1: J Am Diet Assoc 1997 Oct;97(10 Suppl 2):S199-204
Phytochemicals: guardians of our health. 
Craig WJ 
Andrews University, Berrien Springs, MI 49104-0210, USA. 
   Consuming a diet rich in plant foods will provide a milieu of phytochemicals, nonnutritive substances in plants that possess health-protective benefits. Nuts, whole grains, fruits, and vegetables contain an abundance of phenolic compounds, terpenoids, pigments, and other natural antioxidants that have been associated with protection from and/or treatment of chronic disease such as heart disease, cancer, diabetes, and hypertension as well as other medical conditions. The foods and herbs with the highest anticancer activity include garlic, soybeans, cabbage, ginger, licorice, and the umbelliferous vegetables. Citrus, in addition to providing an ample supply of vitamin C, folic acid, potassium, and pectin, contains a host of active phytochemicals. The phytochemicals in grains reduce the risk of cardiovascular disease and cancer. Publication Types: Review 
Review, tutorial 
PMID: 9336591, UI: 97477588 
 

2: Am J Clin Nutr 1999 Sep;70(3 
Suppl):459S-463S 
Plausible mechanisms for the protectiveness of whole grains. Slavin JL, Martini MC, Jacobs DR Jr, Marquart L Department of Food Science and Nutrition, University of Minnesota, St Paul, MN 55108, USA. jslavin@che2.che.umn.edu 
Dietary guidelines recommend the consumption of whole grains to prevent chronic diseases. Epidemiologic studies support the theory that whole grains are protective against cancer, especially gastrointestinal cancers such as gastric and colon cancer, and cardiovascular disease. Components in whole grains that may be protective include compounds that affect the gut environment, such as dietary fiber, resistant starch, and oligosaccharides. Whole grains are also rich in compounds that function as antioxidants, such as trace minerals and phenolic compounds, and phytoestrogens, with potential hormonal effects. Other potential mechanisms whereby whole grains may protect against disease include binding of carcinogens and modulation of the glycemic response. Clearly, the range of protective substances in whole grains is impressive and advice to consume additional whole grains is justified. Further study is needed regarding the mechanisms behind this protection so that the most potent protective components of whole grains will be maintained when developing whole grains into acceptable food products for the public. Publication Types: Review Review, tutorial PMID: 10479218, UI: 99408683 

3: Int J Mol Med 1998 Apr;1(4):747-53 Effect of dietary phytochemicals on cancer development. Waladkhani AR, Clemens MR Medizinische Abteilung I, Krankenanstalt Mutterhaus der Borromaerinnen, 54219 Trier, Germany. Vegetables, fruits, and whole grains contain a wide variety of phytochemicals that have the potential to modulate cancer development. There are many biologically plausible reasons why consumption of plant foods might slow or prevent the appearance of cancer. These include the presence in plant foods of such potentially anticarcinogenic substances as carotenoids, chlorophyll, flavonoids, indole, isothiocyanate, polyphenolic compounds, protease inhibitors, sulfides, and terpens. The specific mechanisms of action of most phytochemicals in cancer prevention are not yet clear but appear to be varied. Considering the large number and variety of dietary phytochemicals, their interactive effects on cancer risk may be extremely difficult to assess. Phytochemicals can inhibit carcinogenesis by inhibiting phase I enzymes, and induction of phase II enzymes, scavenge DNA reactive agents, suppress the abnormal proliferation of early, preneoplastic lesions, and inhibit certain properties of the cancer cell. Publication Types: Review Review, tutorial PMID: 9852292, UI: 99074484 

4: Nutr Cancer 1997;27(1):14-21 Whole-grain consumption and chronic disease: protective mechanisms. Slavin J, Jacobs D, Marquart L Department of Food Science and Nutrition, University of Minnesota, St. Paul 55108, USA. jslavin@che2.che.umn.edu Dietary guidance recommends consumption of whole grains to reduce the risk of chronic diseases including cancer and cardiovascular disease. Epidemiologic studies support the belief that whole grains are protective against cancers, especially gastrointestinal cancers such as gastric and colonic, and cardiovascular disease. Components in whole grains that may be protective are diverse and include compounds that affect the gut environment, i.e., dietary fiber, resistant starch, and other undigestible compounds in whole grains, compounds that function as antioxidants such as trace minerals and phenolic compounds, and compounds that are phytoestrogens with potential hormonal effects. Many of the protective compounds in whole grains are also in fruits and vegetables, but some plant compounds are more concentrated in whole grains, such as phenolic compounds including ferulic and caffeic acid. Other potential mechanistic effects of whole grains include binding of carcinogens and modulation of glycemic index. Clearly, the range of protective substances in whole grains is impressive, and advice to consume additional whole grains is justifiable. Publication Types: Review Review, tutorial PMID: 8970176, UI: 97125072

 5: QJM 1999 Sep;92(9):527-30 Interaction of dietary antioxidants in vivo: how fruit and vegetables prevent disease? Eastwood MA 
Department of Medicine, University of Edinburgh, Western General Hospital Trust, UK. 
Epidemiological studies indicate that fruit and vegetables are health-promoting and protective against disease, particularly cardiovascular disease and cancer. Possible plant nutrients providing this protection include antioxidants and dietary fibre. Clinical trials with antioxidant supplements give inconsistent results for protection against lung cancer in smokers, invasive cervical cancer, oesophageal and gastric cancers, colorectal polyps and coronary heart disease. The antioxidants used in trials may be contributing to a more complex system. Antioxidants have differing solubilities which partition across the phases of tissues, cells and macromolecular structures: water-soluble ascorbate, glutathione and urate; lipid-soluble tocopherols and carotenoids, and intermediatory-soluble flavonoids and hydroxycinnamic acids. The health protection provided by fruit and vegetables could arise through an integrated reductive environment delivered by plant antioxidants of differing solubility in each of the tissue, cellular and macromolecular phases. Publication Types: Review Review, tutorial PMID: 10627873, UI: 20093343

 6: Am J Clin Nutr 1999 Sep;70(3 Suppl):491S-499S Health-promoting properties of common herbs. Craig WJ 
Department of Nutrition, Andrews University, Berrien Springs, MI 49104-0210, USA. wcraig@andrews.edu 
Herbs have been used as food and for medicinal purposes for centuries. Research interest has focused on various herbs that possess hypolipidemic, antiplatelet, antitumor, or immune-stimulating properties that may be useful adjuncts in helping reduce the risk of cardiovascular disease and cancer. In different herbs, a wide variety of active phytochemicals, including the flavonoids, terpenoids, lignans, sulfides, polyphenolics, carotenoids, coumarins, saponins, plant sterols, curcumins, and phthalides have been identified. Several of these phytochemicals either inhibit nitrosation or the formation of DNA adducts or stimulate the activity of protective enzymes such as the Phase II enzyme glutathione transferase (EC 2.5.1.18). Research has centered around the biochemical activity of the Allium sp. and the Labiatae, Umbelliferae, and Zingiberaceae families, as well as flaxseed, licorice root, and green tea. Many of these herbs contain potent antioxidant compounds that provide significant protection against chronic diseases. These compounds may protect LDL cholesterol from oxidation, inhibit cyclooxygenase and lipoxygenase enzymes, inhibit lipid peroxidation, or have antiviral or antitumor activity. The volatile essential oils of commonly used culinary herbs, spices, and herbal teas inhibit mevalonate synthesis and thereby suppress cholesterol synthesis and tumor growth. Publication Types: Review Review, tutorial PMID: 10479221, UI: 99408686

