Reu e e al. Spo s Medicine - Open (2023) 9:35
h ps://doi.o g/10.1186/s40798-023-00579-3
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Spo s Medicine - Open
Does Highe In ensi y Inc ease heRa e
o Responde s oEndu ance T aining When
To al Ene gy Expendi u e Remains Cons an ?
ARandomized Con olled T ial
Ma cel Reu e 1,2* , F iede ike Rosenbe ge 2,3, And eas Ba z1,2, And eas Venho s 1, Lau a Blanz1,2,
Anne Hecks eden4 and Tim Meye 1
Abs ac
Backg ound S anda dized aining p esc ip ions o en esul in la ge a ia ion in aining esponse wi h a subs an-
ial numbe o indi iduals ha show li le o no esponse a all. The p esen s udy examined whe he he esponse in
ma ke s o ca dio espi a o y i ness (CRF) o mode a e in ensi y endu ance aining can be ele a ed by an inc ease in
aining in ensi y.
Me hods Thi y-one heal hy, un ained pa icipan s (46 ± 8 yea s, BMI 25.4 ± 3.3 kg m−2 and
˙
V
O2max
34 ± 4 mL min−1 kg−1) ained o 10 weeks wi h mode a e in ensi y (3 day week−1 o 50 min pe session a 55%
HR ese e). He ea e , he alloca ion in o wo g oups was pe o med by s a i ied andomiza ion o age, gende and
VO2max esponse. CON (con inuous mode a e in ensi y) ained o ano he 16 weeks a mode a e in ensi y, INC
(inc eased in ensi y) ained ene gy-equi alen o 8 weeks a 70% HR ese e and hen pe o med high-in ensi y in e al
aining (4 × 4) o ano he 8 weeks. Responde s we e iden i ied as pa icipan s wi h VO2max inc ease abo e he echni-
cal measu emen e o .
Resul s The e was a signi ican di e ence in
˙
V
O2max esponse be ween INC (3.4 ± 2.7 mL kg−1 min−1) and CON
(0.4 ± 2.9 mL kg−1 min−1) a e 26 weeks o aining (P = 0.020). A e 10 weeks o mode a e aining, in o al 16 o 31
pa icipan s we e classi ied as VO2max esponde s (52%). A e ano he 16 weeks con inuous mode a e in ensi y ain-
ing, no u he inc ease o esponde s was obse ed in CON. In con as , he ene gy equi alen aining wi h inc eas-
ing aining in ensi y in INC signi ican ly (P = 0.031) inc eased he numbe o esponde s o 13 o 15 (87%). The ene gy
equi alen highe aining in ensi ies inc eased he a e o esponde s mo e e ec i ely han con inued mode a e
aining in ensi ies (P = 0.012).
Conclusion High-in ensi y in e al aining inc eases he a e o esponse in VO2max o endu ance aining e en when
he o al ene gy expendi u e is held cons an . Main aining mode a e endu ance aining in ensi ies migh no be he
bes choice o op imize aining gains.
T ial Regis a ion Ge man Clinical T ials Regis e , DRKS00031445, Regis e ed 08 Ma ch 2023—Re ospec i ely egis e ed,
h ps:// www. d ks. de/ DRKS0 00314 45
*Co espondence:
Ma cel Reu e
[email p o ec ed]
Full lis o au ho in o ma ion is a ailable a he end o he a icle
Page 2 o 11
Reu e e al. Spo s Medicine - Open (2023) 9:35
Key poin s
• P olonging an ae obic aining p og am a e 10weeks wi h cons an in ensi y o 55% HR ese e and cons an
ene gy expendi u e o 16 mo e weeks will no inc ease he a e o aining esponde s.
• Inc easing aining in ensi y o 70% HR ese e a cons an ene gy expendi u e is no su icien o u he inc ease
he a e o esponde s a e a 10-week mode a e-in ensi y aining pe iod.
• T aining in he high in ensi y domain inc eases he a e o esponde s in ene gy-ma ched aining in e en ions.
Keywo ds Ae obic i ness,
˙
V
O2max, HIIT, Ene gy expendi u e, Endu ance aining, Non esponde , Response
In oduc ion
Endu ance aining is an e ec i e way o imp o e ca di-
o espi a o y i ness (CRF) and posi i ely impac on isk
ac o s o ca dio ascula disease [1–3]. Ye , i is also
known ha adap a ions o a s anda dized aining g ea ly
di e be ween indi iduals. Pe sons showing only mino
o no adap ions o aining s imuli a e equen ly e med
non esponde s. The e o e, conside a ion o indi idual
a iabili y in aining esponse has become inc easingly
impo an in aining s udies in ecen yea s. The He -
i age s udy was one o he i s examples o la ge-scale
in e en ion s udies ha has epo ed a la ge he e ogene-
i y in esponses o VO2max a e a s anda dized aining
in e en ion [4]. The phenomenon o li le o no aining
esponse has been in es iga ed by o he esea che s since
hen [5–7]. Ross and colleagues compa ed eigh endu -
ance aining s udies and ound a ange o adap ions om
minus 33% o plus 118%, independen o exe cise du a-
ion, in ensi y and ial sample size [8].
