reduced risk of various diseases (Kuhnau 1976, Hollman and Katan 1999, Hollman 2001,

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1 Apple Phenolics and Their Health Benefits Numerous studies conducted on apple phenolics showed positive outcomes and a strong relationship between the phenolic compounds, which have antioxidant activity, and reduced risk of various diseases (Kuhnau 1976, Hollman and Katan 1999, Hollman 2001, Lee, Kim et al. 2003, Liu 2003, Boyer and Liu 2004, Barth, Fähndrich et al. 2005, Martínez- Navarrete, del Mar Camacho Vidal et al. 2008, Jan, Kamli et al. 2010, Fu, Xu et al. 2011). Apple phenolics may protect human cells from oxidative damage and has been associated with prevention of several diseases (Hollman and Katan 1999, Hollman 2001, Lee, Kim et al. 2003, Liu 2003, Boyer and Liu 2004). Cancers Research suggests that apple phenolics may reduce the risk of lung cancer (Boyer and Liu 2004), especially among current and past smokers (Cutler, Nettleton et al. 2008). In general, individual fruits and vegetables are not related with lung cancer risk in humans, however, apples are among the few examples of fruits which are strongly associated with a significantly reduced risk of lung cancer (Hertog, Feskens et al. 1994). As reviewed by Boyer and Liu (2004) studies in Finland and Hawaii found apple phenolics reduce lung cancer risk and concluded that only apples were inversely related to the risk of lung cancer. According to Fiuza et al. (2004), gallic acid derivatives in apple phenolics are known to cause apoptosis in tumor cell lines as well as inhibiting lymphocyte proliferation. In addition, apple flavonoids were shown to have a synergistic effect in reducing cancer risk (Hertog, Feskens et al. 1994). Quercetin glycosides and procyanidin have been linked with strong antioxidant activity in in vitro observation (Knekt, Isotupa et al. 2000). Quercetin has also demonstrates the ability to retard the growth of cancer cells in colon 6

2 and liver (in vitro) (Eberhardt, Lee et al. 2000, Rossi, Negri et al. 2006, McCann, Gill et al. 2007). Cardiovascular diseases Apple phenolics may help reducing the risk of cardiovascular diseases (Hollman and Katan, 1999; Knekt et al., 1996; Sesso et al., 2003). Apple phenolics help to improve circulation. Research shows that apple apple phenolics may help to reduce the risk of thrombotic stroke. This may result from their contribution in the reduction of cholesterol level, especially LDL (bad cholesterol). Respiratory health According to a study from Australia, apple phenolics may reduce the risk of asthma and bronchial hypersensitivity (Woods, Walters et al. 2003), while other known antioxidants such as vitamin E, retinol and vitamin C have no effect (Shaheen, Sterne et al. 2001). A similar inverse relationship was found in studies conducted in Netherlands, Wales and Finland, Shaheen, Sterne et al. (2001) suggested that incorporating apple phenolics in one s diet will decrease the severity of asthma and its symptoms. Diabetes The risk of developing type II diabetes may also be lowered by apple phenolics intake. Boyer and Liu (2004) reviewed a human observational study, in which it was suggested that apple phenolics might reduce the risk by 28%. In addition to their lowering diabetes risk, apple phenolics and fibre help in lowering the blood glucose level and balancing the body s insulin response (Knekt, Kumpulainen et al. 7

3 2002, Clifford 2004, Scalbert, Manach et al. 2005, Bhushan, Kalia et al. 2008, Hanhineva, Törrönen et al. 2010, Muraki, Imamura et al. 2013). A recently published health population study further emphasises that apple was amongst the fruits with a significant reduction effect of the risk of having type II diabetes (up to 23%). This positive health effect was observed when the phenolics were absorbed and bioavailable (Muraki, Imamura et al. 2013). In other studies based on animal models and a number of human studies, apple phenolics (mainly chlorogenic acid and quercetin) have been linked to attenuated postprandial glycemic responses and fasting hyperglycemia and improved acute insulin secretion and insulin sensitivity (Clifford 2004, Scalbert, Manach et al. 2005, Hanhineva, Törrönen et al. 2010). References 1. Barth, S. W., C. Fähndrich, A. Bub, H. Dietrich, B. Watzl, F. Will, K. Briviba and G. Rechkemmer (2005). "Cloudy apple juice decreases DNA damage, hyperproliferation and aberrant crypt foci development in the distal colon of DMH-initiated rats." Carcinogenesis 26(8): Bhushan, S., K. Kalia, M. Sharma, B. Singh and P. S. Ahuja (2008). "Processing of apple pomace for bioactive molecules." Critical Reviews in Biotechnology 28(4): Boyer, J. and R. H. Liu (2004). "Apple phytochemicals and their health benefits." Nutrition Journal 3: Clifford, M. N. (2004). "Diet-derived phenols in plasma and tissues and their implications for health." Planta Medica 70(12):

