Prevention of cancer: vegetables and plants

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.     

Chemoprevention of cancer: phenolic antioxidants (BHT, BHA)

1. The synthetic phenolic antioxidants (e.g. BHT, BHA) added to human and animal food are able to lengthen the life of organisms and lower the incidence of cancer caused by chemical compounds. 2. On the other hand they may not be rendered completely harmless since they can cause lung damage (BHT) or promote the action of some carcinogens (BHA). 3. They could act as compounds preventing cancer either via interception of harmful free radicals, activating the detoxifying enzymes of the body, inhibiting the formation of ultimately carcinogenic metabolites and their binding to DNA, and modifying the immune response of the organism. 4. Their action is influenced by their own chemical structure, the composition of carcinogen, the strain, sex and age of experimental animals, the tissue upon which they are supposed to act and the time of their administration in relation to the time of the carcinogen insult. 5. These compounds are concentrated in adipose tissue, liver and kidney. They are excreted within tens of hours mainly in urine. 6. The acceptable daily intake of BHA is at present considered to be 0.6 mg kg-1 body wt day-1. In spite of their possible tumor-promoting properties they could not be considered overtly toxic. Their pronounced chemoprotective role against some forms of chemical carcinogenesis deserves considerable attention.     

Micronutrient intake and risk of colon and rectal cancer in a Danish cohort

Background: Micronutrients may protect against colorectal cancer. Especially folate has been considered potentially preventive. However, studies on folate and colorectal cancer have found contradicting results; dietary folate seems preventive, whereas folic acid in supplements and fortification may increase the risk. Objective: To evaluate the association between intake of vitamins C, E, folate and beta-carotene and colorectal cancer risk, focusing on possibly different effects of dietary, supplemental and total intake, and on potential effect modification by lifestyle factors. Design: In a prospective cohort study of 56,332 participants aged 50–64 years, information on diet, supplements and lifestyle was collected through questionnaires. 465 Colon and 283 rectal cancer cases were identified during follow-up. Incidence rate ratios of colon and rectal cancers related to micronutrient intake were calculated using Cox proportional hazard analyses. Results: The present study found a protective effect of dietary but not supplemental folate on colon cancer. No association with any other micronutrient was found. Rectal cancer did not seem associated with any micronutrient. For both colon and rectal cancer, we found an interaction between dietary folate and alcohol intake, with a significant, preventive effect among those consuming above 10 g alcohol/day only. Conclusions: This study adds further weight to the evidence that dietary folate protects against colon cancer, and specifies that there is a source-specific effect, with no preventive effect of supplemental folic acid. Further studies should thus take source into account. Vitamins C, E and beta-carotene showed no relation with colorectal cancer.     

Signal transduction pathways leading to cell cycle arrest and apoptosis induction in cancer cells by Allium vegetable-derived organosulfur compounds: a review

Epidemiological studies continue to support the premise that dietary intake of Allium vegetables (e.g., garlic, onions and so forth) may lower the risk of various types of cancer. Anticarcinogenic effect of Allium vegetables is attributed to organosulfur compounds (OSCs) that are generated upon processing of these vegetables. Preclinical studies have provided convincing evidence to indicate that Allium vegetable-derived OSCs including diallyl sulfide, diallyl disulfide and diallyl trisulfide are highly effective in affording protection against cancer in laboratory animals induced by a variety of chemical carcinogens. Inhibition of carcinogen activation through modulation of cytochrome P450-dependent monooxygenases and/or acceleration of carcinogen detoxification via induction of phase II enzymes (glutathione transferases, quinone reductase, etc.) are believed to be responsible for protective effects of OSCs against chemically induced cancers. More recent studies have indicated that some naturally occurring OSC analogues can suppress proliferation of cancer cells in culture and inhibit growth of transplanted tumor xenografts in vivo by inducing apoptosis and/or by perturbing cell cycle progression. This review summarizes current knowledge on signal transduction pathways leading to perturbations in cell cycle progression and apoptosis induction by OSCs.     

Fats and atheroma: a retrial.

