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