BrJ7 Sports Med 1997;31:183-190

Physiological implications of altitude training forendurance performance at sea level: a review

Damian M Bailey, Bruce Davies

SummaryAcclimatisation to environmental hypoxia initi-ates a series of metabolic and musculocardio-respiratory adaptations that influence oxygentransport and utilisation. Whilst it is clear thatadequate acclimatisation, or better still, beingborn and raised at altitude, is necessary toachieve optimal physical performance at alti-tude, scientific evidence to support the poten-tiating effects after return to sea level is atpresent equivocal. Despite this, elite athletescontinue to spend considerable time andresources training at altitude, misled by subjec-tive coaching opinion and the inconclusivefindings of a large number of uncontrolledstudies. Scientific investigation has focused onthe optimisation of the theoretically beneficialaspects of altitude acclimatisation, which in-clude increases in blood haemoglobin concen-tration, elevated buffering capacity, and im-provements in the structural and biochemicalproperties of skeletal muscle. However, not allaspects of altitude acclimatisation are benefi-cial; cardiac output and blood flow to skeletalmuscles decrease, and preliminary evidencehas shown that hypoxia in itself is responsiblefor a depression of immune function andincreased tissue damage mediated by oxidativestress. Future research needs to focus on theseless beneficial aspects of altitude training, theimplications of which pose a threat to both thefitness and the health of the elite competitor.

Paul Bert was the first investigator to showthat acclimatisation to a chronically reducedinspiratory partial pressure of oxygen (PIo,)invoked a series of central and peripheraladaptations that served to maintain adequatetissue oxygenation in healthy skeletal muscle,'physiological adaptations that have been subse-quently implicated in the improvement in exer-cise performance during altitude acclimatisa-tion. However, it was not until half a centurylater that scientists suggested that the additivestimulus of environmental hypoxia could po-tentially compound the normal physiologicaladaptations to endurance training and acceler-ate performance improvements after return tosea level. This has stimulated an exponentialincrease in scientific research, and, since 1984,22 major reviews have summarised the physio-logical implications of altitude training for bothaerobic and anaerobic performance at altitudeand after return to sea level. Of these reviews,only eight have specifically focused on physicalperformance changes after return to sea level,2-9the most comprehensive of which was recentlywritten by Wolski et al. 9Few reviews have considered the potentially

less favourable physiological responses tomoderate altitude exposure, which include

decreases in absolute training intensity,'0 de-creased plasma volume," depression ofhaemo-poiesis and increased haemolysis,12 increases insympathetically mediated glycogen depletionat altitude,'3 and increased respiratory musclework after return to sea level.'4 In addition,there is a risk of developing more serious medi-cal complications at altitude, which includeacute mountain sickness, pulmonary oedema,cardiac arrhythmias, and cerebral hypoxia. 5The possible implications of changes in im-mune function at altitude have also beenlargely ignored, despite accumulating evidenceof hypoxia mediated immunosupression."

In general, altitude training has been shownto improve performance at altitude, whereas nounequivocal evidence exists to support theclaim that performance at sea level is improved.Table 1 summarises the theoretical advantagesand disadvantages of altitude training for sealevel performance.

This review summarises the physiologicalrationale for altitude training as a means ofenhancing endurance performance after returnto sea level. Factors that have been shown toaffect the acclimatisation process and the sub-sequent implications for exercise performanceat sea level will also be discussed.

