Controlled studies were conducted to find out the plasma values of ascorbic
acid, dehydroascorbic acid (DHA), urinary excretion of ascorbic acid and blood
levels of glutathione in patients with viral hepatitis, alcoholic hepatitis,
cirrhosis of liver and carcinoma of liver. Leucocyte ascorbic acid and DHA/AA
index were also determined in order to assess the ascorbic acid status of these
patients. It was observed that the plasma and leucocytes contents of ascorbic
acid were significantly subnormal with markedly decreased urinary excretion in
these patients. Decreased level of glutathione and significantly higher level of
DHA reflect an over all reducing status of the body is markedly deranged in
these conditions. Further it was observed that the DHA/AA ratios were
significantly altered in these groups of patients.

BACKGROUND: An ever increasing demand to evaluate the effect of dietary
supplements on specific health conditions by use of a "significant scientific"
standard has prompted the publication of this study. OBJECTIVE: To study the
effect of megadose Vitamin C in preventing and relieving cold and flu symptoms
in a test group compared with a control group. DESIGN: Prospective, controlled
study of students in a technical training facility. SUBJECTS: A total of 463
students ranging in age from 18 to 32 years made up the control group. A total
of 252 students ranging in age from 18 to 30 years made up the experimental or
test group. METHOD: Investigators tracked the number of reports of cold and flu
symptoms among the 1991 test population of the facility compared with the
reports of like symptoms among the 1990 control population. Those in the control
population reporting symptoms were treated with pain relievers and
decongestants, whereas those in the test population reporting symptoms were
treated with hourly doses of 1000 mg of Vitamin C for the first 6 hours and then
3 times daily thereafter. Those not reporting symptoms in the test group were
also administered 1000-mg doses 3 times daily. RESULTS: Overall, reported flu
and cold symptoms in the test group decreased 85% compared with the control
group after the administration of megadose Vitamin C. CONCLUSION: Vitamin C in
megadoses administered before or after the appearance of cold and flu symptoms
relieved and prevented the symptoms in the test population compared with the
control group.

So far over 60 studies have examined the effects of vitamin C on the common
cold. No effect on common cold incidence was observed in the six largest
studies, indicating that vitamin C has no preventive effects in normally
nourished subjects in the Western countries. There are, however, smaller studies
reporting benefit. In three trials of subjects under heavy acute physical
stress, common cold incidence decreased by on average 50%, and in four trials of
British males common cold incidence decreased by on average 30% in the vitamin C
groups. The dietary vitamin C intake in the UK is low, and consequently the
benefit may be due to the correction of marginal deficiency, rather than high
vitamin doses. Regular vitamin C supplementation (> or =1 g/day) has quite
consistently reduced the duration of colds, but the size of the benefit has
varied greatly. In the four largest studies the duration of colds was reduced
only by 5%. In two of these studies, however, absence from school and work was
reduced by 14-21% per episode, which may have practical importance. Three
controlled studies recorded a reduction of at least 80% in the incidence of
pneumonia in the vitamin C group, and one randomised trial reported substantial
treatment benefit from vitamin C in elderly UK patients hospitalized with
pneumonia or bronchitis. It seems that the preventive effects of supplementation
are mainly limited to subjects with low dietary vitamin C intake, but
therapeutic effects may occur in wider population groups. Further carefully
designed trials are needed to explore the effects of vitamin C.

In this study, the antioxidant protection of ascorbic acid (AA) supplementation
during different unfed periods (24, 48, 120 h) was determined with blood lipid
peroxidation level (thiobarbituric acid reactive substances, TBARS) and compared
with plasma antioxidant sulfydryl group (RSH) content. Weight loss was induced
by increasing the unfed period together with vitamin C supplementation. Blood AA
levels decreased by starvation but increased by vitamin C supplementation. RSH
content in plasma also decreased with the unfed period; these decreases became
apparent by vitamin C supplementation. TBARS formation increased significantly
by AA supplementation in the 120-h starvation period.

