Vitamin D and Cancer

A report issued earlier this year (available on Medscape once you register) on Vitamin D levels in breast cancer, identified low levels of this nutritional factor as a risk for breast cancer. Dr. Kristin Skinner reported at the American Association of Breast Surgeons, that the most aggressive forms of breast cancer (i.e. ER negative, triple negative or basal-like) were associated with lower blood levels of vitamin D.

This is one of many reports associating vitamin D levels with disease. Indeed, so many reports on this topic have been published that vitamin D consumption in the U.S. has exploded. While some physicians have made careers promoting the concept, the science of vitamin D is indeed credible and very interesting.

What is vitamin D? Well, although we refer to it as a vitamin, it is, in fact, a hormone. It is obtained from the diet or from exposure to sun. The most potent form of vitamin D is that associated with sunlight exposure. Once in the body, vitamin D interacts with cells at very specific receptors. The term receptor reflects the role of these “landing sites” contained within the cell’s nucleus. As the vitamin D molecule traverses the cell membrane and enters the cell nucleus, it binds with the vitamin D receptor, which connects to the chromosome at a hormone response element and drives the cell machinery forward.

The vitamin D receptor is part of a large collection of genes called the steroid super gene family. These include receptors for estrogen, progesterone, testosterone, and, yes, vitamin D.

What makes the field so interesting is the interaction between these factors. Inside the nucleus are a large variety of receptors. Vitamin D and the other molecules are known as ligands. When the ligands enter the nucleus, they must compete for receptors. This leads to a complicated collection of down-stream events that are unique to the individual. If, for example, your nucleus has a number of orphan receptors (receptors with unclear ligand associations) and these orphan receptors have some binding affinity for the vitamin D, then the down-stream signaling will reflect this new biology.

Many studies have associated vitamin D levels with disease. Prostate cancer, colon cancer, even blood-born tumors may, in part, arise in vitamin D deficient states. But, the most compelling evidence in several analyses supports its protective effect against colon cancer. In one study there was a 15 percent risk reduction for every 10 ug/ml increase in circulating blood levels of calciferol (Gandini S, Int J Cancer. March 11, 2011). What is interesting about the report from the University of Rochester is that it was the most aggressive forms of breast cancer that were found to be associated with Vitamin D deficiency. To date, the correlations with the more common forms of breast cancer have been less positive.

Cardiovascular disease and musculoskeletal diseases are also associated with vitamin D levels. So critical is vitamin D to the well-being of the human that mankind could not easily migrate far north from the equator until he found a source of vitamin D unrelated to the skin synthesis. This source proved to be fish and animals that survived by eating fish. Older readers will remember cod liver oil as a remedy doled out by grandparents. It is ironic that cod liver oil is an excellent source of vitamin D.

While deficiencies of vitamin D are likely to be deleterious, substantially exceeding the normal levels of 30 micrograms/ml have not been shown to further enhance health. It is prudent for patients to monitor their vitamin D levels and highly appropriate for physicians to recommend replacement. Interestingly, a scientific colleague recently commented that sun exposure, by providing active vitamin D, is greatly under appreciated as a healthful activity. He wondered whether the broad use of sunscreens would ultimately save or cost more lives when the aggregate impact of vitamin D levels upon cancer and health is finally understood.

The Bad News is, You’re Going to Survive

There is a common tendency on the part of cancer patients, upon receiving their diagnosis, is to act as if their life is over and that there is nothing they do to affect it.

Given the dismal outcome for many solid tumor patients, the tendency to give up is understandable. What often happens is the patient starts bingeing, eating and drinking too much, gaining weight, and foregoing all the lifestyle changes they had worked so hard to incorporate before the diagnosis. They’ll stop exercising and continue to smoke, figuring it has no impact.

But, what if you’re not dying? What if your first anniversary passes and you’re still well? How about your second, or third?

This has been the experience of several of my patients, who jokingly now admit that they’ve never been in worse physical condition, largely due to “letting themselves go” after the diagnosis. In response, we suggest that patients maintain a normal lifestyle even in the face of the most difficult diagnoses. Appropriate nutrition, physical activity and emotional well-being all contribute to good outcomes.

