"Virgin London Marathon: Man dies after collapsing at the finish line" The Independent. April 14. 2014 "Two runners die during half marathon in North Carolina" Daily Mail. April 14.2014 No one ever wants to read these headlines, especially on the same morning. Win are headlines such as these seemingly more frequent? This article will look at the actual risk rate of sudden cardiac death (SCD) with excessive endurance training (ET). What role do genetics and age play in this, and what arc the physiological changes that occur with excessive endurance training? Is there a threshold where exercise benefits become a risk, and can any of the pathophysiology of ET be mitigated? The Risk: Arc the risks really on the increase? To fully understand this, it is important to note in the past 35 years that there has been a 20-fold increase in those running marathons. Although tragic, the actual rate of SCD among marathoncrs is rare, reported to be one in every 100.000 participants.1 The risk remains the same, but the number of tragic events has increased due to the overall increase in actual participants. Age and Genetics: Do genetics and age play a role in SCD in endurance exercise? With younger runners (< 40 yrs). there are often underlying genetic defects unknown to the runner that increases risk. These include hypcrtrophic cardiomyopathy. anomalous coronary arteries, dilated cardiomyopathy. and congenital long QT syndrome. Those > 40 yrs of age tend to have coronary artery disease (CAD) or myocardial ischemia.2 The younger population group is seven times less likely to survive than the older group due to the underlying cause of the cardiac pathology. The older group is more likely to have cardiac ischemia, which is far more responsive to resuscitation efforts, a key factor when events occur on-site during an event1. The younger group suffering an event frequently lias an underlying condition of hypcrtrophic cardiac myopathy. Most do not have any premonitory symptoms or suspicion of this condition to predict a negative event. Pathophysiology: Other than genetic cardiac defects and myocardial ischemic infarct. is there anything else going on as a result of excessive endurance exercise? The research suggests there may well be. Both structural and electrical cardiac remodeling are associated with excessive endurance training. "Phidippides cardiomy opathy" is the suggested condition that may be a result of excessive endurance training, a term introduced by Dr. Peter McCullough. a cardiologist and former marathon runner.1" In 490 BC. Phidippides. a seasoned long-distance mnner. ran from Marathon to Athens to deliver the news of a victory, and upon delivering it. he preceded to drop dead. The distance from Marathon to Athens was a 26.2-mile run signifying the first marathon: this is where the name was derived. A more modern day example of possible Phidippides cardiomyopathy is the death of Micah True in 2012. This legendary ultrama-rathoner. who ran up to 100 miles a day. was found dead at the age of 58 while out on a 12-milc training mn. Autopsy showed an enlarged, scarred heart, and cause of death was considered to be lethal arrhythmia.1-' Training and the Athletes Heart: At rest, cardiac output is approximately 5 L/min. but with vigorous exercise, it will increase to 25 to 35 L/min. a five- to seven-fold increase.1 Is the heart meant to sustain this type of load increase for long periods? What arc the physiological changes that occur with this type of cardiac overload? Hcmodynamic changes occur that result in enlarged left and right ventricular volumes, increased LV wall thickness, increased cardiac mass, and increased left atrial size. These changes in the general population would be seen as pathological with poor cardiac outcome predicted, but they have been considered as a normal adaptation for the athlete. These changes actually may not be as benign as once thought. Over time, this chronic dilation may result in patchy cardiac scarring in response to excessive overload, which then may be a trigger for arrhythmias and fibrillation. 1-:-' This sustained cardiac output from training leading to transitory chamber dilation and the induction of patchy cardiac fibrosis may lead to "Phidippides cardiomyopathy."3 Biomarkers signaling pathology: Biomarkcrs typically used to assess cardiac damage as seen in cardiac infarct include cardiac troponin. creatine kinase MB. and B-type natriuretic peptide. Studies have shown that during and after marathon running. 