EFSA Jou nal. 2025;23:e9276.
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e sa.onlinelib a y.wiley.com/jou nal/1831-4732
SCIENTIFIC OPINION
Scien i ic Opinion on addi ional scien i ic da a ela ed o he
sa e y o monacolins om ed yeas ice submi ed pu suan o
A icle 8(4) o Regula ion (EC) No 1925/2006
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 DeHenauw |
Ka en Ildico Hi sch- E ns | Ángeles Jos | Inge Mangelsdo | B eige McNul y |
And oniki Naska | K is ina Pen ie a | Al onso Siani | F ank Thies | Leona d Ma ije ić |
Sil ia Val ueña Ma inez | Alexand e Maciuk
Adop ed: 29 Janua y 2025
DOI: 10.2903/j.e sa.2025.9276
Abs ac
The Panel on Nu i ion, No el Foods and Food Alle gens (NDA) was asked o de-
li e a scien i ic opinion on he sa e y o monacolins om ed yeas ice (RYR),
which ha e been placed unde Union sc u iny in Pa C o Annex III in acco dance
wi h A icle 8(4) o Regula ion (EC) No 1925/2006. The NDA Panel e iewed he
addi ional scien i ic da a submi ed du ing he pe iod o sc u iny, which included
analy ical da a on he composi ion o RYR supplemen s, he in ake o monaco-
lins om o he die a y sou ces, in i o bioaccessibili y and cy o oxici y da a o
monacolins s. o he s a ins, nu i igilance/pos - ma ke ing da a, case epo s and
clinical s udies. Based on he new nu i igilance da a p o ided, he NDA Panel ei -
e a es he conce ns o he ANS Panel (EFSA ANS Panel, 2018) ha exposu e o mo-
nacolin K om RYR a in ake le els as low as 3 mg/day could lead o se e e ad e se
e ec s on he musculoskele al sys em, including habdomyolysis, and on he li e .
The NDA Panel concludes ha he da a submi ed by in e es ed pa ies du ing he
Union sc u iny pe iod do no allow es ablishing he sa e y o monacolins in RYR
supplemen s below 3 mg/day o o iden i y a daily in ake o monacolins om RYR
in ood supplemen s ha does no aise sa e y conce ns o he gene al popula-
ion o ulne able subg oups he eo .
KEYWORDS
ood supplemen s, lo as a in, monacolins, Monascus pu pu eus, ed yeas ice
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
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MONACOLINS FROM RED YEAST RICE PLACED UNDER UNION SCRUTINY
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
1.1.1. Backg ound ....................................................................................................................................................................................3
1.1.2. Te ms o Re e ence.......................................................................................................................................................................3
1.2. In e p e a ion o he Te ms o Re e ence ............................................................................................................................................3
1.3. P e ious EFSA assessmen s on monacolins om RYR ....................................................................................................................3
2. Da a and Me hodologies ......................................................................................................................................................................................4
2.1. Da a ...................................................................................................................................................................................................................4
2.2. Me hodologies..............................................................................................................................................................................................6
3. Assessmen ................................................................................................................................................................................................................6
3.1. Analy ical da a abou he cha ac e isa ion o RYR p epa a ions ................................................................................................6
3.2. Da a on he die a y in ake o monacolins om ood sou ces o he han RYR ......................................................................8
3.3. In i o da a o RYR/monacolin K s. o he s a ins ...........................................................................................................................8
3.4. Nu i igilance/pos - ma ke ing da a on ad e se e en s ela ed o he use o RYR p oduc s ...........................................9
3.5. Case epo s o ad e se e en s om he scien i ic li e a u e ....................................................................................................11
3.6. New clinical da a including sa e y endpoin s .................................................................................................................................11
4. Discussion................................................................................................................................................................................................................ 12
5. Conclusions ............................................................................................................................................................................................................. 12
6. S eps aken by EFSA ............................................................................................................................................................................................. 13
Abb e ia ions ................................................................................................................................................................................................................. 13
Acknowledgemen s ..................................................................................................................................................................................................... 14
Reques o .........................................................................................................................................................................................................................14
Ques ion numbe ..........................................................................................................................................................................................................14
Copy igh o non- EFSA con en .............................................................................................................................................................................. 14
Panel membe s ..............................................................................................................................................................................................................14
Re e ences........................................................................................................................................................................................................................ 14
Appendix A ...................................................................................................................................................................................................................... 17
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MONACOLINS FROM RED YEAST RICE PLACED UNDER UNION SCRUTINY
1 | INTRODUCTION
1.1 | Backg ound and Te ms o Re e ence as p o ided by he eques o
1.1.1 | Backg ound
Regula ion (EC) No 1925/20061 es ablishes he ules go e ning he addi ion o i amins and mine als and o ce ain o he
subs ances o oods and, in pa icula , A icle 8 he eo de ines he p ocedu e o be ollowed o p ohibi ing, es ic ing, o
placing unde Communi y sc u iny a gi en subs ance.
1.1.2 | Te ms o Re e ence
On 1 June 2022, pu suan o A icle 1(2) o Commission Regula ion (EU)2022/860,2 amending Annex III, Pa C, o Regula ion
(EC) No 1925/2006, he Commission has placed unde Union sc u iny ‘Monacolins om ed yeas ice’.
The Eu opean Commission (EC) eques s he Eu opean Food Sa e y Au ho i y's (EFSA) opinion on whe he he scien i ic
da a con ained in he iles submi ed o o be submi ed o e alua ion by ood business ope a o s o any o he in e es ed
pa ies demons a e he sa e y o subs ances placed unde Union sc u iny men ioned abo e.
