Positive Health Online

Worldwide, prostate cancer is the second most frequent cancer diagnosed in men. It is the sixth most common cause of death in men,[1] and mortality rates vary widely across geographic areas.[2] The age-adjusted incidence of prostate cancer in 2002 for China was 1.6 per 100,000, while the figure for northern America was 119.9 per 100,000.[3] Over the past 25 years, there has been a steady increase in the number of new cases of prostate cancer in certain countries. This is the result of introducing the digital rectal exam and prostate specific antigen (PSA) serum testing. Some environmental factors for a diagnosis of prostate cancer include diet, smoking, lack of exercise, exposure to sunlight and environmental contaminants.[4] The migration of men from low-risk countries to high-risk countries increases the risk of developing prostate cancer, mainly because men adopt the diet and way of life of the new country.[5] 

This article describes evidence-based dietary and chemo-prevention strategies for prostate cancer. It addresses specific micronutrients and dietary patterns, and their effect on prostate cancer risk. An ongoing clinical trial involving a vitamin and a mineral and their individual or joint effect on prostate cancer development is discussed.

Lycopene

Data from epidemiological studies suggests that high levels of the circulating antioxidant lycopene and possibly other beneficial compounds in tomato-based products are associated with a reduction in prostate cancer development.[6] The evidence for this finding exists in both cohort and case-control studies.[1]

A large prospective cohort study,[7] known as the Health Professionals Follow-Up Study (HPFS), has assessed the relationship between the consumption of 46 vegetables, fruits and related products containing five of the most common carotenoids (i.e. a-carotene, lycopene, lutein, ß-carotene, ß-cryptoxanthin), and the risk of developing prostate cancer. In this study, concurrent plasma levels of the five carotenoids were measured in a subgroup of participants. Tomato sauce had higher corresponding plasma levels of lycopene, compared to tomatoes and pizza, which are also primary sources of lycopene. It is the cooking process of tomatoes that allows lycopene to be released. Results of the study show that the intake of 2-4 servings of tomato sauce per week was associated with a significantly (P=0.001) decreased risk for prostate cancer, especially the advanced type. Tomatoes and pizza also had a significant (P=0.03 and P=0.05, respectively) reduction in prostate cancer risk, while tomato juice had no reduction in risk.[7] In this study, tomato sauce reduced the risk of total prostate cancer by one-third, and aggressive prostate cancer by nearly one-half.[6] The four remaining carotenoids studied were not inversely associated with prostate cancer risk. Of particular interest in this study, the median intake of tomato-based products for African-American men was 38% lower than the overall median. The authors speculate that a low intake of tomatoes might contribute to a higher incidence of prostate cancer among African-Americans.[7]

Another prospective study,[8] has evaluated further data from the same cohort (i.e. HPFS) to determine if a frequent intake of lycopene is associated with prostate cancer risk. This study used multiple dietary assessments on 2,481 prostate cancer cases from 1986 onward for twelve years, whereas the 1995 HPFS, mentioned above, used only one dietary assessment on 773 prostate cancer cases from 1986 onward for six years. Results of this 2002 study concur with previous findings that the intake of tomato sauce significantly (P<0.001) reduced the risk of prostate cancer. Results also show that bio-available lycopene significantly (P=0.003) reduced the risk of prostate cancer. Approval for this study was granted by the Harvard School of Public Health Human Research Committee.
   

Selenium

There is strong evidence from clinical cohort studies and trials that selenium most likely guards against prostate cancer.[1] A secondary analysis from a large-scale clinical trial which primarily focused on skin cancer shows that selenium may lower the risk of prostate cancer.[9] In this study, 1312 subjects were randomized to receive either a daily selenium supplement or a placebo. They were followed for an average of 4.5 years. Secondary results show that the incidence of prostate cancer is 63% lower for the group receiving elemental selenium. Foods in which selenium is present include fish, meat, eggs and cereals. In geographic regions worldwide, selenium content in foods reflects soil levels of selenium.[10]

Calcium

There is substantial evidence from both cohort and case-control studies that calcium-rich diets are  implicated as causation factors of prostate cancer.[1] A meta-analysis[11] has examined the relationship between dairy product and/or calcium intake and the risk of prostate cancer. Twelve prospective trials, whose findings were published between 1966 and 2005, were selected for this analysis. The trials had to have used an observational study design and had to have listed data regarding incident or advanced prostate cancer or regarding mortality from prostate cancer. They also had to have published data regarding associations as relative risks or odds ratios according to categories of calcium or dairy product intake. Results show that men with an increased intake of dairy products and calcium were 11% and 39%, respectively, more likely to be diagnosed with prostate cancer, compared to men with a decreased intake of the same foods. The authors of this meta-analysis advise that older men exercise caution when considering the Dietary Guidelines for Americans 2005,[12] which recommend that people increase their intake of dairy products.

