L-Alanine, L-Glycine, L-alanyl-L-Glutamine (Sustamine®)
Mechanism of Action +
### The Pharmacokinetics of Dipeptide Absorption
The primary limitation of free-form L-glutamine supplementation is its poor systemic bioavailability. Enterocytes (the cells lining the intestinal tract) and immune cells within the gut utilize free glutamine as their primary fuel source. Consequently, up to 70-80% of ingested free L-glutamine is sequestered by the splanchnic bed before it can reach systemic circulation. L-alanyl-L-glutamine circumvents this biological bottleneck through its dipeptide structure. Instead of relying on standard sodium-dependent amino acid transporters, the dipeptide is absorbed via the PEPT1 (Peptide Transporter 1) system. This transporter is highly efficient and less susceptible to competitive inhibition by other amino acids. Because the dipeptide bond remains intact during intestinal transport, the gut cells do not recognize it as free glutamine, allowing it to pass into the portal vein and systemic circulation. Clinical pharmacokinetic studies demonstrate that this mechanism results in plasma glutamine levels that are 224% higher than those achieved with an equivalent dose of free L-glutamine.
### Intracellular Hydration and Osmotic Regulation
Once in the bloodstream, endogenous peptidases cleave the dipeptide into its constituent amino acids: L-alanine and L-glutamine. Both amino acids play synergistic roles in cellular hydration. L-alanine actively increases the concentration of intracellular potassium. Because water follows osmotic gradients, this localized increase in potassium draws water into the myocyte (muscle cell), promoting a state of hyperhydration. This cellular swelling is not merely cosmetic; it acts as an anabolic signal, reducing protein breakdown and stimulating protein synthesis. Concurrently, L-glutamine is metabolized into ammonia in the kidneys. This process, known as ammoniagenesis, is critical for maintaining the body's acid-base (pH) balance during intense exercise. By buffering the accumulation of hydrogen ions (which cause muscle burning and fatigue), glutamine helps maintain an optimal cellular environment for sustained muscular contraction and fluid balance.
### Gluconeogenesis and the Glucose-Alanine Cycle
During strenuous endurance exercise, muscle glycogen stores are rapidly depleted. To maintain blood glucose levels and provide continuous energy, the body relies on the glucose-alanine cycle (Cahill cycle). In the muscle, pyruvate (a byproduct of glycolysis) is transaminated to form L-alanine. This alanine is released into the bloodstream and transported to the liver, where it is converted back into pyruvate and used as a substrate for gluconeogenesis (the creation of new glucose). By providing an exogenous source of L-alanine through Sustamine, the body is supplied with a direct precursor for hepatic gluconeogenesis, thereby sparing muscle tissue from being catabolized to provide these amino acids.
### Insulin Sensitivity and Nutrient Partitioning
Beyond its structural and energetic roles, the L-alanyl-L-glutamine dipeptide exhibits signaling properties that enhance nutrient uptake. Glutamine has been shown to stimulate the secretion of Glucagon-Like Peptide-1 (GLP-1) from intestinal L-cells. GLP-1 is an incretin hormone that potentiates glucose-dependent insulin secretion. By enhancing insulin release in the presence of carbohydrates (such as in a sports drink), Sustamine facilitates the rapid transport of glucose and amino acids into muscle cells. This synergistic action on glucose transport accelerates glycogen replenishment during and immediately after exercise, significantly reducing recovery time and preparing the muscle for subsequent bouts of high-intensity effort.
What is Sustamine? +
How does L-alanyl-L-glutamine differ from regular L-glutamine? +
What are the effects of L-alanyl L-glutamine supplementation on time to exhaustion and dehydration stress? +
Can L-glutamine lower blood pressure? +
What is the function of alanine and glutamine? +
Does glutamine increase creatinine? +
Who should not take glycine? +
Who should avoid L-Glutamine? +
Does taking L-Glutamine have any side effects? +
Who should not take amino acid supplements? +
What is the recommended dosage for Sustamine? +
When is the best time to take Sustamine? +
Is Sustamine safe for daily use? +
Can Sustamine help with muscle recovery? +
Does Sustamine improve hydration? +
How does Sustamine affect blood sugar? +
Is Sustamine vegan or vegetarian? +
Can I stack Sustamine with BCAAs or EAAs? +
Everything About L-Alanine, L-Glycine, L-alanyl-L-Glutamine (Sustamine®) Article
## The Evolution of Glutamine Supplementation
For decades, L-Glutamine has been a staple in the supplement stacks of bodybuilders and endurance athletes alike. As the most abundant amino acid in human muscle tissue and blood, its roles in protein synthesis, immune function, and gut health are undeniable. However, traditional free-form L-Glutamine has a fatal flaw: poor systemic bioavailability. When you consume standard L-Glutamine powder, the cells lining your intestinal tract (enterocytes) and your gut-associated immune cells consume up to 80% of it for their own energy needs. Very little actually makes it into your bloodstream to reach your muscles. Furthermore, free-form glutamine is highly unstable in water, degrading rapidly into ammonia and pyroglutamic acid when mixed in a shaker cup.