Low-density lipoproteins (LDL) mildly oxidized by copper ions or UV radiations
exhibit a cytotoxic effect to cultured endothelial cells. Rutin, a polyphenolic
flavonoid, ascorbic acid, and alpha-tocopherol were able to inhibit the
peroxidation of LDL and their subsequent cytotoxicity. The mixture of the three
compounds (rutin/ascorbic acid/alpha-tocopherol, 4/4/1) exhibited a
supra-additive antioxidant effect. The inhibition of the cytotoxic effect was
well correlated with that of TBARS formation. Another important conclusion is
that these antioxidants were able to prevent directly at the cellular level the
cytotoxic effect of oxidized LDL, since cells preincubated with them were
protected against the cytotoxic effect of previously oxidized LDL. The
protective effect of antioxidants was limited because of their own toxicity. The
antioxidant mixture permitted a maximal cytoprotective effect with relatively
lower concentrations to be obtained and the cytotoxicity of high concentrations
to be avoided. In conclusion, rutin, ascorbic acid, and alpha-tocopherol
constitute two lines of defense in protecting cells against injury owing to
oxidation of LDL (1) at the LDL level, by inhibiting the LDL oxidation and the
subsequent cytotoxicity, and (2) at the cellular level, by protecting the cells directly, i.e., by increasing their resistance against the cytotoxic effect of oxidized LDL.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in microsomes
isolated from cultured lymphoid (IM-9) cells or freshly isolated human
leukocytes was markedly decreased by either ascorbic acid or its oxidized
derivative, dehydroascorbate. Inhibition of IM-9 leukocyte HMG-CoA reductase
activity was log linear between 0.01 and 10 mM ascorbic acid (25 and 81%
inhibition, respectively) and 0.1 and 10 mM dehydroascorbate (5 and 75%
inhibition, respectively). Inhibition was noncompetitive with respect to HMG-CoA
(Km = 10.2 microM (RS); ascorbic acid, Ki = 6.4 mM; dehydroascorbate, Ki = 15
mM) and competitive with respect to NADPH (Km = 16.3 microM; acetic acid, Ki =
6.3 mM; dehydroascorbate, Ki = 3.1 mM). Ascorbic acid and dehydroascorbate are
interconverted through the free radical intermediate monodehydroascorbate.
Reducing agents are required to convert dehydroascorbate to
monodehydroascorbate, but prevent formation of the free radical from ascorbate.
In microsomes from IM-9 cells, the reducing agent, dithiothreitol, abolished
HMG-CoA reductase inhibition by ascorbate but enhanced inhibition by
dehydroascorbate. In addition, the concentration of monodehydroascorbate present
in ascorbate solutions was directly proportional to the degree of HMG-CoA
reductase inhibition by 1.0 mM ascorbate. Fifty per cent inhibition of enzyme
activity occurred at a monodehydroascorbate concentration of 14 microM. These
data indicate that monodehydroascorbate mediates inhibition of HMG-CoA reductase
by both ascorbate and dehydroascorbate. This effect does not appear to be due to
free radical-induced membrane lipid modification, however, since both ascorbate
and dehydroascorbate inhibited the protease-solubilized, partially purified
human liver enzyme. Since inhibition of HMG-CoA reductase occurs at
physiological concentrations of ascorbic acid in the human leukocyte (0.2-1.72
mM), this vitamin may be important in the regulation of endogenous cholesterol
synthesis in man.

Aqueous extract of cigarette smoke (CS) contains some stable oxidants, which
oxidize human plasma proteins, bovine serum albumin, amino acid homopolymers,
and also cause extensive oxidative degradation of microsomal proteins. Similar
observations are made when the aqueous extract of cigarette smoke is replaced by
whole phase CS solution or whole phase cigarette smoke. CS-induced microsomal
protein degradation is a two step process: (i) oxidation of proteins by the
oxidants present in the CS and (ii) rapid proteolytic degradation of the
oxidized proteins by proteases present in the microsomes. Using aqueous extract
of CS equivalent to that produced from one-twentieth of a cigarette, the
observed initial and postcigarette smoke treated values of different parameters
of oxidative damage per milligram of microsomal proteins are respectively: 0.24
and 1.74 nmoles for carbonyl formation, 125.4 and 62.8 fluorescence units for
tryptophan loss, 10.2 and 33.4 fluorescence units for bityrosine formation, and
58.3 and 12.2 nmoles for loss of protein thiols. When compared with sodium
dodecyl sulphate polyacrylamide gel electrophoresis profiles of untreated
microsomal proteins, the extent of microsomal protein degradation after
treatment with whole phase CS solution or aqueous extract of CS is above 90%.
Ascorbate (100 microM) almost completely prevents cigarette smoke-induced
protein oxidation and thereby protects the microsomes from subsequent
proteolytic degradation. Glutathione is partially effective, but other
antioxidants including superoxide dismutase, catalase, vitamin E, probucol,
beta-carotene, mannitol, thiourea, and histidine are ineffective. The gas phase
cigarette smoke contains unstable reactive oxygen species such as superoxide
(O2*-) and hydrogen peroxide (H2O2) that can cause substantial oxidation of pure
protein like albumin but is unable to produce significant oxidative damage of
microsomal proteins. Gas phase cigarette smoke-induced albumin oxidation is not
only inhibited by ascorbate and glutathione but also by superoxide dismutase,
catalase and mannitol. The stable oxidants in the cigarette smoke are not
present in the tobacco and are apparently produced by the interaction of
O2*-/H2O2/OH* of the gas phase with some components of the tar phase
during/following the burning of tobacco.

