Protecting the Prostate with Botanicals, Nutritional Compounds & Diet

Compiled by John G. Connor, M.Ac., L.Ac., Edited by Barbara Connor, M.Ac., L.Ac.

Table of Contents
Introduction
    Some Risk Factors    
Foods to Avoid
Useful Foods
Excerpts from the Scientific Literature on the Effects of  Botanicals on Human Prostate Cancer

Introduction:
This is a summary of an article by Donald Yance entitled: “Prostate Cancer.  A Revolutionary Wholistic Approach featuring Applications for Botanical and Nutritional Medicine.”  I am taking the liberty of summarizing it for the benefit of our male patients as Barbara and I find the information contained in his article invaluable. In order to keep this summary short I am not including any of Donald Yance’s references to the scientific literature which he so painstakingly documents throughout his 55 page article.  He includes 1120 references to the scientific literature.  

Donald Yance feels that in the wake of the failure of conventional treatment modalities, especially refractory prostate cancer, a new revolutionary approach based on phyto-therapy-based compounds is the most effective modality to improve the outcome of this disease. He feels that research in this area is leading to effective means to prevent or delay the progression of the disease by strategies implementing the use of botanical and nutritional compounds together with diet.

It has been found that by combining herbal extracts against cancer it significantly enhances their activity in the cell lines tested compared with extracts alone.

Please refer to our Integrative Oncology Consulting Program article to find out more about how Barbara and I work with cancer. Barbara and I hope you find this article helpful and useful in maintaining good prostate health.

