Prostate Cancer

Prostate cancer is a malignancy of the prostate. It is characterized by unregulated replication of cells creating tumors, with the possibility of some of the cells spreading to other sites (metastasis).

This article includes a discussion of studies that have assessed whether certain vitamins, minerals, herbs, or other dietary ingredients offered in dietary or herbal supplements may be beneficial in connection with the reduction of risk of developing prostate cancer, or of signs and symptoms in people who have this condition.

This information is provided solely to aid consumers in discussing supplements with their healthcare providers. It is not advised, nor is this information intended to advocate, promote, or encourage self use of these supplements for cancer risk reduction or treatment. Furthermore, none of this information should be misconstrued to suggest that dietary or herbal supplements can or should be used in place of conventional anticancer approaches or treatments.

It should be noted that certain studies referenced below, indicating the potential usefulness of a particular dietary ingredient or dietary or herbal supplement in connection with the reduction of risk of prostate cancer, are preliminary evidence only. Some studies suggest an association between high blood or dietary levels of a particular dietary ingredient with a reduced risk of developing prostate cancer. Even if such an association were established, this does not mean that dietary supplements containing large amounts of the dietary ingredient will necessarily have a cancer risk reduction effect.

Prostate cancer is the most common cancer among men in the United States. Although the cause is not known, most researchers believe that alterations in testosterone metabolism and/or bodily responses to testosterone are involved.

Throughout the world, autopsy reports show that evidence of microscopic prostate cancer is extremely common in older men. However, most men who have such microscopic disease are never diagnosed with, nor do they die from, prostate cancer. Unlike this dormant form of the disease, the incidence of potentially life-threatening prostate cancer varies greatly in different parts of the world. Researchers believe that some factors, possibly involving diet or lifestyle issues, determine the risk of having potentially life-threatening prostate cancer.

American men are at high risk of being diagnosed with such prostate cancer, and African-American men are at particularly high risk, for reasons that are not completely clear. A family history of prostate cancer increases the risk to a limited extent. Farmers, mechanics, workers in tire and rubber manufacturing, sheet metal workers, and workers exposed to cadmium have also been reported to be at increased risk.

Rating	Nutritional Supplements	Herbs
	Lycopene Selenium (reduces risk) Vitamin E (reduces risk)	PC-SPES (take only under medical supervision)
	Coenzyme Q10 Melatonin	Shiitake
Reliable and relatively consistent scientific data showing a substantial health benefit. Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit. For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

What are the symptoms of prostate cancer?

Prostate cancer usually grows slowly, initially producing no symptoms. Later in the course of the disease, symptoms that overlap with symptoms of prostatic hyperplasia, a very common benign condition, may appear. Some of these symptoms include frequent urination (including having to urinate more frequently at night), pain on urination, a weak urinary stream, dribbling after urination, and a sensation of incomplete emptying. In addition, blood may appear in urine. None of these symptoms is specific to prostate cancer; the diagnosis of this disease requires the help of a doctor.

If prostate cancer spreads to a distant part of the body, it most often is found in bone, a condition that may cause bone pain. Late stages of the disease are associated with severe weight loss, untreatable fatigue-inducing anemia, and finally death.

Dietary changes that may be helpful for prostate cancer
The following dietary changes have been studied in connection with prostate cancer.

Avoidance of alcohol
Although the effect of drinking alcohol on prostate cancer risk appears weak, some association between beer drinking and an increased risk may exist, according to an analysis of most published reports.¹

Tomatoes
Tomatoes contain lycopene—an antioxidant similar in structure to beta-carotene. Most lycopene in our diet comes from tomatoes, though traces of lycopene exist in other foods. Lycopene has been reported to inhibit the proliferation of cancer cells in test tube research.²

A review of published research found that higher intake of tomatoes or higher blood levels of lycopene correlated with a reduced risk of cancer in 57 of 72 studies. Findings in 35 of these studies were statistically significant.³ Evidence of a protective effect for tomato consumption was stronger for prostate cancer than for most other cancers.

