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Trying PQQ


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#91 hav

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Posted 13 October 2012 - 07:12 PM

Out of curiosity I just tried it myself using 1 pink capsule of le-brand pqq w/bio-pqq with most of it under the tongue and a little on top of it. Developed a dark green color on parts of the top of my tongue as well as a green coloring around the bottoms of my front lower teeth. But didn't notice a stimulatory effect. Brushing cleaned up the teeth but the tongue coloring is still there after about 15 minutes.

Howard

#92 dear mrclock

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Posted 13 October 2012 - 08:46 PM

lol hav here mine turned blue to dark blue. again, even brushing my teeth and tongue, the color was there 15-20 minutes later or so.

what is up with various colors in different mouths ? and yeh ill get pix when i do it again but i really wanna throw it out dont see point taking it.

#93 Turnbuckle

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Posted 13 October 2012 - 09:53 PM

lol hav here mine turned blue to dark blue. again, even brushing my teeth and tongue, the color was there 15-20 minutes later or so.

what is up with various colors in different mouths ? and yeh ill get pix when i do it again but i really wanna throw it out dont see point taking it.


Sounds like a batch contaminated with MB. MB is so strong a colorant that an invisible amount would turn blue once dissolved. Try dumping a little in a glass of water and see what happens.

#94 Hebbeh

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Posted 13 October 2012 - 10:30 PM

lol hav here mine turned blue to dark blue. again, even brushing my teeth and tongue, the color was there 15-20 minutes later or so.

what is up with various colors in different mouths ? and yeh ill get pix when i do it again but i really wanna throw it out dont see point taking it.


Sounds like a batch contaminated with MB. MB is so strong a colorant that an invisible amount would turn blue once dissolved. Try dumping a little in a glass of water and see what happens.


I dumped a Life Extension capsule in a glass with about an inch of water. It wasn't very soluble but with a little effort, I got maybe 80-90% to appear in solution and the water turned pink like the powder. Looked a little like pink lemonade.

#95 dear mrclock

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Posted 13 October 2012 - 11:44 PM

just tried it with water. it turned pink. so i did the mouth experiment too, it was pink as well. strange why last time my mouth turned all blue... maybe i drank or ate something before that and there was a reaction. i just cant remember what i had and i wonder if that was a sign of some bad reaction....

also i was curious can pqq be fed to plants ?

#96 Turnbuckle

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Posted 14 October 2012 - 12:29 AM

just tried it with water. it turned pink. so i did the mouth experiment too, it was pink as well. strange why last time my mouth turned all blue... maybe i drank or ate something before that and there was a reaction. i just cant remember what i had and i wonder if that was a sign of some bad reaction....

also i was curious can pqq be fed to plants ?


Do you have MB in the house? If you don't, then maybe only some of the capsules are contaminated.

#97 anagram

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Posted 14 October 2012 - 02:05 AM

this is so strange, every time i try PQQ, none of it turns blue or dark green. the only time i have ever seen PQQ turn dark green was when I forgot a capsule in my pocket and went about the day(a very got day at that), and a small portion of the capsule was greenish like the semi-reduced state of PQQ is.( i know what semi reduced PQQ looks like from doing a reduction experiment with PQQ and vitamin c, the colur change went from pink to green to dark red)

#98 Kevnzworld

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Posted 14 October 2012 - 02:38 AM

But the question remains, why would anyone take PQQ sublingually anyway? All of the studies have it ingested orally. There is no evidence that I've seen that it should be taken differently. I take B 12 sublingually because stomach acid degrades it, DHEA to avoid a liver pass. But PQQ?


#99 dear mrclock

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Posted 14 October 2012 - 04:10 AM

b12 is degraded by stomach acid ? are you saying its impossible to get it from food then ?

just tried it with water. it turned pink. so i did the mouth experiment too, it was pink as well. strange why last time my mouth turned all blue... maybe i drank or ate something before that and there was a reaction. i just cant remember what i had and i wonder if that was a sign of some bad reaction....

also i was curious can pqq be fed to plants ?


