: Am J Clin Nutr. 2003 Sep;78(3 Suppl):517S-520S. : Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals.
Liu RH.
Department of Food Science and the Institute of Comparative and Environmental Toxicology, Cornell University, Ithaca, NY 14853, USA.

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
: Am J Clin Nutr. 2003 Sep;78(3):414-21. : Food and nutrient intakes and asthma risk in young adults.
Woods RK, Walters EH, Raven JM, Wolfe R, Ireland PD, Thien FC, Abramson MJ.
Department of Epidemiology & Preventive Medicine, Central and Eastern Clinical School, Monash University, and The Alfred Hospital, Melbourne, Victoria, Australia.

BACKGROUND: Some aspects of diet are relatively newly recognized potential risk factors for asthma, but the evidence to date is conflicting. OBJECTIVE: The goal was to determine whether the food and nutrient intakes of adults with asthma differ from those of adults without asthma. DESIGN: This was a community-based, cross-sectional study of 1601 young adults ( +/- SD age: 34.6 +/- 7.1 y) who were initially recruited by random selection from the federal electoral rolls in Melbourne in 1999. Subjects completed a detailed respiratory questionnaire, a validated semiquantitative food-frequency questionnaire, skin-prick testing, and lung function tests, including a methacholine challenge test for bronchial hyperreactivity (BHR). A total of 25 nutrients and 47 food groups were analyzed by using multiple logistic regression with alternate definitions of asthma and atopy as the outcomes. RESULTS: Whole milk appeared to protect against current asthma (odds ratio: 0.66; 95% CI: 0.46, 0.97), doctor-diagnosed asthma (0.73; 0.54, 0.99), BHR (0.68; 0.48, 0.92), and atopy (0.71; 0.54, 0.94). Conversely, soy beverage was associated with an increased risk of current asthma (2.05; 1.19, 3.53), doctor-diagnosed asthma (1.69; 1.04, 2.77), and BHR (1.65; 1.00, 2.71). Apples and pears appeared to protect against current asthma (0.83; 0.71, 0.98), asthma (0.88; 0.78, 1.00), and BHR (0.88; 0.77, 1.00). CONCLUSIONS: The consumption of dairy products, soy beverages, and apples and pears, but not of nutrients per se, was associated with a range of asthma definitions. Dietary modification after diagnosis is one possible explanation for this finding. 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.
Am J Cardiol. 2003 Dec 1;92(11):1335-9. : Relation of dietary fat and fiber to elevation of C-reactive protein.
King DE, Egan BM, Geesey ME.
Department of Family Medicine, Medical University of South Carolina, Charleston, South Carolina, USA

We examined the relation of dietary fiber, fat, and other dietary factors to levels of highly sensitive C-reactive protein (CRP) in 4,900 adult participants in the 1999 to 2000 National Health and Nutrition Examination Survey (NHANES 99-00), which was a cross-sectional study of a nationally representative sample of noninstitutionalized United States residents. After controlling for demographic factors, body mass index, smoking, alcohol consumption, exercise, and total caloric intake, subjects in the third and fourth highest quartiles of fiber consumption had a lower risk of elevated CRP (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.43 to 0.96; OR 0.58, 95% CI 0.38 to 0.88, respectively) compared with the lowest quartile. Saturated fat consumption was modestly associated with elevated CRP (third quartile: OR 1.58, 95% CI 1.02 to 2.44; fourth quartile 1.44, 95% CI 0.80 to 2.58). The findings suggest that inflammation may link dietary fiber and fat to cardiovascular disease.
Am J Kidney Dis. 2003 Jul;42(1):44-52. : Relationship between C-reactive protein, albumin, and cardiovascular disease in patients with chronic kidney disease.
Menon V, Wang X, Greene T, Beck GJ, Kusek JW, Marcovina SM, Levey AS, Sarnak MJ.