The controversy over medical endorsement of dietary measures to reduce cholesterol intake has been reconsidered. The results of several published reports that apparently do not confirm the association between diet, cholesterol concentrations, and ischaemic heart disease (IHD) were found to be largely inapplicable to the argument. Results of primary prevention trials, however, suggested that lowering the cholesterol concentration had a beneficial effect in reducing morbidity from IHD. The "average Western diet" is particularly associated with accelerated or premature atherosclerotic disease, yet the saturated fatty acid component of the diet may be only one of several factors relevant to IHD. Such diets are usually high in refined carbohydrate and total energy intake. Disordered nutrition generally, and other environmental and constitutional factors seem to be important in the aetiology of IHD. A prudent diet, incorporating decreased intake of fats, simple sugars, and refined carbohydrate, with polyunsaturated fats comprising less than 25% of total energy intake, may be the best method of reducing the incidence of IHD and other diseases of overnutrition.     

Protective role of Apigenin on the status of lipid peroxidation and antioxidant defense against hepatocarcinogenesis in Wistar albino rats.

Apigenin, a dietary plant derived flavone subclass of flavonoid is expected to play a role in cancer chemoprevention and cancer chemotherapy. Here we designed our experiment to establish whether treatment of apigenin (25 mg/kg body weight) for 14 consecutive days to (N-nitrosodiethylamine) DEN induced (200 mg/kg body weight; by single ip. injection) and phenobarbital promoted (0.05% through drinking water for 14 successive weeks) rats provide protection against the oxidative stress caused by the carcinogen. The level of lipid peroxidation (LPO) markedly increased in carcinogen administered animals, which was brought back to near normal by apigenin treatment. In contrast the activities/levels of the antioxidant status both in liver and kidney were decreased in carcinogen administered animals, which was recouped back to near normal upon apigenin administration. From our findings we concluded that apigenin prevents LPO and protects antioxidant system in DEN induced and phenobarbital promoted hepatocellular carcinogenesis.     

Dietary fibre and colon cancer: epidemiologic and experimental evidence.

Epidemiologic studies have identified two dietary factors, a relatively high intake of fat and a relatively low intake of fibre, that are associated with colon cancer in humans. However, a recent study has shown a low risk of large bowel cancer in a rural Finnish population with a high dietary intake of fat, but also a high intake of fibre. Observations in humans and studies in animals have indicated that dietary fibre may protect against colon carcinogenesis by binding bile acids in the intestinal tract, by a direct effect on the colonic mucosa and by an indirect effect on the metabolism of carcinogens. The strength of protection varies with the type of fibre.     

Will the 'Good Fairies' Please Prove to us that Vitamin E Lessens Human Degenerative Disease?

Recent research about the role of free radical derivatives of oxygen and nitrogen in biological systems has highlighted the possibility that antioxidants, such as vitamin E, that prevent these processes in vitro may be capable of carrying out a similar function in living organisms in vivo. There is increasing evidence that free radical reactions are involved in the early stages, or sometimes later on, in the development of human diseases, and it is therefore of particular interest to inquire whether vitamin E and other antioxidants, which are found in the human diets, may be capable of lowering the incidence of these diseases. Put simply, the proposition is that by improving human diets by increasing the quantity in them of antioxidants, it might be possible to reduce the incidence of a number of degenerative diseases. Of particular significance to these considerations is the likely role of the primary fat-soluble dietary antioxidant vitamin E in the prevention of degenerative diseases such as arteriosclerosis, which is frequently the cause of consequent heart attacks or stroke, and prevention of certain forms of cancer, as well as several other diseases. Substantial evidence for this proposition now exists, and this review is an attempt to give a brief account of the present position. Two kinds of evidence exist; on the one hand there is very substantial basic science evidence which indicates an involvement of free radical events, and a preventive role for vitamin E, in the development of human disease processes. On the other hand, there is also a large body of human epidemiological evidence which suggests that incidence of these diseases is lowered in populations having a high level of antioxidants, such as vitamin E, in their diet, or who have taken steps to enhance their level of intake of the vitamin by taking dietary supplements. There is also some evidence which suggests that intervention with dietary supplements of vitamin E can result in a lowered risk of disease, in particular of cardiovascular disease, which is a major killer disease among the developed nations of the world. The intense interest in this subject recently has as its objective the possibility that, by making some simple alterations to dietary lifestyle, or by enhancing the intake of vitamin E by fortification of foods, or by dietary supplements, it may be possible to reduce substantially the risk of a large amount of common, highly disabling human disease. By this simple means, therefore it may be possible to improve substantially the quality of human life, in particular for people of advancing years.     

