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Exercise-Associated Hyponatremia and Hydration Status in 161-km Ultramarathoners


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Medicine & Science in Sports & Exercise: April 2013 - Volume 45 - Issue 4 - p 784-791
doi: 10.1249/MSS.0b013e31827985a8
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Exercise-associated hyponatremia (EAH), defined as a blood sodium concentration ([Na+]) <135 mmol·L–1 during or within 24 h after prolonged physical activity (9), seemed to be an uncommon issue when first described in the scientific literature in 1985 (24). At least nine deaths from EAH have subsequently confirmed the potential seriousness of this condition (27), and EAH incidences have been reported to be as high as 18% in an Ironman triathlon (35), 28% in a standard 42-km marathon (8), 50% in an endurance cycling event (37), and 30%–51% in 161-km ultramarathon runs (15,21,37).

The Western States Endurance Run (WSER) is the premier 161-km ultramarathon traversing mountain trails. Participants travel from Squaw Valley, California, through the Sierra Nevada to Auburn, California. Although a case report of EAH from the sixth official running of the event in 1982 published in a non–peer-reviewed magazine represented one of the first reports of EAH (20), there were no formal studies of EAH at northern California ultramarathons until decades later. A stimulus for such work came in 2006, when spectators at the finish of the WSER watched the first runner collapse multiple times in the final 300 m. This runner had reportedly gained 2 kg during the run and was found to be hyponatremic via on-site analysis at the finish. Fortunately, he survived, but the assistance he received in crossing the finish line was grounds for disqualification.

In the initial study of EAH at northern California 161-km ultramarathons, the incidence of EAH was found to be 51% (21). That study also noted that more than half of the hyponatremic finishers had lost >3% of their body weight, which was in contrast to previous studies from shorter duration competitions in which EAH was relatively rare in subjects who had lost weight (1,11,25,33,34). Our research for the subsequent 4 yr demonstrated some interesting differences compared with findings previously reported from investigations at other events including a positive, rather than inverse, relationship between postrace [Na+] and change in body weight (15).

The present work combines and reanalyzes our data from 5 yr of EAH investigations at northern California 161-km ultramarathons, with the following purposes: 1) to explore the effect of ambient temperature on hydration status at the finish; 2) to gain insight into the level of body weight loss that might impair performance through examining the relationship of change in body weight with performance; 3) to define the relationship of postrace [Na+] with change in body weight across the 5 yr of investigations; 4) to explore the interactions among EAH incidence, ambient temperature, and hydration state; and 5) to examine whether the effect of hydration state on EAH incidence is statistically different for the present work compared with findings previously reported.


Institutional review board approval was granted for this work from the VA Northern California Health Care System with a waiver of consent. Most of the data were collected from the 2009 through 2012 WSER, which takes place during the last weekend in June. The course is almost entirely on single track mountain trails with 5500 m of cumulative climb and 7000 m of cumulative descent. Because this race was cancelled in 2008 due to nearby forest fires, studies that year were performed at the 161-km Rio Del Lago Endurance Run (RDL) on the last weekend of September. The course for this race is primarily single-track trail with elevation change of 2743 m and overlaps some with the WSER course. Both races had 24 aid stations stocked with various fluids and nutritional items as well as salt tablets. Participants had 30 h to complete the races.

At each race, prerace body weight was measured during registration the day before the race. This took place in the afternoon and evening for the RDL and in the morning for the WSER. Postrace body weight was measured immediately upon completion of the race. All measurements were made with calibrated battery-operated digital scales placed on solid level surfaces. At races where multiple scales were used, both measurements for a given runner were performed with the same scale. In 2008 and 2009, subjects were barefoot and clothed in running attire for the measurements. In 2010, 2011, and 2012, each measurement was made with the runner clothed in running wear and shoes. Attention was consistently given to the removal of other items, such as waist packs, before measurements being performed.

