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Galectin-3 & the Evolution of Prostate Care: Beyond the PSA Test

Don't miss Dr. Issac Eliaz, MD, LAc, MS, lead a Vendor Workshop, Friday, July 12, from 11:15am to 12:00pm, in Keystone, Colorado. Visit www.naturopathic.org/conference.asp to register.

Prostate treatment and maintenance of prostate health can be challenging – regardless of which medical approach or combination is applied. Diagnostic and therapeutic protocols for this critical area of men’s health have attracted heated debate among experts -- particularly regarding PSA testing, early intervention, and other aspects of prostate care that are being called into question as the body of established data continues to evolve.

Prostate conditions can be indistinct and difficult to diagnose as symptoms are often vague and their significance varied. Furthermore, the prostate is influenced by a number of shifting factors such as hormonal profiles, toxic body burden, heavy metal exposure and nutritional imbalances. Prostate cancer (PCa) in particular generates a series of questions, some of them currently unanswerable. With recent data challenging the efficacy and value of the prostate specific antigen (PSA) test, what are the alternatives? And even when a biopsy confirms cancer is present, what does that say about the prognosis?

These issues are of great importance. According to the American Cancer Society, around 240,000 men will be diagnosed with prostate cancer this year. More than 28,000 will die of the disease. Other conditions, such as prostatitis and benign prostatic hyperplasia (BPH) cause pain and discomfort and reduce quality of life.

Over time, research advancements will lead to new treatments, but people are suffering today. As integrative/naturopathic physicians, are we doing enough now, with our existing tools, to provide the maximum clinical benefit for prostate patients?

PSA Test: Uses and Limitations
On the surface, the PSA test would appear to be a lifesaver, and for many years it was treated as such. However, new research demonstrates that widespread PSA screening does not necessarily improve prostate cancer outcomes, for a number of reasons.

First, the PSA test does not measure prostate cancer aggressiveness. Many prostate cancers grow slowly and may never pose a threat. Yet once cancer has been detected, the standard clinical approach is to aggressively address it through surgery, radiation, androgen deprivation therapy (ADT) or a combination. These conventional approaches raise the problem of unnecessary procedures, which can cause a range of side effects.

Conversely however, the PSA test may also have trouble identifying aggressive cancers early. Essentially, the test may be too quick to detect slow-moving cancers – leading to unnecessary procedures -- and too slow to detect aggressive ones.

This does not mean that the PSA test lacks clinical significance. Rather, it means that the test must be taken in context with complementary diagnostics, patient history and the variable nature of the PSA test, which can be influenced by medications, seasons, time of the day, BPH, and -- very important, the size of the prostate, among other influences. When treating a PCa patient with elevated PSA, or when seeing a patient with prostate complaints and elevated PSA, it’s useful to follow up on the PSA, but we shouldn’t rely on it.

We can lower PSA by reducing the prostate volume, or by decreasing inflammation or eliminating prostate infections. However, a lowered PSA doesn’t mean that the patient is free of PCa. Rather, reducing prostate inflammation is an essential component of strategic PCa treatment, as it reduces risk of mutation into a more aggressive carcinoma, and reduces risk of metastasis.

Galectin-3: A New Prostate Cancer Bio-Marker
Research published March, 2013 in Oncotarget suggests that the tumorigenic biomarker galectin-3 serves as a compliment to better interpret PSA test results. Authors of the study found galectin-3 present at higher levels in the prostate sera of patients with active prostate cancer.

In last month’s AANP Conference blog post, I discussed the active role of elevated serum galectin-3 in cancer progression, congestive heart failure, and numerous other inflammatory and fibrotic conditions and diseases. When present at normal levels, the protein galectin-3 regulates cellular growth and communication. However, elevated galectin-3 levels can indicate a number of degenerative conditions, including cardiovascular disease and cancer. Galectin-3 is pro-inflammatory and is actively involved in numerous pathogenic processes related to inflammation, fibrosis, tumorigenesis, proliferation and metastasis. It’s not only a byproduct of cancer metabolism, but rather an active culprit in carcinogenesis and other pro-inflammatory and fibrosis-related processes.

This fast growing body of data has previously demonstrated the role of elevated galectin-3 in prostate cancer; a 2009 study in The American Journal of Pathology showed that reducing levels of galectin-3 inhibited prostate cancer metastasis.

However, the 2013 Oncotarget study is the first to indicate the application of the galectin-3 assay concurrently with the PSA test. In my practice, I routinely recommend testing galectin-3 levels concurrently with PSA, together with other diagnostic tools. Clinically, I find that the galectin-3 assay offers a larger diagnostic context and clearer perspective into the progression of the disease.
In 2011, the galectin-3 serum assay was approved by the FDA and is currently covered by most health insurances in the diagnosis and prognosis of CHF and cardiovascular disease. It is my hope that studies such as the Oncotarget study help to expedite the approval of this important test in the diagnosis and prognosis of cancer and other diseases.

