Absorption, utilization, and safety of aspartic acid

Area of Science:

• Biochemistry
• Neuroscience
• Metabolism

Background:

• Dicarboxylic amino acids, aspartate and glutamate, are crucial in intermediary metabolism, particularly in mitochondria.
• These amino acids play significant roles in nitrogen and energy metabolism.
• Previous studies indicated neurotoxic effects, including neuronal necrosis, in newborn mice upon administration of high glutamate and aspartate doses.

Purpose of the Study:

• To investigate the neurotoxic effects of glutamate and aspartate in animal models, focusing on species differences.
• To determine the plasma concentration thresholds for neuronal necrosis induction.
• To assess the potential risk to primates and humans from dietary intake of these amino acids.

Main Methods:

• Administration of high doses of glutamate and aspartate to neonatal mice and infant subhuman primates.
• Monitoring for neurotoxic effects, specifically neuronal necrosis.
• Measuring plasma levels of glutamate and aspartate to establish concentration thresholds.

Main Results:

• Neonatal mice exhibited neurotoxicity and neuronal necrosis at high plasma concentrations (60-80 mumol/dl) of glutamate and aspartate.
• Infant primates did not develop neuronal necrosis even with plasma glutamate levels ranging from 50 to 1,600 mumol/dl.
• Significant elevations in plasma amino acid levels are necessary for neurotoxicity, with species-dependent thresholds.

Conclusions:

• Neuronal necrosis from glutamate and aspartate is species-specific, with neonatal mice being highly sensitive and primates showing resistance.
• The risk of neurotoxicity to healthy primates and humans from reasonable dietary intake of dicarboxylic amino acids is low.
• High doses of these amino acids are toxic to neonatal mice, but not under typical human or primate consumption levels.