Calcium is a mineral that is needed for basic blood vessel, muscle, and nerve functions, cell-to-cell signaling, and hormone release. It is the most common mineral in the body. The body stores calcium mainly in bone tissue.

How is calcium given or taken?

The main sources of calcium are in foods and dietary supplements. About one-third of dietary calcium comes from milk and milk products like cheese and yogurt. Vegetable sources include Chinese cabbage, kale, and broccoli. Foods may have calcium added, such as fruit juices and drinks, tofu, and cereals.

Most research about calcium and prostate cancer risk has studied calcium in the diet and not calcium in supplements.

Have any laboratory or animal studies been done using calcium?

In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

Laboratory and animal studies have tested the effects of calcium in prostate cancer. See the Laboratory/Animal/Preclinical Studies section of the health professional version of Prostate Cancer, Nutrition, and Dietary Supplements for information on laboratory and animal studies done using calcium.

Have any studies of calcium been done in people?

Studies of people in many parts of the world have been done to find out if there is a link between dairy products, calcium, and prostate cancer risk.

Population studies

• Population studies of dairy products, dietary calcium, and prostate cancer risk have shown mixed results. Age, body mass index, and other nutrients in dairy products may affect study results.
• More studies are needed to find out if calcium and/or dairy products affect prostate cancer risk.

Clinical trial to prevent prostate cancer

• In a randomized clinical trial reported in 2005, men were given calcium or a placebo for 4 years and were followed for 12 years. During the first 6 years of the study, there were fewer cases of prostate cancer in the calcium group compared to the placebo group. After 10 years, there was no difference in the number of prostate cancers in the calcium group compared to the placebo group.

Combined studies

• A 2005 review found a possible link between an increased risk of prostate cancer and a diet high in dairy products and calcium.
• A review of cohort studies published between 1996 and 2006 found that milk and dairy products in the diet did increase the risk of prostate cancer.
• A 2008 review of 45 observational studies found no link between dairy products and the risk of prostate cancer.
• A 2013 review for the U.S. Preventive Services Task Force found that taking Vitamin D and/or calcium supplements showed no overall effect on rates of cancer or deaths from cancer, including prostate cancer.
• A 2015 review of 32 cohort studies found that high amounts of milk, low-fat milk, cheese, total dietary calcium, and dairy calcium in the diet may increase the risk of prostate cancer. Calcium supplements and non-dairy calcium were not linked with an increased risk of prostate cancer.

Is calcium approved by the U.S. Food and Drug Administration (FDA) for use as a cancer treatment in the United States?

The U.S. Food and Drug Administration has not approved the use of calcium as a treatment for cancer.

The FDA does not approve dietary supplements as safe or effective. The company that makes the dietary supplements is responsible for making sure that they are safe and that the claims on the label are true and do not mislead the consumer. The way that supplements are made is not regulated, so all batches and brands of calcium supplements may not be the same.

Tea comes from the Camellia sinensis plant. The way tea leaves are processed determines the type of tea produced.

Health benefits studied in green tea are thought to be from compounds called polyphenols. Polyphenols are a large group of plant chemicals that include catechins (antioxidants that help protect cells from damage caused by free radicals). Catechins make up most of the polyphenols in green tea.

Catechins in green tea can vary widely, depending on the source of the tea leaves and the way they are processed. This makes most of the chemical factors linked to the health benefits of green tea hard to identify.

Some studies suggest that green tea may protect against cardiovascular disease and some types of cancer, including prostate cancer. There is not enough evidence to show if green tea can prevent or treat prostate cancer.

How is green tea given or taken?

People usually drink green tea or take it as dietary supplements.

Have any laboratory or animal studies been done using green tea?

In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

Laboratory and animal studies have tested the effects of green tea in prostate cancer. See the Laboratory/Animal/Preclinical Studies section of the health professional version of Prostate Cancer, Nutrition, and Dietary Supplements for information on laboratory and animal studies done using green tea.

Have any studies of green tea been done in people?

Population studies and clinical trials have been done to find out if green tea can prevent or treat prostate cancer. Results have been mixed.

Population studies

• Overall, population studies suggest that green tea may help protect against prostate cancer in Asian populations. Prostate cancer deaths in Asia are among the lowest in the world. As more people drink green tea worldwide, including in the United States, more population studies will help find out if green tea or green tea catechins helps protect against prostate cancer.