Do you have MB in the house? If you don't, then maybe only some of the capsules are contaminated.


dont have anything like MB, and i dont care to have. must be some reaction with something i drank or ate just before i tried the pqq. that is what i suspect. maybe i can repeat this but i dont see the point. i think pqq is useless unless it can be fed to plants as i asked previously. i always feed my left over supplements to plants for some weird reason...

#100 anagram

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Posted 14 October 2012 - 10:05 PM

i think its possible that plants may utilize PQQ in a more bioavalible way than humans, as it is a growth factor for them but not for humans, however its role in human life extension is still extremly important. During mitochondria biogenesis, cells use less oxygen, which is one of he factors behind caloric restriction's life extending properties. PQQ also interacts with DNA in a beneficial way, increasing transcription of genes that control oxidation. PQQ on its own is a potent antioxidant and prevents lipid oxidation, and these are just a few examples of how beneficial PQQ is. I personally find it to be both stimulating and inhibiting, which is a characteristic i have never experienced with any other nootropic. PQQ has powerful anticancer properties but also promotes the growth of healthy cells/nerve cells. in general it is a good supplement and taking it sublingually or dissolved in a liquid(kinda difficult) is a good way to get it into your body. I have to note that taking it for an extended period of time can cause a sort of depressive state which I find to be akin to that experienced while taking Taurine, however PQQ's effects are much much longer lasting. I have felt sort of down after taking PQQ anywhere from a few hours to a few days(especially if i have used modafinil, caffeine, or magnesium in conjunction with PQQ.) this depression is kind of good because, it gives me motivation to do the things that are fulfilling instead of sitting at my computer doing nothing.

Tips on taking PQQ-
If PQQ is making your mouth blue, you should take PQQ as a morning supplement, so that there isent much to reduce the PQQ in your mouth turning the PQQ to its greenish state. taking it in the morning is also good because it theoretically increases mir-132 via CREB pathways so taking it in the morning will stabalize your circadian rhythem. If you do CR, PQQ, I find, greatly enhances the mental fog associated with lower caloric intake, but makes you not as hungery.

Edited by anagram, 14 October 2012 - 10:09 PM.


#101 anagram

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Posted 15 October 2012 - 03:34 AM

note-
mir-132 is a micro RNA that is your bodys endogenous acetycholineesterase inhibitor. it is implicated in controlling the circadian rhythem, decreasing inflamation in the brain, increasing BDNF and other growth factors, and increaing neurogenesis. but contrary from mir-132's activity blocking in lowering inflamation in the brain, it increases inflamation outside the brain by silencing sirt1(resveratrol gene) and allowing for NF-kB (sirt1 and NF-kb are part of the same enzyme) to be active. the blocking of sirt1 increases acetylation.

#102 dear mrclock

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Posted 15 October 2012 - 06:56 AM

does anything specifically influence mir-132 ?

#103 hav

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Posted 15 October 2012 - 04:29 PM

Pqq.. theoretically increases mir-132 via CREB pathways ...

note-
mir-132 is a micro RNA that is your bodys endogenous acetycholineesterase inhibitor. it is implicated in controlling the circadian rhythem, decreasing inflamation in the brain, increasing BDNF and other growth factors, and increaing neurogenesis. but contrary from mir-132's activity blocking in lowering inflamation in the brain, it increases inflamation outside the brain by silencing sirt1(resveratrol gene) and allowing for NF-kB (sirt1 and NF-kb are part of the same enzyme) to be active. the blocking of sirt1 increases acetylation.


I wonder if the coloration I experienced might relate to an interaction between resveratrol and pqq. Fwiw, I had just cycled to my weekly resveratrol stack the same morning, probably about a half hour before I tried the pqq on and under my tongue. In any event, your comment about pqq and sirt1 made me wonder about a possible pqq/resveratrol antagonism but I couldn't find any research in pubmed directly on that subject. Only one I found mentioning resveratrol and pqq was this, but no mention of sirt1. I did find this interesting discussion on another site that indirectly overlaps a little of what you mentioned with a few research citations:

http://pyrroloquinol...and-pgc1-alpha/

Although it all seems theoretical and speculative and there's clearly differences of opinion, it makes me wonder if it might be wise to not take pqq and resveratrol together until research sheds a little more light on the issues. I'm thinking of moving pqq to my resveratrol off-week when my stack includes astragalus extract where I don't see any theoretical conflicts.