Studies were located using five major data-base searches, which included Medline, Em-base, Science Citation Index, Sports Discus,and Sport, in addition to extensive handsearching and cross referencing. All publishedEnglish studies, dating back from the presentday to 1956, that included physiological meas-urements during exercise before and afterhypoxic training were incorporated in the over-all analysis. Ninety one investigations wereselected, which included 772 hypoxicallytrained experimental and 209 normoxicallytrained control subjects.The investigations were subdivided accord-

ing to whether a normoxically trained controlgroup was incorporated into the experimentaldesign. Other classifications were made de-pending on the characteristics of the hypoxicstimulus, which included type (normobaric orhypobaric hypoxia; continuous or intermit-tent), duration, and magnitude (calculatedambient Po,), and timing of physiological test-ing after the descent to sea level.The continued popularity of altitude training

has been influenced by two factors. Firstly,hypoxia in itself increases blood haemoglobin(Hb) concentration, which has been shown toimprove endurance performance. Secondly,several of the best endurance runners in theworld have originated from East African coun-tries that are based at altitude (1500-2000 m).Is it possible that either living and/or training at

School ofAppliedSciences, University ofGlamorgan,Pontypridd,Mid-Glamorgan,United KingdomD M BaileyB Davies

Correspondence to:D M Bailey.

Accepted for publication8 May 1997

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Table 1 Physiological changes during altitude acclimatisation in native lowlanders; timecourse and theoretical implications for exercise performance at sea level

ResponsePhysiological advantages time Physiological disadvantages Response time

Increased free fatty acid Weeks Increased ventilation Immediatemobilisation

Increased haemoglobin Days Decreased cardiac output DaysIncreased capillarity Months/ Decreased blood flow Days

years?Increased oxidative Weeks Immunosupression Immediate?/enzyme activity days

Increased mitochondrial Weeks Increased oxidative stress and tissue Immediatevolume damage

Increased dehydration ImmediateJet lag ImmediateDecreased training intensity ImmediateAcute mountain sickness DaysSunburn due to increased ultraviolet ImmediateB (290-320nm)Catecholamine mediated glycogen Days-weeksdepletionIncreased haemolysis Weeks

altitude may contribute to their runningsuccess?

Physiological rationale for altitudetrainingAUTOLOGOUS BLOOD REINFUSION ANDENDURANCE PERFORMANCEOne of the most documented physiologicaladaptations to a reduced Ppo2 is the increasedrelease of erythropoietin, which causes atransient increase in red blood cell mass.'7 Theimplications of secondary polycythaemia toboth submaximal and maximal indices ofendurance performance have been clearlyshown by studies that have artificially inducederythrocythaemia after either autologous bloodreinfusion' or subcutaneous injections ofrecombinant human erythropoietin.'9 20 Table2 summarises the major research findings. Ithas been reported that absolute maximaloxygen uptake (Vo2MAx) values are increasedby about 200 ml/min per g/dl increase in Hb,irrespective of the methods by which poly-cythaemia is induced.2'However, the use of blood doping as an

ergogenic aid is considered unethical andpotentially dangerous and is banned by theInternational Olympic Committee.22

PHYSIOLOGICAL ADAPTATIONS OF THE NATIVE

HIGHLANDER: A SUPERIOR ATHLETE?Figure 1 illustrates the apparently dispropor-tionate running success of the native high-lander. This figure represents data obtained

Table 2 Effects of autologous blood reinfusion on Vo2 MAX

Volume of blood Change in Hb after Change in Vo2 MAX afterAuthorlreference reinfused (ml) reinfusion (%) reinfusion (%)

Ekblom'9 1350 +9* +8*Celsing2' 2250 +11 +7**Buick23 900 +8** +5**Spriet24 1200 NR +7*Williams25 920 +7** NRGoforth26 760 +4* +11**Robertson27 750 +28* +13*Robertson28 475 +16* +10*Thompson29 1000 +12* +11*Sawka30 600 +10* +11*Robertson31 475 + 16* +10**

* Significantly different from before reinfusion (P < 0.05).** Significantly different from before reinfusion (P < 0.01).NR, not reported.

