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Title
Intestinal beta-carotene absorption and cleavage in men: response
of beta-carotene and retinyl esters in the triglyceride-rich
lipoprotein fraction after a single oral dose of beta-carotene.
Author
van Vliet T; Schreurs WH; van den Berg H
Address
TNO Nutrition and Food Research Institute, Zeist, Netherlands.
Source
Am J Clin Nutr, 62(1):110-6 1995 Jul
Abstract
Postprandial response curves of beta-carotene and retinyl esters
in a triglyceride-rich lipoprotein (TRL) fraction were evaluated
as a potential measure of beta-carotene uptake and cleavage.
beta-Carotene, retinyl ester, and triglyceride concentrations
in the TRL fraction (density < 1.006 kg/L) and plasma were
measured in 10 men for 8 or 16 h after an oral dose of 15 mg
beta-carotene. The beta-carotene response, unlike the triglyceride
and retinyl ester response, can be evaluated in the TRL fraction
but not in plasma. Intraindividual variations in the triglyceride-adjusted
response of beta-carotene and retinyl palmitate in TRL fractions
were 23% and 20% and interindividual variations were 42% and
36%, respectively. A low beta-carotene response was associated
with a high ratio between retinyl palmitate and beta-carotene
responses (r = -0.56, P = 0.013). In conclusion, the measurement
of beta-carotene and retinyl esters in the TRL fraction after
a dose of beta-carotene with a vitamin A-free meal may be an
appropriate method to study beta-carotene uptake and cleavage.
Title
Discrimination in absorption or transport of beta-carotene isomers
after oral supplementation with either all-trans- or 9-cis-beta-carotene.
Author
Gaziano JM; Johnson EJ; Russell RM; Manson JE; Stampfer MJ; Ridker
PM; Frei B; Hennekens CH; Krinsky NI
Address
Division of Preventive Medicine, Brigham and Women's Hospital
and Harvard Medical School, Boston, MA 02111-1837, USA.
Source
Am J Clin Nutr, 61(6):1248-52 1995 Jun
Abstract
Human subjects (n = 24) were supplemented with 100 mg beta-carotene/d
for 6 d, either as synthetic all-trans-beta-carotene or a natural
beta-carotene preparation derived from the alga Dunaliella salina,
which consists of a 50:50 mixture of all-trans- and 6-cis-beta-carotene.
This loading dose was followed by a 23-d maintenance dose consisting
of alternate-day supplementation with 50 mg all-trans-beta-carotene
or either 66 or 100 mg of the natural 50:50 isomeric mixture.
The loading dose resulted in significant increases in plasma
concentrations of both isomers, with the all-trans-beta-carotene-supplemented
group showing a 7.2- and 5.0-fold increase in the all-trans and
9-cis concentrations in plasma, respectively. The group receiving
the 50:50 mixture showed a 4.0- and 3.7-fold increase in the
all-trans and 9-cis concentrations in plasma, respectively, without
any apparent dose-dependency. However, even with the 50:50 mixture,
the 9-cis concentrations were only a small fraction of the total
plasma beta-carotene. Results after an additional 23-d period
of alternate-day supplementation were not significantly different
from those described above for the 6-d supplementation. Increases
in low-density-lipoprotein concentrations of total beta-carotene
correlated strongly with the increases seen in plasma concentrations.
Lipid-soluble antioxidants vitamin E and ubiquinol were unaffected
by beta-carotene supplementation. However, the amount of lycopene
in the low-density lipoprotein decreased during this supplementation
period. A strong discrimination between these two geometric isomers
of beta-carotene was demonstrated, although the tissue site of
discrimination was not determined.
Title
Changes in beta-carotene levels by long-term administration of
natural beta-carotene derived from Dunaliella bardawil in humans.
Author
Morinobu T; Tamai H; Murata T; Manago M; Takenaka H; Hayashi
K; Mino M
Address
Department of Pediatrics, Osaka Medical College, Takatsuki, Japan.
Source
J Nutr Sci Vitaminol (Tokyo), 40(5):421-30 1994 Oct
Abstract
Long-term administration of a beta-carotene preparation derived
from Dunaliella bardawil, a beta-carotene-rich algae, was studied
in healthy young male volunteers. The daily administration of
60 mg of the beta-carotene preparation (30 mg of all-trans beta-carotene
and 30 mg of 9-cis beta-carotene) was performed and beta-carotene
concentrations were determined in the plasma, red blood cells
(RBC), platelets (PLT), and mononuclear cells (MN). The all-trans
beta-carotene level increased four-, two-, and threefold the
baseline in plasma, PLT, and MN, respectively. Basal levels of
9-cis beta-carotene in plasma, PLT, and MN were low and found
as one-tenth, one-fifth, and one-fifth of all-trans beta-carotene,
which increased three-, two-, and 1.5-fold the baseline, respectively.