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Clinical trials to prevent or treat prostate cancer

• In 2 randomized clinical trials in men with high-grade prostatic intraepithelial neoplasia (HGPIN), those treated with green tea catechins had lower rates of prostate cancer than those treated with a placebo. The findings suggest that green tea catechins may lower the risk of prostate cancer in patients at high risk for the disease.
• Patients scheduled to have a radical prostatectomy were given green tea, black tea, or soda five times/day for 5 days. Bioavailable tea polyphenols were found in prostate tissue samples of patients who drank either green tea or black tea. In addition, prostate cancer cells treated with blood taken from patients after they drank tea grew and divided more slowly than cells treated with blood taken from patients before they drank tea.
• Fifty patients scheduled to have a radical prostatectomy were given green tea extract or a placebo daily for 3 to 6 weeks. Patients treated with green tea had lower blood levels of prostate specific antigen (PSA) and insulin-like growth factor -1 (a protein linked with increased risk of prostate cancer) than patients treated with placebo, but these differences were small.
• Patients scheduled to have a radical prostatectomy were given either green tea, black tea, or water every day. In this study, only the men drinking green tea showed a small but notable decrease in PSA levels.
• A small group of hormone-refractory prostate cancer patients were given green tea extract capsules for up to 5 months. The study showed that the green tea treatment was well tolerated by most of the patients. However, all 19 patients had disease progression within 1 to 5 months.
• Patients with androgen-independent prostate cancer that had spread to other places in the body were given powdered green tea extract. Of the forty-two participants, one had a decrease in blood PSA levels which did not last longer than 2 months. Green tea extract was well tolerated by most of the study patients. However, there were 6 reports of serious side effects, including insomnia, confusion, and fatigue. The findings suggest that green tea extract may have limited benefits in patients with advanced prostate cancer.

Have any side effects or risks been reported from green tea?

A trial of oral green tea extract in patients with solid tumors reported that a safe dose was equal to 7-8 cups (120 ml /cup) of tea 3 times a day for 6 months. Side effects were found to be caused by the caffeine.

Clinical trials have reported on the safety of long-term use of green tea compounds to prevent prostate cancer. In a United States trial, men at risk of prostate cancer were given green tea extract or a placebo for 1 year. There were more side effects in the group receiving the green tea extract than in the group receiving the placebo.

In safety studies of patients with prostate cancer, short-term green tea use for up to 90 days was well tolerated. One study found that the most reported side effects of green tea were anorexia, heartburn, nausea, and diarrhea. These were mild except for two reports of severe anorexia and dyspnea. In advanced cancer patients, side effects reported include insomnia, confusion, and fatigue.

Is green tea approved by the U.S. Food and Drug Administration (FDA) for use as a cancer treatment in the United States?

The U.S. Food and Drug Administration has not approved the use of green tea as a treatment for cancer or any other medical condition.

The FDA Division of Drug Oncology Products recommends that green tea extract should be taken with food by patients in clinical trials and that liver function tests should be considered during treatment.

Green tea is available in the United States in food products and dietary supplements. The FDA does not approve dietary supplements as safe or effective. The company that makes the dietary supplements is responsible for making sure that they are safe and that the claims on the label are true and do not mislead the consumer. The way that supplements are made is not regulated, so all batches and brands of green tea supplements may not be the same.

Lycopene is a carotenoid (a natural pigment made by plants). It is red in color and mixes with or dissolves in fats. Lycopene protects plants from light-related stress and helps them use the energy of the sun to make nutrients. Lycopene is found in fruits and vegetables like tomatoes, apricots, guavas, and watermelons.

The main source of lycopene is tomato-based products. Lycopene is more bioavailable (easier for the body to use) in processed tomato products like tomato paste and tomato puree than in raw tomatoes.

Lycopene has been studied for its role in cardiovascular disease and cancer.

How is lycopene given or taken?

Lycopene may be eaten in food or taken in dietary supplements.

Have any laboratory or animal studies been done using lycopene?

In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

Laboratory and animal studies have tested the effects of lycopene in prostate cancer. See the Laboratory/Animal/Preclinical Studies section of the health professional version of Prostate Cancer, Nutrition, and Dietary Supplements for information on laboratory and animal studies done using lycopene.

Have any studies of lycopene been done in people?

Population studies and clinical trials have been done to find out if lycopene can prevent or treat prostate cancer. Clinical trials have shown mixed results.

Population studies

• Population studies in men have found that high amounts of lycopene in the diet are linked with a lower risk of prostate cancer.
• Some studies have shown that lycopene levels in the blood and tissue of patients with cancer are lower than in those who do not have cancer. However, other studies have not shown this.
• Reviews done in 2015 and 2017 analyzed studies of lycopene in the diet and lycopene levels in the blood. Both reviews found that higher lycopene intake was linked with lower prostate cancer risk and that higher blood levels of lycopene were also linked with lower prostate cancer risk.
• A 2006 study done in patients who took part in the National Cancer Institute’s Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial found no link between lycopene and tomatoes in the diet and prostate cancer risk. However, in men with a family history of the disease, higher amounts of lycopene in the diet were linked with a lower risk of prostate cancer.

Sources and types of lycopene, types of diets, genetic risk factors, obesity, tobacco and alcohol use, may play a part in mixed study results. Most research has studied the effects of lycopene on the risk of all prostate cancers, and has not studied effects of lycopene on low-grade compared with high-grade disease.

