The Hyponatremia of Exercise, Part 1

In 1981, I received a letter from a competitor in that year’s Comrades ultramarathon (1), a 56-mile race in my home country, South Africa. The Comrades Marathon is considered by many to be one of the great running races of the world. I have completed the race seven times, so I understand something of its joys and tribulations.

In her letter, this 46-year-old runner described how her husband had removed her from the race after she had run 43 miles. She was confused and did not recognize her husband. Three hours later she was unconscious and fighting for her life. For the next four days, her life hung in the balance. Had the doctors responsible for her care misdiagnosed her condition, they easily could have treated her inappropriately, leading to her death.

The condition from which she was suffering had never before been described in any marathon runner ever, anywhere in the world. Today, this condition is known as exercise-associated hyponatremic encephalopathy (EAHE).

EAHE occurs in certain predisposed persons who drink to excess, ahead of thirst, for 4 or more hours during prolonged endurance exercise typical of marathon running, ultra-distance cycling and the Ironman triathlon. United States military personnel also became at high risk after the 1980s. The key predisposing factor that turns overdrinking into a potentially fatal condition is the coexistence of a paradoxical condition, syndrome of inappropriate antidiuretic hormone secretion (SIADH), in these predisposed individuals (2).

The hormone ADH normally is secreted in persons who are becoming dehydrated for whatever reason. The ADH causes the kidneys to retain water, thereby potentially reversing the dehydration. In persons who are overdrinking and by definition cannot be dehydrated, ADH secretion should be suppressed, allowing the kidneys to excrete any fluid ingested in excess.

Failure to suppress ADH secretion, however, means that all the excess ingested fluid is retained within the body in persons who develop EAHE during exercise. As a result, the total body water content rises. Crucially, the amount of water in the brain increases, but since the brain is encased in a rigid skull, its capacity to swell is limited.

Instead, as the state of overhydration worsens, the pressure within the skull increases. And when that pressure becomes excessive, blood flow to parts of the brain that are key to our survival — such as the areas that regulate our breathing — are blocked, leading to death from respiratory arrest.

With inappropriate treatment, this tragedy can happen within minutes.

Over the next 30 years, key colleagues and I worked on discovering the cause of EAHE, its treatment, and ultimately, its prevention. In 2012, the story of those 30 years of scientific labor was published in Waterlogged: The Serious Problem of Overhydration in Endurance Sports (3).

I told that story against a backdrop that, before I entered my professional work as a medical scientist/medical practitioner, I had not imagined. That backdrop was an intensely hostile battle, lasting decades, with scientists who believe a contrary wisdom that ultimately proved to be false. This belief is based on four key unproven doctrines.

In the minds of those scientists, these unproven doctrines determine what and how much athletes should drink during exercise. The four doctrines are:

1. That heatstroke, the most dangerous complication of prolonged endurance activities like marathon running and Ironman triathlons, is caused exclusively by dehydration.
2. That heatstroke can be prevented purely by a drinking routine that keeps the body from becoming “dehydrated” during exercise — what I have called the “Zero-Percent Dehydration Doctrine.”
3. That EAHE is caused by sodium losses from the body, particularly in a group of athletes highly predisposed because they are “salty sweaters.”
4. That the ingestion of an electrolyte-containing sports drink can prevent the development of EAHE, even in those who overdrink during exercise.

According to these four doctrines, all athletes must be advised to drink as much of an electrolyte-containing sports drink as they can tolerate during all forms of exercise, regardless of the intensity of the exercise, its duration, or the environmental conditions in which the exercise is performed, and regardless of any other characteristics of the individual athletes.

The problem for all of us who oppose these certainties is that all four doctrines align perfectly with the commercial objectives of what was then a nascent sports drink industry.

In challenging the science, we were also challenging the might of powerful and influential commercial interests that even then were beginning to explore ways of controlling and directing the scientific messages that the public would hear. And their interests, we would show, did not always suggest that their highest priority was the health and safety of the users of their products.

In this series of columns, my first on the CrossFit website, I will start at the beginning and describe how all this happened. Much of the material I will present has not been published before. It was in the final Waterlogged manuscript that I submitted but was left out in the editing process.

