A Literature Review done for my Masters in Sports Medicine (MsSpMed), University of Queensland, Australia 2017

• INTRODUCTION
• DEFINITIONS AND SYMPTOMS
• INCIDENCE
• RISK FACTORS
• Female Gender
• Excessive Fluid Intake
• Post-race Weight Gain
• Long Completion Time
• Post race recall of volume of water consumed
• NSAIDs
• Hydrating with plain water
• OTHER POSTULATED RISK FACTORS
• Warmer Temperatures
• Increased frequency of Hydration Points
• Pre-race Hyponatremia
• Runner’s Experience
• RECOMMENDATIONS
• More research necessary
• Education is key
• Conclusion
• REFERENCES

INTRODUCTION

Ever since Exercise- Associated Hyponatremia (EAH) was first reported in 1981 at the 88km Comrades Marathon25, numerous studies have been carried out on ultra-distance events such as the Ironman Triathlon. In a large compilation of these events which studied 2135 ultra-distance  athletes, Noake’s et al. reported an EAH prevalence of 6%7. Few studies were done on marathoners as it was believed that the amount of fluid required to dilute sodium in the blood to produce hyponatremia was “inconceivable” in the much shorter 42km marathon, as described by Barr and Costill in 198628. It was only in 1988, when the first case of hyponatremia was reported in a marathon runner27, that researchers began to study the incidence of EAH in this population. With numerous deaths8 as a result of EAH and with the numbers of marathon runners surging in recent years to reach a high of 550,637 finishers in 2014 in the USA alone23, this has recently become a major focus in Sports Medicine research.

In my practice in Sports Medicine where we provide numerous medical covers for running events such as the annual Singapore Marathon, it will be important to come prepared knowing what to expect in the medical tents. In addition, the role of the medical director is to enforce education on pertinent topics among the participants prior to the race. This literature review aims to uncover the incidence of EAH among marathoners and the key risk factors that lead to this condition.

DEFINITIONS AND SYMPTOMS

Hyponatremia is defined by sodium levels in the blood of less than 135mmol/L26  and its symptoms include bloating, puffiness, nausea, fatigue and giddiness. In severe cases, symptoms which correlate to possible cerebral edema include headache, seizures, confusion and even death can occur25.  Patients are usually asymptomatic at sodium values between 130-135mmol/L but usually become symptomatic when it goes below 130mmol/L9.

INCIDENCE

A literature search was done on PubMed to identify research studies done on the marathon population with regards to the incidence of EAH in marathons. The results are presented in Table 1.

As seen from the table 1, the incidence of EAH can range widely at marathon events around the world. There are however several flaws in methodology in some papers. For example, the incidence of hyponatremia can even be as high as 22% as shown in the prospective observation study of the 2000-2004 Houston Marathon but because of its small sample size (96 participants over 4 years) 29, this result may not be a true representation of other marathons.

Also, the largest single-event study done was at the Boston Marathon in 2002 which involved 488 participants24. However, like most other studies11, 14,15, 17, 18, 22, it  only measured post-race sodium levels. This limits our interpretation of the results as up to 3.9% of runners may be hyponatremic before the start of the race21. Only 3 studies2, 21, 29 measured pre- and post sodium levels but their sample sizes were small at less than 200 participants.

Another limitation of several of these studies15,17,18,20,22 is that they only focused on runners who seek medical treatment. This method of sample selection does not recognise that not all symptomatic patients will seek medical help and may decide to institute self treatment by resting at home after the event.  In addition, the tipping point at which hyponatremia becomes symptomatic is highly unpredictable and there have been documented cases of patients only becoming confused or drowsy as long as 6 -8 hours after a race, only to be found with EAH at the hospital16.

RISK FACTORS

Studies that evaluated the risk factors and their results  are summarised in table 2.

Female Gender

There is a strong relationship between the incidence of EAH and being a female. However, this may not be because of their sex per se and may be due to other confounding factors. For example,  females  generally have a lower body-mass index and  may end up drinking  proportionately more fluids24. Thus it is difficult to conclude that this observation is truly due to gender differences. This also explains why not all studies found this relationship to be true.