I is no clea whe he adjus ing he aining modali ies
(e.g., aining olume o in ensi y) has a posi i e in lu-
ence on he a e o esponde s. The dose– esponse ela-
ionship o endu ance aining is in luenced by aining
olume, in ensi y and aining equency [9–11]. Highe
doses o aining ha e p o en o elici mo e p onounced
aining adap ions [12, 13]. Fu he mo e, Bona iglia and
colleagues ha e shown ha be ween-subjec a iabili y in
aining esponse is due o he aining dose and ex e nal
ac o s a he han in e indi idual di e ences in ain-
abili y [14]. The ex en o which modi ica ions o ei he
in ensi y o olume a e he leading ac o is a ques ion
wi h la ge ele ance o exe cise aining p esc ip ions
o achie e he in ended aining adap ions. The e is e i-
dence ha aining p o ocols wi h highe in ensi ies such
as high-in ensi y in e al aining (HIIT) a e mo e e ec-
i e in elici ing inc eases in VO2max han mode a e in en-
si y aining [10, 15, 16].
Due o he high a iabili y o adap ions o endu -
ance aining, i has been sugges ed ha he e icacy o
aining in e en ions has o be analysed beyond me e
compa ison o main e ec s like VO2max [17, 18]. In his
ega d, a common app oach is o compa e he a es o
non esponde s be ween g oups [6, 19]. In e ms o in e -
indi idual a ia ions in aining esponse, Bona iglia
and colleagues [12] ound ha highe doses o aining
p oduce highe a es o esponse. In a di ec compa i-
son o mode a e in ensi y aining wi h ene gy-ma ched
HIIT, Ma u ana and colleagues [7] ound a g ea e e ec
on VO2max and a lowe non esponde a e o HIIT.
Mon e o and Lundby [19] obse ed ha highe aining
dose h ough inc eased olume is an e ec i e app oach
o achie e a meaning ul esponse in VO2max o pa ici-
pan s showing no esponse a e an ini ial aining in e -
en ion. Howe e , his ine i ably leads o mo e ime
consump ion. And since he s udy was lacking a con ol
g oup, he ques ion o whe he ex ended exposu e o
he same aining dose is su icien o elici a esponse
emains unanswe ed. Fo a s anda dized EE, pa icipan s
who pe o med aining wi h highe in ensi ies we e less
likely o show a non esponse han pa icipan s aining
wi h lowe in ensi ies [6]. Howe e , i should be no ed
ha in his s udy he aining equency was 5 week−1
and he e o e p esumably highe han in mos aining
beginne s. These indings indica e ha o non espond-
e s who a e unable o pe o m mo e o longe ain-
ing sessions, aining wi h highe in ensi ies migh be a
p omising al e na i e o achie e g ea e and con inuous
aining adap ions.
A me hodological di icul y is he iden i ica ion o
non esponde s, as he e is no uni o m es ablished de i-
ni ion o high-, low- o non esponse. Indi iduals a e
e med esponde s when hei indi idual esponse
exceeds a ce ain h eshold. The h eshold o non e-
sponse has o example been as se as a VO2max imp o e-
men ≤ 0L min−1 [20], o less han 5% [21, 22]. Mo eo e ,
some s udies use a coe icien o a ia ion o 5.6% [5]
de i ed om he li e a u e. Al hough hese h esholds a e
a s aigh o wa d me hod o ca ego ize esponde s, hey
do no conside he ue aining-induced esponse. In
his con ex , mo e a en ion has been gi en o he neces-
si y o dis inguishing he ue aining-induced esponse
om wi hin-subjec a iabili y and measu emen e o s
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Reu e e al. Spo s Medicine - Open (2023) 9:35
o he speci ic se ing [17]. Acco dingly, some au ho s
ha e sugges ed o use speci ic s udy designs such as
epea ed es ing o eliabili y ials o analyse ue ain-
ing esponses [23, 24]. A mo e indi idualized app oach
o ake he day- o-day biological e o and measu emen
e o in o accoun when in e p e ing and ca ego izing
he esponse is calcula ing he echnical e o o meas-
u emen (TEM) and using i as h eshold o adap ions
[24, 25]. I should be no ed ha a dicho omous app oach
in which indi iduals a e labelled as (non-) esponde s on
he basis o a single h eshold is no wi hou c i icism.
A single esponse h eshold is mo e likely o dis inguish
a “ ue” esponse om an unce ain esponse han a
“ ue” non esponse [26, 27]. Mo eo e , classi ying sub-
jec s as non esponde s on he basis o a single pa ame e
neglec s he wide ange o possible biological aining
adap a ions [28]. Ano he me hodological challenge in
es ing he independen e ec o aining in ensi y lies in
he necessi y o con ol o he o e all aining dose ( ol-
ume × in ensi y). This can be achie ed by es ima ing and
s anda dizing he o al ene gy expendi u e (EE) be ween
di e en aining modali ies.
In his s udy, we sough o compa e esponse a es
be ween 26weeks o mode a e in ensi y aining (55%
HR ese e) and aining wi h an inc ease in aining in en-
si y ( o 70%HR ese e and o 95%HRmax) a e 10 and
18 weeks, espec i ely. The di e ences on he g oup
le el a e subjec in ano he publica ion and no dis-
cussed in de ail he e [29]. I was hypo hesized ha non-
esponse a e can be educed o e en elimina ed h ough
an inc ease in in ensi y wi h ene gy expendi u e held
cons an .
Ma e ial andMe hods
All pa icipan s signed w i en in o med consen . The
s udy p ocedu es we e in acco dance wi h he Decla a-
ion o Helsinki and he s udy was app o ed by he E hics
Commi ee o he Medical Associa ion o Saa land (iden-
i ica ion numbe 219/19).
