Complementary Medicine for Prostate Cancer: Effects of Soy and Fat Consumption

Abstract

Complementary medicine has become an increasing area of interest for patients and researchers around the world. The utilization of some of these therapies by many individuals makes it imperative to understand if they have a role in cancer or other disease treatment. Soy products have generated a large interest because a variety of laboratory and epidemiologic research suggests these items may play a role in the prevention of prostate cancer. Clinical trials are addressing this issue and whether or not these products could also improve prognosis of prostate cancer. Additionally, other soy-based capsules (ipriflavone) have received some research, but the largest clinical study to date does not support the use of these supplements to reduce hot flashes and/or osteoporosis risk. Dietary fat reduction to prevent prostate cancer is supported by numerous case-control studies over the past 25 years. However, recent prospective studies suggest that fat reduction may not play a strong role in prevention of prostate carcinoma. Soy products and fat reduction may have a symbiotic relationship. Any healthy lifestyle or dietary change should be encouraged, because it may reduce the risk of cardiovascular disease, which is still the number one cause of mortality.

A large-scale survey examining trends in the use of alternative medicine in the United States from 1990 to 1997 reported that the use of alternative medicine had increased from 34% to 42% in that time.¹ More visits to alternative health practitioners are reported today than total visits to all primary care physicians. Managed care organizations and insurance companies have started to increase coverage of some specific alternative therapies, such as acupuncture and massage therapy.² Most U.S. medical schools have also begun to offer courses in this discipline.³ Other countries around the world have also reported a large increase in the use of alternative treatments. For example, separate studies suggest that one third of the Finnish and approximately 50% of the Australian population have used some type of alternative medicine.^4,5

One of the fastest growing areas of alternative or “complementary” medicine is the use of dietary changes and dietary supplements or herbal therapies. Herbal treatment sales exceeded $2.5 billion in 1996 and have been projected to increase by 25% every year.⁶ One of the largest surveys conducted on the attitudes of individuals using supplements found that most people do not discuss their usage with their physician, because they do not believe physicians know much about them and that they may be biased against their use.⁷ In addition, individuals were unexpectedly supportive of some type of regulation. Supplement use during clinical trials may also be an area of concern. A recent report found that many of the participants from a colon cancer trial were using supplements.⁸ The authors believe that such large-scale use may result in investigators having to monitor supplement use more closely or increase participant numbers, because utilization could change the results of various cancer clinical trials.

Numerous complementary therapies could be discussed in this manuscript; however, few have gained more attention than fat consumption or soy and soy supplements.⁹ The reason for such attention to these two interventions has to do with the large geographical variation in the ageadjusted incidence of prostate cancer.¹⁰ Autopsy series demonstrate that the incidence of latent prostate cancer is approximately equal in men from Asia and the United States.¹¹ Nevertheless, African American men have the highest incidence of prostate cancer, which is roughly 30 times greater than Japanese men, and about 120 times greater than that observed in men from Shanghai, China.¹⁰ Japanese immigrants in the U.S. experience increases in incidence to about half that of the indigenous population within one or two generations.¹² This rather fast epidemiological change and international comparisons in diet demonstrate that dietary differences, such as fat and soy consumption, may be partially responsible for the phenomena.

Soy

International epidemiologic studies over the past several decades support the theory that a Western diet is a primary reason for the greater incidence of chronic diseases found in the U.S. and other regions of the world.^13–15 Specific aspects of the diet in Asian countries, which are not found in the Western diet and which may be important in disease prevention, are a high consumption of plant estrogens (or “isoflavones”), especially from soy products, and a low consumption of fat. For example, the average intake of soy protein in Americans is about 1 to 3 mg/day, whereas that in Asian countries is more than 50 mg/day.^16,17 Approximately 90% of Asian children consume soy products on a regular basis, and most began consuming them by the age of 18 months.¹⁸