Excessive Fluid Intake

This is one of most recognised cause of EAH. It is difficult to track fluid intake during a race  and thus studies use several surrogate measures to evaluate this such as the following:

Post-race Weight Gain

Recent studies showed that the minimum weight loss a runner should have over the course of a marathon is 0.75kg to reduce the risk of developing EAH29 as weight loss is also attributed from other sources such as metabolic fuel13, highlighting that a neutral weight balance post-race suggests excessive fluid intake, increasing the risk of hyponatremia. This relationship is is demonstrated clearly in the study by Almond et al. at the 2002 Boston Marathon which involved weighing 488 runners pre and post race and comparing it to their post race sodium levels as seen in Figure 124.

Long Completion Time

There is an inverse linear relationship found between lower serum sodium levels and longer finishing times, putting runners who spend the longest time on the course at highest risk of hyponatremia as shown in Figure 2. However, this relationship can only be true if these runners end up drinking more fluids during the race by being longer on the course and not all slow runners will end up with hyponatremia. Thus this association is likely due to the confounding effects of excessive fluid intake and does not imply causality.

Post race recall of volume of water consumed

There is an inverse relationship between post race recall fluid intake and plasma sodium change during the marathon as seen in Figure 3 and  is supported by several other studies. However, this may be subjected to strong recall bias as runners who suffered from hyponatremia may be inclined to remember drinking larger volumes of water.

NSAIDs

NSAIDs causing hyponatremia have been a long known association due to its potentiating effects of Anti Diuretic Hormone on the collecting ducts in the kidneys leading to fluid retention and serum sodium dilution. Patients who presented with severe hyponatremia after a race were 5 times more likely to be on NSAIDs20. However this was one of the few studies on marathoners and had a small sample size of 60 patients. Studies on triathletes were also not conclusive19.  As NSAIDs are easily available over the counter and frequently used my runners with minor injuries, it is crucial that more studies be done on this association so that proper advice can be given to runners in the future.

Hydrating with plain water

Even though it is logical that hydrating with plain water increases the risk of hyponatremia from dilution, only one study investigated on this risk factor but no association was found24. One possible reason for this is that the relative hypotonicity of most commercial sports drinks have a sodium concentration of 18mmol/L, less than one-fifth the concentration of normal saline24 and thus will have minimal effect on serum sodium levels.

More studies are required in this area to determine the best composition of electrolytes in sports drinks to reduce the risk of hyponatremia and other electrolyte imbalances in endurance sports.

OTHER POSTULATED RISK FACTORS

Warmer Temperatures

Temperature of the race has been suggested to affect the incidence of EAH. The reason for this is postulated to be due to 2 mechanisms. First,  the repression of the feeling of thirst in colder climates as well as lower sweat rates  results in a reduced risk of overconsumption of fluids2. Secondly, runners typically slow down significantly due to heat to allow the body to complete the race safely22. This protective mechanism is mistaken often by runners to be secondary to dehydration, thus encouraging them to actively rehydrate,  leading to increased tendency to over hydration22.

Based on this hypothesis, a marathon in hot and humid Singapore would see a higher incident rate of hyponatremia but this was not the case as seen from Table 1. It is suggested that environment-induced sweating was greater as compared to exercise intensity-induced sweating in cooler climates, and thus a reduced risk of overhydration17. Another factor that needs to be considered is whether the athlete is acclimatised to race in that particular climate,  as this can affect sweat rates and concentrations regardless of the race condition.

More research need to be done in this area to ascertain the relationship between temperature and EAH as this may impact  the hydration strategies of elite athletes travelling to places of warmer temperatures for competition.

Increased frequency of Hydration Points

In the 2002 Christchurch Marathon, where there were no incidence of hyponatremia, the authors postulated that one of the possible reasons was that hydration points were placed at 5km intervals for a total of 8 stations. This contrasts with numerous other studies18, 21, 22 with a higher incidence of hyponatremia in which fluid stations were at 1.6km intervals (i.e. More than 3 times as frequent). Perhaps this with the common practice and advice of “drinking at every station” possibly led to the difference in incidence rates. It is also to be noted that having hydration points ever 5km is still within the recommended guidelines for hydration point frequency laid out in the International Marathon Medical Directors Association.

Further studies need to be done to find the optimum frequency rates of hydration points to ensure the safety of all participants.

Pre-race Hyponatremia

Only one study recorded that 3.9% of runners were hyponatremic even before the start of the race21 but wether these runners remained hyponatremic at the end of the race remains unknown. However, this is of particular concern as this may mean that due to poor knowledge, participants may be putting themselves at higher risk by overhydrating even before the race, unknowingly sabotaging their own performance and health. This further highlights the importance of the following recommendations.

