VANCOUVER, BC—Lipoic acid is safe, well tolerated, and offers neuroprotection in patients with secondary progressive multiple sclerosis (MS), results from a “highly promising pilot study” presented at the 68th AAN Annual Meeting have shown.

The 2-year randomized, double-blind trial found that lipoic acid, an inexpensive small molecule oral antioxidant, demonstrated “a significant reduction in whole brain atrophy, a trend towards beneficial effects on walking speed and reduction in falls, and overall safety and tolerability,” Rebecca I. Spain, MD, MSPH, of the VA Portland Health Care System and Oregon Health & Science University, Portland, OR, and colleagues reported.

The study randomized 54 patients with secondary progressive MS to either placebo or lipoic acid 1200mg/day. Of these subjects, 51 took at least 1 dose and were included in the analysis, 24 in the placebo group and 27 in the lipoic acid group.

Reduction in MRI whole brain atrophy was the primary outcome. “Secondary outcomes included atrophy of brain substructures, spinal cord atrophy, retinal and macular atrophy, changes in neurological exam, walking, cognition, fatigue, and quality of life,” they noted.

Average age was 57.9 ± 6.7 years in the lipoic acid group and 59.7 ± 6.1 years in the placebo group; 59% and 63%, respectively, were female, and, in both groups, 96% were Caucasian. Average disease duration was 30.9 ± 9.3 years with a median EDSS of 5.5 (3.0–8.0) in the lipoic acid group; in the placebo group, disease duration was 29.1 ± 9.9 years with a median EDSS of 6 (3.0–9.0).

The adverse event that occurred at a significantly higher rate in the lipoic acid group was gastrointestinal disorders (21% vs. 6% in the placebo group; P=0.007); specifically, gastrointestinal upset (17% vs. 3%; P=0.004). Injury from falls was significantly higher in the placebo group, 38%, compared with 15% in the lipoic acid group (P=0.03).

Lipoic acid “is found in trace quantities in foods like liver, spinach, and yeast,” Dr. Spain noted; however, “the major source is endogenous synthesis. The lipoic acid/dihydrolipoic acid redox couple is a key co-factor for pyruvate dehydrogenase in mitochondria, which may relate to its mechanism of action in MS,” she added.

In a mouse model of MS—experimental autoimmune encephalomyelitis—lipoic acid has been shown to decrease inflammation as well as optic and spinal cord atrophy.

“A larger trial is necessary to confirm the effects of brain atrophy, determine the clinical benefits, and further affirm the safety of lipoic acid in the progressive MS population,” the investigators concluded.