EFSA Jou nal. 2025;23:e9319.
|
1 o 12
h ps://doi.o g/10.2903/j.e sa.2025.9319
e sa.onlinelib a y.wiley.com/jou nal/1831-4732
SCIENTIFIC OPINION
Pac an®, a powde ob ained om c anbe ies, and de ence
agains bac e ial pa hogens in he lowe u ina y ac :
E alua ion o a heal h claim pu suan o A icle 13(5) o
Regula ion (EC) No 1924/2006
EFSA Panel on Nu i ion, No el Foods and Food Alle gens (NDA) | Dominique Tu ck |
To s en Bohn | Mon aña Cáma a | Jacqueline Cas enmille | S e aan de Henauw |
Ka en- Ildico Hi sch- E ns | Angeles Jos | Alexand e Maciuk | Inge Mangelsdo |
B eige McNul y | And oniki Naska | K is ina Pen ie a | F ank Thies | Ionu C aciun |
Thibaul Fiole | Al onso Siani
Adop ed: 5 Ma ch 2025
DOI: 10.2903/j.e sa.2025.9319
Abs ac
Following an applica ion om Gi audan, submi ed o au ho isa ion o a heal h
claim pu suan o A icle 13(5) o Regula ion (EC) No 1924/2006 ia he Compe en
Au ho i y o I aly, he EFSA Panel on Nu i ion, No el Foods and Food Alle gens
(NDA) was asked o deli e an opinion on he scien i ic subs an ia ion o a heal h
claim ela ed o Pac an® and de ence agains bac e ial pa hogens in he lowe
u ina y ac . The Panel conside s ha he ood Pac an®, a powde ob ained om
c anbe ies, is su icien ly cha ac e ised. De ence agains bac e ial pa hogens in
he lowe u ina y ac is a bene icial physiological e ec . The applican iden i-
ied wo human in e en ion s udies which in es iga ed he e ec o Pac an® on
he incidence o u ina y ac in ec ions (UTI) as being pe inen o he claim. In
weighing he e idence, he Panel ook in o accoun ha one human in e en ion
s udy showed a bene icial e ec o Pac an® consumed daily a doses o 500 mg o
6 mon hs on he incidence o symp oma ic, cul u e- con i med UTI in women wi h
a his o y o ecu en UTI, whe eas such an e ec was no consis en ly obse ed
in ano he s udy unde simila condi ions. The Panel also ook in o accoun ha
limi ed e idence has been p o ided o a mechanism by which Pac an® could exe
he claimed e ec . The Panel concludes ha he e idence p o ided is insu icien
o es ablish a cause and e ec ela ionship be ween he consump ion o Pac an®
and he de ence agains bac e ial pa hogens in he lowe u ina y ac .
KEYWORDS
c anbe y, heal h claim, u ina y ac in ec ion
This is an open access a icle unde he e ms o he C ea i e Commons A ibu ion-NoDe i s License, which pe mi s use and dis ibu ion in any medium, p o ided he
o iginal wo k is p ope ly ci ed and no modi ica ions o adap a ions a e made.
© 2025 Eu opean Food Sa e y Au ho i y. EFSA Jou nal published by Wiley-VCH GmbH on behal o Eu opean Food Sa e y Au ho i y.
Co espondence: ni @e sa.eu opa.eu
The decla a ions o in e es o all scien i ic
expe s ac i e in EFSA's wo k a e a ailable
a h ps:// open. e sa. eu opa. eu/ expe s
2 o 12
|
PACRAN® AND DEFENCE AGAINST BACTERIAL PATHOGENS IN THE LOWER URINARY TRACT
CONTENTS
Abs ac ................................................................................................................................................................................................................................1
1. In oduc ion...............................................................................................................................................................................................................3
1.1. Backg ound and Te ms o Re e ence as p o ided by he eques o .........................................................................................3
1.2. In e p e a ion o he Te ms o Re e ence ............................................................................................................................................3
2. Da a and Me hodologies ......................................................................................................................................................................................3
2.1. Da a ...................................................................................................................................................................................................................3
2.2. Me hodologies..............................................................................................................................................................................................4
2.3. Public consul a ion ......................................................................................................................................................................................5
3. Assessmen ................................................................................................................................................................................................................5
3.1. Cha ac e isa ion o he ood/cons i uen ...........................................................................................................................................5
3.2. Rele ance o he claimed e ec o human heal h ...........................................................................................................................5
3.3. Scien i ic subs an ia ion o he claimed e ec ..................................................................................................................................6
4. Conclusions ................................................................................................................................................................................................................9
5. Documen a ion as p o ided o EFSA ...............................................................................................................................................................9
6. S eps aken by e sa .............................................................................................................................................................................................. 10
Abb e ia ions ................................................................................................................................................................................................................. 10
Acknowledgemen s .....................................................................................................................................................................................................10
Reques o .........................................................................................................................................................................................................................10
Ques ion numbe ..........................................................................................................................................................................................................10
Copy igh o non- EFSA con en .............................................................................................................................................................................. 10
Panel membe s .............................................................................................................................................................................................................. 10
Re e ences.........................................................................................................................................................................................................................11
18314732, 2025, 4, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9319 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [09/06/2025]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
|
3 o 12
PACRAN® AND DEFENCE AGAINST BACTERIAL PATHOGENS IN THE LOWER URINARY TRACT
1 | INTRODUCTION
1.1 | Backg ound and Te ms o Re e ence as p o ided by he eques o
Regula ion (EC) No 1924/2006 ha monises he p o isions ha ela e o nu i ion and heal h claims, and es ablishes ules
go e ning he Communi y au ho isa ion o heal h claims made on oods. As a ule, heal h claims a e p ohibi ed unless hey
comply wi h he gene al and speci ic equi emen s o his Regula ion, a e au ho ised in acco dance wi h his Regula ion,
and a e included in he lis s o au ho ised claims p o ided o in A icles 13 and 14 he eo . In pa icula , A icle 13(5) o his
Regula ion lays down p o isions o he addi ion o claims (o he han hose e e ing o he educ ion o disease isk and
o child en's de elopmen and heal h), which a e based on newly de eloped scien i ic e idence o include a eques o he
p o ec ion o p op ie a y da a, o he Communi y lis o pe mi ed claims e e ed o in A icle 13(3). Acco ding o A icle 18
o his Regula ion, an applica ion o inclusion in he Communi y lis o pe mi ed claims e e ed o in A icle 13(3) shall be
submi ed by he applican o he na ional compe en au ho i y o a Membe S a e, which will make he applica ion and
any supplemen a y in o ma ion supplied by he applican a ailable o he Eu opean Food Sa e y Au ho i y (EFSA).
