The Hyponatremia of Exercise, Part 2

As reviewed in more detail elsewhere, Gatorade developer Dr. Robert Cade published three articles describing his studies of fluid, electrolyte, and carbohydrate replacement during exercise (1-3). The first two studies were quite simple and probably were published only to meet Cade’s legal requirement to publish the chemical composition of Gatorade in a scientific publication in order to retain the Gatorade brand name.

Based on these studies, Gatorade would become an iconic and trusted brand. In Cade’s own words: “I am proud that Gatorade was based on research into what the body loses in exercise. The other sports drinks were created by marketing companies” (4).

However, as we review the historical record, it is perhaps appropriate to revisit my analysis of the findings of those first three foundational studies that established Gatorade as a viable product, as well as the other influential research used to establish a “Science of Hydration.”

The following text is adapted from my book Waterlogged: The Serious Problem of Overhydration in Endurance Sports (5).

Cade’s research considered a total of 97 individual athletic performances. In 22 of these performances, subjects did not drink anything during exercise. An objective assessment of these studies allows the following conclusions:

1. Glucose ingestion improves running performance in races of 7 miles (11 kilometers) and 26 miles (42 kilometers).
2. American football players safely can practice for 2 hours in the heat without ingesting fluid.
3. Athletes safely can run 7 miles in moderate heat without drinking.
4. Rectal temperatures did not reach dangerous levels even in those who did not drink in any of these experiments.
5. No athletes developed heat illness, heat cramps, or other medical conditions, even when they did not drink. Thus, these conditions are not caused exclusively by dehydration in those who do not drink during exercise.
6. Sweat rates during exercise were modest (~1 L/hr).
7. Athletes lost substantial amounts of sodium in their sweat. Yet their blood sodium concentrations rose. Thus, athletes do not need to ingest sodium-containing sports drinks to prevent the development of exercise-associated hyponatremia (EAH).

It is probably fair to say that the scientific contributions of Cade’s original studies “of what the body loses in exercise” were less than stellar — certainly not enough to explain the subsequent commercial triumph of what would become perhaps the most successful sports supplement/drink of all time.

Instead, two other studies — one from South Africa and funded by the South African Sugar Association (6) and the other (7) conducted by the premier exercise physiologist of the day, Dr. David Costill of Ball State University, and funded by Stokely-Van Camp, the original owners of the Gatorade brand—would be used by the Gatorade Sports Science Institute (GSSI) to establish a novel field of scientific inquiry: the Science of Hydration.

The Wyndham and Strydom Heatstroke Study

The origins of the South African paper arise in the South African gold mining industry, which beneath the city of Johannesburg, South Africa, operates some of the deepest gold mines in the world.

The challenges posed by such deep mining are immense; for the humans involved in extracting the gold, the great challenge is the heat and risk that they might develop heatstroke. This problem worsens in the deeper mines as the temperature of the rock face rises with any increase in depth. Techniques such as more effective cooling of the working areas, increased mechanization, and better heat acclimatization of the miners significantly reduced the incidence of heatstroke in the South African mines so that by the 1970s, the problem had been well controlled if not yet completely eliminated.

As a result, Professors Cyril Wyndham and Nic Strydom, two of the human physiologists most involved in this research at that time, had some spare energy to expand their research to other areas of exercise in hot environments, including marathon running.

In 1968, Wyndham and Strydom were approached by the South African Sugar Association (SASA) to conduct a study of the effects of an increased intake of sugar on running performance in marathons. They then designed and conducted a study in which a group of local marathon runners completed three 21.5-mile races at monthly intervals on the same course at the same time of day (8). For the week before one race, participants increased their sugar intake by adding sugar to their foods; before the other two races, they ate their normal diets without added sugar. The added sugar increased their weekly sugar intake by about 450 grams.