from athletes who were born and raised at amedian altitude of 2000 m above sea level. Thisphenomenon has prompted several compara-tive investigations into what, if any, physiologi-cal adaptations mediated by hypoxia couldcontribute to their superiority in distance run-ning events. Much interest has focused on thefour steps of the oxygen transport system,namely alveolar ventilation, lung diffusion, cir-culatory oxygen transport, and tissue oxygenextraction. Studies have shown that the nativehighlander is characterised by a larger pulmo-nary diffusion capacity32 and adaptations in thestructural and metabolic organisation of skel-etal muscle that result in a tighter couplingbetween ATP hydrolysis and oxidativephosphorylation.33 These are the major factorsthat facilitate oxygen transport and utilisation.The significance of these adaptations has beenelucidated in a series of investigations that havereported higher values for VO2MAXI,34 poweroutput,35 arterial oxygen saturation,36 and cer-ebral oxygen delivery37 during maximal exerciseand decreased blood lactate33 3 and ammoniaconcentrations38 for a given submaximal workrate.To what extent these physiological adapta-

tions are acquired as the result ofinheritance orhypobaric hypoxia is not well defined. Theinfluence of genetic factors on quantitativeoxygen transport was recently investigated in aunique study by Beall et al.39 They identified amajor gene that enhances arterial oxygen satu-ration in sedentary Tibetan natives. The physi-ological significance of this was shown byNiermeyer et al,40 who concluded that geneticadaptations to hypobaric hypoxia resulted inimproved oxygenation and conferred resistanceto subacute infantile mountain sickness. Theseadaptations were more pronounced in a cohortof Tibetan newborns whose ancestors haveresided at altitude for 50 000 to 100 000 years,in comparison with Han newborns whoseancestors had resided at altitude for only 45years.4' In general, these findings would suggestthat a lifetime or perhaps generations ofaltitude exposure are responsible for thebiological distinctiveness of the high altitudepopulation.

Altitude training and sea level enduranceperformance in native lowlandersTable 3 summarises the effects of altitudetraining on sea level endurance performance.The weight of scientific evidence does not sup-port the potentiating effects of altitude train-ing. However, it is becoming clearer that anumber of methodological deficiencies maypreclude the potential synergistic effects ofhypoxia and physical exercise, the physiologicalimplications of which will be discussed in thefollowing sections.

Intensity and duration ofthe hypoxicstimulus and associated haematologicaladaptationThere is still much controversy about the opti-mal altitude and duration required for athletesto train in an attempt to optimise enduranceperformance at sea level. Much attention has

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m Rest of the Worldm Native Highlander

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80

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CL500 40

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Figure 1 Percentage of Olympic medals for middle and long distance running events wonby native highlanders since 1960.

Table 3 Effects of hypoxic training on sea level endurance performance

Time testedHypoxic Exposure after altitude Submaximal Change in Vo2 Controlstimulus Altitude (m) time (days) (days) improvement uA.x (%) group

Potentiating effects

CH42 1300-2500 28 1 Yest +4t NoCH43 1900 21 1/14 Yest NS/NS NoCH44 2100-2700 14 2 Yest NS NoCH45 2300 23 3/21 Yest +8t/+ 10t NoCH46 2500 28 7 ND +6t NoIH47 3049-4268 23 3-4 Yest NS NoCH48 3800 35 14 ND +14t NoIH49 4020 21/28 1 Yest +8t/+26t NoCH50 1250-2500 28 7 Yest +4t YesIH5 2300 21-28 1 Yest NS YesIH52 2300 28 1-2 Yest ND YesIH53 4000 70 1 Yest NS Yes

No potentiating effectsCH45 2300 14 1 No NS NoCH54 1695-2700 7 4 ND NS NoCH55 2240 20 4/22 ND +6/+9* NoCH56 2300 42 4-5 No NS NoCH57 2300 70 5 ND NS NoCH58 2800 10 2-4 No +7* NoCH59 3090 17 1 ND NS NoCH60 3110 21 7 ND -5* NoCH61 4000 48-63 2-15 No NS NoIH62 4000 21 1 ND NS NoCH38 2000 14 6/12 ND NS/NS YesCH63 1600-1800 18-28 7 ND NS YesCH64 1640 28 20 No NS YesCH65 1700-2000 28 7 No NS YesCH66 2300 21 1 No NS YesIH67 2250 28 1 ND + 17.5* YesIH67 3450 28 1 ND +10.0* YesIH68 2500 28 1 No NS YesIH69 2500 35 1 ND NS YesCH70 2600 11 1 ND NS YesIH71 3100 19 6 No NS YesIH72 3345 42 1 ND NS YesIH73 4020 15 1 ND NS YesIH74 4100-5700 21 1 ND NS YesCH75 4300 28 1-5 ND NS Yes