Within a few minutes after finishing the race, blood was drawn from the seated runner into heparinized tubes via an antecubital vein (2009–2012) or into a heparinized capillary tube via an earlobe prick (2008). Onsite analysis with portable analyzers (I-Stat; Abbott, Princeton, NJ) was used to determine serum [Na+] at the 2008 through 2010 events, and a clinical laboratory (Beckman Coulter DXC 800 Chemistry Analyzer; Beckman Coulter, Brea, CA) was used for measurement of plasma [Na+] in 2011 and 2012. The onsite analyses were performed within a few minutes of collection. Samples analyzed in the clinical laboratory were centrifuged within 30 min of collection and stored in an ice chest with cool packs until reaching the laboratory.

On the basis of the same serum or plasma [Na+] cutoff points as Noakes et al. (25), we refer to >145 mmol·L–1 as hypernatremia, 135 to ≤145 mmol·L–1 as normonatremia, 129 to <135 mmol·L–1 as biochemical hyponatremia, and <129 mmol·L–1 as clinically significant hyponatremia. For comparison purposes, the same cutoff points for hydration state based on body weight change were also adopted, where ≥0 weight change is overhydration, <0 to –3% change is euhydration, and <–3% change is dehydration. Although we recognize that a body weight loss of ∼1% could reasonably be expected from fat use during a 161-km ultramarathon (36), we also have noted that body weight is typically ∼1% higher immediately before the race than during registration the prior day (14). Therefore, we have retained the –3% cutoff value for dehydration used by Noakes et al. (25).

Historical temperature data, recorded at 20- to 60-min intervals, were available for two nearby locations for the WSER and from a single location relatively central to the RDL course. Using the same methods as previously reported for the WSER (26), temperatures from the weather station near the race start were linked to the period over which most runners were on the first third of the course. Temperatures from the weather station near the race finish were linked to the period over which runners would have been on the last two-thirds of the course. The midpoint temperatures were calculated as the temperatures halfway between the minimum and the maximum temperatures. Average temperatures were determined from the area under the temperature versus time course curves. We acknowledge that use of the temperatures from these weather stations invariably underestimated the actual temperatures through some parts of the course.

For compiling race performance data, it was necessary to normalize finish times because the fastest times varied from year to year largely because of temperature conditions. “Relative performance” was calculated by dividing the difference in the individual’s finish time from the winning time for that year by the race time limit (30 h), and presenting as a percentage.

Large data sets were tested for normality with the D’Agostino and Pearson omnibus normality test. Because data did not pass normality testing, Spearman correlation analyses were used to examine the associations between variables, and the Kruskal–Wallis test with Dunn’s multiple comparison test was used in the group comparison. Associations between variables with small sample sizes were examined with Pearson correlations. The frequency of those found to be overhydrated and either euhydrated or dehydrated were compared with prior published data with Fisher’s exact test. Statistical significance was set at P < 0.05.


Prerace and postrace body weight data were obtained for determination of body weight change for 887 observations. Overall, 18.5% were dehydrated, 46.6% were euhydrated, and 34.9% were overhydrated. The percentage of runners who were dehydrated ranged from 7.3% to 48.9% across years, whereas the percentage who were overhydrated ranged from 6.7% to 47.5%. When examined for relationships with ambient temperature (Fig. 1), significant correlations were found for percentage change in body weight with maximum temperature (r = –0.81, P = 0.048), and percentage of dehydrated runners with maximum temperature (r = 0.83, P = 0.04) and midpoint temperature (r = 0.86, P = 0.03). Neither percentage change in body weight (r = –0.70, P = 0.09) or percentage of dehydrated runners (r = 0.71, P = 0.09) were significantly correlated with average temperature. The percentage of runners who were overhydrated was not significantly correlated with maximum temperature (r = –0.72, P = 0.09), midpoint temperature (r = –0.74, P = 0.07) or average temperature (r = –0.58, P = 0.15). Change in body weight differed across years (P < 0.0001) with each pairwise comparison being significant except between the 2 yr with the greatest body weight loss (2008 and 2010), and between the years with the next greatest body weight loss (2009 and 2011).

Relationships for percentage change in body weight (postrace minus prerace) and percentage of dehydrated finishers with maximum and midpoint ambient temperatures. Solid lines display the linear regressions for correlations that were significant. See text for correlation coefficients and P values. The brackets represent 1 SD.

