It has been demonstrated that L-aspartic acid is an appropriate prodrug for colon-specific drug delivery[1]. Preadministration of 100 mM L-Aspartic acid and 100 mM L-Glu increases the amount of L-[3H]Asp that is still in the brain at 5 minutes by 206 and 178%, respectively; L-[3H]Asp efflux transport is unaffected by 100 mM D-Asp. The coadministration of 100 mM L-Aspartic acid and 100 mM L-Glu, respectively, increases that value for L-[3H]Glu at 20 minutes by 145 and 156%, but not by D-Asp. It's noteworthy to note that L-Aspartic acid appears to traverse the BBB seven times faster than L-Glu does[2].

Absorption, Distribution and Excretion
L-Aspartate is absorbed from the small intestine via active transport. In 15-day-old and adult mice, plasma aspartate concentrations increased 30 minutes after oral or intraperitoneal injection of 1 g/kg L-aspartate. Subsequently, plasma concentrations decreased exponentially with a half-life of 0.2 hours. No significant changes in plasma concentrations were observed after oral or intraperitoneal injection of 10 mg/kg and 100 mg/kg L-aspartate. Following ingestion, L-aspartate is absorbed from the small intestine via active transport. After absorption, L-aspartate enters the portal circulation and is transported from there to the liver. In the liver, most L-aspartate is metabolized into proteins, purines, pyrimidines, and L-arginine, with the remainder being catabolized. L-aspartate is not metabolized in the liver but enters the systemic circulation and is distributed to various tissues of the body. The cations bound to L-aspartate can independently interact with various substances in the body and participate in various physiological processes. /L-Aspartic Acid/
……The contents of D-aspartic acid and L-aspartic acid in the brain tissue of rats at different growth stages (1 day before birth to 90 days after birth) were determined. D-aspartic acid was detected in all brain tissue samples tested, but the content varied. The highest concentration of D-aspartic acid was found in the rat brain 1 day before birth, at 81 nmol/g wet tissue. The level of D-aspartic acid in the rat brain decreased rapidly after birth, while the level of L-aspartic acid increased with age.
This study used commercially available wheat germ phosphoenolpyruvate carboxylase to perform the enzymatic synthesis of C-(4)-L-aspartic acid. The distribution of radioactive compounds in rats showed that they accumulated in higher amounts in the salivary glands, proventriculus, pancreas, and lungs. Within 60 minutes of intravenous injection of 11C-(4)-L-aspartic acid, approximately 60% was exhaled as 11CO2, indicating that the fourth carbon atom of this radioactive compound readily undergoes decarboxylation. The brain efflux index has been used to elucidate the efflux transport mechanism of acidic amino acids (such as L-aspartic acid (L-Asp), L-glutamate (L-Glu), and D-aspartic acid (D-Asp)) across the blood-brain barrier (BBB). After microinjection into the brain, approximately 85% of L-[3H]Asp and 40% of L-(3H)Glu were cleared from the ipsilateral brain within 10 and 20 minutes, respectively. The efflux rate constants for L-(3H)Asp and L-(3H)Glu were 0.207 and 0.0346 min⁻¹, respectively. However, D-(3H)Asp was not cleared from brain tissue within 20 minutes. Excessive unlabeled L-Asp and L-Glu inhibited the efflux of L-(3H)Asp and L-(3H)Glu, while D-Asp had no inhibitory effect on either efflux transport. Aspartate efflux across the blood-brain barrier appears to be stereoselective. This study combined thin-layer chromatography (TLC) and bioimaging analysis to attempt to detect L-(3H)Asp and L-(3H)Glu metabolites in ipsilateral cerebral cortex and jugular venous plasma after microinjection into parietal cortex zone 2. The results showed that large amounts of intact L-(3H)Asp and L-(3H)Glu were present in all tested samples (including jugular venous plasma), directly demonstrating that at least a portion of L-Asp and L-Glu in the interstitial fluid crosses the blood-brain barrier intact. To compare the transport of acidic amino acids in brain parenchymal cells, brain slice uptake experiments were also conducted. Although D-(3H)Asp had the highest slice/culture medium ratio, followed by L-[3H]Glu and L-[3H]Asp, there was no difference in the initial uptake rate between L-(3H)Asp and D-(3H)Asp, indicating that the uptake of aspartate by brain parenchymal cells is not stereospecific. These results suggest that the blood-brain barrier may act as an efflux pump for L-Asp and L-Glu, reducing the concentration of interstitial fluid in brain tissue, and as a static barrier for D-Asp.