Some Risk Factors:
  • Overweight and obese men are more likely than their normal weight counterparts to be diagnosed with prostate cancer.  Obesity, however, may appear protective for prostate cancer in younger men.
  • In prostate cancer, as well as most of the common cancers, a known risk factor is increased abdominal fat.  With increased abdominal fat come several endocrine alterations which can initiate or drive prostate cancer.  These include insulin resistance, leptin resistance, and estrogen dominance.  Abdominal fat in men, as in women, relates to more estrogen and while men do need some and hence have the enzymes to make it, too much can disrupt normal prostate cell function and initiate a malignancy.
  • Lack of sunlight. Geographic distribution of prostate cancer mortality is the inverse of that of UV radiation.
  • Exposure to pesticides.  Working with pesticides may increase a man’s risk of prostate cancer.
Foods to Avoid:
  • Red meat consumption:  The cooking of red meats at high temperatures, or on charcoal grills, is known to lead to the formation of both heterocyclic aromatic amine and polycyclic aromatic hydrocarbon carcinogens.  Components of the Western diet – namely red meat and foods that increase glycemic load – appear to play an important role in the process of the p53 mutation that then causes cancer.
  • Excess consumption of commercial dairy products also appears to increase the risk of prostate cancer, an effect that may be more attributable to calcium intake than to dietary fat or protein.
  • High calcium and nonfat dairy products are also associated with an increased risk of prostate cancer.  Of note, although the majority of calcium was consumed from dairy foods and from skim milk in particular, other factors in dairy foods such as dairy fat and protein were not associated with prostate cancer risk.
Useful Foods:
  • High intake of tomatoes, which contain lycopene, and of cruciferous vegetables which contain sulforaphane, and diindole methane (DIM) are protective against prostate cancer development.  Other reddish foods, such as watermelon, papaya and pink grapefruit, may also contain lycopene, but at lower concentrations than in tomatoes.  Cooking broccoli and tomatoes is better than eating them raw.
  • Greater levels of selenium, vitamin E and lycopene have been shown to reduce prostate cancer risk in one out of every four Caucasian males; and those who inherit a specific genetic variation that is particularly sensitive to oxidative stress.
  • Eating a diet with omega-3 fatty acids from oily fish could stop the spread of prostate cancer, according to recent research.  Gammalinolenic acid (GLA) and eicosapentaenoic acid (EPA) have independently been reported to suppress growth of prostate cancer in part by regulating the LOX pathways.
  • Pomegranate juice has shown to inhibit prostate cancer and slow down the growth of existing prostate cancer.
  • Avocados have been shown to inhibit the growth of prostate cancer cells as well.
  • Flax seeds supplemented in the diet of men with prostate cancer reduced both the proliferation rate and increased apoptosis.  Flaxseeds have potent antiestrogenic effects on estrogen receptor positive breast cancer, and recently were found to down-regulate cancer-induced vascular endothelial growth factor (VEGF).
  • The results of a recent study showed that soy isoflavone intake was associated with a 50% reduction in the incidence of prostate cancer.  Donald Yance recommends consumption of high-quality soy foods, preferably fermented such as tempeh, miso and tamari, but permits tofu and a small intake of soy milk.  He also recommends fermented soy powder.
  • The phenolic antioxidant resveratrol, found in berries and grapes, inhibits the formation of prostate tumors by acting on the regulatory genes such as p53, while activating a cascade of genes involved in cell cycle and apoptosis including p300, Apaf-1, cdk inhibitor p21, p57 (KIP2), p53 induced Pig 7, Pig 8, Pig 10, cyclin D and DNA fragmentation factor 45.
Excerpts from the Scientific Literature on the Effects of Various Botanicals on Human Prostate Cancer:
  • Panax Ginseng 
    • Ginseng shows proliferative activity against human prostate cancer cell.  Ginsenoside Rg3 activated the expression of cyclin-kinase inhibitors, p21 and p27, often found down-regulated in prostate cancer. Ginsenoside Rg3 arrested LNCaP cells at G1 phase, and subsequently inhibited cell growth through a capase-3-mediated apoptosis mechanism, leading to a reduction in the androgen receptor and 5 alpha-reductase enzyme.  PSA levels were also reduced.
  • Ashwagandha (Withania somnifera)
    • One of the steroidal lactones, known as Withaferin A (WA), induced Par-4-dependent apoptosis in androgen-refractory prostate cancer cells.
  • Chinese Skullcap (Scutellaria baicalensis)
    • Scutellaria baicalensis (SB) and Glycyrrhiza uralensis (Chinese licorice) inhibited cell growth of prostate cancer and down-regulated PSA levels.  Baicalein effectively suppressed growth and PSA expression, and induced G(1)/S arrest in LNCaP cells.
    • In another study the inhibition of proliferation of prostate cancer cells after a short period of exposure to baicalin was associated with induction by apoptosis.
    • Recent research data demonstrates that SB has a similar effect in the induction of apoptosis in a human prostate cancer cell line LNCaP (lymph node carcinoma of the prostate).
    • Baicalin has shown to induce apoptosis and inhibit proliferation of prostate cancer cells, and has direct anti-tumor effects on human prostate cancer cells.
  • Turmeric (Curcuma longa)
    • Curcumin was shown to decrease the proliferative potential and induce apoptosis potential of both androgen-dependent and androgen-independent prostate cancer.  Curcumin is an therapeutic anti-cancer agent, as it significantly inhibits prostate cancer growth.
    • Curcumin induced cytotoxicity in the LNCaP prostate cancer cell line.
    • Curcumin may inhibit the growth factor collaboration between the prostate cancer cells and the osteoblast/stromal cells, thus exhibiting a potential to prevent the establishment of bony metastases.
    • Another study concluded that Curcumin appears to constitute a potential agent for the prevention of cancer progression, or at least of the initial phase of metastasis in prostate cancer.
    • Another study found that through inhibiting AR (androgen receptor) expression, Curcumin reduced the function of PSA promoter and inhibited PSA protein expression.
· Green Tea Camellia sinensis)
o   Evidence from epidemiologic studies indicate that frequent consumption of green tea is inversely associated with the risk of several types of human cancer, including prostate cancer.
o    The anti-cancer effects of Green tea extract appear to be greatly enhanced by other anti-cancer compounds including curcumin, selenium, lycopene and Grape skin and seed.
o    Ongoing research is demonstrating that the anti-cancer effects of Green tea extract together with pomegranate concentrate (40% ellagic acid) against prostate cancer are synergistic and very promising.
o    In one study when the scientists measured the proliferation of prostate cancer cells, there was a significant decrease in how fast new cancer cells appeared for the men who had consumed either green or black tea.
o    In another study it was found that prostate cancer risk declined with increasing frequency, duration and quantity of green tea consumption.  The dose response relationships were also significant, suggesting that green tea is protective against prostate cancer.
o    The polyphenols present in green tea help prevent the spread of prostate cancer by targeting molecular pathways that shut down the proliferation and spread of tumor cells, as well as inhibiting the growth of tumor nurturing blood vessels.
o    Other results indicate that polyphenols from black tea inhibit the IGF-I signal transduction pathway, which has been linked to increased prostate cancer incidence in human populations and, therefore could prevent prostate cancer.
o    Another study suggests that habitual drinking of tea and intakes of vegetables and fruits rich in lycopene could lead to a reduced risk of prostate cancer.
o    It is more efficacious to take powdered green tea extract (95% polyphenols/40% EGCG) rather than drinking tea as a cancer adjuvant therapy.
o    Caffeine has been shown to potentiate tea polyphenols, such as EGCG, so it is preferable not to decaffeinate the tea.