S udy Design andRandomiza ion
Two aining g oups o un ained indi iduals pe -
o med 26 weeks o endu ance aining. The con ol
g oup (CON) kep all aining a iables cons an o e
he 26 weeks, whe eas he in e en ion g oup (INC)
inc eased aining in ensi y a e 10 and again a e
18 weeks o aining ( o de ails see aining below).
The exe cise EE was s anda dized on a wi hin-subjec
basis by p opo ionally lowe ing he aining olume in
INC when he aining in ensi y was inc eased. T ead-
mill es s o olun a y exhaus ion we e pe o med h ee
imes a baseline (T01, T02, T03), a e 10weeks (weeks
10), a e 18weeks (weeks 18) and a e 26weeks (weeks
26) o aining. Using a minimiza ion echnique a week
10, subjec s we e alloca ed o ei he CON o INC [30,
31]. Fac o s o balancing we e age, sex, baseline VO2max,
VO2max esponse a week 10 (yes/no), and he magni ude
o VO2max esponse a week 10. The objec i e o his p o-
cedu e was o balance he amoun o esponde s in bo h
g oups. Fo his eason he in aindi idual a iabili y in
VO2max (mL min−1) was used as each pa icipan ’s h esh-
old o esponse [5]. The in aindi idual a iabili y (iV)
ep esen s he day- o-day a iabili y o VO2max be ween
T02 and T03 and was calcula ed as ollows:
Pa icipan s
Fo y-eigh (48), un ained subjec s we e ec ui ed o
pa icipa ion. Inclusion c i e ia we e, age 30–60 yea s,
un ained s a us (las 6 mon hs: < 1 h week−1 endu -
ance- ype physical ac i i y) and non-smoking ( o
a oid e ec s om cessa ion/ educ ion). Exclusion c i-
e ia we e BMI > 30 kg m−2, es ing blood p essu e
(RR es ) ≥ 160/100mmHg, o al choles e ol ≥ 300mg dL−1,
maximum oxygen up ake (VO2max) > 50mL kg−1 min−1 o
men; > 45mL kg−1 min−1 o women, i on de iciency (Fe -
i in ≤ 34ng mL−1), hy oid dys unc ion (TSH ≤ 0.34 mU
L−1 ≥ 4.0ng mL−1), medica ions wi h po en ial in luence
on a ge pa ame e s (e.g. be a-blocke s) and p egnancy.
Thi y- wo pa icipan s (46 ± 8 yea s, 25.4 ± 3.3 kg m−2
and 34 ± 4mL min−1 kg−1) comple ed he 26weeks ain-
ing p og amme o which one da a se could no be ana-
lysed due o echnical issues. A pa icipan low cha is
gi en in Fig.1. A baseline and a weeks 10, he e we e no
be ween-g oup di e ences o CON and INC (P > 0.05).
Pa icipan s’ cha ac e is ics a e displayed in Table1.
T aining
Pa icipan s pe o med 26weeks o walking o jogging
on 3day week−1. Fo he i s 10weeks all pa icipan s
ained a mode a e in ensi y (50min pe session a 55%
HR ese e [%HRR]). A e week 10, INC inc eased in ensi y
o 70% HRR and o a HIIT p o ocol a e week 18. HIIT
was pe o med wi h a 10min wa m-up a 70% HRmax ol-
lowed by 4 imes 4min a 95% HRmax in e spe sed wi h
3min a 70% HRmax and a cool-down a he same in en-
si y. CON ained wi h mode a e in ensi y h oughou
he en i e cou se o he s udy. The leng h o aining ses-
sions we e adjus ed o main ain a cons an wi hin-subjec
EE. Adhe ence o he p esc ibed aining in ensi y was
eco ded wi h a hea a e moni o (Sigma R1 Duo + ID.
F ee, Sigma-Elek o GmbH, Neus ad , Ge many).
iV =|T02 −T03|/meanT02T03
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Reu e e al. Spo s Medicine - Open (2023) 9:35
Ene gy Expendi u e
Oxygen up ake a he indi idual exe cise hea a es was
measu ed du ing he eadmill es s and used o es ima e
he EE o pa icipan s exe cise hea a es by use o an
a e age calo ic equi alen (4.85kcal L−1 O2) [32]. The
EE o a ce ain hea a e was hen mul iplied wi h he
p esc ibed aining ime a ha hea a e. By adjus ing
session leng h, he o e all wi hin-subjec EE was kep
cons an in INC h oughou all in e en ion phases. Fo
HIIT, his implied an indi idual adjus men o he cool-
down leng h.