A significant relationship (r = 0.092, P = 0.006) was present between percentage change in body weight and relative performance such that faster runners tended to lose more weight (Fig. 2). Yet, variability was considerable and even among the top runners, change in body weight varied from approximately 1% gain to 6% loss.

Relationship of percentage change in body weight (postrace minus prerace) with relative performance for 887 observations at 161-km ultramarathons. “Relative performance” was determined by dividing the difference in the individual’s finish time from the winning time for that year by the race time limit (30 h) and presenting as a percentage.

The relationship of postrace [Na+] with change in body weight is shown in Figure 3 for 669 observations. A significant correlation (r = 0.17, P < 0.0001) was present between the two variables such that increasing weight loss was associated with lower [Na+].

Relationship of postrace [Na+] with percentage change in body weight (postrace minus prerace) for 669 observations at 161-km ultramarathons. Note that only 2 of the 3 observations of combined overhydration and hypernatremia are evident because two runners had a weight gain of 0.1% and [Na+] of 147 mmol·L−1. See text for explanation of the four groups based on [Na+] and the three groups based on hydration state.

Table 1 shows the detailed distribution of runners into the four groups on the basis of [Na+] and three groups based on hydration status. Most finishers (83.4%) were normonatremic and a small proportion (1.5%) were hypernatremic. There were 88 who had biochemical hyponatremia and an additional 13 with clinically significant hyponatremia accounting for a total of 101 (15.1%) with EAH. Of the group with EAH, 23.8% were overhydrated, 40.6% were euhydrated, and 35.6% were dehydrated. Considering the incidence of EAH relative to hydration status, 9.8% of those with overhydration, 13.8% of those with euhydration, and 28.1% of those with dehydration had EAH.

Classification of 669 observations from 161-km ultramarathon participants into postrace hydration and blood [Na+] status.

Regarding symptoms among those runners with EAH, most either had no neurological symptoms or mild nonspecific neurological symptoms (dizziness, lightheadedness, confusion), some of which have been reported elsewhere (4). None were known to have had seizures or respiratory distress suggesting they did not have significant EAH encephalopathy or pulmonary edema.

The collective 15.1% incidence of EAH varied across years from 4.6% to 51.0% and decreased linearly (P = 0.01) for the period examined. The relationship of EAH incidence each year with ambient temperature that year (Fig. 4) was significant when considering maximum temperature (r = 0.85, P = 0.03) and midpoint temperature (r = 0.96, P = 0.005), but not average temperature (r = 0.74, P = 0.08). There was a significant relationship between EAH incidence each year and percentage of overhydrated finishers (r = –0.90, P = 0.04) and percentage of dehydrated finishers (r = 0.97, P = 0.007) observed in that year (Fig. 5).

Incidence of EAH each year relative to maximum and midpoint ambient temperatures for that year. Solid lines display the linear regressions for correlations that were significant.
Incidence of EAH relative to percentage of overhydrated and dehydrated finishers the same year. The percentage of overhydrated and dehydrated finishers for each event was based on the 887 observations with both prerace and postrace body weights.

Comparing the present findings with those of Noakes et al. (25) for hydration status among those with EAH revealed that overhydration was significantly less (P = 0.0008) common in the present work. However, when considering only the two cooler races (2011 and 2012), our data revealed no difference (P = 0.5) compared with the findings of Noakes and colleagues, whereas the two hottest races (2008 and 2009) were different (P < 0.0001) from those of Noakes and coworkers. Specifically, considering the two cooler races, runners with EAH were overhydrated 52% of the time and were dehydrated 4% of the time. In contrast, considering the two hottest races, runners with EAH were overhydrated 8% of the time and were dehydrated 55% of the time.