· Milk Thistle (Silymarin marianum)
o    Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner in prostate cancer cells.
o    The antiangiogenic effect of Silymarin were also exemplified in a study whereby exposure of DU145 prostate, as well as MCF-7 and MDA-MB-468 breast cancer cells to Silymarin resulted in a dose-dependent decrease in the secreted vascular endothelial growth factor (VEGF).
o    In a recent study, the potential of silibinin as an anticancer agent was examined.  It demonstrated an ability to down-regulate telomerase activity and PSA levels.
o    In another study it was concluded that silibinin, possesses potent antiproliferative, proapoptotic and antiangiogenic efficacy against prostate cancer.
o    Studies aiming at testing in vivo efficacy of Silymarin/silibinin revealed that dietary feeding of silibinin to animals bearing prostate cancer significantly inhibits tumor growth.

· Reishi (Ganoderma lucidum)
o    Reishi powdered extract (RPE) has demonstrated strong activity against a wide range of prostate cancer cell lines.
o    RPE induces apoptosis, inhibits cell proliferation, and suppresses cell migration of highly invasive human prostate cancers cells PC-3.
o    Ganoderma lucidum inhibited constitutively active transcription factors AP-1 and NF-jB in breast MDA-MB-231 and prostate PC-3 cancer cells.

· Licorice
o    Recent studies have shown that licorice possesses prostate cancer inhibiting ability especially when combined with other herbs including Chinese skullcap and rabdosia r.

· Frankincense (Boswellia serrata)
o    Boswellic acids have shown to modulate the immune system and inhibit a number of cancers including glioblastoma, melanoma, colon, several forms of leukemia and prostate cancer.

· Nettles (Urtica dioica & Urens)
o    Extracts of nettle roots are highly effective in treatment of benign prostatic hyperplasia (BPH) and this has been confirmed by numerous clinical trials.

· Pygeum (Pygeum africanum)
o    Pygeum africanum extract (PAE) has shown an ability to inhibit prostate cancer proliferation.
o    In another study it was found that the therapeutic effect of PAE is due at least in part to the inhibition of growth factors responsible for the prostatic overgrowth in man.

· Red Clover (Trifolium pratense)
o    Red clover extract rich in isoflavones, which act as phytoestrogen compounds, interferes with the hypothalamic-pituitary-testicular axis in prostate cancer patients by inducing testicular resistance to LH, reducing circulating levels of androgen, and thus decreasing prostate cancer proliferation.

