Starting at least with the biblical story of Adam and Eve, apples have long been a fixture of the human experience of food. It may have been the first domesticated tree, and its fruits have evolved over thousands of years until today there are at least 7,500 known cultivars of apples grown worldwide. China produces about one-third of all the apples on the planet, followed by the United States (with just under 10 percent of the total), even though the tree wasn’t brought to the North American continent until the 1600s, when the first orchard appeared near Boston.
Though relatively low in vitamin C compared to other fruits, apples contain numerous phenolic phytochemical antioxidants, primarily quercetin and epicatechin. They also possess more than a dozen vitamins and minerals. Research has demonstrated a wide array of health benefits of consuming apples, including helping to lower weight and cholesterol and reducing the risk of various cancers, cardiovascular disease, and neurodegenerative declines due to aging.
Apple juice concentrate prevents oxidative damage and impaired maze performance in aged mice. Tchantchou F, Chan A, Kifle L, Ortiz D, Shea TB. J Alzheimers Dis. 2005 Dec;8(3):283-7. Key Finding: “Supplementation with apple juice concentrate prevented neurodegenerative effects. These findings also support the efficacy of antioxidant supplementation, including consumption of antioxidant rich foods such as apples, in preventing the decline in cognitive performance that accompanies normal aging.”
Apple juice prevents oxidative stress and impaired cognitive performance caused by genetic and dietary deficiencies in mice. Rogers EJ, Milhalik S, Orthiz D, Shea TB. J Nutr Health Aging. 2004;8(2):92-7. Key Finding: “Herein, we demonstrate that apple juice concentrate, administered ad libitum in drinking water, can compensate for the increased reactive oxygen species and decline in cognitive performance in maze trials observed when normal and transgenic mice lacking apolipoprotein E are deprived of folate and vitamin E.”
Diets enriched in foods with high antioxidant activity reverse age-induced decreases in cerebellar beta-adrenergic function and increases in proinflammatory cytokines. Gemma C, Mesches MH, Sepesi B, Choo K, Holmes DB, Bickford PC. J Neurosci. 2002 Jul 15;22(14):6114-20. Key Finding: “Antioxidants and diets supplemented with foods high in oxygen radical absorbance capacity (ORAC) reverse age-related decreases in cerebellar beta-adrenergic receptor function. Aged male Fischer 344 rats were given apple (5 mg dry weight), spirulina (5 mg) or cucumber (5 mg) daily for 14 days. Electro physiologic techniques revealed a significant decrease in beta-adrenergic receptor function in aged control rats. Spirulina reversed this effect. Apple had an intermediate effect, and cucumber (low ORAC) had no effect, indicating that the reversal of beta-adrenergic receptor function decreases might be related to the ORAC dose.”
Procyanidin C1 from apple extracts inhibits Fc epsilon RI-mediated mast cell activation. Nakano N, Nishiyama C, Tokura T, Nagasako-Akazome Y, Ohtake Y, Okumura K, Ogawa H. Int Arch Allergy Immunol. 2008;147(3):213-21. Key Finding: “Polyphenol-enriched fractions extracted from unripe apples (Rosacea, Malus spp.) consisting of procyanidins have an anti-allergenic effect. It suppresses Fc epsilon RI-mediated mast cell activation by inhibiting intracellular signaling pathways. These observations provide evidence for the anti-allergenic effects of the procyanidin-enriched apple extract.”
Antiallergic effect of apple polyphenols on the allergic model mouse. Akiyama H, Sakushima J, Taniuchi S, Kanda T, Yanagida A, Kokima T, Tshima R, Kobayashi Y, Goda Y, Toyoda M. Biol Pharm Bull. 2000 Nov;23(11):1370-3. Key Finding: “These findings suggest that apple condensed tannins have an antiallergic effect on type I allergic symptoms.”
Effects of banana, orange, and apple on oxidative stress-induced neurotoxicity in PC12 cells. Heo HJ, Choi SJ, CHoi SG, Shin DH, Lee JM, Lee CY. J Food Sci. 2008 Mar;73(2):H28-32. Key Finding: “These results suggest that fresh apples, bananas, and oranges in our daily diet along with other fruits may protect neuron cells against oxidative-stress-induced neurotoxicity and may play an important role in reducing the risk of neurodegenerative disorders such as Alzheimer’s disease.”
Efficiency of apples, strawberries, and tomatoes for reduction of oxidative stress in pigs as a model for humans. Pajk T, Rezar V, Levart A, Salobir J. Nutrition. 2006 Apr;22(4):376-84. Key Finding: “Our findings support the hypothesis that supplementation with apples, strawberries, or tomatoes effectively decreases oxidative stress by decreasing MDA formation in the body and by protecting mononuclear blood cells against increased DNA damage. This effect was particularly pronounced in the group supplemented with a fruit mixture; among the single fruit supplements, the most beneficial effect was obtained with apples.”
Effect of apple extracts on NF-kappaB activation in human umbilical vein endothelial cells. Davis PA, Polagruto JA, Valacchi G, Phung A, Soucek K, Keen CL, Gershwin ME. Exp Biol Med. 2006 May;231(5):594-8. Key Finding: “We suggest that flavonoid-rich apple extract down regulates NF-kappaB signaling and that this is indicative of an antioxidant effect of the flavonoids present.”
Major Phytochemicals in apple cultivars: contribution to peroxyl radical trapping efficiency. Vanzani P, Rossetto M, Rigo A, Vrhovsek U, Mattivi F, D’Amato E, Scarpa M. J Agric Food Chem. 2005 May 4;53(9):3377-82. Key Finding: “Forty-one samples of apples (peel plus pulp) obtained from eight cultivars were examined for concentration of some important phytochemicals and for antioxidant activity. The antioxidant efficiency of the apple extracts and of representative pure compounds for each group of phytochemicals (five major polyphenol groups) was measured. The antioxidant efficiency calculated on the basis of the contribution of the pure compounds was lower than the antioxidant efficiency of the apple extracts. The higher efficiency of apples appears to be strictly related to the overwhelming presence of oligomeric proanthocyanidin.”