Plasma and RBC alpha-tocopherol levels were not changed by the
intake of beta-carotene. No side effects or toxicities were documented
in any of the subjects during the administration period. In conclusion,
the bioavailability of beta-carotene derived from Dunaliella
bardawil was preferential for all-trans beta-carotene, although
a small amount of the 9-cis form was detected in the plasma and
blood cells.
Title
Expression of mRNA for the gap-junctional protein connexin43
in human colonic tissue is variable in response to beta-carotene
supplementation.
Author
Frommel TO; Lietz H; Mobarhan S
Address
Department of Medicine, Loyola University Medical Center, Maywood,
IL 60153
Source
Nutr Cancer, 22(3):257-65 1994
Abstract
Increased expression of the gap-junctional protein connexin43
(Cx43) is reported to be increased in mouse and human dermal
fibroblasts in vitro in response to beta-carotene treatment.
In the present study, we determined the level of Cx43 mRNA expression
in colonic mucosa from normal subjects and subjects with a prior
history of colonic polyps or cancer before and after three months
of administration of a placebo or beta-carotene. RNA was reverse
transcribed and used in a polymerase chain reaction assay employing
primers selected from the human Cx43 gene sequence. Cx43 mRNA
expression was normalized on the basis of beta 2-microglobulin
mRNA expression. The beta-carotene concentration in colonic mucosa,
as well as serum and diet, was also determined to establish a
correlation between Cx43 expression and beta-carotene concentration.
In an initial analysis of samples collected from 10 subjects
before supplementation, the quantity of Cx43 mRNA was variable
and did not correlate with beta-carotene intake or the concentration
of beta-carotene in tissue or serum. In samples collected at
zero and three months from eight subjects who were controls or
received a placebo, there was no correlation between Cx43 mRNA
level and tissue or serum beta-carotene concentration. In samples
collected from subjects before and after three months of beta-carotene
supplementation, there was a significant increase in tissue and
serum beta-carotene concentration in all subjects and an increase
in Cx43 mRNA expression after supplementation relative to baseline
in four of six samples. The high variability in Cx43 expression
indicates that induction of Cx43 mRNA expression is not solely
dependent on the concentration of beta-carotene in diet, serum,
or tissue. However, the results from subjects supplemented with
beta-carotene suggest that induced expression may occur in colonic
tissue of some individuals. some individuals.
Title
Mongolian gerbils (Meriones unguiculatus) absorb beta-carotene
intact from a test meal.
Author
Pollack J; Campbell JM; Potter SM; Erdman JW Jr
Address
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign
61801.
Source
J Nutr, 124(6):869-73 1994 Jun
Abstract
Because a yellow color has been observed in the fat pads of Mongolian
gerbils fed a nonpurified diet, we designed the current study
to determine whether adult male gerbils would absorb beta-carotene
intact from a test meal. Thirty-five gerbils (80-90 g) were adapted
to the laboratory and fed a standard purified diet free of beta-carotene
for 16-19 d. Gerbils were then fed a test meal consisting of
279 nmol of beta-carotene as 10% water-soluble beadlets suspended
in 0.5 mL of Ensure. Gerbils (n = 5) were killed at 0, 2, 4,
6, 12, 24 or 72 h after the test meal, blood was obtained by
cardiac puncture, and tissues were taken for beta-carotene analysis.
No beta-carotene was detected in serum at 0 or 72 h, whereas
beta-carotene was present at all other sampling times. Serum
beta-carotene peaked at 4 h, at a level of 88 nmol/L. beta-Carotene
was detected in the liver of all groups; however, the concentration
increased from -34 pmol/g to a maximum concentration of 926 pmol/g
at 24 h after the test meal. Other tissues also contained beta-carotene.
The results demonstrate that Mongolian gerbils, like ferrets
and preruminant calves, absorb beta-carotene intact when beta-carotene
is provided at a physiological level in a test meal. This species
may be particularly useful for evaluation of the role of antioxidants,
such as beta-carotene, in LDL oxidation.
