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 1995—37 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.
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.
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
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.
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,