Prostate Cancer

Health Library Search:

<< Back

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.

Product checklist for prostate cancer

Rating

Nutritional Supplements

Herbs

Lycopene

Selenium (reduces risk)

Vitamin D

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.
2Stars

Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star

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.

Medical options for prostate cancer

Prescription drug treatment for prostate cancer focuses on anti-hormone therapy, which interferes with the body’s ability to make testosterone. Medications used include diethylstilbestrol (Stilphostrol®),goserelin (Zoladex®), leuprolide (Lupron®), flutamide (Eulexin®), bicalutamide (Casodex®), and ketoconazole (Nizoral®). Though the treatments cannot cure prostate cancer, they often slow the cancer’s growth and reduce the tumor size.

Treatment of men with prostate cancer varies depending on the age and health of the patient, extent of the cancer, and to some degree, the views of the oncologist. Surgical removal of the prostate gland is often performed if the cancer appears to be contained within the prostate gland. Surgical removal of the testicles (orchiectomy) might be recommended to halt testosterone production. Radiation, with or without surgery, is also commonly used to treat men with prostate cancer. External beam radiation delivers radioactivity from a machine. With brachytherapy, radiation is emitted from tiny radioactive seeds that are inserted directly into the prostate. Men who are older and appear to have less aggressive disease might delay treatment until symptoms develop—a plan called “watchful waiting.” Watchful waiting is sometimes considered a reasonable approach, because the side effects of treatment are usually significant, while their therapeutic benefits often appear to be relatively small and sometimes unclear. In addition, since prostate tumors often grow slowly, older men often die from diseases unrelated to the prostate cancer.

Dietary changes that may be helpful

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. It is not clear, however, whether this association reflects a cause-effect relationship.

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

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

Vitamins that may be helpful

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 in this article.) 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 People taking 2,000 IU per day of Vitamin D should be supervised by a doctor.

In another preliminary study, men with prostate cancer that had relapsed after surgery or radiation therapy were treated with 2,000 IU of vitamin D per day for nine months. In approximately half of the men, the prostate-specific antigen (PSA) level decreased, suggesting that the progression of the disease had been halted or reversed; this decrease was sustained for 5 to 17 months.⁶⁶ In addition, the study was done in Toronto, Canada, where the amount of sunlight is limited and vitamin D status tends to be low. It is not known whether vitamin D supplementation would be as effective in geographical regions such as the Southern United States, where the amount of sunlight is greater.

Melatonin
Years ago, a preliminary study suggested that melatonin may help stabilize the condition of some people with advanced cancers.⁶⁷ Since then, Italian researchers have been investigating the effects of melatonin in cancer patients, often with partial success.⁶⁸ ⁶⁹ ⁷⁰ ⁷¹ ⁷² ⁷³ ⁷⁴ ⁷⁵ ⁷⁶ ⁷⁷ ⁷⁸ ⁷⁹

Patients with advanced prostate cancer who had previously not responded to drug therapy (triptorelin) were given melatonin plus triptorelin in a preliminary trial.⁸⁰ 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.⁸¹

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.⁸² The amount of coenzyme Q10 given to these men was 600 mg per day; after four months, PSA scores began to decline.⁸³ 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.⁸⁴

In a preliminary report, high amounts of shark cartilage were administered by enemas or suppositories to eight late-stage cancer patients.⁸⁵ 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.⁸⁶

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.⁸⁷ 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.⁸⁸ No evidence of a therapeutic effect was found.⁸⁹

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.⁹⁰ Zinc has interfered with the growth of prostate cancer cells in test tube research.⁹¹ 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?
Refer to the individual supplement for information about any side effects or interactions.

