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Life Extension Magazine December 2013
As We See It  

Prostate Cancer Prevention Controversy

By William Faloon

Why We Suggest Certain Drugs

When it comes to combatting cancer, Life Extension long ago learned that the initial treatment regimen should be aggressive enough to deprive tumor cells of an opportunity to mutate into forms that are resistant to future therapies. If we know of a relatively side effect-free drug that works via a single or multiple mechanisms to impede tumor survival, we’re going to include it in our comprehensive surveillance program.

Let’s talk first about metformin. It was used in England in 1958 but did not make it into the United States until 199537 years later!157 I am familiar with metformin because the FDA tried to have me incarcerated for recommending it as an anti-aging drug long before it was “approved” to treat type II diabetes.

12-core Prostate Needle Biopsy  

What’s been happening over the last ten years is an explosion of published studies that consistently show that metformin reduces the risks of certain tumors and may be an effective cancer treatment.158-165

People ask me all the time, how can an anti-diabetic drug work so well against cancer? The encouraging news is that metformin functions via multiple mechanisms to create a less favorable environment for tumor progression.166-175 We know that insulin (and glucose) increase the risk of many tumors.176 This is of particular concern to obese men with prostate tumors. Metformin lowers blood glucose and insulin levels. The sidebar on the next page reveals the multiple anti-cancer mechanism of metformin.

There are nutrients that can have similar effects such as standardized green coffee extract.177 We nonetheless suggest that a man with an elevated or rising PSA should ask his doctor to consider prescribing metformin. The starting dose can be 500 mg of extended release (Metformin ER) taken with breakfast each day. Under the supervision of the patient’s local medical doctor, the dose can be increased to 500 mg ER taken at breakfast and at dinner. (Dose ranges for non-extended release metformin are 250 - 850 mg taken before no more than three meals a day.) Metformin is an inexpensive generic drug and can be taken along with nutrients (like green coffee extract) that similarly function to reduce glucose/insulin.

Metformin does more than slash tumor-promoting glucose/insulin levels. It also acts directly on cancer cells to induce apoptosis and/or inhibit proliferation.91 Metformin does this conserving the process by which food is converted to energy.169-172 Healthy cells react to metformin by adjusting their functions to use less energy. A cancer cell, on the other hand, that is forced to minimize energy consumption is less able to exhibit aggressive metastatic or proliferative behavior.178 In other scenarios, the energy stress caused by metformin is sufficient to cause cancer cell death.

The National Cancer Institute is sponsoring a clinical study where metformin will be tested to see if it can slow the progression of prostate cancer in men undergoing active surveillance (watchful waiting) with low-grade tumors.179 We hope the study design includes the measurement of 2-hour post-prandial (2 hours after meals) blood glucose levels as well as glycosylated hemoglobin (HbA1c) to ascertain that optimal dosing of study subjects has been achieved.

Anti-Cancer Actions of Metformin

Numerous studies show the anti-diabetic drug metformin can slow growth of existing cancers and decrease risk of developing new cancers. Some studies show metformin may protect against prostate cancer and aid in treatment. Here are some of its anti-cancer mechanisms:

  • Metformin reduces levels of glucose, insulin, and insulin-like growth factors that fuel tumor growth.166-169
  • Metformin activates a powerful molecule called AMPK
    (adenosine monophosphate-activated protein kinase) that subjects cancer cells to unique metabolic stresses not experienced by healthy tissues. (Activated AMPK promotes death [apoptosis] of malignant cells and prevents their development.)169,170
  • Metformin independently inhibits mTOR (mammalian target of rapamycin) that regulates cell growth, energy metabolism, cell motility, cell survival, and protein synthesis.171,172
  • Metformin mimics the benefits of a hormone called adiponectin in activating AMPK-dependent growth inhibition in prostate cancer cells.173
  • Metformin blocks cancer cell reproductive cycles by decreasing levels of a growth-promoting protein called cyclin D1.174
  • Metformin increases production of a protein (p27) that inhibits the cell division cycle.174
  • Metformin suppresses vascular endothelial growth factor (VEGF) thereby cutting off the blood supply to tumors.175

At a cancer conference earlier this year, the results of a study were reported of 22 men (median age 64, median PSA 6 ng/mL) with confirmed prostate cancer that were given 500 mg of metformin three times a day 41 days prior to surgery (prostatectomy). In response to metformin the men showed the expected reductions in glucose and insulin growth factor-1 (IGF-1) blood levels, along with abdominal fat loss.180 What got the researchers excited was that compared to biopsied specimens, the surgically removed prostate glands showed a 32% reduction in a marker of cell proliferation (Ki-67) and a favorable alteration in a pathway tumor cells use to proliferate out of control (via mTOR).181

Knowledgeable members point out that curcumin interferes with these tumor growth pathways via similar mechanisms, which we at Life Extension have long been familiar with.182 My argument for recommending metformin is that it should produce potent additive effects to curcumin. Moreover, we still don’t know what the upper dose limits are for metformin and/or curcumin for cancer treatment, so taking both may have some obvious advantages.