Vitamin E

Of the eight forms of vitamin E, a-tocopherol is considered the most biologically active. With its antioxidant properties, it may directly affect prostate growth by decreasing concentrations of testosterone.[1]

In Finland, a large-scale placebo-controlled double-blind trial[13] has studied the effect of  a
-tocopherol 50 mg and ß-carotene 20 mg supplementation on prostate cancer risk. This trial is known as the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study). The original purpose of the trial was to investigate the prevention of lung cancer. A total of 29,133 male smokers aged 50-69 years at entry were randomly designated to receive either the vitamin E or ß-carotene supplement, or both, or placebo, daily for 5-8 years. Subjects who had prior cancer, serious illness or those who previously used vitamin E, vitamin A or ß-carotene supplements were excluded from the study. Secondary results of this trial show that subjects receiving the vitamin E supplement had a significant (P = 0.02) 32% reduction in incidence of prostate cancer, compared with subjects not receiving the vitamin E supplement. These findings were evident for clinical prostate cancer but not for the latent type. Men receiving the vitamin E supplement also had a 41% reduction in mortality from prostate cancer, but this was based on fewer events. The ATBC study supports the hypothesis that a-tocopherol may be an important micronutrient for the prevention of prostate cancer.[13]

 

Table 1. Dietary recommendations for prostate health
Food/Habits	Respective Bio-active Compounds
High intake of vegetables (e.g. green leafy) and fruits	Carotenoids, phyto-chemicals, oxalic & phytic acid
Whole grain cereals	Complex CHOs, vitamin E, phyto-estrogens
Legumes (e.g. soy products)	Isoflavones, phyto-sterols
Frequent intake of fish containing omega-3 fatty acids	EPA, DHA, selenium
Tea (e.g. black and green)	Polyphenol
Low intake of red meat and dairy products	Saturated fat, zinc, calcium (negative effect)
Avoid fried and grilled meat
Avoid overeating
Note: Based on information from Itsiopoulos et al, 2009; Stacewicz-Sapuntzakis et al, 2008. Abbreviations: CHO, carbohydrate; EPA, Eicosapentaenoic Acid; DHA, Docosahexaenoic Acid

Dietary Patterns

Table 1 lists foods (i.e. mostly of plant origin) and their respective bio-active compounds which may prevent or slow the progression of prostate cancer. Various phyto-chemicals in the whole diet may act in synergy, and therefore consuming increased amounts of a single food may be fruitless and in some cases harmful. The Western diet includes foods of animal origin (e.g. dairy foods, meat) and in many cases, excess energy intake, both of which are linked to prostate cancer.[4]

An Australian case-control study[14] has examined the total diet rather than individual nutrients or foods, and its effect on prostate cancer risk. The dietary intake was assessed using food-frequency questionnaires from 10 years prior to cancer diagnosis. This was advantageous because prostate cancer has a long latency period. Three specific dietary patterns were identified: vegetable; Western; health-conscious. The vegetable pattern included foods such as all vegetables, jam, honey and apples. The Western pattern included foods such as whole milk, white bread, cakes, potato chips, French fries, eggs, red and processed meat, hamburgers, fried fish and full alcohol beer. The health-conscious pattern included foods such as steamed or grilled fish, tinned fish, chicken, rice, pasta, legumes, tofu, bean sprouts, nuts, yoghurt or ricotta cheese, red or white wine. Results show that the Western diet presented a statistical significantly increased risk for aggressive and non-aggressive prostate cancer, whereas neither the vegetable nor health-conscious diet conferred an increased risk.

Table 2. Foods common to the Mediterranean Diet

Fresh fruits and vegetables (e.g. tomatoes, pasta sauce, onions, garlic, wild edible greens)

Whole grain cereals

Marine foods (e.g. octopus)

Fish and seafood (e.g. snails)

Free range hen eggs

Goat and sheep’s milk

Legumes in bean salads, soups, casseroles, or dried snacks (e.g. roasted chickpeas)

Nuts (e.g. walnuts, almonds) and seeds (e.g. pumpkin, sesame)

Olive oil (i.e. pure, virgin and extra virgin)

Wine

Note: Based on information from Itsiopoulos et al, 2009

Mediterranean Diet   

Foods common to the Mediterranean diet are listed in Table 2. A review paper[5] evaluating scientific evidence from epidemiological trials supports a positive relationship between the Mediterranean diet and a decreased risk of prostate cancer. In the Mediterranean diet, tomatoes, vegetables and legumes are usually eaten with olive oil, the principal added fat. The oil base allows lipophilic lycopene to be more easily absorbed in the intestine.[8] Meats containing saturated fat (e.g. processed meats) are rare in this diet. Free range hens feed on wild greens, worms and insects which are rich in omega-3 fatty acids. People consuming the Mediterranean diet mainly obtain calcium from dairy products such as goat or sheep's milk which, compared to cow's milk, has a different calcium to phosphate ratio. This may in part explain why men living in the Mediterranean have a reduced risk of prostate cancer, compared to those living in the US and Australia.