Protection by quercetin and quercetin-rich fruit juice against induction of oxidative DNA damage and formation of BPDE-DNA adducts in human lymphocytes. Wilms LC, Hollman PC, Boots AW, Kleinjans JC. Mutat Res. 2005 Apr 4;582(1-2):155-62. Key Finding: “Lymphocytes from female volunteers who consumed a quercetin-rich blueberry/apple juice mixture for four weeks were treated ex vivo with an effective dose of H(2)O(2) and benzo(a)pyrene, respectively, at three different time points during the intervention. Results in vitro; a significant dose-dependent protection by quercetin against both the formation of oxidative DNA damage and of BPDE-DNA adducts was observed. Results in vivo; four weeks of juice intervention led to a significant increase in the total antioxidant capacity of plasma. The combination of our findings in vitro and ex vivo provides evidence that quercetin is able to protect against chemically induced DNA damage in human lymphocytes, which may underlie its suggested anticarcinogenic properties.”
Radical scavenging activities of peels and pulps from cv. Golden Delicious apples as related to their phenolic composition. Chinnici F, Bendini A, Gaiani A, Riponi C. J Agric Food Chem. 2004 Jul 28;52(15):4684-9. Key Finding: “The relationship between phenolic composition and radical scavenging activity of apple peel and pulp was investigated. A good correlation between the sum of polyphenols and the radical scavenging activities was found. Among the single classes of compounds, procyanidins (in peel and pulps) and flavonols (in peels) were statistically correlated to the total antioxidant activities.”
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. J Agric Food Chem. 2003 Sep 10;51(19):5780-5. Key Finding: “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 content of all studied indices in apple and pear peel was significantly higher than in peeled fruits. 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.”
Diets enriched in foods with high antioxidant activity reverse age-induced decreases in cerebellar beta-adrenergic function and increases in proinflammatory cytokines. Gemma C, Mesches MH, Sepesi B, Choo K., Holmes DB, Bickford PC. J Neurosci. 2002 Jul 15;22(14):6114-20. Key Finding: “Antioxidants and diets supplemented with foods high in oxygen radical absorbance capacity (ORAC) reverse age-related decreases in cerebellar beta-adrenergic receptor function. Aged male Fischer 344 rats were given apple (5 mg dry weight), spirulina (5 mg) or cucumber (5 mg) daily for 14 days. Electro physiologic techniques revealed a significant decrease in beta-adrenergic receptor function in aged control rats. Spirulina reversed this effect. Apple had an intermediate effect, and cucumber (low ORAC) had no effect, indicating that the reversal of beta-adrenergic receptor function decreases might be related to the ORAC dose.”
Dietary intake of flavonoids and asthma in adults. Garcia V, Arts IC, Sterne JA, Thompson RL, Shaheen SO. Eur Respir J. 2005 Sep;26(3):449-52. Key Finding: “No evidence was found for a protective effect of three major subclasses of dietary flavonoids on asthma. They were catechins, flavonols and flavones. It is possible that other flavonoids or polyphenols present in apples may explain the protective effect of apples on obstructive lung disease.”
Food and nutrient intakes and asthma in young adults. Woods RK, Walters EH, Raven JM, Wolfe R, Ireland PD, Thien FC, Abramson MJ. Am J Clin Nutr. 2003 Sep;78(3):414-21. Key Finding: “Apples and pears appeared to protect against current asthma. Intervention studies using whole foods are required to ascertain whether such modifications of food intake could be beneficial in the prevention or amelioration of asthma.”
Dietary antioxidants and asthma in adults: population-based case-control study. Shaheen SO, Sterne JA, Thompson RL, Songhurst CE, Margetts BM, Burney PG. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1823-8. Key Finding: “Apple consumption was negatively associated with asthma. The associations between apple and red wine consumption and asthma may indicate a protective effect of flavonoids.”
Antioxidant activity of apple peels. Wolfe K, Wu X, Liu RH. J Agric Food Chem. 2003 Jan 29;51(3):609-14. Key Finding: “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.”
Antioxidant and antiproliferative activities of common fruits. Sun J, Chu YF, Wu X, Liu RH. J Agric Food Chem. 2002 Dec 4;50(25):7449-54. Key Finding: “Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolic, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. This study was designed to investigate the profiles of total phenolic. Cranberry had the highest total phenolic content followed by apple. Cranberry had the highest total antioxidant activity followed by apple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect followed by lemon and apple.”
Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. Hollman PC, Van Triip JM, Buysman MN, Van der Gaag MS, Mengelers MJ, De Vries JH, Katan MB. FEBS Lett. 1997 Nov 24;418(1-2):152-6. Key Finding: “We fed nine subjects a single large dose of onions, which contain glucose conjugates of quercetin, apples, which contain glucose and non-glucose quercetin glycosides, or pure quercetin-3-rutinoside, the major quercetin glycoside in tea. Plasma levels were then measured. Bioavailability of quercetin from apples and of pure quercetin rutinoside was both 30% relative to onions. Peak levels were achieved less than 0.7 after ingestion of onions, 2.5 h after apples and 9 h after the rutinoside. Half-lives of elimination were 28 h for onions and 23 h for apples. We conclude that conjugation with glucose enhances absorption from the small gut. Because of the long half-lives of elimination, repeated consumption of quercetin-containing foods will cause accumulation of quercetin in blood.”
Effects of apple juice on risk factors of lipid profile, inflammation and coagulation, endothelial markers and atherosclerotic lesions in high cholesterolemic rabbits. Setorki M, Asgary S, Eidi A, Rohani AH, Esmaceil N. Lipids Health Dis. 2009 Oct 5;8:39. Key Finding: “Apple juice can effectively prevent the progress of atherosclerosis. This is likely due to antioxidant and anti-inflammatory effect of apple juice.”