CH, Chronic hypobaria; IH, intermittent hypobaria; ND, no data.* Level of significance not reportedt Significantly different from pre-altitude value (P<0.05).t Significantly different from pre-altitude value (P<0.01).NS, not significantly different from pre-altitude value (P>0.05).

focused on the erythropoietic response tohypoxia and subsequent haematological adap-tation. Considering the inverse relationshipbetween Po, and resting Hb concentration, 76 itwould seem logical that the higher the athlete

can train the better. However, other factors thatinhibit exercise performance are exacerbatedwith a reduction in Po2. Acute mountainsickness presents at altitudes above 2000 to3000 M,77 with the possibility of the elite athletesuffering physiological symptoms at even loweraltitudes.'5 Prolonged exposure to altitudesabove 4500 m has been shown to result in areduction in muscle mass, the underlyingphysiological mechanisms for which have beenrecently reviewed by Kayser.78 Finally, theeffects of training at a lower Po, may result in areduction in work rate, so that detraining mayoverride the potential benefits of altitudeacclimatisation.'8

Hypoxia and detrainingA recent study has shown that VO2MAX issignificantly reduced at an altitude as low as610 m above sea level in elite enduranceathletes.80 This is a phenomenon peculiar toabout 50% of trained subjects, with VoMAxvalues of above 65 ml/kg per min or 4litres/min.8' These elite athletes develop moresevere levels of arterial hypoxaemia duringmaximal and submaximal exercise than seden-tary controls both under normoxic and hypoxicconditions.82 83 Several mechanisms have beenproposed to explain these findings, whichinclude hypoventilation, venoarterial shunting,ventilation-perfusion inequality, and analveolar-capillary diffusion limitation.8485These observations led early investigators to

hypothesise that altitude exposure may resultin a detraining response.79 Daniels andOldridge57 have shown the importance of train-ing intensity at altitude and its effects on sealevel performance. They suggested that inter-mittent exposures to altitudes of 2300 to 3300m and sea level optimised the balance betweenhypoxic acclimatisation and training intensity.Despite the experimental limitations of a singlegroup design, two world records and 12personal best times were recorded by athleteson return to sea level, which presented areasonable endorsement for such an approach.However, from our experience, it is equallypossible to have expected similar improve-ments in a control group training at sea level.64The detraining effect induced during

chronic exposure to hypobaric hypoxia hasbeen quantified in a sequence of studies byLevine et al.42 50 68 In their most recent study,5039 competitive runners were randomly as-signed to four weeks of (a) living high (2500 m)and training low (1250 m), (b) living high(2500 m) and training high (2500 m), or (c)living low (150 m) and training low (150 m).They showed that, although VO2MAX valuessignificantly improved 5 km race performancetimes by 4% in the two altitude trained groups,the running velocity that corresponded toVo2MAx and the ventilatory threshold at sealevel were significantly improved only in thegroup that lived high and trained low. An un-usual finding was that 5 km performance timewas 31 seconds slower in the sea level controlgroup, which would suggest that the trainingstimulus was not absolutely controlled duringthe experimental period. Nevertheless, it was

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concluded that the potentiating effects ofaltitude training were due to a high altitudeacclimatisation effect (improved haematology)and a low altitude training effect (increasedtraining intensity). Thus the authors advocatedthe practice of living high and training low asthe optimal approach to altitude training. Thishas popularised the use of "altitude houses"recently developed in Finland which areportable hypobaric chambers used by elite ath-letes, who alternate living and sleeping atsimulated altitude with normobaric training.86However, the effectiveness of this procedureshould at present be considered equivocal, andfurther scientific investigation is warranted toendorse this approach to altitude training.

