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Highlights:
  • The first ever double-blind placebo controlled human trial of apple polyphenol extracts and 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 lucid and important presentation, Cornell scientists outline a new approach to treating high cholesterol, and conclude that "apple phytochemicals can potentially improve human cardiovascular health by both lowering blood LDL cholesterol and preventing LDL oxidation."

  • Research from Cornell University suggests "a strong link between dietary intake of apple phenolics and flavonoids and reduced risk of cardiovascular disease."

  • Two more human study reported that apple juice and apple polyphenol extracts reduced plasma LDL oxidation in healthy volunteers.

  • German researchers reported in February that phloretin, an apple polyphenol, reduces arterial platelet aggregation and adhesion, and may have a beneficial effect in both the onset and progression of cardiovascular disease.

  • In a large-scale human study in Finland, researchers found that consumption of phytochemicals from apples and onions, but not other fruits and vegetables, was associated with fewer deaths by heart disease, and fewer deaths overall.

New Clinical Trial:
Serum Cholesterol-Lowering Effect of Apple Polyphenols in Healthy Subjects, Journal of Oleo Science, Vol. 54 (2005) , No. 3 143-151
Newly Posted Studies:
Cardioprotective potentials of apple phytochemicals in LDL oxidation and LDL receptor expression Cornell Institute of Food Science Symposium, May 22-24 2005
Differential inhibition of oxidized LDL-induced apoptosis in human endothelial cells treated with different flavonoids, Br J Nutr, May 1, 2005; 93(5): 581-91.
Chronic treatment with flavonoids prevents endothelial dysfunction in spontaneously hypertensive rat aorta, J Cardiovasc Pharmacol, Jul 2005; 46(1): 36-40.
The Flavonoid Phloretin Suppresses Stimulated Expression of Endothelial Adhesion Molecules and Reduces Activation of Human Platelets, J. Nutr. 135:172-178, February 2005

Flavonoid intake and coronary mortality in Finland: a cohort study, BMJ. 1996
Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals, American Journal of Clinical Nutrition 2003
Apple Juice Consumption Reduces Plasma Low-Density Lipoprotein Oxidation in Healthy Men and Women, Journal of Medicinal Food, 2000
Novel low-density lipoprotein (LDL) oxidation model: antioxidant capacity for the inhibition of LDL oxidation, J Agric Food Chem. 2004
Flavonoid intake and risk of chronic diseases, American Journal of Clinical Nutrition 2002
Apple juice inhibits human low density lipoprotein oxidation, Life Sci. 1999
Apple and pear peel and pulp and their influence on plasma lipids and antioxidant potentials in rats fed cholesterol-containing diets, J Agric Food Chem. 2003
Comparative content of some bioactive compounds in apples, peaches and pears and their influence on lipids and antioxidant capacity in rats, J Nutr Biochem. 2002
Effects of commonly consumed fruit juices and carbohydrates on redox status and anticancer biomarkers in female rats, Nutr Cancer. 2003

 

Journal of Oleo Science, Vol. 54 (2005) , No. 3 143-151
Serum Cholesterol-Lowering Effect of Apple Polyphenols in Healthy Subjects

Yoko NAGASAKO-AKAZOME1), Tomomasa KANDA1), Mitsuo IKEDA1) and Hiroyuki SHIMASAKI2)

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 tablets containing 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 cholesterol level.
 
Cornell Institute 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 University

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 apple extracts affected the expression of sterol regulatory-element binding proteins (SREBPs). Apple phytochemicals 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 oxidation and 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 oxidation.
Br J Nutr, May 1, 2005; 93(5): 581-91
Differential inhibition of oxidized LDL-induced apoptosis in human endothelial cells treated with different flavonoids

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 atherosclerotic diseases. 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, quercetin and 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.