· Saw palmetto (Serenoa repens)
o    Saw palmetto is an effective dual inhibitor of 5alpha-reductase isoenzyme activity in the prostate.
o    In another study saw palmetto extract inhibited proliferation of prostate-derived cell lines in a dose-dependent fashion.  The berry extract also reduce Cox-2 expression and Cox-2 expression is associated with an increased incidence of prostate cancer.  So, saw palmetto further suppresses prostate cancer by reducing COX-2 expression and this would provide basis for prostate cancer chemoprevention and justify long-term consumption of saw palmetto extract-containing formulations.
o    Donald Yance classifies saw palmetto as a nutritive anti-catabolic agent with many applications in health promotion, and specifically as a general prostate tonic.

· Resveratrol
o    Japanese Knotweed (Polygonum cuspidatum) is the richest known source of resveratrol.
o    Resveratrol inhibits proliferation and induces apoptosis of DU145 and LNCaP cells in concentrations exceeding 5 microM; and altered cell cycle distribution of all prostate cancer cell lines in concentrations as low as 0.5 microM.
o    In another study resveratrol suppressed the proliferation of human prostate cancer cells with atypical apoptotic feature, interfering with the expression of HSP70.
o    In one study resveratrol-induced apoptosis and proliferation arrest were evidenced in prostate derived cells PZ-HPV-7 (non-tumorigenic line), LNCaP (androgen-sensitive cancer line, and PC-3 (androgen-insensitive cancer line. Resveratrol induced a decrease in proliferation rates and an increase in apoptosis in cancer cell lines in a dose and time-dependent manner.
o    In another study grape (red wine) consumption reduces prostate cancer by more than 50%.  There was also a 60% lower incidence of the more aggressive types of prostate cancer.  The more clinically aggressive prostate cancers were where the strongest reduction in risk was observed.
o    Resveratrol has antitumoral activity in androgen-sensitive, and androgen-nonsensitive human prostate tumors by inhibiting survival pathways such as that mediated by PI3K (an androgen receptor sensitive pathway.)

· Ellagic acid
o    Pomegranate extract, standardized to ellagic, was recently tested in humans for absorption and was found highly absorbable.  However, the superior bioactivity of pomegranate compared to its purified polyphenols illustrated the multifactorial effects and chemical synergy of the action of multiple compounds compared to single purified active ingredients.  This is why it is important not to simply isolate out a compound, but to use a concentrate that is standardized to an active compound or group of compounds, which still contains a whole-plant/food concentrate.
o    Pomegranate extract (PE) demonstrated an ability to block endogenous, active, estrogen biosynthesis and inhibited aromatase activity by 60-80%.
o    In another study ellagic acid showed a synergistic effect against hormone refractory prostate cancer with chemotherapy.
o    Ellagic acid and resveratrol demonstrated a synergistic effect against prostate cancer.
o    A recent study showed that a daily glass of pomegranate juice can hold back prostate cancer and could even prevent men dying of the disease.  There was also evidence that pomegranate juice was actually killing prostate cancer cells.  Just one 8 oz. glass of juice per day increased the stability period of prostate cancer four-fold, scientists found.  Simply by drinking pomegranate juice, a man of 65 to 70 with prostate cancer could complete his normal life span without having to undergo harsh medical treatments.

· Isothiocyanates (ITCs)
o    Cruciferous vegetables such as cabbage, broccoli and Brussels sprouts that are widely consumed are especially rich in glucosinalates which are converted by plant myrosinase and gastrointestinal microflora to isothiocyanates.
o    Organic cabbage sprouts are the richest source of phenethyl isothiocyanate, which when combined with curcumin has shown to be a potent suppressor of prostate cancer.
o    ITCs have recently been shown to inhibit neurological diseases by controlling inflammation, and through the enhancement of levels of glutathione in the brain, which reduces oxidative stress.
o    Sulforaphane (SFN) is an isothiocyanate found abundantly in organic broccoli sprouts, and to a much less extent in cruciferous vegetables.  Little to no SFN is found in non-organic commercial broccoli.
o    In one study SFN inhibited the growth of human prostate cancer cells, and another showed it stopped the growth of colon cancer cells.  Several recent studies also showed that SFN kills Helicobacter pylori, the bacteria that cause stomach ulcers and can lead to stomach cancer.
o    SFN causes autophagy to inhibit release of cytochrome C and induced apoptosis in human prostate cancer cells.

