A remarkable new study has validated a method to slow prostate cancer progression that was long ago recommended to Life Extension members.
What made this study even more noteworthy is where it was presented.
The annual gathering of the American Society of Clinical Oncology (ASCO) is considered the world’s most prestigious cancer forum. More than 25,000 oncology experts attend this meeting, and the media eagerly reports on meaningful advances in cancer prevention and treatment.
At the 2013 ASCO meeting, findings from a study were released that underscored how effective certain natural compounds can be as a prostate cancer therapy.
In this placebo-controlled, double-blind trial of treatment-refractory prostate cancer patients, a four-nutrient supplement resulted in a 63.8% median reduction in the increase of PSA levels.1 The PSA marker is used by oncologists to determine progression or regression of prostate cancer, and to evaluate whether treatments are working or failing.
In the study presented at ASCO, patients with a PSA relapse after radiotherapy or surgery for localized prostate cancer took two daily capsules containing pomegranate seed, broccoli, green tea, and turmeric. Over a six-month period, median PSA levels increased only 14.7% in the supplement group—compared to 78.5% in the placebo group!1 PSA levels remained stable, or below, baseline values for a compelling 46% of the supplement patients—but for only 14% of the placebo patients.
Prostate cancer is the most common malignancy in US men (excluding non-melanoma skin cancer),2 affecting one male in every six.3 Autopsy findings show a significant percentage of men have underlying prostate cancer without even knowing it.4-6
This article will present evidence about the prostate cancer preventing effects of a wide range of nutrients. What makes this topic so compelling are the recent findings presented at ASCO showing that pomegranate seed, green tea, broccoli, and turmeric (source of curcumin) were so effective in prostate cancer patients.1 The implication is that these nutrients may also afford considerable protection against prostate cancer progression.
A comprehensive defense against prostate cancer involves healthy diet, supplemental nutrients, hormone balance, and annual PSA screening. The foods and nutrients described herein have been documented in published studies to target prostate cancer and help prevent or attenuate its development. As a bonus, they also confer huge protection against other age-related disorders.
Since there are overlapping mechanisms of action amongst many of these foods/nutrients, it may not be necessary to take every one of them. Most impressive, however, is the voluminous amount of scientific evidence that substantiates the anti-cancer properties of these nutrients. Yet mainstream medicine remains largely in the dark.
Nutrients for Prostate Cancer Prevention
Flaxseeds provide a rich supply of lignans and essential fatty acids that promote prostate health. The lignans in flaxseed are believed to offer protection against chronic disease and cancer, including hormone-dependent malignancies.7-9
A large study demonstrated that men with higher enterolactone levels were up to 72% less likely to have prostate cancer than those with the lowest levels.10 Studies have confirmed that flaxseed supplementation lowers PSA levels, and significantly reduces the proliferation of normal prostate cells and prostate cancer cells.9,11 A pilot study on men who were scheduled to have a repeat prostate biopsy found that supplementation with flaxseeds, as part of a low-fat diet, lowered levels of PSA and prostate cell proliferation.9
Research has shown that boron can reduce the risk of prostate cancer.12 In one study, men with the highest boron intake showed a 54% lower risk of prostate cancer compared to those with the least intake.13
In a validated animal model of prostate cancer, researchers found that oral administration of various concentrations of a boron-containing solution led to 25-38% decreases in tumor size, and 86-89% reductions in PSA levels.14 The suggestion that supplemental boron may help to shrink prostate tumors while also decreasing levels of PSA is exciting. That’s because PSA—in addition to being an important prostate cancer marker—may itself be a contributor to prostate cancer promotion.15
Boron compounds inhibit the activity of prostate-specific antigen (PSA).14 Higher boron levels in the blood lower the risk of prostate cancer by reducing intracellular calcium signals and storage.16 At normal concentrations, boron operates selectively—inhibiting prostate cancer cell proliferation while allowing normal prostate cells to grow.17
The typical daily intake range for boron is 1-8 milligrams daily, however individuals living in boron rich environments may consume far greater than this amount.18 If lab studies can be replicated in human patients, higher daily dosages may become an effective and low-cost adjuvant therapy. Life Extension® members already obtain boron (3-6 mg) in their supplements.
3. Cruciferous Vegetables
In recently released studies, three phytochemicals derived from cruciferous vegetables (such as broccoli) have shown promise in inhibiting prostate cancer in experimental models.19,20 Because their chemical names are challenging— indole-3-carbinol, 3,3’-diindolylmethane, and phenethyl isothiocyanate—they are better known as I3C, DIM, and PEITC, respectively.
I3C has several different actions that help prevent and inhibit prostate cancer. It helps activate detoxification pathways, prevents cancer cell growth, induces apoptosis, regulates gene expression, protects DNA from damage, and modulates a variety of cell signaling pathways.20-23
DIM has been shown to protect against prostate cancer by inhibiting the phosphorus-transferring enzyme Akt, inhibiting the master DNA-transcription regulator nuclear factor-kappaB (NF-kB)—and blocking the crosstalk between them.24 This is a novel mechanism through which DIM inhibits cell growth and induces apoptosis in prostate cancer cells, but not in non-tumorigenic prostate epithelial cells.24 The ability of DIM to target aberrant epigenetic changes coupled with its ability to promote the detoxification of carcinogens, make it an effective chemopreventive agent as it is able to target multiple stages of prostate carcinogenesis.18
In a study released in May 2013, PEITC was found to suppress a compound known as PCAF (P300/CBP-associated factor)—which in turn inhibits androgen receptor-regulated transcriptional activity in prostate cancer cells.19 Daily suggested dosages are 14 milligrams for DIM, and 80-160 milligrams for I3C. An I3C dosage of 200-600 milligrams daily is suggested as an adjuvant for prostate cancer therapy. Dosages for PEITC are not well-established.
4. Vitamin D
As the New England Journal of Medicine clarified, “Cancer results from the accumulation of mutations in genes that regulate cellular proliferation.”25 In other words, cancer is essentially caused by the genetic mutations that occur over the lifespan. The fascinating impact of vitamin D is that it protects against cancer by enabling us to regain control over the genes that regulate cell proliferation. Vitamin D affects at least 200 human genes.26 These genes are responsible for regulating crucially important aspects of cells: their proliferation, differentiation, and apoptosis.
