LE Magazine October 2002
Page 3 of 4
Serum micro nutrients and upper
aerodigestive tract cancer.
Numerous dietary studies have found that vegetables and
fruits protect against upper aerodigestive tract cancer. To
evaluate the role of beta-carotene and other specific
carotenoids, a nested case-control study using prediagnostic
serum was conducted among 6832 American men of Japanese
ancestry examined from 1971 to 1975. During a surveillance
period of 20 years, the study identified 28 esophageal, 23
laryngeal and 16 oral-pharyngeal cancer cases in this cohort.
The 69 cases were matched to 138 controls. A liquid
chromatography technique, designed to optimize recovery and
separation of the individual carotenoids, was used to measure
serum levels of lutein, zeaxanthin, beta-cryptoxanthin,
lycopene, alpha-carotene, beta-carotene, retinol, retinyl
palmitate, and alpha-, delta-, and gamma tocopherol. With
adjustment for cigarette smoking and alcohol intake, we found
that alpha-carotene, beta-carotene, beta-cryptoxanthin, total
carotenoids and gamma tocopherol levels were significantly
lower in the 69 upper aerodigestive tract cancer patients than
in their controls. Trends in risk by tertile of serum level
were significant for these five micro nutrients. These
significant trends persisted in cases diagnosed 10 or more
years after phlebotomy for the three individual carotenoids
and total carotenoid measurements. The odds ratios for the
highest percentile were 0.19 (95% confidence interval,
0.05-0.75) for alpha-carotene, 0.10 (0.02-0.46) for
beta-carotene, 0.25 (0.06-1.04) for beta-cryptoxanthin, and
0.22 (0.05-0.88) for total carotenoids. When the cases were
separated into esophageal, laryngeal, and oral-pharyngeal
cancer, both alpha-carotene and beta-carotene were
consistently and strongly associated with reduced risk at each
site. The findings suggest that alpha-carotene and other
carotenoids, as well as beta-carotene, may be involved in the
etiology of upper aerodigestive tract cancer.
Cancer Epidemiol Biomarkers Prev 1997
Jun;6(6):407-12
Dietary antioxidant vitamins and death
from coronary heart disease in postmenopausal women.
BACKGROUND: The role of dietary antioxidant vitamins in
preventing coronary heart disease has aroused considerable
interest because of the knowledge that oxidative modification
of low-density lipoprotein may promote atherosclerosis.
METHODS. We studied 34,486 postmenopausal women with no
cardiovascular disease who in early 1986 completed a
questionnaire that assessed, among other factors, their intake
of vitamins A, E and C from food sources and supplements.
During approximately seven years of follow-up (ending December
31, 1992), 242 of the women died of coronary heart disease.
RESULTS. In analyses adjusted for age and dietary energy
intake, vitamin E consumption appeared to be inversely
associated with the risk of death from coronary heart disease.
This association was particularly striking in the subgroup of
21,809 women who did not consume vitamin supplements (relative
risks from lowest to highest quintile of vitamin E intake,
1.0, 0.68, 0.71, 0.42 and 0.42; P for trend 0.008). After
adjustment for possible confounding variables, this inverse
association remained (relative risks from lowest to highest
quintile, 1.0, 0.70, 0.76, 0.32 and 0.38; P for trend, 0.004).
There was little evidence that the intake of vitamin E from
supplements was associated with a decreased risk of death from
coronary heart disease, but the effects of high-dose
supplementation and the duration of supplement use could not
be definitely addressed. Intake of vitamins A and C did not
appear to be associated with the risk of death form coronary
heart disease. CONCLUSIONS. These results suggest that in
postmenopausal women the intake of vitamin E from food is
inversely associated with the risk of death from coronary
heart disease and that such women can lower their risk without
using vitamin supplements. By contrast, the intake of vitamins
A and C was not associated with lower risks of dying from
coronary disease.
N Engl J Med 1996 May
2;334(18):1156-62
Differential effects of alpha and
gamma tocopherol on low-density lipoprotein oxidation,
superoxide activity, platelet aggregation and arterial
thrombogenesis.
OBJECTIVES: This study was designed to examine the
differential effects of alpha and gamma tocopherol on
parameters of oxidation-antioxidation and thrombogenesis.
