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Vitamin C status and collagen cross-link ratios in Gambian children

Published online by Cambridge University Press:  08 March 2007

K. Munday ,
A. Fulford  and
C. J. Bates
K. Munday
Affiliation:
MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL, UK
A. Fulford
Affiliation:
MRC International Nutrition Group, Keneba, The Gambia, West Africa
C. J. Bates*
Affiliation:
MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL, UK
*
*Corresponding author: Dr Chris Bates, fax +44 1223 437515, email [email protected]
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Abstract

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Vitamin C (ascorbate) is essential for hydroxylation of prolyl and lysyl residues in nascent collagen, the failure of which leads to connective tissue lesions of scurvy. Of the pyridinium-type cross-links in mature collagen, pyridinoline requires more hydroxylysyl residues than does deoxypyridinoline. Our study tested the hypothesis that pyridinoline:deoxypyridinoline ratios in urinary degradation products may vary with ascorbate status in man. These ratios were compared between British and Gambian prepubertal boys, mean age 8·3 years, and in Gambian boys between two seasons with contrasting ascorbate availability. The mean cross-links ratio in 216 British boys was 4·36 (sd 0·71), significantly greater (P<0·0001) than in sixty-two Gambian boys: 3·83 (sd 0·52). In the Gambians the cross-links ratio was significantly higher in the dry season (with high ascorbate intake and status) than in the rains (with low intake and status). A 7-week controlled intervention was carried out in Gambian boys during the rainy season (the ‘hungry’ season, when vitamin C-containing foods are virtually unavailable): 100 mg ascorbate/d was given to one group of thirty-two Gambian boys and placebo to another group. The intervention did not, however, significantly alter the cross-link ratio, possibly because the response time and/or intervention–response delay is >7 weeks. If confirmed, the putative association between ascorbate and collagen cross-link ratios in man could become the basis for a functional test for adequacy of ascorbate status.

Keywords

Vitamin CCollagenCross-linksGambian children
Type
Research Article
Information
British Journal of Nutrition , Volume 93 , Issue 4 , April 2005 , pp. 501 - 507
Copyright
Copyright © The Nutrition Society 2005

