--- In morelife@yahoogroups.com, Ólafur Páll Ólafsson <olafurpall@...>
wrote:

> For clarity and to prevent misunderstanding it would have been better
> to have the above quote from the abstract within quote marks to
> clearly separate it from the sentence you wrote below.

I'll stay away from the advanced Yahoo editor next time.

> There is need for more research in this area but in
> general I do not think glycation of lipids is as harmful as that of
> proteins.

That seems to be the case from what I can tel.

> > The next study however seems to be for protein glycation
> > (http://pubmed.gov/17449494, August 2007:
> > Streptozotocin (STZ)-induced diabetic rats were treated by oral
> > administration of PLP or pyridoxamine (PM), another active form of
> > vitamin B6, at a dose of 600 mg/kg/day for 16 weeks. ... PLP was
> > superior to PM in inhibiting accumulation of AGEs, expression of
> > TGF-beta1, type 1 collagen, and fibronectin, and the development of
> > diabetic nephropathy.
>
> Now this is a study I had not seen before. I am surprised to see that
> PLP was found to be superior to pyridoxamine in that study. Except for
> this study, the only study of which I am aware that directly compares
> PLP to pyridoxamine is this one: http://pmid.us/8602828 . That is an
> in vitro study. In that study pyridoxamine was found to be the most
> effective antiglycating compound followed by PLP, pyridoxal and
> pyridoxine. Why PLP was found to be more effective than pyridoxamine
> in the above study is difficult to say. There are reasons to suspect
> this would not apply to humans.
>
> The absorption of phosphorylated forms of vitamin B6 generally starts
> with hydrolysis by alkaline phosphatase in the digestive tract. PLP
> thus will be hydrolized to pyridoxal before being absorbed. If this is
> the case PLP should not be any more effective than pyridoxal as an
> antiglycative agent when taken orally. However when very high doses
> are taken some of the PLP may escape hydrolysis and be absorbed
> intact. From the full text of http://pmid.us/479949 :
>
> "At physiological doses PLP is absorbed largely after hydrolysis to
> PL, though a small percentage is absorbed without hydrolysis. This
> direct absorption of PLP which is several fold slower than PL could be
> important only at doses well above physiological level."
>
> Normally the majority of PLP will be hydrolized and absorbed as
> pyridoxal but when high doses are taken some of it may be absorbed
> intact. How high is difficult to say though but this may explain the
> results of the above study since in that study a very high dose of PLP
> was used. Most certainly some of it was absorbed intact without first
> being hydrolized allowing PLP to provide beneficial antiglycating
> protection.

Perhaps there is a role for sublingual or bucchal P5P? It sounds like
not much might be needed.

> But I don't think this means PLP by an oral route is
> superior to pyridoxamine for humans. The dose used in the above study
> amounts to about 12g of PLP for a 70kg human. That is an extremely
> large dose! To put it into perspective vitamin B6 generally causes
> neurotoxicity at doses in excess of 1g per day in humans. There are
> even reports of neurotoxicity from taking vitamin B6 in doses as low
> as 100-300mg http://pmid.us/16320662 . For prevention 400mg per day of
> vitamin B6 is about the most I would recommend to any adult human.
> Thus as is so often the case this study has no applicability to
> chronic human intakes of vitamin B6 for prevention.
>
> Furthermore pyridoxamine has several studies supporting it's efficacy
> against glycation in both humans and animals while PLP has much fewer.
> Newertheless this study does suggest that PLP may be superior to
> pyridoxal as well as the commonly used pyridoxine when it comes to
> antiglycative function particularly when high doses of PLP are taken.
>
> > Finally, in this study, http://pubmed.gov/18004515,
> > Amino acids react with methylglyoxal to form advanced glycation end
> > products. This reaction is known to produce free radicals. In this
> > study, cleavage to plasmid DNA was induced by the glycation of lysine
> > with methylglyoxal in the presence of iron(III). This system was found
> > to produce superoxide as well as hydroxyl radicals. The abilities of
> > various vitamins to prevent damage to plasmid DNA were evaluated.
> > Pyridoxal-5-phosphate showed maximum protection, while pyridoxamine
> > showed no protection. The protective abilities could be directly
> > correlated to inhibition of production of hydroxyl and superoxide
> > radicals. Pyridoxal-5-phosphate exhibited low radical scavenging
ability
> > as evaluated by its TEAC, but showed maximum protection probably by
> > interfering in free radical production. Pyridoxamine did not inhibit
> > free radical production.
>
> I am surprised by the results of the above study, particularly these
> parts:
> "The protective abilities could be directly correlated to inhibition
> of production of hydroxyl and superoxide radicals. ... Pyridoxamine
> did not inhibit free radical production."
>
> This is surprising in light of the fact that pyridoxamine has been
> shown to be able to scavenge free radicals, including the hydroxyl
> radical http://pmid.us/18374270 .
>
> This study suggests that under some conditions PLP may be superior to
> pyridoxamine with respect to inhibiting glycation. But keep in mind
> that this is an in vitro study. A large portion of the PLP taken
> orally will generally be hydrolized to pyridoxal before being absorbed.
>
> > Is there something I'm missing, or is P5P better at preventing AGE
> > formation?
>
> Under some conditions yes pyridoxal-5-phosphate is better at
> preventing AGE formation, while under some conditions pyridoxamine is
> better. Overall however the evidence is strongly in favor of
> pyridoxamine being the most effective antiglycative agent, at least by
> an oral route. First of all because much of the PLP will be hydrolized
> during digestion to pyridoxal whose antiglycating ability is much
> poorer than that of pyridoxamine or PLP. Also because in general there
> are far more in vivo studies supporting the effectiveness of
> pyridoxamine in preventing AGE formation than there are for PLP.
>
> In conclusion among the B6 vitamers I think pyridoxamine is the best
> orally administered antiglycative agent for humans. But the evidence
> indicates that PLP, while not as effective as pyridoxamine, would be a
> good choice over pyridoxine the form that not only appears to be the
> least effective for glycation but unfortunately is the most common one
> also in supplements.
>
> > Stephen

Thank you very much for your reply. It's fortunate for us that you
were in the middle of looking into this.

You should also take a look at this post at imminst.org:

http://www.imminst.org/forum/index.php?showtopic=27493&view=findpost&p=297712

I've brought up some of the commentary you made over there. I hope
that is OK -- I don't want to step on anyone's toes. In his post
there, Michael argues that P5P is the better anti-glycation agent, but
that pyridoxamine has better safety data behind it. On the whole I'm
leaning back more to PM, but am curious about bypassing hydrolisis of P5P.

StephenB