Nut Consumption, Pancreatic Cancer and Woody Allen

In the 1973 Woody Allen movie ”Sleeper,” Miles Monroe (played by Allen), is the nerdy owner of the Happy Carrot health food store who undergoes cryostasis (deep freeze) only to be awakened 200 years later. He finds himself in a place where all that he had come to know has disappeared. Two physicians observing him from a distance comment on his unusual dietary request: wheat germ, organic honey and tiger’s milk. Puzzled, one physician asks why he would want such odd foods. The second physician explains that 200 years earlier, low fat foods were considered healthy. “What, no deep fat, no steak, no cream pies, or hot fudge?” she asks incredulously. “No”, he explains, “those were thought to be unhealthy…. precisely the opposite of what we now know to be true.”

I was reminded of this scene by a paper published in the British Journal of Cancer (BJC). Based on observations from 75,680 women in the Nurses’ Health Study, investigators showed that the regular consumption of nuts was inversely associated with the risk of pancreatic cancer. Indeed, those who consumed one ounce of almonds, Brazil nuts, cashews, hazelnuts, macadamias, pecans, pine nuts, pistachios or walnuts, three times per week had a 35 percent reduction in the risk of pancreatic cancer (P = 0.007). This was found to be independent of age, height, obesity, smoking, diabetes, or other dietary factors. Although the study was funded by the International Tree Nut Council Nutrition Research and Education Foundation, they had no participation in the design or analysis of the data.

The consumption??????????????????????????????????????????????????????????????????????????? of nuts has previously been shown to be highly beneficial. In a Spanish study of 7,000 people, ages 55 to 90, those who ate three servings per week had a 55 percent reduction in death from cardiovascular disease and a 40 percent reduction in death from cancer. Clearly, the association between nut consumption and health is both strong and broad based, as it extends from cardiovascular disease to cancer.

The majority of the calories in nuts come from lipids (fats) including monounsaturated and polyunsaturated fats like oleic acid, found in olive oil, linoleic, gamma-linolenic and alpha-linolenic acids as well as the saturated fats, stearic and palmitic acids. Of the nuts commonly consumed the highest lipid content is in macadamia nut, followed by peanuts, pecans, cashews, walnuts, pine nuts, hazel nuts, pistachios, almonds and chestnuts. The protein content of nuts favors peanuts and pine nuts. A number of micronutrients are also found in nuts including flavonoids, stilbenes, proanthocyanidins, calcium, iron, B6 and magnesium.

The BJC study stands in strong contradistinction to the oft-repeated admonition that nuts should be avoided, as voiced for many years by health experts and dieticians. The fat avoidance craze of recent decades held that foods containing lipids were to be eschewed. Health conscious individuals were encouraged to eat grains and carbohydrates.

Today we recognize the important benefits of lipids and find that higher fat and high protein diets are gaining traction over the older food pyramid. We now find that high carbohydrate intake may in part be responsible for many contemporary maladies suggesting that the agrarian revolution of 10,000 years ago that made high calorie/low fiber grains readily available may ultimately prove to have been more a curse than a blessing.

An expert is one whose “faculty for judging or deciding rightly, justly, or wisely” is recognized and granted sway over society. But who judges the experts? The current BJC study suggests that in many fields of science and medicine the experts can be wrong. How many people denied themselves the pleasure and, we now come to learn, the health benefits of nuts based upon expert recommendations?

In our contemporary diagnosis and management of cancer, might the experts be leading us astray in other areas? Perhaps we should all ponder that point as we nibble on a few Macadamia nuts.

Outliving Cancer: Surviving Even the Deadliest Forms of Cancer

FINAL book cover-lo resMy book of the same title (Outliving Cancer, Basic Health 2013) is an exploration of cancer biology through the lens of individual patients.

The conceptual framework within which my laboratory operates, reflects the basic premise that cancer doesn’t grow too much it dies too little. Thus, effective cancer therapy (regardless of contemporary wisdom) provides benefit only when the drugs induce cell death. While the forms of cell death may vary from necrotic, to apoptotic, autophagic and others, it is, in the end, the death of the cell that heralds a successful outcome.

We, along with a small group of collaborators, have pioneered the concept of individualized cancer care using each patient’s tumor as the study model. Fresh biopsies exposed to chemotherapies and signal transduction inhibitors, live or die depending upon their relative sensitivity to the drugs in question.

The simple elegance of our platform has provided immense insight into cancer biology, insights we describe in the book, which may ultimately lead to a greater understanding of all human diseases.

Having successfully applied this approach in many diseases, we have published findings in leukemia, breast, ovarian, and most recently, in lung cancers. We are now very excited by observations in one of the most difficult cancers – pancreatic. Ongoing work in this disease will be the subject of upcoming clinical trials.

