Relationship between resting ventilatory chemosensitivity and maximal oxygen uptake in moderate hypobaric hypoxia.

This study tested the hypothesis that the extent of the decrement in (.)Vo(2max) and the respiratory response seen during maximal exercise in moderate hypobaric hypoxia (H; simulated 2,500 m) is affected by the hypoxia ventilatory and hypercapnia ventilatory responses (HVR and HCVR, respectively). Twenty men (5 untrained subjects, 7 long distance runners, 8 middle distance runners) performed incremental exhaustive running tests in H and normobaric normoxia (N) condition. During the running test, (.)Vo(2), pulmonary ventilation (Ve) and arterial oxyhemoglobin saturation (Sa(O(2))) were measured, and in two ventilatory response tests performed during N, a rebreathing method was used to evaluate HVR and HCVR. Mean HVR and HCVR were 0.36 +/- 0.04 and 2.11 +/- 0.2 l.min(-1).mmHg(-1), respectively. HVR correlated significantly with the percent decrements in (.)Vo(2max) (%d(.)Vo(2max)), Sa(O(2)) [%dSa(O(2)) = (N-H).N(-1).100], and (.)Ve/(.)Vo(2) seen during H condition. By contrast, HCVR did not correlate with any of the variables tested. The increment in maximal Ve between H and N significantly correlated with %d(.)Vo(2max). Our findings suggest that O(2) chemosensitivity plays a significant role in determining the level of exercise hyperventilation during moderate hypoxia; thus, a higher O(2) chemosensitivity was associated with a smaller drop in (.)Vo(2max) and Sa(O(2)) under those conditions.     

Ventilatory chemosensitive adaptations to intermittent hypoxic exposure with endurance training and detraining.

The present study was performed to clarify the effects of intermittent exposure to an altitude of 4,500 m with endurance training and detraining on ventilatory chemosensitivity. Seven subjects (sea-level group) trained at sea level at 70% maximal oxygen uptake (VO2 max) for 30 min/day, 5 days/wk for 2 wk, whereas the other seven subjects (altitude group) trained at the same relative intensity (70% altitude VO2 max) in a hypobaric chamber. VO2 max, hypoxic ventilatory response (HVR), and hypercapnic ventilatory response, as an index of central hypercapnic chemosensitivity (HCVR) and as an index of peripheral chemosensitivity (HCVRSB), were measured. In both groups VO2 max increased significantly after training, and a significant loss of VO2 max occurred during 2 wk of detraining. HVR tended to increase in the altitude group but not significantly, whereas it decreased significantly in the sea-level group after training. HCVR and HCVRSB did not change in each group. After detraining, HVR returned to the pretraining level in both groups. These results suggest that ventilatory chemosensitivity to hypoxia is more variable by endurance training and detraining than that to hypercapnia.     

Energy expenditure and influence of physiologic factors during marathon running

This study examined energy expenditure and physiologic determinants for marathon performance in recreational runners. Twenty recreational marathon runners participated (10 males aged 41 +/- 11.3 years, 10 females aged 42.7 +/- 11.7 years). Each subject completed a V(.-)O2max and a 1-hour treadmill run at recent marathon pace, and body composition was indirectly determined via dual energy X-ray absorptiometry. The male runners exhibited higher V(.-)O2max (ml x kg(-1) x min(-1)) values (52.6 +/- 5.5) than their female counterparts (41.9 +/- 6.6), although ventilatory threshold (T-vent) values were similar between groups (males: 76.2 +/- 6.1 % of V(.-)O2max, females: 75.1 +/- 5.1%). The male runners expended more energy (2,792 +/- 235 kcal) for their most recent marathon as calculated from the 1-hour treadmill run at marathon pace than the female runners (2,436 +/- 297 kcal). Body composition parameters correlated moderately to highly (r ranging from 0.50 to 0.87) with marathon run time. Also, V(.-)O2max (r = -0.73) and ventilatory threshold (r = -0.73) moderately correlated with marathon run time. As a group, the participants ran near their ventilatory threshold for their most recent marathon (r = 0.74). These results indicate the influence of body size on marathon run performance. In general, the larger male and female runners ran slower and expended more kilocalories than smaller runners. Regardless of marathon finishing time, the runners maintained a pace near their T-vent, and as T-vent or V(.-)O2max increased, marathon performance time decreased.     

