Continued from PROSTATE CANCER: ADJUVANT THERAPY
Lycopene
Recent studies have shown a statistically significant inverse relationship between the ingestion of tomatoes, tomato sauce, and pizza with the development of prostate cancer. In a 6-year study by Giovannucci et al. (J. Natl. Cancer. Inst., 1995) involving the intake of carotenoids and retinol in 47,894 men, lycopene-rich foods significantly lowered the risk of PC. Men who ingested 10 or more servings of tomatoes in several forms (sauce, juice, raw, or on pizza) had a 41% reduction in PC, while those who ate four to seven servings a week had a 22% reduction. Tomatoes and tomato sauce contain high amounts of lycopene, a carotenoid. Lycopene is the most predominant carotenoid in plasma and in various tissues, including the prostate gland. Lycopene is the most efficient scavenger of singlet oxygen among the common carotenoids. Lycopene is not converted to vitamin A. The major contributors to the specific carotenoids are shown below:
| Carotenoid Class |
Vegetable or Fruit |
| ß-carotene |
Carrots, yams, sweet potatoes, spinach |
 -carotene |
Carrots, mixed vegetables |
| Lutein |
Spinach, broccoli, kale, mustard, chard |
| Lycopene |
Tomatoes, tomato sauce, pizza, tomato juice |
| ß-cryptoxanthin |
Oranges |
Another study evaluated the effect of lycopene on the development of mammary cancers in a mouse model. This showed a significant suppression of tumor growth in those mice receiving a diet supplemented with lycopene. Decreases in thymidylate synthetase within the breast tissue, lower levels of serum-free fatty acids, and decreased plasma prolactin levels by the pituitary were characteristic of the lycopene-supplemented group (Nagasawa et al., Anticancer Res., 1995). Interestingly, the source of lycopene was a beta-carotene-rich algae called Dunaliella bardawil.
Recently, Kucuk et al. reported on 30 men with localized PC scheduled for radical prostatectomy. They were randomly assigned to receive either 15 mg of lycopene (Lyc-o-Mato, LycoRed, Beer Sheva, or Israel) orally twice daily, or no intervention for 3 weeks prior to surgery. Prostate specimens were step-sectioned, entirely embedded, and evaluated for pathological stage, Gleason score, the volume of PC, as well as the extent of PIN (a pathological finding often associated with PC) in the gland. The specimens were also examined for biomarkers of cell proliferation, differentiation, and apoptosis. Comparisons were made between intervention and control groups. Serum and tissue lycopene levels increased by 22% in the intervention group. At RP, within the treated group, 8 of 12 patients (67%) had organ-confined PC, and 84% had tumors < 4 cc, compared to 44% and 55%, respectively, in the control group. Lesser glandular involvement by PIN was also observed in the intervention group. The expression of biomarkers of proliferation decreased, whereas the markers of differentiation and apoptosis increased in the intervention group. Serum PSA level also decreased significantly in the intervention group but not in the control group. The results suggest a role for lycopene in PC prevention. This is a very exciting study, and the full report should be published shortly. We currently advise patients with active PC to include 30 mg a day of lycopene in their diet.
Lifestyle Changes to Prevent and Treat Prostate Cancer
- Restrict Total Caloric Intake to 500 Calories a Meal
We believe that diet should be regarded as having serious biochemical relevance to the health of the individual. You are, for the most part, what you eat. Western society, and especially the United States, are over-consumers of calories. Excessive caloric consumption is a significant factor that adversely effects longevity. Caloric restriction has been shown to be an important factor in augmenting the immune system and improving longevity. We need to rethink how much food we need to eat. Our ideal body weight should be taken seriously. If we were to do this alone, we would virtually eliminate diabetes, hypertension, hypercholesterolemia, stroke, heart disease, and a significant amount of cancer from our lives. Patients should strive at a general figure of 500 calories a meal, and 100 calories per snack. Modifications of this are based on the level of activity, age, and body surface area. Nutritional software or nutritional counseling should be an integral part of our approach to good health.
