Special section: Complementary therapies for prostate disease

| March 1, 2008

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Special section: Complementary therapies for prostate disease

What works and what doesn't?

Treating erectile dysfunction and incontinence

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Special section: Complementary therapies for prostate disease

If you have been diagnosed with prostate disease, chances are that you've thought about trying some type of complementary therapy in addition to conventional medical treatment from a physician. If so, you are not alone. An estimated 27% to 43% of American men with prostate cancer use at least one form of complementary therapy. Similar findings have been reported in Canada and Europe. Although statistics are harder to find for how many men use complementary therapies for other prostate conditions and their side effects, a wide array of products are promoted for these conditions, suggesting that there are many who do.

Even so, the issue of complementary therapies doesn't often come up during a visit to the physician. Patients tend not to mention the non-prescription therapies they are using, and doctors may not ask about them. Often this is a function of time: a man and his doctor may have only 10 or 15 minutes together in a typical office visit.

What works and what doesn't?

The National Center for Complementary and Alternative Medicine (NCCAM), a division of the National Institutes of Health, defines alternative medicine as therapies used in place of conventional medicine, while complementary medicine consists of therapies used together with conventional medicine. Although the term integrative medicine is becoming popular with physicians and patients who want to fully integrate both conventional and complementary practices, for the sake of clarity this report will use the term complementary to mean any non-conventional therapy. For any patient using complementary therapies, it is best to use them along with — rather than as a substitute for — conventional medical therapy from your physician, and to tell your doctor which complementary therapies you are using.

Complementary therapies fall into three categories based on safety and efficacy. The first category consists of those that are both safe and have evidence of effectiveness; the second includes those that are safe but lack evidence of efficacy; and the third consists of those that are unsafe and have been proved ineffective. The middle category is by far the largest. It includes herbs such as saw palmetto (see Table 9), which some men take for BPH. These herbs and botanicals are probably safe when used alone. But in many cases there is no evidence that they actually have any effect, or the only evidence has come from small pilot studies rather than from high-quality clinical trials. So the evidence is suggestive, not conclusive. In some cases, supplements have proved to be dangerous, as was the case with a supplement called PC SPES, taken off the market in 2002 (see "A cautionary tale").

A cautionary tale

Most herbs, and other nonregulated substances sold without prescription are known legally as "dietary supplements." Because these products are not controlled by the Food and Drug Administration, products sometimes contain substances that are not on the label.

For example, in 2006, the FDA warned consumers against using several products being promoted for erectile dysfunction that contained sildenafil (Viagra) or vardenafil (Levitra) but did not list these ingredients on the label. This is dangerous because these ingredients react with nitrates found in some prescription drugs (such as nitroglycerin) and may lower blood pressure to dangerous levels. People with diabetes, high blood pressure, high cholesterol, or heart disease often take nitrates. ED is a common problem in men with these conditions who may seek products to treat ED without knowing that they contain the active ingredients used in FDA-approved ED drugs.

In another example, a herbal product known as PC SPES was promoted for years as being good for "prostate health." The National Center for Complementary and Alternative Medicine (NCCAM) funded four research studies to determine its efficacy, safety, and mechanism of action.

The research ended abruptly in 2002, however, when the FDA issued a warning that men taking PC SPES developed blood clots; some patients died. Shortly after the FDA warning, NCCAM halted the studies (although it eventually restarted the laboratory trials). The U.S. distributor issued a voluntary recall and eventually went out of business. It was later discovered that some batches of PC SPES were contaminated with DES, an estrogen. This helped explain a puzzling side effect many patients had experienced while taking PC SPES — breast enlargement and soreness that could result from taking female hormones. Scientists also discovered that other batches of PC SPES contained indomethacin, a pain reliever, and warfarin, a blood thinner.

It's important for a patient to have a frank conversation with his physician about any complementary therapies he is taking. Patients and physicians need to be aware that herbs can interact with other herbs, and with prescribed medications. Herbs can enhance the effects of medications, or sometimes negate any benefit. One of the most common interactions involves herbs that affect the liver by acting on cytochrome P450 enzymes (see "Korean red ginseng"). Many other herbs, such as St. John's wort, have this effect.

One practical approach is to avoid taking too many supplements at one time. Try one herb or botanical first, and see if you tolerate it without any side effects before adding anything else. That's similar to the way physicians prescribe medications.

Men should also be aware that nothing is standardized with respect to over-the-counter supplements. The FDA, which regulates the efficacy and purity of prescription and over-the-counter drugs, doesn't have the authority to do the same with dietary supplements.

In terms of specific foods, there is reason to believe that fish and selenium might be important in reducing risk of developing prostate cancer (see Table 10). But there's almost no evidence that changing your diet after diagnosis will have any impact on prostate cancer progression. Of course, eating a healthful diet, and including some of these specific components, won't do harm and would improve overall health, which would help men going through treatment for prostate cancer.

