Introduction
Gastrointestinal (GI) complaints are common among athletes with rates in the range of 30% to 70% (12,15,56). The vast majority of literature on this subject comes from the study of runners, cyclists, triathletes, and weightlifters. The most common upper GI complaints include heartburn, nausea and vomiting, and epigastric pain. Each of these symptoms may be present in multiple disease states of differing levels of severity.
Athletes will present for treatment when their symptoms interfere with training and competition; therefore, it is important that the physician taking care of athletes is comfortable in handling these common complaints. This article will attempt to review the literature on the most common causes of upper GI complaints in athletes and provide the reader with a guide for diagnostic workup and therapeutic intervention where possible.
Epidemiology
Both the intensity of sport and the type of sporting activity have been shown to be contributing factors in the development of GI symptoms. Among elite endurance athletes, the prevalence of GI complaints may be as high as 70% (35), while in a group of recreational athletes, Rehrer et al. (42) reported a prevalence of between 25% and 50%. Multiple other studies confirm approximately 50% upper gastrointestinal (UGI) symptom rate for athletes during heavy exercise (5,18,28,35). In studies on esophageal reflux and exercise capacity, both the frequency and the duration of esophageal reflux episodes have been shown to increase with exercise intensity greater than or equal to 90% V˙O2max (12,60). In terms of sport, runners experience lower GI symptoms more commonly than upper GI symptoms, whereas cyclists commonly experience both upper and lower GI symptoms (35). In a direct comparison of esophageal reflux and heartburn among conditioned athletes during their sporting activities, weightlifters had the most heartburn and esophageal reflux followed by runners and then cyclists (10).
Pathophysiology
Three important factors have been postulated as contributing to the pathophysiology of GI complaints in athletes: mechanical forces, altered GI blood flow, and neuroendocrine changes. Mechanical forces are those such as increased intra-abdominal pressure, mechanical trauma to the abdominal organs from repetitive motion, and body position during exercise such as the bent-over position found in cyclists (50). Changes in GI mucosal activity also may cause GI symptoms and can be due to either mechanical forces or neuroendocrine control. Changes in neural activity such as increased sympathetic tone and decreased parasympathetic tone along with the secretion of multiple vasoactive substances have been documented during exercise (5). The shunting of blood away from the splanchnic circulation during exercise can lead to ischemia of the GI mucosa, which can cause increased GI membrane permeability, which may lead to endotoxemia. GI symptoms experienced by athletes may be the result of the ischemic insult of shunting or the reperfusion which takes place in the ischemic area of the gut after the cessation of exercise (29). Rowell (46) reported that splanchnic blood flow could be reduced by 43% during upright exercise at 70% V˙O2max. Another study by Clausen (9) reported that at maximal exercise, splanchnic blood flow may be reduced by up to 80%. Perko et al. (34) reported results similar to those of Rowell with reductions in splanchnic (43%) and mesenteric (32%) blood flows during semisupine submaximal cycle ergometry in fasted humans. Interestingly, when the investigators provided a liquid meal prior to exercise, the decrease in GI blood flow was attenuated.
When GI ischemia becomes symptomatic during exercise, it can result in many of the common symptoms reported by athletes during intense exercise such as nausea, vomiting, abdominal pain, and (bloody) diarrhea (29). Ter Steege et al. (56) propose that the most likely explanation for athletes with GI complaints is that GI ischemia during activity leads to reperfusion damage afterward. The reperfusion damage may cause the phenomenon of “leaky mucosa” and subsequent endotoxemia, which has been shown to cause GI complaints and bowel dysfunction (2,23). In one of the largest reviews of long-distance runners to date, ter Steege et al. (56) showed a strong relationship between GI complaints during a competitive run and an increased number of complaints after the run, suggesting a role of GI ischemia in the pathophysiology of running-induced GI symptoms as further support to this hypothesis.
