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Prostate Cancer Prevention

by Hans R. Larsen, MSc ChE and William R. Ware, PhD

The American Society of Clinical Oncology and the American Urological Association (ASCO and AUA) have issued a new guideline on the use of 5-alpha reductase inhibitors (5-ARI) for cancer chemoprevention. They found 15 randomized clinical trials that met their inclusion criteria. The main conclusion was that 5-ARI therapy during a 7-year period reduces the relative risk of developing prostate cancer by 25%. The absolute risk reduction however was only 1.4% which leads to about 71 persons needed to treat to prevent one cancer. Another way of looking at this result is that if 1000 men were followed over a period of 7 years, 59 would be expected to develop prostate cancer, and if they all took the 5-ARI, 45 would still develop cancer. This risk reduction is consistent with the result from the Prostate Cancer Prevention Trial which started in 1993 and was stopped in 2004 because of this same risk reduction. However, enthusiasm that should have arisen from this trial result, based on the 25% figure, was dramatically dampened by the suggestion that finasteride increased the risk of high-grade cancer. A majority (8 of 10) of members of the ASCO-AUA panel judged this higher observed incidence of high-grade cancer in the finasteride group to be due to confounding and thus not real. Finasteride is prescribed to relieve the symptoms of benign prostate hyperplasia (BPH - enlarged prostate) and 11 to 40 men experience side effects for every 1000 taking the drug. These include decreased sex drive and erectile dysfunction. The position taken by the ASCO-AUA is that men who are asymptomatic with a PSA equal to or less than 3.0 ng/mL may benefit from a discussion of the benefits of 5-ARIs vs. the risk of side effects. For men taking the drug for symptoms associated with BPH, the guidelines suggest that a discussion is in order to acquaint them with the possibility of increased risk of high-grade cancer, but as pointed out, the panel considered this risk unlikely, and thus given the need for the drug in the context of BPH, the potential cancer prevention is an added bonus. An additional problem with 5-ARI therapy is an approximate 50% drop in PSA which must then adjusted when applying cut-offs for triggering a biopsy. The panel did not take a position or a revised cut-off.

While obtaining a 25% risk reduction seems very appealing merely by popping a pill daily, individuals who would otherwise not take 5-ARIs need to seriously consider the very high number needed to treat to prevent one cancer. It is not hard to find physicians who regard 71 as too high to justify an intervention that is not totally risk free. There is also cost to consider. Finasteride can cost up to $60 U.S. per month.
Kramer BS, Hagerty KL, Justman S et al. Use of 5alpha-Reductase Inhibitors for Prostate Cancer Chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline. J Urol 2009 Apr;181(4):1642-57

Several but not all follow-up studies on the impact of dietary or supplemental vitamin E on the incidence and progression of prostate cancer found a positive benefit, and there is an ongoing clinical trial in this regard involving the combination of vitamin E and selenium (the SELECT phase III trial). A recent study from the National Cancer Institute of the NIH and New York University has contributed to this subject. In this prospective study, Wright et al followed a cohort of almost 300,000 men who were cancer free at enrollment. Baseline supplemental and dietary intakes of alpha-, beta-, gamma- and delta-tocopherols were obtained from a questionnaire. At the end of 5 years follow-up over 10,000 prostate cancer cases were identified. Supplemental vitamin E (alpha-tocopherol) intake was not found to be associated with prostate cancer risk even at intakes equal to or greater than 800 IU/day. However, dietary gamma-tocopherol was found to be significantly and strongly inversely related to prostate cancer risk, with a 32% risk reduction when the highest vs. the lowest quintiles were compared. The median intake in the highest quintile was 20.8 mg/day with a range of 18.5 to 57.5. Furthermore, this beneficial effect was particularly evident among men with a low selenium intake. Gamma-tocopherol is the most commonly consumed form of vitamin E in the US diet. The authors list as major sources margarine, butter, salad dressings, fried potatoes, oils (mostly corn) cookies and brownies.

The potential anti-cancer properties of gamma-tocopherol appear to be under appreciated, given that most people appear to think of vitamin E only in terms of the common supplement, the alpha form. In a recent review titled Gamma-Tocopherol--An Underestimated Vitamin?, Wagner et al discuss a number of studies that relate to this question. One found a 5-fold reduction in prostate cancer risk for the highest vs. lowest quintiles of gamma-tocopherol intake. Another serum level study also found the same 5-fold reduction. However, a large trial involving U.S. physicians that also looked at serum levels failed to find a similar association. In addition, Wagner et al point out that gamma-tocopherol is more effective than alpha-tocopherol in inhibiting prostate cancer cells, reducing oxidative DNA damage and scavenging certain mutagens. Obviously, more studies are needed, but the evidence of the benefits of gamma-tocopherol in regard to prostate cancer is accumulating. In fact, it may occur to some readers that the SELECT trial may not be using the ideal form of vitamin E and that a negative outcome of this trial when it finally reports might well kill interest in vitamin E in general, including the gamma form.

Gamma-tocopherol is also available in supplements, generally as mixed tocopherols. Careful label reading is required since IU may be quoted (conversion 0.15 IU per mg) but it is common for only a total in IUs or milligrams for the beta, gamma and delta combined to be displayed. Products are available that contain 200 or more mg per capsule of the gamma form. Given that many individuals do not eat foods rich in the gamma form of vitamin E, supplements containing this form appear to be of interest.
Wright ME et al., 2007. Supplemental and dietary vitamin E intakes and risk of prostate cancer in a large prospective study. Cancer Epidemiol Biomarkers Prev. 16(6):1128-1135
Wagner KH, Kamal-Eldin A, Elmadfa I, 2004. Gamma-tocopherol--an underestimated vitamin? Ann Nutr Metab. 48(3):169-188
Weinstein SJ et al., 2007. Serum and dietary vitamin E in relation to prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 16(6):1253-1259

Another micronutrient that is frequently associated with prostate cancer is lycopene, the principal source of which is the tomato. Early studies suggested that both tomato products and circulating lycopene were associated with a reduced risk of prostate cancer. Jokes were even made about the merits in this context of eating lots of pizza. Bioavailability issues arose and it was found that products such as tomato paste were preferable to raw tomatoes. Two recent publications relate to this matter, one a report on a follow-up trial, the other a U.S. Food and Drug Administration (FDA) review done because processed food producers wished to make health claims for tomato products.

The follow-up trial was part of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). Participants were selected who underwent annual standardized screening for prostate cancer (PSA at entry and annually for 5 years and a digital rectal exam at entry and annually for 3 years). Thus this was a PSA-era study. No association was found between serum lycopene and total prostate cancer diagnosis risk or aggressive prostate cancer risk. The authors conclude that, consistent with other recent publications, these results suggest that lycopene or tomato- based regimens will not be effective in prostate cancer prevention.

The FDA report was based on a review of the literature and found "no credible evidence to support the association between lycopene intake and a reduced risk of prostate cancer." However, they mention finding very limited evidence to support the association between tomato consumption and reduced risks of prostate cancer.

This latter report prompted Edward Giovannucci, a very well known epidemiologist from Harvard, to write an editorial trying to reconcile the FDA position with earlier studies that did indeed show benefit. His thesis is that the newer studies fail to find benefit from lycopene or tomato products because the studies are all done in the PSA era. Before the widespread use of PSA testing for screening purposes, most cancers that were diagnosed had progressed to a relatively advanced stage. What was being detected were manifestations of advanced disease such as metastasis and tumor growth outside the prostate itself. In the PSA era, most of the cancers detected would never have attracted clinical attention and include small, low-grade and indolent tumors. Thus studies of tomatoes and lycopene in the PSA era with the endpoint of cancer diagnosis are looking at the question of benefits during the early stages of disease development, whereas in earlier times, the potential benefit extended over a much longer period in the natural history of the disease. Consistent with this, Giovannucci points out that in the Health Professional's Follow-Up study (HPFS), the initial analysis of the data for the period 1986 to 1992 found an inverse association between tomato sauce intake and total prostate cancer incidence and the association was stronger for advanced cancer. Later analysis for the period 1992-1998 which was during the PSA era, the association was attenuated and weak but a strong association persisted for metastatic cancer. Combined data for these two periods gave a 66% risk reduction for = 2 servings per week to <1 serving per month. Finally an analysis of the data found no association between tomato sauce and the risk of diagnosis of organ-confined disease. Thus in the PSA era, the benefits of tomato sauce with regard to advanced cancer were swamped by the huge numbers of early non-advanced cases. In the HPFS study, Giovannucci comments that only strict criteria for aggressive behavior such as invasion into the seminal vesicle or metastasis were adequate to detect the association between tomato paste and an increased risk of fatal prostate cancer. He also points out that the FDA review was not designed to take into account these issues and the data needed are sparse.

