It is well established that
smokers are at increased risk for developing atherosclerosis and ischemic
heart disease. The exact mechanism(s) that links smoking to an increased risk
for the development of accelerated atherosclerosis is not fully understood. In
recent years, evidence has mounted that a pro-oxidant/antioxidant imbalance
plays a significant role in promoting the atherogenic process. Cigarette smoke
contains large amounts of pro-oxidants that can directly initiate the process
of lipid peroxidation as well as deplete the body of nutrient antioxidants.
Additionally, smoking elevates plasma and low-density lipoprotein (LDL) levels
of peroxidation, and favors LDL oxidation in vivo. Antioxidants like vitamins
C and E are responsible for counteracting free radical-mediated oxidative
Numerous studies have shown that chronic, marginal deficiencies of vitamins C
and E cause atherosclerosis-like lesions in numerous animal models, and that
supplements of vitamin C or E reduces the number of these lesions. Most
studies of this relationship in humans have examined levels of vitamins C and
E in the plasma, often with equivocal results. A recent study has attempted to
more accurately look at the relationship between antioxidant vitamin status,
smoking, and coronary heart disease by examining not only the plasma vitamin
levels, but also the antioxidant capacity and vitamin levels of arterial wall
tissue taken from smokers and nonsmokers undergoing cardiac bypass surgery.
This study confirmed earlier results showing that smoking lowers the plasma
level of vitamin C, but not vitamin E.
Additionally, smokers had significantly higher plasma concentrations of lipid
peroxides. However, for the first time this research demonstrated that, in
smokers, a pro-oxidant/antioxidant imbalance can be found in the arterial wall
tissue. In this tissue, significant decreases in vitamin E and C levels were
found, along with a significant increase in tissue lipid peroxides. The
integrated function between vitamins C and E in the arterial wall appears to
be crucial for controlling oxidation and protecting LDL from oxidation. In
fact, some researchers have suggested that both vitamins must be supplemented
together to lower peroxidation. In smokers, the lowered tissue antioxidant
capacity was associated with a lower content of vitamin C and higher lipid
peroxidation in plasma, whereas plasma vitamin E levels were not significantly
different from nonsmokers. The authors note that cigarette smoke has been
shown to rapidly deplete vitamin C in plasma, which is quickly followed by
lipid peroxidation. The lower vitamin C levels found in smokers is considered
to be a direct consequence of vitamin C utilization as an antioxidant due to
the smoke-related pro-oxidant load.
It was also found in the study that there is a direct relationship between
plasma and tissue vitamin levels. In smokers, decreased plasma vitamin C
appears to lower tissue vitamin C levels. This probably results in a decrease
in tissue vitamin E levels, despite normal serum levels, because vitamin C
acts as an antioxidant reservoir by sparing and regenerating vitamin E.
been shown that plasma lipid peroxidation begins when vitamin C is depleted,
while lipid peroxidation in tissue systems initiates only when vitamin E falls
below a critical level. Accordingly, in this study the plasma levels of lipid
peroxides was inversely and significantly related to the vitamin C level,
whereas in arterial tissue the lipid peroxidation products were significantly
and inversely related to the vitamin E content. In both smokers and
nonsmokers, only tissue vitamin E and tissue lipid peroxidation products were
significantly correlated with the degree of coronary atherosclerosis. This
suggests that tissue vitamin E levels are crucial in protecting vessels from
atherosclerosis, and that low serum vitamin C decreases tissue levels of both
vitamin C and vitamin E. Because tissue levels of vitamin E can be
significantly reduced despite normal serum levels, this study calls into
question the absolute value of serum antioxidant measurements in both smokers
and nonsmokers. It seems likely that a pro-oxidant/antioxidant imbalance
operating in the arterial tissue is crucial to promoting atherosclerosis, due
to the correlation between the severity of atherosclerotic lesions and the
content of vitamins and lipid peroxide products in arterial tissue.
source of nutrients and supplements.
did we qualify them ?
Vitamin Research Products Inc. 2001
A. Mazzetti, D. Lapenna, S.D. Pierdomenico, et al, Atherosclerosis 1995; 112: