Numerous studies demonstrate that free glutamine can be added to commercially available crystalline amino acid-based preparations before their administration. Instability during heat sterilization and prolonged storage and limited solubility (35 g/L at 20°C) hamper the use of free glutamine in the routine clinical setting. Indeed, there are many well-controlled and valuable trials with free glutamine, yet its use is restricted to clinical research. The obvious limitations of using free glutamine initiated an intensive search for alternative substrates. Synthetic glutamine dipeptides are stable under heat sterilization and highly soluble; these properties qualify the dipeptides as suitable constituents of nutritional preparations. Industrial production of these dipeptides at a reasonable price is an essential prerequisite for implications of dipeptide-containing solutions in clinical practice. Recent development of novel synthesis procedures allows increased capacity in industrial-scale production. Basic studies with synthetic glutamine-containing short-chain peptides provide convincing evidence that these new substrates are cleared rapidly from plasma after parenteral administration, without being accumulated in tissues and with negligible loss in urine. The presence of membrane-bound as well as tissue-free extracellular hydrolase activity facilitates a prompt and quantitative peptide hydrolysis, the liberated amino acids being available for protein synthesis and/or generation of energy. In the clinical setting, glutamine dipeptide nutrition beneficially influences outcome (nitrogen balance, immunity, gut integrity, hospital stay, morbidity and mortality). The provision of conditionally indispensable glutamine should be considered a necessary replacement of a deficiency rather than a supplementation. The beneficial effects observed with glutamine dipeptide nutrition should be seen simply as a correction of disadvantages produced by the inadequacy of conventional clinical nutrition. The availability of stable dipeptide preparations certainly facilitates, for the first time, adequate amino acid nutrition of critically ill, malnourished or stressed patients in the routine clinical setting and, thus, represents a new dimension in artificial nutrition.