The role of endotoxemia, however, is not entirely clear. One hypothesis is that decreased intravascular volume secondary to volume depletion caused by insensible water loss during prolonged sporting activity may exacerbate ischemia caused by decreased splanchnic blood flow (41). A current theory to explain the role ischemia has in symptoms is that as a result of the ischemic injury, the gastrointestinal mucosa is damaged and becomes increasingly permeable to substances that it normally acts as a barrier toward (e.g., endotoxin, food antigens, digestive enzymes, and bile) (31,58,59). The leakage of these substances locally and into the systemic circulation can create local and/or systemic inflammatory reactions that may contribute to the observed GI symptoms or more serious conditions such as endotoxemia (19).
Endotoxemia results from mucosal compromise allowing entry of lipopolysaccharide from the gut lumen into the portal circulation and is associated with nausea, vomiting, and diarrhea (4). Jeukendrup et al. (19) suggested that endotoxemia was not the direct cause of GI symptoms but rather an intermediate step contributing to release of cytokines tumor necrosis factor-α and interleukin-6. In addition, reduced GI blood flow may decrease the body’s ability to dissipate heat from the abdominal organs. Rowell et al. (47) have shown that abdominal cavity temperature approaches that of active skeletal muscle in exercising humans. Heat-related injury to GI mucosa, therefore, may be another possible etiology for the observed increase in GI permeability.
In studies of exercise with runners with restricted water intake, gastroduodenal and intestinal permeability have been shown to be increased significantly (P < 0.008) in fluid-restricted individuals compared with resting individuals (26). These results indicate that fluid restriction during 1 h of steady-state running increases GI permeability above resting levels (26). In contrast, it has been shown that ingestion of a liquid meal before exercise can help maintain GI blood flow (34). These results suggest that ensuring adequate access to fluids may be an important step toward preventing ischemia related to decreased splanchnic blood flow.
Gastroesophageal Reflux Disease
According to the Montreal consensus definition, gastroesophageal reflux disease (GERD) is defined as “a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications” (21). Therefore, a diagnosis of GERD may be made on the basis of symptoms alone or through diagnostic studies that may reveal complications of esophageal reflux such as tissue damage. This definition of GERD has not been applied uniformly throughout the literature, which makes comparisons between studies in this area difficult. The classic presenting symptom of esophageal reflux is that of burning epigastric pain. However, reliance on classical symptoms excludes many patients with GERD who experience atypical symptoms including hoarseness, cough, sore throat, bronchitis, asthma, recurrent pneumonia, intermittent choking, or chest pain. Both DeMeester et al. (13) and Schofield et al. (48) report on patients with exertional chest pain initially thought to be secondary to angina, who were found, in fact, to have normal coronary arteries but documented esophageal reflux upon further testing.
GERD is the most common cause of upper GI symptoms in athletes. As mentioned earlier, GERD increases with increased intensity of exercise, is more common with endurance sports, and is worse with postprandial exercise. Both the number and the duration of esophageal reflux episodes increase when exercise intensity is greater than or equal to 90% V˙O2max (12,60). Runners have three times more esophageal reflux when running 45 min after completing a meal than in a fasting state (10). Activities with large increases in intra-abdominal pressure contribute to symptoms as well. The increase in abdominal pressure likely accounts for the increase in GI symptoms observed in weightlifters and cyclists.
Esophageal motility also is affected during exercise. Transient lower esophageal sphincter (LES) relaxation, increased pressure gradient between the stomach and esophagus, and decreased esophageal clearance all have been associated with physical exertion and are all factors in the production of GER symptoms (51). Decreased splanchnic blood flow with maximal exercise is believed to play a role in delayed gastric emptying, thereby promoting GER (37). The mode of exercise exerts some effect as running decreases motility (duodenal) more than cycling (36). This leads to decreased clearance of esophageal contents and impairment of the protective effect of esophageal contraction in maintaining LES pressure.