 7: Cancer Causes Control 1991 Nov;2(6):427-42 Vegetables, fruit, and cancer. II. Mechanisms. Steinmetz KA, Potter JD 
Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55455. 
The epidemiologic literature on the relationship between vegetable and fruit consumption and human cancer at a variety of sites was reviewed systematically in Part I. It was concluded that consumption of higher levels of vegetables and fruit is associated consistently, although not universally, with a reduced risk of cancer at most sites, and particularly with epithelial cancers of the alimentary and respiratory tracts. Possible mechanisms by which vegetable and fruit intake might alter risk of cancer are addressed here. A large number of potentially anticarcinogenic agents are found in these food sources, including carotenoids, vitamins C and E, selenium, dietary fiber, dithiolthiones, glucosinolates and indoles, isothiocyanates, flavonoids, phenols, protease inhibitors, plant sterols, allium compounds, and limonene. These agents have both complementary and overlapping mechanisms of action, including the induction of detoxification enzymes, inhibition of nitrosamine formation, provision of substrate for formation of antineoplastic agents, dilution and binding of carcinogens in the digestive tract, alteration of hormone metabolism, antioxidant effects, and others. It appears extremely unlikely that any one substance is responsible for all the associations seen. Possible adverse effects of vegetable and fruit consumption are also examined. One way to consider the relationships reviewed here is to hypothesize that humans are adapted to a high intake of plant foods that supply substances crucial to the maintenance of the organism, but only some of which are currently called 'essential nutrients.' Cancer may be the result of reducing the level of intake of foods that are metabolically necessary--it may be a disease of maladaptation. Publication Types: Review Review, academic PMID: 1764568, UI: 92110498

 8: IARC Sci Publ 1996;(139):61-90 Vegetables, fruit and phytoestrogens as preventive agents. Potter JD, Steinmetz K 
Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. 
The practice of medicine-both past and present-often involves the prescription of specific foods (almost always plants) or their potent derivatives, to treat a wide spectrum of illnesses. Foods that have been ascribed healing properties include the Cruciferae, the allium family, celery, cucumber, endive, parsley, radish and legumes. Review of the epidemiological data, including both cohort and case-control studies, of all cancer sites strongly suggests that plant foods also have preventive potential and that consumption of the following groups and types of vegetables and fruits is lower in those who subsequently develop cancer: raw and fresh vegetables, leafy green vegetables, Cruciferae, carrots, broccoli, cabbage, lettuce, and raw and fresh fruit (including tomatoes and citrus fruit). Other data suggest that foods high in phytoestrogens, particularly soy (which contains isoflavones), or high in precursor compounds that can be metabolized by gut bacteria into active agents, particularly some grains and vegetables with woody stems (which contain precursors to lignans), are plausibly associated with a lower risk of sex-hormone-related cancers. The human evidence for these latter associations is not strong. There are many biologically plausible reasons why consumption of plant foods might slow or prevent the appearance of cancer. These include the presence in plant foods of such potentially anticarcinogenic substances as carotenoids, vitamin C, vitamin E, selenium, dietary fibre (and its components), dithiolthiones, isothiocyanates, indoles, phenols, protease inhibitors, allium compounds, plant sterols, and limonene. Phytoestrogens are also derived from some vegetables and berries as well as grains and seeds. Most of the data for the observations on the anticarcinogenic potential of all of these compounds have come from animal and in vitro studies. At almost every one of the stages of the cancer process, identified phytochemicals are known to be able to alter the likelihood of carcinogenesis-occasionally in a way that enhances risk but usually in a favourable direction. For example, glucosinolates and indoles, thiocyanates and isothiocyanates, phenols, and coumarins can induce a multiplicity of phase II (solubilizing and usually inactivating) enzymes; ascorbate and phenols block the formation of carcinogens such as nitrosamines; flavonoids and carotenoids act as antioxidants, essentially disabling the carcinogenic potential of specific compounds; lipid-soluble compounds such as carotenoids and sterols may alter membrane structure or integrity; some sulphur-containing compounds suppress DNA and protein synthesis; carotenoids can suppress DNA synthesis and enhance differentiation; and phytoestrogens compete with estradiol for estrogen receptors in a way that is generally antiproliferative. Consumption of diets low in plant foods results in a reduced intake of a wide variety of those substances that can plausibly lower cancer risk. In the presence of a diet and lifestyle high in potential carcinogens (whether derived from fungal contamination, cooking or tobacco) or high in promoters (such as salt and alcohol), overall risk of cancer at many epithelial sites is elevated. Plant foods appear to exert a general risk-lowering effect; the patterns of exposure to cancer initiators and promoters and of genetic susceptibility may determine the variations in the site-specific risks of cancer seen across populations. Publication Types: Review Review, tutorial PMID: 8923020, UI: 97081777 


9: Acta Med Austriaca 1997;24(3):108-13 
[Cancer preventive value of natural, non-nutritive food constituents]. [Article in German] 
Frohlich RH, Kunze M, Kiefer I 
Institut fur Sozialmedizin, Universitat Wien. Numerous epidemiologic studies have shown that a diet rich in vegetables, fruits and fiber is associated with a decreased risk of cancer, particularly of epithelial tumors. Especially this association is evident for various citrus fruits, carrots, leafy green vegetables, as well as cruciferous-(sorts of cabbage, broccoli) and leak vegetables (garlic, onions, etc.). In the course of investigation of the protective mechanisms exerted by vegetable foodstuffs, a great number of secondary plant products such as carotenoids, sulfides, glucosinolates, plant sterols saponins, terpens, phytoestrogens, flavones, protease inhibitors, or phenolic acids, which are substantial constituents of our daily food, have changed their meaning from a non-nutritive constituent to a probably cancer preventive biological-active substance. But also fermentable, soluble fibers and substances in fermented foods can exert protective effects on development of cancer. Mostly the anticarcinogenic action of biological-active substances is limited to an early stage of carcinogenesis. Therefore it seems to be important to start prevention of cancer by nutrition as early as possible and adhere to it over a long period. Publication Types: Review Review, tutorial PMID: 9312973, UI: 97404753 


10: J Am Diet Assoc 1996 Oct;96(10):1027-39 
Vegetables, fruit, and cancer prevention: a review. Steinmetz KA, Potter JD 
World Cancer Research Fund, London, England. In this review of the scientific literature on the relationship between vegetable and fruit consumption and risk of cancer, results from 206 human epidemiologic studies and 22 animal studies are summarized. The evidence for a protective effect of greater vegetable and fruit consumption is consistent for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon. The types of vegetables or fruit that most often appear to be protective against cancer are raw vegetables, followed by allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes. Substances present in vegetables and fruit that may help protect against cancer, and their mechanisms, are also briefly reviewed; these include dithiolthiones, isothiocyanates, indole-3-carbinol, allium compounds, isoflavones, protease inhibitors, saponins, phytosterols, inositol hexaphosphate, vitamin C, 
D-limonene, lutein, folic acid, beta carotene, lycopene, selenium, vitamin E, flavonoids, and dietary fiber. Current US vegetable and fruit intake, which averages about 3.4 servings per day, is discussed, as are possible noncancer-related effects of increased vegetable and fruit consumption, including benefits against cardiovascular disease, diabetes, stroke, obesity, diverticulosis, and cataracts. Suggestions for dietitians to use in counseling persons toward increasing vegetable and fruit intake are presented. Publication Types: Review Review, academic 
PMID: 8841165, UI: 96438830