1.2 | In e p e a ion o he Te ms o Re e ence
As sa e y conce ns we e aised in ela ion o he consump ion o monacolins om ed yeas ice (RYR) in ood supplemen s
a doses o 10 mg/day, and indi idual cases o se e e ad e se eac ions had been epo ed a doses as low as 3 mg/day
(EFSA ANS Panel,2018), monacolins om RYR we e placed unde Union sc u iny (Commission Regula ion (EU) 2022/860)
and Annex III (Pa B) o Regula ion (EC) No 1925/2006 was amended o indica e ha he indi idual po ion o he p oduc
o daily consump ion shall p o ide less han 3 mg o monacolins om RYR.
The main easons o placing monacolins om RYR ood supplemen s unde Union sc u iny (Reci al 18 o Commission
Regula ion (EU) 2022/860) we e he scien i ic unce ain ies in ela ion o he possibili y o ha m ul e ec s on heal h associ-
a ed wi h he use o monacolins om RYR and ha EFSA (EFSA ANS Panel,2018) could no iden i y a le el o in ake ha does
no gi e ise o conce ns abou ha m ul e ec s o heal h o he gene al popula ion, and as app op ia e, o ulne able
subg oups o he popula ion.
In he con ex o he e ms o e e ence and he easons gi en in he eci als o Commission Regula ion (EU) 2022/860
o placing monacolins om RYR unde Union sc u iny, he Panel unde s ands ha EFSA is eques ed o assess whe he he
da a p o ided by ood business ope a o s (FBO) o any o he in e es ed pa ies du ing he sc u iny pe iod a e su icien o:
a. add ess he scien i ic unce ain ies aised by he EFSA ANS Panel (2018) in ela ion o he sa e y assessmen o
monacolins om RYR; and
b. allow he iden i ica ion o a daily in ake o monacolins om RYR in ood supplemen s3 ha does no aise sa e y conce ns
o he gene al popula ion o ulne able subg oups he eo .
The e o e, his assessmen needs o be ead in conjunc ion wi h he EFSA ANS Panel opinion(2018), whe e all he in-
o ma ion and da a a ailable in ela ion o he sa e y o monacolins om RYR up o he sc u iny pe iod is p esen ed and
assessed, including he chemical homology wi h he choles e ol- lowe ing medica ion lo as a in and a (compa a i e) as-
sessmen o he ADME and epo ed ad e se e ec s in humans.
This assessmen conce ns he sa e y o monacolins om RYR in ood supplemen s only. Po en ial bene icial heal h e -
ec s o monacolins om RYR and isk–bene i analyses a e ou o he scope o his manda e.
This assessmen does no conce n quali y aspec s o RYR p oduc s a ailable in he ma ke , such as he po en ial p es-
ence o con aminan s (e.g. ungi and hei myco oxins such as ci inin) o adul e an s (e.g. addi ion o syn he ic s a ins).
1.3 | P e ious EFSA assessmen s on monacolins om RYR
The EFSA NDA Panel has assessed wo heal h claim applica ions on monacolin K om RYR and main enance o no mal
blood LDL- choles e ol concen a ions wi h a a ou able ou come (EFSA NDA Panel,2011, 2013). To ob ain he claimed e ec ,
1Regula ion (EC) No 1925/2006 o he Eu opean Pa liamen and o he Council o 20 Decembe 2006 on he addi ion o i amins and mine als and o ce ain o he
subs ances o oods. OJ L 404, 30.12.2006, p. 26–38.
2Commission Regula ion (EU) 2022/860 o 1 June 2022 amending Annex III o Regula ion (EC) No 1925/2006 o he Eu opean Pa liamen and o he Council as ega ds
monacolins om ed yeas ice. OJ L 151, 2.6.2022, p. 37–41.
3Acco ding o eci al 6 o Regula ion (EC) No 2022/860, he use o RYR p epa a ions in o he ood ca ego ies is subjec o an au ho isa ion unde Regula ion (EC) 2015/2283
on no el oods.
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MONACOLINS FROM RED YEAST RICE PLACED UNDER UNION SCRUTINY
10 mg o monacolin K om e men ed RYR should be consumed daily. The a ge popula ion was adul s in he gene al pop-
ula ion. In he amewo k o Regula ion (EC) No 1924/2006, a sa e y assessmen is no o eseen in heal h claim e alua ions.
In ela ion o he es ic ions o use, he NDA Panel e e ed o he opinion by he EFSA CONTAM Panel on ci inin (a
neph o oxic myco oxin), which can be p oduced by some s ains o Monascus pu pu eus (EFSA CONTAM Panel,2012). The
maximum le el o ci inin (100 μg/kg) in ood supplemen s based on ice e men ed wi h he ed yeas Monascus pu pu eus
is egula ed [Regula ion (EU) 2023/915].
In ela ion o he es ic ions o use, he NDA Panel also e e ed o he Summa y o P oduc Cha ac e is ics (SmPC) o
lo as a in- con aining medicinal p oduc s a ailable on he EU ma ke , as monacolin K in lac one o m is iden ical o lo as a-
in. The SmPC, among o he s, includes special wa nings and p ecau ions o use ha e e o he isk o myopa hy/ habdo-
myolysis, which is inc eased by concomi an use o lo as a in wi h ce ain o he medicinal p oduc s, and discou ages he
use o lo as a in by p egnan and lac a ing women [EFSA NDA Panel,2011, 2013; Regula ion (EU) 2022/860]. In ha con ex ,
Membe S a es aised po en ial sa e y conce ns associa ed wi h he consump ion o oods con aining monacolins om
RYR (ANSES,2014; CSS,2016; DFG, 2016).
Consequen ly, in 2017, he Eu opean Commission ini ia ed he p ocedu e unde A icle 8(2) o Regula ion (EC) No
1925/2006 and asked EFSA o:
• e iew he exis ing scien i ic da a on he possible link be ween he in ake o monacolins om RYR and ha m ul e ec s
on heal h.
