Ci a ion: Ca nei o-Ba e a, A.;
Ama o-Gahe e, F.J.; Ju ado-Fasoli, L.;
Sáez-Roca, G.; Ma ín-Ca asco, C.;
Tinahones, F.J.; Ruiz, J.R. E ec o a
Weigh Loss and Li es yle
In e en ion on Die a y Beha io in
Men wi h Obs uc i e Sleep Apnea:
The INTERAPNEA T ial. Nu ien s
2022,14, 2731. h ps://doi.o g/
10.3390/nu14132731
Academic Edi o s: Ma ia
Izquie do-Pulido and Ma ía
Fe nanda Ze ón-Ruge io
Recei ed: 10 June 2022
Accep ed: 27 June 2022
Published: 30 June 2022
Publishe ’s No e: MDPI s ays neu al
wi h ega d o ju isdic ional claims in
published maps and ins i u ional a il-
ia ions.
Copy igh : © 2022 by he au ho s.
Licensee MDPI, Basel, Swi ze land.
This a icle is an open access a icle
dis ibu ed unde he e ms and
condi ions o he C ea i e Commons
A ibu ion (CC BY) license (h ps://
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4.0/).
nu ien s
A icle
E ec o a Weigh Loss and Li es yle In e en ion on Die a y
Beha io in Men wi h Obs uc i e Sleep Apnea:
The INTERAPNEA T ial
Almudena Ca nei o-Ba e a 1,2,* , F ancisco J. Ama o-Gahe e 2,3 , Lucas Ju ado-Fasoli 2,3 , Ge mán Sáez-Roca 4,
Ca los Ma ín-Ca asco 4, F ancisco J. Tinahones 5,6 and Jona an R. Ruiz 2,7,*
1Sleep and Heal h P omo ion Labo a o y, Mind, B ain and Beha io Resea ch Cen e (CIMCYC),
Uni e si y o G anada, 18011 G anada, Spain
2P omo ing Fi ness and Heal h h ough Physical Ac i i y Resea ch G oup (PROFITH), Spo and Heal h
Uni e si y Resea ch Ins i u e (iMUDS), Depa men o Physical Educa ion and Spo s,
Facul y o Spo Sciences, Uni e si y o G anada, 18071 G anada, Spain; ama o @ug .es (F.J.A.-G.);
ju ado asoli@ug .es (L.J.-F.)
3EFFECTS-262 Resea ch G oup, Depa men o Medical Physiology, School o Medicine,
Uni e si y o G anada, 18071 G anada, Spain
4Unidad de T as o nos Respi a o ios del Sueño, Se icio de Neumología, Hospi al Uni e si a io Vi gen
de las Nie es, 18014 G anada, Spain; [email p o ec ed] (G.S.-R.); [email p o ec ed] (C.M.-C.)
5Cen o de In es igación Biomédica en Red Fisiopa ología de la Obesidad y la Nu ición (CIBEROBN),
Ins i u e o Heal h Ca los III, 28029 Mad id, Spain; [email p o ec ed]
6Depa men o Endoc inology, Vi gen de la Vic o ia Hospi al, Ins i u o de In es igación Biomédica de
Málaga (IBIMA), Uni e si y o Málaga, 29590 Málaga, Spain
7Ins i u o de In es igación Biosani a ia, ibs.G anada, 18012 G anada, Spain
*Co espondence: aca nei o@ug .es (A.C.-B.); uizj@ug .es (J.R.R.)
Abs ac :
This s udy in es iga ed he e ec s o an eigh -week in e disciplina y weigh loss and
li es yle in e en ion on die a y beha io in men who we e o e weigh /had obesi y and mode a e-
o-se e e obs uc i e sleep apnea (OSA). I was based on da a om INTERAPNEA (ClinicalT ials.go
ID: NCT03851653); a andomized clinical ial conduc ed om Ap il 2019 o Ap il 2020. Men
aged 18–65 yea s wi h mode a e- o-se e e OSA and a body mass index
≥
25 kg/m
2
we e andomly
assigned o a usual-ca e g oup o an eigh -week in e disciplina y weigh loss and li es yle in e en ion
combined wi h usual-ca e. Die a y beha io was assessed h ough he Food Beha io Checklis (FBC)
and he Medi e anean Die Adhe ence Sc eene (MEDAS). O he 89 pa icipan s who unde wen
andomiza ion, 75 comple ed he in e en ion endpoin assessmen , 89 pa icipan s being he e o e
included in he in en ion- o- ea analyses, and 75 in he pe -p o ocol app oach. As compa ed wi h
usual-ca e, he in e en ion g oup had g ea e imp o emen s a in e en ion endpoin in die a y
beha io , as measu ed by he FBC o al sco e (20% inc ease in FBC o al sco e, mean be ween-g oup
di e ence, 8.7; 95% con idence in e al, 5.7 o 11.7), and MEDAS o al sco e (33% inc ease in MEDAS
o al sco e, mean be ween-g oup di e ence, 2.1; 95% CI 1.3 o 2.9). A 6 mon hs a e in e en ion,
he in e en ion g oup also had g ea e imp o emen s in bo h he FBC o al sco e (15% inc ease) and
MEDAS o al sco e (25% inc ease), wi h mean be ween-g oup di e ences o 7.7 (CI 95%, 4.4 o 10.9)
and 1.7 (CI 95%, 0.9 o 2.6), espec i ely. An eigh -week in e disciplina y weigh loss and li es yle
in e en ion esul ed in meaning ul and sus ainable imp o emen s in die a y beha io , including
adhe ence o he Medi e anean die in men who we e o e weigh / had obesi y and CPAP- ea ed
mode a e- o-se e e OSA.