11: Crit Rev Food Sci Nutr 1994;34(5-6):473-97 
Antioxidants and hormone-mediated health benefits of whole grains. Thompson LU 
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario. 
Lignans and phytoestrogens have been associated with protective effect against hormone-related diseases, for example, cancer of the breast and prostate, and potential mechanisms for this effect have been reported. Antioxidants also appear to have some protective effect against diseases associated with reactive free radicals such as coronary heart disease and cancer. Whole grains contain some of these substances particularly the mammalian lignan precursors, vitamin E, other phenolic compounds, Se, and phytic acid. These substances may in part be responsible for the reduced risk of cancer and coronary heart disease associated with intake of high-fiber diets containing whole grains. Because they are more associated with the fiber in the outer layers of the grain, the intake of whole vs. refined grain is emphasized for optimum health benefits. Publication Types: Review Review, tutorial PMID: 7811379, UI: 95110431 

12: J Am Diet Assoc 1999 Feb;99(2):213-8 Characteristics and occurrence of phenolic phytochemicals. King A, Young G Agricultural Research Department of Virginia State University, Petersburg, USA. Phenolic phytochemicals are the largest category of phytochemicals and the most widely distributed in the plant kingdom. The 3 most important groups of dietary phenolics are flavonoids, phenolic acids, and polyphenols. Flavonoids are the largest group of plant phenols and the most studied. Phenolic acids form a diverse group that includes the widely distributed hydroxybenzoic and hydroxycinnamic acids. Phenolic polymers, commonly known as tannins, are compounds of high molecular weight that are divided into 2 classes: hydrolyzable and condensed tannins. Quantification of food phenolics is just beginning, and preliminary results indicate high variability, even within a given food. Phenolics are biologically active compounds that may possess some disease-preventive properties. Evidence for their ability to prevent cancer or heart disease is preliminary and conflicting. The health benefits of phytochemicals have been reported in the popular press, and the public will come to dietitians for answers to their questions about phytochemicals. Publication Types: Review 
Review, tutorial 
PMID: 9972191, UI: 99138138


13: Ugeskr Laeger 1994 Dec 19;156(51):7675-9 
[The effect on health of dietary antioxidants and antioxidant supplements]. 
[Article in Danish] 
Sandstrom B, Astrup AV, Dyerberg J, Holmer G, Poulsen HE, Stender S, Kondrup J, Gudmand-Hoyer E 
Ernaeringsradet, Kobenhavn. 
Reactive free oxygen radicals are formed in the reactions involved in normal cell metabolism. This formation is closely regulated e.g. by dietary antioxidants. Present knowledge suggests that an imbalance, with surplus of free radicals, can play a role in the pathogenesis of certain types of cancer, atherosclerosis, and cataract. A number of epidemiological studies have demonstrated a reduced risk of developing these diseases in persons who consume a diet with a high content of vegetables and fruit, which contains large quantities of the antioxidants: beta-carotene, vitamins C and E. Intervention studies, using supplements of these antioxidants, have so far not been able to show a beneficial effect. The apparently protective effect of fruit and vegetables may be due to other active ingredients. In Denmark the average intake of vegetables and fruit is low, and it is estimated that an increased consumption of these foods could reduce the occurrence of certain cancer types and atherosclerosis. In contrast, there is no evidence that antioxidant supplements would provide protection against disease, and their safety remains to be established. Publication Types: Review Review, tutorial PMID: 7839531, UI: 95141484 

14: Adv Exp Med Biol 1996;401:207-12 Nutritional implications of dietary phytochemicals. Messina M, Messina V 
Although increasing the levels of phytochemicals in foods via traditional breeding or genetic engineering would appear to pose less of a risk, there is still the possibility of over consumption given the ease with which phytochemical content can be increased. According to the recent position paper by the American Dietetic Association on phytochemicals, "the dietetics professional ... is the specialist who should make recommendations concerning appropriate dietary intake to optimize the potential benefits of phytochemical-rich or functional foods in overall health." For dietitians to make these recommendations, it will be necessary for the nutrition community to make a concerted effort to incorporate information on phytochemicals into nutrition manuals and professional resources. As it is, most of the research and discussion of phytochemicals is conducted by professionals not related or only peripherally related to the field of nutrition. This is truly an exciting time to be involved in the nutrition field. We have moved a head from thinking that only a relatively small number of dietary factors possess biological activity to recognizing that there are hundreds and perhaps thousands of such factors. It will be many years before our understanding of phytochemicals approaches our knowledge of vitamins and minerals- and it is worth nothing that our knowledge of vitamins and minerals is still incomplete. But it does appear that the phytochemicals help explain why plant-based diets, in general, are associated with a reduced risk of many chronic diseases. And in fact, his may be the most important outcome from use of phytochemicals. The nutrition community now has more reasons for encouraging consumers to eat plant-based diets. Publication Types: Review Review, tutorial PMID: 8886139, UI: 97040849 


15: Nutr Cancer 1995;24(3):221-9 
Whole grain intake and cancer: a review of the literature. Jacobs DR Jr, Slavin J, Marquart L 
Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55454, USA. 
There has been little research concerning the health effects of whole grain intake in humans. We have synthesized 15 american and European case-control and prospective studies of whole grain intake. Most subjects were middle aged or older. The studies employed disparate dietary methods, and the foods referred to and quantities eaten are ill defined. Nevertheless there is a striking consistency in reduced risk for colorectal and gastric cancers associated with intake of whole grain, also found in isolated studies of endometrial cancer and coronary heart disease. Because reduced risk was not associated with refined grain intake, these findings do not appear to be confounded by participant confusion concerning refined vs. whole grains. The independence of these findings from reduced risk associated with fruit and vegetable intake is not established. There should be further research to establish whether whole grain intake is protective against chronic disease. Publication Types: Review Review, tutorial PMID: 8610041, UI: 96193060 

16: Nutr Cancer 1992;18(1):1-29 Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Block G, Patterson B, Subar A 
Dept. of Social and Administrative Health Sciences, School of Public Health, University of California, Berkeley 94720. Approximately 200 studies that examined the relationship between fruit and vegetable intake and cancers of the lung, colon, breast, cervix, esophagus, oral cavity, stomach, bladder, pancreas, and ovary are reviewed. A statistically significant protective effect of fruit and vegetable consumption was found in 128 of 156 dietary studies in which results were expressed in terms of relative risk. For most cancer sites, persons with low fruit and vegetable intake (at least the lower one-fourth of the population) experience about twice the risk of cancer compared with those with high intake, even after control for potentially confounding factors. For lung cancer, significant protection was found in 24 of 25 studies after control for smoking in most instances. Fruits, in particular, were significantly protective in cancers of the esophagus, oral cavity, and larynx, for which 28 of 29 studies were significant. Strong evidence of a protective effect of fruit and vegetable consumption was seen in cancers of the pancreas and stomach (26 of 30 studies), as well as in colorectal and bladder cancers (23 of 38 studies). For cancers of the cervix, ovary, and endometrium, a significant protective effect was shown in 11 of 13 studies, and for breast cancer a protective effect was found to be strong and consistent in a meta analysis. It would appear that major public health benefits could be achieved by substantially increasing consumption of these foods. Publication Types: Review Review literature PMID: 1408943, UI: 93027543 