These same observations apply to the PLCO study which was done in the PSA era. Thus it appears that tomatoes and lycopene provide benefit only in terms of influencing advanced cancer or offering benefit that is only significant when the exposure is over the full initiation and progression of the disease, as was the case in the early studies. It would appear that abandoning cooked tomato products like tomato sauce, and as well even supplemental lycopene, on the basis or recent studies is somewhat premature. Furthermore, it may be unrealistic to assume that studies will be carried out that might resolve the issues discussed, given the widespread PSA screening at present is the norm.
Peters U et al., 2007. Serum lycopene, other carotenoids, and prostate cancer risk: a nested case- control study in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev. 16(5):962-968
Kavanaugh CJ, Trumbo PR, Ellwood KC, 2007. The U.S. Food and Drug Administration's evidence-based review for qualified health claims: tomatoes, lycopene, and cancer. JNCI Cancer Spectrum. 99(14):1074- 1085

Dietary fatty acids have also been the subject of studies in the context of prostate cancer risk. Results have just been reported regarding these nutrients based on data collected in the Physician's Health Study. While this study had as its primary goal the evaluation of aspirin and beta-carotene in the primary prevention of heart disease and cancer, the cohort provided the opportunity for case-control studies of other questions. One such study has just reported which involved almost 15,000 apparently healthy men who provided blood samples in 1982. Blood fatty acid levels were measured for 476 men who developed prostate cancer during the 13-year follow- up and as well as for their matched controls. It was found that higher levels of the long-chain fatty acids mainly found in marine foods, and of linoleic acid, mainly found in non-hydrogenated vegetable oils, were associated with reduced risk of prostate cancer. In both, the relative risk reductions were about 40% when the highest quintile of serum level was compared to the lowest. The authors comment that in addition, their data suggest that the intake of polyunsaturated fatty acids appear unlikely to increase prostate cancer risk and that in addition, the intake of these fatty acids may in addition help prevent other common chronic diseases such as heart disease and diabetes. Thus these substances may have a broad implication in chronic disease prevention.
Chavarro JE et al., 2007. A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 16(7):1364-1370

Although several studies have found vitamin D to be protective against both breast and colorectal cancers, the evidence for a protective effect in regard to prostate cancer is sparse and somewhat ambiguous. A recent study using data from the Physicians Health Study (14,916 participants) concluded that there was no significant difference in circulating vitamin D (1,25-dihydroxyvitamin D and 25-hydroxyvitamin D) between men with prostate cancer and the controls.

These results are surprising because of several recent studies that connect sun exposure to a reduced risk of prostate cancer. In one 528 prostate cancer patients and 442 basal cell carcinoma cases (a UV induced cancer) were examined for a correlation between cancer and sun exposure. Both groups were measured the same way as regards sun exposure. For those with the highest sun exposure, the risk of basal cell carcinoma was the highest, and for those with prostate cancer it was the lowest. In another study, increased sun exposure decreased prostate cancer mortality. In a study that looked at geographical distributions of UV intensity and prostate cancer mortality in the US, the expected variation with latitude was observed, i.e. those living in the higher latitudes had higher risk. Why this is not reflected in the Physicians Health Study as a more dramatic correlation between serum 25(OH)D and prostate cancer is not clear.
Gann PH et al., 1996. Circulating vitamin D metabolites in relation to subsequent development of prostate cancer. Cancer Epidemiol Biomarkers Prev. 5(2):121-6
Rukin NJ et al., 2007. A comparison of sunlight exposure in men with prostate cancer and basal cell carcinoma. Br.J Cancer. 96(3):523-528 Colli JL, Colli A, 2006. International comparisons of prostate cancer mortality rates with dietary practices and sunlight levels. Urol Oncol. 24(3):184-194
Schwartz, GG, Hanchette, CL, 2006. UV, latitude, and spatial trends in prostate cancer mortality: all sunlight is not the same (United States). Cancer Causes Control. 17(8):1091-1101

SELECT is a double-blind, randomized clinical trial that is testing an intervention of vitamin E (400 IU/day of dl-alpha tocopherol, the synthetic form) and selenium (200 microg/day) in order to test the hypothesis generated by earlier studies that such a combination reduces the risk of prostate cancer. This is a large multinational study involving 35,000 men age 50 and older. According to a press release from the National Cancer Institute on October 28, an initial, independent review of the study data revealed that neither the combination nor the supplements used individually reduced the incidence of prostate cancer. The trial has been terminated but there will be continued follow-up that will remain blinded. This comes as a disappointment to those who regarded the earlier work as providing a fairly strong argument for the use of this pair of supplements in prostate cancer prevention.

When the trial design was announced, there was discussion in the literature regarding the form of vitamin E used since natural vitamin E is much more effective in general and the form in food is in fact gamma tocopherol. It is doubtful that the trial will be repeated with either the natural form or the gamma form and thus we will never know if the null result was due to the use of the synthetic form of vitamin E. Nevertheless, the form of selenium used is generally considered to be satisfactory from the point of view of bioavailability (L-selenomethionine), and it alone was not effective in this trial. But, it has been pointed out that statin drugs interfere with the synthesis of selenoproteins, glutathione peroxidase and in particular selenoprotein N. But the SELECT trial has not indicated results from stratification to see if selenium alone was effective in statin non- users. In the age group studied, there were no doubt a large number of statin users who may have had the beneficial effects of selenium blocked by the statin enzyme inhibition. In fact, it has been postulated that the inhibition of selenoproteins may be related to the side effects of statins such as rhabdomyolysis and polyneuropathy. Thus this study was far from ideal to answer the target question and in fact may have been fatally flawed.
Moosmann B, Behl C. Selenoprotein synthesis and side-effects of statins. The Lancet 2004 March 13;363(9412):892-4

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Eating fish may help prevent prostate cancer
MANCHESTER, UNITED KINGDOM. Men face a much more dangerous form of prostate cancer if tumor cells from the prostate gland metastasize and migrate and invade other parts of the body, such as bone marrow. New research suggests that oily fish may help prevent this process. It appears that omega-3 fats contained in oily fish can prevent the cancer spreading to bone marrow, a process which may be encouraged by the other major group of polyunsaturated fatty acids - omega-6 fats. Researchers at the Christie Hospital in Manchester found evidence for this effect in laboratory tests, where they showed that omega-3 fats can inhibit invasion by prostate cancer cells, potentially reducing the threat of metastasis. They also found that omega-6 fatty acids, found in vegetable oils, nuts and seeds, increased the risk of tumor cells spreading into bone marrow. This invasion was blocked by omega-3 fats, which are found in oily fish such as salmon, mackerel and tuna. The researchers believe that cancerous tumors may use omega 6 fats as a high-energy food, enabling rapid growth. Omega-3 fats are known to interfere with the various functions of omega-6 fats, they explain, and this was confirmed by the current findings. This effectively removes the cancer's 'free lunch', a fact that may have clinical importance. Eating a diet with the right balance of omega-3 and omega-6 fats may well help to keep prostate cancer within the prostate gland where it may be monitored safely or more easily treated with surgery or radiotherapy, they conclude, adding that a healthy balance of these two types of fat would be about half as much omega-3 as omega-6. Many cancers, including breast and prostate cancer, seem to invade bone marrow rather than other parts of the body. If it could be shown that this is influenced by the proportion of different types of fat, then scientists may be able to develop drugs that prevent metastasis.
Brown, M.D. et al. Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs. British Journal of Cancer, Vol. 94, March 27, 2006. pp. 842-53

Design of the SELECT trial
HOUSTON, TEXAS. It is estimated that 230,000 American men will be diagnosed with prostate cancer and that 30,000 men will die from the disease in 2004. There are currently no pharmaceutical drugs that have been proven effective in preventing prostate cancer. Finasteride (Proscar) showed some promise in reducing overall cancer incidence but was, unfortunately, associated with a significant increase in advanced cancers. Finasteride is therefore no longer considered suitable for prostate cancer prevention. In contrast, two natural agents, selenium and vitamin E, have been found effective in prostate cancer prevention. The Nutritional Prevention of Cancer (NPC) study concluded that supplementing with 200 micrograms/day of elemental selenium (in the form of high-selenium yeast) reduced prostate cancer risk by 63%. The large Finnish ATBC study concluded that supplementing with 50 mg/day (50 IU/day) of synthetic alpha-tocopheryl-acetate reduced prostate cancer risk and mortality by 32% and 41% respectively.