Keywo ds:
obs uc i e sleep apnea; obesi y; weigh loss; li es yle in e en ion; die a y beha io ;
Medi e anean die
Nu ien s 2022,14, 2731. h ps://doi.o g/10.3390/nu14132731 h ps://www.mdpi.com/jou nal/nu ien s
Nu ien s 2022,14, 2731 2 o 20
1. In oduc ion
Obs uc i e sleep apnea (OSA), cha ac e ized by episodic uppe -ai way obs uc ions
du ing sleep, a ec s nea ly a billion adul s aged 30–69 yea s globally [
1
] and is s ongly
associa ed wi h neu ocogni i e impai men , diminished quali y o li e, and an inc eased
likelihood o hype ension, cance , and me abolic, ca dio ascula , and ce eb o ascula
diseases [
2
–
10
]. Al hough con inuous posi i e ai way p essu e (CPAP) is he i s -line ea -
men o OSA—a de ice se ing o educe uppe -ai way collapse du ing sleep
[11]—CPAP
adhe ence a es a e subop imal [
12
], and long- e m bene i s beyond educ ion o apnea-
hypopnea e en s pe hou o sleep (i.e., he apnea-hypopnea index; AHI) and o he indexes
and pa ame e s emain unce ain [13–15].
Gi en he complex and ecip ocal in e ac ion be ween OSA and obesi y [
16
], weigh
loss and li es yle in e en ions, including die a y change and exe cise, a e s ongly ec-
ommended [
17
,
18
] and appea s o signi ican ly imp o e OSA se e i y, ca diome abolic
como bidi ies, and, hus, heal h- ela ed quali y o li e [
19
–
24
]. Howe e , mos p e ious
s udies in his ega d only include calo ie- es ic ed die s [
25
], which may no be he mos
e icien app oach o long-las ing and sus ainable die a y beha io change [
26
,
27
]. Ins ead,
al e na i e app oaches, such as Medi e anean die s and o he die a y s a egies ocusing
on nu i ional educa ion and beha io change, ha e been p oposed as po en ial s a egies
o choice o OSA managemen [
26
–
28
]. S ill, al hough e ec i e a imp o ing die a y beha -
io s in pe sons wi h and wi hou ca dio ascula isk ac o s and o he condi ions [
29
–
33
],
he e is no e idence o da e on he e ec s o his app oach on he unheal hy die a y beha -
io s and poo quali y o he die commonly ound in pa ien s wi h OSA [
34
–
36
]. Simila ly,
and consecu i ely, he e is no s udy in es iga ing he associa ion o changes in die a y
beha io s and changes in OSA se e i y and ela ed ou comes, such as body weigh and
composi ion in adul s wi h OSA and who a e o e weigh /ha e obesi y.
The In e disciplina y Weigh Loss and Li es yle In e en ion (INTERAPNEA) ial is
an open-label, pa allel-g oup, andomized con olled ial aimed a es ing he e icacy o an
eigh -week weigh loss and li es yle in e en ion o he imp o emen o OSA se e i y, body
weigh and composi ion, and ca diome abolic como bidi ies in men wi h OSA and who
a e o e weigh /ha e obesi y [
37
]. This s udy included wo g oups: a usual-ca e/con ol
g oup, which ecei ed CPAP as he s anda d ca e o OSA, and a weigh loss and li es yle
in e en ion g oup, which ecei ed an eigh -week in e disciplina y in e en ion, including
nu i ional beha io change, ae obic exe cise, sleep hygiene, and alcohol and obacco cessa-
ion, combined wi h usual-ca e. Changes in OSA se e i y and body weigh a 6 mon hs
a e in e en ion indica ed ha pa icipan s in he in e en ion g oup educed a signi -
ican ly g ea e amoun o hei ini ial AHI and body weigh (57% and 7%, espec i ely)
han hose in he usual-ca e/con ol g oup (2% and 1%) [
20
]. INTERAPNEA p o ides
an oppo uni y o examine he e ec s o a beha io -induced weigh loss in e en ion on
die a y beha io and die quali y in men wi h mode a e- o-se e e OSA who ecei ed,
among o he in e en ion componen s, nu i ional educa ion and beha io change.
The aim o his s udy was he e o e o examine he e ec s o an eigh -week in e disci-
plina y weigh loss and li es yle in e en ion, as compa ed wi h usual-ca e (i.e., CPAP), on
die a y beha io in men wi h CPAP- ea ed mode a e- o-se e e OSA and who we e o e -
weigh /had obesi y. Addi ionally, we pu sued o in es iga e he associa ions o changes in
die a y beha io and adhe ence o he Medi e anean die wi h changes in OSA se e i y
and body weigh and composi ion ou comes. Thus, his s udy is he i s o in es iga e
he bene icial e ec s o his app oach on die a y beha io and, in u n, he associa ion o
changes in his ou come wi h changes in OSA se e i y and body weigh and composi ion
in men wi h mode a e- o-se e e OSA. We hypo hesized ha he in e en ion g oup would
ha e g ea e sus ainable imp o emen s in hese die a y ou comes han he con ol g oup.
Simila ly, we expec ed ha changes in die a y beha io and adhe ence o he Medi e anean
die would be signi ican ly associa ed wi h changes in OSA se e i y and body weigh and
composi ion ou comes.
Nu ien s 2022,14, 2731 3 o 20
2. Ma e ials and Me hods
2.1. S udy Design
The p esen wo k is an ancilla y s udy o he INTERAPNEA andomized clinical
ial [
37
], conduc ed om Ap il 2019 o Oc obe 2020. De ailed in o ma ion on he s udy
a ionale, design, and me hodology has p e iously been published [
37
]. This ial is in com-
pliance wi h he Consolida ed S anda ds o Repo ing T ials (CONSORT), was app o ed
by he Clinical Resea ch E hics Commi ees o he Uni e si y o G anada (G anada, Spain),
Vi gen de las Nie es Uni e si y Hospi al (G anada, Spain), and Jun a de Andalucía (Spain)
(0770-N-19), and is egis e ed in he Na ional Ins i u es o Heal h da abase (ClinicalT i-
als.go NCT03851653).