Will the 'Good Fairies' Please Prove to us that Vitamin E Lessens Human Degenerative Disease?

Recent research about the role of free radical derivatives of oxygen and nitrogen in biological systems has highlighted the possibility that antioxidants, such as vitamin E, that prevent these processes in vitro may be capable of carrying out a similar function in living organisms in vivo. There is increasing evidence that free radical reactions are involved in the early stages, or sometimes later on, in the development of human diseases, and it is therefore of particular interest to inquire whether vitamin E and other antioxidants, which are found in the human diets, may be capable of lowering the incidence of these diseases. Put simply, the proposition is that by improving human diets by increasing the quantity in them of antioxidants, it might be possible to reduce the incidence of a number of degenerative diseases. Of particular significance to these considerations is the likely role of the primary fat-soluble dietary antioxidant vitamin E in the prevention of degenerative diseases such as arteriosclerosis, which is frequently the cause of consequent heart attacks or stroke, and prevention of certain forms of cancer, as well as several other diseases. Substantial evidence for this proposition now exists, and this review is an attempt to give a brief account of the present position. Two kinds of evidence exist; on the one hand there is very substantial basic science evidence which indicates an involvement of free radical events, and a preventive role for vitamin E, in the development of human disease processes. On the other hand, there is also a large body of human epidemiological evidence which suggests that incidence of these diseases is lowered in populations having a high level of antioxidants, such as vitamin E, in their diet, or who have taken steps to enhance their level of intake of the vitamin by taking dietary supplements. There is also some evidence which suggests that intervention with dietary supplements of vitamin E can result in a lowered risk of disease, in particular of cardiovascular disease, which is a major killer disease among the developed nations of the world. The intense interest in this subject recently has as its objective the possibility that, by making some simple alterations to dietary lifestyle, or by enhancing the intake of vitamin E by fortification of foods, or by dietary supplements, it may be possible to reduce substantially the risk of a large amount of common, highly disabling human disease. By this simple means, therefore it may be possible to improve substantially the quality of human life, in particular for people of advancing years.     

Selenium-mediated inhibition of mammary carcinogenesis

Using the dimethylbenz(a)anthracene-induced mammary tumor model in rats, our studies indicated that there was a dose-response relationship between dietary selenium supplementation and the inhibition of mammary carcinogenesis. The degree of inhibition was proportional to the level of dietary selenium up to 5 ppm, at which point toxicity in the form of a reduction in weight gain was evident. Moreover, it was observed that the chemopreventive efficacy of selenium was influenced by the dose of carcinogen as well as the fat intake of the animals. By supplementing selenium for defined periods of time, we concluded that selenium inhibited both the initiation and the promotion phases of chemical carcinogenesis, and that a continuous intake of selenium was necessary to achieve maximal suppression of tumor growth. In an attempt to improve the efficacy of lower levels of selenium, we conducted another series of experiments in which selenium and vitamin E were tested in combination. Results showed that although vitamin E alone had no prophylactic effect against tumorigenesis, it potentiated the ability of selenium to inhibit the development of mammary tumors. Further investigation suggested that the anticarcinogenic action of selenium could not be explained by its antioxidant function in lipid peroxidation. On the other hand, vitamin E might be able to provide a more favorable climate against oxidant stress to facilitate selenium in exerting its inhibitory effect through some other mechanisms.     

Childhood energy intake and adult mortality from cancer: the Boyd Orr Cohort Study.

