Life Extension Magazine December 2013
A Natural Arsenal for Prostate Cancer Prevention
By Michael Downey
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.