The effects of classic altitude training on hemoglobin mass in swimmers.

Aim of the study was to determine the influence of classic altitude training on hemoglobin mass (Hb-mass) in elite swimmers under the following aspects: (1) normal oscillation of Hb-mass at sea level; (2) time course of adaptation and de-adaptation; (3) sex influences; (4) influences of illness and injury; (5) interaction of Hb-mass and competition performance. Hb-mass of 45 top swimmers (male 24; female 21) was repeatedly measured (~6 times) over the course of 2 years using the optimized CO-rebreathing method. Twenty-five athletes trained between one and three times for 3-4 weeks at altitude training camps (ATCs) at 2,320 m (3 ATCs) and 1,360 m (1 ATC). Performance was determined by analyzing 726 competitions according to the German point system. The variation of Hb-mass without hypoxic influence was 3.0 % (m) and 2.7 % (f). At altitude, Hb-mass increased by 7.2 ± 3.3 % (p < 0.001; 2,320 m) and by 3.8 ± 3.4 % (p < 0.05; 1,360 m). The response at 2,320 m was not sex-related, and no increase was found in ill and injured athletes (n = 8). Hb-mass was found increased on day 13 and was still elevated 24 days after return (4.0 ± 2.7 %, p < 0.05). Hb-mass had only a small positive effect on swimming performance; an increase in performance was only observed 25-35 days after return from altitude. In conclusion, the altitude (2,320 m) effect on Hb-mass is still present 3 weeks after return, it decisively depends on the health status, but is not influenced by sex. In healthy subjects it exceeds by far the oscillation occurring at sea level. After return from altitude performance increases after a delay of 3 weeks.

Live high, train low at natural altitude.

For decades altitude training has been used by endurance athletes and coaches to enhance sea-level performance. Whether altitude training does, in fact, enhance sea level performance and, if so, by what means has been the subject of a number of investigations. Data produced principally by Levine and Stray-Gundersen have shown that living for 4 weeks at 2500 m, while performing the more intense training sessions near sea level will provide an average improvement in sea level endurance performance (duration of competition: 7-20 min) of approximately 1.5%, ranging from no improvement to 6% improvement. This benefit lasts for at least 3 weeks on return to sea level. Two mechanisms have been shown to be associated with improvement in performance. One is an increase in red cell mass ( approximately 8%) that results in an improved maximal oxygen uptake ( approximately 5%). That must be combined with maintenance of training velocities and oxygen flux to realize the improvement in subsequent sea level performance. We find no evidence of changes in running economy or markers of anaerobic energy utilization. Our results have been obtained in runners ranging from collegiate to elite. Wehrlin et al. have recently confirmed these results in elite orienteers. While there are no specific studies addressing the use of living high, training low in football players, it is likely that an improvement in maximal oxygen uptake, all other factors equal, would enhance football performance. This benefit must be weighed against the time away (4 weeks) from home and competition necessary to gain these benefits.

Effect of altitude on football performance.

Altitude will impact football performance through two separate and parallel pathways related to the hypobaric (physical) and hypoxic (physiological) components of terrestrial altitude: (a) the decrease in partial pressure of oxygen reduces maximal oxygen uptake and impairs "aerobic" performance by reducing maximal aerobic power, increasing the relative intensity of any given absolute level of work, and delaying recovery of high-energy phosphates between high-intensity "interval" type efforts; (b) the decrease in air density reduces air resistance which will facilitate high-velocity running, but will also alter drag and lift thereby impairing sensorimotor skills. These effects appear to have their greatest impact very early in the altitude exposure, and their physiological/neurosensory consequences are ameliorated by acclimatization, though the extent of restoration of sea level type performance depends on the absolute magnitude of the competing and living altitudes.

Exercise economy does not change after acclimatization to moderate to very high altitude.