Many patients may not want to take medications for the symptoms. Since GERD may respond to changes in eating habits alone, one treatment strategy for athletes with exertional GERD is to initiate a trial of lifestyle and training modifications for 4 to 6 wk prior to considering acid suppressive medications, namely, proton pump inhibitors (PPI). The American College of Gastroenterology has recommended lifestyle modification to include elevation of the head of the bed, decreased fat intake in the diet, smoking cessation, and avoiding recumbency for 3 h postprandially (14). Simons (50) also has recommended avoiding solid food and high-carbohydrate drinks prior to strenuous activity and rather trying liquid meals with lower carbohydrate content and being sure to keep well hydrated around the time of the activity (49). When carbohydrate intake is a priority during exercise, drinks containing up to a maximum of 10% glucose are thought to be the safest and tend to cause the fewest upper GI symptoms (33).
If symptoms persist or if the history and physical examination suggest GERD in the athlete, a 2-wk trial of a once-daily PPI such as 20-mg omeprazole or 30-mg lansoprazole, taken prior to a meal, should be instituted (14). If symptoms improve >80%, therapy can be continued for 4 to 8 wk. If not, twice-daily PPI may be necessary. According to expert opinion, recurrent symptoms within 3 months suggest a disease that may need further workup and, if related to GERD, may be managed best with continuous therapy, while recurrence after 3 months off medications can be managed by repeated courses of acute therapy as necessary (20). Endoscopy is indicated when empiric therapy has failed; continuous therapy is required; atypical symptoms such as dysphagia, odynophagia, bleeding, anemia, and weight loss are present; or if symptoms are long-standing (14).
Nausea and Vomiting
Athletes commonly experience episodes of nausea and vomiting with strenuous or prolonged exercise (12,22,53). Even healthy volunteers without prior GERD demonstrate esophageal reflux on manometry when put through vigorous exercise (8). The presence of reflux of stomach contents along with changes in esophageal motility, sphincter tone, and GI ischemia causing increased mucosal permeability likely contributes to the increased incidence of nausea and vomiting associated with exercise. Postprandial exercise exhibits a similar increase in the incidence of nausea and vomiting as was observed with GERD (17,24). The symptoms of nausea and vomiting, however, are not limited to training or competing, as many athletes will have symptoms even at rest, when not training (35). Sullivan et al. (55) showed that bloating and vomiting were even more common in runners when not training.
Preventing nausea and vomiting can be difficult because the etiology is not always clear. Also, data on symptoms related to fluid and carbohydrate intake during activity are often contradictory. The official American College of Sports Medicine (ACSM) nutritional guidelines state that during exercise, primary goals for nutrient consumption are to replace fluid losses and provide carbohydrates for maintenance of blood glucose levels (1). For events shorter than 1 h, carbohydrate replenishment in amounts currently found in popular sport drinks (6% to 8%) are optimal for performance, whereas rates of 30 to 60 g·h−1 should be used for events lasting longer than 1 h (1). Pfeiffer et al. (39,40) have shown that while a carbohydrate load higher than ACSM recommendations during activity may be associated with a higher incidence of nausea and flatulence, it also is associated with faster finishing times in Ironman athletes during competition.
General recommendations for nausea and vomiting include avoiding solid food 3 h prior to an athletic event. If symptoms of nausea and heartburn during activity are significant, a trial of PPI or H2 blocker therapy may be instituted. It has been shown that H2 blockers and PPI can be helpful for treatment of both esophageal reflux and nausea, and these should be utilized for affected athletes participating in activities likely to bring about symptoms (3,21). The use of nonsteroidal anti-inflammatory drugs (NSAID) has been shown to increase nausea and vomiting in ultramarathon runners (17). Therefore, these medications should be used with caution or discontinued prior to a race or other strenuous activities.