17: Comp Biochem Physiol B 1989;93(2):201-12 
Prevention of cancer: vegetables and plants. Hocman G Research Institute of Preventive Medicine, Bratislava, Czechoslovakia. 
1. Results of epidemiological studies indicate that a human diet rich in vegetables may lower the incidence of cancer. 2. This preventive effect of the vegetable diet against cancer could be ascribed to lowered intake of energy (joules) and its content of vitamins and carotene. 3. The consumption of vegetables means also less meat and fats as well as increased fiber content and specific chemopreventive compounds (indoles, plant phenols) present in such a diet. 4. The supposed mechanisms of prevention may include enhanced enzymatic detoxification of harmful compounds, and inhibition of their binding to cellular DNA, their adsorption on fiber, detoxification of radical forms of carcinogens by natural antioxidants in plants and probably many other ways too. Publication Types: Review Review, tutorial PMID: 2550172, UI: 89377139 

18: J Am Diet Assoc 1991 Jul;91(7):836-40 Increasing use of soyfoods and their potential role in cancer prevention. 
Messina M, Messina V 
Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD 20892. 
The United States produces approximately half of the world's soybeans. Although most of what is produced is used as animal feed, soy-protein products (eg, soy-protein flour, concentrates, and isolates) are used extensively by the food industry, primarily for their functional characteristics, such as emulsification. During the past decade, however, there has been a marked increase in the use of both traditional soyfoods, such as tofu and soymilk, and second-generation soyfoods, products which generally simulate familiar American dishes. Recently, attention has focused on the possible role of soybean consumption in reducing cancer risk. Soybeans contain, in relatively high concentrations, several compounds with demonstrated anticarcinogenic activity. Two of these compounds--protease inhibitors and phytic acid--have traditionally been viewed as antinutrients. The scientific community has begun to appreciate the potential importance of nonnutritive dietary compounds (phytochemicals) in foods such as soybeans. Dietitians need to become more aware of the phytochemical content of foods and the possible effect of phytochemicals on health and disease. Publication Types: Review Review, academic PMID: 2071799, UI: 91302663 


19: Indian J Med Res 1998 Nov;108:167-81 
Bioactive phytochemicals with emphasis on dietary practices. Krishnaswamy K, Raghuramulu N 
National Institute of Nutrition (ICMR), Hyderabad. Diet can modify the pathophysiological processes of various metabolic disorders and can be an effective preventive strategy for various disease processes most of which are known to involve oxidative damage. Both nutrient and non-nutrient components of the diet have been recognized for their anti-oxidant and other potential benefits. Plant foods contain phytochemicals such as flavonoids, phenolic acids, etc., which show biological activity. Some common foods used in Indian culinary practices were assessed for their anti-oxidant, anti-mutagenic and anti-carcinogenic effects and vitamin D activity and evaluated for their plausible biological effects. Green leafy vegetables had the highest anti-oxidant activity followed by wheat and rice. Cooking decreased this activity. Eugenol, the active principle of clove, was shown to offer protection against CCl4 induced hepatotoxicity in rats. It also showed anti-peroxidative activity in addition to decrease in O2 formation. Studies on the anti-carcinogenic effect of turmeric/curcumin revealed that both are potent anti-mutagens in vivo and reduce the adducted DNA levels in liver of rates challenged with B(a)P. In another study, Syrian hamsters receiving turmeric/curcumin through diet or local paint on cheek pouch had lower tumour burden as well as adducted DNA level against 7-12-DMBA challenge. Turmeric/curcumin were found to be better anti-tumour agents when given in the post initiation phase of carcinogenesis. The beneficial effect of turmeric was found to be due to its anti-oxidant potential. Studies on humans at risk of palatal cancer due to reverse smoking showed that turmeric (1 g/day) for 9 months had a significant impact on the regression of precancerous lesions. Onion and garlic also possess anti-mutagenic principle. Further studies on the bioactive phytochemicals in plants showed that certain plants belonging to Solanaceae (Cestrum diurnum, Lycopersicon esculentum and Solanum melongena) have calcinogenic potential and vitamin D like activity. In view of the vast data on bioactive principles from plants, it is suggested that dietary prevention coupled with other life-style changes in perhaps the right answer for prevention of cancer and other chronic diseases in India. Publication Types: Review Review, tutorial PMID: 9863273, UI: 99080641 


20: Nutr Rev 1996 Aug;54(8):255-7 
Fruits and vegetables: protective or just fellow travelers? Nestle M Department of Nutrition and Food Studies, New York University, NY 10012-1172, USA. 
Virtually all national and international dietary recommendations include advice to eat more fruits and vegetables. A recent study finds that people who do so are more likely to practice other healthful behaviors that can confound studies of lifestyle factors and chronic disease risk. This finding emphasizes the importance of following dietary recommendations as a whole and of developing more research on the health impact of overall dietary patterns. Publication Types: Review Review, tutorial 
PMID: 8961755, UI: 97121088


21: J R Soc Health 1996 Dec;116(6):360-6 
Diet in the prevention of cancer: what are the chances of avoidance? Walker AR 
Department of Tropical Diseases, School of Pathology of the University of the Witwaterstand, South Africa. 
In most western populations, cancer causes about a fifth of all deaths, and in developing populations, 5-15%, with the likelihood of further rises. Diet is considered responsible for about a third of cases of cancer and smoking another third. Dietarily, for cancer avoidance, recommendations made include eat less, eat much less fat especially saturated fat, and eat more plant foods, i.e. cereals, but very particularly vegetables and fruit. However, only high consumptions of the latter are consistently associated with a lower risk of cancers, notably of the digestive and respiratory tracts. For each change urged, meaningful compliance will be very difficult, due largely to conservativeness as well as to the higher cost of a 'prudent' diet. Notwithstanding, urges to make dietary changes, particularly relating to plant foods, must be continued, especially with regard to persons familially susceptible and, additionally, with the recognition that the measures recommended also serve to lessen susceptibility to cardiovascular diseases. Compliance, even by a small proportion, could result in large numbers benefiting due to the universality of the burden from cancer. Publication Types: Review Review literature PMID: 8987339, UI: 97140941 


22: J Am Diet Assoc 1995 Apr;95(4):493-6 Position of the American Dietetic Association: phytochemicals and functional foods. Never before has the focus on the health benefits of commonly available foods been so strong. The philosophy that food can be health promoting beyond its nutritional value is gaining acceptance within the public arena and among the scientific community as mounting research links diet/food components to disease prevention and treatment. Dietitians are uniquely qualified and positioned to translate the available sound scientific evidence into practical dietary applications for the consumer and to provide the food industry and the government with valuable insight and expertise for future research, product development, and regulation of phytochemicals and functional foods. Increasing the availability of healthful foods, including functional foods, in the American diet is critical to ensuring a healthier population. As the nutrition experts, dietetics professionals must be the leaders in this new, exciting, and meaningful field as it evolves. Publication Types: Review Review, tutorial 
PMID: 7699197, UI: 95213520

