130 replies to this topic

[trh001]

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?

Michael's right, of course. The short answer is: caution, overall. The slightly longer short answer is it may be too high, and all of the doses could use refinement. It's based on what I *recall* of the entry level dose for diabetics (where did I read this?), which was higher (I thought around 600mg), followed by scale back, to maintenance doses of 300-400mg (I *seem* to recall), but nothing solid, no. It appears to have less toxicity than thiamine, though as noted in another post, produced ROS at *lower* dosages, relative to higher, though the net effect seems to be positive. All very vague at this stage, but I've only been taking for a few weeks at this dose, and am plowing through the papers now.

At least I'm not taking 3 grams of C. (see other references on genotoxicity...it's a healthy devil's advocate position, and as much poking fun at myself for having taken high doses as a young optimist, while reading Pauling's work. "Bowel Tolerance Limit!" was his war cry.)

As for Taurine, I can generate a list of references. Will probably post something later tonight. It's based upon (again, interim, as I'm still poking around) results of my searches that suggest it may have a benefit similar to Histidine wrt glycation, though I have no evidence to suggest it might be involved in a family of peptides associated with cellular senescence, such as the carnosine/anserine Histidine peptides.

[syr_]

At least I'm not taking 3 grams of C. 

I am [lol]

[trh001]

...and, I'm not saying it's not a good thing, just another example of how difficult it is to find solid footing, at least for me, with the shifting literature.

[FunkOdyssey]

Michael's right, of course. The short answer is: caution, overall. The slightly longer short answer is it may be too high, and all of the doses could use refinement. It's based on what I *recall* of the entry level dose for diabetics (where did I read this?), which was higher (I thought around 600mg), followed by scale back, to maintenance doses of 300-400mg (I *seem* to recall), but nothing solid, no. It appears to have less toxicity than thiamine, though as noted in another post, produced ROS at *lower* dosages, relative to higher, though the net effect seems to be positive. All very vague at this stage, but I've only been taking for a few weeks at this dose, and am plowing through the papers now.

At least I'm not taking 3 grams of C. smile.gif (see other references on genotoxicity...it's a healthy devil's advocate position, and as much poking fun at myself for having taken high doses as a young optimist, while reading Pauling's work. "Bowel Tolerance Limit!" was his war cry.)

As for Taurine, I can generate a list of references. Will probably post something later tonight. It's based upon (again, interim, as I'm still poking around) results of my searches that suggest it may have a benefit similar to Histidine wrt glycation, though I have no evidence to suggest it might be involved in a family of peptides associated with cellular senescence, such as the carnosine/anserine Histidine peptides.

Hey trh, are you still taking 600mg of benfotiamine? What conclusion did you come to on the benfotiamine dosage? Also, where are those references for taurine's anti-glycation activity you promised? Inquiring minds want to know

[Pablo M]

The reference I found to taurine was in conjunction with a vegetarian diet:
Pubmed link

BTW, "bowel tolerance" was not Pauling's war cry. Here's a quote from Vitamin C, the Common Cold and the Flu:

I estimate that for many people 1g to 2g per day is approximately the optimum rate of ingestion. There is evidence that some people remain in very good health[...] through the ingestion of only 250mg of ascorbic acid per day. The requirements of a few[...] may be even smaller.

[FunkOdyssey]

Yeah, I guess this was no big secret, just news to me, as I'm finding them all over the place now. Here's a good one:

Acta Physiol Scand. 2004 Jul;181(3):297-303.  Related Articles, Links
    Click here to read
    Stimulation of glucose utilization and inhibition of protein glycation and AGE products by taurine.

    Nandhini AT, Thirunavukkarasu V, Anuradha CV.

    Department of Biochemistry, Faculty of Science, Annamalai University, Tamil Nadu, India.