Howard

Edited by hav, 15 October 2012 - 05:00 PM.


#104 anagram

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Posted 15 October 2012 - 08:38 PM

i understand that there is little to none reserch on PQQ actvating mir-132, however it can be hypotheised from the fact that PQQ activates CREB. On another note, I love combining PQQ with caloric restriction because I feel fantastic the day after. I would not recommend doing the combo to anyone with scizophrenia because I felt very manic while I was doing it. If anyone has scizophrenia, I would strongly suggest avoiding high dose PQQ with caloric restriction, the experience I had was sort of intense. I doubt anyone will ever get scizophrnia from PQQ but I must warn those who are taking it that If you take it and dont eat much anything else for the rest of the day, it makes everything a little more intense(difficult to describe), but the results are pretty great and I have only every experienced anything good from CR while on PQQ.

supplements that are synergetic with PQQ-
(TMG)
(B vitamines)
(choline)
(glutamine)
(NF-kb antagonists(dim,Sulforaphane), mir-132 makes more NF-kb activity by silencine sirt1)


Edited by anagram, 15 October 2012 - 08:53 PM.


#105 anagram

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Posted 16 October 2012 - 11:29 PM

there is a chance im wrong, but I think that taking PQQ is much better than resveratrol. My reason being that studies show that resveratrol increases sirt1 activity, however at the same time, it increases NF-kb activity. NF-kB is increased if Sirt1 is increased because NF-kB is a substrate on sirt1. it is unfortunatly unknown if anything increases just sirt1 and not NF-kB as well. Because NF-kB increases immflamation, it is unsuprising that users of resveratrol experience weird pains while on it, but the increase in NF-kB could be extremly counterproductive to life extension. It is possible that repetedly causeing an increase in NF-kB could cause some sort of downregulation(which would mean less sirt1), however that part is just speculation. PQQ on the other hand does not cause the same increase in NF-kB, but does silence the expression of sirt1. whether or not PQQ eventually causes an increase in sirt1 via downstream upregulation is unknown, however it seems likley that somthing along those lines might occur.

resveratrol = increased sirt1 + NF-kB : downstream effects in humans increased immflamation
PQQ = decreased sirt1 and normal NF-kB : downstream effects( PQQ increases PCG-1α which is also activated by sirt1 so its possible that PQQ increases sirt1 expression)

you may be thinking that the yeast studies with resveratol prove its efficacy in life extension, but you are forgetting that yeast dont have acetylcholine as a neurotransmitter, and because sirt1 is a deacetylator, in humans taking resveratrol, there could be a decrease or at least some sort of mechanisem to keep sirt1 at normal levels to protect acetylcholine from degredation.

regardless of the mode of action, considering the possibility of downregulating sirt1, I think im going to stay away from resveratrol( it does exaclty what PQQ does, except in a painful way immflamatory way that leads to down stream down regulation in NF-kB and therfore sirt1)

there is a chance im wrong, but considering an increase in NF-kB could be counterproductive to life extension, and repetedly causeing an increase in NF-kB could cause some sort of downregulation in NF-kB (which would mean less sirt1), however that part is just based of the fact that cancer grows if NF-kB is active(possibly due to more sirtu1) and resveratrol reduces the risk of some forms of cancer, but it has no effect on existing cancers which already have a up regulationin NF-kB. PQQ on the other hand does not cause the same increase in NF-kB, but does silence the expression of sirt1. whether or not PQQ causes an increase in sirt1 via downstream upregulation is unknown, however it seems likley that somthing along those lines might occur.

