We unleash your business potential by maximize the business innovation.
Send EmailArginine Alpha-Ketoglutarate, L-Arginine Alpha-Ketoglutarate, Arginine AKG, AAKG, 5256-76-8
Arginine Alpha-Ketoglutarate (AAKG)
CAS Number: 5256-76-8
Chemical Formula: C₁₁H₂₀N₄O₇
Molecular Weight: ~320.30 g/mol
EC Number: 226-059-7
Synonyms: AAKG, Arginine AKG, L-Arginine Alpha-Ketoglutarate, Arginine 2-Oxoglutarate, Alpha-Ketoglutaric Acid L-Arginine Salt, Arginine 2-Oxopentanedioate, Arginine α-Ketoglutarate
1. CHEMICAL IDENTITY
| Parameter | Information |
|---|---|
| Product Name | Arginine Alpha-Ketoglutarate |
| IUPAC Name | (2S)-2-Amino-5-guanidinopentanoic acid; 2-oxopentanedioic acid |
| CAS Number | 5256-76-8 |
| Molecular Formula | C₁₁H₂₀N₄O₇ |
| Molecular Weight | ~320.30 g/mol |
| EC Number | 226-059-7 |
| Chemical Class | Amino Acid Salt; Nutritional Supplement |
| Structure | Salt form of L-Arginine (amino acid) + Alpha-Ketoglutaric Acid |
2. PHYSICAL PROPERTIES
| Parameter | Value |
|---|---|
| Physical State | Solid |
| Color | White to off-white |
| Appearance | Crystalline powder |
| Odor | Characteristic (slightly acidic) |
| Taste | Slightly sour |
| Melting Point | ~155-160°C (decomposes) |
| Density (20°C) | ~1.5 g/cm³ |
| Hygroscopicity | Moderately hygroscopic |
| Particle Size (typical) | 100% through 40 mesh; varies by grade |
3. SOLUBILITY PROPERTIES
| Solvent | Solubility (20°C) |
|---|---|
| Water | Soluble (~100-150 g/L) |
| Ethanol | Slightly soluble |
| Methanol | Slightly soluble |
| Acetone | Insoluble |
| Ether | Insoluble |
| Phosphate Buffer (pH 7.4) | Freely soluble |
Note: Solubility increases with temperature. Solutions maintain best stability at pH 5-7.
4. CHEMICAL STRUCTURE
| Component | Structure |
|---|---|
| L-Arginine | C₆H₁₄N₄O₂ |
| Alpha-Ketoglutaric Acid | C₅H₆O₅ |
| AAKG Salt | 1:1 molecular ratio |
| Guanidino Group | NH₂-C(=NH)-NH- (critical for NO synthesis) |
| Ketone Groups | Two ketone groups on AKG (2-oxoglutarate) |
Structural Note: The alpha-ketoglutarate component stabilizes the arginine molecule and participates independently in the Krebs cycle (energy metabolism).
5. SPECIFICATIONS (Typical – High Quality Grade)
| Parameter | Specification | Method |
|---|---|---|
| Assay (AAKG on dried basis) | 98.0 – 102.0% | HPLC/Titration |
| L-Arginine Content | 55-60% | Titration |
| Alpha-Ketoglutarate Content | 40-45% | Titration |
| Moisture (Karl Fischer) | ≤5.0% | Karl Fischer |
| pH (1% solution, 25°C) | 6.0 – 7.5 | Potentiometric |
| Heavy Metals (as Pb) | ≤10 ppm | AAS/ICP |
| Arsenic (As) | ≤1.5 ppm | AAS |
| Lead (Pb) | ≤1.5 ppm | AAS |
| Cadmium (Cd) | ≤1.0 ppm | AAS |
| Mercury (Hg) | ≤0.1 ppm | AAS |
| Residue on Ignition | ≤0.5% | Gravimetric |
| Loss on Drying | ≤5.0% | Gravimetric |
| Specific Rotation ([α]²⁰/D) | +14.5° to +17.5° | Polarimeter |
| Chloride (Cl) | ≤0.05% | Titration |
| Sulfate (SO₄) | ≤0.05% | Gravimetric |
| Microbial Total Plate Count | ≤1,000 cfu/g | Plate Count |
| Yeast and Mold | ≤100 cfu/g | Plate Count |
| E. coli | Negative | PCR/Culture |
| Salmonella | Negative | PCR/Culture |
6. MOLECULAR RATIO AND PURITY GRADES
| Grade | Purity | Typical Use |
|---|---|---|
| 1:1 (Standard AAKG) | ~98% | Sports nutrition, pre-workout |
| 2:1 (Arginine:AKG) | ~98% | Higher arginine concentration |
| Pharmaceutical Grade | ≥99% | Clinical studies, medical use |
| Food Grade | ≥98% | Food supplements |
Most Common Commercial Form: 1:1 Molar ratio (Arginine:Alpha-Ketoglutarate)
7. MECHANISM OF ACTION
| Pathway | Effect |
|---|---|
| Nitric Oxide (NO) Pathway | L-Arginine → Nitric Oxide Synthase (NOS) → Nitric Oxide (NO) → Vasodilation → Increased blood flow and oxygen delivery to muscles |
| Krebs Cycle (AKG) | Alpha-Ketoglutarate enters the Krebs cycle → ATP production → Enhanced cellular energy metabolism |
| Protein Synthesis | Arginine stimulates growth hormone release → Increased protein synthesis → Muscle growth and repair |
| Ammonia Detoxification | Alpha-Ketoglutarate participates in the urea cycle → Removes excess ammonia → Reduces fatigue |
8. BIOLOGICAL ROLES AND BENEFITS
| Role | Description |
|---|---|
| Vasodilation (Blood Flow) | Increases nitric oxide production → Widens blood vessels → Better "pump" during exercise |