BACKGROUND: Experimental studies have shown that antioxidants,
such as vitamin E (alpha tocopherol), improve atherosclerotic
plaque stability and vasomotor function, and decrease platelet
aggregation and tendency to thrombus formation. METHODS:
Sprague Dawley rats were fed chow mixed with alpha or gamma
tocopherol (100 mg/kg/day) for 10 days. A filter soaked in 29%
FeCl3 was applied around the abdominal aorta to study the
patterns of arterial thrombosis. The aortic blood flow was
observed and continuously recorded using an ultrasonic Doppler
flow probe. ADP-induced platelet aggregation, low-density
lipoprotein oxidation induced by phorbol 12-myristate
13-acetate (PMA)-stimulated leukocytes, superoxide anion
generation and superoxide dismutase (SOD) activity were also
measured. RESULTS: Both alpha and gamma tocopherol decreased
platelet aggregation and delayed time to occlusive thrombus
(all p < 0.05 vs. control). Both alpha and gamma tocopherol
decreased arterial superoxide anion generation, lipid
peroxidation and LDL oxidation (all p < 0.05 vs. control),
and increased endogenous SOD activity (p < 0.05). The
effects of gamma tocopherol were more potent than those of
alpha tocopherol (p < 0.05). CONCLUSIONS: This study
indicates that both alpha- and gamma tocopherol decrease
platelet aggregation and delay intraarterial thrombus
formation, perhaps by an increase in endogenous antioxidant
activity. Alpha tocopherol is significantly more potent than
alpha-tocopherol in these effects.
J Am Coll Cardiol 1999
Oct;34(4):1208-15
Optimal nutrition: vitamin E.
Interest in the role of vitamin E in disease prevention has
encouraged the search for reliable indices of vitamin E
status. Most studies in human subjects make use of static
markers, usually alpha-tocopherol concentrations in plasma or
serum. Plasma or serum alpha-tocopherol concentrations of <
11.6, 11.6-16.2, and > 16.2 mumol/l are normally regarded
as indicating deficient, low and acceptable vitamin E status
respectively, although more recently it has been suggested
that the optimal plasma alpha-tocopherol concentration for
protection against cardiovascular disease and cancer is >
30 mumol/l at common plasma lipid concentrations in
combination with plasma vitamin C concentrations of > 50
mumol/l and > 0.4 mumol beta-carotene/l. Assessment of
vitamin E status has also been based on alpha-tocopherol
concentrations in erythrocytes, lymphocytes, platelets,
lipoproteins, adipose tissue, buccal mucosal cells and LDL,
and on alpha-tocopherol: gamma-tocopherol in serum or plasma.
Erythrocyte susceptibility to haemolysis or lipid oxidation,
breath hydrocarbon exhalation, oxidative resistance of LDL,
and alpha-tocopheryl quinone concentrations in cerebrospinal
fluid have been used as functional markers of vitamin E
status. However, many of these tests tend to be non-specific
and poorly standardized. The recognition that vitamin E has
important roles in platelet, vascular and immune function in
addition to its antioxidant properties may lead to the
identification of more specific biomarkers of vitamin E
status.
Proc Nutr Soc 1999
May;58(2):459-68
Gamma-tocopherol decreases
ox-LDL-mediated activation of nuclear factor-kappaB and
apoptosis in human coronary artery endothelial cells.
Gamma-tocopherol, produced by many plants, is the major
form of tocopherol in the United States diet. It is an
effecient protector of lipids against peroxidative damage.
Epidemiologic studies show that supplementation of diet with
gamma-tocopherol is inversely related to the risk of death
from cardiovascular disease. This study was conducted to
examine the role of gamma-tocopherol in oxidized LDL
(ox-LDL)-induced nuclear factor (NF)-kappaB activation and
apoptosis in human coronary artery endothelial cells (HCAECs).
Cultured HCAECs were treated with ox-LDL (10-40 microgram/ml).
Incubation of HCAECs with ox-LDL resulted in apoptosis of
HCAECs, as determined by TUNEL and DNA laddering. Ox-LDL
degraded IkappaB protein and activated NF-kappaB in HCAECs
(both P < 0.01 vs control), as determined by Western blot.
Treatment of cells with gamma-tocopherol attenuated
ox-LDL-mediated degradation of IkappaB and activation of
NF-kappaB (both P < 0.01 vs ox-LDL alone). The presence of
gamma-tocopherol also reduced ox-LDL-induced apoptosis (P <
0.01 vs ox-LDL alone). A high concentration of
gamma-tocopherol (50 micromol/L) was more effective than the
low concentration of gamma-tocopherol (10 micromol/L) in this
process. These observations show that ox-LDL induces apoptosis
of HCAECs at least partially by activation of NF-kappaB signal
transduction pathway. Gamma-tocopherol significantly decreases
ox-LDL-induced apoptosis of HCAECs by inhibiting the
activation of NF-kappaB.
Biochem Biophys Res Commun 1999 May
27;259(1):157-61
Vitamin E deficiency in variant
angina.