OBJECTIVE: To examine the relation between energy intake in childhood and adult mortality from cancer. STUDY DESIGN: Cohort study. SETTING: 16 rural and urban centres in England and Scotland. SUBJECTS: 3834 people who took part in Lord Boyd Orr''s Carnegie survey of family diet and health in prewar Britain between 1937 and 1939 who were followed up with the NHS, central register. Standardised methods were used to measure household dietary intake during a one week period. MAIN OUTCOME MEASURES: Cancer mortality. RESULTS: Significant associations between childhood energy intake and cancer mortality were seen when the confounding effects of social variables were taken into account in proportional hazards models (relative hazard for all cancer mortality 1.15 (95% confidence interval 1.06 to 1.24), P = 0.001, for every MJ increase in adult equivalent daily intake in fully adjusted models). This effect was essentially limited to cancers not related to smoking (relative hazard 1.20; 1.07 to 1.34; P = 0.001), with similar effects seen in men and women. CONCLUSION: This positive association between childhood energy intake and later cancer is consistent with animal evidence linking energy restriction with reduced incidence of cancer and the association between height and human cancer, implying that higher levels of energy intake in childhood increase the risk of later development of cancer. This evidence for long term effects of early diet confirm the importance of optimal nutrition in childhood and suggest that the unfavourable trends seen in the incidence of some cancers may have their origins in early life.     

Dietary copper and dimethylhydrazine affect protein kinase C isozyme protein and mRNA expression and the formation of aberrant crypts in colon of rats.

Low dietary copper has been shown to decrease the expression of various protein kinase C (PKC) isozymes and increase the risk of colon cancer development in experimental animals. The purpose of this study was to investigate the relationship between dietary copper and carcinogen administration on PKC isozyme accumulation and aberrant crypt foci (ACF) formation in rats fed 0.9 and 7.7 microg Cu/g diet. After 24 and 31 d on the diets, the rats were injected with either dimethylhydrazine (DMH) (25 mg/kg i.p.) or saline and killed at two time points (2 wk and 8 wk after DMH). Rats fed low dietary copper had significantly lower (p<0.0001) hematocrits, hemoglobin, ceruloplasmin activity and plasma and liver copper concentrations than rats fed adequate dietary copper. Ingestion of low dietary copper significantly (p<0.005) increased the formation of DMH-induced ACF (116.8 vs 59.6). Low dietary copper significantly (p<0.05) decreased the concentration of PKC alpha, delta, and zeta in the colon at 2 wk but not at 8 wk. Thus, changes in PKC isoform protein concentration may be related to increased susceptibility of copper-deficient animals to colon cancer.     

A review of clinical trials in dietary interventions to decrease the incidence of coronary artery disease

Of the associations between dietary elements and coronary artery disease (CAD), the greatest body of evidence deals with the beneficial effect of reducing the dietary intake of saturated fatty acids and cholesterol. Furthermore, it is well established, on the basis of convincing evidence, that reduction in serum total cholesterol results in reduction in coronary morbidity and mortality, as well as in regression of other atherosclerotic manifestations.In fact, dietary intervention studies revealed that it is possible to reduce the incidence of coronary death and nonfatal myocardial infarction, as well as manifestations of atherosclerosis in cerebral and peripheral arteries, by reducing dietary intake of saturated fat and cholesterol. In two recently reported dietary interventions the incidence of coronary events, especially coronary mortality, and total mortality were reduced by increased intake of n-3 long-chain polyunsaturated fatty acids and by a modification of the diet toward a Mediterranean-type diet (rich in α-linolenic acid. In addition to those findings, the potential efficacy of the dietary newcomers phytostanol and phytosterol esters on reducing coronary incidence is discussed in the present review.     

Vitamin B6-mediated suppression of colon tumorigenesis,cell proliferation,and angiogenesis (review)

This review describes current research on the preventive effect of dietary vitamin B(6) against colon tumorigenesis and its possible mechanisms. Studies in cell culture have demonstrated that high levels of vitamin B(6) suppress growth of some cancer cells. From these studies it has been considered that supraphysiological doses of vitamin B(6) suppress tumor growth and metastasis. However, recent rodent study has indicated that azoxymethane-induced colon tumorigenesis in mice is suppressed by moderate doses of dietary vitamin B(6.) Epidemiological studies also support an inverse relationship between vitamin B(6) intake and colon cancer risk. Potential mechanisms underlying the preventive effect of dietary vitamin B(6) have been suggested to include the suppression of cell proliferation, oxidative stress, nitric oxide (NO) synthesis, and angiogenesis.     

