Pyridoxamine: Jarrow Defends its Legal Rights

Thought I would inform you all that AOR has a new anti-AGE supplement called "AGE Amidori." They claim to have the first pharmaceutical grade pyridoxamine available anywhere.
http://aor.ca/products/age_amidori.php

Funny that pyridoxamine seems to be legal in Canada while it is now in a grey area in the US. This could be a first in the history of dietary supplements.

Aren't those doses very low?

That was my first thought as well.

Low? Um, depends on the price :-).

But true, even when considering that one would take this together with a good multi like ortho-core the pyridoxamine and benfotiamine is somewhat low. I would have hoped for 50mg pyridoxamine and 80mg Benfotiamine or maybe a bit more Benfortiamine. 33mg Pyridoxamine is however plenty more on the safe side depending on your individual metabolism... i use 50 pyridoxamine and 80mg benfotiamine since that is quite affordable and hopefully not exagerated for someone not having any clinical problem except aging and stuff.

Click HERE to rent this advertising spot for SUPPLEMENTS (in thread) to support LongeCity (this will replace the google ad above).

Smart nutrition pyridoxamine 6 bottles each 60 caps X 100 mg for sale. I have my own years supply and bought these for a someone who does not want them (don't ask...he's diabetic and is sure the one or two doses he took elevated his blood sugar). You will get 6 unopened and sealed bottles as I substituted one of my sealed ones for his opened bottle.

Cost is whatever I paid (I think it was the quantity discount price smart nutrition had) + shipping. Expiration date on bottles is 3/2007.

Oh and PM me if interested.

100mg each? Bit much perhaps? Question is, does the Pyridoxamine form contribute to the total B6 one consumes as there is a generally safe limit of what, 200mg? I suppose most take a decent amount of one or the other B6 forms so it really ads up fast, no?

(as usual pardon my ignorance but i think even dumb question can help. at least me :-) )

LifeMirage's AntiAging-Nootropic Regimen...

Glycation Inhibitors:

Benfotiamine 300mg (w/f)
Pyridoxamine 300mg

whoa, massive. Well, mine is above :-) but i'm by far not as dedicated (and informed) on it compared to most here let alone LifeMirage. Plus i really don't want to spend a fortune on it. Then again i'm 31 already and really *really* should get started. sigh.

well, i'd love to be enlightened too (though i should read up some on my own eh? all asking and taking is no good...) for the record i take ortho-core and ortho-mind as the base for my stack.

From Paul Wakfer's Morelife.org

Doses of vitamin B6 in the range 500-1000 mg/day have resulted in a small number of instances of neurotoxicity*, and photosensitivity. However, in all of these instances the vitamer given was PN which is converted to PL and PLP in the liver without involvement elsewhere. Since PM is not active until converted to PMP or PLP (via PMP)R, its diversion to glycation and AGE inhibitions may mean that dosages of PM which create B6 toxicity are greater than of PN. Unfortunately, this has not been experimentally proven or disproven.

*N Engl J Med 1983 Aug 25;309(8):445-8
Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome.
Schaumburg H, Kaplan J, Windebank A, Vick N, Rasmus S, Pleasure D, Brown MJ.
PMID: 6308447

does anyone know what the half-life of pyridoxamine is?
Is it OK to take 100mg in one go say in the morning or should this be spread out over the day in a drink or something?

Since PM is not active until converted to PMP or PLP (via PMP)R, its diversion to glycation and AGE inhibitions may mean that dosages of PM which create B6 toxicity are greater than of PN. Unfortunately, this has not been experimentally proven or disproven.

J Appl Toxicol. 2004 Nov-Dec;24(6):497-500. Pyridoxine (vitamin B6) neurotoxicity
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA.