2.2. Pa icipan s
Pa icipan s we e ec ui ed om he sleep-diso de ed b ea hing uni o he collabo a -
ing hospi al (Vi gen de las Nie es Uni e si y Hospi al). Po en ial pa icipan s we e men
aged 18–65 yea s wi h CPAP- ea ed mode a e- o-se e e OSA (i.e., AHI equal o g ea e
han 15 e en s pe hou o sleep) and a body mass index (BMI) equal o o g ea e han
25 kg/m
2
. The sole inclusion o men in ou sample was no only based on he highe
incidence and p e alence o OSA in his popula ion [
1
], bu also on he well-e idenced di -
e ences be ween men and women in OSA pheno ypes [
38
] and he e ec i eness o weigh
loss in e en ions [
20
,
37
,
39
–
41
]. Exclusion c i e ia included p esen pa icipa ion in a
weigh loss p og am, p esence o any psychological/psychia ic diso de , and/o any o he
p ima y sleep diso de which was no seconda y o OSA. Upon p o iding w i en in o med
consen , po en ial pa icipan s we e clinically/physically examined o ensu e easibili y
o inclusion in he s udy. Successi ely, sc eening/baseline measu emen s, including an
o e nigh as ing blood es , comple e ull-nigh polysomnog aphy, a se o ques ionnai es
measu ing subjec i e a iables, and measu emen s o body composi ion and an h opo-
me ic pa ame e s, we e conduc ed on each pa icipan . The ial was conduc ed in h ee
consecu i e se s o ~30 pa icipan s. A o al o 89 men we e inally andomly assigned o
ei he he in e en ion g oup (40 pa icipan s) o he usual-ca e g oup (49 pa icipan s) by
means o a compu e -gene a ed simple (un es ic ed) andomiza ion (Figu e 1). The 8-week
assessmen (in e en ion endpoin ) was comple ed by 75 pa icipan s, 15.7% (14 pa icipan s)
being los a ollow-up, mainly due o he COVID-19 pandemic (10 pa icipan s).
2.3. In e en ions
The in e disciplina y weigh loss and li es yle in e en ion was p ecisely designed
ollowing he la es clinical p ac ice guidelines o OSA [
17
,
18
] and obesi y manage-
men
[42,43]
. I las ed eigh weeks and was composed o i e componen s: nu i ional
beha io change; mode a e-in ensi y ae obic exe cise; smoking cessa ion; alcohol a oid-
ance; and sleep hygiene. Pa icipan s ecei ed 60–90 min sessions weekly pe componen ,
each session being led by quali ied pe sonnel in he ield (i.e., human nu i ion and di-
e e ics, physical ac i i y and spo sciences, psychology, and sleep medicine). B ie ly,
he co ne s one o his in e disciplina y in e en ion was he use o he T ans heo e ical
Model o Heal h Beha io Change [
44
], a well- ecognized biopsychosocial model based
on in eg a ing key s a egies, p ocesses, and p inciples o beha io change heo ies in o a
comp ehensi e in e en ional app oach o he achie emen o sus ainable heal h- ela ed
beha io s. Consciousness aising, sel - ee alua ion, s imulus con ol, goal-se ing, sel -
moni o ing, and sel -e icacy we e some o he beha io al change p ocesses and s a egies
used. De ails o he con en o he in e en ion ha e p e iously been published [37].
The usual-ca e/con ol g oup ecei ed CPAP he apy, oge he wi h a single session
o 30 min add essing gene al ad ice on weigh loss and li es yle change. Ne e heless,
he weigh loss and li es yle in e en ion was o e ed o all pa icipan s om his g oup a
ial comple ion.
Nu ien s 2022,14, 2731 4 o 20
Nu ien s 2022, 14, x FOR PEER REVIEW 4 o 21
Figu e 1. Flow-cha diag am o he INTERAPNEA andomized clinical ial.
2.3. In e en ions
The in e disciplina y weigh loss and li es yle in e en ion was p ecisely designed
ollowing he la es clinical p ac ice guidelines o OSA [17,18] and obesi y managemen
[42,43]. I las ed eigh weeks and was composed o i e componen s: nu i ional beha io
change; mode a e-in ensi y ae obic exe cise; smoking cessa ion; alcohol a oidance; and
sleep hygiene. Pa icipan s ecei ed 60–90 min sessions weekly pe componen , each ses-
sion being led by quali ied pe sonnel in he ield (i.e., human nu i ion and die e ics, phys-
ical ac i i y and spo sciences, psychology, and sleep medicine). B ie ly, he co ne s one
o his in e disciplina y in e en ion was he use o he T ans heo e ical Model o Heal h
Beha io Change [44], a well- ecognized biopsychosocial model based on in eg a ing key
s a egies, p ocesses, and p inciples o beha io change heo ies in o a comp ehensi e in-
e en ional app oach o he achie emen o sus ainable heal h- ela ed beha io s. Con-
sciousness aising, sel - ee alua ion, s imulus con ol, goal-se ing, sel -moni o ing, and
sel -e icacy we e some o he beha io al change p ocesses and s a egies used. De ails o
he con en o he in e en ion ha e p e iously been published [37].
The usual-ca e/con ol g oup ecei ed CPAP he apy, oge he wi h a single session
o 30 min add essing gene al ad ice on weigh loss and li es yle change. Ne e heless, he
Figu e 1. Flow-cha diag am o he INTERAPNEA andomized clinical ial.