Spermine and gene methylation: a mechanism of lifespan extension induced by polyamine-rich diet

The polyamines spermidine and spermine are synthesized in almost all organisms and are also contained in food. Polyamine synthesis decreases with aging, but no significant decrease in polyamine concentrations were found in organs, tissues, and blood of adult animals and humans. We found that healthy dietary patterns were associated with a preference for polyamine-rich foods, and first reported that increased polyamine intake extended the lifespan of mice and decreased the incidence of colon cancer induced by repeated administration of moderate amounts of a carcinogen. Recent investigations have revealed that changes in DNA methylation status play an important role in lifespan and aging-associated pathologies. The methylation of DNA is regulated by DNA methyltransferases in the presence of S-adenosylmethionine. Decarboxylated S-adenosylmethionine, converted from S-adenosylmethionine by S-adenosylmethionine decarboxylase, provides an aminopropyl group to synthesize spermine and spermidine and acts to inhibit DNMT activity. Long-term increased polyamine intake were shown to elevate blood spermine levels in mice and humans. In vitro studies demonstrated that spermine reversed changes induced by the inhibition of ornithine decarboxylase (e.g., increased decarboxylated S-adenosylmethionine, decreased DNA methyltransferase activity, increased aberrant DNA methylation), whose activity decreases with aging. Further, aged mice fed high-polyamine chow demonstrated suppression of aberrant DNA methylation and a consequent increase in protein levels of lymphocyte function-associated antigen 1, which plays a pivotal role on inflammatory process. This review discusses the relation between polyamine metabolism and DNA methylation, as well as the biological mechanism of lifespan extension induced by increased polyamine intake.     

Relation of changes in amount and type of dietary fat to fecapentaenes in premenopausal women

Correlation studies suggest that fecal mutagenicity is increased in groups eating high-fat diets, the same groups who are often found to have high colorectal cancer incidence and mortality. The fecapentaenes are the best characterized class of fecal mutagens, but the relationship of dietary fat intake to the excretion of these potent genotoxins is unknown. We studied the effect of changes in amount and type of dietary fat on fecapentaene levels in 31 premenopausal women 20-40 years of age who participated in a controlled feeding study. After a pre-diet free-living period lasting 1 menstrual cycle, women were placed on a high-fat (40% energy from fat) diet for 4 menstrual cycles and then switched to a low-fat (20% energy from fat) diet for an additional 4 menstrual cycles. One-half the subjects were maintained throughout the study at a ratio of polyunsaturated-to-saturated fatty acids (P/S ratio) of 1.0, the other half at 0.3; body weight was constant. All meals during the controlled diet periods were prepared at the Human Study Facility of the Beltsville Human Nutrition Research Center. Fecapentaene and fecapentaene precursor levels were measured in acetone extracts from 3-day pooled stool samples collected during the study. No differences in fecapentaene or precursor levels were observed between the high- and low-fat diets at either P/S ratio. Fecapentaene and precursor levels were higher while on controlled diets than during the pre-diet free-living period, and levels declined again in the post-diet free-living period. We conclude that dietary fat has no significant effect on fecapentaene or precursor levels in acetone extracts of stool in premenopausal women. The effect of other dietary or non-dietary factors on fecapentaenes remains unknown.     

Pitfalls of enzyme-based molecular anticancer dietary manipulations: food for thought

Dietary approaches to cancer chemoprevention increasingly have focused on single nutrients or phytochemicals to stimulate one or another enzymatic metabolizing system. These procedures, which aim to boost carcinogen detoxification or inhibit carcinogen bioactivation, fail to take into account the multiple and paradoxical biological outcomes of enzyme modulators that make their effects unpredictable. Here, we critically examine the scientific and medical evidence for the idea that the physiological roles of specific enzymes may be manipulated by regular, long-term administration of isolated nutrients and other chemicals derived from food plants. Instead, we argue that consumption of healthful diets is most likely to reduce mutagenesis and cancer risk, and that research efforts and dietary recommendations should be redirected away from single nutrients to emphasize the improvement of dietary patterns as a principal strategy for public health policy.     