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Metabolism/Metabolites
For L-aspartate, oxaloacetate is a product of oxidative deamination or transamination; α-alanine is a product of decarboxylation.
/Excerpt from Table/
Metabolic Pathways and Products/In Animals/: Aspartic acid + carbamoyl phosphate/generates/phosphorus + carbamoyl aspartic acid to pyrimidine; Aspartic acid/generates/fumaric acid + NH3; Aspartic acid/generates/aspartic acid semialdehyde/generates/homoserine/generates/(I)threonine, (II) methionine or (III) lysine…/Excerpt from Table/
Metabolic Pathways and Products/In Animals/: Aspartic acid provides nitrogen for the purine ring…Aspartic acid + IMP to generate adenosine succinate, adenosine succinate to generate AMP + fumarate…/Excerpt from Table/
After ingestion, L-aspartic acid is absorbed from the small intestine via active transport. After absorption, L-aspartic acid enters the portal circulation and is transported from there to the liver, where it is mostly metabolized into proteins, purines, pyrimidines, and L-arginine, with the remainder being catabolized. D-aspartic acid is not metabolized in the liver but enters the systemic circulation and is transported to various tissues throughout the body. The cation bound to L-aspartic acid can independently interact with various substances in the body and participate in various physiological processes. /L-aspartic acid; D-aspartic acid/

Interactions
Aspartic acid, to some extent, prevented the development of morphine-dependent physiological symptoms in BALB/c mice. The effects of amino acids on nickel chloride embryotoxicity and placental transport were investigated. Day 10 rat embryos were cultured in rat serum containing nickel chloride or NiCl2-63 (0.34 or 0.68 μM NiCl2, with or without the addition of L-histidine (2 μM), L-aspartic acid, glycine (2 or 8 μM), or L-cysteine (2 μM)). Embryo survival, growth, and malformations were assessed after 26 hours. The Ni-63 content in the embryos and yolk sac, as well as the binding degree of Ni-63 to proteins in the culture medium, were also measured. 0.34 μM nickel chloride alone had no effect on embryonic development. 0.68 μM nickel caused growth retardation and brain and tail abnormalities. Compared with 0.68 μM nickel-63 alone, co-incubation of 0.68 μM nickel with L-histidine, L-cysteine, or L-aspartic acid reduced the incidence and/or severity of nickel chloride-induced growth retardation and brain defects, and decreased the concentration of nickel-63 in the yolk sac. In the presence of L-histidine, L-cysteine, or L-aspartic acid, nickel-63 binding was transferred from high-molecular-weight proteins in the culture medium to low-molecular-weight components. The effects of oral administration of D-aspartic acid and/or L-aspartic acid (aspartic acid) on rat body weight were investigated. Rats administered D- or D-+L-isomers showed greater reductions in body weight, as well as in protein, triglycerides, and glycogen, compared with rats administered L-isomers alone. The results are discussed with reference to the antagonistic effects of amino acids on opioids.

[1]. Blood-brain barrier produces significant efflux of L-aspartic acid but not D-aspartic acid: in vivo evidence using the brain efflux index method. J Neurochem. 1999 Sep;73(3):1206-11.

[2]. In vivo pharmacokinetic study for the assessment of poly(L-aspartic acid) as a drug carrier for colon-specific drug delivery. J Pharmacokinet Biopharm. 1995 Aug;23(4):397-406.

