Introduction
Prostate cancer has become such a frequently diagnosed condition that much research has been undertaken to understand its etiologic factors and how the disease onset can be prevented or delayed. Although the primary risk factor for developing prostate cancer is aging, increasing attention is being devoted to understanding the role of diet and nutrition in relation to the development and progression of all cancers.
In 2002, the American Institute for Cancer Research published a study in which a panel of 16 experts reviewed 4500 studies related to diet and cancer. They concluded that 200,000 of the 600,000 cancer deaths in the United States each year could be prevented through a combination of dietary changes, adequate physical activity, and maintenance of appropriate body weight. They also noted that avoidance of tobacco and alcohol could prevent an additional one third of cancers.
The concept of preventing or influencing cancer growth has been studied since the early 1900s. Various studies in animal models have indicated that the growth rate of a cancer could be affected by the type of diet the animal was fed. In 1942, Tannenbaum demonstrated in animal models that a high-fat diet stimulated cancer growth.1 In 1982, The National Academy of Science presented convincing evidence concerning the relationship between dietary fat and cancer.2 All of the subsequent epidemiologic studies, animal-model studies, and investigations into the biochemical and molecular biologic processes that involve cancer have emphasized the role that diet plays in the process of carcinogenesis.
Prostate cancer is associated with various hormonal perturbations, genetic predisposition to cancer, oxidative DNA damage caused by chronic prostate inflammation, excessive fat intake, obesity, excessive intake of estrogens and phytoestrogens, and the consumption of burned or charred foods. Although DNA damage is common, various repair systems ordinarily correct the problem. The inability of the various DNA-repair mechanisms to function properly allows an altered cell to proceed through cell division instead of being corrected or eliminated. One such system is the glutathione S -transferase P1-1 (GSTpi) repair mechanism, which has been found to be functionally inactive in men with prostate cancer. Increasing data demonstrate the role of aging, diet, environment, lifestyle, and stress-related factors in this process.
Diet is perhaps the most important factor that can be controlled by an individual. The strongest association between diet and prostate cancer seems to be obesity. The significant prevalence of overeating and the resultant obesity, coupled with other risk factors, may explain the increasing incidence of this disease. Numerous studies have shown that obese men have a greater risk of dying from prostate cancer, developing a more aggressive cancer, and experiencing disease recurrence after surgery or radiation therapy.
Overweight men who lose weight seem to reduce their risk of developing prostate cancer. Obese men tend to have lower serum testosterone levels and serum prostate-specific antigen (PSA) levels and are more likely to experience an early recurrence of cancer following primary therapy. The Cancer Prevention Study demonstrated that men with a body mass index (BMI) of greater than 32.5 kg/m2 were 35% more likely to die of prostate cancer than men whose BMI was less than 25%.
Interestingly, every prostate-cancer study with survival as the endpoint has found that most patients die from causes other than prostate cancer, mostly cardiovascular disease. Therefore, the merits of nutritional measures are compounded by the fact that they are beneficial in preventing prostate cancer and in preventing and managing cardiovascular disease.
Many studies have been performed and many are in progress to understand the molecular biology that links diet with prostate cancer. These studies are difficult to perform and often yield conflicting results. Translating data from studies in animal models to humans is often fraught with error but provides important leads in designing, conducting, and interpreting large studies in humans.
Dietary Fat and Prostate Cancer
Per-capita fat consumption is highest in North American and Western European men; rates of prostate-cancer deaths are also highest in these groups. Conversely, the countries in the Pacific Rim have the lowest death rates and the lowest fat consumption. Whittemore et al studied the relationship of diet, physical activity, and body size in black, white, and Asian men living in North America.3 The only factor that correlated with prostate cancer was the amount of dietary fat. The same was true in Hawaiian men; the highest prevalence of prostate cancer was in men with the highest intake of saturated fat.4
Interestingly, the introduction of Western diets in Japan, where the traditional diet contains low fat, has led to an increased incidence of aggressive prostate cancer. Giovannucci et al reported that men who consumed high levels of fat were more likely not only to develop prostate cancer but also to develop a more aggressive form of the disease.5 Men with the highest intake of red meat were 2.64 times as likely to develop prostate cancer as men with the lowest intake.