- Eliminate Smoking, Reduce Alcohol Consumption,
and Exercise Properly
If we were to eliminate major factors relating to oxidative damage such as cigarette smoking and excessive alcohol consumption, in conjunction with dietary restrictions, we would eliminate 80% of disease as we know it today. In the context of caloric excess, we have additional co-factors such as lack of routine exercise and over consumption of dietary fat. The Anti-Oxidant Revolution, 1994, by Kenneth Cooper, M.D., focuses on the causal association of over-exercise and the generation of injurious freeradicals with resultant increases in degenerative diseases and cancer. We agree with Cooper that exercise should be low impact and that we should routinely use free radical scavengers, especially at times when we are more physically active, and certainly when we are exposed to excessive free radical damage, i.e., sunlight, high altitude, and activities that generate tissue damage. It is ironic that we bring our automobiles in for a periodic oil change to remove the products of oxidative damage, but we do not attempt a similar maneuver for our own bodies to prevent oxidative damage due to the wear and tear of everyday life.
- Avoid Excessive Carbohydrate Intake to Prevent Hyperinsulinemia and the Generation of Unfavorable Eicosanoids
The dietary fat issue is significant. There are studies that show dietary fat to increase the growth rate of PC in animal models of human PC. However, the emphasis on dietary fat per se has taken attention away from caloric over-consumption. Fat excess, however, is linked to excessive calorie consumption, since fat contains twice as many calories, gram for gram, as protein or carbohydrate. In addition, the ratio of protein to carbohydrate in our meals is related to how our body reacts to the intake of food and how it handles calories that are ingested. The reader is advised to read Barry Sears's book The Zone, 1995, and Anti-Aging Zone, 1999, for an in-depth discussion of the dangers of over-consumption of carbohydrates and the ill effects of hyperinsulinemia that occur as a result. Our patients are advised to incorporate Sears's approach into their lives while consuming fewer calories a day and exercising moderately. The value of generating favorable eicosanoids is discussed in detail in both of these books. The free radical-generating fatty acid called arachidonic acid, an unfavorable eicosanoid, has been shown to stimulate PC cell growth. The molecular pathway of arachidonic stimulation involves the inflammatory enzyme 5-lipooxygenase. Recent papers show that inhibition of arachidonic acid leads to PC programmed cell death, or apoptosis (Ghosh and Myers, Proc. Natl. Acad. Sci. USA, 1998). Lipooxygenase also is involved in the formation of abnormal blood clots. Nutrients that specifically inhibit 5-lipooxygenase include garlic. Fish oil supplements (EPA), an omega-3 fatty acid, have been shown to suppress arachidonic acid formation. Prostaglandins are synthesized from arachidonic acid by the enzyme cyclooxygenase. A particularly dangerous prostaglandin is PGE2, which is involved in many chronic inflammatory diseases. The administration of PGE2 to prostate, breast, and colon-cancer cells resulted in increased cellular proliferation. An ibuprofen derivative called Flurbiprofen inhibited PGE2-induced PC cell growth (Tjandrawinata et al., Br. J. Cancer, 1997). Aspirin, ibuprofen, and fish oil are other available agents that inhibit PGE2 synthesis. The eicosanoid pathways are shown in Figure 2.
Figure 2. Eicosanoid Pathways
- Use Free Radical Scavengers (Selenium and Vitamin E) to
Prevent Oxidative Damage
In conjunction with dietary restriction of calories and alteration in the nature of the calories consumed as well as moderating our exercise, there is evidence that aging, degenerative disease, and cancer are all expressions of varying degrees of cellular oxidative damage. In fact, fat itself induces the generation of fatty acid peroxides that generate damaging free radicals. The concept here is that living organisms are subject to oxidation just as metal is subject to rusting. As part of aging, we see the sequelae of such oxidation manifested in the graying of hair, short-term memory loss, cataract formation, gum and jaw recession, vascular disease, cardiac disease, degenerative joint disease, and sun-induced skin changes ranging from wrinkling to skin cancer. The majority of items in health food stores today are antioxidants.