Isoflavonoids, such as the isoflavones genistin and daidzin and their aglycones, genistein and daidzein, are found mostly in soybeans and soy products and are converted into these latter products by gut bacteria.¹⁹ It is believed that this conversion or hydrolysis is a prerequisite for their absorption from the intestinal tract. Genistein can be converted to p-ethyl phenol, and daidzein can be converted into the isoflavonoid metabolites equol and O-desmethylangolensin (O-DMA).^20,21 These bacterial metabolites can be detected in the blood and urine. Isoflavones are classified as phytoestrogens, because they contain some estrogenic activities, and their structure is similar to that of the steroid estrogens.²² These phytoestrogens are believed to have hypocholesterolemic, antiproliferative, anticarcinogenic, antiosteoporotic, and beneficial hormone- altering characteristics.^23–25

Soy and Prostate Cancer

Androgens have been shown to impact prostate cancer initiation and promotion.²⁶ Castrated men have a lower incidence of prostate cancer.^27–29 Conversion of testosterone into dihydrotestosterone (DHT) by 5-alphareductase may be a partial factor in the development of prostate disease.³⁰ Young adult Japanese men have reduced levels of 5-alpha-reductase activity.³¹ Androgen blockade treatment may prevent the progression of advanced hormone-sensitive prostate cancers.³² Young adult U.S. African American males may have higher levels of serum testosterone³³; diabetic men with lower levels of this male hormone may have a lower risk of prostate cancer.³⁴ Other hormones, specifically prolactin and estrogen, could also have a role in prostate cancer development.³⁵ Men with liver cirrhosis and lower prostate cancer incidence have been also been found to have hyperestrogenism and lower levels of male hormone.^36,37

Prostate cancer mortality differences among Asian men versus American men may be partially due to the greater consumption of soy products in these countries.³⁸ Asian men have higher serum and urinary excretion levels of phytoestrogens compared to American males.³⁹ In addition, prostate size in Japanese men does not increase as dramatically with age as compared to men from Western countries.⁴⁰ Soy has been found to protect estrogenized animal models from prostatic dysplasia.⁴¹ The growth of benign prostatic hyperplasia (BPH) and prostate cancer tissue from recently removed surgical specimens and tested in vitro has been inhibited by genistein.⁴² Biochanin A, a genistein precursor, and genistein itself have inhibited the growth of hormone-sensitive and hormone-insensitive cancer cell lines,^43,44 and both have decreased prostate-specific antigen (PSA) levels of LNCaP cells in vitro.⁴⁵ More specifically, prostate cancer growth may be inhibited by genistein through a variety of mechanisms, such as interfering with tyrosine kinase growth factor and other similar growth factors and receptors^46–49; affecting topoisomerase II⁵⁰; inhibiting angiogenesis⁵¹; and encouraging apoptosis via a cell adhesion mechanism.⁵²

A clinical case report of a 66-year-old man who consumed 160 mg of red clover phytoestrogens daily for the week prior to his radical prostatectomy partially supports the notion that phytoestrogens may induce apoptosis through a hormone suppression mechanism.⁵³ The patient’s surgical specimen showed mild patchy microvacuolations and extensive apoptosis, but no pathologic changes were found in normal prostate cells. The author of the manuscript noted that this was similar to changes observed with prescribed estrogen treatment or androgen deprivation.⁵⁴ Soy and red clover have been found in vitro to be two of the six highest estradiol-binding herbs out of 150 tested with a human breast cancer cell line.⁵⁵ The estrogenic characteristics of these and other phytoestrogens could provide further understanding into the general pathways they interact with in humans.²³ For example, inhibition of luteinizing hormone (LH) secretion has been observed in women consuming phytoestrogens.⁵⁶ However, significant decreases in testosterone have not been observed in Japanese men consuming these products.^33,57 Perhaps slight changes in a variety of hormones over several decades may be sufficient to delay the onset of clinically significant prostate cancer. Phytoestrogens have been shown to inhibit 5-alpha-reductase, which may be a partial explanation for lower activity levels of this key enzyme in Japanese men and subsequently a lower incidence of prostate carcinoma.³³