The correlation between obesity and prostate cancer has also been emphasized by studies of metabolic syndrome, which refers to a group of conditions that includes central adiposity, hypertension, dyslipidemia, and high serum glucose levels. Men with metabolic syndrome have been shown to have a higher incidence of prostate cancer.
The typical American male obtains about one third of his daily energy intake from dietary fat. The correlation between fat consumption and the risk of prostate cancer seems to depend on the specific types of fat and their constituent fatty acids. An even number of carbon atoms are contained in all fatty acids, which can be separated into 3 classes, as follows:
- Saturated fatty acids, such as stearic acid, contain no carbon-carbon double bonds.
- Monounsaturated fatty acids, such as oleic acid, have a single carbon-carbon bond.
- Polyunsaturated fatty acids, including linoleic acid and eicosapentaenoic acid, have 2 or more carbon-carbon bonds.
Fatty acids are generally found in foods and in fat deposits as triglycerides or neutral fat, in which 3 fatty acids are esterified to a single molecule of glycerol. In cell membranes, fatty acids exist as phospholipids, in which one of the fatty esters is replaced by a head group such as choline, serine, or inositol. Phospholipids are integral components of cellular membranes; they are responsible for maintaining cellular integrity and for regulating membrane enzymes, cell-signaling processes, and the construction of cellular receptors.
Fatty acids provide a source of concentrated energy for cellular metabolic needs through the sequential removal and oxidation of 2 carbon units. The complete oxidation of a fatty acid provides 9 kcal per gram of energy; for contrast, protein and carbohydrates provide 4 kcal per gram of energy. Separating the intrinsic effects of fat intake from those associated with high caloric intake is difficult because of the high energy content of fatty acids.
Saturated fat comprises the largest proportion of fat in Western diets and is consumed primarily in animal-derived foods. Although the intake of animal fats and saturated fats correlates with prostate cancer risk, this association is not as strong when adjusted for total energy intake. In addition, a direct cause and effect has not been established. Several mechanisms have been suggested to explain the relationship between saturated fatty acids and prostate cancer. They involve insulinlike growth factor-1 (IGF-I), hormonal metabolism, and free-radical damage. A low-fat diet seems to correlate with lower levels of IGF-I, testosterone, and estradiol levels and higher levels of insulin growth factor-binding protein-1 and sex hormone-binding globulin levels.
A lot of recent attention has been devoted to the benefits of the omega-3 and the deleterious effects of the omega-6 long-chain fatty acids. The marine omega-3 fatty acids are potent antioxidants that have demonstrated a beneficial effect in the development of prostate cancer based on results from animal and epidemiologic studies. Whether the omega-3 fatty acids or the ratio between omega-3 and omega-6 is important has not been elucidated. Trans fat is an industrially created unsaturated fat that is neither necessary nor beneficial.
MacLean and colleagues reviewed 38 articles describing the effects of dietary supplementation of omega-3 on cancer risk.6 They found no correlation between consumption of omega-3 dietary supplements and the incidence of intestinal tumors, bladder cancer, lymphoma, ovarian cancer, or pancreatic cancer. In their analysis of prostate cancer, they found one estimate of decreased risk and one of increased risk for advanced cancer. Fifteen other estimates showed no association.
Ritch et al studied a group of 148 Jamaican men because of the high incidence of cancer death and the very high intake of the polyunsaturated fatty acid omega-6 in this population.7 They evaluated the relationship between the intake of dietary fatty acids and prostate cancer biopsy grade and volume and concluded that omega-6 fatty acids stimulated prostate cancer cell growth, whereas omega-3 fatty acids inhibited cancer cell growth.