Key findings of this work are that there was a weak direct relationship between postrace [Na+] and percentage change in body weight, and that 36% of those with EAH were dehydrated whereas only 24% of those with EAH were overhydrated. These findings contrast with those from previous studies at other endurance events where [Na+] has almost universally been found to be negatively related to percent change in body weight (1,5,7,8,11,18,25,33–35,39). Furthermore, Noakes et al. (25) showed in a compilation of 2135 observations at various endurance events that among those with EAH, only 25% were dehydrated whereas 45% were overhydrated. Simply stated, EAH was more commonly associated with overhydration in the work of Noakes and colleagues, and more commonly associated with dehydration in the present work.

Noakes et al. (25) have argued against a depletional mechanism for EAH based on their observation of a low incidence of EAH among dehydrated athletes and demonstration of osmotic inactivation of sodium among several athletes who developed EAH. Their findings have favored a dilutional model, compounded by inadequate suppression of arginine vasopressin and osmotic inactivation of circulating sodium and/or failure to mobilize osmotically inactive sodium from internal stores. The role of arginine vasopressin in EAH is now well supported (9,10,27,31,32). Noakes et al. indicated that the relationship between postrace [Na+] and change in body weight must be in the form of an inverted-U for a depletional mechanism to be involved. Our data seem to provide the other side of the inverted-U curve to support the depletional model of EAH. Yet, as discussed in the following paragraphs, sodium loss is not the only potential explanation for our findings. Impairment in mobilization of osmotically inactive sodium stores and/or inappropriate inactivation of osmotically active sodium are alternative explanations.

In addition to our finding of a lower incidence of EAH with overhydration compared with dehydration and euhydration, the present work found a relatively high overall incidence of overhydration. Overhydration, as defined by a stable weight or any weight gain, was present at rates of 11.5 to 47.5% and averaged 36.5% across all 887 observations during the five study years. This is a much higher incidence of overhydration than has been found in other studies where it has been reported to be 10%–11% or less (17,25,40). Such findings seem consistent with the historical emphasis on maintaining hydration levels along with the high conventional use of sodium supplementation at the events examined in the present work (12,21,36). Despite the lower incidence of EAH among those who were overhydrated, we interpret the present findings to indicate that many runners in this group could have benefited from reduced fluid and sodium intake.

An explanation for the present finding of a higher incidence of EAH with dehydration than previously found might relate to ambient temperature conditions. Maximum ambient temperatures from the events in the compilation report of Noakes et al. (25), as well as the other events reporting an inverse relationship between postevent [Na+] and percent change in body weight, were generally comparable to or lower than that of the coolest event examined in the present analysis. Considering only the two coolest events in the present analysis and the compilation data of Noakes and colleagues, a similar percentage of 45%–52% of those with EAH were overhydrated. It was only under the higher ambient temperature conditions where we saw the proportion of overhydration among runners with EAH to be significantly lower. It was under these conditions where we also observed the highest incidence of EAH.

Under higher ambient temperature conditions, one would presume that a greater sodium loss through sweat could play a role in the high incidence of EAH with dehydration. Furthermore, the longer duration of the events considered in this work (∼15–30 h) compared with the events included in the compilation of Noakes et al. (25) (mostly <18 h) is another contributing factor to additional sodium loss in sweat. Alternatively, considering the model proposed by Noakes and colleagues, there might also be impairment in mobilization of osmotically inactive sodium stores and/or inappropriate inactivation of osmotically active sodium. The relative importance of each of these factors cannot be definitively determined from the present work. Whether chronic sodium supplementation during training and racing by many of the participants in northern California ultramarathons (12) might cause adaptations such as higher sweat sodium losses, impaired mobilization of osmotically inactive sodium stores and/or enhanced inactivation of osmotically active sodium is unclear.

