The first ever double-blind placebo
controlled human trial of apple
polyphenol extracts and serum cholesterol shows "significant
reduction" in LDL and total cholesterol. An interview with researchers
on the details of this groundbreaking study will be available soon.
In a well-conceived and important
presentation, Cornell scientists outline a new approach to treating high
cholesterol, and conclude that
phytochemicals can potentially improve human cardiovascular health by
both lowering blood
LDL cholesterol and
Studies in humans, animals, and labs show that
apple polyphenolextracts, juices and diet lower LDL cholesterol and
triglycerides, and protect against lipid peroxidation.
Apple polyphenols clearly inhibit
which may be even more
important than overall cholesterol levels in prevention of cardiovascular disease.
Serum Cholesterol-Lowering Effect of Apple
Polyphenols in Healthy Subjects
Yoko NAGASAKO-AKAZOME1), Tomomasa KANDA1), Mitsuo IKEDA1) and Hiroyuki
1) Fundamental Research Laboratory, Asahi Breweries, Ltd.
2) Department of Biochemistry, Teikyo University School of Medicine
Abstract: We performed a clinical
study using healthy male and female subjects who had slightly
elevated cholesterol levels in their serum to examine the effects of food
apple polyphenols (Applephenon®), which are effective for improving
serum cholesterol concentrations in rats, on lipid metabolism in humans. The
total period of this study was four weeks and we obtained blood samples at
week 0 and week 4. Total
cholesterol levels of the intervention groups decreased significantly and
dose-dependently compared with that of the control group. We also
found LDL-cholesterol decreased
significantly and HDL-cholesterol increased. No abnormalities
were detected in biochemical examinations of any of the subjects during the
test period. We concluded that the study product is
useful as a food additive that
improves serum cholesterol concentrations. Such improvement is
expected to decrease the risk of
atherosclerosis for people with a slightly elevated total
of Food Science Symposium, May 22-24 2005
Cardioprotective potentials of apple
phytochemicals in LDL oxidation and LDL receptor expression
Yi-Fang Chu and Rui Hai Liu, Cornell
Cardiovascular disease is the
leading cause of death in most industrialized countries. Both
elevated blood LDL cholesterol level and LDL oxidation lead to an enhanced
atherogenicity. Therapeutic strategies have been developed based on
targeting the pathogenesis; one is to prevent LDL oxidation by increasing
antioxidant levels, and another, as employed by statin drugs, is to lower
levels of plasma LDL cholesterol by increasing LDL uptake by hepatocytes
through LDL receptors and subsequent sterol excretion through bile acids.
Our objectives were to determine: 1) the effect of
apple extracts on
human LDL oxidation; 2) if apple
extracts affected hepatic LDL receptor expression and the level
of intracellular cholesterol in HepG2 hepatocytes; 3) if
affected the expression of sterol regulatory-element binding proteins (SREBPs).
were extracted using 80% acetone. LDL was isolated from human plasma by
sequential ultracentrifugation. Prevention of human LDL oxidation was
studied using a LDL Oxidation Model for Antioxidant Capacity (LOMAC) assay.
The expression of LDL receptors and SREBPs in HepG2 hepatocytes was
quantified by western blotting. Intracellular cholesterol was measured by
gas chromatography. Apple
extracts had potent antioxidant capacity against human LDL oxidationand increased delay and
suppression of LDL oxidation in a dose-dependent manner.
Apple extracts also significantly
induced expression of hepatic LDL receptors in a dose-dependent
manner (p<0.05) and increased intracellular uptake of cholesterol by HepG2
hepatocytes (p<0.05). These results suggest that
apple phytochemicals could lower
plasma LDL cholesterol by enhancing uptake of LDL in liver and
increase subsequent sterol excretion as bile acids. The attenuated level of
active SREBP expression by apple
phytochemicals indicates a decrease in intracellular lipogenesis
and cholesterol synthesis,
similar to the results caused by statin drugs such as Lipitor.
Apple phytochemicals can potentially improve human cardiovascular health by
both lowering blood LDL
cholesterol and preventing LDL
Br J Nutr,
May 1, 2005; 93(5): 581-91
Differential inhibition of oxidized
LDL-induced apoptosis in human endothelial cells treated with different
YJ Jeong, YJ Choi, HM Kwon, SW Kang, HS Park, M Lee, and YH Kang
Division of Life Sciences, Hallym University, Chuncheon, South Korea.