1.2 | In e p e a ion o he Te ms o Re e ence
EFSA is eques ed o e alua e he scien i ic da a submi ed by he applican in acco dance wi h A icle 16(3) o Regula ion
(EC) No 1924/2006. On he basis o ha e alua ion, EFSA will issue an opinion on he scien i ic subs an ia ion o a heal h
claim ela ed o Pac an® and de ence agains bac e ial pa hogens in he lowe u ina y ac .
The p esen opinion does no cons i u e, and canno be cons ued as, an au ho isa ion o he ma ke ing o Pac an®, a
posi i e assessmen o i s sa e y, no a decision on whe he Pac an® is, o is no , classi ied as a oods u . I should be no ed
ha such an assessmen is no o eseen in he amewo k o Regula ion (EC) No 1924/2006.
In he con ex o his opinion, he e m ‘die a y ib e’ is used as synonymous o non- diges ible ca bohyd a es (EFSA NDA
Panel, 2010) and no as de ined by Regula ion (EU) 1169/2011, which se s he addi ional equi emen o ha ing a bene icial
physiological e ec o edible ca bohyd a e polyme s ob ained om ood aw ma e ial by physical, enzyma ic o chemical
means, and o edible syn he ic ca bohyd a e polyme s.
I should also be highligh ed ha he scope, he p oposed wo ding o he claim and he condi ions o use as p oposed
by he applican may be subjec o changes, pending he ou come o he au ho isa ion p ocedu e o eseen in A icle 18(4)
o Regula ion (EC) No 1924/2006.
2 | DATA AND METHODOLOGIES
2.1 | Da a
In o ma ion p o ided by he applican
See also he sec ion S eps aken by EFSA a he end o his opinion.
Food/cons i uen as s a ed by he applican
Acco ding o he applican , he ood o which he heal h claim is made is a ‘D ied c anbe y powde , a p op ie a y ing edien
sold unde he b and name Pac an®’. The powde is ‘ob ained om he No h Ame ican c anbe y ui (Vaccinium mac oca -
pon Ai on).’
Heal h ela ionship as claimed by he applican
Acco ding o he applican , he heal h e ec ela es o he de ence agains bac e ial pa hogens in he lowe u ina y ac .
‘The speci ic body unc ion ha is he subjec o he claimed e ec is he de ence agains pa hogens. The si e o in ec ion is he
lowe u ina y ac , which e e s o he bladde and he u e h a. The pa hogenic mic oo ganisms a e bac e ia.’ The ou come
a iable p oposed o assess he claimed e ec is he ‘incidence o symp oma ic cul u e- con i med UTI1 (≥ 105 CFU/mL). The
symp oms o UTI a e p oposed o be diagnosed clinically and he UTI is p oposed o be con i med by mic obiological cul u e
u inalysis o a clean- ca ch mid- s eam u ine sample and he indi idual u opa hogens iden i ied’.
1UTI: u ina y ac in ec ions, CFU: colony o ming uni s.
18314732, 2025, 4, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9319 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [09/06/2025]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
4 o 12
|
PACRAN® AND DEFENCE AGAINST BACTERIAL PATHOGENS IN THE LOWER URINARY TRACT
Mechanism by which he ood/cons i uen could exe he claimed e ec as p oposed by he applican
The applican claims ha he e ec de i es om ‘c anbe y compounds o in e e e wi h bac e ial adhesion in he u ina y
ac . This an i- adhesi e p ope y is belie ed o educe he abili y o bac e ia o colonise he u ina y ac . I bac e ia a e unable
o adhe e o u oepi helial cells, hey canno g ow and canno igge an in ec ion’. Acco ding o he applican , ‘c anbe y com-
pounds may in e e e wi h he o ma ion o bac e ial bio ilms on he u oepi helial cells’. Some o ganic acids in c anbe y may
ha e ‘an ibac e ial e ec s’. Addi ionally, ‘ he c oss alk be ween c anbe y compounds and he gu mic obiome may po en ially
impac he suscep ibili y o UTIs’. These ‘c anbe y compounds’ include ‘p oan hocyanidin wi h ype A linkage’, o he phenolic
compounds and phenolic me aboli es' and ‘soluble die a y ib es’.
Wo ding o he heal h claim as p oposed by he applican
The applican has p oposed he ollowing wo ding o he heal h claim ‘D ied c anbe y powde con ibu es o he de ence
agains bac e ial pa hogens in he lowe u ina y ac ’.
Speci ic condi ions o use as p oposed by he applican
Acco ding o he applican , he a ge popula ion o he in ended heal h claim is ‘adul women wi h a his o y o ecu en
UTI’. The ecommended dose o Pac an® p oposed by he applican o achie e he claimed e ec is ‘500 mg o d ied c an-
be y powde once daily’.
Da a p o ided by he applican
The heal h claim applica ion on Pac an® pu suan o A icle 13(5) o Regula ion (EC) No 1924/2006 was p esen ed in a com-
mon and s uc u ed o ma as ou lined in he Scien i ic and echnical guidance o he p epa a ion and p esen a ion o a
heal h claim applica ion (EFSA NDA Panel, 2021b).
As ou lined in he Gene al scien i ic guidance o s akeholde s on heal h claim applica ions (EFSA NDA Panel, 2021a), i
is he esponsibili y o he applican o p o ide he o ali y o he a ailable e idence.