Concept of a critical Po2 andhaematological adaptationFew athletes can afford the costs inherent in a"live high, train low" approach to altitudetraining. Therefore is it possible that a "thresh-old" altitude exists that optimises the benefitsof haematological acclimatisation and mini-mises the negative effects of detraining? Weil eta/87 have presented the most comprehensiveevidence indicating the existence of such athreshold, albeit in sedentary highland natives(B Levine, personal communication). Theyidentified a biphasic relationship between thearterial partial pressure of oxygen (Pao,) andred blood cell mass, and shown a clearinflection point at a "critical" Pao, of 67 mmHg, equivalent to an interpolated arterialoxygen saturation of 92%. This point corre-sponds to the steeper portion of the oxygen-Hbdissociation curve. The equivalent Po, wouldequate to about 135 mm Hg, which is compa-rable with an altitude of 2200-2500 m abovesea level required to stimulate sufficienthaemopoiesis at rest to influence enduranceperformance.4 However, it has been shown thatthe decrement in Vo2MAX measured in hypo-baric hypoxia is directly proportional toVolv02mxmeasured in normoxia.88 This wouldsuggest that elite athletes are more prone todeveloping arterial hypoxaemia and may gainmore benefit haematologically by training atlower altitudes in comparison with sedentarycontrols. This contention was supported byIngjer et al,4" who showed that three weeks ofaltitude training at 1900 m in elite cross coun-try skiers was sufficient to elevate Hb by 5%(P<0.02) and decrease blood lactate concen-tration during a standardised submaximal test,despite no changes in VO2MAX. However, itshould be noted that these authors did notmeasure their subjects' plasma volumes, andtheir comments that the polycythaemia wasindependent of a haemoconcentration remainsonly speculative. The scarcity of training stud-ies conducted at moderate altitudes of 1500 to2000 m in elite athletes does not allowdefinitive conclusions to be made.

Optimal durationFew data are available on the optimal time anathlete should spend training at altitude. Onthe basis of subjective coaching opinion asopposed to objective scientific evidence, it

would appear that three weeks are sufficient togain a performance advantage at sea level.89However, the longer the duration of thehypoxic stimulus the greater the erythropoieticresponse and associated haematologicaladaptation.'7 This was shown by Berglund,90who summarised the haematological changesduring previous altitude training studies con-ducted between 1829 and 3048 m. Heidentified a "true" increase in Hb concentra-tion of 1% per week, which was independent ofa haemoconcentration. Thus, assuming thatthe detraining response could be minimisedand polycythaemia did not approach patho-logical values, the longer the athlete spends ataltitude, the greater the potential benefit forendurance performance.

Iron status during altitude trainingHypoxia in itself increases iron demand andmobilisation,9 92 such that endurance athletestraining at altitude may be prone to irondeficiency. Lack of this critical erythropoieticfactor has been shown to inhibit complete hae-matological adaptation.93 Despite its im-portance, few studies have actually reportediron status of athletes during their hypoxicexposure. Suboptimal iron stores may accountfor the vast majority of training studies thathave failed to show increases in Hb concentra-tion and endurance performance on return tosea level after the hypoxic exposure. Thedifferences in iron status may also characterisethe highly individualised haematological re-sponses observed during altitude training.43

