Disease and stress lower both plasma and leukocyte ascorbate concentrations (Thurnham, 1994, 1997). It has been recognised for many years that smokers have lower plasma ascorbate concentrations than non-smokers, even when dietary intake is taken into account. The effect is similar to that seen during surgical stress or infection but the stress of smoking is more easily studied (Thurnham, 2000).
It has been argued that smokers have an increased turnover of vitamin C, so in order to maintain their body pool and circulating levels at similar levels to those of non-smokers, intake would need to be higher, 80mg/d (Kallner et al, 1981; Smith and Hodges, 1987). However, an alternative explanation might be that vitamin C can act as a pro-oxidant in plasma, hence the body may be lowering concentrations to minimise the potential pro-oxidant damage caused by smoking and other stresses (Thurnham, 1994). The mechanism which reduces plasma vitamin C is also linked to the processes activated by the onset of disease. One of the earliest features of the body's response to trauma is a release of neutrophils from the bone marrow (Sipe, 1985). Such neutrophils are able to actively accumulate vitamin C (Moser and Weber, 1984) and rapid falls in plasma and leucocyte vitamin C following trauma have been reported (Vallance et al, 1978).
The need to lower circulating vitamin C concentrations in the presence of trauma may be linked to an increased risk of reaction between vitamin C and iron (Thurnham, 1994). During infection, the capacity to bind iron in plasma does not diminish and in fact several acute phase proteins with the capacity to bind iron increase (eg ferritin and lactoferrin). Nevertheless there is increased likelihood that iron and other transition metals are released in the immediate locality surrounding damaged tissues (Chevion et al, 1993), and therefore vitamin C concentrations may be reduced to minimise the risk of aggravating the damage still more. Reactions between iron and vitamin C are known to occur in situations where tissue integrity is reduced. So amounts of dietary vitamin C that would normally be tolerated easily can cause acute haemolysis and coma in persons with conditions where their red cells are more susceptible to oxidative stress such as glucose-6-phosphate dehydrogenase deficiency or nocturnal haematuria (Thurnham, 1994).
There are also other groups within industrialised countries where there may be risks associated with elevated intakes of vitamin C. In North European communities, genetic haemochromatosis has a gene frequency of 1 in 20, such that approximately 1 in every 300 individuals are at risk of iron overload. Although they appear apparently healthy, giving vitamin C without an iron-chelating agent to such people can potentially produce serious clinical effects (Halliwell, 1994). As indicated above, iron is usually bound to transport, storage or tissue proteins and the body is therefore protected from its damaging reactions. If localised or more general breakdown of tissue integrity should occur during infection, inflammation, strenuous exercise or other traumas resulting in an acute phase response, then metal ions are potentially released into the circulation. In addition as we get older, we get sicker and in humans with advanced atherosclerotic lesions, catalytic metal ions capable of free radical reactions can be measured. In fact, the contents of such a lesion will stimulate Off formation in the presence of peroxide and ascorbate in vitro. Should older people take large doses of antioxidant vitamins? The Finnish study suggests that people who have been smokers for many years and may well be on their way to developing cancer and/or cardiovascular disease, are harmed by high dose b-carotene treatment (ATBC Cancer
Prevention Study Group, 1994). Furthermore, there are controversial suggestions that high body copper and/or iron stores are associated with increased risk of cancer and cardiovascular disease. This could mean that in the event of injury or trauma, more iron and copper would be available to catalyse free radical reactions (Halliwell, 1994). As stated earlier, a decline in plasma ascorbate at the onset of oxidative stress is probably beneficial, for although vitamin C is helping to scavenge radicals and recycle vitamin E, its reduction in plasma may prevent any problems if metal ions are released. Furthermore, it must be remembered that oxidised vitamin C can be regenerated within erythrocytes and other tissues (Chaudiere and Ferrari-Iliou, 1999), and if the radical scavenging properties of vitamin C are to be maintained, regeneration of reduced vitamin C has to be increased if plasma concentrations are lower. Hence, giving high doses of vitamin C to sick people may not be a good idea.
Fruits and vegetables are associated with a decreased risk of cardiovascular disease and many types of cancer and neurodegenerative disease, but the role of vitamin C in this effect is uncertain (Halliwell, 2001). Supplementation trials with vitamin C using biomarkers of oxidative damage to DNA bases to measure levels of oxidative DNA damage in vivo showed little evidence of a beneficial effect, except where vitamin C intakes were low. In addition, no conclusive evidence of a protective effect of vitamin C in studies on strand breaks, micronuclei or chromosomal aberrations were found (Halliwell, 2001). There is some evidence that diet-derived vitamin C may decrease gastric cancer in some populations but whether this is due to its antioxidant or other properties is uncertain.
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Among the evils which a vitiated appetite has fastened upon mankind, those that arise from the use of Tobacco hold a prominent place, and call loudly for reform. We pity the poor Chinese, who stupifies body and mind with opium, and the wretched Hindoo, who is under a similar slavery to his favorite plant, the Betel but we present the humiliating spectacle of an enlightened and christian nation, wasting annually more than twenty-five millions of dollars, and destroying the health and the lives of thousands, by a practice not at all less degrading than that of the Chinese or Hindoo.