• p o ide ad ice on a daily in ake o monacolins om RYR ha does no gi e ise o conce ns abou ha m ul e ec s o
heal h, o he gene al popula ion, and as app op ia e, o ulne able subg oups o he popula ion.
In 2018, he EFSA Panel on Food Addi i es and Nu ien Sou ces added o Food (ANS) issued an opinion on he sa e y o
monacolins in RYR (EFSA ANS Panel,2018) wi hin he amewo k o A icle 8(2) o Regula ion (EC) No 1925/2006.
In i s opinion, he EFSA ANS Panel(2018) no ed ha monacolin K in lac one o m is iden ical o lo as a in, he ac i e ing e-
dien o se e al medicinal p oduc s au ho ised o he ea men o hype choles e olemia in he EU. Monacolin K om RYR
is a ailable in ood supplemen s a a ying ecommended daily in akes o i s e ec on he main enance o no mal blood
LDL choles e ol le els. The es ima ed exposu e o monacolin K was wi hin he ange o he apeu ic doses o lo as a in. The
ANS Panel no ed ha he p o ile o ad e se e ec s o RYR was simila o ha o lo as a in. Based on case epo s, he mos
impo an a ge o gans/ issues o ad e se e en s we e musculoskele al and connec i e issues (including habdomyolysis),
li e , ne ous sys em, gas oin es inal ac , skin and subcu aneous issue, in descending o de o occu ence. The a ailable
in o ma ion on he ad e se e ec s epo ed in humans was judged o be su icien o conclude ha monacolins om RYR in
ood supplemen s we e o signi ican sa e y conce n a he use le el o 10 mg/day. The ANS Panel u he no ed ha indi idual
cases o se e e ad e se eac ions ( habdomyolysis, hepa i is and skin diso de s) o monacolins om RYR which equi ed hospi-
alisa ion had been epo ed a in akes as low as 3 mg/day aken o pe iods o be ween 2 weeks and 1 yea .
On he basis o he in o ma ion a ailable and he se e al unce ain ies highligh ed in i s opinion, he ANS Panel was
unable o iden i y a le el o in ake o monacolins om RYR in ood supplemen s ha does no gi e ise o conce ns abou
ha m ul e ec s o heal h, o he gene al popula ion, and as app op ia e, o ulne able subg oups o he popula ion (EFSA
ANS Panel,2018).
In 2019, he Eu opean Commission asked EFSA o p o ide echnical assis ance on wo scien i ic publica ions ha
we e submi ed o he Commission by an in e es ed pa y ollowing he adop ion o he scien i ic opinion by he ANS
Panel(2018). These we e a sys ema ic e iew and me a- analysis o andomised con olled ials (RCT) on he sa e y o RYR
supplemen a ion (Fogacci e al.,2019) and a na a i e e iew and expe opinion aiming a weighing he isks and bene i s
o using RYR in ood supplemen s and he d ug lo as a in as blood choles e ol- lowe ing agen s (Banach e al.,2019). EFSA
no ed ha he RCTs p o ided we e no designed o de ec ad e se e ec s as he sample size was no su icien o ha pu -
pose, and ha compa a i e isk–bene i analyses we e no use ul in add essing he sa e y conce ns aised by he a ailable
case epo s o ad e se e ec s associa ed wi h he consump ion o RYR in humans.
2 | DATA AND METHODOLOGIES
2.1 | Da a
Du ing he pe iod o Union sc u iny, o eseen by A icle 8(4) o Regula ion (EC) No 1925/2006, ou in e es ed pa ies [Socie à
I aliana di Scienze Applica e alle Pian e O icinali e ai P odo i pe la Salu e (SISTE), Eu opean Fede a ion o Associa ions
o Heal h P oduc Manu ac u e s (EHPM), Linneus Consul ing Se ices and Hyloba es Consul ing s l as ep esen a i e o
Asociación Española de Complemen os Alimen icios (AFEPADI)] submi ed da a. All he documen s submi ed by each
in e es ed pa y a e lis ed in alphabe ical o de o he i s au ho .
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MONACOLINS FROM RED YEAST RICE PLACED UNDER UNION SCRUTINY
SISTE submi ed:
• A na a i e e iew including he analysis o se ious ad e se e en s ( habdomyolysis and acu e hepa i is), associa ed wi h
he consump ion o RYR epo ed o he US Food and D ug Adminis a ion (Banach & No a a,2023), which included e -
e ence o pos - ma ke ing nu i igilance sa e y da a o speci ic ood supplemen s con aining RYR (Banach e al.,2021).
• An RCT on he e ec s (including ad e se e ec s) o a ood supplemen con aining RYR and p o iding o al monacolins
< 3 mg/day (Cice o e al.,2024).
• A na a i e e iew on he occu ence o muscle symp oms and li e dys unc ion associa ed wi h he consump ion o RYR
supplemen s, using a ailable da a om ad e se e en epo ing sys ems and me a- analyses (No a a & Banach,2024).
EHPM submi ed:
• A inal epo o he Task Fo ce o RYR o EHPM on nu i igilance da a (EHPM,2024), including an upda e on pos -
ma ke ing nu i igilance sa e y da a o a speci ic ood supplemen con aining RYR (Banach e al.,2024, unpublished).
• A s udy abou he phy ochemical p o ile, pha macological e ec s and sa e y o a ious RYR samples in compa ison wi h
lo as a in, using in i o/in silico models (Rigillo e al.,2025).
Linneus Consul ing Se ices submi ed:
• A epo including he monacolin con en in comme cially a ailable RYR p oduc s ( ood supplemen s) and in i o cy o-
oxici y assessmen s o RYR samples s. lo as a in, and o monacolin K s. sim as a in and a o as a in, using a human
HepG2 cell line model (Linneus Consul ing Se ices,2024).