For more than 60 years, muscle mechanical efficiency has been thought to remain unchanged with acclimatization to high altitude. However, recent work has suggested that muscle mechanical efficiency may in fact be improved upon return from prolonged exposure to high altitude. The purpose of the present work is to resolve this apparent conflict in the literature. In a collaboration between four research centers, we have included data from independent high-altitude studies performed at varying altitudes and including a total of 153 subjects ranging from sea-level (SL) residents to high-altitude natives, and from sedentary to world-class athletes. In study A (n=109), living for 20-22 h/day at 2500 m combined with training between 1250 and 2800 m caused no differences in running economy at fixed speeds despite low typical error measurements. In study B, SL residents (n=8) sojourning for 8 weeks at 4100 m and residents native to this altitude (n=7) performed cycle ergometer exercise in ambient air and in acute normoxia. Muscle oxygen uptake and mechanical efficiency were unchanged between SL and acclimatization and between the two groups. In study C (n=20), during 21 days of exposure to 4300 m altitude, no changes in systemic or leg VO(2) were found during cycle ergometer exercise. However, at the substantially higher altitude of 5260 m decreases in submaximal VO(2) were found in nine subjects with acute hypoxic exposure, as well as after 9 weeks of acclimatization. As VO(2) was already reduced in acute hypoxia this suggests, at least in this condition, that the reduction is not related to anatomical or physiological adaptations to high altitude but to oxygen lack because of severe hypoxia altering substrate utilization. In conclusion, results from several, independent investigations indicate that exercise economy remains unchanged after acclimatization to high altitude.

Hemoglobin and hematocrit values after saline infusion and tourniquet.

This study attempted to contribute to standardization of blood testing in sport, and to investigate the effect of artificial dilution with saline. In 10 healthy, physically active males and 3 healthy physically active females hemoglobin (Hb), hematocrit (Ht), and % reticulocytes (%retics) were measured at different time points to look for possible fluctuations during day time, while the subjects had regular coffee breaks and lunch. In 7 of the subjects in a separate experiment 500 ml of saline were infused around 8 am and Hb, Ht, and %retics were measured before and every hour thereafter until 7 hours after infusion. In addition Ht was measured on a hematological analyzer as well as with a centrifuge. In a separate experiment the effect of tourniquet duration on Hb and Ht was studied in 9 of the subjects. The results show that Hb, Ht, and %retics are stable from 8 am to 4 pm, but that infusion of 500 ml of saline induces an acute decrease in Hb and Ht within one hour (Hb decreased from 15.2+/-0.9 g/dl to 14.5+/-1.0 g/dl, and Ht from 45.6+/-2.8 % to 44.0+/-2.5 %). The decline in Hb and Ht was maintained during the 7-hour observation period. Ht values of the same samples measured with a hematological analyzer and a centrifuge were not different. Application of the tourniquet did significantly affect Hb and Ht values only from two minutes, and thereafter Hb and Ht remained stable during the rest of the 5-minute tourniquet. With blood testing in sport these results have to be taken into consideration.

Hormonal responses in athletes: the use of a two bout exercise protocol to detect subtle differences in (over)training status.

In overtrained athletes, several signs and symptoms have been associated with the imbalance between training and recovery. However, reliable diagnostic markers for distinguishing between well-trained, overreached (OR) and overtrained (OT) athletes are lacking. A hallmark feature of overtraining syndrome (OTS) is the inability to sustain intense exercise and recover for the next training or competition session. We therefore devised a test protocol utilizing two bouts of maximal work. With this test protocol we tried to establish a difference in hormonal responses between the training status of T and OR athletes. Seven well-trained cyclists participated in this study and were tested before and after a training camp. We also present the data of one OT motocross athlete who was clinically diagnosed as overtrained. All athletes performed two maximal exercise tests separated by 4 h. Blood was analyzed for cortisol, adrenocorticotrophic hormone (ACTH), growth hormone and prolactin (PRL). Performance decreased by 6% between the first and the second exercise test in the OR group and by 11% in the OT subject. Moreover, during the second exercise test there were more marked differences between the T and OR athletes; in particular, the OT subject did not show an increase in some of the hormonal responses. PRL increased only by 14% in the OT subject's second test and there was a 7% decrease in ACTH. The two exercise approach enables us to detect subtle performance decrements that will not be identified by one exercise trigger. The hormonal responses to the second exercise test were different between the T and OR athletes (the increase in the T group was higher than in the OR that was higher than in the OT). The results of the case presentation of an overtrained athlete provide evidence of an altered and dysfunctional hypothalamic-pituitary axis response to two bouts of maximal exercise. These findings can be used to develop markers for diagnosis of OTS and to begin to address the pathologic mechanism operative in the syndrome, as well as providing an outcome measure to evaluate possible therapeutic regimes.

Determinants of erythropoietin release in response to short-term hypobaric hypoxia.

