The Long-Term Consumption of Oats in Celiac Disease Patients Is Safe: A Large Cross-Sectional Study

nu ien s A icle The Long-Te m Consump ion o Oa s in Celiac Disease Pa ien s Is Sa e: A La ge C oss-Sec ional S udy Ka i Aal onen 1,2, Pil i Lau ikka 3, Heini Huh ala 4, Ma kku Mäki 1, Ka i Kaukinen 2,3,5 and Kalle Ku ppa 1,* 1Cen e o Child Heal h Resea ch, Tampe e Uni e si y Hospi al, 33521 Tampe e, Finland; [email p o ec ed] (K.A.); [email p o ec ed] (M.M.) 2The Facul y o Medicine and Li e Sciences, Uni e si y o Tampe e, 33014 Tampe e, Finland; [email p o ec ed] 3Celiac Disease Resea ch Cen e, Tampe e Uni e si y Hospi al, 33521 Tampe e, Finland; [email p o ec ed] 4Facul y o Social Sciences, Uni e si y o Tampe e, 33014 Tampe e, Finland; [email p o ec ed] 5Depa men o In e nal Medicine, Tampe e Uni e si y Hospi al, 33521 Tampe e, Finland *Co espondence: [email p o ec ed]; Tel.: +358-3-3551-8403 Recei ed: 17 May 2017; Accep ed: 12 June 2017; Published: 15 June 2017 Abs ac : A s ic glu en- ee die (GFD) can be di e si ied by non-con amina ed oa s, bu he e is a sho age o long- e m s udies conce ning i s sa e y. We compa ed long- e m ea men ou comes and ac o s associa ed wi h he in oduc ion o oa s be ween celiac pa ien s on a GFD wi h o wi hou oa s. Eigh hund ed six y-nine p e iously diagnosed celiac pa ien s we e in e iewed. The alida ed Gas oin es inal Symp om Ra ing Scale (GSRS), Psychological Gene al Well-Being (PGWB), and Sho -Fo m 36 Heal h Su ey (SF-36) ques ionnai es we e used o assess symp oms and quali y o li e, se ological es s we e pe o med, and esul s o his ology we e con i med om pa ien eco ds. We ound he median du a ion o GFD o be 10 yea s and 82% using oa s. Fac o s p edic ing he consump ion o oa s we e diagnosis a e he yea 2000, ad ice om a die i ian, de ec ion by sc eening, and mild clinical p esen a ion. Oa consume s and non-consume s did no di e in die a y adhe ence (96.5% s. 97.4%, p= 0.746), he p e alence o symp oms (22.9% s. 22.5%, p= 0.931), posi i i y o endomysial an ibodies (8.8% s. 6.0%, p= 0.237), his ological eco e y a e one yea (63.1% s. 60.0%, p= 0.773), malignancy (4.8% s. 3.3%, p= 0.420), os eopo osis/os eopenia (9.2% s. 11.0%, p= 0.489), o ac u es (26.9% s. 27.9%, p= 0.791). The oa consume s had be e SF-36 physical ole limi a ions and gene al heal h sco es. Based on ou esul s, he long- e m consump ion o oa s in celiac disease pa ien s is sa e and may imp o e quali y o li e. Keywo ds: glu en- ee die ; ea men ; complica ions; symp oms; quali y o li e 1. In oduc ion By eason o inc easing ecogni ion o he di e se clinical p esen a ion o celiac disease, combined wi h new se ological ools o i s de ec ion, he condi ion has eme ged as one o he mos common nu i ion- ela ed diseases [ 1 , 2 ]. The ue incidence o he disease seems also o be ising, u he emphasizing he conside able public heal h and economic signi icance o i s op imal managemen [3,4] . In heo y, ea men is simple, as he essen ial en i onmen al igge , glu en, is known and can be elimina ed by a glu en- ee die (GFD). No wi hs anding i s undispu able bene icial e ec s, a li e-long GFD has i s disad an ages. I is challenging o main ain and may lead o a es ic ed and nu i ionally subop imal die . Fu he , many GFD p oduc s ha e low ibe and high a and suga con en , p edisposing pa ien s o example o cons ipa ion, obesi y, and ca dio ascula diseases [5,6]. Nu ien s 2017,9, 611; doi:10.3390/nu9060611 www.mdpi.com/jou nal/nu ien s Nu ien s 2017,9, 611 