Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer.

"Bioactive compounds" are extranutritional constituents that typically occur in small quantities in foods. They are being intensively studied to evaluate their effects on health. The impetus sparking this scientific inquiry was the result of many epidemiologic studies that have shown protective effects of plant-based diets on cardiovascular disease (CVD) and cancer. Many bioactive compounds have been discovered. These compounds vary widely in chemical structure and function and are grouped accordingly. Phenolic compounds, including their subcategory, flavonoids, are present in all plants and have been studied extensively in cereals, legumes, nuts, olive oil, vegetables, fruits, tea, and red wine. Many phenolic compounds have antioxidant properties, and some studies have demonstrated favorable effects on thrombosis and tumorogenesis and promotion. Although some epidemiologic studies have reported protective associations between flavonoids or other phenolics and CVD and cancer, other studies have not found these associations. Various phytoestrogens are present in soy, but also in flaxseed oil, whole grains, fruits, and vegetables. They have antioxidant properties, and some studies demonstrated favorable effects on other CVD risk factors, and in animal and cell culture models of cancer. However, because phytoestrogens act both as partial estrogen agonists and antagonists, their effects on cancer are likely complex. Hydroxytyrosol, one of many phenolics in olives and olive oil, is a potent antioxidant. Resveratrol, found in nuts and red wine, has antioxidant, antithrombotic, and anti-inflammatory properties, and inhibits carcinogenesis. Lycopene, a potent antioxidant carotenoid in tomatoes and other fruits, is thought to protect against prostate and other cancers, and inhibits tumor cell growth in animals. Organosulfur compounds in garlic and onions, isothiocyanates in cruciferous vegetables, and monoterpenes in citrus fruits, cherries, and herbs have anticarcinogenic actions in experimental models, as well as cardioprotective effects. In summary, numerous bioactive compounds appear to have beneficial health effects. Much scientific research needs to be conducted before we can begin to make science-based dietary recommendations. Despite this, there is sufficient evidence to recommend consuming food sources rich in bioactive compounds. From a practical perspective, this translates to recommending a diet rich in a variety of fruits, vegetables, whole grains, legumes, oils, and nuts.

[1]  H. Gylling,et al.  Reduction of serum cholesterol in postmenopausal women with previous myocardial infarction and cholesterol malabsorption induced by dietary sitostanol ester margarine: women and dietary sitostanol. , 1997, Circulation.

[2]  F. Ursini,et al.  Effect of dietary monounsaturated and polyunsaturated fatty acids on the susceptibility of plasma low density lipoproteins to oxidative modification. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[3]  Lawrence A Leiter,et al.  Effects of high- and low-isoflavone soyfoods on blood lipids, oxidized LDL, homocysteine, and blood pressure in hyperlipidemic men and women. , 2002, The American journal of clinical nutrition.

[4]  J. German,et al.  The health benefits of wine. , 2003, Annual review of nutrition.

[5]  J. Williams,et al.  Resveratrol, a polyphenolic compound found in wine, inhibits tissue factor expression in vascular cells : A possible mechanism for the cardiovascular benefits associated with moderate consumption of wine. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[6]  S. Brown,et al.  The inhibition of the oxidation of low density lipoprotein by (+)-catechin, a naturally occurring flavonoid. , 1992, Biochemical pharmacology.

[7]  J. Milner Mechanisms by which garlic and allyl sulfur compounds suppress carcinogen bioactivation. Garlic and carcinogenesis. , 2001, Advances in experimental medicine and biology.

[8]  S. Cole,et al.  Intake of vegetables rich in carotenoids and risk of coronary heart disease in men: The Physicians' Health Study. , 2001, International journal of epidemiology.

[9]  E. Feskens,et al.  Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study , 1993, The Lancet.

[10]  M. Wargovich,et al.  Garlic (Allium sativum): A review of its relationship to cancer , 1989 .

[11]  S. Ojala,et al.  Effect of soybean phytoestrogen intake on low density lipoprotein oxidation resistance. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Simons,et al.  Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women. , 2000, The American journal of cardiology.

[13]  C. Teng,et al.  Antiplatelet effects and vasorelaxing action of some constituents of Formosan plants. , 1993, Journal of natural products.

[14]  A. Dart,et al.  Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[15]  K. Setchell,et al.  Dietary isoflavones: biological effects and relevance to human health. , 1999, The Journal of nutrition.