resveratrol = increased sirt1 + NF-kB : downstream effects in humans increased immflamation
PQQ = decreased sirt1 and normal NF-kB : downstream effects( PQQ increases PCG-1α which is also activated by sirt1 so its possible that PQQ increases sirt1 expression)

opinion- I think im going to stay away from resveratrol( it does exaclty what PQQ does, except in a painful way immflamatory way that leads to down stream down regulation in NF-kB and therfore sirt1). PQQ probebly also interacts with nicotanic receptors and or 5ht receptors, If you look at PQQs structure, you can see the pyridine and pyrrolidine structures(similar to nicotine and piracetam) in it and or a indole structure, so it probebly has minor effects as a nootropic, other than being a wonderful antioxidant. on the other hand, has anyone ever considered that resveratrol even looks bad, its like some kind of aromatic hydrocarbon, which are known for increasing NF-kb. PQQ is actually made by living creatures like yeast and tomatos and even though I dont agree with the "because its natural its safe argument", PQQ just seems much "safer" in comparision to resveratrol.


to get onto the topic of longevity, I think we have to look at the precise role of sirt1. sirt1 is a deacetylator like acetylcholinesterase and several other deacetylase enzymes(primarily found in immune cells). amino acids like ornithine can be decarboxylated to polyamines which can turn into spermidine( increases rats life spans by double). deacetylating DNA may slow transcription of proteins and slow caloric intake by the cell, deacetylase enzymes may then produce hydrogen(energy) in the metabolically slowed cell by continueing to turn acetyl groups into carbon dioxide(in the process removing a hydrogen which can be used for energy) however this is just a theory of mine.

Edited by anagram, 17 October 2012 - 12:14 AM.


#106 niner

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Posted 17 October 2012 - 12:19 AM

there is a chance im wrong, but I think that taking PQQ is much better than resveratrol. My reason being that studies show that resveratrol increases sirt1 activity, however at the same time, resveratrol increases NF-kb activity. NF-kB is generally increased if Sirt1 is increased because NF-kB has sirt1 in it.(it is unfortunatly it is unknown if anything increases just sirt1 and not NF-kB as well). because NF-kB increases immflamation, it is unsuprising that people experience weird pains while on resveratrol, but the increase in NF-kB could be counterproductive to life extension, and repetedly causeing an increase in NF-kB could cause some sort of downregulation(which would mean less sirt1), however that part is just speculation. PQQ on the other hand does not cause the same increase in NF-kB, but does silence the expression of sirt1. whether or not PQQ causes an increase in sirt1 via downstream upregulation is unknown, however it seems likley that somthing along those lines might occur.


You should probably check your sources on this stuff. Resveratrol doesn't increase nf-kB; if anything it reduces it. Nf-kB doesn't have sirt1 in it; that's more or less impossible. PQQ silences the expression of sirt1? I don't think sirt1 has anything to do with acetylcholine.

#107 anagram

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Posted 17 October 2012 - 01:02 AM

on PQQ silencing mir-132
PQQ increases CREB in the brain, CREB increases mir-132 activity in the brain and body. mir-132 silences expression of sirt1 and acetylcholinesterase. sirt1 belongs to a family of deacetylators and will deacetylate some lingids that attatch to its substrate.

about NF-kB
http://www.ncbi.nlm....pubmed/19819989

what the article means explained in simple terms -
miR-132 has been implicated in promoting inflammation in adipocytes. The target for RNA silencing in this case is SirT1, a deacetylase enzyme. The p65 subunit of NF-κB is a SirT1 substrate

this would suggest that to increase SirT1, you are inadvertantly increasing NF-kB because sirt1 is on NF-kB

#108 niner

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Posted 17 October 2012 - 03:26 AM

on PQQ silencing mir-132
PQQ increases CREB in the brain, CREB increases mir-132 activity in the brain and body. mir-132 silences expression of sirt1 and acetylcholinesterase. sirt1 belongs to a family of deacetylators and will deacetylate some lingids that attatch to its substrate.

about NF-kB
http://www.ncbi.nlm....pubmed/19819989

what the article means explained in simple terms -
miR-132 has been implicated in promoting inflammation in adipocytes. The target for RNA silencing in this case is SirT1, a deacetylase enzyme. The p65 subunit of NF-κB is a SirT1 substrate

this would suggest that to increase SirT1, you are inadvertantly increasing NF-kB because sirt1 is on NF-kB


I can't find any evidence in the literature relating PQQ to miR-132.

