Lysine is the essential amino acid that is one of the most important building blocks of the collagen — it is required for the synthesis of the hydroxylysine (through the lysine hydroxylase enzyme, which requires the vitamin C as a cofactor), and it is the amino acid that is the site of the intermolecular cross-linking of the collagen fibres (through the lysyl oxidase enzyme, which creates the covalent cross-links between the lysine and the hydroxylysine residues in the adjacent collagen molecules). The collagen is the most abundant protein in the human body (constituting approximately 25-30% of the total body protein), and it is the primary structural component of the skin, the bones, the cartilage, the tendons, the ligaments, the blood vessels, and the teeth — and the lysine is one of the most important amino acids for the collagen synthesis and for the maintenance of the connective tissue integrity. The hydroxylysine residues in the collagen are essential for the formation of the stable triple helix structure of the collagen (because they form the hydrogen bonds that stabilise the triple helix at body temperature), and they are also the sites of the glycosylation (the attachment of the glucose and the galactose units to the collagen, which is essential for the proper assembly and the secretion of the collagen fibrils). The cross-linking of the collagen fibres by the lysyl oxidase is essential for the tensile strength and the mechanical integrity of the collagen — without adequate lysine and cross-linking, the collagen fibres are weak, the connective tissue is fragile, and the skin ages prematurely. Without adequate lysine and collagen synthesis, the skin is thin and wrinkled, the bones are weak and osteoporotic, the tendons and ligaments are fragile and prone to the injury, and the wounds heal poorly — the hallmark of the lysine deficiency and of the connective tissue weakness.
Lysine and the Bone Health
Lysine is particularly important for the bone health because it is required for the collagen synthesis in the bone matrix — the bone matrix is primarily composed of the type I collagen (which provides the tensile strength and the flexibility of the bone), and the lysine-dependent cross-linking of the collagen is essential for the mechanical strength and the fracture resistance of the bone. The lysine also improves the calcium absorption from the intestine (by modulating the calcium transport across the intestinal epithelium) and reduces the calcium excretion in the urine (by reducing the calcium流失 from the bone and by increasing the renal reabsorption of the calcium) — making it one of the most important amino acids for the prevention and the treatment of the osteoporosis. A study in 30 osteoporosis patients found that the lysine supplementation at 500mg daily (combined with 400mg of arginine daily) for 6 months significantly improved the calcium absorption (by 15-20%), reduced the calcium excretion (by 10-15%), and increased the bone mineral density (by 3-5%) — demonstrating the potent bone-protective effect of the lysine in humans.
The clinical importance of the lysine for the connective tissue and for the bone health is underscored by the observation that the lysine supplementation improves the wound healing and reduces the bone loss in people with the osteoporosis and in the post-menopausal women. A study in 20 elderly patients with the pressure ulcers found that the lysine supplementation at 500mg daily (combined with the vitamin C and the zinc) significantly improved the wound healing rate (by 30-40%, as measured by the wound size reduction) — demonstrating the potent wound-healing effect of the lysine in humans.
Practical Application
For general lysine supplementation for the connective tissue and the bone support, the evidence-based approach is to supplement with 500-1500mg of L-lysine daily (as the pure L-lysine powder or capsule, taken in divided doses). The lysine should be taken on the empty stomach (30-60 minutes before the meals or 2 hours after the meals) for the optimal absorption, and it should be taken with the vitamin C (which is required for the lysine hydroxylation and for the collagen synthesis) and with the proline and the glycine (which are the other major amino acids in the collagen and which work synergistically with the lysine for the collagen synthesis). The lysine is generally well-tolerated with no significant adverse effects at doses up to 3000mg daily, and it does not have any known drug interactions or contraindications — though people with the kidney disease or the liver disease should use the lysine with caution and under the supervision of a qualified healthcare practitioner. For comprehensive connective tissue and bone support, lysine pairs well with the vitamin C (which is essential for the lysine hydroxylation and for the formation of the hydroxylysine, which is the key step in the collagen synthesis), with the zinc and the copper (which are cofactors for the lysyl oxidase enzyme and which are essential for the cross-linking of the collagen fibres), with the silica (which supports the collagen cross-linking and which has complementary effects on the bone and the connective tissue health), and with the calcium and the vitamin D (which are the primary nutrients for the bone mineralisation and which work synergistically with the lysine for the bone health).




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