Unquestionably, the motivation for the study was a series of Scandinavian studies showing that athletes who increased their carbohydrate intake before long-distance endurance events apparently improved their performances (9). I say “apparently” as these early studies did not provide definitive evidence of a beneficial effect. This dietary intervention became known as carbohydrate-loading. In essence, the SASA study wished to determine whether pre-race carbohydrate-loading with sugar also would provide a performance benefit.

The original goal of the study was partially successful. Runners ran 5 minutes faster after carbohydrate-loading with sugar. But that part of the study was eclipsed entirely by another (somewhat erroneous) observation that became the “foundation myth” on which the GSSI would construct its novel Science of Hydration.

For their contribution to the study, Wyndham and Strydom measured body weight changes and post-race rectal temperatures in all competitors in both races (6). And when they examined the data, they came to an exciting conclusion: There was a strong linear relationship between the extent to which the runners’ rectal temperatures rose during the race and the amount of weight they lost during the race—the latter a measure of their degree of “dehydration” (Figure 1).

The conclusion was obvious: The more “dehydrated” the athletes became, the higher their post-race rectal temperatures. And if they lost more than about 7.5% of their body weight (vertical line), their body temperatures would exceed 42 degrees Celsius and they would develop heatstroke.

Thus, Wyndham and Strydom, two of the most experienced heatstroke researchers in the world, concluded that heatstroke in runners is caused by dehydration. Their professional status as two of the world’s greatest authorities on heatstroke and its prevention was enough to terminate debate. They had discovered a universal biological truth. End of discussion.

But this conclusion represents the classic error that is taught in Bad Science 101. This definitive conclusion cannot be drawn for the following reasons:

First, no runner developed heatstroke during any of these races. In fact, none became ill. So, the authors could not draw any conclusions about heatstroke — either its cause or prevention. Instead, the race winners were among the hottest and most dehydrated of the race finishers. An equally reasonable conclusion might have been that those who wish to win marathon races should aim to drink as little as possible during these races in order to develop the highest body temperatures of all the athletes in the race.

Second, the study was not designed to test whether drinking during exercise can prevent heatstroke. This is a post-hoc (after the event) conclusion drawn by the authors after they had searched through their data just in case anything interesting suddenly might present itself. This is known as data mining. It is a popular technique used in nutritional epidemiology and explains why so much of nutritional epidemiology is fictitious and in need of urgent repair (10).

Third, the finding that two factors appear to be related does not mean that the one causes the other. Both could be explained by their co-dependence on a third factor for which the study was not controlled. That third factor might then be the real cause of heatstroke.

Recall that in this study, only two factors were controlled, the run distance and whether the athletes ate more sugar in the week before one of the three races.

Two crucial factors that were not controlled were (i) the speed at which the athletes ran and (ii) the amount of fluid they ingested during the race.

Without control of those two factors, we (and the authors) cannot draw any reasonable conclusions about any possible relationship between the level of “dehydration” and post-race rectal temperature.

The only thing Wyndham and Strydom succeeded to do was describe what happened. Hence, this type of “experiment” is called a descriptive study. In his classic book (11), French physiologist Claude Bernard, universally revered as the father of experimental physiological research, described the difference between observation and experimentation: “Observation is investigation of a natural phenomenon, and experiment is investigation of a phenomenon altered by the investigator” (p. 15, emphasis added). Wyndham and Strydom merely described an observation; they did not perform an experiment since they did not alter the manner in which those running races were conducted.

By varying the rates of fluid ingestion on two or more occasions, it would have been possible to produce different levels of dehydration in the same athletes when they performed exactly the same exercise in identical conditions. Only by comparing the effects of different levels of dehydration in the same athletes running the same distances at the same speeds in the same environmental conditions on at least two occasions could the authors have begun to determine the independent effect of dehydration on body temperature (when all the other variables that could potentially influence body temperature were controlled and thus the same in all the different experiments).

Instead, Wyndham and Strydom’s study controlled none of these variables and attempted to draw conclusions by combining data from three uncontrolled observational studies in which athletes drank as they wished when they ran 21.5-mile foot races at their own chosen (and potentially different) paces in environmental conditions that were not exactly the same in both trials. Thus, the authors risked finding a spurious relationship that might have been caused by any number of variables that they had failed to control during the different races.