· Wasabi
o    Wasabi contains a diversity of unique ISTs which are effective inhibitors of cancer.  Extracts from Wasabi have been shown repeatedly to be effective against stomach, breast, prostate, colon and melanoma cancers.

· DIM (3,3’-diindolylmethane)
o    Indole-3-carbinol (13C) is a compound that occurs naturally in Brassica vegetables such as cabbage and broccoli.  DIM (3,3’-diindolylmethane) is a dimmer of 13C that is formed under acidic conditions and unlike 13C is more stable with higher anti-cancer effects.
o    DIM promotes healthier estrogen metabolism by preventing the receptor binding of “stronger” more stimulating estrogens.  DIM induces Phase I and II enzyme-pathways involved in carcinogen metabolism.
o    The ingestion of DIM may benefit CaP patients and reduce disease recurrence by eliminating micro-metastases that are often present in patients who undergo radical prostatectomy.
o    Further tests showed that DIM inhibits the actions of dihydrotestosterone (DHT), the primary androgen involved in prostate cancer.  DHT works by stimulating the expression of prostate specific antigen (PSA), PSA acts as a growth factor for prostate cancer, however when androgen-dependent cells were treated with DIM, the level of PSA decreased, which suggests that DIM functions at a gene expression level.  DIM significantly halted proliferation of androgen-dependent human prostate cancer cells.

· Quercetin
o    In a double-blind trial, 67% of patients taking quercetin had an improvement of prostatitis symptoms compared to a 20% response rate in the placebo group.
o    Quercetin has been shown to inhibit the growth of several human cancer cell lines including breast, prostate, ovarian, squamous cell, cervical, bladder and gastric cancers, acute myeloid and acute lymphoid leukemia and some lymphomas.
o    Quercetin at concentrations of 25 and 50 micro M significantly inhibited the growth of the highly aggressive PC-3 prostate cancer cell line and the moderately aggressive DU-145 prostate cancer cell line.
o    Quercetin is found in apples, onions, broccoli, eucalyptus, green, black and red tea and blue-green algae.

· Lycopene
o    The carotenoid lycopene is found abundantly in tomatoes and tomato products.  Consumption of tomato products with olive oil significantly raises the plasma antioxidant activity of lycopene.
o    In a recent study involving men with clinically localized prostate cancer the lycopene group had an 18% reduction in PSAs while the control group had a 14% increase.  Overall the investigators found that the treated group had smaller tumors, which were more likely to be confined to the prostate.
o    Researchers found that the tomato carotenoids phytofluene, zeta-carotene and lycopene significantly reduced growth of prostate cancer cells.  Donald Yance does not believe in supplementing with synthetic lycopene.
o    In another study significant inverse associations with prostate cancer were observed with plasma concentrations of lycopene and zeaxanthin.  The higher the plasma concentration of carotenoids the lower the incidence of prostate cancer.
o    In one study lycopene decreased the expression of two prostatic cytokines, IGF-I and IL-6, both regarded as risk factors for prostate cancer.
o    In another study lycopene exposure suppressed phophatidylinositol 3-kinase-dependent proliferative and survival signaling in androgen-responsive LNCaP and androgen-independent PC3 cells through the induction of G0/G1 cell cycle arrest.

