not versed in chemistry, but I do know that PQQ has *some* effect on the redox sites involving Glutathione/Glutamate/NMDA. What that effect is I don't know. I can also say cautiously that I don't understand the chemistry behind anything I take, so it is possible that the information I offer is partially or totally innaccurate (thought I'm not just making it up =P ).
@Luxflux: I am very interested in your response to PQQ and how you've tied that to NMDA function. I also have had really awful experiences with PQQ, very shortly after taking it. I have taken two different brands, 2 small doses and one half-dose on three separate occasions without changing anything else and taken separate from any other supplements.
I respond very well to NMDA enhancers/glutathione enhancers (sarcosine, NAC, pregnenolone) and respond *horribly* to PQQ. I heard that it effects glutathione synthesis in some way, which probably effects the redox aspect of NMDA receptors. For me, it gave me significant brain fog about an hour after ingesting, without fail, no matter what other things I had been taking. So if you have hypoglutamatergic function(or suspect you do), be careful with this one.
I would say "brain fog" was part of it, but the experience was more like something I imagine diabetics in severe hypoglycemia experience: Couldn't think/concentrate, irritable, weak/fatigued, super-depressed or "down" mood. The worst of this lasted for hours and didn't really get better for another day. About an hour or two after taking, each time, there was also this unusual craving for carbs and sweets, which is not at all normal for me.
Until I saw your post, all my research just turned up that PQQ gave results for everyone falling on spectrum somewhere between "wonderful and energy-boosting" and "did nothing." So, I had been thinking perhaps it was a clue to some metabolic weirdness with me.
How did you arrive at glutamatergic hypofunction as the cause? Interestingly enough, I am beginning to (cautiously) experiment with pregnenolone with very positive results. NAC is also a staple of mine.
Beyond that, I take CoQ10 and Lipoic acid(which as far as I know effect mitochondrial function, among other things) with only positive results. In light of these two pieces of information, I concluded as best I could that it was probably due to the relationship with the glutamate system.
Short of brain fog, I don't remember specific symptoms. I may or may not have experienced the things you are saying. I still have some PQQ left, I may try one capsule this weekend and see what happens. If I do I'll report back.
Regardless of the actual causes behind my poor experiences, at least there is an n = 1 case where someone with low NMDA function had a bad experience with PQQ. Hope this helps you find some answers.
This may be a segue to a new thread or PM, but have you ever taken any of the commercial genetics tests (e.g., 23andMe?) I have a small number of fairly rare results for which it would be interesting to see if any match up. My curiousity is particularly focused on some SNPs on the CRF, HPD (homozygous for "Hawkinsinuria,") also CYP2D6*6.
Any family history of schizophrenia? I believe glutamatergic hypofunction is a part of one of the models for underlying causes. I have close family members on both sides with SCZ.
I was diagnosed as schizophrenic at age 13 (I'm 32 now). The prognosis for teenage onset is rather poor, but I was fortunate to beat the odds. I've not taken medication for 10 years now, and my IQ has increased about 15 points over the last 20 years (It's supposed to degenerate over time, a full standard deviation is quite uncommon). Initially I remedied it via high dose EPA fish oil, but found that compromised glutathione/NMDA systems were probably to blame.
I have not taken any genetic testing, but from anecdotal evidence from family members I believe one of the genetic sources to my illness is problems with calcium ion channels. Do you have any snps that relate to that? IMO, this is one of the cores to schizophrenia and related illnesses, though there are probably many paths to the same pathology.
I did take another pqq cap, problems were still there, but they were more mild. I think it is due to the increased antioxidants I am taking that cross the BBB (longvida and NA-R-ALA in particular).