“The vitamers related to pyridoxine (pyridoxal, pyridoxamine) and the coenzyme (pyridoxal 5-phosphate) did not cause clinical signs or lesions similar to those produced by pyridoxine even when injected in maximum tolerated doses.”

www.Diabetesincontrol.com

“Pharmacokinetic assessments were performed after the first (0 to 12 hours) and last (0 to 48 hours) dose of each dosing level. After the first dose of each dosing level, the time of maximum concentration was approximately 2.5 hours. The maximum drug concentration was 1 and 1.5 µg/hr/mL at 250 and 500 mg doses, respectively. Pharmacokinetic parameters observed after multiple dosings were not significantly different than after a single dose, indicating lack of drug accumulation, Dr. Degenhardt said.”

www.docguide.com

ADA: Pyridoxamine Appears to be Safe, Well Tolerated for Patients with Diabetic Nephropathy

By Bruce Sylvester
ORLANDO, FL -- June 8, 2004 -- Investigative pyridoxamine (Pyridorin, PYR-206) appears to be both safe and well tolerated as treatment for diabetic nephropathy, say researchers.
Reporting here on June 6 at annual meeting of the American Diabetes Association, Thorsten Degenhardt, PhD, presenter and project director for BioStratum, Durham, North Carolina, stated, "We did not really see any dose toxicity in our study. Pyridoxamine seems to be safe and it was well-tolerated by this patient population."

I knew the quoted bit, and sort of got from the rest that 100mg about 2.5 hours before Christmas dinner or any large sugary meal would be good.
Oh it's you - did you get my pm?

Have any new sources for Pyridoxamine been found. I'm slowly but surely using up my supplies.

If you guys don't come up with a supplier, Airsealed can still offer it as i stated previously in this thread.

um, see my previous posts in this thread. i kinda repeat myself :-)

There may be hope:

from http://triangle.bizj.../17/story2.html

On Sept. 14, the Council for Responsible Nutrition, a Washington, D.C.-based trade association, challenged BioStratum's petition with the FDA, saying it has proof that pyridoxamine was sold for years prior to 1994.

"If this went to court, somebody would trot out some (sales) order," says John Hathcock, a vice president of scientific and international affairs at CRN. "We firmly believe such evidence exists."

Any claim that pyridoxamine is not a dietary supplement will be "laughed at," says Hathcock.

There are a few good things about america...

If your in the U.S.A the store I work at has 3 bottles right now(jarrow pyridoxall) 1-800-424-5194
will be getting more.

Have any new sources for Pyridoxamine been found.  I'm slowly but surely using up my supplies.

Where can I find read some decent info about the benefits of using pyridoxamine, and its dosage/usage a day, how often, etc. I failed to find anything useful myself , and I have a few jarrow formula bottles sitting ere.

Alright for Jarrow....

http://www.fda.gov/O...002-01-vol1.pdf

While there are othe options for interfering with glycation, here's what appears to be a first for a close cousin of Pyridoxamine: P5P. The authors propose it's use in diabetic patients. Perhaps Biostratum can file a more comprehensive complaint, and ultimately control the sale of the entire family of B6 vitamers.

Cheers! T-

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J Lipid Res. 2006 Feb 9; [Epub ahead of print] Related Articles, Links


Aminophospholipid glycation and its inhibitor screening system: A new role of pyridoxal 5'-phosphate and pyridoxal as lipid glycation inhibitor.

Higuchi O, Nakagawa K, Tsuzuki T, Suzuki T, Oikawa S, Miyazawa T.

Peroxidized phospolipid-mediated cytotoxity involves in the pathophysiology of diseases (i.e., an abnormal increase of phosphatidylcholine hydroperoxide, PCOOH, found in plasma of type 2 diabetic patients). The PCOOH accumulation may relate to Amadori-glycated phosphatidylethanolamine (deoxy-D-fructosyl PE, namely Amadori-PE), since Amadori-PE causes oxidative stress. However, lipid glycation inhibitor has not been discovered yet due to lack of a lipid glycation model study useful for inhibitor screening. Consequently, we optimized and developed a lipid glycation model considering various reaction conditions (glucose concentration, temperature, buffer type and pH) between phosphatidylethanolamine (PE) and glucose. Using the developed model, various protein glycation inhibitors (aminoguanidine, pyridoxamine, aspirin 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 anti-glycative property. As results, pyridoxal 5'-phosphate and pyridoxal (vitamin B(6) derivatives) were the most effective anti-glycative compounds. These pyridoxals could easily be condensed with PE before glucose/PE reaction occurred. Since we found that PE-pyridoxal 5'-phosphate adduct was detectable in human red blood cells and that elevated plasma Amadori-PE concentration in streptozotocin-induced diabetic rats was decreased by dietary supplementation of pyridoxal 5'-phosphate, it is likely that pyridoxal 5'-phosphate acts as lipid glycation inhibitor in vivo, which possibly contributes to diabetes prevention.