Not considering the findings of the present work, the incidence of EAH has been observed to be as high as 18% in an Ironman triathlon (35), 28% in a standard 42-km marathon (8), 38% in a 161-km run (37), and 50% in an endurance cycling event (37), but it has also been reported to be as low as 0%–0.6% in other endurance events (5,6,19,23,28,29). In the compilation report of Noakes et al. (25), [Na+] was <135 mmol·L–1 in 7% of 2135 observations, whereas the overall incidence in the present work was more than double that at 15.1%. Furthermore, rates of 30%–51% were observed during the initial three study years of this work. As noted earlier, ambient temperatures at the events examined in the present work were generally higher than at the events involved in the compilation work of Noakes and coworkers as well as the other studies which have reported a low EAH incidence. Our finding of a significant relationship of EAH incidence with ambient temperature suggests that environmental conditions are an important factor in the incidence, as well as the mechanism, of EAH. Interestingly, the highest EAH incidences have been reported in the coolest (37) and the hottest events (15,21) supporting the role of different underlying etiologies for EAH. Furthermore, the strong inverse relationship between EAH incidence and percentage of overhydrated finishers (Fig. 5), where the greatest frequency of overhydration occurred in the more recent and cooler years with the lowest EAH incidence, suggests that mechanisms other than dilutional were important under the high ambient temperature conditions associated with the present work.

Another factor that may account for the generally higher incidence of EAH observed in this work than prior studies relates to a proposed link between rhabdomyolysis and EAH (4,12,13,31,32,38). It has been theorized that EAH could promote rhabdomyolysis through changes in intracellular potassium or calcium concentrations which could reduce the stability of the cell membrane, or through hypotonic extracellular fluid osmotically drawn into the muscle cell, such that swelling mechanically decreases cell membrane stability. Conversely, the strong relationship between postexercise blood interleukin-6 and creatine kinase concentrations (32) and the recognition that interleukin-6 is a nonosmotic stimulus for arginine vasopressin secretion in nonexercising humans provides support for rhabdomyolysis as a stimulus for EAH via the syndrome of inappropriate antidiuretic hormone (SIADH) mechanism (31,38). Given the physiological demands of the events studied herewith as demonstrated by the high creatine kinase concentrations we have previously reported (13), this effect could provide an explanation for the unusually high incidence of EAH at these events. We must acknowledge however that prior work at a 56-km ultramarathon showed no statistical association between postrace interleukin-6 and arginine vasopressin concentrations (10).

Given that the lowest incidence of EAH took place in the most recent two events we examined, we cannot exclude the possibility of a change in athlete behavior playing a role. We also acknowledge that the initial three study years used portable analyzers opposed to a clinical laboratory in the fourth and fifth years. We do not believe that the different methods played an important role in the findings because different operators used different blood collection techniques and different portable analyzers. Additionally, there is evidence supporting the validity of the portable analyzers that were used (22).

In the present work, a small percentage of runners (n = 10, 1.5%) were hypernatremic at the finish. Six of these runners were euhydrated, but 1 was dehydrated and 3 were overhydrated. In contrast, Noakes et al. (25) observed a higher proportion of hypernatremia (13%), and among those with hypernatremia, 4% were overhydrated, 37% were euhydrated and 59% were dehydrated. Thus, the small percentage of runners with hypernatremia in our work tended to be at a higher hydration state than the athletes in the compilation of Noakes and coworkers. The combination of overhydration and hypernatremia can only occur through excessive sodium intake and/or mobilization of internal sodium stores along with overconsumption of fluids. Our three runners in this group reported taking in approximately 8.5, 9.5 to 20.5 gm of sodium just in supplements during the run. Large quantities of sodium intake are not unusual in the events from which the present data were drawn (12,21,36). It is unclear if these high levels of sodium intake are enough to overwhelm the natural mechanisms for maintaining blood sodium homeostasis, or if unnecessary mobilization of internal sodium stores is also involved in these cases with combined overhydration and hypernatremia.

Body weight change varied from an 8% loss to a 10% gain in the present work. Such changes in body weight are comparable with those previously reported from other endurance competitions (16,17,25,29,30,33,34,39,40). More importantly, a weight loss of >3% was common (18.5% of 887 observations), and weight loss of this magnitude or greater was observed even among top performers. There was also a weak relationship between performance and change in body weight such that those with the greatest weight loss tended to be the fastest (Fig. 2). Body weight losses more than 3%–4% have been shown to be common among athletes with the best performances in various endurance events (17,29,30,39,40), so the present findings confirm that performance is not impaired by such levels of weight loss. That the best performances can be achieved with this much weight loss raises issue with guidelines indicating that body weight loss of >2% should be avoided under the assertion that such levels of dehydration will impair aerobic exercise performance, as they do in very controlled laboratory settings (2,3). In events of the duration examined in this work, it would be expected that dehydration would be avoided with weight loss up to 3%–4% due to water release bound to glycogen and from substrate use. Observations that top performers participating in competitive events often lose this much weight provides support for this premise. Therefore, although the present findings provide no evidence for whether the guidelines may be suitable for exercise durations of a few hours, they suggest that the guidelines do not seem appropriate for endurance efforts extending to 30 h.