| Oxygen Delivery | Enhanced blood flow delivers more oxygen to working muscles → Improved endurance |
| Energy Production | AKG fuels the Krebs cycle → Increased ATP synthesis → Delayed fatigue |
| Muscle Protein Synthesis | Stimulates anabolic hormones (growth hormone, insulin) → Faster recovery |
| Ammonia Removal | Alpha-ketoglutarate binds ammonia → Reduces muscle fatigue and soreness |
| Antioxidant Support | AKG supports glutathione production → Protects against oxidative stress |
9. APPLICATIONS – SPORTS NUTRITION
| Application | Function |
|---|---|
| Pre-Workout Supplements | Primary ingredient for "pump" effect; increases blood flow to muscles |
| Muscle Growth Formulas | Supports protein synthesis and growth hormone release |
| Endurance Supplements | Delays fatigue; improves oxygen delivery |
| Post-Workout Recovery | Accelerates muscle repair; reduces soreness |
| Strength Training Products | Enhances power output and training volume |
| Stacked Formulations | Often combined with Creatine, Citrulline Malate, Beta-Alanine, and L-Glutamine |
Typical Pre-Workout Dosing: 2,000 – 6,000 mg per serving
10. APPLICATIONS – CLINICAL AND PHARMACEUTICAL
| Application | Mechanism |
|---|---|
| Cardiovascular Support | Improves endothelial function; lowers blood pressure (mild effect) |
| Wound Healing | Arginine promotes collagen synthesis and tissue repair |
| Liver Support | AKG aids liver detoxification and ammonia metabolism |
| Immune Function | Arginine supports T-cell function and immune response |
| Nitric Oxide Deficiency | Supplement for individuals with low NO production |
11. APPLICATIONS – FUNCTIONAL FOODS AND BEVERAGES
| Product Type | Function |
|---|---|
| Sports Drinks | Performance enhancement; electrolyte balance |
| Protein Bars | Muscle recovery and growth support |
| Functional Waters | Hydration with NO-boosting benefits |
| Ready-to-Drink Shakes | Pre-workout or post-workout nutrition |
12. COMPARISON: AAKG vs. L-Arginine (Free Form)
| Property | AAKG (1:1) | L-Arginine (Free Form) |
|---|---|---|
| Stability | Higher (salt form) | Lower (degrades faster) |
| Solubility | Better | Good |
| Taste | Less bitter (more neutral) | Bitter |
| Absorption | May be enhanced | Standard |
| NO Production | Comparable | Comparable |
| Additional Benefit | AKG (energy metabolism) | None |
| Cost per gram | Higher | Lower |
| Typical Dose | 3-6 g/day | 3-6 g/day |
13. COMPARISON: AAKG vs. Arginine Silicate (Nitrosigine®)
| Property | AAKG | Arginine Silicate |
|---|---|---|
| Bioavailability | Good | Enhanced (prolonged release) |
| NO Duration | Short-term (1-2 hours) | Extended (3-5 hours) |
| Clinical Evidence | Extensive (older studies) | Growing |
| Cost | Moderate | Higher |
| Popularity | Very high (long history) | Increasing |
14. COMPARISON: AAKG vs. Citrulline Malate
| Property | AAKG | Citrulline Malate |
|---|---|---|
| NO Production | Direct arginine → NO | Arginine recycling (increased plasma arginine) |
| Fatigue Reduction | Moderate | Superior |
| Dose | 3-6 g/day | 6-8 g/day |
| Taste | Slightly sour | Sour (malate component) |
| Cost | Moderate | Moderate |
| Best For | Acute pump, blood flow | Endurance, fatigue reduction |
15. SYNERGISTIC COMBINATIONS
| Ingredient | Synergy Effect |
|---|---|
| Citrulline Malate | Increased plasma arginine levels; reduced fatigue |
| Creatine Monohydrate | Strength and power; ATP recycling |
| Beta-Alanine | Delayed muscle fatigue; carnosine synthesis |
| L-Glutamine | Immune support; muscle recovery |
| Taurine | Enhanced hydration; muscle function |
| Nitrate (Beetroot Extract) | Additive NO production; vasodilation |
16. SAFETY AND TOXICOLOGICAL PROFILE
| Parameter | Value |
|---|---|
| Acute oral toxicity (rat, LD₅₀) | >5,000 mg/kg (low toxicity) |
| Acute dermal toxicity (rabbit, LD₅₀) | >2,000 mg/kg |
| Skin irritation | Non-irritating |
| Eye irritation | Mildly irritating (powder) |
| Skin sensitization | Not a sensitizer |
| Genotoxicity | Negative (Ames test) |
| Carcinogenicity | Not classified as carcinogenic |
| Reproductive toxicity | No evidence at recommended doses |
GHS Classification: Not classified as hazardous under normal conditions of use.
