The Role of Dietary Fat throughout the Prostate Cancer Trajectory

Prostate cancer is the second most common cancer diagnosed world-wide; however, patients demonstrate exceptionally high survival rates. Many lifestyle factors, including obesity and diet, are considered risk factors for advanced prostate cancer. Dietary fat is a fundamental contributor to obesity and may be specifically important for prostate cancer patients. Prostate cancer treatment can result in changes in body composition, affecting quality of life for survivors by increasing the risk of co-morbidities, like cardiovascular disease and diabetes. We aim to examine dietary fat throughout the prostate cancer treatment trajectory, including risk, cancer development and survivorship. Focusing on one specific nutrient throughout the prostate cancer trajectory provides a unique perspective of dietary fat in prostate cancer and the mechanisms that may exacerbate prostate cancer risk, progression and recurrence. Through this approach, we noted that high intake of dietary fat, especially, high intake of animal and saturated fats, may be associated with increased prostate cancer risk. In contrast, a low-fat diet, specifically low in saturated fat, may be beneficial for prostate cancer survivors by reducing tumor angiogenesis and cancer recurrence. The insulin-like growth factor (IGF)/Akt signaling pathway appears to be the key pathway moderating dietary fat intake and prostate cancer development and progression.     

膳食营养素摄入与前列腺癌

为探讨膳食营养素与前列腺癌的关系，对１０２例前列腺癌患者进行了１∶１配比的病例对照研究。根据近三月食物摄入量的平均值计算蛋白质、脂肪、糖类等１１种营养素及总执量的日平均摄入量，采用配对ｔ检验和条件Ｌｏｇｉｓｔｉｃ回归分析。结果表明：脂肪、糖类、视黄醇当量等的摄入量大能增加前列腺癌的危险性，维生素Ｃ、维生素Ｂ１等能降低其危险性，各营养素的多变量调整ＯＲ值及９５％可信区间分别为脂肪１．６５（１．３９～１．９６）、碳水化合物１．２２（１．１３～１．３１）、视黄醇当量３．１２（２．１８～４．７５）、维生素Ｃ０．６１（０．４６～０．８０）、维生素Ｂ１０．０２９（０．００９～０．０９）。本文还对各营养素增加或降低前列腺癌危险性的可能机制进行了讨论。     

An Investigation into the Association between DNA Damage and Dietary Fatty Acid in Men with Prostate Cancer

Prostate cancer is a growing problem in New Zealand and worldwide, as populations adopt a Western style dietary pattern. In particular, dietary fat is believed to be associated with oxidative stress, which in turn may be associated with cancer risk and development. In addition, DNA damage is associated with the risk of various cancers, and is regarded as an ideal biomarker for the assessment of the influence of foods on cancer. In the study presented here, 20 men with prostate cancer adhered to a modified Mediterranean style diet for three months. Dietary records, blood fatty acid levels, prostate specific antigen, C-reactive protein and DNA damage were assessed pre- and post-intervention. DNA damage was inversely correlated with dietary adherence (p = 0.013) and whole blood monounsaturated fatty acids (p = 0.009) and oleic acid (p = 0.020). DNA damage was positively correlated with the intake of dairy products (p = 0.043), red meat (p = 0.007) and whole blood omega-6 polyunsaturated fatty acids (p = 0.015). Both the source and type of dietary fat changed significantly over the course of the dietary intervention. Levels of DNA damage were correlated with various dietary fat sources and types of dietary fat.     