Clinical trials using soy, its various isolated compounds, such as genistein, and at a variety of dosages are required to determine if the in vitro and epidemiologic data are tantamount to an actual clinical benefit. Clinical trials using soy or soy products are currently being conducted at numerous institutions.^58,59 Additionally, clinical research should not be limited to soy only, given the potential benefit of numerous other phytoestrogens in nature. For example, lignans, another phytoestrogen found in high concentration in flaxseed, has demonstrated potent anticancer characteristics in vitro, in vivo, and possibly in a number of epidemiologic studies.⁶⁰ A recent pilot study of men consuming flaxseed and a lowfat diet before radical prostatectomy showed that flaxseed may have provided a clinical benefit via hormone suppression for men with lower Gleason scores (6 or less) before conventional treatment.⁶¹

Soy and Cardiovascular Disease

Research suggests a potential benefit for soy product intake and a lower incidence of early heart disease. International comparison studies have found lower rates of this disease in Asian countries along with a higher consumption of soy products compared to Western countries.⁶² Although this relationship is most likely confounded by other dietary differences, such as a lower overall intake of saturated fat, laboratory studies support the cardiovascular effects of soy.^63,64 Rabbits consuming soy protein have increased low-density lipoprotein (LDL) removal from the circulation. Soy protein may also increase the activity of hydroxymethylglutaryl-coenzyme A reductase and cholesterol 7-alpha-hydroxylase, which further eliminates cholesterol in bile acids.⁶⁵ Soy may possess additional benefits beyond its phytoestrogen content, such as its amino acid, vitamin E, and fiber content.⁶⁶ Clinical studies support the role of soy products in cardiovascular diseas protection. A meta-analysis of clinical studies suggests that three servings/day of soy protein (approximately 25 g) or greater may be sufficient to significantly decrease cholesterol levels in men and women.⁶⁷ The majority of this benefit has been attributed to the phytoestrogen content of soy. Severa other studies have not supported this finding. For example, no significant changes in cholesterol occurred with 20 men given 60 g of soy protein/day for 28 days.⁶⁸ A similar lack of effect was observed for postmenopausal women given soy flour for 12 weeks.⁶⁹

More controlled studies are needed to further understand the potential cardiovascular benefits of soy products. The potential ability of phytoestrogen treatment to lower lipoprotein(a) levels should be an area of future research. This independent risk factor for coronary heart disease has been amenable to prescribed estrogen,⁷⁰ but not with a variety of non-soy dietary or lifestyle changes.^71,72 Some animal studies suggest that plant estrogens could have some effect on lipoprotein(a),⁷³ but other more direct investigations are needed to support or refute this theory.

Soy Supplements and Hot Flashes

A variety of natural health books and other publications seem to espouse the use of soy pills for hot flashes. These claims are based on the isoflavone or plant estrogen content of soy products and the observation that Asian women who regularly consume these products report a lower rate of hot flashes compared to similar women in other countries who do not routinely use these products.⁷⁴ Another potential reason soy supplements may have gained some attention is the search for an alternative product with a low incidence of side effects that could be safe for survivors of breast cancer.

A well-designed, randomized, placebo-controlled trial was recently completed using a higher-concentration isoflavone soy pill for women treated for breast cancer who also experience a high number and severity of hot flashes.⁷⁵ Women were randomized and after a 1-week baseline period of no therapy were given either placebo or soy pills for 4 weeks. Patients self-documented daily hot flash frequency, intensity, and side effects using a daily questionnaire. A total of 177 women were initially randomized and 149 women provided adequate and complete data at the end of 9 weeks. The results of this trial were enlightening but disappointing. The soy pill was not found to be any more effective than placebo at reducing hot flashes. In fact, more patients at the conclusion of the trial actually preferred the placebo to the soy supplement. Again, although disappointing, this trial provided valuable data about the potential value of these supplements for a variety of conditions, data which could only be gleaned from a well-designed, randomized study.

Critics of this study may call into question the dosage of isoflavones used.⁷⁵ The soy supplement was a 150 mg/day isoflavone supplement, which is actually at the upper end of isoflavone levels reported in population studies to apparently reduce hot flashes in Asian women.⁷⁶ One could also contend that women in this trial were experiencing severe hot flashes because some were taking breast cancer medications, and that would make it difficult to ameliorate these symptoms with any treatment. However, studies have shown that some prescription medications are able to reduce hot flashes in women being treated for breast cancer, and other cancer patients, by as much as 80%,^77,78 so it is also difficult to argue this point, but safety with any agent should always be considered.