High plasma level of cholesterol is a well-known risk factor for
Oxidized LDL induces cellular and nuclear damage that leads to
apoptotic cell death. We tested the hypothesis that flavonoids may function
as antioxidants with regard to LDL incubated with 5 mum-Cu(2+) alone or in
combination with human umbilical vein endothelial cells (HUVEC).
Cytotoxicity and formation of thiobarbituric acid-reactive substances
induced by Cu(2+)-oxidized LDL were examined in the presence of various
subtypes of flavonoid. Flavanols, flavonols and flavanones at a non-toxic
dose of 50 mum markedly inhibited
LDL oxidation by inhibiting the formation of peroxidative products.
In contrast, the flavones luteolin and apigenin had no such effect, with >30
% of cells killed after exposure to 0.1 mg LDL/ml. Protective flavonoids,
especially (-)-epigallocatechin gallate,
quercetin, rutin and
hesperetin, inhibited HUVEC nuclear condensation and fragmentation induced
by Cu(2+)-oxidized LDL. In addition, immunochemical staining and Western
blot analysis revealed that anti-apoptotic Bcl-2 expression was enhanced
following treatment with these
protective flavonoids. However, Bax expression and caspase-3
cleavage stimulated by 18 h incubation with oxidized LDL were reduced
following treatment with these protective flavonoids. The down-regulation of
Bcl-2 and up-regulation of caspase-3 activation were reversed by the
cytoprotective flavonoids, (-)-epigallocatechin gallate,
hesperetin, at >/=10 mum. These
results suggest that flavonoids may differentially prevent Cu(2+)-oxidized
LDL-induced apoptosis and promote cell survival as potent antioxidants.
Survival potentials of certain flavonoids against cytotoxic oxidized LDL
appeared to stem from their disparate chemical structure.
Furthermore, dietary flavonoids
may have therapeutic potential for protecting the endothelium from oxidative
stress and oxidized LDL-triggered atherogenesis.
inhibits human low density lipoprotein oxidation.
Pearson DA, Tan CH, German JB, Davis PA,
Department of Food Science and Technology, University of California at
Davis, 95616, USA.
Dietary phenolic compounds, ubiquitous in vegetables and fruits and their
juices possess antioxidant activity that may have beneficial effects on
human health. The phenolic composition of six commercial apple juices, and
of the peel (RP), flesh (RF)
and whole fresh Red Delicious apples (RW), was determined by high
performance liquid chromatography (HPLC), and total phenols were determined
by the Folin-Ciocalteau method. HPLC analysis identified and quantified
several classes of phenolic compounds: cinnamates, anthocyanins,
flavan-3-ols and flavonols. Phloridzin and hydroxy methyl furfural were also
identified. The profile of phenolic compounds varied among the juices. The
range of concentrations as a percentage of total phenolic concentration was:
hydroxy methyl furfural, 4-30%; phloridzin, 22-36%; cinnamates, 25-36%;
anthocyanins, n.d.; flavan-3-ols, 8-27%; flavonols, 2-10%. The phenolic
profile of the Red Delicious appleextracts differed from those of the
juices. The range of concentrations of phenolic classes in fresh
appleextracts was: hydroxy methyl furfural, n.d.; phloridzin, 11-17%; cinnamates,
3-27%; anthocyanins, n.d.-42%; flavan-3-ols, 31-54%; flavonols, 1-10%. The
ability of compounds in apple juices
and extracts from fresh apple to protect LDL was assessed using an in
vitro copper catalyzed human LDL oxidation system. The extent of LDL
oxidation was determined as hexanal production using static headspace gas
chromatography. The apple juices and
extracts, tested at 5 microM gallic acid equivalents (GAE),
all inhibited LDL oxidation.
The inhibition by the juices ranged from 9 to 34%, and inhibition by RF, RW
and RP was 21, 34 and
38%, respectively. Regression
analyses revealed no significant correlation between antioxidant activity
and either total phenolic concentration or any specific class of phenolics.
Although the specific components in the
apple juices and
contributed to antioxidant activity have yet to be identified, this study
found that both fresh apple and commercial apple juices inhibited
copper-catalyzed LDL oxidation. The in vitro antioxidant activity of apples
support the inclusion of this fruit and its juice in a healthy human diet.