· EPA and DHA Essential Fatty Acids
o    Fish oil is rich in omega-3 fatty acids, EPA and DHA. Both EPA and DHA have been shown in multiple experiments to inhibit metastasis of several cancers including breast, prostate and colon cancer.
o    EPA and DHA intakes are related to both lower total prostate cancer risk and advanced prostate cancer risk.  Men with the highest quintiles of EPA and DHA combined had an 11 percent lower total prostate cancer risk and advanced prostate cancer risk was 26 percent lower, according to the risk analysis.
o    In one study it was found that a diet rich in commercial n-6 fatty acids (soy, corn and vegetable oils) increased the spread of prostate tumor cells into bone marrow, while n-3 fatty acids blocked the invasion.
o    Researchers found that the main metabolite of AA, prostaglandin E2, enables prostate cancer cells to spread to the bone marrow.  However, when EPA and DHA were present at just half the concentration of the n-6 fatty acid, this spread of cancer cells was stopped.  Tumors appear to exploit the n-6 fats as a high energy source – giving them the energy they need to maintain a high growth rate – and to create important signaling molecules.  N-3 fats are known to interfere with the various functions of omega 6 fats.
o    Dietary gamma-linolenic acid, found in oils of Pine seed, Primrose, Black current seed and Borage seed also inhibit prostate cancer via suppression of elevated generation of PGE(2) and 5S-HETE.

· Vitamin D
o    Recent laboratory and epidemiological studies indicate that a high circulating level of 1,25 (OH)2D vitamin D, the biologically active form of vitamin D, inhibits prostate carcinogenesis.
o    Cumulative sunlight exposure during the summer months was a better predictor of survival in men with prostate cancer (as well as other cancers) compared to the winter months.  This observation added to a growing body of evidence that vitamin d metabolites play an important role in cancer survival. 
o    A recent study found that 1alpha, 25-dihydroxyvitamin D3 could prevent prostate cancer progression by interrupting the interleukin-8 signaling required in tumor angiogenesis.
o    Two recent studies showed that vitamin D3 (1,25-VD) inhibited the function of protease enzymes that are involved in tumor invasion in prostate cancer.
o    In men with advanced prostate cancer, vitamin D supplementation reduced blood clots, a common complicat5ion that occurs and contributes both to cancer progression and mortality.
o    Vitamin D has also shown to enhance the anti-tumor effects of radiation and chemotherapy against prostate cancer.

· Selenium
o    Many epidemiologic observations support selenium as a protective agent against the development of cancer.  Both case-control and randomized placebo-controlled trials in humans also suggest that selenium can decrease the risk of developing prostate cancer.
o    In the now famous Clark study, a 63% reduction in prostate cancer was found in men who received 200 micrograms of selenium from selenium-enriched yeast containing mostly selenomethionine.
o    In another study the incidence of prostate cancer was reduced in the selenium arm by two-thirds compared to placebo.
o    Selenium is found in Brazil nuts, tuna and sunflower seeds.

· Copper
o    In a study done to test for the efficacy of copper deficiency to retard tumor growth in the Dunning prostate cancer model it was observed that there was significant reduction in size of the primary tumor in mice rendered copper deficient.

· Zinc
o    Zinc induces cell of the intestinal tract to produced metallothionein protein which has a very high affinity for copper and is excreted in the stool  This means that any newly ingest copper does not reach the blood circulation system. 
o    Foods rich in Phytic acid, such as pasta and soy foods, reduce the absorption of zinc, so try to avoid taking zinc along with these foods.
o    Cancerous prostate cells contain less zinc than healthy prostate cells and this may lead to the cancer’s ability to spread.

· Vitamin E (gamma-tocopherol)
o    High concentrations of gamma-tocopherol, the most common dietary form of vitamin E (found in seed oils such as Sea Buckthorn, walnut and pumpkin) are associated with a statistically significant reduction in the risk of prostate cancer.

· Boron
o    Men who ate the greatest amount of boron were 64% less likely to develop prostate cancer compared to men who consumed the least amount of boron.
o    A closer look at boron in another study found that it inhibits the proliferation of prostate cancer cell lines DU-145 and LNCaP in a dose-dependent manner.
o    Boron-rich foods include plums, grapes, avocados, prunes and nuts such as almonds and peanuts.

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Compassionate Acupuncture and Healing Arts, providing craniosacral acupuncture, herbal and nutritional medicine in Durham, North Carolina. Phone number 919-309-7753.

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