The trial’s duration may also be questioned, but at this isoflavone dosage peak plasma concentrations should be achieved within 6 to 8 hours after taking the pills.⁷⁹ Therefore, it would also be difficult to criticize the duration of treatment used in this study.⁷⁵ It was also noteworthy that 36% of women in this study who took the placebo reported their ho flash frequency was reduced by 50%, compared with 24% of patients taking the soy pill. This also demonstrates the importance of determining the placebo response in most supplement studies, because it can be quite pronounced. Few symptoms of treatment have a more consistent and large placebo response than those observed for hot flashes. Perhaps this is because it is a symptom whose clinical response is determined by the patient and/or because a variety of other lifestyle factors, including room temperature, stress, and certain foods and beverages seem to effect vasomotor symptoms.⁸⁰

Other soy-based products need further evaluation, but another welldesigned randomized trial was also recently completed.⁸¹ Again, this was a study of women experiencing hot flashes, but these originated from their post-menopausal status. Women received either a soy protein powder or placebo (casein) over a 3-month period. The soy protein supplement contained 76 mg of isoflavones daily in the form of a 60-g powder. This supplement was reported to significantly reduce hot flashes compared to placebo at the end of the trial. However, a closer look at this study encourages considering a different perspective before making any clinical conclusions. The actual mean reduction in hot flash number per day was only 1.59 compared to placebo. This was not tantamount to a dramatic effect, and the placebo response in this study was 30%. These results are similar to what has been reported with other supplements (vitamin E).⁸²

Another important finding of this soy study was that of the 104 patients at baseline, 11 dropped out of the soy group and 14 from the placebo group, mostly because of the gastrointestinal side effects that occurred with either agent.⁸¹ Approximately 25% of the original study group experienced constipation, bloating, nausea, vomiting, and even intimidation because of the large amount of daily powder they needed to consume from soy or placebo. Higher dosages of this and other soy products could be accomplished in future studies with a potential for greater results; however, there would be a primary concern over a larger dramatic increase in the number of subjects experiencing adverse gastrointestinal symptoms. Furthermore, a greater withdrawal rate could potentially abruptly end such a clinical study if an appropriate number of individuals were unable to reach completion. Additionally, quality of life could be significantly affected during such a trial. Another interesting finding from the soy protein trial was that the Kupperman index, which is the standard scale of rating overall menopausal symptoms, did not change in this study with either intervention.

A final option in future studies would be to include the use of a supplement that is greater in plant estrogens than those used previously. This option is questionable, because one could argue that it is tantamount to using conventional estrogens or standard treatment for these individuals. The argument seems to revolve around the issue of safety versus efficacy: increase safety and then efficacy becomes the primary issue, but increase efficacy and then safety becomes the concern.

Incorporating realistic and moderate amounts (1–2 servings/day) of traditional soy products, such as soybeans, miso, tempeh, tofu, and soymilk in the diet is probably the safest current recommendation, instead of high isoflavone soy supplements.⁶⁰ These products, despite a minimal effect on hot flashes, may provide some benefit, and overall they seem safe and healthy.

The search for more efficacious and safe agents should be a priority, and current studies are addressing this issue. For example, acupuncture treatment in a pilot study seems to have an impact on vasomotor symptoms from cancer treatment, but a randomized trial still needs to be completed.⁸³ Other research with conventional agents seems to hold more promise. Antidepressant medications have some early success, and the dosages of these medications are lower than those normally used for clinical depression.⁸⁴ The possible use of some dietary supplements that are reported to relieve depression wouldalso be of interest in future research.