Like our pancreatic cancer patient,who I need to put on a diet, many patients over indulge. In a way, this is a new wrinkle in the old adage, “If I knew I was going to live this long, I would’ve taken better care of myself.”

A New Wrinkle on an Old Remedy

For many years, naturopaths and health-conscious individuals have recommended the consumption of grape seed extracts. Chemical analyses of grape seeds have provided a treasure trove of active ingredients including resveratrol, anthocyanins, pro-anthocyanins, and numerous terpenes. Many of these substances are potent antioxidants and there is reason to believe that they may have meaningful health benefits.

As one of the editors of the Journal of Medicinal Food, I was asked to review an article on the chemical activities of grape seed extracts. I then wrote an editorial describing the interesting findings in this study and their biological relevance. The most interesting aspect of this well-conducted analysis was the description of a wholly new mechanism of action for the substances found in grape seeds. What the authors found was that the chemical species in grape seed extracts influence gene expression through a process knows as histone acetylation. What makes this so interesting is the fact the histone acetylation is one of the fundamental regulators of genetic expression and a critical part of the new field of science known as epigenetics.

Epigenetics is the field of study that examines heritable attributes that are not incorporated into DNA sequence. These epi-phenomena take existing genes and determine whether or not they will actually be expressed. The reason that this is so important is that it shines a very bright light on the limitations of genomic analyses (studies that examine the DNA sequence in tissues). Clearly, if the consumption of foodstuffs (like grape seed) can alter gene expression then the use of genomic profiles to predict cellular behavior can only be viewed as highly simplistic.

We are continually impressed by the complexity of biology and are humbled when we consider the intersecting pathways that take us from gene to function.

Does Anyone Deserve to get Cancer?

It was not long ago that cancer carried a painful stigma. Patients afflicted with this terrible disease not only suffered with physical pain, but the emotional stress of what was once considered a “dirty” diagnosis. In my practice, I have often encountered patients from various cultures who ask that I not mention the word ‘cancer’ to their mother or father when I describe the treatments I must administer. In some countries, the cancer diagnosis is never mentioned and the treatment employed must, wherever possible, avoid the obvious features of cancer chemotherapy — like hair loss. Indeed, in some Asian countries, immune and nutritional therapies are more popular than chemotherapies as these allow patients to avoid the obvious side effects of cancer treatment.

While we in the U.S. consider ourselves “enlightened,” some of these attitudes persist within our culture, particularly with regard to cancers that had historically been associated with lifestyle or other exposures. Unfortunately, lung cancers and some cancers of the upper digestive tract are viewed in this way even today.

While cigarette smoking remains a principle causative factor in lung cancer, the percentage of men and women who smoke continues to fall while the incidence of non-smoking related cancers is on the rise. We are now witness to a growing realization that more than 20 percent of lung cancers occur in patients with distinct genetic predispositions unrelated to lifestyle or cigarette exposure. In addition, our increasingly polluted environment provides us all an unhealthy helping of carcinogens with almost every breath.

To suggest that lung cancer patients in some way constitute a population less deserving of our care and attention is an affront to the very principles of medical practice.

I, for one, find my increasingly good responses in lung cancer among my most gratifying successes. This heretofore untreatable malignancy is now revealing responses that challenge the successes in the “treatable” cancers like breast and ovarian. As some of our patients with metastatic disease are now alive at five and six years, we are certain that rationally delivered treatments can have the same beneficial impact upon this disease as any other. Every patient deserves the opportunity to receive the best, most effective, least toxic treatment. Our job is to match our patients with their best options, regardless of who they are, how they got the cancer or any contributing factors that may or may not have been responsible.

No one deserves cancer.

There is Nothing New Under the Sun

The most sophisticated Western medical centers, purveyors of allopathic medicine, spent decades denigrating natural products as “quackery.” Nutritional supplements, antioxidants and natural extracts were viewed as the purview of hippies and nuts. Yet, a brief examination of the most active compounds in cancer therapy today quickly establishes how wrong-headed this mindset was. In addition to the taxanes (extracts of taxus brevifolia and taxus baccata), the camptothecins (extracts of camptotheca acuminata), the vinca alkaloids and the epothilones, are host of simple small molecules like retinoids, platins and arsenic trioxide.