We measured blood erythropoietin (EPO) concentration, arterial O(2) saturation (Sa(O(2))), and urine PO(2) in 48 subjects (32 men and 16 women) at sea level and after 6 and 24 h at simulated altitudes of 1,780, 2,085, 2,454, and 2,800 m. Renal blood flow (Doppler) and Hb were determined at sea level and after 6 h at each altitude (n = 24) to calculate renal O(2) delivery. EPO increased significantly after 6 h at all altitudes and continued to increase after 24 h at 2,454 and 2,800 m, although not at 1,780 or 2,085 m. The increase in EPO varied markedly among individuals, ranging from -41 to 400% after 24 h at 2,800 m. Similar to EPO, urine PO(2) decreased after 6 h at all altitudes and returned to baseline by 24 h at the two lowest altitudes but remained decreased at the two highest altitudes. Urine PO(2) was closely related to EPO via a curvilinear relationship (r(2) = 0.99), although also with prominent individual variability. Renal blood flow remained unchanged at all altitudes. Sa(O(2)) decreased slightly after 6 h at the lowest altitudes but decreased more prominently at the highest altitudes. There were only modest, albeit statistically significant, relationships between EPO and Sa(O(2)) (r = 0.41, P < 0.05) and no significant relationship with renal O(2) delivery. These data suggest that 1) the altitude-induced increase in EPO is "dose" dependent: altitudes > or =2,100-2,500 m appear to be a threshold for stimulating sustained EPO release in most subjects; 2) short-term acclimatization may restore renal tissue oxygenation and restrain the rise in EPO at the lowest altitudes; and 3) there is marked individual variability in the erythropoietic response to altitude that is only partially explained by "upstream" physiological factors such as those reflecting O(2) delivery to EPO-producing tissues.

"Living high-training low" altitude training improves sea level performance in male and female elite runners.

Acclimatization to moderate high altitude accompanied by training at low altitude (living high-training low) has been shown to improve sea level endurance performance in accomplished, but not elite, runners. Whether elite athletes, who may be closer to the maximal structural and functional adaptive capacity of the respiratory (i.e., oxygen transport from environment to mitochondria) system, may achieve similar performance gains is unclear. To answer this question, we studied 14 elite men and 8 elite women before and after 27 days of living at 2,500 m while performing high-intensity training at 1,250 m. The altitude sojourn began 1 wk after the USA Track and Field National Championships, when the athletes were close to their season's fitness peak. Sea level 3,000-m time trial performance was significantly improved by 1.1% (95% confidence limits 0.3-1.9%). One-third of the athletes achieved personal best times for the distance after the altitude training camp. The improvement in running performance was accompanied by a 3% improvement in maximal oxygen uptake (72.1 +/- 1.5 to 74.4 +/- 1.5 ml x kg(-1) x min(-1)). Circulating erythropoietin levels were near double initial sea level values 20 h after ascent (8.5 +/- 0.5 to 16.2 +/- 1.0 IU/ml). Soluble transferrin receptor levels were significantly elevated on the 19th day at altitude, confirming a stimulation of erythropoiesis (2.1 +/- 0.7 to 2.5 +/- 0.6 microg/ml). Hb concentration measured at sea level increased 1 g/dl over the course of the camp (13.3 +/- 0.2 to 14.3 +/- 0.2 g/dl). We conclude that 4 wk of acclimatization to moderate altitude, accompanied by high-intensity training at low altitude, improves sea level endurance performance even in elite runners. Both the mechanism and magnitude of the effect appear similar to that observed in less accomplished runners, even for athletes who may have achieved near maximal oxygen transport capacity for humans.

Separation of isomers of nonylphenol and select nonylphenol polyethoxylates by high-performance liquid chromatography on a graphitic carbon column.

p-Nonylphenol (NP) is a ubiquitous degradation product of nonylphenol polyethoxylate (NPE) surfactants and has been reported to be an endocrine disrupter. It is composed of numerous structural isomers resulting from the various branching patterns of the C-9 group. Twenty-two isomers in a technical mix of NP have been identified with high-resolution capillary GC-MS. In most HPLC analyses, nonylphenol elutes as a single, broad peak. In the method described here, HPLC using a graphite carbon column resulted in the resolution of a technical mixture of NP into 12 peaks or groups of isomers. This method was also applied to select NPEs with one to 10 ethoxy units with similar results. Separation was achieved by gradient elution with 1% acetic acid in water and acetonitrile. Elution of individual isomers 4-butylphenol and 4-propylphenol under the same gradient conditions indicate that increased branching of an alkyl group results in shorter retention times than for the less substituted alkyl groups. This method can be used to fractionate NP based on structure and assess the potential for different isomers (or groups of structurally similar isomers) to act as endocrine disrupters.

The effects of altitude training are mediated primarily by acclimatization, rather than by hypoxic exercise.