During the course of the 5 yr of the present work, 101 runners were observed to have EAH and 13 of those had [Na+] values <129 mmol·L–1. Yet, none of these runners were known to have developed serious symptoms such as seizures or respiratory distress, unlike the disqualified runner of 2006 who was overhydrated and hospitalized with clinical evidence of cerebral encephalopathy. This casts doubt about the level of concern that should be placed on EAH in our environment. It also raises the question of whether our lack of serious symptoms, despite the high incidence of EAH, could be because our cases are not primarily dilutional in origin. The severe symptomatic cases reported to date in the literature have been associated with fluid overload (9), whereas no severe symptomatic cases of EAH encephalopathy associated with dehydration have been verified in the literature. However, we believe that a cautious attention to this high incidence of EAH is warranted because asymptomatic EAH can rapidly progress to severe illness particularly within a short period after ceasing exercise (9) and because it is unclear if serious symptoms can present with EAH when associated with dehydration. Therefore, the findings of this work have important clinical relevance. Given the relatively high incidence of EAH during 161-km ultramarathons, medical personnel should be cognizant of the condition and prepared for proper management. They should also understand that a sizable proportion of runners who have lost considerable weight may be hyponatremic. Because aggressive hydration with hypotonic fluids is contraindicated and could have disastrous consequences in athletes with EAH (9,27), such practice without knowledge of the blood [Na+] must be avoided.

In summary, the present work demonstrates that EAH incidence can be as high as 30%–51% in 161-km ultramarathons and is more commonly observed in hotter ambient temperature conditions when overhydration is lowest and dehydration is greatest. We interpret these findings as support for the involvement of sodium depletion, impaired mobilization of osmotically inactive sodium stores, and/or inappropriate inactivation of osmotically active sodium in EAH in addition to prior evidence for a dilutional mechanism. The lower incidence of EAH with overhydration should not be interpreted as a protective effect from this hydration state but rather corroborates the excessive intake of fluid and sodium by some of these runners. Given that weight loss >3% does not seem to have an adverse effect on performance, endurance athletes participating in events of this duration are advised against excessive sodium supplementation and aggressive fluid replacement above the osmotically regulated dictates of thirst.

This material is the result of work supported with resources and the use of facilities at the VA Northern California Health Care System. The work was also supported by the WSER Foundation.

The authors thank their coauthors from previous publications from which some of the present data were attained and those who were previously acknowledged in those publications. They also thank the following individuals for their assistance who have not been previously acknowledged: Dr. Megan Anderson, Colleen Conners-Pace MA, Lisa Downey, Steve Itano, Dr. Christine Mathiesen, Dr. Vanessa McGowan, Danny Miller, Kevin Mullins, Kyle Yang, and Dr. Jeremy Wren. They are especially grateful to the runners who have selflessly given themselves for the advancement of knowledge.

The authors declare no conflict of interest.

The contents reported here do not represent the views of the Department of Veterans Affairs or the United States Government, nor do the results of the present study constitute endorsement by the American College of Sports Medicine.