Based on these and other findings, the National Cancer Institute has embarked upon a major trial, the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The trial, opened for recruitment in July 2001, now has a total enrollment of 35,534 men with a median age of 62 years (range of 50-93 years) who were free of prostate cancer. The expected follow-up time is 7-12 years. After much deliberation and a thorough review of the literature, the SELECT Steering Committee decided that the supplements to be evaluated would be 200 micrograms/day of elemental selenium in the form of L-selenomethionine and 400 IU/day of synthetic alpha-tocopheryl acetate. The trial design will involve 5 pair-wise comparisons of prostate cancer incidence, in association with vitamin E vs placebo, selenium vs placebo, vitamin E plus selenium (combination) vs placebo, combination vs vitamin E, and combination vs selenium. The Steering Committee points out that there is strong evidence that 200 micrograms/day of elemental selenium is entirely safe, as is up to 1000 mg/day of vitamin E. They acknowledge that natural alpha-tocopherol is significantly more effective than synthetic alpha-tocopheryl acetate and that gamma-tocopherol may be even more effective than either as far as prostate cancer prevention is concerned. However, due to the fact that more clinical trial data is available on synthetic alpha-tocopheryl acetate they decided to go ahead with this form. All study participants will also receive a daily multivitamin devoid of selenium and vitamin E, but including 400 IU of vitamin D3.
Lippman, SM, et al. Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Journal of the National Cancer Institute, Vol. 97, January 19, 2005, pp. 94-102

Editor's comment: It is indeed gratifying to see such a massive undertaking by the National Cancer Institute aimed at evaluating natural supplements in the prevention of prostate cancer. Personally, I would have liked to see the vitamin E component consist of a 50:50 mixture of natural alpha- and gamma-tocopherols, but the Steering Committee obviously decided that there was not enough evidence to support this. In any case, involving over 35,000 men in a 7- to 12-year trial of selenium and vitamin E clearly shows that hopes are high that these two natural compounds will prove effective in prostate cancer prevention and that they are entirely safe. In view of this, I see no reason to wait 10 or more years for the results to be published. All men should supplement with selenomethionine and natural vitamin E (preferably a 50:50 mixture of alpha- and gamma-tocopherols).

Diabetes protects against prostate cancer
ATLANTA, GEORGIA. The possible protective effect of diabetes against prostate cancer has been investigated once more, this time in a prospective study. Earlier studies have shown a reduction in risk of 10 to 40 per cent, and some suggest that diabetes is protective only several years after diagnosis. Researchers from the American Cancer Society used data on a group of 72,670 men from the Cancer Prevention Study II Nutrition Cohort. Information on diabetes and prostate cancer was gathered in 1982, 1992, 1997, 1999 and 2001. Prostate cancer was diagnosed in 5,318 men (7.3 per cent), who tended to be older and with a higher BMI.

The researchers found that overall; diabetes reduced the risk of prostate cancer by 33 per cent once age, race, education and prostate-specific antigen testing were taken into account. However, risk was significantly increased (by 23 per cent) in the first three years after diabetes diagnosis, compared with non- diabetic men, and only began to be protective after four years. The protective effect remained consistent when stage or grade of prostate cancer at diagnosis was examined. These results are consistent with the hypothesis that diabetes is associated with reduced risk of prostate cancer but only several years after diagnosis of diabetes, say the authors. The protective effect may be due to the reduced insulin levels found in men who have been diabetic for some time, as prostate cancer has been linked to high circulating levels of insulin.

The findings in the present study are consistent with results from a Health Professionals Follow-up Study, which also found an increased risk following diagnosis of diabetes and a protective effect after several years. In this study, prostate cancer risk was lowest 10 years after diabetes diagnosis, a reduction of 46 per cent. On the other hand, a recent case-control study within the US Physicians' Health Study found a reduction in risk of 36 per cent, but with no link to the time since diabetes diagnosis.
Rodriguez, C et al. Diabetes and Risk of Prostate Cancer in a Prospective Cohort of US Men. American Journal of Epidemiology, Vol. 161, January 2005, pp. 147-152

Fish oils help prevent prostate cancer
BETHESDA, MARYLAND. Alpha-linolenic acid (ALA) is a major component of flax seed oil and has been associated with significant cardiovascular benefits. Some studies, however, have shown that a high intake of ALA is associated with an increased risk of prostate cancer. A prestigious team of researchers from the National Cancer Institute, the Harvard Medical School, the Harvard School of Public Health, and the Karolinska Institutet in Stockholm has just released the results of a study aimed at settling the controversy as to whether or not ALA is detrimental when it comes to prostate cancer. The researchers also determined the effect of other fatty acids, including fish oils, on prostate cancer risk.

The study involved 47,866 male American health professionals who were followed over a 14-year period beginning in 1986. The participants completed detailed food frequency questionnaires in 1986, 1990 and 1994. By the year 2000, 2965 new cases of prostate cancer had been reported with 448 of these being advanced (metastasized) or fatal. The overall incidence of new prostate cancer detected over the 14- year period was 0.5% per year.

The researchers found no correlation between ALA intake and overall prostate cancer risk, but did observe a strong association between a high ALA intake and the risk of advanced prostate cancer. Men with a high ALA intake (greater than 0.58% of energy or about 1.3 grams/day) were twice as likely to develop advanced prostate cancer as were men with a lower intake (less than 0.37% of energy or about 0.8 grams/day) even after adjusting for all other known variables that could affect the risk. The risk was slightly higher for ALA from non-animal sources than for ALA from meat and dairy sources. There was a trend for red meat, mayonnaise and salad dressings to be associated with a higher risk. The intake of two other abundant fatty acids, linoleic acid and arachidonic acid, was not related to prostate cancer risk.

The team of researchers found a protective effect associated with a high intake of fish oils - eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Men with a daily intake of more than 0.214% of daily energy (about 470 mg/day) were 11% less likely to develop prostate cancer than were men with an intake less than 0.057% of energy (about 125 mg/day). The beneficial effect of EPA plus DHA was particularly pronounced in regard to the incidence of advanced prostate cancer. Fish oil supplements were slightly less effective than fish oils from fatty fish perhaps indicating that vitamin D and vitamin A are necessary to obtain the maximum benefit.
Leitzmann, MF, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. American Journal of Clinical Nutrition, Vol. 80, July 2004, pp. 204-16

Selenium and prostate cancer risk
BOSTON, MASSACHUSETTS. At least five major clinical trials have concluded that higher levels of selenium (in blood or toenail clippings) are associated with a sharply reduced risk of prostate cancer. The Nutritional Prevention of Cancer (NPC) trial found that supplementing with 200 micrograms/day of selenium cuts prostate cancer risk in half. Researchers at the Harvard Medical School now weigh in with another study confirming the beneficial effects of selenium. Their study involved 22,000 healthy, male physicians who were enrolled in the study in 1982 and had blood samples taken at that time. Sufficient samples to analyze for selenium content and PSA level were available for 586 men diagnosed with prostate cancer as well as for 577 controls matched for age and smoking status.

After 13 years of follow-up the researchers concluded that study participants with a plasma selenium level of 0.12-0.19 ppm had a 50% lower incidence of advanced prostate cancer than did men with a level of 0.06-0.09 ppm. The correlation was only apparent in men with a PSA level of more than 4 ng/mL and was particularly strong for those with a baseline (1982) PSA level greater than 10 ng/mL. For these men a high selenium level corresponded to a 70% decrease in the risk of advanced prostate cancer. The researchers also observed a trend for a lower incidence of localized prostate cancer with high selenium levels, but this trend was not statistically significant. They conclude that selenium is perhaps not too effective in preventing the initiation of prostate cancer, but that it is highly effective in slowing down tumor progression. They believe that selenium acts by selectively killing off cells whose DNA has been extensively damaged, by inhibiting cellular proliferation, and by its role as a key component of glutathione peroxidase, which protects cells from peroxide damage.
Li, H, et al. A prospective study of plasma selenium levels and prostate cancer risk. Journal of the National Cancer Institute, Vol. 96, May 5, 2004, pp. 696-703
Taylor, PR, et al. Science peels the onion of selenium effects on prostate carcinogenesis. Journal of the National Cancer Institute, Vol. 96, May 5, 2004, pp. 645-47 (editorial)

Editor's comment: The evidence is now indeed overwhelming that selenium helps protect against prostate cancer. While this study concluded that the protection mainly involves slowing down tumor progression, other studies have shown that selenium also helps prevent initiation of the cancer. Thus daily supplementation with 200 micrograms of selenium should be an integral part of all supplementation programs for men.