Growth Pattern and Dietary Intake of Children with Chronic Renal Insufficiency

The growth pattern and dietary intake of 33 children with varying degrees of renal insufficiency has been investigated. The development of impaired renal function in infancy has a more deleterious effect on linear growth than has its onset in later years. A reduction in growth velocity may occur once the glomerular filtration rate falls below 25 ml/min/1·73m². There was a significant reduction of the energy, protein, and vitamin D intakes of children with renal insufficiency compared with those recommended for their age, and of energy intake compared with that of normal children of their own height. Reduced growth velocity occurred when energy intake fell below 80% of that recommended. The reduction in the intake of energy and nutrients in these children may in part be responsible for their growth retardation.     

Effect of dietary fibre on nitrogen retention and fibre associated threonine losses in growing pigs

Apart from being an energy source, dietary fibre is also discussed to act as anti-nutritional factor reducing apparent precaecal protein and amino acid (AA) digestibility due to reduced absorption or increased endogenous secretion or both. However, the amounts of protein and AA of endogenous origin determined at the terminal ileum in cannulated animals do not represent the total losses associated with endogenous secretion. A high proportion of secreted protein is reabsorbed and does not reach the terminal ileum, and losses occur during synthesis of endogenous protein. Therefore, the present study used an alternative indirect approach, taking the reduction of nitrogen (N) retention in a threonine (Thr) limited diet as a sensitive indicator for fibre-associated Thr losses. Two experiments were conducted with 12 castrated male pigs each between 37 and 75 kg body weight to measure the effect of the intake of Thr and 150 and 300 g/d fibre from wheat bran (Exp. 1), or 150 g/d fibre from rape seed, cassava leaves, and cassava root peels, respectively (Exp. 2), on N retention. During two (Exp. 1) and three (Exp. 2) balance periods the animals were subjected to the dietary treatments according to a cross-over design. All animals received 1350 g/d of a wheat-soybean-based diet supplemented with free AA to ensure Thr being the first-limiting AA. To determine the effect of Thr on N retention, intake of the basal diet was reduced to 1150 g/d and supplemented with corn starch to reach equal energy intake and an unchanged AA pattern. With increasing BW additional starch was added to all diets to ensure a constant energy intake of 1.25 MJ ME/kg BW(0.75). Since the fibre sources contained small amounts of Thr, N retentions were corrected for precaecal digestible Thr intake originating from the fibre sources according to the Thr effect on N retention as determined in experiment 1. Corrected N retentions were affected by fibre level (p = 0.007) and source (p < 0.001). Fibre-associated Thr losses amounted to 3.3, 3.2, 1.2, and 1.1 g/kg fibre from wheat bran, rapeseed, cassava leaf, and cassava root peel, respectively. It is concluded that Thr losses per gram of dietary fibre depend on the fibre source and that fibre concentration and source in pig diets should be considered as a factor affecting Thr requirement.     

Variability of mammary carcinogenesis induction in female Sprague-Dawley and Wistar:Han rats: the effect of season and age

It is important to determine and clarify the variability of mammary carcinogenesis induction in animal experimental studies particularly in connection with chemoprevention projects. The circannual seasonal rhythms of hormone levels or various parameters within the immune system may involve factors participating in mammary gland carcinogenesis. In our study, 19 experiments were conducted and all of them lasted for about 25 weeks after chemical carcinogen administration (DMBA or NMU) under standard laboratory conditions. Females of two rat strains - a medium susceptible Sprague-Dawley strain and a very low susceptible Wistar:Han were used. We observed not only the effect of seasonal changes but also the effect of age after single or repeated carcinogen administration. The seasonal dependence of mammary carcinogenesis with higher tumor incidence during long days in comparison with winter short days has been demonstrated in Sprague-Dawley rats. In experiments on the Wistar:Han strain, certain features of seasonal character were recorded, although the very low susceptibility of this strain to mammary carcinogenesis might have influenced the results. A limited period of carcinogen administration in early puberty around postnatal days 43-46 (higher susceptibility), when compared to the period after postnatal day 50, is the factor significantly increasing incidence and frequency of mammary carcinogenesis in the Sprague-Dawley strain. Our results indicate the need to consider the effect of season and age of animals at the time of carcinogen administration on rat mammary carcinogenesis induction. However, the application of the results obtained in one strain of experimental animals may only lead to misleading conclusions.