Leggit, Jeffrey C. MD, CAQ SM
Upper gastrointestinal (UGI) complaints during exercise are common. Depending on the intensity of effort and the type of activity, rates of up 60% are reported (6,34). Affected athletes are unable to obtain peak performance and often curtail events because of symptoms (7). UGI symptoms occur anywhere from the upper esophagus to the umbilicus, with the predominant location being from the distal esophagus to the gastroduodenal junction. There is significant overlap in symptoms among multiple disease states, which can lead to difficulty in diagnosis and treatment. The prevailing UGI conditions affecting athletes are gastroesophageal reflux disease (GERD) and functional heartburn (10,16).
No sport is immune, but the prevalence of UGI complaints appears to be higher in running and weightlifting (22). The majority of surveys reported in the literature are confined to these activities; therefore, the clinician is left to extrapolate the findings into other sports. Unfortunately, these surveys also encompass all GI complaints, not differentiating between upper and lower symptoms. Although it does appear that runners experience more GI symptoms in total, the portion reporting upper symptoms alone is 30%, while the portion reporting lower symptoms alone is 60%. Contrast this with cyclists, who report approximately equal percentages of upper and lower symptoms. Confirmation of these findings was found in a study of triathletes, an interesting population since they participate in both running and cycling (5).
GERD Definition and Etiology
The definition of GERD is not agreed upon uniformly, which raises difficulty in comparing studies. Gastroesophageal reflux literally means the movement of gastric contents from the stomach into the esophagus. This phenomenon is found in practically all healthy individuals to some degree (23). The term GERD denotes a pathologic state. A position statement by the American Gastroenterological Association (AGA) advocates using the Montreal consensus definition, where GERD is defined as "a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications" (23). A distinguishing feature of the Montreal definition is the absence of the term "nonerosive reflux disease." It subdivides esophageal syndromes into those with and without esophageal injury. Those with mucosal injury include esophagitis, stricture, Barrett's esophagus, and adenocarcinoma. Those without esophageal injury include typical GERD and reflux chest pain syndrome. In the absence of esophageal injury, heartburn symptoms of insufficient frequency or severity to be perceived as troublesome by the patient do not meet the Montreal definition of GERD (32). Note that functional heartburn is not included in the Montreal definition of GERD. Functional heartburn is believed to represent a hypersensitivity syndrome (16).
Using this Montreal consensus definition, the mere presence of gastric content with a pH lower than 4 does not constitute GERD. It only means that acidic reflux is present (24). There must be symptoms and/or tissue damage to be considered GERD. Unfortunately, several studies do not adhere to this strict definition and only rely on reflux with pH lower than 4 as the surrogate marker for GERD without correlating reflux to actual symptoms.
GERD is thought to occur from some combination of transient lower esophageal relaxation (tLESR), a hypotensive lower esophageal sphincter, or anatomic abnormalities such as a hiatal hernia or weakened sphincter. In addition to these etiologies, exercise-related GERD may be influenced by neuroendocrine systems, decreased blood flow, or physical compression of organs, which can cause an increased intraabdominal pressure. tLESR predominates with mild disease, whereas hiatal hernia and weak sphincter predominate with more severe disease (3). Obesity is a major modifiable risk factor, but generally is not a significant contributor in the athletic population. There is a variant of GERD termed duodenogastroesophageal reflux (DGER), formerly referred to as alkaline or bile reflux. DGER is defined as the esophageal reflux of duodenal contents that may include biliary secretions, pancreatic enzymes, and bicarbonate. DGER is one of the causative factors for refractory GERD, despite maximal dose of proton pump inhibitors (PPI) (20).
The postprandial state increases reflux more compared with the fasting state (3). This holds true for at least the first 60 min after a meal (6). In addition, ingesting carbohydrate drinks also increases reflux episodes compared with water ingestion. This potentially is problematic considering the popularity of carbohydrate drink replenishment (27).
