FNS  Vol.5 No.13 , July 2014
Apple as a Source of Dietary Phytonutrients: Bioavailability and Evidence of Protective Effects against Human Cardiovascular Disease
Abstract: The dietary consumption of fruit and vegetable is associated with a lower incidence of degenerative diseases such as cardiovascular disease. Most recent interest has focused on the bioactive phenolic compounds in vegetable products. All varieties of apple contain several antioxidants and polyphenols that possess many biological activities, such as antioxidant and anti-inflammation properties. The review describes the nutritional properties of apples and their derivatives, with a particular attention to polyphenol compounds. Moreover, the health benefits of apples and the potential molecular mechanisms against cardiovascular disease are reviewed.
Cite this paper: Ferretti, G. , Turco, I. and Bacchetti, T. (2014) Apple as a Source of Dietary Phytonutrients: Bioavailability and Evidence of Protective Effects against Human Cardiovascular Disease. Food and Nutrition Sciences, 5, 1234-1246. doi: 10.4236/fns.2014.513134.

[1]   Hu, F.B. (2003) Plant-Based Foods and Prevention of Cardiovascular Disease: An Overview. The American Journal of Clinical Nutrition, 8, 544S-551S.

[2]   He, F., Nowson, C.A., Lucas, M. and MacGregor, G.A. (2007) Increased Consumption of Fruit and Vegetables Is Related to a Reduced Risk of Coronary Heart Disease: Meta-Analysis of Cohort Studies. Journal of Human Hypertension, 21, 717-728.

[3]   Riboli, E. and Norat T. (2003) Epidemiologic Evidence of the Protective Effect of Fruit and Vegetables on Cancer Risk. The American Journal of Clinical Nutrition, 78, 559S-569S.

[4]   Steinmetz, K.A. and Potter, J.D. (1996) Vegetables, Fruit, and Cancer Prevention: A Review. Journal of the American Dietetic Association, 96, 1027-1039.

[5]   Scalbert, A. and Williamson, C. (2000) Dietary Intake and Bioavailability of Polyphenols. Journal of Nutrition, 130, 2073S-2085S.

[6]   Monach, C., Scalbert, A., Morand, C., Remesy, C. and Jimenez, L. (2004) Polyphenols: Food Sources and Bioavailability. The American Journal of Clinical Nutrition, 79, 727-747.

[7]   Boyer, J. and Liu, RH. (2004) Apple Phytochemicals and Their Health Benefits. Nutrition Journal, 12, 3-5.

[8]   Wolfe, K., Wu, X. and Liu, R.H. (2003) Antioxidant Activity of Apple Peels. Journal of Agricultural and Food Chemistry, 51, 609-614.

[9]   Eberhardt, M., Lee, C. and Liu, R.H. (2000) Antioxidant Activity of Fresh Apples. Nature, 405, 903-904.

[10]   Miura, D., Miura, Y. and Yagasaki, K. (2007) 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. Bioscience, Biotechnology, and Biochemistry, 71, 2743-2750.

[11]   Osada, K., Suzuki, T. and Kawakami, Y. (2006) Dose-Dependent Hypocholesterolemic Actions of Dietary Apple Polyphenol in Rats Fed Cholesterol. Lipids, 41, 133-139.

[12]   Kosmala, M., Kolodziejczyk, K., Zduńczyk, Z., Juskiewicz, J. and Boros, D. (2011) Chemical Composition of Natural and Polyphenol-Free Apple Pomace and the Effect of This Dietary Ingredient on Intestinal Fermentation and Serum Lipid Parameters in Rats. Journal of Agricultural and Food Chemistry, 14, 9177-9185.

[13]   Yan, H. and Kerr, W.L. (2013) Total Phenolics Content, Anthocyanins, and Dietary Fiber Content of Apple Pomace Powders Produced by Vacuum-Belt Drying. Journal of the Science of Food and Agriculture, 93, 1499-1504.

[14]   Del Rio, D., Rodriguez-Mateos, A., Spencer, J.P., Tognolini, M., Borges, G. and Crozier A. (2013) Dietary (Poly) Phenolics in Human Health: Structures, Bioavailability, and Evidence of Protective Effects against Chronic Diseases. Anti-oxidants Redox Signaling, 18, 1818-1892.

[15]   Podsedek, A., Wilska-Jeska, J., Anders, B. and Markowski, J. (2000) Compositional Characterisation of Some Apple Varieties. European Food Research and Technology, 210, 268-272.

[16]   Kahle, K., Kraus, M. and Richling, E. (2005) Polyphenol Profiles of Apple Juices. Molecular Nutrition & Food Research, 49, 797-806.