Prostate cancer is considered to be one of cancers that is influenced by hormonal environment. Perturbations in the sex steroids seem to play an important role in the genesis of prostate and breast cancer. The link between obesity and the types of dietary fat is not completely elucidated, but greater BMI is associated with lower serum levels of testosterone and sex hormone-binding globulin and higher levels of estradiol. Serum levels of androstenedione are decreased, but the peripheral conversion of androstenedione to estrone and estradiol is increased.
The Role of Meat in Prostate Cancer
Epidemiologic studies have suggested a correlation between red-meat intake and prostate cancer. This is particularly true of meats that are cooked at high temperatures and charred, including processed meats such as sausages, bacon, and hot dogs.
Heterocyclic amines and N -nitrosamines have been added to the list of potential carcinogens by the US Department of Health and Human Services. The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is found in grilled beef, pork, chicken, lamb, fish, and processed meats.
In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, Cross et al prospectively studied the association between meat and meat mutagens (PhIP) and prostate cancer risk.8 Neither the total amount ingested nor the type of meat (ie, red, white) ingested was associated with prostate cancer risk. However, ingestion of more than 10 g/d of very-well-done meat increased the likelihood of disease by 1.4 times over no consumption. Men who were in the highest quintile for PhIP were 1.2 times more likely to develop prostate cancer and had the highest intake of charred meats.
These carcinogens are produced in larger amounts with longer cooking times, increased temperature, barbecuing, and frying.
Energy Consumption
Total energy consumption may be another important factor in the development of prostate cancer. Excessive caloric intake, regardless of its source, may lead to obesity, which correlates with an increased risk of prostate cancer. Wang et al injected prostate cancer cells from the androgen-sensitive cell line (LNCaP cells) into nude mice.9 Initially, all of the animals were placed on a diet in which 40% of their caloric intake came from fat. When the tumors were established and measurable, the diet was changed. Tumor growth was markedly inhibited in the animals in whom dietary fat contributed no more than 20% of the total caloric intake.
Mukherjee et al also studied the effects of energy intake.10 They transplanted cancer cells from the Dunning R3327-H and from LNCaP into severe combined immunodeficiency (SCID) mice. Diet was not restricted in one group. A second group was castrated and subdivided into 2 subgroups—one with an energy-intake restriction of 20% and one with a restriction of 40%. Finally another group was not castrated but had caloric restriction. The results indicated that, regardless of castration (which alone diminishes cancer growth), all of the groups in whom energy was restricted developed cancer that was smaller and slower-growing, had decreased microvessel density, and had a decreased cell-proliferation index.
Huffman et al tested the hypothesis that body mass or composition affects the benefits or hazards associated with caloric restriction or overeating, respectively, regardless of energy intake.11 Based on their results in a transgenic mouse model, they concluded that the ability of caloric restriction to inhibit cancer development and progression is partially mediated by changes in energy balance, body mass, and body composition rather than just caloric intake. This implies that the risk of developing prostate cancer depends more on excess caloric retention, which leads to obesity, rather than just excessive caloric consumption. Although these data are compelling in animal models that can be carefully controlled, whether these results can be expected in humans is unknown.
What's Wrong With Eating Fat?
Foods that contain fat are an essential component of our diet, so these foods should not be avoided. The problem lies in overeating and in excessive caloric consumption, regardless of source, which is converted to bodily fat. Therefore, excessive fat intake is problematic. Ornish et al have shown that a vegan diet supplemented with antioxidants, aerobic exercise, and stress-management techniques can lower PSA levels by a modest 0.25 ng/mL (or 4%).12 However, reducing PSA production does not always mean that the cancer cells have become inactive.
A report from the International Agency for Research on Cancer indicated that 10% of all cancers in the United States were related to obesity. Epidemiologic studies have indicated that 27.6% of men and 33.4% of women are considered obese (as defined by a BMI >30 kg/m2).