Clinical trials to prevent or treat early prostate cancer

• Men with benign prostate hyperplasia (BPH) or prostate cancer were given tomato sauce dishes for 3 weeks before surgery to remove the prostate. The study found that they had lower prostate specific antigen (PSA) levels and more cancer cell death found in the prostate when examined after surgery than a similar group of patients who did not receive the tomato sauce dishes.
• A study of 40 men with high-grade prostatic intraepithelial neoplasia (HGPIN) who took lycopene supplements for 2 years had a greater decrease in PSA levels than those who did not. During follow-up, adenocarcinomas were diagnosed more often in patients who did not take the supplements. The study showed that lycopene may be useful to prevent HGPIN from developing into prostate cancer.
• In another study of men at high risk of prostate cancer (such as men with HGPIN), those who took a daily multivitamin with no lycopene and those who took the same multivitamin plus lycopene daily for 4 months showed no difference in PSA levels.

Clinical trials to treat prostate cancer

• Men with prostate cancer that had not spread were given lycopene supplements for 3 weeks before surgery to remove the prostate. Those who received lycopene supplements had smaller tumors and lower PSA levels than those who did not. Another study of men with prostate cancer that had not spread showed that men who took lycopene supplements for 1 year had lower PSA velocity (a measure of how fast PSA levels in the blood increase over time) after treatment.
• Men who had biochemical relapse of prostate cancer (a rise in the blood level of PSA after treatment with surgery or radiation) were given different doses of lycopene supplements for 1 year. Results showed that lycopene was safe and had no side effects, but did not change PSA levels.
• A study in 46 men with androgen-independent prostate cancer (tumors that do not need androgen to grow) who took lycopene in either tomato paste or tomato juice daily for 4 months showed that only one patient had a lower PSA level. Several men reported diarrhea, nausea, and bloating after having tomato paste or tomato juice.

There are other trials of combination therapies that include lycopene in the Combination Therapies section of this summary.

Have any side effects or risks been reported from lycopene?

Lycopene has been given in many clinical trials with very few side effects. Patients have reported few side effects, such as gastrointestinal symptoms (e.g. diarrhea, nausea and vomiting, bloating, gassiness and stomach irritation). In one study, symptoms went away when lycopene was taken with meals.

Is lycopene approved by the U.S. Food and Drug Administration (FDA) for use to prevent or treat cancer in the United States?

The U.S. Food and Drug Administration has not approved the use of lycopene as a treatment for cancer or any other medical condition.

Lycopene is available in the United States in food products and dietary supplements. The FDA does not approve dietary supplements as safe or effective. The company that makes the dietary supplements is responsible for making sure that they are safe and that the claims on the label are true and do not mislead the consumer. The way that supplements are made is not regulated, so all batches and brands of lycopene supplements may not be the same.

Pectin is a type of polysaccharide (a carbohydrate with many small sugar molecules that are chemically linked). Pectin is found in the cell walls of most plants and has gel-like qualities that are useful in making many types of food and medicine.

Citrus pectin is found in the peel and pulp of citrus fruits such as oranges, grapefruit, lemons, and limes. Citrus pectin can be modified (changed) with high pH and heat to break its molecules into smaller pieces. Modified citrus pectin (also called MCP) can be digested and absorbed by the body.

How is MCP given or taken?

MCP may be taken by mouth in powder or capsule form.

Have any laboratory or animal studies been done using MCP?

In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

Laboratory and animal studies have tested the effects of MCP in prostate cancer. See the Laboratory/Animal/Preclinical Studies section of the health professional version of Prostate Cancer, Nutrition, and Dietary Supplements for information on laboratory and animal studies done using MCP.

Have any studies of MCP been done in people?

Few studies have been done in prostate cancer patients.

In a study of patients with advanced solid tumors, including prostate cancer, MCP powder in water was given 3 times/ day for at least 8 weeks. The study reported improved overall health, fatigue, pain, and insomnia. About one-fourth of patients showed stable disease after 8 weeks of treatment and fewer had stable disease after 24 weeks.

In a study of the effect of MCP on prostate-specific antigen (PSA) doubling time (how long it takes PSA levels in the blood to increase by 100 percent), prostate cancer patients who had rising PSA levels were given MCP capsules 3 times/ day for 12 months. After treatment, 7 out of 10 patients showed a slowing of PSA doubling time.

Have any side effects or risks been reported from MCP?

Two studies of MCP showed that most patients had few side effects. Itching, stomach upset, and gassiness were reported in one study. In another study, 3 patients had abdominal cramps and diarrhea that went away when their treatment was stopped.

Is MCP approved by the U.S. Food and Drug Administration (FDA) for use to prevent or treat cancer in the United States?

The U.S. Food and Drug Administration has not approved the use of MCP as a treatment for cancer or any other medical condition.

MCP is available in the United States in food products and dietary supplements. The FDA does not approve dietary supplements as safe or effective. The company that makes the dietary supplements is responsible for making sure that they are safe and that the claims on the label are true and do not mislead the consumer. The way that supplements are made is not regulated, so all batches and brands of MCP supplements may not be the same.

The pomegranate (Punica granatum L.) is a fruit grown in Asia and in the Mediterranean, Southeast Asia, East Indies, Africa, and the United States. Pomegranate has been used as medicine for hundreds of years.

