title: Lipoic acid in multiple sclerosis: a pilot study.
abstract: Lipoic acid (LA) is an antioxidant that suppresses and treats an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis. The purpose of this study was to determine the pharmacokinetics (PK), tolerability and effects on matrix metalloproteinase-9 (MMP-9) and soluble intercellular adhesion molecule-1 (sICAMP-1) of oral LA in patients with MS. Thirty-seven MS subjects were randomly assigned to one of four groups: placebo, LA 600 mg twice a day, LA 1200 mg once a day and LA 1200 mg twice a day. Subjects took study capsules for 14 days. We found that subjects taking 1200 mg LA had substantially higher peak serum LA levels than those taking 600 mg and that peak levels varied considerably among subjects. We also found a significant negative correlation between peak serum LA levels and mean changes in serum MMP-9 levels (T = -0.263, P =0.04). There was a significant dose response relationship between LA and mean change in serum sICAM-1 levels (P =0.03). We conclude that oral LA is generally well tolerated and appears capable of reducing serum MMP-9 and sICAM-1 levels. LA may prove useful in treating MS by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS.
authors.affiliation: Department of Veterans Affairs Medical Center, Portland, OR, USA.
authors.forename: V
authors.initials: V
authors.lastname: Yadav
authors.forename: G
authors.initials: G
authors.lastname: Marracci
authors.forename: J
authors.initials: J
authors.lastname: Lovera
authors.forename: W
authors.initials: W
authors.lastname: Woodward
authors.forename: K
authors.initials: K
authors.lastname: Bogardus
authors.forename: W
authors.initials: W
authors.lastname: Marquardt
authors.forename: L
authors.initials: L
authors.lastname: Shinto
authors.forename: C
authors.initials: C
authors.lastname: Morris
authors.forename: D
authors.initials: D
authors.lastname: Bourdette
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism; D010865:Pilot Projects; D012995:Solubility; D008063:Thioctic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000975:Antioxidants; D018799:Intercellular Adhesion Molecule-1; D008063:Thioctic Acid; D020780:Matrix Metalloproteinase 9