CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2003;1:345–355

1. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2003;1:345–355 Exercise and Gastrointestinal Function and Disease: An Evidence-Based Review of Risks and Benefits LUKE BI* and GEORGE TRIADAFILOPOULOS‡ The benefit of exercise on the gastrointestinal system is unclear. Although exercise commonly is perceived to improve chronic constipation and has been shown to reduce the incidence of colorectal cancer, it may cause nausea, reflux, abdominal cramps, and occasionally gastrointestinal bleeding. A substantial part of this review is more applicable to trained athletes and individuals who are highly active and, as such, are at risk to experience the side effects of exercise. The most significant effects of exercise on gastrointestinal function occur at higher levels of activity (>70% VO2 max).

2. Gastroesophageal Reflux Disease (GERD ) Athletes, especially runners, have reported gastroesophageal reflux disease (GERD) symptoms that limit both their training and competition. Strenuous exercise may cause belching, abdominal fullness, regurgitation, heartburn, and chest pain in up to 45% to 90% of athletes. Runners showed the most reflux in duration and frequency whereas only some weight trainers had evidence of reflux. Cyclists, performing exercise with the least amount of body agitation, had the smallest amount of reflux. Significantly more reflux after meals compared with fasting. Studies in normal volunteers and patients with GERD indicate that an increased frequency of transient lower esophageal sphincter relaxations is the main mechanism.

3. Both histamine receptor antagonists and proton pump inhibitors are effective in treating patients with GERD and they may prevent exercise-induced reflux during Exercise. GERD, especially if precipitated by activity, frequently mimics angina-like chest pain in patients and athletes. Many studies have shown the association of GERD with noncardiac, angina-like pain. There is sufficient evidence that rigorous exercise, particularly running, can induce significant gastroesophageal reflux in trained and nontrained subjects alike, and medical therapy is effective in reducing reflux frequency and duration. Most exertional reflux is treatable by modification of exercise habits (e.g., bicycling instead of running) and fasting before exercise

4. Gastric Emptying and Gastric Acid Production Water and electrolyte loss as well as glycogen depletion may limit performance during severe, prolonged exercise. The rate of gastric emptying is reduced only slightly at a workload up to 71% of maximum oxygen uptake. Light exercise either accelerates or has no effect on gastric emptying whereas severe, exhaustive exercise beyond a critical number of 70% to 80% VO2max delays emptying of liquids and solids. Increased sympathetic tone and the release of catecholamines may be responsible for inhibition of gastric emptying with vigorous exercise. Gastric acid secretion decreased, with increasing levels of exercise reaching a 40% decrease at maximal level of exercise.

5. Taken together, these studies suggest that mild to moderate exercise has little effect on gastric secretion whereas strenuous, prolonged activity inhibits gastric acid production. Recommendations must be tailored carefully for athletes in different situations Peptic Ulcer Disease Study of the link between the incidence of peptic ulcer diseases and the levels of physical activity. High and moderate physical activity reduced the relative risk for duodenal ulcers in men. Significant protective effect of physical activity against stomach cancer only in men reporting moderate to vigorous exercise.

6. Inflammatory Bowel Disease Inflammatory bowel disease (IBD) is a chronic debilitating disease characterized by remissions and exacerbations and requires long-term medical or surgical therapy. As in most chronic illnesses, physical activity may promote overall well-being and potentially reverse or retard osteopenia and osteoporosis. IBD patients with osteoporosis have a much higher risk for fractures, which can result in significant morbidity. These results support a training benefit of low-impact exercise, although the benefit is rather inconsistent in retarding bone loss in IBD patients. Constipation and Gastrointestinal Motility Regular physical exercise has long been advocated as a first-line, standard treatment of chronic constipation. There has been no scientific evidence supporting exercise therapy for constipated patients.

7. The experimental subjects noted a significant decrease in their bowel transit times at the end of the study. 10 active, healthy adults in a cross-over trial that alternated moderate treadmill running, resting, and cycling, and showed dramatic acceleration of whole-gut transit after submaximal exercise. Similar studies with strict diet control confirm that short- to medium-term exercise has no noticeable impact on bowel transit across different populations, regardless of age, activity level, sex, and training status. Colorectal Cancer The role of physical exercise in colorectal cancer prevention has been studied extensively. nearly all have shown the protective effect of physical activities on widely varied populations across different study designs. There is less convincing evidence that physical activity protects against rectal cancer

8. Even modest levels of exercise (11.3 METh/wk, or equivalent to 1 h of running, 2 h of tennis, or 3 h of walking at a moderate pace) can substantially reduce colon cancer risk. Physical exercise exerts an independent protective effect. Perhaps by providing an immunoprotective effect, exercise enhances the immune response by promoting T-cell, B-cell, natural killer cell, and interleukin 1 levels. Gastrointestinal Bleeding Surveys of endurance athletes revealed a high incidence of different types of upper (nausea, vomiting, belching, and heartburn) as well as lower gastrointestinal disturbances (bloating, abdominal cramps, urgency to defecate, diarrhea, and hematochezia). Running was associated most heavily with gastrointestinal problems. 707 participants of a 1984 Oregon marathon documented an alarmingly high incidence of lower-tract GI symptoms among the runners who competed

9. More than one third of runners reported the urge to defecate during or immediately after running. Bowel movement (35%) and diarrhea (19%) were frequent after vigorous running and bloody diarrhea occurred in about 1.2% to 2.4% of runners. Occult bleeding is found in as much as one fourth of marathon runners. Participants with occult bleeding were significantly younger and also had faster finishing times, suggesting an association with training status and the amount of exertion. The mean hemoglobin, hematocrit, and ferritin levels were consistently lower in runners than in controls. Competitive long distance running induces gastrointestinal blood loss and may contribute to anemia. Prolonged physical exertion at high intensity can decrease splanchnic perfusion by 70% to 80% in young healthy subjects because blood is shunted to the muscles and skin. Although prolonged and intensive physical training such as marathons can be dangerous, mild regular exercise likely exerts some protection against lower gastrointestinal hemorrhage.

10. Interestingly, there has been no direct link between cycling and GI bleeding. The lack of evidence in this area suggests that prolonged physical vertical bouncing of the gastrointestinal organs compounded by ischemia in marathon running could play some kind of role in exacerbating exercise-induced gastrointestinal bleeding. Liver Disease Physical activity and regular exercise performance have no adverse effect on liver functions.

11. Neurogastroenterol. Mot. (1999) 11, 431±439 The effect of physical exercise on parameters of gastrointestinal function M. A. VAN NIEUWENHOVEN, F. BROUNS  & R-J. M. BRUMMER Exercise decreases splanchnic blood flow. Therefore exercise may induce alterations in gastrointestinal (GI) function. In the present study we investigated the effect of high-intensity exercise on oesophageal motility, gastro-oesophageal refux, gastric pH, gastric emptying, orocaecal transit time (OCTT), intestinal permeability and glucose absorption simultaneously, using an ambulatory protocol. After an overnight fast, the subjects arrived at the laboratory at 08.00. A thin catheter allowing the registration of oesophageal motility, gastro-oesophageal refux and intragastric pH was inserted transnasally. Subsequently the subjects received a standard liquid breakfast (4 mL kg±1 bodyweight, pH = 5.8), and remained seated in a chair for 60 min.

12. During this period resting values for oesophageal motility, gastric pH and gastro-oesophageal refux were obtained. Subsequently the subjects emptied their bladders, mounted a stationary bicycle ergometer in the cycling trial, or remained seated in the resting trial. In the cycling trial a warming-up was performed for 10 min at 100 W. During the final minute of this warming-up a carbohydrate-electrolyte solution (CES) (2mL kg±1 body weight), was ingested. Testing procedures Oesophageal parameters: Two solid-state pressure sensors measured oesophageal pressure at 13 cm (P1) and 3 cm (P3) above the LES, respectively. The catheter was connected to an ambulatory data-recorder, thus allowing continuous registration of pH and pressure. Gastro-oesophageal refux: A refux episode was defined as a period in which the pH in the oesophagus, at 5 cm above the LES, was lower than 4.