[16]  J. Sabaté,et al.  A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study. , 1992, Archives of internal medicine.

[17]  S. Wiseman,et al.  Plasma and lipoprotein levels of tea catechins following repeated tea consumption. , 1999, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[18]  W. Zhao,et al.  Implications from and for food cultures for cardiovascular disease: diet, nutrition and cardiovascular diseases in China. , 2001, Asia Pacific journal of clinical nutrition.

[19]  W. Willett,et al.  Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers. , 2000, Journal of the National Cancer Institute.

[20]  D. Jacobs,et al.  Oat products and lipid lowering. A meta-analysis. , 1992, JAMA.

[21]  W. Willett,et al.  A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women. , 1988, The New England journal of medicine.

[22]  E. Parks,et al.  Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine , 1993, The Lancet.

[23]  Alicia Hernandez,et al.  Olive Phenol Hydroxytyrosol Prevents Passive Smoking–Induced Oxidative Stress , 2000, Circulation.

[24]  L. Beilin,et al.  Phenolic content of various beverages determines the extent of inhibition of human serum and low-density lipoprotein oxidation in vitro: identification and mechanism of action of some cinnamic acid derivatives from red wine. , 1996, Clinical science.

[25]  J. Manson,et al.  Whole-grain consumption and risk of coronary heart disease: results from the Nurses' Health Study. , 1999, The American journal of clinical nutrition.

[26]  W. Hauser,et al.  The Protective Effect of Moderate Alcohol Consumption on Ischemic Stroke , 1999 .

[27]  E. Rimm,et al.  Relation between Intake of Flavonoids and Risk for Coronary Heart Disease in Male Health Professionals , 1996, Annals of Internal Medicine.

[28]  N. Krinsky Overview of Lycopene, Carotenoids, and Disease Prevention , 1998, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[29]  J. Ordovás,et al.  Hypercholesterolemic effect of dietary cholesterol in diets enriched in polyunsaturated and saturated fat. Dietary cholesterol, fat saturation, and plasma lipids. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[30]  K. Agarwal Therapeutic actions of garlic constituents , 1996, Medicinal research reviews.

[31]  T. J. Doyle,et al.  Tea consumption and cancer incidence in a prospective cohort study of postmenopausal women. , 1996, American journal of epidemiology.

[32]  S. Sivak,et al.  Effect of Garlic on Total Serum Cholesterol , 1993, Annals of Internal Medicine.

[33]  A. Dapkevicius Isolation, identification and evaluation of natural antioxidants from aromatic herbs cultivated in Lithuania , 2002 .

[34]  J. Dwyer,et al.  Tofu and soy drinks contain phytoestrogens. , 1994, Journal of the American Dietetic Association.

[35]  T. T. Yang,et al.  Inhibitory effect of Chinese green tea on endothelial cell-induced LDL oxidation. , 2000, Atherosclerosis.

[36]  S. Meyboom,et al.  Effect of phenol-rich extra virgin olive oil on markers of oxidation in healthy volunteers , 2001, European Journal of Clinical Nutrition.

[37]  T. Truelsen,et al.  Intake of beer, wine, and spirits and risk of stroke : the copenhagen city heart study. , 1998, Stroke.

[38]  B. Holub,et al.  Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. , 1998, The Journal of nutrition.

[39]  C. M. Hasler,et al.  Functional foods: their role in disease prevention and health promotion , 1998 .

[40]  T. Moriguchi,et al.  Antioxidant and Radical Scavenging Effects of Aged Garlic Extract and its Constituents , 1994, Planta medica.

[41]  Jiang He,et al.  Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. , 2002, The American journal of clinical nutrition.

[42]  M. Gould Prevention and therapy of mammary cancer by monoterpenes , 1995, Journal of cellular biochemistry. Supplement.

[43]  C. Rice-Evans,et al.  Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants. , 1995, Archives of biochemistry and biophysics.

[44]  S. Ikemoto Cholesterol-lowering Effects of Dietary Fiber , 2000 .

[45]  Y. Ju,et al.  Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. , 2001, Cancer research.

[46]  H. Teede,et al.  Dietary soy has both beneficial and potentially adverse cardiovascular effects: a placebo-controlled study in men and postmenopausal women. , 2001, Journal of Clinical Endocrinology and Metabolism.

