The majority of athletes who develop hyponatremia demonstrate an increase in total body water (TBW) relative to that of total body exchangeable sodium (15, 29, 30). This develops from by the ingestion of hypotonic fluids (water or sports drinks) in excess of sweat, urine, and insensible (mainly respiratory and gastrointestinal) losses (i.e., drinking in excess). It is likely that conditioned behavior as well as inappropriate hydration recommendations (that are often taken to the extreme such as recommendations to “drink as much as possible”) account for this excessive fluid intake (9, 22). This is compounded by the wide availability of fluids along event courses.

The data supporting overhydration as the major mechanism involved in EAH is derived from the observations of weight gains seen in the majority of, but not all, athletes who become symptomatic with EAH (30). These rapid weight gains can only occur through ingestion of fluids in excess of body losses. As an example of the magnitude of these fluid intakes, individuals with normal glomerular filtration rates who are ingesting a Western diet can excrete between 500 and 1,000 mL/h of water. When non-renal losses of water (such as sweat and insensible fluid losses) are included into the net fluid balance equation, individuals can excrete 1,000–1,500 mL/h of dilute urine before developing water retention (15). While some athletes may drink this much, many do not and thus additional factors must be involved in the development of EAH.

Arginine vasopressin is the major hormonal regulator of water excretion, and abnormalities in AVP secretion are likely operative in the majority of athletes with EAH (25, 53–56). Under normal circumstances, AVP is suppressed in the presence of hypoosmolality. In some athletes, AVP is not appropriately suppressed (as typified by the finding of inappropriately elevated urine osmolality) (25, 52–56). This release of AVP leads to water retention in the distal tubule of the kidney and impaired water excretion. Coupled with excessive water intake, inappropriate water retention will lead to hyponatremia. Several potential stimuli to AVP release in exercising athletes include non-specific stresses (pain, emotion, and physical exercise), nausea/vomiting, hypoglycemia, exposure to heat, and medication use (such as non-steroidal anti-inflammatory drugs and selective serotonin reuptake inhibitors) (57–61).

A more speculative mechanism is that AVP may be stimulated by the release of inflammatory cytokines (25). In particular, interleukin-6 (IL-6) has been shown to increase during exercise by both physiologic (as it is involved in the mobilization of energy stores during exercise) and pathologic means (with muscle inflammation from breakdown) and may serve as a stimulus for AVP production. A study on 15 participants in ultramarathons, found a significant positive correlation between AVP and IL-6 (r = 0.31, P < 0.05) but not between AVP and blood glucose or ambient temperature (52).

While AVP is secreted in response to volume depletion, the typical levels of volume depletion in athletes are less than 7–10%; the threshold for AVP release. However, a study on rowers during a 4-week training camp revealed an inappropriate lack of AVP suppression occurring with EAH (plasma copeptin levels were used as a surrogate marker of AVP). In this case, the potential non-osmotic stimuli to AVP were thought to be related to hypovolemia as reflected by an association with increased hematocrits (5). Thus, the role of hypovolemia as stimulus for EAH may be underappreciated.

The issue as to the contribution of sweat sodium loss to the development of EAH remains controversial. Sodium loss from sweat is highly variable between individuals, and compared with the general population, endurance athletes have lower sweat sodium levels (62, 63). The loss of hypotonic sweat would be expected to raise the serum sodium. However, sweat loss could contribute to the development of hyponatremia in two manners: (1) if the degree of fluid loss was sufficient to produce significant volume depletion and provides a stimulus to AVP release, thereby impairing excretion of water and/or (2) through ingestion of fluids that were more hypotonic than the fluid losses. This scenario may contribute to the finding of EAH developing in some athletes with net weight loss.

A large amount of the total body sodium may exist in bone, skin, and cartilage stores that are not osmotically active but potentially recruitable into an osmotically active form (64). This may be as large as one fourth of the total sodium in the body. These sodium stores are reversibly bound to substances such as glycosaminoglycans and may be “dynamic,” meaning that that sodium can enter and exit this pool (65). Sodium exiting this pool may buffer the serum sodium and lower the risk of hyponatremia. On the other hand, sodium entering this pool may exacerbate hyponatremia (66). It has been hypothesized that athletes who develop EAH either cannot activate the exchangeable pool of sodium in response to sodium losses or alternatively sodium may move into non-osmotically active forms (30). The mechanisms that control the exchange of sodium between these compartments are unknown, and this mechanism remains speculative. However, these exchangeable sodium stores may be the explanation why some athletes gain significant weight yet do not become hyponatremic.

In addition to the excessive intake of water, glycogen metabolism may be an important component in the cause of hyponatremia that occurs without weight gain because each kilogram of glycogen can contain upwards of 3 kg of associated metabolic water (15). As glycogen is metabolized, water is released and if not excreted could lead to depression of the serum sodium.

As renal water excretion is dependent upon the delivery of filtrate to the diluting segments of the distal nephron, the neurohormonal activation of the sympathetic nervous system and renin–angiotensin–aldosterone system that occurs with endurance exercise may be contributory and permissive (15). This is due to the fact that catecholamines and angiotensin II increase sodium and water reabsorption in the proximal tubule. This means that there will be decreased filtrate that is delivered to the distal diluting segments of the kidney, eventually leading to impairments of free water excretion.

Another contributing factor at the end of an event may be rapid absorption of fluids from the gastrointestinal tract. In athletes who may have a large amount of fluid in the stomach (from recent ingestion) and have elevated AVP levels, rapid absorption of this fluid (as gastrointestinal blood flow post-event increases) along with impaired free water excretion may set up athletes to develop hyponatremia (15).