The applican has submi ed a con iden ial and a non- con iden ial e sion o a dossie ollowing he Gene al scien i ic
guidance o s akeholde s on heal h claim applica ions (EFSA NDA Panel, 2021a) and he Scien i ic and echnical guidance
o he p epa a ion and p esen a ion o a heal h claim applica ion (EFSA NDA Panel, 2021b).
The applica ion con ains pe sonal da a claimed as con iden ial by he applican : names, add esses, signa u es, email
and elephone o na u al pe sons, de ails o he analy ical me hods and quan i a i e alues.
The applica ion con ains da a claimed as p op ie a y: da a suppo ing he cha ac e iza ion o he ood/cons i uen ,
Vos alo a e al. (2015). s udy, unpublished s udy A (human in e en ion s udy), unpublished s udy B (me a-analysis o
human in e en ion s udies) unpublished s udies C and D (ex i o s udies).
In acco dance wi h A . 38 o Regula ion (EC) No 178/2002,2 and aking in o accoun he p o ec ion o con iden ial in o -
ma ion and o pe sonal da a in acco dance wi h A icles 39a o 39e o he same Regula ion, and o he Decision o EFSA's
Execu i e Di ec o laying down p ac ical a angemen s conce ning anspa ency and con iden iali y,3 he non- con iden ial
e sion o he dossie has been published in he OpenEFSA po al.4
2.2 | Me hodologies
The app oach used by he NDA Panel o he e alua ion o heal h claims is explained in he Gene al scien i ic guidance
o s akeholde s on heal h claim applica ions (EFSA NDA Panel, 2021a). In assessing each speci ic ood/heal h ela ionship,
which o ms he basis o a heal h claim, he NDA Panel conside s he ollowing key c i e ia:
(i) he ood/cons i uen is de ined and cha ac e ised;
(ii) he claimed e ec is based on he essen iali y o a nu ien ; OR he claimed e ec is de ined and is a bene icial physi-
ological e ec o he a ge popula ion and can be measu ed in i o in humans;
(iii) a cause and e ec ela ionship is es ablished be ween he consump ion o he ood/cons i uen and he claimed
e ec ( o he a ge g oup unde he p oposed condi ions o use).
Each o hese h ee c i e ia needs o be assessed by he NDA Panel wi h a a ou able ou come o a claim o be subs an-
ia ed. In addi ion, an un a ou able ou come o he assessmen o c i e ion (i) and/o (ii) p ecludes he scien i ic assessmen
o c i e ion (iii).
2Regula ion (EC) No 178/2002 o he Eu opean Pa liamen and o he Council o 28 Janua y 2002 laying down he gene al p inciples and equi emen s o ood law,
es ablishing he Eu opean Food Sa e y Au ho i y and laying down p ocedu es in ma e s o ood sa e y. OJ L 31, 1.2.2002, pp. 1–48.
3Decision a ailable a : h ps://www.e sa.eu opa.eu/si es/de aul / iles/co po a e_publica ions/ iles/210111- PAs- p e- submission- phase- and- public- consul a ions.pd .
4h ps:// open. e sa. eu opa. eu/ ques ions/ EFSA- Q- 2022- 00411 .
18314732, 2025, 4, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9319 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [09/06/2025]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
|
5 o 12
PACRAN® AND DEFENCE AGAINST BACTERIAL PATHOGENS IN THE LOWER URINARY TRACT
The scien i ic equi emen s o heal h claims ela ed o ‘ he de ence agains bac e ial pa hogens in he lowe u ina y
ac ’, a e ou lined in a speci ic EFSA guidance on he scien i ic equi emen s o heal h claims ela ed o he immune sys-
em, he gas oin es inal ac and de ence agains pa hogenic mic oo ganisms (EFSA NDA Panel, 2016).
2.3 | Public consul a ion
Acco ding o A . 32c(2) o Regula ion (EC) No 178/2002 and o he Decision o EFSA's Execu i e Di ec o laying down he
p ac ical a angemen s on p e- submission phase and public consul a ions, EFSA ca ied ou a Public Consul a ion on he
non- con iden ial e sion o he applica ion om 5 Feb ua y 2025 o 26 Feb ua y 2025 (PC- 1304) o which no commen s
we e ecei ed.
3 | ASSESSMENT
3.1 | Cha ac e isa ion o he ood/cons i uen
The ood p oposed by he applican as he subjec o he heal h claim is Pac an®, a c anbe y powde ob ained om a blend
o whole No h Ame ican c anbe ies (V. mac oca pon, syn. V. mac oca pon Ai on o V. mac oca pon L).
Pac an® consis s o d ied c anbe y solids. The applican claims ha se e al ood cons i uen s in Pac an® (p oan hocyan-
idins wi h ype A linkage, o he phenolic acids and i s me aboli es, o ganic acids and soluble die a y ib es) a e esponsible
o he claimed e ec .
P oan hocyanidins (PACs) a e oligome s and polyme s o la an- 3- ols (ca echins and epica echins) wi h ype A o B
linkages be ween he monome ic uni s. The ype A linkages a e es ic ed o c anbe ies and a ew o he common oods
(Gu e al., 2004). The con en o la an- 3- ols as monome s (ca echins and epica echins) was measu ed by high- pe o mance
liquid ch oma og aphy (HPLC), he con en o PACs by he B unswick Labo a o y 4- dime hylaminocinnamaldehyde
(BL- DMAC) colo ime ic assay (P io e al., 2010) wi h he use o A2 dime s anda d, and he con en o PACs by he
The pe cen age o ype A and ype B linkages in
PACs was assessed by liquid ch oma og aphy–high esolu ion mass spec ome y (LC–HRMS). The
o la an- 3- ols and (PACs) was assessed by HPLC– luo escence de ec ion (FLD). The
and PAC con en , he abundance o ype A and B linkages and he o la an- 3- ol
we e speci ied. The Panel conside s ha he analy ical me hods used o he
quan i ica ion o abo e- men ioned ood cons i uen s a e app op ia e.