[17]   Thakur, B.R., Singh, R.K., Handa, A.K. and Rao, M.A. (1997) Chemistry and Uses of Pectin—A Review. Critical Reviews in Food Science and Nutrition, 37, 47-73.

[18]   Olano-Martin, E., Gibson, G.R. and Rastell, R.A. (2002) Comparison of the in Vitro Bifidogenic Properties of Pectins and Pectic-Oligosaccharides. Journal of Applied Microbiology, 93, 505-511.

[19]   EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). EFSA Journal, 8, 1747-1745.

[20]   Lister, C.E., Lancaster, J.E., Sutton, K.H. and Walker, J.R.L. (1994) Developmental Changes in the Concentration and Composition of Flavonoids in Skin of a Red and a Green Apple Cultivar. Journal of the Science of Food and Agriculture, 64, 155-161.

[21]   Escarpa, A. and Gonzales, M.C. (1998) High Performance Liquid Chromatography with Diode-Array Detection for the Determination of Phenolic Compounds in Peel and Pulp from Different Apple Varieties. Journal of Chromatography A, 823, 331-337.

[22]   Schieber, A., Keller, P., Streker, P., Klaiber, I. and Carle, R. (2001) Detection of Isorhamnetin Glycosides in Extracts of Apples (Malus domestica cv. “Brettacher”) by HPLC-PDA and HPLC-APCIMS/MS. Phytochemical Analysis, 13, 87-94.

[23]   Lea, A.G.H. and Arnold, G.M. (1978) The Phenolics of Ciders: Bitterness and Astringency. Journal of the Science of Food and Agriculture, 29, 478-483.

[24]   Santos-Buelga, C. and Scalbert, A. (2000) Proanthocyanidins and Tannin-Like Compounds—Nature, Occurrence, Dietary Intake and Effects on Nutrition and Health. Journal of the Science of Food and Agriculture, 80, 1094-1117.<1094::AID-JSFA569>3.0.CO;2-1

[25]   Guyot, S., Marnet, N., Laraba, D., Sanoner, P. and Drilleau, J.F. (1998) Reversed-Phase HPLC Following Thiolysis for Quantitative Estimation and Characterization of the Four Main Classes of Phenolic Compounds in Different Tissue Zones of a French Cider Apple Variety. Journal of Agricultural and Food Chemistry, 46, 1698-1705.

[26]   Denis, M.C., Furtos, A., Dudonné, S., Montoudis, A., Garofalo, C., Desjardins, Y., Delvin, E. and Levy, E. (2013) Apple Peel Polyphenols and Their Beneficial Actions on Oxidative Stress and Inflammation. PLoS ONE, 8, Article ID: e53725.

[27]   Landete, J.M. (2012) Updated Knowledge about Polyphenols: Functions, Bioavailability, Metabolism, and Health. Critical Reviews in Food Science and Nutrition, 52, 936-948.

[28]   Bergmann, H., Triebel, S., Kahle, K. and Richling, E. (2010) The Metabolic Fate of Apple Polyphenols in Humans. Current Nutrition & Food Science, 6, 19-35.

[29]   Richling, E. (2012) Bioavailability of Dihydrochalcones. In: Spencer, J.P.E. and Crozier, A., Eds., Flavonoids and Related Compounds: Bioavailability and Function, CRC Press, Boca Raton, 157-165.

[30]   Marks, C., Mullen, W., Borges, G. and Crozier, A. (2009) Absorption, Metabolism, and Excretion of Cider Dihydrochalcones in Healthy Humans and Subjects with an Ileostomy. Journal of Agricultural and Food Chemistry, 57, 2009-2015.

[31]   Hollands, W.J., Hart, D.J., Dainty, J.R., Hasselwander, O., Tiihonen, K., Wood, R. and Kroon, P.A. (2013) Bioavailability of Epicatechin and Effects on Nitric Oxide Metabolites of an Apple Flavanol-Rich Extract Supplemented Beverage Compared to a Whole Apple Puree: A Randomized, Placebo-Controlled, Crossover Trial. Molecular Nutrition & Food Research, 57, 1209-1217.

[32]   Hollman, P.C., van Trijp, J.M., Buysman, M.N., van der Gaag, M.S., Mengelers, M.J., de Vries, J.H. and Katan, M.B. (1997) Relative Bioavailability of the Antioxidant Flavonoid Quercetin from Various Foods in Man. FEBS Letters, 418, 152-156.