One patient with pancreatic cancer comes to mind. Steve Lockwood presented to medical attention in the Spring of 2010 with weight loss, abdominal pain, and unrelenting low back pain. He was seen by a local medical oncologist after a CT scan revealed a large mass in the pancreas, extensive liver metastases and disease throughout the abdomen. He then sought the opinion of UCLA and the City of Hope.  Neither institution could offer any solutions. Luckily his wife, a nurse, had heard about our work and brought him to Rational Therapeutics.

His tumor markers were doubling every week. He couldn’t eat and required daily intravenous hydration, as well as high dose narcotics to get through each day. He was deteriorating so rapidly that I had concerns that he might be too ill for me to help. We decided to conduct an open liver biopsy. As his tumor markers, CA19.9, climbed into the multiple thousands, we found a three-drug combination to be the most active for his tumor.

Within a week, the pain began to subside. After two weeks, it was demonstrably better. By the time we began treatment cycle two, he had begun to gain weight and came off pain medications entirely.

Two cycles later, his tumor markers were normal and his PET CT remarkably improved. An additional cycle later, his PET CT was normal.

While there are many difficult cancers, metastatic pancreatic cancer figures among the worst. The fact that we could find a treatment was cause for celebration. The fact that Steven now remains in remission, after three years, is nothing short of a miracle. As I have written before, there are two kinds of cancer patients: those we can treat and those we can’t. Steve Lockwood turned out to be one of those patients we could.

Like Niebuhr’s Serenity prayer, oncologists need the serenity to accept the cancers they cannot treat, the courage to treat those that they can, and the wisdom to know the difference. It is our use of laboratory assays to select treatments that provides us with that particular form of wisdom.

Assessing the Benefit-Risk Ratio of Nitrates

Many readers may have come across a recent report linking the consumption of processed meats (sausage, bacon cold cuts, etc.) to the incidence of pancreatic cancer. Intriguingly, the higher risk seemed to only apply to men and not women. The explanation for this remains obscure, but may reflect other dietary habits more common to men or other factors, such as increased alcohol consumption or smoking. But this is only a speculation.

The presumptive mechanism of cancer causation seems to revolve around the presence of nitrates in these cured meats. Nitrates are added to meats as preservatives. Preservatives function to inhibit bacterial growth responsible for food spoilage. Nitrates under the acid conditions in the stomach, are converted to nitrites. And it is these nitrites, primarily in the form of nitrosamines, which may be the culprits.

When we exam these findings several issues must be considered. First, however nefarious the consuming public may think the meat packing industry, I for one am fully convinced that these companies do not add nitrates to cause cancer. Quite the contrary. The most dangerous organisms found in foodstuffs, through spoilage and lethal food toxins, are the anaerobic organisms. The most frightening of all is clostridium botulinum, which produces the fatal condition known as botulism. Nitrates converted to nitrites are potent inhibitors of clostridia.

In the grand scheme of things, it is highly likely, in fact certain, that many, many more people have been saved from nitrites in food than would ever die from pancreatic cancer. These risk-benefit ratios are the subjects that keep epidemiologists up at night.

Nitrates in food are not the only possible man-made exposures that we encounter on a daily basis. Take for example chlorinated water. The “chlorine” in water is, for all intents and purposes, bleach. That’s right every time you drink tap water you are being exposed to tiny quantities of bleach. It is probably unnecessary for me to explain to the average reader, the risks and hazards of common household bleach, which is a solution of hypochlorite. And, however toxic that bottle under your sink may seem, remember that is only a 5 percent solution.

Another example is fluoride. While the benefits of fluoridation of water are numerous, including bone density and improved hardness of the enamel of teeth, demonstrably reducing tooth decay, fluorine itself is not, at least theoretically, free of risk. We know that sodium fluoride is an inhibitor of phosphodiesterase, an enzyme responsible for regulating cyclic AMP and cyclic GMP levels in the cell. These protein kinase A signals events may be tonically affected by changing levels of fluoride in the cell, to what end it is hard to say.

Like chlorination or fluoridation of water, nitrates in food represent risks that we as a society have accepted, based upon what we deem as acceptable benefit-risk ratios.

It is possible, that the increased incidence of food-borne illness and enteric infections, increased dental caries associated with the elimination of all these risks, may far exceed the hazards associated with these exposures.

The human species evolved over millennia in an environment exploding with free radical activity, fortunately we have developed defenses, superoxide dismutase, glutathione, peroxidase, catalase, etc., that counteract the toxic effects of these chemical compounds. Whether the man-made exposure substantively changed the balance will be a topic of discussion for years to come.