23: Biosci Biotechnol Biochem 1996 Jan;60(1):1-8 
Anti-tumor promotion with food phytochemicals: a strategy for cancer chemoprevention. 
Murakami A, Ohigashi H, Koshimizu K 
Department of Biotechnological Science, Kinki University, Wakayama, Japan. 
Cancer chemoprevention is currently regarded as a promising avenue for cancer control. In particular, the inhibition of tumor promotion (anti-tumor promotion) in multistage carcinogenesis is expected to be an efficient strategy, because tumor promotion is experimentally accomplished through the long-term, repetitive exposures of rodents to a tumor promoter, and premalignant lesions caused by a tumor promoter regress, at least in their earlier stages. In this review, we first describe the background of cancer chemoprevention studies as well as recent results of clinical trials. Subsequently, some hypothetical biological and cellular pathways in tumor promotion are explored. In addition, the anti-tumor promoting properties of vegetables, fruits, and edible marine algae, together with their active constituents and action mechanisms thus far known, are also described. Anti-tumor promotion with food phytochemicals may be characterized as an efficient and reliable strategy for cancer chemoprevention. Publication Types: Review Review, tutorial PMID: 8824818, UI: 96422201 


24: Adv Exp Med Biol 1999;472:207-21 
Phytochemicals as modulators of cancer risk. Bradlow HL, Telang NT, Sepkovic DW, Osborne MP Strang Cancer Research Laboratory, New York, NY 10021, USA. These results, describing antitumor activity of some of the phytochemicals that have been actively studied, suggest that dietary changes could play a role in decreasing the incidence of a variety of tumors. 13C and the other compounds discussed may well be only prototypes for other as yet unexplored phytochemicals present in the diet. There have been no attempts to explore the possibilities of synergistic action among the various phytochemicals, 13C, limonene, curcumin, epigallocatechin gallate, sulforaphene, or genistein. Mixtures of these compounds might well show potency at lower doses for each of the compounds and show even greater promise than that already demonstrated. Publication Types: Review Review, tutorial PMID: 10736628, UI: 20200867 

25: Adv Exp Med Biol 1996;401:25-34 Plant phenolics as potential cancer prevention agents. Newmark HL Memorial Sloan Kettering Cancer Center New York, New York 10021, USA. The frequent consumption of fresh fruits and vegetables is associated with a lower cancer incidence in humans, and in experimental carcinogenesis. There are several groups of substances in plant foods which may contribute to this inhibition of tumor development. Almost all fresh fruits, vegetables and cereal grains contain appreciable amounts of naturally occurring plant phenolics. A brief overview will be presented of the most common plant phenolics in human foods and their chemical and biochemical properties. Plant phenolics, originally hypothesized to inhibit mutagenesis and/or carcinogenesis by virtue of antioxidant or electrophile trapping mechanisms, can also act as potent modulators of arachidonic metabolism cascade pathways. Certain plant phenols can be effective inhibitors of chemical mutagens, in vitro, and/or carcinogenesis in vivo. The historical origins, hypotheses of actions, current status and potential adverse effects of the utility of plant phenolics to reduce risk of cancer are discussed, as well as future possibilities and needs and objectives for future research. Publication Types: Review Review, tutorial PMID: 8886124, UI: 97040834 


Cancer Causes Control 1995 Jul;6(4):292-302 The University of Minnesota Cancer Prevention Research Unit vegetable and fruit classification scheme (United States). Smith SA, Campbell DR, Elmer PJ, Martini MC, Slavin JL, Potter JD Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, 55454 USA. High vegetable and fruit (V&F) intake has been associated with a lower risk of many cancers. However, the specific V&F, the active compounds present in V&F, and the dose at which they confer protection are unknown. Standard methods for assessing, classifying, and quantifying V&F exposures in epidemiologic studies have not been established. Differences among studies occur due to inherent differences among V&F, and across dietary assessment methods, study populations, etiologic hypotheses, and analytic methods. The V&F classification scheme presented here characterizes and quantifies V&F consumption for elucidating risk relationships, identifying chemopreventive compounds present in V&F, and facilitating identification of potential biomarkers of V&F intake. Broad criteria define which plant foods count as V&F. Formation of food groups is based on proposed biological mechanisms of action. Five main groups are included: Total V&F; Total Vegetables; Total Fruits; and two groups orthogonal to these -- the Botanical and Phytochemical groups. Subgroups are specified within each main group. V&F exposure is quantified as the absolute amount consumed (weight) or as the number of household servings. This classification scheme has public health applications and may be used to examine associations with chronic diseases other than cancer. PMID: 7548716, UI: 96006875 

27: Am J Clin Nutr 1991 Jan;53(1 Suppl):226S-237S Nutritional approach to cancer prevention with emphasis on vitamins, antioxidants, and carotenoids. Weisburger JH 
American Health Foundation, Valhalla, NY 10595-1599. The main human cancers are associated with complex life-style related causative, enhancing, and inhibiting factors. Tobacco smoking or chewing exposes humans to genotoxic carcinogens and to promoting substances. Likewise, Western dietary traditions involve certain carcinogens and promoters, whereas Oriental traditions implicate other carcinogens and promoters. Importantly, in virtually all situations regular intake of fruits and vegetables appreciably lowers the risk of cancer. This paper reviews the causes of the main human cancers and analyzes the mechanisms of the protective effects of fruits and vegetables. Prevention of human cancer requires the definition of optimal levels of recommended daily allowances of micronutrients. Publication Types: Review Review, tutorial PMID: 1985392, UI: 91090020 

28: Br J Cancer 1992 Oct;66(4):673-9 Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. Shibata A, Paganini-Hill A, Ross RK, Henderson BE Department of Preventive Medicine, University of Southern California, School of Medicine, Los Angeles 90033-0800. A cohort of 11,580 residents of a retirement community initially free from cancer were followed from 1981 to 1989. A total of 1,335 incident cancer cases were diagnosed during the period. Relative risks of cancer were calculated for baseline consumption of vegetables, fruits, beta-carotene, dietary vitamin C, and vitamin supplements. After adjustment for age and smoking, no evidence of a protective effect was found for any of the dietary variables in men. However, an inverse association was observed between vitamin C supplement use and bladder cancer risk. In women, reduced cancer risks of all sites combined and of the colon were noted for combined intake of all vegetables and fruits, fruit intake alone, and dietary vitamin C. Supplemental use of vitamins A and C showed a protective effect on colon cancer risk in women. There was some suggestion that beta-carotene intake and supplemental use of vitamin A, C, and E were associated with reduced risk of lung cancer in women, but none of these results were statistically significant. These inverse associations observed in women seem to warrant further investigation, although there was inconsistency in results between the sexes. PMID: 1419605, UI: 93040999 

