DL-Aspartic Acid: Metabolic Roles, Dietary Impact, and Pathophysiological Implications

DL-Aspartic acid is a nonessential amino acid. This means it can be made from other substances in your body. It helps make other amino acids and some nucleotides. DL-Aspartic acid also plays a role in energy production in the body. It also helps send chemical signals through the nervous system. Definition-Aspartic acid or aspartate, also known as amino succinic acid is a non-essential amino acid that is synthesized itself in the human body through different sources of foods. It is mainly responsible for synthesizing proteins and regulating hormones so also known as building blocks. In 1868, DL-Aspartic acid (the ionic form is known as aspartate) was isolated from legume in plant seeds and is apparently known as an amino acid obtained as a product of the hydrolysis of proteins.  DL-Aspartic acid is a non-essential amino acid, so your healthy body is able to produce its own supply. Besides, it can also be found in such food sources as dairy, beef, poultry, sugar cane and molasses. Individuals with diets low in protein or having eating disorders or malnutrition may suffer from the results of DL-Aspartic acid deficiency like extreme fatigue or depression.

Changes in dietary intake of DL-Aspartic acid

This study aimed to investigate a possible correlation between amino acid intake and glycemic markers among overweight, still metabolically healthy individuals who practiced IF.  Repeated measures analysis of variance showed that both groups experienced a reduction in BMI after diets compared to baseline values (TRE: 28.3 ± 6.7 kg/m2 [baseline] vs. 27.5 ± 6.3 kg/m2 [7 weeks], p < .001 and OF: 29.0 ± 6.0 kg/m2 [baseline] vs. 28.2 ± 5.4 kg/m2 [7 weeks], p < .001). During the dietary intervention, a significant decrease in the daily intake of DL-Aspartic acid (8.77 vs. 5.90 g; p < .01), alanine (4.42 vs. 2.99 g; p < 0.01), and methionine (2.10 vs. 1.44 g; p < .01) was observed in the TRE group. Such differences were not documented in the control group for any of the amino acids examined. The TRE group had a lower intake of DL-Aspartic acid than the OF group at seven (p = .03) and 12 weeks (p < .01). In the TRE group, FPG presented a decreasing trend during the study: 90.14 mg/dl (baseline) vs. 84.50 mg/dl (7 weeks) vs. 83.29 mg/dl (12 weeks), with the difference significant between baseline and 12 weeks (p = 0.021).[1]

General linear models for repeated measures showed that the change in DL-Aspartic acid intake presented a positive correlation with FPG values in the TRE group, suggesting that the greater the reduction from baseline to 12 weeks, the lower the expected FPG concentrations at the final time point (p = .039). However, the significance diminished when BMI and body fat were included in the model (p = .049). In the TRE group, the effect of changes in alanine and methionine intake on FPG values at 12 weeks was found to be marginally nonsignificant (p = .052 and p = .054, respectively). To our knowledge, this pilot study is the first to assess the impact of amino acid intake on glucose homeostasis in people practicing IF.  Reduced DL-Aspartic acid intake during and after intermittent fasting presented a positive correlation with fasting glucose. The positive effects of intermittent fasting on glucose metabolism could be partially related to a decrease in the ingestion of specific amino acids.

DL-Aspartic acid in Health and Disease

DL-Aspartic acid exists in L- and D-isoforms (L-Asp and D-Asp). Most L-Asp is synthesized by mitochondrial aspartate aminotransferase from oxaloacetate and glutamate acquired by glutamine deamidation, particularly in the liver and tumor cells, and transamination of branched-chain amino acids (BCAAs), particularly in muscles. DL-Aspartic acid has two negatively charged carboxyl groups at physiological pH and is transported through cell membranes via specific transporters together with glutamic acid, the other dicarboxylic amino acid found in the body. DL-Aspartic acid is a nutritionally non-essential amino acid discovered by hydrolysis of asparagine. Aspartate exists in two isoforms; the main form is L-aspartic acid (L-Asp), and D-aspartic acid (D-Asp) is present in much smaller amounts: L-Asp has exceptional importance in urea synthesis, purine-nucleotide cycle (PNC), malate–aspartate shuttle (MAS), gluconeogenesis, and neurotransmission, and it is the substrate for the synthesis of proteins, asparagine, arginine, nucleotides, and of several substances that play a role in the development of nervous tissue and neurotransmission.[2]

Although DL-Aspartic acid is classified as a nutritionally non-essential amino acid, meaning that it can be synthesized in sufficient quantities in the body in all physiologic and pathologic conditions, there are several disorders in which aspartate metabolism is significantly disturbed. Both L-Asp and D-Asp residues can be dehydrated on the side chain carbonyl and form D-aspartic acid. It has been shown that isoAsp formation triggers autoimmune responses to self-proteins. L-Asp supply can decrease ammonia levels in two ways. First, DL-Aspartic acid can, via cAST, increase the formation of glutamate (L-Asp + 2-OG → OA + Glu), which is a substrate for ammonia detoxification to glutamine in muscles. The second, L-Asp, can increase the flux through the urea cycle and enhance ammonia detoxification in the liver. The ammonia-lowering substance employed in the treatment of hepatic encephalopathy is LOLA (L-ornithine L-aspartate).  Increased levels of DL-Aspartic acid and phenylalanine, which cross the blood–brain barrier, can play a role in changes in brain neurochemistry. Excess L-Asp can disrupt NMDA receptor signaling and be converted by cAST into glutamate, which is linked to the hyperexcitability of neurons. Excess of phenylalanine impairs the transport of tyrosine and tryptophan through the blood–brain barrier, inhibits the flux through tyrosine hydroxylase and tryptophan hydroxylase, and inhibits the synthesis of dopamine, norepinephrine, and serotonin.

References

[1]Karras SN, Koufakis T, Dimakopoulos G, Popovic DS, Kotsa K. Changes in dietary intake of aspartic acid during and after intermittent fasting correlate with an improvement in fasting glucose in overweight individuals. J Diabetes. 2023 Feb;15(2):181-184. doi: 10.1111/1753-0407.13351. Epub 2023 Jan 9. PMID: 36624580; PMCID: PMC9934951.

[2]Hole?ek M. Aspartic Acid in Health and Disease. Nutrients. 2023 Sep 17;15(18):4023. doi: 10.3390/nu15184023. PMID: 37764806; PMCID: PMC10536334.