[47]  P. J. Jones,et al.  Dietary phytosterols: a review of metabolism, benefits and side effects. , 1995, Life sciences.

[48]  A. Elis,et al.  Hypocholesterolemic effect of lycopene and beta-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophages. , 1997, Biochemical and biophysical research communications.

[49]  A. Whittemore,et al.  Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[50]  P. Hollman,et al.  Consumption of quercetin and kaempferol in free-living subjects eating a variety of diets. , 1997, Cancer letters.

[51]  D. Morel,et al.  Impact of LDL carotenoid and alpha-tocopherol content on LDL oxidation by endothelial cells in culture. , 1998, Journal of lipid research.

[52]  A. H. Khan,et al.  A double-blind crossover study in moderately hypercholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids. , 1996, The American journal of clinical nutrition.

[53]  James W. Anderson,et al.  Meta-analysis of the effects of soy protein intake on serum lipids. , 1995, The New England journal of medicine.

[54]  G. Duthie,et al.  The effect of whisky and wine consumption on total phenol content and antioxidant capacity of plasma from healthy volunteers , 1998, European Journal of Clinical Nutrition.

[55]  L. Lanningham-Foster,et al.  Grape extract inhibits lipid peroxidation of human low density lipoprotein. , 1995, Biological & pharmaceutical bulletin.

[56]  A. Folsom,et al.  Whole-grain intake may reduce the risk of ischemic heart disease death in postmenopausal women: the Iowa Women's Health Study. , 1998, The American journal of clinical nutrition.

[57]  K. Kondo,et al.  Inhibition of LDL oxidation by cocoa , 1996, The Lancet.

[58]  G. Serrero,et al.  Resveratrol, a natural product derived from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells , 1999, Journal of cellular physiology.

[59]  P. Whelton,et al.  Legume consumption and risk of coronary heart disease in US men and women: NHANES I Epidemiologic Follow-up Study. , 2001, Archives of internal medicine.

[60]  F. Sánchez-Muniz,et al.  Eicosanoid production, thrombogenic ratio, and serum and LDL peroxides in normo- and hypercholesterolaemic post-menopausal women consuming two oleic acid-rich diets with different content of minor components , 2001, British Journal of Nutrition.

[61]  M. Siimes,et al.  Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. , 1995, Journal of lipid research.

[62]  A. Komori,et al.  Cancer inhibition by green tea. , 1998, Mutation research.

[63]  M. Criqui,et al.  Does diet or alcohol explain the French paradox? , 1994, The Lancet.

[64]  A. Qureshi,et al.  Coupling the cholesterol- and tumor-suppressive actions of palm oil to the impact of its minor constituents on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. , 1995, Prostaglandins, leukotrienes, and essential fatty acids.

[65]  A. Takeshita,et al.  Relation between green tea consumption and the severity of coronary atherosclerosis among Japanese men and women. , 2000, Annals of epidemiology.

[66]  Frank Hu,et al.  The Effect of Fruit and Vegetable Intake on Risk for Coronary Heart Disease , 2001, Annals of Internal Medicine.

[67]  James W. Anderson,et al.  Whole Grain Foods and Heart Disease Risk , 2000, Journal of the American College of Nutrition.

[68]  E. Rimm,et al.  Flavonol and flavone intakes in US health professionals. , 2002, Journal of the American Dietetic Association.

[69]  T. Sellers,et al.  Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. , 2000, The American journal of clinical nutrition.

[70]  E. Harrison,et al.  Low fat and high monounsaturated fat diets decrease human low density lipoprotein oxidative susceptibility in vitro. , 2001, The Journal of nutrition.

[71]  S. Fukushima,et al.  Cancer prevention by organosulfur compounds from garlic and onion , 1997, Journal of cellular biochemistry. Supplement.

[72]  R. Tyrrell,et al.  Tea flavonoids and cardiovascular health. , 2001, QJM : monthly journal of the Association of Physicians.

[73]  R. Bostick,et al.  Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[74]  G. Yang,et al.  Tea and tea polyphenols in cancer prevention. , 2000, Advances in experimental medicine and biology.

[75]  M. Katan,et al.  Tea flavonoids and cardiovascular disease: a review. , 1997, Critical reviews in food science and nutrition.

