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Research at Cornell University  
Some of the latest research on apple polyphenols comes from Cornell University and Chang.Y. Lee, Cornell professor of food science at the university's New York State Agricultural Experiment Station in Geneva, N.Y. Lee is responsible for some of the latest research on apple polyphenol extracts and colon cancer, and current studies on the benefits of apple polyphenol extracts in Alzheimer's Disease.

New: Important news on cholesterol and heart disease from Cornell University.


As you read through the impressive research from Cornell, keep in mind that although most of the studies conclude that people should eat more apples, the materials actually used in the studies are apple polyphenol extracts, not whole apples.

The use of standardized apple polyphenol extracts makes sense in terms of laboratory testing, but using the apple polyphenol extracts may also make sense for people wanting to realize the reported health benefits, for the following reasons:

  • Apple extracts are the actual compounds showing the results in many of the studies.

  • The polyphenol bioavailability of apple peel powder extracts may be higher than from whole apples, which must be digested to extract the phytochemicals.

  • The concentration of polyphenols in apple peel extracts makes it possible to consume higher doses. (Many studies you will read report dose-dependent effects, with higher dosages providing greater benefits.)

  • The quantity of apple polyphenols varies greatly between apple varieties, fruit maturity, and length of cold storage time.

The most thorough review of the available research on apple polyphenols was published in May 2004 in Nutrition Journal, under the title "Apple phytochemicals and their health benefits." This is a superb collection of the research on apple polyphenols and phytochemicals and their emerging role in human health. This review study receives our highest recommendation, and is the best place to start for an overview of the science behind these disease-fighting compounds. It is available to you in both HTML and PDF formats
Nutrition Journal 2004, 3:5
Apple phytochemicals and their health benefits, HTML format

Apple phytochemicals and their health benefits, PDF format

More Studies from Cornell  
 
Apple Phenolics Protect in Vitro Oxidative Stress-induced Neuronal Cell Death, Journal of Food Science Online, 2004
Novel low-density lipoprotein (LDL) oxidation model: antioxidant capacity for the inhibition of LDL oxidation, J Agric Food Chem., 2004
Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals, American Journal of Clinical Nutrition, 2003
Antioxidant activity of apple peels, J Agric Food Chem., 2003
Apple peels as a value-added food ingredient, J Agric Food Chem., 2003
Antioxidant and antiproliferative activities of common fruits, J Agric Food Chem., 2002
Major phenolics in apple and their contribution to the total antioxidant capacity, J Agric Food Chem., 2003
Antiproliferative activity of apples is not due to phenolic-induced hydrogen peroxide formation, J Agric Food Chem., 2003
Preventive effects of vitamin C on carcinogenesis, correspondence, Carcinogenesis 1997
News from Cornell  
An apple a day could help protect against brain-cell damage that triggers Alzheimer's, Parkinsonism, Cornell studies find, Cornell News, PDF, HTML
Vitamin C prevents cancer by blocking hydrogen peroxide, but apple chemical works even better, Cornell and Korean scientists report, Cornell News, PDF
Phytochemicals in apples have anti-cancer benefits, Cornell Chronicle, PDF
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.

 

J Food Sci. November/December 2004, Vol 69, No 9

Apple Phenolics Protect in Vitro Oxidative Stress-induced Neuronal Cell Death

CITATION: Heo HJ, Kim DO, Choi SJ, Shin DH, Lee CY. 2004. Apple Phenolics Protect in Vitro Oxidative Stress-induced Neuronal Cell Death. J Food Sci 69(9):S357-60.
ABSTRACT: Oxidative stress induced by reactive oxygen species may be linked to neurodegenerative diseases. Fresh Red Delicious apples, having 232.9 mg/100 g vitamin C equivalent antioxidant capacity, protected the rat pheochromocytoma neuronal (PC-12) cells from H2O2-induced oxidative toxicity in vitro in a dose-dependent manner. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction assay showed significant increase in cell viability when PC-12 cells were treated with apple extracts. This indicates that the apple phenolics protected oxidative stress-induced neurotoxicity. Because oxidative stress is also known to increase neuronal cell membrane breakdown, we further investigated by lactate dehydrogenase and trypan blue exclusion assays. Apple phenolics inhibited oxidative stress-induced membrane damage in neuronal cells. Therefore, these results may suggest that naturally occurring antioxidants, such as phenolic phytochemicals in fresh apples, may reduce the risk of neurodegenerative disorders.
KEYWORDS: apple, oxidative stress, neurodegeneration, phenolic phytochemicals, reactive oxygen species
Submitted 5/13/04, Revised 6/23/04, Accepted 7/7/04, Published on Web 10/28/2004
Authors Heo,
Kim, and Lee are with Dept. of Food Science and Technology, Cornell Univ., Geneva, NY 14456. Authors Choi and Shin are with Graduate School of Biotechnology, Korea Univ.,
Seoul, Korea. Direct inquiries to author Lee (E-mail: CYL1@cornell.edu).