Just as many factors are responsible for the relationship between cancer and obesity, no single solution exists. One intriguing theory relates to the role that insulin plays in this process. Men with diabetes, although obese, are less likely to develop prostate cancer. Insulin is an important growth factor, and levels of insulin growth factor and its receptor have been shown to be elevated in persons with prostate cancer. Keeping insulin values low may retard the growth rate of prostate cancer cells; this can be achieved only through diet.
A glycemic index was developed for persons with diabetes in order to take advantage of the small amounts of insulin they may produce. This index ranks carbohydrates in different foods on a scale of 0-100, depending on how much those foods increase blood sugar levels after consumption. The consumption of low glycemic foods lowers blood sugar levels and decreases insulin production. According to this theory, low levels of insulin growth factor would prevent cancer cells from growing as rapidly.
In the 1920s, Ohsawa popularized the concept of a macrobiotic diet, which produces about the lowest glycemic index. This stringent diet consists primarily of whole grains and vegetables. Even most fruits are excluded. In contrast, the diabetic diet restricts only those foods with the highest glycemic index, including dried dates, corn flakes, jelly beans, doughnuts, white bread, table sugar, white rice, and similar foods.
Although these dietary modifications, coupled with exercise and lifestyle modifications, may affect cancer growth rates, the cancer cells, through mutation, can overcome almost anything. These dietary recommendations should be initiated along with appropriate therapy for the cancer. Relying on diet alone to treat prostate cancer is unrealistic.
The Role of Inflammation in the Induction of Prostate Cancer
Klein and his colleagues at the Cleveland Clinic have produced a working hypothesis that shows the link between inflammation and prostate cancer.13 Prostatic inflammation is associated with oxidative stress, which stimulates the production of reactive oxidative species (ROS) and reactive nitrogen species (RNS). These bind to DNA and cause mutations. Oxidative stress derived from endogenous and exogenous sources are associated with DNA damage that occurs with aging and plays a role in carcinogenesis. Polyunsaturated fatty acids induce the production of ROS, resulting in the formation of lipid radicals that can cause DNA damage. Semen can also be oxidative because of the occasional presence of leukocytes and a substantial amount of polyunsaturated fatty acids.
Several mechanisms that can prevent and repair oxidative damage have been identified. Antioxidant enzymes such as phospholipase A-2 remove altered fatty acids, ROS, and RNS, preventing mutations. This one example of the beneficial effects of dietary antioxidants and evidence that the consumption of foods that promote the production of ROS and RNS should be limited or avoided.
Dietary Nutrients and Supplements
All of the dietary nutrients that may reduce the risk of developing prostate cancer are readily available. Whether substituting or adding dietary supplements is advantageous continues to be investigated. The general consensus is that anything that is ingested in food is better than an artificial supplement. However, quantifying the amount of these nutrients in serum and tissues has been difficult. Therefore, the necessary amount of a given supplement is unknown. Conflicting reports that are confusing both to the public and to physicians frequently appear in the media. Differences in study populations, methodology, and interpretation of data complicate the comparison of studies.
Antioxidants such as beta-carotene, vitamin A, and vitamin E are being taken with the goal of reducing oxidative damage and its potentially harmful effects. Many primary and secondary prevention trials have been conducted, but whether these supplements reduce oxidative damage is uncertain. Bjelakovic and colleagues performed a meta-analysis of 68 randomized trials involving 232,606 participants to evaluate the effects of beta-carotene, vitamins A and E, vitamin C, and selenium.14 They found that beta-carotene, vitamin A, and vitamin E significantly increased mortality rates, whether taken alone or in combination. As for vitamin C and selenium, they concluded that these antioxidants require further study.
