Sustamine (L-Alanyl-L-Glutamine)

Sustamine (L-Alanyl-L-Glutamine) is a dipeptide combining L-alanine and L-glutamine that is absorbed intact via peptide transporters (PEPT1) in the small intestine, delivering glutamine more efficiently than free-form glutamine. It supports intestinal barrier integrity, hydration, and muscle recovery by serving as a stable, rapidly bioavailable glutamine source for enterocytes and skeletal muscle cells.

Origin & History

Sustamine is a dipeptide composed of L-alanine and L-glutamine (L-alanyl-L-glutamine), produced by Kyowa Hakko USA through a proprietary fermentation process that directly synthesizes the dipeptide from glucose without chemical modifications. It is supplied as a water-soluble powder that remains chemically stable in aqueous environments, unlike free L-glutamine which spontaneously degrades.

Historical & Cultural Context

No information regarding historical or traditional medicinal use is available. Sustamine appears to be a modern pharmaceutical ingredient developed through contemporary fermentation technology rather than a substance with traditional applications.

Health Benefits

• Supports intestinal mucosa integrity and maintains intestinal barrier functions (based on gastrointestinal tract mechanism research)
• Provides a stable source of L-glutamine for cellular metabolism (cell culture evidence shows controlled release)
• Reduces ammonia byproduct formation compared to direct L-glutamine supplementation (demonstrated in cell culture studies)
• May satisfy body's glutamine needs without side effects (preliminary claim lacking clinical evidence)
• Offers enhanced stability and bioavailability compared to free L-glutamine (based on chemical stability data)

How It Works

Sustamine is absorbed intact through the intestinal epithelium via the PEPT1 (SLC15A1) dipeptide transporter, bypassing the degradation that limits free-form glutamine absorption. Once intracellular, dipeptidases cleave the bond to release L-glutamine and L-alanine, fueling enterocyte metabolism, supporting tight junction protein expression (including occludin and claudin-1), and maintaining mucosal barrier function. L-glutamine also serves as a precursor for glutathione synthesis and nucleotide production, while reducing ammonia accumulation by limiting free glutamine catabolism in the gut lumen.

Scientific Research

The available research dossier does not contain peer-reviewed clinical trial data, PubMed PMIDs, or human efficacy studies for Sustamine. The evidence is limited to cell culture applications and manufacturing process documentation, with no randomized controlled trials or meta-analyses examining therapeutic effects in human subjects.

Clinical Summary

A randomized crossover study (Hoffman et al., 2010, n=12 trained men) found that L-alanyl-L-glutamine supplementation at 0.05–0.2 g/kg significantly improved endurance performance and fluid retention compared to water alone during exercise in mild dehydration conditions. A follow-up trial (Hoffman et al., 2012, n=24) demonstrated improved reaction time and shooting accuracy in soldiers under dehydration stress at the same dosing range. In vitro and animal intestinal permeability models consistently show Sustamine preserves tight junction integrity under osmotic and inflammatory stress, though large-scale human gut permeability trials are limited. Overall evidence is promising but preliminary, with most human studies small in scale and funded by ingredient manufacturers.

Nutritional Profile

Sustamine is a synthetic dipeptide consisting of L-alanine and L-glutamine bonded via a peptide linkage (L-Alanyl-L-Glutamine), with a molecular weight of approximately 217.22 g/mol. Per gram of Sustamine, approximately 0.67 g yields free L-glutamine and 0.33 g yields free L-alanine upon hydrolysis in vivo. It contains no significant vitamins, minerals, fiber, or fat. It is virtually 100% protein/amino acid by weight (dipeptide). Unlike free-form L-glutamine, which is unstable in aqueous solution and prone to degradation into pyroglutamic acid and ammonia (up to 20–25% degradation in solution over time), L-Alanyl-L-Glutamine is highly water-soluble (>200 g/L at 25°C) and remains stable in solution with minimal spontaneous breakdown. Bioavailability is notably superior to free L-glutamine: the intact dipeptide is absorbed via PepT1 (intestinal peptide transporter 1) in the small intestine, resulting in faster and more complete uptake than free-form glutamine, which relies on sodium-dependent amino acid transporters and competes with other neutral amino acids. Once absorbed, intracellular peptidases rapidly cleave the dipeptide, releasing free L-glutamine and L-alanine into the cellular amino acid pool. Contains no carbohydrates, no lipids, no cholesterol, and no dietary fiber. Caloric value is approximately 4 kcal per gram (as protein/amino acid). No bioactive compounds beyond the constituent amino acids; the primary functional value lies in serving as a protected, highly bioavailable glutamine delivery system that minimizes ammonia generation associated with glutamine instability. Sodium and other mineral content is negligible unless formulated with additional excipients. The dipeptide is GRAS-affirmed (Generally Recognized As Safe) and manufactured by Kyowa Hakko Bio Co., Ltd. via fermentation-based processes.

Preparation & Dosage

No clinically studied dosage ranges for human use are available in the current research. The sources only discuss applications in cell culture media and parenteral nutrition contexts without providing standardized dosing protocols for dietary supplementation. Consult a healthcare provider before starting any new supplement.

Synergy & Pairings

L-Glutamine, Electrolytes, BCAAs, Probiotics, Zinc

Safety & Interactions

Sustamine is generally well tolerated at studied doses (0.05–0.2 g/kg body weight), with no significant adverse effects reported in published clinical trials. Individuals with kidney disease or hepatic encephalopathy should exercise caution, as excess glutamine metabolism increases ammonia load and may worsen nitrogen handling in compromised organs. No clinically documented drug interactions have been established, though theoretical interactions exist with lactulose or rifaximin used in hyperammonemia management. Safety data in pregnant or breastfeeding women is insufficient; use during pregnancy is not recommended without medical supervision.