Cruciferous vegetables
Cabbage, Brussels sprouts, broccoli, and cauliflower belong to the Brassica family of vegetables, also known as “cruciferous” vegetables. In test tube and animal studies, these foods have shown to have anticancer activity,⁴ possibly due to several substances found in them, such as indole-3-carbinol,⁵ glucaric acid (calcium D-glucarate),⁶ and sulforaphane.⁷ A recent preliminary study of men newly diagnosed with prostate cancer showed a 41% decreased risk of prostate cancer among men eating three or more servings of cruciferous vegetables per week, compared with those eating less than one serving per week.⁸ Protective effects of cruciferous vegetables were thought to be due to their high concentration of the carotenoids lutein and zeaxanthin, as well as their stimulatory effects on the breakdown of environmental carcinogens associated with prostate cancer.⁹

Meat and how it is cooked
Meat contains high amounts of arachidonic acid. Some by-products of arachidonic acid have promoted prostate cancer in animals.10 Preliminary reports have suggested that frequently eating well-done steak¹¹ or cured meats¹² may also increase the risk of prostate cancer in men, though the association between prostate cancer and other meats has not been consistently reported.

Fish
Fish eaters have been reported to have low risk for prostate cancer.¹³ The omega-3 fatty acids found in fish are thought by some researchers to be the components of fish responsible for protection against cancer.¹⁴

Low-fat diet and prevention
When combined with a low-fiber diet, men consuming a high-fat diet have been reported to have higher levels of testosterone,15 which might increase their risk of prostate cancer. The risk of prostate cancer correlates with dietary fat from country to country,16 a finding supported in some,^{17 18} but not all,¹⁹ preliminary trials. In one study, prostate cancer patients consuming the most saturated fat (from meat and dairy), and followed for over five years, had over three times the risk of dying from prostate cancer compared with men consuming the least amount of saturated fat.²⁰

Avoidance of alpha-linolenic acid
Alpha-linolenic acid is a fatty acid found in many foods. Most,^{21 22 23} but not all,²⁴ studies have found that high dietary or blood levels of alpha-linolenic acid correlate with an increased risk of prostate cancer.

Concentrations of alpha-linolenic acid are much higher in flaxseed oil, canola oil, soybean oil, and certain nuts compared to the concentrations found in meat. However, because so much meat is consumed as part of many western diets, a significant portion of dietary alpha-linolenic acid often does come from meat. Therefore, at least in theory, alpha-linolenic may merely be a marker for meat consumption. When researchers have adjusted for the intake of meat or saturated fat, however, a correlation between alpha-linolenic acid and prostate cancer risk has remained.^{25 26} On the other hand, in a preliminary study of men with prostate cancer, supplementation with 30 grams of ground flaxseed per day for approximately one month appeared to decrease the rate of tumor growth.²⁷

How alpha-linolenic acid might increase the risk of prostate cancer remains unclear. Alpha-linolenic acid has promoted the growth of prostate cancer cells in one test tube study,²⁸ but inhibited prostate cell growth in another.²⁹

Soy
Genistein is an isoflavone found in soybeans and many soy foods, such as tofu, soy milk, and some soy protein powders. Except for soy sauce and soy protein concentrates processed with alcohol, most soy-based foods contain significant amounts of isoflavones, such as genistein. Genistein inhibits growth of prostate cancer cells, helps kill these cells,30 and has other known anticancer actions, according to test tube research findings.³¹

In preliminary research, men who consumed soy milk more than once per day were reported to have a significantly lower risk of prostate cancer compared with other men.³² Some researchers are now saying that genistein may eventually be shown to have the potential to treat prostate cancer,³³ while others say only that enough evidence exists to recommend that future genistein research be devoted to the subject of prostate cancer prevention.³⁴

Lifestyle changes that may be helpful for prostate cancer
The following lifestyle change has been studied in connection with prostate cancer.

Maintaining healthful body weight
Several studies have reported that the risk of prostate cancer increases with increasing body weight.^{35 36}

Nutritional supplements that may be helpful for prostate cancer

The following nutritional supplements have been studied in connection with prostate cancer.