50% of participates showed an increase in these biomarkers. along with renal dysfunction, including elevations in scrum urea nitrogen, serum creatininc. and cystitis C Biomarkers that indicate cardiac damage that should not be detectable in the normal population should be of concern when seen in the athlete after an endurance event. There is recovery tliat occurs with time where biomarkers and the cardiac structure return to normal. However, with repeating cycles of training, recovery, training, this repetitive cardiac disturbance may result in structural changes of resulting fibrosis and scarring, which then alters electrical dynamics, possibly leading to arrhythmias and fibrillation. A stud y looking at 102 healthy male runners ages 50 to 72 who had completed five marathons in the past three years compared to aged match controls revealed 12% of the runners had patchy myocardial scarring, threefold higher than the age matched controls. Also, the CAD event rate within the next two years was significantly higher in the runners:1 Another study assessing blood pressure and aortic elasticity in 47 "chronically" trained marathoners compared to 46 controls showed significantly higher systolic blood pressure and aortic stiffness in the marathoners. It is important to note aortic stiffness is an independent predictor of cardiovascular (CV) risk for any population group.2 It is fur thcr disheartening to learn that long-term marathoners had higher coronary artery calcium and plaque volume as shown on CT coronary angiography than the sedentary controls." Beyond the discussed hemodynamic changes and resulting structural and electrical changes during ET. other noted damage may come from the elevated cat-echolamine levels with resulting coronary vasoconstriction. elevated heart rate (HR) resulting in decreased diastolic filling time, changes in fatty acid metabolism, and lactic acidosis. all of which may result in further metabolic dysfunction.13 Oxidativc stress as a result of free radical production further exacerbates damage and may signal the immune system to generate cytokincs that stimulate fibroblasts proliferation, resulting in the scarring and fibrosis seen in some athletes.2 As previously noted, fibrosis and scarring is a potent trigger for arrhythmias and fibrillation, which ultimately is the cause of death. A common question after realizing the risks for SCD are predominately silent and unknown to the runner is: Arc there screening methods available that should be implemented for those wanting to engage in ET? Those with CAD may have the small benefit of symptoms during training, which triggers a physician visit and follow-up that may identify risk before a tragic event. For genetic conditions that are the cause of SCD in the younger runners, such as In pertrophic cardioim opathy, a heart murmur may be detected in 75% of the cases with an echocardiogram or ultrasound being the gold standard for diagnosis." However, in the case of Phidippides cardiomvopathy (cardiac fibrosis. scarring, and blood flow changes), which is often silent and as a result of training, the most effective diagnostic tool is a cardiac MRI. With the number of participants, the stretch in healthcare spending, and the cost of such a test, it clearly becomes cost prohibitive as a screening tool.3 There is a possibility a cardiac biomarkcr: galcctin-3 is used as a predictor in cardiac failure and could be used to assess cardiac fibrosis. a factor in Phidippides cardiomvopathy.1 This may offer a cost-effective screening tool in the future. Mitigating the Effects: This is an area of debate that science has not yet provided answers. Excessive endurance training generates a great deal of free radicals."s" Free radical production can overwhelm the buffering capacity of the body and deplete the antioxidant systems, leading to cellular damage, including damage to DNA. lipids. and proteins. The ability for the body to repair and heal is dependent on numerous factors, including healthy nutrition, sleep, recovery time, and stress management. It also has been shown the rate of upper respiratory tract infections increases in those after a major endurance event: this has been postulated to be due to decreased immune function based on the stress of the event, and/or a depletion in key antioxidant/ immune factors.1011 It could be hypothesized that the level of nutrients typically provided by a standard diet will not provide the level of protection needed when demand increases to the extent it docs in ET. The body has an elaborate system to manage free radicals including the antioxidant enzymes, such as catalase. superoxidc dismutasc. and glutathione peroxidase along with Vitamins C. E. and A. glutathione. CoQIO .and flavonoids. Although there is inconsistency in the research that supplementation with antioxidants will offset oxidativc damage or will improve performance, there is research indicating the role for supplementation in other areas worth noting. Vitamins E or C have been shown to partially prevent skeletal muscle damage caused by exhaustive cxercise.s This could be worth further consideration for possible protection of cardiac muscle. It seems highly plausible that providing the body with additional support nutrients to improve immune function and manage or reduce oxidativc stress would have some benefit in health long term. Just measuring short-term results, such as improved performance, may be shortsighted. Recovery is considered one of the most important factors in training. This involves restoring glycogen stores via carbohydrate sources, protein for