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Testosterone and Alzheimer's disease
BETHESDA, MARYLAND. Researchers at the National Institute of Aging have found an association between the level of circulating free testosterone and the development of Alzheimer's disease (AD). Their study involved 574 men who joined the Baltimore Longitudinal Study of Aging since 1958 at ages between 32 and 87 years. The men had their total testosterone and sex hormone binding globulin (SHBG) measured at baseline and several times thereafter during an average 19-year follow-up period. The researchers found that a low free testosterone index (FTI) was associated with an increased risk of AD both at baseline and at the last measurement before the actual diagnosis of AD. FTI is equal to total serum testosterone level divided by SHBG level. Neither total testosterone nor SHBG levels, on their own, were associated with AD risk. Patients diagnosed with AD were approximately 7 years older than men not diagnosed with AD and also tended to be leaner (lower body mass index). Age and smoking were associated with increased risk, whereas education, BMI, diabetes, and hormone supplementation were associated with a reduced risk. After adjusting for all other variables the researchers concluded that each 10-unit increase in FTI corresponds to a 26% reduction in the risk of AD. They urge large-scale clinical trials to see if supplementation with testosterone might reduce the risk of Alzheimer's disease.
Moffat, SD, et al. Free testosterone and risk for Alzheimer disease in older men. Neurology, Vol. 62, January 2004, pp. 188-93
Henderson, VW and Hogervorst, E. Testosterone and Alzheimer's disease: Is it men's turn now? Neurology, Vol. 62, January 2004, pp. 170-71

Editor's comment: Testosterone supplementation should be approached with great caution and only done with the cooperation of a physician as it may increase the risk of prostate cancer.

Cancer trends in the USA
ATLANTA, GEORGIA. The annual report on the status of cancer in the United States has just been released. The report is a joint effort of the American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries. Overall cancer incidence rates were essentially stable between 1995 and 2000, but may be increasing slightly if allowing for reporting delays. Overall cancer death rates have remained steady from 1998 to 2000. More than half of all cancer diagnoses and deaths involve lung cancer, breast cancer, prostate cancer or colorectal cancer (cancer of the colon or rectum).

Lung cancer
Lung cancer incidence and mortality have been declining among men since 1991, but have increased among women. This is no doubt due to the fact that smoking control programs have been far more effective among men than among women. The average annual death rate from lung cancer was 56.8 per 100,000 for men and 40.7 for women (1996-2000). Lung cancer rates were lowest in Utah, the state with the lowest adult prevalence of smoking (13%) and the highest in Kentucky, the state with the highest adult smoking prevalence (31%).

Breast cancer
The incidence of female breast cancer has increased continually since 1986 particularly among white women. Death rates, however, have decreased steadily since the early 1990s possibly due to the more extensive use of mammography screenings. The average annual death rate from breast cancer (1996- 2000) was 27.7/100,000 with slightly higher rates observed among black women.

Prostate cancer
The incidence of prostate cancer has increased by 2.3% per year since 1994 and more recently by 3.0% per year among white men and by 2.3% per year among black men. Death rates, on the other hand, have been steadily declining and now stand at 32.9/100,000 (30.2 among white men and 73.0 among black men). Some experts argue that the increased use of PSA testing is responsible for the decline in mortality; however, the subject of screening for cancers is a highly controversial one. Dr. M.J. Quinn of the UK National Cancer Intelligence Centre points out that the use of the prostate specific antigen (PSA) test for screening purposes is not recommended by the US Preventive Services Task Force or in the European Code Against Cancer. He is clearly opposed to the use of PSA testing for screening purposes and points out that it may lead to unnecessary biopsies and dangerous treatments without any proven reduction in mortality.

Cancer of the colon and rectum
The incidence of colorectal cancer has stabilized since 1995 for both men and women and death rates have declined. Overall mortality rate for the period 1996-2000 was 21.2 per 100,000, but was particularly high among black men at 34.6/100,000.

The report concludes that overall cancer incidence and death rates began to stabilize in the mid to late 1990s, but have lately shown signs of increasing again.
Weir, Hannah K, et al. Annual report to the nation on the status of cancer, 1975-2000, featuring the uses of surveillance data for cancer prevention and control. Journal of the National Cancer Institute, Vol. 95, September 3, 2003, pp. 1276-99 Quinn, MJ. Cancer trends in the United States - A view from Europe. Journal of the National Cancer Institute, Vol. 95, September 3, 2003, pp. 1258-61

Selenium absorption by prostate tissue
BRISBANE, AUSTRALIA. There is considerable evidence that selenium may be protective against prostate cancer and there are currently several large clinical trials underway to determine definitively if selenium supplementation decreases the incidence of prostate cancer. Selenium is an important constituent of the body's naturally produced antioxidant, glutathione peroxidase, and its cancer preventive effect may be associated with increased glutathione levels.

If selenium proves to be cancer preventive it is clearly important to know whether selenium levels as measured in a blood sample correlates with actual selenium levels in prostate tissue. Researchers at the University of Queensland recently set out to answer this question. Their clinical trial involved 51 men who had been scheduled for transurethral resection for prostate enlargement. The men were randomly assigned to serve as controls or to receive selenium yeast tablets daily for one month prior to surgery. The tablets provided a total of 200 micrograms/day of selenium. Blood samples were taken at the beginning of the 30-day trial and on the day of surgery and the selenium content of red blood cells was compared to the selenium content of prostate tissue removed during surgery.

The researchers found that the red blood cell level of selenium had increased from 173 ng/mL to 209 ng/mL in the supplemented group with no significant change among controls. The selenium level in prostate tissue from supplemented men was significantly higher than among controls (241 ng/g versus 196 ng/g). The researchers conclude that selenium supplementation is effective in raising selenium levels in both prostate tissue and red blood cells, but conclude that selenium values from blood testing do not correlate with values obtained from testing of prostate tissue.
Gianduzzo, TRJ, et al. Prostatic and peripheral blood selenium levels after oral supplementation. Journal of Urology, Vol. 170, September 2003, pp. 870-73

Prostate cancer: Risk factors and prevention
UMEAA, SWEDEN. Professor Henrik Gronberg, MD of Umeaa University in Sweden presents an excellent review of current prostate cancer research. It is estimated that over 500,000 new cases of prostate cancer was diagnosed worldwide in the year 2000. The incidence varies widely from less than 2 per 100,000 in China to 137 per 100,000 among African-Americans. It is clear that there is both a genetic and lifestyle factor involved in prostate cancer risk. Japanese men, for example, have a four times greater incidence of prostate cancer if they reside in the USA than if they reside in Japan.

Several studies have found a clear association between the western lifestyle and an increased risk of prostate cancer. A high intake of fat, meat and dairy products has been found to be particularly detrimental. Consuming fried or charcoal-grilled red meat has been clearly associated with increased risk. A high intake of alpha-linolenic acid and calcium from dairy products has both been associated with higher risk. A Swedish study found that men who consumed 600 mg/day of calcium from dairy products had a 32% greater risk than those consuming 150 mg/day or less.

Smoking, degree of physical activity, and alcohol consumption have not been associated with an increased risk and neither has vasectomy.