Tes ing
The i s baseline es (T01) se ed as habi ua ion o he
maximal eadmill es and a medical examina ion wi h
es ing and exe cise elec oca diog am (ECG). The ol-
lowing wo baseline measu emen s (T02, T03) we e
pe o med o de e mine he in aindi idual a iabili y
and he TEM o
˙
V
O2max. The baseline da a ep esen s he
mean om bo h es s. Be o e each eadmill es , an h o-
pome ic da a (heigh , weigh , BMI and body a ) as well
as hemodynamic cha ac e is ics ( es ing hea a e and
blood p essu e) we e aken. Body a pe cen age was es i-
ma ed by a 10-si e skin old me hod wi h a Ha penden
Fig. 1 Pa icipan low cha . Heal h issues we e espi a o y ac in ec ions o musculoskele al p oblems (e.g. o e use inju ies)
Table 1 Pa icipan s cha ac e is ics a baseline
Values a e means ± SD; BMI body mass index, HR hea a e, BP blood p essu e,
˙
V
O2max maximum oxygen up ake, Vmax maximum speed, Lamax maximum lac a e,
RERmax maximum espi a o y exchange a io, P = be ween-g oup di e ences a
baseline
Men Women P
n13 18
An h opome ic da a
Age (yea s) 47 ± 9 46 ± 8 0.65
Heigh (cm) 176.0 ± 6.8 167.2 ± 6.6 0.01
Weigh (kg) 83.9 ± 12.4 68.2 ± 11.1 0.01
BMI (kg m−2) 27.0 ± 2.9 24.3 ± 3.3 0.02
Body a (%) 21.3 ± 2.9 23.6 ± 3.9 0.09
Hemodynamic cha ac e is ics a es
HR (bpm) 68 ± 7 69 ± 8 0.79
Sys olic BP (mmHg) 124 ± 8 118 ± 9 0.06
Dias olic BP (mmHg) 83 ± 6 78 ± 8 0.04
Peak exe cise pe o mance
VO2max (mL min−1) 3019 ± 378 2231 ± 324 < 0.01
VO2max (mL min−1 kg−1) 36.3 ± 4.1 33.1 ± 4.2 0.04
Vmax (km h−1) 12.1 ± 1.1 10.4 ± 1.2 0.01
HRmax (b m−1) 186 ± 15 183 ± 11 0.47
Lamax (mmol L−1) 9.3 ± 2.0 8.7 ± 2.4 0.42
RERmax 1.2 ± 0.1 1.2 ± 0.1 0.89
Page 5 o 11
Reu e e al. Spo s Medicine - Open (2023) 9:35
calipe . Hemodynamic measu es a es we e aken a e
a en-minu e- es in supine posi ion. T eadmill es s we e
pe o med on a Woodway ELG 70 (Woodway GmbH,
Weil am Rhein, Ge many) and gas exchange measu e-
men s we e conduc ed con inuously using a b ea h-by-
b ea h sys em (Me aLyze ® 3B, Co ex Biophysik GmbH,
Leipzig, Ge many) which was calib a ed acco ding o
manu ac u e ’s ins uc ion.
T eadmill es P o ocol
The eadmill was se o a cons an incline o 0.5%.
All es s s a ed a 4.0 km h−1. E e y 3 min, speed
was inc eased by 1.0 km h−1. The submaximal hea
a e (HRsubmax) du ing he g aded exe cise es was
aken a he end o las 3min s age. When he espi a-
o y exchange a io (REF) exceeded 0.95 o a leas
30s his was de ined as las 3min s age. A e wa ds,
he es s con inued using a ampwise p o ocol wi h a
speed inc emen o 0.8km h−1 pe minu e un il ol-
un a y exhaus ion [33]. Maximal pa ame e s we e only
analysed i a leas wo o he ollowing c i e ia we e
ul illed: (1) HRmax ≥ 220-age, (2) maximal blood lac a e
concen a ion > 8mmol L−1, (3) maximal RER > 1.1 [34].
Responde Classi ica ion
Responde s we e iden i ied a e he 26-week ain-
ing in e en ion by de e mining he TEM, which is
desc ibed as a conse a i e measu e o assesso e o
and day- o-day a ia ion in conduc ing an exe cise es
[6]. This applica ion is conside ed e y eliable in p o-
iding an es ima e o he echnical e o which is una -
ec ed by a change in he mean [35]. Values ≤ 1 × TEM
we e conside ed a non esponse, > 1 × TEM a esponse.
As some au ho s sugges a mul iple o he TEM
(2 × TEM) as a mo e conse a i e measu e o esponse
[23], hese h esholds a e gi en in Fig.2, oo. The TEM
was calcula ed by di iding he s anda d de ia ion o he
di e ence sco e (Sdi ) by
√2
[35].
Fig. 2 Indi idual changes compa ed o baseline in VO2max [mL min−1 kg−1] a e 10, 18 and 26 weeks o aining o CON and INC. The h ough line
dis inguishes ini ial esponde s om non esponde s (1 × TEM = single echnical e o , 2 × TEM = mul iple echnical e o ); + elimina ed non esponse;
− esponse u ned in o non esponse. Each ba ep esen s one subjec . The o de o ba s is consis en in all igu es. The g oup mean is illus a ed
h ough he ba in he backg ound

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Reu e e al. Spo s Medicine - Open (2023) 9:35
S a is ical Analyses
The sample size was es ima ed a p io i using an e ec
size o compa ison be ween g oups om wo ou o
ou a ms o a p e ious INC aining in e en ion s udy
by Helge ud e al. (“4 × 4” s. “LSD”: dppc2 = 0.547) [10].
G*Powe ( e sion 3.1.9.4) was used o calcula e he
sample size o an ANOVA (main and in e ac ion e ec
in VO2max [mL min−1 kg−1]) wi h α = 0.05, 80% powe , 2
g oups, 2 es ime poin s. This led o a equi ed sample
size o n = 29 in o al o 15 subjec s pe g oup, espec-
i ely. Taking in o accoun an es ima ed d op-ou a e
o 28% [36], he aim was o s a he s udy wi h n > 40
espec i ely n > 20 pe g oup.