In recent years, a multitude of studies have shown cancer risk reductions of 50% and greater based on higher vitamin D status.27-30 People with higher vitamin D levels have lower risks of lethal prostate cancer, as well as reduced risks of other cancers.26,27,31-34 Individual blood testing is needed to determine individual-appropriate dosages, which typically range from 2,000 to 10,000 international units (IU) daily for prevention. Life Extension suggests an optimal vitamin D blood level of 50-80 nanograms per milliliter (ng/mL).
5. Soy Isoflavones
Some studies show that the highest intake of soy-based foods correlates with a 42-75% lower risk of prostate cancer.35-38 Early animal studies found that this difference is most likely attributable to soy isoflavones inhibiting prostate tumor growth by acting directly against tumor cells and indirectly against tumor neovasculature (growth of new blood cells).37 Human studies support this evidence.
Japanese scientists took blood samples from over 14,000 men during 1988-1990. Their analysis clearly established that elevated serum levels of all three isoflavones assessed—genistein, daidzein, and equol—imparted strong protective effects against prostate cancer.39 Men with the highest circulating levels of genistein, daidzein, and equol reduced prostate cancer risk by 62%, 59%, and 66%, respectively. Genistein and daidzein are found in soy, and equol is derived from daidzein by bacterial flora in the intestines.39-41 Also, genistein was shown to have “potent anti-proliferative effects” against human prostate cells42 and inhibit metastatic potential of sex gland cancers such as prostate cancer.43 Genistein also blocks an enzyme that destroys an anticancer vitamin D metabolite in cancer cells.44 A suggested dosage of soy isoflavones is 135-270 milligrams daily with food.
6. Green Tea Extract
Laboratory research with cultures has long suggested that green tea catechins, including epigallocatechin-3 gallate (EGCG), may inhibit the growth of cancer cells. Evidence from human studies now demonstrates that green tea compounds can help prevent prostate cancer. A clinical trial demonstrated that green tea catechins were 90% effective in preventing prostate cancer in men with pre-malignant lesions.45 Researchers recruited 60 men, aged 45-75. Thirty participants received 200 milligrams of green tea catechins (50% EGCG) three times daily, while the other 30 subjects received a placebo. Biopsies were conducted at six and 12 months. Remarkably, only one man in the treatment group was diagnosed with prostate cancer, compared to nine men in the control group who developed the disease. No significant side effects or adverse reactions were reported.45 The lead researcher concluded that “90% of chemoprevention efficacy could be obtained by [green tea catechin] administration in men prone to developing prostate cancer.”45
Green tea polyphenols have also shown efficacy as an adjunctive therapy. Prostate cancer patients were given 1,300 milligrams of green tea polyphenols, mostly EGCG, prior to the time of radical prostatectomy. They showed significant reductions in PSA and other tumor promoters such as vascular endothelial growth factor.46 Suggested dosages of EGCG are 300-350 milligrams daily, and adjuvant cancer therapy dosages of EGCG range up to 3,000 milligrams daily . The FDA, however, does not believe there is sufficient evidence to say that green tea reduces prostate cancer risk. A federal judge ruled against the FDA’s attempt to suppress claims that green tea may reduce prostate cancer risk. 47
7. Omega-3 Fatty Acids
In scientific studies, high blood levels of the omega-3 fatty acids DHA and EPA (docosahexaenoic acid and eicosapentaenoic acid, respectively) have been demonstrated to correspond to a lower risk of developing prostate cancer.48 EPA has been shown to suppress the formation of the omega-6 fatty acid arachidonic acid (AA) by inhibiting the enzyme delta-5-desaturase.49 EPA has also been found to contribute to the inhibition of uPA —a substance known as urokinase-type plasminogen activator believed to play a role in prostate cancer invasion and metastasis.50
Although cold water fish such as tuna, sardines, herring, and salmon provide a rich omega-3 source, commercially available pharmaceutical-grade fish oils also deliver large amounts of EPA and DHA.51 Suggested dosages are 2-4 grams of fish oil concentrate supplying 700-1,400 milligrams of EPA and 500-1,000 milligrams of DHA, daily with food. For adjuvant cancer therapy, recommended dosages are 4-8 grams of fish oil concentrate supplying up to 2,800 milligrams of EPA and up to 2,000 milligrams of DHA, daily with food.
Curcumin strikes at multiple targets in prostate cancer.52,53 It induces apoptosis, interferes with the spread of cancer cells, and regulates inflammatory responses through the master regulator nuclear factor-kappaB (NF-kB), a protein complex that controls the transcription of DNA.54-57 Natural molecules that inhibit NF-kB can limit inflammatory changes.58 Prostate cancer is often dependent on sex hormones for its growth; curcumin reduces expression of sex-hormone receptors (androgen receptors and androgen receptor-related cofactors) in the prostate.59,60 This speeds androgen receptor breakdown and impairs cancer cells’ ability to respond to the effects of testosterone.61,62
Both in vitro and in vivo models demonstrate that curcumin inhibits prostate cancer promotion by blocking metastases of cancer cells in the prostate, and by regulating enzymes required for tissue invasiveness.63,64 In certain human prostate cancer cell lines, curcumin completely inhibited a type of phosphorus-transferring enzyme known as Akt (also known as protein kinase B or PKB), suggesting that curcumin inhibits prostate cancer cell growth through this Akt-inhibiting mechanism.65 Curcumin has been shown to inhibit angiogenesis in prostate cancer cells in vivo.66 A novel manufacturing technology has produced a patented curcumin formulation that absorbs up to seven times better than conventional curcumin.67 If supplementing with this highly absorbed curcumin formulation (BCM-95®), suggested preventive dosage is 400 milligrams daily with food. A suggested dosage of this formulation for adjuvant cancer therapy may be 800-1,200 milligrams daily with food.
