Chemistry Reference
In-Depth Information
energy production because of limited carnitine biosynthesis may explain the
fatigue
and
muscle
weakness
observed
in
humans
with
ascorbic
acid
deficiency.
Ascorbate is also involved in the hepatic microsomal hydroxylation of
cholesterol in the conversion and excretion of cholesterol as bile acids via
7
-hydroxycholesterol (Tsao, 1997). These reactions require the microso-
mal enzymatic system containing cytochrome P-450 hydroxylase. Impaired
cholesterol transformation to bile acids causes cholesterol accumulation in
the liver and blood and atherosclerotic changes in coronary arteries. Hydro-
xylation and demethylation of aromatic drugs and carcinogens by hepatic
cytochrome P-450 appears to be enhanced by reducing agents such as
ascorbate (Tsao, 1997). Ascorbic acid is the most potent enhancer of non-
haem iron absorption, both in its natural form in fruits and vegetables and
when added as the free compound (Hallberg et al., 1987; Hurrell, 1992). In
addition, ascorbic acid increases the bioavailability of all fortification
compounds.
12.6.5.
Ascorbate and Chronic Disease
The oxidation of LDL particles and the accumulation of oxidized LDL
in the vessel wall are key early events in the progression of atherosclerosis
(Parthasarathy et al., 1999; Binder et al., 2002). High plasma concentrations
of ascorbate not only correlate with lower concentrations of oxidized LDL
(Carr et al., 2000b) but also function to protect endothelial cells against the
detrimental effects of oxidized LDL once this is formed (Siow et al.,1999).
Since ascorbate is water soluble and is not incorporated in LDL particles, it
has been proposed that it may prevent the oxidation of LDL particles by
scavenging free radical species in the aqueous milieu, and it is also capable of
regenerating
-TOH from
-TO
.
, which is formed on inhibition of lipid
peroxidation by vitamin E (Carr et al., 2000c). Ascorbyl radicals formed in
this process may be reduced to ascorbate by dismutation, chemical reduction
or enzymatic reduction.
Increased risk of chronic disease, including coronary heart disease,
cancer and cataracts, is associated with low intake or plasma concentra-
tions of vitamin C (Riemiersma, 1994; Gey, 1995). Plasma ascorbate levels
were inversely related to mortality from all causes, and from cardiovascular
disease and ischaemic heart disease in men and women in the EPIC-Nor-
folk prospective study (Khaw et al., 2001). A 20% fall in risk of all-cause
mortality, independent of other risk factors, was associated with a 20 mmol/
l rise in ascorbate, approximately equivalent to a 50 g/day increase in fruit
and vegetable intake. Boekholdt et al. (2006) observed that a high plasma
concentration of ascorbate was inversely related to various cardiovascular