The pomegranate is made up of the following:

• The peel, which makes up half the fruit and contains polyphenols and minerals.
• The seeds.
• The aril (outer layer surrounding the seeds), which contains phenolics and flavonoids including anthocyanins, which give the pomegranate fruit and juice their red color.

How is pomegranate given or taken?

Pomegranate fruit and juice may be eaten in the diet or taken in dietary supplements.

Have any laboratory or animal studies been done using pomegranate?

In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

Laboratory and animal studies have tested the effects of pomegranate in prostate cancer. See the Laboratory/Animal/Preclinical Studies section of the health professional version of Prostate Cancer, Nutrition, and Dietary Supplements for information on laboratory and animal studies done using pomegranate.

Have any studies of pomegranate been done in people?

Three clinical trials studied the effect of pomegranate products on prostate-specific antigen doubling time (PSADT) in patients with recurrent prostate cancer who had rising PSA levels after surgery or radiation therapy.

• In a phase II study reported in 2006, 48 patients were given pomegranate juice daily for up to 33 months. Those who drank pomegranate juice had a slowing of PSA doubling time (how long it takes PSA levels in the blood to increase by 100%).
• In a phase II study reported in 2013, patients were given 2 different doses of pomegranate extract for up to 18 months. Both doses of pomegranate extract were related to a slowing of PSA doubling time.
• In a phase III placebo-controlled clinical trial reported in 2015, 183 patients were given either pomegranate juice, pomegranate extract, or a placebo. The study found no difference in the PSA doubling time for the 3 groups.

These studies differed in PSA levels of the patients enrolled and whether there was a placebo group. All three trials found that pomegranate extract was safe. Further studies may be able to show if patients with certain genetic markers will benefit from pomegranate products.

Have any side effects or risks been reported from pomegranate?

Two studies of pomegranate juice in either prostate cancer patients or patients with erectile dysfunction reported no serious side effects.

Is there any reason people should avoid pomegranate juice?

Some pomegranate products may contain added sugar. Certain groups, such as the American Institute for Cancer Research (AICR), recommend avoiding sugary drinks. For more information, see the AICR website.

Is pomegranate approved by the U.S. Food and Drug Administration (FDA) for use to prevent or treat cancer in the United States?

The U.S. Food and Drug Administration has not approved the use of pomegranate as a treatment for cancer or any other medical condition.

Pomegranate is available in the United States in food products and dietary supplements. The FDA does not approve dietary supplements as safe or effective. The company that makes the dietary supplements is responsible for making sure that they are safe and that the claims on the label are true and do not mislead the consumer. The way that supplements are made is not regulated, so all batches and brands of pomegranate supplements may not be the same.

Selenium is a trace mineral (a nutrient that is essential to humans in tiny amounts). Selenium is found in certain proteins that are active in many body functions, including reproduction and immunity. Food sources of selenium include meat, vegetables, and nuts. The amount of selenium found in the food depends on the amount of selenium in the soil where the food grows. Selenium is stored in the thyroid gland, liver, pancreas, pituitary gland, and kidneys.

Selenium may play a role in many diseases, including cancer. Results of the large National Cancer Institute -sponsored Selenium and Vitamin E Cancer Prevention Trial (SELECT) warn men with prostate cancer against taking selenium supplements above the recommended dose.

How is selenium given or taken?

Selenium may be eaten in food or taken in dietary supplements.

Have any laboratory or animal studies been done using selenium?

In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

Laboratory and animal studies have tested the effects of selenium in prostate cancer. See the Laboratory/Animal/Preclinical Studies section of the health professional version of Prostate Cancer, Nutrition, and Dietary Supplements for information on laboratory and animal studies done using selenium.

Have any studies of selenium been done in people?

Population studies and clinical trials have been done to find out if selenium can prevent or treat prostate cancer. Studies have shown mixed results.

Population studies

• One study tracking men for up to 10 years found that those who had high levels of selenium in their blood had a lower risk of prostate cancer. However, a 2009 study of prostate cancer patients found that men with high selenium levels were at greater risk of being diagnosed with aggressive prostate cancer. These differences may be due to genetic factors.

Clinical trials to prevent or treat prostate cancer

• In a 2013 study, men at high risk for prostate cancer were given either daily doses of high-selenium yeast or a placebo for up to 5 years. There were no differences in prostate cancer rates or PSA velocity in men who took the selenium supplement compared to those who took the placebo.
• In an earlier study, men with high-grade prostatic intraepithelial neoplasia (HGPIN) were given either a selenium supplement or a placebo for 3 years or until they were diagnosed with prostate cancer. The results suggested that selenium supplements had no effect on prostate cancer risk.
• Sixty men were given either a selenium supplement or a placebo for 6 weeks. Blood samples were collected at the start and the end of the study. Compared to the placebo group, men who received selenium supplements showed higher activity of two selenium enzymes in their blood and lower levels of PSA at the end of the study.
• The Health Professionals Follow-Up Study included 4,459 men diagnosed with prostate cancer that had not spread. The study found that taking selenium supplements after diagnosis may increase the risk of death from prostate cancer and recommended that men with prostate cancer use caution in taking selenium supplements.
• A review of fifteen studies combined found that blood selenium levels were not linked with risk for prostate cancer overall, but men with high selenium levels in the blood had a lower risk of aggressive prostate cancer. In addition, higher levels of selenium measured in toenails were linked with lower risk of both aggressive and nonaggressive prostate cancer.