9. Coenzyme Q10
Low blood levels of coenzyme Q10 (CoQ10 or Q10) have been found in patients with a variety of cancer types.68,69 Several published animal and human studies have demonstrated CoQ10’s remarkable effects against some cancers,70-77 but research into its potentially protective effects against prostate cancer has been very limited. In 2005, after reviewing anecdotal reports appearing in the peer-reviewed scientific literature, the National Cancer Institute (NCI) reported that coenzyme Q10 has been anecdotally reported to lengthen the survival of patients with cancer of the prostate, as well as several other cancers.78 Despite these findings, the NCI pointed out that the absence of a control group in the human studies and other scientific weaknesses made it impossible to determine whether these beneficial results were directly related to CoQ10 therapy.78
Later that same year, University of Miami researchers reported research showing that adding coenzyme Q10 in vitro to the most common prostate cancer cell line, PC3, inhibited cell growth by 70% over 48 hours.79 Evidence suggested that there had been a reduction in the expression of a key, anti-apoptotic gene protein, bcl-2, and through this mechanism, CoQ10 had restored the ability for apoptosis, allowing the cancer cells to kill themselves. “The most amazing part,” said UM research associate Niven Narain, “is that we’ve been able to restore a cancer cell’s ability to kill itself, while not impacting normal cells.”79 The suggested preventive dosage of coenzyme Q10 is 100 milligrams daily, and a suggested adjuvant dosage is 200-500 milligrams daily, both taken after a meal.
10. Gamma-Tocopherol Vitamin E
A large study showed that the risk of prostate cancer declines with increasing concentrations of the alpha-tocopherol form of vitamin E, with the highest level corresponding to a 35% lower risk; however, these protective effects were only observed when levels of gamma-tocopherol and levels of selenium were also high.80
Men with the highest gamma-tocopherol levels, those in the highest fifth of the distribution, were found to have a 5-fold greater reduction in the risk of developing prostate cancer than men in the lowest fifth.80 Other research has shown that vitamin E reduces the growth rate of existing prostate cancers that are specifically exacerbated by a high-fat diet—reducing tumor growth rate within a high-fat diet to the same tumor growth rate as in a lower-fat (ideal) diet.81
While both alpha- and gamma-tocopherols are potent antioxidants, gamma-tocopherol has a unique function. Because of its different chemical structure, gamma-tocopherol scavenges reactive nitrogen species, which can damage proteins, lipids, and DNA, and promote carcinogenesis.82-85 The suggested dosage of gamma-tocopherol is 200-250 milligrams daily, and the suggested adjuvant therapy dosage is 400-1,000 milligrams daily, taken with food.
Lycopene is a carotenoid occurring abundantly in tomatoes. The relationship between its ingestion and prostate health is well established.86-94 One laboratory experiment found that lycopene inhibited the growth of normal human prostate cells.92 Then, a clinical trial conducted on prostate cancer patients demonstrated that lycopene supplementation decreases the growth of prostate cancer.93 In another compelling study, healthy men with the highest lycopene levels in their blood were shown to have a 60% reduced risk of developing prostate cancer.94
Scientists found that lycopene works by reducing oxidative stress in prostate tissue; lowering inflammatory signaling; preventing DNA damage; modulating expression of endocrine growth factors; and may block cancer cells from growing out of control through enhanced communication between cancer cells at “gap junctions.”89,91 Lycopene also may slow the new blood vessel growth that prostate cancers need for development.91 Suggested dosages of 15-30 milligrams daily are for prevention and up to 45 milligrams daily with food for adjuvant support in existing prostate cancer.
The body only needs small quantities of selenium.95 But blood levels of this mineral decrease with age, placing middle-aged to older men at high risk for inadequate selenium levels. Lower levels of selenium in the blood can correspond to an increased risk of an enlarged prostate, the condition known as benign prostatic hyperplasia (BPH).96 Low selenium levels were also found to parallel a four- to five-fold higher risk of prostate cancer.97 Remarkably, supplementation with selenium has been demonstrated to produce an up to 63% reduced risk of prostate cancer.98,99 The mechanism behind this protection appears to be related to an antiproliferative effect, resulting from selenium’s upregulation of cell-cycle regulators.100
However, confusion arose in 2009 due to publication of a single negative study that substantially contributed to misinformation about the value of selenium against prostate cancer. Known as SELECT—for Selenium and Vitamin E Cancer Prevention Trial—the study appeared to show that selenium, alone or in combination with vitamin E, had no detectable effect on preventing cancers.101,102 Many experts have since condemned the trial’s methodology and conclusions103—and for a number of reasons.
One problem with the 2009 study was that it used only a single form of selenium.101,104 This selenium compound is just one of several different forms in which selenium is available for nutritional supplementation. Data indicate that three forms of selenium—the two organic forms called L-selenomethionine and selenium-methyl L-selenocysteine, plus the inorganic form known as sodium selenite—have different degrees of action with regard to the effect on any incipient cancer cells that might be developing.105-107 Using one form weakened the potential protective benefits in the study.
More importantly, the highly flawed 2009 SELECT study used only one form of vitamin E, a synthetic form known as dl-alpha tocopheryl acetate. We have known for about 15 years that when alpha tocopherol is taken by itself, it displaces critically important gamma tocopherol—the form of vitamin E that is the most protective against prostate cancer.84,108-112 By supplementing aging men with only one form of vitamin E, synthetic dl-alpha tocopheryl acetate, scientists in the 2009 SELECT study may have unwittingly increased subjects’ prostate cancer risk by depriving prostate cells of critical gamma tocopherol. Then, a 2011 meta-analysis of nine randomized, controlled clinical trials including 152,538 participants established that selenium supplementation cut risk for all cancers by 24%. The cancer-preventive effect rose to 36% in people with low baseline selenium levels.113
Based on research involving non-melanoma skin cancer patients—in which patients received either 200 micrograms daily of selenium or a placebo—researchers concluded that selenium supplementation can slash the risk of dying from any type of cancer by 50%.114 Also, selenium’s efficacy could potentially be enhanced: one study observed the protective effects of high selenium levels against prostate cancer only when the concentrations of gamma-tocopherol, an isomer of vitamin E, were also high—suggesting that these two nutrients may work best together.80 It is suggested that selenium be taken at dosages of 200 micrograms daily with food.
