L-Alanine, L-Glycine, L-Alanyl-L-Glutamine (as Sustamine®)
Mechanism of Action +
### Dipeptide Transport and Cellular Hydration (L-Alanyl-L-Glutamine) Standard L-Glutamine suffers from poor systemic bioavailability because enterocytes (intestinal cells) and the liver rapidly sequester it for their own energy needs before it reaches systemic circulation. L-Alanyl-L-Glutamine (Sustamine®) circumvents this limitation by utilizing the PepT1 (Peptide Transporter 1) system. PepT1 is a proton-coupled symporter located on the apical membrane of enterocytes that absorbs dipeptides and tripeptides much more efficiently than single amino acid transporters absorb free amino acids. Once inside the enterocyte, the dipeptide is hydrolyzed into free alanine and glutamine, which then enter the portal vein. This mechanism significantly increases serum glutamine levels. At the cellular level, glutamine is metabolized to ammonia, which influences acid-base balance, while alanine increases intracellular potassium concentrations. This osmotic shift draws water into the cell, promoting profound intracellular hydration, which is critical during heat stress and prolonged endurance exercise.
### The Glucose-Alanine Cycle and Energy Metabolism (L-Alanine) L-Alanine is a highly glucogenic amino acid. During intense exercise, branched-chain amino acids (BCAAs) are transaminated in skeletal muscle, transferring their amino groups to alpha-ketoglutarate to form glutamate. Glutamate then transfers the amino group to pyruvate (a byproduct of glycolysis) to form L-Alanine. This alanine is released into the bloodstream and transported to the liver, where it undergoes the reverse reaction (transamination) to regenerate pyruvate, which is then used for gluconeogenesis (the creation of new glucose). This newly formed glucose is shuttled back to the working muscles. Supplementing with L-Alanine (and the alanine provided by Sustamine) supports this cycle, helping to spare muscle glycogen and maintain blood glucose levels during prolonged exertion.
### Central Nervous System Inhibition and Thermoregulation (L-Glycine) L-Glycine is the smallest amino acid and serves a dual role in the central nervous system (CNS). It acts as an obligatory co-agonist with glutamate at NMDA (N-methyl-D-aspartate) receptors, which are involved in learning and memory. More importantly for recovery, glycine acts as a primary inhibitory neurotransmitter in the brainstem and spinal cord via glycine receptors (GlyRs). Activation of GlyRs increases chloride ion influx, hyperpolarizing the neuronal membrane and reducing excitability. In the context of sleep, oral ingestion of 3 grams of glycine has been shown to passively diffuse across the blood-brain barrier, acting on NMDA receptors in the suprachiasmatic nucleus (the body's circadian pacemaker). This induces peripheral vasodilation, which lowers core body temperature—a physiological prerequisite for the onset of deep, restorative slow-wave sleep.
What is Sustamine? +
What are the effects of L-alanyl L-glutamine supplementation on time to exhaustion and dehydration stress? +
Can L-glutamine lower blood pressure? +
Does L-glutamine help joint pain? +
Does glutamine increase creatinine? +
Are there any negative side effects of L-Glutamine? +
What are the side effects of taking glycine supplements? +
Who can't take L-Glutamine? +
Is L-Glutamine safe for the liver and kidneys? +
How does Sustamine compare to regular L-Glutamine? +
What is the recommended dosage for Sustamine? +
When is the best time to take this blend? +
Does L-Alanine improve athletic performance? +
How does L-Glycine improve sleep? +
Can I take Sustamine on an empty stomach? +
Does Sustamine build muscle? +
What is the glucose-alanine cycle? +
Can Sustamine be stacked with other supplements? +
Everything About L-Alanine, L-Glycine, L-Alanyl-L-Glutamine (as Sustamine®) Article
## Introduction to the Ultimate Amino Acid Blend
When it comes to sports nutrition, amino acids are often lumped into broad categories like BCAAs or EAAs. However, specific amino acids and dipeptides—namely L-Alanine, L-Glycine, and L-Alanyl-L-Glutamine (trademarked as Sustamine®)—serve highly specialized, functional roles that go far beyond basic muscle protein synthesis. This unique combination targets three critical pillars of human performance and recovery: deep cellular hydration, energy metabolism, and central nervous system recovery (sleep).
While standard L-Glutamine has long been a staple in bodybuilding lore, modern clinical research has revealed its fatal flaw: poor systemic bioavailability. Enter Sustamine®, a dipeptide that rewrites the rules of glutamine absorption. Combined with the sleep-enhancing power of L-Glycine and the energy-yielding properties of L-Alanine, this blend represents a sophisticated approach to intra-workout endurance and post-workout recovery.
## How Sustamine® Revolutionizes Hydration
### The Problem with Standard L-Glutamine Glutamine is the most abundant conditionally essential amino acid in the human body. During periods of intense physical stress, trauma, or prolonged exercise, intramuscular glutamine levels plummet. Naturally, athletes began supplementing with free-form L-Glutamine to replenish these stores. However, clinical trials repeatedly showed that oral L-Glutamine failed to enhance athletic performance or significantly raise muscle glutamine levels.