Interval between descent and eventThere is some evidence to suggest that endur-ance performance is affected by the timing ofthe descent to sea level after a sojourn toaltitude. The general consensus amongst topcoaches would suggest that endurance per-formance is optimised after 14 days at sea levelafter a bout of altitude training,89 yet there is noscientific evidence to support this claim.Suslov94 characterised the undulating nature ofendurance performance after altitude training.His research was based on over 1000 competi-tive track results obtained from middle andlong distance runners after different periods ofaltitude training (1300-2500 m) and repeatedsea level Vo2MAX tests conducted after trainingat 1800 m. He identified a decrease in compe-tition performance during the first two days atsea level and the first phase of enhanced workcapacity occurring between days 3 and 7,followed by a decrease between days 8 and 10.Performance was shown to continue to im-prove between days 12 and 13, with the bestresults achieved on days 18 to 20. He alsoidentified an additional upsurge in perform-ance between days 36 and 48 after altitude. Hefailed to identify the physiological mechanismsresponsible for this phenomenon.Few studies have tested subjects on more

than one occasion after return to sea level.Asahina et al55 and Faulkner et at" did not showany significant changes in VoMAX values aftereither 3 or 22 days at sea level. Ingjer et at"showed that after a group of elite cross country

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80to

70._

30

n 201

.E

M Control groupM No control group

H-_

_-

_

_-_-

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Figure 2 Number of hypoxic training studies conducted with or without a normoxicaltrained control group since 1950.

skiers had trained for three weeks at an altitof 1900 m, submaximal blood lactate valwere lower than pre-altitude values on dabut not day 14 at sea level. The authconcluded that a 0.8 g/dl increase inconcentration measured on day 1 was respsible for the observed improvement in s

maximal exercise. However, their failurequantify plasma volume and blood flchanges weakens the validity of their haemalogical findings. Svedenhag et al" studie(group of Swedish middle distance runners v

trained for a period of two weeks at altiti(2000 m) and were tested after 6 and 12 don return to sea level. They did not identifysignificant changes in VoimAx, maximal oxyldeficit, and submaximal blood lactate valcompared with pre-altitude values or betwdays 6 and 12 at sea level. However, t]showed a significant reduction in heart r

Borg rating of perceived exertion, and plasammonia concentration during a standardisubmaximal treadmill test, which was m

apparent after 12 days at sea level.The physiological mechanisms responsi

for these subtle changes in performance atlevel remain elusive. Intermittent altitntraining has been shown to increase the hypcventilatory response in a group of sedentsubjects, whereas an equivalent traininggramme at sea level had no effect.'4 9 Acexposure to altitude in the native lowlanmay potentiate the hypoxic ventilatorysponse because of an increased periph(chemoreceptor sensitivity, which would sutquently increase the work performed byrespiratory muscles. This has not been quaified in the elite athlete but may be implicate(the performance decrements shortly a

return to sea level. Plasma volume has bshown to decrease by 25% during chrcexposure to hypobaric hypoxia" and may tas long as two months to normalise.9' Areturn to sea level, this may remain depresfor six days,96 which may also negatively aflperformance. Altitude training may alsovolve considerable travelling time, and

negative impact of jet lag on exercise perform-ance cannot be ignored.97

Measurement of the altitude effectindependent of trainingFigure 2 shows that, since 1956, only 27 (30%)of the 91 hypoxic training studies reviewedhave incorporated a normoxically trained con-trol group. This makes it impossible todetermine whether the physiological changesthat occur after a bout of altitude training canbe attributed to an improvement in physicalconditioning or to the additive effects ofhypoxia itself.To our knowledge, the altitude training

studies conducted by Asano et al,5" Terrados etal,5' 52 and Levine et al' would appear to be theonly investigations employing a control groupthat have reported statistically significant im-provements in aerobic performance after re-

ly turn to normoxia. Asano et al" studied ten elitemiddle to long distance male runners, whotrained for a ten week period at the same rela-

ude tive exercise intensity at either sea level or aues simulated altitude of 4000 m. After training,Y 1 there were no improvements in Vo2MAX at seaors level, yet 10 km personal best running timesHb improved by about 6% (P<0.05). Using a oneon- legged training model, Terrados et alr" 52 attrib-ub- uted the potentiating effects of intermittentto hypobaric training to increases in citrate