Evidence suggests that zinc may play an important and direct role in the prostate. For example, studies found that total zinc levels in the prostate are much higher than in other soft tissues in the body, and those with prostate cancer have been shown to have exceedingly low levels of zinc in the prostate.115,116 Also, in normal prostate cells, zinc is highly concentrated intracellularly in the glandular epithelium—but adenocarcinoma cells taken from prostate tumors have lost their ability to amass zinc.117-119 Supplementation with 15 milligrams of zinc daily showed a trend toward modestly reduced risk of all invasive prostate cancers, but there was a significant 66% reduction in risk of advanced prostate cancer.120 This indicates that zinc supplements may be beneficial in some subgroups of men for the most advanced forms of the disease. There was also a greater reduction in prostate cancer risk from zinc supplementation among men whose vegetable intake was high.120 Suggested preventive and adjuvant zinc dosages range between 15 and 50 milligrams a day.
14. Milk Thistle
Evidence demonstrates that the compounds in milk thistle—isosilybin, silibinin, and silymarin—offer protection against prostate cancer. Both silibinin and silymarin and are strong antioxidants and inhibit human carcinoma cell growth and DNA synthesis.121 Silibinin was found in animal research to exert cancer-fighting effects against an advanced form of human prostate tumor cells, resulting in a decrease in proliferation and an increase in programmed cancer-cell death.122,123 Silymarin may block cancer cell development and growth; it was found to contain one or more constituents that induce cancer cell apoptosis and inhibit mitogenic (cell-division promoting) and survival signaling by prostate cancer cells, showing silymarin’s ability to tackle cancer from a number of different angles.124 Both silymarin and silibinin inhibit the secretion of pro-angiogenic factors from tumor cells, which are necessary for these cells to recruit the blood supply required for their continued growth.122
In animal research, silibinin was found to exert cancer-fighting effects against an advanced form of human prostate tumor cells, resulting in decreased proliferation and increased cancer-cell apoptosis.123 Silibinin has high bioavailability in the prostate after oral administration, and scientists concluded that it has strong potential to be developed as an intervention for hormone-refractory (castration-resistant) human prostate cancer.121 Silibinin may also work synergistically with the chemotherapy drug doxorubicin to help kill cancer cells, making it a potential candidate for adjuvant therapy.122
However, isosilybin B—a lesser known constituent that comprises no more than 5% of silymarin and is absent from silibinin—appears to be more potent against prostate cancer cells than the other milk thistle substances.125 Scientists reported that other compounds may require much higher concentrations to achieve the same anti-cancer effect elicited by a relatively small dose of isosilybin B.125 It is important to note that some preparations sold as milk thistle extract, silymarin, or silibinin may contain little, or even no, isosilybin B. A typical suggested dosage of a quality standardized milk thistle extract is 750 milligrams daily , taken with or without food.
15. Gamma-Linolenic Acid (GLA)
Gamma-linolenic acid (GLA) is an omega-6 essential fatty acid found mostly in plant-based oils. Not all omega-6 fatty acids behave the same: for example, the omega-6s called linoleic acid and arachidonic acid tend to be unhealthy because they promote inflammation; GLA, on the other hand, may serve to reduce inflammation.126 Much of the GLA taken as a supplement is converted to a substance called DGLA (dihomo-gamma-linolenic acid), an omega-6 fatty acid with demonstrated anti-inflammatory effect.126 Similar to the effect of the omega-3 fatty acid eicosapentaenoic acid (EPA), GLA has been found to inhibit the production of urokinase-type plasminogen activator (uPA), a substance believed to play a role in the invasiveness and metastasis of cancer cells.49
Scientists have also found that GLA metabolites suppress the activity of 5alpha-reductase, an enzyme that converts testosterone to a more potent androgen (5alpha-dihydrotestosterone or DHT) and that is involved in the pathway of prostate cancer.127 It is believed that GLA may also increase the effectiveness of some anticancer drug treatments.126 The suggested GLA dosage for prevention is 300 milligrams daily, or for adjuvant therapy, 700-900 milligrams daily, both with food.
Limited evidence suggests that higher zeaxanthin levels may be protective against prostate cancer.128 In a 2001 study, a scientific team analyzed the plasma levels of various substances in a group of participants that included 65 patients with prostate cancer and 132 cancer-free controls. They found that, relative to those in the lowest quartile, those in the highest quartile of plasma zeaxanthin had a 78% reduced risk of prostate cancer.128 More study is needed to explore this potential benefit. Appropriate zeaxanthin supplementation amounts for prostate cancer defense have not been determined, but 3.75 milligrams daily is a current suggested dosage.
Use of pomegranate (Punica granatum L. var. spinosa ) juice, peel, and oil has been shown to possess anticancer activities, including interference with tumor cell proliferation, cell cycle, invasiveness, and angiogenesis.129 Apoptosis was implicated as a mechanism for this interference with prostate cancer cell proliferation in a laboratory study in which researchers found that pomegranate extract increases expression of a protein that promotes cancer cell death, while decreasing expression of a protein that inhibits cancer cell death.130 Later, in a 2012 study, scientists found that the in vitro cytotoxic activity of an extract of pomegranate against prostate cancer cells was dose-dependent—and they also suggested that this antiproliferative effect followed an apoptosis-dependent pathway.131
Further clarifying pomegranate’s effects against prostate cancer cells, scientists found evidence of induced beneficial gene expression—inhibiting pro-inflammatory, DNA-related protein nuclear factor kappa B (NF-kB)132 and downregulating production of cancer-stimulating androgen receptors in prostate cells.133 The suggested dosage for prostate cancer prevention is 80-120 milligrams daily (of punicalagins), and for adjuvant cancer therapy, 280-375 milligrams daily (of punicalagins), with or without food.