PMID: 15975156
 J. Nutr. 135:172-178, February 2005
Biochemical and Molecular Actions of Nutrients

The Flavonoid Phloretin Suppresses Stimulated Expression of Endothelial Adhesion Molecules and Reduces Activation of Human Platelets

Verena Stangl*,1, Mario Lorenz*, Antje Ludwig*, Nicole Grimbo*, Carola Guether*, Wasiem Sanad*, Sabine Ziemer , Peter Martus**, Gert Baumann* and Karl Stangl*
* Medizinische Klinik und Poliklinik, Schwerpunkt Kardiologie, Angiologie, Pneumologie; Institut für Laboratoriumsmedizin und Pathobiochemie; and ** Institut für Medizinische Informatik, Biometrie und Epidemiologie, Charité der Humboldt-Universität, Campus Mitte, Berlin, Germany
1To whom correspondence should be addressed. E-mail: verena.stangl@charite.de.

Atherosclerosis is a chronic inflammatory disease accompanied by the expression of endothelial adhesion molecules. Phloretin is a plant-derived phytochemical that is mainly present in apples. Because phloretin is reported to promote antioxidative activities, we investigated the effects of phloretin on cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin) in human umbilical vein endothelial cells (HUVECs). Phloretin prevented TNF- -stimulated upregulation of VCAM-1, ICAM-1, and E-selectin expression in a concentration-dependent manner. To the same extent as for TNF- , phloretin also inhibited IL-1ß-induced upregulation in expression of all 3 adhesion molecules. Inhibition of cytokine-induced adhesion molecule expression for VCAM-1, ICAM-1, and E-selectin was detected already at the level of mRNA. Preincubation with phloretin dose-dependently attenuated TNF- -stimulated adhesion of monocytic THP-1 cells to HUVECs and human aortic endothelial cells. Phloretin did not affect TNF- -stimulated activation of nuclear factor B (NF- B) but inhibited activation of interferon regulatory factor 1, a transcription factor involved in the regulation of endothelial cell adhesion molecule expression. In human platelets, phloretin diminished adenosine diphosphate (ADP) and thrombin receptor-activating peptide–stimulated expression of the activated form of the GPIIb/IIIa complex and reduced platelet aggregation stimulated by ADP. Thus phloretin may have beneficial effects in the onset and progression of cardiovascular diseases.

© 2005 The American Society for Nutritional Sciences
 

J Cardiovasc Pharmacol, Jul 2005; 46(1): 36-40.
Chronic treatment with flavonoids prevents endothelial dysfunction in spontaneously hypertensive rat aorta.

A Machha and MR Mustafa

Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Flavonoids are known to possess cardioprotective properties. Vascular endothelial function is a surrogate marker for cardiovascular diseases, including hypertension. We have studied the effects of chronic flavonoid treatment on vascular endothelial functions in spontaneously hypertensive rats (SHR). Starting from 6-7 weeks old, SHR were given flavonoids (baicalein, flavone, or quercetin) orally (10 mg/kg, once daily) to the SHRs for 4 weeks. Aortas from all the flavonoid-treated animals showed remarkably higher endothelium-dependent relaxations to acetylcholine, to a similar extent as those pretreated with the angiotensin-converting enzyme inhibitor, captopril. However, in contrast to other experimental groups, flavone pretreatment also enhanced the endothelium-independent relaxations to sodium nitroprusside. In addition, treatment with either flavone or quercetin induced a significant attenuation in systolic blood pressure of the hypertensive animals. The present results suggest that chronic treatment with the flavonoids (baicalein, flavone, and quercetin) preserves vascular endothelial functions in hypertensive animals through several possible actions, including increasing endothelial nitric oxide production and bioavailability and reduction in blood pressure.
 

BMJ. 1996 Feb 24;312(7029):478-81

Flavonoid intake and coronary mortality in Finland: a cohort study.

Knekt P, Jarvinen R, Reunanen A, Maatela J.

National Public Health Institute, Helsinki, Finland.

