April, 2018

Throwing Nightshade

By Michael J. Katin, MD

It was in 1830 that one of the major events in American culinary history, if such an expression might even be possible, occurred in Salem, New Jersey, when Robert Johnson ate a basket of tomatoes in front of a crowd and did not drop dead of acid poisoning. It was nearly one hundred years later that a different Robert Johnson sold his soul to the devil at a crossroads in Clarksdale, Mississippi, in exchange for mastery of the blues guitar, with no tomatoes involved. In any event, even though tomatoes had already been consumed in southern Europe for years, they had still been considered poisonous in Britain and the United States, and Robert Johnson's dramatic demonstration allowed the tomato industry in New Jersey to take root and blossom (sorry, couldn't help it), without which there would have been no Campbell's soup produced in Camden, New Jersey, no V-8 juice produced by Campbell's, no Carmela Soprano's Sunday Gravy, and no President Chris Christie.

Over the past several years it has been increasingly common to read that substances that were thought to be hazardous to our health may have had their risk overstated and, even more interestingly, might actually be beneficial. These would include dark chocolate, eggs, butter, tripe, and coffee. The next time you sit down to a hearty dinner of hot buttered tripe, washed down with Vietnamese egg coffee and chocolate, remember that you're probably extending your life by at least two weeks.

The most amazing thing is that not only have all these products had redemption, but the most ostracized consumable of all is now undergoing re-evaluation. Yes, this would be the outcast member of the nightshade family, tobacco!

Its relative, the tomato, was rehabbed over one hundred years ago and now it's come time for tobacco to be accepted as the miracle plant that it is. Both tobacco and tomatoes can be chewed (although there seems to be an opening for marketing tomato-flavored chewing tobacco ), and there are some other culinary adaptations (deep fried tobacco flakes being the most popular), but the most important use of tobacco may be in......cancer treatment!

The question has been raised as to why tobacco does what it does. The original concept was that tobacco exists to increase sex appeal. Why would the Nicotiana tabacum plant possibly care about that? A less anthropocentric reason would be that molecules in the tobacco plant are noxious to insects, fungi, and viruses, and it is only through a happy twist of fate that nicotine binds to nicotinic acetylcholine receptors in the human body to release neurotransmitters that affect mood, appetite, and memory. Except for the part about COPD, lung cancer, bladder cancer, and arteriosclerotic disease, nicotine is a fantastic drug!

Aside from the benefits of smoking in other diseases (ulcerative colitis! Parkinson's disease!) , there are now multiple ways that the tobacco plant can help fight cancer. Tobacco contains defensins, which are cysteine-rich proteins that act as deterrents to bacteria and fungi. In January, 2017, a research article described that defensing NaD1, from the ornamental tobacco plant Nicotiana alata, can induce cell membrane lysis in tumor cells Ironically, cigarette smoke suppresses human beta defensin production in oral mucosa, increasing the risk of overgrowth of pathogens and malignant transformation.

In addition, tobacco plants produce cembranoids, which are not combat robots or helical coils but rather molecules that also protect tobacco from fungi. For years this class of compounds has been evaluated for anti-cancer purposes, including preliminary findings in 2007 that there could be several mechanisms, such as inhibiting protein phosphorylation. By 2010, a major publication in Planta Medica from the University of Louisiana in Monroe investigated natural, biocatalytic, and semisynthetic cembranoids and found that 2 compounds had significant anti-migratory activity against two highly-metastatic human prostate cancer cell line. One of the researchers disclosed that his laboratory had support from Philip Morris from 2005-2007. It was not disclosed how the cancer cells were able to light their cigarettes.

As if tobacco itself isn't beneficial enough, a common additive, coumarin, may also be very useful in cancer treatment. Coumarin is found in a large variety of plants, including Chinese cassia cinnamon and minimally in the more commonly used Ceylon cinnamon. It is also found in woodruff, bison grass, cherry blossoms, and tonka beans. Conspiracy theories hold that coumarin was added to tobacco by Southerners
http://medicolegal.tripod.com/coumarin.htm distraught by their loss in the American Civil War, as payback to the North. Regardless of the reason, it had been a commonly added flavoring to many things other than tobacco, at least until the FDA in 1954 banned its use in food, and is also renowned as rat poison, since rodents metabolize it differently than do humans; large amounts of coumarin can still be hazardous to humans because of hepatotoxicity and nephrotoxicity. Even without being added to foods, it is still consumed by many people through ingestion of cherries, apricots, strawberries, and black currants. Probably worth the risk. In any event, coumarin and its derivatives have a plethora of potentially beneficial properties in addition to offing rats. Coumarin-based organoselenium can reduce myelotoxicity of carboplatinum and has even been shown to enhance effects of carboplatinum in two human cancer cell lines. Even better, osthole another derivative of coumarin, may cure every disease known to humankind.

There's even one more contribution tobacco may make to our health. As if it's not enough that it willfully gives up its leaves to be chopped up and burned to make people happy, the loyal little Nicotiana tobacum plant may now have another important role: surrogate motherhood. Etoposide is produced from the Himalayan mayapple plant and enzymes from that organism were able to be reconstituted in tobacco plants, helped significantly because tobacco genetics has been studied so extensively due to research by industry!! Many more plant-originated compounds may yet be found to be able to be generated in this manner. Ironic.

What other botanical species have been studied so extensively for so many years, to maximize profitability?* For all we know, soon we might hear that someone's found medical benefits from marijuana!

Maybe next month.

*Actually, a lot of them, but they're not as interesting.

Emanuel Countdown: Dr. Ezekiel Emanuel's biographies list his birth year as 1957 but, interestingly, do not list a birth date. He has expressed that he does not wish to live past his 75th birthday. Giving him every benefit of the doubt, he will have his 75th birthday no later than December 31, 2032. Including April 1, 2018, this leaves 5,389 days to his goal.