Title
beta-Carotene inhibition of chemically induced toxicity in vivo
and in vitro.
Author
Kornhauser A; Wamer WG; Lambert LA; Wei RR
Address
Center for Food Safety and Applied Nutrition, Food and Drug Administration,
Washington, DC 20204.
Source
Food Chem Toxicol, 32(2):149-54 1994 Feb
Abstract
In the past several years there has been a great deal of interest
in the antioxidant beta-carotene and other micronutrients for
their protective potential against various toxic insults. Two
studies concerning the protective effects of beta-carotene, which
were conducted in our laboratory, are reported here. The first
involved the role of beta-carotene in modifying two-stage skin
tumorigenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA)
and promoted by phorbol 12-myristate 13-acetate (PMA, TPA). In
this study, the protective effects of two types of dietary beta-carotene,
a beadlet formulation and crystalline beta-carotene, were compared
in two strains of mice (Skh:HR-1 and CR:ORL Sencar). Mice were
maintained on food fortified with 3% beta-carotene or on control
diets. Mice receiving the beta-carotene-supplemented diets had
fewer tumours than mice in the control groups. However, only
in the Skh strain of mice was this difference statistically significant.
In the second study, an in vitro experiment, BALBc 3T3 mouse
fibroblasts were used to determine beta-carotene's accumulation
in cells and the ability of these cells to metabolize beta-carotene
to vitamin A. This in vitro model was also used to show a beta-carotene
protective effect towards 8-MOP phototoxicity. These studies
contributed to the increasing evidence of in vivo and in vitro
protection by beta-carotene against chemically induced toxicity.
Title
The effect of vitamin E and beta carotene on the
incidence of lung cancer and other cancers in male smokers. The
Alpha-Tocopherol, beta carotene Cancer Prevention
Study Group [see comments]
Source
N Engl J Med, 330(15):1029-35 1994 Apr 14
Abstract
BACKGROUND. Epidemiologic evidence indicates that diets high
in carotenoid-rich fruits and vegetables, as well as high serum
levels of vitamin E (alpha-tocopherol) and beta carotene,
are associated with a reduced risk of lung cancer. METHODS. We
performed a randomized, double-blind, placebo-controlled primary-prevention
trial to determine whether daily supplementation with alpha-tocopherol,
beta carotene, or both would reduce the incidence
of lung cancer and other cancers. A total of 29,133 male smokers
50 to 69 years of age from southwestern Finland were randomly
assigned to one of four regimens: alpha-tocopherol (50 mg per
day) alone, beta carotene (20 mg per day) alone,
both alpha-tocopherol and beta carotene, or placebo.
Follow-up continued for five to eight years. RESULTS. Among the
876 new cases of lung cancer diagnosed during the trial, no reduction
in incidence was observed among the men who received alpha-tocopherol
(change in incidence as compared with those who did not, -2 percent;
95 percent confidence interval, -14 to 12 percent). Unexpectedly,
we observed a higher incidence of lung cancer among the men who
received beta carotene than among those who did
not (change in incidence, 18 percent; 95 percent confidence interval,
3 to 36 percent). We found no evidence of an interaction between
alpha-tocopherol and beta carotene with respect
to the incidence of lung cancer. Fewer cases of prostate cancer
were diagnosed among those who received alpha-tocopherol than
among those who did not. beta carotene had little
or no effect on the incidence of cancer other than lung cancer.
Alpha-tocopherol had no apparent effect on total mortality, although
more deaths from hemorrhagic stroke were observed among the men
who received this supplement than among those who did not. Total
mortality was 8 percent higher (95 percent confidence interval,
1 to 16 percent) among the participants who received beta
carotene than among those who did not, primarily because
there were more deaths from lung cancer and ischemic heart disease.
CONCLUSIONS. We found no reduction in the incidence of lung cancer
among male smokers after five to eight years of dietary supplementation
with alpha-tocopherol or beta carotene. In fact,
this trial raises the possibility that these supplements may
actually have harmful as well as beneficial effects.
Title
Effects of supplemental beta-carotene, cigarette smoking, and
alcohol consumption on serum carotenoids in the Alpha-Tocopherol,
Beta-Carotene Cancer Prevention Study.
Author
Albanes D; Virtamo J; Taylor PR; Rautalahti M; Pietinen P; Heinonen
OP
Address
National Cancer Institute, Bethesda, MD 20892, USA.