2.4. Assessmen s
Assessmen s a baseline, in e en ion endpoin , and 6 mon hs a e in e en ion we e
comple ed o e a one o wo-week pe iod, including a as ing blood es , a ull-nigh
ambula o y polysomnog aphy, a se o ques ionnai es, and a ull-body dual ene gy X- ay
abso p iome y (DXA) scanne . All pa icipan s we e ins uc ed o e ain om using CPAP
o 7 days be o e each s udy assessmen . A comple e desc ip ion o he INTERAPNEA
ial assessmen s, including de ailed in o ma ion on he polysomnog aphy pe o med and
o he es s and measu es, can be ound in a p e iously published pape [37].
The p ima y ou comes o his s udy we e changes om baseline o in e en ion end-
poin and 6 mon hs a e in e en ion in sel - epo ed die a y beha io , as measu ed by he
Food Beha io Checklis (FBC) ques ionnai e [
45
], and adhe ence o he Medi e anean die ,
which was assessed h ough he Medi e anean Die Adhe ence Sc eene (MEDAS) [46].
The FBC is composed by 22 i ems and se en sub-scales ela ed o ui and ege a-
bles consump ion (nine i ems), milk/dai y consump ion ( wo i ems), ood secu i y (one
i em), die quali y ( ou i ems), as ood consump ion ( h ee i ems), swee ened be e ages
consump ion ( wo i ems), and mea consump ion (one i em). Sco es ange om 23 o 85,
highe sco es indica ing heal hie die a y beha io .
Nu ien s 2022,14, 2731 5 o 20
Simila ly, he MEDAS is a widely used 14-i em sc eene o assess adhe ence o he
Medi e anean die a y pa e n h ough ques ions ela ed o ood in ake habi s and ood
consump ion equency. To al sco es ange om 1 o 14, highe sco es indica ing g ea e
compliance wi h he Medi e anean die . Sco es equal o g ea e han 10 indica e high
adhe ence o he Medi e anean die .
Objec i e sleep ou comes included in his s udy we e AHI, de ined as he numbe o
apnea and hypopnea episodes pe hou o sleep, oxygen desa u a ion index, which is he
numbe o oxygen desa u a ion
≥
3% pe hou o sleep, and sleep e iciency (%), calcula ed
as he a io o o al sleep ime o o al ime in bed. These sleep ou comes we e measu ed
h ough a ull-nigh in-labo a o y polysomnog aphy.
Body weigh and composi ion ou comes included body weigh (kg), which was mea-
su ed wi h a calib a ed scale and s adiome e (model 799, Elec onic Column Scale, Ham-
bu g, Ge many); neck, ches , and wais ci cum e ences (cm); and a mass (kg) and isce al
adipose issue (g), which we e measu ed h ough a ull-body DXA scanne (Disco e y Wi,
Hologic, Inc., Bed o d, MA, USA).
2.5. S a is ical Analysis
Linea mixed-e ec s models [
47
] we e used in o de o es ima e in e en ion e ec s on
he s udy ou comes. These models included g oup, assessmen ime, and hei in e ac ion
e ms, es ima ions being conduc ed h ough he es ic ed maximum-likelihood me hod
and an uns uc u ed co a iance ma ix adjus ing o wi hin-pa icipan clus e ing esul ing
om he epea ed-measu es design. All alues p esen ed in he ables a e model-based
es ima es, his model assuming ha missing alues we e missing-a - andom. Ne e heless,
a logis ic model p edic ing a i ion p opensi y based on baseline alues o se o pa ici-
pan s, ial g oup, OSA se e i y, age, and BMI was used. Only se o pa icipan s p edic ed
a i ion due o he occu ence o he COVID-19 pandemic a he ial endpoin , which was
he in e en ion endpoin assessmen o he hi d se o pa icipan s.
Analyses and es ima ions we e pe o med wi h bo h an in en ion- o- ea app oach
(including all pa icipan s as o iginally alloca ed a e andomiza ion) and a pe -p o ocol
app oach es ic ed o pa icipan s wi h a CPAP usage equal o g ea e han ou hou s pe
nigh on 70% o nigh s and, ega ding he in e en ion g oup, a leas 80% o a endance
a e a in e en ion sessions.
In addi ion, associa ion o changes in die a y beha io o e ime wi h changes in sleep
and body weigh and composi ion ou comes we e examined by epea ed measu es co ela-
ion analysis—a s a is ical echnique used o de e mine he wi hin-indi idual associa ion
o pai ed measu es assessed on wo o mo e occasions o mul iple indi iduals [
48
]. All
analyses we e pe o med using R e sion 4.0.3 (R P ojec o S a is ical Compu ing; Bos on,
MA, USA).
3. Resul s
3.1. Pa icipan s’ Cha ac e is ics
Baseline cha ac e is ics o he s udy pa icipan s by g oup a e p esen ed in Table 1. The
majo i y o pa icipan s en olled we e middle-aged men (mean
±
SD age,
54.1 ±8.0 yea s
),
wi h se e e OSA (mean
±
SD AHI, 41.3
±
22.2 e en s/h) and obesi y (
mean ±SD
BMI,
34.4 ±5.4 kg/m2
). The e we e no signi ican be ween-g oup di e ences in any o he
baseline alues.

Nu ien s 2022,14, 2731 6 o 20
Table 1. Baseline cha ac e is ics o he s udy pa icipan s.