[33]   Du Pont, M.S., Bennett, R.N., Mellon, F.A. and Williamson, G. (2002) Polyphenols from Alcoholic Apple Cider Are Adsorbed, Metabolized and Excreted by Humans. Journal of Nutrition, 132, 172-175.

[34]   Serrano, J., Puupponen-Pimi?, R., Dauer, A., Aura, A.M. and Saura-Calixto, F. (2009) Tannins: Current Knowledge of Food Sources, Intake, Bioavailability and Biological Effects. Molecular Nutrition & Food Research, 53, S310-S329.

[35]   Déprez, S., Mila, I. and Scalbert, A. (1999) Carbon-14 Biolabeling of (+)-Catechin and Proanthocyanidin Oligomers in Willow Tree Cuttings. Journal of Agricultural and Food Chemistry, 47, 4219-4230.

[36]   Déprez, S., Brezillon, C., Rabot, S., Philippe, C., Mila, I., Lapierre, C. and Scalbert, A. (2000) Polymeric Proanthocyanidins Are Catabolized by Human Colonic Microflora into Low-Molecular-Weight Phenolic Acids. Journal of Nutrition, 130, 2733-2738.

[37]   Stracke, B.A., Rüfer, C.E., Bub, A., Seifert, S., Weibel, F.P., Kunz, C. and Watzl, B. (2010) No Effect of the Farming System (Organic/Conventional) on the Bioavailability of Apple (Malus domestica Bork., Cultivar Golden Delicious) Polyphenols in Healthy Men: A Comparative Study. European Journal of Nutrition, 49, 301-310.

[38]   Jensen, E.N., Buch-Andersen, T., Ravn-Haren, G. and Dragsted, L. (2009) Mini-Review: The Effects of Apples on Plasma Cholesterol Levels and Cardiovascular Risk—A Review of the Evidence. Journal of Horticultural Science & Biotechnology, 34-41.

[39]   Auclair, S., Silberberg, M., Gueux, E., Morand, C., Mazur, A., Milenkovic, D. and Scalbert, A. (2008) Apple Polyphenols and Fibers Attenuate Atherosclerosis in Apolipoprotein E-Deficient Mice. Journal of Agricultural and Food Chemistry, 56, 5558-5563.

[40]   Hyson, D.A. (2011) A Comprehensive Review of Apples and Apple Components and Their Relationship to Human Health. Advances in Nutrition, 2, 408-420.

[41]   Toh, J.Y., Tan, V.M., Lim, P.C., Lim, S.T. and Chong, M.F. (2013) Flavonoids from Fruit and Vegetables: A Focus on Cardiovascular Risk Factors. Current Atherosclerosis Reports, 15, 368.

[42]   Eren, E., Yilmaz, N. and Aydin, O. (2013) Functionally Defective High-Density Lipoprotein and Paraoxonase: A Couple for Endothelial Dysfunction in Atherosclerosis. Cholesterol, 2013, Article ID: 792090.

[43]   Maiolino, G., Rossitto, G., Caielli, P., Bisogni, V., Rossi, G.P. and Calò, L.A. (2013) The Role of Oxidized Low-Density Lipoproteins in Atherosclerosis: The Myths and the Facts. Mediators of Inflammation, 2013, Article ID: 714653.

[44]   Knekt, P., Jarvinen, R., Reunanen, A. and Maatela, J. (1996) Flavonoid Intake and Coronary Mortality in Finland: A Cohort Study. British Medical Journal, 312, 478-481.

[45]   Assmann, G. and Schulte, H. (1988) The Prospective Cardiovascular Münster (PROCAM) Study: Prevalence of Hyperlipidemia in Persons with Hypertension and/or Diabetes Mellitus and the Relationship to Coronary Heart Disease. American Heart Journal, 116, 1713-1724.

[46]   Chai, S.C., Hooshmand, S., Saadat, R.L., Payton, M.E., Brummel-Smith, K. and Arjmandi, B.H. (2012) Daily Apple versus Dried Plum: Impact on Cardiovascular Disease Risk Factors in Postmenopausal Women. Journal of the Academy of Nutrition and Dietetics, 112, 1158-1168.

[47]   Ravn-Haren, G., Dragsted, L.O., Buch-Andersen, T., Jensen, E.N., Jensen, R.I., Németh-Balogh, M., Paulovicsová, B., Bergstr?m, A., Wilcks, A., Licht, T.R., Markowski, J. and Bügel, S. (2013) Intake of Whole Apples or Clear Apple Juice Has Contrasting Effects on Plasma Lipids in Healthy Volunteers. European Journal of Nutrition, 52, 1875-1889.