PMID: 16470027 [PubMed - as supplied by publisher]

Another reference (below, has free full text) supporting, perhaps, the use of P5P in higher amounts, adjunctive, or alternative wrt Pyridoxamine lack of availability.

I had been taking 50mg of P5P per day as my preferred form of B6, however on an interim basis, I'm increasing it to 25mgx4, to keep blood/tissue levels high.

--------------
J Am Soc Nephrol. 2005 Jan;16(1):144-50. Epub 2004 Nov 24. Related Articles, Links


Pyridoxal phosphate and hepatocyte growth factor prevent dialysate-induced peritoneal damage.

Nakamura S, Niwa T.

Department of Clinical Preventive Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan.

Glucose-based peritoneal dialysate (PD) is responsible for increased accumulation of advanced glycation end products (AGE) in the peritoneum of continuous ambulatory peritoneal dialysis patients. Pyridoxal 5'-phosphate (PLP), a derivative of vitamin B(6), protects proteins from glycation. Hepatocyte growth factor (HGF) heals damaged tissues in a reciprocal manner against TGF-beta1. First, with the use of gas chromatography-mass spectrometry, whether PLP traps 3-deoxyglucosone (3DG), a major glucose degradation product in PD, was determined. Then, whether rat peritoneal tissue damages induced by intraperitoneal administration of glucose-based PD is ameliorated by PLP or HGF was examined. In vitro incubation with PLP markedly decreased concentration of 3DG in a dose-dependent manner, demonstrating the 3DG-trapping effect of PLP. The peritoneum of PD-treated rats was significantly thickened compared with that of physiologic saline-treated rats. Both PLP and HGF prevented the thickening of rat peritoneum induced by PD and ameliorated accumulation of AGE and expression of TGF-beta1, vascular endothelial growth factor, and type 1 collagen and a number of blood vessels. Furthermore, expression of HGF was significantly increased in the peritoneum of PLP-treated rats compared with that of PD-treated rats. In conclusion, PLP shows 3DG-trapping effect. PLP and HGF prevented peritoneal thickening; accumulation of AGE; expression of TGF-beta1, vascular endothelial growth factor, and type 1 collagen; and neoangiogenesis in rat peritoneum induced by PD.

PMID: 15563557 [PubMed - indexed for MEDLINE]

I'm taking 66mg of Pyridoxamine ED and I think i'll stick with this dose.

I'm taking 66mg of Pyridoxamine ED and I think i'll stick with this dose.

This is the pannel of supplements I currently take wrt literature on proteome/proteasome/proteosomal function (see:
http://www.imminst.o...=0&#entry99335)

Am also taking a similar dose of Pyridoxamine (until it runs out). Not sure where I'll acquire more. Have about 2 years worth, at 50mg/day. Hopefully the Biostratum issue will have resolved in favor of public domain before then.

------------------------

L-Carnosine (one large dose in AM (750mg), smaller dose in PM (250mg) as part of MEO by LEF)

L-Histidine: 500mg x 4, for now. May alternate between high and low dosing if literature supports stimulation of proteosomal activity with high doses.

N-t-BHA: ca. 30mg x 2

PyridoxAMINE (source specs showed nearly free of any immpurity 99%+ ...no longer available OTC) ca. 25mg x2

P5P: 25-50mg x4, depending on literature search.

Benfotiamine 150mg x4
Thiamine 50mg as part of MEO from LEF

I missed that thread (I answered you now about panthetine).
I'm curious to try NtBHA

Just found this:

http://www.jarrow.co....php?prodid=255

...purhcase here, for ca. $20/60 caps.

http://www.vitaminli...roduct_id/47409

50mg per cap of pyridoxamine. Also, since this isn't synthetic, your risk of impurity (historically a problem with pyridoxamine synthesis) is not an issue.

This may, long term, circumvent the patent claims of Biostratum, should they succeed. Similar situations exist wrt "red yeast rice" and statins, and though challenged, seem to persist.

MR recommends 500mg a day to replicate human phase II studies that showed plasma levels similar to those that produced benefits in rats.

That would get expensive REAL quick... hmm

Do you have a reference for these phase II studies? I'd like to take a peak.