The intensity of exercise is a contributing factor. Both the number and duration of reflux episodes increases when exercise intensity is greater than or equal to 90% V˙O2max (27,34). Activities with large increases in intraabdominal pressure contribute to symptoms, as well. This factor most likely accounts for the increased symptoms in weightlifting. Exertional GERD is more common in those who have GERD at rest, but there is a distinct subset that manifests symptoms only while exercising. For this subset, performance is diminished by the inability to compete at maximum performance or activities are curtailed because of GERD symptoms (7).
The clinician must ensure that more serious pathology is ruled out. There is a large differential that includes cardiac, pulmonary, vascular, and GI illnesses. Myocardial ischemia, pulmonary embolism, aortic vessel disease, severe peptic ulcer disease, and pancreatitis always must be considered. The clinician needs to be convinced that these potentially catastrophic entities are not likely and, if unsure, use diagnostic testing for confirmation. Fortunately, the more common differential is not life threatening and includes esophagitis (infectious, pill, or eosinophilic), peptic ulcer disease, nonulcer or functional dyspepsia, biliary tract disease, and esophageal motor disorders. The key difference between functional dyspepsia and functional heartburn is the location of symptoms. Functional dyspepsia is confined to the epigastric region, whereas functional heartburn rises to the level of the retrosternum (30). Alarm symptoms that warrant a more aggressive, rapid diagnostic work-up are weight loss, dysphagia, and an epigastric mass. These symptoms can be associated with esophageal cancers.
Pill esophagitis is worth noting, especially in the athletic population. The most common medications causing pill esophagitis are the nonsteroidal antiinflammatories that enjoy widespread use in athletes (14). The other large pharmaceutical category is antibiotics, most notoriously tetracyclines. This medication can cause pill-esophagitis if the pill remains in the esophagus for a prolonged period. The same mechanism, only more severe, applies to mefloquine. Appropriate counseling is required when prescribing mefloquine, and alternative medications should be considered.
The cardinal symptoms of GERD are heartburn and regurgitation. Heartburn is defined as a burning sensation retrosternally and regurgitation as the perception of refluxed gastric contents into the mouth or hypopharynx (23). Unfortunately, the sensitivity of these symptoms is poor, with reported rates of 38% and 6% respectively. The specificity, though, is much higher at 89 and 95% (8). Meaning if these symptoms are absent, GERD is an unlikely diagnosis.
Work-up includes a thorough history and review of systems. The clinician must inquire both about GERD symptoms and those of the conditions in the differential diagnosis listed above. One of the key elements in the review of systems is to correlate symptoms to meals and exercise. Physical examination is aimed mostly at ruling out other entities, but must include a thorough evaluation to ensure the absence of any abdominal masses or signs of biliary tract disease.
Diagnostic testing for GERD is area of controversy both in terms of what test to order and when to order it. The most cost-effective method recommended by the AGA is empirical medical treatment followed by timely reassessment. There are some caveats with this approach, though. Rapid diagnostic testing is recommended when alarm symptoms are present: weight loss, significant dysphasia, or abdominal mass on exam. Diagnostic testing also is recommended when symptoms are refractory to maximal medical therapy (1).
Diagnostic testing for GERD recently has evolved, and there are a variety of modalities available, each with its own strengths and weaknesses. Reflux pH measurement can be obtained via a traditional catheter-based method or a wireless system. The benefit of the wireless system is that it can remain in place longer, up to 96 h, which offers testing on and off therapy. Equally important, the wireless system allows the patient to participate in normal activities of daily living. This is critical, considering one of the criticisms of the catheter probe is the rate of false negatives because of the patient not performing tasks which evoke their symptoms (20). Esophageal impedance testing is an additional modality that detects reflux irrespective of pH, discerns gas from liquid reflux, and determines the esophageal distribution of the reflux material (23). To determine the pH, an additional probe must be added to the impedance catheter. The esophageal impedance/pH catheter is subject to the same limitations mentioned with the pH probe catheter. DGER is diagnosed with a fiber-optic sensor placed, which detects bile due to its spectrophotometric absorption properties. Manometry is used when motor disorders are being entertained. Endoscopy provides direct visualization and the ability to biopsy the esophagus (16,28). It is included in almost any diagnostic evaluation. The American College of Gastroenterology (ACG) has developed a practice guideline that advises gastroenterologists as to the best combination of tests depending on the clinical situation. Unfortunately, the guidelines are adhered to less than 50% of the time (20).