2 o 11 The mains ay o he GFD is he exclusion o die a y whea , ba ley, and ye, while he consump ion o oa s emains con o e sial. Oa s ha e di e en s o age p o ein composi ion han he h ee o he ce eals, and he sho - e m sa e y o oa s in celiac disease pa ien s was p oposed as a back as he 1990s [ 7 ] and u he suppo ed by subsequen clinical ials [ 8 – 10 ]. In some s udies, howe e , oa s we e ound o cause symp oms o e en occasional small-in es inal damage [ 11 , 12 ] o o igge immunological esponses in expe imen al models [ 13 , 14 ]. The possibili y o using oa s would ha e a majo heal h impac , as i is nu i ious and a good sou ce o ibe , which may educe cons ipa ion and he isk o ype 2 diabe es [ 8 ]. Oa s may also lowe ha m ul choles e ol le els, enhance immune de ense, and p o ec agains hea disease and cance [ 15 – 17 ]. Finally, oa s could di e si y he GFD and educe indi idual a and suga in ake. The main limi a ion in he cu en e idence o he consump ion o oa s in celiac disease pa ien s is he sca ci y o long- e m s udies [ 8 , 18 ]. Mo e in o ma ion would be needed, in pa icula ega ding his ological and se ological healing and quali y o li e. In Finland, oa s has adi ionally been a majo ing edien in he daily die , and in pu i ied o m i was accep ed mo e han 15 yea s ago and widely used among celiac disease pa ien s [ 19 ]. This p o ided an excellen oppo uni y o compa e long- e m ea men ou comes be ween la ge and well-de ined coho s o pa ien s on a GFD wi h o wi hou oa s. Addi ionally, we in es iga ed ac o s associa ed wi h he in oduc ion o oa s as a pa o he GFD a he ime o he celiac disease diagnosis. 2. Ma e ials and Me hods 2.1. Pa ien s and S udy Design P e iously diagnosed biopsy-p o en celiac disease pa ien s who had been on a GFD o a iable pe iods o ime we e ec ui ed by a na ionwide sea ch ia newspape ad e isemen s and wi h he help o na ional and local celiac disease socie ies. The o iginal diagnosis could ha e been made a any age, bu in he p esen s udy only pa ien s cu en ly o e 16 yea s o age we e included. Exclusion c i e ia we e uncon i med diagnosis and ma kedly lacking medical in o ma ion ei he be o e o a he ime o he diagnosis. A e en e ing he s udy, all olun a y pa icipan s we e in e iewed wi h s uc u ed ques ions by an expe ienced physician o s udy nu se. The in e iewe s sys ema ically es ablished a a ie y o celiac disease- ela ed clinical and demog aphic da a as de ined below in de ail. Fu he , he pa icipan s illed s uc u ed gas oin es inal symp om and quali y o li e ques ionnai es, and labo a o y samples we e d awn o u he se ological analyses. Besides pe sonal in e iews, he medical eco ds o each pa ien we e scanned in o de o con i m he celiac disease diagnosis and clinical da a, and o u he explo e all ele an his ological and se ological indings and labo a o y alues. A e da a collec ion, he pa icipan s we e di ided in o wo g oups based on he consump ion o non-consump ion o oa s in hei GFD, and all s udy a iables we e compa ed be ween hese g oups. The E hical Commi ee o Pi kanmaa Hospi al Dis ic app o ed he s udy design, pa ien ec ui men , and da a collec ion. W i en in o med consen was ob ained om all en olled pa icipan s. 2.2. Clinical In o ma ion Demog aphic da a, celiac disease in he amily, ime, and si e (p ima y ca e, seconda y ca e o e ia y ca e, p i a e sec o ) o he diagnosis, clinical p esen a ion (e.g., gas oin es inal symp oms, ex ain es inal symp oms, and de ec ed by sc eening), p e ious and