Why? The human gut. The cells lining your intestines (enterocytes) and your liver are incredibly greedy for glutamine, using it as their primary fuel source. When you consume standard L-Glutamine powder, up to 70-80% of it is sequestered by the gut and liver before it ever reaches your bloodstream.
### The Dipeptide Solution: PepT1 Transporters Sustamine® (L-Alanyl-L-Glutamine) solves this biological roadblock. By bonding L-Glutamine to L-Alanine, Kyowa Hakko created a stable dipeptide. The human digestive tract possesses specialized transport proteins called PepT1 (Peptide Transporter 1) that are specifically designed to absorb dipeptides and tripeptides rapidly.
Because Sustamine is a dipeptide, it bypasses the free-amino-acid transporters and is shuttled directly into the enterocyte via PepT1. Once inside, it is cleaved into free alanine and glutamine, which then flood into the systemic circulation. This results in significantly higher blood glutamine levels compared to taking free-form glutamine.
### Intracellular Hydration Once in the bloodstream, the magic of this dipeptide unfolds. L-Alanine actively increases the concentration of potassium inside your cells. Because water follows electrolytes, this potassium influx draws water directly into the muscle cell. Simultaneously, glutamine is metabolized into ammonia, which alters the cellular pH balance, further encouraging fluid retention. The result is profound intracellular hydration—a state that delays fatigue, prevents cramping, and maintains cellular volume during grueling, sweat-inducing workouts.
## L-Alanine: The Unsung Hero of Energy
It is crucial not to confuse L-Alanine with Beta-Alanine. Beta-Alanine is famous for causing the "tingles" (paresthesia) and buffering lactic acid. L-Alanine, on the other hand, is a non-essential, glucogenic amino acid that plays a starring role in the **Glucose-Alanine Cycle**.
During intense training, your muscles break down branched-chain amino acids (BCAAs) for energy. The nitrogen byproduct of this breakdown is attached to pyruvate to form L-Alanine. This L-Alanine is shipped through the blood to the liver, where the liver strips the nitrogen away and converts the remaining carbon skeleton back into glucose (gluconeogenesis). This fresh glucose is then sent back to the muscles to fuel continued contractions. By supplementing with L-Alanine (and the alanine yielded from Sustamine), you provide your body with readily available substrates to keep this energy cycle spinning, sparing your precious muscle glycogen stores.
## L-Glycine: The Architect of Sleep and Recovery
While Sustamine and Alanine handle the intra-workout hydration and energy demands, L-Glycine is the ultimate post-workout recovery agent. Glycine is the smallest amino acid, but it packs a massive punch in the central nervous system.
### Lowering Core Body Temperature To enter deep, restorative slow-wave sleep, your core body temperature must drop. Glycine facilitates this by passively crossing the blood-brain barrier and acting on NMDA receptors in the suprachiasmatic nucleus (the brain's circadian clock). This triggers peripheral vasodilation—increasing blood flow to your extremities—which dissipates heat and lowers your core temperature.
### Calming the Central Nervous System Glycine also acts as an inhibitory neurotransmitter in the brainstem and spinal cord. By binding to Glycine Receptors (GlyRs), it allows chloride ions to enter neurons, hyperpolarizing them and reducing their excitability. This "quiets" the nervous system, making it easier to transition from the sympathetic "fight or flight" state of a hard workout into the parasympathetic "rest and digest" state required for sleep.
Clinical trials (such as the landmark 2007 study by Yamadera et al.) have consistently shown that 3 grams of L-Glycine taken before bed significantly improves subjective sleep quality, reduces the time it takes to fall asleep, and drastically cuts down on daytime fatigue the following morning.
## Clinical Dosing and Protocol
To reap the benefits of these ingredients, proper dosing is non-negotiable: * **Sustamine® (L-Alanyl-L-Glutamine):** Clinical trials demonstrating improved time-to-exhaustion and hydration utilize doses between **1.0g and 3.0g**. Taking less than 1g is unlikely to yield significant performance benefits. It is best consumed 30 minutes pre-workout or sipped intra-workout alongside electrolytes. * **L-Glycine:** For sleep enhancement, the clinically validated dose is **3.0g**, taken 30 to 60 minutes before bed. * **L-Alanine:** While there is no standard standalone dose for performance, the alanine provided within the Sustamine dipeptide is sufficient to support the glucose-alanine cycle during exercise.
## The Bottom Line
This specific combination of amino acids is a masterclass in targeted sports nutrition. Sustamine® rescues glutamine from the graveyard of poor bioavailability, turning it into a potent cellular hydrator. L-Alanine keeps the metabolic engine running via gluconeogenesis. Finally, L-Glycine ensures that the nervous system can power down and recover through optimized sleep architecture. Whether you are an endurance athlete battling the heat or a bodybuilder looking to maximize cellular volume and recovery, this blend offers scientifically backed, tangible benefits.