The Selenium and Vitamin E Cancer Prevention Trial (SELECT)

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a large clinical trial begun by the National Institutes of Health in 2001 to study the effects of selenium and/or vitamin E on the development of prostate cancer. Over 35,000 men, aged 50 years and older, were randomly assigned to receive one of the following combinations daily for 7-12 years:

• Vitamin E and a placebo.
• Selenium and a placebo.
• Vitamin E and selenium.
• Two placebos.

First results of SELECT reported in 2009 found no difference in the rate of prostate cancer among the 4 groups. In the Vitamin E alone group, there was a slight increase in the rate of prostate cancer and in the selenium alone group, there was a slight increase in the rate of diabetes. Even though these changes were not clearly shown to be due to the supplement, the men in the study were advised to stop taking the study supplements.

Updated results of SELECT in 2011 showed that selenium supplements had no effect on prostate cancer risk; however, men taking vitamin E alone had a 17% increase in prostate cancer risk compared to men in the placebo group.

In 2014, further results of SELECT showed that selenium supplements in men with low selenium levels at the start of the trial had no effect on prostate cancer risk; however, selenium supplements in men who had high levels of selenium at the start of the trial increased the risk of high-grade prostate cancer.

Several factors may have affected study results, including the dose of vitamin E and the form of selenium used. The authors concluded that men should avoid selenium at doses that are higher than the recommended dietary intake.

A cohort study of 1,434 men in SELECT suggested that changes in certain genes which control the ways selenium and vitamin E are used by the body may have an effect on the risk of prostate cancer.

Are there any risks in taking selenium supplements, and have any side effects been reported?

Selenium supplements have been well tolerated in many clinical trials. In two published trials, there were no differences reported in adverse effects between placebo or treatment groups. However, in the SELECT trial, the use of selenium supplements was linked with a slight increase in the rate of diabetes mellitus.

Is selenium approved by the U.S. Food and Drug Administration (FDA) for use as a cancer treatment in the United States?

The U.S. Food and Drug Administration has not approved the use of selenium supplements for the treatment or prevention of cancer.

Selenium is available in the United States in food products and dietary supplements. The FDA does not approve dietary supplements as safe or effective. The company that makes the dietary supplements is responsible for making sure that they are safe and that the claims on the label are true and do not mislead the consumer. The way that supplements are made is not regulated, so all batches and brands of selenium supplements may not be the same.

The soybean plant has been grown in Asia for food for hundreds of years. The soybean can be made into products, such as soy milk, miso, tofu, soy flour, and oil.

Soy foods contain phytochemicals that may have health benefits. Isoflavones are the most widely studied compounds in soy. Major isoflavones in the soybean include genistein (which may be the most bioactive isoflavone), daidzein, and glycitein.

Isoflavones are phytoestrogens (estrogen -like substances found in plants) that attach to estrogen receptors in cells. Genistein has been shown to affect many pathways in prostate cancer cells involved in the growth and spread of cancer.

How is soy given or taken?

Soy may be eaten in food or taken in dietary supplements.

Have any laboratory or animal studies been done using soy?

In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

Laboratory and animal studies have tested the effects of soy in prostate cancer. See the Laboratory/Animal/Preclinical Studies section of the health professional version of Prostate Cancer, Nutrition, and Dietary Supplements for information on laboratory and animal studies done using soy.

Have any studies of soy been done in people?

Population studies and clinical trials have been done to find out if soy can prevent or treat prostate cancer. Studies have shown mixed results.

Population studies

• A 2009 review of many studies combined showed that men eating large amounts of nonfermented soy foods (for example, tofu and soybean milk) had a lower risk of prostate cancer. Eating large amounts of fermented foods (for example, miso) was not found to affect the risk of prostate cancer.
• A 2013 review showed that PSA levels and sex hormone levels were not different in men treated with soy, compared with men who were not treated with soy.