 

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.

PMID: 15506821 [PubMed - in process]

 

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.

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.

We recently reported that phytochemical extracts from fruit have strong antioxidant and antiproliferative effects and proposed that the combination of phytochemicals in fruit and vegetables is critical to powerful antioxidant and anticancer activity (31–33). For example, the total antioxidant activity of phytochemicals in 1 g of apples with skin is equivalent to 83.3 ΅mol vitamin C equivalents—that is, the antioxidant value of 100 g apples is equivalent to 1500 mg of vitamin C. This is much higher than the total antioxidant activity of 0.057 mg of vitamin C (the amount of vitamin C in 1 g of apples with skin). In other words, vitamin C in apples contributed only < 0.4% of total antioxidant activity (31). Thus, most of the antioxidant activity comes from phytochemicals, not vitamin C. The natural combination of phytochemicals in fruit and vegetables is responsible for their potent antioxidant activity. Apple extracts also contain bioactive compounds that inhibit tumor cell growth in vitro. Phytochemicals in 50 mg apple with skin per milliliter (on a wet basis) inhibit tumor cell proliferation by 42%. Phytochemicals in 50 mg apple without skin per milliliter inhibit tumor cell proliferation by 23%. The apple extracts with skin significantly reduced the tumor cell proliferation when compared with the apple extracts without skin

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J Agric Food Chem. 2003 Jan 29;51(3):609-14.
Antioxidant activity of apple peels.

Wolfe K, Wu X, Liu RH.

Institute of Comparative and Environmental Toxicology and Department of Food Science, Stocking Hall, Cornell University, Ithaca, New York 14853-7201, USA.

Consumption of fruits and vegetables has been shown to be effective in the prevention of chronic diseases. These benefits are often attributed to the high antioxidant content of some plant foods. Apples are commonly eaten and are large contributors of phenolic compounds in European and North American diets. The peels of apples, in particular, are high in phenolics. During applesauce and canned apple manufacture, the antioxidant-rich peels of apples are discarded. To determine if a useful source of antioxidants is being wasted, the phytochemical content, antioxidant activity, and antiproliferative activity of the peels of four varieties of apples (Rome Beauty, Idared, Cortland, and Golden Delicious) commonly used in applesauce production in New York state were investigated. The values of the peels were compared to those of the flesh and flesh + peel components of the apples. Within each variety, the total phenolic and flavonoid contents were highest in the peels, followed by the flesh + peel and the flesh. Idared and Rome Beauty apple peels had the highest total phenolic contents (588.9 +/- 83.2 and 500.2 +/- 13.7 mg of gallic acid equivalents/100 g of peels, respectively). Rome Beauty and Idared peels were also highest in flavonoids (306.1 +/- 6.7 and 303.2 +/- 41.5 mg of catechin equivalents/100 g of peels, respectively). Of the four varieties, Idared apple peels had the most anthocyanins, with 26.8 +/- 6.5 mg of cyanidin 3-glucoside equivalents/100 g of peels. The peels all had significantly higher total antioxidant activities than the flesh + peel and flesh of the apple varieties examined. Idared peels had the greatest antioxidant activity (312.2 +/- 9.8 micromol of vitamin C equivalents/g of peels). Apple peels were also shown to more effectively inhibit the growth of HepG(2) human liver cancer cells than the other apple components. Rome Beauty apple peels showed the most bioactivity, inhibiting cell proliferation by 50% at the low concentration of 12.4 +/- 0.4 mg of peels/mL. The high content of phenolic compounds, antioxidant activity, and antiproliferative activity of apple peels indicate that they may impart health benefits when consumed and should be regarded as a valuable source of antioxidants.

PMID: 12537430 [PubMed - indexed for MEDLINE]

 

J Agric Food Chem. 2003 Mar 12;51(6):1676-83.
Apple peels as a value-added food ingredient.

Wolfe KL, Liu RH.

Institute of Comparative and Environmental Toxicology, Cornell University, Ithaca, New York 14853-7201, USA.