Phenolics from purple grape, apple, purple grape juice and apple juice prevent early atherosclerosis induced by an atherogenic diet in hamsters. Decorde K, Teissedre PL, Auger C, Cristol JP, Rouanet JM. Mol Nutr Food Res. 2008 Apr;52(4):400-7. Key Finding: “The results show for the first time that long-term consumption of antioxidants supplied by apple and purple grape, especially phenolic compounds, prevents the development of atherosclerosis in hamsters.”
Apply polyphenols and fibers attenuate atherosclerosis in apolipoprotein E-deficient mice. Auclair S, Silberberg M, Gueux E, Morand C, Mazur A, Milenkovic D, Scal-bert A. J Agric Food Chem. 2008 Jul 23;56(14):5558-63. Key Finding: “Apple constituents supplied at nutritional doses limit the development of atherosclerotic lesions in the aorta of apo E-deficient mice. On the basis of the results, we hypothesize that apple fibers and polyphenols may play a role in preventing atherosclerosis disease by decreasing uric acid plasma level.”
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, Ciz M, Soliva-Fortuny R, Park YS, Jung ST, Trakhtenberg S, Martin-Belloso O. J Nutr Biochem. 2002 Oct;13(10):603-610. Key Finding: “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. Apple is preferable for dietary prevention of atherosclerosis and other diseases.”
Antiproliferative effects of apple peel extract against cancer cells. Reagan-Shaw S, Eggert D, Mukhtar H, Ahmad N. Nutr Cancer. 2010;62(4):517-24. Key Finding: “Our data demonstrated that apple peel extract, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines. Our data showed a significant decrease in growth and clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells, and breast carcinoma Mcf-7 and Mcf-7:Her18 cells. Apple peels should not be discarded from the diet.”
Case-control study on beneficial effect of regular consumption of apples on colorectal cancer risk in a population with relatively low intake of fruits and vegetables. Jedrychowski W, Maugeri U, Popiela T, Et al. Eur J Cancer Prev. 2010 Jan;19(1):42-7. Key Finding: “A total of 592 incident cases of colorectal cancer were compared to a group of 765 controls chosen from patients at the same hospital. The reduced risk of colorectal cancer was already observed at the consumption of at least one apple a day, but at the intake of more than one apple a day the risk was reduced by about 50%. The effect may result from their rich content of flavonoid and other polyphenols which can inhibit cancer onset and cell proliferation.”
An apple a day may hold colorectal cancer at bay: recent evidence from a case-control study. Jedrychowski W, Maugeri U. Rev. Environ Health. 2009 Jan-Mar;24(1):59-74. Key Finding: “The risk of colorectal cancer was inversely correlated with daily number of apple servings, but the most significant reductions of OR estimates were observed for an intake one or more apple servings daily. No other fruit was significantly associated with altering the risk of colorectal cancer.”
Apple procyanidins activate apoptotic signaling pathway in human colon adenocarcinoma cells by a lipid-raft independent mechanism. Maldonado-Ceils ME, Bousserouel S, Gosse F, Lobstein A, Raul F. Biochem Biophys Res Commun. 2009 Oct 16;388(2):372-6. Key Finding: “These results highlight the potential of procyanidins as a direct activator of TRAIL-death receptors in cell membrane even in the absence of lipid rafts.”
Synergistic effect of apple extracts and quercetin 3-beta-d-glucoside combination on antiproliferative activity in MCF-7 human breast cancer cells in vitro. Yang J, Liu RH. J Agric Food Chem. 2009 Sep 23;57(18):8581-6. Key Finding: “The results suggest that the apple extracts plus Q3G combination possesses a synergistic effect in MCF-7 cell proliferation. The two-way combination of apple plus Q3G was conducted. In this two-way combination, the EC(5) values of apple extracts and Q3G were 2- and 4-fold lower, respectively, than those of apple extracts and Q3G alone. The combination index (Ci) values at 50 and 95% inhibition rates were 0.76 +/- 0.39-fold, respectively.”
Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy. Laszczyk MN. Panta Med. 2009 Dec;75(15):1549-60. Key Finding: Apple peels are rich in triterpenes. “Triterpenes are useful to treat cancer by several modes of action. The pharmacological potential of triterpenes of the lupane, oleanane or ursane type for cancer treatment seems high.”
Impact of apple polyphenols on GSTT2 gene expression, subsequent protection of DNA and modulation of proliferation using LT97 human colon adenoma cells. Miene C, Klenow S, Veeriah S, Richling E, Glei M. Mol Nutr Food Res. 2009 Oct;53(10):1254-62. Key Finding: “Apple extract enhances expression of glutathione S-transferases (e.g. GSTTe) in human colon cells. Storage of apple extract caused changes in phenolic composition along with loss of activity regarding GSTT2 induction and amplified growth inhibition. Apple extract can protect against oxidative induced DNA damage. Nevertheless, chemo preventive effects of apple extract strongly depend on the specific composition, which is modified by storage.”
Prevention of colon carcinogenesis by apple juice in vivo: impact of juice constituents and obesity. Koch TC, Briviba K, Watzl B, Fahndrich C, Bub A, Rechkemmer G, Barth SW. Mol Nutr Food Res. 2009 Oct;53(10):1289-302. Key Finding: “The development of colon cancer is positively associated with obesity and inversely associated with the intake of fiber, fruit and vegetables. Apple juice contains a specific spectrum of polyphenols and other components that may reduce the risk of colon cancer. Epidemiologic studies suggest an inverse correlation between apple consumption and colon cancer risk. The present review summarizes the preventive potential of apples juices and different apple constituents on biomarkers related to colon carcinogenesis.”
GSTT2, a phase II gene induced by apple polyphenols, protects colon epithelial cells against genotoxic damage. Petermann A, Miene C, Schulz-Raffelt G, Palige K, Holzer J, Glei M, Bohmer FD. Mol Nutr Food Res. 2009 Oct;53(10):1245-53. Key Finding: “We found that polyphenolic apple extracts can directly enhance GSTT2 promoter activity. Induction of phase II genes may contribute to primary chemoprevention of colon cancer by apple polyphenols.”