Herbs that may be helpful

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.⁹² ⁹³ ⁹⁴ ⁹⁵ ⁹⁶ 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.⁹⁷ 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.⁹⁸ Testosterone levels are almost always decreased by PC-SPES therapy, according to most studies, which presumably accounts, in part, for the therapeutic effect.⁹⁹ ¹⁰⁰

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).¹⁰¹ ¹⁰² ¹⁰³ 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®).¹⁰⁴ ¹⁰⁵ 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.¹⁰⁶ ¹⁰⁷ ¹⁰⁸

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.¹⁰⁹ There has been one case report of excessive bleeding occurring in a man who was taking PC-SPES. ¹¹⁰ 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.¹¹¹ ¹¹² ¹¹³ ¹¹⁴ Injection of lentinan repeatedly has been found to have beneficial effects on the immune systems of cancer patients.¹¹⁵ ¹¹⁶ Two trials reported that lentinan injections prolonged life in people with a variety of advanced cancers.¹¹⁷ ¹¹⁸ Another trial found that intravenous lentinan increased five-year survival rates in prostate cancer patients compared with those not given lentinan.¹¹⁹ 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?
Refer to the individual herb for information about any side effects or interactions.

References:

1. Dennis LK. Meta-analysis for combining relative risks of alcohol consumption and prostate cancer. Prostate 2000;42:56–66.

2. Levy J, Bosin E, Feldman B, et al. Lycopene is a more potent inhibitor of human cancer cell proliferation than either α-carotene or β-carotene. Nutr Cancer 1995;24:257–66.

3. Giovannucci E. Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J Natl Cancer Inst 1999;91:317–31.

4. Beecher CW. Cancer preventive properties of varieties of Brassica oleracea: a review. Am J Clin Nutr 1994;59(suppl):1166–70S.

5. Cover CM, Hsieh SJ, Cram EJ, et al. Indole-3-carbinol and tamoxifen cooperate to arrest the cell cycle of MCF-7 human breast cancer cells. Cancer Res 1999;59:1244–51.

6. Walaszek Z, Hanausek-Walaszek M, Minton JP, Webb TE. Dietary glucarate as anti-promoter of 7,12-demethylbenz [a]anthracene-induced mammary tumorigenesis. Carcinogenesis 1986;7:1463–6.

7. Zhang Y, Kensler TW, Cho CG, et al. Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc Natl Acad Sci USA 1994;91:3147–50.

8. Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst 2000;92(1):61–8.

9. Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst 2000;92(1):61–8.

10. Ghosh J, Myers C Jr. Arachidonic acid metabolism and cancer of the prostate. Nutrition 1998;14:48–57 [editorial].

11. Norrish AE, Ferguson LR, Knize MG, et al. Heterocyclic amine content of cooked meat and risk of prostate cancer. J Natl Cancer Inst 1999;91:2038–44.

12. Schuurman AG, van den Brandt PA, Dorant E, Goldohm RA. Animal products, calcium and protein and prostate cancer risk in the Netherlands Cohort Study. Br J Cancer 1999;80:1107–13.

13. Kune GA. Eating fish protects against some cancers: epidemiological and experimental evidence for a hypothesis. J Nutr Med 1990;1:139–44 [review].

14. Rose DP, Connolley JM. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther 1999;83:217–44.

15. Dorgan JF, Judd JT, Longcope C, et al. Effects of dietary fat and fiber on plasma and urine androgens and estrogens in men: a controlled feeding study. Am J Clin Nutr 1996;64:850–5.

16. Peinta KJ, Esper PS. Is dietary fat a risk factor for prostate cancer? J Natl Cancer Inst 1993;85:1538–9 [editorial/review].

17. Giovannucci E, Rimm EB, Colditz GA, et al. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst 1993;85:15571–9.

18. Le Marchand L, Kolonel LN, Wilkens LR, et al. Animal fat consumption and prostate cancer: a prospective study in Hawaii. Epidemiology 1994;5:276–82.

19. Schuurman AG, van den Brandt PA, Dorant E, et al. Association of energy and fat intake with prostate carcinoma risk: results from the Netherlands Cohort Study. Cancer 1999;86:1019–27.

20. Meyer F, Bairati I, Shadmani R, et al. Dietary fat and prostate cancer survival. Cancer Causes Control 1999;10:245–51.