1. Almond CS, Shin AY, Fortescue EB, et al.. Hyponatremia among runners in the Boston Marathon. N Engl J Med. 2005; 352: 1550–6.
2. American Dietetic Association; Dietitians of Canada; American College of Sports Medicine, Sawka MN, Burke LM, Eichner ER, et al.. American College of Sports Medicine Position Stand. Exercise and fluid replacement. Med Sci Sports Exerc. 2007; 39 (2): 377–90.
3. American Dietetic Association; Dietitians of Canada; American College of Sports Medicine, et al. American College of Sports Medicine Position Stand. Nutrition and athletic performance. Med Sci Sports Exerc. 2009; 41 (3): 709–31.
4. Bruso JR, Hoffman MD, Rogers IR, Lee L, Towle G, Hew-Butler T. Rhabdomyolysis and hyponatremia: a cluster of five cases at the 161-km 2009 Western States Endurance Run. Wilderness Environ Med. 2010; 21 (4): 303–8.
5. Bürge J, Knechtle B, Knechtle P, Gnädinger M, Rüst CA, Rosemann T. Maintained serum sodium in male ultra-marathoners—the role of fluid intake, vasopressin, and aldosterone in fluid and electrolyte regulation. Horm Metab Res. 2011; 43 (9): 646–52.
6. Glace BW, Murphy CA, McHugh MP. Food intake and electrolyte status of ultramarathoners competing in extreme heat. J Am Coll Nutr. 2002; 21: 553–9.
7. Harris G, Reid S, Sikaris K, McCrory P. Hyponatremia is associated with higher NT-proBNP than normonatremia after prolonged exercise. Clin J Sport Med. 2012; 22 (6): 488–94.
8. Hew TD. Women hydrate more than men during a marathon race. Clin J Sport Med. 2005; 15: 148–53.
9. Hew-Butler T, Ayus JC, Kipps C, et al.. Statement of the Second International Exercise-Associated Hyponatremia Consensus Development Conference, New Zealand, 2007. Clin J Sport Med. 2008; 18: 111–21.
10. Hew-Butler T, Jordaan E, Stuempfle KJ, et al.. Osmotic and nonosmotic regulation of arginine vasopressin during prolonged endurance exercise. J Clin Endocrinol Metab. 2008; 93 (6): 2072–8.
11. Hew-Butler TD, Sharwood K, Collins M, Speedy D, Noakes T. Sodium supplementation is not required to maintain serum sodium concentrations during an Ironman triathlon. Br J Sports Med. 2006; 40: 255–9.
12. Hoffman MD, Fogard K, Winger J, Hew-Butler T, Stuempfle KJ. Characteristics of those with exercise-associated hyponatremia after a 161-km run. Res Sports Med. (in press).
13. Hoffman MD, Ingwerson JL, Rogers IR, Stuempfle KJ, Hew-Butler T. Increasing creatine phosphokinase concentration at the 161-km Western States Endurance Run. Wilderness Environ Med. 2012; 23: 56–60.
14. Hoffman MD, Stuempfle KJ, Fogard K, Hew-Butler T, Winger J, Weiss RH. Urine dipstick analysis for identification of runners at risk for acute kidney injury following an ultramarathon. J Sports Sci. 2013; 31 (1): 20–31.
15. Hoffman MD, Stuempfle KJ, Rogers IR, Weschler LB, Hew-Butler T. Hyponatremia in the 2009 161-km Western States Endurance Run. Int J Sports Physiol Perform. 2012; 7 (1): 6–10.
16. Hsu TF, Chen YJ, Chou SL, et al.. Urine output and performance of runners in a 12-hour ultramarathon. Clin J Sport Med. 2009; 19 (2): 120–4.
17. Kao WF, Shyu CL, Yang XW, et al.. Athletic performance and serial weight changes during 12- and 24-hour ultra-marathons. Clin J Sport Med. 2008; 18 (2): 155–8.
18. Knechtle B, Knechtle P, Rosemann T. Do male 100-km ultra-marathoners overdrink? Int J Sports Physiol Perform. 2011; 6 (2): 195–207.
19. Knechtle B, Knechtle P, Rosemann T. No exercise-associated hyponatremia found in an observational field study of male ultra-marathoners participating in a 24-hour ultra-run. Phys Sportsmed. 2010; 38 (4): 94–100.