repair of tissue. RBC. and immune factors, and rein dration and electrolytes balance. One area that has been recently documented is a 4:1 combination of car bohydratc to protein in recovery from prolonged exercise. Exercise >60-9() minutes depletes the body's energy supply. Without proper fuel and subsequent energy production, the machinery of the body cannot function optimally. The combination of protein with carbohydrate postexercise not only provides greater muscle glycogen refueling, hence energy supply, it also stimulates greater muscle protein synthesis.12 More recently, the use of salmon protein hydrolysatc has been supported due to its slightly higher protein percentage than whey and improved digestive kinetics. One can wait for the science to mature in this area, or forge ahead considering the safety profile of utilizing supplements versus their risk. This seems to be the consensus considering a recent survey of 329 triathlctcs indicated 89% felt they could not get the nutrients needed from food alone." They reported reason for use from improved energy and improved performance, to disease prevention. Exercise Benefits: It is clear exercise has mam positive benefits, but at what limit? As noted by Dr. CTKcefe and others, exercise is like a drug, and there may be a safe upper dose. What has been shown is that runners had a 19% overall reduction in all-cause mortality compared to nonrunncrs. However, it was in a LJ-shaped distribution where too little had no benefit, an effective range, and then an excessive range where the benefits were no longer seen and in fact were worse. In this assessment, three factors were considered including distance, speed, and frequency of rtinning. The effective range was seen with running two to five times a week at a distance of 1 to 20 miles per week at a pace of six to seven miles per hour; this produced the lowest rates of all-cause mortality. Increasing past these values resulted in a loss of survival benefit.1 In summary. Phidippides cardiomyopathy appears to be a pathopln siological response to excessive endurance training. Exercise has a drug-like response to some extent in that it is dose dependent in its safety. To keep it simple, the recommendation that seems to prevail is moderation is best. However, the races continue and the participants continue to line up. At the very least, it makes sense to take some preventive measures while the science continues to develop and offer a more definitive picture. Victoria Coleman. DC is a 20-year veteran in healthcare delivery both clinically and in business development. She currently is the VP of Clinical Education for Atrium Innovations® where her mission is to further, through education and service, the use oj nutracueticals Jor health promotion. Dr. Coleman is also a certified Functional Medicine Practitioner and avid fitness enthusiast. References: /. O'Keefe, J., Patil, II., Ixivie, C, Magalski, A., Vogel, R., Mc-Cullough, P., Potential Adverse Cardiovascular Effects from Excessive Endurance lixercise. Mayo din Proc. June (2012): 87(6): 587-5 95 2. Patil, H.. O'Keefe, J, Lavie, C, Magalski, A., Vogel. R.. Me Cu Hough, P., Cardiovascular Damage Resulting from Chronic Excessive Endurance Exercise. Missouri Medicine. July-August (2012): 4: 312-320. Trivax, J., McCullough, P., Phidippides Canliomyopathy: A Review and Case Illustration. Clin. Cardio. 35.2. 69-73 (2012) Brvuckmann, /'.', Mohlenkamp, S. \'assenstein, K, et al. Myocar- dial late gadolinium enhancement: prevalence, pattern, and prog noslic relevance in marathon runners. Radiology. 2009; 251:50-7 5. Shwartz , J., Merkel-Kraus, S., DuvalS., Does Elite athleticism enhance or inhibit comnary arteiy plague formation. Paper pre seated at: American College ofCanliology 2010 Scientific Sessions March 16, 2010; Atlanta. GA. Krvll, D., Why do healthv people die running marathons? http: www.forbes.com sites davidkmll 2014 04 15 why- do -healthy-people-die-running-marathons I'rso, ML., Clarkson, P., Oxidative stress, exercise, and antioxi dant supplementation. Toxicology. 189, 41-54 (2003) I iiia, J., Gomez-Cabrera, M-C, Lloret, A.,Marquez. R., Miiiana, B., Pallanlo, FA'., Sastrv, J., Five Radicals in Exhaustive Physical Exercise: Mechanism of Production, and Protection bv Antioxi dants. Life. 50: 271-277 (2000) 9. Clarkson, P., Thompson, II., Antioxidanls: what mle do they play in physical activity and health? Am J Clin Nutr August 2000, vol 72 no. 2 637s-646s. Walsh, NP, Gleeson, M, Shepani, RJ., Woods. JA., Bishop, NC. 1'leshner, A/., Grven, C, Pedersen, BK., Hqffman-Goetz, L., Rogers, CJ., Northoff, H., Abbasi.A., Simon, P., Position State ment. Pan one: Immune function and exeivise. Exetx: Immunol Rev. 2011: 17:6-63 Xieman, D., Risk of'Upper Respiratory Tract Infection in Atli letes: An Epidemiologica and Immunologic Perspective. JAlhl Train. 1997 Oct-Dec; 32(4):344-349 Kerksick, C, Harvey, T, Stout, J., et al. International Society of Sports Sutrition position stand: Nutrient timing. 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