low synthase activity and myoglobin content. TheLto- findings of Levine et al5' have already beend a described in this review.vho Whilst previous investigations have dealt pri-ude marily with aerobic responses to altitude train-lays ing, there is some evidence to suggest thatany anaerobic performance is improved on returngen to sea level.' 98 9 Mizuno et at14 showed that[ues exercise time to exhaustion after altitude train-een ing improved by 17% (P<0.05) when com-hey pared with pre-altitude values, which theyate, attributed to a 6% increase (P<0.05) in muscle,ma buffer capacity. However, the validity of thesetsed findings is questionable because of the lack of aore normoxically trained control group. A well

controlled investigation by Martino et al,9"ible which incorporated a performance matchedsea control group based at sea level, investigatedude the effects of three weeks of altitude training at)xic 2800 m on anaerobic measures of swimming:ary performance. Sea level sprint performancepro- time over 100 m was 2.4 seconds quicker in theute altitude trained group than the control groupLder (P<0.05). The largest improvements in there- altitude trained group were noted in an uppereral body Wingate test. Peak power output in-)se- creased by 27.9W more than the control groupthe (P<0.05). In a recent investigation, Nummelanti- et al99 showed that ten days of living highd in (-2200 m) and training low (sea level) resultedtfter in greater improvements in 400 m runningteen time (P<0.05) and running velocity at a fixed)mnc concentration of blood lactate (P<0.05) whentake compared with an equivalent programme offter sea level training.;sed However, the vast majority of altitude train-[ect ing studies have not identified performancein- improvements at sea level. Whilst a decrease inthe absolute training intensity may be implicated,'"

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a decrease in muscle perfusion may also play acontributory role; oxygen transport, deter-mined as a product of blood flow and arterialoxygen concentration is regulated duringchanges in Pao,. Reductions in blood flow dur-ing the inhalation of a hyperoxic gas mixtureregulates oxygen delivery to the workingmuscles, such that total oxygen delivery issimilar to that observed in normoxia'°°. Auto-regulation of this mechanism has been investi-gated at altitude and after return to sealevel."'0 102 Whilst chronic exposure to hypo-baric hypoxia increased arterial oxygen contentas the result of an increase in Hb concentra-tion, sympathetically mediated arterial vaso-constriction and a reduction in total cardiacoutput caused a reduction in blood flow, thuspreventing an increase in oxygen transport.'0'This decrease in muscle perfusion has beenshown to persist after return to sea level. Using"'Xe, blood flow to the vastus lateralis wasshown to decrease by up to 39% (P<0.001)during submaximal exercise after a threemonth expedition to 8398 m.'0'

Favier et alr suggested that the negativefindings reported in the literature could, inpart, be attributed to the fact that subjects werenot fully acclimatised to hypobaric hypoxia. Ina unique experiment they used three groups ofsedentary high altitude residents, who trainedfor 30 minutes a day at a constant work rate ona bicycle ergometer, during a six week period.Group 1 trained at a Po, that was equivalent toan interpolated altitude of 3345 m at 70% ofVo2mAx determined in hypoxia. The remainingtwo groups trained under normoxic conditionsat either the same relative work rate (70% ofthe normoxic VO2MAX) or the same absolutework rate (70% of the hypoxic VO2mAx) as thehypoxically trained group. An incremental testto exhaustion was performed by all groups innormoxia and hypoxia immediately before andafter training in an attempt to ascertain thephysiological responses to submaximal andmaximal exercise. The authors showed thatVO2MAX values improved similarly in all groups.However, they suggested that a lower reductionin base excess and bicarbonate stores observedin the hypoxically trained group could onlypotentially benefit anaerobic metabolism and,although time to exhaustion was not measured,facilitate exercise performance.