Ursolic acid attenuates oxidative stress-mediated hepatocellular carcinoma induction by diethylnitrosamine in male Wistar rats. Gayathri R, Priya DK, Gunaseekaran GR, Sakthisekaran D. Asian Pac J Cancer Prev. 2009;10(5):933-8. Key Finding: “Ursolic acid is a natural triterpenoid found in apple peel. Since ursolic acid has been found to be a potent antioxidant, it can be suggested as an excellent chemo preventive agent in overcoming diseases like cancer which are mediated by free radicals.”
Fresh apples suppress mammary carcinogenesis and proliferative activity and induce apoptosis in mammary tumors of the Sprague-Dawley rat. Liu JR, Dong HW, Chen BQ, Zhao P, Liu RH. J Agric Food Chem. 2009 Jan 14;57(1):297-304. Key Finding: “Whole apple extracts possess potent antioxidant activity and antiproliferative activity against cancer cells in vitro. The objections of this study were to determine the anticancer activity of apple extracts in a rat mammary cancer model induced by 7,12-dimtheylbenz (a)anthracene (DMBA) in vivo and to determine if apple extracts inhibited cell proliferation and affected apoptosis in mammary cancer tissues in vivo. These results demonstrate the potent capacity of fresh apples to suppress DMBA-initiated mammary cancers in rats.”
Apple polyphenol phloretin potentiates the anticancer actions of paclitaxel through induction of apoptosis in human hep G2 cells. Yang KC, Tsai CY, Wang YJ, Wei PL, Lee CH, Chen JH, Wu CH, Ho YS. Mol Carcinog. 2009 May;48(5):420-31. Key Finding: “Phloretin, which can be obtained from apples, apple juice and cider, is a known inhibitor of the type II glucose transporter. In vitro and in vivo studies were performed to assess phoretin antitumor activity when combined with paclitaxel for treatment of human liver cancer cells. The Hep G2-xenografted tumor volume was reduced more than fivefold in the Phloretin + paclitaxel treated mice compared to the paclitaxel treated group. These results suggest that Phloretin may be useful for cancer chemotherapy and chemoprevention.”
Cancer chemo preventive potential of apples, apple juice, and apple components. Gerhauser C. Planta Med. 2008 Oct;74(13):1608-24. Key Finding: “Apple products have been shown to prevent skin, mammary and colon carcinogenesis in animal models. Epidemiological observations indicate that regular consumption of one or more apples a day may reduce the risk for lung and colon cancer.”
Phytochemicals of apple peels: isolation, structure elucidation, and their antiproliferative and antioxidant activities. He X, Liu RH. J Agric Food Chem. 2008 Nov 12;56(21):9905-10. Key Finding: “Most tested flavonoids and phenolic compounds had high antioxidant activity when compared to ascorbic acid and might be responsible for the antioxidant activities of apples. These results showed apple peel phytochemicals have potent antioxidant and antiproliferative activities.”
Apple phytochemical extracts inhibit proliferation of estrogen-dependent and estrogen-independent human breast cancer cells through cell cycle modulation. Sun J, Liu RH. J Agric Food Chem. 2008 Dec 24;56(24):11661-7. Key Finding: “The data showed that apple phytochemical extracts significantly inhibited human breast cancer MCF-7 and MDA-MB-231 cell proliferation. These results suggest that the anti-proliferative activities of apple phytochemical extracts toward human breast cancer cells might be due to the modulation effects on cell cycle machinery.”
Fractionation of polyphenol-enriched apple juice extracts to identify constituents with cancer chemo preventive potential. Zessner H, Pan L, Will F, Klimo K, Knauft J, Niewoher R, Hummer W, Owen R, Richling E, Frank N, Schreier P, Becker H, Gerhauser C. Mol Nutr Food Res. 2008 Jun;52 Supply 1:528-44. Key Finding: Apple juice extract was fractionated to determine which constituents contribute to potential chemo preventive activities. “Overall, apple juice constituents belonging to different structural classes have distinct profiles of biological activity in these in vitro test systems. Since carcinogenesis is a complex process, combination of compounds with complementary activities may lead to enhanced preventive effects.”
Apple procyanidins induce tumor cell apoptosis through mitochondrial pathway activation of caspase-3. Miura T, Chiba M, Kasai K, Nozaka H, Nakamura T, Shoji T, Kanda T, Ohtake Y. Carcinogenesis. 2008 Mar;29(3):585-93. Key Finding: “Our results indicate that the oral administration of apple procyanidins inhibits the proliferation of tumor cells by inducing apoptosis through the intrinsic mitochondrial pathway.”
Apple polyphenols modulate expression of selected genes related to toxicological defense and stress response in human colon adenoma cells. Veeriah S, Miene C, Habermann N, Hofmann T, Klenow S, Sauer J, Bohmer F, Wolfl S, Pool-Zobel BL. Int J Cancer. 2008 Jun 15;122(12):2647-55. Key Finding: “Apples contain significant amounts of flavonoids that are potentially cancer risk reducing by acting antioxidative or antiproliferative and by favorably modulating gene expression. The purpose of this study was to investigate whether polyphenols from apples modulate expression of genes related to colon cancer prevention. The observed altered gene expression patterns in LT97 cells, resulting from apple extract treatment, points to a possible protection of the cells against some toxicological insults.”
Effect of selected phytochemicals and apple extracts on NF-kappaB activation in human breast cancer MCF-7 cells. Yoon H, Liu RH. J Agric Food Chem. 2007 Apr 18;55(8):3167-73. Key Finding: “These results suggest that apple extracts and curcumin have the capabilities of inhibiting TNF-alpha-induced NF-kappaB activation of MCF-7 cells by inhibiting the proteasomal activities instead of IkappaB kinase activation.”