[76]  M. Woodward,et al.  Dietary antioxidant vitamins and fiber in the etiology of cardiovascular disease and all-causes mortality: results from the Scottish Heart Health Study. , 1999, American journal of epidemiology.

[77]  J. D. Wagner,et al.  Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery atherosclerosis of male cynomolgus monkeys. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[78]  S. Miura,et al.  Green tea polyphenols (flavan 3-ols) prevent oxidative modification of low density lipoproteins: an ex vivo study in humans. , 2000, The Journal of nutritional biochemistry.

[79]  M. A. Tanner,et al.  Inhibition of 7,12-dimethylbenz(a)anthracene- and N-nitrosomethylurea-induced rat mammary cancer by dietary flavonol quercetin. , 1988, Cancer research.

[80]  P. J. Jones,et al.  Alcohol, red wine and cardiovascular disease. , 2001, The Journal of nutrition.

[81]  S. Clinton,et al.  Lycopene: chemistry, biology, and implications for human health and disease. , 2009, Nutrition reviews.

[82]  H. Black,et al.  Garlic powder and plasma lipids and lipoproteins: a multicenter, randomized, placebo-controlled trial. , 1998, Archives of internal medicine.

[83]  N. Suzuki,et al.  Polyphenols in chocolate, which have antioxidant activity, modulate immune functions in humans in vitro. , 1997, Cellular immunology.

[84]  O. Texier,et al.  Quercetin metabolites in plasma of rats fed diets containing rutin or quercetin. , 1995, The Journal of nutrition.

[85]  E. Giovannucci,et al.  Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. , 1999, Journal of the National Cancer Institute.

[86]  Paul Knekt,et al.  Flavonoid intake and coronary mortality in Finland: a cohort study , 1996, BMJ.

[87]  D. Kitts Bioactive substances in food: identification and potential uses. , 1994, Canadian journal of physiology and pharmacology.

[88]  P. Boyle,et al.  Meta-analysis of studies on breast cancer risk and diet: the role of fruit and vegetable consumption and the intake of associated micronutrients. , 2000, European journal of cancer.

[89]  D Kromhout,et al.  Serum total cholesterol and long-term coronary heart disease mortality in different cultures. Twenty-five-year follow-up of the seven countries study. , 1995, JAMA.

[90]  J. Weisburger Evaluation of the Evidence on the Role of Tomato Products in Disease Prevention 1 , 1998, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[91]  Kiyohiko Mabuchi,et al.  A prospective study of green tea consumption and cancer incidence, Hiroshima and Nagasaki (Japan) , 2004, Cancer Causes & Control.

[92]  S. Agarwal,et al.  Tomato lycopene and its role in human health and chronic diseases. , 2000, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[93]  D Kromhout,et al.  Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. , 1995, Archives of internal medicine.

[94]  C. Silagy,et al.  A meta‐analysis of the effect of garlic on blood pressure , 1994, Journal of hypertension.

[95]  S. Cole,et al.  Fruit and vegetable intake and risk of cardiovascular disease: the Women's Health Study. , 2000, The American journal of clinical nutrition.

[96]  K. von Bergmann,et al.  Effect of low-dose sitostanol on serum cholesterol in patients with hypercholesterolemia. , 1986, Atherosclerosis.

[97]  Johanna T. Dwyer,et al.  Flavonoids: Dietary occurrence and biochemical activity , 1998 .

[98]  C. Scaccini,et al.  Effect of dietary oils on lipid peroxidation and on antioxidant parameters of rat plasma and lipoprotein fractions. , 1992, Journal of lipid research.

[99]  A. Folsom,et al.  Is whole grain intake associated with reduced total and cause-specific death rates in older women? The Iowa Women's Health Study. , 1999, American journal of public health.

[100]  G. T. Liu,et al.  Antioxidant activity of two dibenzocyclooctene lignans on the aged and ischemic brain in rats. , 1992, Free radical biology & medicine.

[101]  M. Gould,et al.  Limonene chemoprevention of mammary carcinoma induction following direct in situ transfer of v-Ha-ras. , 1994, Cancer research.

[102]  P. Wolf,et al.  Protective effect of fruits and vegetables on development of stroke in men. , 1995, JAMA.

[103]  J. Donovan,et al.  Antioxidants in chocolate , 1996, The Lancet.