The effects of intermittent exposure to hypoxia during endurance exercise training on the ventilatory responses to hypoxia and hypercapnia in humans

The present study was performed to investigate the effects of a combination of intermittent exposure to hypoxia during exercise training for short periods on ventilatory responses to hypoxia and hypercapnia (HVR and HCVR respectively) in humans. In a hypobaric chamber at a simulated altitude of 4,500 m (barometric pressure 432 mmHg), seven subjects (training group) performed exercise training for 6 consecutive days (30 min · day⁻¹), while six subjects (control group) were inactive during the same period. The HVR, HCVR and maximal oxygen uptake (V˙O_{2 max}) for each subject were measured at sea level before (pre) and after exposure to intermittent hypoxia. The post exposure test was carried out twice, i.e. on the 1st day and 1 week post exposure. It was found that HVR, as an index of peripheral chemosensitivity to hypoxia, was increased significantly (P < 0.05) in the control group after intermittent exposure to hypoxia. In contrast, there was no significant increase in HVR in the training group after exposure. The HCVR in both groups was not changed by intermittent exposure to hypoxia, while V˙O_{2 max} increased significantly in the training group. These results would suggest that endurance training during intermittent exposure to hypoxia depresses the increment of chemosensitivity to hypoxia, and that intermittent exposure to hypoxia in the presence or absence of exercise training does not induce an increase in the chemosensitivity to hypercapnia in humans. Accepted: 18 March 1998     

Pineal mediation of the thermoregulatory and behavioral activating effects of beta-endorphin

Intraventricular administration of the opioid peptide, beta-endorphin to goldfish altered their body temperatures and activity levels. Low doses (0.5-5.0 pg g-1 body weight) of beta-endorphin significantly increased behaviorally selected body temperatures while higher doses (15 pg g-1) decreased the preferred temperatures selected in horizontal thermal gradients. There was a significant day-night rhythm in the extent of these effects. These thermoregulatory effects could be blocked and reversed by systemic administration of the opiate antagonist, naloxone, supporting mediation of the thermoregulatory effects at opioid receptors. In addition, administration of naloxone by itself significantly decreased preferred temperature. Removal of the pineal gland significantly increased the preferred temperatures selected by goldfish and eliminated the thermoregulatory effects of beta-endorphin administration in both the day and the night. The behavioral activity effects of beta-endorphin were dependent on the thermal conditions. In fish held at a constant temperature (20 degrees C) beta-endorphin caused a dose-dependent increase in activity, while in individuals held in thermal gradients administration of beta-endorphin had no effects on activity. In both situations naloxone caused a decrease in activity levels. Pinealectomy also eliminated the behavioral activating effects of beta-endorphin, though it had no apparent effects on the actions of naloxone. These results indicate that the pineal gland is involved in the mediation of the thermoregulatory and behavioral activating effects of beta-endorphin. Speculations are made as to the possible mechanisms of action of the pineal gland in mediating the effects of opioid neuropeptides.     

The validity of incremental exercise testing in discriminating of physiological profiles in elite runners

The goal of this study was to determine whether traditional ergoespirometric incremental exercise testing carried out to the point of exhaustion could be useful in distinguishing the physiological profiles of elite runners that compete in races that lasted about 8 minutes versus those that lasted about 2 hours. Ten male marathon runners (performance time: 2:12:04, coefficient of variation (CV) = 2.33%) and 8 male 3000 m steeplechase runners (performance time: 8:37.83, CV = 2.12%) performed an incremental test on the treadmill (starting speed 10 km·h-1; increments, 2 km·h-1; increment duration, 3 min to exhaustion). Heart rate (HR), VO2, and lactate concentrations were measured at the end of each exercise level. At maximal effort, there were no differences between the groups regarding VO2max and maximal HR; however, the workload time, vVO2max and peak treadmill velocity were significantly higher in the 3000 m steeplechase group (p<0.05). At submaximal effort, there were no significant differences between groups for VO2 (ml·kg-1·min-1), HR, or lactate. Our results show that this type of testing was not sufficient for discriminating the physiological profiles of elite runners who competed in middle-distance versus long-distance events (e.g. in the marathon and the 3000 m steeplechase).     

