Lipoic Acid: New Research & the New Paradigm
By Linda on Feb 12, 2010 in Toxins
“In fact, to our knowledge there are few compounds as multifaceted as Lipoic acid as a bioactive agent. It is an inducer of cellular signaling pathways, insulin mimetic, a hypotriglyceridemic agent, a vasorelaxant/anti-hypertensive compound, a metal chelator and an adjuvant for neurocognitive function. Thus, it will be important to define the precise cause-and-effect relationship between Lipoic acid and its cellular targets of immediate action. 4””
No other Zeolite has this function.
Garry F. Gordon MD,DO,MD(H)
President, Gordon Research Institute
www.gordonresearch.com
http://www.geronova.com/content/lipoic-acid-new-research-new-paradigm
Lipoic Acid: New Research & the New Paradigm
Submitted by David Carlson on Mon, 08/17/2009 – 23:11
One of the things I love about my job is that I get to read and study and think a lot about lipoic acid. In fact, I try to relate almost every new chemistry, biochemistry or molecular biology paper back to how it relates to lipoic acid which leads to frequent accusations that Im a one dimensional lipoic acid geek. I prefer to think of it as being focused as I have also realized I am an inefficient multi-tasker. Undeterred by these (sometimes) playful jabs, I get to spend time digging through the dusty old archives searching for gems of information as well as reviewing and digesting the hot off the press and even ahead of press articles.
Over the years Ive learned that time spent in the library can be as or more productive than time spent in the lab. Im currently attempting to post new info as soon as I find it and it is particularly rewarding when I find new papers supporting my theories. Until recently I never imagined joining the blogosphere until I realized it is much faster to blog the findings and theories than to design and run the experiments to prove them and to get the findings published. Sometimes it takes several years to get from a concept or hypothesis to a completed experiment and publication. Im in touch with many lipoic acid researchers around the world but they frequently have their own agenda which is driven partially by interest but mostly by funding opportunities. Academics spend a significant of time vying for limited government funding.
Ive been working for the last couple of years compiling all the lipoic acid stereochemistry research I could find.1 I have been writing a comprehensive review article to advance my insights & ideas concerning the mechanisms of action of lipoic acid and specifically the role of stereochemistry which needs to be completed and submitted this year.2
Some of what I had to say has been recently said. Last year, Hagens group at LPI published a paper supporting their (and my) theories that lipoic acid is not really an in vivo antioxidant in the classical sense but is a stressor that induces cellular protective mechanisms.3
Yesterday, I got a Pub Med alert to the ahead of press review by the same group.4 The article is excellent and fairly comprehensive and at least raises the question of the role of stereochemistry in the mechanisms of action which was neglected in previous reviews 9,10 but doesnt go far enough to show the evidence to date indicates R-lipoic acid is superior in most cases to racemic alpha lipoic acid or S-lipoic acid. Please see my 1st blog, R-lipoic acid is the Eutomer of LA.11
So I have new motivation to finish and to publish my paper despite the up to date and comprehensive nature of the review article by Torys group. Shay et al advance many of the ideas and theories that Ive been developing over the years and introduced in an on-line publication5 and discussed in more detail in my OCC presentation.2
Anthony Smith, Tory Hagen and David Carslon – OCC Conference, 2008.
To be fair and honest, although I realized long ago that lipoic acid was much more than an antioxidant and despite its categorization as such most likely does not exert its in vivo benefits as a scavenger of ROS, RNS, RSS7 and may in fact act via pro-oxidant mechanisms, it is difficult to know to what extent my ideas were influenced through countless hours of discussion with Dr Anthony Smith; one of our scientific advisors while he was working with us on our early lipoic acid pharmacokinetic studies.8 Anthony got his doctorate and did post doc work in Hagens lab & is one of the co-authors of the new article and was deeply indoctrinated into this mindset. Hopefully my work had some influence on him and the LPI group as well.
Regardless of where the ideas originated, I am excited that these theories, supported by in vivo dose, concentration and time considerations rather than the heroic and unrealistic concentrations and incubation times used in vitro are finally getting out to a wider audience as it will change the way people think about lipoic acid. It also means that my ideas are being confirmed and validated by one of the worlds most respected lipoic acid research groups. That is always rewarding.
Despite what everyone thinks they know about lipoic acid, it is clear that lipoic acid is not (primarily) an in vivo antioxidant, at least in the sense of a radical scavenger. I am convinced that as this finding becomes more widely known it will direct lipoic acid research into the future and will become much more widely appreciated by the public for its unique characteristics and roles in improving the health span.
According to Shay et al;
In fact, to our knowledge there are few compounds as multifaceted as lipoic acid as a bioactive agent. It is an inducer of cellular signaling pathways, an insulin
mimetic, a hypotriglyceridemic agent, a vasorelaxant/anti-hypertensive compound, a metal chelator and an adjuvant for neurocognitive function. Thus, it will be important to define the precise cause-and-effect relationship between lipoic acid and its cellular targets of immediate action. 4
I should also add that it will be important to find its cellular targets of delayed action since it may induce downstream effects even after it has been metabolically transformed and cleared from the body.
1. http://www.geronova.com/content/research-overview
2. Further characterization of lipoic acid enantiomers provide new research opportunities. Stereochemistry, Pharmacokinetics & Metabolism: Toward a Comprehensive Mechanism of Action. Oxygen Club of California PowerPoint presentation by David A.Carlson, March,15, 2008.
The power point can be downloaded from http://www.geronova.com/content/research-overview
3. Petersen Shay K, Moreau RF, Smith EJ, Hagen TM. Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity. IUBMB Life. 2008 Jun;60(6):362-7. Review.
4. Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential. Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Biochim Biophys Acta. 2009 Aug 4.
5. http://www.geronova.com/docs/controlled_release_lipoicacid.pdf
6. http://www.geronova.com/content/anthony-smith-phd
7. Reactive Oxygen Species, Reactive Nitrogen Species & Reactive Sulfur Species
8. http://www.thorne.com/altmedrev/.fulltext/12/4/343.pdf.
9. Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 1997 Sep;29(3):315-31. Review.
10. Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress.
Curr Med Chem. 2004 May;11(9):1135-46. Review.
11. http://www.geronova.com/content/r-lipoic-acid-eutomer-lipoic-acid