Upper GI Bleeding/Gastritis/Ulcers
Previous studies have shown that athletes are at risk for gastritis, ulcers, and upper GI bleeding (6,32,49,52). The mechanical trauma and decreased splanchnic blood flow during exercise have been proposed as contributing factors to GI mucosal damage associated with exercise (43,54). Choi et al. (7) found at least one GI mucosal lesion in 22 of 24 professional long-distance runners in one study, which showed a positive response to a 2-wk course of ranitidine therapy. Other studies have reported conflicting data on H2 blockers in GI bleeding (3,11,30). A 2-wk prophylactic regimen of oral proton pump inhibition was shown to decrease successfully the incidence of gastrointestinal bleeding in ultramarathon runners (57). These results support gastric acid secretion as a possible causative factor in the development of gastric mucosal damage in athletes. A short-course PPI or even H2 blocker therefore may be a reasonable choice prior to a prolonged period of exercise in those athletes who commonly experience gastritis or GI bleeding with heavy exercise.
Because of the widespread use of aspirin and NSAID for the relief of pain related to training, athletes may be at increased risk of damage to the GI mucosa. Both aspirin and NSAID have been shown to increase intestinal permeability, which may increase the gastrointestinal symptoms (25,49). NSAID have been shown to cause gastropathy and ulcerations through local and systemic effects induced by the blockade of cyclooxygenase and the cytoprotective gastric prostaglandins (44,45). Having athletes avoid the use of aspirin or NSAID prior to an event is reasonable if the athlete has a history of GI symptoms, ulcers, or bleeding. If a patient continuously uses NSAID despite symptoms or previous ulceration or bleeding, it would be beneficial to add a PPI for GI protection (38,61). Proper counseling of athletes including side effects and adverse reactions may help when recommending limited use of NSAID.
Side Stitch/Exercise-Related Transient Abdominal Pain
Exercise-related transient abdominal pain (ETAP) or its more common name, a “side stitch,” is a common complaint in runners and is characterized as an acute, sharp, cramping, or pulling sensation in the abdomen, occasionally radiating to the shoulder, that occurs during exercise and resolves spontaneously. Patients often will have to decrease their level of exercise when they experience the pain (27). A retrospective report by Morton and Callister (27) indicate that over 60% of runners have experienced ETAP within the past year. ETAP is experienced commonly by runners starting a new or increased running routine. Often, continued training results in less episodes of pain related to ETAP; Morton and Callister (27) have observed that well-trained runners are less likely to experience the side stitch.
In a study by ter Steege et al. (56) of different distance runs in the same event, severe side stitch was reported significantly more often in the 10-km running group compared with the 42-km group (4.9% vs 1.7%, P = 0.01) and also was reported significantly more frequently in women than in men (8.2% vs 1.8%, P < 0.001). Belching, side stitch, and an urge to defecate were found in almost half of the runners questioned (56). Despite its very characteristic symptomatology, the etiology of the pain remains unclear. Theories for the cause of pain include a lack of blood flow to the diaphragm during exercise leading to pain from ischemia, pain from stress on subdiaphragmatic ligaments, and irritation of the parietal peritoneum (16). Each of the theories has data to the contrary, suggesting that we do not understand fully yet the etiology of ETAP.
All proposed treatments are anecdotal, with no proven effective way to prevent or treat a painful episode. One proposed method of treatment is the practice of rhythmic breathing, which involves coordination of inhalation and exhalation with foot strikes while running. Eichner (16) suggests alternating exhalation to the opposite foot strike as the runner normally uses and exhaling through the mouth while narrowing the lips as if exhaling through a straw. This is also known as “pursed-lip breathing.” Others have not proposed a treatment but rather encouraged athletes to continue training through the pain, noting that the more well-trained runners complain of ETAP less as they increase their overall fitness.
Approach to an Athlete With Upper GI Symptoms
When evaluating an athlete with upper GI symptoms, it is of utmost importance to obtain a thorough history with a detailed account of symptomatology as it relates to exercise, food, and fluid consumption. A complete list of medications and supplements the athlete may be taking should be included in the initial evaluation, as these may play a role in the development of symptoms.
