Three TRP Channel Agonists and One Absentee Antagonist.

Having known E. Randy Eichner, MD, FACSM, for many years, we have always found his unique style of homespun delivery highly entertaining, as was evident in his recent commentary, Fighting Muscle Cramps With Two Spices and One Hot Fruit (1). Dr. Eichner offers his opinions based on his interpretation of 84 slides from an ACSM symposium that he found online and one scientific abstract. Dr. Eichner likes to describe ‘‘in plain words’’ (1) the science he distills for his audience and he is a master storyteller in that regard. Unfortunately, peppering his argument with words such as ‘‘cramp busters,’’ ‘‘investment banker,’’ and ‘‘cult brand’’ illustrates Dr. Eichner’s passionate bias, unnecessarily inflames what should be a science-based discussion, and obscures the scientific facts. To borrow from Dr. Eichner (1), ‘‘Let us explain. ’’ For the past 2 years, we have both been involved with the applied science related to the activation of oral TRP receptors by natural spices and how that activation alters electrical characteristics of muscle cramps induced by voluntary isometric contraction of the triceps surae muscle of the calf. One of us (BM) helped organize and moderate a 2016 ACSM symposium on the origin and prevention of exercise-associated muscle cramps (EAMC). Dr. Eichner’s distillation of that symposium in his column was so clear and one sided, one might think that he was actually there. Because Dr. Eichner did not attend the symposium, he did not hear the speakers’ comments, context, or slide descriptions. Nor was he privy to the 30-min audience Q&A and commentary involving some excellent scientific discussion. Based in part on his absentee analysis, Dr. Eichner paints the underlying science (including a study performed in WLK’s laboratory) as ‘‘weak’’ and ‘‘unconvincing,’’ but without much in the way of substantive scientific criticism. We all welcome thoughtful review and analysis of the research we conduct V that is the essence of peer review, a pillar of the scientific enterprise. Curiously, Dr. Eichner had no access to the science he denigrated, aside from his absentee slide review and reading one abstract presented at the 2016 Experimental Biology meeting. Sadly, had Dr. Eichner attended either meeting, he would have had the opportunity to engage in a discussion of the science V the healthy give and take that moves science forward. Dr. Eichner has not had access to the full data set, its analysis, a detailed description of the study design, or the full range of variables examined, yet he feels comfortable maligning the science. In his ironically titled ‘‘Pearls and Pitfalls’’ column and in a series of email exchanges with us, Dr. Eichner argues that a placebo response accounts for the statistically significant findings, that is, that subjects saw through the alternate taste profile of our vehicle control. Of course, that conspiracy theory depends on each subject, while in the throes of a painful calf cramp, being able to consciously manipulate the electromyographical signal directly overlying an individual muscle. As researchers, we fully acknowledge that no method of blinding is ever perfect; however, we can vouch for the fact that the double blinded, vehicle controlled, randomized crossover design met or exceeded all commonly employed research practices for similar studies. Contrary to Dr. Eichner’s absentee analysis, neither the symposium speakers at the ACSM Annual Meeting nor the abstract he cites argued that dehydration, electrolyte imbalances, fatigue, or other factors are not involved in the initiation of EAMC. Had he been present, he also would have heard the discussion describing how not all cramps are alike in terms of triggering factor, environmental circumstance, or internal milieu. Those points were made by several speakers and again during the audience discussion that ensued. Performing unbiased, high-quality laboratory studies is difficult, and that is particularly true when studying EAMC. The perfect experimental protocol has yet to be developed. We appreciate healthy skepticism because that helps fuel the critical thinking required to refine theories, clarify mechanisms, and expand our overall knowledge. There is no doubt that more research is needed to help us understand how TRP channel agonists alter the electrical characteristics of EAMC in ways that prevent or diminish cramping. Homespun criticism of research of which one has no first-hand (or even second-hand) knowledge is a pitfall, not a pearl. We would encourage Dr. Eichner to remain open-minded as future research findings generate a clearer understanding of how ‘‘two spices and one hot fruit’’ can prevent and treat EAMC.