The Physicians' Health Study II, a long-term randomized controlled trial involving male physicians, recently found that neither vitamin E nor C supplementation reduced the risk of cancer—prostate or otherwise.15
Carotenoids
Carotenoids are micronutrient antioxidants that are found in orange or yellow fruits and vegetables and in some dark leafy vegetables such as spinach and Brussels sprouts. The most common dietary carotenoids include beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene. Lycopene, a beta-carotene, is the most efficient antioxidant in this group and is the predominant carotenoid in the plasma and in various tissues, including the prostate. It is found in watermelon, tomato and all tomato-based products, pink grapefruit, apricots, papaya, guava, and persimmons. Carrots contain high levels of carotene but contain little lycopene.
Four large clinical trials have evaluated the role of beta-carotene and the risk of developing prostate cancer. In general, these studies indicate that risk of prostate cancer is reduced in men who have low serum levels of beta-carotene and are treated with supplements. A high intake of tomato products (≥10 servings per week) was associated with a 35% decreased risk of advanced prostate cancer; this was independent of fruit, vegetable, and olive-oil intake. Additional studies have reported that the incident risk of prostate cancer was reduced by 25%-80%. Some other studies did not find this association, but some of these were conducted in populations in whom lycopene intake may have been too low to make an association. Studies comparing high and low intake of tomatoes reported 10-20% statistically significant reduction in prostate cancer risk in men with high intakes. Cooked tomato products had a stronger effect than raw tomato products.
The other carotenoids seem to be beneficial but not to the degree that has been reported with lycopene. Lu et al reported a 70%-80% reduction in prostate cancer risk in men with high levels of plasma lutein, beta-cryptoxanthin, and zeaxanthin.16 The incidence of prostate cancer in men with low baseline levels of serum beta-carotene or lycopene was reduced when their serum levels were corrected, but the risk was higher in those in whom the levels were already higher.
Cruciferous vegetables
Broccoli, cauliflower, cabbage, Brussels sprouts, bok choy, and kale have high levels of the anticarcinogenic phytochemicals sulforaphane and indole-3 carbinol. These nutrients induce the production of antioxidant enzymes that can protect cells from oxidative damage. Sulforaphane helps to induce apoptosis in damaged cells. In animal studies, indole-3 carbinol has been shown to exhibit antiproliferative and antimetastatic properties.
Canene-Adams and coworkers studied the antitumor activity in the Dunning prostate-cancer animal model. They fed rats various combinations of tomatoes and broccoli and found that tumor growth was significantly reduced owing to reduced cancer cell proliferation and increased apoptosis. The implication is that plant-derived nutrients are more beneficial in combination than alone.
Selenium
Selenium is an essential, nonmetallic, trace element that is widely distributed throughout the body. It is a component of multiple antioxidant enzymes and participates in various functions. Epidemiologic studies indicate that selenium is a potential prostate-cancer preventative and decreases the growth rate of prostate-cancer cells. Plasma, serum, and tissue levels of selenium are inversely associated with the risk of developing prostate cancer. Selenium is found in Brazil nuts, walnuts, fish (including canned tuna and shellfish), beef, turkey, chicken, eggs, whole grains, garlic, onions, broccoli, cabbage, and mushrooms.
Animal experiments and epidemiologic evidence suggest that selenium has an anticarcinogenic effect due to its action on apoptotic pathways, inhibition of cell proliferation, and antiangiogenesis. Several studies have reported that high selenium levels confer a 50-65% reduction in the risk of prostate cancer over low selenium levels. The Nutrition Prevention of Cancer Trial reported that the incidence of prostate cancer in men who received selenium supplements was 50% less than in men who received placebo.
The SELECT trial is studying the effects of selenium and vitamin E alone and in combination. This study has enrolled 35,000 men. Results should be available by 2012. One of the problems in obtaining adequate dietary selenium is that the level of selenium in a given plant depends on the soil in which it is growing. For example, produce from the Imperial Valley has a higher selenium content than plants grown elsewhere.