PMID: 10353589 [PubMed - indexed for MEDLINE]
Journal of Medicinal Food,
Volume 3, Number 4, 2000
Consumption Reduces Plasma Low-Density Lipoprotein Oxidation in Healthy Men
DIANNE HYSON, M.S., R.D.,1DEBORAH STUDEBAKER-HALLMAN, B.S.,1PAUL A. DAVIS,
Ph.D.,1,2and M. ERIC GERSHWIN.
Epidemiological studies show that consumption of fruits and vegetables is
associated with beneficial effects on human health including reduced risk of
coronary artery disease (CAD).
Fruits and their juices contain phytochemicals that inhibit in vitro
low-density lipoprotein (LDL) oxidation and may account, in part, for
their protective effect. However, reports of in
antioxidant effects from fruit intake are limited. We conducted a human
trial to examine the in vivo effect of consumption of apples (both
whole and juice) in an unblinded, randomized,
crossover design. Healthy men and women added 375 ml of unsupplemented apple
juice or 340 g of cored whole apple to their
daily diet for 6 weeks, then crossed over to the alternate product for 6
weeks. Blood samples were obtained at baseline and after each dietary
period. Compliance was monitored via biweekly 5-day food records, bodyweight
checks, and meetings with study personnel. There were no significant
differences between groups in intake of dietary fat, cholesterol, total
carbohydrate, sugar, or calories throughout the study. Dietary fiber intake
increased by 22% with whole apple consumption.
Body weight, fasting serum lipid concentration, and other lipoprotein
parameters were unchanged. Apple juice
consumption increased ex vivo copper (Cu )-mediated LDL oxidation lag
time by 20% compared with baseline. Apples and apple
juice both reduced conjugated diene formation. Moderate
apple juice consumption provides in vivo
antioxidant activity. In view of the current understanding of CAD,
the observed effect on LDL might be
associated with reduced CAD risk and supports the inclusion of apple juice in a healthy human diet.
Nutr J. 2004 May
Apple phytochemicals and their health benefits.
Boyer J, Liu RH.
Department of Food Science and Institute of Comparative and Environmental
Toxicology, Cornell University, Ithaca, New York 14853-7201 USA. RL23@cornell.edu
Evidence suggests that a diet high in fruits and vegetables may decrease the
risk of chronic diseases, such as cardiovascular disease and cancer, and
phytochemicals including phenolics, flavonoids and carotenoids from fruits
and vegetables may play a key role in reducing chronic disease risk. Apples
are a widely consumed, rich source of phytochemicals, and epidemiological
studies have linked the consumption of apples with reduced risk of some
cancers, cardiovascular disease, asthma, and diabetes. In the laboratory,
apples have been found to
have very strong antioxidant activity, inhibit cancer cell proliferation,
decrease lipid oxidation, and lower
cholesterol. Apples contain a variety of phytochemicals, including
quercetin, catechin, phloridzin and chlorogenic acid, all of which are
strong antioxidants. The phytochemical composition of apples varies greatly
between different varieties of apples, and there are also small changes in
phytochemicals during the maturation and ripening of the fruit. Storage has
little to no effect on applephytochemicals, but processing can greatly
affect applephytochemicals. While extensive research exists, a literature
review of the health benefits of apples and their phytochemicals has not
been compiled to summarize this work. The purpose of this paper is to review
the most recent literature regarding the health benefits of
apples and their
phytochemicals, phytochemical bioavailability and antioxidant behavior, and
the effects of variety, ripening, storage and processing on applephytochemicals.
PMID: 15140261 [PubMed - as supplied by publisher]
J Lipid Res. 2004
Apple procyanidins decrease cholesterol
esterification and lipoprotein secretion in Caco-2/TC7 enterocytes.
Vidal R, Hernandez-Vallejo S, Pauquai T, Texier O, Rousset
M, Chambaz J, Demignot S, Lacorte JM.
Decrease of plasma lipid levels by
polyphenols was linked to impairment of
hepatic lipoproteins secretion. However, intestine is the first epithelium
that faces dietary compounds and contributes to lipid homeostasis by
secreting triglyceride-rich lipoproteins during the postprandial state. The
purpose of this study was thus to examine the effect of
apple and wine
polyphenolsextracts on lipoprotein synthesis and secretion in human,
Caco-2/TC7 enterocytes apically supplied with complex lipid micelles.