Soybean products (soy milk or tofu) have been found to have a preventive effect as has a high intake of tomato products, lycopene, selenium, and vitamin E. Supplementation with selenium reduced risk by 66% in one study while vitamin E supplementation lowered it by 40%. A large study involving 32,400 men is currently underway to confirm the benefits of vitamin-E and selenium supplementation. Results are expected by 2013.
Gronberg, Henrik. Prostate cancer epidemiology. The Lancet, Vol. 361, March 8, 2003, pp. 859-64

Prostate cancer and antioxidants
BALTIMORE, MARYLAND. There is growing evidence that certain micronutrients, more specifically antioxidants, may help prevent some forms of cancer. Selenium, for example, has been found highly effective in preventing prostate cancer. Researchers at the Johns Hopkins School of Public Health now report that gamma-tocopherol, the form of vitamin-E found in most foods, is also effective in preventing prostate cancer. Their study involved over 20,000 male residents of Washington County, Maryland who had donated blood in 1974 and 1989. A total of 324 men had developed prostate cancer by 1996. These men were each matched with two healthy controls in regard to age, race, and date of blood donation. Comparing the blood levels of micronutrients in cases and controls found no significant differences in concentrations of alpha-carotene, beta-carotene, total carotene, beta-cryptoxanthin, lutein, lycopene, retinol, and ascorbic acid (vitamin-C). There was, however, a difference in gamma-tocopherol levels between cases and controls with controls having significantly lower levels. For the men who donated blood in 1989 it was observed that men with the highest gamma-tocopherol levels had an almost 5 times lower incidence of prostate cancer than did those with the lowest levels. There was also some evidence that higher circulating levels of retinyl palmitate (formed from vitamin-A and stored in the liver) were protective against prostate cancer. The researchers conclude that gamma-tocopherol may help protect against prostate cancer, but note that lycopene did not appear to have any protective effect.
Huang, Han-Yao, et al. Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer. American Journal of Epidemiology, Vol. 157, February 15, 2003, pp. 335- 44

PC-SPES reborn?
LOS ANGELES, CALIFORNIA. A team of University of California (San Diego) researchers recently reported that PC-SPES, a much touted herbal remedy for prostate cancer, had been found to be heavily contaminated and had been taken off the market. Nevertheless, researchers at the UCLA Center for Human Nutrition in Los Angeles now report that they have found PC-SPES to be highly effective in preventing the initiation and progression of colon cancer. They evaluated PC-SPES in vitro using three different colon cancer cell lines. They found that the herbal compound caused a 95 per cent inhibition of cell proliferation in all three lines. In contrast, estradiol did not stop cell proliferation at all. Thus it is unlikely that the observed effect of PC-SPES is due to possible contamination with diethylstilbestrol, another estrogenic compound. The researchers also evaluated PC-SPES (250 mg/kg/day) in laboratory mice genetically engineered to develop multiple tumours in the gastrointestinal tract within a few weeks after birth. They found that mice treated 5 times a week for 10 weeks with PC-SPES developed 58 per cent less tumours than did control mice. They conclude that the components of PC-SPES, either independently or in combination, act to produce a drastic reduction in tumour initiation and progression in the gastrointestinal tract.
Huerta, Sergio, et al. PC-SPES inhibits colon cancer growth in vitro and in vivo. Cancer Research, Vol. 62, September 15, 2002, pp. 5204-09

Tomato sauce and prostate cancer
CHICAGO, ILLINOIS. Several studies have observed that tomatoes and tomato products, especially tomato sauce, have a protective effect against prostate cancer. Researchers at the University of Illinois now report that tomato sauce is also effective in slowing down and perhaps even reversing existing prostate cancer. Their study involved 32 patients with prostate cancer who were scheduled to undergo a radical prostatectomy. The participants underwent a baseline examination to determine their lycopene levels, their PSA (prostate specific antigen) level, and the level of oxidative damage to their DNA (in leukocytes). They were then fed a pasta dish with tomato sauce (3/4 of a cup of commercial spaghetti sauce) once a day for three weeks. The additional daily lycopene intake from the sauce was 30 mg.
At the end of the three-week period lycopene levels in the blood plasma had doubled and lycopene levels in prostate tissue had tripled. The average PSA level had declined from 10.9 ng/mL to 8.7 ng/mL - a drop of 17.5 per cent. The DNA damage indicator in leukocytes dropped by 21.4 per cent after the intervention. The DNA damage level in actual prostate tissue (removed during surgery) was found to be 28.3 per cent lower in the tomato sauce group than in a reference group of seven prostate cancer patients who had not consumed the tomato sauce diet. The researchers conclude that their study "suggests a role for tomato sauce and possibly for lycopene in the prevention and treatment of prostate cancer."
Chen, Longwen, et al. Oxidative DNA damage in prostate cancer patients consuming tomato sauce- based entrees as a whole-food intervention. Journal of the National Cancer Institute, Vol. 93, December 19, 2001, pp. 1872-79

Selenium prevents prostate cancer
STANFORD, CALIFORNIA. Several large studies have shown that men with low blood (plasma) levels of selenium have a significantly increased risk of prostate cancer. Now medical researchers at Stanford University and the Johns Hopkins University School of Medicine weigh in with another report that clearly shows the protective effect of selenium. Their study involved 52 men diagnosed with prostate cancer and 96 age-matched controls with no detectable prostate disease. The men had an average age of 69 years and were all enrolled in the Baltimore Longitudinal Study of Aging. Plasma levels of selenium measured in blood samples taken four to five years prior to the diagnosis of prostate cancer were compared for cancer patients and controls. The researchers found that men with selenium levels below 10.7 micrograms/dL had a four to five times higher incidence of prostate cancer than did men with levels above 10.7 micrograms/dL. They also noted a significant decline in selenium levels with age.

The researchers believe that much of the beneficial effect of selenium is due to its vital role in maintaining adequate levels of the body's main antioxidant, glutathione peroxidase. They conclude that selenium supplementation may reduce the risk of prostate cancer and that supplementation may be particularly important for older men. NOTE: The recommended daily intake of selenium is 55 micrograms with an upper safe limit of 400 micrograms/day. However, most supplementation studies have used 200 micrograms/day.
Brooks, James D., et al. Plasma selenium level before diagnosis and the risk of prostate cancer development. Journal of Urology, Vol. 166, December 2001, pp. 2034-38

Prostate cancer and lycopene
DETROIT, MICHIGAN. Epidemiological studies have shown that a high intake of tomatoes markedly reduces the risk of prostate cancer. It is believed that this beneficial effect is due to lycopene, the most common carotenoid in tomatoes. A team of researchers from Wayne State University, McGill University, University of Maryland, and the University of Hawaii has just concluded a clinical trial aimed at evaluating the benefits of lycopene supplementation in prostate cancer patients. The study included 26 men with clinically localized prostate cancer who were scheduled to undergo radical prostatectomy (removal of the prostate gland). The men were randomized into a control group and an intervention group. The intervention group received one 15-mg lycopene capsule with breakfast and dinner for three weeks prior to surgery. Blood samples were taken before the start of supplementation and three weeks later just before surgery. The removed tumors and surrounding tissue were examined by pathologists.

The researchers conclude that lycopene supplementation lowers PSA levels; they observed an average 18 per cent decrease in the lycopene group as compared to a 14 per cent increase in the control group. The level of the tumor suppressing protein Cx43 in the malignant part of the tumor was found to be substantially higher in the lycopene group. It was also apparent that tumors tended to be smaller and more sharply defined (less encroachment into surrounding healthy tissue) in the lycopene group. No adverse effects of the lycopene supplementation were reported by the patients or their physicians. The researchers conclude that lycopene is likely to be beneficial for both prevention and treatment of prostate cancer, but urge larger trials to confirm this.
Kucuk, Omer, et al. Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiology, Biomarkers & Prevention, Vol. 10, August 2001, pp. 861-68 [72 references]

Sun exposure prevents prostate cancer
STAFFORDSHIRE, UNITED KINGDOM. British researchers have confirmed that exposure to sunlight helps prevent prostate cancer. Their study involved 210 men diagnosed with prostate cancer and 155 men with an enlarged prostate, but no prostate cancer (controls). The men were interviewed in order to estimate their lifetime sun exposure. Men with the lowest exposure were found to have a three times greater incidence of prostate cancer than did men with a high lifetime exposure. Sunburns in childhood were found to be particularly protective with men having had one or more childhood sunburns being six times less likely to develop prostate cancer than men who had not experienced childhood sunburns.

A history of regular foreign holidays, presumably in sunnier climes, also had a protective effect with men having had such holidays having a 60 per cent lower risk of prostate cancer. Regular sun bathing was also found to be protective. The risk of prostate cancer was not associated with skin type, hair colour or eye colour, and the associations with sun exposure were not affected by including occupation, vasectomy or dietary factors in the analysis.
The researchers are not sure why sun exposure is protective, but speculate that vitamin D and parathyroid hormone may somehow be involved.