Source
Am J Clin Nutr, 66(2):366-72 1997 Aug
Abstract
We determined whether serum carotenoid or retinol concentrations
were altered by beta-carotene supplementation in the Alpha-Tocopherol,
Beta-Carotene Cancer Prevention Study and whether such effects
were modified by alcohol consumption or cigarette use. Participants
in this substudy were 491 randomly selected men aged 58-76 y
from the metropolitan Helsinki study center [237 receiving supplemental
beta-carotene (20 mg/d) and 254 not receiving such supplementation].
Dietary carotenoids, retinol, and alcohol, and serum beta-carotene,
alpha-tocopherol, retinol, and cholesterol were assessed at baseline.
After an average of 6.7 y of supplementation, serum was collected
and carotenoid, retinol, and alpha-tocopherol concentrations
were determined by HPLC. Serum carotenoid fractions were highly
correlated with each other (P < or = 0.0001). Compared with
the unsupplemented group, the beta-carotene group had significantly
higher serum concentrations of beta-carotene (1483%), alpha-carotene
(145%), and beta-cryptoxanthin (67%) (P < or = 0.0001). Retinol
concentrations were 6% higher (P = 0.03) and lutein was 11% lower
(P = 0.02) in the supplemented group. Serum lycopene, zeaxanthin,
and alpha-tocopherol did not differ according to beta-carotene-supplementation
status. Although these beta-carotene-group differences were not
significantly altered by amount of alcohol consumption, higher
consumption (> 12.9 g/d, median) was related to lower (10-38%)
concentrations of carotenoids, particularly beta-carotene, alpha-carotene,
and beta-cryptoxanthin, in both the supplemented and unsupplemented
groups. Smoking status did not significantly influence the supplementation-related
differences in serum carotenoid and retinol values but concentrations
of carotenoids were generally highest in participants who quit
smoking while in the study and lowest in current smokers of >
or = 20 cigarettes/d. This study showed that serum concentrations
of non-beta-carotene carotenoids are altered by long-term beta-carotene
supplementation and confirms the adverse effects of alcohol and
cigarette smoking on serum carotenoids.
Title
beta-Carotene in breast milk and serum is increased after a single
beta-carotene dose.
Author
Canfield LM; Giuliano AR; Neilson EM; Yap HH; Graver EJ; Cui
HA; Blashill BM
Address
Department of Biochemistry, University of Arizona, Tucson
85721, USA. canfield@ccit.arizona.edu |
Am J Clin Nutr, 66(1):52-61 1997 Jul
Abstract
Normal lactating mothers were administered a single dose of 60
or 210 mg beta-carotene and changes in serum and milk retinol,
alpha-tocopherol, and carotenoids were monitored for 8 d. Average
serum beta-carotene concentrations increased 4.1- and 4.0-fold
after the 60- and 210-mg doses, respectively. Milk beta-carotene
concentrations increased 4.1- and 3.0-fold after the 60- and
210-mg doses, respectively. Maximum serum concentrations were
reached 24 h after both supplements, although concentrations
of milk beta-carotene continued to rise for 2-3 d. After 8 d,
both serum and milk beta-carotene continued to rise for 2-3 d.
After 8 d, both serum and milk beta-carotene concentrations remained
about twofold higher than baseline concentrations. Increases
in serum or milk beta-carotene concentrations were not dose-dependent.
Initial serum and milk concentrations of beta-carotene predicted
increases after supplementation, and increases in serum beta-carotene
concentrations predicted those in milk. Concentrations of milk
carotenoids were less than one-tenth their respective concentrations
in serum. Lutein, beta-cryptoxanthin, lycopene, alpha-carotene,
retinol, and alpha-tocopherol concentrations in serum or milk
did not change significantly after beta-carotene supplementation.
Retinol esters account for most of the retinol equivalents in
the milk of well-nourished mothers. Initial and maximum concentrations
of beta-carotene in serum and milk were strongly correlated for
individual mothers. Collectively, the data showed that a single
60-mg supplement of beta-carotene sustained elevated beta-carotene
concentrations in serum and milk for > 1 wk in normal mothers
but did not affect concentrations of other major carotenoids,
retinol, or alpha-tocopherol.