cu en smoking, and he p esence o celiac disease-associa ed (e.g., de ma i is he pe i o mis, ype 1 diabe es, and au oimmune hy oidal disease) o o he ch onic diseases and malignancies we e es ablished. In addi ion, he p e alence o os eopo osis, os eopenia, and any ac u es was explo ed. The du a ions o symp oms be o e diagnosis (<1 yea , 1–5 yea s, >5 yea s) and hei se e i y (mild, mode a e, se e e) bo h a diagnosis and a p esen we e eco ded. The yea o he diagnosis was u he sub-classi ied as be o e 1990, be ween 1990 and 1999, and a e 2000. The in e iewe s also inqui ed whe he pa icipan s had egula ollow-up by heal h ca e. Nu ien s 2017,9, 611 3 o 11 2.3. Se ology and His ology Cu en se um IgA-class endomysial (EmA) and ansglu aminase 2 (TG2ab) an ibody alues we e measu ed in all pa icipan s upon s udy en y. EmA was assessed by indi ec immuno luo escence using a human umbilical co d as subs a e. Ti e s o 1: ≥ 5 we e conside ed posi i e and u he dilu ed up o 1:4000 un il nega i e. TG2ab we e assessed by comme cial enzyme-linked immunoso ben assay (QUANTA Li e h- TG IgA, INOVA Diagnos ics, San Diego, CA, USA), and alues >40 U/L we e conside ed posi i e. The co esponding IgG-class EmA and TG2ab an ibodies we e measu ed in pa ien s wi h selec i e IgA de iciency. Since no maliza ion o he an ibodies on a GFD may ake some ime [ 8 , 19 , 20 ], subjec s die ing o less han wo yea s we e excluded om he se ological ollow-up analyses. Resul s o diagnos ic and ollow-up biopsies a e one yea on GFD we e collec ed om he hospi al pa hology epo s. In ou clinical ou ine, se e al small-bowel mucosal biopsies a e aken om each pa ien bo h upon celiac disease suspicion and du ing he ollow-up endoscopy. The his ological samples a e hen o wa ded o he pa hology depa men , whe e well-o ien a ed specimens a e ca e ully e alua ed acco ding o ou s anda d ope a ing p ocedu es [ 21 ]. Se e i y o mucosal damage is u he ca ego ized as pa ial (PVA), sub o al (SVA), o o al (TVA) illous a ophy, hese co esponding oughly o Ma sh–Obe hübe g ades IIIa, IIIb, and IIIc. 2.4. Ques ionnai es Sel -pe cei ed gas oin es inal symp oms we e in es iga ed wi h a alida ed Gas oin es inal Symp om Ra ing Scale (GSRS) ques ionnai e. The su ey consis s o 15 sepa a e que ies, which can be di ided in o i e sub-domains: indiges ion, dia hea, cons ipa ion, abdominal pain, and e lux. Each sub-sco e is calcula ed as he a e age o h ee ele an i ems and he o al sco e as he a e age o all 15 i ems. Answe s a e sco ed using a se en-g ade Like scale (possible poin s om 1 o 7) wi h highe sco es deno ing mo e se e e gas oin es inal symp oms [22]. The Sho -Fo m 36 Heal h Su ey (SF-36) was used o assess quali y o li e and gene al heal h [ 23 , 24 ]. I comp ises 36 i ems ep esen ing eigh di e en sub-sec ions: physical unc ioning, physical ole limi a ions, emo ional ole limi a ions, i ali y, men al heal h, social unc ioning, bodily pain, and gene al heal h. Each i em is sco ed om 0 o 100, and he i ems in he same sec ion a e a e aged oge he o o m he eigh sepa a e sub-dimensions. Highe sco es indica e be e heal h and social unc ioning. The Psychological Gene al Well-Being (PGWB) ques ionnai e is ano he widely used measu e o quali y o li e and gene al well-being [ 25 ]. PGWB consis s o 22 ques ions ep esen ing six di e en sub-domains as ollows: anxie y, dep ession, well-being, sel -con ol, gene al heal h, and i ali y. The i ems use a six-g ade scale (poin s om 1 o 6) and he sco es a e added oge he in each di e en sub-domain and as a o al sco e ha can ange om 22 o 132 poin s. Highe sco es indica e be e heal h- ela ed quali y o li e and well-being [26]. 