PCa Commentary
 

Tomatoes: Their Promise Of Control Of Prostate Cancer Is Ripening - An Update (December 2003)

The article, "Do Tomatoes Prevent Prostate Cancer", in the January issue of PCa Commentary concluded with the thought that "the usefulness of tomato products in combating PC is a very strong hypothesis, but awaits additional confirmation." Strong support was presented in an editorial in JNCI, Nov. 5, 2003 and in an associated article, "Prostate Carcinogenesis in N-methyl-N-nitrosourea (NMU)-Testosterone Treated Rats Fed Tomato Powder, Lycopene, or Energy Restricted Diets." Rats are considered to be to be excellent experimental animals for prostate cancer study because their presentation of prostate cancer closely mimics the characteristics of the human disease. In this study endogenous testosterone secretion was suppressed, the carcinogen NMU was injected, and prostate tissue growth was stimulated with depo-testosterone. Three different diets were tested: one augmented with whole tomato powder, one with solely lycopene and one offering a placebo. Result: "In the tomato powder group, the risk of developing lethal prostate cancer was reduced by a statistically significant 26% compared to that in the control rats; by contrast, the group receiving lycopene only experienced a 9% (and not statistically significant) risk reduction compared with the controls". The authors of the article were motivated by an interest in determining "whether lycopene itself is associated with reduced risk or whether it is simply a biomarker that is indicative of exposure to tomato products that may contain other phytochemicals with anti-prostate cancer properties."

This is an important area that needs clarification, especially since the preponderance of nutritional studies that have suggested a benefit of tomato derived nutrients in surpressing prostate cancer have been based on the ingestion of tomato products and not lycopene as a isolated supplement. Although lycopene is the most abundant and potent anti-oxidant (carotenoid) contained in tomatoes, there are at least ten other substances that could modulate prostate cancer, the next most abundant being the family of carotenes.

An excellent coverage of the fundamental biology underlying this issue is "Overview of Mechanism of Action of Lycopene" by David Heber, Exp Biol Med (Maywood) 227(10): 886-93, 2002. Tomatoes are red because of their lycopene content. During the green, early period of tomato development the lycopene is converted to beta-carotene by the enzyme lycopene cyclase. But as ripening occurs this enzyme is down-regulated resulting in the accumulation of lycopene and, voila!, the red color. Lycopene, and other carotenoids, inhibit cancer cell growth by interfering with cell cycle progression and interrupting proliferative stimulae from growth factor receptor signaling, and also by strengthening cell-to-cell adhesion.

Ansari reported a small, but intriging study in BJU Int. Sep 2000, "A comparison of lycopene and orchidectomy [O/L] vs orchidectomy alone in the management of advanced prostate cancer." Twenty seven men received 2 mg lycopene twice daily and 27 were controls. Follow-up extended for two years. Results: after 2 years the mean PSA in the orchidectomy/lycopene group was 3.01 ng/ml v. 9.02; complete PSA response for O/L was 78% v. 40%; disease progression, O/L was 7% v. 28%. Of the 19 men who died, 7 had received lycopene v. 12 in the controls (P=<0.001). This study begs confirmation since the doses of lycopene seem nearly trivial, considering that the average daily lycopene dietary intake in the Canadian population is 25.2 mg. The North Central Cancer Therapy Group (protocol NCCTG-NO351) has proposed a study: "Phase II Study of Lycopene in Patients With Asymptomatic Androgen-Independent Metastatic Prostate Cancer Who Have an Elevated Prostate-Specific Antigen Level." The principle investigator of this Mayo Clinic sponsored protocol has told me that in keeping with current trend, "tomato-based products" (and not lycopene capsules) will supply the 15 mg of lycopene in the twice daily administrations.

It may be that there is a per dose absorption limit to lycopene ingestion. Charles Meyers, M.D., Prostate Forum, October 2003, reported data that suggests that 6 mg of lycopene may be the maximal amount that can be absorbed per ingestion. Dr. Meyers suggests "at least 10 mg lycopene per day", but really there is no data specifying the "proper" dose of lycopene or the optimal amount of tomato products. The current trend, however, is toward recommending that these nutrients be consumed in their natural food form.

Some practical information about lycopene content in foods was presented in the article "Lycopene Content of Tomato Products: Its Stability, Bioavailability and In Vivo Antioxidant Properties", Journal of Medicinal Food, Vol.4, No.1, 2001. Lycopene is bound in the cellular matrix of tomatoes and processing (heating) breaks down this matrix and makes the lycopene more absorbable. Heating in oil accomplishes this especially well. Their study used 500 ml (50 mg lycopene) of processed tomato juice (not freshly squeezed) or 126 grams (40 mg lycopene) of tomato sauce (about 1/2 cup) and both of these amounts doubled the serum levels of lycopene over control.

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