Editor's Note: Excessive sun exposure has been linked to an increased risk of certain non-melanoma skin cancers. These cancers, however, are rarely fatal whereas prostate cancer often is. So on balance, cultivating a healthy suntan is still a good idea.
Luscombe, Christopher J., et al. Exposure to ultraviolet radiation: association with susceptibility and age at presentation with prostate cancer. The Lancet, Vol. 358, August 25, 2001, pp. 641-42 (research letter)

Fish consumption helps prevent prostate cancer
STOCKHOLM, SWEDEN. Several studies have shown an inverse relationship between blood levels of fish oils (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and the risk of prostate cancer. A study just completed by medical researchers at the Karolinska Institute confirms this association.

he Swedish study involved 3136 pairs of male twins born between 1886 and 1925. The participants completed food frequency questionnaires in 1961 and 1967 and were then followed up for 30 years. By December 31, 1997 the researchers had recorded 466 diagnoses of prostate cancer (340 fatal ones). The average age of diagnosis was 76.7 years. After adjusting for other known risk factors the researchers conclude that men who never eat fish have a two- to three-fold higher risk of prostate cancer than do men who eat moderate to high amounts. The researchers emphasize that only fatty fish such as salmon, herring and mackerel, which contain high amounts of omega-3 fatty acids (EPA and DHA), would be expected to be beneficial.
Terry, Paul, et al. Fatty fish consumption and risk of prostate cancer. The Lancet, Vol. 357, June 2, 2001, pp. 1764-66 (research letter)

Lycopene and cancer
TORONTO, CANADA. Lycopene is a carotenoid found in tomatoes, tomato products, and in other fruits. It is a powerful antioxidant with a singlet-oxygen quenching capacity 10 times greater than that of vitamin E. It is the most abundant carotenoid in human plasma and is highly concentrated in the adrenal glands, testes, prostate, and breast tissue. Several studies have found an inverse correlation between serum and tissue levels of lycopene and the risk of breast and prostate cancers. Other studies have linked a high intake of tomatoes to a 50 per cent reduction in cancer mortality among elderly Americans. One study found that men who consumed 10 or more servings of tomato products per week reduced their risk of prostate cancer by 35 per cent. A more recent study found that supplementation with a tomato extract significantly lowered the level of prostate-specific antigen (PSA) in patients with prostate cancer. High tissue (adipose) levels of lycopene have also been found to be protective against heart attacks. No published studies have shown any adverse effects of high lycopene levels or a high intake of tomato products. It has been hypothesized that lycopene prevents cancer and heart disease by protecting lipids, lipoproteins (especially low-density lipoprotein), proteins, and DNA. There is also evidence that lycopene counteracts the proliferation of cancer cells induced by insulin-like growth factors.
Agarwal, Sanjiv and Rao, AV. Tomato lycopene and its role in human health and chronic diseases. Canadian Medical Association Journal, Vol. 163, September 19, 2000, pp. 739-44 [70 references]

Eat your broccoli and avoid prostate cancer
SEATTLE, WASHINGTON. There is abundant evidence that a high intake of fruits and vegetables is protective against many types of cancer. Researchers at the Fred Hutchinson Cancer Research Center now report that the intake of vegetables, but not fruits, is significantly associated with prostate cancer risk. Their study involved 628 men from the Seattle area between the ages of 40 and 64 years who had been diagnosed with prostate cancer between January 1 and December 31, 1996. An age-matched sample of 602 men without prostate cancer served as the control group. All participants were interviewed and completed a 99-item food frequency questionnaire which included 12 fruit items and 21 vegetable items. The participants were asked to estimate their intake of the foods (ranging from "never or less than once per month" to "2+ per day") over the 3-5 years preceding the date of diagnosis or date of interview (for controls).

The intake of fruit did not significantly affect prostate cancer risk. However, men who consumed 28 or more servings of vegetables per week were found to have a 35 per cent lower risk than men who consumed fewer than 14 servings per week. When limiting the analysis to cruciferous vegetables only the protective effect was found to be even more pronounced. Men who ate three or more servings of cruciferous vegetables (broccoli, cauliflower, brussel sprouts, cabbage) per week had a 41 per cent lower risk of developing prostate cancer than did men who ate less than one serving a week. A high intake of lutein plus zeaxanthin (2000 micrograms/day or more) was associated with a 32 per cent decrease in risk, but this association was not statistically significant. The researchers found no correlation between the intake of tomato products or lycopene and prostate cancer risk.
Cohen, Jennifer, et al. Fruit and vegetable intakes and prostate cancer risk. Journal of the National Cancer Institute, Vol. 92, January 5, 2000, pp. 61- 68

My favourite Supplements

Beta-carotene and cancer
BOSTON, MASSACHUSETTS. Numerous epidemiological studies have concluded that high intakes of fruits and vegetables are associated with lower risks of cancer. It was originally thought that beta- carotene was the protective component, but six large-scale clinical trials have failed to confirm any cancer-protective effects. Two of the trials involving heavy smokers showed a significant 18 per cent increase in lung cancer among the smokers who took beta-carotene. One very large trial involving 22,071 American physicians showed no benefits and no harm from 12 years of supplementation with 50 mg of synthetic beta-carotene every second day.

Researchers at the Harvard Medical School have just released the results of a major study aimed at evaluating the effects of beta-carotene supplementation among women. The study involved almost 40,000 healthy female health professionals (aged 45 years or older). The women were randomized into two groups with one group receiving 50 mg of synthetic beta-carotene on alternate days and the other group receiving a placebo. The 2.1-year supplementation phase of the study was followed by a two-year observation period. At the end of the four years 747 cases of cancer and 218 cases of cardiovascular incidents (heart attack, stroke, and death) had occurred among the women. There were no significant differences in the incidence of cancer, cardiovascular events or death from all causes in the two groups. This also held true when just the smokers among the women were considered.
The researchers conclude that beta-carotene supplementation is neither harmful nor beneficial to people at average risk for cancer except in the case of prostate cancer. The Physicians' Health Study found that men who supplemented with 50 mg of beta-carotene every second day for 12 years had a significantly lower incidence of prostate cancer.
Lee, I. Min, et al. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. Journal of the National Cancer Institute, Vol. 91, December 15, 1999, pp. 2102-06

Fish oils help prevent prostate cancer
AUCKLAND, NEW ZEALAND. Medical researchers in New Zealand provide convincing evidence that an increased consumption of fish oils helps reduce the risk of developing prostate cancer. Their study involved 317 men who had been diagnosed with prostate cancer during 1996-97 and 480 age-matched controls. Blood samples were obtained from all participants and the erythrocyte (red blood cell) phosphatidylcholine fraction of the plasma was analyzed for EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), the two main components of fish oils.

Evaluation of the collected data showed a clear correlation between blood level of EPA and DHA and the presence of prostate cancer. Study participants with levels in the highest quartile were found to have a 40 per cent lower incidence than participants with levels in the lowest quartile. This relationship held true even when adjusted for age, height, use of NSAIDs (non- steroidal anti-inflammatory drugs), socio-economic status, and estimated intake of lycopene and polyunsaturated fats.

The researchers also found that men with low socio-economic status, a low intake of lycopene, and non-regular use of NSAIDs were more likely to develop prostate cancer. They did not, however, find any correlation between self- reported intake of EPA and DHA indicating that food frequency questionnaires are not an accurate method for estimating fish oil intake. The researchers speculate that fish oils may prevent the progression of prostate cancer by inhibiting the biosynthesis of eicosanoids from arachidonic acid.
Norrish, A.E., et al. Prostate cancer risk and consumption of fish oils: a dietary biomarker-based case-control study. British Journal of Cancer, Vol. 81, No. 7, December 1999, pp. 1238-42

Diet is vital in cancer prevention
SACRAMENTO, CALIFORNIA. It is estimated that 35% of all cancers are directly associated with the typical American diet; another 30% is directly related to smoking. A high fat intake is associated with cancer of the colon, breast, prostate, rectum, and endometrium. These cancers are also associated with obesity as are cancers of the kidney, cervix, and thyroid. Alcohol consumption is implicated in cancers of the breast, rectum, mouth, and esophagus. The consumption of charred, smoked, salted, and pickled foods is associated with cancer of the stomach and esophagus. On the other hand, an increased fiber intake has been found to protect against colon cancer - presumably because it speeds up elimination of waste through the bowels. An increased consumption of fruit and vegetables has been found to have a protective effect against lung, colon, breast, prostate, bladder, mouth, cervix, and stomach cancer. The Amercian Cancer Society has recommended that efforts be made to change the typical American diet so that it contains no more than 30% fat (% of total calories) - in 1985 the average diet contained 36%. It also recommends 5 or more servings of fruit and vegetables per day (1986 average was 2.5) and 6 or more servings a day of breads, cereals, and legumes (1986 average was 3). The Society would like to see these dietary changes implemented by the year 2000 and estimates that 166,000 cancer deaths and 315,000 new cases of cancer could be avoided every year if they were.
Bal, Dileep G. and Foerster, Susan B. Dietary strategies for cancer prevention. Cancer (Supplement), Vol. 72, No. 3, August 1, 1993, pp. 1005- 10
Byers, Tim. Dietary trends in the United States. Cancer (Supplement), Vol. 72, No. 3, August 1, 1993, pp. 1015-18