2.5. Glu en-F ee Die Du a ion and s ic ness o he GFD we e asked om all pa icipan s. Sel - epo ed die a y adhe ence was u he classi ied as s ic GFD (no lapses), occasional lapses (lapses less han once a mon h), and no GFD (mo e common lapses). In addi ion, he sou ce o die a y ad ice a he ime o diagnosis was es ablished and ca ego ized as no ad ice, die i ian, o o he (e.g., physician o nu se). Finally, egula consump ion o oa s as pa o he GFD was asked abou and classi ied as ei he use o no use. The GFD label may be used o uncon amina ed oa s p oduc s ha con ain glu en less han 20 pa s pe million. Nu ien s 2017,9, 611 4 o 11 2.6. S a is ical Analysis Ca ego ical a iables a e p esen ed as pe cen ages and con inuous a iables as medians wi h anges o wi h qua iles as app op ia e. Ca ego ical a iables we e compa ed using c oss- abula ion wi h a chi-squa e es . To compa e medians be ween he s udy g oups, he non-pa ame ic Mann–Whi ney U es was used. All s a is ical analyses we e made using SPSS e sion 23. p- alues < 0.05 we e conside ed s a is ically signi ican . Age and sex we e conside ed as possible con ounding ac o s in each analysis. 3. Resul s 3.1. Baseline Da a and Fac o s P edic ing Oa Consump ion Al oge he 869 indi iduals (median age 53 yea s, emales 75.5%) ul illed he s udy c i e ia and we e en olled. O hese, 715 (82%) consumed oa s as pa o hei GFD. A he ime o celiac disease diagnosis 4.4% o he pa icipan s we e unde 16 yea s o age. Oa -consume s we e a ew yea s olde a diagnosis, while he e was no di e ence in gende dis ibu ion (Table 1). Fac o s p edic ing oa -consump ion in he GFD we e celiac disease diagnosis a e he yea 2000, de ec ion o he disease by sc eening, mild clinical p esen a ion a diagnosis, and die a y ad ice gi en by a die i ian. The consump ion o oa s was no dependen on amily his o y o celiac disease, si e o diagnosis, du a ion o symp oms be o e diagnosis, o se e i y o small-bowel mucosal damage (Table 1). 3.2. Follow-Up Resul s The e we e no signi ican di e ences in cu en ages be ween he wo s udy g oups, bu hose consuming oa s had on a e age been a sho e ime on a GFD be o e en olmen (Table 2). Howe e , pa ien s in bo h g oups had been on a GFD app oxima ely a median o 10 yea s (Table 2). They epo ed excellen and compa able die a y adhe ence, and he e we e also no signi ican di e ences be ween he g oups in cu en sel - epo ed symp oms, esul s o ollow-up biopsy o p e alence o celiac disease au oan ibody posi i i y (Table 2). In addi ion, he median TG2ab alues we e a he same le el (oa s 12.0 U/L s. no oa s 10.0 U/L, p= 0.077). The s udy g oups did no di e in he p e alence o os eopo osis, ac u es, o malignancies, bu subjec s on he oa -con aining GFD we e less o en cu en smoke s (Table 2). Fu he , hey we e mo e o en comple ely ee o o he ch onic diseases (16.9% s. 10.4%, p- alue = 0.044). In mo e de ailed analysis, howe e , no signi ican di e ences be ween he g oups we e ound in he p e alence o any speci ic celiac disease-associa ed condi ion (e.g., ype 1 diabe es o au oimmune hy oidal disease) o o he ch onic disease when ca ego ized in o majo disease g oups (me abolic, endoc inological, hema ologic, immunologic, oph halmologic, o ola yngological, gas oen e ological, psychia ic, espi a o y, locomo o , neu ological, gynecological, u ologic, and ca dio