29: Mov Disord 1997 Mar;12(2):190-6 Dietary antioxidants and other dietary factors in the etiology of Parkinson's disease. 
Scheider WL, Hershey LA, Vena JE, Holmlund T, Marshall JR, Freudenheim Department of Social and Preventive Medicine, State University of New York at Buffalo 14214, USA. It has been suggested that dietary antioxidants reduce Parkinson's disease (PD) risk by neutralizing free radicals, thus preventing injury to neurons in the substantia nigra. This case-control study examined the possible role of long-term dietary antioxidant intake in PD etiology. Cases (n = 57) were males 45-79 years old with at least two cardinal signs of PD and no evidence of other forms of parkinsonism or dementia. Age-matched friend controls (n = 50) were chosen from lists provided by the cases. Usual dietary intake 20 years ago, including vitamins E and C and carotenoids, was assessed by a 102-item food frequency questionnaire. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression. Antioxidant intake, adjusted for age, education, smoking, rural living, and total energy intake, was not associated with reduced PD risk. Trends toward greater PD risk were associated with higher intakes of vitamin C and carotenoids, especially xanthophylls, reflecting higher intakes by PD cases of fruit and certain vegetables. Intakes of sweet foods, including fruit, were associated with higher PD risk, suggesting that the observed trends may be due to a preference for sweet foods. This study does not provide support for a protective effect of long-term dietary antioxidant intake on PD risk. PMID: 9087977, UI: 97242997 

30: Bibl Nutr Dieta 1995;(52):75-91 Cardiovascular disease and vitamins. Concurrent correction of 'suboptimal' plasma antioxidant levels may, as important part of 'optimal' nutrition, help to prevent early stages of cardiovascular disease and cancer, respectively. Gey KF Institute of Biochemistry and Molecular Biology, University of Berne, Switzerland. Epidemiological surveys provided abundant evidence that under steady-state conditions diets rich in antioxidants (from vegetables/fruits and suitable vegetable oils) reduce the relative risk of premature death from CVD and cancer. Material relative risks seem to disappear at 'optimal' antioxidant plasma levels in the order of > or = 50 micromol/l vitamin C, > or = 30 micromol/l lipid-standardized vitamin E > (alpha-tocopherol/cholesterol ratio > or = 5.1-5.2), > or = 2.2 micromol/l vitamin A, and > or = 0.4 micromol/l beta-carotene or > or = 0.4-0.5 micromol/l alpha-plus beta-carotene. Levels 25-35% below these thresholds predict an at least 2-fold higher risk. 'Suboptimal' levels of any single antioxidant may increase the relative risk independently. Accordingly, 'suboptimal' levels of several antioxidants predict a further increase of risk. Data on habitual voluntary multivitamin supplements providing an adequate supply of either vitamins A, C or E, and of beta-carotene in smokers, indicates that steady-state 'optimization' reduces more or less regularly the relative risk of CVD and cancer respectively. Simple counting of multivitamins regardless of their composition did not reveal any risk reduction. The antioxidant-related health benefits seem to depend on an adequacy of all antioxidants, and possibly of nonantioxidant nutrients as well. Thereby, an overall 'optimal' antioxidant defense system may be more important than excess of any particular 'magic bullet' antioxidant. Although antioxidants may represent a crucially important fraction within a health-maintaining diet, any nonantioxidant conutrients remain to be identified which could condition the health benefits of antioxidants. In randomized antioxidant intervention trials during 5-6 years in middle-aged to elderly subjects in China and Finland, only earlier stages of CVD and cancer respectively were prevented by rectifying previously poor levels. Correspondingly, the incidence of prostate cancer (developing mostly not until the male menopause) was reduced by correction of a previously poor vitamin E status in Finland. In contrast, irreversible precancerous lesions (such as esophageal dysplasia), clonically established common cancers (highly probable for the lung of elderly heavy smokers) as well as (presumably advanced, complicated) vascular lesions of chronic smokers did not respond favorably. (ABSTRACT TRUNCATED) Publication Types: Review Review, tutorial PMID: 8779654, UI: 96245681 


31: Tidsskr Nor Laegeforen 1994 Feb 28;114(6):702-5 
[Diet and cancer risk].
[Article in Norwegian]
Vatten LJ 
Institutt for miljo- og, samfunnsmedisinske fag, Medisinsk Teknisk Senter, Trondheim. 
Reduction in the incidence of competing diseases will steadily increase the relative importance of cancer as a cause of death. A curative break-through has occurred for some, but definitive solutions in the treatment of a majority of cancers remain undiscovered. Attempts at primary and secondary prevention have been encouraging in some areas, but progress is slow, and suggests that the search for causes of cancer should be intensified. It has been estimated that between 30% and 60% of all cancers may be attributable to dietary factors. The main hypothesis has suggested that intake of animal fat increases the risk. This hypothesis has been extensively tested, especially in relation to cancer of the breast and colon, and ecological studies, which have correlated use of dietary fat with incidence or mortality between countries, have confirmed the hypothesis. For cancer of the colon, it has also been verified in case-control and cohort studies, but analytical epidemiological studies have failed to show a consistent positive association between dietary fat and risk of breast cancer. Simultaneously, dietary factors with protective potential have received increasing attention. An overview of all studies which have investigated the relation between dietary fruit and vegetables and the risk of cancer showed a highly consistent protective effect, indicating that fruit and vegetables may provide general protection against cancer. Maybe the search for a "magic" protective factor is blocking this already documented insight, which suggests that daily intake of five servings of fruits or vegetables may have a strong and consistent protective effect on risk of cancer. PMID: 8191455, UI: 94248937 

32: Am J Clin Nutr 1994 May;59(5 Suppl):1162S-1165S Micronutrients and cancer risk. Willett WC Department of Epidemiology, Harvard School of Public Health, Boston, MA 
02115. 
An abundance of epidemiologic evidence, based on numerous and remarkably consistent observations that persons who consume high intakes of fruits and vegetables have reduced risks of most human cancers, supports the concept that micronutrients may play important roles in the prevention of human cancers. Many studies suggest that carotenoid compounds in fruits and vegetables may be important in reducing risk of lung cancer. At least some forms of fiber may contribute to reduced risk of colon cancer, but recent analyses of colonic polyps suggest that folic acid may also play a protective role. Evidence for breast cancer is more limited but protective associations with vitamin A from both carotenoid and preformed sources have been seen in several studies. Although we cannot be certain which compounds are responsible, the evidence is overwhelming that an abundant intake of fruits and vegetables can play an important role in reducing cancer incidence. Publication Types: Review Review, tutorial PMID: 8172117, UI: 94226079 

33: Cancer Lett 1997 Mar 19;114(1-2):195-202 Vitamins and cancer. van Poppel G, van den Berg H 
TNO Nutrition and Food Research Institute, Zeist, The Netherlands. The prospect that high intake of certain vitamins may confer protection against cancer has drawn substantial attention during the last decades. This paper gives a concise update of the role of a number of promising vitamins in prevention of cancer. Vitamin A and its analogues have an important role in cellular processes related to carcinogenesis. However, blood vitamin A levels are under strict control and a high intake of preformed vitamin A does not seem to be relevant for cancer prevention. The antioxidant vitamins C and E and beta-carotene may also have other biological activities than free radical trapping that relate to their cancer preventive properties. Mechanisms include immune stimulation, inhibition of nitrosamine formation, enhancement of cell communication and an influence on metabolic activation of carcinogens. Epidemiological data for the antioxidant vitamins are promising, but cannot rule out that another factor or combination of factors in fruits and vegetables might be responsible for a protective effect. The B vitamin folic acid is one of these potential factors that is currently thought to have an influence on DNA methylation and thus on proto-oncogene expression. Folic acid seems to be promising and deserves further study. Vitamin D might be relevant in colon cancer development due to its close links with calcium metabolism that might influence cell proliferation. Overall, results are promising, but the first human intervention trials on (antioxidant) vitamins and human cancer have yielded somewhat disappointing results. At this moment the data seem insufficient to make recommendations for vitamin supplementation to prevent cancer. The results are certainly in line with the advice that a diet rich in fruits and vegetables will help reduce cancer risk. Publication Types: Review Review, tutorial PMID: 9103291, UI: 97256450 