18. Saw Palmetto
Saw palmetto (Serenoa repens or Sabal serrulata) is now one of the most widely used phytotherapies for BPH (benign prostatic hyperplasia) in the US,134,135 a condition characterized by an enlarged prostate gland. However, evidence has been emerging that saw palmetto also has biological activity in prostate cancer cells and may defend against prostate cancer.136 For instance, a saw palmetto extract was shown to inhibit the activity of 5-alpha-reductase,137 an enzyme that converts testosterone to the most potent androgen and that is involved in the pathway of prostate cancer. Saw palmetto also appears to have anti-inflammatory properties and—crucially—a tendency to promote apoptosis in prostate cancer cells.138,139
In one study, researchers described how they used saw palmetto extract to slow the growth of prostate cancer cells in vitro. This growth-inhibitory effect was more potent on prostate cancer cells than on other cancer cell lines on which they tested saw palmetto.140 One new mechanism identified by this group of scientists was the saw palmetto-induced reduction in the expression of cyclooxygenase-2 (COX-2) in prostate cancer cells. Cancer cells often use COX-2 as biological fuel to hyperproliferate, and as the researchers presenting this report concluded, “We hypothesize that COX-2 inhibition induced by saw palmetto berry extract may provide an important basis for potential chemopreventative action.” 140 A typical suggested dose of saw palmetto is 320 milligrams daily.
By working through over a dozen anticancer mechanisms and selectively targeting cancer cells, resveratrol inhibits prostate cancer at multiple stages of development.141 This potent compound, found in grapes and other plants, was first isolated in 1940 and is now viewed as a potential defense against this disease.141-143 In a study that examined the effect of various polyphenols on different types of prostate cancer cells, scientists concluded that resveratrol was the most potent against advanced prostate cancer cells.144
Resveratrol has the ability to modulate the activity of estrogen and testosterone at both the cellular (receptor) and molecular (genetic) levels.145-147 In fact, after examining its effects on hormone-responsive genes in prostate cancer cells, researchers concluded that, “Resveratrol may be a useful chemopreventive/chemotherapeutic agent for prostate cancer.”147 Also, resveratrol reverses increases in PSA in cancer cells.147,148 For example, in one study, four days of resveratrol treatment resulted in an 80% reduction in PSA levels in prostate cancer cells.148 Resveratrol also modulates growth factors, protects DNA, blocks cancer-causing chemicals and radiation, and fights free radicals and inflammation.149,150 The same anticancer gene activated by non-steroidal anti-inflammatory drugs (NSAIDs) demonstrates enhanced expression by resveratrol.151
Using a DNA microarray—a scientific research tool that simultaneously examines how particular phytocompounds affect thousands of genes—scientists found that resveratrol exerts a striking effect on cancer-related genes. Among other things, resveratrol activates tumor suppressor genes, other genes that destroy cancer cells, and genes that control the cell cycle—while suppressing genes that allow cancer cells to communicate with one another.152 This ability to get inside cancer cells and activate or deactivate genes is a powerful weapon against cancer growth—especially since resveratrol exerts its effects without toxicity.145 Many resveratrol supplements on the market are diluted. For pure resveratrol, the suggested dosage is 20-250 milligrams a day, taken with or without food.
20. Supplemental Lignans
Many different plant sources provide rich sources of lignans—and this may partially explain why men who eat healthier diets enjoy sharply reduced rates of prostate cancer.153,154 Lignan molecules are involved in plant defense mechanisms.154 But experimental evidence suggests that dietary lignans also offer humans significant protection against tumors in a variety of organs—including tumors of the prostate.155-158 In fact, researchers found that men with higher blood levels of lignans have the lowest incidence of prostate cancer.10 Bacteria in the intestines convert dietary and supplemental lignans into mammalian lignan compounds called enterolactones, which enter the bloodstream.159
Findings from human, animal, and in vitro studies indicate that enterolactones protect against hormone-dependent cancers.160-162 Tyrosine kinases are activated in metastatic prostate cancer cells, and enterolactones help to inhibit the tyrosine kinase enzyme.163 Enterolactones have been shown to inhibit 5-alpha-reductase, an enzyme that converts testosterone to a more potent androgen.164 Anti-angiogenesis effects and cancer-cell apoptosis were found to be enhanced by enterolactones in animal models of hormone-related cancers, including prostate cancer.165,166 Enterolactone also functions via several mechanisms to reduce estrogen input to cells and has been shown in a number of studies to be a factor in the development of benign prostate enlargement and prostate cancer.162,167-170
A dosage of 20-50 milligrams daily of lignans is suggested to defend against prostate cancer. For adjuvant prostate cancer support, 75-125 milligrams daily is suggested.
21. Vitamin K
The anti-tumor potential of vitamin K has been a part of scientific research since 1947.171 Researchers have observed tumor cell destruction in prostate cancer patients following supplementation with a combination of vitamin C and vitamin K3, the synthetic form of vitamin K.172 (This same combination was later developed into the prostate cancer drug Apatone®, which has shown similar results.173)
Subsequently, a study that followed 11,319 men for an average of 8.6 years found that those with the highest intake of vitamin K2 were 63% less likely to develop advanced prostate cancer.174 The same research team found no effect on prostate cancer from vitamin K1 supplementation. Optimum prostate cancer prevention dosages for vitamin K2 are not known, but typically suggested daily dosages are 1,000 micrograms for the menaquinone-4 form of K2 (MK-4) and 200 micrograms for the menaquinone-7 (MK-7) form.
A plant fat and phytosterol known as beta-sito-sterol, used in several European prostate drugs, has been found to block the growth of prostate cancer cells. A study on an androgen-dependent line of prostate cancer cells showed that beta-sitosterol decreased cancer cell growth by 24% and increased apoptosis four-fold.175 These findings correlated with a 50% increase in production of ceramide,175 an important cell membrane component believed to induce apopotosis.176
In another study, an androgen-dependent line of human prostate cancer cells (PC-3 cell line) was implanted in mice, and scientists compared both the in vivo and in vitro effects of a 2% mixture of beta-sitosterol with those of a 2% mixture of cholesterol on these cells. Compared to controls, beta-sitosterol, as well as another phytosterol known as campesterol, inhibited growth of the prostate cancer cells by 70% and 14%, respectively.177 By contrast, the cholesterol mixture increased cell growth by 18%. Various other parameters were also measured.