• An analy ical epo o RYR me aboli es in di e en e hanolic ex ac s (SUPPLEMENTARY_MATERIALS_TOT).
Hyloba es Consul ing s l, ep esen a i e o AFEPADI, submi ed:
• A summa y epo /documen o he e idence o es ablishing a heal h- based guidance alue (HBGV) o RYR (< 3 mg/
day) (AFEPADI,2024), including a scien i ic s a emen om he Ame ican Hea Associa ion (AHA) on s a in sa e y and
associa ed ad e se e en s (Newman e al.,2019) and e e ence o a ood- bo ne ou b eak in Japan linked o he consump-
ion o RYR p oduc s (Hashimo o e al.,2024).
• A lis o e e ences included in he submission (AFEPADI20240703MonacolinRe e enceP o ided.pd ).
• A published a icle abou he lo as a in con en in Pleu o us os ea us, o oys e mush oom (edible mush oom) (Ala cón
e al.,2003).
• A published a icle abou he in luence o he gu mic obio a on he con e sion o monacolin K o i s ac i e β- hyd oxy
acid o m (BBel án e al.,2019).
• A published a icle abou he on- label and o - label uses o lo as a in as a d ug (Duong & Bajaj,2023).
• EFSA's ex e nal scien i ic epo abou he occu ence o ci inin in ood (López Sánchez e al.,2017).
• A na a i e e iew abou he use o s a ins in child en (Fio en ino & Chia elli,2023).
• A na a i e e iew abou s a ins (Haja ,2011).
• A co e le e om AFEPADI (Hylo2024SignedLe e .pd ).
• A published a icle abou a new analy ical me hod [nuclea magne ic esonance (NMR) assay] o assessing o al s a in
con en and β- Hyd oxy β- me hylglu a yl- coenzyme A (HMG- CoA) educ ase inhibi ion in RYR supplemen s (Lachenmeie
e al.,2012).
• A published sys ema ic e iew and me a- analysis on he use o s a ins in child en wi h amilia hype choles e olaemia
(Radaelli e al.,2018).
• A published a icle on he con en o myco oxins and na u al s a ins in comme cially a ailable RYR ood supplemen s
(Righe i e al.,2021).
• A sys ema ic e iew abou he bene icial and ad e se e ec s o Xuezhikang, a pa ially pu i ied ex ac o e men ed
RYR, in he seconda y p e en ion o co ona y hea disease (CHD) combined wi h dyslipidaemia (Shang e al.,2012).
• An analy ical guideline o RYR, as a basis o es ablish he speci ica ions o he p oduc [SIFITLab Labo a o io d'analisi di Siena
e al. (2018b) ( ansla ion in English) and SIFITLab Labo a o io d'analisi di Siena e al. (2018a) (o iginal documen in I alian)].
• A na a i e e iew abou ci inin occu ence in ood supplemen s (Sil a e al.,2021).
• A published a icle abou he quan i ica ion o lo as a in in Aga icus bispo us (mush oom species) (Tsian as e al.,2021).
• A published a icle con aining he e alua ion o he quali y p o ile o ood supplemen s con aining RYR ma ke ed in I aly
(Vi iello e al.,2023).
• A documen abou he i s iden i ica ion o M. pu pu eus (Wen ,1895).
The Panel conside s ha he ollowing documen s submi ed a e no pe inen o he sa e y assessmen o monacolins
om RYR, which do no include quali y aspec s o RYR supplemen s in he ma ke (see Sec ion1.3), and will no be consid-
e ed u he in his opinion:
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MONACOLINS FROM RED YEAST RICE PLACED UNDER UNION SCRUTINY
• The publica ions by Wen (1895), Bel án e al.(2019) and Sil a e al.(2021);
• Analy ical guideline o es ablish he speci ica ions o RYR p oduc s [SIFITLab Labo a o io d'analisi di Siena e al. (2018a)
(o iginal documen in I alian) and SIFITLab Labo a o io d'analisi di Siena e al. (2018b) ( ansla ion in English)];
• Da a ela ed o a ecen ood in oxica ion ou b eak in Japan ha has been a ibu ed o he con amina ion o RYR p od-
uc s du ing he e men a ion s age wi h Penicillium adame zoides. This ungus p oduces pube ulic acid, which can in-
duce enal dys unc ion (MHLW,2024);
• Na a i e e iews (Duong & Bajaj,2023; Fio en ino & Chia elli,2023; Haja , 2011), he sys ema ic e iew (Radaelli e al.,2018)
and he consensus s a emen om he AHA (Newman e al.,2019) on he sa e y o s a ins, which collec i ely add ess he
ade- o be ween bene icial and ad e se e ec s o he on- label and o - label use o s a ins o he ea men o hype -
choles e olaemia and/o he p e en ion o ca dio ascula diseases in di e en popula ion g oups, including child en and
adolescen s and do no p o ide ele an in o ma ion o he sa e y assessmen o monacolins om RYR, including he iden-
i ica ion o a daily dose o monacolin K om RYR in ood supplemen s ha does no aise sa e y conce ns o humans.
In acco dance wi h A icle 38 o Regula ion (EC) No 178/20024 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 39, 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,5 he non-
con iden ial e sions o he da a submi ed by he in e es ed pa ies a e published in OpenEFSA.6
Acco ding o A . 32c (2) o Regula ion (EC) No 178/2002 and acco ding o he Decision o EFSA's Execu i e Di ec o
laying down he p ac ical a angemen s on he p e- submission phase and public consul a ions, EFSA ca ied ou a public
consul a ion (PC- 1090) om 13 Augus o 03 Sep embe 2024 on he non- con iden ial e sion o he submissions by in e -
es ed pa ies. No commen s we e ecei ed.