Other Soy-Based Supplements-Ipriflavone

Synthetic derivatives of the naturally occurring soy isoflavones (eg, daidzein) can be purchased as a dietary supplement in the United States.⁸⁵ The most popular is probably “ipriflavone,” which has gained some interest as a potential antiosteoporotic compound because of its estrogenlike qualities. This supplement is also marketed and sold in a variety of countries, including Japan, Hungary, and Italy. Studies suggest that it inhibits bone resorption and stimulates osteoblasts in vitro and in vivo in osteoporosis experimental models.^86,87 Several clinical studies demonstrate that ipriflavone taken with calcium is an effective agent against postmenopausal osteoporosis.^85,888–⁹¹ In addition, 39 women receiving luteinizing hormone releasing hormone (LHRH) treatment were also given 600 mg of ipriflavone and 500 mg of calcium daily.⁹² No further bone loss was demonstrated after 6 months compared to those on placebo, who did experience a significant negative change. The placebo group experienced significant increases in bone loss markers, such as urinary hydroxyproline and plasma osteocalcin. An additional short-term study of women on LHRH treatment demonstrated similar results.⁹³

The evidence from past clinical studies with postmenopausal women or those women on LHRH treatment that ipriflavone prevents osteoporosis is interesting, but studies of longer duration are needed. This supplement should be tested in men receiving androgen suppression for prostate cancer, but a recent concern may change the enthusiasm to continue research with this dietary supplement.⁹⁴

The most recent and longest study of ipriflavone was published at the time of this article’s submission.⁹⁴ It was a 4-year, prospective, randomized, multicenter international study. Postmenopausal white women (n = 474) aged 45 to 75 years with established osteoporosis were included in this study. All patients received 500 mg/day of calcium and were also randomly assigned to receive 200 mg 3 times/day of ipriflavone (n = 234), or placebo (n = 240). Changes in bone mineral density (BMD) or biochemical markers were not found to be statistically different between the two groups. Vertebral fractures were also identical in the two groups during the entire study period. However, lymphocyte concentrations decreased significantly in 29 women (12.4%) receiving ipriflavone. Fifty-two percent of the 29 women recovered spontaneously by 1 year and 81% by 2 years. Therefore, the lack of any significant effect along with the potential to induce lymphocytopenia does not make ipriflavone a viabl option currently for any individual concerned about reducing the risk of further osteoporosis and/or fractures with this supplement. The ability of ipriflavone to reduce the risk of further bone loss in women or men without osteoporosis or those on hormone suppression remains to be determined. Additionally, the potential for lymphocytopenia or other possible adverse effects must also be further investigated.

Fat and Prostate Cancer

Few lifestyle or dietary factors related to cancer risk seem to have received more attention recently than fat consumption.⁹ Prostate cancer is no exception, although overall data may be misconstrued, because data from all types of research (from laboratory to case-control to prospective studies) have not necessarily been assimilated correctly in one manuscript. In addition, a comparison of prostate cancer to other cancers needs to be accomplished to understand further the potential role of fat and prostate cancer.

Some animal models examining the relationship between prostate cancer and diet have found an inhibition of tumor growth with a lower fat intake, or an increased growth with a high fat intake^95,96; however, other animal studies that have ensured isonutrient intakes have not been able to effect the growth of transplanted prostate tumors or the induction of this cancer using increased dietary fat.^97,98 A recent extensive animal study found that cancer growth was independent of the percentage of fat in the diet, as long as the total energy was restricted.⁹⁹ The reduction observed in cancer growth was actually similar in all types of energy-restricted laboratory animals. These experiments suggest than an overall reduction in energy intake and not just fat per se, is the best method to reduce the risk or progression of prostate cancer.¹⁰⁰ These studies also suggest that fat in combination with some other unknown dietary factor(s) may be responsible for increasing tumor growth.

Ecologic/international comparisons and case-control studies suggest that some environmental factor, possibly fat consumption, may increase the risk of prostate cancer. A fairly close correlation exists between average per capita fat intake and prostate cancer mortality in a variety of countries throughout the world.¹⁴ After emigration to the United States, Japanese and Chinese within one generation experience notable increases in prostate cancer risk compared to their native counterparts.^101,102 These findings are similar to what has been observed with breast carcinoma.¹⁰³

An expanding number of case-control investigations over the past several decades have found an increase in prostate cancer risk with increasing fat or fat-type food consumption.^104–126 A variety of specific fat types have also been associated with risk. For example, saturated or hydrogenated fats have been associated with a higher risk in many case-control studies,^{105,109,112,116,120–122} although it is difficult to draw clear conclusions from these studies because of the greater potential for recall bias and confounding. Therefore, large-scale prospective studies are still required to shed some light on this issue.