Clinical trials to prevent or treat prostate cancer

• In a study of Japanese men who had a prostate biopsy but who did not have cancer, some received a daily supplement of soy isoflavones and curcumin, while others received a placebo. After 6 months, there were no differences in PSA levels between the supplement group and the placebo group. However, among patients with higher PSA levels at the start, those who received soy had decreases in PSA levels compared to patients in the placebo group.
• Men at risk for prostate cancer or with low-grade prostate cancer were given either soy protein, alcohol -washed soy protein (which is lower in isoflavones), or milk protein (which has no isoflavones) for 6 months. PSA levels did not differ among the groups at 3 months or 6 months. Fewer cases of prostate cancer were found after 6 months in men who had either type of soy protein than in men who had milk protein.
• In a trial of genistein (a major isoflavone), prostate cancer patients scheduled for radical prostatectomy received either a placebo or genistein for 3-6 weeks before surgery. PSA levels in patients who received genistein decreased while PSA levels in those who received the placebo increased.
• In a trial of soy isoflavone, prostate cancer patients scheduled for prostatectomy received either isoflavone capsules or a placebo for up to 6 weeks before surgery. There was no difference in PSA, testosterone, or cholesterol level changes between the two groups.
• A trial of a soy protein supplement studied patients with early-stage prostate cancer. Those who received the supplement for 12 weeks had greater decreases in PSA and testosterone levels than those who received placebo.
• Trials of whole soy were done in men scheduled for surgery to remove the prostate. In one study, patients given soy supplements for 2 weeks before surgery showed much higher levels of isoflavones in prostate tissue than in blood. In another study, patients who ate high-phytoestrogen bread (containing soy or soy and linseed) had greater decreases in PSA levels than those who ate wheat bread.
• Two trials of a soy isoflavone supplement were done in prostate cancer patients receiving antiandrogen therapy. Side effects of antiandrogen therapy may include sexual dysfunction, lower quality of life, and changes in mental functioning. In both studies, men who received the isoflavone supplement for 12 weeks showed no improvement in side effects of antiandrogen therapy compared to men who received a placebo.

Have any side effects or risks been reported from soy?

Soy products and isoflavones have been taken by prostate cancer patients with very few side effects in many clinical trials. The most commonly reported side effects were minor gastrointestinal symptoms.

Is soy approved by the U.S. Food and Drug Administration (FDA) for use to prevent or treat cancer in the United States?

The U.S. Food and Drug Administration has not approved the use of soy as a treatment for cancer or any other medical condition.

Soy is available in the United States in food products and dietary supplements. The FDA does not approve dietary supplements as safe or effective. The company that makes the dietary supplements is responsible for making sure that they are safe and that the claims on the label are true and do not mislead the consumer. The way that supplements are made is not regulated, so all batches and brands of soy supplements may not be the same.

Vitamin D is a fat-soluble vitamin found in fatty fish, fish liver oil, eggs, and enriched dairy products.

Vitamin D has many actions in the body, including the following:

• Helps absorb calcium from food in the small intestine.
• Improves muscle strength and immune system function.
• Lowers inflammation.
• Maintains levels of calcium and phosphate in the blood.

Vitamin D is needed for bone growth and protects against osteoporosis in adults. Vitamin D level is usually checked by measuring the amount of 25-hydroxyvitamin D in the blood.

How is vitamin D given or taken?

Vitamin D is made naturally by the body when exposed to sunlight. Vitamin D may also be eaten in food or taken in dietary supplements.

Have any laboratory or animal studies been done using vitamin D?

In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

Laboratory and animal studies have tested the effects of vitamin D in prostate cancer. See the Laboratory/Animal/Preclinical Studies section of the health professional version of Prostate Cancer, Nutrition, and Dietary Supplements for information on laboratory and animal studies done using vitamin D.

Have any studies of vitamin D been done in people?

Many population studies and clinical trials have been done to find out if vitamin D may be useful to prevent or treat prostate cancer. Studies have shown mixed results.

Population studies

• Vitamin D levels in patients with prostate cancer that had not spread were checked every year for 5 years. Throughout the study, lack of vitamin D was found in these patients.
• Another study in patients with prostate cancer suggested that medium or high levels of vitamin D in the blood may be linked with better outcomes than lower levels. These findings show that vitamin D levels may play a part in whether or not the disease will get worse.
• One thousand patients with prostate cancer and 1000 control patients in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study were followed for up to 20 years. Results suggest that men with higher blood levels of vitamin D had a greater risk of developing prostate cancer than men with lower vitamin D levels.
• In a case-cohort analysis from the Selenium and Vitamin E Cancer Prevention Trial (SELECT), men who had moderate blood levels of vitamin D were found to have a lower risk of aggressive prostate cancer than men who had either lower or higher levels of vitamin D.
• Vitamin D from sunlight exposure has been studied for possible effects on prostate cancer rates. A 2006 study found that PSA levels rise at a slower rate during the spring and summer compared to other times of the year, suggesting this may be due to higher vitamin D levels during those months. Another study found that while men with low levels of sun exposure had increased risk of all prostate cancers, those with prostate cancer who had less sun exposure showed lower risk of advanced disease.
• A study of patterns of deaths in the United States from 1950 to 1994 showed that higher death rates from prostate cancer occurred in parts of the country with lower levels of UV radiation from sunlight. These findings support the theory that lack of vitamin D increases the risk for prostate cancer.

Combined population studies

• A 2008 review of 45 observational studies found no link between intake of vitamin D and prostate cancer risk.
• A 2011 review of 25 studies found no link between either vitamin D in the diet or blood levels of vitamin D and the risk of prostate cancer.
• A 2014 review of 21 studies found that high levels of vitamin D may be linked with a higher risk of prostate cancer. Many factors may affect these findings, since some studies propose men from higher income groups may have higher vitamin D levels and are more likely to get PSA testing, leading to higher rates of reported prostate cancer.