For training at altitude to be effective, it must provide some advantage above and beyond similar training at sea level. This advantage could be provided by: 1) acclimatization to altitude which improves oxygen transport and/or utilization; 2) hypoxic exercise which "intensifies" the training stimulus; or 3) some combination of both. Controlled studies of "typical" altitude training, involving both altitude acclimatization and hypoxic exercise have never been shown to improve sea level performance. This failure has been attributed to reduced training loads at altitude. One approach developed by Levine and Stray-Gundersen, called "living high-training low" has been shown to improve sea level performance over events lasting 8-20 minutes. This strategy combines altitude acclimatization (2,500 m) with low altitude training to get the optimal effect. The opposite strategy, "living low-training high" is proposed by Dr. Hoppeler in this debate. In defense of the primacy of the altitude acclimatization effect, data will be presented to support the following: 1). Living high-training low clearly improves performance in athletes of all abilities; 2). The mechanism of this improvement is primarily an increase in erythropoietin leading to increased red cell mass, VO2max, and running performance; 3). Rather than intensifying the training stimulus, training at altitude leads to the opposite effect--reduced speeds, reduced power output, reduced oxygen flux--and, following the principal of symmorphosis, is not likely to provide any advantage for a well trained athlete; 4). At the moderate altitudes used by most athletes, resting oxygen delivery to skeletal muscle is well preserved, arguing against any detrimental effect on "protein synthesis"; 5). It is possible however, that at significantly higher altitudes, acclimatization leads to appetite suppression, inhibition of protein synthesis, muscle wasting, excessive ventilatory work, and metabolic compensation that is NOT advantageous for a competitive athlete.

Exploratory analysis of the effects of particulate characteristics on the variation in partitioning of nonpolar organic contaminants to marine sediments.

The partitioning of nonpolar organic contaminants to marine sediments is considered to be controlled by the amount of organic carbon present. However, several studies propose that other characteristics of sediments may affect the partitioning of contaminants. For this exploratory analysis, we measured 19 sediment characteristics from five marine sediments and 11 characteristics of humic acids extracted from the sediments. These characteristics included elemental composition, grain size, soot carbon, polarity indices and molar ratios. Each individual characteristic and combinations of these characteristics were then used to normalize partition coefficients (Kp) generated for three organic contaminants: lindane, fluoranthene and a tetrachlorinated biphenyl (PCB). A coefficient of variation (CV) was then calculated for each contaminant to determine which normalization characteristic (individually or in combination) resulted in the lowest variability in partitioning between study sediments. For lindane and the PCB. normalization by the amount of sediment organic carbon resulted in the lowest variability in partition coefficients with CVs of 16.2% and 37.7%. respectively. However, normalization of fluoranthene by silt content resulted in lower CVs than those generated by organic carbon normalization: 31.0% vs. 37.6%. Normalization of contaminants Kp's by combined values of sediment characteristics resulted in lower CVs but only by a few percent. Using humic acid characteristics, humic organic carbon reduced variability between sediments most effectively. But only the normalized fluoranthene values had a CV (i.e., 25.4%) lower than the one based on normalization by sediment characteristics. When combined, humic acid characteristics resulted in lower CVs than normalization by individual or combinations of sediment characteristics for fluoranthene and the PCB with CVs of 19.3% and 28.7%, respectively. This analysis indicates variability associated with the partitioning of some organic contaminants to marine sediments can be further reduced when normalization by sediment characteristics other than organic carbon are utilized.

Skeletal muscle morphology and exercise response in congenital generalized lipodystrophy.

OBJECTIVE: Congenital generalized lipodystrophy (CGL) is an autosomal recessive genetic disorder characterized by almost complete absence of adipose tissue, muscular appearance, and severe insulin resistance since birth. We investigated whether insulin resistance in CGL patients is associated with abnormal muscle morphology and whether increased muscularity imparts increased muscle strength and exercise capacity RESEARCH DESIGN AND METHODS: We obtained quadriceps muscle biopsies to study muscle fiber types and capillary density in three African-American women (aged 17-20 years) with CGL. We also assessed quadriceps muscle strength, muscle metabolism, and maximal O2 consumption in the patients. RESULTS: Quadriceps muscle biopsies revealed a markedly higher percentage of type II (fast-twitch glycolytic) muscle fibers in patients with CGL versus sedentary young women (75-78 vs. 47-57%, respectively). The capillary-to-fiber ratio (2.7-3.0), however, was normal. Cross-sectional areas of type I (slow-twitch oxidative) (1,262-2,685 microm2) and type II (2,304-3,594 microm2) fibers were far below the normal values (3,811-4,310 and 3,115-4,193 microm2, respectively), suggesting muscle hyperplasia but not hypertrophy The quadriceps muscle strength, as measured by Cybex, was below average; the maximal O2 consumption (23-32 ml x kg(-1) x min(-1)) was also below average. 31P nuclear magnetic resonance spectroscopy of the forearm muscles revealed normal pH and metabolic responses to static and dynamic exercises. CONCLUSIONS: We conclude that insulin resistance in patients with CGL is associated with an increased proportion of type II muscle fibers but not reduced capillary density. Increased muscularity in CGL is due to muscle hyperplasia and is not associated with increased muscle strength.