Omega-3 Fatty Acid Consumption and Prostate Cancer: A Review of Exposure Measures and Results of Epidemiological Studies

Animal studies have shown that dietary omega-3 polyunsaturated fatty acids (n-3) may play a role in the development of prostate cancer, but the results of epidemiologic studies have been equivocal. Associations in humans may vary depending on study design, measurement methodology of fatty acid intake, intake ranges, and stage of cancer development. To address this, we identified 36 published studies through PubMed (Medline) from 1993 through 2013 on long-chain n-3s and prostate cancer. Exposure measurements included dietary assessment and biomarker levels. Associations for total, early, and late stage prostate cancer were examined by subgroup of study design and exposure measure type and by using forest plots to illustrate the relative strength of associations within each subgroup. We also tested for potential threshold effects by considering studies that included measurement cut-points that met intake levels recommended by the American Heart Association. We found no consistent evidence supporting a role of n-3s in either the causation or prevention of prostate cancer at any stage or grade. Results did not vary appreciably by study design, exposure measurement, intake level, or stage of cancer development.     

Dietary Factors Modulating Colorectal Carcinogenesis

The development of colorectal cancer, responsible for 9% of cancer-related deaths, is favored by a combination of genetic and environmental factors. The modification of diet and lifestyle may modify the risk of colorectal cancer (CRC) and prevent neoplasia in up to 50% of cases. The Western diet, characterized by a high intake of fat, red meat and processed meat has emerged as an important contributor. Conversely, a high intake of dietary fiber partially counteracts the unfavorable effects of meat through multiple mechanisms, including reduced intestinal transit time and dilution of carcinogenic compounds. Providing antioxidants (e.g., vitamins C and E) and leading to increased intraluminal production of protective fermentation products, like butyrate, represent other beneficial and useful effects of a fiber-rich diet. Protective effects on the risk of developing colorectal cancer have been also advocated for some specific micronutrients like vitamin D, selenium, and calcium. Diet-induced modifications of the gut microbiota modulate colonic epithelial cell homeostasis and carcinogenesis. This can have, under different conditions, opposite effects on the risk of CRC, through the production of mutagenic and carcinogenic agents or, conversely, of protective compounds. The aim of this review is to summarize the most recent evidence on the role of diet as a potential risk factor for the development of colorectal malignancies, as well as providing possible prevention dietary strategies.     

Dietary components that counteract the increased risk of colorectal cancer related to red meat consumption

Western-style diets are associated with an increased risk of colorectal cancer (CRC). In particular, a strong correlation has been documented between CRC and the consumption of large amounts of red meat, especially processed red meat. Compared with white meat, red meat contains high levels of haem iron, a molecule that can exert a variety of genotoxic and other adverse effects on the colonic epithelium. According to current international guidelines, the reduction of red meat intake combined with the consumption of food containing antioxidant and chemoprotective substances may significantly reduce the risk of developing CRC. The dietary strategies that can help to contrast the harmful effects of haem iron are reported and discussed in this review.     

Arginine and Arginases Modulate Metabolism,Tumor Microenvironment and Prostate Cancer Progression

Arginine availability and activation of arginine-related pathways at cancer sites have profound effects on the tumor microenvironment, far beyond their well-known role in the hepatic urea cycle. Arginine metabolism impacts not only malignant cells but also the surrounding immune cells behavior, modulating growth, survival, and immunosurveillance mechanisms, either through an arginase-mediated effect on polyamines and proline synthesis, or by the arginine/nitric oxide pathway in tumor cells, antitumor T-cells, myeloid-derived suppressor cells, and macrophages. This review presents evidence concerning the impact of arginine metabolism and arginase activity in the prostate cancer microenvironment, highlighting the recent advances in immunotherapy, which might be relevant for prostate cancer. Even though further research is required, arginine deprivation may represent a novel antimetabolite strategy for the treatment of arginine-dependent prostate cancer.     

Selenium and Prostate Cancer Prevention: Insights from the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention.     