Tomato sauce protects against prostate cancer
BOSTON, MASSACHUSETTS. It is estimated that by the year 2000 about 40,000 men will die of prostate cancer every year in the United States alone. So far, no effective prevention has been found and treatment is of dubious value and has serious side effects. Now researchers at the Harvard Medical School report that consumption of tomato sauce and tomatoes provides significant protection against the development of prostate cancer. Their study involved over 47,000 male health professionals 812 of which developed prostate cancer in the period between 1986 and 1992. All participants in the study completed validated food-frequency questionnaires in 1986, 1988, 1990 and 1992. Analysis of the collected data clearly showed that men with a high consumption of tomato sauce, tomatoes, and pizza have a significantly lower risk of developing prostate cancer. The protective effect of tomato sauce (ripe tomatoes cooked in oil) was particularly noteworthy; men who consumed tomato sauce two to four times per week had a 35 per cent lower risk of developing prostate cancer than did men who never ate tomato sauce. The researchers believe that it is the high content of lycopene which gives tomato products their protective effect. They also speculate that oil or fat is necessary for proper absorption of the lycopene from the tomatoes. Tomato juice on its own has no protective effect and its lycopene is poorly absorbed. However, if tomato juice is cooked in oil and then ingested the blood level of lycopene rises very significantly within 24 hours. The researchers believe that lycopene protects against prostate cancer because it is a very powerful antioxidant, more than twice as effective as beta-carotene, and because it is the most abundant carotenoid in the prostate gland. No protective effect was found for vitamin A, beta- carotene, alpha-carotene, lutein or beta-cryptoxanthin. The researchers also found that a high intake of fruit and vegetables other than tomatoes had no significant protective effect.
Giovannucci, Edward, et al. Intake of carotenoids and retinol in relation to risk of prostate cancer. Journal of the National Cancer Institute, Vol. 87, No. 23, December 6, 1995, pp. 1767-76

Physical activity protects against prostate cancer
BOSTON, MASSACHUSETTS. Researchers at the Harvard School of Public Health and the Cooper Institute for Aerobics Research report that physically active men are much less likely to develop prostate cancer than are less active men. Their study involved almost 13,000 men aged 20 to 80 years who had a medical examination at the Cooper Clinic between 1970 and 1989. The men were questioned as to their participation in sports and other physical activities and underwent a maximal exercise treadmill test to determine their cardiorespiratory fitness. The researchers conclude that men with the highest cardiorespiratory fitness level (>21 minutes) are four times less likely to develop prostate cancer than are men with a low cardiorespiratory fitness level (<13.7 minutes). The protective effect was only found in men below 60 years of age. The researchers also found that men who are physically active (energy expenditure >1000 kcal/week) have about a three times smaller risk of developing prostate cancer than do men who are less active (energy expenditure <1000 kcal/week). The researchers believe that high testosterone levels are involved in the development of prostate cancer and that physical activity and cardiorespiratory fitness tend to lower these levels.
Oliveria, Susan A., et al. The association between cardiorespiratory fitness and prostate cancer. Medicine and Science in Sports and Exercise, Vol. 28, No. 1, January 1996, pp. 97-104

Vitamin A may prevent prostate cancer
HOUSTON, TEXAS. Vitamin A (retinol) and its biologically active metabolite, retinoic acid, are known to be useful in the prevention and treatment of certain cancers such as acute promyelocyte leukemia. Now researchers at the Baylor College of Medicine report that vitamin A may also play a role in the prevention and treatment of prostate cancer. The researchers analyzed prostate tissue from patients with stage 3+ prostate cancer, tissue from patients with benign prostate hyperplasia (enlarged prostate), and normal tissue. They made several interesting observations:

  • All tissues tested contained retinol and retinoic acid in various concentrations. The retinol concentration in tissue from enlarged prostates was 2.5 times higher than in normal tissue or tissue from cancer patients. Tissue from cancer patients contained near normal levels of retinol, but only barely detectable levels of retinoic acid.
  • The prostate contains enzymes which enables it to convert retinol supplied in the diet to the biologically active retinoic acid.
The researchers speculate that enlarged prostate tissue contains more retinol than normal and cancerous tissue either because it is less efficient in converting it to retinoic acid or because enlarged prostate tissue is more efficient in absorbing retinol from the blood. They also suggest that the low level of retinoic acid in cancer patients could be due to a more rapid degradation of retinoic acid in cancer tissue. The researchers conclude that retinol (vitamin A) and carotenoids may be useful both in the prevention and treatment of prostate cancer.
Pasquali, Daniela, et al. Abnormal level of retinoic acid in prostate cancer tissues. Journal of Clinical Endocrinology and Metabolism, Vol. 81, No. 6, June 1996, pp. 2186-91

My favourite Supplements

Selenium protects against cancer
TUCSON, ARIZONA. Several studies have shown that the incidence and mortality from many cancers are higher in geographical areas where the selenium content of forage crops is low. Now an impressive group of researchers from more than half a dozen universities in the United States report that selenium supplementation helps prevent cancer. The Nutritional Prevention of Cancer Study Group found that cancer mortality was cut in half in a group of patients who supplemented with selenium. The double-blind, randomized, placebo- controlled cancer prevention trial involved 1312 patients aged 18 to 80 years (75 per cent males) who had previously been diagnosed with basal or squamous cell carcinomas of the skin. The purpose of the trial, started in 1983, was to test the hypothesis that selenium supplementation helps prevent skin cancer. Half the patients were randomized to receive 200 micrograms/day of selenium supplied as a 0.5 gram high-selenium brewer's yeast tablet (Nutrition 21, LaJolla, CA); the other half received a placebo. Patients were treated for a mean of 4.5 years and had a mean total follow-up period of 6.4 years. At the end of the study the researchers concluded that selenium supplementation does not prevent skin cancer. They did, however, find strong evidence that selenium supplementation is very effective in preventing other types of cancer. The overall mortality rate from cancer in the supplemented group was found to be only half of that in the placebo group. The reduction in mortality and incidence was particularly impressive in the case of cancers of the lung, prostate, colon, and rectum. The incidence and mortality rate from lung cancer was twice as high in the placebo group as in the selenium group. Supplement users developed only one third the number of prostate cancers as did the members of the placebo group and the incidence of colon and rectal cancer was similarly reduced in the supplement group. Unfortunately, there was not enough data to statistically evaluate the effect of selenium supplementation on the incidence of breast and ovarian cancers. The researchers were so impressed with the results of the trial that they decided to stop it early so that all patients could benefit from selenium supplementation. They believe selenium combats cancer by inhibiting the late stage promotion and progression of tumors. No toxic effects of selenium supplementation were observed.
Clark, Larry C., et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. Journal of the American Medical Association, Vol. 276, No. 24, December 25, 1996, pp. 1957-63
Colditz, Graham A. Selenium and cancer prevention - promising results indicate further trials required. Journal of the American Medical Association, Vol. 276, No. 24, December 25, 1996, pp. 1984-85 (editorial)

Beans and garden peas may reduce risk for prostate cancer
Leeds, England. Preliminary evidence has shown that eating baked beans and garden peas may reduce the risk for developing prostate cancer. A recent study interviewed 328 English-speaking men previously diagnosed with prostate cancer before the age of 75 years and 328 age-matched population controls. The purpose of the study was to investigate the association between diet and prostate cancer. Interviews included questions on basic demographic details, smoking, family history and food intake during the last five years. Main dietary concerns were fat intake (saturated, monounsaturated, or polyunsaturated fatty acids) and the intake of carotenes (beta-carotene and lycopene). Participants were also asked if they had taken vitamins or other supplements. The researchers found no statistically significant differences in the intake of fats or carotenes between the prostate cancer patients and controls. They do point out however, that total fat intake (in per cent of total energy intake) of both patients and controls was quite high (34-43 per cent) and that they can draw no conclusion as to what effect a low fat intake would have on the risk of developing prostate cancer.