[48]   Nagasako-Akazome, Y., Kanda, T., Ohtake, Y., Shimasaki, H. and Kobayashi, T. (2007) Apple Polyphenols Influence Cholesterol Metabolism in Healthy Subjects with Relatively High Body Mass Index. Journal of Oleo Science, 56, 417-428.

[49]   Hyson, D., Studebaker-Hallman, D., Davis, P.A. and Gershwin, M.E. (2000) Apple Juice Consumption Reduces Plasma Low-Density Lipoprotein Oxidation in Healthy Men and Women. Journal of Medicinal Food, 3, 159-166.

[50]   Barth, S.W., Koch, T.C., Watzl, B., Dietrich, H., Will, F. and Bub, A. (2012) Moderate Effects of Apple Juice Consumption on Obesity-Related Markers in Obese Men: Impact of Diet-Gene Interaction on Body Fat Content. European Journal of Nutrition, 51, 841-850.

[51]   Lorin, J., Zeller, M., Guilland, J.C., Cottin, Y., Vergely, C. and Rochette, L. (2014) Arginine and Nitric Oxide Synthase: Regulatory Mechanisms and Cardiovascular Aspects. Molecular Nutrition & Food Research, 58, 101-116.

[52]   Loke, W.M., Hodgson, J.M., Proudfoot, J.M., McKinley, A.J., Puddey, I.B. and Croft, K.D. (2008) Pure Dietary Flavonoids Quercetin and (?)-epicatechin Augment Nitric Oxide Products and Reduce Endothelin-1 Acutely in Healthy Men. American Journal of Clinical Nutrition, 88, 1018-1025.

[53]   Galleano, M., Pechanova, O. and Fraga, C.G. (2010) Hypertension, Nitric Oxide, Oxidants, and Dietary Plant Polyphenols. Current Pharmaceutical Biotechnology, 11, 837-848.

[54]   Bondonno, C.P., Yang, X., Croft, K.D., Considine, M.J., Ward, N.C., Rich, L., Puddey, I.B., Swinny, E., Mubarak, A. and Hodgson, J.M. (2012) Flavonoid-Rich Apples and Nitrate-Rich Spinach Augment Nitric Oxide Status and Improve Endothelial Function in Healthy Men and Women: A Randomized Controlled Trial. Free Radical Biology and Medicine, 52, 95-102.

[55]   Auclair, S., Chironi, G., Milenkovic, D., Hollman, P.C., Renard, C.M., Mégnien, J.L., Gariepy, J., Paul, J.L., Simon, A. and Scalbert, A. (2010) The Regular Consumption of a Polyphenol-Rich Apple Does Not Influence Endothelial Function: A Randomised Double-Blind Trial in Hypercholesterolemic Adults. European Journal of Clinical Nutrition, 64, 1158-1165.

[56]   Andre, C.M., Greenwood, J.M., Walker, E.G., Rassam, M., Sullivan, M., Evers, D., Perry, N.B. and Laing, W.A. (2012) Anti-Inflammatory Procyanidins and Triterpenes in 109 Apple Varieties. Journal of Agricultural and Food Chemistry, 60, 10546-10554.

[57]   González-Jiménez, E., Montero-Alonso, M.A. and Schmidt-Ríovalle, J. (2013) C-Reactive Protein as a Biochemical Marker of Cardiovascular Risk. Nutrición Hospitalaria, 28, 2182-2187.

[58]   Chen, Y.R. and Zweier, J.L. (2014) Cardiac Mitochondria and Reactive Oxygen Species Generation. Circulation Research, 114, 524-537.

[59]   Ko, S.H., Choi, S.W., Ye, S.K., Cho, B.L., Kim, H.S. and Chung, M.H. (2005) Comparison of the Antioxidant Activities of Nine Different Fruits in Human Plasma. Journal of Medicinal Food, 8, 41-46.

[60]   Machlin, J. and Bendich, A. (1987) Free Radical Tissue Damage: Protective Role of Antioxidant Nutrients. FASEB Journal, 1, 441-445.

[61]   Carbone, K., Giannini, B., Picchi, V., Lo Scalzo, R. and Cecchini, F. (2011) Phenolic Composition and Free Radical Scavenging Activity of Different Apple Varieties in Relation to the Cultivar, Tissue Type and Storage. Food Chemistry, 127, 493-500.

[62]   Wolfe, K., Wu, X.Z. and Liu, R.H. (2003) Antioxidant Activity of Apple Peels. Journal of Agricultural and Food Chemistry, 51, 609-614.

[63]   Zardo, D.M., Silva, K.M., Guyot, S. and Nogueira, A. (2013) Phenolic Profile and Antioxidant Capacity of the Principal Apples Produced in Brazil. International Journal of Food Sciences and Nutrition, 64, 611-620.