BACKGROUND: C-Reactive protein (CRP) level is elevated in kidney failure and may be related to malnutrition and cardiovascular disease (CVD). Data are limited regarding relationships between CRP levels and glomerular filtration rate (GFR), nutritional indices, and CVD in patients with earlier stages of kidney disease. METHODS: CRP was assayed from samples from the Modification of Diet in Renal Disease (MDRD) Study (n = 801). CRP distributions were compared between the MDRD Study and National Health and Nutrition Examination Survey (NHANES; 1999 to 2000). Associations between CRP level and GFR, nutritional indices, serum albumin levels, and CVD risk factors were examined in the MDRD Study. RESULTS: Geometric means of CRP, adjusted for age and sex, were similar in NHANES (0.23 mg/dL) and the MDRD Study (0.22 mg/dL). In the MDRD Study, CRP level was related directly to measures of body fat and CVD risk factors, inversely with serum albumin level and energy intake, and unrelated to GFR. In multivariable analysis adjusting for other determinants of serum albumin level, high CRP level (>0.6 mg/dL) was associated with a 0.07-g/dL (0.7-g/L; 95% confidence interval [CI], 0.03 to 0.12) lower mean serum albumin level. After adjusting for traditional CVD risk factors, the odds of CVD were 1.73 (95% CI, 1.07 to 2.78) times greater in subjects with a high CRP level. CONCLUSION: GFR level does not appear to influence CRP level in the earlier stages of chronic kidney disease. CRP levels are independently associated with serum albumin level and CVD prevalence. Inflammation may be involved in the pathophysiological state of malnutrition and CVD in the earlier stages of predominantly nondiabetic kidney disease.
J Am Dent Assoc. 2003 Sep;134(9):1185-92. :
Tooth loss and dietary intake.
Hung HC, Willett W, Ascherio A, Rosner BA, Rimm E, Joshipura KJ.
Department of Epidemiology, Harvard School of Public Health, Boston, USA.

BACKGROUND: Several studies have reported that impaired dentition status is associated with poor nutritional intake. However, most of these studies are cross-sectional and thus are unable to clarify the temporal sequence. METHODS: We assessed the longitudinal relation between tooth loss and changes in consumption of fruits and vegetables and of nutrients important for general health among 31,813 eligible male health professionals. RESULTS: Subjects who lost five or more teeth had a significantly smaller reduction in consumption of dietary cholesterol and vitamin B12, greater reduction in consumption of polyunsaturated fat and smaller increase in consumption of dietary fiber and whole fruit than did subjects who had lost no teeth. Men who had lost teeth also were more likely to stop eating apples, pears and raw carrots. CONCLUSIONS: The results support the temporal association between tooth loss and detrimental changes in dietary intakes, which could contribute to increased risk of developing chronic diseases. PRACTICE IMPLICATIONS: Dietary evaluation and recommendations can be incorporated into dental visits to provide a greater benefit to patients.
Int J Cancer. 2003 Jun 20;105(3):413-8. : Intake of fruits, vegetables and selected micronutrients in relation to the risk of breast cancer.
Malin AS, Qi D, Shu XO, Gao YT, Friedmann JM, Jin F, Zheng W.
Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.

High fruit and vegetable intake has been linked with a reduced risk of breast cancer, but evidence is not consistent. We investigated the associations of breast cancer risk with vegetables, fruits and related micronutrient intake in a population-based case-control study among Chinese women in Shanghai, where dietary patterns differ substantially from other study populations. Included in the study were 1,459 incident breast cancer cases and 1,556 frequency-matched controls. Usual dietary habits were assessed by in-person interviews. Logistic regression was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to measure strength of the associations. There was no association between breast cancer risk and total vegetable intake. The risk of breast cancer declined, however, with increasing intake of dark yellow-orange vegetables (trend test, p = 0.02), Chinese white turnips (trend test, p Am J Clin Nutr. 2003 Jun;77(6):1400-8. : Flavonoid intake and the risk of cardiovascular disease in women.
Sesso HD, Gaziano JM, Liu S, Buring JE.
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215,

BACKGROUND: Despite emerging evidence of the role of flavonoids in cardiovascular disease (CVD) prevention, the association remains unclear. OBJECTIVE: We examined whether flavonoids and selected flavonols and flavones or their food sources are associated with CVD risk. DESIGN: Women (n = 38 445) free of CVD and cancer participated in a prospective study with a mean follow-up of 6.9 y. On the basis of a food-frequency questionnaire, total flavonoids and selected flavonols and flavones were categorized into quintiles, and food sources were categorized into 4 groups. Relative risks were computed for important vascular events (519 events; excluding revascularizations) and CVD (729 events), including myocardial infarction, stroke, revascularization, and CVD death. RESULTS: The mean flavonoid intake was 24.6 +/- 18.5 mg/d, primarily as quercetin (70.2%). For both CVD and important vascular events, no significant linear trend was observed across quintiles of flavonoid intake (P = 0.63 and 0.80, respectively). No individual flavonol or flavone was associated with CVD. Broccoli and apple consumption were associated with nonsignificant reductions in CVD risk: 25-30% and 13-22%, respectively. A small proportion of women (n = 1185) consuming > or =4 cups (946 mL) tea/d had a reduction in the risk of important vascular events but with a nonsignificant linear trend (P = 0.07). CONCLUSIONS: Flavonoid intake was not strongly associated with a reduced risk of CVD. The nonsignificant inverse associations for broccoli, apples, and tea with CVD were not mediated by flavonoids and warrant further study.
Acta Odontol Scand. 2003 Apr;61(2):100-4. : Dental health behavior, gastroesophageal disorders and dietary habits among Norwegian recruits in 1990 and 1999.
Myklebust S, Espelid I, Svalestad S, Tveit AB.
Faculty of Odontology, University of Bergen, Norway.