Often, the diagnosis is apparent readily from the initial history taking alone. It is of paramount importance, however, for the physician to be mindful of the broad differential diagnosis for upper GI discomfort and to ensure that more dangerous etiologies such as GI malignancy, peptic ulcer, cardiac ischemia, aortic vascular disease, pulmonary embolism, hepatitis, and pancreatitis have been ruled out comfortably. All patients should be asked about red-flag symptoms such as weight loss, dysphagia, black or bloody stools, and abdominal masses, and a full physical examination should be performed with these etiologies in mind. Follow-up testing based on concerning findings in the history of physical examination may include electrocardiogram (EKG) or cardiac stress testing, lipid panel, complete blood count, complete metabolic profile, and amylase, lipase, erythrocyte sedimentation rate (ESR), and fecal occult blood testing.
Patients without red-flag symptoms and with a diagnosis of GERD, nausea and vomiting, or ETAP may benefit from following some simple guidelines for changes to their eating and drinking patterns around the time of high-intensity or prolonged exercise. After the initial visit, having the patient record a log of symptoms with date, time, duration and intensity of symptoms, type of exercise activity, fluid status, and food and fluid intake complete with type, quantity, and timing can be invaluable to the treating physician.
We closely follow the ACSM guidelines on nutrition and athletic performance. We recommend limiting solid food on the day of activity to more than 3 h prior to exercise. Low-fat and low-fiber meals that contain between 200 and 300 g of carbohydrate are encouraged on the day of activity, around 4 h prior to the event. We have the athletes use liquid meals to stay hydrated prior to the activity and maintain enough carbohydrate in the body during the activity. The ideal liquids have lower carbohydrate content, optimally less than 10% glucose. Athletes are encouraged to ingest between 5 and 7 mL·kg−1 (0.08 to 0.1 oz·lb−1) body weight of these liquids 4 h prior to the athletic activity to optimize hydration status and allow enough time for excretion of excess fluid if necessary.
During exercise lasting longer than 1 h, it is important to replace between 30 and 60 g·h−1 of carbohydrate and between 6 and 12 oz of fluid lost as sweat. Ideally, the athlete should be encouraged to use the same low-carbohydrate electrolyte-replenishing fluids or carbohydrate gels for replacement every 15 to 20 min during activity. After the activity has ended, replacing fluid and electrolyte losses also is important. The athletes are encouraged to drink between 16 and 24 oz of fluid for every pound lost during exercise, and salty foods or snacks are encouraged to replete the electrolyte losses. Carbohydrate replenishment after exercise should be in the range of 1 to 1.5 g·kg−1 body weight and should be ingested soon after exercise.
If symptoms of GERD, nausea, or vomiting persist, a 2-wk trial of a once-daily PPI such as 20-mg omeprazole or 30-mg lansoprazole, taken prior to a solid meal, should be instituted. It has been shown that both H2 blockers and PPI can be helpful for the treatment of both GERD and nausea, and these should be utilized for affected athletes participating in activities likely to bring about symptoms. If symptoms of ETAP persist, some sports medicine physicians recommend continued training through the pain, noting that more well-trained runners complain of ETAP less often. In addition, one may have the athlete try the previously mentioned method of rhythmic breathing, with the coordination of inhalation and exhalation with foot strikes while running.
Conclusions
In summary, UGI symptoms are very common in the athletic population, occurring in up to 70% of elite athletes. Commonly, athletes present because symptoms are interfering with their desired activity. The most common upper GI symptoms experienced by athletes are heartburn, nausea, vomiting, and epigastric pain. The three main factors in the pathophysiology of these UGI symptoms are mechanical forces, altered GI blood flow, and neuroendocrine changes associated with exercise. As a result of those factors, GERD, nausea, vomiting, gastritis, peptic ulcers, GI bleeding, or ETAP may develop. The physician taking care of athletes must be adept at recognizing these common entities and be able to rule out more serious pathological conditions. Once identified, there are prevention and treatment guidelines in place that the sports medicine physician should become familiar with in order to provide the highest quality care to the athletes he or she treats.
