Comparison of vitamin C deficiency with food restriction on collagen cross-link ratios in bone, urine and skin of weanling guinea-pigs

Abstract

Mild-to-moderate vitamin C depletion in weanling guinea-pigs affects pyridinoline:deoxypyridinoline (collagen cross-link) ratios in femur shaft and urine, attributed to impairment of hydroxylation of collagen lysine. We investigated: (1) whether the picture at two time points is compatible with progressive accumulation of abnormal collagen; (2) whether any changes are seen in skin, where little deoxypyridinoline occurs; (3) whether total food restriction has similar effects. Male weanling Dunkin-Hartley guinea-pigs were fed diets containing either 0·5 (vitamin C-restricted) or 160·0-320·0 (vitamin C-adequate) mg vitamin C/d. Two groups receiving the vitamin C-adequate diet received it ad libitum. Two other groups received the vitamin C-adequate diet in a restricted amount, limited to that which permitted nearly the same growth rate as in the vitamin C-restricted groups. Animals were fed for 4 or 8 weeks; urine was collected, and vitamin C and collagen indices were measured. In the femur shaft, the hydroxyproline content per unit weight was unaffected by vitamin C restriction or by total food restriction. Deoxypyridinoline was increased and the pyridinoline:deoxypyridinoline ratio was decreased in vitamin C-restricted groups, but not in food-restricted groups. Changes in the value of the ratio were greater after 8 than after 4 weeks. Urine indices mirrored bone indices. In skin, the main effect of vitamin C restriction was to reduce hydroxyproline. Here, the cross-link ratios changed less markedly than in bone, and there was less deoxypyridinoline. We conclude that the picture at two time points is compatible with a progressive accumulation of pyridinoline-enriched collagen in vitamin C-deprived animals, that the picture in skin differs from that of bone and urine, and that cross-link changes are not produced by total food restriction.

Vitamin C: the known and the unknown and Goldilocks

“…Independent of its effects on hydroxylation, ascorbate may stimulate collagen synthesis (Geesin et al , ; Sullivan et al , ). Collagen synthesis may be decreased in scorbutic animals (Peterkofsky, ; Kipp et al , ; Tsuchiya and Bates, ). Reduced collagen cross‐links may be a marker of vitamin C deficiency in the guinea pig (Tsuchiya and Bates, ) but this may not be specific to vitamin C deficiency.…”

“…Collagen synthesis may be decreased in scorbutic animals (Peterkofsky, 1991;Kipp et al, 1996;Tsuchiya and Bates, 2003). Reduced collagen cross-links may be a marker of vitamin C deficiency in the guinea pig (Tsuchiya and Bates, 2003) but this may not be specific to vitamin C deficiency. Although many features of human scurvy appear to be due to weakening of connective tissue, it has not been shown that these lesions are due to defective collagen synthesis.…”

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

“…Evidence that optimal vitamin C status may be critical for optimal pyridinium cross-link formation, which in turn may be reflected uniquely by the cross-link ratio pyridinoline:deoxypyridinoline in bone collagen and in the urinary collagen degradation products of bone turnover, has been obtained from two sources. The first was a series of controlled vitamin C intake studies on guinea-pigs, which, like man, are totally dependent on dietary sources of vitamin C. In weanling guinea-pigs, following a wide range of vitamin C intakes and with a correspondingly wide range of tissue vitamin C concentrations, the pyridinoline: deoxypyridinoline cross-link ratio in the long bones and in urinary collagen degradation products were both highly sensitive to the vitamin C supply (Tsuchiya & Bates, 1997, 1998, 2003Bates, 1999). This dependence of the cross-link ratios on vitamin C was specific, insofar that it was not significantly affected by total food restriction (Tsuchiya & Bates, 2003).…”

“…This may result in a shift in collagen cross-link patterns, away from a preponderance of the hydroxylysyl -pyridinoline (here called pyridinoline) cross-link-type, towards the alternative lysyl -pyridinoline (here called deoxypyridinoline) one, which requires one less hydroxylysyl residue since it is replaced by a lysyl residue (Robins, 1994;Bailey et al 1998). Such an alteration in cross-link pattern, potentially the result of a mild dietary vitamin C deficiency, has been demonstrated in guinea-pigs (Tsuchiya & Bates, 1997, 1998, 2003 and in human subjects with the genetic disorder Ehlers -Danlos syndrome type VI. In the latter, a structurally altered lysyl hydroxylase enzyme requires abnormally large amounts of vitamin C in order to achieve partially adequate function (Pinnell et al 1972;Quinn & Krane, 1976;Miller et al 1979;Acil et al 1995).…”

Role of Vitamin C in Osteoporosis Development and Treatment—A Literature Review

“…The observation of guinea pigs has appointed the bone tissue as the second most vulnerable to VC deficiency organ [21], which was associated with improper collagen synthesis. Severe vitamin C deficiency inhibited animal growth [22] and was associated with a significant change in collagen composition, namely deoxypyridinoline and the pyridinoline: eoxypyridinoline ratio in the femur shaft [23]. Bone mineral content and density has also been shown to decrease in scorbutic guinea pigs, paired by a thinner growth plate and larger osteoclast surface and impaired collagen synthesis at articular cartilage and tendons [24].…”