Runner’s Experience

Despite studies suggest that more experienced runners are more well versed in their hydration strategies3, this does not appear to the case. The Boston marathon is the only marathon with a qualifying time indicating that these runners are definitely more experienced than those in other races. The incident rates however, are on par with several of the other marathons with no qualifying time but also higher than some marathons such as the Christchurch and Singapore marathon.

This inconsistency in results may suggest that across all levels of experience in running, knowledge is lacking with regards to the risks of overhydration and EAH.

RECOMMENDATIONS

More research necessary

Excessive fluid intake, measured with surrogates of post-race weight, post-race recall and longer completion time, has been shown to be the strongest predictor of EAH occurrence. Other risk factors will require more in-depth study to determine the exact relationship these include the effect of NSAID use, temperature, type of fluids for hydration, hydration points frequency and the female gender. Results will impact the hydration strategies of elite athletes and amateur athletes alike in the marathon as well as standard practices of race organization.  It will also be ideal that studies measure pre and post race sodium levels with large sample sizes to allow understanding of Sodium changes during a race.

Education is key

As seen from the above, excessive fluid intake is the main risk factor for the development of EAH and education is the only way to address this. This is critical as it has been shown that runners’ knowledge on hydration strategies is very poor in general3, 12 and this is made worse by erroneous advice given by online sources, friends and even unknowing coaches to drink “beyond the point of thirst”. This is likely due to the previous belief that regards thirst as an unreliable reflection of body hydration status but this has proven not to be the case.

The International EAH Consensus Development Conference, International Marathon Medical Directors Association (IMMDA) and the American College of Sports Medicine has all recently released updated guidelines in 201526, 20064 and 200710 respectively. In these publications, it is advised that runners drink to thirst and no more than 400-800ml/hour. On top of this, it is recognised that sweat loss rate is highly dependant on individual and one should consider weighing oneself  pre and post a long training run to determine a specific hydration strategy. It is also advised that wherever possible, drinks containing sodium and other electrolytes should be provided for at hydration points.

Hydration advice should be printed in event handbooks and also disseminated via email prior to the race. An example is given in Figure 4.

Event organisers should also work with the medical team to plan out frequency of hydration points to reduce the risk of overhydration with the possibility of having them at 5km intervals, at the higher end of the IMMDA guidelines.

Conclusion

Incidence of EAH is wide-ranging among marathon events but is a condition that should be kept at the back of the mind when operating a medical tent at running events. Besides excessive fluid intake being recognised as the biggest predictor of EAH, other risk factors need to be further evaluated. Education of runners by coaches, medical directors  and race organisers is crucial to address the main risk factor of excessive fluid intake. Event organisers and medical directors should be well versed in the guidelines available by the various agencies and adhere to them strictly.

REFERENCES

1. NOAKES TD, GOODWIN N, RAYNER BL, BRANKEN T, TAYLOR RKN. Water intoxication. Medicine & Science in Sports & Exercise. 1985;17(3).

2. Mettler S, Rusch C, Frey WO, Bestmann L, Wenk C, Colombani PC. Hyponatremia Among Runners in the Zurich Marathon. Clinical Journal of Sport Medicine. 2008;18(4):344-349.

3. O’neal EK, Wingo JE, Richardson MT, Leeper JD, Neggers YH, Bishop PA. Half-Marathon and Full-Marathon Runners’ Hydration Practices and Perceptions. Journal of Athletic Training. 2011;46(6):581 - 591.

4. Hew-Butler T, Verbalis JG, Noakes TD. Updated Fluid Recommendation: Position Statement From the International Marathon Medical Directors Association (IMMDA). Clinical Journal of Sport Medicine. 2006;16(4):283-292.

5. Hew-Butler T, Verbalis JG, Noakes TD. Updated Fluid Recommendation: Position Statement From the International Marathon Medical Directors Association (IMMDA). Clinical Journal of Sport Medicine. 2006;16(4):283-292.

6. Draper SB, Mori KJ, Lloyd-Owen S, Noakes T. Overdrinking-induced hyponatraemia in the 2007 London Marathon. Case Reports. 2009;2009(mar26 1).

7. Noakes TD, Sharwood K, Speedy D, et al. Three independent biological mechanisms cause exercise-associated hyponatremia: Evidence from 2,135 weighed competitive athletic performances. Proceedings of the National Academy of Sciences. 2005;102(51):18550-18555.