13. Gastric emptying: The assessment and mathematical evaluation of 13C-enrichment was carried out as follows: The drink administered at t = 40 during the exercise episode contained 150 mg sodium [1±13C]-acetate in order to determine the gastric emptying rate using the 13C-acetate breath test. OCTT: The drink administered at t = 0 of the exercise episode contained a nondigestible soluble carbohydrate allowing the measurement of OCTT via H2 measurement in breath. Intestinal permeability and glucose absorption: The drink administered at t = 0 of the exercise episode contained 5 g lactulose 0.5 g rhamnose and 0.35 g 3-O-D-methyl M-glucose.

14. Oesophageal motility The data from the oesophageal motility measurements are displayed in Table 2. The peristaltic velocity appeared to be increased during cycling, compared to rest. The number of peristaltic contractions, the peristaltic pressure at P1 and the duration of the peristaltic contractions at P1 and P3 were lower during cycling. Gastric pH There were no significant differences between the pre-exercise, the exercise and the post-exercise episodes in both median gastric pH (P = 0.767, 0.208 and 0.933, respectively), and the percentage of time in which the gastric pH was lower than 4 (P = 0.314, 0.889 and 0.612, respectively). Gastro-oesophageal refux There were no significant differences between the pre-exercise, the exercise and the post-exercise episodes in both the number of refux episodes (P = 0.129, 0.610 and 0.786, respectively) and the duration of refux as a percentage of time (P = 0.237, 0.612, and 0.463, respectively).

15. Gastric emptying and OCTT: Neither gastric emptying nor the OCTT show differences between the rest and the cycling trials. 13C-TTP in the rest trial was 29.3 min (17.4±42.2) and in the cycling trial it was 28.7 min (21.6±34.2) (P = 0.33). OCTT in the rest trial was 117.5 min (105.0±165.0), and in the cycling trial it was 140.0 min (105.0±195.0) (P = 0.17). Intestinal permeability and glucose absorption: The lactulose/rhamnose ratio was significantly higher in the rest trial, compared to the cycling trial (0.015 (0.0076±0.027) and 0.0067 (0.0017±0.0141), respectively, P = 0.009). Our study demonstrates that physical exercise has an effect on oesophageal function. Oesophageal function was measured at 3 cm (P3) and 13 cm (P1) above the LES. At 3 cm above the LES the oesophagus is entirely composed of smooth muscle tissue. At 13 cm above the LES, however, the oesophagus also contains striated muscle tissue. Exercise may lead to a substantial decrease in GI blood flow of more than 50%.

16. Therefore exercise may induce alterations in GI-function. The results of the present study indicate that there are no differences in gastro-oesophageal reflux, gastrointestinal transit time or gastric pH between a resting and a cycling trial. The present study demonstrates that the gastric pH does not change as a result of exercise. the gastric emptying rate was not affected by exercise at a cycling load of 70% Wmax, which corresponds with approximately 80% VO2max. Intestinal glucose uptake is a carrier-mediated transport process. Our results demonstrated a decreased absorptive capacity for glucose uptake in the cycling trial. Jejunal glucose absorption is also decreased during cycling.

17. Gut 2001;48:435–439 Potential benefits and hazards of physical activity and exercise on the gastrointestinal tract. Peters, vanBerge-Henegouwen, de Vries, et al “Exercise” is considered as voluntary activation of skeletal muscle leading to short term effects (for minutes or hours) while “physical activity” is considered as repetitive exercise periods leading to long term effects (for days, weeks, months, or years). Hazards Gastrointestinal symptoms such as nausea, heartburn, diarrhoea, and gastrointestinal bleeding are common during exercise, especially during vigorous sports such as long distance running and triathlons. In general, these symptoms are transient and can be considered protective for critical organ damage: its progressive nature causes the athlete to reduce exercise intensity or duration.

