What is lycopene?

Lycopene is a carotenoid (a natural pigment made by plants). Lycopene protects plants from 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 in the American diet 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.

Eating carotenoids, including lycopene, along with dietary fat may help the body absorb them. For example, one study showed that more lycopene was absorbed from diced tomatoes cooked with olive oil than diced tomatoes cooked without olive oil.

Lycopene in the diet may affect antioxidant activity and communication between cells . Laboratory and animal studies have shown that lycopene may help lower the risk of prostate , skin , breast , lung , and liver cancers . However, clinical trials of whether lycopene lowers cancer risk have shown mixed results.

How is lycopene administered or consumed?

Lycopene may be consumed in the diet or taken in dietary supplements.

Have any preclinical (laboratory or animal) studies been conducted using lycopene?

Laboratory research and animal studies have been done to find out if lycopene may be useful in preventing or treating prostate cancer.

Studies of lycopene in the laboratory have shown the following:

• Prostate cancercellstreated with lycopene had changes in their cell division cycle, leading to less cancer cell growth.
• In prostate cancer cells treated with lycopene,cholesterollevels were lower, leading to less cancer cell growth & more cancer cell damage.
• Treating prostate cancer cells with lycopene may change the wayandrogen (malehormone) is taken up and used in the cells, causing less cancer cell growth.
• Combining lycopene with standard cancerdrugs may help stop the growth of different types of prostate cancer cells more than when drugs are used alone. Used together with a cancer drug, lycopene may block the wayinsulin-like growth factor(IGF) is taken up by the cells, causing less cancer cell growth.

Studies of animal models of prostate cancer treated with lycopene have shown the following:

• Strains of mice created to develop prostate cancer that acts like human cancer were fed a diet with either lycopene beadlets or tomato paste. Mice on the lycopene beadlet diet had a greater decrease in prostate cancer rates than mice on the tomato paste diet. This suggests that lycopene might have more cancer protective effects than tomato paste.
• Combining lycopene with a substance found in dried tomatoes (FruHis) slowed the growth of prostate cancer cells in rats more than either lycopene or FruHis alone.
• A study of miceinjected with human prostate cancer cells showed that mice treated with either lycopene orbeta carotene supplements had lesstumorgrowth.
• A study of mice injected with human prostate cancer cells and treated with a certainchemotherapydrug, lycopene, or both showed that those treated with chemotherapy and lycopene lived longer and had smaller tumors than those treated with chemotherapy alone.

Have any population studies or clinical trials (research studies with people) of lycopene been conducted?

Several population studies and clinical trials have been done to find out if lycopene may be useful in preventing or treating prostate cancer.

Population studies

Population studies look for risk factors and ways to control disease in large groups of people. Population studies of prostate cancer risk have shown the following mixed results:

• Studies of large groups of men have not found a link between levels of lycopene in thebloodand the risk of developing prostate cancer.
• Several studies found that men who ate more tomatoes had a slightly lower risk of prostate cancer.
• A study found no link between lycopene and tomatoes in the diet and prostate cancer risk in the overall population. However, in men with afamily historyof the disease, higher amounts of lycopene in the diet were linked with a lower risk of prostate cancer. Another study in the same group of men found no difference in blood levels of lycopene between healthy men and men who developed prostate cancer.

Clinical trials of preventing prostate cancer

Clinical trials designed to study whether lycopene is useful in preventing prostate cancer have shown the following:

• Men withbenign prostate hyperplasia (BPH) or prostate cancer were given tomato sauce dishes for 3 weeks before scheduledsurgery to remove the prostate. The study found that they had lowerprostate 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.
• Men withhigh-grade prostatic intraepithelial neoplasia(HGPIN) who took lycopene supplements for 2 years had a greater decrease in PSA levels and fewer cases of prostate cancer than those who did not. This indicated that lycopene may be useful in preventing 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 (30 mg/ day) for 4 months showed no difference in PSA levels.