Title
Randomised trial of alpha-tocopherol and beta-carotene supplements
on incidence of major coronary events in men with previous myocardial
infraction [see comments]
Author
Rapola JM; Virtamo J; Ripatti S; Huttunen JK; Albanes D; Taylor
PR; Heinonen OP
Address
National Public Health Institute, Helsinki, Finland. Janne.Rapola@ktl.fi
Source
Lancet, 349(9067):1715-20 1997 Jun 14
Abstract
BACKGROUND: Epidemiological data suggest that the intake of antioxidants
such as alpha-tocopherol (vitamin E) and beta-carotene has an
inverse correlation with the incidence of coronary heart disease.
The results from clinical trials of antioxidant supplementation
in people with known coronary heart disease are inconclusive.
METHODS: We studied the frequency of major coronary events in
1862 men enrolled in the alpha-tocopherol beta-carotene Cancer
Prevention Study (smokers aged between 50 and 69 years) who had
a previous myocardial infarction. In this randomised, double-blind.
placebo-controlled study, men had received dietary supplements
of alpha-tocopherol (50 mg/day), beta-carotene (20 mg/day), both,
or placebo. The median follow-up was 5.3 years. The endpoint
of this substudy was the first major coronary event after randomisation.
Analyses were by intention to treat. FINDINGS: 424 major coronary
events (non-fatal myocardial infarction and fatal coronary heart
disease) occurred during follow-up. There were no significant
differences in the number of major coronary events between any
supplementation group and the placebo group (alpha-tocopherol
94/466; beta-carotene 113/461; alpha-tocopherol and beta-carotene
123/497; placebo 94/438 [log-rank test, p = 0.25]). There were
significantly more deaths from fatal coronary heart disease in
the beta-carotene (74/461, multivariate-adjusted relative risk
1.75 [95% CI 1.16-2.64], p = 0.007) and combined alpha-tocopherol
and beta-carotene groups (67/497, relative risk 1.58 [1.05-2.40],
p = 0.03) than in the placebo group (39/438), but there was no
significant increase in the alpha-tocopherol supplementation
group (54/466, relative risk 1.33 [0.86-2.05], p = 0.20). INTERPRETATION:
The proportion of major coronary events in men with a previous
myocardial infarction who smoke was not decreased with either
alpha-tocopherol or beta-carotene supplements. In fact, the risk
of fatal coronary heart disease increased in the groups that
received either beta-carotene or the combination of alpha-tocopherol
and beta-carotene; there was a non-significant trend of increased
deaths in the alpha-tocopherol group. We do not recommend the
use of alpha-tocopherol or beta-carotene supplements in this
group of patients.
Title
Natural beta-carotene and whole body irradiation in rats.
Author
Ben-Amotz A; Rachmilevich B; Greenberg S; Sela M; Weshler Z
Address
Israel Oceanographic & Limnological Research, Haifa, Israel.
Source
Radiat Environ Biophys, 35(4):285-8 1996 Nov
Abstract
beta-carotene and other carotenoids are reported to be potent
free radical quenchers, singlet oxygen scavengers, and lipid
antioxidants. Whole-body irradiation is known to cause an immunosuppression
effect in mammals through the possible initiation and production
of reactive oxygen species. We decided to test the possible antioxidative
effect against whole-body irradiation of a natural beta-carotene,
composed of equal amounts of the all-trans and 9-cis isomers,
obtained from the unicellular alga Dunaliella bardawil. Rats
were fed on ground commercial food enriched with natural beta-carotene
(50 mg/kg diet). On completion of 1 week with beta-carotene,
the rats were exposed to a single dose of 4 Gy whole-body irradiation,
after which their livers and blood were removed for beta-carotene
and retinol analysis in comparison with control livers of animals
irradiated or not, or supplemented with beta-carotene after irradiation.
A normal increase in body weight with no ill effects was noted
in the groups of rats whose diet was supplemented by beta-carotene
before and after irradiation, compared with the reduction in
the specific growth rate in the group of rats irradiated without
beta-carotene. Liver beta-carotene and retinol decreased significantly
after irradiation compared with the rats which were not irradiated.
This decrease was not shown in rats fed beta-carotene prior to
irradiation, and the effect of irradiation was partially cured
by supplementation with beta-carotene after irradiation. High-pressure
liquid chromatography (HPLC) analysis of the irradiated animals
showed a selective decline in 9-cis beta-carotene and in retinol
over all-trans beta-carotene and retinyl-esters. These results
suggest that 9-cis beta-carotene and retinol protect in vivo
against the cellular damage by free radicals induced after whole-body
irradiation. |
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