References

Acil, Y, Vetter, U, Brenner, R, Muller, PK & Brinckmann, J (1995) Ehlers–Danlos syndrome type VI: cross-link pattern in tissue and urine sample as a diagnostic marker. J Am Acad Dermatol 33, 522–524.Google Scholar
Acil, Y, Brinckmann, J, Notbohm, H, Muller, PK & Batge, B (1996) Changes with age in the urinary excretion of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). Scand J Clin Lab Invest 56, 275–283.CrossRefGoogle ScholarPubMed
Anonymous (1984) Elucidation of the biochemical role of ascorbic acid. Nutr Rev 42, 392–394.Google Scholar
Bailey, AJ, Paul, RG & Knott, L (1998) Mechanisms of maturation and ageing of collagen. Mech Ageing Dev 106, 1–56.CrossRefGoogle ScholarPubMed
Bank, RA, Robins, SP, Wijmenga, C, Breslau-Siderius, LJ, Bardoel, AF, van der Sluijs, HA, Pruijs, HE, TeKoppele, JM (1999) Defective collagen crosslinking in bone, but not in ligament or cartilage, in Bruck syndrome: implications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17. Proc Natl Acad Sci USA 96, 1054–1058.Google Scholar
Banse, X & Sims, TJ (2002) Mechanical properties of adult vertebral cancellous bone: correlation with collagen intermolecular cross-links. J Bone Min Res 17, 1621–1628.CrossRefGoogle ScholarPubMed
Barnes, MJ & Kodicek, E (1972) Biological hydroxylations and ascorbic acid with special regard to collagen metabolism. Vitam Horm 30, 1–43.CrossRefGoogle ScholarPubMed
Bates, CJ (1999) Collagen crosslink ratios in bone and urine of guinea-pigs fed with graded intakes of vitamin C. Proc Nutr Soc 58 63AGoogle Scholar
Bates, CJ, Prentice, AM & Paul, AA (1994) Seasonal variations in vitamins A, C, riboflavin and folate intakes and status of pregnant and lactating women in a rural Gambian community. Eur J Clin Nutr 48, 660–668.Google Scholar
Beardsworth, LJ, Eyre, DR & Dickson, IR (1990) Changes with age in the urinary excretion of lysyl- and hydroxylysylpyridinoline, two new markers of bone collagen turnover. J Bone Min Res 5, 671–676.Google Scholar
Branca, F, Robins, SP, Ferro-Luzzi, A & Golden, MHN (1992) Bone turnover in malnourished children. Lancet 340, 1493–1496.CrossRefGoogle ScholarPubMed
Branca, F, Spagnoli, A, Cianfarani, S, Spadoni, G, Golden, MHN, Boscherini, B, Valtuena, S & Robins, SP (2002) Urinary excretion of pyridinium crosslinks in short children treated with growth hormone. J Pediatr Endocrinol Metab 15, 27–34.Google Scholar
Dembure, PP, Janko, AR, Priest, RE & Elsas, LJ (1987) Ascorbate regulation of collagen biosynthesis in Ehlers–Danlos syndrome. Metabolism 36, 687–691.Google Scholar
Dolan, AL & Arden, NK (1998) Assessment of bone in Ehlers Danlos syndrome by ultrasound and densitometry. Ann Rheum Dis 57, 630–633.CrossRefGoogle ScholarPubMed
Douglas, AS, Miller, MH, Reid, DM, Hutchison, JD, Porter, RW & Robins, SP (1996) Seasonal differences in biochemical parameters of bone remodeling. J Clin Pathol 49, 284–289.Google Scholar
Elsas, LJ, Miller, RL & Pinnell, SR (1978) Inherited human collagen lysyl hydroxylase deficiency: ascorbic acid response. J Pediatr 92, 378–384.CrossRefGoogle ScholarPubMed
Fraser, WD (1998) The collagen crosslinks pyridinoline and deoxypyridinoline: a review of their biochemistry, physiology, measurement, and clinical applications. J Clin Ligand Assay 21, 102–110.Google Scholar
Ginty, F, Flynn, A & Cashman, K (1998) Inter and intra-individual variations in urinary excretion of pyridinium crosslinks of collagen in healthy young adults. Eur J Clin Nutr 52, 71–73.CrossRefGoogle ScholarPubMed
Gregory, J, Lowe, S, Bates, C, Prentice, A, Jackson, L, Smithers, G, Wenlock, R & Farron, M (2000) National Diet and Nutrition Survey: Young People Aged 4 to 18 Years. Volume 1: Report of the Diet and Nutrition Survey. London: The Stationery Office.Google Scholar
Hanson, DA & Eyre, DR (1996) A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telopeptides in urine. J Bone Min Res 7, 1251–1258.Google Scholar
Kivirikko, KI & Myllyla, R (1982) Posttranslational enzymes in the biosynthesis of collagen: intracellular enzymes. Meth Enzymol 82, 245–304.Google Scholar
Miller, RL, Elsas, LJ & Priest, RE (1979) Ascorbate action on normal and mutant human lysyl hydroxylases from cultured dermal fibroblasts. J Invest Dermatol 72, 241–247.CrossRefGoogle ScholarPubMed
Myllyla, R, Majamaa, J, Gunzler, V, Hanauske-Abel, HM & Kivirikko, KI (1984) Ascorbate is consumed stoichiometrically in the uncoupled reactions catalysed by prolyl-4-hydroxylase and lysyl hydroxlase. J Biol Chem 259, 5403–5405.Google Scholar
Pasquali, M, Still, MJ, Vales, T, Rosen, RI, Evinger, JD, Dembure, PP, Longo, N & Elsas, LJ (1997) Abnormal formation of collagen cross-links in skin fibroblasts cultured from patients with Ehlers–Danlos syndrome type VI. Proc Assoc Am Physicians 109, 33–41.Google Scholar
Pinnell, SR, Krane, SM, Kenzora, JE & Glimcher, MJ (1972) A heritable disorder of connective tissue. Hydroxylysine-deficient collagen disease. N Engl J Med 286, 1013–1020.Google Scholar
Quinn, RS & Krane, SM (1976) Abnormal properties of collagen lysyl hydroxylase from skin fibroblasts of siblings with hydroxylysine-deficient collagen. J Clin Invest 57, 83–93.Google Scholar
Rauch, F, Seibel, MJ, Woitge, H, Kruse, K & Schonau, E (1995) Increased urinary excretion of collagen crosslinks in girls with Ullrich–Turner syndrome. Acta Paediatr 84, 66–69.Google Scholar
Robins, SP (1994) Biochemical markers for assessing skeletal growth. Eur J Clin Nutr 48, Suppl. 1, S199–S209.Google ScholarPubMed
Royce, PM & Barnes, MJ (1985) Failure of highly purified lysyl hydoxylase to hydroxylate lysyl residues in the non-helical regions of collagen. Biochem J 230, 475–480.Google Scholar
Seibel, MJ, Robins, SP & Bilezikian, JP (1992) Urinary pyridinium crosslinks of collagen. Specific markers of bone resorption in metabolic bone disease. Trends Endocrinol Metab 3, 263–270.CrossRefGoogle ScholarPubMed
Tsuchiya, H & Bates, CJ (1997) Vitamin C and copper interactions in guinea-pigs and a study of collagen cross-links. Br J Nutr 77, 315–325.CrossRefGoogle Scholar
Tsuchiya, H & Bates, CJ (1998) Changes in collagen cross-link ratios in bone and urine of guinea pigs fed graded dietary vitamin C: a functional index of vitamin C status. J Nutr Biochem 9, 402–407.CrossRefGoogle Scholar
Tsuchiya, H & Bates, CJ (2003) Comparison of vitamin C deficiency with food restriction on collagen cross-link ratios in bone, urine and skin of weanling guinea-pigs. Br J Nutr 89, 303–310.CrossRefGoogle Scholar
Vuilleumier, JP & Keck, E (1989) Fluorometric assay of vitamin C in biological materials, using a centrifugal analyser with fluorescence attachment. J Micronutr Anal 5, 25–34.Google Scholar