My good friend Bill Bestermann, MD, a preventive vascularist at the Holston Medical Group in Kingsport, TN, has published an important article in CardioRenal Medicine. This paper, a long time coming, is not research but a highly informed thought piece that explains a new, previously unappreciated potential mechanism for the diabetes drug Metformin. It has far reaching implications for the management of many chronic diseases.
Bill first introduced this concept here on C&C in a piece called Metformin, Asymmetric Dimethylarginine and Cancer: The Keys to the Kingdom or a Tool to Pick the Lock?. He began to think seriously about some of these issues a year and a half ago after learning that my wife Elaine had been diagnosed with primary peritoneal (ovarian) cancer. It goes without saying that I am deeply, personally grateful for this contribution.
What’s most important about this most recent paper is that it was rigorously reviewed for CardioRenal Medicine, and so has at least the initial imprimatur of scientific credibility. I hope it now gets the additional attention I believe it deserves.
I’d urge all my clinician colleagues to review it carefully. I believe you’ll be appropriately inspired by both its elegance and its profound clinical ramifications.
WILLIAM H. BESTERMANN
The current scientific paradigms that shape our view of chronic conditions are simply inadequate. Clinical medical scientists might think much more seriously about questions like these: Why is it that metformin reduces the risk of heart attack, stroke, and cancer while other drugs lower the glucose and do not protect from these conditions? Why is it that studies of patients treated with insulin suggest an increase in cancer? Why is it that a single dose of metformin or a statin-type drug reduces heart attack size by half in experimental animals? Why are patients who take certain medications for high blood pressure more likely to develop diabetes.
Today, basic scientists have laid the foundations to begin to answer these questions and the answers are important as we work to improve the quality of care. In practical terms, our scientific literature places little value on work that translates new science into practice. That is part of the reason that there is a large gap between what is known and what we do. This is the first of a series of articles that we hope will serve to help in closing that gap. The link between cancer and other chronic conditions is important. If we can reduce the risk of cancer even slightly by refining the way we manage other chronic diseases, then that is important work.
Another reason for this article and Urgent Science is a very personal one. Brian Klepper, the founder of CareandCost, has recorded the struggle that his brave wife Elaine endures with ovarian cancer now. I myself have been cured of a very aggressive type of lymphoma. How many of our friends and family have been struck down by these ailments. We need to improve our rate of translation. We invite you to read this first piece carefully and if you have refinements or additions that will help the broader medical community understand these problems better, we invite you to send us your constructive comments. We promise to take them seriously and use them to improve what we all know about the newest science and how it might be used to help our patients.
Bill Bestermann is a vascular physician at the Holston Medical Group in Kingsport, TN.
From Brian – The germ of today’s extremely provocative post by Bill Bestermann, MD was the moment in early May when he learned that my wife, Elaine, had primary peritoneal (ovarian) cancer. Bill’s focus for many years had been on vascular disease, but he dove into the literature on cancer, metformin and ADMA, and was energized by what he found.
He called a few days later and asked two questions. ”Did you know that diabetics on metformin get cancer at half the incidence of those not on metformin? Or that diabetics with breast cancer on metformin have their cancers ameliorate at triple the rate of those who are not on it?” I didn’t, but these facts intrigued Dr. Bestermann enough that he relentlessly pursued the science.
The article below, not original research but an important synthesis that leads us to a new understanding, is what came out of that effort. It’s message is ground-breaking – genuinely a paradigm shift in how we might think about chronic disease – and is an specifically aimed at practicing physicians. We have provided all citations, with links, not only to allow verification of source information, but also allow the interested reader to dive deeply into the topic. We are well aware that the science in this piece may be beyond lay readers, and we apologize for this divergence from a more general format.
We are delighted and humbled that Dr. Bestermann has allowed us to publish this piece here. It has been peer reviewed and found to be sound by several capable physician-scientists. One of the goals of Care & Cost is to make the science that can impact clinical practice immediately available.
That said, I believe the content in an article of this caliber and potential impact should also be recast and allowed to work through the more traditional physician publication machinery as well.
“The human body is composed of four cardinal fluids called humors….In the normal body, these four fluids were held in perfect if somewhat precarious balance. In illness, this balance was upset by the excess of one fluid.”
This review is about metformin and cancer, but within a much broader context. It points to an important new science involving critical common core pathways that underlie the origins of multiple common chronic conditions. These pathways involve traditional signaling modifications like phosphorylation, but they also involve a fascinating new science of epigenetics and the methylation of proteins that are involved in inappropriate gene activation.
Continue reading “Metformin, Asymmetric Dimethylarginine, and Cancer : The Keys to the Kingdom or a Tool to Pick the Lock?”