Endogenous opioids and ventilatory responses to hypercapnia in normal humans

Though administration of opioid peptides depresses ventilation and ventilatory responsiveness, the role of endogenous opioid peptides in modulating ventilatory responsiveness is not clear. We studied the interaction of endogenous opioids and ventilatory responses in 12 adult male volunteers by relating hypercapnic responsiveness to plasma levels of immunoactive beta-endorphin and by administering the opiate antagonist naloxone. Ventilatory responsiveness to hypercapnia was not altered by pretreatment with naloxone, and this by itself suggests that endogenous opioids have no role in modulating this response. However, there was an inverse relationship between basal levels of immunoactive beta-endorphin in plasma and ventilatory responsiveness to CO2. Furthermore, plasma beta-endorphin levels rose after short-term hypercapnia but only when subjects had been pretreated with naloxone. We conclude that measurement of plasma endorphin levels suggests relationships between endogenous opioid peptides and ventilatory responses to CO2 that are not apparent in studies limited to assessing the effect of naloxone.     

Possible involvement of endogenous beta-endorphin in the pathophysiological mechanisms of Pichinde virus-infected guinea pigs.

Previously, we demonstrated that naloxone, an opiate antagonist, prolonged survival of strain 13 guinea pigs infected with Pichinde virus. Thus, endogenous opiates may be involved in the pathogenesis of this viral disease. To determine whether endogenous opiate levels were affected by Pichinde viral infection, beta-endorphin concentrations in plasma and cerebrospinal fluid (CSF) of normal and infected strain 13 guinea pigs were measured by radioimmunoassay. Cerebrospinal fluid beta-endorphin concentrations were 78.0 +/- 13.2 pg/ml on postinoculation day (PID) 7, 59.0 +/- 5.6 pg/ml on PID 12, and 58.8 +/- 5.4 pg/ml on PID 14. These values were significantly higher than baseline levels of CSF beta-endorphin: 30.8 +/- 1.9 pg/ml. Plasma beta-endorphin concentrations of infected animals increased significantly to 202.1 +/- 17.9 pg/ml on PID 7 and to 154.2 +/- 21.4 pg/ml on PID 12 from a mean baseline value of 84.2 +/- 13.1 pg/ml. After a primer intravenous injection of beta-endorphin (10, 15, or 30 micrograms/kg), followed by constant infusion of beta-endorphin (15, 45, or 90 micrograms/kg.hr) to control noninfected guinea pigs, heart rate (except with the lowest dose) and mean blood pressure decreased markedly. Under these experimental conditions, concentrations of plasma and CSF beta-endorphin increased simultaneously with different magnitude. Because both Pichinde viral infection and beta-endorphin administration produced a similar trend of cardiovascular disturbances, leading to hypotension and bradycardia, increased concentrations of plasma and CSF beta-endorphin may play a partial role in the pathophysiological mechanisms of Pichinde virus infection.     

Cerebrospinal fluid immunoreactive beta-endorphin concentration is increased by voluntary exercise in the spontaneously hypertensive rat

The effect of voluntary exercise on cerebrospinal fluid (CSF) levels of immunoreactive beta-endorphin has been studied in the spontaneously hypertensive rat (SHR). The exercise consisted of 5-6 weeks of spontaneous running in wheels and the average running distance was 3.5 +/- 0.4 km/24 h. CSF samples were obtained under anaesthesia from the cisterna magna. Five experimental groups were examined, four groups of runners and one group of sedentary controls. The runners were sampled either (a) shortly (0-3 h) after termination of exercise, or after the wheel had been locked for (b) 24, (c) 48 or (d) 96 h. The runners in group a had significantly higher immunoreactive beta-endorphin levels than the controls. The levels remained increased as compared with controls after 24 and 48 h of enforced abstinence but had returned to control after 96 h. The data indicate that voluntary exercise induces adaptive changes in central beta-endorphin systems.     

Effect of caffeine on ventilatory responses to hypercapnia, hypoxia, and exercise in humans