As a result, despite being highly accomplished scientists who made remarkable contributions to the understanding of the human’s physiological response to exercise in the heat (including seminal work that helped reduce the scourge of heatstroke in the deep South African goldmines (12)), by failing to design an appropriately controlled experiment, Wyndham and Strydom promoted the incorrect conclusion that the level of dehydration is causally related to rectal temperature response during exercise.

This error would haunt the exercise sciences for the next 40 years. It legitimized the concept that dehydration during exercise is dangerous. This, in turn, opened the door for a host of studies, many funded by the fledgling sports drink industry, the scientific goal of which may have been to establish the value of drinking during exercise; but which, I argue, may also have served a primarily commercial purpose.

Wyndham and Strydom’s study established the erroneous “foundation myth,” which holds that dehydration is the single most important factor affecting the rise in rectal temperature during exercise and the risk that heatstroke or other medical “dangers” will develop during prolonged exercise, especially in the heat.

Their error was based on a failure to consider that both these variables are dependent on a third factor: how fast the different athletes ran during these races.

And it was not as if the authors did not understand this. They had published a prior study demonstrating that the most important variable affecting the miners’ rectal temperatures during exercise was how hard they were working, measured as the rate at which they were metabolizing (using) oxygen (13).

Others had come to exactly the same conclusion (14,15). By ignoring this factor, they failed to exclude the possibility that any relationship between dehydration and rectal temperature was likely spurious and might have been explained by this third factor, specifically the metabolic rate maintained during exercise, which also is known to determine the sweat rate (16,17) that in turn determines the rate at which dehydration develops during exercise.

So it is perhaps not surprising that in the SASA study, the fastest runners had the highest post-race body temperatures (see Figure 1), as already was noted in an earlier study by Pugh et al. (18). What is more, as in the study by Pugh et al., the fastest marathon runners also lost the most weight. The authors of that study specifically commented: “The present evidence implies that tolerance of a high body temperature is a necessary condition of success in marathon runners.”

There is no evidence to suggest that Pugh et al. considered these high body temperatures and significant weight losses (even of up to 6% of body weight) as unhealthy, unexpected, or “dangerous.”

Wyndham and Strydom were of quite a different opinion, titling their article, “The dangers of an inadequate water intake during marathon running.” Their error was based on the use of journalistic hyperbole to boost the scientific impact of their study. They studied only weight loss and rectal temperatures, not “dangers.” Nor did they identify any runner for whom dehydration had proved dangerous.

But the consequence was that those too lazy to read the article with even a modicum of curiosity presumed that Wyndham and Strydom had discovered a universal biological truth: that heatstroke during marathon running is caused exclusively by dehydration as a consequence of not drinking sufficiently.

The paper was very significant in my life. I entered medical school in the same year that the article was published. Within a year, I had become interested in exercise and started writing lay articles. My first article published in a book (19) was based on what I then believed to be this biological truth that Wyndham and Strydom had discovered.

But two key events in subsequent years made me realize that my scientific heroes had to be wrong. In 1981, I served as race physician at a national cross-country championship in severe heat, at which a number of runners developed heatstroke (20) even though the longest race on that day was only 12 kilometers (not enough to cause severe dehydration).

Then, in another study, I measured a rectal temperature of 38 degrees Celsius in the winner of a 4-hour ocean kayak event (21), even though the kayaker had not drunk at all for the 4 hours and had lost 4.1% of his body weight. These two events proved to me that the Wyndham and Strydom hypothesis had to be wrong.

It set me on a path toward attempting to disprove their hypothesis (22, 23), which is what science is meant to be about.