21. Gann PH, Hennekens CH, Sacks FM, et al. Prospective study of plasma fatty acids and risk of prostate cancer. J Natl Cancer Inst 1994;86:281–6.

22. Giovannucci E, Rimm EB, Colditz GA, et al. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst1993;85:1571–9.

23. Harvei S, Bjerve KS, Tretli S, et al. Prediagnostic level of fatty acids in serum phospholipids: omega-3 and omega-6 fatty acids and the risk of prostate cancer. Int J Cancer 1997;16:71:545–51.

24. Schuurman AG, van den Brandt PA, Dorant E, et al. Association of energy and fat intake with prostate carcinoma risk: results from the Netherlands Cohort Study. Cancer 1999;86:1019–27.

25. Gann PH, Hennekens CH, Sacks FM, et al. Prospective study of plasma fatty acids and risk of prostate cancer. J Natl Cancer Inst 1994;86:281–6.

26. Giovannucci E, Rimm EB, Colditz GA, et al. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst1993;85:1571–9.

27. Demark-Wahnefried W, Price DT, Polascik TJ, et al. Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology2001;58:47–52.

28. Pandalai PK, Pilat MJ, Yamazaki K, et al. The effects of omega-3 and omega-6 fatty acids on in vitro prostate cancer growth. Anticancer Res 1996;16:815–20.

29. De Toit PJ, van Aswegen CH, du Plessis DJ. The effect of essential fatty acids on growth and urokinase-type plasminogen activator production in human prostate DU-145 cells. Prostaglandins Leuko Essent Fatty Acids 1996;55:173–7.

30. Davis JN, Singh B, Bhuiyan M, Sarkar FH. Genistein-induced upregulation of p21WAF1, downregulation of cyclin B, and induction of apoptosis in prostate cancer cells. Nutr Cancer 1998;32:123–31.

31. Barnes S, Peterson TG, Coward L. Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer. J Cell Biochem Suppl 1995;22:181–7.

32. Jacobsen BK, Knutsen SF, Fraser GE. Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study (United States). Cancer Causes Control 1998;9:553–7.

33. Geller J, Sionit L, Partido C, et al. Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture. Prostate 1998;34:75–9.

34. Moyad MA. Soy, disease prevention, and prostate cancer. Semin Urol Oncol 1999;17:97–102.

35. Talamini R, La Vecchia C, Decarli A, et al. Nutrition, social factors and prostatic cancer in a Northern Italian population. Br J Cancer 1986;53:817–21.

36. Andersson S-O, Wolk A, Bergstrom R, et al. Body size and prostate cancer: a 20-year follow-up study among 135,006 Swedish construction workers. J Natl Cancer Inst 1997;89:385–9.

37. Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with α-tocopherol and β-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998;90:440–6.

38. Cook NR, Stampfer MJ, Ma J, et al. Beta-carotene supplementation for patients with low baseline levels and decreased risks of total and prostate carcinoma. Cancer 1999;86:1783–92.

39. Cook NR, Stampfer MJ, Ma J, et al. Beta-carotene supplementation for patients with low baseline levels and decreased risks of total and prostate carcinoma. Cancer 1999;86:1783–92.

40. Medina D. Mechanisms of selenium inhibition of tumorigenesis. Adv Exp Med Biol 1986;206:465–72.

41. Beisel WR. Single nutrients and immunity. Am J Clin Nutr 1982;35:417–68.

42. Medina D, Morrison DG. Current ideas on selenium as a chemopreventative agent. Pathol Immunopathol Res 1988;7:187–99.

43. Shamberger RJ, Rukoven E, Lonfield AK, et al. Antioxidants and cancer. I. Selenium in the blood of normals and cancer patients. J Natl Cancer Inst 1973;4:863–70.

44. Willett WC, Polk BF, Morris JS, et al. Prediagnostic serum Selenium and risk of cancer. Lancet 1983;42:130–4.

45. Fex G, Pettersson B, Akesson B. Low plasma selenium as a risk factor for cancer death in middle-aged men. Nutr Cancer 1987;10:221–9.