[104]  Frank B. Hu,et al.  Dietary pattern analysis: a new direction in nutritional epidemiology , 2002, Current opinion in lipidology.

[105]  J. Bushman Green tea and cancer in humans: a review of the literature. , 1998, Nutrition and cancer.

[106]  C. Rice-Evans,et al.  Antioxidant activities of flavonoids as bioactive components of food. , 1996, Biochemical Society transactions.

[107]  S. Sasazuki Case-control study of nonfatal myocardial infarction in relation to selected foods in Japanese men and women. , 2001, Japanese circulation journal.

[108]  J. Crouse,et al.  A randomized trial comparing the effect of casein with that of soy protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins. , 1999, Archives of internal medicine.

[109]  James W. Anderson,et al.  Dietary fiber prevents carbohydrate-induced hypertriglyceridemia , 2000, Current atherosclerosis reports.

[110]  R. Mensink,et al.  Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. , 1998, The American journal of clinical nutrition.

[111]  L Bravo,et al.  Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. , 2009, Nutrition reviews.

[112]  R. S. Lee,et al.  Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. , 2000, Cardiovascular research.

[113]  F. Speizer,et al.  Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies. , 2001, JAMA.

[114]  B. Rosner,et al.  Cholesterol-lowering effects of dietary fiber: a meta-analysis. , 1999, The American journal of clinical nutrition.

[115]  P. Crowell,et al.  Prevention and therapy of cancer by dietary monoterpenes. , 1999, The Journal of nutrition.

[116]  R. Salkeld,et al.  Serum Antioxidants and Myocardial Infarction: Are Low Levels of Carotenoids and α‐ Tocopherol Risk Factors for Myocardial Infarction? , 1994, Circulation.

[117]  P. Guallar-Castillón,et al.  Socioeconomic level, sedentary lifestyle, and wine consumption as possible explanations for geographic distribution of cerebrovascular disease mortality in Spain. , 1997, Stroke.

[118]  G. Wong,et al.  Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. , 1991, Carcinogenesis.

[119]  C. Borek,et al.  Antioxidant health effects of aged garlic extract. , 2001, The Journal of nutrition.

[120]  J. Vinson,et al.  Plant Flavonoids, Especially Tea Flavonols, Are Powerful Antioxidants Using an in Vitro Oxidation Model for Heart Disease , 1995 .

[121]  William L. Haskell,et al.  Potential Health Benefits of Dietary Phytoestrogens: A Review of the Clinical, Epidemiological, and Mechanistic Evidence1 , 1998 .

[122]  R. Lamuela-Raventós,et al.  Virgin olive oil phenolic compounds: binding to human low density lipoprotein (LDL) and effect on LDL oxidation. , 2000, International journal of clinical pharmacology research.

[123]  P. Wilson,et al.  Whole-grain intake is favorably associated with metabolic risk factors for type 2 diabetes and cardiovascular disease in the Framingham Offspring Study. , 2002, The American journal of clinical nutrition.

[124]  G. de Gaetano,et al.  Protection from cardiovascular disease by wine and its derived products. Epidemiological evidence and biological mechanisms. , 2000, World review of nutrition and dietetics.

[125]  Norman R. Farnsworth,et al.  Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes , 1997, Science.

[126]  A. Rao,et al.  Bioavailability and in vivo antioxidant properties of lycopene from tomato products and their possible role in the prevention of cancer. , 1998, Nutrition and cancer.

[127]  S. Wiseman,et al.  Dietary non-tocopherol antioxidants present in extra virgin olive oil increase the resistance of low density lipoproteins to oxidation in rabbits. , 1996, Atherosclerosis.

[128]  Adesh K. Jain,et al.  Can garlic reduce levels of serum lipids? A controlled clinical study. , 1993, The American journal of medicine.

[129]  J. Freedman,et al.  Select Flavonoids and Whole Juice From Purple Grapes Inhibit Platelet Function and Enhance Nitric Oxide Release , 2001, Circulation.

[130]  P. Murphy,et al.  Bioavailability of soybean isoflavones depends upon gut microflora in women. , 1995, The Journal of nutrition.

[131]  P. J. Jones,et al.  Comparable efficacy of hydrogenated versus nonhydrogenated plant sterol esters on circulating cholesterol levels in humans. , 2009, Nutrition reviews.