Full text of this study is available here

OBJECTIVE: To study the association between dietary intake of flavonoids and subsequent coronary mortality. DESIGN: A cohort study based on data collected at the Finnish mobile clinic health examination survey from 1967-72 and followed up until 1992. SETTINGS: 30 communities from different parts of Finland. SUBJECTS: 5133 Finnish men and women aged 30-69 years and free from heart disease at baseline. MAIN OUTCOME MEASURE: Dietary intake of flavonoids, total mortality, and coronary mortality. RESULTS: In women a significant inverse gradient was observed between dietary intake of flavonoids and total and coronary mortality. The relative risks between highest and lowest quarters of flavonoid intake adjusted for age, smoking, serum cholesterol concentration, blood pressure, and body mass index were 0.69 (95% confidence interval 0.53 to 0.90) and 0.54 (0.33 to 0.87) for total and coronary mortality, respectively. The corresponding values for men were 0.76 (0.63 to 0.93) and 0.78 (0.56 to 1.08), respectively. Adjustment for intake of antioxidant vitamins and fatty acids weakened the associations for women; the relative risks for coronary heart disease were 0.73 (0.41 to 1.32) and 0.67 (0.44 to 1.00) in women and men, respectively. Intakes of onions and apples, the main dietary sources of flavonoids, presented similar associations. The relative risks for coronary mortality between highest and lowest quarters of apple intake were 0.57 (0.36 to 0.91) and 0.81 (0.61 to 1.09) for women and men, respectively. The corresponding values for onions were 0.50 (0.30 to 0.82) and 0.74 (0.53 to 1.02), respectively. CONCLUSIONS: The results suggest that people with very low intakes of flavonoids have higher risks of coronary disease.

Excerpts: "The consumption of apples and onions was inversely associated with total and coronary mortality
. The relations were again stronger in women than in men. Adjustment for the intake of other fruits and vegetables, not notably including flavonoids, did not materially alter the results (data not shown)."

"Our results thus support the suggested beneficial effect of flavonoid intake against coronary heart disease."

PMID: 8597679 [PubMed - indexed for MEDLINE]

 
American Journal of Clinical Nutrition, Vol. 78, No. 3, 517S-520S, September 2003

Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals1,2,3,4

Rui Hai Liu

1 From the Department of Food Science and the Institute of Comparative and Environmental Toxicology, Cornell University, Ithaca, NY.

Full text of this study is available here.

Cardiovascular disease and cancer are ranked as the first and second leading causes of death in the United States and in most industrialized countries. Regular consumption of fruit and vegetables is associated with reduced risks of cancer, cardiovascular disease, stroke, Alzheimer disease, cataracts, and some of the functional declines associated with aging. Prevention is a more effective strategy than is treatment of chronic diseases. Functional foods that contain significant amounts of bioactive components may provide desirable health benefits beyond basic nutrition and play important roles in the prevention of chronic diseases. The key question is whether a purified phytochemical has the same health benefit as does the whole food or mixture of foods in which the phytochemical is present. Our group found, for example, that the vitamin C in apples with skin accounts for only 0.4% of the total antioxidant activity, suggesting that most of the antioxidant activity of fruit and vegetables may come from phenolics and flavonoids in apples. We propose that the additive and synergistic effects of phytochemicals in fruit and vegetables are responsible for their potent antioxidant and anticancer activities, and that the benefit of a diet rich in fruit and vegetables is attributed to the complex mixture of phytochemicals present in whole foods.

Excerpts: "Oxidative stress can cause oxidative damage to large biomolecules such as proteins, DNA, and lipids, resulting in an increased risk for cancer and cardiovascular disease. To prevent or slow down the oxidative stress induced by free radicals, sufficient amounts of antioxidants need to be consumed. Fruit and vegetables contain a wide variety of antioxidant compounds (phytochemicals) such as phenolics and carotenoids that may help protect cellular systems from oxidative damage and lower the risk of chronic diseases."

"Role of phytochemicals in the prevention of cardiovascular disease
Numerous investigations have been undertaken that suggest a strong link between dietary intake of phytochemicals and reduced risk of cardiovascular disease. Dietary flavonoid intake was significantly inversely associated with mortality from coronary artery disease and inversely related (more weakly but still significantly) with incidence of myocardial infarction. In a study in Finland, intake of apples and onions, both high in quercetin, was inversely correlated with total mortality and coronary mortality. In a recent Japanese study, the total intake of flavonoids (quercetin, myricetin, kaempferol, luteolin, and ficetin) was inversely correlated with the plasma total cholesterol and low-density lipoprotein (LDL) cholesterol concentrations. Intake of quercetin alone was inversely related to total cholesterol and LDL plasma levels.