BACKGROUND: Oxidative modification of LDL has been
suggested to increase coronary vasoreactivity to agonists. A
deficiency of vitamin E, a major antioxidant, may be related
to the occurrence of coronary artery spasm. METHODS AND
RESULTS: Vitamin E levels were determined with the use of
high-performance liquid chromatography in normolipidemic
subjects, including 29 patients with active variant angina
(group 1), 13 patients with inactive stage of variant angina
without anginal attacks during the past 6 months (group 2), 32
patients with a significant (>75%) organic coronary
stenosis and stable effort angina (group 3), and 30 patients
without coronary artery disease (group 4). Total lipid levels
in blood were calculated as total cholesterol plus
triglyceride levels. The plasma alpha-tocopherol levels as
well as alpha-tocopherol/lipids were significantly lower in
group 1 than in groups 2 through 4. Also, the plasma
gamma-tocopherol levels were significantly lower in group 1
than in groups 2 through 4. The vitamin E levels were not
significantly different between group 1 patients with and
those without a significant organic stenosis. In group 1, both
alpha- and gamma-tocopherol levels were significantly elevated
after a > or = six-month angina-free period. The
alpha-tocopherol levels in the LDL fraction were significantly
lower in group 1 than in group 4. Plasma alpha-tocopherol
levels were significantly correlated with those in the LDL
fractions. In six patients of group 1 still having anginal
attacks while receiving calcium channel blockers, the addition
of vitamin E acetate (300 mg/d) significantly elevated plasma
alpha-tocopherol levels and inhibited the occurrence of
angina. CONCLUSIONS: Plasma vitamin E levels were
significantly lower in patients with active variant angina
than in subjects without coronary spasm, suggesting an
association between vitamin E deficiency and coronary artery
spasm.
Circulation 1996 Jul 1;94(1):14-8
Gamma-tocopherol: an efficient
protector of lipids against nitric oxide-initiated
peroxidative damage.
Nitric oxide released by macrophages during inflammation
reacts with active oxygen to form peroxynitrite. Peroxynitrite
nitrates protein and peroxidizes lipids. Gamma-tocopherol
traps peroxynitrite and is more effective than
alpha-tocopherol in protecting lipids against such
peroxidation.
Nutr Rev 1997 ct;55(10):376-8
Gamma-tocopherol traps mutagenic
electrophiles such as NO(X) and complements alpha-tocopherol:
physiological implications.
Peroxynitrite, a powerful mutagenic oxidant and nitrating
species, is formed by the near diffusion-limited reaction of
.NO and O2.- during activation of phagocytes. Chronic
inflammation induced by phagocytes is a major contributor to
cancer and other degenerative diseases. We examined how
gamma-tocopherol (gammaT), the principal form of vitamin E in
the United States diet, and alpha-tocopherol (alphaT), the
major form in supplements, protect against
peroxynitrite-induced lipid oxidation. Lipid hydroperoxide
formation in liposomes (but not isolated low-density
lipoprotein) exposed to peroxynitrite or the .NO and O2.-
generator SIN-1 (3-morpholinosydnonimine) was inhibited more
effectively by gammaT than alphaT. More importantly, nitration
of gammaT at the nucleophilic 5-position, which proceeded in
both liposomes and human low density lipoprotein at yields of
approximately 50% and approximately 75%, respectively, was not
affected by the presence of alphaT. These results suggest that
despite alphaT’s action as an antioxidant gammaT is
required to effectively remove the peroxynitrite-derived
nitrating species. We postulate that gammaT acts in vivo as a
trap for membrane-soluble electrophilic nitrogen oxides and
other electrophilic mutagens, forming stable carbon-centered
adducts through the nucleophilic 5-position, which is blocked
in alphaT. Because large doses of dietary alphaT displace
gammaT in plasma and other tissues, the current wisdom of
vitamin E supplementation with primarily alphaT should be
reconsidered.
Proc Natl Acad Sci U S A 1997 Apr
1;94(7):3217-22
Effect of alpha- and gamma-tocopherol
as well as cholesterol on lipid peroxidation.
For a period of 15 weeks growing rats were fed low fat
diets containing equimolar doses of alpha- and
gamma-tocopherol (180 and 174 ppm) as well as mixtures of
alpha- and gamma-tocopherol (3:1; 1:1; 1:3) without
cholesterol or with 1% cholesterol. The influence of these
supplements on lipid peroxidation and tocopherol retention in
the liver were investigated. The tocopherol status was
estimated by measuring the activities of creatine kinase and
transaminases (GOT, GPT) in plasma as well as by in vitro
hemolysis of erythrocytes. The in vitro hemolysis rate was
only lowered by alpha-tocopherol and the mixtures of alpha-
and gamma-tocopherol. In response to lipid peroxidation in the
liver, alpha-tocopherol was the more efficient antioxidant,
whereas gamma-tocopherol was more efficient in the diet.
Cholesterol had a lowering effect on lipid peroxidation in
vitro and in vivo; cholesterol in combination with
alpha-tocopherol had a stabilizing effect on the erythrocyte
membrane. Moreover, there was a positive effect of cholesterol
on tocopherol retention in the liver. The biological activity
of gamma-tocopherol in relation to alpha-tocopherol was
calculated according to the test criterium; it ranged from 22%
to 100%.
Z Ernahrungswiss 1986
Mar;25(1):47-62
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