If the history and physical exam indicates GERD as the most probable diagnosis, the AGA and the Canadian Association of Gastroenterology recommend empiric medical therapy with PPI as initial treatment followed by reassessment in 2 wk (2,7,25,31). PPI is maximally effective when taken at least 30 min before the first meal of the day (19). Many treatment failures are due to noncompliance both in terms of proper dosing times and in daily continuous use (10). The choice of PPI does not seem to matter, and it is acceptable to start with once-daily therapy. The AGA suggests 80% symptom improvement as a measure of success (1). If symptoms are improved but not to the satisfaction of the patient, expert opinion is essentially unanimous in recommending twice-daily dosing of PPI (USPSTF grade B, quality fair) (1). Antacids are effective for symptoms once they have begun, but have little role in prevention. Histamine2 receptor antagonists (H2RA) work quicker than PPI but are only half as effective. There is little evidence for combining medicines except for the rare patient with persistent nocturnal symptoms despite twice-daily PPI therapy. In these patients, H2RA dosed at nighttime may be appropriate (1).
Successful treatment should be continued for at least 8 wk. At this time a decision must be made whether to continue treatment indefinitely or initiate a step-down approach. In the step-down approach, the goal is to find the least amount of medication necessary for symptom alleviation. Twice-daily therapy is reduced to once a day. If the patient is on once-daily therapy, a trial off medications or as-needed dosing can be attempted. According to expert opinion, recurrent symptoms within 3 months suggests a disease best managed with continuous therapy, while recurrence after 3 months off medications can be managed by repeated courses of acute therapy as necessary (21). There is very little data on the efficacy of step-down therapy. Disappointedly, one study noted that only 21% of patients who were fully responsive to PPI therapy remained medication-free at 1-yr follow-up (4).
The evidence for the treatment of exertional GERD is far from conclusive. Peters and colleagues studied triathletes and long-distance runners who had GERD symptoms but were on no medication. They performed a randomized, double-blind, placebo-controlled crossover trial with PPI therapy for 1 wk before exercise testing to see the effect on symptoms. PPI therapy significantly reduced the frequency and duration of reflux, defined as reflux pH lower than 4, during running. However, no significant effect was seen on the actual symptoms of heartburn, regurgitation, or chest pain. The logical question then would be whether the patient's symptoms were truly from GERD. Unfortunately, the study did not report on rest symptoms before or during the study period. This information would have been crucial as it was stated earlier that the far majority of athletes with true exertional GERD will have GERD at rest, as well (28). The inability to reach any conclusion in this study highlights the point raised previously about using a uniformly accepted definition of GERD in order to compare studies.
For patients whose symptoms are not controlled with twice-daily PPI therapy, the first step is to review the history and physical exam to ensure GERD still is the most likely diagnosis. If the clinician still is convinced that the patient has GERD, compliance must be reviewed with an emphasis on the first dose being taken 30 min before the first meal of the day and the second dose taken 12 h later. Changing PPI is another option. There is a difference in metabolism in certain patient populations, and the bioavailability of each PPI differs slightly (10). If these fail to abate the patient's symptoms, a consult to gastroenterology is recommended. The consultant most likely will perform some or all of the diagnostic tests described earlier.
For the athlete with exertional GERD only, event-driven treatment is an option. This strategy employs medication just prior to physical activity. Bear in mind that H2RA works rapidly, generally within in an hour, while antacids work once symptoms have begun. If PPI is to be used, they should be started at least 48 h prior to the desired event and preferably 7 d prior. The evidence for these treatments is purely expert-based, as the literature is inconclusive on treating exertional GERD. The prudent clinician will base treatment decisions individually and often perform a medication trial in simulated competition conditions. Those athletes with severe or unrefractory symptoms despite maximal therapy may have other factors contributing to their GERD, such as concomitant hital hernia, or may have a different diagnosis. In these cases, referral is warranted for definitive testing to confirm the diagnosis.