ascula diso de s) (da a no shown). Fu he mo e, he e was no signi ican di e ence be ween oa consume s and non-consume s in a endance o egula ollow-up by heal h ca e (Table 2). In line wi h he cu en sel -es ima ed o e all symp oms, he g oups showed no di e ence in GSRS o al o any sub-dimension sco es (Table 3). The e was no di e ence in heal h- ela ed quali y o li e when measu ed by PGWB o al and sub-sco es, bu in SF-36 oa -consume s yielded be e sco es on physical ole limi a ions and gene al heal h (Table 3). Nu ien s 2017,9, 611 5 o 11 Table 1. Clinical and his ological cha ac e is ics and p esence o die a y ad ice a diagnosis in 869 celiac disease pa ien s cu en ly on a glu en- ee die wi h o wi hou oa s. Oa s n= 715 No Oa s n= 154 % % p-Value Age a diagnosis, median ( ange), yea s 43 (1–81) 41 (1–79) 0.048 Females 75.9 73.4 0.502 Celiac disease in he amily 66.9 66.0 0.824 Si e o diagnosis 0.789 P ima y ca e 14.4 12.3 Seconda y ca e o e ia y ca e 72.7 74.0 P i a e sec o 12.9 13.6 Yea o diagnosis <0.001 <1990 16.4 32.5 1990–1999 33.3 31.2 2000– 50.3 36.4 Clinical p esen a ion a diagnosis 0.004 Gas oin es inal symp oms 156.6 65.6 Ex ain es inal symp oms 228.1 29.2 Sc een-de ec ed in a - isk g oups 315.2 5.2 Se e i y o symp oms be o e diagnosis 40.006 No o mild 37.2 23.7 Mode a e 12.6 9.6 Se e e 50.2 66.7 Du a ion o symp oms be o e diagnosis 0.186 <1 yea 22.2 24.3 1–5 yea s 35.8 27.8 >5 yea s 42.0 47.9 Diagnos ic his ology 0.726 To al illous a ophy 26.4 24.0 Sub o al illous a ophy 37.6 41.3 Pa ial illous a ophy 36.0 34.7 Die a y ad ice a diagnosis 0.006 No ad ice 19.7 27.2 Die i ian 69.3 55.8 Physician/nu se/o he 11.0 17.0 1 E.g., abdominal pain, cons ipa ion, dia hea, malabso p ion. 2 E.g., a h i is, den al enamel de ec s, in e ili y, neu ologic symp oms, os eopo osis. 3 E.g., ela i es o he pa ien s and subjec s wi h ype 1 diabe es melli us o au oimmune hy oidal disease. Da a we e a ailable in >90% o he subjec s in each ca ego y excep in 474%. Table 2. Age a he cu en s udy and a a ie y o ollow-up da a in 869 celiac disease pa ien s cu en ly on a glu en- ee die (GFD) wi h o wi hou pu i ied oa s. Oa s n= 715 No Oa s n= 154 % % p-Value Age a p esen , median ( ange), yea s 53 (17–89) 55 (21–85) 0.716 Time on GFD, median ( ange), yea s 9 (1–47) 13 (1–53) <0.001 Cu en sel - epo ed die a y adhe ence 0.746 S ic GFD 96.5 97.4 Occasional lapses 3.2 2.6 No GFD 0.3 0.0 Cu en sel - epo ed symp oms 0.931 No 75.5 75.5 Mild o mode a e 22.9 22.5 Se ious 1.6 2.0 Follow-up his ology on a GFD 10.773 Healed mucosa 63.1 60.0 In lamma ion/pa ial illous a ophy 33.5 35.3 Sub o al/ o al illous a ophy 3.4 4.7 Nu ien s 2017,9, 611 6 o 11 Table 2. Con . Oa s n= 715 No Oa s n= 154 % % p-Value Follow-up se ology on a GFD 2 Posi i e EmA 8.8 6.0 0.273 Posi i e TG2ab 12.2 10.1 0.471 Any malignancy 4.8 3.3 0.420 Os eopo osis o os eopenia 9.2 11.0 0.489 Any ac u e 26.9 27.9 0.791 Cu en smoking 8.2 14.9 0.009 Regula ollow-up by he heal h ca e 29.0 28.7 0.926 1 Follow-up biopsy was aken a e a median o one yea ( ange: 1–25 yea s) in bo h g oups. 2 Pa ien s wi h a GFD less han wo yea s we e excluded om he analysis. EmA: Endomysial an ibodies; TG2ab: T ansglu aminase 2 an ibodies. Da a we e a ailable in >90% o he subjec s in each a iable excep in ollow-up his ology 54%. Table 3. Gas oin es inal Symp om Ra ing Scale (GSRS), Sho -Fo m (36) Heal h Su ey (SF-36), and Psychological Gene al Well-Being (PGWB) ques ionnai e sco es in 590 celiac disease pa ien s cu