46. Salonen J, Salonen R, Lappetelainen R, et al. Risk of cancer in relation to serum concentrations of selenium and vitamins A and E; matched case-control analysis of prospective data. BMJ 1985;290:417–20.

47. Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA 1996;276:1957–63.

48. Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA 1996;276:1957–63.

49. Kucuk O, Sarkar FH, Sakr W, et al. Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev 2001;10:861–8.

50. Matlaga BR, Hall MC, Stindt D, Torti FM. Response of hormone refractory prostate cancer to lycopene. J Urol 2001;166:613.

51. Chan JM, Giovannucci E, Andersson S-O, et al. Dairy products, calcium, phosphorus, vitamin D, and risk of prostate cancer (Sweden). Cancer Causes Control 1998;9:559–66.

52. Giovannucci E, Rimm E, Wolk A, et al. Calcium and fructose intake in relation to risk of prostate cancer. Cancer Res 1998;58:442–7.

53. Yang CY, Chiu HF, Tsai SS, et al. Calcium and magnesium in drinking water and risk of death from prostate cancer. J Toxicol Environmental Health, Part A 2000;60:17–26.

54. Kristal AR, Stanford JL, Cohen JH, et al. Vitamin and mineral supplement use is associated with reduced risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 1999;8:887–92.

55. Chan JM, Giovannucci E, Andersson S-O, et al. Dairy products, calcium, phosphorus, vitamin D, and risk of prostate cancer (Sweden). Cancer Causes Control 1998;9:559–66.

56. Hartman TJ, Dorgan JF, Virtamo J, et al. Association between serum α-tocopherol and serum androgens and estrogens in older men. Nutr Cancer 1999;35:10–5.

57. Eicholzer M, Stäelin H, Lüdin E, Bernasconi F. Smoking, plasma vitamins C, E, retinol, and carotene, and fatal prostate cancer: seventeen-year follow-up of the Prospective Basel Study. Prostate 1999;38:189–98.

58. Hartman TJ, Albanes D, Pietinen P, et al. The association between baseline vitamin E, selenium, and prostate cancer in the alpha-tocopherol, beta-carotene cancer prevention study. Cancer Epidemiol Biomarkers Prev 1998;7:335–40.

59. Chan JM, Stampfer MJ, Ma J, et al. Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol Biomarkers Prev 1999;8:893–9.

60. Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998;90:440–6.

61. Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998;90:440–6.

62. Studzinski GP, Moore DC. Sunlight––can it prevent as well as cause cancer? Cancer Res 1995;55:4014–22 [review].

63. Van Veldhuizen PJ, Taylor SA, Williamson S, Drees BM. Treatment of vitamin D deficiency in patients with metastatic prostate cancer may improve bone pain and muscle strength. J Urol 2000;163:187–90.

64. Van Veldhuizen PJ, Taylor SA, Williamson S, Drees BM. Treatment of vitamin D deficiency in patients with metastatic prostate cancer may improve bone pain and muscle strength. J Urol 2000;163:187–90.

65. Van Veldhuizen PJ, Taylor SA, Williamson S, Drees BM. Treatment of vitamin D deficiency in patients with metastatic prostate cancer may improve bone pain and muscle strength. J Urol 2000;163:187–90.

66. Woo TCS, Choo R, Jamieson M, et al. Pilot study: potential role of vitamin D (cholecalciferol) in patients with PSA relapse after definitive therapy. Nutr Cancer 2005;51:32–6.

67. Lissoni P, Barni S, Crispino S, et al. Endocrine and immune effects of melatonin therapy in metastatic cancer patients. Eur J Cancer Clin Oncol 1989;25:789–95.

68. Neri B, De Leonardis V, Gemelli MT, et al. Melatonin as biological response modifier in cancer patients. Anticancer Res 1998;18:1329–32.

69. Lissoni P, Barni S, Crispino S, et al. Endocrine and immune effects of melatonin therapy in metastatic cancer patients. Eur J Cancer Clin Oncol 1989;25:789–95.

