23 Mar Glutamine For Tissue Health
There’s a reason most cercial protein powders are loaded with the amino acid glutamine. Glutamine is the most abundant non-essential amino acid, and is the primary fuel for enterocytes lining the small intestine. (Rather than using glucose as an energy source for themselves, enterocytes use glutamine in order to spare the glucose they transport from the intestinal lumen into the bloodstream for use by other body tissues.) Like other non-essential nutrients, glutamine becomes conditionally essential under certain circumstances. Physical trauma, illness, injury, and major surgery can increase the body’s need for glutamine above and beyond what can be synthesized internally, making supplementation beneficial for those who need extra support for tissue repair and regeneration.
The role of glutamine in providing a structural substrate for building skeletal muscle is obvious—glutamine accounts for over 50% of the unbound amino acid pool in human skeletal muscle. But glutamine is also a key factor for forming connective tissue and supporting healthy joints. The primary structural protein of connective tissue—including skin, tendons, ligaments, and joints—is collagen. Glutamine indirectly increases the biosynthesis of collagen, mostly via conversion to two of its intermediate metabolites: glutamate and pyrroline-5-carboxylate (P5C). The latter, P5C, is an intermediate in the synthesis of proline, with proline and a modified form, hydroxyproline, being two of the key building blocks for the collagen triple helix.
Cultured human skin fibroblasts exposed to glutamine and these intermediates showed dramatic increases in collagen biosynthesis. P5C proved to be the most effective for stimulating collagen formation in the shortest amount of time. After just 6 hours of incubation with P5C, the skin fibroblasts showed a three-fold increase in collagen synthesis, and levels were 260% of control values at 12 hours. At 6, 12, and 24 hours of incubation, glutamate induced increases in collagen synthesis to 180%, 400%, and 120% of control values. After the same time exposures, glutamine increased collagen synthesis to around 112%, 115%, and 230% of control values, respectively. All three substances stimulate increases collagen synthesis, but P5C seems to act directly, while glutamine acts through its intermediates.
One of the molecular mechanisms by which glutamine may exert this influence on connective tissue health is by increasing the expression of genes involved in collagen formation. Cultured human fibroblasts incubated with glutamine showed a dose-dependent effect of glutamine on collagen synthesis, via increased transcription of collagen-specific mRNA. The mean increases in collagen and non-collagen protein synthesis were 63% and 18%, respectively. At 0.15 mM glutamine concentration, alpha 1(I) and alpha 1(III) collagen mRNA expression were increased by 1.7-and 2.3-fold respectively. So in addition to its structural role in protein, glutamine also serves a signaling functioning at the molecular level when it comes to collagen generation.
Glutamine may also play a role in the maintenance of healthy bones. Here again, glutamine’s function seems to be one of signaling. Mouse osteoblasts cultured with either glucose alone or glucose plus glutamine showed increased mineralization with the added glutamine, but not with glucose alone. By itself, glucose stimulated osteoblast proliferation, but had no significant effect on osteocalcin expression. However, when glucose was combined with glutamine, there was significant increase in osteocalcin activity and mineralization.
Owing to glutamine’s roles in skeletal muscle synthesis and supporting healthy connective tissue and bone, many diverse patient groups may benefit from supplemental amounts of this nutrient. One specific population group that might do especially well with extra glutamine is athletes, who experience above-average wear and tear on their joints, and whose muscles undergo constant micro-damage and repair. Compared to placebo, supplemental collagen hydrolysate led to significant improvements in joint pain in athletes while at rest, standing, walking, lifting, and carrying objects. And with glutamine playing such a critical role in collagen synthesis, glutamine supplementation or supplementation with bone- and joint-specific blends that include this amino acid could be beneficial for recovery from intense physical activity.