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• Researchers at the University of Washington have increased the lifespan of mice by 18.5%, by genetically engineering intracellular overexpression of the catalase enzyme. Polyphenols found in apples increase catalase expression.

• Apple polyphenols show anti-cancer benefits, and may prevent or treat other age-related diseases including heart disease, Alzheimer's Disease, stroke, diabetes, and mental decline.

• In one study, apple phytochemicals reversed age-related brain function decline in rats.

• A large-scale study on elderly human subjects in the Netherlands showed that polyphenols from apple, but not from tea, reduced the risk of lung cancer.

Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS.

Departments of Genome Sciences; Center for Molecular and Mitochondrial Medicine and Genetics, Departments of Biological Chemistry and Ecology and Evolutionary Biology, University of California, Irvine, Irvine CA 92697, USA.

To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to the peroxisome (PCAT), nucleus (NCAT), or mitochondrion (MCAT). Median and maximum lifespans were maximally increased (average 5 months, and 5.5 months, respectively) in MCAT animals. Cardiac pathology and cataract development were delayed, oxidative damage was reduced, H2O2 production and H2O2-induced aconitase inactivation were attenuated, and the development of mitochondrial deletions was reduced. These results support the free radical theory of aging and reinforce the importance of mitochondria as a source of these radicals.

PMID: 15879174 [PubMed - as supplied by publisher]

Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals^1,2,3,4

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 µmol 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

31. Eberhardt MV, Lee CY, Liu RH. Antioxidant activity of fresh apples. Nature 2000;405:903–4.[Medline]
32. Sun J, Chu Y-F, Wu X, Liu RH. Antioxidant and antiproliferative activities of fruits. J Agric Food Chem. 2002;50:7449–54.[Medline]
33. Chu Y-F, Sun J, Wu X, Liu RH. Antioxidant and antiproliferative activities of vegetables. J Agric Food Chem. 2002;50:6910–16.[Medline]

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.

Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, One University Avenue, Lowell, MA 01854, USA.

Increased oxidative stress contributes to the decline in cognitive performance during normal aging and in neurodegenerative conditions such as Alzheimer s disease. Dietary supplementation with fruits and vegetables that are high in antioxidant potential have in some cases compensated for dietary and/or genetic deficiencies that promote increased oxidative stress. 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. In addition, we demonstrate that this protective effect is not derived from the sugar content of the concentrate.

PMID: 14978604 [PubMed - indexed for MEDLINE]

Apple juice prevents oxidative stress induced by amyloid-beta in culture.

Ortiz D, Shea TB.

Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA.

Increased oxidative stress contributes to the decline in cognitive performance during normal aging and in neurodegenerative conditions such as Alzheimer's disease. Dietary supplementation with fruits and vegetables that are high in antioxidant potential have in some cases compensated for oxidative stress. Herein, we examined whether apple juice could alleviate the neurotoxic consequences of exposure of cultured neuronal cells to amyloid-beta (Abeta), since at least a portion of the neurotoxicity of Abeta is due to oxidative stress. Apple juice concentrate (AJC; 70 degree brix) was diluted into culture medium of SH-SY-5Y human neuroblastoma cells that had been differentiated for 7 days with 5 microM retinoic acid concurrent with the addition of 20 microM Abeta. AJC prevented the increased generation of reactive oxygen species (ROS) normally induced by Abeta treatment under these conditions. AJC also prevented Abeta-induced calcium influx and apoptosis, each of which results in part due to increased ROS. These findings suggest that the antioxidant potential of apple products can prevent Abeta-induced oxidative damage.

PMID: 15004325 [PubMed - indexed for MEDLINE]

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.

James A. Haley Veterans Affairs Medical Center, Tampa, Florida 33612, USA.

Antioxidants and diets supplemented with foods high in oxygen radical absorbance capacity (ORAC) reverse age-related decreases in cerebellar beta-adrenergic receptor function. We examined whether this effect was related to the antioxidant capacity of the food supplement and whether an antioxidant-rich diet reduced the levels of proinflammatory cytokines in the cerebellum. Aged male Fischer 344 rats were given apple (5 mg dry weight), spirulina (5 mg), or cucumber (5 mg) either in 0.5 ml water by oral gavage or supplied in the rat chow daily for 14 d. Electrophysiologic techniques revealed a significant decrease in beta-adrenergic receptor function in aged control rats. Spirulina reversed this effect. Apple (a food with intermediate ORAC) had an intermediate effect on cerebellar beta-adrenergic receptor physiology, and cucumber (low ORAC) had no effect, indicating that the reversal of beta-adrenergic receptor function decreases might be related to the ORAC dose. The mRNA of the proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha) and TNFbeta was also examined. RNase protection assays revealed increased levels of these cytokines in the aged cerebellum. Spirulina and apple significantly downregulated this age-related increase in proinflammatory cytokines, whereas cucumber had no effect, suggesting that one mechanism by which these diets work is by modulation of an age-related increase in inflammatory responses. Malondialdehyde (MDA) was measured as a marker of oxidative damage. Apple and spirulina but not cucumber decreased MDA levels in the aged rats. In summary, the improved beta-adrenergic receptor function in aged rats induced by diets rich in antioxidants is related to the ORAC dose, and these diets reduce proinflammatory cytokine levels.

PMID: 12122072 [PubMed - indexed for MEDLINE]

Dietary catechins and epithelial cancer incidence: the Zutphen elderly study.

Arts IC, Hollman PC, Bueno De Mesquita HB, Feskens EJ, Kromhout D.

National Institute of Public Health and the Environment (RIVM), Department of Chronic Diseases Epidemiology, PO Box 1, NL-3720 BA Bilthoven, The Netherlands. ilja.arts@rivm.nl

The flavonoids, a group of more than 4,000 polyphenolic antioxidants, are potential cancer preventive components of fruits and vegetables. Catechins, one of the 6 major groups of flavonoids, are present in high concentrations in tea as well. Our objective was to evaluate the association between intake of catechins and incidence of epithelial cancers with data from the Zutphen Elderly Study, a prospective cohort study among 728 men aged 65-84 years in 1985. The average catechin intake at baseline was 72 mg/day (range, 0-355 mg/day). After 10 years of follow-up, 96 incident epithelial cancers were recorded, including 42 cases of lung cancer. After multivariate adjustment, catechin intake was not associated with epithelial cancer (risk ratio [RR] from lowest to highest tertile: 1.00, 0.75, 0.94; p for trend: 0.82), or lung cancer (RR from lowest to highest tertile: 1.00, 0.72, 0.92; p for trend: 0.80). Catechins not from tea were borderline significantly inversely associated with lung cancer incidence (RR and 95% confidence interval [CI] for a 7.5-mg increase in intake: 0.66, 0.42-1.05), whereas catechins from tea were not. Catechins from apple, the major source of non-tea catechins, were also related to lung cancer incidence (RR and 95% CI for a 7.5-mg catechin increase: 0.67, 0.38-1.17). Because tea, the major catechin source in this population, was not associated with cancer risk, it seems unlikely that catechins are responsible for the observed inverse trend between non-tea catechins and lung cancer incidence. However, differences in bioavailability of the various catechins may play a role; effects on individual cancer sites cannot be excluded and merit further investigation. Copyright 2001 Wiley-Liss, Inc.

PMID: 11291060 [PubMed - indexed for MEDLINE]