Effect of rhEPO administration on serum levels of sTfR and cycling performance.

PURPOSE: We assessed the possibility of using soluble transferrin receptor (sTfR) as an indicator of doping with recombinant erythropoietin (rhEPO). METHODS: A double-blind, placebo-controlled study was conducted with the administration of 5,000 U of rhEPO (N = 10) or placebo (N = 10) three times weekly (181-232 U x kg(-1) x wk-1) for 4 wk to male athletes. We measured hematocrit and the concentration of hemoglobin, sTfR, ferritin, EPO, and quantified the effects on performance by measuring time to exhaustion and maximal oxygen uptake (VO2max) on a cycle ergometer. RESULTS: Hematocrit increased from 42.7 +/- 1.6% to 50.8 +/- 2.0% in the EPO group, and peaked 1 d after treatment was stopped. In the EPO group, there was an increase in sTfR (from 3.1 +/- 0.9 to 6.3 +/- 2.3 mg x L(-1) , P < 0.001) and in the ratio between sTfR and ferritin (sTfR-ferritin(-1)) (from 3.2 +/- 1.6 to 11.8 +/- 5.1, P < 0.001). The sTfR increase was significant after 1 wk of treatment and remained so for 1 wk posttreatment. Individual values for sTfR throughout the study period showed that 8 of 10 subjects receiving rhEPO, but none receiving placebo, had sTfR levels that exceeded the 95% confidence interval for all subjects at baseline (= 4.6 mg x L(-1)). VO2max increased from 63.6 +/- 4.5 mL x kg(-1) x min(-1) before to 68.1 +/- 5.4 mL x kg(-1) x min(-1) 2 d post rhEPO administration (7% increase, P = 0.001) in the EPO group. Hematocrit, sTfR, sTfR-ferritin(-1), and VO2max did not change in the placebo group. CONCLUSION: Serum levels of sTfR may be used as an indirect marker of supranormal erythropoiesis up to 1 wk after the administration of rhEPO, but the effects on endurance performance outlast the increase in sTfR.

Changes in hemoglobin values in elite cross-country skiers from 1987-1999.

Hemoglobin data have been available from ski teams beginning from 1987, and from 1989 to 1999 we have followed hemoglobin values in elite cross-country skiers in international competitions. The mean values at the 1989 World Nordic Ski Championships were lower than population reference values, as would be expected from plasma volume expansion associated with endurance training. However, an increase, particularly in the maximal values, became obvious in 1994 and rose further in 1996. These extreme values provide both a health risk to the individual athlete and unfair competition. After a rule limiting hemoglobin values was introduced, the drop of the highest values was remarkable: among men 15 g/l (0.23 mmol/l) and among women 42 g/l (0.65 mmol/l). It would appear that the rule had achieved its goal of limiting extreme hemoglobin values. Yet the mean hemoglobin concentrations in men and women have continued to rise, suggesting the continued use of artificial methods to increase total hemoglobin mass.

Evidence for restricted muscle blood flow during speed skating.

