A controlled trial of amino acid therapy in amyotrophic lateral sclerosis: I. Clinical, functional, and maximum isometric torque data.

We conducted a two center, double-blind, placebo-controlled treatment trial with oral branched chain amino acids (BCAA) (L-leucine 12 g, L-isoleucine 8 g, and L-valine 6.4 g daily) or L-threonine (4 g daily) with pyridoxal phosphate (160 mg daily) for six months in patients with amyotrophic lateral sclerosis (ALS). The effect of treatment on disease progression was estimated every two months by recording clinical muscle strength, maximum isometric muscle torque in selected muscles, forced vital capacity (FVC), activities of daily living pertaining to the upper and lower limbs, and timed tasks. Ninety-five patients were randomized to receive BCAA (n = 31), L-threonine (n = 32), or placebo (n = 32), of whom 77 (81%) completed the trial. Mean weight loss in the placebo group was 1.1 kg and in the L-threonine group was 3.2 kg; the BCAA group gained 0.2 kg (p = 0.04). The estimated decline in FVC was about 2.5 times greater in the BCAA and L-threonine groups as compared to placebo (p = 0.03). Otherwise, no significant differences were found in the changes observed in clinical, functional, timed, or maximum torque measures among treatment groups. The amino acids were well tolerated. The results of our study failed to show a beneficial effect of BCAA or L-threonine treatment for six months on the disease course in ALS. The higher rate of loss of pulmonary function in patients treated with BCAA or L-threonine may have been due to chance, but an adverse effect of these amino acids cannot be ruled out.