As Western scientists have developed a greater understanding of cellular circuitry and cancer metabolism, they have been dragged, kicking and screaming, to the admission that nature is indeed the best organic chemist.

Recent reports of a Chinese herb combination called PHY906 are but the latest example of this reality. Careful analysis reveals PHY906 — a combination of four herbs — contains 64 compounds including flavonoids, saponins and monoterpenes. As an editor of the Journal of Medicinal Foods, I have published and edited many articles on related topics. The terpenes are among the most important and ubiquitous bioactive compounds found in nature, with effects on cholesterol metabolism, Ras gene signaling, and mitochondrial function.

PHY906 is one more example of the adage that “there is nothing new under the sun.”

The Role of Natural Products in the Treatment of Cancer

Cancer medicine utilizes small molecules as therapeutics. Many compounds in use today are derivatives of plant alkaloids. Among the most widely used drugs derived from plant alkaloids are the taxanes, vinca alkaloids and topoisomerase inhibitors. Antibiotic anti-tumor agents including anthracyclines, Bleomycin and Mytomycin-C have been isolated from streptomyces bacterial cultures. Several antimetabolites also have their origins in natural products.

It is evident that nature is an excellent source of effective treatments. Unfortunately, there has been hesitancy on the part of the conventional oncology community to incorporate other natural products into therapeutics. Nonetheless, a wide variety of plant extracts have significant anti-tumor activity. Among the compounds under investigation are the cyclic triterpenes, mono- and di-terpenes, as well as stilbenes and derivatives of scutellaria and glyzrrha. In addition to cytotoxic activity, many plants are effective in chemoprevention. Extracts of grape (resveratrol), chocolate, green tea (catechins), as well as colored fruits (anthocyanins) and berries (ellagic acid) can elicit protective responses, some mediated by the KEAP-1, NRF-2 pathway. Click here to read a previous article that discusses the medicinal qualities of garlic, wine and chocolate.

The arbitrary distinction between commercial therapeutics and nutritional substances has created an unnecessary barrier between conventional therapists and those who practice complimentary care. A growing cadre of physicians is developing expertise in natural product therapeutics in parallel to their traditional training. Chinese herbal and Indian ayurvedic medicine instruct physicians in the appropriate use of natural therapies. An explosion of interest in resveratrides, curcuminoids and terpenes are fueling a rebirth of interest in these naturopathic approaches.

As an editor of the Journal of Medicinal Food, I have contributed to the literature on the medicinal value of foodstuffs and natural products. Original articles on the benefits of garlic have been followed by the study of the monoterpene limonene and contributions on Chinese herbal medicines, chocolate extracts and grape seed extracts. Our laboratory has been engaged in the formal analysis of many natural products and we have reported exciting results with several classes of compounds. In one instance, an Australian extract was administered successfully in the treatment of advanced renal cancer under FDA IND. We are convinced that an exciting opportunity for cancer treatment exists in the formal study and rigorous evaluation of these biologically active molecules and combinations.

Garlic, Wine and Chocolate – The Effects of Nutrition on Cancer

One of my most popular lectures is titled: Garlic, Wine and Chocolate. Not surprisingly, almost everyone likes to have a medical reason to eat fine food, drink fine wine and eat dessert. As an editor of the Journal of Medicinal Food, our mission is to examine the scientific basis of foods as medicinal substances.

In our inaugural issue in 1998, I authored the lead article on garlic as a medicinal. Garlic contains more than a dozen active chemical substances, many of which have been shown to have antiviral, antibacterial, blood pressure and cholesterol lowering, as well as anti-cancer benefits. We have also published definitive studies on wine and grape extracts, with a focus on resveratrol, proanthocyanins and other polyphenols; as well as an entire issue on chocolate (the extract of cacao), which examined the potent antioxidants and immune modulatory compounds found therein.

With this background, lectures on these topics have been a natural direction for our public education series through our affiliated hospitals and educational institutions. For readers in the Southern California area, you are invited to attend lectures of this type open to the public. Please leave a comment if you are interested in more information or copies of the above-mentioned articles.