But now it lives again. Without it, the full story of Waterlogged has not been told.

How the World’s First Commercially Successful Sports Drink Came Into Being

Before 1965, athletes cared little about drinking to improve performance or prevent the supposedly dreaded consequences of dehydration during exercise.

So it was that most of the great athletic performances up to that time had been achieved by athletes who drank minimally, if at all.

When Ron Hill won the 26-mile marathon at the 1970 Commonwealth Games in Edinburgh, completing what was then perhaps the world’s fastest time on an accurately measured course, he did not drink at all during the race and lost 3.9 percent of his body weight (4).

He was neither the first nor probably the last runner to win a major marathon footrace without drinking. In his first 26-mile marathon, Emil Zatopek won a third Olympic gold medal at the 1952 Helsinki Olympic Games, also without drinking. He also established a new world marathon record. Jim Peters set the four fastest-ever marathon times in the world between 1953 and 1954, including his final world record of 2:17:39, without drinking during any of the races. Ethiopian Abebe Bikila also did not drink anything when he set the new Olympic and world marathon records of 2:15:16 in the 1960 Rome Olympic Games.

The official history reports that none of these athletes appeared to be distressed when they finished these races despite their high body temperatures and levels of “dehydration” (5, 6). In fact, when Bikila repeated this feat four years later in the Tokyo Olympics, again setting world and Olympic marathon records of 2:12:11, he spent four minutes waiting for the second-place runner to finish and “doing postrace calisthenics to loosen up, his freshness making the race appear almost easy” (6).

Hill especially was known as one of the more intellectual runners in the history of the sport; his Ph.D. in chemistry makes him one of few world-class marathon runners to be so qualified. Thus, it seems likely that Hill chose not to drink during the best race of his life because he had researched the topic and decided that this was the best approach. This indicates that the advice to marathon runners that they should not drink during exercise, first advocated in the earliest book on marathon training published in English in 1910 (7), was still the prevailing opinion 60 years later.

Pre-season training for American football, done in the height of summer, also historically used a no-drinking policy to strengthen the will of the athletes. In The Junction Boys (8), Jim Dent describes how 10 days in training “hell” with then-Texas A&M coach Bear Bryant in Junction, Texas, forged a championship college football team out of the 35 players who survived the experience: “Surviving the sandspurs, the cactus, the heat and the practices without water was tough on me and my teammates. But I also felt the Junction helped mold us into the football team we would become—undefeated Southwest Conference Champions two years later” (8).

Or as one-time Baltimore Colt Bill Curry remembers: “Oh, and, one more thing: during the two, two-and-half-hour practice sessions for six August weeks in Baltimore (in 97°F heat), there was no water on the practice field. That’s right no water. Hard to imagine nowadays when the importance of hydration is a given, but back then the conventional wisdom was that water was for weaklings and that real men—real football players—could do without and be the tougher for it. It’s just amazing nobody died” (9).

But then the unexpected happened.

It was August 1965. Dwayne Douglas, assistant coach of the University of Florida (UF) Gators freshman football team, was lunching with Dr. Dana Shires, who was working as a fellow with Dr. Robert Cade in the renal unit in the College of Medicine at UF. Cade was directing the unit.

During the lunch, Douglas mentioned that 25 players from his freshman football team were admitted to hospital the previous weekend suffering from heat exhaustion and dehydration. Concerned, he asked Shires “to come up with something to negate the strain that the brutal summer heat had inflicted upon his players” (10). Shires promised she would discuss the problem with Cade and find a solution.

Since Cade and Shires knew little, if anything, about exercise, sweating, dehydration, heat exhaustion, and heat stroke, they sent Dr. Alex de Quesada, another of Cade’s fellows, to the UF Medical School library. He had five dollars in his pocket and instructions to return with the key research papers to help answer their questions.

De Quesada returned 2 hours later with “almost everything” that had ever been written on these topics. His key discovery was a paper by Dr. Sidney Malawer, who by remarkable coincidence had worked at the UF Medical College the previous year.

