Reducing Prostate Cancer Deaths
by Stephen B. Strum, M.D.
In the past we only measured the total PSA. In the last ten years we have learned that components of the PSA, such as free PSA and complexed PSA, have special clinical significance in the diagnosis of this disease. Fractionation of PSA into these components refines our detective work. It enables an enhanced focus on those patients with abnormalities in Free PSA who have a higher risk for PC. Therefore, when we have a patient with an elevated or increasing PSA, we can get a sense of his risk for having PC by asking for a free PSA level and free PSA percentage. The lower the free PSA percentage, the greater the risk for PC.1-3
Vitamins and antioxidants
Of all the vitamins and micronutrients, the largest number of medical papers have been published on the positive effects of lycopene versus PC. Lycopenes are members of the carotenoid family. Most of you are familiar with the carotenoids and flavonoids, the two main families of micronutrients. Both carotenoids and flavonoids are pigments synthesized by plants. The carotenoids impart the yellow, orange and red color to fruits and vegetables. The other family, the flavonoids, cause the blues, purples, emerald green and some red coloration of fruits and vegetables. Some of the major carotenoids and their vegetable, fruit or food sources is shown in Table 1.
Lycopenes have been shown to be of value in reducing the overall incidence of PC,4,9-11 the incidence of aggressive PC,12,13 as well as causing reductions in PC growth,14 PSA levels15,16 and even pathologic conditions associated with PC occurrence such as high-grade prostatic intra-epithelial neoplasia (HGPIN).17 More detailed descriptions of a few of these articles follow.
A dietary history of significant lycopene consumption has been related to a lower risk of aggressive and extra-prostatic PC.13 In this study, the combined intake of tomatoes, tomato sauce, tomato juice, and pizza (accounting for 82% of lycopene intake) was inversely associated with risk of prostate cancer for consumption frequency greater than 10 versus less than 1.5 servings per week. The other non-lycopene product identified that was associated with a lower PC risk was strawberries. One serving (0.5 cup) per week of strawberries was correlated with a 20% decreased risk of prostate cancer.11
Lu et al reported that the higher the plasma level of lycopene, the lower the incidence of PC. When comparing the highest versus the lowest lycopene levels, the risk of developing PC was reduced approximately 80%. The only other carotenoid approaching this zeaxanthin with a similar risk reduction.18 A study by Vogt showed that the risk for aggressive PC diminished by 63% when comparing highest versus lowest lycopene levels. In this study, serum lycopene concentrations were significantly lower in Blacks than in Whites, raising the possibility that differences in lycopene exposure may contribute to the racial disparity in incidence.12
The largest relevant dietary study, a prospective study in male health professionals found that consumption of two to four servings of tomato sauce per week was associated with about a 35% risk reduction of total prostate cancer and a 50% reduction of advanced (extraprostatic) prostate cancer. Tomato sauce was by far the strongest predictor of plasma lycopene levels in this study.19 These associations persisted in analyses controlling for fruit, vegetable consumption and for olive oil use and were observed separately in men of Southern European or other Caucasian ancestry.20
The consumption of cooked tomatoes was substantially and significantly associated with a reduction in insulin-like growth factor-1 (IGF-1) levels, with a mean (95% CI) change of -31.5% (range from -49.1% to -7.9%) for an increment of one serving per day. The authors concluded that the strongest known dietary risk factor for prostate cancer (lycopene deficit, as reflected in a reduced intake of cooked tomatoes) is somehow related to an important endocrine factor (IGF-1) in the cause of this disease.21
The easiest way I have found to combine a healthy intake of lycopenes into my diet is by using marinara sauce on various foods. For example, at breakfast, an egg-white omelet containing eggplant and bell peppers (ratatouille omelet) covered with marinara sauce is healthy as a source of protein, contains a substantial fiber content and is restricted in the amount of simple carbohydrates. Stewed tomatoes can be served as a vegetable side dish with lunch or dinner. Additionally, if one were intolerant to tomato-based products due to gastrointestinal reflux disease, supplementation with products containing lycopene would be a worthwhile consideration. Life Extension (LE), a nutraceutical company in Ft. Lauderdale, Florida sells a number of products containing lycopene, and additional products containing zeaxanthin. Healthy Origins sells a product called Lyc-O-mato that is a lycopene-based product. (Table 2)
Measures to prevent PC must be a routine part of the counsel that general practitioners and internists give their patients. Vitamin E and selenium are foundational antioxidants that should be started early in life to prevent oxidative damage to the prostate tissue and other tissues of the body. Although definitive studies regarding what age such supplements should be started at are currently lacking, I would suggest beginning such a regimen at age 25 and continuing this approach as a life-long practice. Vitamin E has been shown to reduce the incidence of PC by 32% and death due to PC by 41%.22 Basic research studies have shown that vitamin E reduces growth rates of PC tumors transplanted into mice and stimulated by a high fat diet.23 A study published in the Journal of the National Cancer Institute determined that statistically significant protective associations for high levels of selenium and alpha-tocopherol (vitamin E), were observed only when gamma-tocopherol (the gamma isomer of vitamin E) levels were high.24 A suggested dose of natural vitamin E as d-alpha tocopherol succinate would be 400 i.u. (equivalent to 270 mg) combined with 210 mg of d-gamma tocopherol in conjunction with selenium at a dose of 200 mcg per day. A table of the readily available d-gamma tocopherol supplements comparing doses and costs may be found at http://pcri.org/education/nutrprod/vite.html.
Studies by Clark, et al as well as Yoshizawa et al have shown that selenium reduced the incidence of PC in men by 63%.25,26 Selenium intake of at least 200 mcg a day and vitamin E should be a standard recommendation made to all men.
Omega 3 fatty acids (marine fish oils)
The importance of fats with beneficial activity has been under-emphasized throughout all of healthcare, including PC prevention and treatment. Every cell in the human body has a cell membrane that encloses the basic machinery of the cell. The cell membrane is comprised of fatty acids or lipids. The integrity of the cell depends on the health and function of its cell membrane. One of the functions of the cell membrane involves the production of hormonal substances called eicosanoids. These are the oldest hormones -- messengers involved in communication between cells. Eicosanoids trace their origin back 500 million years to production by sponges. Hormones are usually peptides or steroids, produced by one tissue and conveyed by the bloodstream to another to exert a physiological effect on cell growth or metabolism; in short, a chemical messenger aimed at maintaining a healthy state of affairs within the complex society of cells, tissues and organ systems. All of medicine, in fact all of life, represent issues of communication and balance.
The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexenoic acid (DHA) are critical regulators of the eicosanoid hormonal pathways. EPA and DHA (extracted from fish oil) direct eicosanoid production away from the bad or unfavorable eicosanoids such as the omega-6 fatty acid arachidonic acid (AA) and its metabolic products. (Figure 2) By inhibiting this latter pathway (shown in red in Figure 2) DGLA is metabolized in favor of good eicosanoids, such as PGA1 and PGA2.
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