Annurca apple polyphenols have potent demethylating activity and can reactivate silenced tumor suppressor genes in colorectal cancer cells. Fini L, Selgard M, Fogliano V, Graziani G, Romano M, Hotchkiss E, Daoud YA, De Val EB, Boland CR, Ricciardiello L. J Nutr. 2007 Dec;137(12):2622-8. Key Finding: Annurca apple, a variety of southern Italy, is rich in polyphenols that are associated with anticancer properties. We evaluated the mechanisms of putative anticancer effects of Annurca polyphenol extract in in vitro models of sporadic colorectal cancers. We observed a significant reduction in expression of DNMT proteins after treatment without changes in messenger RNA. In conclusion, Annurca polyphenol have potent demethylating activity through the inhibition of DNMT proteins.”
Polyphenols are intensively metabolized in the human gastrointestinal tract after apple juice consumption. Kahle K, Huemmer W, Kempf M, Scheppach W, Erk T, Richline E. J Agric Food Chem. 2007 Dec 26;55(26):10605-14. Key Finding: “Polyphenols are secondary plant compounds showing anticarcinogenic effects both in vitro and in animal experiments and may thus reduce the risk of colorectal cancer in man. The identification of polyphenol metabolites formed via their passage through the small intestine of healthy ileostomy subjects after apple juice consumption is presented. Ninety percent of the consumed procyanidins were recovered in the ileostomy effluent and therefore would reach the colon under physiologic circumstances. The gastrointestinal passage seems to play an important role in the colonic availability of apple polyphenols.”
Effect of apple polyphenol extract on hepatoma proliferation and invasion in culture and on tumor growth, metastasis, and abnormal lipoprotein profiles in hepatoma-bearing rats. Miura D, Miura Y, Yagasaki K. Biosci Biotechnol Biochem. 2007 Nov;71(11):2743-50. Key Finding: “The effect of dietary apple polyphenol extract on growth and the metastasis of AH109A hepatomas were investigated in vivo. Apple polyphenol extract reduced the growth and metastasis of solid hepatomas and significantly suppressed the serum lipid peroxide level in rats transplanted with AH109A. Apple polyphenol extract also suppressed the serum very-low-density lipoprotein + low-density lipoprotein cholesterol level.”
Polyphenolic apple juice extracts and their major constituents reduce oxidative damage in human colon cell lines. Schaefer S, Baum M, Eisenbrand G, Dietrich H, Will F, Janzowski C. Mol Nutr Food Res. 2006 Jan;50(1):24-33. Key Finding: “Apple juice extracts distinctly reduce oxidative cell damage in human colon cell lines, an effect, which in part can be accounted for by their major constituents.”
Apple flavonoids inhibit growth of HT29 human colon cancer cells and modulate expression of genes involved in the biotransformation of xenobiotics. Veeriah S, Kautenburger T, Habermann N, Sauer J, Dietrich H, Will F, Pool-Zobel BL. Mol Carcinog. 2006 Mar;45(3):164-74. Key Finding: “We conclude that apple flavonoids modulate toxicological defense against colon cancer risk factors. In addition to the inhibition of tumor cell proliferation, this could be a mechanism of cancer risk reduction.”
Apples prevent mammary tumors in rats. Liu RH, Liu J, Chen B. J Agric Food Chem. 2005 Mar 23;53(6):2341-3. Key Finding: “This study demonstrated that whole apple extracts effectively inhibited mammary cancer growth in the rat model; thus, consumption of apples may be an effective therapy for cancer protection.”
Does an apple a day keep the oncologist away? Gallus S, Talamini R, Giacosa A, Montella M, Ramazzotti V, Franceschi S, Negri E, La Vecchia C. Ann Oncol. 2005 Nov;16(11):1841-4. Key Finding: “We analyzed data from multicenter case-control studies conducted between 1991 and 2002 in Italy. This investigation found a consistent inverse association between apples and risk of various cancers.”
The relationship between intake of vegetables and fruits and colorectal adenoma-carcinoma sequence. Lee SY, Choi KY, Kim MK, Kim KM, Lee JH, Meng KH, Lee WC. Korean J Gastroenterol (from Korean). 2005 Jan;45(1):23-33. Key Finding: “These findings suggest that the intake of vegetables and fruits may act differently in developmental steps of colorectal adenoma-carcinoma sequence. For this study, 539 cases with histopathologically confirmed incidental colorectal adenoma, 162 cases with colorectal cancer and 2,576 controls were collected. In females, the high intake of raw green and yellow vegetables was found to be negatively associated with the risk of adenoma with mild dysplasia. In male, the high intake of banana, pear, apple and watermelon among fruits were negatively associated with the risk of colorectal cancer.”
Chemo preventive properties of apple procyanidins on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis. Gosse F, Guyot S, Roussi S, Lobstein A, Fischer B, Seiler N, Raul F. Carcinogenesis. 2005 Jul;26(7):1291-5. Key Finding: “Our results show that apple procyanidins alter intracellular signaling pathways, polyamine biosynthesis and trigger apoptosis in tumor cells. These compounds antagonize cancer promotion in vivo. In contrast with absorbable drugs, these natural, non-toxic, dietary constituents reach the colon where they are able to exert their antitumor effects.”
Lung cancer risk among nonsmoking women in relation to diet and physical activity. Kubik A, Zatloukal P, Tomasek L, Pauk N, Petruzelka L, Plesko I. Neoplasma. 2004;51(2):136-43. Key Finding: “Excess lung cancer risk was associated with consumption of red meat among nonsmokers. Protective effects were observed for apples among smokers only.”
Biological activity of carotenoids in red paprika, Valencia orange and golden delicious apple. Molnar P, Kawase M, Satoh K, Sohara Y, Tanaka T, Tani S, Sakagami H, Nakashima H, Motohashi N, Gyemant N, Molnar J. Phytother Res. 2005 Aug;19(8):700-7. Key Finding: “Carotenoid fractions were extracted from red paprika, Valencia orange peel and the peel of Golden delicious apple. Apple showed potent anti-H. Pylori activity. The extracts were inactive against HIV. Apple and orange showed slightly higher cytotoxic activity against three human tumor cells lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG, and human promyelocytic leukemic HL-60 cells. Paprika scavenged efficiently. The data suggest the potential importance of carotenoids as possible anti-H. Pylori and multidrug resistance reversal agents.”