Pac an® also con ains o he la onoids such as an hocyanins and la onols, as well as phenolic acids and non- phenolic
o ganic acids (such as quinic acid, ci ic acid and malic acid). Fla onoids we e measu ed by HPLC coupled wi h UV/ isible
de ec ion, whe eas phenolic acids and o ganic (non- phenolic) acids we e measu ed by HPLC coupled wi h a mass de ec o .
Based on he analysis o 5 ba ches, he applican p o ided anges o he con en o indi idual phy ochemicals pe 100 g
o d ied c anbe y powde .
oligosaccha ides in Pac an®, mainly , and o al die a y ib e, we e quan i ied.
In o ma ion abou he manu ac u ing p ocess, he s abili y and he ba ch- o- ba ch a iabili y has been p o ided. The
con en o la onoids (including monome ic and polyme ic uni s o la an- 3- ols), non- phenolic o ganic acids and die a y
ib e in c anbe y p oduc s can be measu ed by es ablished me hods.
The Panel conside s ha Pac an®, a powde ob ained om c anbe ies which is he subjec o he heal h claim, is su i-
cien ly cha ac e ised in ela ion o he claimed e ec .
3.2 | Rele ance o he claimed e ec o human heal h
The claimed e ec p oposed by he applican is ‘de ence agains bac e ial pa hogens in he lowe u ina y ac ’. The
p oposed a ge popula ion is ‘adul women wi h a his o y o ecu en u ina y ac in ec ion (UTI)’.
P esence o bac e ia in he u ina y ac may cause symp oma ic UTIs. UTI is he mos common in ec ion in gi ls and
women, wi h he incidence ising wi h age and sexual ac i i y. Symp oma ic UTIs a e usually accompanied by bac e iu ia
a le els o ≥ 105 CFU/mL o mid- s eam u ine, and i has been es ima ed ha u opa hogenic s ains o Esche ichia coli a e
he mos common cause o UTIs (Ronald, 2002).
The scien i ic e idence o he subs an ia ion o unc ion claims ela ed o de ence agains pa hogens in he lowe
u ina y ac can be ob ained om human in e en ion s udies showing an e ec on clinical ou comes ela ed o UTIs
(e.g. incidence, se e i y and/o du a ion o symp oms). Wi h espec o he s udy g oup, subjec s wi hou an in ec ion a
baseline, including subjec s a high isk o in ec ion wi hou an in ec ion a baseline, could be sui able s udy g oups o
he scien i ic subs an ia ion o claims on de ence agains pa hogens (EFSA NDA Panel, 2016).
The endpoin p oposed by he applican o assess he claimed e ec in human in e en ion s udies is he incidence o
symp oma ic, cul u e- con i med (bac e iu ia a le els ≥ 105 CFU/mL) UTI in adul women a high isk o UTI (i.e. wi h a his-
o y o ecu en UTI) and no UTI a baseline.
18314732, 2025, 4, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9319 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [09/06/2025]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
6 o 12
|
PACRAN® AND DEFENCE AGAINST BACTERIAL PATHOGENS IN THE LOWER URINARY TRACT
The Panel conside s ha de ence agains bac e ial pa hogens in he lowe u ina y ac is a bene icial physiological
e ec .
3.3 | Scien i ic subs an ia ion o he claimed e ec
The applican pe o med a li e a u e sea ch in Janua y 2024 in he da abases MEDLINE and ScienceDi ec wi hou
ime o language es ic ion o e ie e human s udies using keywo ds in ela ion o he ood cons i uen (c anbe y,
V. mac oca pon, Pac an, p oan hocyanidin) and keywo ds ela ed o he claimed e ec (u ina y ac , u ina y ac in ec ion,
UTI, bladde in ec ion, kidney in ec ion, enal in ec ion, cys i is, pyeloneph i is, bac e iu ia, pyu ia, dysu ia, polyu ia,
oligu ia, haema u ia, an i- adhesion, an i- adhe ence, adhesion, adhe ence, bac e ial pa hogen, pa hogenic mic oo ganism,
pa hogenic o ganism, u opa hogen, E. coli). The ull sea ch s a egy wi h keywo ds, he PICO ques ion (Popula ion,
In e en ion, Compa a o s, Ou comes) and eligibili y c i e ia we e p o ided by he applican .
F om he li e a u e sea ch, he applican iden i ied wo published human in e en ion s udies in es iga ing he e ec
o Pac an® supplemen a ion on he incidence o UTI in women (Sengup a e al., 2011; Vos alo a e al., 2015). In a p e ious
opinion (EFSA NDA Panel, 2014), he NDA Panel e alua ed Sengup a e al. (2011) and an unpublished s udy ( e e ed o as
‘unpublished s udy A’ in ha assessmen in 2014). The Panel could no d aw conclusions om Sengup a e al. (2011) due o
me hodological limi a ions o he s udy, p omp ing he applican o exclude i om he cu en applica ion. The p e iously
unpublished s udy A has since been published as Vos alo a e al. (2015). Fo he p esen applica ion, in esponse o an
addi ional da a eques (ADR), he applican p o ided he ull s udy epo o Vos alo a e al. (2015) and is conside ed as
pe inen o he scien i ic subs an ia ion o he claim.
In he cu en applica ion, he applican also submi ed one unpublished human s udy (unpublished s udy A, claimed
as p op ie a y by he applican ), including he p o ocol, he s a is ical analysis plan and he s udy epo , and one me a-
analysis (unpublished s udy B, claimed as p op ie a y by he applican ), pooling he esul s om he wo s udies (Vos alo a
e al., 2015; unpublished s udy A), as pe inen o he claim.