There is some evidence that chronic diseases, such as cancer and cardiovascular disease, may occur as a result of oxidative stress. Apple peels have high concentrations of phenolic compounds and may assist in the prevention of chronic diseases. Millions of pounds of waste apple peels are generated in the production of applesauce and canned apples in New York State each year. We proposed that a valuable food ingredient could be made using the peels of these apples if they could be dried and ground to a powder without large losses of phytochemicals. Rome Beauty apple peels were treated with citric acid dips, ascorbic acid dips, and blanches before being oven-dried at 60 degrees C. Only blanching treatments greatly preserved the phenolic compounds, and peels blanched for 10 s had the highest total phenolic content. Rome Beauty apple peels were then blanched for 10 s and dried under various conditions (oven-dried at 40, 60, or 80 degrees C, air-dried, or freeze-dried). The air-dried and freeze-dried apple peels had the highest total phenolic, flavonoid, and anthocyanin contents. On a fresh weight basis, the total phenolic and flavonoid contents of these samples were similar to those of the fresh apple peels. Freeze-dried peels had a lower water activity than air-dried peels on a fresh weight basis. The optimal processing conditions for the ingredient were blanching for 10s and freeze-drying. The process was scaled up, and the apple peel powder ingredient was characterized. The total phenolic content was 3342 +/- 12 mg gallic acid equivalents/100 g dried peels, the flavonoid content was 2299 +/- 52 mg catechin equivalents/100 g dried peels, and the anthocyanin content was 169.7 +/- 1.6 mg cyanidin 3-glucoside equivalents/100 g dried peels. These phytochemical contents were a significantly higher than those of the fresh apple peels if calculated on a fresh weight basis (p < 0.05). The apple peel powder had a total antioxidant activity of 1251 +/- 56 micromol vitamin C equivalents/g, similar to fresh Rome Beauty peels on a fresh weight basis (p > 0.05). One gram of powder had an antioxidant activity equivalent to 220 mg of vitamin C. The freeze-dried apple peels also had a strong antiproliferative effect on HepG(2) liver cancer cells with a median effective dose (EC(50)) of 1.88 +/- 0.01 mg/mL. This was lower than the EC(50) exhibited by the fresh apple peels (p < 0.05). Apple peel powder may be used in a various food products to add phytochemicals and promote good health.


PMID: 12617604 [PubMed - indexed for MEDLINE]


 
J Agric Food Chem. 2003 Mar 12;51(6):1718-23

Antiproliferative activity of apples is not due to phenolic-induced hydrogen peroxide formation.

Liu RH, Sun J.

Department of Food Science and
Institute of Comparative and Environmental Toxicology, Cornell University, Ithaca, New York 14853-7201, USA. RL23@cornell.edu

Anticancer compound screening of natural products using tumor cell lines has been commonly used to identify anticancer drugs. Two highly significant anticancer drugs, paclitaxel (Taxol) and camptothecin, were discovered using tumor cell lines by the U.S. National Cancer Institute (NCI) screening program of plants. It has been recently reported that the inhibition of cancer cell proliferation by fruit extracts was indirectly caused by phenolic-induced H(2)O(2) production in the cell culture media, suggesting that many previously reported effects of flavonoids and phenolic compounds on cultured cells might be from an artifact of H(2)O(2)-induced oxidative stress. The objective of the present study was to determine if apple extracts induced H(2)O(2) formation in common cell culture media and to investigate if the antiproliferative activity of apple extracts was due to phenolic-induced H(2)O(2) formation. It is reported here that apple extracts did not induce H(2)O(2) formation in WME, DMEM, or DMEM/Ham F12 media with the cell culture conditions tested. These same extracts inhibited proliferation of HepG(2) and Caco-2 cells. Therefore, antiproliferative activity of apple extracts was not due to the phenolic-induced H(2)O(2) production in cell culture media. In addition, H(2)O(2) added to the culture medium at 100 microM did not cause inhibition of cell proliferation in either HepG(2) liver cancer cells or Caco-2 colon cancer cells in vitro.

PMID: 12617611 [PubMed - indexed for MEDLINE]

 

J Agric Food Chem. 2002 Dec 4;50(25):7449-54

Antioxidant and antiproliferative activities of common fruits.

Sun J,
Chu YF, Wu X, Liu RH.

Department of Food Science, Cornell University, Ithaca, New York 14853-7201, USA.

Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolics, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. However, the phenolic contents and their antioxidant activities in fruits and vegetables were underestimated in the literature, because bound phenolics were not included. This study was designed to investigate the profiles of total phenolics, including both soluble free and bound forms in common fruits, by applying solvent extraction, base digestion, and solid-phase extraction methods. Cranberry had the highest total phenolic content, followed by apple, red grape, strawberry, pineapple, banana, peach, lemon, orange, pear, and grapefruit. Total antioxidant activity was measured using the TOSC assay. Cranberry had the highest total antioxidant activity (177.0 +/- 4.3 micromol of vitamin C equiv/g of fruit), followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit, and pineapple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect with an EC(50) of 14.5 +/- 0.5 mg/mL, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach. A bioactivity index (BI) for dietary cancer prevention is proposed to provide a new alternative biomarker for future epidemiological studies in dietary cancer prevention and health promotion.