Clinical trials of treating prostate cancer

Clinical trials designed to study whether lycopene is useful in treating prostate cancer have shown the following:

• Men with prostate cancer that had not spread were given lycopene supplements (30mg/ day) 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. This study suggests that lycopene may be helpful in treating prostate cancer. Another study of men with prostate cancer that had not spread showed that men who took lycopene supplements (10mg/ day) had lowerPSA velocity(a measure of how fast PSA levels in the blood increase over time) after treatment.
• Men who hadbiochemical relapse of prostate cancer (a rise in the blood level of PSA after treatment with surgery orradiation ) were given differentdoses of lycopene supplements (ranging from 15 mg/ day to 120 mg/day) for 1 year. Study results showed that lycopene seemed safe & had noside effects , but did not change PSA levels in biochemicallyrelapsedprostate cancer.
• Men withhormone-refractory prostate cancer (HRPC) (tumors that do notrespond to treatment withhormones) were given lycopene supplements for periods of 3 or 6 months in 2 different studies. These studies showed mixed results in lowering PSA levels in men with HRPC.
• Men withandrogen-independentprostate cancer (tumors that do not need androgen to grow) consumed lycopene in either tomato paste or tomato juice daily for 4 months. Study results showed that lycopene may not be effective in lowering PSA levels in androgen-independent cancer.

Have any side effects or risks been reported from lycopene?

Lycopene has been consumed by prostate cancer patients with very few side effects in many clinical trials. Doses ranging from 10 to 120 mg/ day have caused only occasional 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 . Because dietary supplements are regulated as foods, not as drugs, FDA approval is not required unless specific claims about disease prevention or treatment are made. An FDA review in 2007 found that there was not enough evidence to allow a claim that lycopene helps lower cancer risk.

What is modified citrus pectin?

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 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 administered or consumed?

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

Have any preclinical (laboratory or animal) studies been conducted using MCP?

A study in prostate cancer cells compared 3 different kinds of pectin: citrus pectin, PectaSol (a dietary supplement with MCP), and fractionated pectin powder. Prostate cancer cells treated with the pectin powder had more damage than those treated with citrus pectin or PectaSol. However, when citrus pectin was modified by heating it, it caused the same amount of damage to prostate cancer cells as the pectin powder.

Only a few studies have reported the effects of MCP in animal models of cancer , including one prostate cancer study. Rats injected with prostate cancer cells and treated with MCP showed less spread of the cancer to the lungs but no effect on tumor growth at the original cancer site.

Have any population studies or clinical trials (research studies with people) of MCP been conducted?

A few studies in prostate cancer patients suggest that MCP may have some anticancer benefits.

In a study of patients with advanced solid tumors , including prostate cancers, MCP powder in water was given 3 times/ day for at least 8 weeks. The study showed some quality of life improvements in physical functioning, overall health, fatigue , pain, and insomnia . About one-fourth of patients showed stable disease after 8 weeks of treatment and a smaller number had stable disease for more than 24 weeks. Since the study did not include a group of patients who did not receive MCP for comparison, it was not designed to be able to tell if any of these changes were due to the addition of MCP. The primary goal of the study was to determine if MCP would be well tolerated by cancer patients, and it was.

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 6 PectaSol 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 very 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. Because dietary supplements are regulated as foods, not as drugs , FDA approval is not required unless specific claims about disease prevention or treatment are made.

What is pomegranate?

The pomegranate fruit (Punica granatum L.) is native to Asia and grown throughout the Mediterranean, Southeast Asia, East Indies, Africa, and the United States. Pomegranate has been used for medicinal purposes since ancient times.

Different parts of the pomegranate fruit have bioactive compounds (chemicals found in small amounts that have actions in the body that may promote good health). These include:

• the peel, which makes up half the fruit and contains bioactive compounds such as phenolics,flavonoids , and ellagitannins (the main source ofantioxidantactivity);
• the seeds, which contain punicic acid, an omega-5fatty acid; and
• 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 administered or consumed?

