Lipoic acid research

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Lipoic acid research

Postby dignan » Tue Apr 25, 2006 8:34 am

Here's another bit of evidence for lipoic acid...



Lipoic acid downmodulates CD4 from human T lymphocytes by dissociation of p56(Lck).

Biochem Biophys Res Commun. 2006 Apr 5
Marracci GH, Marquardt WE, Strehlow A, McKeon GP, Gross J, Buck DC, Kozell LB, Bourdette DN.
Portland Veterans Affairs Medical Center, R&D-65, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA; Department of Neurology, Oregon Health and Science University, Portland, OR, USA.

Lipoic acid is an antioxidant that suppresses and treats a model of multiple sclerosis, experimental autoimmune encephalomyelitis. We now demonstrate that treatment of human PBMC and T cell lines with LA downmodulated CD4 expression in a concentration-dependent manner.

LA treatment of Con A stimulated PBMC specifically removed CD4 from the T-cell surface, but not CD3. Epitope masking by LA was excluded by using monoclonal antibodies targeting different domains of CD4. Incubation on ice inhibited CD4 removal following LA treatment, suggesting that endocytosis was involved in its downmodulation.

LA is in a unique category of compounds that induce CD4 downmodulation by various mechanisms (e.g., gangliosides). We hypothesized that LA might induce dissociation of p56(Lck) from CD4, thus leading to its downmodulation. Immunoblot analyses demonstrated reduced co-precipitation of p56(Lck) from Jurkat T-cells following LA treatment and precipitation of CD4. This unique immunomodulatory effect of LA warrants further investigation.

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Postby dignan » Mon May 01, 2006 8:07 am

More on lipoic acid from the same researchers. Makes me wonder if they are going to do another trial soon. The last time they did a trial, they maxed out at 1200mg twice a day and didn't note any significant side effects and larger doses seemed more effective. They said at that time that the next step would be to administer the lipoic acid by injection I believe...



Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis.

J Neuroimmunol. 2006 Apr 24; [Epub ahead of print]
Chaudhary P, Marracci GH, Bourdette DN.
Department of Neurology, L226, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.

Lipoic acid (LA) suppresses and treats murine experimental autoimmune encephalomyelitis (EAE), which models multiple sclerosis. However, the mechanisms by which LA mediates its effects in EAE are only partially known.

In the present study, LA (25, 50 and 100 mug/ml) inhibited upregulation of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-alpha (TNF-alpha) stimulated cultured brain endothelial cells. Immunohistochemical analysis of spinal cords from SJL mice that had received LA (100 mg/kg/day) following immunization to induce EAE exhibited markedly reduced expression of ICAM-1 and VCAM-1 compared with that of EAE mice receiving saline. Co-localization analysis showed that ICAM-1 and VCAM-1 expression increased over endothelial cells (staining positive for von Willebrand factor, vWF) in EAE and that LA decreased the expression levels to that observed in naive mice. Spinal cords from mice receiving LA had significantly reduced inflammation (decreased CD4 and CD11b staining) as compared to EAE mice that received saline.

Overall, our data suggest that the anti-inflammatory effects of LA in EAE may be partly due to inhibition of ICAM-1 and VCAM-1 expression by central nervous system (CNS) endothelial cells.

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Postby ljm » Wed May 03, 2006 2:26 pm

Interesting. Anyone on board taking mega does of alpha lipoic acid? I'm taking 200 mg x 2 per day. However, I expect there is some synergy with other antioxidants.
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Re: Lipoic acid research

Postby NHE » Wed May 03, 2006 3:35 pm

ljm wrote:Interesting. Anyone on board taking mega does of alpha lipoic acid? I'm taking 200 mg x 2 per day.

Biotin, which is a B vitamin, can become depleted when taking lipoic acid at doses 100mg or greater per day. Therefore, it may be helpful to take a B supplement along with high doses of lipoic acid or to at least get your B vitamin levels checked. Note that some lipoic acid supplement formulations, such as Humax R-Lipoic Acid, contain added biotin to help compensate for this problem.

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Alpha Lipoic Acid Mega Dose

Postby Shayk » Wed May 03, 2006 6:38 pm

ljm

I'm not exactly sure what a mega dose is but I'm taking 1200 mg./day, all at once.

This article also discusses it. The entire article is available free in pdf format.

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More on Alpha Lipoic Acid

Postby Shayk » Mon Aug 07, 2006 7:42 pm

A bit more encouraging (I think) info about alpha lipoic acid.

This recent research focuses on a role for ALA in stabilizing the BBB.
In conclusion, we show that LA has a protective effect on EAE development not only by affecting the migratory capacity of monocytes, but also by stabilization of the BBB, making LA an attractive therapeutic agent for the treatment of MS.

This link contains lots of info on lipoic acid. The section on MS and ALA has links to related research.

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