A questionnaire was given to representative samples of Norwegian recruits in 1990 and 1999 to explore dental health habits, history of gastroesophageal disorders and diet with possible relations to dental erosion. The samples were 792 (mean age 20.9 years) and 676 (mean age 21.6 years), respectively, and the corresponding responses were 62% and 100%. Minor differences in self-reported dental health habits and gastroesophageal disorders were found. The respondents' dentists had provided information about dental erosion for 8.2% of the respondents in 1990 versus 14.5% in 1999. There was an increase in the reported frequency of daily intake of juice from 17% to 24% (P = 0.006) and carbonated soft drink from 54% to 61% (P = 0.025) in the period 1990-99. The frequency of training activity showed minor changes, but in 1999 it was more common to drink during exercise (94% versus 74% in 1990, P < 0.001), and the majority drank water. Sixteen percent of recruits ate oranges daily in 1990; in 1999 this had dropped to 11% (P = 0.012). The corresponding proportion that ate apples daily had dropped from 17% to 8% in the period (P < 0.001). It is likely that lifestyle factors related to diet among young men have changed in the period 1990-99 in a direction that may increase the prevalence of dental erosions
Eur J Cancer Prev. 2003 Apr;12(2):135-43. : Oral cancer in Southern India: the influence of body size, diet, infections and sexual practices.
Rajkumar T, Sridhar H, Balaram P, Vaccarella S, Gajalakshmi V, Nandakumar A, Ramdas K, Jayshree R, Munoz N, Herrero R, Franceschi S, Weiderpass E.
Cancer Institute (WIA), Adyar, Chennai 600 020, India.

Between 1996 and 1999, we carried out a study in Southern India on risk factors for oral cancer. The study included 591 incident cases of cancer of the oral cavity (282 women) and 582 hospital controls (290 women). Height was unrelated to oral cancer risk. Body mass index (weight in kilograms/height in metres squared) was inversely associated with risk (P for trend<0.001). Paan chewers with low BMI were at particularly high risk. Risk was increased among subjects consuming meat (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.00-2.37), ham and salami (OR 4.40, 95% CI 2.88-6.71) two or more times per week. Frequent consumption of fish, eggs, raw green vegetables, cruciferous vegetables, carrots, pulses, apples or pears, citrus fruit, and overall consumption of vegetables and fruit decreased oral cancer risk (P for trend for each of these items less than or equal to 0.001). The risk associated with low consumption of vegetables was higher among smokers than among non-smokers. Men, but not women, who practised oral sex had an increased oral cancer risk (OR 3.14, 95% CI 1.15-8.63). Women with more than one sexual partner during life were at increased oral cancer risk (OR 9.93, 95% CI 1.57-62.9).
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
: Nutrition. 2003 Mar;19(3):253-6. : 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.
Instituto de Medicina Social, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