    AIM: Pathological effects of the process of non-enzymatic glycation of proteins are reflected in chronic complications of diabetes mellitus. We investigated the antiglycating effect of taurine in high fructose fed rats in vivo and the inhibiting potency of taurine in the process of in vitro glycation. Additionally, we investigated whether taurine enhances glucose utilization in the rat diaphragm. METHODS: Rats fed a high fructose diet (60% total calories) were provided 2% taurine solution for 30 days. The effects of taurine on plasma glucose, fructosamine, protein glycation and glycosylated haemoglobin in high fructose rats were determined. For in vitro glycation a mixture of 25 mm glucose and 25 mm fructose was used as glycating agent, bovine serum albumin as the model protein and taurine as the inhibitor. Incubations were carried out in a constant temperature bath at 37 degrees C for 3-30 days. Amadori products and advanced glycation end products (AGEs) formed were measured. In vitro utilization of glucose was carried out in the rat diaphragm in the presence and absence of insulin in which taurine was used as an additive. RESULTS: The contents of glucose, glycated protein, glycosylated haemoglobin and fructosamine were significantly lowered by taurine treatment to high fructose rats. Taurine prevented in vitro glycation and the accumulation of AGEs. Furthermore, taurine enhanced glucose utilization in the rat diaphragm. This effect was additive to that of insulin and did not interfere with the action of insulin. CONCLUSIONS: These results underline the potential use of taurine as a therapeutic supplement for the prevention of diabetic pathology.

    PMID: 15196090

The only question that remains is dosage.

[scottl]

The genotoxicity of vit c has been debunked. I"m pretty sure I posted a ref regarding this. If I get around to it, I'll post it again.

[trh001]

Michael's right, of course. The short answer is: caution, overall. The slightly longer short answer is it may be too high, and all of the doses could use refinement. It's based on what I *recall* of the entry level dose for diabetics (where did I read this?), which was higher (I thought around 600mg), followed by scale back, to maintenance doses of 300-400mg (I *seem* to recall), but nothing solid, no. It appears to have less toxicity than thiamine, though as noted in another post, produced ROS at *lower* dosages, relative to higher, though the net effect seems to be positive. All very vague at this stage, but I've only been taking for a few weeks at this dose, and am plowing through the papers now.

At least I'm not taking 3 grams of C. smile.gif (see other references on genotoxicity...it's a healthy devil's advocate position, and as much poking fun at myself for having taken high doses as a young optimist, while reading Pauling's work. "Bowel Tolerance Limit!" was his war cry.)

As for Taurine, I can generate a list of references. Will probably post something later tonight. It's based upon (again, interim, as I'm still poking around) results of my searches that suggest it may have a benefit similar to Histidine wrt glycation, though I have no evidence to suggest it might be involved in a family of peptides associated with cellular senescence, such as the carnosine/anserine Histidine peptides.

Hey trh, are you still taking 600mg of benfotiamine? What conclusion did you come to on the benfotiamine dosage? Also, where are those references for taurine's anti-glycation activity you promised? Inquiring minds want to know

I become easily distracted (work, women, small shiny objects...) but will get back to this at some point soon. The breadth of reprints I'm reading through has increased somewhat of late, and my time budget shrank a bit. Wrt the former, I've been focusing a bit on personal needs re. my low HDL, and what that might mean, and how best to tackle it, so it dilutes things a bit.

Yes, am still taking 600mg per day of Benfotiamine, though I plan on cutting back at some point, if the literature warrants, and if I can see no benefit to an initial higher dose being maintained for some time to compensate for a life filled with glycatory sin (I ate too much Captain Crunch and roast beef, as a child).

Re. Taurine, you seem to have stumbled on a gold mine ("It's Bonanza, Little Joe"...only a boomer will appreciate the reference) so I'll field any specific questions moving forward, but the literature is, as you've found, pretty well stocked.

Best, Tim

[trh001]

Following up: re. my reference earlier in this thread (somewhere) to Benfotiamine's antioxidant status not likely being linked to its efficacy in studies on AGE and diabetes, and in fact has been shown to compromise REDOX in some studies.

Aside from the mechanism elucidated in...

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

Other studies....

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

...have shown that (and since I can't cut and paste the PDF, I'll just quote one summary statement and note the thrust of this aspect of the discussion) "Taken together, these studies suggest that benfotiamine might exert vascular and renal benefits by modulating mechanisms independent or down-stream of ROS formation." ...this per citation of other work showing, variously: ROS production by Benfotiamine, no effect on glutathione status, or negative effect on glutathione status.

[trh001]

Benfotiamine clinical trial dosages seem to have been in the 150-600mg range.
--------------------------

600mg per day for 4 weeks:

http://www.benfotiam...nfo600Study.pdf

150mg-320mg for 6 weeks:

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

400mg/day for 3 weeks:

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

[carnosine]

I've been taking the powder form about 250 mg twice a day with food.

Aside from the taste no problems.