18. Incidence rates during prolonged exercise vary mostly from 20% to 50%, depending on factors such as mode, duration, and intensity of exercise, type of symptom, age, training status, sex, dietary intake, occurrence of gastrointestinal symptoms at rest, and method of investigation. In particular, exercise intensity seems to be an important factor provoking gastrointestinal symptoms. The mechanisms by which exercise causes gastrointestinal symptoms are not well known. Decreased gastrointestinal blood flow, increased gastrointestinal motility, increased mechanical bouncing, and altered neuroendocrine modulation are postulated. All of these mechanisms are associated with exercise intensity. While most gastrointestinal symptoms do not hamper the athlete’s health, gastrointestinal bleeding may be a serious problem. In addition to gastrointestinal symptoms, unfavourable effects of exercise on liver function and peptic ulcer disease have been reported.

19. Benefits The potential benefits of physical activity concern mainly effects on cancer risk, cholelithiasis, gastrointestinal haemorrhage, inflammatory bowel disease, diverticular disease, and constipation. GASTROINTESTINAL CANCERS To date, the risk of oesophageal, bile duct, or gall bladder cancers have not been examined in relation to physical activity. Concerning stomach cancer, the data are controversial: one study reported a reduced risk while two did not. No relationship between physical activity and risk of pancreatic cancers has been found, whereas rectal cancer risk was unrelated to physical activity in the majority of studies. In contrast, there is overwhelming evidence that physical activity reduces the risk of colon cancer: there is consistent evidence that physically active men and women are at a reduced risk of colon cancer (up to 50% reduction in incidence).

20. Studies analysing dose-response relationships suggest that more intense activity may confer greater protection against the risk of colon cancer than less intense activity. The primary postulated mechanism is that physical activity reduces intestinal transit time which would limit the time of contact between the colon mucosa and cancer promoting contents. Two recent large prospective studies showed a relative risk (RR) of cholelithiasis of 0.63 in men and 0.69 in women when comparing the most active with the most inactive subjects, whereas sedentary lifestyle (watching television or sitting) resulted in an increased risk (RR 1.11–3.32). A clear dose-response relationship was observed, independent of several potential risk factors, strongly suggesting that (symptomatic) cholelithiasis can be prevented by physical activity, even beyond its benefit for control of body weight or diet.

21. GASTROINTESTINAL HAEMORRHAGE The only study which examined gastrointestinal haemorrhage and physical activity was a prospective cohort study with three years of follow up in 8205 elderly subjects. Only severe gastrointestinal haemorrhage was investigated. For those participants doing the activity at least three times per week, RR was significantly lower for walking (0.6) and for the summary variable (0.7) in comparison with sedentary subjects, independent of several other risk factors such as age, sex, mobility, body mass index, or health status. The RR for gardening (0.8) and vigorous physical activity (0.7) was not significantly lower. The authors hypothesised that a relatively increased gastrointestinal blood flow in physically active subjects reduced the risk of gastrointestinal haemorrhage. One should keep in mind that the findings of this study were restricted to severe haemorrhage in elderly subjects and that no data are available for less severe forms of haemorrhage or for younger subjects.

22. INFLAMMATORY BOWEL DISEASE A limited number of studies have investigated the preventive effect of physical activity on Crohn’s disease (CD) or ulcerative colitis (UC). Sedentary and physically less demanding occupations were associated with a higher risk of inflammatory bowel disease than physically demanding occupations. While the preventive effect of physical activity remains inconclusive, it has become clear that physical activity is not harmful for patients with inflammatory bowel disease. Physical activity should be promoted as these patients have muscle weakness and are at risk of osteoporosis. This risk is especially high with glucocorticoid medication, which causes muscle atrophy and weakness, osteoporosis, and osteopenia. In addition, physical activity may reduce disease activity and improve physical health, general well being, perceived stress, and quality of life.

