I figured I would answer this question by Steve since I am in the
midst of doing a lot of research on pyridoxamine.

META
[Which I knew, and, therefore, hoped that you would answer the message
to save me the trouble - and provide something that most readers would
likely evaluate as better than what I would have done.

Later note: but also with some peer-review suggestions by me. --Paul]
/META

--- In morelife@yahoogroups.com, "spboulet" <stephen@...> wrote:
>
> I ran across several studies that seem to indicate that P5P is a
> superior supplement to pyridoxamine for glycation prevention, contrary
> to my expectations. First up is http://pubmed.gov/16470027, May 2006:
> However, lipid glycation inhibitor has not been discovered yet because
> of the lack of a lipid glycation model useful for inhibitor screening.
> We optimized and developed a lipid glycation model considering various
> reaction conditions (glucose concentration, temperature, buffer type,
> and pH) between PE and glucose. Using the developed model, various
> protein glycation inhibitors (aminoguanidine, pyridoxamine, and
> carnosine), antioxidants (ascorbic acid, alpha-tocopherol, quercetin,
> and rutin), and other food compounds (L-lysine, L-cysteine, pyridoxine,
> pyridoxal, and pyridoxal 5'-phosphate) were evaluated for their
> antiglycative properties. Pyridoxal 5'-phosphate and pyridoxal (vitamin
> B(6) derivatives) were the most effective antiglycative compounds.

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.

> Above I think the claim is made for lipid and not protein glycation.

That is correct. In that study pyridoxal and pyridoxal 5-phosphate
were both found to be far better lipid glycation inhibitors than
pyridoxamine under the in vitro conditions used in that study. But
proteins and lipids are very different in their properties. The fact
that protein glycation has been shown to be very harmful does not
necessarily mean lipid glycation is also very harmful. Keep in mind
that the function of proteins and enzymes (most enzymes are proteins)
is highly dependent on their shape and form. When a protein becomes
glycated the first step in the glycation is the attachment of a sugar
molecule to an amino group on the protein. After the attachment the
shape and form of the protein has changed. Depending on where the
glycation occurred on the protein this can have various effects such
as e.g. reduced function of the protein. The role of lipids in the
body is different. 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.

> 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. 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