Hypoxia and immune functionChanges in total leucocyte, granulocyte, mono-cyte, lymphocyte, natural killer cell, and T cellcount, helper/suppression cell ratio, cell prolif-eration in response to mitogens, and serumimmunoglobin levels have all been implicatedin some form of immunosuppression, whichmay subsequently cause underperformance inthe athlete at sea level.'0' The additive stress ofa reduction in the inspiratory Po0, in conjunc-tion with the extensive training loads employedby athletes at altitude, may explain why someinvestigators have reported physiological evi-dence for a less favourable modulation ofimmune function in vivo during acute andchronic exposure to hypobaric hypoxia.6' 10-106

Human studies have shown that chronic expo-sure to hypobaric hypoxia results in a suppres-sion of cell mediated immunity, whereas B cellfunction remains unimpaired."6 Animal studieshave further shown that murine host defencesagainst bacterial pathogens are also impaired inhypoxia. The contributory immunomodula-tory role of endogenous glucocorticoids andneuropeptides, which are increased at altitude,may contribute to the observed alterations inimmune competence. In an experiment thatemployed elite distance runners and matchedcontrols, we showed that plasma glutamineconcentrations decreased significantly in com-parison with pre-altitude values after 20 days ofendurance training at an altitude of 1640 mabove sea level (Po, = 135 mm Hg) (D MBailey et al, unpublished work). A reduction inglutamine concentration has been identified in"overtrained" athletes and may be a contribu-tory factor leading to immunosuppression andunderperformance.'0' It is difficult to commenton the physiological mechanisms responsiblefor these changes, but there is evidence thatsuggests that chronically elevated levels ofcirculating catecholamine levels decrease therate of glutamine transport out of muscle incu-bated in vitro (Parry-Billings M, unpublisheddata). In addition to this, Wagenmakers'0' hasproposed an alternative mechanism, againrelated to elevated catecholamine levels ob-served at altitude." He suggested that hypoxiainduced glycogen depletion would result in areduction in the availability of tricarboxylicacid cycle intermediates, in particular2-oxoglutarate. This is required for the activa-tion of the branched chain amino acidaminotransferase reaction, which ultimatelyproduces glutamine. The implications of theimmunosupressive influence of hypobaric hy-poxia for endurance performance warrants fur-ther investigation in order to elucidate potentialmechanisms that may modulate performanceafter return to sea level.

Reactive oxygen species at altitudeThere is a limited body of evidence suggestingthat oxidative injury mediated by free radicalsis increased at altitude.'09"' Simon-Schnass'09identified significant increases in indirect indi-ces of free radical mediated lipid peroxidationat altitude, which included increased pentaneexcretion and thiobarbituric acid reactive sub-stances, decreased erythrocyte filterability, andincreased leucocyte and granulocyte counts.Daily supplementation with an antioxidantsuch as tocopherol (vitamin E) equivalent to300-400 mg has been shown to improveendurance performance, by theoretically limit-ing tissue damage.'09 "O An accelerated produc-tion of the highly toxic hydroxyl radical mayoccur as a consequence of an increasedproduction of free iron derived from altitudeinduced and training induced destruction ofred blood cells."' Thus it would appear thathypobaric hypoxia significantly increases oxi-dative stress, which has been shown tonegatively influence energy metabolism andmembrane integrity.

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Altitude trainingfor endurance performance at sea level 189

Summary and future researchPhysiological acclimatisation to a chronicallyreduced Ppo, is a prerequisite to achieveoptimal physical performance in environmen-tal hypoxia. However, scientific evidence tosupport the claim that either continuous orintermittent hypoxic training will enhance sealevel performance remains at present equivo-cal. Future research should focus onmethodological technicalities that optimise thebalance between the favourable and lessfavourable responses to hypoxia and potentialmediators of performance after return to sealevel. Preliminary evidence showing that theadditive stress of hypobaric hypoxia mayprovoke an adverse immune response and fur-ther potentiate free radical mediated oxidativeinjury has important implications which, ifconfirmed by scientific rigor, would present athreat to both the fitness and health of the elitecompetitor.

Our research was supported by the British Olympic Associationand the British Athletics Federation. We would also like toacknowledge Mr N Papps of Ordnance Survey, UK, and Mr SGreenberg for their keen assistance in collecting data containedin fig 1.

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