PMID: 12452674 [PubMed - indexed for MEDLINE]

 

J Agric Food Chem. 2003 Oct 22;51(22):6516-20

Major phenolics in apple and their contribution to the total antioxidant capacity.

Lee KW,
Kim YJ, Kim DO, Lee HJ, Lee CY.

Department of Food Science and Technology, Cornell University, Geneva, NY 14456, USA.

The contribution of each phytochemical to the total antioxidant capacity of apples was determined. Major phenolic phytochemicals of six apple cultivars were identified and quantified, and their contributions to total antioxidant activity of apples were determined using a 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging assay and expressed as vitamin C equivalent antioxidant capacity (VCEAC). Average concentrations of major phenolics and vitamin C in six apple cultivars were as follows (mg/100 g of fresh weight of apples): quercetin glycosides, 13.20; procyanidin B(2), 9.35; chlorogenic acid, 9.02; epicatechin, 8.65; phloretin glycosides, 5.59; vitamin C, 12.80. A highly linear relationship (r (2) > 0.97) was attained between concentrations and total antioxidant capacity of phenolics and vitamin C. Relative VCEAC values of these compounds were in the order quercetin (3.06) > epicatechin (2.67) > procyanidin B(2) (2.36) > phloretin (1.63) > vitamin C (1.00) > chlorogenic acid (0.97). Therefore, the estimated contribution of major phenolics and vitamin C to the total antioxidant capacity of 100 g of fresh apples is as follows: quercetin (40.39 VCEAC) > epicatechin (23.10) > procyanidin B(2) (22.07) > vitamin C (12.80) > phloretin (9.11) > chlorogenic acid (8.75). These results indicate that flavonoids such as quercetin, epicatechin, and procyanidin B(2) rather than vitamin C contribute significantly to the total antioxidant activity of apples.

PMID: 14558772 [PubMed - indexed for MEDLINE]

 

Carcinogenesis 1997; 18: 37-42. [Correspondence]
Preventive effects of vitamin C on carcinogenesis

Sir--Some dietary phenolic substances have stronger antioxidant and antiproliferative effects than vitamin C, but vitamin C in fruits and vegetables is still an important bioactive constituent. However, the mechanism for the inhibitory effects of vitamin C on carcinogenesis has not yet been discovered, except for its free-radical scavenging activity against oxidative DNA damage.

We have noted that vitamin C has preventive effects on inhibition of hydrogen peroxide (H2O2)-induced gap-junction intercellular communication (GJIC). GJIC is essential for maintaining the homoeostatic balance through modulation of cell proliferation and differentiation in multicellular organisms. Inhibition of GJIC is strongly related to the carcinogenic process, especially to tumour promotion.1 H2O2, a tumour promoter, induces inhibition of GJIC and hyperphosphorylation of connexin43 protein (Cx43), which mainly modulates GJIC.1 We investigated the effects of vitamin C on GJIC and phosphorylation pattern of connexin43 in rat liver epithelial cells treated with H2O2, according to our previous methods.1

Inhibition of GJIC and hyperphosphorylation of connexin43 induced by H2O2 was prevented by pretreatment of the cells with 100 ΅mol/L vitamin C (figure). By contrast, free-radical scavengers, such as propylgallate and trolox did not prevent inhibition of GJIC by H2O2.1 Vitamin C might, therefore, have antitumour promoting effects through a different mechanism, rather than the scavenging effects of free radicals on carcinogenesis. Our results suggest that the mechanistic basis for cancer preventive action of vitamin C might be related to the effects against the inhibition of GJIC by free radicals. In addition, we noted that quercetin, a phytochemical found in apples, has stronger effects than vitamin C in this system (unpublished data).

Preventive effects of vitamin C on inhibition of GJIC and hyperphosphorylation of Cx43 in rat liver epithelial cells

GJIC=mean number of communicating cells measured by scrape loading dye transfer method: Cx43 analysed by western blot. A=untreated control; B=H2O2 only; C=treated with 100 ΅mol/L vitamin C. P0, P1, and P2=phosphorylation patterns of Cx43 in untreated cells; P3=hyperphosphorylation pattern of Cx43 in cells treated with H2O2.

The most powerful weapon against cancer is prevention, and we postulate that a diet rich in phytochemical will reduce the risk of cancer. When considering cancer-preventive strategies, inhibition of tumour promotion (a reversible and long-term process) is more practical than that of tumour initiation (irreversible and short-term).

Ki Won Lee, Hyong Joo Lee, Kyung-Sun Kang, *Chang Yong Lee


Departments of Food Science and Technology, and Veterinary Public Health, Seoul National University, Korea; and *Department of Food Science, Cornell University, Geneva, NY 14456, USA (e-mail:cyl1@cornell.edu)

(more research)

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