4 5. Cutler, G. J., J. A. Nettleton, J. A. Ross, L. J. Harnack, D. R. Jacobs Jr, C. G. Scrafford, L. M. Barraj, P. J. Mink and K. Robien (2008). "Dietary flavonoid intake and risk of cancer in postmenopausal women: The Iowa Women's Health Study." International Journal of Cancer 123(3): Eberhardt, M. V., C. Y. Lee and R. H. Liu (2000). "Antioxidant activity of fresh apples." Nature 405(6789): Fiuza, S. M., C. Gomes, L. J. Teixeira, M. T. Girão Da Cruz, M. N. D. S. Cordeiro, N. Milhazes, F. Borges and M. P. M. Marques (2004). "Phenolic acid derivatives with potential anticancer properties - A structure-activity relationship study. Part 1: Methyl, propyl and octyl esters of caffeic and gallic acids." Bioorganic and Medicinal Chemistry 12(13): Fu, L., B. T. Xu, X. R. Xu, R. Y. Gan, Y. Zhang, E. Q. Xia and H. B. Li (2011). "Antioxidant capacities and total phenolic contents of 62 fruits." Food Chemistry 129(2): Hanhineva, K., R. Törrönen, I. Bondia-Pons, J. Pekkinen, M. Kolehmainen, H. Mykkänen and K. Poutanen (2010). "Impact of dietary polyphenols on carbohydrate metabolism." International Journal of Molecular Sciences 11(4): Hertog, M. G. L., E. J. M. Feskens, P. C. H. Hollman, M. B. Katan and D. Kromhout (1994). "Dietary flavonoids and cancer risk in the Zutphen elderly study." Nutrition and Cancer 22(2): Hollman, P. C. H. (2001). "Evidence for health benefits of plant phenols: Local or systemic effects?" Journal of the Science of Food and Agriculture 81(9): Hollman, P. C. H. and M. B. Katan (1999). "Dietary flavonoids: Intake, health effects and bioavailability." Food and Chemical Toxicology 37(9-10):

5 13. Jan, A. T., M. R. Kamli, I. Murtaza, J. B. Singh, A. Ali and Q. M. R. Haq (2010). "Dietary flavonoid quercetin and associated health benefits-an overview." Food Reviews International 26(3): Knekt, P., S. Isotupa, H. Rissanen, M. Heliövaara, R. Järvinen, S. Häkkinen, A. Aromaa and A. Reunanen (2000). "Quercetin intake and the incidence of cerebrovascular disease." European Journal of Clinical Nutrition 54(5): Knekt, P., J. Kumpulainen, R. Järvinen, H. Rissanen, M. Heliövaara, A. Reunanen, T. Hakulinen and A. Aromaa (2002). "Flavonoid intake and risk of chronic diseases." American Journal of Clinical Nutrition 76(3): Kuhnau, J. (1976). "The flavonoids: A class of semi-essential food components: Their role in human nutrition." World Review of Nutrition and Dietetics(24): Lee, K. W., Y. J. Kim, D. O. Kim, H. J. Lee and C. Y. Lee (2003). "Major phenolics in apple and their contribution to the total antioxidant capacity." Journal of Agricultural and Food Chemistry 51(22): Liu, R. H. (2003). "Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals." American Journal of Clinical Nutrition 78(3 SUPPL.): 517S-520S. 19. Martínez-Navarrete, N., M. del Mar Camacho Vidal and J. José Martínez Lahuerta (2008). "The bioactive compounds of fruits and their effects on health (in Spanish)." Actividad Dietetica 12(2): McCann, M. J., C. I. R. Gill, G. O' Brien, J. R. Rao, W. C. McRoberts, P. Hughes, R. McEntee and I. R. Rowland (2007). "Anti-cancer properties of phenolics from apple waste on colon carcinogenesis in vitro." Food and Chemical Toxicology 45(7):

6 21. Muraki, I., F. Imamura, J. E. Manson, F. B. Hu, W. C. Willet, R. M. v. Dam and Q. Sun (2013). "Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies." British Medical Journal 347: f Rossi, M., E. Negri, R. Talamini, C. Bosetti, M. Parpinel, P. Gnagnarella, S. Franceschi, L. Dal Maso, M. Montella, A. Giacosa and C. La Vecchia (2006). "Flavonoids and colorectal cancer in Italy." Cancer Epidemiology Biomarkers and Prevention 15(8): Scalbert, A., C. Manach, C. Morand, C. Rémésy and L. Jiménez (2005). "Dietary polyphenols and the prevention of diseases." Critical Reviews in Food Science and Nutrition 45(4): Shaheen, S. O., J. A. C. Sterne, R. L. Thompson, C. E. Songhurst, B. M. Margetts and P. G. J. Burney (2001). "Dietary antioxidants and asthma in adults: Population-based case-control study." American Journal of Respiratory and Critical Care Medicine 164(10 I): Woods, R. K., E. H. Walters, J. M. Raven, R. Wolfe, P. D. Ireland, F. C. K. Thien and M. J. Abramson (2003). "Food and nutrient intakes and asthma risk in young adults." American Journal of Clinical Nutrition 78(3):

Dietary Flavonol Intake May Lower Stroke Risk in Men and Women 1,2

The Journal of Nutrition Nutritional Epidemiology Dietary Flavonol Intake May Lower Stroke Risk in Men and Women 1,2 PeterC.H.Hollman, 3,4 * Anouk Geelen, 3 and Daan Kromhout 3 3 Wageningen University,