en ly on a glu en- ee die wi h o wi hou oa s. Oa s n= 484 No Oa s n= 106 Median Qua iles Median Qua iles p-Value GSRS sco es 1 To al 1.9 1.5–2.5 2.0 1.5–2.7 0.460 Indiges ion 2.3 1.8–3.3 2.5 1.7–3.3 0.864 Dia hea 1.3 1.9–2.3 1.7 1.0–2.3 0.164 Cons ipa ion 1.7 1.0–2.7 2.0 1.0–2.7 0.318 Abdominal pain 2.0 1.3–2.3 2.0 1.3–2.7 0.506 Re lux 1.5 1.0–2.0 1.5 1.0–2.5 0.329 SF-36 sco es 2 Physical Func ioning 95 80–100 90 69–100 0.081 Role limi a ions, physical 100 50–100 75 25–100 0.020 Role limi a ions, emo ional 100 67–100 100 67–100 0.802 Vi ali y 70 55–85 70 55–85 0.808 Men al heal h 80 72–88 84 68–92 0.701 Social unc ioning 88 75–100 88 75–100 0.470 Bodily pain 78 58–90 68 49–90 0.532 Gene al heal h 65 50–80 60 40–75 0.048 PGWB sub-sco es 3 To al 106 94–115 104 95–116 0.526 Anxie y 25 21–27 25 22–27 0.658 Dep ession 17 15–18 16 15–18 0.215 Well-being 18 15–20 17 14–20 0.628 Sel -con ol 16 14–17 16 14–17 0.952 Gene al heal h 13 11–15 13 10–15 0.128 Vi ali y 18 16–20 18 16–21 0.515 Highe sco es deno e ei he 1 mo e se e e symp oms, 2 be e heal h and social unc ioning, o 3 be e heal h- ela ed quali y o li e. 4. Discussion We demons a ed ha celiac disease pa ien s consuming oa s as pa o a longs anding GFD did no di e in symp oms and celiac se ology, and had simila o e en somewha be e quali y o li e om hose no consuming oa s. Fu he , he e was no di e ence be ween he g oups in small-bowel mucosal damage in con ol biopsy a e one yea on a GFD. These indings a e in line wi h mos p e ious sho - e m s udies showing no ha m om oa consump ion in celiac disease pa ien s [ 7 , 9 , 10 ], and u he s ongly suppo he long- e m sa e y o oa s. Nu ien s 2017,9, 611 7 o 11 One o ou aims was o explo e ac o s associa ed wi h he in oduc ion o oa s as pa o he GFD, an issue ega ding which he e a e no p e ious scien i ic da a. We ound oa s o be signi ican ly mo e widely consumed among pa ien s diagnosed a e he yea 2000 han by hose diagnosed ea lie . This migh be pa ly a esul o physicians’ inc eased accep ance o oa s in he celiac die . Pa ien s diagnosed by sc eening and wi h less se e e symp oms we e also mo e likely o consume oa s, possibly since hey and hei physicians a e less hesi an o y oa s in cases o mild clinical p esen a ion. This is e y likely u he a ibu ed o he inc easing consump ion o oa s o e ime, as he sc eening o celiac disease has also inc eased du ing he 2000s [ 27 ]. In e es ingly, pa ien s who isi ed die i ians consumed oa s mo e o en han hose ecei ing die a y ad ice om o he heal h ca e p o essionals. Die i ians gene ally ha e a sligh ly di e en pe spec i e on ch onic diseases han clinicians [ 28 ], and in celiac disease pa ien s hey may ocus mo e on he nu i ional bene i s o oa s and ecommend i i no speci ically o bidden by he esponsible physician. O no e ega ding issues no associa ed wi h he in oduc ion o oa s was he le el o heal h ca e a which he diagnosis was made. This migh no necessa ily ha e been pe inen , as i has been epo ed ha he ea men o ch onic diseases di e s signi ican ly be ween gene al p ac i ione s and specialis s [ 29 ]. The mo e uni o m esul s in Finland migh be due o he widely used na ionwide ea men guidelines o celiac disease [ 30 ] and he inc easing ans e o he diagnos ics om e ia y cen e s o p ima y ca e [ 27 ]. We belie e ha he cons an ly ising numbe o celiac pa ien s makes such a decen aliza ion necessa y, and he e should no be majo di e ences in implemen a ion o he GFD be ween di e en le els o heal h ca