For example, the phytosterol mixtures inhibited the invasion of the prostate cancer cells into Matrigel-coated membranes—a measure of cancer invasiveness—by 78%, compared to controls, while the cholesterol mixture increased invasiveness by 43%.177 Also, migration of the prostate tumor cells through 8-micron pore membranes—a measure of tumor motility—was reduced by 60-93% when they were in the phytosterol mixtures, but it was increased by 67% when in the cholesterol.177 In a measure of adhesiveness and ability to form tumor clumps, phytosterol supplementation reduced the binding of these cancer cells to laminin by 15-38% and to fibronectin by 23%, while cholesterol increased cell-binding to type IV collagen by 36%.177 The research team concluded that—indirectly in vivo as a dietary supplement, and directly in vitro in tissue culture media—phytosterols inhibited the growth and metastasis of these (PC-3) prostate cancer cells. Beta-sitosterol, however, was determined to be much more effective than campesterol in offering this protection in most parameters assessed.177
In later research on the mechanism involved, scientists determined that phytosterols such as beta-sito-sterol may induce the inhibition of tumor growth by stimulating apoptosis and arresting cells at different locations in the cell cycle, and that this may involve alterations in reactive oxygen species and production of prostaglandin.178 A suggested phytosterol dosage is 169 milligrams twice daily with or without food.
In studies on human cancer cells, scientists observed that the vegetable extract apigenin inhibits angiogenesisand cell proliferation.179-181 These effects were confirmed in an animal experiment in which scientists transplanted an androgen-dependent line of human prostate cancer cells into mice bred to serve as a model for tumor growth conditions.182 A liquid suspension containing either apigenin or placebo was given to the mice daily, via a gastric tube, for eight or ten weeks. Administering apigenin to mice—beginning either two weeks before, or two weeks after, inoculation with the cells—inhibited the volume of prostate cancer cells in a dose-dependent manner by as much as 59% and 53%, respectively.182 Induction of apoptosis in the tumor xenografts was observed. In the same study, exposure of prostate cancer cells to apigenin in a culture for as little as 24 hours appeared to inhibit cell cycle progression by nearly 69%.182
Scientists believe these effects may result from apigenin’s modulation of the IGF (insulin-like growth factors) axis, which plays signaling roles in cell proliferation and cell death.183 Later research demonstrated that apigenin also inhibits motility and invasiveness of prostate carcinoma cells.184 The importance of supplementation for prostate protection is reflected in the fact that Americans typically consume only 13 milligrams of flavonoids (including flavones like apigenin) daily,183 however a suggested apigenin preventive dosage is 25-50 milligrams daily, and adjuvant dosage for prostate cancer patients may exceed 100 milligrams daily.
24. Ginger (Zingiber officinale)
A study reported in 2013 demonstrated that ginger phytochemicals work synergistically to inhibit the proliferation of human prostate cancer cells (PC-3 cell line).185 In past research, ginger showed anti-inflammatory, antioxidant, and antiproliferative activities, suggesting a promising role as a chemopreventive agent.186,187 Then, a 2012 study became the first report to clearly demonstrate the anticancer activity of orally taken, whole ginger extract for the therapeutic management of prostate cancer.187 This breakthrough research found that ginger resulted in growth inhibition, cell-cycle arrest, and induced caspase-dependent intrinsic apoptosis in prostate cancer cells.187 In vivo studies by this team showed that—without any detectable toxicity—ginger significantly inhibited tumor growth in xenografts of a line of prostate cancer cells (PC3) subcutaneously implanted in nude mice.187
Specifically, the scientific team orally fed a solution containing ginger extract to the tumor-implanted mice for eight weeks. Daily measurements of tumor volume were performed. Tumors in control mice that received a placebo solution showed unrestricted growth. But tumors in mice that received the ginger extract solution showed a time-dependent inhibition of growth over the eight-week period. Remarkably, the tumor burden in the ginger group was reduced by about 56% after just eight weeks of feeding.187 Tumor tissue from ginger extract-treated mice showed a reduced proliferation index and “widespread apoptosis” compared with controls.187 Ginger treatment was well tolerated, and the test mice maintained normal weight gain and showed no signs of discomfort during the treatment regimen. Most importantly, orally taken ginger extract did not exert any detectable toxicity in normal, rapidly dividing tissues such as the gut and bone marrow.
Although further research is urgently needed, this study suggests that ginger extract has anticancer effects against human prostate cancer cells. No dosage for this purpose has been determined, but the study team performed allometric scaling calculations to extrapolate the mice dosage to humans. The human equivalent dose of ginger extract was found to be approximately 567 milligrams daily for a 154-pound (70 kilogram) human adult.187,188 This may be viewed as an adjuvant therapy dosage, and an appropriate preventive dosage would be significantly less.
25. Inositol Hexaphosphate (IP6)
Inositol hexaphosphate, or IP6, is a phytochemical found in cereals, soy, legumes, and other fiber-rich foods.189 Building on earlier in vitro research showing that IP6 strongly inhibits growth and induces differentiation of human prostate cancer cells (PC-3 cells),190 scientists designed an animal study. They injected mice with a line of human prostate cancer cells (DU145 cells) and then gave them either normal drinking water or water that included 1% or 2% IP6 for 12 weeks. The hormone-refractory (castration-resistant) prostate cancer growth was reduced 47% in the 1% IP6-solution mice and reduced 66% in the 2% IP6-solution mice, compared to littermates without the IP6-enriched drinking water diet.191
Then, in 2013, scientists designed an IP6 experiment on TRAMP mice, which are genetically modified to develop metastatic prostate cancer.192 For 24 weeks, mice with prostate cancer were given drinking water that was 0%, 1%, 2%, or 4% IP6. The study team periodically conducted magnetic resonance imaging (MRI) tests on each mouse prostate to assess prostate volume and tumor vascularity. The animals that received higher concentrations of IP6 showed a “profound” reduction in prostate tumor size, due in part to the compound’s antiangiogenic effect (the ability of the compound to reduce new blood vessel formation).192 The researchers discovered a decrease in a glucose transporter protein, known as GLUT-4, in the prostates of IP6-treated mice, and observed that IP6 decreased glucose metabolism and membrane phospholipid synthesis—meaning there was substantial energy deprivation with the tumor itself. This demonstrates “a practical and translational potential of IP6 treatment in suppressing growth and progression of prostate cancer in humans.”192
26. N-Acetylcysteine (NAC)
N-acetylcysteine, or NAC, is a metabolite of the amino acid cysteine, which is found in many protein-containing foods.193 It is used both as a prescription drug and a dietary supplement. As a drug, it is given orally to treat acetaminophen overdose; as a supplement, it is used as an antioxidant and to promote metabolism of glutathione, a potent endogenous antioxidant.194 Research now indicates it can inhibit growth and block the metastasis of prostate cancer. In an in vitro study, researchers found that NAC significantly inhibited androgen-independent prostate carcinoma cells (PC-3 cells) in a dose- and time-dependent manner—suggesting a potent antiproliferative effect and the promise that NAC may be of benefit in the management of prostate cancer.195
Scientists then conducted another lab study to assess the effect of NAC on the metastasis of human prostate cancer cells. They found that NAC inhibited the growth, migration, and invasion of two cell lines (DU145 and PC3 cells).196 Also, NAC significantly reduced the ability of the prostate cancer cells to attach themselves (to collagen IV-coated surfaces).196 Inhibition occurred in both cell lines. The team concluded that NAC has high potential to attenuate migration of human prostate cancer cells and to suppress the growth of primary and secondary tumors—and they suggested NAC may represent an affordable and low-toxicity, adjuvant-therapy option for prostate cancer.196 Dosages of 600 milligrams daily are typical, but higher dosages may be needed for adjuvant cancer therapy.
