In a study of 37 multiple sclerosis patients, subjects were randomized to 4 groups, including placebo (2 male and 7 female subjects, median age 50 years); alpha lipoic acid at 600 mg, 2 times daily (1 male and 6 female subjects, median age 49 years); alpha lipoic acid at 1,200 mg, once daily (1 male and 8 female subjects, median age 54 years); and alpha lipoic acid at 1,200 mg of lipoic acid, twice daily (0 male and 8 female subjects, median age 44.5 years), administered for 14 days. Subjects who took 1,200 mg of lipoic acid daily had significantly higher peak serum lipoic acid levels compared with those who took 600 mg, and the peak levels varied considerably among subjects. There was a significant negative correlation between peak serum lipoic acid levels and mean changes in serum metalloproteinase-9 levels. There was a significant dose response relationship between lipoic acid and mean change in serum soluble intercellular adhesion molecule-1 levels. This study suggests that oral lipoic acid is well tolerated and may be able to reduce serum metalloproteinase-9 and soluble intercellular adhesion molecule-1. Lipoic acid may be beneficial in treating multiple sclerosis by inhibiting metalloproteinase-9 activity and interfering with T-cell migration into the central nervous system.