Malawer’s paper (11) shows that the addition of glucose in increasing concentrations in salt-containing solutions increases the rate at which both sodium and water are absorbed by the intestine. Maximum rates of water absorption are achieved from the most concentrated glucose solutions. Increasing the glucose concentration of a drink has a much greater effect on water absorption than an increase in sodium concentration. But the obvious conclusion (at that time) was that a drink containing both glucose and sodium would be especially valuable for athletes requiring instantaneous fluid replacement when exercising in severe heat.

On the basis of their physiological hunch that players need water, salt, and glucose when exercising in the heat, Cade and his team set about developing the prototypical sports drink. Importantly, since the ingredients they chose were freely available food stuffs, they were spared the inconvenience of requiring FDA approval before they could test and market their product.

Initially, their concoction tasted like “toilet bowl cleaner,” but the addition of lemon juice on the advice of Cade’s wife made the solution drinkable. By September 1965, the drink was ready for initial testing.

The coach of the varsity football team, Ray Graves, consented for the University of Florida freshman team to be studied. But he drew the line at allowing his varsity players to be studied.

Cade and his team began their research in September 1965 by studying weight, blood, and urine changes during practice in two players. When the results showed promise, Cade and his team were ready for their first full-on clinical trial during an actual football game. The drink became known as “Cade’s Ade” and “Cade’s Cola.”

So, on Oct. 1, 1965, the freshman team lined up against the varsity B team in a traditional game known as the Toilet Bowl. Because of their experience and superior size (approximately 20 pounds per man), the varsity B team was expected to win comfortably. In the second half of the game, the freshman team received “Cade’s Ade” while the varsity B team drank only water.

By the end of the first half, the freshman team was trailing 13-0, but the introduction of the new drink produced a dramatic change. The freshman team scored “touchdown after touchdown” without conceding any more points.

Coach Graves was so impressed by this turnabout that he asked Cade to supply the varsity team with the drink for the game to be played the next day against heavily favored Louisiana State University (LSU). At the time, LSU was ranked as the nation’s fifth-best college football team.

Working overnight, Cade’s team produced 100 liters of the special drink; it was stored overnight in the hospital’s walk-in freezer. The next day, Cade filled hundreds of Dixie cups and placed them near the Gators, who had not been informed of the nature of the experiment in which they unwittingly were key participants. Cade personally handed the players the solution and told them it was a glucose and electrolyte mixture. He added, “If you drink it during the game you’ll be stronger and feel better in the third and fourth quarters” (10).

Remarkably, the Gators came from behind to win the game 14 to 7.

Thus one of history’s most lucrative sports marketing legends was born. The product now is called Gatorade.

In truth, the role Cade’s solution played that day cannot be known and was probably small since “not many players partook of the drink during its surprise introduction on the sideline that day” (10). The effect could have been due to a powerful placebo effect since the LSU players had not been informed that they were part of an experiment and were therefore not a valid control group. Without a proper control group, it’s not possible to draw any definitive conclusions.

The 1965 Gators ended the season with a 7-4 record, which they improved to 8-2 the next year. They became known as the best football team ever to wear the Gator uniform. Their particular strength was their ability to be the stronger team in the second half. Naturally, Cade presumed that his solution was the reason for this superior ability.

On the other hand, the Gators were fortunate to have Stephen O. Spurrier as their quarterback. Spurrier would win the 1966 Heisman Trophy in part because of his ability to secure late victories for his team; hence his nickname, S.O.S.

Spurrier’s center, all-American Bill Carr, said, “I think Gatorade gave us a physiological and psychological edge and then Steve just made things happen. He had such a great ability to manage the clock and he had us all believing every time we stepped out there.” Spurrier, on the other hand, was less certain that there was a special Gatorade effect: “I don’t have any answer for whether the Gatorade helped us be a better second-half team or not. We drank it but whether it helped us in the second half, who knows.” Spurrier reportedly drank Coca-Cola, not Gatorade, during these games.

Their successful 1966 season saw the Gators invited to the Orange Bowl, played on Jan. 1, 1967. There, Coach Graves’ team outplayed the Georgia Tech team, scoring 20 of its winning 27 points in the second half; Georgia Tech scored 6 points in each half. After the game, Georgia Tech coach Bobby Dodds told Graves, “We didn’t have Gatorade (and) that made the difference.”