Prospective studies completed thus far have provided different conclusions compared to what has been observed with other studies. The first prospective study documented 63 fatal cases of prostate cancer from Japan and did not find a significant correlation between meat consumption and risk.¹²⁷ Other studies have generally supported the observations from the first prospective study: some associations have been found, but medically significant findings were not demonstrated. A 21-year follow-up study of Seventh-day Adventists failed to find a significant relationship between meat or poultry, milk, cheese, and eggs and death from prostate cancer.¹²⁸ A more important finding from this study was that overweight men had a significantly higher risk of dying from prostate cancer compared to non-obese men. The third prospective study was of approximately 8000 men of Japanese ancestry residing in Hawaii.¹²⁹ No relationship between fat and prostate cancer risk was found. An inverse and significant relationship was found with increased rice or tofu consumption.

Another prospective study of Seventh-day Adventist men who were followed for 6 years and 180 cases of prostate cancer failed to find an association between fat and prostate cancer risk.¹³⁰ The consumption of other dietary items, such as beans, lentils, peas, and tomatoes were significantly associated with lower risks of prostate cancer. Another large study called the “Lutheran Brotherhood Cohort Study” had a follow-up of 20 years and again found no association for fat-type foods, but the risk increased for current smokers.¹³¹

The Health Professionals Follow-Up Study was the second largest cohort study ever published on diet and prostate cancer risk.¹³² There was an association with fat, but no statistically significant differences were found. The only significant association was found for red meat intake. This led researchers of this study t believe that the preparation of this food and/or other components in meat were responsible for the excess risk. For example, a variety of carcinogens produced during the cooking of animal fat may be responsible for the increased risk.^133,134 In addition, this and other meats are also a large source of certain minerals (zinc and calcium), which may be associated with a further increased risk.^135,136 Another prospective investigation, the Physicians’ Health Study, also found an association between red meat intake and risk of prostate cancer, but it was not statistically significant.¹³⁷ A cohort of approximately 25,000 Norwegian men documented only 72 cases with an average 12-year follow-up.¹³⁸ A significant risk was observed for men consuming main meals of hamburger/meatballs at least 9 or more times per week. However, an inverse relationship was found for men eating main meals with meat. This could have been a chance discovery or it could potentially partially support the cooking method and risk hypothesis. Also noteworthy was the significant relationship of greater risk associated with an increased body mass index (BMI).

The Netherlands Cohort Study was the largest prospective investigation between fat and prostate cancer risk.¹³⁹ Over 58,000 men were followed for more than 6 years, and over 600 cases of prostate cancer were recorded. This study used an extensive 150-item food frequency questionnaire. No associations were observed between total fat and other sub-types of fat and the risk of prostate cancer. In fact, there was an association between a decreased risk of prostate cancer and an increased consumption of alpha-linolenic acid. This was of interest, because other prospective studies found the opposite relationship with this same fatty acid.^132,137 The average fat intake as a percentage of total calories in this cohort was fairly high (approximately 40%), so any potential influence of extremely low intakes of fat or reduced energy intake and prostate cancer was not mentioned and could not be hypothesized.¹³⁹

The most recent investigation (not prospective) was from Saudi Arabia, but this was a cross-sectional screening study to determine prostate cancer prevalence.¹⁴⁰ A total of 161 cases were documented within this study of over 2000 men screened. No relationship between fat intake, mainly from meat and dairy products, and prostate cancer risk was observed. Again, the average fat intake was large (40% of total calories), and saturated fat intake accounted for approximately 50% of the total fat intake. Once again, no information concerning low levels of fat intake and risk could be hypothesized from this study. The authors of this study did comment that a large amount of fiber, cereals, cooked tomatoes, rice, tea, fruits, vegetables, and other healthy dietary items are consumed in the average Saudi diet. These healthy items could have been responsible for the lack of an association between fat and prostate cancer.