Our results clearly demonstrate that
apple, but not wine polyphenolsextract, dose-dependently decreases the esterification of cholesterol and the enterocyte secretion of lipoproteins.Applepolyphenols decrease apoB secretion by inhibition of apoB synthesis
without increasing the degradation of the newly synthesized protein. In our
conditions, cholesterol uptake, apoB mRNA and MTP activity were not modified
by apple polyphenols. The main monomers present in our mixture did not
interfere with the intestinal lipid metabolism. By contrast,
reproduced the inhibition of both cholesterol ester synthesis and
lipoprotein secretion. Overall, our results are compatible with a mechanism
of action of polyphenols resulting into an impaired lipid availability that
could induce inhibition of intestinal lipoprotein secretion and
contribute to the hypolipidemic
effect of these compounds in vivo.
Excerpts: "In the same
dose-dependently lowered the secretion of all classes of newly synthesized
lipids, resulting at 500 µg/ml
in a 77% decrease in cholesterol
esters (0.032 ±
0.008 vs 0.14 ±
0.02 pmol / dish; p< 0.001), a
61% decrease in phospholipids
(0.24 ± 0.07 vs
0.61 ± 0.12 nmol /
dish; p<0.001) and a 92% decrease in
triglycerides (0.16 ±
0.1 vs 1.9 ±
0.4 nmol /dish; p <0.001) in the
15 basal media.
Again, no effect on the secretion of lipids was observed
with wine polyphenols, whatever their concentration.
PMID: 15576849 [PubMed - as supplied by publisher]
J Agric Food Chem.
2003 Sep 10;51(19):5780-5.
Apple and pear
peel and pulp and their influence on plasma lipids and antioxidant
potentials in rats fed cholesterol-containing diets.
Leontowicz M, Gorinstein S, Leontowicz H, Krzeminski R,
Lojek A, Katrich E, Ciz M, Martin-Belloso O, Soliva-Fortuny R, Haruenkit R,
Department of Animal Physiology, Faculty of Veterinary Medicine, Warsaw
Agricultural University, Nowoursynowska 166, 02-787 Warsaw, Poland.
The aim of this study was to assess the
bioactive compounds of apple and
pear peel and pulp in vitro and their influence on plasma lipids and
antioxidant potentials in vivo. The antioxidant potentials measured by
1,1-diphenyl-2-picrylhydrazyl (DPPH), beta-carotene bleaching
(beta-carotene), and nitric oxide inhibition radical scavenging (NO) tests
in apple peel and pulp were significantly higher than in pear peel and pulp,
respectively. The ethanol extract of apple peels showed the strongest inhibition of lipid peroxidation as
a function of its concentration and was comparable to the antioxidant
activity of butylated hydroxyanisole. The pear pulp extract had the weakest
antioxidant ability, whereas other extracts such as apple pulp and pear peel
were nearly equal. The antioxidant activities comprised contributions from
phenolic acids, and flavonoids and correlated well with
polyphenols and flavonoids. The correlation coefficients between polyphenols
and antioxidant activities by DPPH, beta-carotene, and NO were as follows:
0.9207, 0.9350, and 0.9453. Contrarily, the correlation coefficient between
the content of dietary fiber and the antioxidant activities test was low.
The content of all studied indices in apple and pear peel was significantly
higher than in peeled fruits (p < 0.05).
Diets supplemented with fruit peels
exercised a significantly higher positive influence on plasma lipid levels
and on plasma antioxidant capacity of rats than diets with fruit
Counteracts the Development of Hypercholesterolemia, Oxidative Stress, and
Renal Dysfunction in Obese Zucker Rats
Olivier Aprikian2, Jérôme Busserolles, Claudine Manach, André
Mazur, Christine Morand, Marie-Jeanne Davicco, Catherine Besson, Yves
Rayssiguier, Christian Rémésy and Christian Demigné3
Unité des Maladies
Métaboliques et Micronutriments, INRA de Clermont-Ferrand/Theix and CRNH
d’Auvergne, 63122 St-Genes-Champanelle, France
whom correspondence should be addressed. E-mail: firstname.lastname@example.org.