8. GmbH FAZ. Drei Tage nach Hitze-Triathlon: Ironman-Teilnehmer stirbt an Hirnschwellung. FAZNET. 2015. http://www.faz.net/aktuell/rhein-main/ironman-teilnehmer-stirbt-an-hirnschwellung-13692450.html. Accessed August 10, 2015.

9. Speedy DB, Noakes TD, Schneider C. Exercise-associated hyponatremia: A review. Emergency Medicine Australasia. 2001;13(1):17-27.

10. Exercise and Fluid Replacement. Medicine & Science in Sports & Exercise. 2007;39(2):377-390.

11. Shephard RJ. The incidence of exercise-associated hyponatraemia in the London marathon. Yearbook of Sports Medicine. 2011;2011:316-318.

12. Williams J, Brown VT, Malliaras P, Perry M, Kipps C. Hydration Strategies of Runners in the London Marathon. Clinical Journal of Sport Medicine. 2012;22(2):152-156.

13. Noakes T. Fluid Replacement during Marathon Running. Clinical Journal of Sport Medicine. 2003;13(5):309-318.

14. Reid SA, Speedy DB, Thompson JMD, et al. Study of Hematological and Biochemical Parameters in Runners Completing a Standard Marathon. Clinical Journal of Sport Medicine. 2004;14(6):344-353.

15. Davis D, Marino A, Vilke G, Dunford J, Videen J. Hyponatremia in marathon runners: Experience with the inaugural rock’n' roll marathon. Annals of Emergency Medicine. 1999;34(4):40-41.

16. Goudie AM. Exercise-associated hyponatraemia after a marathon: case series. Journal of the Royal Society of Medicine. 2006;99(7):363-367.

17. Lee JKW, Nio AQX, Ang WH, et al. First Reported Cases of Exercise-Associated Hyponatremia in Asia. International Journal of Sports Medicine. 2011;32(04):297-302.

18. HSIEH M, ROTH R, DAVIS DL, LARRABEE H, CALLAWAY CW. Hyponatremia in runners requiring on-site medical treatment at a single marathon. Medicine and Science in Sports and Exercise. 2002;34(2):185-189.

19. WHARAM PC, SPEEDY DB, NOAKES TD, THOMPSON JMD, REID SA, HOLTZHAUSEN L-M. NSAID Use Increases the Risk of Developing Hyponatremia during an Ironman Triathlon. Medicine & Science in Sports & Exercise. 2006;38(4):618-622.

20. Davis DP, Videen JS, Marino A, et al. Exercise-associated hyponatremia in marathon runners: a two-year experience. The Journal of Emergency Medicine. 2001;21(1):47-57.

21. Mohseni M, Silvers S, McNeil R, et al. Prevalence of Hyponatremia, Renal Dysfunction, and Other Electrolyte Abnormalities Among Runners Before and After Completing a Marathon or Half Marathon. Sports Health: A Multidisciplinary Approach. 2011;3(2):145-151.

22. Hew TD, Chorley JN, Cianca JC, Divine JG. The Incidence, Risk Factors, and Clinical Manifestations of Hyponatremia in Marathon Runners. Clinical Journal of Sport Medicine. 2003;13(1):41-47.

23. 2014 Running USA Annual Marathon Report. 2015. http://www.runningusa.org/marathon-report-2015?returnTo=annual-reports. Accessed August 12, 2015.

24. Almond CSD, Shin AY, Fortescue EB, et al. Hyponatremia among Runners in the Boston Marathon. New England Journal of Medicine. 2005;352(15):1550-1556.

25. NOAKES TD, GOODWIN N, RAYNER BL, BRANKEN T, TAYLOR RKN. Water intoxication. Medicine & Science in Sports & Exercise. 1985;17(3).

26. Hew-Butler T, Rosner MH, Fowkes-Godek S, et al. Statement of the 3rd International Exercise-Associated Hyponatremia Consensus Development Conference, Carlsbad, California, 2015. British Journal of Sports Medicine. 2015.

27. Nelson PB, Robinson AG, Kapoor W, et al. Case report: Hyponatremia in a marathoner, Phys Sportsmed 1988; 16:78-87

28. Barr SI, Costill DL. Water: Can the endurance athlete get too much of a good thing? J Am Diet Assoc 1989; 89: 1629-1632

29. Chorley J, Cianca J, Divine J. Risk factors for exercise-associated hyponatremia in non-elite marathon runners. Clin J Sports Med. 2007; 17(6): 471-477