23. DIVERTICULAR DISEASE Diverticular disease was more prevalent among subjects with sedentary occupations than in more active occupations. An increase in colonic motor activity via hormonal, vascular, and mechanical aspects, leading to a reduction in colonic transit time, was postulated as an underlying mechanism. CONSTIPATION Several cross sectional studies have shown an inverse independent relationship between constipation and physical activity. Underlying mechanisms are unclear but a favourable effect on colonic motility, decreased blood flow to the gut, biomechanical bouncing of the gut during running, compression of the colon by abdominal musculature, and increased fibre intake as a result of increased energy expenditure have all been reported.

24. Biological mechanisms The mechanisms by which exercise and physical activity influence the gastrointestinal tract are poorly understood although decreased gastrointestinal blood flow, increase in gastrointestinal motility, increased mechanical bouncing, and neuro-immuno-endocrine alterations are postulated. However, most of the described mechanisms have only been investigated after acute bouts of exercise. Whether or not these mechanisms are predictive of the long term effects of physical activity remains to be elucidated. GASTROINTESTINAL BLOOD FLOW During exercise, blood will primarily be shunted to the skin and exercising muscles at the expense of the gastrointestinal tract. 60–70% decrease in splanchnic blood flow in humans exercising at 70% of maximal oxygen consumption (V~O2max). At maximal exercise intensity, splanchnic blood flow may be reduced by about 80%.

25. Ischaemic damage has been proposed as a causal mechanism of gastrointestinal bleeding during and after exercise. Although gastrointestinal blood loss is transient, increased faecal á1 antitrypsin and lysozyme concentrations after exercise have been found, indicative of local mucosal damage with an inflammatory response. In theory, critical ischaemic levels and accumulation of metabolic waste products may induce malabsorption, hypersecretion, and increased gastrointestinal permeability with endotoxaemia. Findings for the effect of exercise on absorption and acid secretion are inconsistent: both a decrease or no change in absorption and acid secretion have been reported. Exercise induced increases in intestinal permeability and mild leakage of endotoxins into the portal circulation have only been found at higher intensities. GASTROINTESTINAL MOTILITY AND BILE SALT METABOLISM Data on the effect of exercise and physical activity on gastrointestinal motility are scarce and mostly indirectly obtained and limited to acute exercise

26. MECHANICAL BOUNCING The frequency of most gastrointestinal symptoms is almost twice as high during running than during other endurance sports such as cycling or swimming, where up and down movements are more limited. The mechanical vibration of the body is more than doubled in running compared with cycling. The way in which this bouncing of the gut affects gastrointestinal function is still unknown. NEURO-IMMUNO-ENDOCRINE ALTERATIONS Many hormones associated with gastrointestinal function at rest (secretion, absorption, and motility) alter during exercise, in terms of plasma concentrations: cholecystokinin, vasoactive intestinal peptide, secretin, pancreatic polypeptide, somatostatin, peptide histidine isoleucine, peptide YY, gastrin, glucagon, motilin, catecholamines, endorphins, and prostaglandins.

27. With respect to immune function, the current opinion is that physical activity of moderate intensity may protect against infections by inducing changes in the activity of macrophages, natural killer cells, lymphokine activated killers cells, neutrophils, and regulating cytokines. Severe exercise, however, can result in a transient reduction in natural killer cells and production of free radicals, which temporarily increases the risk of infection. Knowledge of optimal intensity and duration of physical activity for an optimal immunomodulating effect in athletes and in patients with gastrointestinal related diseases is lacking. Conclusions Strenuous exercise may induce gastrointestinal symptoms such as heartburn or diarrhoea, which may deter people from participating in physical activity. Repeated gastrointestinal bleeding during training and competition may occasionally lead to iron deficiency and anaemia. However, these and other symptoms can often be prevented with appropriate precautions.

28. Physical activity, mostly performed at a relatively low intensity, may also have protective effects on the gastrointestinal tract.