Two sys ema ic e iews o andomised con olled ials (RCTs) we e also submi ed by he applican . The i s sys ema ic
e iew ocused on non- an ibio ic op ions o he p e en ion o ea men o uncomplica ed UTIs in adul women (Konesan
e al., 2022). Among he 12 s udies es ing c anbe y p oduc s, only one used Pac an® (Vos alo a e al., 2015). The second
e iew, a sys ema ic e iew and me a- analysis (Williams e al., 2023) add essed he e icacy o a ious c anbe y p oduc s
(juice, powde o able s) in educing he isk o UTIs ac oss di e en popula ion g oups. This e iew included 50 RCTs, wi h
45 RCTs e alua ing he e ec o c anbe y p oduc s on he incidence o symp oma ic, cul u e- e i ied UTIs compa ed o
placebo, wa e o no speci ic ea men . O hese, 26 RCTs p o ided su icien da a o a me a- analysis. A subg oup analysis
es ic ed o women wi h ecu en UTIs included eigh s udies wi h 1555 pa icipan s. Only wo s udies wi hin his sub-
g oup (Sengup a e al., 2011; Vos alo a e al., 2015) in es iga ed he e ec s o Pac an®.
The Panel conside s ha no conclusions can be d awn om hese sys ema ic e iews o he scien i ic subs an ia ion
o he claim, as i is unclea whe he he c anbe y p oduc s used in mos o he included RCTs mee he speci ica ions
p o ided o Pac an®, he ood ha is he subjec o he claim. The Panel no es ha he wo RCTs conduc ed wi h Pac an®
(Sengup a e al., 2011; Vos alo a e al., 2015) had al eady been iden i ied by he applican du ing he li e a u e sea ch.
Human in e en ion s udies
Two human in e en ion s udies (Vos alo a e al., 2015; unpublished s udy A) ha e in es iga ed he e ec o a c anbe y
powde on he i s ecu ence o UTI. The applican claims ha he c anbe y powde used in bo h s udies complies wi h
he con iden ial speci ica ions p o ided o Pac an®.
A double- blind, andomised, pa allel, wo- a ms, placebo- con olled, single- cen e s udy (Vos alo a e al., 2015) was
conduc ed in sexually ac i e women. Women wi h a leas wo episodes o UTI ea ed wi h an ibio ics in he p e ious
yea we e ec ui ed. Pa icipan s wi h symp oma ic UTI a baseline, diseases ( ela ed o he u ina y ac , sexually ans-
missible diseases, immunodep ession, ca dio ascula disease, gas oin es inal, me abolic, enal, hepa ic, neu ological o
ac i e musculoskele al diso de s) o aking medica ions a ec ing he u ina y ac , and p egnan and/o b eas - eeding
women we e excluded. 182 women aged 17–75 yea s we e andomised o consume ei he Pac an® con aining 0.56% sol-
uble PACs measu ed by he BL- DMAC me hod (P io e al., 2010) a a dose o 500 mg/day (n = 89) o placebo (n = 93) daily
o 6 mon hs. Pac an® and placebo capsules we e iden ical in appea ance. Compliance was assessed using he numbe
o le - o e capsules a each isi (a weeks 12, 24 and a he las ea men day), and p oduc in ake was epo ed on a
daily die a y ca d.
The p ima y endpoin was he i s ecu ence o symp oma ic UTI, de ined as one o mo e symp oms (pollakiu ia,
bu ning sensa ion on mic u i ion, haema u ia o u bid u ine o malodo ous u ine, sub- pel ic pain, geni al p u i us, e e ,
dysu ia) and he p esence o bac e iu ia a le els ≥ 105 CFU/mL. I a UTI was con i med, he in ake o he s udy p oduc s
was paused du ing an ibio ic ea men . In esponse o an ADR, he applican explained ha he in e en ion p oduc was
paused o a oid any po en ial in e ac ion be ween Pac an® and he an ibio ic ea men . Addi ionally, his pause ep e-
sen ed 3–6 days ou o he 184 days o ollow- up. The p opo ion o women expe iencing a leas one UTI du ing he s udy
was modelled using a log–log binomial eg ession adjus ed o age, age- adjus ed his o y o UTI and log obse a ion ime
as an o se e m. Seconda y endpoin s included ime o i s ecu ence o symp oma ic UTI (Cox eg ession analysis), o al
18314732, 2025, 4, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9319 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [09/06/2025]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
|
7 o 12
PACRAN® AND DEFENCE AGAINST BACTERIAL PATHOGENS IN THE LOWER URINARY TRACT
numbe o UTI du ing he 6 mon hs o he s udy (Poisson eg ession analysis), bac e ia iden i ica ion and coun in u ine
and u inalysis.
In he publica ion, he esul s we e p esen ed o 176 women (n = 83 in he Pac an® g oup and n = 93 in he placebo
g oup). Six pa icipan s om he Pac an® g oup we e excluded om he s a is ical analysis because hey did no mee
he inclusion c i e ia: h ee we e younge han 18 yea s and h ee had only one episode o UTI in he p e ious 12 mon hs.
The Panel no es ha only he Pac an® g oup was a ec ed by hese exclusions. As men ioned in he p e ious opinion on
Pac an® (EFSA NDA Panel, 2014), p o ocol de ia ions ela ed o he age c i e ia in he ini ial analysis om he publica ion
(exclusion o h ee women younge han 18 yea s and inclusion o h ee women olde han 60 yea s) we e no ea ed
equally. Upon eques by EFSA, he applican p o ided he ull s udy epo . The Panel no ed inconsis encies be ween he
ull s udy epo and he published s udy (Vos alo a e al., 2015) o he age eligibili y c i e ion (18–60 yea s in he p o ocol
and 18–75 yea s in he published a icle) and o baseline cha ac e is ics ( alues in he Pac an® g oup a e iden ical o he
89 andomised pa icipan s in he publica ion and he 83 pa icipan s analysed in he s udy epo ). The applican cla i ied
ha he e was a mis ake in he desc ip i e able o he publica ion by Vos alo a e al. (2015).