Beta-carotene
In a double-blind trial, supplementation with synthetic beta-carotene led to a 23% increase in the risk of prostate cancer in smokers, though this increase did not reach statistical significance.³⁷ However, in a double-blind study of mostly nonsmoking men, supplementation with synthetic beta-carotene led to a statistically significant 32% reduction in risk of prostate cancer in those who initially had the lowest blood levels of beta-carotene.³⁸ In the same report, supplementation with synthetic beta-carotene in men who had the highest blood levels of beta-carotene at the beginning of the trial led to a 33% increase in the risk of prostate cancer, though this finding may have been due to chance.³⁹

No trials have investigated the effect of natural beta-carotene supplements on the risk of prostate cancer.

Selenium
Selenium has been reported to have diverse anticancer actions.^{40 41} Selenium inhibits cancer in animals.⁴² Low soil levels of selenium (probably associated with low dietary intake), have been associated with increased cancer incidence in humans.⁴³ Blood levels of selenium have been reported to be low in patients with prostate cancer.⁴⁴ In preliminary reports, people with the lowest blood levels of selenium had between 3.8 and 5.8 times the risk of dying from cancer compared with those who had the highest selenium levels.^{45 46}

The strongest evidence supporting the anti-cancer effects of selenium supplementation comes from a double-blind trial of 1,312 Americans with a history of skin cancer who were treated with 200 mcg of yeast-based selenium per day or placebo for 4.5 years and then followed for an additional two years.⁴⁷ Although no decrease in skin cancers occurred, a dramatic 50% reduction in overall cancer deaths and a 37% reduction in total cancer incidence were observed. A statistically significant 63% decrease in prostate cancer incidence was reported.⁴⁸

Lycopene
In a preliminary trial, 26 men with prostate cancer were randomly assigned to receive lycopene (15 mg twice a day) or no lycopene for three weeks before undergoing prostate surgery. Prostate tissue was then obtained during surgery and examined. Compared with the unsupplemented men, those receiving lycopene were found to have significantly less aggressive growth of cancer cells.⁴⁹ In addition, a case report has been published of a 62-year-old man with advanced prostate cancer who experienced a regression of his tumor after starting 10 mg of lycopene per day and 300 mg of saw palmetto three times per day. As saw palmetto has not been previously associated with improvements in prostate cancer, the authors of the report attributed the response to the lycopene.⁵⁰ Long-term controlled studies are needed to confirm these promising initial reports.

Calcium
Warning: Calcium supplements should be avoided by prostate cancer patients.

Increasing calcium intake from food, water, and supplements has been associated with an increased risk of prostate cancer in some preliminary studies51 52 but not in others.53 54 A few researchers now believe that increasing calcium intake may increase the risk of prostate cancer by reducing the amount of vitamin D activated in the kidneys.55 (Vitamin D may protect against prostate cancer. See the Vitamin D discussion below.) If the relationship between higher calcium intake and increased risk of prostate cancer were to be confirmed by future research, then the question would arise whether the negative effect of calcium from food and supplements could be overcome by taking vitamin D supplements.

Vitamin E
Relatively high blood levels of vitamin E have been associated with relatively low levels of hormones linked to prostate cancer.56 While a relationship between higher blood levels of vitamin E and a reduced risk of prostate cancer has been reported only inconsistently,57 58 supplemental use of vitamin E59 has been associated with a reduced risk of prostate cancer in smokers. In a double-blind trial studying smokers, vitamin E supplementation (50 IU of vitamin E per day for an average of six years) led to a 32% decrease in prostate cancer incidence and a 41% decrease in prostate cancer deaths.60 Both findings were statistically significant.61 The effects of vitamin E have yet to be studied in men already diagnosed with prostate cancer.

Vitamin D
Where sun exposure is low, the rate of prostate cancer has been reported to be high.62 In the body, vitamin D is changed into a hormone with great activity. This activated vitamin D causes “cellular differentiation”—essentially the opposite of cancer.

In a preliminary trial, 7 of 16 men who had prostate cancer that had spread to bone and who had been unresponsive to conventional treatment were found to have evidence of vitamin D deficiency.63 All 16 were given 2,000 IU of vitamin D per day for 12 weeks, and levels of pain were recorded for 14 of these men. Vitamin D supplementation led to reduced pain in 4 of the 14 men, and 6 showed evidence of increased strength.64 Those with vitamin D deficiency were more likely to respond, compared with those who were not deficient.65 While anyone with vitamin D deficiency should be treated with vitamin D, taking 2,000 IU per day requires a doctor’s supervision.