may have selective effects on abnormalities associatedwith the
plurimetabolic syndrome. Therefore, the effects of20%
supplementation on plasma and tissue lipidsand on protection
against susceptibility to oxidative stressand renal dysfunction
were investigated in Zucker lean (Fa/-)or obese (fa/fa)
rats. The experimental diets were equilibratedfor sugar supply,
contained 0.25 g/100 g cholesterol and providedonly one third of
the vitamin E requirement. Obese Zucker ratswere
hypercholesterolemic with cholesterol accumulation in LDLand HDL
fractions. The apple
diet lowered plasma and LDL cholesterol(-22 and -70%,
respectively, P < 0.01) in obese Zucker ratsand,
in parallel, reduced triglyceride
accumulation in heartand liver. Zucker rats fed the
diet also had a largerintestinal pool and greater fecal
excretion of bile acids. Theheart concentration and urinary
excretion of malondialdehydewere reduced by appleconsumption in obese Zucker rats, suggestingbetter
protection against peroxidation.
Glucosuria and proteinuriain obese Zucker rats were also
suppressed by the apple
diet.In conclusion, despite their moderate fiber content,
applesimprove substantially the lipid status and peroxidative parametersin obese Zucker rats, suggesting that other plant constituentssuch as polyphenols
are involved in these effects.
Biophys Res Commun. 2002 Jul 5;295(1):9-13.
activity of phloretin: the disclosure of a new antioxidant pharmacophore in
Rezk BM, Haenen GR, van der Vijgh WJ, Bast A.
Department of Pharmacology and Toxicology, Faculty of
Medicine, Universiteit Maastricht P.O. Box 616, 6200 MD Maastricht, The
Phloretin is a
dihydrochalcone flavonoid that
displays a potent antioxidant activity in peroxynitrite scavenging
and the inhibition of lipid
peroxidation. Comparison with structurally related compounds revealed
that the antioxidant pharmacophore of phloretin is
2,6-dihydroxyacetophenone. The potent activity of 2,6-dihydroxyacetophenone
is due to stabilisation of its radical via tautomerisation. The antioxidant
pharmacophore in the dihydrochalcone phloretin, i.e., the
2,6-dihydroxyacetophenone group, is different from the antioxidant
pharmacophores previously reported in flavonoids. (c) 2002 Elsevier Science
PMID: 12083758 [PubMed - indexed for MEDLINE]
J Nutr Biochem.
content of some bioactive compounds in apples, peaches and pears and their
influence on lipids and antioxidant capacity in rats.
Leontowicz H, Gorinstein S, Lojek A, Leontowicz M, Ci;z M, Soliva-Fortuny
R, Park YS, Jung ST, Trakhtenberg S, Martin-Belloso O.
Department of Physiology, Biochemistry, Pharmacology and
Toxicology, Faculty of Veterinary Medicine, WarsawAgriculturalUniversity,
Nowoursynowska 166, 02-787, Warsaw, Poland
The aim of this study was to compare some
bioactive compounds in apples,
peaches and pears and their influence on lipids and antioxidant capacity in
rats. The content of total
polyphenols (g/100g) was 0.23 +/- 0.03; 0.22 +/-
0.03 and 0.68 +/- 0.1 in peeled fruits and 0.48 +/- 0.04, 0.47 +/- 0.04 and
1.2 +/- 0.12 in peels of peaches, pears and apples, respectively. Caffeic,
p-coumaric and ferulic acids and the
total radical-trapping antioxidative potential (TRAP) values in peeled
apples and their peels were significantly higher than in peaches and
pears, respectively. Contrarary, no significant differences in the content
of dietary fiber among the studied fruits were found. The content of all
studied indices in peels was significantly higher than peeled fruits (p <
0.05 ). A good correlation between the total
polyphenols and the TRAP values
was found in all fruits. Diets
supplemented with apples and to a less extent with peaches and pears
have improved lipid metabolism and
increased the plasma antioxidant potential especially in rats fed
with added cholesterol. The highest
content of biologically active compounds and the best results in the
experiment on rats makes apple preferable for dietary prevention of
atherosclerosis and other diseases.
PMID: 12550072 [PubMed - as supplied by publisher]