Selenium comes in several forms, each of which may produce differing biologic effects. The protective activities of selenium compounds are thought to be mediated through a metabolite of selenium called methyselenol. Selenomethionine modulates transcript levels of genes involved in cell-cycle and apoptosis pathways, androgen signaling, signal transduction, and transcriptional regulation. At high concentrations, selenomethionine decreases expression of PSA. Studies with methylselenic acid have shown that similar biologic pathways are affected but gene expression has distinct differences.
In the SELECT trial, selenomethionine was administered at a dose of 200 μg/d. Selenomethionine is the major component of high-selenium yeast and was considered to be practical and safe.
Vitamin E
Vitamin E is a mixture of various antioxidant tocopherols that are particularly effective against unsaturated fatty acids and that protect against oxidative cell-membrane damage. It also seems to lower testosterone levels. Vitamin E is a lipid-soluble antioxidant found in vegetable oils, nut oils (eg, almonds, cottonseeds, safflowers, sunflowers), hazelnuts, sweet potatoes, whole grains, and leafy vegetables. Gamma-tocopherol is the most prevalent form of vitamin E in the diet, whereas alpha-tocopherol, found in dietary supplements, is the most biologically available form.
Crispen et al studied the mechanism of action of alpha-tocopherol succinate (vitamin E succinate).17 They studied the transcription factors nuclear factor kappa B (NF-kappa-B) and activator protein-1 (AP-1), which are known to contribute to the development and progression of prostate cancer by regulating the genes involved in proliferation, apoptosis, angiogenesis, and metastasis. Their experiments with vitamin E succinate treatment revealed an inhibition of NF-kappa-B but an augmentation of AP-1. They also found that this treatment reduced the expression of interleukin (IL)–6, IL-8, and vascular endothelial growth factor (VEGF) and suppressed cell adhesion. Androgen-dependent LNCaP cells were sensitized to androgen deprivation. These results support the role of vitamin E as a chemopreventive.
The Alpha-Tocopherol, Beta-Carotene cancer prevention trial reported a 30-40% decrease in prostate cancer incidence and mortality.18 Men involved in this study were given 50-IU supplements of alpha-tocopherol daily or a placebo. The Health Professionals Follow-up Study reported a decreased risk of advanced prostate cancer. In both of these studies, the benefit was identified only in smokers. Studies of gamma-tocopherol have shown variable responses.
The Prostate, Lung, Colorectal, and Ovarian Screening trial (PLCO) studied dietary vitamin E, beta-carotene, and vitamin C intake and evaluated prostate cancer risk. This was a questionnaire study, and the doses reported by the participants varied. The results did not provide strong evidence for the ingestion of large amounts of antioxidants, either from the diet or from supplements, for the prevention of prostate cancer, although smokers did derive some benefit.
The SELECT trial is currently underway to determine if the combination of vitamin E and selenium reduces prostate cancer risk over either agent taken alone.
Vitamin D
The major and most important source of vitamin D is sunlight but is also contained in dairy products, eggs, vitamin D–fortified cereals, and fatty fish such as salmon and tuna. Many men are vitamin deficient, and this substance can readily be measured in the serum.
Giovannucci et al have reported that adequate levels of vitamin D significantly reduce total cancer incidence and mortality.19 This epidemiologic study showed that most of the protective effect came from sunlight, and only a modest exposure to sunlight can provide adequate levels of vitamin D. Dietary supplements are available for those in whom sunlight is not available or is restricted. However, the recommended dose of 400 IU daily is too low to maintain skeletal health and probably has limited anticancer effects. A dose of 400 IU raises serum levels a very small amount (3 ng/mL). Serum levels can be obtained and the dose titrated to reach normal levels.
High-dose vitamin D has been combined with docetaxel (Taxotere) chemotherapy in the treatment of androgen-independent cancer in men. A new formulation of calcitriol, DN-101, has been used in clinical trials; this combination has shown benefit compared with Taxotere or high-dose Vitamin D alone.