Pomegranate may be consumed in the diet or taken in dietary supplements.

Have any preclinical (laboratory or animal) studies been conducted using pomegranate?

Laboratory studies of pomegranate in cancer cell lines include the following:

• A study of 13 pomegranatecompounds showed some were able to slow the growth and spread ofprostate cancer cells and to cause cell death. Higherdoseswere found to be more effective. Punicic acid (a bioactive compound found in pomegranate seeds) was shown to have the strongest effect in causing cell death.
• Three types of prostate cancer cell lines were treated with either pomegranateextract , pomegranate juice, or two of their bioactive compounds. All pomegranate treatments were shown to increase cell death and decrease the spread of cancer cells, with higher doses found to be more effective. In the cell line that was dependent onandrogen (malehormone) for growth, all treatments affected the way androgen was taken up and used.
• Other studies in cancer cell lines found that the anticancer activity of pomegranate included effects on certainenzymes and pathways involved in cancer, such as theinsulin-like growth factor(IGF) system.

Studies of animal models of prostate cancer in which the animals were given pomegranate have shown the following:

• A study of miceinjected with prostatetumor-forming cells found that mice that drank pomegranate extract in water had tumors that were smaller and took longer to develop than tumors in mice that drank normal water.
• In a study of strains of mice created to develop prostate cancer that acts like human cancer, all mice that were given normal water for 28 weeks developed tumors. Only one-fifth to one-third of the mice that received pomegranate extract in water developed tumors, with the mice that received the highest amounts of pomegranate extract having the fewest tumors.

Have any clinical trials (research studies with people) of pomegranate been conducted?

One clinical trial that studied pomegranate juice in prostate cancer patients has been fully reported. Patients with rising prostate-specific antigen (PSA) levels after surgery or radiation therapy were given 8 ounces of pomegranate juice daily for up to 33 months. Drinking pomegranate juice was related to a slowing of PSA doubling time (how long it takes PSA levels in the blood to increase by 100 percent). In addition, when prostate cancer cells (LNCaP) in the lab were treated with study patients' blood before and after the study, there was a decrease in cell growth and increase in cell death following pomegranate treatment.

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 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. Because dietary supplements are regulated as foods, not as drugs , FDA approval is not required unless specific claims about disease prevention or treatment are made.

What is soy?

The soybean plant has been grown in Asia for food since ancient times. Soy first arrived in Europe and North America in the 18th century. The soybean can be processed into a wide variety of products including soy milk, miso, tofu, soy flour, and oil.

Soy foods contain many phytochemicals that may have health benefits. Isoflavones are the most widely researched compounds in soy. Major isoflavones in the soybean include genistein (which may be the most bioactive isoflavone), daidzein , and glycitein. Isoflavones protect the soybean plant from stress and have antioxidant , antimicrobial , and antifungal actions.

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 administered or consumed?

Soy may be consumed in the diet or taken in dietary supplements.

Have any preclinical (laboratory or animal) studies been conducted using soy?

Laboratory research and animal studies have been done to find out if soy may be useful in preventing or treating prostate cancer.

Studies of soy in the laboratory have shown the following:

• Several laboratory studies have found that treating human prostate cancer cells with isoflavones (such as genistein or daidzein) interferes with pathways in prostate cancer cells related toinflammationand cancer growth and spread.
• Some laboratory studies have found that treating prostate cancer cells with whole soyextract (containing all the major isoflavones) or combining other plant-based compounds with isoflavones may have more anticancer effects than using single isoflavones. One study compared treating human prostate cancer cells with soy isoflavones,curcumin (a yellow pigment of the spiceturmeric that is being studied in cancerprevention ), or a combination of the two compounds. Results showed that combining curcumin and isoflavones was more effective in loweringprostate-specific antigen(PSA) levels than using either compound alone.