The role of sodium ingestion during events remains a matter of debate, and there are little data supporting the concept that inadequate sodium intake either prior or during an event contributes to the development of EAH. Hoffman et al. found that hyponatremia, as well as exercise-associated muscle cramping, dehydration, and nausea or vomiting, was unrelated to total sodium intake in participants of a 161 km ultramarathon (67, 68). This was confirmed in a case study which demonstrated that oral sodium supplementation does not necessarily prevent symptomatic EAH associated with overhydration (69). On the other hand, another study demonstrated that longer term (10 days) reduction in dietary sodium intake can cause reductions in plasma sodium concentration before as well as during exercise when fluid losses and ingestion are large and may consequently have adverse effects on physiological and functioning during such exercise (70).

There has been debate in the literature as to the prevalence and role of hypovolemia in the pathogenesis of EAH. Earlier data supported the fact that the vast majority of EAH cases were in athletes with net weight gain and hypervolemia. However, in the past few years, more data have supported that hypovolemia is more prevalent than previously thought. In a recent Czech study on ultra-endurance races, 85% of the hyponatremic athletes were volume depleted based on body weight changes (71). Weight loss in EAH cases supports volume depletion as a contributor to EAH perhaps through non-osmotic AVP secretion as described above coupled with sodium losses.

There are many misconceptions regarding hydration needs during exercise that foster the belief that athletes and individuals performing even moderate levels of exercise should “drink as much fluid as possible” (93). Unfortunately, there are also various contests and challenges that are prevalent on the Internet that urge participants to drink as much water as possible in short periods of time, often with fatal consequences (94). Hoffman et al. assessed the quality of information currently available to the public on the Internet regarding hydration recommendations during exercise (95). Not surprisingly, the quality of information was poor even for those sites that would be considered “medical” or “scientific.” For example, only 7.3% of 110 web sites discussed that fluid intake should be based upon thirst, and the potential risk of hyponatremia from overhydration was noted by less than half the websites (95). Dissemination of more appropriate hydration guidelines is critical, and we recommend that education programs stress the following concepts that are evidence based:

Excessive fluid replacement that goes beyond thirst has not been shown to decrease the development of fatigue, muscle cramping or exertional heat stroke (9).

Finally, we strongly recommend “grass-roots” efforts to adopt educational strategies to improve knowledge of safe hydration practices. These efforts should target a broad audience but must focus on those individuals such as coaches, event support staff and medical personnel that are most likely to have the greatest influence on the behavior of athletes. There is evidence that such strategies do work to lower the incidence of EAH when implemented (99–102). Furthermore, education programs should include recognition of the signs and symptoms of EAH as well as the need for immediate medical attention.

While there is common consensus that the primary strategy to prevent EAH is to avoid drinking excessive fluids, the role of sodium supplements in decreasing the risk of EAH remains controversial (68). Previous work on the influence of sodium supplementation on plasma sodium levels has shown variable results. Vrijens and Rehrer showed that fluid replacement with a sports drink containing 18 mmol/L of sodium as compared with water, led to an attenuated fall in plasma sodium during 3 h of cycling in the heat (103). Anastasiou et al. showed that even small amounts of sodium ingested during 3 h of racing in the heat were sufficient to attenuate the decrease in plasma sodium (104). Similar findings were observed by Twerenbold et al. during a 4 h running time trial in temperatures ranging from 5 to 19°C. Again, sodium ingestion resulted in a smaller decrease in the plasma sodium concentration from pre- to post-run measurements in female athletes (105). Conversely, Barr et al. reported no differences in the plasma sodium concentration at the end of 6 h of ergometer use in the heat, when either a water or saline solution was ingested (106).

More recent data have led to continued controversies regarding the value of sodium supplementation. A case report has been recently published in which a runner with a prior history of EAH consulted a sports nutritionist who advised him to consume considerable amounts of supplemental sodium, which did not prevent him from developing symptomatic EAH during a subsequent long run (69). A study involving 156 participants of a 161 km race found a weakly positive relationship between sodium supplementation and post-race serum sodium concentrations; the authors concluded that sodium supplementation had a minimal contribution on the prevention of hyponatremia (68). In nine endurance-trained men, each following a low- or high-sodium diet for 9 days, Koenders et al. found that, despite decreased urinary sodium losses, plasma sodium was lower in the patients on low-sodium diet before and throughout exercise. They concluded that the general population recommendations to lower salt intake may not be appropriate for endurance athletes, particularly those training in the heat that may be at risk for EAH (70).

Turner et al. examined the novel hypothesis that sodium excreted in sweat during physical activity offsets a significant fraction of excess dietary sodium intake, and hence may contribute part of the health benefits of exercise. Hence, replacing sodium lost in sweat during exercise may improve physical performance and slightly lower the risk of EAH, but may attenuate the long-term health benefits of exercise (107).

In conclusion, as reported on the Statement of the 3rd International Exercise-Associated Hyponatremia Consensus Development Conference, while sodium ingestion during a race may attenuate the fall in blood sodium concentrations, it cannot prevent EAH in the setting of excessive fluid intake (94). It is the amount of fluid ingested rather than the amount of sodium ingested during exercise that drives the final blood sodium concentrations. Sodium-containing sports drinks, which are hypotonic, will not prevent EAH in athletes who overdrink during exercise.