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.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

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