Table 8: Complementary therapies for prostatitis
Substance that may work
Substance and possible mechanism of action	Assessment
Quercetin A bioflavonoid, a chemical that contributes to color in plants. Has antioxidant and anti-inflammatory effects.	One small randomized controlled study has evaluated quercetin for the treatment of chronic nonbacterial prostatitis (chronic pelvic pain syndrome). The study involved 30 men who took quercetin for a month. Investigators reported in 1999 in Urology that 67% of men taking quercetin reported improvement of symptoms, compared with 20% of men taking placebo.

Table 9: Complementary therapies for benign prostatic hyperplasia (BPH)
Substances that may work
Substance and possible mechanism of action	Assessment
Beta sitosterol Mixture of several extracts of plants containing substances that mimic cholesterol; not clear how it alleviates BPH symptoms.	One review of four randomized trials involving a total of 519 men, published in 1999 in BJU International, concluded that beta sitosterol improves urinary symptoms, but cautioned that long-term safety and effectiveness were unknown.
Pygeum Derived from the bark of an African evergreen tree; not clear how it works, but some researchers have proposed that it reduces inflammation or slows prostate growth.	One study, involving 263 men recruited at eight sites in Europe, found that participants who took pygeum experienced improvement in urinary symptoms.
Saw palmetto Derived from the berry of the saw palmetto tree; not clear how it works, although a leading theory is that it affects male hormones. Safety considerations: May increase the risk of bleeding when taken with herbs and drugs that also have this effect (such as garlic, aspirin, anticoagulants, antiplatelet medications, NSAIDs); should not be taken with drugs that affect levels of male hormones.	Probably the best-studied herb for BPH treatment, but studies are conflicting. A review of 18 studies involving 2,939 men, published in 1998 in The Journal of the American Medical Association, concluded that saw palmetto supplements improved urinary symptoms about as much as the medication finasteride (Proscar). But a randomized trial involving 225 men who took saw palmetto for a year, published in 2006 in The New England Journal of Medicine, found no evidence that saw palmetto was any better at improving urinary symptoms than placebo.