34: Br Med Bull 1993 Jul;49(3):679-99 Prospects for the prevention of free radical disease, regarding cancer and cardiovascular disease. Gey KF Vitamin Unit, University of Berne, Switzerland. Free radicals may be involved in the aetiology of cancer and cardiovascular diseases. In epidemiological studies poor plasma levels of all essential antioxidants are associated with increased relative risks; in particular, low levels of carotene and vitamin E with the risk of cancer and ischemic heart disease, respectively. The studies suggest that for optimal synergistic protection the plasma antioxidant levels should simultaneously exceed the threshold values of 28-30 mumol/l lipid-standardized vitamin E, 40-50 mumol/l vitamin C, 0.4-0.5 mumol/l carotene and 2.2-2.8 mumol/l lipid-standardized vitamin A. However the preventive efficacy of an optional antioxidant status is still to be proven in randomized intervention trials. Although these antioxidant micronutrients may be the primary protective components of vegetable-rich 'preventive' diets, the potentials of other plant components await exploration, eg carotenoids other than beta-carotene, bioflavonoids and oxygen-sensitive B-vitamins. 
Publication Types:
Review
Review, academic 
PMID: 8221032, UI: 94036055


35: Ann Clin Res 1987;19(5):313-20 
Dietary recommendations in cancer prevention. Bruce A Swedish Food Administration, Uppsala. 
In order to prevent diet-induced cancer, many countries regulate the use of food additives (e.g. nitrites) and control the level of harmful substances, such as pesticide residues and mycotoxins in food. In most affluent countries therefore, these factors play a minor role in cancer causation. The dietary intake of agents preventing cancer, such as nutrients, dietary fibre and some natural components in plants is probably of much greater importance in cancer prevention. So far there are only general recommendations promoting increased consumption of food rich in these substances. Some international and national organizations have published dietary guidelines specifically intended to decrease the risk of cancer. In many respects, the recommendations given in these guidelines do not differ from those published during the last decades with the aim of preventing, for example, cardiovascular diseases. They all stress the need to decrease the intake of fat and sodium and to increase the consumption of foods rich in dietary fibre and nutrients such as vitamins A, C and E. Publication Types: Review Review, tutorial PMID: 3327443, UI: 88162063 

36: Int J Epidemiol 1990;19 Suppl 1:S32-42 Protective dietary factors and lung cancer. 
Fontham ET 
Department of Pathology, Louisiana State University Medical Center, New Orleans 
70112. 
Since the first report of a protective effect of dietary vitamin A on lung cancer risk was issued in 1975, a succession of retrospective (case-control) and prospective (cohort) epidemiological studies have examined the association. Food frequency questionnaires have been used to assess dietary intake of food groups and to generate indices of specific dietary components, in particular retinol and carotene. Serum levels of retinol, carotenoids, and other micronutrients have been determined as well, and related to risk of lung cancer. The dietary studies have been notably consistent, finding an approximate 50% reduction in risk associated with high compared to low consumption of carotene-containing fruits and vegetables. Unresolved issues include gender differences, histological specificity and the interaction with cigarette smoking as well as the role of other possible protective factors found in these foods--indoles, vitamin C, trace minerals. Most studies in which serum beta-carotene was assayed in prospectively collected blood samples have found lower levels of beta-carotene in people who subsequently developed lung cancer. Unlike carotene, blood retinol levels do not reflect dietary intake under normal conditions and, as might be expected, have failed to show a consistent relation with risk of lung cancer. Although epidemiological studies have not strongly supported the role of preformed retinol as a protective agent, animal studies have provided convincing evidence that retinol and synthetic retinoids are protective against epithelial tumours including those of the lung. A number of on-going clinical trials are testing the efficacy of retinol, beta-carotene, synthetic retinoids and alpha-tocopherol for preventing cancer of the lung, especially in high risk groups such as heavy smokers, miners and asbestos workers. It is hoped that these trials will help explain the nature of the observed protective effect of fruit and vegetables. Publication Types: Review Review, multicase PMID: 2258274, UI: 91078917 

37: Am J Clin Nutr 1991 Jan;53(1 Suppl):251S-259S Vegetables, fruits, and carotenoids and the risk of cancer. Ziegler RG Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 
20892. 
Low intake of vegetables, fruits, and carotenoids is consistently associated with increased risk of lung cancer in both prospective and retrospective studies. In addition, low levels of beta-carotene in serum or plasma are consistently associated with the subsequent development of lung cancer. The simplest explanation is that beta-carotene is protective. Since retinol (preformed vitamin A) is not related in a similar manner to lung cancer risk, beta-carotene appears to function through a mechanism that does not require conversion into vitamin A. However, the importance of other carotenoids and other constituents of vegetables and fruit has not been adequately explored. Both prospective and retrospective studies suggest that vegetable and fruit intake may reduce the risk of cancers of the mouth, pharynx, larynx, esophagus, stomach, colon, rectum, bladder, and cervix. But because of fewer studies and less consistency among studies, the epidemiologic evidence is at present less persuasive than for lung cancer. Publication Types: Review Review, tutorial PMID: 1985395, UI: 91090023 

38: Am J Clin Nutr 1996 Jun;63(6):985S-990S Oxidative damage and defense. Jacob RA, Burri BJ 
USDA, Agricultural Research Service, Western Human Nutrition Research Center, San Francisco, CA 94129, USA. Increased production of reactive oxygen species is a feature of most, if not all, human disease, including cardiovascular disease and cancer. Dietary antioxidants may be especially important in protecting against human diseases associated with free radical damage to cellular DNA, lipids, and proteins. Ascorbic acid is an effective water-soluble antioxidant, and epidemiologic studies suggest that increased ascorbate nutriture is associated with reduced risk of some degenerative diseases, especially cancer and eye cataracts. Population studies have also shown that high vitamin E intakes are associated with decreased risk of coronary heart disease, possibly as a result of inhibition of atherogenic forms of oxidized low-density lipoprotein. Recent data suggest that beta-carotene provides protection against lipid peroxidation in humans, as well as provitamin A activity. Yet, present data are not sufficient to quantitate micronutrient requirements needed to protect against oxidative damage. The antioxidant roles of many food constituents, such as polyphenols, have not been clarified. Most antioxidants can act as prooxidants under certain conditions, and more research is needed to determine the occurrence and importance of this in vivo. The few controlled intervention trials carried out so far have shown mixed results as to the potential of antioxidant supplements for reducing the incidence of chronic diseases. Definitive recommendations on antioxidant intakes for disease prevention must await evidence from controlled studies and intervention trials, some currently in progress. Overall, the present data suggest that protection against oxidative damage and related disease is best served by the variety of antioxidant substances found in fruit and vegetables. Publication Types: Review Review, tutorial PMID: 8644698, UI: 96237792 


39: Pathol Biol (Paris) 1996 Jan;44(1):42-5 
Update on dietary antioxidants and cancer. Gaziano JM, Hennekens CH Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215-1204, USA. 
 