e. One main inding among long- e m ou comes was he absence o any di e ence be ween oa s and no-oa s g oups in ei he sel - epo ed o e all symp oms o hose measu ed by alida ed ques ionnai e. This is in line wi h mos p e ious sho - e m s udies [ 7 , 9 , 10 , 31 ] and ou ecen smalle ollow-up s udy [ 8 ], in which oa s did no inc ease symp oms on a GFD. Howe e , in ou ea lie andomized ial oa -consume s epo ed mo e dia hea han hose wi hou oa s [ 11 ], and in a 12-week challenge s udy om No way some celiac pa ien s expe ienced abdominal discom o and bloa ing when s a ing oa s [ 12 ]. Howe e , since any apid change in he amoun o die a y ibe can cause gas oin es inal symp oms e en in non-celiacs [ 32 ], he eac ion o ibe - ich oa s migh be only a ma e o nonspeci ic adap a ion a he han ue immunological ac i a ion. In ac , also in he wo a o emen ioned s udies [ 11 , 12 ], mos pa ien s wi h ini ial symp oms la e ole a ed oa s as a pa o hei GFD. Oa s may hus cause symp oms in a small g oup o celiac pa ien s, bu hey a e usually mild and a oidable by a g adual inc ease in daily consump ion. Ano he impo an esul he e was he equal sel -pe cei ed quali y o li e in he oa s and no-oa s g oups as measu ed by alida ed PGWB and SF-36 ques ionnai es. In ac , oa -consume s had e en somewha ewe physical ole limi a ions and be e gene al heal h when measu ed by he SF-36. Simila ly, oa consump ion was no associa ed wi h dec eased quali y o li e in he abo e-men ioned andomized ial om ou g oup [ 11 ], and in ano he s udy celiac pa ien s epo ed oa consump ion as making he GFD easie o main ain by di e si ying he die nu i ionally, lowe ing cos s and imp o ing as e [ 33 ]. In e es ingly, in he cu en s udy, we also ound oa -consume s o smoke less. This indica es in gene al a heal hie li es yle, which appa en ly helps main ain good heal h and quali y o li e. The consump ion o oa s also did no p edispose o a highe isk o celiac an ibody posi i i y o his ological damage on a GFD. This is especially impo an gi en ha he long- e m complica ions o celiac disease a e conside ed o be a consequence o an ongoing in es inal lesion, whose se e i y he an ibody le els also e lec [ 34 ]. The excellen mo phological mucosal eco e y wi h oa s is in line wi h he indings in ou andomized s udy [ 11 ] and mo e ecen s udies [ 8 , 35 , 36 ]. In he i s [ 11 ] and las [ 36 ] o hese s udies, oa consume s e inced a sligh ly highe densi y o duodenal in aepi helial lymphocy es (IELs). The inc ease was, howe e , seen mos ly in so-called γδ + IELs, o which e en ual signi icance is unclea and no necessa y pa hologic. Mo eo e , he inc eased le els o IELs had no e ec wha soe e on he o he measu ed ou comes and was no seen in he o he wo s udies [ 8 , 35 ]. The ac ha he his ological damage was no ully healed a he one yea con ol biopsy in up o 40% Nu ien s 2017,9, 611 8 o 11 o he pa ien s in bo h oa s and no oa s g oups he e does no e lec poo die a y adhe ence, bu ins ead is in line wi h p e ious s udies showing ha , despi e a s ic GFD, he illous eco e y o en akes a conside ably longe ime o eco e [ 36 ]. Ou esul s a e suppo ed by s udies om o he g oups also showing no e ec o oa s in eco e y o he illous a chi ec u e [ 18 , 37 – 40 ]. Ne e heless, one pa ien in he abo e-men ioned No wegian s udy [ 12 ] de eloped illous a ophy while using pu i ied oa s, and in expe imen al models o celiac disease, ce ain oa cul i a s ha e igge ed immunological esponses [ 27 ]. The e a e also epo s o al e ed epi