Enter L-alanyl-L-glutamine, commercially known as Sustamine®. By enzymatically bonding L-Glutamine to L-Alanine, scientists created a dipeptide that completely changes the pharmacokinetic game. This comprehensive guide explores how this unique compound bypasses the gut, supercharges cellular hydration, and significantly extends time to exhaustion in hard-training athletes.
## How Sustamine Works: The Dipeptide Advantage
The secret to Sustamine's efficacy lies in its dipeptide structure. The human digestive tract has specific transporters designed exclusively for dipeptides and tripeptides, most notably the PEPT1 transporter.
When you ingest Sustamine, it does not compete with other single amino acids for absorption. More importantly, because the glutamine is bound to alanine, the gut cells do not recognize it as free glutamine and therefore do not metabolize it for energy. The dipeptide passes seamlessly through the intestinal wall and into the portal vein. Once in systemic circulation, endogenous enzymes cleave the bond, releasing massive amounts of pure L-Alanine and L-Glutamine directly into the blood.
Clinical trials have proven the superiority of this mechanism. A 2012 study published in *Nutrition Research* demonstrated that ingesting L-alanyl-L-glutamine resulted in plasma glutamine levels that were 224% higher than ingesting an equivalent dose of free-form L-glutamine. You get more than double the results while using significantly less product.
## Cellular Hydration and Fatigue Resistance
Sustamine is primarily utilized as an advanced hydration and endurance agent. The two amino acids work in perfect synergy to keep your muscles firing during grueling workouts.
### The Role of L-Alanine L-Alanine is heavily involved in the glucose-alanine cycle. During intense training, your muscles break down glucose for energy, producing pyruvate. Pyruvate is converted into alanine, which travels to the liver to be converted back into fresh glucose. By supplementing with the alanine found in Sustamine, you provide your body with a direct substrate for energy production, sparing your muscle tissue from being broken down. Additionally, alanine increases the concentration of potassium inside the cell, which acts as an osmotic magnet, drawing water into the muscle belly for intense cellular hydration and a noticeable "pump."
### The Role of L-Glutamine While alanine drives water into the cell, glutamine acts as a powerful pH buffer. As you exercise, hydrogen ions accumulate in the muscle, causing the burning sensation that ultimately forces you to stop. Glutamine is metabolized in the kidneys to produce ammonia, a process that actively buffers these acidic hydrogen ions, maintaining a stable pH and delaying the onset of muscular failure.
## Clinical Evidence: Pushing Past the Wall
The theoretical mechanisms of Sustamine translate directly to real-world athletic performance. In a landmark 2015 study conducted at the University of Central Florida and published in the *Journal of the American College of Nutrition*, researchers tested the effects of Sustamine on 12 highly trained endurance athletes.
The athletes were subjected to a brutal protocol: a one-hour treadmill run at 75% of their VO2 max, immediately followed by a run to absolute exhaustion at 90% VO2 max. The researchers tested four conditions: no hydration, a standard sports drink, a sports drink with a low dose of Sustamine (600mg/L), and a sports drink with a high dose of Sustamine (2g/L).
The results were definitive. Time to exhaustion was significantly longer in both the low-dose and high-dose Sustamine groups compared to the no-hydration group. Interestingly, the standard sports drink alone did not significantly improve time to exhaustion over no hydration—it was the addition of the dipeptide that made the statistical difference. Furthermore, plasma glutamine concentrations remained significantly elevated at the 60-minute mark in the high-dose group, proving that the dipeptide was actively circulating and providing fuel during the most critical moments of the workout.
## Dosing Strategies for Maximum Performance
Because Sustamine is so highly bioavailable, you do not need the massive 10-gram scoops often associated with standard glutamine.
**For Endurance and Hydration:** The clinical standard is 1 to 3 grams, taken 30 minutes prior to exercise or sipped throughout the workout in an intra-workout beverage. The UCF study noted significant benefits using concentrations of 600mg to 2g per liter of fluid.
**For Recovery:** Taking 1 to 2 grams immediately post-workout alongside your protein and carbohydrates can accelerate glycogen replenishment. Glutamine stimulates the release of GLP-1, an incretin hormone that enhances insulin secretion, driving nutrients rapidly into depleted muscle cells.
## Safety and Tolerability
Sustamine is the only GRAS (Generally Recognized As Safe) L-Alanyl-L-Glutamine dipeptide approved for use in foods and beverages. It is vegetarian, allergen-free, tasteless, and odorless. Because it is highly stable in liquids, it will not degrade into toxic byproducts when left in a shaker cup, a common issue with free-form glutamine. It is exceptionally well-tolerated, with no significant adverse side effects reported in healthy individuals at standard clinical doses.