[64]   Wojdylo, A., Oszmiański, J. and Laskowski, P. (2008) Polyphenolic Compounds and Antioxidant Activity of New and Old Apple Varieties. Journal of Agricultural and Food Chemistry, 56, 6520-6530.

[65]   Lea, A.G.H. and Tinberlake, C.F. (1974) The Phenolics of Ciders: 1. Procyanidins. Journal of the Science of Food and Agriculture, 25, 1537-1545.

[66]   Goupy, P., Amiot, M.J., Richard-Forget, F., Duprat, F., Aubert, S. and Nicolas, J. (1995) Enzymatic Browning of Model Solutions and Apple Phenolic Extracts by Apple Polyphenol Oxidase. Journal of Food Science, 60, 497-501.

[67]   Burda, S., Oleszek, W. and Lee, C.Y. (1990) Phenolic Compounds and Their Changes in Apples during Maturation and Cold Storage. Journal of Agricultural and Food Chemistry, 38, 945-948.

[68]   Sánchez-Moreno, C. (2002) Compuestos polifenólicos: Efectos fisiológicos: Actividad antioxidante. Alimentaria, 329, 29-40.

[69]   Maffei, F., Tarozzi, A., Carbone, F., Marchesi, A., Hrelia, S., Angeloni, C., Forti, G. and Hrelia, P. (2007) Relevance of Apple Consumption for Protection against Oxidative Damage Induced by Hydrogen Peroxide in Human Lymphocytes. British Journal of Nutrition, 97, 921-927.

[70]   Briviba, K., Stracke, B.A., Rufer, C.E., Watzl, B., Weibel, F.P. and Bub, A. (2007) Effect of Consumption of Organically and Conventionally Produced Apples on Antioxidant Activity and DNA Damage in Humans. Journal of Agricultural and Food Chemistry, 55, 7716-7721.

[71]   Vieira, F.G., Di Pietro, P.F., da Silva, E.L., Borges, G.S., Nunes, E.C. and Fett, R. (2012) Improvement of Serum Antioxidant Status in Humans after the Acute Intake of Apple Juices. Nutrition Research, 32, 229-232.

[72]   Lotito, S.B. and Frei, B. (2004) The Increase in Human Plasma Antioxidant Capacity after Apple Consumption Is Due to the Metabolic Effect of Fructose on Urate, Not Apple-Derived Antioxidant Flavonoids. Free Radical Biology and Medicine, 37, 251-258.

[73]   Avci, A., Atli, T., Eruder, I., Varli, M., Devrim,E., Turgay, S. and Durak, I. (2007) Effect of Apple Consumption on Plasma and Erythrocyte Antioxidant Parameters in Elderly Subjects. Experimental Aging Research, 33, 429-437.

[74]   Steinberg, D., Parthasarathy, S., Carew, T.E., Khoo, J.C. and Witztum, J.L. (1989) Beyond Cholesterols Modifications of Low-Density Lipoprotein that Increase Its Atherogenicity. New England Journal of Medicine, 320, 915-924.

[75]   Steinbrecher, U.P., Parthasarathy, S., Leake, D.S., Witztum, J.L. and Steinberg, D. (1984) Modification of Low Density Lipoprotein by Endothelial Cells Involves Lipid Peroxidation and Degradation of Low Density Lipoprotein Phospholipids. Proceedings of the National Academy of Sciences of the United States of America, 81, 3883-3887.

[76]   Henriksen, T., Mahoney, E.M. and Steinberg, D. (1983) Enhanced Macrophage Degradation of Biologically Modified Low Density Lipoprotein. Arteriosclerosis, Thrombosis, and Vascular Biology, 3, 149-159.

[77]   Zhu, Q.Y., Huang, Y. and Chen, Z.Y. (2000) Interaction between Flavonoids and α-Tocopherol in Human Low Density Lipoprotein. Journal of Nutritional Biochemistry, 11, 14-21.

[78]   Zhao, S., Bomser, J., Joseph, E.L. and Di Silvestro, R.A. (2013) Intakes of Apples or Apple Polyphenols Decrease Plasma Values for Oxidized Low-Density Lipoprotein/β2-Glycoprotein I Complex. Journal of Functional Foods, 5, 493-497.

[79]   Matsuura, E., Kobayashi, K., Inoue, K., Lopez, L. and Shoenfeld, Y. (2005) Oxidized LDL/β2-Glycoprotein I Complexes: New Aspects in Atherosclerosis. Lupus, 14, 736-741.