Clinical trials to treat prostate cancer

• A clinical trial treated patients with prostate cancer that had recurred (come back) with calcitriol (the active form of vitamin D) and naproxen for 1 year. Results showed that calcitriol and naproxen slowed the rate of rising PSA levels in study patients, suggesting it may slow disease progression.
• In a 2010 study, patients with prostate cancer that did not respond to hormone therapy were treated with calcitriol and dexamethasone. The results showed no effect on PSA levels.
• In a 2009 study, patients with locally advanced or metastatic prostate cancer were treated with vitamin D. The study reported that one in every 5 patients who took vitamin D had improved PSA levels, suggesting that vitamin D may be an effective therapy for patients with advanced prostate cancer.

Have any side effects or risks been reported from vitamin D?

Vitamin D can be toxic when taken at high doses over many years. Taking high levels of Vitamin D can cause too much calcium to be absorbed in the intestines, leading to rapid increases in blood calcium levels. This condition is called hypercalcemia.

In a group of 26 studies, Vitamin D was reviewed for safety, how well it works, and whether it interacts with drugs used to treat prostate cancer and other tumors. The reviewers found the risk of drug interactions to be low.

A number of studies looked at the safety of high-dose vitamin D and how well it works with chemotherapy (docetaxel) to treat men with androgen-independent prostate cancer. No high levels of toxicity were found compared to treatment with docetaxel alone.

Is vitamin D approved by the U.S. Food and Drug Administration (FDA) for use as a cancer treatment in the United States?

The U.S. Food and Drug Administration has not approved the use of vitamin D as a treatment for cancer.

Vitamin D is available in the United States in food products and dietary supplements. The FDA does not approve dietary supplements as safe or effective. The company that makes the dietary supplements is responsible for making sure that they are safe and that the claims on the label are true and do not mislead the consumer. The way that supplements are made is not regulated, so all batches and brands of vitamin D supplements may not be the same.

Vitamin E is a nutrient that may protect against chronic diseases such as cardiovascular disease. Vitamin E is being studied in the prevention of some types of cancer.

There are eight forms of vitamin E: four tocopherols (alpha-, beta-, gamma-, and sigma-) and four tocotrienols (alpha-, beta-, gamma-, and sigma-). Alpha-tocopherol, the form of vitamin E found in dietary supplements, is found in greater amounts in the body and is the most active. Most vitamin E in the diet comes from gamma-tocopherol. Food sources of vitamin E include vegetable oils, nuts, and egg yolks.

Vitamin E is an antioxidant that protects cell membranes from damage caused by free radicals. Vitamin E also has other functions involved in cell signaling pathways and gene expression.

How is vitamin E given or taken?

Vitamin E may be eaten in food or taken in dietary supplements.

Have any studies of vitamin E been done in people?

Population studies and clinical trials have been done to find out if vitamin E may prevent or treat prostate cancer. Results have been mixed.

Population studies

• The National Institutes of Health -American Association of Retired Persons (NIH-AARP) Diet and Healthy Study studied whether vitamin E in supplements and in the diet of volunteers may prevent prostate cancer. After 5 years, no link between vitamin E supplements and prostate cancer risk was found. However, a lower risk of advanced prostate cancer was found in those who took high amounts of gamma-tocopherol.
• In a 2010 study that measured blood levels of trace elements and vitamin E, those who had prostate cancer had lower blood levels of vitamin E than those who did not have prostate cancer. In addition, those who had higher PSA levels had lower levels of vitamin E in their blood.
• In a review of combined studies with 370,000 men from several countries, higher blood levels of alpha-tocopherol were linked with a lower risk of prostate cancer in all patients.

Clinical trials to prevent or treat prostate cancer

• In the Physicians’ Health Study II, men received either vitamin E supplements and/or vitamin C supplements and were followed for about 8 years. The overall rates of prostate cancer were similar in the men who received vitamin E supplements and in those who did not, suggesting that vitamin E may not prevent prostate cancer. Vitamin E did not affect total cancer or death rates.
• The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study (ATBC) trial measured blood levels of alpha-tocopherol and dietary intake of vitamin E in men who were followed for up to 19 years. Results showed no link between vitamin E in the diet and prostate cancer risk, but showed that higher levels of alpha-tocopherol in the blood may be linked with a lower risk for developing advanced prostate cancer.
• Men in the ATBC trial who developed prostate cancer were studied to find out if serum alpha-tocopherol levels affected survival time. Higher serum alpha-tocopherol levels, at both time of diagnosis and at the 3-year time point, were linked with improved prostate cancer survival.
• A 2011 study of men who took part in The Carotene and Retinol Efficacy Trial (CARET) found that, among those who were current smokers, higher levels of serum alpha-tocopherols and gamma-tocopherols were linked with lower risk of aggressive prostate cancer.

The Selenium and Vitamin E Cancer Prevention Trial (SELECT)

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a large clinical trial to study the effects of selenium and/or vitamin E on the development of prostate cancer. Over 35,000 men, aged 50 years and older, were randomly assigned to receive one of the following combinations daily for 7-12 years:

• Vitamin E and a placebo.
• Selenium and a placebo.
• Vitamin E and selenium.
• Two placebos.