Advances in diagnosis and treatment of cancer, as well as increased understanding of the mechanisms of the disease, have provided and will certainly continue to provide enormous benefit to affected individuals. At the same time, interventions that may prevent common cancers from developing in healthy people could, at least in theory, afford even greater benefits to society as a whole. The hypothesis that antioxidant vitamins might reduce cancer risk is based on a large body of both basic and human epidemiologic research. A large number of case-control and cohort studies provide remarkably consistent data suggesting that consumption of foods rich in antioxidant vitamins reduce risks of developing epithelial cancers. These data raise the question of a possible role of antioxidants, such as vitamins C and E, and beta carotene, in the primary prevention of cancer as well ar cardiovascular disease but do not provide a definitive answer. Despite the lack of clear benefit, there has been a rapid increase in the consumption of supplements of these micronutrients. Limited randomized trial data on the role of supplemental antioxidants are available. A number of randomized trials are currently underway designed to test the hypothesis that antioxidants prevent chronic diseases and to evaluate the long term safety of the widespread practice of supplementation. Well designed and well conducted large-scale randomized trials are necessary to provide a definitive positive or negative result on which public policy can be based, or a null result that is truly informative and that can then safely permit the rechanneling of already limited resources to other areas of research. Publication Types: Review Review, tutorial PMID: 8734299, UI: 96318989 


40: Am J Med 1994 Sep 26;97(3A):2S-4S; discussion 22S-28S Antioxidant 
vitamins and cancer.
Hennekens CH 
Department of Medicine and Ambulatory Care and Prevention, Harvard Medical School, Boston, Massachusetts. 
 
  Cancer is the second leading cause of death in the United States as well as most developed countries. Although advances in treatment have afforded tremendous benefits to large numbers of patients, effective primary prevention measures could, in theory, have an even greater public health impact. Diet has been postulated to account for as much as 35% of all human cancers, raising the possibility that specific constituents of diet with cancer chemopreventive effects could be identified. Risk reductions of even 20-30%, which is the most likely magnitude of any protective effect of nutritional agents, could have a significant public health impact on so common and serious a disease. Antioxidant vitamins are among the constituents of diet hypothesized to exert chemopreventive effects. Antioxidant vitamins, which include beta-carotene (pro-vitamin A), vitamin E, and vitamin C, are hypothesized to decrease cancer risk by preventing tissue damage by trapping organic free radicals and/or deactivating excited oxygen molecules, a by-product of many metabolic functions. Over 100 observational epidemiologic studies have assessed the relationship of dietary antioxidant intake or blood nutrient levels with cancer risk. Such studies are not entirely consistent but provide support for the hypothesis that antioxidant vitamin intake may decrease cancer risk. However, the chief limitation of such observational studies is their inability to control for all factors associated with vitamin intake that might independently affect cancer risk. Such unknown or unmeasured confounding variables could account for all or part of any observed associations. For this reason, definitive data on the role of antioxidant vitamins and cancer can derive only from properly conducted large-scale randomized trials of sufficient sample size, dose, and duration of treatment and follow-up. Two large-scale trials have been completed, and several are currently ongoing among well-nourished populations at high risk for cancer as well as among individuals at usual risk. Over the next several years, these trials should provide clear evidence concerning the role of antioxidant vitamins in the prevention of cancer. Such data are crucial for both individual clinical decision making as well as rational public health policy. Publication Types: Review Review, tutorial PMID: 8085583, UI: 94367840 

41: Hematol Oncol Clin North Am 1991 Feb;5(1):43-68 Antioxidant micronutrients in cancer prevention. Dorgan JF, Schatzkin A Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland. 
 
Antioxidant micronutrients are one of the body's primary defenses against free radicals and reactive oxygen molecules. Carotenoids, vitamin C, and vitamin E trap these molecules, and selenium is an essential component of an antioxidant enzyme. There is considerable support from animal studies for a protective effect of antioxidant micronutrients on cancer. However, the role of these micronutrients in cancer prevention in humans is less clear. Diet studies suggest protective effects of fruits and vegetables on risk of cancer at several sites. Inverse associations between dietary carotenoids and serum beta-carotene and lung cancer have been observed repeatedly. Vitamin C has also been consistently inversely associated with risk of oral and esophageal cancer in diet studies and with stomach cancer in both diet and plasma studies. It remains unknown, however, whether carotenoids and vitamin C or some other component of fruits and vegetables, the primary sources of these micronutrients, prevent cancer in humans. Selenium has been inversely correlated with cancers at numerous sites in ecologic studies, but observational studies do not provide strong support for a protective effect of selenium on cancer at any site. There also is not strong support for a protective effect of vitamin E on cancer in humans. Results of studies on the association of antioxidant micronutrients with cancer at many sites are inconsistent. This could be due to lack of a true protective effect or could be related to methodologic problems in assessing dietary intake in epidemiologic studies. Publication Types: Review Review literature PMID: 2026568, UI: 91224907 

42: Nutr Clin Pract 1995 Feb;10(1):19-25 Role of antioxidants in health maintenance. Sardesai VM 
 
Free radicals are produced in the body as by products of normal metabolism and as a result of exposure to radiation and some environmental pollutants. Because they are highly reactive, they can damage cellular components and are implicated in a variety of diseases. Free radicals are normally neutralized by efficient systems in the body that include the antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and the nutrient-derived antioxidant small molecules (vitamin E, vitamin C, carotenes, flavonoids, glutathione, uric acid, and taurine). In healthy individuals, a delicate balance exists between free radicals and antioxidants. In some pathologic conditions such as diabetes, and in critically ill patients, oxidative stress causes the level of antioxidants to fall below normal. Antioxidant supplements for such conditions are expected to be of benefit. As a preventive measure against certain diseases, the best approach for healthy individuals is to regularly consume adequate amounts of antioxidant-rich foods, eg, fruits and vegetables. Publication Types: Review 
Review, tutorial 
PMID: 7898413, UI: 95206219 

 
44: Biochem Soc Trans 2000 Feb;28(2):16-22 
Human metabolic pathways of dietary flavonoids and cinnamates. Williamson G, Day AJ, Plumb GW, Couteau D Institute of Food Research, Norwich Research Park, Colney, UK. 
  Flavonoids and cinnamates are widespread phenolic secondary metabolites synthesized by plants for defensive purposes. Many foods and beverages contain high levels of phenolic compounds. Certain phenolics in the diet are particularly bioactive and have pronounced effects on mammalian cells. These effects, together with epidemiological studies and animal models, have led to the hypothesis that dietary phenolics contribute to the health benefits of a diet rich in fruit and vegetables. This paper examines the biochemistry of the uptake and metabolic route of two groups of plant phenolics, the flavonols and hydroxycinnamates.