The authors declare no conflict of interest and do not have any financial disclosures.
References
1. American Dietetic Association; Dietitians of Canada; American College of Sports Medicine; Rodriguez NR, Di Marco NM, Langley S. American College of Sports Medicine position stand. Nutrition and athletic performance. Med. Sci. Sports Exerc. 2009; 41: 709–31.
2. Ashton T, Young IS, Davison GW, et al.. Exercise-induced endotoxemia: the effect of ascorbic acid supplementation. Free Radic. Biol. Med. 2003; 35: 284–91.
3. Baska RS, Moses FM, Deuster PA. Cimetidine reduces running-associated gastrointestinal bleeding. A prospective observation. Dig. Dis. Sci. 1990; 35: 956–60.
4. Brock-Utne JG, Gaffin SL, Wells MT, et al.. Endotoxaemia in exhausted runners after a long-distance race. S. Afr. Med. J. 1988; 73: 533–6.
5. Brouns F, Beckers E. Is the gut an athletic organ? Digestion, absorption and exercise. Sports Med. 1993; 15: 242–57.
6. Choi SC, Choi SJ, Kim JA, et al.. The role of gastrointestinal endoscopy in long-distance runners with gastrointestinal symptoms. Eur. J. Gastroenterol. Hepatol. 2001; 13: 1089–94.
7. Choi SJ, Kim YS, Chae JR, et al.. Effects of ranitidine for exercise induced gastric mucosal changes and bleeding. World J. Gastroenterol. 2006; 12: 2579–83.
8. Clark CS, Kraus BB, Sinclair J, Castell DO. Gastroesophageal reflux induced by exercise in healthy volunteers. JAMA. 1989; 261: 3599–601.
9. Clausen JP. Effect of physical training on cardiovascular adjustments to exercise in man. Physiol. Rev. 1977; 57: 779–815.
10. Collings KL, Pierce Pratt F, Rodriguez-Stanley S, et al.. Esophageal reflux in conditioned runners, cyclists, and weightlifters. Med. Sci. Sports Exerc. 2003; 35: 730–5.
11. Cooper BT, Douglas SA, Firth LA, et al.. Erosive gastritis and gastrointestinal bleeding in a female runner. Prevention of the bleeding and healing of the gastritis with H2-receptor antagonists. Gastroenterology. 1987; 92: 2019–23.
12. de Oliveira EP, Burini RC. The impact of physical exercise on the gastrointestinal tract. Curr. Opin. Clin. Nutr. Metab. Care. 2009; 12: 533–8.
13. DeMeester TR, O’Sullivan GC, Bermudez G, et al.. Esophageal function in patients with angina-type chest pain and normal coronary angiograms. Ann. Surg. 1982; 196: 488–98.
14. DeVault KR, Castell DO; American College of Gastroenterology. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am. J. Gastroenterol. 2005; 100: 190–200.
15. Dimeo F, Knauf W, Geilhaupt D, Boning D. Endurance exercise and the production of growth hormone and haematopoietic factors in patients with anaemia. Br. J. Sports Med. 2004; 38: e37.
16. Eichner ER. Stitch in the side: causes, workup, and solutions. Curr. Sports Med. Rep. 2006; 5: 289–92.
17. Glace B, Murphy C, McHugh M. Food and fluid intake and disturbances in gastrointestinal and mental function during an ultramarathon. Int. J. Sport Nutr. Exerc. Metab. 2002; 12: 414–27.
18. Halvorsen FA, Lyng J, Glomsaker T, Ritland S. Gastrointestinal disturbances in marathon runners. Br. J. Sports Med. 1990; 24: 266–8.
19. Jeukendrup AE, Vet-Joop K, Sturk A, et al.. Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men. Clin. Sci. (Lond.). 2000; 98: 47–55.
20. Jozkow P, Wasko-Czopnik D, Medras M, Paradowski L. Gastroesophageal reflux disease and physical activity. Sports Med. 2006; 36: 385–91.