[FunkOdyssey]

Jarrow Pyridoxall seems to still be available online all over the place -- can anyone find a cheaper source than this?

http://www.herbspro....90011180135.htm

They're selling it for $16.19 a bottle.

[rflalonde]

Nutrition Dome has Jarrow Pyridoxall for $14.70 a bottle if you buy four bottles. Including the shipping costs of $5.80, that makes $64.60 for four bottles, 60 caps per bottle, 50 mg per cap, a total of 12 grams. $64.60 divided by 12 = $5.38 per gram.
LifeLink has PrimAGE for $35.95 a bottle. I just bought 3 bottles. Shipping and sales tax came to $13.82, so the total was $121.67. Each bottle has 60 caps, 200 mg per cap, a total of 36 grams. $121.67 divided by 36 = $3.38 per gram, a much better price than Nutrition Dome or HerbsPro.

[rflalonde]

I forgot to mention that LifeLink shipped the PrimAGE by overnight carrier, and delivered it to my front door. The envelope felt cool to the touch; I hope that means it wasn't sitting in the back of a sun-baked delivery truck before it was delivered.

[FunkOdyssey]

LifeLink has PrimAGE for $35.95 a bottle. I just bought 3 bottles. Shipping and sales tax came to $13.82, so the total was $121.67. Each bottle has 60 caps, 200 mg per cap, a total of 36 grams. $121.67 divided by 36 = $3.38 per gram, a much better price than Nutrition Dome or HerbsPro.

I'm not sure how this post managed to fade into obscurity -- this is by far the best deal on Pyridoxamine I've ever seen. Unfortunately, I've never heard of Lifelink before. What do you guys think of them?

http://www.lifelinkn...cts/PrimAGE.asp

[FunkOdyssey]

They also say it contains both Pyridoxamine and P5P, but they don't specify how much of each. In fact, they don't provide any ingredient list at all. The site is giving me an unprofessional vibe that makes me wary.

[rflalonde]

The LifeLink capsules contain 200 mg pyridoxamine and 50 mg P-5-P each. It was rather thoughtless of them not to mention this on their website, and I knowingly took a chance when I ordered; but everything worked out well. Maybe these guys should take pyridoxamine themselves.

[FunkOdyssey]

I'm going to ask them for the full list of ingredients (active, inert, filler, etc), where they get the raw material, how the product is manufactured, and how purity is ensured. I'll report back with their reply.

[neogenic]

I am not sure if this product contains pyridoxamine or they extrapolating data on the compound with the inclusion of b6.

http://valuenutritio...arcap60cap.html

[FunkOdyssey]

Here is the response I received from LifeLink regarding PrimAGE:

Thank you for your enquiry about LifeLink's product, PrimAGE™. As LifeLink's consultant on this product, I've been asked to answer your questions.

Your enquiry has reminded us that we've been intending to update each of the product descriptions on LifeLink's website by adding an ingredient list. Other projects have kept pushing this one aside, but we're now giving this project high priority.

To answer your specific questions about PrimAGE:

The ingredients in PrimAGE are as follows.

Active ingredients:
Pyridoxamine dihydrochloride...200 mg
Pyridoxal-5-Phosphate...20 mg

Inactive ingredients:
Magnesium stearate
Gelatin

------- Pyridoxamine dihydrochloride

The pyridoxamine dihydrochloride in PrimAGE is imported through the importer KDN-Vita International. It is manufactured by a company in mainland China, the identity of which we've been asked by KDN-Vita not to divulge for competitive reasons. (It is not manufactured by DNP -- DNP is an import company, not a manufacturer.)

The manufacturer's chemical analysis of the pyridoxamine dihydrochloride in our product had the following results:

Assay......................... 98.0%
Loss on Drying..................... 0.30%
Melting Point.....................  225.2 - 226.2 C
Nitrogen.....................  11.38%
Chloride.....................  29.16%
Sulfated Ash.................. .07%
pH............................ 2.5

Pyridoxamine is synthesized from pyridoxine by treatment with ammonia. The majority of the 2% impurity shown in the assay is undoubtedly unreacted pyridoxine — however, we do not have documentation to prove it. We are considering having future batches recrystallized to eliminate most of this pyridoxine, although this would increase the price of the product.

------- Pyridoxal-5-Phosphate

The pyridoxal-5-phosphate in PrimAGE is imported through the importer BI Nutraceuticals. It, too, is manufactured by a company in mainland China, the identity of which we've been asked by BI Nutraceuticals not to divulge for competitive reasons. (Again, it is not manufactured by DNP -- DNP is an import company, not a manufacturer.)