The chemopreventive effects of antioxidants (vitamin E, beta-carotene, vitamin C
and red ginseng) on oxidative DNA and protein (globin) damages were
comparatively investigated in the peripheral blood of smokers (> or = 20
cigarettes/day). Smokers showed a lower baseline level of plasma micronutrients
(vitamin C and beta-carotene) (P < 0.01) and higher baseline level of oxidative
DNA or protein damage than non-smokers (N = 5; P < 0.05). During daily
supplementation of antioxidants (200 IU vitamin of E, 9 mg of beta-carotene, 500
mg of vitamin C, or 1.8 g of red ginseng) for 4 weeks, smokers plasma
antioxidant concentrations increased linearly, while their mean levels of
8-hydroxydeoxyguanosine (8-OHdG) and carbonyl contents decreased compared with
those in smokers supplemented with a placebo (P < 0.05). Levels of urinary and
plasma cotinine remained steady in smokers regardless of supplementation with
antioxidants. 8-OHdG and carbonyl content decreased in a time-dependent manner
(as the total intake dose increased) after supplementation with vitamin E
(8-OHdG, 33.8%; carbonyl content, 43.6%) or red ginseng (8-OHdG, 31.7%; carbonyl
content, 21.3%). These preliminary data suggest that supplementation with
antioxidants might protect smokers from oxidative damages and could reduce
cancer risk or other diseases caused by free radicals associated with smoking.

A study has been conducted to investigate whether the oxidative damage produced
in the liver of rats exposed to cigarette smoke can be effectively combatted
with vitamin C, one of the antioxidant vitamins. We assessed the liver
antioxidants (vitamins E, C and A), scavenging enzymes and lipid peroxide
products of rats exposed to cigarette smoke and simultaneously given vitamin C
(200 mg 100 g[-1] body wt.) for 90 days. Malondialdehyde (MDA), conjugated
dienes, hydroperoxides and free fatty acids (FFA) were significantly increased
in liver of smoke-exposed groups. The activity of superoxide dismutase and
catalase and vitamin E and C contents were significantly lower than controls.
But vitamin A, glutathione (GSH) content and glutathione peroxidase (GSH Pxase)
activity were enhanced. Vitamin C supplementation to smoke-exposed rats showed
increased resistance to lipid peroxidation and increased activity of scavenging
enzymes. The GSH content, vitamin C and FFA were brought to normal levels. Thus,
this study seems to suggest that an intake of a mega dose of vitamin C can
protect the liver from oxidant damage caused by cigarette smoke.

Although the evidence for oxidative stress for air pollution in the human lung
is fragmentary, the hypothesis that oxidative stress is an important, if not the
sole, mechanism of toxicity of oxidizing air pollutants and tobacco smoke is
compelling and growing. First, biochemical mechanisms have been worked out for
oxidation of lung lipids by the gas phase of cigarette smoke, NO2 and O3. The
oxidation of lung lipids can be prevented by both vitamins C and E. Vitamin C is
more effective in preventing oxidation by NO2, and vitamin E is more effective
against O3. Second, multiple species of experimental animals develop lung
disease similar to human bronchitis and emphysema from exposure to NO2 and O3,
respectively. The development of these diseases occurs over a near lifetime
exposure when the levels of NO2 or O3 are at near ambient air pollution values.
Third, isolated human cells are protected against oxidative damage from NO2 and
O3 by both vitamins C and E. Fourth, the vitamin C level in the lung either
declines on exposure to NO2 for short-term exposures or increases on chronic
cigarette smoke exposure. The effects of cigarette smoking on serum vitamin C is
apparently complex and may be related to the daily intake of vitamin C as well
as smoking. Serum vitamin C levels may be poor indicators of lung demands when
daily vitamin C intakes are above 100 mg/day. Fifth, vitamin C supplementation
protects against the effects of ambient levels of air pollution in adults as
measured by histamine challenge. An augmented response to histamine challenge
may represent increased lung permeability brought about by air pollution. In
experimental animal and human experiments, the amount of vitamin C or E that
afforded protection was in excess of the current recommended dietary allowance.
Although animal studies do not provide evidence for complete protection against
NO2 or O3, they do illustrate that current recommended daily allowances are
inadequate for maximum protection against air pollution levels to which over 100
million Americans are exposed. The problem of air pollution and its effects on
humans is truly of global concern. Air pollution is not restricted to North
America or Japan where it was first recognized, but is a major public health
problem in Europe as well. When data are available, air pollution probably will
be shown to be a major public health problem in all urban areas of the world.