L-Aspartic acid is the L-enantiomer of aspartic acid. It is a metabolite of E. coli, a mouse metabolite, and a neurotransmitter. It belongs to the aspartic acid family of amino acids, is a protein-synthesizing amino acid, and is both an aspartic acid and an L-α-amino acid. It is the conjugate acid of L-aspartic acid (1-) and an enantiomer of D-aspartic acid. It is one of the common non-essential amino acids, usually existing in its L-form. It is found in plants and animals, especially in sugarcane and sugar beets. It may be a neurotransmitter. L-Aspartic acid is found in or produced by E. coli (K12 strain, MG1655 strain). Aspartic acid has been reported in Streptomyces frugifolius, Pinus tabuliformis, and other organisms with relevant data. Aspartic acid is a non-essential amino acid in humans, carries a negative charge, and plays an important role in the synthesis of other amino acids, as well as in the citric acid cycle and urea cycle. Asparagine, arginine, lysine, methionine, isoleucine, and some nucleotides are synthesized from aspartic acid. Aspartic acid also functions as a neurotransmitter. (NCI04)
It is one of the common non-essential amino acids existing in the L-form. It is found in plants and animals, especially in sugarcane and sugar beets. It may be a neurotransmitter.

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Pharmacological Indications
Currently, there is no evidence that aspartic acid is a performance enhancer, i.e., a synergist.

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Mechanism of Action
Some researchers claim that L-aspartic acid has a synergistic effect, improving performance in both prolonged and short-duration high-intensity exercise. It is speculated that L-aspartic acid, especially potassium magnesium aspartate, can conserve muscle glycogen reserves and/or promote faster glycogen synthesis during exercise. It is also speculated that L-aspartic acid can enhance performance in short-duration high-intensity exercise by acting as a substrate for energy production in the Klinefelter cycle and by stimulating the purine nucleotide cycle.

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Therapeutic Uses
Veterinary Drug: Used to reduce blood ammonia levels, and is said to be valuable in overcoming fatigue. Dosage: Oral administration or as a feed additive for the treatment of hyperammonemia and ammonia poisoning in poultry rats caused by stress. /Aspartic Acid/
Parenteral Nutrition
/Explanation/: L-Aspartic acid is a glycogenic amino acid that can also promote energy production by participating in the tricarboxylic acid cycle. Based on these effects, some claim that aspartic acid supplementation has an anti-fatigue effect on skeletal muscle, but this claim has never been proven. /L-Aspartic Acid/
It has been claimed that L-aspartic acid is a special mineral transporter that can transport cations such as magnesium into cells. However, magnesium aspartate has not shown higher biological activity compared to other magnesium salts. Others claim that L-aspartic acid has a synergistic effect, improving performance in both prolonged and short-duration high-intensity exercise. It has been hypothesized that L-aspartic acid, especially potassium magnesium aspartate, can conserve muscle glycogen reserves and/or promote rapid glycogen synthesis during exercise. Still others hypothesize that L-aspartic acid can enhance performance in short-duration high-intensity exercise by acting as a substrate for energy production in the Klinefelter cycle and by stimulating the purine nucleotide cycle. However, an animal study using injected aspartic acid failed to find any evidence of glycogen conservation or synergistic effects. A recent double-blind human study of male weightlifters also found no effect from aspartic acid supplementation; another study on the effects of aspartic acid on short-duration high-intensity exercise also found no effect. L-Aspartic Acid /
For more complete data on the therapeutic uses of L-aspartic acid (6 types), please visit the HSDB record page.