The manufacturer's chemical analysis of the pyridoxal-5-phosphate in our product had the following results:

Assay by HPLC............ 99.6%
Total Heavy Metals.... less than 20 ppm
pH....................... 2.85

----------

PrimAGE is formulated and packaged in the United States in a cGMP lab (current Good Manufacturing Practices Laboratory as defined and enforced by the FDA). LifeLink prefers to keep the identity of this packaging supplier proprietary at the present time. It is, however, one of the major supplement suppliers in the U.S.

Again, thank you for your enquiry. We may receive more detailed information from our importers in the near future, and if we do I'll pass it on to you.

Russell Mills, Ph.D.
Consultant to LifeLink

So the pyridoxamine is 98% pure, and they think the remaining 2% is unreacted pyridoxine. Personally, I wouldn't take a chance with it.

[rflalonde]

Nutrition Dome has Jarrow Pyridoxall for $14.70 a bottle if you buy four bottles.  Including the shipping costs of $5.80, that makes $64.60 for four bottles, 60 caps per bottle, 50 mg per cap, a total of 12 grams.  $64.60 divided by 12 = $5.38 per gram.
LifeLink has PrimAGE for $35.95 a bottle.  I just bought 3 bottles.  Shipping and sales tax came to $13.82, so the total was $121.67.  Each bottle has 60 caps, 200 mg per cap, a total of 36 grams.  $121.67 divided by 36 = $3.38 per gram, a much better price than Nutrition Dome or HerbsPro.

LENutri.com has a better deal on pyridoxamine; $39.99 for 110-275 mg capsules. 110 x 0.275 = 30.25 grams. $39.99 divided by 30.25 = $1.32 per gram. This is WAY less than PrimAGE at $3.38 per gram. One might even say suspiciously less.

[meatwad]

LENutri.com has a better deal on pyridoxamine; $39.99 for 110-275 mg capsules. 110 x 0.275 = 30.25 grams. $39.99 divided by 30.25 = $1.32 per gram. This is WAY less than PrimAGE at $3.38 per gram. One might even say suspiciously less.[/SIZE][/font][/quote]

[thumb] LENutri.com gets alot of $&@( because of that vid clip [tung]

[curious_sle]

heh, well not only due to the clip *cough*. Their business acumen (track record) is less then sterling to say the least. search a bit for the name of the owner here on the boards yourself.

i still maintain the cheepest source for the jarrows product (damn fine one) is the one i mentioned several times now in this thread.

[DukeNukem]

Anyone know where this ended up with the FDA? I've done some googling but cannot find anything. Also, I'm looking to buy more of Jarrow's Pyridoxall, but it doesn't seem to be available any more. But, I just ordered straight pyridoxamine from LEF (50mg caps), though Jarrow's formula was a superior mix, especially with the pyridoxal-5-phosphate. Darn.

Edited by DukeNukem, 02 September 2008 - 04:18 PM.

[stephen_b]

I'm interested in this too. I think it's really crappy that a company was able to get the FDA to block this.

DukeNukem, I did find some stock, and have far more than I need. PM me if interested.

Stephen

[david ellis]

The next democratic candidate for president is a socialist:

"We're going to take things away from you on behalf of the common good."

Senator Hillary Rodham Clinton
Democratic Party Fundraiser
June 28th 2004


Though she is now in the process of appearing to be moderate so she can get elected.

Yes the US is headed that way. Now all we need is a 21st century Edward Gibbon to document it all.

Hold on Scott1, you have quoted Hillary Clinton accurately. But, here is the context, she was speaking to a group of very rich democrats. She was telling the rich democrats that President Bush's tax cuts for the extremely rich would be set back to a parity with the previous taxes under President Clinton. And they still gave her money. Is that socialist? No. Is that class warfare? Yes, President Bush has set up a tax system where Warren Buffett's secretary pays a much higher percentage than Warren Buffett. That is class warfare. And Hillary planned to trim the unfair advantage the rich held. She was going to use the new money to balance her budget. Something George W never worried about.

Use Snopes or mediamatters to fact-check stuff like this and we can begin to talk about our real differences.

[peteinpok]

Anyone know where this ended up with the FDA? I've done some googling but cannot find anything. Also, I'm looking to buy more of Jarrow's Pyridoxall, but it doesn't seem to be available any more. But, I just ordered straight pyridoxamine from LEF (50mg caps), though Jarrow's formula was a superior mix, especially with the pyridoxal-5-phosphate. Darn.