Intake of fruits, vegetables and selected micronutrients in relation to the risk of breast cancer. Malin AS, Qi D, Shu XO, Gao VT, Friedman JM, Jin F, Zheng W. Int J Cancer. 2003 Jun 20;105(3):413-8. Key Finding: “Intake of fruits, except watermelons and apples, was inversely associated with breast cancer risk. Our study suggests that high intake of certain vegetables and fruits may be associated with a reduced risk of breast cancer.”
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. Nutr Cancer. 2003;45(1):46-52. Key Finding: “The results of the present study suggest that commonly consumed fruit juices {apple juice, orange juice, black currant juice} can alter lipid and protein oxidation biomarkers in the blood as well as hepatic quinine reductase activity and that quercetin may not be the major active principle.”
Antioxidant and antiproliferative activities of common fruits. Sun J, Chu YF, Wu X, Liu RH. J Agric Food Chem. 2002 Dec 4;50(25):7449-54. Key Finding: “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. This study was designed to investigate the profiles of total phenolics. Cranberry had the highest total phenolic content followed by apple. Cranberry had the highest total antioxidant activity followed by apple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect followed by lemon and apple.”
Evaluation of the immunomodulatory activity of Aronia in combination with apple pectin in patients with breast cancer undergoing postoperative radiation therapy. Yaneva MP, Botushanova AD, Grigorov LA, Kokov JL, Todorova EP, Krachanova MG. Folia Med (Bulgaria). 2002;44(1-2):22-5. Key Finding: “The aim of the present study was to evaluate the immunomodulatory activity of Aronia in combination with apple pectin in patients with breast cancer in the course of postoperative radiation therapy. The study comprised 42 women (19 to 65 years of age) receiving 15 g of apple pectin in combination with 20 ml of Aronia concentrate (Bioactive Substance Laboratory-Plovdiv) twice daily during postoperative radiation. Assays of immunity parameters in the patients receiving Aronia in combination with apple pectin showed that CD4 and CD8 T cell counts increased significantly. In control patients (non-apple pectin) T cell level lowered.”
Intake of Flavonoids and Lung Cancer. Le Marchand LL, Murphy SP, Hankin JH, Wilkens LR, Kolonel LN. J Natl Cancer Inst. 2000 Jan 19;92(2):154-60. Key Finding: “After adjusting for smoking and intakes of saturated fat and B-carotene, we found statistically significant inverse associations between lung cancer risk and the main food sources of the flavonoids quercetin (onions and apples) and naringin (white grapefruit.)”
Diet and its preventive role in prostatic disease. Denis L, Morton MS, Griffiths K. Eur Urol. 1999;35(5-6):377-87. Key Finding: “Vegetarian men have a lower incidence of prostate cancer than omnivorous males. Apples and onions are excellent sources of flavonoids. These plant compounds can interfere with steroid metabolism and bioavailability, and also inhibit enzymes which are crucial to cellular proliferation.”
Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. Knekt P, Jaryinen R, Seppanen R, Hellovaara M, Teppo L, Pukkaia E, Aromaa A. Am J Epidemiol. 1997 Aug 1;146(3):223-30. Key Finding: “Of the major dietary flavonoid sources, the consumption of apples showed an inverse association with lung cancer incidence. The results are in line with the hypothesis that flavonoid intake in some circumstances may be involved in the cancer process, resulting in lowered risks.”
Dietary flavonoids and cancer risk in the Zutphen Elderly Study. Hertog MG, Feskens EJ, Hollman PC, Katan MB, Krombout D. Nutr Cancer. 1994;22(2):175-84. Key Finding: “A high intake of flavonoids from vegetables and fruits only was inversely associated with risk of cancer of the alimentary and respiratory tract. These results suggest the presence of other non-vitamin components with anti-carcinogenic potential in these foods. We conclude that intake of flavonoids, mainly from tea, apples and onions, does not predict a reduced risk of all-cause cancer or of cancer of the alimentary and respiratory tract in elderly men. The effect of flavonoids on risk of cancer at specific sites needs further investigation in prospective cohort studies.”
Flavonoid intake and the risk of cardiovascular disease in women. Sesso HD, Gaziano JM, Liu S, Buring JE. Am J Clin Nutr. 2003 Jun;77(6):1400-6. Key Finding: “Women free of CVD and cancer participated in a prospective study using a food frequency questionnaire. Flavonoid intake was not strongly associated with a reduced risk of cardiovascular disease. The insignificant inverse associations for broccoli, apples, and tea with CVD were not mediated by flavonoids and warrant further study.”
Antioxidant and antiproliferative activities of common fruits. Sun J, Chu YF, Wu X, Liu RH. J Agric Food Chem. 2002 Dec 4;50(25):7449-54. Key Finding: “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. This study was designed to investigate the profiles of total phenolics. Cranberry had the highest total phenolic content followed by apple. Cranberry had the highest total antioxidant activity followed by apple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect followed by lemon and apple.”
Apple juice consumption reduces plasma low-density lipoprotein oxidation in healthy men and women. Hyson D, Studebaker-Hallman D, Davis PA, Gershwin ME. J Med Food. 2000 Winter;3(4):159-66. Key Finding: “Moderate apple juice consumption provides in vivo antioxidant activity. In view of the current understanding of coronary artery disease, the observed effect on LDL might be associated with reduced CAD risk and supports the inclusion of apple juice in a healthy human diet.”
Dietary catechins in relation to coronary heart disease death among postmenopausal women. Arts IC, Jacobs DR Jr, Harnack LJ, Gross M, Folsom AR. Epidemiology. 2001 Nov;12(6):668-75. Key Finding: Apple catechins were inversely associated with coronary heart disease death. There was a strong inverse association between the intake of (+)-catechin and (-)-epicatechin and coronary heart disease.”