In another preliminary trial, 14 men with prostate cancer unresponsive to conventional treatment were given activated vitamin D66 —the form of vitamin D believed to have anti-tumor action against prostate cancer.67 A reduction in prostate specific antigen (PSA) scores, a marker for prostate cancer progression, occurred in only two men, and in no case did the PSA score decline by as much as 50%. In a small preliminary trial, activated vitamin D slowed the rate at which PSA increased.68 Activated vitamin D is a prescription hormone with significant side effects requiring careful monitoring by a physician.

The ability of vitamin D or its activated form to prevent cancer or effectively treat people who have cancer remains unproven.

Melatonin
Years ago, a preliminary study suggested that melatonin may help stabilize the condition of some people with advanced cancers.69 Since then, Italian researchers have been investigating the effects of melatonin in cancer patients, often with partial success.70 71 72 73 74 75 76 77 78 79 80 81

Patients with advanced prostate cancer who had previously not responded to drug therapy (triptorelin) were given melatonin plus triptorelin in a preliminary trial.82 PSA scores, a marker of disease progression, fell (i.e., improved) more than 50% in 8 of 14 patients.

Patients with advanced cancer have been reported to have improved survival and fewer side effects from taking chemotherapy when given melatonin plus chemotherapy vs. chemotherapy alone.83

Coenzyme Q10
In an unpublished report, after one year, 10 of 15 prostate cancer patients experienced a 78% decrease in the level of PSA—a marker of cancer activity.84 The amount of coenzyme Q10 given to these men was 600 mg per day; after four months, PSA scores began to decline.85 Such undocumented case reports require confirmation from published research trials.

Shark cartilage
Growth of cancerous tumors requires a large blood supply. Substances that interfere with the development of new vessels that supply blood to tumors are thought by many researchers to have potential anticancer effects. Such substances are called “antiangiogenic.” Shark cartilage has been reported to have antiangiogenic activity.86

In a preliminary report, high amounts of shark cartilage were administered by enemas or suppositories to eight late-stage cancer patients.87 After 7 to 11 weeks, 6 of the 8 were reported to show significant reductions in tumor size, though the long-term outcomes of these patients were not reported.88

In a telephone survey of cancer patients, 11 of 18 patients claimed a reduction in tumor size had resulted from the use of shark cartilage, 17 of 21 reported an improvement in their quality of life, and 7 of 7 prostate cancer patients reported a reduction in PSA scores—a marker of cancer progression.89 However, a report limited to patients capable of responding by phone necessarily omits patients who have died while taking shark cartilage and includes no objective medical information. The meaning of these findings, supported by a company selling shark cartilage, remains unclear.

In a preliminary trial, 60 late-stage cancer patients were given 1 gram of shark cartilage for every 2.2 pounds of body weight per day in three divided doses and followed for 12 weeks or longer.90 No evidence of a therapeutic effect was found.91

Because the evidence remains weak and mixed, shark cartilage remains unproven as a treatment for men with prostate cancer.

Zinc
Prostate cancer patients have been reported to have subnormal levels of zinc within the prostate, which might facilitate the growth of cancer, according to some researchers.92 Zinc has interfered with the growth of prostate cancer cells in test tube research.93 However, no trials have directly explored whether zinc supplements help prevent prostate cancer or can effectively treat men who already have the disease.

Are there any side effects or interactions with prostate cancer?

Refer to the individual supplement for information about any side effects or interactions.

Herbs that may be helpful for prostate cancer

The following herbs have been studied in connection with prostate cancer.

PC-SPES
“PC” in this formula’s name stands for prostate cancer, while “SPES” is the Latin word for hope. The complete formula consists of isatis (Isatis indigotica), licorice (Glycyrrhiza glabra) and/or Gan cao (G. uralensis), Chinese scullcap (Scutellaria baicalensis), reishi (Ganoderma lucidum), saw palmetto (Serenoa repens), Asian ginseng (Panax ginseng) or sanqi ginseng (P. pseudoginseng), denodrantherm (Denodrantherma morifolium), and rabdosia (Rabdosia rubescens).