Quercetin is a flavonoid found in a broad range of fruits and vegetables.197 Lab research has suggested that quercetin inhibits prostate cancer development. Scientists found that quercetin produces a 69% reduction in the growth of highly aggressive prostate cancer cells, a greater than 50% upregulation of tumor-suppressor genes, and a 61-100% downregulation of cancer-promoting oncogenes.197 A study suggested that quercetin works partially by blocking the androgen receptors used to sustain growth by prostate cancer cells—potentially preventing these cells from forming tumors.198 Another quercetin anticancer mechanism was revealed in a study on human prostate cancer (PC-3) cells. Quercetin induced the mitochondrial apoptotic signaling pathway and endoplasmic reticulum stress, triggering DNA damage and apoptotic death in these cells.199 Other research confirmed that quercetin inhibits the migration and invasiveness of prostate cancer cells.200 A suggested preventive dosage is 500 milligrams daily and an adjuvant prostate cancer dosage is 1,000-3,000 milligrams daily. (The lower dosage of 500 milligrams daily is currently being tested in a double-blind, human clinical trial on the effect of quercetin on the rate of increase in PSA and on the incidence of prostate cancer, but these results are not expected to be available until 2014.201)
Constituents called triterpenes in the fungus Ganoderma lucidum, better known as reishi mushroom, provide important anti-inflammatory and anti-proliferative effects that play a role in cancer.202 These mechanisms, combined with the polysaccharides and other components in reishi, can inhibit cancer—including prostate cancer cells.203,204 While reishi has been heavily studied for its ability to enhance immunity, some scientists adopted a novel approach to researching potential effects of fungi against prostate cancer. They evaluated the ability of various fungus extracts to act from within the cell to interfere with the androgen receptor and thus, inhibit prostate cancer growth.203,204
These researchers investigated over 200 fungus extracts for their anti-androgenic activity—and of these, G. lucidum (reishi) was one of two mushrooms selected for further investigation.204 This extract also blocked cell proliferation and decreased cancer cell viability.204 Reishi inhibited androgen-sensitive, human prostate adenocarcinoma cells (LNCaP cells).203 The published report concluded that, “G. lucidum extracts have profound activity against LNCaP cells that merits further investigation as a potential therapeutic agent for the treatment of prostate cancer.”203 A suggested preventive dosage of reishi extract is 980 milligrams daily (standardized to contain 13.5% polysaccharides and 6% triterpenes). For adjuvant support in prostate cancer, dosages range from 980 up to 3,000 milligrams daily (standardized to contain 13.5% polysaccharides and 6% triterpenes).
Aging humans are at increased risk of health complications and mortality via the upregulation of a proinflammatory enzyme called 5-lipoxygenase, or 5-LOX.205 The 5-LOX enzyme generates a cascade of dangerous inflammatory effects throughout the body—which results in increased vulnerability of the organs to disease and functional deficits, particularly as the aging process progresses.205,206 This enzyme stimulates the manufacture of pro-inflammatory molecules called leukotrienes, which are linked in abundant research to numerous age-related diseases—including cancer.205,207-210 Compounds in the flowering plant genus Boswellia—beta-boswellic acid, keto-beta-boswellic acid, and acetyl-keto-beta-boswellic acid (AKBA)—were shown to induce apoptosis in cancer cells.211 But a purified extract of Boswellia has been specifically shown to selectively inhibit the 5-LOX enzyme.212-214
This purified extract—5-Loxin®—is standardized for AKBA content and protects against inflammatory diseases, including prostate cancer, through several mechanisms. For example, virtually all human cancer cell lines, including prostate cancer cells, induce production of a protein-degrading enzyme called matrix metalloproteinase (MMP), which cancer cells employ to tear apart containment structures within the prostate gland that would normally encase them. This allows the prostate cancer cells to break through healthy prostate tissue and metastasize.215 However, 5-Loxin® has been shown to prevent expression of MMP—inhibiting the spread of prostate cancer cells.
Prostate cancer cells also use adhesion molecules called VCAM-1 and ICAM-1—which are directly involved in inflammatory processes—to facilitate their spread throughout the body. 5-Loxin® was shown to prevent the upregulation of these adhesion molecules.214 Also, the process of angiogenesis that feeds blood to developing cancer tumors is tightly linked to chronic inflammation.216 A typical suggested dosage of 5-Loxin® is 70-100 milligrams daily with or without food. Individuals with prostate cancer may consider dosages of 170 to 270 milligrams a day of 5-Loxin®.