70. Lissoni P, Barni S, Ardizzoia A, et al. A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms. Cancer 1994;73:699–701.

71. Lissoni P, Barni S, Ardizzoia A, et al. Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin. Oncology 1992;49:336–9.

72. Lissoni P, Paolorossi F, Tancini G, et al. Is there a role for melatonin in the treatment of neoplastic cachexia? Eur J Cancer 1996;32A:1340–3.

73. Lissoni P, Barni S, Tancini G, et al. A randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma. Br J Cancer 1994;69:196–9.

74. Lissoni P, Brivio F, Ardizzoia A, et al. Subcutaneous therapy with low-dose interlekin-2 plus the neurohormone melatonin in metastatic gastric cancer patients with low performance status. Tumori 1993;79:401–4.

75. Aldeghi R, Lissoni P, Barni S, et al. Low-dose interlekin-2 subcutaneous immunotherapy in association with the pineal hormone melatonin as a first-line therapy in locally advanced or metastatic hepatocellular carcinoma. Eur J Cancer 1994;30A:167–70.

76. Lissoni P, Paolorossi F, Tancini G, et al. A phase II study of tamoxifen plus melatonin in metastatic solid tumour patients. Br J Cancer 1996;74:1466–8.

77. Lissoni P, Barni S, Mandalà, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

78. Lissoni P, Brivio O, Brivio F, et al. Adjuvant therapy with the pineal hormone melatonin in patients with lymph node relapse due to malignant melanoma. J Pineal Res 1996;21:239–42.

79. Neri B, Fiorelli C, Moroni F, et al. Modulation of human lymphoblastoid interferon activity by melatonin in metastatic renal cell carcinoma. Cancer 1994;73:315–9.

80. Lissoni P, Cazzanga M, Tancini G, et al. Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone. Eur Urol 1997;31:178–81.

81. Lissoni P, Barni S, Mandalà, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

82. William Judy, personal communication.

83. William Judy, personal communication.

84. Sheu JR, Fu CC, Tsai ML, Chung WJ. Effect of U-995, a potent shark cartilage-derived angiogenesis inhibitor, on anti-angiogenesis and anti-tumor activities. Anticancer Res 1998;18:4435–41.

85. Lane IW, Contreras E Jr. High rate of bioactivity (reduction in gross tumor size) observed in advanced cancer patients treated with shark cartilage material. J Naturopathic Med 1992;3:86–8.

86. Lane IW, Contreras E Jr. High rate of bioactivity (reduction in gross tumor size) observed in advanced cancer patients treated with shark cartilage material. J Naturopathic Med 1992;3:86–8.

87. Milner M. Follow-up of cancer patients using shark cartilage. Alternative Complementary Ther 1996;2:99–109.

88. Miller DR, Anderson GT, Stark JJ, et al. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 1998;16:3649–55.

89. Miller DR, Anderson GT, Stark JJ, et al. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 1998;16:3649–55.

90. Costello LC, Franklin RB. Novel role of zinc in the regulation of prostate citrate metabolism and its implications in prostate cancer. Prostate 1998;35:285–96.

91. Liang JY, Liu YY, Zou J, et al. Inhibitory effect of zinc on human prostatic cell growth. Prostate 1999;40:200–7.

92. DiPaola RS, Zhang H, Lambert GH, et al. Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. New Engl J Med 1998;339:785–91.

93. Kameda H, Small EJ, Reese DM. A phase II study of PC-SPES, an herbal compound, for the treatment of advanced prostate cancer (PCa). Proc Am Soc Clin Oncol 1999;18:320a [abstract].

94. De la Taille A, Hayek OR, Buttyan R, et al. Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: a preliminary investigation on human cell lines and patients. BJU Int 1999;84:845–50.

95. Small EJ, Frohlich MW, Bok R, et al. Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. J Clin Oncol 2000;18:3595–603.

96. De la Taille A, Buttyan R, Hayek O, et al. Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer. J Urology 2000;164:1229–34.