The traditional Cretan Mediterranean diet is considered to have strong health benefits. Foods in this diet contain high amounts of omega-3 fatty acids, plant-derived bioactive phyto-chemicals (e.g. flavonoids), selenium, vitamins E and C, all of which may possess anticancer properties. Cruciferous vegetables (e.g. broccoli, cauliflower) are common in this diet.[5] The Cretan diet has a ratio of omega-6 to omega-3 fatty acids of 2:1, whereas in western and northern Europe, the ratio is 15:1. The people of Crete eat significant amounts of fatty fish (e.g. salmon, tuna, trout, herring, and mackerel).[15]

Asian Diet

A case-control study has evaluated the effect of the traditional Japanese diet, which is rich in phyto-oestrogens (i.e. isoflavones) mainly because of soy products, on prostate cancer risk. Food-frequency questionnaires were used to measure average daily intakes of food from five years prior to prostate cancer diagnosis. A significant (p<0.05) reduction in prostate cancer risk in this study is accredited to the intake of fatty fish and natto (i.e. fermented soybeans). Results also show that the consumption of all soybean products lowers the risk for prostate cancer.[16]

A population-based case-control study in India[17] has assessed whether or not a low fat diet rich in fruits and vegetables can decrease the risk of developing prostate cancer. Findings, consistent with many previous studies, show that men who consumed greater than 2 kg of fruits and vegetables per week are protective of prostate cancer, compared to men who consumed less than that amount. Soya-based foods (e.g. tofu, soy milk) are a staple in the Asian diet.

Dietary Fats

There are conflicting research reports related to total dietary fat being associated with prostate cancer risk.[1] However, there are some noteworthy studies which associate specific types of fats with a risk of prostate cancer. Dietary a-linolenic acid (ALA) may increase this risk, while two long chain omega-3 fatty acids (i.e. eicosapentaenoic Acid [EPA]; docosahexaenoic Acid [DHA]) may decrease the risk. Anti-inflammatory effects of EPA and DHA may offer protection from prostate cancer.[5]

Terry et al[18] have reviewed many recent epidemiological studies (i.e. cohort and case-control) regarding high and low consumption of fish/marine fatty acids within populations, and the risk of prostate and other hormone-dependent cancers. Only a few of these prostate cancer studies accounted for the intake of specific types of fish or marine fatty acids in their research findings. This is noteworthy because relatively high concentrations of EPA and DHA are found in cold water fatty fish such as salmon, mackerel, sardines and herring. Rather low concentrations are found in sole, halibut and cod. It is important to understand that higher fatty fish consumption naturally occurs in certain populations (e.g. Scandinavia), while lower consumption of the same occurs in other populations (e.g. United States). Terry et al[18] conclude that fish containing EPA and DHA appears to protect against the development and progression of prostate cancer. However, the evidence that fish containing marine fatty acids alters the risk of this cancer is still uncertain. The authors recommend future human intervention trials to study the effect of a dietary omega-6 fatty acid to omega-3 fatty acid ratio on prostate cancer risk.

In many countries, a healthy dietary omega-6 to omega-3 profile can be achieved by using more omega-3 cooking oils (e.g. olive, perilla, flaxseed, rapeseed, walnut oils) and less omega-6 cooking oils (corn, sunflower, safflower, cottonseed, soybean oils). Eating fish two to three times per week should offset the omega-6 fatty acids from meat and dairy products.[15]

Sugar and Grains

A population-based study[2] has identified dietary factors associated with increased mortality from prostate cancer. Data from 71 countries was analyzed. In this study statistics show a relationship between sugar consumption and prostate cancer mortality. Sugar consumption (i.e. from 8 to 577 calories per day) widely ranged among diets from different countries. The authors speculate that increased insulin and increased insulin-like growth factor-1 (IGF-1) plasma levels, which may result from a high intake of sugar, may increase the prostate cancer risk. Also in this study, cereal grain consumption strongly reduced the risk of prostate cancer mortality. Rice, ahead of wheat and barley, was found to have the strongest connection with decreasing prostate cancer mortality. The authors suspect that phyto-estrogens (i.e. lignan, plant stanols, and sterols) in cereal may offer anti-cancer protection.