The effect of oral caffeine on resting ventilation (VE), ventilatory responsiveness to progressive hyperoxic hypercapnia (HCVR), isocapnic hypoxia (HVR), and moderate exercise (EVR) below the anaerobic threshold (AT) was examined in seven healthy adults. Ventilatory responses were measured under three conditions: control (C) and after ingestion of either 650 mg caffeine (CF) or placebo (P) in a double-blind randomized manner. None of the physiological variables of interest differed significantly for C and P conditions (P greater than 0.05). Caffeine levels during HCVR, HVR, and EVR were 69.5 +/- 11.8, 67.8 +/- 10.8, and 67.8 +/- 10.9 (SD) mumol/l, respectively (P greater than 0.05). Metabolic rate at rest and during exercise was significantly elevated during CF compared with P. An increase in VE from 7.4 +/- 2.5 (P) to 10.5 +/- 2.1 l/min (CF) (P less than 0.05) was associated with a decrease in end-tidal PCO2 from 39.1 +/- 2.7 (P) to 35.1 +/- 1.3 Torr (CF) (P less than 0.05). Caffeine increased the HCVR, HVR, and EVR slopes (mean increase: 28 +/- 8, 135 +/- 28, 14 +/- 5%, respectively) compared with P; P less than 0.05 for each response. Increases in resting ventilation, HCVR, and HVR slopes were associated with increases in tidal volume (VT), whereas the increase in EVR slope was accompanied by increases in both VT and respiratory frequency. Our results indicate that caffeine increases VE and chemosensitivity to CO2 inhalation, hypoxia, and CO2 production during exercise below the AT.     

MicroRNAs as Biomarkers for Acute Atrial Remodeling in Marathon Runners (The miRathon Study – A Sub-Study of the Munich Marathon Study)

Introduction

Physical activity is beneficial for individual health, but endurance sport is associated with the development of arrhythmias like atrial fibrillation. The underlying mechanisms leading to this increased risk are still not fully understood. MicroRNAs are important mediators of proarrhythmogenic remodeling and have potential value as biomarkers in cardiovascular diseases. Therefore, the objective of our study was to determine the value of circulating microRNAs as potential biomarkers for atrial remodeling in marathon runners (miRathon study).

Methods

30 marathon runners were recruited into our study and were divided into two age-matched groups depending on the training status: elite (ER, ≥55 km/week, n = 15) and non-elite runners (NER, ≤40 km/week, n = 15). All runners participated in a 10 week training program before the marathon. MiRNA plasma levels were measured at 4 time points: at baseline (V1), after a 10 week training period (V2), immediately after the marathon (V3) and 24h later (V4). Additionally, we obtained clinical data including serum chemistry and echocardiography at each time point.

Results

MiRNA plasma levels were similar in both groups over time with more pronounced changes in ER. After the marathon miR-30a plasma levels increased significantly in both groups. MiR-1 and miR-133a plasma levels also increased but showed significant changes in ER only. 24h after the marathon plasma levels returned to baseline. MiR-26a decreased significantly after the marathon in elite runners only and miR-29b showed a non-significant decrease over time in both groups. In ER miRNA plasma levels showed a significant correlation with LA diameter, in NER miRNA plasma levels did not correlate with echocardiographic parameters.

Conclusion

MiRNAs were differentially expressed in the plasma of marathon runners with more pronounced changes in ER. Plasma levels in ER correlate with left atrial diameter suggesting that circulating miRNAs could potentially serve as biomarkers of atrial remodeling in athletes.     

Metabolic adaptation to prolonged exercise.

A study was undertaken to evaluate and to examine the role of substrate supply in 50 healthy subjects after long distance events, such as 10 km, 25 km, and marathon races. The metabolic, variables of carbohydrate metabolism were greatest in 10-km runners, with the highest increase in glucose, lactate, and pyruvate, while in marathon runners only moderate changes were observed. Marathon competitors gave the greatest decrease in insulin concentration whereas glucagon and cortisol showed a contrary tendency. As for lipid concentrations, the most remarkable point was that after the marathon competition the best runners had the highest increase in free fatty acids; the longer the race, the higher were the beta-hydroxybutyrate and acetoacetate levels after the competition. It is important to emphasize that the limiting factor up to 90 min duration is the competitor's ability to deplete the stores of glycogen. Beyond 90 min (or 25 km) the decrease in insulin, the rise in cortisol and the higher concentration of ketnne bodies found indicate a change in metabnlic response.     