2.2 | Me hodologies
The scien i ic e alua ion was based on he da a submi ed du ing he pe iod o sc u iny, and i was pe o med in line wi h
he p inciples desc ibed in he EFSA Guidance on anspa ency in he scien i ic aspec s o isk assessmen (EFSA,2009)
and ollowed he ele an exis ing guidance documen s om he EFSA Scien i ic Commi ee. The isk assessmen was pe -
o med acco ding o he EFSA Guidance on sa e y assessmen o bo anicals and bo anical p epa a ions in ended o use as
ing edien s in ood supplemen s (EFSA Scien i ic Commi ee,2009).
3 | ASSESSMENT
The da a submi ed by in e es ed pa ies o EFSA aim a add essing he unce ain ies iden i ied by he ANS Panel(2018),
which p ecluded es ablishing a HBGV o monacolins in RYR ood supplemen s. The NDA Panel conside s as pe inen o
ha pu pose:
• Analy ical da a abou he cha ac e isa ion o RYR p epa a ions (Lachenmeie e al.,2012; Linneus Consul ing Se ices,2024;
Righe i e al.,2021; Rigillo e al.,2025; Vi iello e al.,2023);
• Da a on he die a y in ake o monacolins om ood sou ces o he han RYR (AFEPADI,2024);
• In i o/in silico da a o RYR/monacolin K s. o he s a ins (Linneus Consul ing Se ices,2024; Rigillo e al.,2025);
• Nu i igilance/pos - ma ke ing da a on ad e se e en s ela ed o he use o RYR p oduc s (Banach & No a a,2023; Banach
e al.,2021; Banach e al.,2024, unpublished; No a a & Banach,2024; EHPM,2024; AFEPADI,2024);
• Case epo s o ad e se e en s om he scien i ic li e a u e (Banach & No a a,2023);
• New clinical da a including sa e y endpoin s (Shang e al.,2012; Cice o e al.,2024, unpublished).
3.1 | Analy ical da a abou he cha ac e isa ion o RYR p epa a ions
The ollowing unce ain ies in ela ion o he cha ac e isa ion o RYR p epa a ions we e highligh ed by he ANS Panel(2018):
a. he composi ion and con en o monacolins (and hei ela i e abundance) in ood supplemen s con aining RYR;
b. monacolins in RYR a e used in mul i- ing edien bo anical p epa a ions, he componen s o which ha e no been ully
e alua ed indi idually o in combina ion; and
c. he a io be ween monacolin K lac one and monacolin K hyd oxy acid (HA) is a iable in ood supplemen s con aining RYR.
4Regula 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.
5Decision a ailable online: h ps:// www. e sa. eu opa. eu/ en/ co po a e- pubs/ ans pa en cy- egul a ion - p ac ical- a an gemen s.
6The non- con iden ial e sion o he dossie , ollowing EFSA's assessmen o he applican 's con iden iali y eques s, is published on Open.EFSA and is a ailable a he
ollowing link: h ps:// open. e sa. eu opa. eu/ ques ions/ EFSA- Q- 2023- 00424 .
18314732, 2025, 2, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9276 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [13/05/2025]. 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
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7 o 17
MONACOLINS FROM RED YEAST RICE PLACED UNDER UNION SCRUTINY
Rigillo e al.(2025) analysed 14 comme cial- g ade RYR ood supplemen s wi h a decla ed o al monacolin K con en
anging om < 0.15% o 5% w/w using a high- pe o mance liquid ch oma og aphy wi h diode a ay de ec ion (HPLC- DAD)
me hod, which allows quan i ying he con en o o al monacolin K (as he sum o monacolin K in lac one and HA o ms)
and he con en o o he monacolins (as he sum o monacolin M, monacolin L, monacolin L HA, monacolin X, compac in,
dihyd omonacolin K and dehyd omonacolin K). To al monacolin K anged om 0.05% o 5.25% w/w in he analysed sam-
ples, showing de ia ions om he decla ed amoun s ( om −5% o +20%), while o he monacolins showed high a iabili y,
accoun ing o 3%–30% (mean 23%) o o al monacolins. The a io be ween monacolin K in lac one o m and monacolin K
in HA o m anged om app oxima ely 1:1–34:1 in he es ed samples. The a e age con en o o al polyphenols and o al
i e penes was 0.92% and 3.63% w/w, espec i ely, and did no co ela e wi h he o al con en o monacolins.
In he epo by Linneus Consul ing Se ices(2024), phy ochemical analyses we e conduc ed in 27 samples o RYR ood
supplemen s comme cially a ailable on he I alian ma ke and supplied by di e en companies. The con en o monacolin K
in lac one (MK- L), HA (MK- HA) and dehyd o- (DMK) o ms and he con en o o he monacolins (M- SEC; he sum o monacolin
L, compac in, monacolin J, monacolin L HA, monacolin X and monacolin M) we e quan i ied using HPLC- DAD- MS/MS and
high- esolu ion mass spec ome y (HRMS) me hods. The measu ed con en o o al monacolins ( om 0.45% o 7.84% w/w),
including all o ms o monacolin K and o he monacolins, di e ed om he decla ed con en ( om –37% o +62% w/w) in
mos samples o which his in o ma ion was a ailable. The a io MK- L:MK- HA a ied om 2.5:1 o 114:1 ac oss RYR samples.