The First Gatorade-Funded Study of David Costill and Colleagues

David Costill enjoys a special place in the pantheon of influential exercise physiologists who pioneered the modern exercise sciences. He just had begun his career at Ball State University in Muncie, Indiana, at the same time that Cade was developing Gatorade. In 1969, Costill approached Stokely-Van Camp with an idea: He wished to study what happened to marathon runners when they drank fluids during laboratory exercise. Naturally, Cade was interested, as it complemented his work with University of Florida football players.

For his study (7), Costill invited four top marathon runners to Ball State University to run for 2 hours on an indoor treadmill while they drank either nothing, a Gatorade solution, or water at a rate of 100 milliliters every 5 minutes. This gave a rate of 1.2 L/hr, a figure that reappears frequently in later Gatorade-funded studies.

Included in the trial was Amby Burfoot, who had just won the 1968 Boston Marathon. During that race, in keeping with the practice of the time, Burfoot had not ingested any fluids and finished healthy and untroubled despite the loss of 6.5% (4.1 kg) of his body weight.

None of the runners was able to continue drinking at this high rate for the full 2 hours of the trial. The authors reported: “All the runners experienced extreme sensations of fullness during the final five or six feedings (after 75 minutes of exercise). At the end of 100 minutes of running and feeding, it became apparent that further attempts to ingest fluid would have been intolerable.” As I will describe in subsequent columns, when the American College of Sports Medicine (ACSM) produced its 1996 Position Stand: Exercise and Fluid Replacement (24) — what might be called the “drink as much as tolerable” guidelines — it simply ignored this finding.

There were two other key findings of the Costill study. The first was that the rise in body temperature was not influenced by fluid ingestion for the first 60 minutes of exercise (Figure 2). The second was that at 120 minutes, the runners’ rectal temperatures were about 0.7 degrees Celsius lower when they ingested either water or Gatorade than when they drank nothing.

If Wyndham and Strydom’s idea was correct, there was one obvious conclusion: Drinking copiously during exercise is all one needs to do to prevent heatstroke.

Despite accepting easy money from the sports drink industry, Costill retained his scientific integrity — a characteristic from which others could have benefitted. Years later he wrote, “A number of ‘sports drinks’ containing carbohydrates are currently on the market, grossing more than $100 million each year. Unfortunately, many of the claims used to sell these drinks are based on misinterpreted and often inaccurate information” (25).

In 1975, Costill was invited to author the first ACSM position statement on the “Prevention of Heat Injuries During Distance Racing” (26). Notably, these guidelines were developed well before the sports drink industry had developed its Science of Hydration. Costill’s advice was simple: Athletes “should be encouraged to frequently ingest fluids during competition.” “Frequently” was considered to be every 3 to 4 kilometers in races of 10 miles or longer, which suggests that Costill did not think it particularly important for athletes to drink during exercise if they were running fewer than 10 miles.

I will argue that if we had accepted this advice as a final solution and ignored the Science of Hydration,” we would have been of greater assistance to the world’s athletes.

Carl Gisolfi and the Thermal Effects of Prolonged Exercise in the Heat

Later in his career at the University of Iowa, Dr. Carl Gisolfi became a favorite of the ACSM and sports drink industry, specifically for his role in developing and promoting their Science of Hydration” (his worth was acknowledged when the ACSM inaugurated an annual Gatorade-sponsored Carl Gisolfi tutorial lecture and the Carl Gisolfi Fun Run at its annual congress).

Perhaps Gisolfi’s most important contribution to the Science of Hydration had to be hidden because it produced one finding that undermined the logical foundation for the belief that sports drinks are better than water during exercise. Gisolfi showed that when drunk by mouth, the rate of water absorption is not different from a drink like Gatorade that includes both glucose and sodium than from a glucose-only drink (27, 28). This finding conflicts with the finding of S. J. Malawer, et al. (29), upon which the original formulation of the Gatorade brand was based (30). When fluid is drunk by mouth, it passes into the small intestine, where sodium is added from secretions of the pancreas. This added sodium then negates any benefits provided by the added sodium in the sports drink.

In any case, it never has been shown that the rate at which a drink is absorbed in the intestine plays any role in determining its value for use during exercise.