30. Watercress Extract
Epidemiological evidence suggests that increased intake of cruciferous vegetables reduces the risk of prostate cancer, prompting scientists to identify the specific compounds responsible for this cancer-preventive effect. They found that a metabolite of phenethyl isothiocyanate (PEITC) that is abundant in watercress inhibits the proliferation of prostate cancer cells and their ability to form tumors.217 And watercress is the richest source of a glucosinolate known as nasturtiin—which is transformed into PEITC in the digestive tract.218
A delicate balance of estrogens is crucially important for men’s health as well as women’s. In a study that examined the ratio of estrogen metabolites relative to prostate cancer risk, elevated levels of the more active metabolite, 16-hydroxyestrone, were linked with an increased risk of prostate cancer.219
Cruciferous vegetables such as watercress are very rich in the compounds indole-3-carbinol (I3C) and3,3’-diindolylmethane (DIM), which beneficially modulate estrogen metabolism—correlating with a reduced risk of prostate220-222 cancer.
The constituents in watercress were also found to induce phase I and phase II liver enzymes, providing detoxification support that could explain their ability to inhibit the cancer-provoking effects of a variety of chemical compounds.223 The suggested dosage for watercress extract is 50-100 milligrams daily, taken with or without food.
Grapeseed extract contains a mixture of phenolic compounds including flavonoids, anthocyanins, and stilbene compounds such as resveratrol.224 Emerging research suggests it may be a chemopreventive agent.225,226 Several investigators reported a reduction or delay of prostate tumor incidence when male animals were fed grapeseed extract.227 Also, grapeseed proanthocyanidins inhibited human prostate carcinoma cells in lab culture.228 However, it wasn’t until 2011 that scientists investigated the association of long-term grapeseed supplementation with prostate cancer risk in human males.226
In a 2011 prostate cancer study of more than 35,000 men aged 50 to 76, researchers found that, compared to non-users, men who supplemented with any amount of grapeseed extract reduced their risk of prostate cancer by 41%.226 However, men with a high 10-year average use of grapeseed supplements experienced a remarkable 62% reduction in prostate cancer risk.226
Studies on consumption of wine—which contains grapeseed phenols—found no association with prostate cancer risk.229-231 Also, two large studies on food-based intake of flavonoids, flavonols, and flavones found no association with prostate cancer risk.232,233 Scientists reporting the compelling beneficial results of grapeseed extract supplementation on prostate cancer risk in the 2011 study (above) suggested that, “One explanation for the discrepancy…is that users of grapeseed supplements may be exposed to higher doses of these phenolic compounds than they would from their regular diet.”226 The suggested preventive dosage is 50-100 milligrams daily, and the suggested adjuvant therapeutic dosage is 300 milligrams daily.
Glycyrrhizin, a triterpene compound isolated from the roots of licorice has been found to exhibit potent in vitro cytotoxic activity against both hormone-dependent (LNCaP), and hormone-independent (DU-145), lines of human prostate cancer.234 In one study, glycyrrhizin inhibited cell proliferation in these cell lines in a time- and dose-dependent manner.234 The decreased viability was found to be due to apoptosis. Glycyrrhizin also caused DNA damage in these cell lines in a time-dependent manner.234 This suggests that this licorice compound has therapeutic potential against prostate cancer, although a recommended dosage has not been determined.
33. Modified Citrus Pectin
Pectin is a highly complex, branched polysaccharide fiber that is present in most plants and is particularly abundant in citrus fruits like oranges, lemons, and grapefruit.235 Citrus pectin, in its original form, has a limited solubility in water and therefore limited bioavailability to humans.235 But in its modified form after hydrolysis, a special formulation of modified citrus pectin becomes a unique water-soluble fiber.235,236 This modified form has been shown to bind to the important galectin molecules on the surface of cells.236 Scientists believe that this ability of the modified citrus pectin to adhere to molecules—specifically to the galectin-3 molecule—is responsible for its demonstrated ability to inhibit cancer cells.237-239 This preventive effect was shown in animal research. For example, oral administration of modified citrus pectin inhibited the spontaneous extraprostatic colonization of injected cells from a prostate cancer cell line and in a dose-dependent fashion.240
Cancer cells must communicate with one another to invade, colonize, and proliferate in healthy tissue; but this proprietary citrus pectin appears to disrupt this inter-cellular communication, slowing metastasis. The American Cancer Society suggests that modified citrus pectin may “be useful for preventing or slowing the growth of metastatic tumors in very early stages of development.”241 For instance, 70% of prostate cancer patients treated orally for 12 months with a modified citrus pectin preparation experienced a slow-down in the rise of prostate-specific antigen, or PSA, concentrations in the blood—without side effects.239 A suggested dosage is 5-15 grams daily, taken without food.
34. Four-Nutrient Supplement – Pomegranate, Broccoli, Green Tea, and Turmeric
As discussed, inhibiting effects against prostate cancer have been reported in published studies for a number of individual nutrients, including pomegranate extract,130,131 broccoli compounds (I3C, DIM, and PEITC)18-20 green tea extract,45,46 and curcumin (a key compound in turmeric).52,63,64 A recent, double-blind study documented the potency—and possible synergism—of a supplement that combines powders from all four of these food sources.1
Patients with a PSA relapse after radiotherapy or surgery for localized prostate cancer were randomized to receive capsules of either placebo or the four-nutrient supplement, three times daily. After six months, the median increase in PSA levels in the supplemented group was only 14.7%, while the median PSA increase in the placebo group was 78.5%.1 A striking 46% of the supplemented subjects showed PSA levels that were at or below baseline values, compared to only 14% of the placebo subjects. Among supplemented patients, 92.6% were able to continue on active surveillance, compared to just 74% of the placebo patients.1 There were no statistically significant side effects.1 This identical formula is now commercially available, though it’s likely that many Life Extension® members have already been taking comparable potencies in supplements that contain these specific nutrients.
This article described a huge number of nutrients that have been shown in published scientific studies to help reduce prostate cancer risk.
These nutrients function via multiple mechanisms to inhibit the development and progression of prostate cancer and/or induce cancer cell apoptosis (cell destruction).
The latest research—including a remarkable, controlled clinical trial1—reveals the dramatic effectiveness of combining some of these nutrients in men who failed initial treatment for prostate cancer. This is the kind of controlled study that mainstream doctors look to when assessing the efficacy of a particular therapy.
Aging men have an incredible opportunity to reduce their risk of prostate cancer, and while doing so, protect against most other degenerative diseases as well.
Long-time members of the Life Extension Foundation® should appreciate this voluminous data as they have been taking many of these nutrients over a multi-decade time period.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
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