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Drug Warnings
There have been reports that L-aspartic acid may cause mild gastrointestinal side effects, including diarrhea. L-Aspartic Acid /
Due to a lack of long-term safety studies, L-aspartic acid salts should be avoided in children, pregnant women, and breastfeeding women. L-Aspartic Acid /
This study evaluated the effects of oral potassium magnesium aspartate (K+MgAsp) on the physiological responses of seven healthy men (VO2 max = 59.5 ml × kg-1 × min-1) walking on a treadmill at approximately 62% VO2 max intensity for 90 minutes. Each participant took 7.2 g of K+MgAsp within 24 hours prior to exercise and was compared with a control group and a placebo group. No significant differences were observed in resting or exercise-induced ventilation (VE), oxygen uptake (VO2), carbon dioxide production (VCO2), respiratory exchange rate (RO), heart rate (HR), or blood pressure (BP) among the control, placebo, and K+MgAsp groups. Furthermore, there were no differences among the three groups in exercise-induced weight loss and rectal temperature increase, or in changes in serum lactate, creatine kinase, lactate dehydrogenase, and plasma volume percentage before and after exercise. These results indicate that oral administration of K+MgAsp before exercise has no effect on cardiopulmonary, hemolytic, and metabolic responses during 90 minutes of exercise at approximately 62% VO2 max intensity. /Potassium Magnesium Aspartate/
This study investigated the effect of aspartate (ASP) supplementation on plasma ammonia concentration (NH4+) during and after resistance training (RTW). This study employed a crossover double-blind design, randomly selecting 12 male weightlifters who received either ASP or vitamin C, with a one-week interval between the two trials. Both ASP and vitamin C were administered 5 hours before recovery training (RTW) and continued for 2 hours. RTW included bench press, incline bench press, shoulder press, triceps press, and biceps curl, with a load of 70% of 1RM. After RTW, performance was assessed using the bench press test (BPT) to failure (65% of 1RM). (NH4+) levels were measured before exercise, at 20 and 40 minutes during exercise, immediately after exercise, and 15 minutes after exercise. Treatment-time ANOVA, paired t-tests, and comparative analyses were used to determine differences in means. Results showed no significant differences in (NH4+) and BPT between the two groups. (NH4+) levels significantly increased in both the ASP and vitamin C groups from before exercise to immediately after exercise. In strength trainers, acute aspartate (ASP) supplementation does not lower ammonia (NH4+) levels during and after high-intensity recovery training. /Aspartate Potassium Magnesium/

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Pharmacodynamics
L-Aspartate is considered a non-essential amino acid, meaning that under normal physiological conditions, the body synthesizes enough of this amino acid to meet its needs. L-Aspartate is formed from the transamination of oxaloacetate, an intermediate in the tricarboxylic acid cycle. This amino acid is a precursor in the synthesis of proteins, oligopeptides, purines, pyrimidines, nucleic acids, and L-arginine. L-Aspartate is a glycogenic amino acid, and it can also promote energy production through its metabolism in the tricarboxylic acid cycle. Based on these activities, it has been claimed that aspartate supplementation has an anti-fatigue effect on skeletal muscle, but this claim has never been proven.

C4H7NO4

133.1027

133.037

56-84-8

25608-40-6;1115-63-5 (mono-potassium salt);14007-45-5 (potassium salt);17090-93-6 (hydrochloride salt);2001-89-0 (di-potassium salt);2068-80-6 (magnesium (2:1) salt);21059-46-1 (calcium salt);3792-50-5 (mono-hydrochloride salt);39162-75-9 (calcium (2:1) salt);5598-53-8 (di-hydrochloride salt)

5960

White to off-white solid powder

1.5±0.1 g/cm3

264.1±30.0 °C at 760 mmHg

>300 °C (dec.)(lit.)

113.5±24.6 °C

0.0±1.1 mmHg at 25°C

1.531

-0.67

3

5

3

9

133

1

C([C@@H](C(=O)O)N)C(=O)O

CKLJMWTZIZZHCS-REOHCLBHSA-N

InChI=1S/C4H7NO4/c5-2(4(8)9)1-3(6)7/h2H,1,5H2,(H,6,7)(H,8,9)/t2-/m0/s1

(2S)-2-aminobutanedioic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

1M NaOH : 100 mg/mL (~751.31 mM)
H2O : ~2 mg/mL (~15.03 mM)
DMSO :< 1 mg/mL

Solubility in Formulation 1: 1 mg/mL (7.51 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)