No. (%) a
Cha ac e is ics bCon ol (n= 49) In e en ion (n= 40)
Age, mean (SD), y 55.3 (8.5) 52.6 (7.1)
Sex, % Men 49 (100) 40 (100)
Educa ional le el
P ima y Educa ion 13 (26.5) 10 (25.0)
Seconda y Educa ion 10 (20.4) 6 (15.0)
Voca ional Educa ion 13 (26.5) 17 (42.5)
Highe Educa ion 13 (26.5) 7 (17.5)
Ma i al s a us
Single 7 (14.3) 2 (5.0)
Ma ied 34 (69.4) 34 (85.0)
Di o ced 8 (16.3) 4 (10.0)
Occupa ional s a us
Employed 27 (55.1) 21 (52.5)
Sel -employed 8 (16.3) 12 (30.0)
Unemployed 4 (8.2) 5 (12.5)
Re i ed 10 (20.4) 2 (5.0)
Medical Condi ions c
Hype ension 33 (67.4) 27 (67.5)
Diabe es Melli us II 12 (24.5) 10 (25.0)
Ca dio ascula disease 9 (18.4) 7 (17.5)
O he medical condi ions 29 (59.2) 26 (65.0)
Medica ion c
An ihype ensi e 31 (63.3) 24 (60.0)
S a ins 15 (30.6) 7 (17.5)
O al an idiabe ic 5 (10.2) 2 (5.0)
Insulin 3 (6.1) 1 (2.5)
Be a-blocke s 7 (14.3) 5 (12.5)
Polymedica ion d14 (28.6) 6 (15.0)
Body mass index, mean (SD), kg/m233.9 (4.8) 35.0 (6.0)
Body weigh , mean (SD), kg 99.6 (18.3) 103.3 (17.5)
Fa mass, mean (SD), kg 33.8 (9.0) 34.9 (10.6)
Visce al adipose issue, mean (SD), g 1049.2 (260.3) 1017.3 (285.2)
Neck ci cum e ence, mean (SD), cm 45.5 (3.9) 45.0 (3.8)
Ches ci cum e ence, mean (SD), cm 117.4 (9.9) 118.0 (10.3)
Wais ci cum e ence, mean (SD), cm 117.9 (12.2) 119.0 (12.4)
Apnea-hypopnea index, mean (SD), e en s/h
41.1 (21.3) 41.6 (23.5)
Obs uc i e sleep apnea se e i y
Nu ien s 2022,14, 2731 7 o 20
Table 1. Con .
No. (%) a
Cha ac e is ics bCon ol (n= 49) In e en ion (n= 40)
Mode a e 20 (40.8) 15 (37.5)
Se e e 29 (59.2) 25 (62.5)
Oxygen desa u a ion index, mean (SD),
e en s/h 45.4 (21.1) 45.4 (27.7)
Sleep e iciency, mean (SD), % 85.6 (8.1) 86.0 (9.1)
a
Resul s a e p esen ed as mean (s anda d de ia ion) o no mally dis ibu ed nume ical a iables and as absolu e
numbe ( ela i e equency) o ca ego ical a iables.
b
No signi ican be ween-g oup di e ences we e obse ed
in any o he baseline cha ac e is ics.
c
Pa icipan s could ha e mo e han one condi ion o medica ion.
d
De ined
as he use o i e o mo e medica ions.
3.2. Changes in Die a y Beha io
The e was a signi ican ly imp o emen in die a y beha io in he in e en ion g oup
han in he con ol g oup, wi h a mean be ween-g oup di e ence in FBC o al sco e o
8.7 (95% CI,
−
5.7 o
−
11.7; p< 0.001) and 7.7 (95% CI,
−
4.4 o 10.9; p< 0.001) om
baseline o in e en ion endpoin and 6 mon hs a e in e en ion, espec i ely (Table 2
and Figu e 2). Co espondingly, pa icipan s in he in e en ion g oup also signi ican ly
educed consump ion o swee ened be e ages (p< 0.05), inc eased consump ion o ui s
and ege ables (p< 0.001), and, hus, enhanced die quali y (p< 0.001) (FBC subscales).
Simila esul s we e ob ained using he pe -p o ocol app oach (Table S1). Acco ding o
changes om in e en ion endpoin o 6 mon hs a e in e en ion, pa icipan s in he
in e en ion g oup p ese ed imp o emen s in hese die a y beha io and die quali y
ou comes, al hough a sligh educ ion in ui s and ege ables consump ion was ound
(Table S2 and Figu e S1).
Rega ding adhe ence o he Medi e anean die , pa icipan s in he in e en ion g oup
also had a g ea e inc ease in he compliance wi h he Medi e anean die , as measu ed
by MEDAS a bo h in e en ion endpoin and 6 mon hs a e in e en ion, wi h mean
be ween-g oup di e ences o 2.1 (95% CI, 1.3 o 2.9; p< 0.001) and 1.7 (95% CI, 0.9 o 2.6;
p< 0.001), espec i ely (Table 2and Figu e 2). Simila esul s we e ob ained using he
pe -p o ocol app oach (Table S1). Imp o emen s in he adhe ence o he Medi e anean
die a he in e en ion endpoin we e main ained 6 mon hs a e in e en ion (Table S2
and Figu e S1).
3.3. Associa ion o Changes in Die a y Beha io o e Time wi h Changes in Sleep and Body Weigh
and Composi ion Ou comes
Changes in die a y beha io o e ime as measu ed by FBC o al sco e we e signi -
ican ly associa ed wi h changes in sleep ou comes; an inc ease in FBC o al sco e being
ela ed wi h educed AHI and oxygen desa u a ion index and inc eased sleep e iciency
(all p
≤
0.001; Table 3and Figu e 3). Wi h ega ds o body composi ion and an h opome ic
ou comes, changes o e ime in FBC o al sco e we e in e sely associa ed wi h changes in
body weigh , a mass, isce al adipose issue, and neck, ches , and wais ci cum e ences
(all p< 0.001; Table 3and Figu es 4and 5).