The most common reason for failed therapy is that the actual diagnosis is functional heartburn. The Rome III diagnostic criteria for functional heartburn are burning retrosternal discomfort or pain, absence of evidence that GERD is the cause of the symptom, absence of histopathology-based esophageal motility disorders, and symptoms onset of at least 6 months (16). To adhere to this definition, referral for diagnostic workup is required. Functional heartburn is also known as esophageal hypersensitivity. It is similar to the visceral hyperalgesia described in conditions such as irritable bowel syndrome or functional dyspepsia (10). Studies suggest that up to 60% of patients with signs and symptoms compatible with GERD who do not respond to properly timed twice a day PPI therapy have functional heartburn. Treatment includes biofeedback, tricyclic antidepressants, and possibly a prokinetic agent. The latter two have significant side effects, which may be unacceptable to the athlete. Unfortunately, these treatment strategies seldom are successful in terms of full symptom relief (16) (see the Figure for treatment algorithm).
FIGURE Patient prese...Image Tools
Another perplexing symptom is reflux chest pain syndrome, also known as noncardiac chest pain. As mentioned earlier, according to the Montreal consensus group it is one of the esophageal syndromes without mucosal injury. Prevalence of reflux chest pain syndrome in the community is reported around 30% (9). Because of the significant morbidity and mortality associated with ischemic heart disease, cardiac etiology must be ruled out. Once the clinician is assured that the source of the symptoms is not related to cardiac ischemia, a therapeutic trial with PPI is recommended.
Surgery has a limited role in GERD treatment. 11,000 antireflux surgeries were performed in 1985, but rose to 31,695 in 1999. This increase is attributed to the introduction of the laparoscopic Nissen fundoplication in 1991 (1). Longitudinal studies have found that up to 62% still require medical therapy (17). This lack of long-term efficacy has led to a 30% decrease in surgery rates from 1999 to 2003 (15). The best evidence for antireflux surgery is persistent esophagitis refractory or intolerant to maximal PPI therapy (USPTF Grade A). Typical GERD symptoms without esophagitis refractory or intolerant to maximal PPI therapy have less robust evidence (USPTF Grade B) and even less evidence exists for extraesophageal symptoms attributed to GERD (USPTF Grade C). Those patients well managed on medical therapy gain nothing from antireflux surgery and should be advised as such (USPTF Grade A). Of note though, there are several new surgical procedures using an endoluminal approach, which hold promise (15). At this time there is insufficient high-quality data to make a truly objective recommendation. The role of surgery in the athlete must be balanced between the morbidity from GERD compared with the time required for surgical recovery and the possibility of procedural complications.
Complications From GERD
Complications from GERD can be subdivided into those confined to the esophagus and those manifesting as extraesophageal symptoms. Those confined to the esophagus include peptic strictures and Barrett's esophagus. Both are a consequence of esophagitis. Treatment of strictures requires dilation, with continuous PPI therapy to prevent further episodes of esophagitis. Progression and regression of esophagitis are not predictable events at this time. Esophagitis and Barrett's esophagus are found in patients without typical symptoms in up to 40% and 15%, respectively, making it difficult to make definitive recommendations about prevention and treatment (1).
Despite the ubiquity in practice, there seems to be no direct evidence supporting the use of routine endoscopy to screen for Barrett's esophagus or esophageal adenocarcinoma (1).
No data support the use of routine endoscopy for patients with recent-onset uncomplicated heartburn that responds to medical therapy. The risk of Barrett's esophagus progressing to esophageal adenocarcinoma is estimated at 0.5% per year (29). This fact has caused the American Society of Gastrointestinal Endoscopy and the ACG to support at least one lifetime endoscopy for patients with chronic GERD symptoms (1). This recommendation is based on expert opinion with little and even contradictory evidence. Two large Barrett's esophagus surveillance programs concluded that although a small number of incident esophageal adenocarcinomas were detected, there was no improvement in survival attributable to the surveillance program (33). Another study noted that only 38% of patients ultimately diagnosed with esophageal adenocarcinoma had Barrett's esophagus noted on endoscopies performed precancerous (1).
