My investigation into both exogenous and endogenous AGEs have naturally led me to researching anti-glycation molecules. Since AGEs seem to play a substantial role in heath deterioration and aging, it is only reasonable I try to not only mitigate their consumption and internal formation, but also supplement to provide additional anti-glycation effects. My previous post led me to the discovery of a controversial anti-glycation molecule. When I started researching it, I found several other anti-glycation molecules that aren’t so iffy in terms of safety. In this post I am going to summarize the most common anti-glycation molecules, even the iffy ones, and in a following post (or two) I am going to discuss how Michale Rae approaches anti-glycation in his supplement regime (updated Fall 2009) and what I am going to change in my own supplementation to provide anti-glycation support outside of diet control.

Pyridoxamine (Vit B6)
Vitamin B6 is comprised of 3 different compounds: pyridoxamine, pyridoxal, and pyridoxine. Of these three, pyridoxamine (usually sold in the form pyridoxamine dihydrochloride) is converted in the body to the active form of P5P (pyridoxal-5-phosphate), which inhibits the formation of AGEs (you can also buy P5P separatly).
I’m not sure how this will affect it’s availability, but there was a petition filed in 2007 by a pharmaceutical company (although this isn’t the only petition and this argument appears to date back to 2005) to make it unlawful to sell dietary supplements containing P5P because the company was investigating its cardiovascular benefits. In Feburary 2009, it was announced that Vit6 in the form of pyridoxamine dihydrochloride cannot be used in dietary supplements. There is a grandfather clause in effect allowing ingredients that have been on the market for more that 15years to remain. I have filed this in the growing filing cabinet in my head under: Things That Make Sie ‘Grrrr’. So…grrrrr.

Pimagedine (aminoguanidine)
This molecule is used in the treatment of dietetic nephropathy, mostly in Europe from what I understand, and it is known to inhibit glycation leading to AGE formation. Animal studies also indicated this drug prevented age related heart enlargement, and increased collagen in the arterial walls. Human trials, however, indicated toxicity issues, so the dosage at which toxicity occurs was questioned by The Life Extension Foundation since the company running the studies and the FDA would not release the toxicity information (this was back in 2001). The LEF observed that a max dose of 200mg three times a day seemed to be safe, but only recommend that dose to diabetic customers while recommending that healthy adults only take a max of 300mg per day, and stated they need to have routine blood test preformed to watch for possible unknown kidney or liver toxicities. Apparently in the human trials, the drug proved to be very beneficial in the short term, but ended up being too toxic for longer trials to continue. Side effects included flu-like symptoms, anemia, and the development of anti-nuclear antibodies (present in high numbers in people with auto-immune disorders).
So, while this drug has great potential, the side effects could undermine a Life Extensionist’s goals. However, I have seen many accounts of people still using it without any noticeable effects, but I personally think this compound breaks the “First Do No Harm” rule.

Taurine
Taurine is a derivative of the amino acid cycteine. Taurine is mostly found in seafood and meat, so people following a vegan diet intake a negligible amount in their diet and many take supplements to avoid deficiency. This molecule is actually in indicated in a wide range of physiological functions, and in the past few years has also been found to be an anti-glycation inhibitor thus preventing formation of AGEs.
This may be the reason vegans and vegetarians are reported to have higher serum levels of AGEs even though they have a much lower dietary intake when compared to some omnivores who intake an average of 58mg of taurine per day whereas vegans have an intake of almost 0mg unless they supplement.

Benfotiamine
Benfotiamine is a derivative of thiamine, vitamin B1. It has proven effective for treating complications of diabetes due to it’s speculative ability to reduce the formation of AGEs. However, despite it’s possible ability to lower AGE concentrations in the body, it has also been found to be a possible cancer risk by providing a suitable environment for cancer growth.
While this doesn’t seem to be as obviously scary as the previous supplement, due to lingering uncertainties I am not comfortable taking it.

Carnosine
Carnosine is a combination of the amino acids histidine and beta-alanine. Because of it’s ability to inhibit glycation reactions that form AGEs, antioxidant properties, and metal chelator abilities, it has been proposed as an anti-aging supplement. While carnosine does occur in the body, it is also found in meat as well as dairy and egg products. Again, this could be another reason why serum AGEs are higher in vegan/vegetarians when compared to meat eaters.

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Alagebrium (ALT-711)
This is the first drug to be clinically tested specifically for the purpose of breaking cross-links caused by AGEs. Phase I and II trials were actually very promising, but the company, Alteon, stopped active research after phase II due to lack of funds. In 2007, the company was bought and the name was changed to Synvista Therapeutics, Inc, and are operating in the USA, but they outsource their research. On January 13, 2009, they announced progress in phase II of clinical trials for alagebrium. Strangely, on January 28, 2009, they announced an end to their clinical trials for alagebrium stating that it is in the best interest of the company for finical reasons to terminate all clinical trials for alagebrium and another drug SYI-2074 and instead focus on the value of their diagnostic assets.
There is a note at the end of the wiki -take it however you want, but I know crap like this happens in labs/research facilities; I was in medical chemistry in grad school- that even though this medication achieved dramatic positive results, it is very easy and cheap to replicate. This makes the molecule a risk in terms of patent protection (it became very available on the black/gray market after successful Phase I&II trails), so buyers cannot be satisfied they are buying an exclusively owned product, thus the product was unable to achieve backing by venture capitalist before Phase III trials and FDA approval was finalized.