Furthermore, because metformin is a drug, it tends to get more attention from researchers, perhaps because it is easier to obtain funding for drug studies. A European study published this year showed that metformin was effective against advanced castration-resistant prostate cancer. The doctors who conducted this study concluded:

To our knowledge, our results are the first clinical data to indicate that metformin use may improve PSA-recurrence free survival, distant metastasis-free survival, prostate cancer specific mortality, overall survival and reduce the development of castration resistant prostate cancer in prostate cancer patients. Further validation of metformin’s potential benefits is warranted.183

Daily Use of Aspirin May Decrease Prostate Risks

Researchers studied 2,447 men over 12 years, examining them every other year. After adjusting for age, diabetes, hypertension, and other factors, they found that men who took a daily aspirin or another NSAID (like ibuprofen) reduced their risk of moderate or severe urinary symptoms by 27% and lowered their risk of an enlarged prostate by 47%. Even more intriguing was the finding that men who consumed aspirin or another NSAID were 48% less likely to have an elevated level of prostate-specific antigen (PSA).187

Aspirin inhibits the cyclooxygenase (COX-1 and COX-2) enzymes, which are also involved in the arachidonic acid inflammatory pathway.188,189 COX-2 in particular is known to promote the proliferation of prostate cancer cells.56

Interestingly, men who are on androgen deprivation therapy to treat prostate cancer often show rising insulin levels that can stimulate tumor growth.167,184 By taking metformin, some of the side effects of androgen deprivation therapy can be mitigated, as was shown in this newly published European study.

So while nutrients like curcumin and green coffee extract and others may share functions that are similar to metformin, we cannot ignore the strong data showing specific benefits to low-cost metformin.

Another hormone that prostate tumors use to escape eradication is prolactin,39 and this can easily be suppressed by taking 0.25 mg to 0.5 mg of cabergoline (Dosintex®) two to three times weekly.185

Aspirin functions in multiple ways to interfere with prostate cancer propagation and metastasis and it may induce genetic changes that facilitate apoptosis.186 There is too much data about the potential role of aspirin as an adjuvant cancer treatment for men with rising PSAs not to use it.

What if PSA Screen Detects a Potential Problem?

If an annual PSA screen reveals a potential problem, a man has an early opportunity to:

  1. Review state-of-the-art studies to establish his status regarding the presence of prostate cancer.
  2. Confirm the diagnosis and get a Gleason score reading by an expert in prostate cancer pathology.
  3. Utilize published nomograms and neural nets to present the patient probabilities of organ-confined prostate cancer, capsular penetration, or disease progression to seminal vesicles and/or lymph nodes.
  4. Obtain refined laboratory studies and imaging studies to confirm or refute the above.
  5. Sit down with a physician that is least biased on a particular procedure and discuss the pros and cons of all therapies, including active surveillance.
  6. Investigate and discuss all co-related illnesses that might have gone unrecognized but that play a role in stimulating prostate cancer growth.

Treat Yourself As If You Already Have Prostate Cancer

This article is supposed to be about prostate cancer prevention, and here I am talking about therapies overlooked by most doctors that may facilitate enhanced treatment outcomes.

The reason we can’t ignore treatments is that aging men should accept the reality that in all likelihood there are malignant cells in their prostate glands now. This makes it easier to consistently follow prevention programs that can reduce the risk that clinically diagnosed disease will ever manifest. It also keeps one on the lookout for non-toxic treatments that may also have preventative benefits.

As I have related in the past, when my PSA reading came back at 1.4 ng/mL in year 2003, I treated it as if I had early stage prostate cancer by adopting healthier dietary choices and taking every nutrient and drug that had shown efficacy in prostate cancer prevention. Ten years later my PSA is 0.4 ng/mL.

I will remain on an aggressive prostate cancer treatment regimen and in the process reduce my risk for virtually every other age-related disease.

The articles in this month’s issue provide comprehensive approaches for the prevention of prostate cancer, including a comprehensive overview demonstrating the prostate cancer prevention benefits in response to Avodart® and finasteride. Men with any type of prostate malignancy may also benefit, as the programs we advocate for prevention may also facilitate better overall treatment.

For longer life,

For Longer Life

William Faloon

Don’t Accept Archaic Diagnostics

The highly variable skills of the urologist performing TRUSP (transrectal ultrasound guided needle biopsy of the prostate) is of great concern when a biopsy is needed.

Too often the urologist uses the TRUSP to target the prostate gland per se, rather than abnormal areas within the prostate. Rarely do we see a dedicated TRUSP report that mentions all of the important findings that can and should be related by the urologist e.g., gland volume, PSA density, status of the capsule and seminal vesicles, as well as location of hypoechoic and hyperechoic lesions within the prostate. Using the TRUSP to target the prostate gland, and not the various lesions within the gland is akin to diluting a vintage wine with ice cubes. (For illustration and a description of a model TRUSP report, see Appendix F of the book A Primer on Prostate Cancer by Strum and Pogliano available from Life Extension Media by calling 1-800-544-4440 or logging on to www.lef.org)

The varying quality of the ultrasound device and whether it is a standard gray-scale ultrasound or a color Doppler ultrasound is also significant. Color Doppler ultrasound, for instance, discloses pathologic states of increased blood vessel growth (angiogenesis) that is associated with more clinically aggressive prostate cancer, which is often of a higher Gleason score.18

MRI (magnetic resonance imaging) using DWI (diffusion weighted imaging) will also add to understanding the risk a particular patient with prostate cancer faces. That’s because when color Doppler ultrasound is combined with MRI-DWI, a predictive value regarding the level of aggressiveness of the prostate cancer may be established.19

In this manner, selecting only those men whose prostate cancers are most likely to be “bad actors” and who need invasive therapy can be accomplished, while sparing those men with cancers of low grade, which are often amenable to changes in lifestyle, diet, and use of supplements.