The Montreal consensus statement divides extraesophageal syndromes into those with an established association and ones with a proposed association. Established syndromes include chronic cough, laryngitis, asthma, and dental erosions. Proposed associations are recurrent pharyngitis, otitis media, sinusitis, and pulmonary fibrosis. It is estimated that 34% to 89% of asthmatics have GERD, and up to 40% of asthmatics have esophagitis (30). The wide disparity in percentages owes to the fact that GERD is not uniformly defined in multiple studies, as stated previously. A randomized, placebo-controlled trial found that asthma symptoms improved with PPI treatment only for the subgroup of patients with nocturnal GERD symptoms but showed no benefit in those without nocturnal GERD symptoms, even if they had typical daytime GERD symptoms (26). Should a trial of PPI therapy be performed in a patient with asthma who has typical GERD symptoms, success is defined as a 20% improvement in peak expiratory flow rates, improvement in asthma symptoms, or a 20% decrease in oral steroid dose (18). For those who do not improve with an empiric trial, definitive testing is required with referral to a gastroenterologist and perhaps a pulmonologist. The etiology of extraesophageal symptoms is multifactorial, and PPI treatment is only one facet of adequate treatment. It is highly unlikely that GERD is a significant contributor to extraesophageal symptoms without concomitant typical esophageal symptoms. Therefore, evidence does not support the widespread use of empiric therapy for asthma or chronic cough with PPI without typical esophageal symptoms, and this practice should be discouraged (13,28).
Risks With Chronic Medical Therapy
PPI and H2RAs may increase osteoporosis because of decreased calcium absorption, but this occurs over decades of daily therapy (35). Long-term PPI therapy may increase the risk of hip fracture (12). The etiology is unclear, but it may be from the same mechanism leading to osteoporosis. The U.S. Food and Drug Administration announced in 2010 that all PPI will include a warning about possible increased fracture risk due to seven observational studies published between 2006 and 2010 (11). The previous sections advocate for attempted step-down therapy with the goal of finding the lowest dose that can control symptoms. Other long-term risks of chronic PPI therapy have not borne out, and the medication is relatively safe except for the risks noted here.
Athletes are susceptible to GERD and functional heartburn just like the general population. For the athlete, the largest risk factor for having exertional GERD is having symptoms of GERD at rest. If signs and symptoms are compatible with GERD and the clinician has considered more serious pathology unlikely, a therapeutic trial with a PPI is warranted before diagnostic testing. Success is defined as 80% improvement in rest symptoms. After 8 wk of successful therapy, a step-down approach may be attempted. The treatment for pure exertional GERD is similar but is guided by expert opinion only. Surgery has a narrow role, but new techniques are evolving that may change the risk-to-benefit ratio. Chronic PPI therapy generally is safe, but there is a small risk of osteoporosis with concomitant fractures. There is no evidence for routine endoscopy screening for Barrett's esophagus or esophageal adenocarcinoma. For those who do not respond, the most likely diagnosis is functional heartburn. This is a diagnosis of exclusion, and referral to gastroenterology is warranted for diagnostic testing.
1. American Gastroenterological Association. American Gastroenterological Association Institute technical review on the management of gastroesophageal reflux disease. Gastroenterology.
2. Armstrong D, Marshall JK, Chiba N, et al
. Canadian consensus conference on the management of gastroesophageal reflux disease in adults - update 2004. Can. J. Gastroenterol.
3. Barham CP, Gotley DC, Alderson D. Precipitating causes of acid reflux episodes in ambulant patients with gastro-oesophageal reflux disease. Gut.
4. Bjornsson E, Abrahamsson H, Simren M, et al
. Discontinuation of proton pump inhibitors in patients on long-term therapy: a double-blind, placebo-controlled trial. Aliment Pharmacol. Ther.