IBM’s S a is ical Package o he Social Science (SPSS
27; IBM; USA) was used o s a is ical analysis. Sex di -
e ences a baseline we e examined using - es s o inde-
penden samples. Mann–Whi ney-U-Tes s we e used o
compa e baseline cha ac e is ics be ween esponde s and
(unce ain)non esponde s. The pe cen age o espond-
e s was calcula ed on he numbe o indi iduals who me
less han 1 × TEM be ween week 10 and week 26 o each
g oup. Fishe ’s Exac Tes was used o compa e he a e
o esponde s be ween g oups a week 10, week 18 and
week 26. The McNema Tes was used o compa e he
a es o esponse be ween week 10 and week 26 wi hin-
g oup. A P alue o < 0.05 o he α-e o was conside ed
s a is ically signi ican .
Resul s
Compliance, Exe cise In e en ion andTes C i e ia
Rega ding equency o aining, adhe ence o p esc ibed
exe cise hea a e and EE, he e we e no s a is ically
signi ican g oup di e ences (P > 0.05). CON comple ed
79.6 ± 6.95 and INC 79.8 ± 8.09 sessions. The a e age EE
pe aining session es ima ed by indi ec calo ime y
was 401 ± 105kcal wi h no g oup di e ence (P = 0.914).
A e age exe cise HR up o week 10 was 100 ± 2% (CON)
and 101 ± 2% (INC) o p esc ibed HR, om week 10 o
week 18 i was 101 ± 4% (CON) and 99 ± 1% (INC) and
om week 18 o week 26 i was 99 ± 1% (CON) and
97 ± 2% (INC). The d op-ou a e was 35% (Fig.1). HRmax
(b min−1), Lamax (mmol L−1) and RERmax indica ed maxi-
mal exhaus ion in bo h g oups om baseline (CON:
186 ± 12; 9.5 ± 2.2; 1.2 ± 0.1; INC: 182 ± 13; 8.4 ± 2.1;
1.2 ± 0.1) o weeks 26 (CON: 185 ± 11; 9.5 ± 2.2; 1.3 ± 0.1;
INC: 181 ± 12; 9.4 ± 2.0; 1.3 ± 0.1).
TE
M
=
Sdi
√2
Baseline Analysis
The e we e no g oup-di e ences a baseline o an h o-
pome ic da a o age (P = 0.73), BMI (P = 0.95), BF
(P = 0.41), hemodynamic cha ac e is ics a es o HR
(P = 0.65), BPsys (P = 0.44), BPdias (P = 0.29) and peak
exe cise da a o ela i e VO2max (P = 0.57), absolu e
VO2max (P = 0.71), Vmax (P = 0.50), HRmax (P = 0.44),
Lamax (P = 0.17) and RERmax (P = 0.52). Baseline cha -
ac e is ics a e shown in Table1. The e we e no di e -
ences be ween esponde s and non esponde s a baseline
o age (P = 0.06), BMI (P = 0.62), HR es (P = 0.65), BPsys
(P = 0.32), BPdias (P = 0.38), ela i e VO2max (P = 0.98),
absolu e VO2max (P = 0.86) and Vmax (P = 0.86).
Mean Responses
Baseline da a as well as changes o e ime o all pa am-
e e s a e p esen ed in Table2.
A e 26weeks o aining INC imp o ed
˙
V
O2max sig-
ni ican ly by 3.4 ± 2.7mL kg−1 min−1 (P = 0.002) as well
as om week 18 o week 26 (P = 0.002). Changes in CON
we e no signi ican (0.4 ± 2.9mL kg−1 min−1). Fo ela-
i e VO2max, imp o emen s we e signi ican ly highe o
INC han o CON (P = 0.02). The mean alues o ela-
i e VO2max a baseline and a e weeks 10, weeks 18 and
weeks 26 o CON we e 34.9 ± 3.6, 35.6 ± 4.5, 34.1 ± 3.9,
35.3 ± 4.0mL kg−1 min−1 and o INC we e 34.0 ± 5.2,
35.2 ± 5.5, 35.0 ± 5.1, 37.4 ± 4.9 mL kg−1 min−1, as
desc ibed elsewhe e in mo e de ail [29].
Ra e o Responde s
Changes in VO2max a e 10, 18 and 26weeks o aining
o CON and INC a e shown in Table2. INC inc eased
he a e o esponde s mo e e ec i ely han CON
(P = 0.012).
A e 10weeks o aining a an in ensi y o 55%HRR,
he e we e no be ween-g oups di e ences in he a e o
esponde s o ela i e VO2max (CON: 50%; INC: 53%;
P = 0.569), HR es (CON: 56%; INC: 33%; P = 0.179) and
HRsubmax (CON: 50%; INC: 47%; P = 0.569).
A e 18weeks o aining he e we e also no be ween-
g oups di e ences in he a e o esponde s o ela i e
VO2max (CON: 25%; INC: 47%; P = 0.189), HR es (CON:
62%; INC: 40%; P = 0.186) and HRsubmax (CON: 50%; INC:
67%; P = 0.283).
A e 26weeks o aining he di e ences in he a e o
esponde s we e g ea e o INC han o CON o ela-
i e VO2max (CON: 37%; INC: 87%; P = 0.009) and HR es
(CON: 25%; INC: 87%; P < 0.001) bu no o HRsubmax
(CON: 63%; INC: 67%; P = 0.553).
Wi hin g oup analysis showed ha he a e o esponse
was inc eased be ween week 10 and week 26 in INC o
ela i e VO2max om 53 o 87% (P = 0.063) and HR es
Page 7 o 11
Reu e e al. Spo s Medicine - Open (2023) 9:35
om 33 o 87% (P = 0.008). F om week 18 o week 26 INC
inc eased he a e o VO2max esponde s om 47 o 87%
(P = 0.031).