Additional Diagnostics
There are many other diagnostic tools that can provide greater context for the PSA test. Prostatic acid phosphatase (PAP) is a more traditional prostate test which may indicate that the cancer has metastasized to the bones. PAP can point to the tendency for a more aggressive PCa in general, even in the absence of evident metastasis.

Hormone testing is also critical. For example, men with higher testosterone levels respond more favorably to treatment. Estrogen is also a factor, as elevated levels in men can correlate with increased risk of prostate cancer, as well as more aggressive disease. This is also true of prolactin. Patients should also be tested for progesterone, DHEAS and DHT. If total estrogens are elevated, testing the different estrogens and related metabolites becomes important.

There are a number of important, non-hormonal markers as well. Elevated CEA or IGF-1 levels may indicate cancer aggressiveness. PCA3, a recently developed gene-based test, can help elucidate a patient’s risk. This test can be used to follow up low volume and low Gleason score prostate cancer and may replace the risky practice of annual biopsies as part of the standard “watchful waiting”/active surveillance approach.

In addition, imaging should play a key role in diagnosing and staging the disease. MRI, MRI-S, PET, CT, color Doppler ultrasound and bone scans can all help determine the severity of the cancer.
In the eye of the skilled holistic and integrative physician, these profiles and other details gathered prior to intervention can offer a picture of the whole person, shedding light on the individual causes of their prostate conditions and specifically, PCa. Such an integrative evaluation helps direct patients and practitioners to the appropriate tools which can lead to a reversal of these condition(s). One of the key principles in addressing PCa is maximum diagnosis and minimum intervention.

Nutritional Approaches: Research on Modified Citrus Pectin
With elevated galectin-3 as a therapeutic target impacting prostate carcinogenesis, inflammation and other pathogenic processes, we need to find effective ways to block the protein. One proven agent which is gaining increased attention is modified citrus pectin (MCP) – a form of pectin which is modified enzymatically, reducing its molecular weight to less than15 kilodaltons and esterification to less than 10 percent. These adjustments significantly increase the bioavailability of MCP by allowing it to enter the circulation from the GI tract; they also give MCP greater bioactivity in binding to galectin-3. MCP also safely binds and eliminates heavy metals such as lead, mercury, arsenic and others from the circulation and digestion, without affecting essential minerals as demonstrated in several published clinical studies. This is another critical component in prostate care, as harmful heavy metals tend to accumulate in prostate tissue.

A growing number of studies have found that MCP inhibits cancer cell aggregation and angiogenesis, and promotes apoptosis through the inhibition of galectin-3. Several clinical studies on MCP in the treatment of PCa have shown significant benefit:

•  A 2003 phase II clinical study published in Prostate Cancer and Prostatic Diseases analyzed the effects of MCP in men with biochemical relapse of prostate cancer after local therapy. Results showed that 5 grams of MCP three times per day for one year more than doubled PSA doubling time in 70% of subjects.

•  A 1999 clinical study presented at the International Conference on Diet and Prevention of Cancer in Finland found that prostate cancer patients who received MCP significantly increased their PSA doubling time.

•  A 1995 animal study, published in the Journal of the National Cancer Institute, found that MCP blocked prostate cancer adhesion to endothelial cells, reducing lung metastasis by 50 percent.

MCP has also been shown to synergistically enhance chemotherapeutic agents, while mitigating their side effects. A 2012 preclinical study published in Cell Biology International showed that combining Doxorubicin (Dox) with MCP increased the anti-cancer activity of both agents. MCP synergistically enhanced the cytotoxic effects of Dox in both androgen-dependent and androgen-independent prostate cancer, allowing for a significant reduction in the dosage of Dox.

Research demonstrates that a number of herbal and botanical ingredients, such as turmeric root, honokiol from Magnolia bark, saw palmetto berry, grape skin, pomegranate, quercetin, pumpkin seed, pygeum bark, and certain medicinal mushrooms can have a profound impact on prostate health via multiple pharmacological mechanisms. Actions include hormone modulation, immune modulation, anti-inflammatory actions, liver and detoxification support, direct toxicity, regulation of apoptosis, and prevention of angiogenesis, among others.

Strategic Interventions
One of the guiding principles of integrative medicine is to strategically incorporate therapies from a broad range of clinical traditions, depending on the patient’s needs. In cancer care, practitioners use every appropriate method available to clearly diagnose and stage the disease. We apply conventional treatments when indicated, such as ADT therapy, and maximize these therapies with dietary and lifestyle changes, targeted complementary modalities, and nutraceutical adjuncts that modulate hormones, boost immunity, reduce inflammation and actively fight the cancer via multiple mechanisms. By adopting such a multifaceted approach, we can identify each patient’s unique needs; address the underlying causes of their condition and strategically integrate leading therapeutic advancements to effectively restore health.