Isoflavones (soy)
Soy is a rich source for the isoflavones genistein, daidzein, and equol, which have been shown to affect cell-growth pathways and angiogenesis. Isoflavones have also been shown to affect the production and metabolism of androgen and estrogens, which play an important role in the development and progression of prostate cancer. The traditional Western diet entails minimal soy consumption, and few epidemiologic studies that provide useful recommendations have been performed as a result. Isoflavones studied in animal studies indicate a beneficial effect in the prevention and reduction in the growth rate of prostate cancer.
Polyphenols (green tea)
Polyphenols are found in varying amounts in most fruits and vegetables, as well as green tea and red wine. These agents act via antioxidant, antiproliferative, and antiangiogenesis pathways and have proapoptotic effects.
Some of the more popular polyphenols have been the catechins in green tea, which have been shown inhibit cancer-cell growth in both animal and epidemiologic studies. Epigallocatechin (EGCG) is a principal ingredient in the dried leaves of the evergreen shrub Camellia sinensis, which is native to Asia. This substance interferes with biochemical reactions associated with cellular proliferation and enhances apoptosis. EGCG is a potent inhibitor of the carcinogenic heterocyclic amines (PhIP), which are produced from overcooked or charred meat.20,21,22,23,24
Commercially prepared green-tea extracts contain 60% polyphenols, the source of bioflavonoids, which are potent antioxidants. Bettuzzi et al administered either a placebo or 600 mg/d of green-tea extract to 60 men with high-grade prostatic intraepithelial neoplasia (HGPIN), a potential precursor for prostate cancer.25 All of the men underwent repeat biopsy after one year, and only one man in the treated group was found to have a cancer (compared with 9 in the placebo-treated group).
Calcium
Higher milk intake has been consistently shown to be associated with an increased risk of developing advanced prostate cancer. Whether this is related to the high fat content in milk or to the amount of calcium has not been clarified. Giovannucci et al hypothesized that the high calcium intake could lower 1,25(OH)2 vitamin D levels, which would promote increased dedifferentiation of the cancer cells.26 They examined the records of 47,750 men who were participating in the Health Professionals Follow-up Study. They found that dietary or supplemental calcium was independently associated with increased risk. More importantly, calcium intake of greater than 1500 mg/d was associated with lower vitamin D-2 levels and a higher risk of developing an aggressive cancer.
Gao et al also provided evidence that suggested the risk associated with calcium intake27 , but Severi and colleagues obtained data from the Melbourne Collaborative Cohort Study that did not support this contention.28 The interpretation of these findings is that calcium is good but too much may be harmful.
Zinc
Zinc is commonly used as a dietary supplement. Healthy individuals with a balanced diet consume about 11 mg of zinc per day. Zinc is found in meat, vegetables such as chickpeas and beans, and nuts. Many individuals consume large amounts of supplemental zinc because of the possible health benefits that have been promoted by commercial interests.
The findings that zinc levels are decreased in men with prostate cancer and that zinc suppresses prostate-cancer cell growth and invasion have led to the hypothesis that zinc may play a protective role. However, the Health Professionals Follow-Up Study showed an increased risk of prostate cancer in men who consumed more than 100 mg/d. High-dose zinc has been shown to promote prostate-cancer development. Studies in persons taking large amounts of zinc have also reported adverse effects on the urinary tract.
Summary
Although nutrition plays a role in the development of prostate cancer, no specific diet can prevent or eradicate this disease. Prostate cancer, like other cancers, is an extremely complex process. No single factor (eg, diet) can explain the various facets of this disease.