In CON he e was a non-signi ican dec ease in he
a e o esponse o ela i e VO2max om 50 o 37%
(P = 0.754) and HR es om 44 o 25% (P = 0.25) om
week 10 o week 26.
Discussion
This s udy in es iga ed he ole o an inc ease in ain-
ing in ensi y while main aining EE o inc easing
he esponde a e o endu ance aining in heal hy
un ained subjec s. Wi h an a e age EE pe aining ses-
sion o 400kcal, posi i e e ec s can be achie ed by bo h
mode a e and in ensi e aining. As expec ed, a high
in e indi idual a ia ion o he esponse was obse ed.
Table 2 Baseline alues and changes a e 10, 18 and 26 weeks o aining o g oup and esponse
Δ = changes a e 10, 18 and 26weeks o aining o CON and INC in VO2max[mL min−1 kg−1]; VO2max [mL min−1], Vmax [km h−1]; HR es [b min−1]; HRsubmax [b min−1];
alues a e p esen ed as means ± SD; = esponde , n = non esponde ; n (%) = numbe ( a e) o esponde s/non esponde s
Baseline Δ weeks 0–10 n (%) Δ weeks 10–18 n (%) Δ weeks 18–26 n (%)
VO2max [mL min−1 kg−1]
CON
34.9 ± 3.5 2.5 ± 1.4 [8 (50)] 1.5 ± 3.5 [4 (25)] 2.0 ± 2.2 [6 (37)]
n 34.9 ± 3.9 − 1.1 ± 1.1 [8 (50)] − 2.4 ± 2.3 [12 (75)] 0.7 ± 1.3 [10 (63)]
INC
33.0 ± 4.7 2.6 ± 1.1 [8 (53)] 1.3 ± 2.5 [7 (47)] 2.4 ± 2.0 [13 (87)]
n 35.0 ± 5.9 − 0.2 ± 0.8 [7 (47)] − 1.5 ± 2.3 [8 (53)] 2.1 ± 0.1 [2 (13)]
VO2max [mL min−1]
CON
2595 ± 601 167 ± 15 [6 (37)] 171.0 ± 39.6 [2 (12)] 139.3 ± 144.7 [4 (25)]
n 2596 ± 542 − 54 ± 93 [10 (63)] − 151.4 ± 175.1 [14 (88)] 47.8 ± 120.5 [12 (75)]
INC
2645 ± 531 145 ± 64 [9 (60)] 78.7 ± 124.4 [6 (40)] 123.0 ± 142.2 [11 (73)]
n 2343 ± 473 − 3 ± 60 [6 (40)] − 162.1 ± 125.9 [9 (60)] 116.8 ± 129.9 [4 (27)]
Vmax [km h−1]
CON
11.2 ± 1.4 0.8 ± 0.3 [15 (94)] 0.2 ± 0.3 [16 (100)] 0.0 ± 0.3 [16 (100)]
n 13.2 ± 0.0 0.4 ± 0.0 [1 (6)] / ± / [0] / ± / [0]
INC
10.8 ± 1.5 0.8 ± 0.3 [14 (93)] 0.5 ± 0.4 [14 (93)] 0.5 ± 0.4 [14 (93)]
n 12.2 ± 0.0 − 0.4 ± 0.0 [1 (7)] 0.2 ± 0.0 [1 (7)] − 0.6 ± 0.0 [1 (7)]
HR es [b m−1]
CON
74.4 ± 9.2 − 9.0 ± 6.8 [7 (44)] − 0.7 ± 5.8 [6 (38)] − 1.6 ± 5.2 [4 (25)]
n 65.3 ± 6.6 − 1.0 ± 1.6 [9 (56)] 3.5 ± 3.6 [10 (62)] 1.2 ± 3.0 [12 (75)]
INC
70.6 ± 4.2 − 8.2 ± 2.3 [5 (33)] − 7.2 ± 5.7 [6 (40)] − 3.0 ± 3.9 [13 (87)]
n 66.7 ± 6.3 2.3 ± 4.1 [10 (67)] − 0.3 ± 5.7 [9 (60)] − 1.0 ± 2.8 [2(13)]
HRsubmax [b m−1]
CON
137.3 ± 7.7 − 7.4 ± 3.1 [8 (50)] − 1.5 ± 5.7 [8 (50)] − 0.5 ± 4.1 [10 (63)]
n 134.6 ± 16.0 − 2.7 ± 2.3 [8 (50)] 2.1 ± 8.6 [8 (50)] 1.4 ± 4.9 [6 (37)]
INC
132.2 ± 15.6 − 10.8 ± 3.3 [7 (47)] − 3.5 ± 5.5 [10 (67)] − 2.0 ± 7.6 [10 (67)]
n 132.7 ± 8.8 4.2 ± 3.8 [8 (53)] − 4.4 ± 5.7 [5 (33)] 0.9 ± 7.5 [5 (33)]
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Reu e e al. Spo s Medicine - Open (2023) 9:35
Responde s o VO2max we e obse ed in bo h g oups
and by s a i ied andomiza ion equally dis ibu ed
(CON = 50%; INC = 53%). The main indings o his
esea ch a e (1) h ough an inc ease in aining in ensi y
esponse a e o VO2max was inc eased om 53 o 87%
despi e o al EE emaining he same, (2) gi en a cons an
ene gy consump ion, a high in ensi y in e al aining
e ec i ely inc eases he a e o esponde s as indica ed
by an addi ional inc ease in esponse a e be ween week
18 and week 26 (i should be no ed ha his inc ease
occu ed a e 18 weeks o aining had al eady been
comple ed) and (3) he aining s imulus a an in ensi y
o 70%HRR is no su icien o inc ease esponse a e
10weeks o aining a 55%HRR.
