Potential Treatment for ADHD Based on Recovery from Tryptophan-Induced Central Fatigue by Powerful Competitive Inhibition of L-System Amino Acid Transporter

Fatigability in attention deficit hyperactivity disorder (ADHD) is associated with the characteristic inattention behavior. Evidence has indicated that the administration of branched-chain amino acids (BCAAs) to Nagase analbuminemic rats (NARs), a fatigue-prone animal model of ADHD, diminishes central fatigue. This effect is accompanied by competitive inhibition at the L-system amino acid transporter (LAT), which takes tryptophan into the brain. We investigated whether dietary supplementation with BCAAs plus phenylalanine and methionine (BPM) or BCAAs plus 2-amino-2-norbornanecarboxylic acid (BCAAs + BCH) has the effect of synergistically improving central fatigue in rats and humans compared with BCAAs alone. NAR performed exercise duration for 420 minutes (5 out of 5 rats; n = 5/5) using BPM and 542 minutes (n = 5/5) using BCAA + BCH. These were significantly longer than when saline or BCAA alone were administered to rats. When administering BPM supplements to human subjects, they found an efficacy rate of 50% in reducing fatigue compared to a placebo, compared to 38% for BCAA alone. Central fatigue in rats and humans was caused by a common mechanism involving tryptophan as an inducing trigger, and BPM supplementation contributed to the strong amplification effect of competitive inhibition at the LAT, the addition of phenylalanine and methionine. These powerful nutritional strategies improved exercise performance and mood beyond the physiological limits of fatigue. BPM, the natural nutrients, can promote the improvement of ADHD symptoms in humans. Prior to treatment with conventional monoamine reuptake inhibitors, it is necessary to eliminate fatigue by BPM treatment, which is the causative basis of ADHD.