21. Kahrilas PJ, Shaheen NJ, Vaezi MFAmerican Gastroenterological Association Institute, Clinical Practice and Quality Management Committee. American Gastroenterological Association Institute technical review on the management of gastroesophageal reflux disease. Gastroenterology. 2008; 135: 1392–1413, 1413.e1–5.
22. Keeffe EB, Lowe DK, Goss JR, Wayne R. Gastrointestinal symptoms of marathon runners. West. J. Med. 1984; 141: 481–4.
23. Kolkman JJ, Mensink PB. Non-occlusive mesenteric ischaemia: a common disorder in gastroenterology and intensive care. Best Pract. Res. Clin. Gastroenterol. 2003; 17: 457–73.
24. Kondo T, Nakae Y, Mitsui T, et al.. Exercise-induced nausea is exaggerated by eating. Appetite. 2001; 36: 119–25.
25. Lambert GP, Broussard LJ, Mason BL, et al.. Gastrointestinal permeability during exercise: effects of aspirin and energy-containing beverages. J. Appl. Physiol. 2001; 90: 2075–80.
26. Lambert GP, Lang J, Bull A, et al.. Fluid restriction during running increases GI permeability. Int. J. Sports Med. 2008; 29: 194–8.
27. Morton DP, Callister R. Factors influencing exercise-related transient abdominal pain. Med. Sci. Sports Exerc. 2002; 34: 745–9.
28. Moses FM. The effect of exercise on the gastrointestinal tract. Sports Med. 1990; 9: 159–72.
29. Moses FM. Exercise-associated intestinal ischemia. Curr. Sports Med. Rep. 2005; 4: 91–5.
30. Moses FM, Baska RS, Peura DA, Deuster PA. Effect of cimetidine on marathon-associated gastrointestinal symptoms and bleeding. Dig. Dis. Sci. 1991; 36: 1390–4.
31. Pals KL, Chang RT, Ryan AJ, Gisolfi CV. Effect of running intensity on intestinal permeability. J. Appl. Physiol. 1997; 82: 571–6.
32. Papaioannides D, Giotis C, Karagiannis N, Voudouris C. Acute upper gastrointestinal hemorrhage in long-distance runners. Ann. Intern. Med. 1984; 101: 719.
33. Parmelee-Peters K, Moeller JL. Gastroesophageal reflux in athletes. Curr. Sports Med. Rep. 2004; 3: 107–11.
34. Perko MJ, Nielsen HB, Skak C, et al.. Mesenteric, coeliac and splanchnic blood flow in humans during exercise. J. Physiol. 1998; 513 (Pt 3): 907–13.
35. Peters HP, Bos M, Seebregts L, et al.. Gastrointestinal symptoms in long-distance runners, cyclists, and triathletes: prevalence, medication, and etiology. Am. J. Gastroenterol. 1999; 94: 1570–81.
36. Peters HP, de Vries WR, Akkermans LM, et al.. Duodenal motility during a run-bike-run protocol: the effect of a sports drink. Eur. J. Gastroenterol. Hepatol. 2002; 14: 1125–32.
37. Peters HP, Wiersma JW, Koerselman J, et al.. The effect of a sports drink on gastroesophageal reflux during a run-bike-run test. Int. J. Sports Med. 2000; 21: 65–70.
38. Peura DA. Prevention of nonsteroidal anti-inflammatory drug-associated gastrointestinal symptoms and ulcer complications. Am. J. Med. 2004; 117 (Suppl 5A): 63–71S.
39. Pfeiffer B, Cotterill A, Grathwohl D, et al.. The effect of carbohydrate gels on gastrointestinal tolerance during a 16-km run. Int. J. Sport Nutr. Exerc. Metab. 2009; 19: 485–503.
40. Pfeiffer B, Stellingwerff T, Hodgson AB, et al.. Nutritional intake and gastrointestinal problems during competitive endurance events. Med. Sci. Sports Exerc. 2012; 44: 344–51.