We we e able o show ha o s anda dized isocalo ic
aining in e en ions he choice o in ensi y a ec s he
magni ude o ΔVO2max as well as he a e o esponse.
When aining in ensi y was inc eased om 55%HRR o
70%HRR be ween week 10 and 18weeks no inc ease in
esponse a e was obse ed a e 8weeks. Only when
INC pe o med HIIT be ween week 18 and week26, he
esponse a e was signi ican ly inc eased (+ 75%) in mos
pa icipan s. This sugges s ha o isocalo ic in e en-
ions he in ensi y mus be in he high in ensi y domain
o p oduce mo e esponde s. P e ious s udies ha e
al eady shown ha HIIT is mo e e ec i e han mode a e
aining o imp o emen s o CRF when EE is con olled
o [37, 38]. A no el inding o ou s udy is ha he e
does no seem o be a linea ela ionship be ween in en-
si y and esponde a es as aining wi h 70%HRR did no
inc ease esponse a e e ec i ely. I is likely ha ce ain
physiological pa hways leading o highe VO2max a e
ac i a ed pa icula ly h ough a aining s imulus abo e
a ce ain h eshold. The e is e idence ha HIIT yields
g ea e imp o emen s in mi ochond ial con en han
wo k-ma ched mode a e aining [39]. To ma and col-
leagues ela ed he highe e ec i eness o HIIT o a la ge
ac i a ion o as - wi ch ib es and an ad anced mi o-
chond ial biogenesis [40]. Despi e hese wo ks i is s ill
unclea wha he exac pa hways a e ha lead o highe
VO2max. I seems unlikely ha e en o a s anda dized
aining p og amme esponde s imp o e hei ΔVO2max
h ough a uni o m physiological adap ion p ocess [41].
Al hough ou da a show ha HIIT is mo e likely o ig-
ge a esponse in ma ke s o CRF, he e we e s ill 2 ou
o 8 ini ial non esponde s in INC a e 26weeks. This
ag ees wi h indings o Timmons and colleagues [42]
ha 20% o indi iduals show no imp o emen in ae o-
bic capaci y e en a e high in ensi y aining. Conside -
ing Mon e o’s and Lundby’s [19] s udy which shows ha
non esponse can be elimina ed h ough aining doses
o up o 300min pe week, we conclude ha o some
indi iduals an adjus men o HIIT o a gi en aining
dose migh no be su icien and highe o e all aining
doses, i.e. highe EE, a e necessa y in hese cases o elici
a aining esponse inc ease esponse.
The o e all e ec s on VO2max as well as he a e o
esponde s a e he i s 10weeks o CON we e compa-
able wi h o he s udies in es iga ing he e ec s o mod-
e a e in ensi y aining [10, 43]. O e he nex 16weeks,
3 addi ional pa icipan s, om an ini ial 8, became
esponde s. F om he ini ial 8 esponde s a baseline 7
we e ca ego ized as non esponde s ( espec i ely unce -
ain esponde s) a weeks 18 and 5 a week 26. Ou da a
he e o e sugges ha con inued aining a he same
in ensi y does no au oma ically ha e a posi i e e ec
on he a e o esponde s. Addi ionally, in acco dance
wi h in e na ional guidelines [44], we ound ha mode -
a e in ensi y aining migh no always p oduce a las ing
aining esponse when he aining dose is no in ensi-
ied o e ime. One a ionale o his inding is ha he
i s 10weeks o aining igge ed p ima ily adap ions o
he ca dio ascula sys em ha led o imp o ed mecha-
nisms o oxygen anspo and consump ion and he e-
o e an inc ease in VO2max. These adap ions pla eaued
and, in some cases, possibly e en eg essed when he
aining dose emained he same and submaximal adap-
ions (e.g. me abolic sys em, unning economy) p esum-
ably became mo e p onounced o e ime. In his con ex ,
i mus be emphasized ha he exe cise hea a e was no
signi ican ly adjus ed in CON a any poin o e 26weeks
and e ec i ely inc eased o e ime. This may ha e caused
a lowe me abolic s ain o e ime o a gi en hea a e
because o highe me abolic e iciency, which could
cause a dec easing aining s imulus o e ime o hese
indi iduals. This assump ion is suppo ed by indings
by Wea he wax and colleagues who compa ed esponse
a es o a aining p esc ip ion based on %HRR wi h an
indi idualized aining based on en ila o y h esholds
[11]. The esponse a es we e 60% o he s anda dized
and 100% o he indi idualized aining. In line wi h
hese indings and o he s [45, 46] he ques ion emains
whe he esponse a es indica e di e ences in ain-
abili y o a e a consequence o a ia ion in he be ween-
subjec me abolic s ain o a ixed hea a e pe cen age.
Al hough he li e a u e shows ha indi idualized ain-
ing p esc ip ion can p oduce mo e homogenous aining
esponses [47], i should no be o e looked ha in many
p ac ical se ings he necessa y me abolic es ing o ha
ype o p esc ip ion is no easible. Fo he ime being,
he majo i y o indi iduals ha ake up an unsupe ised
exe cise egimen will ely on he in e na ional guidelines
and use hea a e as he only physiological measu e o
moni o aining in ensi y. In his con ex , ou s udy has
shown ha he implemen a ion o high in ensi y e o s
inc eases he likelihood o imp o ed i ness.
