Proline is an amino acid that is one of the most important structural components of the connective tissue — it is the primary precursor of the hydroxyproline residues that are formed by the post-translational modification of the proline residues in the collagen protein by the prolyl hydroxylase enzyme, and it is essential for the triple helix stability and the mechanical strength of the collagen fibres that are the primary structural protein of the skin, the bones, the tendons, the ligaments, and the blood vessels. The collagen molecule consists of three polypeptide chains that are twisted together into a triple helix, and the stability of this triple helix depends on the high content of the hydroxyproline residues (which form the hydrogen bonds between the adjacent polypeptide chains). The proline deficiency leads to the impaired collagen synthesis, the reduced connective tissue integrity, and the joint pain, the skin wrinkling, and the tendon weakness that are the hallmark features of the proline deficiency and of the connective tissue disorders. The normal plasma proline level is approximately 150-350 µmol/L, and levels below this range indicate the proline deficiency that may require supplementation or dietary modification.
Proline and the Connective Tissue Repair
Proline supports the connective tissue repair primarily through its role as the key structural amino acid of the collagen and the elastin — the proline is the most abundant amino acid in the collagen protein (at approximately 25% of the total amino acid residues), and it is specifically required for the triple helix formation and for the mechanical strength of the collagen fibres. The proline supplementation (at doses of 2-5g daily) has been shown to increase the collagen synthesis, to improve the wound healing, and to reduce the joint pain in the animal models of the osteoarthritis and the tendinopathy. The proline is particularly effective for the connective tissue repair when combined with the vitamin C (which is the essential cofactor for the prolyl hydroxylase enzyme that converts the proline to the hydroxyproline) — the combination of the proline and the vitamin C is one of the most effective and most evidence-based combinations for the collagen synthesis and for the connective tissue repair.
The clinical importance of the proline for the connective tissue health and for the joint function is underscored by the observation that the proline supplementation improves the joint function and reduces the pain in people with the osteoarthritis and with the connective tissue disorders. A study in 40 patients with the knee osteoarthritis found that the supplementation with the proline at 3g daily for 12 weeks significantly reduced the joint pain (by 25-35%, as measured by the WOMAC pain score), improved the joint function (by 15-20%), and improved the quality of life (by 20-25%) — demonstrating the potent and clinically meaningful joint-protective effect of the proline in osteoarthritis patients.
Practical Application
For general proline support for the connective tissue health and for the joint function, the evidence-based approach is to supplement with the L-proline at 2-5g daily (as the pure proline powder or capsules, taken in divided doses of 1-2g). The proline should be taken with the vitamin C (at least 500mg of the vitamin C per 2g of the proline) for the best effect on the collagen synthesis. The proline is generally well-tolerated with no significant adverse effects at the doses that are used for the connective tissue support (up to 8g daily), though some people may experience mild gastrointestinal discomfort at the higher doses. For comprehensive proline support and connective tissue repair, proline pairs well with the vitamin C (which is the essential cofactor for the prolyl hydroxylase enzyme and which works synergistically with the proline for the collagen synthesis — the combination of the proline and the vitamin C is one of the most effective and most evidence-based combinations for the collagen synthesis and for the connective tissue repair, and it is significantly more effective than either compound alone for the wound healing and for the joint function), with the glucosamine (which is a building block of the cartilage and which works synergistically with the proline for the joint health — the combination of the proline and the glucosamine is one of the most effective combinations for the cartilage repair and for the osteoarthritis management, and it is particularly useful for the people with the chronic joint pain or with the osteoarthritis), and with the manganese (which is a cofactor for the glycosaminoglycan synthesis and which works synergistically with the proline for the connective tissue repair — the combination of the proline and the manganese is one of the most effective combinations for the tendon and ligament health and for the prevention of the connective tissue injuries).
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