Only one large cohort study has revealed a consistent statistically significant relationship between prostate cancer and prior fat consumption.¹⁴¹ Approximately 20,000 men of multiethnic backgrounds residing in Hawaii were followed for 9 to 14 years. The risk of consuming beef, milk, and high-fat foods were 1.6, 1.4, and 1.6, respectively. A closer evaluation of this study found that a food questionnaire of only 13 items was used. Increased height actually demonstrated the greatest direct risk factor for prostate cancer (P < .01) compared to consumption of fat (P < .05). Height and BMI have been theorized to affect the risk of several cancers.¹⁴² The specific mechanisms have not been elucidated, but sex hormones, growth hormones, and diet may be partially responsible. A greater risk between height and prostate cancer could be expected if a shorter frame demonstrates caloric restriction during childhood and adolescent years. Caloric restriction may decrease cell proliferation and lower the stimulation and concentration from growth factors. Taller men may produce a higher concentration of growth factors during early years of life as the prostate develops. BMI has been gaining acceptance as a possible risk factor for prostate cancer, and may even have a greater negative impact on mortality from this disease. Caloric increases along with greater release of hormones and growth factors may also contribute to this risk. More studies examining the impact of lifestyle after a diagnosis of prostate cancer are needed.

A prospective study of 384 Canadian men with prostate cancer followed men for a median of 5.2 years.¹⁴³ The men consuming the highest levels of saturated fat actually had a significantly increased risk of death from prostate cancer (RR = 3.1), compared to those consuming the lowest levels. However, only 32 cases of fatal prostate cancer were documented in this cohort, so the confidence intervals for this association were fairly large (1.3–7.7). Other types of fat and total fat consumption failed to demonstrate any association between consumption and risk of death from prostate cancer.

Conclusions

Several points should be emphasized in order to gain a better understanding of the current role of complementary medicine in urology:

1. Dietary soy products have a role in the prevention of cardiovascular disease. Whether or not these items play a role in preventing prostate cancer or slowing the progression of this disease remains to be determined. Numerous ongoing clinical trials are addressing this issue.

2. Traditional soy products (soybeans, miso, tempeh, tofu, soy protein powder, soy milk) have received the most epidemiologic study to date. Soy pills have not demonstrated a clinical benefit for reducing hot flashes from cancer treatment. Other soyderivative capsules do not have enough evidence to recommend their use to reduce the risk of osteoporosis; also, some of these capsules may have serious adverse effects. More studies are needed in this area.

3. Recent research suggests that numerous lifestyle changes practiced together could provide the most benefit for reducing risk of prostate cancer.¹⁴⁴ For example, diets low in fat may improve the absorption and action of soyproducts. Obesity may also be a strong risk factor for prostate cancer and could negatively impact prognosis.

4. Dietary fat as a risk factor for prostate cancer has not been supported by recent prospective studies. Saturated fat should be reduced for the cardiovascular benefits, and this is the only fat that has demonstrated a possible negative impact on prognosis.

5. More research is needed on dietary factors, because other cancers were thought to be linked to fat consumption and no associations were found after large prospective studies were completed.¹⁴⁵ Breast cancer is a prime example of why additional research may change the perception that fat (by itself) is strongly linked to cancer.

6. Cardiovascular disease is still the number one cause of overall mortality and a major cause of death after a diagnosis of many cancers. Therefore, complementary medicine should be stressed in relation to its potential benefit in reducing cardiovascular disease- at least until sufficient cancer research is completed.

Main Points.

• Whether or not dietary soy products play a role in preventing prostate cancer or slowing the progression of this disease remains to be determined. Numerous ongoing clinical trials are addressing this issue.

• Soy pills have not demonstrated a clinical benefit for reducing hot flashes from cancer treatment. Other soy-derivative capsules do not have enough evidence to recommend their use to reduce the risk of osteoporosis; also, some of these capsules may have serious adverse effects.

• Diets low in fat may improve the absorption and action of soy products. Obesity may also be a strong risk factor for prostate cancer and could negatively impact prognosis.

• Dietary fat as a risk factor for prostate cancer has not been supported by recent prospective studies. Saturated fat should be reduced for the cardiovascular benefits.

• Complementary medicine should be stressed in relation to its potential benefit in reducing cardiovascular disease-at least until sufficient cancer research is completed.