In he s udy epo , he in en ion- o- ea (ITT) analysis on 182 andomised women (including six comple e s ini ially ex-
cluded) did no show s a is ically signi ican di e ences be ween g oups o he p ima y ou come (nplacebo = 93, nPac an = 89,
RR = 0.50 [95% CI: 0.25; 1.02], p = 0.06). Addi ional sensi i i y analyses excluding women < 18 yea s old (nplacebo = 93,
nPac an = 86, RR = 0.43 [95% CI: 0.20; 0.95], p = 0.03), excluding women wi h one episode o UTIs in he las yea (nplacebo = 93,
nPac an = 86, RR = 0.52 [95% CI: 0.25; 1.06], p = 0.07) o bo h (nplacebo = 93, nPac an = 83, RR no epo ed, p = 0.04), showed ha
he e ec o Pac an® on he p ima y ou come a ied ac oss analyses, and ha he s a is ical signi icance o he esul s de-
pended on unjus i ied exclusions upon p o ocol iola ions, all occu ing in he Pac an® g oup. The Panel conside ed ha
his s udy did no show an e ec o Pac an® on de ence agains bac e ial pa hogens in he lowe u ina y ac (EFSA NDA
Panel, 2014).
In he cu en applica ion, he applican p o ided a e- analysis conside ing he 182 andomised pa icipan s using a
log Poisson gene alised linea model (GLM) wi h obus a iance. The applican claimed ha his new analy ical model,
used in he new s udy p o ided (unpublished s udy A; claimed as p op ie a y by he applican ), is ‘mo e adap ed’ and ‘less
complex’ because he model used in he s udy epo included a e m o he quad a ic associa ion be ween age and UTI
his o y and mul iple a iable cen e ing. The Panel conside s ha he applican did no demons a e wi h quan i a i e indi-
ca o s he supe io i y o his new s a is ical model o e he p e ious one. This new analysis showed s a is ically signi ican
di e ences be ween g oups in ela ion o he p ima y ou come (n = 182, nplacebo = 93, nPac an = 89, p = 0.04). Upon eques by
EFSA, he applican p o ided addi ional sensi i i y analyses excluding pa icipan s who did no mee he inclusion c i e ia
o age (< 18 yea s and > 60 yea s; nplacebo = 90, nPac an = 84; odds a io, OR = 0.44 [95% CI: 0.21; 0.92], p = 0.03), o UTI his o y
(< 2 UTIs in he p e ious 12 mon hs; nplacebo = 93, nPac an = 86; OR = 0.56 [95% CI: 0.29; 1.06], p = 0.08), o bo h (nplacebo = 90,
nPac an = 81; OR = 0.45 [0.21; 0.94], p = 0.03). The Panel no es ha he indings o he ele an sensi i i y analyses a e no con-
sis en wi h hose om he p ima y analysis o he e ec o Pac an® on he p ima y ou come.
The Panel no es ha he choice o he s a is ical model and he applica ion o exclusion c i e ia based on age and UTI
his o y play a signi ican ole in de e mining he magni ude and s a is ical signi icance o he e ec , and ha he lack o
quan i a i e indica o s o jus i y he new pos - hoc s a is ical analysis and he p o ocol de ia ions unde mine he obus -
ness o he indings. Consequen ly, he new pos - hoc s a is ical analysis p o ided by he applican does no jus i y a e i-
sion o he p e ious conclusions by he EFSA NDA Panel (2014) on he s udy by Vos alo a e al. (2015). The Panel conside s
ha his s udy does no show a consis en e ec o Pac an® on he incidence o UTI.
A double- blind, andomised, pa allel, wo- a ms, placebo- con olled, mul icen e s udy a i e si es in Aus alia, was
conduc ed in women aged 18–65 yea s (unpublished s udy A). Women aged 18–65 yea s wi h a BMI be ween > 17.5 and
< 35 kg/m2 and wi h 2–4 UTIs in he las 6 mon hs (o ≥ 3 UTIs ea ed wi h an ibio ics in he las yea ) we e ec ui ed.
Pa icipan s wi h a his o y o > i e UTIs in he las 6 mon hs, his o y o majo diseases (immunodep ession, ca diac, li e ,
gas oin es inal, u ological, enal o me abolic diso de s) o hose aking Vaccinium con aining p oduc s, an ibio ics o
medica ions a ec ing u ina y ac and p egnan and/o b eas - eeding women we e excluded.
A o al o 150 women we e andomised o consume ei he 500 mg/day o Pac an® con aining ~0.4% soluble PACs mea-
su ed by he BL- DMAC me hod (n = 75) o placebo (soy oil, n = 75) o 6 mon hs (unpublished s udy A). Pac an® and placebo
capsules we e iden ical in appea ance and compliance was assessed by coun ing he numbe o e u ned capsules a each
isi (on days 29, 57, 85, 113, 141 and 169).
The p ima y endpoin was he incidence o cul u ed con i med UTI a a le el o > 105 CFU/mL measu ed using log Poisson
eg ession wi h obus a iance. Seconda y endpoin s included incidence o symp oma ic suspec ed UTI, incidence o cul-
u e posi i e UTI symp oms, ime o i s UTI, o al numbe o UTIs, p opo ion o pa icipan s wi h wo o mo e UTIs and
change in u opa hogen p esence and coun on cul u e.