INTRODUCTION: We have previously hypothesized restricted muscle blood flow during speed skating, secondary to the high intramuscular forces intrinsic to the unique posture assumed by speed skaters and to the prolonged duty cycle of the skating stroke. METHODS: To test this hypothesis, we studied speed skaters (N = 10) during submaximal and maximal cycling and in-line skating, in both low (knee angle = 107 degrees) and high (knee angle = 112 degrees) skating positions (CE vs SkL vs SkH). Supportive experiments evaluated muscle desaturation and lactate accumulation during on-ice speed skating and muscle desaturation during static exercise at different joint positions. RESULTS: Consistent with the hypothesis were reductions during skating in VO2peak (4.28 vs 3.83 vs 4.26 L x min(-1)), the VO2 at 4 mmol x L(-1) blood lactate (3.38 vs 1.93 vs 3.31 L x min(-1)), and cardiac output during maximal exercise (33.2 vs 25.3 vs 25.6 L x min(-1)). The reduction in maximal cardiac output was not attributable to differences in HRmax (197 vs 192 vs 193 b x min(-1)) but to a reduction in SVmax (172 vs 135 vs 134 mL x beat(-1)). The reduction in SV appeared to be related to an increased calculated systemic vascular resistance (354 vs 483 vs 453 dynes x s(-1) x cm(-1)). During maximal skating there was also a greater % O2 desaturation of the vastus lateralis based on near infrared spectrophotometry (50.3 vs 74.9 vs 60.4% of maximal desaturation during cuff ischemia). The results were supported by greater desaturation with smaller knee angles during static exercise and by greater desaturation and accelerated blood lactate accumulation during on-ice speed skating in the low vs high position. The results of this study support the hypothesis that physiological responses during speed skating are dominated by restriction of blood flow, attributable either to high intramuscular forces, the long duty cycle of the skating stroke, or both.

Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men.

It has been proposed that excessive insulin resistance in Asian Indians living in urban areas or migrated to western countries is responsible for the higher incidence of type 2 diabetes and coronary heart disease observed in this population. To evaluate whether Asian Indians are more insulin resistant than Caucasians and to define the role of generalized and truncal adiposity, we performed hydrodensitometry, skinfold measurements, and euglycemic-hyperinsulinemic clamps in 21 healthy Asian Indian men and 23 Caucasian men of similar age and body fat content. The glucose disposal rate (Rd) was significantly lower in the Asian Indians than in the Caucasians (3.7+/-1.3 vs. 5.3+/-2.0 mg/min x kg lean body mass, respectively; P = 0.003). Despite similar total body fat content, Asian Indians had higher truncal adiposity than Caucasians (sum of truncal skinfolds, 117+/-37 and 92.4+/-38 mm, respectively). In both Asian Indians and Caucasians, the insulin sensitivity index (Rd/plasma insulin concentrations) was inversely correlated with both total body fat (r = -0.49; P<0.03 and r = -0.67; P<0.001, respectively) and sum of truncal skinfold thickness (r = -0.55; P<0.001 and r = -0.61; P<0.002, respectively). After adjustment for total body fat and truncal skinfold thickness, Asian Indians still had a significantly lower glucose disposal rate (P = 0.04). These results show that Asian Indian men are more insulin resistant than Caucasian men independently of generalized or truncal adiposity. The excessive insulin resistance in Asian Indians is probably a primary metabolic defect and may account for the excessive morbidity and mortality from diabetes and coronary heart disease in this population.

Individual variation in response to altitude training.

Moderate-altitude living (2,500 m), combined with low-altitude training (1,250 m) (i.e., live high-train low), results in a significantly greater improvement in maximal O2 uptake (V(02)max) and performance over equivalent sea-level training. Although the mean improvement in group response with this "high-low" training model is clear, the individual response displays a wide variability. To determine the factors that contribute to this variability, 39 collegiate runners (27 men, 12 women) were retrospectively divided into responders (n = 17) and nonresponders (n = 15) to altitude training on the basis of the change in sea-level 5,000-m run time determined before and after 28 days of living at moderate altitude and training at either low or moderate altitude. In addition, 22 elite runners were examined prospectively to confirm the significance of these factors in a separate population. In the retrospective analysis, responders displayed a significantly larger increase in erythropoietin (Epo) concentration after 30 h at altitude compared with nonresponders. After 14 days at altitude, Epo was still elevated in responders but was not significantly different from sea-level values in nonresponders. The Epo response led to a significant increase in total red cell volume and V(O2) max in responders; in contrast, nonresponders did not show a difference in total red cell volume or V(O2)max after altitude training. Nonresponders demonstrated a significant slowing of interval-training velocity at altitude and thus achieved a smaller O2 consumption during those intervals, compared with responders. The acute increases in Epo and V(O2)max were significantly higher in the prospective cohort of responders, compared with nonresponders, to altitude training. In conclusion, after a 28-day altitude training camp, a significant improvement in 5,000-m run performance is, in part, dependent on 1) living at a high enough altitude to achieve a large acute increase in Epo, sufficient to increase the total red cell volume and V(O2)max, and 2) training at a low enough altitude to maintain interval training velocity and O2 flux near sea-level values.