Based on he a io be ween each monacolin measu ed (MK- L, MK- HA, DMK and M- SEC) and he sum o MK- L and MK- HA
(MK- L/MK- L+MK- HA; MK- HA/MK- L+MK- HA; DMK/MK- L+MK- HA; M- SEC/MK- L+MK- HA), a hie a chical clus e analysis (HCA)
was used o iden i y he di e en pa e ns o ela i e monacolin abundance ac oss RYR samples. The ou clus e s iden i ied
on such bases we e used o selec six RYR samples ha we e ep esen a i e o RYR supplemen s a ailable on he ma ke
o un a ge ed analyses and in i o cy o oxici y es ing (see Sec ion3.3). The Panel no es ha he ou clus e s iden i ied
widely di e ed in he ela i e abundance o MK- L, MK- HA, DMK and M- SEC. The six RYR samples selec ed unde wen e ha-
nol ex ac ion a di e en concen a ions (30%, 50% and 75%), ollowed by un a ge ed analysis by ul a- high- pe o mance
liquid ch oma og aphy- high- esolu ion mass spec ome y (UHPLC- HRMS) me hodology. The majo g oups o compounds
ound in he e hanol ex ac s we e monacolins (25%–30%), azaphilones (19%–23%) and polyke ides (10%–15%), he amoun s
o which a ied depending on he ex ac . O he compounds such as a y acids, lignans, glycosides, s e oids, amino acids,
couma ins, decalins, e penoids, alkaloids and la onoids we e also quan i ied.
An 1H- NMR s udy (Lachenmeie e al.,2012) p o ided in o ma ion abou he monacolin con en in i e comme cially
a ailable RYR p oduc s ob ained om web- shops. To al monacolin con en ( he sum o he lac one and HA o ms o mo-
nacolin K and o he monacolins con aining he hexahyd onaph halene moie y, including monacolins J, L, M o X) anged
be ween 1.5 and 8 mg/capsule (0.45%–1.33% w/w), leading o daily doses o 1.5–24 mg based on he manu ac u e 's
ecommenda ions.
In he s udy by Righe i e al.(2021), 37 RYR ood supplemen s as mono- o mul i- ing edien o mula ions a ailable on
he I alian ma ke we e analysed o hei con en o myco oxins (e.g. ci inin), MK- L and MK- HA. Among hese, nine RYR
p oduc s had a o al monacolin K con en below he label s a emen ( om −27 o −83%), wi h h ee p oduc s ha ing a
negligible con en , while he con en o o al monacolin K was highe han epo ed ( om 10% o 266%) in 25 p oduc s. In
ou p oduc s, he o al monacolin K con en would esul in a daily in ake below 3 mg ollowing he manu ac u e ecom-
menda ions, while in 20 p oduc s, he daily dose would exceed 10 mg, eaching 36 mg in one p oduc . The a io MK- HA/
MK- L+MK- HA ac oss samples a ied om 0.03 o 0.64. The au ho s no ed ha a iable bu small amoun s o sim as a in
(0.1–7.5 μg pe daily dose) we e also ound in 30 RYR ood supplemen s.
Vi iello e al.(2023) es ed 14 RYR ood supplemen s comme cially a ailable on he I alian ma ke wi h a decla ed mo-
nacolin K con en om 1.45 o 10 mg/uni o p oduc ( ilm- coa ed o uncoa ed able s, ha d- shell capsules, so gels). The
au ho s ound ha , in all p oduc s es ed, he measu ed con en o monacolin K de ia ed om he decla ed one ( om
−20.8% o +1.4%) and showed high a iabili y ac oss p oduc s ( om 1.47 o 10.14 mg o al monacolin K/uni o p oduc ).
The Panel acknowledges ha some in o ma ion has been p o ided ega ding he iden i ica ion and quan i ica ion o
compounds o he han monacolins in selec ed RYR samples and he iden i ica ion and quan i ica ion o monacolins and
hei ela i e abundance (Linneus Consul ing Se ices,2024; Rigillo e al.,2025), including he o al monacolins (Lachenmeie
e al.,2012), he amoun o o al monacolin K (Vi iello e al.,2023) and he a io be ween i s lac one and HA o m (Linneus
Consul ing Se ices,2024; Righe i e al.,2021; Rigillo e al.,2025). The Panel also no es, howe e , ha :
a. comme cially a ailable RYR ood supplemen s show high a iabili y in o al monacolin K con en ( om < 0.15%
o 7.48%, w/w), as well as in he amoun o o al monacolins/monacolin K measu ed s. decla ed on he p oduc
label; and
b. he a io be ween monacolin K in i s lac one o m (chemically iden ical o lo as a in) and i s HA o m shows signi ican
a iabili y in ood supplemen s con aining RYR, wi h epo ed a ios anging om 1:1 o 114:1.
The Panel conside s ha , al hough he da a p o ided con ibu e o he knowledge on he composi ion and o al mo-
nacolin p o ile o comme cially a ailable RYR supplemen s, i also s eng hens he conce ns exp essed by he EFSA ANS
Panel(2018) abou he unce ain ies ega ding he cha ac e isa ion o hese p oduc s, pa icula ly in ela ion o he a i-
abili y in con en o o al monacolin K and o he ela i e abundance o i s lac one and HA o ms, as hese wo o ms o
monacolin K a e mos likely esponsible o he ad e se heal h e ec s epo ed in ela ion o he consump ion o RYR
supplemen s.
18314732, 2025, 2, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9276 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [13/05/2025]. 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 17
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MONACOLINS FROM RED YEAST RICE PLACED UNDER UNION SCRUTINY
3.2 | Da a on he die a y in ake o monacolins om ood sou ces o he han RYR
In he documen by AFEPADI(2024), i is a gued ha monacolins (including monacolin K in lac one o m) a e na u ally occu -
ing subs ances ound no only in RYR bu also in a ious species o edible mush ooms (Ala cón e al.,2003; Chen e al.,2013;
Kała e al.,2020; Lam & Okello,2015; Lee e al.,2006; Lin e al.,2013; Lo e al.,2012; Tsian as e al.,2021). Consequen ly, he
in e es ed pa y a gued ha any isk assessmen o isk managemen ac ions conce ning monacolins om RYR should also
conside and apply o o he die a y sou ces.