helial unc ion and a enin-speci ic T-cell s imula ion in a pa o pa ien s on a GFD wi h oa s [ 39 , 41 ]. Al hough hese issues need u he cla i ica ion, ue in ole ance o oa s would appea o be e y a e in clinical p ac ice. The sa e y o oa s in he long e m was u he suppo ed by he equal incidence o malignancies, os eopo osis, and ac u es be ween ou s udy g oups. We would also emphasize ha , al hough oa s a e widely consumed among Finnish pa ien s (he e 82%), ea men esul s a e e y good and e ac o y celiac disease is excep ionally a e [42]. Ou main s eng hs we e he la ge s udy g oups wi h and wi hou oa s, he long ollow-up ime on a GFD, and he use o alida ed ques ionnai es o symp oms and quali y o li e. We also succeeded in collec ing a wide a ie y o clinically ele an ollow-up da a. One limi a ion, on he o he hand, was ha easons behind he non-consump ion o oa s we e no in es iga ed, and i is possible ha in some cases i was ini ially ied bu la e omi ed due o clinical symp oms [ 33 ]. We also had no da a as o he exac indi idual amoun s o cul i a s o oa s consumed, bu his e lec s he eal li e se ing in which he daily consump ion a ies subs an ially bo h be ween and wi hin indi iduals. The mean in ake o oa s in Finland is app oxima ely 18 g pe capi a pe day [ 43 ], and in ou p e ious s udy [ 8 ], he pa ien s consumed 20 g oa s pe day. Thus, we can assume ha he pa icipan s we e consuming app oxima ely he same amoun o oa s as he popula ion in gene al. Ano he ac o we could no con ol he e was ha , ea lie , he pa ien s migh ha e consumed he so-called na u ally glu en- ee p oduc s o which glu en con en was no ce i ied. We also had no da a as o he exac indi idual amoun s o oa s consumed, bu his e lec s he eal li e se ing in which he daily consump ion a ies subs an ially bo h be ween and wi hin indi iduals. The ac ha a pa o he pa icipan s we e membe s o he celiac socie y migh ha e caused a selec ion bias. I is also good o emembe ha , in Finland, p oduc s wi h pu i ied oa s a e widely a ailable and s ic ly egula ed [ 19 ], and cau ion is hus wa an ed be o e gene alizing ou esul s o coun ies wi h less expe ience wi h such g oce ies. To conclude, we p o ided s ong e idence ha he consump ion o oa s as pa o he GFD is sa e also in he long e m in he g ea majo i y o celiac disease pa ien s. Conside ing he a ious heal h bene i s ela ed o he egula consump ion o oa s, we encou age physicians o ecommend i wi h a low h eshold. I is impo an o ensu e he pu i y and high quali y o oa -con aining GFD p oduc s [ 44 ], and, as always in celiac disease pa ien s, ca e ul moni o ing o an adequa e esponse o die a y ea men is manda o y. Acknowledgmen s: This s udy was suppo ed by he Academy o Finland Resea ch Council o Heal h, he Compe i i e Resea ch Funding o Tampe e Uni e si y Hospi al, he Sig id Juselius Founda ion, he Y jö Jahnsson Founda ion, he Founda ion o Pedia ic Resea ch, and he Ma y and Geo g Eh n oo h Founda ion. Au ho Con ibu ions: Ka i Kaukinen, Ma kku Mäki, and Kalle Ku ppa concei ed and designed he s udy; Ka i Kaukinen and Kalle Ku ppa con ibu ed o he acquisi ion o da a; Ka i Aal onen, Pil i Lau ikka, Heini Huh ala, and Kalle Ku ppa analyzed he da a; Ka i Aal onen, Pil i Lau ikka, and Kalle Ku ppa d a ed he manusc ip ; Heini Huh ala, Ka i Kaukinen, and Ma kku Mäki e ised he manusc ip o impo an in ellec ual con en . Con lic s o In e es : The au ho s decla e no con lic o in e es . Re e ences 1. 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