Simila ly, changes o e ime in adhe ence o he Medi e anean die as measu ed
by MEDAS o al sco e we e signi ican ly associa ed wi h changes in sleep ou comes, an
inc ease in MEDAS o al sco e being ela ed o educed AHI and oxygen desa u a ion
index and inc eased sleep e iciency (all p< 0.001; Table 3and Figu e 3). Inc eases o e
ime in MEDAS o al sco e we e also associa ed wi h educ ions in body weigh , a mass,
isce al adipose issue, and neck, ches , and wais ci cum e ences (all p< 0.001; Table 3and
Figu es 4and 5).
Nu ien s 2022,14, 2731 8 o 20
Table 2. Die a y beha io ou comes.
Ou comes
Con ol (n= 49) In e en ion (n= 40) Di e ence be ween
G oups, Mean (95% CI) a
Mean (95% CI) Change om Baseline,
Mean (95% CI) Mean (95% CI) Change om Baseline,
Mean (95% CI)
Food Beha io Checklis , o al sco e d
A baseline 59.1 (56.8 o 61.4) 59.5 (56.9 o 62.0)
A 8 weeks 62.4 (59.9 o 64.9) 3.3 (0.6 o 5.9) 71.5 (68.9 o 74.0) 12.0 (9.5 o 14.5) 8.7 (5.7 o 11.7) c
A 6 mon hs 60.6 (57.9 o 63.4) 1.5 (−1.4 o 4.4) 68.6 (66.0 o 71.3) 9.2 (6.5 o 11.9) 7.7 (4.4 o 10.9) c
F ui and ege ables consump ion sco e
A baseline 21.5 (20.0 o 22.9) 22.6 (21.0 o 24.2)
A 8 weeks 23.1 (21.5 o 24.7) 1.6 (−0.2 o 3.4) 29.5 (27.9 o 31.1) 6.9 (5.2 o 8.6) 5.2 (3.2 o 7.3) c
A 6 mon hs 22.4 (20.7 o 24.2) 0.9 (−1.0 o 2.9) 27.5 (25.8 o 29.1) 4.9 (3.0 o 6.7) 3.9 (1.7 o 6.1) c
Milk/dai y consump ion sco e
A baseline 6.0 (5.5 o 6.4) 5.8 (5.3 o 6.3)
A 8 weeks 5.6 (5.1 o 6.2) −0.3 (−0.9 o 0.2) 5.7 (5.2 o 6.2) −0.1 (−0.6 o 0.4) 0.2 (−0.4 o 0.8)
A 6 mon hs 5.9 (5.3 o 6.4) −0.1 (−0.7 o 0.5) 5.4 (4.9 o 6.0) −0.4 (−0.9 o 0.2) −0.3 (−1.0 o 0.4)
Food secu i y sco e
A baseline 3.1 (2.9 o 3.4) 3.1 (2.8 o 3.3)
A 8 weeks 3.3 (3.0 o 3.5) 0.1 (−0.2 o 0.4) 3.1 (2.8 o 3.4) 0.1 (−0.2 o 0.4) −0.1 (−0.4 o 0.3)
A 6 mon hs 3.2 (3.0 o 3.5) 0.1 (−0.2 o 0.4) 3.2 (2.9 o 3.5) 0.2 (−0.2 o 0.5) 0.1 (−0.3 o 0.5)
Die quali y sco e
A baseline 9.9 (9.3 o 10.5) 9.7 (9.0 o 10.4)
A 8 weeks 10.5 (9.9 o 11.2) 0.7 (−0.1 o 1.4) 12.2 (11.5 o 12.8) 2.5 (1.8 o 3.2) 1.8 (1.0 o 2.6) c
A 6 mon hs 10.3 (9.5 o 11.0) 0.4 (−0.4 o 1.2) 11.8 (11.1 o 12.5) 2.1 (1.4 o 2.9) 1.7 (0.8 o 2.6) c
Nu ien s 2022,14, 2731 9 o 20
Table 2. Con .
Ou comes
Con ol (n= 49) In e en ion (n= 40) Di e ence be ween
G oups, Mean (95% CI) a
Mean (95% CI) Change om Baseline,
Mean (95% CI) Mean (95% CI) Change om Baseline,
Mean (95% CI)
Fas ood consump ion sco e
A baseline 7.4 (7.0 o 7.9) 7.2 (6.7 o 7.7)
A 8 weeks 8.2 (7.6 o 8.8) 0.8 (−0.1 o 1.6) 8.6 (8.1 o 9.1) 1.4 (0.6 o 2.2) 0.6 (−0.3 o 1.6)
A 6 mon hs 7.7 (7.1 o 8.4) 0.3 (−0.6 o 1.2) 8.3 (7.8 o 8.9) 1.1 (0.3 o 2.0) 0.8 (−0.2 o 1.9)
Swee ened be e ages consump ion sco e
A baseline 6.7 (6.5 o 7.0) 6.6 (6.3 o 6.9)
A 8 weeks 7.1 (6.8 o 7.4) 0.3 (−0.1 o 0.7) 7.5 (7.2 o 7.8) 0.9 (0.5 o 1.3) 0.5 (0.1 o 1.0) b
A 6 mon hs 6.9 (6.5 o 7.2) 0.1 (−0.3 o 0.6) 7.4 (7.1 o 7.7) 0.7 (0.3 o 1.1) 0.6 (0.1 o 1.1) b
Mea consump ion sco e
A baseline 1.9 (1.6 o 2.1) 1.9 (1.6 o 2.2)
A 8 weeks 2.1 (1.8 o 2.5) 0.3 (−0.2 o 0.8) 2.3 (2.0 o 2.6) 0.4 (−0.1 o 0.9) 0.1 (−0.5 o 0.7)
A 6 mon hs 2.0 (1.7 o 2.4) 0.2 (−0.4 o 0.7) 2.5 (2.1 o 2.8) 0.6 (0.1 o 1.1) 0.4 (−0.2 o 1.0)
Medi e anean Die Adhe ence Sc eene ,
o al sco e e
A baseline 8.2 (7.7 o 8.7) 8.1 (7.6 o 8.6)
A 8 weeks 8.8 (8.2 o 9.4) 0.6 (−0.1 o 1.3) 10.7 (10.2 o 11.3) 2.7 (1.9 o 3.3) 2.1 (1.3 o 2.9) c
A 6 mon hs 8.5 (7.9 o 9.1) 0.3 (−0.5 o 1.1) 10.1 (9.6 o 10.7) 2.0 (1.3 o 2.8) 1.7 (0.9 o 2.6) c
Abb e ia ions: CI, con idence in e al.