A o al o 14 pa icipan s (11 in he placebo g oup and 3 in he Pac an® g oup) wi hd ew o we e los o ollow- up. The ull
analysis se (FAS) included all andomised pa icipan s wi h a leas one dose o s udy ea men (Pac an® o placebo), and
wi h a leas one pos - baseline alue o he p ima y ou come. Fi e andomised pa icipan s we e excluded om he FAS
analysis ( h ee in he placebo g oup and wo in he Pac an® g oup). In FAS, 72 women in he placebo g oup and 73 women
in he Pac an® g oup we e analysed. The FAS analysis on 145 women showed a s a is ically signi ican e ec o Pac an® on
he incidence o UTI as compa ed o placebo ( ela i e isk, RR = 0.48 [0.26; 0.87], p = 0.01). Among he seconda y endpoin s,
Pac an® inc eased he ime o i s cul u e- con i med UTI (haza d a io, HR = 0.36 [0.18; 0.74], p = 0.01) and educed he o al
numbe o UTIs pe pa icipan (inciden a e a io, IRR = 0.41 [0.21; 0.79], p = 0.01), and he incidence o cul u ed posi i e UTI
18314732, 2025, 4, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9319 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [09/06/2025]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
8 o 12
|
PACRAN® AND DEFENCE AGAINST BACTERIAL PATHOGENS IN THE LOWER URINARY TRACT
symp oms ( equency o u ina ion) (RR = 0.29 [0.13; 0.63], p < 0.01), bu no he incidence o symp oma ic suspec ed UTI, he
p esence o speci ic bac e ia on cul u e o he incidence o o he cul u e posi i e UTI symp oms (dysu ia). The pe p o ocol
(PP) analysis o 107 women complying wi h he in e en ions (58 in he placebo g oup and 59 in he Pac an® g oup) did
no show s a is ically signi ican di e ences be ween g oups o he p ima y ou come o he seconda y ou comes ( ime o
i s UTI, o al numbe o UTI). Upon eques by EFSA, he applican claimed ha he educ ion in sample size could explain
he di e en esul s ob ained in ela ion o he p ima y ou come in he FAS and PP analyses. The Panel no es ha he e-
c ui men was e mina ed p ema u ely and only 150 pa icipan s we e ec ui ed ins ead o 300 pa icipan s, as planned in
he p o ocol. Acco ding o he applican , he o iginal sample size was es ima ed o de ec an absolu e educ ion o 15%
in he a e o symp oma ic UTI ecu ence be ween g oups (80% powe , 5% alpha, 10% d opou a e) gi en an incidence in
he con ol g oup o 35%. The inal sample size calcula ion could de ec an absolu e educ ion o 19% in he a e o symp-
oma ic UTI ecu ence be ween g oups (80% powe , 5% alpha) gi en a lowe incidence in he con ol g oup (30%).
The Panel conside s ha his s udy (unpublished s udy A) shows a bene icial e ec o Pac an® when consumed daily a
doses o 500 mg o 6 mon hs on he incidence o symp oma ic, cul u e- con i med UTI in women wi h a his o y o ecu -
en UTI in ec ions.
Me a- analysis
The applican conduc ed a me a- analysis (unpublished s udy B) pooling he esul s on he incidence o UTIs om he wo
human in e en ion s udies desc ibed abo e (Vos alo a e al., 2015; unpublished s udy A). To ha end, he esul s om
he new pos - hoc, ITT s a is ical analysis o he s udy by Vos alo a e al. (2015) we e used. The Panel no es ha he model
speci ica ion o he e- analysis o one s udy (Vos alo a e al., 2015) has no been quan i a i ely jus i ied and ha he
me hodological choices and codes o he me a- analysis ha e no been su icien ly desc ibed. The Panel conside s ha
his me a- analysis does no p o ide addi ional e idence o he scien i ic subs an ia ion o he claim beyond ha p o ided
by he indi idual s udies.
Mechanism o ac ion
The applican acknowledges ha he p ecise mechanism by which Pac an® could exe a p o ec ion agains bac e ial
pa hogens in he lowe u ina y ac is no ully elucida ed. The ollowing hypo hesis ha e been p oposed:
a. An i- adhesi e ac i i y (AAA)
C anbe y compounds could in e e e wi h he adhesion o bac e ial pa hogens (e.g. P- imb ia ed Esche ichia coli) o
u oepi helial cells and educe hei capaci y o colonise he u ina y ac .
In suppo o his mechanism, he applican p o ided wo s udies showing ha he consump ion o c anbe y juice was
associa ed wi h an inc ease in phenolic compounds and benzoic acids in plasma, and ha hese c anbe y polyphenols
we e exc e ed in u ine (Feliciano e al., 2016; Liu e al., 2015). The applican also submi ed wo double- blind, c oss- o e
RCTs which e alua ed ex i o he AAA on bac e ia in u ine o heal hy olun ee s ollowing he consump ion o 500 mg o
a c anbe y powde complying wi h he speci ica ions o Pac an® (as claimed by he applican ) using he s anda d human
ed blood cell haemagglu ina ion assay (unpublished s udies C and D; claimed as p op ie a y by he applican ). The u ine
o indi iduals consuming Pac an® was mo e e ec i e in inhibi ing adhesion o P- imb ia ed E. coli o ed blood cells han
ha o indi iduals on placebo.
P oan hocyanidins ype A (PAC- A) ha e been shown o dec ease adhesion o P- imb ia ed E. coli o u ina y bladde cells
in i o (Howell e al., 1998) a much highe concen a ions han hose ound in he u ine o animals o humans consuming
c anbe y p oduc s (de González Llano e al., 2019, 2020). In addi ion, abou
(Sec ion 3.1). Whe eas ca echin and epica echin monome s, and a ely dime s, can be abso bed
in ac in he small in es ine, oligome s and polyme s a e ex ensi ely me abolised by he gu mic obio a in o low molecula
weigh phenolics (Manach e al., 2005; P io & Gu, 2005; Se ano e al., 2009). The Panel ag ees wi h he s a emen o he
applican ha PAC- A a e unlikely o be esponsible o he AAA o d ied c anbe y powde obse ed ex i o.
The applican claimed ha o he c anbe y phenolic compounds ha e shown AAA in i o a concen a ions ha
a e close o hose exc e ed in u ine upon consump ion o c anbe y p oduc s (de González Llano e al., 2019; de Llano
e al., 2015; Mena e al., 2017) and ha addi i e o syne gis ic e ec s could explain he AAA o Pac an® ex i o (de González
Llano e al., 2019). The applican also claimed ha soluble oligosaccha ides in c anbe y p oduc s could also con ibu e o
he AAA, as hey a e abso bed and exc e ed in u ine as shown in sows (Coleman e al., 2019; Coleman & Fe ei a, 2020), and
could p e en he o ma ion o bac e ial bio ilms as shown in i o (Sun e al., 2015).