17. RECOMMENDED DOSAGE
| User Type | Daily Dose | Timing | Duration |
|---|---|---|---|
| Recreational Athlete | 2,000 – 3,000 mg | 30-60 min pre-workout | 4-8 weeks |
| Competitive Athlete | 4,000 – 6,000 mg | 30-60 min pre-workout | 8-12 weeks |
| Bodybuilding | 6,000 – 8,000 mg | Split dose (morning + pre-workout) | 12 weeks |
| Clinical Use (Cardiovascular) | 3,000 – 6,000 mg | Divided doses | As directed |
| Loading Phase | Not required | Not applicable | Not applicable |
Important Note: Always follow manufacturer recommendations and consult a healthcare professional before starting supplementation.
18. POTENTIAL SIDE EFFECTS
| Effect | Frequency | Notes |
|---|---|---|
| Mild gastrointestinal discomfort | Low (at high doses) | Diarrhea, nausea, bloating |
| Headache | Low | Vasodilation effect |
| Low blood pressure | Rare | Caution in hypotensive individuals |
| Allergic reaction | Very rare | Rash, itching (discontinue use) |
| Arginine-induced diarrhea | Very rare | Above 10 g/day |
Contraindications:
-
Hypotension (low blood pressure)
-
Herpes simplex (arginine may trigger outbreaks)
-
After heart attack (consult physician)
-
Liver or kidney disease (consult physician)
19. STORAGE AND HANDLING
| Parameter | Requirement |
|---|---|
| Storage Temperature | 15-25°C (room temperature) |
| Humidity | Low humidity (<50% RH) – hygroscopic |
| Container | Tightly sealed (airtight) |
| Light Protection | Protect from direct sunlight |
| Shelf Life (proper storage) | 24-36 months |
| Signs of Degradation | Clumping, discoloration (yellowing), off-odor |
| Special Precautions | Do not refrigerate (may absorb moisture). Keep away from strong oxidizers. |
20. SUMMARY AND CRITICAL INFORMATION
Description: Arginine Alpha-Ketoglutarate (AAKG, CAS 5256-76-8) is a salt composed of the amino acid L-Arginine and Alpha-Ketoglutaric Acid in a 1:1 molar ratio. It is widely used in sports nutrition as a pre-workout ingredient to enhance nitric oxide production, increase blood flow ("pump"), support energy metabolism, and accelerate muscle recovery.
Key Advantages:
-
Increases nitric oxide (NO) production → vasodilation → better blood flow and oxygen delivery
-
AKG component fuels the Krebs cycle → enhanced energy production
-
Supports muscle protein synthesis and growth hormone release
-
Aids ammonia detoxification → reduced fatigue
-
Stable salt form (better than free arginine)
-
Superior solubility compared to free arginine
-
Neutral taste (less bitter than free arginine)
Key Limitations/Considerations:
-
Requires consistent use for sustained effects
-
May cause mild gastrointestinal distress at high doses
-
Lower bioavailability than some newer arginine forms (e.g., arginine silicate)
-
Not suitable for individuals with herpes simplex (arginine may trigger outbreaks)
-
May interact with blood pressure medications
Comparison Summary:
| Feature | AAKG | L-Arginine | Citrulline Malate |
|---|---|---|---|
| NO Production | High | High | Very High (via recycling) |
| Energy Support | Yes (AKG) | No | Yes (Malate) |
| Stability | Good | Moderate | Excellent |
| Taste | Acceptable | Bitter | Sour |
| Best Use | Pre-workout pump | General NO | Endurance |
Typical Formulations (Sports Nutrition):
| Product Type | AAKG Dose per Serving |
|---|---|
| Pre-workout powder | 2,000 – 6,000 mg |
| Pre-workout capsules | 2,000 – 4,000 mg |
| Pump-focused formulas | 4,000 – 6,000 mg |
| Stacked formulas | 2,000 – 3,000 mg (with other NO boosters) |
Safety Summary:
-
Low acute toxicity (LD₅₀ oral >5,000 mg/kg)
-
Generally safe at recommended doses (2-6 g/day)
-
Not classified as hazardous under normal use
-
Contraindicated in hypotensive individuals and those with herpes simplex
-
Always consult healthcare professional before supplementation
Conclusion: AAKG is a well-established, effective ingredient in sports nutrition, particularly for pre-workout formulations aimed at increasing blood flow (muscle pump), improving exercise performance, and accelerating recovery. The alpha-ketoglutarate component provides additional energy metabolism support. While newer arginine-based ingredients have emerged, AAKG remains a popular, cost-effective, and clinically supported choice for athletes and bodybuilders seeking enhanced nitric oxide production and muscle oxygenation.