In the cited paper, they say:

we demonstrate for the first time, the repression of silent information regulator 1 (SirT1) protein levels by miR-132 and propose a pathway where miR-132 represses the SirT1-mediated deacetylation of p65 resulting in NFκB activation and IL-8 and monocyte chemoattractant protein-1 (MCP-1) production.


SirT1 goes down, and NFkB goes up. You're saying that if SirT1 goes up, NFkB also goes up, which is the opposite of what the paper says. sirt1 isn't "on" NFkB; rather, there is a multi-step mechanism through which signals are passed between SirT1 and NFkB via p65.

You were claiming that resveratrol raised NFkB, presumably by activating SirT1, but the opposite would be consistent with the paper. Here's a pubmed search of resveratrol nf-kb. Lots of info there. Resveratrol is involved in multiple signalling pathways.

#109 anagram

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Posted 17 October 2012 - 03:49 AM

i agree that a lot of studies show that resveratrol decreases NF-kB activation however what do you think happens when resveratrol is cleared from the sirt1 binding site? the sirt1 binding site is one NF-kB, so if resveratrol increases sirt1 its increaseing NF-kB at the same time, when sirt1 goes silent, the NF-kB goes active agein. All the studies on resveratrol show that its neuroprotective while its in your body, however none tell the after effects of using it and there influence on NF-kB immflamation. its not going to permenantly going to silence NF-kB, thats like saying drinking alcohol is good for counteracting excytotoxicity, afterward is when the problems arise.

article on histone binding and activation of CREB. PQQ has been shown to activate CREB.
http://www.ncbi.nlm.nih.gov/gene/1387


(quote from wikipedia from mir-132 page) Activators of CREB phosphorylation, for instance forskolin and KSHV binding to endothelial cell targets, can also enhance miR-132 production in vitro.

so by putting two in two I was able to infer that PQQ activates CREB, but one thing you could look up is PQQ's activation of PKA and its role in the phosphorylation of CREB for more details and sources to back my statement up.


#110 anagram

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Posted 17 October 2012 - 09:34 PM

another example of what i am talking about is Vinpocetine. vinpocetine was an alkaloid that was used for long becasue it decreases NF-kB, however we all stoped using it when it was determined that because it inhibited NF-kB, it caused massive immune faulire(decrease in sirt1 killed off immune cells).

#111 niner

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Posted 17 October 2012 - 11:15 PM

another example of what i am talking about is Vinpocetine. vinpocetine was an alkaloid that was used for long becasue it decreases NF-kB, however we all stoped using it when it was determined that because it inhibited NF-kB, it caused massive immune faulire(decrease in sirt1 killed off immune cells).


It does reduce NF-kB, which is usually a good thing, but where do you get the "massive immune failure" idea from? The Commission E monograph? I doubt it says that. Decrease in sirt1 killed off immune cells? Do you have a source for this?

#112 anagram

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Posted 18 October 2012 - 12:47 AM

I have a hypothesis that the reason immune and reproductive cells are able to keep there DNA in good condition for a very long time is due to NF-kB substrates like sirt1 staying active. you know what im talking about when I say massive iimune faulire, agranulocytosis. If you have looked at the threads pertaining to vinpocetine you will see that more than one person has gotten it from taking vinpocetine.
honestly, I dont care if people take resveratrol, I want to see what sort of effects it has long term, I just will not take it personally at the risk of fucking up my immune system(why does resveratrol give me weird pains in my joints?). If you dont aggree with me that lowering NF-kB in the short term is bad then what ever, I like to use the approach of putting two in two, which definetly isent exact or precise but the more evidence I look at, it seems unreasonable to take resveratrol. the way I see it, taking somthing that lowers NF-kB just seems weird because for such a well run enzyme in the body, what are the after effects of inhibiting it? that is just me probebly being over safe but the fact that caffeine, vinpocetine, and some other things inhibit NF-kB as well as resveratrol, I just wonder why dont take caffeine instead, its been shown to be neuroprotective. even resveratrol's advocate Dr.Sinclair has stated that resveratrol only increases the life span of obese mice. has anyone even considered resveratrols possible carcinogenic activity, probebly because resveratrol inhibits topoisomerase(like a lot of anticancer drugs) so your DNA cannot fix itself which could lead to mutations. looking at its inhibition of topoisomerase activity, yet resveratrols ability to enhance some forms of gene expression raises the question of its role of NF-kB(possibly increasing expression of it).

