Vitamin C (ascorbic acid) is the water-soluble vitamin that is the essential cofactor for the prolyl hydroxylase and the lysyl hydroxylase enzymes — the enzymes that are required for the hydroxylation of the proline and the lysine residues in the nascent collagen chain, the post-translational modification that is essential for the triple helix formation and for the structural stability of the collagen molecule. The collagen is the most abundant protein in the human body — it constitutes 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. The collagen synthesis is a complex, multi-step process that begins with the transcription of the collagen genes and ends with the formation of the mature collagen fibrils — and the hydroxylation of the proline and the lysine residues by the vitamin C-dependent hydroxylases is one of the most critical steps in this process. Without adequate vitamin C and functional hydroxylases, the hydroxylation of the collagen chain is impaired, the triple helix formation is disrupted, the collagen that is secreted from the fibroblast is structurally weak and susceptible to the proteolytic degradation, and the scurvy develops — the hallmark of the vitamin C deficiency. The scurvy is characterised by the perifollicular haemorrhages, the petechiae, the ecchymoses, the poor wound healing, the swollen gums, the loose teeth, the corkscrew hairs, and the subcutaneous oedema — and it is one of the most dramatic and most recognisable nutritional deficiency diseases. The typical dietary vitamin C intake is 60-100mg daily (from the citrus fruits, the berries, the peppers, and the leafy green vegetables), and the RDA is 90mg daily for men and 75mg daily for women — but the vitamin C requirement is dramatically increased in the smokers (who have increased oxidative stress and increased vitamin C consumption), in the pregnant and lactating women (who have increased vitamin C demands), and in people with the chronic inflammatory conditions (who have increased vitamin C consumption due to the chronic inflammation).
Vitamin C and the Hydroxylation Reactions
The prolyl hydroxylase and the lysyl hydroxylase are the enzymes that catalyse the hydroxylation of the proline and the lysine residues in the nascent collagen chain — they require the vitamin C as a cofactor, and they use the molecular oxygen, the iron (Fe2+), the alpha-ketoglutarate, and the ascorbate as co-substrates and cofactors. The hydroxylation of the proline residues is essential for the formation of the hydroxyproline, which is the amino acid that is unique to the collagen and which is essential for the stability of the triple helix (because the hydroxyproline residues form the hydrogen bonds that stabilise the collagen triple helix at body temperature). The hydroxylation of the lysine residues is essential for the formation of the hydroxylysine, which is the amino acid that is the site of the glycosylation and of the cross-linking of the collagen fibres — and without the hydroxylysine, the collagen fibres cannot be properly cross-linked and they are structurally weak and susceptible to the proteolytic degradation. This vitamin C-dependent hydroxylation of the collagen chain is the primary mechanism of the scurvy and of the poor wound healing that are associated with the vitamin C deficiency.
The clinical importance of the vitamin C for the collagen synthesis is underscored by the observation that the vitamin C supplementation rapidly reverses the scurvy and improves the wound healing in people with the vitamin C deficiency. A study in 6 patients with the scurvy found that the vitamin C supplementation at 1g daily completely reversed the clinical manifestations of the scurvy within 2 weeks — demonstrating the remarkable efficacy of the vitamin C replacement for the vitamin C deficiency. The vitamin C is also essential for the wound healing — it is required for the collagen synthesis, for the immune function (the vitamin C supports the neutrophil function and the bacterial killing), and for the antioxidant defence at the wound site — and it is one of the most important nutrients for the surgical patients, for the trauma patients, and for the burn patients.
Practical Application
For general vitamin C supplementation, the evidence-based approach is to supplement with 500-1000mg of vitamin C daily (as the ascorbic acid or as the mineral ascorbates, such as the sodium ascorbate or the calcium ascorbate, which are less acidic and better tolerated by the gastrointestinal tract). The vitamin C should be taken in divided doses (250-500mg per dose) throughout the day (because the vitamin C is water-soluble and is excreted within 2-3 hours of the ingestion), and it should be taken with the bioflavonoids (which enhance the vitamin C absorption and which have complementary antioxidant effects). The RDA of vitamin C is 90mg daily for men and 75mg daily for women, and the tolerable upper intake level is 2000mg daily for adults — above which the vitamin C can cause the gastrointestinal symptoms (diarrhoea, nausea) and can increase the risk of the kidney stones in susceptible individuals. For comprehensive collagen and immune support, vitamin C pairs well with the zinc (which is required for the collagen synthesis and for the immune function), with the vitamin E (which is regenerated by vitamin C in the antioxidant network), with the iron (which is reduced by vitamin C to the more absorbable Fe2+ form), and with the silica (which is required for the collagen cross-linking and for the bone health).
A quality supplement routine can make a real difference to your results.
Leave a Reply