"Mechanisms for the prevention of arteriosclerosis by antioxidants have been proposed. In the LDL oxidation hypothesis, oxidized LDL cholesterol has been suggested as the atherogenic factor that contributes to heart disease. Oxidized LDL is typically taken up by macrophage scavenger receptors, thus promoting cholesterol ester accumulation and foam cell formation, which promotes atherosclerotic disease. Dietary antioxidants that are incorporated in LDL are themselves oxidized when these LDL are exposed to prooxidative conditions before any extensive oxidation can occur in the sterol or polyunsaturated fatty acids. In addition, phytochemicals have been shown to have roles in the reduction of platelet aggregation, modulation of cholesterol synthesis and absorption, and reduction of blood pressure. Recently, C-reactive protein, a marker of systemic inflammation, has been reported to be a stronger predictor of cardiovascular disease than LDL cholesterol, suggesting that inflammation is a critical factor in cardiovascular disease. Inflammation not only promotes initiation and progression of atherosclerosis but also causes acute thrombotic complications of atherosclerosis. Therefore, the antiinflammatory activity of phytochemicals may play an important role in the prevention of cardiovascular disease."

 

Journal of Medicinal Food, Volume 3, Number 4, 2000

Apple Juice Consumption Reduces Plasma Low-Density Lipoprotein Oxidation in Healthy Men and Women

DIANNE HYSON, M.S., R.D.,1DEBORAH STUDEBAKER-HALLMAN, B.S.,1PAUL A. DAVIS, Ph.D.,1,2and M. ERIC GERSHWIN.

Full text of this study is available here in PDF format

ABSTRACT

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 vivo 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.

 
American Journal of Clinical Nutrition, Vol. 76, No. 3, 560-568, September 2002

© 2002 American Society for Clinical Nutrition

Original Research Communication

Flavonoid intake and risk of chronic diseases1,2

Paul Knekt, Jorma Kumpulainen, Ritva Järvinen, Harri Rissanen, Markku Heliövaara, Antti Reunanen, Timo Hakulinen and Arpo Aromaa

Background: Flavonoids are effective antioxidants and may protect against several chronic diseases.

Objective: The association between flavonoid intake and risk of several chronic diseases was studied.

Design: The total dietary intakes of 10 054 men and women during the year preceding the baseline examination were determined with a dietary history method. Flavonoid intakes were estimated, mainly on the basis of the flavonoid concentrations in Finnish foods. The incident cases of the diseases considered were identified from different national public health registers.

Results: Persons with higher quercetin intakes had lower mortality from ischemic heart disease. The relative risk (RR) between the highest and lowest quartiles was 0.79 (95% CI: 0.63, 0.99: P for trend = 0.02). The incidence of cerebrovascular disease was lower at higher kaempferol (0.70; 0.56, 0.86; P = 0.003), naringenin (0.79; 0.64, 0.98; P = 0.06), and hesperetin (0.80; 0.64, 0.99; P = 0.008) intakes. Men with higher quercetin intakes had a lower lung cancer incidence (0.42; 0.25, 0.72; P = 0.001), and men with higher myricetin intakes had a lower prostate cancer risk (0.43; 0.22, 0.86; P = 0.002). Asthma incidence was lower at higher quercetin (0.76; 0.56, 1.01; P = 0.005), naringenin (0.69; 0.50, 0.94; P = 0.06), and hesperetin (0.64; 0.46, 0.88; P = 0.03) intakes. A trend toward a reduction in risk of type 2 diabetes was associated with higher quercetin (0.81; 0.64, 1.02; P = 0.07) and myricetin (0.79; 0.62, 1.00; P = 0.07) intakes.

Conclusion: The risk of some chronic diseases may be lower at higher dietary flavonoid intakes.

Key Words: Chronic disease • diet • flavonoids • flavonols • flavanones • flavones • prospective study • free radicals

[Reprint (PDF) Version of Full Study]

 

Life Sci. 1999;64(21):1913-20.
Apple juice inhibits human low density lipoprotein oxidation.

Pearson DA, Tan CH, German JB,
Davis PA, Gershwin ME.