Edited by anagram, 18 October 2012 - 12:47 AM.

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#113 niner

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Posted 18 October 2012 - 01:21 AM

I'm not trying to get anyone to take either resveratrol or vinpocetine. You're stating a lot of things as though they were factual, and while some of them are, an awful lot aren't. People read this stuff, and they are going to get wrong ideas, which we'd like to avoid.

#114 anagram

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Posted 18 October 2012 - 04:00 AM

im sorry If all my theorys are hard to swallow at once, but I am just really bad at laying things out slowly(adhd). your point dosent make sense though, i really have quite a bit to back my theories up including different observations on the subject so I dont understand what could possibly be wrong with my point.


earlier I stated that resveratrol increases NF-kB via some mechanism(I dont even remember, but I know it was right). it was argued that resveratrol dosent increase NF-kB however literally as I am writing this I can see on wikipedia that resveratrol increases testosterone. As I am writing this I am assuming that testosterone increases NF-kB because that would further validate my claim that res increases NF-kB.

bam

http://www.ncbi.nlm....pubmed/19953904
(article on testostrone's effect on NF-kB)


although testosterone only slightly increases NF-kB it would support my claim that via hormonal and gene signalling, resveratrol causes an increase in NF-kB, after silencing it NF-kB.

I finally just googled is resveratrol increases NF-kB, and it does, or at least it does if you beleive pub med. sorry for making all the "fuss", i just posted the pub med article on resveratrol's effect on NF-kB to kill any disagrement with my theory and so you dont have to google if resveratrol increases NF-kB

http://www.ncbi.nlm....pubmed/12716675


could you point out another hypothesis I have stated that you beleived to be false next time? I hope Ill give you satisfactory evidence.

Edited by anagram, 18 October 2012 - 04:09 AM.

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#115 Kevnzworld

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Posted 18 October 2012 - 04:30 AM

This topic is all over the map. NFKB, transcription factor is an immune and inflammatory modulator. Natural substances that suppress NFKB, to my knowledge do not inhibit immune function. They modulate it, and suppress excess or chronic inflammatory reactions. Curcumin is a good example.
The studies that show that resveratrol enhance testosterone? Maybe sperm count, in rats. There is no direct correlation that I have found.

http://jn.nutrition....135/4/757.short
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#116 anagram

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Posted 18 October 2012 - 08:46 PM

(this is a line i copy and pasted from the wikipedia page on NF-kB)
Active NF-κB turns on the expression of genes that keep the cell proliferating and protect the cell from conditions that would otherwise cause it to die via apoptosis.

#117 stephen_b

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Posted 18 October 2012 - 10:09 PM

I find this interesting. In PMID 20663290: in leukemia cells, PQQ actually depletes glutathione as its method of inducing apoptosis. When NAC is added, it depletes glutathione to an even greater extent. "Cellular GSH levels increased following treatment by NAC alone but were severely depleted by co-treatment with NAC and PQQ".

#118 anagram

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Posted 18 October 2012 - 10:13 PM

I find this interesting. In PMID 20663290: in leukemia cells, PQQ actually depletes glutathione as its method of inducing apoptosis. When NAC is added, it depletes glutathione to an even greater extent. "Cellular GSH levels increased following treatment by NAC alone but were severely depleted by co-treatment with NAC and PQQ".


yah I find this very interesting, but a bit difficult to wrap my head around. do you have an theories that might shed light on why this happens?

#119 stephen_b

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Posted 18 October 2012 - 10:35 PM

No idea -- that's above my pay grade.

#120 anagram

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Posted 18 October 2012 - 11:13 PM

well, do you take it?




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