Apple juice inhibits human low density lipoprotein oxidation. Pearson DA, Tan CH, German JB, Davis PA, Gershwin ME. Life Sci. 1999;64(21):1913-20. Key Finding: “The ability of compounds in apple juices and extracts from fresh apple to protect LDL was assessed. The apple juices and extracts all inhibited LDL oxidation. The inhibition by the juices ranged from 9 to 34% and inhibition by apple peel, flesh and whole fresh Red Delicious apple was 21, 34 and 38% respectively. The specific components in the apple juices and extracts that contributed to antioxidant activity have yet to be identified.”
Flavonoid intake and coronary mortality in Finland: a cohort study. Knekt P, Jarvinen R, Reunanen A, Maatela J. BMJ. 1996 Feb 24;312(7029):478-81. Key Finding: “The results suggest that people with very low intakes of flavonoids {such as onions and apples} have higher risks of coronary disease.”
Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Lancet. 1993 Oct 23;342(8878):1007-11. Key Finding: The flavonoid intake of 805 men aged 65-84 years was measured. The major sources of intake were tea, onions and apples. “Flavonoid intake was significantly inversely associated with mortality from coronary heart disease. Flavonoids in regularly consumed foods may reduce the risk of death from coronary heart disease in elderly men.”
Quercetin intake and the incidence of cerebrovascular disease. Knekt P, Isotupa S, Rissanen H, Heliovaara M, Jarvinen R, Hakkinen S, Aromaa A, Reunanen A. Eur J Clin Nutr. 2000 May;54(5):415-7. Key Finding: “The results suggest that the intake of apples is related to a decreased risk of thrombotic stroke. This association apparently is not due to the presence of the antioxidant flavonoid quercetin.”
Inhibition by apple polyphenols of ADP-ribosyltransferase activity of cholera toxin and toxin-induced fluid accumulation in mice. Saito T, Miyake M, Toba M, Okamatsu H, Shimizu S, Noda M. Microbiol Immunol. 2002;46(4):249-55. Key Finding: “The results suggest that polymerized catechin compounds in apple polyphenol extract inhibit the biological and enzymatic activities of cholera toxin and can be used in a precautionary and therapeutic manner in the treatment of cholera patients.”
Apple polyphenols inhibit plasma CETP activity and reduce the ratio of non-HDL to HDL cholesterol. Lam CK, Zhang Z, Yu H, Tsang SY, Huang Y, Chen ZY. Mol Nutr Food Res. 2008 Aug;52(8):950-8. Key Finding: “It was concluded that apply polyphenols favorably improved distribution of cholesterol in lipoproteins, most likely by its inhibition on plasma cholesteryl ester transport protein activity.”
Novel low-density lipoprotein (LDL) oxidation model: antioxidant capacity for the inhibition of LDL oxidation. Chu YF, Liu RH. J Agric Food Chem. 2004 Nov 3;52(22):6818-23. Key Finding: “All vitamin C and E and apple extract concentrations tested resulted in increasing partial suppression and delay of LDL oxidation.”
Apple pectin and a polyphenol-rich apple concentrate are more effective together than separately on cercal fermentation and plasma lipids in rats. Aprikian O, Ducios V, Guyot S, Besson C, Manach C, Bernalier A, Morand C, Remesy C, Demigne C. J Nutr. 2003 Jun;133(6):1860-5. Key Finding: “Apple pectin and the polyphenol-rich fraction were more effective when fed combined together than when fed separately on large intestine fermentations and lipid metabolism, suggesting interactions between fibers and polyphenols of apples.”
Diminution of blood and hepatic cholesterol induced by an apple-supplemented diet in the hamster. Sicart R, Sable-Amplis R, Agid R. CR Seances Soc Biol Fil. (French). Key Finding: “Human daily ingestion of apples caused a significant reduction (16%) of cholesterolemia.”
Chronic obstructive pulmonary disease and intake of fatechines, flavonols, and flavones: the MORGEN Study. Tabak C, Arts IC, Smit HA, Heederik D, Kromhout D. Am J Respir Crit Care Med. 2001 Jul 1;164(1):61-4. Key Finding: “Flavonoids have been suggested to protect against chronic lung disease. We studied intake of catechins, flavonols and flavones in relation to pulmonary function and chronic obstructive pulmonary disease symptoms in 13,651 adults from three Dutch cities. Tea and apples were the main source of catechins, flavonols and flavones. Total intake was inversely associated with chronic cough and breathlessness, but not chronic phlegm. Solid fruit but no tea intake was beneficially associated with chronic obstructive pulmonary disease.”
Associations of dietary flavonoids with risk of type 2 diabetes, and markers of insulin resistance and systemic inflammation in women: a prospective study and cross-sectional analysis. Song Y, Manson JE, Buring JE, Sesso HD, Liu S. J Am Coll Nutr. 2005 Oct;24(5):376-84. Key Finding: “The aim of this study was to examine the association of dietary flavonols and flavone intake with type 2 diabetes, and biomarkers of insulin resistance and systemic inflammation. These results do not support the hypothesis that high intake of flavonols and flavones reduces the development of type 2 diabetes, although we cannot rule out a modest inverse association with intake of apples and tea.”
Dietary fiber in type II diabetes. Asp NG, Agardh CD, Ahren B, Dencker I, Johansson CG, Lundquist I, Nyman M, Sartor G, Schersten B. Acta Med Scand Supple. 1981;656:47-50. Key Finding: “The results indicate that foods rich in dietary fiber (such as whole apples) might be useful in the regulation of type II diabetes.”
Apple polyphenol extracts prevent damage to human gastric epithelial cells in vitro and to rat gastric mucosa in vivo. Garziani G, D’Argenio G, Tuccillo C, Loguercio C, Ritieni A, Morisco F, Del Vecchio Blanco C, Fogliano V, Romano M. Gut. 2005 Feb;54(2):193-200. Key Finding: “Apple extracts prevent exogenous damage to human gastric epithelial cells in vitro and to the rat gastric mucosa in vivo. The effect seems to be associated with the antioxidant activity of apple phenolic compounds. A diet rich in apple antioxidants might exert a beneficial effect in the prevention of gastric diseases.”