Huang published an editorial in the Journal of the National Cancer Institute entitled "Customized Diets for Cancer Prevention According to Genetic Polymorphisms: Are We ready Yet?"29 In this editorial, he summarizes some of the data on the role of nutrient intakes that are reported to modify genetic susceptibility to diseases such as cancer with the expectation that this would provide a scientific basis for cancer prevention via dietary modification. He points out that this concept has been embraced primarily by the entrepreneurs who make dietary recommendations and promote supplements, claiming to be tailored to each individual. In an effort to sell products, marketing terms such as "nutrigenic testing," "personalized supplements," "feed your genes right," and "intelligent diet" are being used.
He thoroughly discredits this concept and goes on to point out the limitations of the various study methods, including observational studies, case-control studies, and cohort studies. He suggests that only randomized, carefully controlled studies can address these important issues.
Nutritional studies are difficult to perform because of the inherent heterogeneity of any study population, the variations in individual lifestyles, and the quantitative and qualitative complexity in food and food products. This explains why so many contradictory reports exist that confuse physicians and the public.
The principle message that has been learned from these studies is that a diet comprised mainly of vegetables, fruits, grains, and fish, combined with restricted caloric intake and exercise has been shown to be beneficial. The ingestion of micronutrients in the diet provides multiple nutrients packaged in their most effective form. A slice of whole-grain bread provides fiber, iron, vitamin E, and folate. Fruit juices such as pomegranate juice provide antioxidants. Micronutrients from supplements are usually pharmacologically or synthetically produced and are ingested in isolation. They are not absorbed as well absorbed as nutrients contained in food, nor do they have the advantage of the nutrient interactions that occur in a food source.
No studies have indicated that these diet recommendations would be of benefit in altering the growth of an existing cancer. However, evidence has shown that these dietary measures are effective in reducing the risk of death from cardiovascular disease.
Keywords
prostate cancer, adenocarcinoma of the prostate, prostatic adenocarcinoma, prostate adenocarcinoma, dietary fat, fat-mediated carcinogenesis, carotinoids, dietary fiber, soy, PC-SPES, selenium, green tea, omega-3, omega-6, saturated fat, monounsaturated fat, polyunsaturated fat, trans fat, obesity, heterocyclic amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, PhIP, N -nitrosamines, insulin, glycemic index, oxidative stress, prostatic inflammation, polyunsaturated fatty acid, antioxidants, antioxidant enzymes, phospholipase A-2, reactive oxidative species, ROS, reactive nitrogen species, RNS, carotenoids, cruciferous vegetables, vitamin E, vitamin D, isoflavones, polyphenols, calcium, zinc, beta-carotene, vitamin A, micronutrient antioxidants, dietary supplements, alpha-carotene, beta-cryptoxanthin, lutein, zeaxanthin, lycopene, sulforaphane, indole-3 carbinol, methyselenol, selenomethionine, methylselenic acid, gamma-tocopherol, alpha-tocopherol, genistein, daidzein, equol,epigallocatechin, EGCG
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References
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Keywords
prostate cancer, adenocarcinoma of the prostate, prostatic adenocarcinoma, prostate adenocarcinoma, dietary fat, fat-mediated carcinogenesis, carotinoids, dietary fiber, soy, PC-SPES, selenium, green tea, omega-3, omega-6, saturated fat, monounsaturated fat, polyunsaturated fat, trans fat, obesity, heterocyclic amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, PhIP, N -nitrosamines, insulin, glycemic index, oxidative stress, prostatic inflammation, polyunsaturated fatty acid, antioxidants, antioxidant enzymes, phospholipase A-2, reactive oxidative species, ROS, reactive nitrogen species, RNS, carotenoids, cruciferous vegetables, vitamin E, vitamin D, isoflavones, polyphenols, calcium, zinc, beta-carotene, vitamin A, micronutrient antioxidants, dietary supplements, alpha-carotene, beta-cryptoxanthin, lutein, zeaxanthin, lycopene, sulforaphane, indole-3 carbinol, methyselenol, selenomethionine, methylselenic acid, gamma-tocopherol, alpha-tocopherol, genistein, daidzein, equol,epigallocatechin, EGCG