Studies of animal models of prostate cancer treated with soy have shown the following mixed results:

• Strains of mice created to develop prostate cancer that acts like human cancer were fed a diet with genistein or acontrol diet. Compared with mice on the control diet, the mice fed the genistein diet had less prostate cancer cell growth and lower levels of growth promotingproteins.
• A study of mice that weregenetically modified to produce prostate cancer found that mice fed a low-dosegenistein diet had more spread of cancer than mice fed either a high-dose genistein diet or a diet with no genistein. This suggests that the effects of genistein on prostate cancer may vary depending on dose and on how early it is given.
• A study in mice implanted with advanced human prostate cancer found that those given daily genistein in peanut oil developed moretumorsin other parts of the body than mice given peanut oil without genistein.
• In a study of combiningradiation therapy with soy isoflavones, mice implanted with prostate cancer cells were treated with genistein, mixed isoflavones (genistein, daidzein, and glycitein), and/ orradiation. Mixed isoflavones were found to be more effective than genistein in slowing prostate tumor growth. Combining mixed isoflavones with radiation was found to be most effective in slowing tumor growth.

Have any population studies or clinical trials (research studies with people) of soy been conducted?

Many population studies and clinical trials have been done to find out if soy may be useful in preventing or treating prostate cancer. Soy products studied include dietary supplements, drinks, and bread.

Population studies

Population studies look for risk factors and ways to control disease in large groups of people. Population studies of soy intake and prostate cancer risk have shown the following:

• A 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.

Clinical trials of preventing prostate cancer

• In a study of Japanese men who underwent a prostatebiopsy but who did not have cancer, some received a dailysupplement of soy isoflavones (40mg ) and curcumin (100 mg), while others received aplacebo. After 6 months, there were no differences in PSA levels between the supplement group and the placebo group overall. However, among patients with higher PSA levels at the start, those who received the supplement had meaningful decreases in PSA levels compared to patients in the placebo group.
• A study was done to find out if a soy diet standard in Asia would be practical for European men to follow. Healthy men ate either a high-soy (2 daily soy servings) or low-soy (usual) diet for 3 months, then crossed over to the other diet. Lower PSA levels were seen with the high-soy diet. Results showed that study volunteers were able to follow the high-soy diet.
• Men at risk for prostate cancer or withlow-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 consumed either type of soy protein than in men who consumed milk protein.

Clinical trials of treating prostate cancer

• In a trial of soy isoflavones, prostate cancer patients with rising PSA levels who had been treated with radiation therapy consumed a soy drink daily for 6 months. The soy drink contained 65-90 mg of isoflavones. Results showed that the soy drink had very fewside effects and slowed PSAdoubling time (how long it takes PSA levels in theblood to increase by 100 percent). These findings indicate that consuming the soy drink may have helped slow theprogressionof prostate cancer.
• In a trial of genistein (a major isoflavone), prostate cancer patients scheduled forradical prostatectomy received either a placebo or genistein (30 mg/ day) for 3-6 weeks beforesurgery. PSA levels in patients who received genistein decreased slightly while PSA levels in those who received the placebo increased slightly.
• A trial of a soy protein supplement (containing 60 mg/ day of isoflavones) studied patients withearly-stage prostate cancer. Those who received the supplement for 12 weeks had slightly greater decreases in PSA andtestosteronelevels than those who received placebo. These results suggest that soy may help slow the progression of prostate cancer.
• 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 prostatetissue than in blood. In another study, patients who ate high-phytoestrogen bread (containing soy or soy andlinseed) had greater decreases in PSA levels than those who ate wheat bread.
• A trial of a soy isoflavone supplement was done in prostate cancer patients receivingantiandrogen therapy . Side effects of antiandrogen therapy may include sexualdysfunction , lowerquality of life, and changes in mental functioning. Men who received the isoflavone supplement (160 mg/day) 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 consumed 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. Because dietary supplements are regulated as foods, not as drugs , FDA approval is not required unless specific claims about disease prevention or treatment are made.