97. Small EJ, Frohlich MW, Bok R, et al. Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. J Clin Oncol 2000;18:3595–603.

98. De la Taille A, Hayek OR, Buttyan R, et al. Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: a preliminary investigation on human cell lines and patients. BJU Int 1999;84:845–50.

99. Small EJ, Frohlich MW, Bok R, et al. Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. J Clin Oncol 2000;18:3595–603.

100. DiPaola RS, Zhang H, Lambert GH, et al. Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. New Engl J Med 1998;339:785–91.

101. DiPaola RS, Zhang H, Lambert GH, et al. Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. New Engl J Med 1998;339:785–91.

102. Small EJ, Frohlich MW, Bok R, et al. Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. J Clin Oncol 2000;18:3595–603.

103. De la Taille A, Buttyan R, Hayek O, et al. Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer. J Urology 2000;164:1229–34.

104. Strum SB. High risk prostate cancer. Prostate Cancer Research Institute Annual Conference, July 31–August 1, 1999, Los Angeles, CA.

105. Kameda H, Small EJ, Reese DM. A phase II study of PC-SPES, an herbal compound, for the treatment of advanced prostate cancer (PCa). Proc Am Soc Clin Oncol 1999;18:320a [abstract].

106. DiPaola RS, Zhang H, Lambert GH, et al. Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. New Engl J Med 1998;339:785–91.

107. Small EJ, Frohlich MW, Bok R, et al. Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. J Clin Oncol 2000;18:3595–603.

108. De la Taille A, Buttyan R, Hayek O, et al. Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer. J Urology 2000;164:1229–34.

109. Weinrobe MC, Montgomery B. Acquired bleeding diathesis in a patient taking PC-SPES. N Engl J Med 2001;345:1213–4 [letter].

110. Weinrobe MC, Montgomery B. Acquired bleeding diathesis in a patient taking PC-SPES. N Engl J Med 2001;345:1213–4 [letter].

111. Miyakoshi H, Aoki T, Mizukoshi M. Acting mechanism of lentinan in human—II. Enhancement of non-specific cell-mediated cytotoxicity as an interferon inducer. Int J Immunopharmacol 1984;6:373–9.

112. Arinaga S, Karimine N, Takamuku K, et al. Enhanced induction of lymphokine activated killer cell after lentinan administration in patients with gastric carcinoma. Int J Immunopharmacol 1992;14:535–9.

113. Matsuoka H, Yano K, Seo Y, et al. Usefulness of lymphocyte subset change as an indicator for predicting survival time and effectiveness of treatment with the immunopotentiator lentinan. Anticancer Res 1995;15:2291–6.

114. Matsuoka H, Seo Y, Wakasugi H, et al. Lentinan potentiates immunity and prolongs the survival time of some patients. Anticancer Res 1997;17:2751–6.

115. Miyakoshi H, Aoki T, Mizukoshi M. Acting mechanism of lentinan in human—II. Enhancement of non-specific cell-mediated cytotoxicity as an interferon inducer. Int J Immunopharmacol 1984;6:373–9.

116. Arinaga S, Karimine N, Takamuku K, et al. Enhanced induction of lymphokine activated killer cell after lentinan administration in patients with gastric carcinoma. Int J Immunopharmacol 1992;14:535–9.

117. Matsuoka H, Yano K, Seo Y, et al. Usefulness of lymphocyte subset change as an indicator for predicting survival time and effectiveness of treatment with the immunopotentiator lentinan. Anticancer Res 1995;15:2291–6.

118. Matsuoka H, Seo Y, Wakasugi H, et al. Lentinan potentiates immunity and prolongs the survival time of some patients. Anticancer Res 1997;17:2751–6.

119. Tari K, Satake I, Nakagomi K, et al. Effect of lentinan for advanced prostate carcinoma. Hinyokika Kiyo (Acta Urol Japon) 1994;40:119–23 [in Japanese].

Learn more about Healthnotes, the company.

Learn more about the authors of Healthnotes.

The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires September 2006.