OBJECTIVE: We investigated the effect of fruit intake on body weight change. METHODS: Hypercholesterolemic, overweight (body mass index > 25 kg/m2), and non-smoking women, 30 to 50 y of age, were randomized to receive, free of charge, one of three dietary supplements: apples, pears, or oat cookies. Women were instructed to eat one supplement three times a day in a total of six meals a day. Participants (411 women) were recruited at a primary care center of the State University of Rio de Janeiro, Brazil. Fifty-one women had fasting blood cholesterol levels greater than 6.2 mM/L (240 mg/dL) and 49 were randomized. Subjects were instructed by a dietitian to eat a diet (55% of energy from carbohydrate, 15% from protein, and 30% from fat) to encourage weight reduction at the rate of 1 kg/mo. RESULTS: After 12 wk of follow-up, the fruit group lost 1.22 kg (95% confidence interval = 0.44-1.85), whereas the oat group had a non-significant weight loss of 0.88 kg (0.37-2.13). The difference between the two groups was statistically significant (P = 0.004). To explore further the body weight loss associated with fruit intake, we measured the ratio of glucose to insulin. A significantly greater decrease of blood glucose was observed among those who had eaten fruits compared with those who had eaten oat cookies, but the glucose:insulin ratio was not statistically different from baseline to follow-up. Adherence to the diet was high, as indicated by changes in serum triacylglycerols, total cholesterol, and reported fruit intake. Fruit intake in the oat group throughout treatment was minimal. CONCLUSIONS: Intake of fruits may contribute to weight loss
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
Free Radic Biol Med. 2002 Dec 15;33(12):1693-702. : Uptake and metabolism of epicatechin and its access to the brain after oral ingestion.
Abd El Mohsen MM, Kuhnle G, Rechner AR, Schroeter H, Rose S, Jenner P, Rice-Evans CA.
Antioxidant Research Group, Wolfson Centre for Age-Related Diseases, GKT School of Biomedical Sciences, King's College, London, England, UK

Epicatechin is a flavan-3-ol that is commonly present in green teas, red wine, cocoa products, and many fruits, such as apples. There is considerable interest in the bioavailability of epicatechin after oral ingestion. In vivo studies have shown that low levels of epicatechin are absorbed and found in the circulation as glucuronides, methylated and sulfated forms. Recent research has demonstrated protective effects of epicatechin and one of its in vivo metabolites, 3'-O-methyl epicatechin, against neuronal cell death induced by oxidative stress. Thus, we are interested in the ability of ingested epicatechin to cross the blood brain barrier and target the brain. Rats were administered 100 mg/kg body weight/d epicatechin orally for 1, 5, and 10 d. Plasma and brain extracts were analyzed by HPLC with photodiode array detection and LC-MS/MS. This study reports the presence of the epicatechin glucuronide and 3'-O-methyl epicatechin glucuronide formed after oral ingestion in the rat brain tissue.
1: J Agric Food Chem. 2002 Aug 14;50(17):4909-15. : New sources of dietary myosmine uptake from cereals, fruits, vegetables, and milk.
Tyroller S, Zwickenpflug W, Richter E.
Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians University, Nussbaumstrasse 26, D-80336 Munich, Germany.

Myosmine has been regarded as a specific tobacco alkaloid until investigations pointed out that nuts and nut products constitute a significant source of myosmine. In the present study it is shown that the occurrence of myosmine is widespread throughout a large number of plant families. Using a method for extraction practicable for all examined foods, quantitative analysis through internal standard addition showed nanograms per gram amounts. Positively tested edibles were staple foods such as maize, rice, wheat flour, millet, potato, and milk and also cocoa, popcorn, tomato, carrot, pineapple, kiwi, and apples. No myosmine was detectable in other vegetables and fruits such as lettuce, spinach, cucumber, onion, banana, tangerines, and grapes. Myosmine is easily nitrosated giving rise to a DNA adduct identical to the esophageal tobacco carcinogen N-nitrosonornicotine. Therefore, the role of dietary myosmine in esophageal adenocarcinoma should be further investigated.
Curr Atheroscler Rep. 2003 Nov;5(6):492-9. : Dietary intake of fruits and vegetables and risk of cardiovascular disease.
Bazzano LA, Serdula MK, Liu S.
Division of Preventive Medicine, Harvard Medical School & Brigham and Women's Hospital, 900 Commonwealth Avenue, Boston, MA 02215, USA.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States and worldwide. In this review, we examine the scientific evidence in support of current dietary recommendations to increase fruit and vegetable intake for CVD prevention. Available evidence indicates that persons who consume more fruits and vegetables often have lower prevalence of important risk factors for CVD, including hypertension, obesity, and type 2 diabetes mellitus. Recent large, prospective studies also show a direct inverse association between fruit and vegetable intake and the development of CVD incidents such as coronary heart disease and stroke. However, the biologic mechanisms whereby fruits and vegetables may exert their effects are not entirely clear and are likely to be multiple. Many nutrients and phytochemicals in fruits and vegetables, including fiber, potassium, and folate, could be independently or jointly responsible for the apparent reduction in CVD risk. Functional aspects of fruits and vegetables, such as their low dietary glycemic load and energy density, may also play a significant role. Although it is important to continue our quest for mechanistic insights, given the great potential for benefits already known, greater efforts and resources are needed to support dietary changes that encourage increased fruit and vegetable intake