The Panel no es he opinion o he Join Expe Commi ee BVL/B A M (BVL/B A M,2016), which e alua ed he occu -
ence o monacolins in ood sou ces and p o ided in ake es ima es. Thei e iew o he a ailable li e a u e on monacolin
con en in se e al edible mush oom species iden i ied se e al me hodological sho comings, pa icula ly conce ning sam-
ple p epa a ion and analy ical me hods used. To add ess hese limi a ions, he Commi ee conduc ed an in e nal s udy
using a alida ed me hod o measu e he monacolin con en in mush ooms. This s udy concluded ha he in ake o mo-
nacolin K lac one would ange om app oxima ely 4 o 11 μg pe 100–200 g o esh mush ooms consumed. The Panel
no es ha hese in ake le els a e se e al o de s o magni ude lowe han he cu en ly allowed maximum daily doses o
monacolin K om RYR when consumed as ood supplemen s [Regula ion (EC) 2022/860]. The e o e, he Panel conside s
ha he daily in ake o monacolin K om RYR would g ea ly exceed he amoun o monacolin K ha would be easonably
expec ed o be consumed in he con ex o a balanced and a ied die .
3.3 | In i o da a o RYR/monacolin K s. o he s a ins
In he s udy by Rigillo e al. (2024), he pha macokine ic di e ences be ween 1 mL o selec ed RYR solu ions wi h a o al
monacolin K con en be ween 1.55 and 5.25% w/w (see Sec ion3.1) and an equi alen concen a ion o pu e lo as a in
we e e alua ed in an in i o model o simula ed diges ion. The median bioaccessibili y a e o lo as a in, exp essed as %
o eco e y a e sample diges ion compa ed o he ini ial (p e- diges ion) amoun used, was 65.23% ± 18.45%, which was
explained by he poo solubili y o lo as a in in he diges i e en i onmen . When eplica ing he simula ed diges ion wi h-
ou enzymes, bu only changing he pH, a compa able eco e y was ob ained. Bioaccessibili y o monacolin K om RYR
samples a ied, bu i was highe han o lo as a in (only one sample had a sligh ly lowe alue), exceeding 80% in some
samples and eaching 100% in one sample, wi h a o al monacolin con en o 3.5% w/w. The au ho s no ed ha he bioac-
cessibili y o RYR samples was posi i ely associa ed wi h he con en o o he monacolins and i e penes and no wi h he
con en o monacolin K.
The in i o cy o oxic e ec s o 14 RYR samples, di e ing in monacolin K con en ( om 0.05% o 5.25% w/w), o al
polyphenols, and i e penes, as well as pu e lo as a in, we e assessed using he cell coun ing ki - 8 (CCK- 8) assay (Rigillo
e al.,2025). Cy o oxici y was measu ed a concen a ions anging om 10 o 200 μg/mL in a ious immo alised o cance -
de i ed cell lines, including human in es inal (Caco- 2), hepa ic (HepG2), kidney (HEK293) cells and mouse muscle (C2C12)
cells. The esul s we e exp essed as IC50 alues, ep esen ing he concen a ion equi ed o educe 50% o cell iabili y.
Mos RYR samples showed IC50 alues exceeding he highes concen a ion es ed, i.e. 200 μg/mL in all cell lines. IC50 al-
ues abo e 100 μg/mL we e shown in HEK293 cells by wo samples and in C2C12 cells by ou samples. When compa ed
wi h lo as a in, he only ema kable di e ence was ha he highes cy o oxici y o lo as a in was obse ed in he C2C12
myoblas cell line.
To in es iga e he molecula mechanisms o s a in- induced oxici y in muscle cells, he au ho s compa ed he e ec s o
selec ed RYR samples and lo as a in on he exp ession o genes in ol ed in muscle unc ion and me abolism, including
myoblas de e mina ion p o ein 1 (MyoD), muscle c ea ine kinase (MCK) and in e leukin- 6 (IL- 6). The C2C12 muscle cells
we e ea ed o 24 h wi h lo as a in (1 μg/mL) o RYRs a he equi alen monacolin K concen a ion, co esponding o
1 μg/mL. The mRNA le els o he selec ed genes we e measu ed by quan i a i e e e se ansc ip ion polyme ase chain
eac ion (RT- qPCR) and in he case o IL- 6, also a p o ein le els. Lo as a in ea men signi ican ly down egula ed MyoD
and up egula ed MCK and IL- 6 compa ed o con ols and RYR samples, sugges ing a ge ed e ec s on muscle physiology.
In con as , RYR samples showed minimal o spo adic e ec s, indica ing a mo e limi ed and a iable impac . Addi ionally,
he exp ession o au ophagy- (A g5 and A g7) and a ophy- ela ed genes (Fbxo32 and T im63) was analysed. Lo as a in sig-
ni ican ly up egula ed A g7 and T im63 mRNA le els compa ed o con ol, while RYR samples did no a ec he exp ession
o hese genes (Rigillo e al.,2025).
In he Linneus Consul ing Se ices epo (2024), an in i o Alama Blue cy o oxici y assay was conduc ed on li e
HepG2 cells exposed o 24 h o a ious concen a ions (0.1–100 μM) o sim as a in, a o as a in, monacolin K and six RYR
p epa a ions wi h a ying monacolin composi ions (0.45–7.84% w/w; see Sec ion3.1). Sim as a in caused signi ican cy-
o oxici y a highe concen a ions (97% a 100 μM, 70% a 50 μM), while a o as a in was less cy o oxic (49% a 100 μM).