First SELECT results reported in 2009 found no differences in rates of prostate cancer among the 4 groups. In the Vitamin E alone group, there was an increase in the rate of prostate cancer and in the selenium alone group, there was an increase in the rate of diabetes. Based on those findings, the men in the study were advised to stop taking the study supplements.

Updated SELECT results in 2011 showed that selenium supplements had no effect on prostate cancer risk, but men taking vitamin E alone, had a 17% increase in prostate cancer risk compared to men in the placebo group.

In 2014, further SELECT results showed that vitamin E supplements alone had no effect on prostate cancer risk in men with high levels of selenium at the start of the trial, but vitamin E supplements increased the risk of low-grade and high-grade prostate cancer in men with lower levels of selenium at the start of the trial.

Several factors may have affected study results, including the dose of vitamin E and the form of selenium used.

A cohort study of 1,434 men in SELECT suggested that variations in certain genes which control the ways selenium and vitamin E are used by the body may have an effect on the risk of prostate cancer, including high-grade prostate cancer.

Have any side effects or risks been reported from vitamin E?

In the Physicians’ Health Study II, there were no different rates of gastrointestinal symptoms, fatigue, drowsiness, skin discoloration or rashes, or migraine between men who took vitamin E and those who took a placebo. However, there was a higher number of hemorrhagic strokes in men who took vitamin E than in men who took a placebo. In the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group, there was also an increase in hemorrhagic strokes among men in the group that took vitamin E.

Earlier results from the SELECT trial showed no different rates of less adverse effects (such as hair loss, inflamed skin, and nausea) in the groups that took vitamin E compared to the other treatment groups. Later follow-up showed an increased risk of prostate cancer among men in the vitamin E alone group.

Is vitamin E approved by the U.S. Food and Drug Administration (FDA) for use as a cancer treatment in the United States?

The U.S. Food and Drug Administration has not approved the use of vitamin E as a treatment for cancer.

Alpha-tocopherols are deemed Generally Recognized as Safe by the FDA.

Vitamin E is available in the United States in food products and dietary supplements. The FDA does not approve dietary supplements as safe or effective. The company that makes the dietary supplements is responsible for making sure that they are safe and that the claims on the label are true and do not mislead the consumer. The way that supplements are made is not regulated, so all batches and brands of vitamin E supplements may not be the same.

Zyflamend is a dietary supplement that contains extracts of 10 different herbs in olive oil:

• Rosemary.
• Turmeric.
• Ginger.
• Holy basil.
• Green tea.
• Hu zhang (Polygonum cuspidatum).
• Chinese goldthread.
• Barberry.
• Oregano.
• Baikal skullcap.

The extracts found in Zyflamend have anti-inflammatory activity and possible anticancer benefits. There is limited evidence about how Zyflamend may act against tumor growth. Zyflamend has been shown to get in the way of the activity of COX-1 and COX-2 enzymes, which promote inflammation and possibly cancer. Zyflamend may also act against the NF-kappa B and lipoxygenase (LOX) families of proteins that stimulate tumor growth.

How is Zyflamend given or taken?

Zyflamend is taken as a dietary supplement in capsule form.

Have any laboratory or animal studies been done using Zyflamend?

In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

Laboratory and animal studies have tested the effects of Zyflamend in prostate cancer. See the Laboratory/Animal/Preclinical Studies section of the health professional version of Prostate Cancer, Nutrition, and Dietary Supplements for information on laboratory and animal studies done using Zyflamend.

Have any studies of Zyflamend been done in people?

A report of one patient with high-grade prostatic intraepithelial neoplasia (HGPIN) who received Zyflamend 3 times/day for 18 months showed that PSA levels were not affected. However, at the end of 18 months of treatment, repeat biopsies of the prostate did not show HGPIN or cancer.

In a phase I safety study of Zyflamend, patients with HGPIN took Zyflamend (780 mg) 3 times/day for 18 months with additional dietary supplements (probiotic supplement, multivitamin, green and white tea extract, Baikal skullcap, docosahexaenoic acid, holy basil, and turmeric). Zyflamend and the added dietary supplements were well tolerated and there were no serious side effects. At the end of 18 months of treatment, more than half of patients had benign biopsy results, about one-fourth had HGPIN, and about one in 8 had prostate cancer.

Have any side effects or risks been reported from Zyflamend?

No toxicity or serious side effects have been reported. Some of the patients had mild heartburn that went away when Zyflamend was taken with food.

Is Zyflamend approved by the U.S. Food and Drug Administration (FDA) for use as a cancer treatment in the United States?

The U.S. Food and Drug Administration has not approved the use of Zyflamend as a treatment for cancer or any other medical condition.

Zyflamend is available in the United States as a dietary supplement. The FDA does not approve dietary supplements as safe or effective. The company that makes the dietary supplements is responsible for making sure that they are safe and that the claims on the label are true and do not mislead the consumer. The way that supplements are made is not regulated, so all batches of Zyflamend supplements may not be the same.