I am a diabetic and as such have taken interest in this issue and pyridoxamine. I cannot find anything that indicates that the FDA made a decision on the petition. Biostratum, the company that initiated this issue and holds (or held) any intellectual property rights on Pyridorin(pyridoxamine) appears to have gone out of business (partly or mostly to do with this issue). I would assume that someone picked up these intellectual property rights but if/and who did/ or what they intend to do with them I have no idea.

I sent an email to the FDA regional representative asking about this issue but never received any reply.....

I spoke to Jarrow (June 2008 I think it was) and they say they have stopped making/selling Pyridoxall due to no other problems but low sales. There may still be some on distributers shelfs but I dont think very much.

Also, studies done by Biostratum on the half life of pyridoxamine in humans showed "No quantitative level of PM was observed in human plasma (<50 ng/mL) following 50 mg dosing." http://www.aapspharm...2003-001280.PDF
The next levels they studied were 250mg and 500mg bid.

At this point I think LifeLink is the source I will continue with.

[krillin]

100 mg/day seems to be as effective as 500 mg/day.

http://content.karge...;file=000108104

Comparison of the pyridoxamine treatment effect size relative to placebo indicated that a treatment effect did not differ between 50 mg twice daily (PYR-206) and escalating 250 mg twice daily (PYR-205/207) dosing (data not shown).

Am J Nephrol. 2007;27(6):605-14.
Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy.
Williams ME, Bolton WK, Khalifah RG, Degenhardt TP, Schotzinger RJ, McGill JB.
Harvard Medical School, Joslin Diabetes Center, Boston, MA 02215, USA. mark.williams@joslin.harvard.edu

BACKGROUND/AIMS: Treatments of diabetic nephropathy (DN) delay the onset of end-stage renal disease. We report the results of safety/tolerability studies in patients with overt nephropathy and type 1/type 2 diabetes treated with pyridoxamine, a broad inhibitor of advanced glycation. METHODS: The two 24-week studies were multicenter Phase 2 trials in patients under standard-of-care. In PYR-206, patients were randomized 1:1 and had baseline serum creatinine (bSCr) <or=2.0 mg/dl. In PYR-205/207, randomization was 2:1 and bSCr was <or=2.0 for PYR-205 and >or=2.0 but <or=3.5 mg/dl for PYR-207. Treated patients (122 active, 90 placebo) received 50 mg pyridoxamine twice daily in PYR-206; PYR-205/207 patients were escalated to 250 mg twice daily. RESULTS: Adverse events were balanced between the groups (p = NS). Slight imbalances, mainly in the PYR-205/207 groups, were noted in deaths (from diverse causes, p = NS) and serious adverse events (p = 0.05) that were attributed to pre-existing conditions. In a merged data set, pyridoxamine significantly reduced the change from baseline in serum creatinine (p < 0.03). In patients similar to the RENAAL/IDNT studies (bSCr >or=1.3 mg/dl, type 2 diabetes), a treatment effect was observed on the rise in serum creatinine (p = 0.007). No differences in urinary albumin excretion were seen. Urinary TGF-beta1 also tended to decrease with pyridoxamine (p = 0.049) as did the CML and CEL AGEs. CONCLUSION: These data provide a foundation for further evaluation of this AGE inhibitor in DN. © 2007 S. Karger AG, Basel.

PMID: 17823506

[peteinpok]

[quote name='krillin' date='6-Sep 2008, 07:13 PM' post='261800']
100 mg/day seems to be as effective as 500 mg/day.......

Interesting. This is a re-review of the old (2002-2003) Biostratum studies data. I guess that even though the 50mg dosing was not significant in the blood (by Biostratum's own studies), it had some effectiveness. Thanks for pointing this article out to me.

Supposedly, mixing pyridoxamine(PM) with P5P also enhances the serum PM levels.

Also, it appears that NephroGenex, Inc. purchased at least some of the rights for Pyridorin from Biostratum. NephroGenex appears to have at least a couple of the previous Biostratum executives/researchers/founders. However, it is not clear if they are still operating (web site has been gone for a while and no new news from them). I guess time will tell.

[sUper GeNius]

Seems like it could be a reasonable request. Is the compound in any herbs or other plants? If not, seems like they are protecting their commercial rights.