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Reu e e al. Spo s Medicine - Open (2023) 9:35
Al hough he magni ude o adap ion o Vmax be ween
he wo g oups we e in a ou o INC, he e we e no
di e ence in he esponse a es o his pa ame e .
This highligh s ha mode a e as well as in ense ain-
ing p o ocols yield imp o emen s in unc ional capac-
i y. Vollaa d and colleagues ha e al eady shown ha o
un ained indi iduals imp o emen s in maximal un-
ning speed a e no ela ed o VO2max [48]. Ou s udy
has con i med hese indings, as he e was no uni o m
pa e n o esponse o Vmax and VO2max. Al hough he
p ognos ic alue o VO2max o o e all heal h and all-
cause mo ali y is widely accep ed, i is s ill unclea
o which deg ee VO2max o he highe le els o physi-
cal ac i i y h ough which i is achie ed a e he causal
ac o o imp o ed heal h [49]. We he e o e sug-
ges u u e esea ch o ocus mo e on he connec ion
be ween non esponse and heal h bene i s, acknowledg-
ing he me hodical challenges in such esea ch designs.
In his con ex i should be no ed ha an adap a ion
below a ce ain h eshold is no equal o a non e-
sponse as he e is a ange o unce ain y be ween “ ue”
esponse and non esponse.
Limi a ions
Ou da a poin ou ha a single pos - es migh no be
su icien o ca ego ize indi iduals as esponde s wi h
ce ain y. We ha e shown ha o a s anda dized aining
in e en ion he e is a conside able wi hin-subjec luc-
ua ion o esponse o e ime. This is in line wi h o he
ecommenda ions o epea ed es ing du ing an exe cise
in e en ion [23, 24]. Ne e heless, he s eng h o his
s udy is ha he wi hin-subjec a iabili y o VO2max was
analysed by wo baseline measu emen s. In ou s udy, he
TEM was 4.2 ± 2.7% and was compa able in bo h g oups.
Thus, i was simila o he o en used coe icien o a i-
a ion o 5.6% epo ed in li e a u e [5]. In o he s udies,
mos subjec s showed a esponse in a leas one pa am-
e e , excep o VO2max [5]. This highligh s ha he e i-
cacy o aining in e en ions should be assessed h ough
se e al measu es.
Since he le el o in aindi idual a iabili y may ha e
an in luence on he esponse, i would be in e es ing o
see how in aindi idual a iabili y changes in he aining
p ocess. Fo his pu pose, Ross and colleagues [8] ecom-
mend including a con ol g oup o measu e he in e in-
di idual esponse a iabili y and o pe o m addi ional
measu emen s a he p e- and pos - es s. Pa icipan s
we e ins uc ed o main ain ea ing habi s as well as daily
physical ac i i y. As we did no eco d he daily physi-
cal ac i i y, we canno ule ou iny in luences om his
sou ce and sugges u u e esea ch o include he in lu-
ence o li es yle habi s on he aining esponse.
Conclusion
The cu en s udy demons a es ha aining in he high
in ensi y domain inc eases he a e o esponde s o
VO2max o mos indi iduals e en when he o al ene gy
expendi u e emains he same. Thus, aining a in ensi-
ies a ound VO2max such as in HIIT is well sui ed o e ec-
i ely inc ease he a e o esponde s. I he speci ica ions
o a s anda dized mode a e endu ance aining emain
cons an a e he pe iod o 10weeks o aining, u he
aining adap a ions a e unlikely. The e o e, aining in
he high in ensi y domain is an e ec i e way o achie e
and main ain a aining esponse wi hou he need o
a highe o al aining olume. This is o pa icula el-
e ance o se ings, whe e indi idualized ainings p e-
sc ip ions a e no easible.
Abb e ia ions
BMI Body mass index
BP Blood p essu e
CON Con ol g oup (mode a e in ensi y)
CRF Ca dio espi a o y i ness
EE To al ene gy expendi u e
HIIT High-in ensi y in e al aining
HR es Res ing hea a e
HR ese e Hea a e ese e
HRsubmax Submaximal hea a e
INC In e en ion g oup (inc easing in ensi y)
iV In aindi idual a iabili y
Lamax Maximum lac a e
RER Respi a o y exchange a io
T01 Habi ua ion o he maximal eadmill es and a medical
examina ion
T02 Baseline measu emen 1
T03 Baseline measu emen 2
TEM Technical e o o measu emen
Vmax Maximum speed
VO2max Maximum oxygen up ake
wk10 10 Weeks o aining
wk18 18 Weeks o aining
wk26 26 Weeks o aining
Acknowledgemen s
No applicable.
Au ho Con ibu ions
MR w o e he i s d a o he manusc ip and analysed and in e p e ed he
da a om he subjec s. Me hodological quali y assessmen s we e conduc ed
by FR, AV and TM. AH con ibu ed o idea concep ion. AB and LB conduc ed
he da a collec ion and supe ised he aining in e en ion. All au ho s ead
and app o ed he inal manusc ip .
Funding
Open Access unding enabled and o ganized by P ojek DEAL. We did no
ecei e any unding o ou wo k om any o ganiza ions.
A ailabili y o Da a and Ma e ials
The da ase s used and/o analysed du ing he cu en s udy a e a ailable om
he co esponding au ho on easonable eques .
Decla a ions
E hics App o al and Consen o Pa icipa e
All pa icipan s signed w i en in o med consen . The s udy p ocedu es we e
in acco dance wi h he Decla a ion o Helsinki and he s udy was app o ed