Gisolfi and J.R. Copping studied six athletes when they ran on an indoor laboratory treadmill for between 1.5 and 2.5 hours at 75% of their maximum capacity while they drank either nothing or cold or warm fluids at a rate of up to 600 mL/hr (31).

The study confirmed what Costill and colleagues (7) had found (Figure 2): Body temperatures were lower by about 0.8 degrees Celsius when fluids were ingested, but this “benefit” was present only after 60 minutes of exercise.

The Role of Convective Cooling

One of the problems of running on an indoor treadmill is that one runs in place. In contrast, when exercising outdoors, one moves through the air, producing convective cooling of the body in proportion to how fast one is running or cycling. When we tested the effects of adequate convective cooling — essentially absent in the studies of Costill and Gisolfi — we showed that proper convective cooling mitigates some of the thermal benefits of drinking during exercise (32).

When we submitted our findings to one reputable North American scientific journal, our study was rejected on the grounds that our ideas of how the body regulates its temperature during exercise are “mythical” and that we have little understanding of heat physiology.

Reviewers for a European journal, on the other hand, applauded us for the rigor of the study. I would guess that the European reviewers had no connections to either the ACSM or the U.S. sports drink industry.

Conclusion

The first studies of fluid ingestion during exercise established that fluid ingestion could lower body temperature during exercise. Wyndham and Strydom apparently had established that a failure to drink during exercise is the principle cause of heatstroke, and these early studies reinforced the belief in a false foundation myth for the subsequent development of the Science of Hydration, which ruthlessly would be promoted by the manufacturers of sports drinks around the world starting in the late 1980s.

As the story I am developing will show, this may have caused the gross overconsumption of fluids during exercise, leading to an epidemic of ill health that includes the tragic deaths of triathletes, marathon runners, military personnel, and American (Gridiron) football players beginning in 1981.

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Additional Reading

• The Hyponatremia of Exercise, Part 1
• The Hyponatremia of Exercise, Part 3
• The Hyponatremia of Exercise, Part 4
• The Hyponatremia of Exercise, Part 5
• The Hyponatremia of Exercise, Part 6
• The Hyponatremia of Exercise, Part 7
• The Hyponatremia of Exercise, Part 8
• The Hyponatremia of Exercise, Part 9
• The Hyponatremia of Exercise, Part 10
• The Hyponatremia of Exercise, Part 11
• The Hyponatremia of Exercise, Part 12

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Professor T.D. Noakes (OMS, MBChB, MD, D.Sc., Ph.D.[hc], FACSM, [hon] FFSEM UK, [hon] FFSEM Ire) studied at the University of Cape Town (UCT), obtaining a MBChB degree and an MD and DSc (Med) in Exercise Science. He is now an Emeritus Professor at UCT, following his retirement from the Research Unit of Exercise Science and Sports Medicine. In 1995, he was a co-founder of the now-prestigious Sports Science Institute of South Africa (SSISA). He has been rated an A1 scientist by the National Research Foundation of SA (NRF) for a second five-year term. In 2008, he received the Order of Mapungubwe, Silver, from the President of South Africa for his “excellent contribution in the field of sports and the science of physical exercise.”

Noakes has published more than 750 scientific books and articles. He has been cited more than 16,000 times in scientific literature and has an H-index of 71. He has won numerous awards over the years and made himself available on many editorial boards. He has authored many books, including Lore of Running (4th Edition), considered to be the “bible” for runners; his autobiography, Challenging Beliefs: Memoirs of a Career; Waterlogged: The Serious Problem of Overhydration in Endurance Sports (in 2012); and The Real Meal Revolution (in 2013).

Following the publication of the best-selling The Real Meal Revolution, he founded The Noakes Foundation, the focus of which is to support high quality research of the low-carbohydrate, high-fat diet, especially for those with insulin resistance.

He is highly acclaimed in his field and, at age 67, still is physically active, taking part in races up to 21 km as well as regular CrossFit training.

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References

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