A half-marathon and a marathon run induce oxidative DNA damage, reduce antioxidant capacity to protect DNA against damage and modify immune function in hobby runners

This study investigated whether a 21.1 km (half-marathon) or a 42.195 km (marathon) run modulates DNA damage, antioxidant capacity in lymphocytes and plasma, and the immune system in healthy hobby runners. Ten and 12 volunteers who completed the Baden-Marathon race in Karlsruhe with a running distance of 21.1 km and 41.195 km, respectively, were assessed 10 days before and immediately after the finish. There was no increase in the levels of endogenous DNA strand breaks immediately after half-marathon or marathon races. A statistically significant increase in the levels of oxidative DNA damage in lymphocytes was found using endonuclease III but not formamidopyrimidine glycolase (Fpg). The resistance of DNA to oxidative damage induced by hydrogen peroxide in isolated lymphocytes was significantly decreased after both races. The levels of plasma antioxidants such as alpha-tocopherol, beta-carotene and lycopene were close to, or higher than, those considered optimal for reducing the risk of cardiovascular diseases and there were no significant changes after the races in antioxidant capacity of LDL (lag-time test) or plasma in ORAC, TEAC or paraoxonase assays. The number and percentage of granulocytes and monocytes able to generate oxidative burst were significantly increased after both races, but the lytic activity of NK cells was significantly increased at the end of the half-marathon; no effect was observed in the marathon runners. Thus, oxidative DNA damage in lymphocytes, decreased the antioxidant capacity to protect lymphocytes against DNA strand breaks and increased the formation of reactive species by phagocytes in well-nourished hobby runners indicating moderate oxidative damage during such high-intensity exercise.     

Vascular endothelial growth factor in exercising humans under different environmental conditions

It was the aim of this study to investigate the time course of changes in the serum concentrations of vascular endothelial growth factor (VEGF) during a regular survival training programme combined with food and fluid deprivation and during a high altitude marathon run. We studied soldiers of the Austrian Special Forces performing survival training at sea-level and marathon runners of the Posta Atletica who crossed the border between Chile and Argentina at altitudes up to 4722 m. Baseline data collected before the 1-week of survival training showed that the soldiers had normal VEGF [n = 8, 246.7 (SD 118.5) pg.ml(-1)] serum concentrations which remained unchanged during the course of the study. Before the high altitude marathon the subjects showed normal VEGF serum concentrations [178 (SD 84.5) pg.ml(-1)]. After the run VEGF concentrations were found to be significantly decreased [41.0 (SD 41.6) pg ml(-1), P < 0.01]. It was concluded that prolonged physical stress during normobaric-normoxia did not alter the VEGF concentrations whereas during severe hypobaric-hypoxia decreased VEGF serum concentrations were measured, at least temporarily, after prolonged physical exercise which might have been due to changes in production, release, removal and/or binding of circulating VEGF.     

Influence of testosterone on ventilation and chemosensitivity in male subjects

There is increasing evidence that men have higher ventilatory responses to chemical stimuli than age-matched women and that certain disorders of respiratory rhythmicity, particularly sleep apnea, occur more commonly in men. Accordingly, we studied the influence of the male hormone, testosterone, on the control of breathing. Twelve hypogonadal males were studied at least 30 (mean +/- SE: 69.7 +/- 8.9) days after discontinuing testosterone replacement and again following hormone administration. In each subject plasma testosterone concentration, metabolic rate [O2 consumption (VO2) and CO2 production (VCO2)], minute ventilation (VE), and chemosensitivity [hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses] were determined on and off hormone replacement. With testosterone administration VO2 increased from 248 +/- 15 to 276 +/- 18 ml/min (P less than 0.05), with VCO2 showing a similar but nonsignificant trend. This was associated with an increase in VE from 8.41 +/- 0.78 to 9.91 +/- 0.75 l/min (P less than 0.05) but no change in PCO2. The HVR, expressed as A, increased 44% with hormone replacement from a value of 122 +/- 23 to 176 +/- 28 (P less than 0.01), whereas the HCVR was minimally affected by testosterone administration. These findings may in part explain the previously described differences between male and female subjects in hypoxic sensitivity.     

Relationship between uphill running performance at altitude and blood metabolite levels

Venous blood samples were obtained from 18 marathon runners before and after the 27 km uphill portion of a 46 km transmountain race at altitudes of 1,950-3,400 m. There was an inverse correlation between blood lactate levels and running time (r = -0.83), with the runners with higher lactate levels completing the race in less time. The faster half of the group had higher blood levels of glucose and lactate and lower free fatty acid levels at 26 km distance and 3,400 m elevation. The elevated lactate concentrations in the blood of the faster runners suggest that anaerobic metabolism can contribute significantly to total energy production during prolonged exercise at high altitude.     

Administration of branched-chain amino acids during sustained exercise--effects on performance and on plasma concentration of some amino acids.