5. Casey E, Dilaawar JM, MacKnight JM. Training room management of medical conditions: sports gastroenterology. Clin. Sports. Med.
6. Collings KL, Pratt FP, Rodriguez-Stanley S, et al
. Esophageal reflux in conditioned runners, cyclists, and weightlifters. Med. Sci. Sports Exerc.
7. DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am. J. Gastroenterol.
8. Ducrotté P, Zeribib P. ReQuest TM. A new questionnaire for the simultaneous evaluation of symptoms and well-being in patients with gastro-oesophageal reflux. Digestion.
2007; 75(Suppl. 1):79-86.
9. Eslick GD, Jones MP, Talley NJ. Non-cardiac chest pain: prevalence, risk factors, impact and consulting - a population-based study. Aliment. Pharmacol. Ther.
11. FDA. Proton Pump Inhibitors (PPI): Class Labeling Change including Nexium, Dexilant, Prilosec, Zegerid, Prevacid, Protonix, Aciphex, Vimovo, Prilosec OTC, Zegerid OTC, and Prevacid 24HR
[Internet]. 2010 [cited 2010 June 1]. Available from: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm213321.htm
13. Ferrari M, Bonella F, Benini L, et al
. Acid reflux into the oesophagus does not influence exercise-induced airway narrowing in bronchial asthma. Br. J. Sports Med.
14. Feucht CL, Patel DR. Analgesics and anti-inflammatory medications in sports: use and abuse. Pediatr. Clin. N. Am.
15. Finks JF, Wei Y, Birkmeyer JD. The rise and fall of antireflux surgery in the United States. Surg. Endosc.
16. Galmiche JP, Clouse RE, Balint A, et al
. Functional esophageal disorders. Gastroenterology.
18. Harding SM, Richter JE, Guzzo MR, et al
. Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome. Am. J. Med.
19. Hatlebakk JG, Katz PO, Camacho-Lobato L, Castell DO. Proton pump inhibitors: better acid suppression when taken before a meal than without a meal. Aliment. Pharmacol. Ther.
20. Hirano I, Richter JE, The Practice Parameters Committee of the American College of Gastroenterology. PRACTICE GUIDELINES ACG practice guidelines: esophageal reflux testing. Am. J. Gastroenterol.
21. Jozkow P, Wasko-Czopnik D, Medras M, Paradowski L. Gastroesophageal reflux disease and physical activity. Sports Med.
23. Kahrilas PJ, Shaheen NJ, Vaezi M. American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease. Gastroenterology.
24. Kahrilas PJ, Quigley EM. Clinical esophageal pH recording: a technical review for practice guideline development. Gastroenterology.
25. Kahrilas PJ, Smout A. Esophageal disorders. Am. J. Gastroenterol.
26. Kiljander TO, Harding SM, Field SK, et al
. Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial. Am. J. Respir. Crit. Care. Med.
27. Oliveira E, Burini RC. The impact of physical exercise on the gastrointestinal tract. Curr. Opin. Clin. Nutr. Metacb. Care.
28. Parmelee-Peters K, Moeller JL. Gastroesophageal reflux in athletes. Curr. Sport Med. Rep.
29. Shaheen NJ, Crosby MA, Bozymski EM, et al
. Is there publication bias in the reporting of cancer risk in Barrett's esophagus? Gastroenterology
. 2000; 119:333-8.
30. Sontag SJ, Harding SM. Gastroesophageal reflux and asthma. In: Goyal RK, Shaker R, editors. Goyal and Shaker's GI Motility Online
. New York: Nature Publishing Group; 2006.
31. Tack J, Talley NJ, Camilleri M, et al
. Functional gastroduodenal disorders. Gastroenterology.
32. Vakil N, van Zanten SV, Kahrilas P, et al
. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am. J. Gastroenterol.
33. Van der BA, Dees J, Hop WC, et al
. Oesophageal cancer is an uncommon cause of death in patients with Barrett's oesophagus. Gut.
34. Viola TA. Evaluation of the athlete with exertional abdominal pain. Curr. Sports Med. Rep.
35. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA.