Vitamin C - Overview of Significant Scientific Information

From the 15th century, scurvy was dreaded by seamen and explorers forced to subsist for months on diets of dried beef and biscuits. Scurvy was described by the Crusaders, during the sieges of numerous European cities, and as a result of the famine in 19th century Ireland. Three important manifestations of scurvy – gingival changes, pain in the extremities, and haemorrhagic manifestations – preceded oedema, ulcerations, and ultimately death. Skeletal and vascular lesions in scurvy probably arise from a failure of osteoid formation. 

In infantile scurvy the changes are mainly at the sites of most active bone growth; characteristic signs are a pseudoparalysis of the limbs caused by extreme pain on movement and caused by haemorrhages under the periosteum, as well as swelling and haemorrhages in areas of the gums surrounding erupting teeth. In adults one of the early, principle adverse effects of the collagen-related pathology may be impaired wound healing. Vitamin C deficiency can be detected from early signs of clinical deficiency, such as the follicular hyperkeratosis, petechial haemorrhages, swollen or bleeding gums, and joint pain, or from the very low concentrations of ascorbate in plasma, blood, or leukocytes. 

The Sheffield studies and later studies in Iowa were the first major attempts made to quantify vitamin C requirements. The studies indicated that the amount of vitamin C required to prevent or cure early signs of deficiency was between 6.5 and 10 mg/day. This range represents the lowest physiologic requirement. The Iowa studies and Kallner et al., established that at tissue saturation, whole body vitamin C content is approximately 20 mg/kg, or 1500 mg, and that during depletion vitamin C is lost at 3 percent of whole body content per day.

Clinical signs of scurvy appear in men at intakes lower than 10 mg/day or when the whole body content falls below 300 mg. Such intakes are associated with plasma ascorbate concentrations below 11 μmol/l or leukocyte levels less than 2 nmol/108 cells. However, the plasma concentrations fall to around 11 μmol/l when dietary vitamin C is between 10 and 20 mg/day. At intakes greater than 25–35 mg/day, plasma concentrations start to rise steeply, indicating a greater availability of vitamin C for metabolic needs. In general, plasma ascorbate closely reflects the dietary intake and ranges between 20 and 80 μmol/l. 

Note that during infection or physical trauma, an increase in the number of circulating leukocytes occurs and these take up vitamin C from the plasma. Therefore, both plasma and leukocyte levels may not be very precise indicators of body content or status at such times. However, leukocyte ascorbate remains a better indicator of vitamin C status than plasma ascorbate most of the time and only in the period immediately after the onset of an infection are both values unreliable.

Intestinal absorption of vitamin C is by an active, sodium-dependent, energy requiring, carrier-mediated transport mechanism and as intakes increase, the tissues progressively become more saturated. The physiologically efficient, renal-tubular reabsorption mechanism retains vitamin C in the tissues up to a whole body content of ascorbate of about 20 mg/kg body weight (30). However, under steady state conditions, as intakes rise from around 100 mg/day there is an increase in urinary output in so that at 1000 mg/day almost all absorbed vitamin C is excreted.

References:

McLaren, D.S. 1992. A colour atlas of nutritional disorders. London, Wolfe Medical Publications.

Bartley, W., Krebs, H.A. & O’Brien, J.R.P. 1953. Vitamin C requirements of Human adults. Medical Research Council Special Report Series No. 280, London, HMSO.

Krebs, H.A. & Vitamin C Subcommittee of the Accessory Food Factors Committee M.R.C. 1948. Vitamin C Requirement of Human Adults: Experimental Study of Vitamin C Deprivation in Man. Lancet, 254: 853-858.

Baker, E.M., Hodges, R.E., Hood, J., Sauberlich, H.E. & March, S.C. 1969. Metabolism of ascorbic-1-14C acid in experimental Human scurvy. Am. J. Clin. Nutr., 22: 549-558.

Baker, E.M., Hodges, R.E., Hood, J., Sauberlich, H.E. March, S.C. & Canham, J.E. 1971. Metabolism of 14C- and 3H-labeled L-ascorbic acid in Human scurvy. Am. J. Clin

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Kallner, A., Hartmann, D. & Hornig, D. 1979. Steady-state turnover and body pool of ascorbic acid in man. Am. J. Clin. Nutr., 32: 530-539.

Moser, U. & Weber, F. 1984. Uptake of ascorbic acid by Human granulocytes. Int. J. Vit.
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Lee, W., Davis, K.A., Rettmer, R.L. & Labbe, R.F. 1988. Ascorbic acid status: biochemical and clinical considerations. Am. J. Clin. Nutr., 48:286-290.

McCormick, D.B. & Zhang, Z. 1993. Cellular assimilation of water-soluble vitamins in the mammal: riboflavin, B6, biotin and C. Proc. Soc. Exp. Biol. Med., 202: 265-270.

Levine, M., Conry-Cantilena, C., Wang, Y., Welch R.W., Washko, P.W., Dhariwal K.R., Park, J.B., Lazarev, A. & Graumlich, J.K. 1996. Vitamin C pharmacokinetics in healthy volunteers: evidence for a Recommended Dietary Allowance. Proc. Natl. Acad.
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Graumlich, J., Ludden, T.M., Conry-Cantilena, C., Cantilena, L.R., Wang, Y. &
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