Previous studies have shown that sustained exercise in human subjects causes an increase in the plasma concentration ratio of free tryptophan: other large neutral amino acids [including the branched-chain amino acids (BCAA)]. This should favour the transport of tryptophan into the brain and also the synthesis of 5-hydroxytryptamine, which is thought to contribute to fatigue during prolonged exercise. A mixture of the three BCAA was given to subjects during a 30-km cross-country race or a marathon (42.2 km) and the effects on mental and physical performances were measured. The mental performance, measured as the performance in the Stroop Colour and Word Test (CWT), was improved after, as compared to before the 30-km cross-country race when a BCAA supplement was given during the race, whereas the CWT scores were similar before and after in the placebo group. The running performance in the marathon was improved for the "slower" runners (3.05 h-3.30 h) when BCAA was taken during the race; however, there was no significant effect on the performance in the "faster" runners (less than 3.05 h). The results showed that both mental and physical performance was improved by an intake of BCAA during exercise. In addition, the effects of exercise on the plasma concentration of the aromatic amino acids were altered when a BCAA supplement was given during the marathon.     

Hypoxia does not increase CSF or plasma beta-endorphin activity

The ability of moderate (30-50 Torr arterial PO2) and severe (less than 30 Torr arterial PO2) hypoxia to generate endogenous opioids that modulate ventilation was studied in unanesthetized goats. Ventilation and its components, arterial blood gas tensions and pH, and plasma and cerebrospinal fluid (CSF) beta-endorphin activity were measured before and after 4 h of sustained moderate or severe hypoxia. Ventilation, as expected, increased with hypoxia. There were no significant changes in either plasma or CSF beta-endorphin activity after sustained hypoxia. To rule out elaboration of endogenous opioids other than beta-endorphin after hypoxia, naloxone or saline was administered to five of the seven goats exposed to 4 h of severe hypoxia, and their ventilatory responses were compared for 30 additional min of hypoxic breathing. No significant differences in ventilation occurred in the two treatment groups during this time period. We conclude that, unlike increases in airway resistance, moderate and severe hypoxia do not cause the elaboration of endogenous opioids that modify respiratory output in unanesthetized adult goats. The apparent ability of hypoxia to cause elaboration of endogenous opioids in the neonate may represent a maturational phenomenon.     

Radioimmunoassay for beta-endorphin (1-18), a novel pituitary peptide derived from proopiomelanocortin

A specific radioimmunoassay was developed for beta-endorphin (1-18). The content of beta-endorphin (1-18) immunoreactivity in rat tissues was as follows: posterior pituitary 260 ng/fragment, anterior pituitary 1.46 ng/mg, hypothalamus 11.9 pg/mg. The levels were undetectable (less than 3 pg/mg) in extrahypothalamic brain, pancreas, small intestine, prostata and testis. Gel filtration and reverse-phase HPLC studies indicated that most of rat anterior pituitary immunoreactivity is due to native beta-endorphin (1-18), whereas the bulk of posterior pituitary immunoreactivity corresponds to more hydrophobic material, probably N-acetyl-beta-endorphin (1-18). Thus, beta-endorphin (1-18) is a quantitatively important novel pituitary peptide derived from proopiomelanocortin. The posterior pituitary is an especially rich source of (N-acetyl)-beta-endorphin (1-18).     

Faecal blood loss in response to exercise.

Recently qualitative tests have indicated that gastrointestinal bleeding during exercise may be an important contributory factor in sports anaemia. In six healthy men who walked 37 km on four consecutive days faecal haemoglobin content remained normal (reference range 0.10-2.53 mg/g faeces) with no significant differences between values. In 28 marathon runners who refrained from taking drugs or food containing blood the median faecal haemoglobin content increased by 0.42 mg/g faeces (95% confidence interval 0.12 to 0.83 mg/g) from 1.06 (0.86 to 1.31) mg/g before the race. In 13 runners who had taken drugs before the race the corresponding increase in the median faecal haemoglobin content was 0.87 (-0.03 to 2.20) mg/g from the value before the race of 0.93 (0.46 to 1.55) mg/g. Prolonged walking had no effect on gastrointestinal blood loss. Intense endurance exercise in the form of marathon running induced a significant but clinically unimportant increase. This may be exaggerated by the ingestion of drugs and assume importance in causing iron deficiency and sports anaemia. The use of drugs, particularly analgesics, by marathon runners should be actively discouraged.