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 apple extracts differed from those of the juices. The range of concentrations of phenolic classes in fresh apple extracts 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 extracts that 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]
J Agric Food Chem. 2004 Nov 3;52(22):6818-23.
Novel low-density lipoprotein (LDL) oxidation model: antioxidant capacity for the inhibition of LDL oxidation.

Chu YF, Liu RH.

Department of Food Science and Institute of Comparative and Environmental Toxicology, Cornell University, Ithaca, New York 14853, USA.

A novel model of peroxyl radical initiated low-density lipoprotein (LDL) oxidation (LDL oxidation model for antioxidant capacity, or LOMAC) was developed to assess the free radical scavenging capacity of antioxidants and the extracts of natural products. A water-soluble free radical initiator, 2,2'-azobis(amidinopropane) dihydrochloride, was used at physiological temperature (37 degrees C) to generate peroxyl radicals to catalyze lipid oxidation of LDL isolated from human plasma samples. Headspace hexanal, a major decomposition product of LDL oxidation, was measured by a headspace gas chromatograph as an indicator of antioxidant capacity of different concentrations of pure antioxidants (vitamins C and E) and the extracts of natural products (fresh apple phytochemical extracts). All vitamin C and E and apple extract concentrations tested resulted in increasing partial suppression and delay of LDL oxidation. On the basis of the median effective dose (EC(50)) calculated for each compound or extract tested, the LOMAC value of 100 g of apple against LDL oxidation was equivalent to 1470 mg of vitamin E or to 402 mg of vitamin C. This study shows that the LOMAC assay can be routinely used to analyze or screen antioxidants or phytochemical extracts against LDL oxidation to prevent cardiovascular disease. The food-specific LOMAC values will be very useful as a new alternative biomarker for future epidemiological studies of cardiovascular disease.

 
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, Trakhtenberg S.

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 polyphenols, 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 pulps.

PMID: 12952433 [PubMed - indexed for MEDLINE]
J Nutr Biochem. 2002 Oct;13(10):603-610.
Comparative 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,
Warsaw Agricultural University, 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]
Nutr Cancer. 2003;45(1):46-52.

Effects of commonly consumed fruit juices and carbohydrates on redox status and anticancer biomarkers in female rats.

Breinholt VM, Nielsen SE, Knuthsen P, Lauridsen ST, Daneshvar B, Sorensen A.

Institute of Food Safety and Nutrition, Division of Biochemical Toxicology, The Danish Veterinary and Food Administration, Morkhoj Bygade 19, 2860 Soborg, Denmark. vib@fdir.dk

Administration of apple juice, black currant juice, or a 1:1 combination of the two juices significantly decreased the level of the lipid peroxidation biomarker malondialdehyde in plasma of female rats, whereas the protein oxidation biomarker 2-amino-adipic semialdehyde, was significantly increased following administration of orange juice, black currant juice, or the 1:1 combination of apple and black currant juice. A significant increase in 2-amino-adipic semialdehyde was also observed in control rats given sucrose, fructose, and glucose in the drinking water at concentrations approximating the average carbohydrate levels in the employed fruit juices.
None of the fruit juices were found to affect the activities of antioxidant enzymes in red blood cells or hepatic glutathione S-transferase. Hepatic quinone reductase activity, on the other hand, was significantly increased by grapefruit juice, apple juice, and black currant juice. The total daily intake of a selected subset of flavonoid aglycones ranged from 0.2 to 4.3 mg, and quercetin was found to be a minor constituent of all the juices investigated. In a parallel study, rats were fed quercetin at doses ranging from 0.001 to 10 g/kg of diet. However, no effects were observed on hepatic glutathione S-transferase or quinone reductase activities, plasma redox status, or the activity of red blood cell antioxidant enzymes. Overall, the results of the present study suggest that commonly consumed fruit juices can alter lipid and protein oxidation biomarkers in the blood as well as hepatic quinone reductase activity, and that quercetin may not be the major active principle. The observation that natural carbohydrates are capable of mediating oxidative stress in vivo warrants further studies due to the central role refined and unrefined carbohydrates play in human nutrition.

PMID: 12791504 [PubMed - indexed for MEDLINE]

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