But Spurrier was less convinced: “We drank Coca-Cola at half time at the game because that is what they gave us.”

Early Development of the Gatorade Brand

On May 16, 1967, Cade sold the Gatorade rights to Stokely-Van Camp, an Indianapolis-based company. The use of Gatorade spread rapidly throughout U.S. collegiate sports. In that year, football powerhouses Notre Dame and Purdue started using the product, which also became the official drink of the NFL in the same year.  By 1969, Gatorade was widely used throughout all U.S. sports.

In 1971, UF took legal action against Cade, the Gatorade Trust, and Stokely-Van Camp. UF believed that it had contributed significantly to the development and marketing of Gatorade and therefore was eligible for royalties from the sale of the product. The court ruled in favor of UF and granted the university 20 percent of the Gatorade royalties retroactively and for the life of the product. Cade and Stokely-Van Camp were given the right to retain the brand name, Gatorade, on condition that Cade describe the chemical composition of his product in a scientific publication, which he subsequently did (12).

By 2005, UF had earned about $100 million from Gatorade royalties and the Gatorade Trust about $400 million.

In 1983, the Quaker Oats Company bought the Gatorade brand and set about the task of increasing the visibility of the product. An early action was to appoint Dr. Robert Murray, Ph.D., as head of the Gatorade Sports Science Institute (GSSI). Murray, a lean and athletic Ironman triathlete, then began to use science, scientists, and influential medical and scientific organizations to advance the commercial success of the product.

Murray continued in this position after 2000, when the Gatorade brand was purchased by PepsiCo and the role of the GSSI was given even greater prominence. But Murray would fall out of favor with PepsiCo, and he was replaced by another lean, athletic Ironman triathlete and sports scientist, Professor Asker Jeukendrup, in 2011.

In the course of Murray’s sovereignty, the myth would develop that “Gatorade is the most thoroughly researched beverage in the world, and the only sports drink with more than 40 years of science to back up its claims that it works, hydrating athletes, replenishing electrolytes and providing fuel for working muscles” (13).

Over the next few columns, we will look more closely at the origins and validity of this claim.

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Additional Reading

• The Hyponatremia of Exercise, Part 2
• 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

1. Noakes TD. Comrades makes medical history—again. S.A. Runner (Sept. 4, 1981): 8-10.
2. Noakes TD, Sharwood K, Speedy D, et al. Three independent biological mechanisms cause exercise-associated hyponatremia: Evidence from 2,135 weighed competitive athletic performances. PNAS 102(2005): 18550-18555.
3. Noakes TD. Waterlogged: The Serious Problem of Overhydration in Endurance Sports. Champaign, IL: Human Kinetics, 2012.
4. Muir AL, Percy-Robb IW, Davidson IA, et al. Physiological aspects of the Edinburgh Commonwealth Games. Lancet 2(1970): 1125-1128.
5. Martin DE, and Gynn RWH. The Marathon Footrace. Springfield, IL: Thomas, 1979.
6. Martin DE, and Gynn RWH. The Olympic Marathon. Champaign, IL: Human Kinetics, 2000.
7. Sullivan JE. Marathon Running. New York, NY: American Sports, 1909.
8. Dent J. The Junction Boys. How Ten Days in Hell With Bear Bryant Forged a Championship Team. New York, NY: Thomas Dunne Books, 1999.
9. Curry G. Ten Men You Meet in the Huddle. New York, NY: ESPN Books, 2009.
10. Rovell D. First in Thirst: How Gatorade Turned the Science of Sweat Into a Cultural Phenomenon. New York, NY: Amacom, 2005.
11. Malawer SJ, Ewton M, Fordtran JS, et al. Interrelation between jejunal absorption of sodium glucose, and water in man. J. Clin. Invest. 44(1965): 1072-1073.
12. Cade JR, Free HJ, De Quesada AM, et al. Changes in body fluid composition and volume during vigorous exercise by athletes. J. Sports Med. Phys. Fitness 1(1971): 172-178.
13. Hein K. Gatorade sues Powerade over ad claims. Brandweek, 13 April 2009. Available here.

All links accessed Feb. 27, 2019.