a
Using he g oup
×
isi in e ac ion e m om a linea mixed-e ec s model, including s udy g oup, ime (baseline, 8 weeks and 6 mon hs),
and s udy g oup
×
ime as ixed e ec s and pa icipan as andom e ec s.
b
p< 0.05 om he ime
×
s udy g oup in e ac ions.
c
p< 0.001 om he ime
×
s udy g oup in e ac ions.
d
The Food Beha io Checklis assesses die a y beha io ( ange, 23–85; highe sco es indica e heal hie die a y beha io ) [
45
].
e
The Medi e anean Die Adhe ence Sc eene assesses
adhe ence o he Medi e anean die ( ange, 0–14; highe sco es indica e g ea e adhe ence; sco es ≥10 indica e high adhe ence o he Medi e anean die ) [46].
Nu ien s 2022,14, 2731 16 o 20
4. Discussion
The p esen s udy demons a es ha an eigh -week in e disciplina y weigh loss and
li es yle in e en ion, inco po a ing no only a nu i ional beha io change componen
bu also inc eased physical ac i i y, sleep hygiene, and alcohol and obacco a oidance is
e ec i e a signi ican ly imp o ing die a y beha io in men wi h CPAP- ea ed mode a e-
o-se e e OSA and o e weigh /obesi y. Acco ding o he esul s epo ed he ein, he
weigh loss and li es yle in e en ion g oup had 20% and 15% inc eases in heal h ul die a y
beha io as measu ed by FBC a in e en ion endpoin and 6 mon hs a e in e en ion,
espec i ely. Simila ly, pa icipan s om his g oup epo ed 33% and 25% inc eases a
in e en ion endpoin and 6 mon hs a e in e en ion, espec i ely, in adhe ence o he
Medi e anean die , as measu ed by MEDAS. Impo an ly, hese imp o emen s in die a y
beha io and inc eases in adhe ence o he Medi e anean die o e ime we e closely
ela ed o imp o emen s in sleep, body composi ion, and an h opome ic ou comes.
These esul s a e consis en wi h he limi ed exis ing e idence suppo ing he bene i-
cial e ec s o beha io al weigh loss in e en ions p omo ing nu i ional educa ion and
beha io change on die a y beha io , die quali y, and/o adhe ence o he Medi e anean
die [
29
–
33
]. Pa node e al. [
29
], in a sys ema ic e iew o he U.S. P e en i e Se ices
Task Fo ce, ound ha heal h ul die in e en ions in adul s wi hou known ca dio ascula
disease isk ac o s we e ela ed o educed o al ene gy and sa u a ed a in ake and in-
c eased ibe and ui s and ege ables consump ion. Simila ly, a sys ema ic e iew by Lin
e al. [
30
,
31
], based on a la ge body o e idence (76 ials), also de e mined ha an in ensi e
combined li es yle counseling signi ican ly imp o ed die a y beha io in pa icipan s wi h
ca dio ascula disease isk ac o s.
S udies explo ing he e ec s o hese die a y and/o li es yle app oaches on die a y
pa e ns and quali y o he die in adul s wi h mode a e- o-se e e OSA a e cu en ly
lacking. Mos p e ious s udies in his ega d only included calo ie- es ic ed die s [
25
],
which, as shown by he Look AHEAD (Ac ion o Heal h in Diabe es) s udy [
49
]— he
la ges andomized ial in his ield o esea ch — may no be he mos -e icien app oach
o die quali y and sus ainable die a y beha io change [
26
,
27
]. Acco ding o co obo a i e
e idence, calo ic es ic ion may esul in compensa o y changes ha cause inc eased
hunge and, in u n, inc eased ene gy in ake as a homeos a ic esponse o a loss [
26
,
50
].
Fu he mo e, calo ic es ic ion has also been associa ed wi h a compensa o y educ ion
in ene gy expendi u e ha p e en s weigh loss in he long e m [
50
]. Mos impo an ly,
his app oach is no ocused on changing die a y pa e ns and die quali y in he long e m,
which a e he key ac o s o weigh loss and bene i s main enance.
The cu en s udy is he i s o epo he bene icial e ec s o an in e disciplina y
weigh loss and li es yle in e en ion on die a y beha io and he associa ion o hese
changes wi h changes in OSA se e i y and ela ed ou comes in adul s wi h mode a e- o-
se e e OSA. Rema kably, hose pa icipan s who achie ed heal hie die a y beha io and
g ea e adhe ence o he Medi e anean die also exhibi ed lowe OSA se e i y, g ea e
weigh loss, and enhanced body composi ion and an h opome ic pa ame e s. The e o e,
nu i ional educa ion and beha io change, ocusing on mac onu ien s in ake and p o-
mo ing he Medi e anean die , is an impo an in e en ion componen o be conside ed
and included in weigh loss and li es yle in e en ions o he managemen o OSA. The
Medi e anean die has been shown o ha e g ea e long- e m bene icial e ec s on weigh
s a us and wais ci cum e ence han low- a and calo ie- es ic ed die s among indi iduals
wi h ype 2 diabe es and o he ca dio ascula isk ac o s [
51
]. In adul s wi h OSA, he
Medi e anean die has also been shown o be ela ed wi h educ ions in body weigh and
abdominal a , which is associa ed wi h educ ions in OSA se e i y [
28
]. Fu he mo e,
gi en i s an i-in lamma o y and an ioxidan p ope ies, he Medi e anean die may po-
en ially comba he in lamma ion and oxida i e s ess ound in OSA, he eby imp o ing
he uppe -ai way neu omuscula con ol and muscle o ce-gene a ing capaci y and hus
p e en ing he occu ence o he uppe -ai way obs uc ions du ing sleep [26].

