Tuesday, July 3, 2007

Vitamin C and cardiovascular disease

Ascorbic acid through its numerous metabolic and
antioxidant effects may inhibit some of the steps
involved in atherosclerosis and thrombosis, thus
reducing the risk of cardiovascular disease. In a casecontrol
study, Ramirez & Flowers (1980) reported
signifi cantly lower (p < 0.001) leucocyte vitamin C
levels in 101 cases of angiographically documented
cardiovascular disease.
19.11.1 Cholesterol metabolism
Studies of animals that either synthesize (rat, rabbit)
or do not synthesize (guinea pig, monkey) vitamin
C have shown that vitamin C is intimately involved
in cholesterol metabolism. Guinea pigs subjected to
chronic vitamin C defi ciency exhibit increased cholesterol
levels in blood plasma and liver due to slower
conversion of cholesterol to bile acids (Ginter et al.,
1971; Ginter, 1973). The impaired conversion results
from a decreased activity of the rate-limiting liver enzyme
cholesterol 7α-hydroxylase (Horio et al., 1989).
When guinea pigs, rats and rabbits are rendered
hypercholesterolaemic by feeding a high-cholesterol
diet, vitamin C supplementation lowers their blood
cholesterol levels.
19.11.2 Lipoprotein profi le
Diets low in vitamin C lead to a redistribution of
cholesterol among the various plasma lipoproteins.
Vitamin C defi ciency in ODS rats (rats with an hereditary
inability to synthesize ascorbic acid) leads to
an increase in potentially pro-atherogenic LDL cholesterol
and a decrease in HDL cholesterol, resulting in
hypercholesterolaemia (Uchida et al., 1990).
19.11.3 Protection of LDL against
peroxidative modifi cation
Physiological concentrations of ascorbic acid protect
LDL against copper-catalysed peroxidative modifi cation
in vitro, maintaining the ability of LDL to be
recognized by appropriate LDL receptors and not by the scavenger receptor of macrophages (Sakuma
et al., 2001). This protective action preserves LDL’s
indigenous lipid-soluble antioxidants, except for
ubiquinol, the reduced form of coenzyme Q (Retsky
& Frei, 1995). Ascorbic acid spares, rather than
regenerates, LDL-associated α-tocopherol, i.e. prevents
α-tocopherol oxidation in the fi rst place. The
dilemma of whether ascorbate acts as a pro-oxidant or
as an antioxidant when interacting with LDL has been
addressed by Lynch et al. (1996). Ascorbate protects
native or mildly oxidized LDL against further metal
ion-dependent oxidation; only if LDL becomes extensively
oxidized does ascorbate acts as a pro-oxidant.
19.11.4 Effects on nitric oxide-mediated
arterial relaxation
Several studies have shown that an acute application
of ascorbic acid enhanced endothelium-dependent
vasodilation in patients with diabetes, coronary artery
disease, hypertension, hypercholesterolaemia, or
chronic heart failure, and in cigarette smokers (Heitzer
et al., 1996; Levine et al., 1996; Ting et al., 1996; Solzbach
et al., 1997; Ting et al., 1997; Hornig et al., 1998).
Long-term ascorbic acid treatment (500 mg per day)
produced a sustained improvement in endotheliumdependent
vasodilation in patients with coronary artery
disease (Gokce et al., 1999). Kanani et al. (1999)
demonstrated that administration of ascorbic acid
prevents induction of endothelial dysfunction by homocysteine.
These fi ndings may be attributable to the
scavenging of superoxide by ascorbate, thus preventing
the reaction between superoxide and nitric oxide
to form hydroxyl radicals and nitrogen dioxide, both
of which can initiate lipid peroxidation.
Heller et al. (1999) demonstrated that pre-incubation
of cultured endothelial cells with ascorbic acid
led to a three-fold increase of the cellular production
of nitric oxide after stimulation with ionomycin or
thrombin. Ascorbate did not induce the expression of
nitric oxide synthase and appeared to act through an
effect on the availability or affi nity of the enzyme cofactor
tetrahydrobiopterin. The fi ndings suggest that
saturation of the vascular tissue with ascorbate provides
the optimum reaction conditions for adequate
nitric oxide synthesis and that a decrease in intracellular
ascorbate leads to endothelial dysfunction.
19.11.5 Enhancement of prostacyclin
The formation of prostacyclin (PGI2), a member of
the prostaglandin family which protects the arterial
wall against deposition of platelets, is inhibited by hydroperoxides
of unsaturated fatty acids. In vitro studies
have shown that physiological concentrations of
ascorbic acid enhance the formation of prostacyclin
by aortic rings by protecting the cyclooxygenase and
PGI-synthase (Beetens & Herman, 1983).
19.11.6 Effects of vitamin C
Rifi ci & Khachadurian (1993) administered vitamin
C (1 g per day) and vitamin E (800 IU per day), both
separately and in combination, to healthy female and
male subjects and examined oxidation of lipoproteins
in vitro. Vitamin E administration alone produced a
52% inhibition and vitamin C alone a 15% inhibition
of copper-catalysed thiobarbituric acid reactive
substances production; the combination of vitamins
produced a 63% inhibition. Harats et al. (1998) reported
that in young healthy male subjects consuming
a diet high in saturated fats, supplementation with
citrus fruits containing an estimated 500 mg per day
of vitamin C reduced the in vitro susceptibility of
LDL to oxidation. Mosca et al. (1997) reported that
antioxidant supplementation with a combination of
800 IU of vitamin E, 1000 mg of vitamin C and 24 mg
of β-carotene signifi cantly reduced the susceptibility
of LDL to oxidation in patients with coronary artery
disease. The response produced by a similar combination
containing half the amounts of each antioxidant
was non-signifi cant.
19.11.7 Epidemiological studies
Current evidence from epidemiological studies on the
role of vitamin C in the prevention of cardiovascular
disease is inconclusive, with some studies showing a
very strong correlation between vitamin C intake and
incidence of cardiovascular events and other studies
showing no correlation at all (Lynch et al., 1996; Institute
of Medicine, 2000).

1 comment:

Get Your View said...

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