The Panel no es ha se e al heal h claim applica ions ela ed o he e ec s o c anbe y p oduc s s anda dised by
hei PAC con en on he AAA o u ine om subjec s consuming c anbe y p oduc s ha e al eady been e alua ed by EFSA
(EFSA, 2009; EFSA NDA Panel, 2011, 2013a, 2013b). Howe e , he s udies p o ided in hose applica ions did no es ablish ha
inhibi ion o he adhesion o E. coli demons a ed ex i o p edic ed he occu ence o a clinically ele an inhibi ion o he
adhesion o E. coli o u oepi helial cells in humans.
18314732, 2025, 4, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9319 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [09/06/2025]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
|
9 o 12
PACRAN® AND DEFENCE AGAINST BACTERIAL PATHOGENS IN THE LOWER URINARY TRACT
b. An ibac e ial e ec s
The applican p o ided a s udy on a mouse model o expe imen al E. coli UTI in ec ion (Jensen e al., 2017). Mice as-
signed o consume ad libi um ei he comme cial (swee ened) c anbe y juice, esh (unswee ened) c anbe y juice, he
hyd ophilic ac ion o c anbe y juice o he combina ion o o ganic acids (quinic, malic, shikimic and ci ic acids) in simila
concen a ions as ound in c anbe y juice, showed lowe bac e ial coun s in he lowe u ina y ac as compa ed o hose
assigned o wa e a e 7 days o ea men , when he animals we e sac i iced. The Panel no es ha his s udy add esses he
e ec o c anbe y juice and o ganic acids in c anbe y p oduc s in he ea men o UTI a he han he isk o de eloping
UTI, ha he c anbe y juice and he mix u e o o ganic acids educed bac e ial coun s in a iable amoun s depending on
he p oduc es ed bu did no cu e in ec ions and ha Pac an® was no es ed. The Panel conside s ha his s udy p o ides
no in o ma ion abou a mechanism by which Pac an® could exe he claimed e ec .
c. Modula ion o /by he gu mic obio a.
The applican claims ha , on he one hand, he gu mic obio a has he capaci y o me abolise c anbe y compounds,
pa icula ly la ge oligome polyphenols, in o low- molecula weigh phenolics (e.g. phenyl- γ- ale olac one) ha a e sub-
sequen ly ound in u ine and ha e shown AAA in i o (Feliciano e al., 2016; Mena e al., 2017). Addi ionally, he mic obio a
can deg ade and e men c anbe y ib e. On he o he hand, hese compounds could modula e he gu mic obio a com-
posi ion, as shown by he shi in Fi micu es:Bac e oide es a io in olun ee s ollowing whole c anbe y ui s consump-
ion (Bekia es e al., 2018; Rod íguez- Mo a ó e al., 2018). In his con ex , i is specula ed ha c anbe y p oduc s could also
dec ease he colonisa ion o he gas oin es inal ac by ex ain es inal pa hogenic E. coli as shown in an in i o model o
gu epi helial cell cul u e (Feliciano e al., 2014), hus dec easing he likelihood o u opa hogens ans e ing o he u ina y
ac . The Panel conside s ha his p oposed mechanism is specula i e and no suppo ed by da a in i o in animals o
humans.
The Panel no es ha , whe eas some e idence has been p o ided o an e ec o Pac an® on inhibi ing adhesion o
P- imb ia ed E. coli o ed blood cells ex i o, an e ec ha is suppo ed by AAA in i o o some c anbe y compounds and
me aboli es, he s udies p o ided do no es ablish ha inhibi ion o he adhesion o E. coli demons a ed ex i o p edic s
he occu ence o a clinically ele an inhibi ion o he adhesion o E. coli o u oepi helial cells in i o in humans. The Panel
also no es ha no con incing e idence has been p o ided o o he mechanisms by which Pac an® could educe he inci-
dence o UTI.
O e all, he Panel conside s ha limi ed e idence has been p o ided o a mechanism by which Pac an® could exe he
claimed e ec .
Weighing o he e idence
In weighing he e idence, he Panel akes in o accoun ha one human in e en ion s udy (unpublished s udy A) showed
a bene icial e ec o Pac an® consumed daily a doses o 500 mg o 6 mon hs on he incidence o symp oma ic, cul u e-
con i med UTI in women wi h a his o y o ecu en UTI in ec ions, whe eas such an e ec was no consis en ly obse ed
in ano he s udy (Vos alo a e al., 2015) unde simila condi ions. The Panel also akes in o accoun ha limi ed e idence
has been p o ided o a mechanism by which Pac an® could exe he claimed e ec .
The Panel concludes ha he e idence p o ided is insu icien o es ablish a cause and e ec ela ionship be ween he
consump ion o Pac an® and he de ence agains bac e ial pa hogens in he lowe u ina y ac .
4 | CONCLUSIONS
On he basis o he da a p esen ed, he Panel concludes ha :
• Pac an®, a powde ob ained om c anbe ies which is he subjec o he heal h claim, is su icien ly cha ac e ised in ela-
ion o he claimed e ec .
• The claimed e ec p oposed by he applican is ‘de ence agains bac e ial pa hogens in he lowe u ina y ac ’. The
p oposed a ge popula ion is ‘adul women wi h a his o y o ecu en u ina y ac in ec ion’. The Panel conside s ha
de ence agains bac e ial pa hogens in he lowe u ina y ac is a bene icial physiological e ec .
• The e idence p o ided is insu icien o es ablish a cause and e ec ela ionship be ween he consump ion o Pac an®
and he de ence agains bac e ial pa hogens in he lowe u ina y ac
5 | DOCUMENTATION AS PROVIDED TO EFSA
Heal h claim applica ion on “D ied c anbe y powe con ibu es o he de ence agains bac e ial pa hogens in he lowe
u ina y ac ” pu suan o A icle 13.5 o Regula ion (EC) No 1924/2006 (Appian numbe : HC- 2024- 21772). Submi ed by
Gi audan.
18314732, 2025, 4, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9319 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [09/06/2025]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
