Vitamin C

BACKGROUND

Vitamin C (L-ascorbic acid or ascorbate) is the generic descriptor for compounds having antiscorbutic activity. Most animals can synthesise vitamin C from D-glucose but humans and other primates, together with guinea pigs, fruit bats, some passeriform birds, some fish and some insects, are exceptions. Humans and primates lack a key enzyme, L-3 gulonolactone oxidase, necessary for the biosynthesis of vitamin C (Nishikimi et al 1994).

Vitamin C is a reducing agent (antioxidant) and it is likely that all of its biochemical and molecular functions relate to this property. In humans, vitamin C acts as an electron donor for eight enzymes, of which three are involved in collagen hydroxylation (including aspects of norepinephrine, peptide hormone and tyrosine metabolism) and two are involved in carnitine biosynthesis (Dunn et al 1984, Eipper et al 1993, 1992, Kaufmann 1974, Kirirkko & Myllyla 1985, Levine et al 1991, Procop & Kiviikko 1995, Peterkovsky 1991, Rebouche 1991). Vitamin C is found in high concentrations in gastric juices (Schorah et al 1991) where it may prevent the formation of N-nitroso-compounds, which are potential mutagens (Correa 1992).

Vitamin C has been shown to protect lipids in human plasma and low density lipoprotein in ex vivo experiments against oxidative damage (Frei 1991). But there is no evidence of in vivo protection. Vitamin C also interacts with other nutrients. It aids in the absorption of iron and copper (Hallberg 1985, Harris & Perceval 1991), the maintenance of glutathione in the reduced form (Henning et al 1991, Johnston et al 1993), the regeneration, or sparing, of alpha-tocopherol (Halpner et al 1998) and the stabilisation of folate (Stokes et al 1975).

Ascorbate is found widely in fruits and vegetables. Fruits such as blackcurrants, guava, citrus, and kiwi fruit and vegetables such as broccoli and sprouts are good sources. The Australian bush food terminalia ferdinandiana is the richest source (Brand et al 1982). However, because of their longer periods of availability, vegetables often contribute more ascorbate to the diet than fruits. In Australia, some 40% of the vitamin C comes from vegetables and 19% from fruits and a further 27% from fruit and vegetable juices (ABS 1998). Vitamin C is very labile and its content in foods varies. Vitamin C content can be affected by season, transport, shelf life, storage time, cooking practices and chlorination of water. Cutting, bruising, heating and exposure to copper, iron or mildly alkaline conditions can destroy ascorbate. It can also be leached into water during cooking.

Intestinal absorption of vitamin C occurs through a sodium-dependent active transport process that is saturable and dose dependent (Rumsey & Levine 1998, Tsao 1997). Kallner et al (1979) showed that some 70–90% of usual intake is absorbed and that absorption fell to 50% or less with increasing doses above 1 g/day. Dose-dependent absorption and renal regulation of ascorbate allow conservation of vitamin C in the body during periods of low intake and regulation of plasma levels at high intakes.

There is a sigmoidal relationship between intake and plasma concentration of vitamin C (Levine et al 1996, Newton et al 1983). Newton et al (1983) showed that for intakes up to 30 mg/day, plasma concentrations are about 11 µmol/L (or 0.2 mg/dL). Above this intake, plasma concentrations increase steeply to 60 µmol/L and plateau at 80 µmol/L, the renal threshold. Levine et al (1996) found that the steep portion of the plasma concentration curve occurred with a daily dose of vitamin C of between 30 and 100 mg and that complete saturation occurred at 1,000 mg daily. Close to steady states, plateau concentrations are reached above 200 mg/day. Absorption is also to some extent dependent on the dosing regimen of vitamin C. For example, there would be better absorption with 250 mg as supplements taken four times daily than 1,000 mg taken once daily.

High levels of vitamin C are found in the pituitary and adrenal lands, leukocytes, eye tissues and fluids and the brain (Horning et al 1975). The biologic half-life of vitamin C is 8–40 days (Kallner et al 1979) and catabolic turnover varies widely, averaging 2.9% over a wide range of intakes (Baker et al 1971). A body pool of less than 300–400 mg is associated with the symptoms of scurvy (Baker et al 1969).

At saturation, the whole body content in males is about 20 mg/kg or 1,500 mg (Baker et al 1969, Kallner et al 1979).

Plasma vitamin C concentrations are reduced by 40% in male smokers. This may be partly due to smokers tending to eat less fruits and vegetables, but after correcting for intakes of fruit and vegetables, smokers still show lower plasma ascorbate than non-smokers (Lykkesfeldt et al 2000). The metabolic turnover of ascorbate is markedly accelerated in smokers (Kallner et al 1981).

Vitamin C deficiency causes scurvy, symptoms of which include skeletal and vascular lesions with gingival changes, pain in the extremities, haemorrhage, oedema, ulcerations and death. In adults, clinical signs occur at intakes of 7–8 mg/day or less (Goldsmith 1961, Rajajalakshmi et al 1965, van Eekelen 1953). In infantile scurvy, the changes are mainly at the sites of active bone growth and include a pseudoparalysis of the limbs (McLaren 1992).

There are several potential indices of vitamin C requirements in humans, including assessment of clinical outcomes, vitamin C turnover and biochemical indices of status (eg plasma, urine, leukocyte). Some studies have raised the question of whether vitamin C has beneficial effects on normal human subjects at intakes, and tissue levels, considerably greater than those needed to prevent or cure scurvy. However, the evidence has been conflicting. There is potential confounding in food intake studies related to the issue of concomitant intakes of other protective nutrients in fruits and vegetables, such as phytochemicals. In addition, studies generally do not provide the dose-response data on which average requirements can be ascertained (COMA 1991, FNB:IOM 2000, FAO:WHO 2002).