In regards to PC, there are now studies that show that vitamin E and selenium use will decrease the incidence as well as the mortality from PC. The ATBC study by Heinonen et al. (J. Natl. Cancer Inst., 1998) demonstrated a 32% decrease in the incidence of PC and a 41% lower mortality rate from PC in men taking alpha-tocopherol (vitamin E). Another study by Fleshner et al. (J. Urol., 1998) showed a reduction in growth rates of transplanted LNCaP cells in athymic mice induced by a high-fat diet (40.5%) by dl-alpha tocopherol (synthetic vitamin E). The landmark study by Clark et al. (JAMA, 1996) provided evidence that 200 mcg of selenium could reduce the incidence of PC by 63%. This is consistent with the observation that selenium inhibited the growth of DU-145-an androgen-independent human cell line of PC-by 50% at a selenium dose of 1 × 10-6 M and by 98% at a dose of 10-4 M. For comparison, selenium serum levels in humans living in high selenium areas may be as high as 10-6 M (Webber et al., Biochem. Biophys. Res. Commun., 1985). Our recommended vitamin E dose for prevention is 400 to 1000 IU a day as mixed tocopherols. Mixed tocopherols contain synthetic vitamin E (d-alpha-tocopherol and dl-alpha-tocopherol) as well as natural vitamin E. A study by Moyad et al. (in press, 1999) indicates gamma tocopherol has more anti-PC activity then conventional d-alpha-tocopherol.
The selenium dose recommended for prevention is 400 mcg a day. This is best given as selenomethionine, usually derived from yeast. Selenium works best in conjunction with vitamin E, which enhances its activity. Vitamin E works best in association with beta-carotene and vitamin C. We recommend 1000 mg of vitamin C to be taken after each meal to prevent fatty acid peroxide generation. In a likewise manner, coenzyme Q10 has been shown to prevent the oxidation of LDL cholesterol. In fact, the prevention of fatty acid oxidation may be just as important as decreasing fat consumption. We suggest coenzyme Q10 be taken at a dose of 200 mg a day. An added benefit of coQ10 is the improvement in heart function and diabetic control as well as the treatment of periodontal disease. CoQ10 works best when given with vitamins E and C.
- Use Genistein to Decrease Cell Adhesion, Slow Proliferation, and Decrease
Metastatic Potential
Incidences of PC are higher in the Western world than in Asia, where soy is consumed as part of the normal diet, producing higher levels of genistein in the blood, which in turn appear to prevent the expression of metastatic capacity in hormone-dependent cancers. Studies have shown that, in a cell-culture system, genistein appears to be cytotoxic and inhibitory of PC cell proliferation (Santibanez et al., Anticancer Res., 1997; Peterson and Barnes, Prostate, 1993). Genistein's protein-tyrosine kinase-inhibiting effects have been identified as a cancer-prevention mechanism. One study examined genistein's effect upon cell adhesion as one possible mechanism by which it could be acting as an antimetastatic agent. A morphogenic analysis revealed that genistein caused cell flattening in a way that prevented metastatic adhesion of PC cell lines. We advise patients to eat a diet rich in soy products such as tofu, soy beans (edamame), soy milk, and miso. We recommend a breakfast and dinner drink that contains soy milk, isolated soy powder, many of the vitamins mentioned above, and strawberries. We use a Vita-Mix blender to pulverize the vitamins and add them to this drink. The protein-to-carbohydrate ratio of this drink is also close to the desired 3:4 ratio that Sears considers "zone" favorable. Life Extension makes a 700 mg Ultra Soy product that contains 134 mg of genistein per capsule as well as the isoflavones daidzein, and glycitein. We would suggest that clinical trials be initiated that would determine the genistein oral intake associated with blood genistein levels similar to those found in Asian men. Currently, we recommend 100 to 200 mg of genistein a day in addition to a diet high in soy products. We also believe that the major source of protein in our diet should come from soy.
- Decrease Cell Proliferation with Pygeum and Silymarin
Pygeum extract also has been shown to specifically inhibit prostate-cell proliferation by inhibiting protein kinase C enzyme activity (Yablonsky et al., J. Urol., 1993). Silymarin has been shown to have an anti-PC effect by virtue of increasing the levels of p27 (Zi et al., Cancer Res., 1998; Gali et al., Proc. Annu. Meet. Am. Assoc. Cancer Res., 1994). Silymarin also has protective effects against liver cell injury and skin cancer (Kropacova et al., Radiat. Biol. Radioecol., 1998; Agarwal et al., Proc. Annu. Meet. Am. Assoc. Cancer Res., 1995; Katiyar et al., J. Natl. Cancer Inst., 1997).
Product availability: Ultra Soy Extract, lycopene, silymarin, Natural Prostate Formula, Gamma E tocopherol, Vitamin C, Super Green Tea Extract Capsules Lightly Caffeinated, selenium and vitamin E can be ordered by phoning 1-800-544-4440 or order OnLine | |