The Vitamins 185therefore require signifi cantly more than 100 mg of
vitamin C/day.
Inhibition of nitrosamine formation
The safety of nitrates and nitrites used in curing meat,
a traditional method of preservation, has been ques-
tioned because of the formation of nitrosamines by
reaction between nitrite and amines naturally present
in foods under the acid conditions in the stomach. In
experimental animals nitrosamines are potent car-
cinogens, and some authorities have limited the
amounts of these salts that are permitted, although
there is no evidence of any hazard to humans from
endogenous nitrosamine formation. Ascorbate can
prevent the formation of nitrosamines by reacting
non-enzymically with nitrite and other nitrosating
reagents, forming NO, NO 2 , and N 2. Again, this is an
effect of ascorbate present in the stomach at the same
time as the dietary nitrites and amines, rather than an
effect of vitamin C nutritional status.
Pharmacological uses of vitamin C
Several studies have reported low ascorbate status in
patients with advanced cancer, which is perhaps an
unsurprising fi nding in seriously ill patients. With
very little experimental evidence, it has been sug-
gested that very high intakes of vitamin C (of the
order of 10 g/day or more) may be benefi cial in
enhancing host resistance to cancer and preventing
the development of the acquired immunodefi ciency
syndrome (AIDS) in people who are human immu-
nodefi ciency virus (HIV) positive. In controlled
studies with patients matched for age, gender, site and
stage of primary tumors and metastases, and previous
chemotherapy, there was no benefi cial effect of high-
dose ascorbic acid in the treatment of advanced
cancer.
High doses of vitamin C have been recommended
for the prevention and treatment of the common
cold, with some evidence that the vitamin reduces the
duration of symptoms. However, the evidence from
controlled trials is unconvincing.
Toxicity of vitamin C
Regardless of whether or not high intakes of ascorbate
have any benefi cial effects, large numbers of people
habitually take between 1 and 5 g/day of vitamin C
supplements (compared with reference intakes of
40–90 mg/day) and some take considerably more.
There is little evidence of signifi cant toxicity from
these high intakes. Once the plasma concentration of
ascorbate reaches the renal threshold, it is excreted
more or less quantitatively with increasing intake, and
there is no evidence that higher intakes increase the
body pool above about 110 μmol/kg body weight.
Unabsorbed ascorbate in the intestinal lumen is a
substrate for bacterial fermentation, and may cause
diarrhea and intestinal discomfort.
Ascorbate can react non-enzymically with amino
groups in proteins to glycate the proteins, in the same
way as occurs in poorly controlled diabetes mellitus,
and there is some evidence of increased cardiovascu-
lar mortality associated with vitamin C supplements
in diabetics.
Up to 5% of the population are at risk from the
development of renal oxalate stones. The risk is from
both ingested oxalate and that formed endogenously,
mainly from the metabolism of glycine. Some reports
have suggested that people consuming high intakes of
vitamin C excrete more oxalate in the urine. However,
no pathway for the formation of oxalate from ascor-
bate is known, and it seems that the oxalate is formed
non-enzymically under alkaline conditions either in
the bladder or after collection, and hence high vitamin
C intake is not a risk factor for renal stone
formation.8.15 Perspectives on the future
Current estimates of requirements and reference
intakes of vitamins are based on the amounts required
to prevent or reverse subtle indices of defi ciency,
and can thus be considered to be amounts required
to prevent defi ciency, but possibly not to promote
optimum nutritional status and health. There is cur-
rently very little evidence on which to base reference
intakes above those required to prevent (subtle bio-
chemical) defi ciency, but indices of enhanced immune
system function and whole-body oxidative stress and
other biomarkers may do so in due course.
There are several compounds that have clearly
defi ned functions in the body but can be synthesized
in apparently adequate amounts, so that they are
not considered to be dietary essentials. These sub-
stances have been receiving increasing attention,
and these, in addition to other compounds, are likely
to continue to stimulate interest and discussion in the
future.