[132]  P. Schnohr,et al.  Type of Alcohol Consumed and Mortality from All Causes, Coronary Heart Disease, and Cancer , 2000, Annals of Internal Medicine.

[133]  S. Ojala,et al.  A soy protein isolate rich in genistein and daidzein and its effects on plasma isoflavone concentrations, platelet aggregation, blood lipids and fatty acid composition of plasma phospholipid in normal men. , 1996, The Journal of nutrition.

[134]  F. Chung,et al.  Conversion of glucosinolates to isothiocyanates in humans after ingestion of cooked watercress. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[135]  T. Gutfinger,et al.  Polyphenols in olive oils , 1981 .

[136]  S. Schwartz,et al.  Lycopene : Chemical and Biological Properties , 1999 .

[137]  A. Gozzini,et al.  Plasma and tissue resveratrol concentrations and pharmacological activity. , 1998, Drugs under experimental and clinical research.

[138]  L. Beilin,et al.  Supplementation with isoflavonoid phytoestrogens does not alter serum lipid concentrations: a randomized controlled trial in humans. , 1998, The Journal of nutrition.

[139]  P. Trumbo,et al.  Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. , 2002, Journal of the American Dietetic Association.

[140]  E. Diamandis,et al.  Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. , 1999, The American journal of clinical nutrition.

[141]  E. Rimm,et al.  Intake of dietary fiber and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. , 1996, Circulation.

[142]  E. Feskens,et al.  Tea flavonols in cardiovascular disease and cancer epidemiology. , 1999, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[143]  E. Vartiainen,et al.  Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. , 1995, The New England journal of medicine.

[144]  C. Scaccini,et al.  Inhibition of human low-density lipoprotein oxidation by caffeic acid and other hydroxycinnamic acid derivatives. , 1995, Free radical biology & medicine.

[145]  F. Kok,et al.  Lycopene and myocardial infarction risk in the EURAMIC Study. , 1997, American journal of epidemiology.

[146]  G. Frühbeck Flavonoid intake and coronary mortality , 1996, BMJ.

[147]  A. Howell,et al.  Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. , 1998, The American journal of clinical nutrition.

[148]  A. Nissinen,et al.  Food intake patterns and 25-year mortality from coronary heart disease: Cross-cultural correlations in the Seven Countries Study , 1999, European Journal of Epidemiology.

[149]  C. Vecchia Mediterranean Epidemiological Evidence on Tomatoes and the Prevention of Digestive-Tract Cancers , 1998 .

[150]  H. Matsuura,et al.  Saponins in garlic as modifiers of the risk of cardiovascular disease. , 2001, The Journal of nutrition.

[151]  E. Schaefer,et al.  Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet. , 2001, The American journal of clinical nutrition.

[152]  I. Young,et al.  Absorption and antioxidant effects of quercetin from onions, in man , 1999, European Journal of Clinical Nutrition.

[153]  P. Talalay,et al.  Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms. , 1994, Cancer research.

[154]  P. Hollman,et al.  Role of dietary flavonoids in protection against cancer and coronary heart disease. , 1996, Biochemical Society transactions.

[155]  A. Waterhouse,et al.  Inhibition of human LDL oxidation by resveratrol , 1993, The Lancet.

[156]  S. Hecht,et al.  INHIBITION OF CARCINOGENESIS BY ISOTHIOCYANATES* , 2000, Drug metabolism reviews.

[157]  S. Bingham,et al.  Phyto-oestrogens: where are we now? , 1998, British Journal of Nutrition.

[158]  D. Thurnham,et al.  Consumption of tomato products with olive oil but not sunflower oil increases the antioxidant activity of plasma. , 2000, Free radical biology & medicine.

[159]  M. Anthony,et al.  Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques. , 1997, Fertility and sterility.

[160]  J. Manson,et al.  Long-term intake of dietary fiber and decreased risk of coronary heart disease among women. , 1999, JAMA.

[161]  A. Folsom,et al.  Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women. , 1999, American journal of epidemiology.

[162]  M. Wilchek,et al.  Effect of Purified Allicin, the Major Ingredient ofFreshly Crushed Garlic, on Cancer Cell Proliferation , 2000, Nutrition and cancer.