Nu ien s 2022,14, 2731 17 o 20
The main s eng h o he cu en s udy is he design and implemen a ion o a no el in-
e disciplina y weigh loss and li es yle in e en ion eadily adap able o eal-wo ld clinical
p ac ice. Ano he no able s eng h is he measu emen o sleep and OSA se e i y h ough
a ull-nigh in-labo a o y polysomnog aphy— he gold-s anda d o he measu emen o
hese ou comes—a each s udy assessmen (baseline, in e en ion endpoin , and 6 mon hs
a e in e en ion). Ne e heless, a limi a ion o he s udy design is he sole inclusion o
men wi h mode a e- o-se e e OSA and o e weigh /obesi y in ou sample, which es ic s
he gene aliza ion o ou indings. Fu he mo e, he s udy du a ion may ha e no been
su icien o de e mine long- e m in e en ion e ec s and bene i s main enance. Ano he
limi a ion is he subjec i e assessmen o die a y beha io and adhe ence o he Medi e -
anean die h ough he FBC and MEDAS, which, al hough widely used, a e sel - epo ed
ques ionnai es. The e o e, u u e well-designed s udies, including women, longe - e m
ollow-ups, and objec i e die a y beha io assessmen s a e needed.
5. Conclusions
In conclusion, in his s udy in ol ing men wi h mode a e- o-se e e OSA and o e -
weigh /obesi y, an eigh -week in e disciplina y weigh loss and li es yle in e en ion,
including die a y beha io change, mode a e-in ensi y ae obic exe cise, sleep hygiene,
and obacco and alcohol a oidance, was ela ed o signi ican imp o emen s in die a y
beha io and adhe ence o he Medi e anean die . Gi en he bene icial e ec s o die a y
beha io change in e en ions and he Medi e anean die on weigh loss and OSA se e i y,
app oaches including hese die a y componen s should be he s a egy o choice o he
comp ehensi e managemen o his inc easingly common sleep-diso de ed b ea hing.
Supplemen a y Ma e ials:
The ollowing suppo ing in o ma ion can be downloaded a : h ps://
www.mdpi.com/a icle/10.3390/nu14132731/s1, Table S1: Die a y beha io ou comes (Pe p o ocol);
Table S2: Die a y beha io ou comes (change om 8 weeks o 6 mon hs a e in e en ion); Figu e S1:
Die a y beha io ou comes (change om 8 weeks o 6 mon hs a e in e en ion).
Au ho Con ibu ions:
Concep ualiza ion, A.C.-B., F.J.T. and J.R.R.; me hodology, A.C.-B., F.J.A.-
G. and L.J.-F.; o mal analysis, A.C.-B.; in es iga ion, A.C.-B., F.J.A.-G., L.J.-F., G.S.-R. and C.M.-C.;
esou ces, A.C.-B., F.J.T. and J.R.R.; da a cu a ion, A.C.-B.; w i ing—o iginal d a p epa a ion,
A.C.-B.
;
w i ing— e iew and edi ing, all au ho s; unding acquisi ion, A.C.-B., F.J.A.-G., L.J.-F. and J.R.R. All
au ho s ha e ead and ag eed o he published e sion o he manusc ip .
Funding:
This s udy was suppo ed by he Spanish Minis y o Educa ion and Voca ional T aining,
h ough g an s p o ided o A.C.-B. (FPU16/01093), F.J.A.-G. (FPU14/04172), and L.J.-F. (FPU19/01609);
he Uni e si y o G anada-LoMonaco S.L. Sleep Resea ch Ca hed a; he Uni e si y o G anada
Plan P opio de In es igación 2016–Excellence ac ions: Uni o Excellence on Exe cise and Heal h
(UCEES) and he Regional Minis y o Economy, Knowledge, En e p ise, and Uni e si ies (CECEU)
o Andalusia (Eu opean Regional De elopmen Funds, SOMM17/6107/UGR).
Ins i u ional Re iew Boa d S a emen :
The s udy was conduc ed in acco dance wi h he Decla-
a ion o Helsinki and app o ed by he Ins i u ional Re iew Boa ds o he Uni e si y o G anada
(G anada, Spain), Vi gen de las Nie es Uni e si y Hospi al (G anada, Spain), and Jun a de Andalucía
(Spain) (0770-N-19).
In o med Consen S a emen :
In o med consen was ob ained om all subjec s in ol ed in he s udy.
Da a A ailabili y S a emen :
Reques s o da a can be made o A.C.-B. (aca nei o@ug .es). Da a, code
book, and analy ic code will be made a ailable upon eques subjec o eam e iew and app o al o
he p oposed analysis.
Acknowledgmen s:
We hank pa icipan s o hei in ol emen in he INTERAPNEA s udy; and Lo
Monaco S.L. and TEA Ediciones S.A. o he alued equipmen and echnical suppo ecei ed o
he esea ch.
Con lic s o In e es :
The au ho s decla e no con lic o in e es . The unde s had no ole in he design
o he s udy; in he collec ion, analyses, o in e p e a ion o da a; in he w i ing o he manusc ip ; o
in he decision o publish he esul s.
Nu ien s 2022,14, 2731 18 o 20
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