Age-Related Changes in Zinc,Copper and Selenium Levels in the Human Prostate

Pathophysiological changes in the prostate gland—benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma (PCa)—are closely related to the age of men. In the prostate gland, zinc is of particular importance for its proper functioning, especially with regard to the effects of hormonal disorders. The aim of this study was to evaluate zinc, copper and selenium concentrations in different parts of the prostate gland in relation to age and the nature of pathological changes. Zinc and copper were determined by the AAS method and selenium by the spectrofluorometric method. The concentration of zinc in the central part of the prostate increases with age, and in patients over 36 years it is twice as high as in the peripheral part, where no increase in the level of this element was observed with the age of patients. The above data confirm a possible influence of zinc on the formation of PCa (located mostly in the peripheral part of the prostate, with low levels of zinc) and BPH in the central part where the levels of this element are the highest. The results apparently confirm the disturbed homeostasis of zinc and other essential elements in the etiology of BPH and PCa.     

Effects of supplementation with vitamins A, C, and E, selenium, and zinc on immune function in a murine sensitization model

OBJECTIVE: We compared the effects of supplementing with vitamins A, C, and E, selenium, and zinc on a range of innate and specific T-helper 1 (Th1) and Th2-driven adaptive immune responses. METHODS: BALB/c mice were fed semi-purified AIN93 diets and randomly assigned to receive a diet supplemented with 120 mg/kg of vitamin A, 2500 mg/kg of vitamin C, 1000 mg/kg of vitamin E, 2 mg/kg of selenium, and 500 mg/kg of zinc (n = 15/group). After 4 wk of supplementation, mice were sensitized by topical application of di-nitro-chlorobenzene (DNCB); 2 wk later mice were challenged; and 5 d later they were killed to assess the effect on a range of innate responses (phagocytic activity, oxidative burst and tumor necrosis factor-alpha), adaptive Th1-driven responses (delayed-type hypersensitivity, DNCB-specific immunoglobulin [Ig] G2a and IgG2b, and interferon-gamma [IFN-gamma]), and adaptive Th2-driven responses (DNCB-specific IgE and IgG1 and interleukin-4 [IL-4]). RESULTS: Immune function was affected only in the vitamin A group. These mice gained less weight and were less capable of resolving the inflammatory response elicited during sensitization. The oxidative burst of blood cells was increased, but production of IFN-gamma and IL-4 and the ratio of IFN-gamma to IL-4 were markedly depressed. In concordance with the latter result, production of Th1-driven IgG2a antibodies was decreased, whereas Th2-driven isotypes were not affected (IgG1, IgE) and mucosal IgA was increased. CONCLUSIONS: These findings confirmed that supplementary amounts of vitamin A above dietary requirements enhance inflammatory responses accompanied by decreased Th1 and increased mucosal responses. However, supplementation of these sufficiently fed, non-stressed, young adult mice with vitamins C and E, selenium, or zinc had no effect on immune function. We speculate that using this model in aged, physiologically, or nutritionally stressed mice may provide outcomes more similar to those in sensitive human populations. If so, this would improve the usefulness of the model to assess, characterize, and rank effects of foods or nutrients on a range of immune functions, including Th1/Th2 polarization.     

Zinc and Breast Cancer Survival: A Prospective Cohort Study of Dietary Intake and Serum Levels

Zinc has been suggested to play a role in breast cancer progression; however, no previous study on zinc levels and the potential effect on breast cancer survival has been conducted. This study investigates recurrence-free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS) in relation to zinc levels, in serum and diet, overall and stratified for phosphorus and selenium levels. The Malmö Diet and Cancer Study, a prospective population-based cohort in Sweden including 17,035 women, was used to identify breast cancer patients diagnosed in the period 1991–2013. Diet was assessed by a validated modified diet history method. A Cox regression analysis yielded hazard ratios (HRs) with 95% confidence intervals adjusted for potential confounders. Out of 1062 patients with invasive breast cancer, 268 recurrences, 205 breast cancer deaths and 228 deaths from other causes were recorded. No overall associations were seen between zinc and RFS, BCSS or OS. However, in women with a high phosphorus intake, a higher BCSS and OS were seen in zinc intake Q2 to Q4 versus Q1; the adjusted HR was 0.41 (0.23–0.73) and 0.64 (0.41–1.00), respectively. The results indicate that the combination of intermediate/high zinc intake and high phosphorus intake may lead to a better breast cancer survival.     