[163]  S. Rankin,et al.  Flavonoids inhibit the oxidative modification of low density lipoproteins by macrophages. , 1990, Biochemical pharmacology.

[164]  J. Viikari,et al.  Cholesterol-lowering effect and sensory properties of sitostanol ester margarine in normocholesterolemic adults , 1997 .

[165]  L. Wilhelmsen,et al.  Coronary risk factors, diet and vitamins as possible explanatory factors of the Swedish north–south gradient in coronary disease: a comparison between two MONICA centres , 1999, Journal of internal medicine.

[166]  C. S. Yang,et al.  Effects of tea consumption on nutrition and health. , 2000, The Journal of nutrition.

[167]  C. Keen,et al.  Cocoa inhibits platelet activation and function. , 2000, The American journal of clinical nutrition.

[168]  J. Manson,et al.  Whole grain consumption and risk of ischemic stroke in women: A prospective study. , 2000, JAMA.

[169]  R. Schulte‐Hermann,et al.  Failure to demonstrate chemoprevention by the monoterpene perillyl alcohol during early rat hepatocarcinogenesis: a cautionary note. , 2000, Carcinogenesis.

[170]  T. Miettinen,et al.  Serum levels, absorption efficiency, faecal elimination and synthesis of cholesterol during increasing doses of dietary sitostanol esters in hypercholesterolaemic subjects. , 1994, Clinical science.

[171]  C. Teng,et al.  Inhibition of platelet aggregation by some flavonoids. , 1991, Thrombosis research.

[172]  Maurizio Servili,et al.  Simple and hydrolyzable phenolic compounds in virgin olive oil. 1. Their extraction, separation, and quantitative and semiquantitative evaluation by HPLC , 1992 .

[173]  J. German,et al.  Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells. , 2001, The American journal of clinical nutrition.

[174]  G. Friedman,et al.  Red wine, white wine, liquor, beer, and risk for coronary artery disease hospitalization. , 1997, The American journal of cardiology.

[175]  B. Sanwal,et al.  MODERN METHODS OF PLANT ANALYSIS , 1955 .

[176]  P. Kris-Etherton,et al.  Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans. , 2001, The American journal of clinical nutrition.

[177]  W. Willett,et al.  Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women. , 2000, Journal of the National Cancer Institute.

[178]  E. Diamandis,et al.  The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. , 1995, Clinica chimica acta; international journal of clinical chemistry.

[179]  S M Grundy,et al.  Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus. , 2000, The New England journal of medicine.

[180]  L. Arab,et al.  Lycopene and cardiovascular disease. , 2000, The American journal of clinical nutrition.

[181]  C. S. Yang,et al.  Inhibition of carcinogenesis by dietary polyphenolic compounds. , 2001, Annual review of nutrition.

[182]  N. Kerry,et al.  Red wine and fractionated phenolic compounds prepared from red wine inhibit low density lipoprotein oxidation in vitro. , 1997, Atherosclerosis.

[183]  S. Hecht,et al.  Chemoprevention of cancer by isothiocyanates, modifiers of carcinogen metabolism. , 1999, The Journal of nutrition.

[184]  P. Heinrich,et al.  Garlic: The Science and Therapeutic Application of Allium Sativum L. and Related Species , 1996 .

[185]  H. Gylling,et al.  Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment , 1994, Diabetologia.

[186]  C. Keen,et al.  Cocoa and wine polyphenols modulate platelet activation and function. , 2000, The Journal of nutrition.

[187]  R. Farndale,et al.  The tyrosine kinase inhibitors methyl 2,5‐dihydroxycinnamate and genistein reduce thrombin‐evoked tyrosine phosphorylation and Ca2+ entry in human platelets , 1993, FEBS letters.

[188]  Mark A Pereira,et al.  Fiber from Whole Grains, but not Refined Grains, Is Inversely Associated with All-Cause Mortality in Older Women: The Iowa Women’s Health Study , 2000, Journal of the American College of Nutrition.

[189]  J. Weisburger,et al.  Tea and Health: The Underlying Mechanisms , 1999, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[190]  G. Burke,et al.  Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys. , 1996, The Journal of nutrition.

[191]  F. Ursini,et al.  Evidence of postprandial absorption of olive oil phenols in humans. , 2000, Nutrition, metabolism, and cardiovascular diseases : NMCD.