An Evaluation of Interindividual Responses to the Orally Administered Neurotransmitter β-Alanine

Previously, we have identified β-alanine as a potential endogenous anticonvulsant molecule. β-Alanine occurs within the human central nervous system and has been identified as both an inhibitory neuromodulator and neurotransmitter that is bioavailable to brain after oral administration. During preliminary compounding trials to ascertain dosing strategies for β-alanine, we noted pronounced differences in the side effect profile experienced by individuals of Asian and Caucasian descent. To investigate whether ethnicity affects β-alanine-induced side effects, we administered 3？g of β-alanine in 200？mL of fruit drink to ten people of each ethnic background and observed them for 30 minutes. Data collected included basic physical statistics (height, age, and weight) and descriptions of all side effects, as reported by participants. We found that participants of Asian descent experienced paraesthesia, but significantly different in time of onset, intensity, and anatomical localization, as compared to the effects experienced by Caucasian participants. Since β-alanine is an endogenous neurotransmitter substance within human brain, these side effect differences were unexpected. 1. Introduction Epilepsy is the most common serious chronic neurological brain disorder afflicting humankind, with no racial, socioeconomic, national, or geographic predilections; it affects more than 50 million people worldwide. The tendency of epilepsy to onset in children renders its socioeconomic impact disproportionate; moreover, the disorder is also associated with high comorbidity and significant life-long stigmatization. Since current anticonvulsant drugs are effective in less than 65% of people (and their use is associated with side effects in more than 50% of people), the need for new, effective, and safe therapies for epilepsy is a continuing neuropharmacological priority [1]. To address this need, we have sought to identify an “endogenous anticonvulsant molecule (ECM)” (i.e.,？？？the brain’s own anti-seizure compound) as a platform around which to develop new drugs. Through this work, we have identified β-alanine as one possible candidate ECM [2, 3]. β-Alanine occurs within the human central nervous system (CNS) and has been identified as both an inhibitory neuromodulator [4] and neurotransmitter [5]. β-Alanine is structurally intermediate between α-amino acid (glycine) and γ-amino acid (GABA) inhibitory neurotransmitters (Figure 1). β-Alanine satisfies the prerequisite classical criteria for being a neurotransmitter: β-alanine occurs naturally in the CNS, is released by