Effect of Dietary Enrichment with Flaxseed,Vitamin E and Selenium,and of Market Class on the Broiler Breast Meat—Part 1: Nutritional and Functional Traits

The effect of dietary enrichment with flaxseed, selenium and vitamin E, and market class on the nutritional and functional value of breast meat was evaluated. A completely randomized block design was set up, where the experimental unit (n = 6000 birds) received conventional or enriched diet and was slaughtered at 37 (light class), 47 (medium class), or 57 (heavy class) days of life. Hence, functional and standard Pectoralis major muscles from every market class were analyzed for FA composition, inorganic elements and vitamin E. Lipid metabolism indices and health lipid indicators were assessed along with the nutritional value. A multiple linear model revealed that in breasts, the dietary treatment significantly influenced (p < 0.05) the FA profile, lipid metabolism and health lipid indices, while the slaughtering weight was related (p < 0.05) to most of elements (e.g., Na, Mg, K, Mn, and Se) and vitamin E. The interdependence of the two factors had strong relations (p < 0.05) with total PUFAs, including linolenic acid, desaturase activities, health lipid indices, trace essential elements and vitamin E. Consequently, enriched meat from heavy chickens showed the best functional and nutritional traits. Overall, the study pointed out that both market class and dietary manipulation are two relevant factors to consider for producing breast meat with higher nutritional and functional value.     

Vitamins as Possible Cancer Biomarkers: Significance and Limitations

The Western-style diet, which is common in developed countries and spreading into developing countries, is unbalanced in many respects. For instance, micronutrients (vitamins A, B complex, C, D, E, and K plus iron, zinc, selenium, and iodine) are generally depleted in Western food (causing what is known as ‘hidden hunger’), whereas some others (such as phosphorus) are added beyond the daily allowance. This imbalance in micronutrients can induce cellular damage that can increase the risk of cancer. Interestingly, there is a large body of evidence suggesting a strong correlation between vitamin intake as well as vitamin blood concentrations with the occurrence of certain types of cancer. The direction of association between the concentration of a given vitamin and cancer risk is tumor specific. The present review summarized the literature regarding vitamins and cancer risk to assess whether these could be used as diagnostic or prognostic markers, thus confirming their potential as biomarkers. Despite many studies that highlight the importance of monitoring vitamin blood or tissue concentrations in cancer patients and demonstrate the link between vitamin intake and cancer risk, there is still an urgent need for more data to assess the effectiveness of vitamins as biomarkers in the context of cancer. Therefore, this review aims to provide a solid basis to support further studies on this promising topic.     

Dietary Natural Compounds and Vitamins as Potential Cofactors in Uterine Fibroids Growth and Development

An analysis of the literature generated within the past 20 year-span concerning risks of uterine fibroids (UFs) occurrence and dietary factors was carried out. A link between Vitamin D deficiency and UFs formation is strongly indicated, making it a potent compound in leiomyoma therapy. Analogs of the 25-hydroxyvitamin D3, not susceptible to degradation by tissue 24-hydroxylase, appear to be especially promising and tend to show better therapeutic results. Although research on the role of Vitamin A in the formation of fibroids is contradictory, Vitamin A-enriched diet, as well as synthetic retinoid analogues, may be preventative or limit the growth of fibroids. Unambiguous conclusions cannot be drawn regarding Vitamin E and C supplementation, except for alpha-tocopherol. Alpha-tocopherol as a phytoestrogen taking part in the modulation of estrogen receptors (ERs) involved in UF etiology, should be particularly avoided in therapy. A diet enriched in fruits and vegetables, as sources of carotenoids, polyphenols, quercetin, and indole-3-carbinol, constitutes an easily modifiable lifestyle element with beneficial results in patients with UFs. Other natural substances, such as curcumin, can reduce the oxidative stress and protect against inflammation in leiomyoma. Although the exact effect of probiotics on uterine fibroids has not yet been thoroughly evaluated at this point, the protective role of dairy products, i.e., yogurt consumption, has been indicated. Trace elements such as selenium can also contribute to antioxidative and anti-inflammatory properties of a recommended diet. In contrast, heavy metals, endocrine disrupting chemicals, cigarette smoking, and a diet low in antioxidants and fiber were, alongside genetic predispositions, associated with UFs formation.     