Influence of apple polyphenols on inflammatory gene expression. Jung M, Triebel S, Anke T, Richling E, Erkel G. Mol Nutr Food Res. 2009 Oct;53(10):1263-80. Key Finding: “Apples and products thereof contain high amounts of polyphenols which show diverse biological activities and may contribute to beneficial health effects, like protecting the intestine against inflammation initiated by chronic inflammatory bowel disease. In the present study we investigated the preventive effectiveness of polyphenol juice extracts on inflammatory gene expression in immune-relevant human cell lines.”
Reduction of colonic inflammation in HLA-B27 transgenic rats by feeding Marie Menard apples, rich in polyphenols. Castagnini C, Luceri C, Toti S, Bigagli E, Caderni G, Femia AP, Giovanneilli L, Lodovici M, Pitozzi V, Salvadori M, Messerini L, Martin R, Zoetendal EG, Gai S, Eijssen L, Evelo CT, Renard CM, Baron A, Dolara P. Br J Nutr. 2009 Dec;102(11):1620-8. Key Finding: “The administration of Marie Menard apples ameliorates colon inflammation in transgenic rats developing spontaneous intestinal inflammation, suggesting the possible use of these and other apple varieties to control inflammation in inflammatory bowel disease patients.”
Orally administered apple procyanidins protect against experimental inflammatory bowel disease in mice. Yoshioka Y, Akiyama H, Nakano M, Shoji T, Kanda T, Ohtake Y, Takita T, Matsuda R, Maitani T. Int Immunopharmacol. 2008 Dec 20;8(13-14):1802-7. Key Finding: “The combined anti-inflammatory and immunomodulatory effects of apple procyanidins on intestinal epithelial cells and intraepithelial lymphocytes suggest that it may be an effective oral preventive agent for inflammatory bowel diseases.”
Dietary apple polyphenols have preventive effects against lengthening contraction-induced muscle injuries. Nakazato K, Ochi E, Waga T. Mol Nutr Food Res. 2010 Mar;54(3):364-72. Key Finding: “Sixteen male Wistar rats were randomly assigned into the apple polyphenol feeding group and a control group. The animals were subjected to lengthening contractions and electrical stimulation and forced ankle dorsiflexion. We conclude that dietary apple polyphenols have protective effects against lengthening contraction-induced muscle injury.”
Dietary apple polyphenols have preventive effects against lengthening contraction-induced muscle injuries. Nakazato K, Ochi E, Waga T. Mol Nutr Food Res. 2009 Oct 28. (Epub ahead of print). Key Finding: “We examined whether polyphenols from dietary apple have protective effects against exercise-induced muscle strain injury. Sixteen male Wistar rats were randomly assigned into the apple and control group diets. The animals were subject to lengthening contractions with electrical stimulation and forced ankle dorsiflexion. The apple group had significantly lower torque deficits than the control group. The apple group also had significantly higher glutathione-S-transferase alpha1 mRNA levels than the control group. We conclude that dietary apple polyphenols have protective effects against lengthening contraction-induced muscle injury.”
Dietary supplementation with apple juice decreases endogenous amyloid-beta levels in murine brain. Chan A, Shea TB. Alzheimers Dis. 2009 Jan;16(1):167-71. Key Finding: “Folate deficiency has been associated with age-related neurodegeneration. We demonstrate herein that dietary deficiency in folate and vitamin E, coupled prooxidant stress induced by dietary iron, increased amyloid-beta levels in normal adult mice. Dietary supplementation with apple juice concentrate in drinking water alleviated the increase in amyloid-beta for both mouse genotypes.”
Dietary supplementation with apple juice concentrate alleviates the compensatory increase in glutathione synthase transcription and activity that accompanies dietary- and genetically-induced oxidative stress. Tchantchou F, Graves M, Ortiz D, Rogers E, Shea TB. J Nutr Health Aging. 2004;8(6):492-6. Key Finding: “These findings provide further evidence that the antioxidant potential of apple juice concentrate can compensate for dietary and genetic deficiencies that otherwise promote neuro-degeneration.”
Identification of hop polyphenolic components which inhibit prostaglandin E2 production by gingival epithelial cells stimulated with periodontal pathogen. Inaba H, Tagashira M, Honma D, Kanda T, Kou Y, Ohtake Y, Amano A. Biol Pharm Bull. 2008 Mar;31(3):527-30. Key Finding: “These results suggest that apple-derived polyphenols is a potent inhibitor of cellular PGE2 production induced by P. gingivalis, and it may be useful for the prevention and attenuation of periodontitis.”
Apple- and hop-polyphenols protect periodontal ligament cells stimulated with enamel matrix derivative from Porphyromonas gingivalis. Inaba H, Tagashira M, Kanda T, Ohno T, Kawai S, Amano A. J Periodontol. 2005 Dec;76(12):2223-9. Key Finding: “Enamel matrix derivative is a tissue regenerative agent used clinically as an adjunct to periodontal surgery. Porphyronan gingivalis, a periodontal pathogen, significantly diminishes the efficacy of EMD. We examined apple and hop-polyphenols to determine their ability to protect periodontal ligament cells from P. gingivalis. Each polyphenol significantly enhanced the viability of periodontal ligament cells infected with P. gingivalis.”
Weight loss associated with a daily intake of three apples or three pears among overweight women. Conceicao de Oliveira M, Sichieri R, Sanchez-Moura A. Nutrtion. 2003 Mar;19(3):253-6. Key Finding: “After 12 week follow-up, the fruit group lost 1.22 kg whereas the oat group had a non-significant weight loss of 0.88 kg. The difference between the two groups was statistically significant. Intake of fruits may contribute to weight loss.”