In several preliminary trials, this formula has been shown to reduce blood levels of prostate specific antigen (PSA, a marker for prostate cancer progression) in men with prostate cancer.94 95 96 97 98 While such a reduction suggests a therapeutic effect, trials have yet to explore whether PC-SPES increases survival in people with prostate cancer.

One trial distinguished prostate cancer patients with androgen-dependent (an earlier, milder form of the cancer) and androgen-independent (a later, more severe form of the cancer) disease.99 PSA scores began to decline in most people within two to six weeks after first receiving PC-SPES. Scores reached their lowest point in an average of 23 weeks in men with androgen-dependent prostate cancer and 16 weeks in men with androgen-independent prostate cancer. PSA scores declined an average of 80% and became undetectable in four out of every five men with androgen-dependent disease. In contrast, 54% of androgen-independent prostate cancer patients had a PSA decline of 50% or more. After an average of about one year, 31 of 32 androgen-dependent prostate cancer patients continued to have normal PSA scores. However, 28 of the 35 patients with androgen-independent prostate cancer ultimately developed PSA increases consistent with progression of their cancer, despite continued use of PC-SPES. Improvement or disappearance of cancer was seen in four patients who had previously had cancer spread to the bone, as well as in one patient who had previously had cancer spread to the bladder. Rarely, PSA levels have risen slightly (less than 20%) during PC-SPES use, according to other studies.100 Testosterone levels are almost always decreased by PC-SPES therapy, according to most studies, which presumably accounts, in part, for the therapeutic effect.101 102

Many men who take the formula have been reported to develop symptoms of estrogen excess, including breast tenderness, enlargement of the breasts, loss of libido, and the more serious problem of blood clots in the veins (venous thrombosis).103 104 105 At least one person who took PC-SPES developed a potentially life-threatening blood clot in the lung. For this reason, some doctors recommend that people taking PC-SPES also take blood-thinning medication, such as heparin or warfarin (Coumadin®).106 107 However, each of these drugs can cause excessive bleeding. Because of the potential side effects of PC-SPES and the complex medical issues involved with the use of blood-thinning drugs, people should never take PC-SPES without the close supervision of a doctor. The amount of PC-SPES used in most studies was 320 to 960 mg three times per day.108 109 110

In February 2002, the sole supplier of PC-SPES in the United States (BotanicLab) issued a recall of the product after the California Health Department reported it contained warfarin, a prescription drug that can cause severe bleeding. However, PC-SPES is known to contain compounds that, though distinct from warfarin, could potentially be mistakenly identified as warfarin using currently available laboratory methods.111 There has been one case report of excessive bleeding occurring in a man who was taking PC-SPES. 112 However, the warfarin concentration in this patient’s blood was not high enough to explain his abnormal bleeding. In addition, allegations have been made that PC-SPES contains small amounts of a synthetic estrogen (diethylstilbestrol; DES). That claim has been disputed by BotanicLab.

Although additional information is needed to determine whether PC-SPES has been adulterated with one or more prescription drugs, at the time of this writing (February 2003) the product is not available in the United States.

Warning:PC-SPES has been reported to cause serious side effects, including potentially life-threatening blood clots. PC-SPES should never be taken without the close supervision of a doctor. PC-SPES is not for sale is certain parts of the world.

Shiitake (Lentinus edodes)
Several trials studying cancer patients have investigated the effects of lentinan, a carbohydrate found in shiitake mushrooms.113 114 115 116 Injection of lentinan repeatedly has been found to have beneficial effects on the immune systems of cancer patients.117 118 Two trials reported that lentinan injections prolonged life in people with a variety of advanced cancers.119 120 Another trial found that intravenous lentinan increased five-year survival rates in prostate cancer patients compared with those not given lentinan.121 It is unknown whether consumption of shiitake mushrooms or lentinan supplements would have the same effects reported in studies using injectable lentinan.

Other herbal therapies
No studies have investigated the effects of the Hoxsey herbal formula, Coriolus versicolor (PSK), the Essiac formula, or most other herbal therapies in men with prostate cancer.

Are there any side effects or interactions with prostate cancer?

Refer to the individual herb for information about any side effects or interactions.