Ongoing Research regarding SELECT

A large population-based randomized controlled study named SELECT (i.e. the Selenium and Vitamin E Cancer Prevention Trial) was created to assess the effectiveness of selenium or vitamin E, in reducing the risk of prostate cancer in healthy men.[19] The basis for this trial is the presumption that selenium and vitamin E possess antioxidant and anticancer properties. Participants in this trial, which started in 2001, include 32,400 North American men (i.e. age = 55 years for Caucasians; age = 50 years for African-Americans) with no prior history or clinical evidence of prostate cancer. Study cases receive a daily oral supplement of selenium and/or vitamin E and control cases receive a daily matched placebo. Intervention will last for a minimum of 7 and a maximum of 12 years. Final results of this study are expected in the year 2013. Preliminary findings for SELECT have been positive in relation to selenium and/or vitamin E reducing the risk of prostate cancer.[5]

Lycopene (i.e. from foods) and selenium (i.e. from foods or supplement) probably offer protection against prostate cancer development. Calcium-rich foods are implicated as causation factors of prostate cancer. More limited scientific evidence suggests that vitamin E and certain dietary patterns are protective of prostate cancer.[1] Additional supportive evidence through well designed trials is necessary to further evaluate the impact of diet and dietary supplements on prostate cancer risk.

References

1. World Cancer Research Fund / American Institute for Cancer Research (WCRF-AICR). Food, nutrition, physical activity and the prevention of cancer: A global perspective. AICR. Washington, DC. 2007.
2. Colli JL and Colli A. International comparisons of prostate cancer mortality rates with dietary practices and sunlight levels. Urologic Oncology 24(3): 184-194. 2006.
3. Parkin DM, Bray F, Ferlay J et al. Global cancer statistics, 2002. CA A Cancer Journal for Clinicians 55(2): 74-108. 2005.
4. Stacewicz-Sapuntzakis M, Borthakur G, Burns JL et al. Correlations of dietary patterns with prostate health. Molecular Nutrition & Food Research 52(1): 114-130. 2008.
5. Itsiopoulos C, Hodge A and Kaimakamis M. Can the Mediterranean diet prevent prostate cancer? Molecular Nutrition & Food Research 53: 000-000. 2009. Dec 2. [Epub ahead of print]
6. Giovannucci E. A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer. Experimental Biology & Medicine 227(10): 852-859. 2002.
7. Giovannucci E, Ascherio A, Rimm EB et al. Intake of carotenoids and retinol in relation to risk of prostate cancer. Journal of the National Cancer Institute 87(23): 1767-1776. 1995.
8. Giovannucci E, Rimm EB, Liu Y et al. A prospective study of tomato products, lycopene, and prostate cancer risk. Journal of the National Cancer Institute 94(5): 391-398. 2002.
9. Clark LC, Combs GF, Turnbull BW et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. Journal of the American Medical Association 276(24): 1957-1963. 1996.
10. McNaughton SA & Marks GC. Selenium content of Australian foods: A review of literature values. Journal of Food Composition and Analysis 15(2): 169-182. 2002.
11. Gao X, LaValley MP and Tucker KL. Prospective studies of dairy product and calcium intakes and prostate cancer risk: a meta-analysis. Journal of the National Cancer Institute 97(23): 1768-1777. 2005.
12. U.S. Department of Health and Human Services and U.S. Department of Agriculture. Dietary guidelines for Americans, 2005. 6th Edition. U.S Government Printing Office. Washington, DC. 2005. Available from:
www.health.gov/dietaryguidelines/dga2005/document/pdf/dga2005.pdf
13. Heinonen OP, Albanes D, Virtamo J et al. Prostate cancer and supplementation with a-tocopherol and ß-carotene: Incidence and mortality in a controlled trial. Journal of the National Cancer Institute 90(6): 440-446. 1998.
14. Ambrosini GL, Fritschi L, De Klerk NH et al. Dietary patterns identified using factor analysis and prostate cancer risk: A case control study in Western Australia. Annals of Epidemiology 18(5): 364-370. 2008.
15. Simopoulos AP. The traditional diet of Greece and cancer. European Journal of Cancer Prevention 13(3): 219-230. 2004.
16. Sonoda T, Nagata Y, Mori M et al. A case-control study of diet and prostate cancer in Japan: Possible protective effect of traditional Japanese diet. Cancer Science 95(3): 238-242. 2004.
17. Sunny L. A low fat diet rich in fruits and vegetables may reduce the risk of developing prostate cancer. Asian Pacific Journal of Cancer Prevention 6(4): 490-496. 2005.
18. Terry PD, Rohan TE and Wolk A. Intakes of fish and marine fatty acids and the risks of cancers of the breast and prostate and of other hormone-related cancers: a review of the epidemiologic evidence. American Journal of Clinical Nutrition 77(3): 532-543. 2003.
19. Klein, EA, Thompson IM, Lippman SM et al. SELECT: the selenium and vitamin E cancer prevention trial. Urologic Oncology 21(1): 59-65. 2003.