Table 10: Complementary therapies for prostate cancer
Many substances used as complementary therapies for prostate cancer, such as vitamins and particular nutrients, are found naturally in food. Men seeking to reduce their risk of developing prostate cancer should eat a healthful diet and engage in regular physical activity. These "lifestyle" habits offer the best all-around protection because they reduce the risk of the No. 1 threat to men — heart disease. Nevertheless, epidemiologic studies (which follow large groups over time) have identified a number of specific dietary factors that appear to affect risk of prostate cancer development. Data are limited, however, about whether dietary changes made after diagnosis will have any impact on cancer progression.
Substances that may reduce risk
Substance and possible mechanism of action		Impact on prostate cancer risk	Impact on prostate cancer progression
Fish Not clear why fish may be protective; one theory is that omega-3 fatty acids contained in fatty fish may inhibit a particular molecular pathway involved in cancer development.		Fair to good evidence exists that eating fish may reduce risk of prostate cancer. Two large prospective studies, for example, found that men who ate fish were less likely to develop prostate cancer or die from it.	May reduce progression, but fewer data are available. A 2006 study found that men with the highest intake of fish after diagnosis were 27% less likely to have their cancer progress than men with the lowest consumption.
Selenium May inhibit several biological pathways that encourage cancer growth, such as cell proliferation and angiogenesis. Safety considerations: Taking too much can cause nausea and vomiting; consult with your doctor if you are undergoing radiation treatment, as this supplement (and any antioxidant) may interfere with treatment.		Strong evidence exists that selenium reduces risk. A 2003 randomized controlled study found that men who took selenium supplements were 50% less likely to develop prostate cancer than those who took placebo pills. Several other studies reported similar findings.	Insufficient evidence exists regarding impact on progression.
Tomatoes The promise of tomatoes and, in particular, the substance lycopene found in tomatoes, has faded. Tomatoes may have a limited ability to lower risk, but which nutrients in tomatoes and how they might work to lower cancer risk are not known.		A 2007 American Journal of Clinical Nutrition study found no association between the consumption of carotenoids (such as lycopene) and prostate cancer prevention. A 2007 review by the FDA published in The Journal of the National Cancer Institute found no evidence to support an association between lycopene (the substance in tomatoes previously thought to lower risk of prostate cancer) and a reduced risk of prostate cancer. The study found only "very limited" evidence of a link between tomato consumption and reduced risk of prostate cancer.	Increasing consumption after diagnosis may reduce progression, but data are limited. A 2006 study found that increased intake of tomato sauce after diagnosis might reduce risk of prostate cancer progression by 30% to 40%. Other studies reporting a protective effect from increased tomato consumption after treatment have been small or poorly designed.
Vitamin E Has antioxidant effects that may be helpful; supplements contain alpha tocopherol, a form of vitamin E. Safety considerations: May increase risk of bleeding if you are taking anticoagulants or antiplatelet medications; may interfere with treatment if you are undergoing radiation therapy (ask your doctor).		Good evidence that this may reduce risk, but the benefit is seen only in men who smoke. The Alpha-Tocopherol Beta-Carotene study, for example, reported that men who smoked and took 50-IU vitamin E supplements a day reduced risk of prostate cancer by 30% to 40%. Other studies have confirmed a protective effect for smokers.	Limited data exist regarding impact on progression.
Substances that may be protective, but evidence is limited
Substance and possible mechanism of action		Impact on prostate cancer risk	Impact on prostate cancer progression
Carotenoids Occur naturally in plants; may have antioxidant properties.		There is some evidence of reduced risk, but data are limited and findings have been mixed. One study reported that men with higher blood levels of particular antioxidants — lutein, beta cryptoxanthin, and zeaxanthin — had a 70% to 80% reduced risk of prostate cancer. But a randomized clinical trial found that men who took beta carotene supplements had an increased risk of prostate cancer if they already had high blood levels of this antioxidant.	Limited data exist regarding impact on progression.
Melatonin Inhibits prostate cancer cell growth in test tubes. Safety considerations: Avoid if you are taking anticoagulants or antiplatelet medications; may increase or decrease blood pressure, and may increase blood sugar levels in people with diabetes.		Insufficient evidence, although some studies have suggested that men with prostate cancer have lower levels of melatonin than other men.	A small study involving 14 men with advanced prostate cancer who were not responding to hormone therapy alone found that taking melatonin supplements in addition to hormone therapy improved response. PSA levels decreased by more than half in eight men, and nine lived longer than one year.
Substances that may be protective, but evidence is limited
Substance and possible mechanism of action	Impact on prostate cancer risk		Impact on prostate cancer progression
Pomegranate juice Contains a variety of antioxidants and flavonoids, which may inhibit cancer growth.	Insufficient evidence regarding impact on developing prostate cancer.		A small 2006 study suggests that men whose PSA is rising after cancer treatment may be able to slow the rate at which PSA increases by drinking 8 ounces of pomegranate juice every day. The study involved 50 men who were followed until their PSA doubled. Investigators found that average PSA doubling time slowed from an average of 15 months before the study began to an average of 54 months afterward.
Soy Contains isoflavones, nutrients that can inhibit cell growth and affect hormones that may fuel the growth of prostate cancer. Safety considerations: May interact with warfarin (Coumadin); check with your doctor for advice.	Limited data exist, but some studies suggest that higher soy intake may reduce risk.		No evidence exists regarding impact on progression.
Vitamin D May inhibit growth of prostate cancer cells.	Epidemiologic studies have produced mixed results.		Limited evidence regarding impact on progression.
Substances that may increase risk
Substance	Impact on prostate cancer risk		Impact on prostate cancer progression
Calcium and dairy products Calcium, whether or not it comes from dairy products, appears to increase risk.	Good evidence that higher intake increases risk. One study found that men who consumed more than 2,000 mg of calcium daily were five times as likely to develop metastatic prostate cancer as those who consumed less than 500 mg of calcium per day. A large epidemiologic study found that intake of more than 1,500 mg of calcium per day might increase the risk of aggressive and fatal prostate cancer, but not the risk of less aggressive, localized cancer.		Studies suggest that high calcium intake may increase the likelihood of progression. One theory is that calcium has different effects, depending on the stage of cancer development or progression.
Meat Early indications that red meat increases risk of prostate cancer have not been supported by newer data.	A large 10-year study failed to confirm a link between red meat and prostate cancer.		Insufficient evidence regarding impact on progression.
Zinc Because zinc contributes to many bodily functions, including healthy immune functioning and wound healing, zinc supplements have sometimes been touted as a cure for various prostate diseases. However, there is no evidence that zinc supplements help — and in prostate cancer, such supplements may cause harm.	Limited evidence that zinc supplements may increase risk. One study found that men who took 100-mg zinc supplements daily were more than twice as likely to develop advanced prostate cancer as men who did not take the supplements.		No data are available regarding impact on progression.

Table 11: Complementary therapies for erectile dysfunction
Substances that may work
Substance and possible mechanism of action	Assessment
Korean red ginseng Derived from a plant root; not clear how it may help alleviate erectile dysfunction, but one theory is that it increases levels of nitric oxide, a chemical that occurs naturally in the body and contributes to erections. Safety considerations: Some formulations may lower blood sugar levels and alter the effects of blood pressure or heart medications; may affect the cytochrome P450 system.	Three small studies suggest that this herb may improve ability to have an erection, but further study is necessary.
L-arginine A precursor to nitric oxide; may help erectile function by increasing blood levels of this substance. Safety considerations: May increase risk of bleeding when used with anticoagulants or antiplatelet drugs, or with herbs such as ginkgo biloba, garlic, or saw palmetto; when used with nitroglycerin or erectile dysfunction drugs, may cause blood pressure to drop; may increase blood sugar levels.	Three small preliminary studies indicate that this substance may benefit men with low levels of nitric oxide, but larger studies are needed. Men at risk for heart disease should avoid taking this substance, as a study of heart attack survivors who took L-arginine was stopped early when six volunteers taking this substance died.
Vitamin supplements May have a synergistic effect when used with erectile dysfunction medication.	A small study of men who did not respond to medication alone found that erectile function and patient satisfaction improved in many who took daily folic acid and vitamin E supplements in addition to sildenafil (Viagra).