Among foods and other nutrients examined, significant associations were observed for garlic (food only or food plus supplements), baked beans, vitamin B6 and garden peas. The association with garlic and vitamin B6 was later found to be statistically insignificant when adjusted for social class. Another recent study in England found that men who ate beans and peas more than once a week had a 37 per cent reduction in risk compared to men who ate these foods less often. The confirmed risks for prostate cancer include age, a family history of prostate cancer, social class and ethnic group/country of residence. A history of prostate cancer in fathers and brothers was associated with a two- to three-fold increased risk for the disease and manual workers were found to have a 63 per cent higher risk of prostate cancer than did non-manual workers. No correlation was found between risk and alcohol intake or smoking. Contrary to other recent studies, the researchers found no effect of increased lycopene intake. However, they point out that their estimate of lycopene intake was very crude and did not account for the wide differences in bioavailability of lycopene from different sources. The researchers also noted that the use of vitamin E supplements was considerably higher among controls, but no significant correlation with cancer rate was observed. The researchers conclude that there is, as yet, no clear correlation between diet and prostate cancer risk but that the effect of a high intake of vitamin B6 (pyridoxine), garlic, peas and beans warrants further investigation.
Key, T.J.A., et al. A case-control study of diet and prostate cancer. British Journal of Cancer, Vol. 76, No. 5, September 1997, pp. 678-87

Finasteride does not prevent prostate cancer
LOS ANGELES, CALIFORNIA. Finasteride (Proscar) is often prescribed for benign prostatic hyperplasia (enlarged prostate gland) and is effective in shrinking the gland and reducing the level of dihydrotestosterone (DHT) which is believed to be involved in the enlargement. It has recently been postulated that finasteride may prevent prostate cancer and a large trial is currently being conducted by the US National Cancer Institute to test this hypothesis. Now researchers at the University of Southern California present a study which shows that finasteride does not reduce the risk of prostate cancer in high risk men, but may in fact increase it. The study involved 52 men with PSA (prostate-specific antigen) levels over 4.0 nanogram/ml and negative biopsies for prostate cancer. The men were randomized to receive either 5 mg/day of finasteride (27 patients) or no medication (25 patients) for a 12-month period. At the end of the trial period prostate biopsies were again performed. Eight patients (30 per cent) of the men in the finasteride group were found to have developed prostate cancer (adenocarcinoma) as compared to one patient (4 per cent) in the control group. The researchers conclude that their study "raises serious questions about the probable efficacy of finasteride in preventing prostate cancer."
Cote, R.J., et al. The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels. British Journal of Cancer, Vol. 78, No. 3, August 1998, pp. 413-18

Selenium intake and prostate cancer
BOSTON, MASSACHUSETTS. The connection between a low selenium content in the soil and regional cancer mortality rates has been known for almost 30 years. Later research has confirmed an association between low blood levels of selenium and the prevalence of colon, lung, and stomach cancers. More recently, a team of American researchers reported that men who supplemented with 200 micrograms of selenium daily had a three times lower risk of developing prostate cancer than did men in the placebo group. All the participants in this study lived in areas of the USA where the soil is selenium-deficient and the normal dietary intake is estimated to be about 90 micrograms/day. Another recent study investigated the association between advanced prostate cancer and toenail concentrations of selenium (an indicator of long term selenium intake). This study found that men with the highest toenail selenium concentrations had a three times lower risk of advanced prostate cancer than did men with the lowest concentrations. The researchers estimate that the daily median selenium intake among men with the lowest toenail concentrations was about 86 micrograms as compared to about 159 micrograms for men with the highest toenail concentrations. Dr. Edward Giovannucci, MD of the Harvard Medical School points out that selenium intakes in the UK have been falling over several decades and now may be as low as 30- 40 micrograms/day. During the same period the incidence and mortality from prostate cancer have increased substantially in England and Wales. Dr. Giovannucci suggests that there may be a connection, but this has not as yet been proven. He concludes that "the evidence (of the benefits of selenium supplementation) available for prostate cancer seems to justify the further assessment of increasing the selenium intake in the population as a priority for public health."
Giovannucci, Edward. Selenium and risk of prostate cancer. The Lancet, Vol. 352, September 5, 1998, pp. 755-56 (commentary)

Lycopene and prostate cancer
BOSTON, MASSACHUSETTS. Several studies have shown that a high dietary intake of tomatoes and tomato-based products especially tomato sauce is associated with a lower risk of prostate cancer. It is assumed that the carotenoid lycopene is the component which is primarily responsible for the protective effect. Now researchers at the Harvard Medical School confirm the validity of this assumption. Their study involved over 22,000 male American physicians aged 40 to 84 years at the start of the study in 1982. The original purpose of the study was to investigate the effects of beta-carotene supplementation (50 mg every other day). However, the availability of stored blood samples made it possible to investigate the effects of other carotenoids as well. By 1995 578 men had developed prostate cancer. These were matched with 1294 cancer-free men according to age and smoking status. Analysis of the blood levels of carotenoids and vitamin E showed that men with the highest lycopene levels and no beta-carotene supplementation had a 41 per cent lower risk of prostate cancer than did men with the lowest levels. No risk reduction associated with lycopene levels was observed in physicians who received beta- carotene supplementation. However, beta-carotene in itself also appeared to be protective with men assigned to supplementation having a 37.3 per cent lower risk than men with low lycopene levels assigned to placebos. Men with high vitamin E (alpha-tocopherol) levels were found to have a lower incidence of aggressive prostate cancer. The researchers conclude that increased consumption of tomato products might reduce prostate cancer risk.
Gann, Peter H., et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Research, Vol. 59, March 15, 1999, pp. 1225-30

DHEA protects against prostate cancer
We do not usually report information based on animal experiments; however, the finding that DHEA can prevent or even reverse prostate cancer in laboratory rats seemed important enough to make an exception.

CHICAGO, ILLINOIS Prostate cancer is the second most common cause of cancer death in Western male populations. It is estimated that about 18 per cent of American men will develop prostate cancer during their lifetime. Some researchers believe that many more have the beginnings of prostate cancer, but die from other causes before the cancer becomes invasive and fatal. Research has shown that the hormone DHEA (dehydroepiandrosterone) inhibits the growth of both human and rat prostate cancer cells in vitro (in test tubes). Now a team of researchers from the National Cancer Institute, the New York University School of Medicine, and the ITT Research Institute reports that DHEA confers significant protection against prostate cancer progression when given to laboratory rats as part of their diet. Their experiment involved rats which were given carcinogenic chemicals to induce precancerous lesions in the prostate. One group of rats had 1000 or 2000 mg of DHEA added to each kilogram of feed starting one week before inducing the cancer. Other groups had 2000 mg of DHEA added per kilogram of diet one week before induction, 20 weeks after induction or 40 weeks after induction. The rats received the DHEA until the experiment was concluded 13 months after cancer induction. Control rats received no DHEA. The researchers found a very significant decrease in the progression to full prostate cancer among the rats given DHEA in their diets. This effect was evident whether the DHEA was given one week before or 20 or 40 weeks after cancer induction. They conclude that DHEA or a suitable derivative may be effective in preventing the development and progression of prostate cancer in humans, but caution that more work is required to ensure the DHEA's hormonal effects (conversion to testosterone and estrogenic activity) are not detrimental.
Rao, K.V.N., et al. Chemoprevention of rat prostate carcinogenesis by early and delayed administration of dehydroepiandrosterone. Cancer Research, Vol. 59, No. 13, July 1, 1999, pp. 3084-89

Testosterone supplementation and prostate cancer
KIRKLAND, WASHINGTON. Conventional medicine wisdom has it that high levels of male sex hormones (androgens) are associated with an increased risk of prostate cancer and a more rapid tumour growth. This has led to the use of chemical or physical castration in an attempt to reduce natural androgen production and thereby deprive the tumour of the androgen it supposedly requires to keep growing. Unfortunately, the effect of castration is often temporary and subsequent tumours tend to be more virulent than the original one.

Now Dr. Richmond Prehn, MD of the University of Washington challenges the assumption that high androgen levels are a risk factor for prostate cancer. Dr. Prehn points out that androgen levels decline with age whereas prostate cancer incidence rises sharply. He suggests that declining androgen levels may not only lead to benign prostate hyperplasia (BPH), but may also be the initiator of uncontrolled cell growth which may ultimately lead to cancer. He further suggests that "androgen supplementation beginning early in the middle years might, among other possible benefits, largely prevent prostate cancer." Dr. Prehn cautions that androgen supplementation may be contra-indicated in older men who already have the seeds of prostate cancer. He also suggests that an alternating regimen of androgen deprivation and androgen supplementation should be evaluated as a therapy for prostate cancer.
Prehn, Richmond T. On the prevention and therapy of prostate cancer by androgen administration. Cancer Research, Vol. 59, September 1, 1999, pp. 4161-64

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