41. Rehrer NJ, Beckers EJ, Brouns F, et al.. Effects of dehydration on gastric emptying and gastrointestinal distress while running. Med. Sci. Sports Exerc. 1990; 22: 790–5.
42. Rehrer NJ, Janssen GM, Brouns F, Saris WH. Fluid intake and gastrointestinal problems in runners competing in a 25-km race and a marathon. Int. J. Sports Med. 1989; 10 (Suppl 1): S22–5.
43. Rehrer NJ, Meijer GA. Biomechanical vibration of the abdominal region during running and bicycling. J. Sports Med. Phys. Fitness. 1991; 31: 231–4.
44. Roth SH. NSAID gastropathy. A new understanding. Arch. Intern. Med. 1996; 156: 1623–8.
45. Roth SH, Bennett RE. Nonsteroidal anti-inflammatory drug gastropathy. Recognition and response. Arch. Intern. Med. 1987; 147: 2093–100.
46. Rowell LB. Human cardiovascular adjustments to exercise and thermal stress. Physiol. Rev. 1974; 54: 75–159.
47. Rowell LB, Brengelmann GL, Blackmon JR, et al.. Splanchnic blood flow and metabolism in heat-stressed man. J. Appl. Physiol. 1968; 24: 475–84.
48. Schofield PM, Whorwell PJ, Brooks NH, et al.. Oesophageal function in patients with angina pectoris: a comparison of patients with normal coronary angiograms and patients with coronary artery disease. Digestion. 1989; 42: 70–8.
49. Schwartz AE, Vanagunas A, Kamel PL. Endoscopy to evaluate gastrointestinal bleeding in marathon runners. Ann. Intern. Med. 1990; 113: 632–3.
50. Simons SM, Kennedy RG. Gastrointestinal problems in runners. Curr. Sports Med. Rep. 2004; 3: 112–6.
51. Simren M. Physical activity and the gastrointestinal tract. Eur. J. Gastroenterol. Hepatol. 2002; 14: 1053–6.
52. Stewart JG, Ahlquist DA, McGill DB, et al.. Gastrointestinal blood loss and anemia in runners. Ann. Intern. Med. 1984; 100: 843–5.
53. Sullivan SN. The gastrointestinal symptoms of running. N. Engl. J. Med. 1981; 304: 915.
54. Sullivan SN, Wong C. Runners’ diarrhea. Different patterns and associated factors. J. Clin. Gastroenterol. 1992; 14: 101–4.
55. Sullivan SN, Wong C, Heidenheim P. Does running cause gastrointestinal symptoms? A survey of 93 randomly selected runners compared with controls. N. Z. Med. J. 1994; 107: 328–31.
56. ter Steege RW, Van der Palen J, Kolkman JJ. Prevalence of gastrointestinal complaints in runners competing in a long-distance run: an Internet-based observational study in 1281 subjects. Scand. J. Gastroenterol. 2008; 43: 1477–82.
57. Thalmann M, Sodeck GH, Kavouras S, et al.. Proton pump inhibition prevents gastrointestinal bleeding in ultramarathon runners: a randomised, double blinded, placebo controlled study. Br. J. Sports Med. 2006; 40: 359–62; discussion 362.
58. Travis S, Menzies I. Intestinal permeability: functional assessment and significance. Clin. Sci. (Lond.). 1992; 82: 471–88.
59. van Nieuwenhoven MA, Brouns F, Brummer RJ. Gastrointestinal profile of symptomatic athletes at rest and during physical exercise. Eur. J. Appl. Physiol. 2004; 91: 429–34.
60. Viola TA. Evaluation of the athlete with exertional abdominal pain. Curr. Sports Med. Rep. 2010; 9: 106–10.
61. Yeomans ND, Tulassay Z, Juhasz L, et al.. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment (ASTRONAUT) Study Group. N. Engl. J. Med. 1998; 338: 719–26.