20. Lang G. Medical findings in the Western States 100 mile. Ultrarunning. 1984; 3 (9): 14–8.
21. Lebus DK, Casazza GA, Hoffman MD, Van Loan MD. Can changes in body mass and total body water accurately predict hyponatremia after a 161-km running race? Clin J Sports Med. 2010; 20: 193–9.
22. Murthy JN, Hicks JM, Soldin SJ. Evaluation of i-STAT portable clinical analyzer in a 367 neonatal and pediatric intensive care unit. Clin Biochem. 1997; 30 (5): 385–9.
23. Noakes TD, Carter JW. Biochemical parameters in athletes before and after having run 160 kilometers. S Afr Med J. 1976; 50: 1562–6.
24. Noakes TD, Goodwin N, Rayner BL, Branken T, Taylor RK. Water intoxication: a possible complication during endurance exercise. Med Sci Sports Exerc. 1985; 17 (3): 370–5.
25. Noakes TD, Sharwood K, Speedy D, et al.. Three independent biological mechanisms cause exercise-associated hyponatremia: evidence from 2,135 weighed competitive athletic performances. Proc Natl Acad Sci. 2005; 102: 18550–5.
26. Parise C, Hoffman MD. Influence of temperature and performance level on pacing a 161-km trail ultramarathon. Int J Sports Physiol Perform. 2011; 6 (2): 243–51.
27. Rosner MH, Bennett B, Hew-Butler T, Hoffman MD. Exercise associated hyponatremia. In: Simon E, editor. Hyponatremia: Evaluation and Treatment. New York: Springer. (in press).
28. Rüst CA, Knechtle B, Knechtle P, Rosemann T. No case of exercise-associated hyponatraemia in top male ultra-endurance cyclists: the ‘Swiss Cycling Marathon’. Eur J Appl Physiol. 2012; 112 (2): 689–97.
29. Sharwood K, Collins M, Goedecke J, Wilson G, Noakes T. Weight changes, sodium levels, and performance in the South African Ironman Triathlon. Clin J Sports Med. 2002; 12: 391–9.
30. Sharwood KA, Collins M, Goedecke JH, Wilson G, Noakes TD. Weight changes, medical complications, and performance during an Ironman triathlon. Br J Sports Med. 2004; 38 (6): 718–24.
31. Siegel AJ. Exercise-associated hyponatremia: role of cytokines. Am J Med. 2006; 119 (7 Suppl 1): S74–8.
32. Siegel AJ, Verbalis JG, Clement S, et al.. Hyponatremia in marathon runners due to inappropriate arginine vasopressin secretion. Am J Med. 2007; 120 (5): 461.e11–7.
33. Speedy DB, Campbell R, Mulligan G, et al.. Weight changes and serum sodium concentrations after an ultradistance multisport triathlon. Clin J Sport Med. 1997; 7 (2): 100–3.
34. Speedy DB, Faris JG, Hamlin M, Gallagher PG, Campbell RG. Hyponatremia and weight changes in an ultradistance triathlon. Clin J Sport Med. 1997; 7: 180–4.
35. Speedy DB, Noakes TD, Rogers IR, et al.. Hyponatremia in ultradistance triathletes. Med Sci Sports Exerc. 1999; 31 (6): 809–15.
36. Stuempfle KJ, Hoffman MD, Weschler LB, Rogers IR, Hew-Butler T. Race diet of finishers and non-finishers in a 100 mile (161 km) mountain footrace. J Am Col Nutr. 2011; 30 (6): 529–35.
37. Stuempfle KJ, Lehmann DR, Case HS, et al.. Hyponatremia in a cold weather ultraendurance race. Alaska Med. 2002; 44 (3): 51–5.
38. Swart RM, Hoorn EJ, Betjes MG, Zietse R. Hyponatremia and inflammation: the emerging role of interleukin-6 in osmoregulation. Nephron Physiol. 2011; 118: 45–51.
39. Wharam PC, Speedy DB, Noakes TD, Thompson JM, Reid SA, Holtzhausen LM. NSAID use increases the risk of developing hyponatremia during an Ironman triathlon. Med Sci Sports Exerc. 2006; 38 (4): 618–22.
40. Zouhal H, Groussard C, Minter G, et al.. Inverse relationship between percentage body weight change and finishing time in 643 forty-two-kilometre marathon runners. Br J Sports Med. 2011; 45 (14): 1101–5.


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