Human pharmacokinetics and metabolism of oral Pyridorin, a novel therapeutic for diabetic nephropathy.

T. P. Degenhardt, R. G. Khalifah, R. J. Schotzinger;
BioStratum, Inc., Durham, NC, USA.



Background and Aims: Pyridorin (pyridoxamine dihydrochloride) is a novel inhibitor of the formation of advanced glycation end products (AGEs) and is currently in clinical development for the treatment of diabetic nephropathy. It has previously been shown that Pyridorin is effective in both the prevention and treatment of diabetic nephropathy in animal models of type 1 and type 2 diabetes. We present the first results from two recently completed phase 1 studies of oral Pyridorin in human volunteers that have enabled an assessment of this drug candidate’s pharmacokinetic profile.
Materials and Methods: In two single-center, placebo-controlled, randomized, double-blind, ascending dose studies, 24 healthy volunteers were randomized in a two to one fashion in the single dose study (6 subjects per dose level) and in a three to one fashion in the seven-day multiple dose study (8 subjects per dose level). PK samples were drawn at a minimum of 13 time points between 0 and 48 hours post-dose and analysed by an LC/MS method.
Results: Following a single oral dose of Pyridorin in the fasted state, Cmax of 1.9, 5.8 and 9.3 mg/mL were measured at doses of 10, 30, and 50 mg/kg, respectively. The Tmax was approximately 2.5 hours for all doses. The AUC0-inf was 6.4, 29 and 67 mg hr/mL at doses of 10, 30 and 50 mg/kg, respectively. The plasma half-life was approximately 2-3 hours. The absolute bioavailability of the 10 mg/kg dose was approximately 35%. The pharmacokinetic parameters derived following a multiple-dose regimen (twice-daily for seven days) were similar to single dose parameters, indicating a lack of accumulation of Pyridorin upon repeat dosing. The data suggest that a dose of approximately 500 mg/day or less in humans would provide average pyridoxamine plasma levels which have been demonstrated to be effective in animal studies of diabetic nephropathy. At this dose in humans, Pyridorin was very well tolerated. The metabolism of Pyridorin appears to follow the known metabolic pathways for the B6 vitamer family, with pyridoxal and 4-pyridoxic acid being the primary detectable metabolites. Even at high doses of Pyridorin, no conversion to pyridoxine has been detected. Liver enzyme studies suggest that the cytochrome P450 system plays little or no role in the metabolism of Pyridorin.
Conclusion: The pharmacokinetic data and information on the metabolism of Pyridorin strongly support the further development of this novel AGE inhibitor for the treatment of diabetic nephropathy.

"The data suggest that a dose of approximately 500 mg/day or less in humans would provide average pyridoxamine plasma levels which have been demonstrated to be effective in animal studies of diabetic nephropathy."

Unpublished (?) orperhaps this is the link....

http://www.ncbi.nlm....l=pubmed_docsum

...in either case, I don't seem to have access, so we can't see the raw data, however they do mention "or less", so that's encouraging. The study was designed to generate some safety data, and see how bioavailable PM is, and to see how long it took to clear, to extrapolate dosing. Who knows...perhaps when they treat diabetics with existing conditions, the efficacious dose will be lower.

Still, it's unclear to me how one might take into consideration studies showing efficacy in treatment in *existing* cases of nephrophathy, vs. life-long prophylactic dosing to avoid less severe, more subtle dysfunction. One could perhaps argue that less may be needed.

Also, given that most of us are taking one or more of a class of compounds that target the proteasome in similar ways, we may be able to get by with much less of each. Carnosine (1g), Histidine (2g) (Taurine, too, now, seems reasonable), Benfotiamine (600mg), Thiamine (100mg), PM (>> ca. 100mg given sources to purchase) and PLP (100mg), NTBHA (ca. 60mg): Hopefully our money is buying us some synergy.

Edited by trh001, 13 March 2006 - 11:43 PM.

Click HERE to rent this advertising spot for SUPPLEMENTS (in thread) to support LongeCity (this will replace the google ad above).

That seems like a high dose of benfotiamine -- I haven't seen more than 300mg recommended anywhere. MR also recommends 300mg. Can you share your reasoning on that?

Also, how does Taurine fit into this picture?