Essential Elements and Isoflavonoids in the Prevention of Prostate Cancer

The intake of selected minerals, especially zinc, calcium and selenium, and high consumption of dietary isoflavones are recognised as factors influencing prostate cancer risk. Moreover, changes in levels of some essential elements are characteristic of the disease. Here, we examined the combined effects of main dietary isoflavonoids (genistein, daidzein and its metabolite, equol) and minerals implicated in prostate cancer, namely zinc, selenium, copper, iron and calcium, on LNCaP prostate cancer cells proliferation. Secondly, we evaluated the influence of the combinations on genotoxicity of model mutagens, 4-nitroquinoline oxide (4NQO) and 2-aminoanthracene (2AA), in the umu test. All combinations of isoflavonoids and minerals inhibited prostate cancer cells growth. However, only mixtures with iron ions had significantly stronger effect than the phytochemicals. Interestingly, we observed that only genistein attenuated genotoxicity of 4NQO. The addition of any tested mineral abolished this effect. All tested isoflavonoids had anti-genotoxic activity against 2AA, which was significantly enhanced in the presence of copper sulphate. Our results indicate that the tested minerals in physiological concentrations had minimal influence on the anti-proliferative activity of isoflavonoids. However, they significantly modulated the anti-genotoxic effects of isoflavonoids against both metabolically activated and direct mutagens. Thus, the minerals intake and nutritional status may modulate protective action of isoflavonoids.     

Adequacy of essential fatty acid, vitamin D and vitamin E intake: Implications for the 'core' and 'extras' food group concept of the Australian Guide to Healthy Eating

Objective: To assess the implications of new recommendations for essential fatty acids, vitamin D and vitamin E on the classification of margarines and vegetable oils as ‘extras’ in the current Australian Guide to Healthy Eating. Design: The role of margarines and vegetable oils as sources of essential fatty acids, vitamin D and vitamin E was examined in two ways. First, data from the 1995 National Nutrition Survey were assessed and, second, sample diets conforming to the Australian Guide to Healthy Eating were modelled and analysed. Subjects: For the assessment of national intake, subjects were a representative sample of 13 858 Australians, surveyed in the 1995 National Nutrition Survey. Main outcome measures: Relative contributions of margarines and oils, the ‘core’ food groups and ‘extras’ categories of the Australian Guide to Healthy Eating to intakes of essential fatty acids and vitamins D and E; changes in nutrient profiles of baseline diets conforming to the Australian Guide to Healthy Eating with or without varying amounts of margarines and oils. Results: ‘Core’ foods and ‘extras’ contributed similar amounts of essential fatty acids and vitamins D and E to the Australian diet, margarines and oils being the major contributor among ‘extras’. The simulated low‐fat, low‐saturated‐fat baseline diets generally failed to meet the adequate intakes for n‐3 and n‐6 polyunsaturates and vitamin D, and vitamin E in some instances. The addition of 25 g of sunflower margarine, but not comparable amounts of canola margarine, olive oil and butter, markedly increased the ratio of polyunsaturated to saturated fatty acids and generally delivered the adequate intakes, vitamin D being the exception. Conclusion: The inclusion of margarines and vegetable oils in diets based on the current Australian Guide to Healthy Eating, and guidance on choice among these foods, is required to provide adequate intakes of linoleic acid, α‐linolenic acid and vitamins D and E and to achieve fatty acid profiles consistent with the prevention of chronic disease.