Monacolin K caused 20% cell dea h only a 100 μM. RYR p epa a ions exhibi ed highe cy o oxici y o e all, wi h 72%–96%
cell dea h a 100 μM and up o 95% a 50 μM. No ably, h ee RYR samples showed sligh cy o oxici y (13%–18%) e en a
0.1 μM. Inc eased cy o oxici y co ela ed wi h highe dehyd omonacolin K con en . These indings sugges ha RYR p epa-
a ions a e mo e cy o oxic han pu e monacolin unde hese condi ions.
The Panel no es ha , based on he submi ed s udies, RYR p epa a ions (wi h o al monacolin K con en anging om
0.05% o 5.25% w/w) demons a e a iable cy o oxic e ec s, which a e gene ally less p onounced han hose obse ed o
lo as a in, pa icula ly in muscle C2C12 cells. Howe e , he IC50 alues epo ed o RYR p epa a ions a e p edominan ly
18314732, 2025, 2, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9276 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [13/05/2025]. 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
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MONACOLINS FROM RED YEAST RICE PLACED UNDER UNION SCRUTINY
h eshold alues (i.e. > 200 μg/mL), indica ing no cy o oxici y wi hin he es ed concen a ion ange. Consequen ly, he
ac ual IC50 alues could be any alue highe han 200 μg/mL, ende ing any de ini i e conclusion inapp op ia e. The anal-
ysis o ansc ip ional le els o a ge genes in ol ed in muscle unc ion and me abolism p o ides a plausible mechanism
o he g ea e oxici y o lo as a in in muscle cells compa ed o RYR p epa a ions. The Panel also no es he highe in i o
cy o oxici y o RYR samples as compa ed o monacolin K and o he s a ins (Linneus Consul ing Se ices epo ,2024) in
he HepG2 cell line, he same cell line ha showed a lack o cy o oxic e ec s wi h bo h lo as a in and RYR samples up o
200 μg/mL in he Rigillo e al. (2024) s udy. These con as ing indings highligh he a iabili y in RYR sample composi ions,
which may hampe cy o oxici y assessmen s. The Panel acknowledges ha , while in i o cy o oxici y s udies may o e
aluable mechanis ic insigh s, hei p edic i e alue o in i o oxici y is limi ed, especially when using immo alised cell
lines, as in he submi ed s udies. The Panel conside s ha , gi en hese limi a ions, hese s udies a e o limi ed alue o he
sa e y assessmen o monacolins in RYR o human consump ion.
3.4 | Nu i igilance/pos - ma ke ing da a on ad e se e en s ela ed o he use o
RYR p oduc s
A na a i e e iew (No a a & Banach,2024) epo ed on ad e se e en s ela ed o muscle and li e as a ge o gans associ-
a ed wi h he consump ion o p oduc s con aining RYR. The FDA Ad e se E en Repo ing Sys em (FAERS) (as o Sep embe
2023) and CFSAN Ad e se E en Repo ing Sys em (CAERS) (as o June 2023) we e used as sou ces o da a.
A o al o 28 cases o ad e se e en s, o which 25 we e classi ied as se ious e en s, we e e ie ed om FAERS. These
included eigh cases o musculoskele al- and connec i e issue- ela ed ad e se e en s, o which h ee we e cases o hab-
domyolysis. Se en women and one man ( om 51 o 78 yea s o age) we e a ec ed. In all cases, RYR was one among o he
ac i e ing edien s in he p oduc suspec ed o be esponsible o he ad e se e ec s, and in h ee cases, he concomi an
use o o he p oduc s/medica ions was no ed. Fou cases o li e - ela ed ad e se e en s we e epo ed, including h ee
cases o hepa ic cy olysis and one case o li e damage (no be e speci ied). Only males ( om 45 o 68 yea s o age) we e
a ec ed. The concomi an use o o he p oduc s/medica ions was no ed in all cases.
The analysis o he CAERS da abase e ie ed 223 cases o ad e se e en s in ela ion o RYR supplemen use. These in-
cluded 53 cases o muscle- ela ed ad e se e en s, wi h myalgia and muscle spasms being he mos common symp oms,
and 29 cases o li e - ela ed ad e se e en s, wi h abno mal li e unc ion es s being he mos common inding. Mul iple
ad e se e ec s we e o en epo ed by he same pe son. In 34 cases o muscle- ela ed ad e se e en s and 10 cases o li e -
ela ed ad e se e en s, RYR was one among o he ac i e ing edien s in he p oduc s suspec ed o be esponsible o he
ad e se e ec s, while in all o he cases, RYR was used in concomi ance wi h he suspec ed p oduc (o he han RYR). When
RYR was epo ed as he suspec ed p oduc , ad e se e en s we e mo e equen in women. The age o a ec ed indi iduals
anged om 36 o 91 yea s (median age: 64 yea s).
The Panel no es ha nei he he FAERS no he CAERS da abase allows concluding on causal ela ionships be ween
he use o RYR- con aining p oduc s and he epo ed ad e se e en s. The Panel also no es ha FAERS does no p o ide
in o ma ion on he doses o RYR consumed, while CAERS epo s a dose o 600 mg o RYR in se e al cases bu epo s no
in o ma ion on he monacolin con en o hese p oduc s.
The pape by Banach e al.(2021) epo s on pos - ma ke ing sa e y da a o he RYR- con aining ood supplemen s
A molipid® (s anda d) and A molipid® Plus (enhanced), a he ecommended dose o one able /day o 1 yea . One able
o A molipid (s anda d) con ained RYR (200 mg, o which 3 mg o monacolin K), olic acid (0.2 mg), CoQ10 (2 mg), as ax-
an hin (0.5 mg) and, in some coun ies, policosanols (10 mg). One able o A molipid Plus (enhanced) con ained Be be is
a is a a ex ac (588 mg, o which 500 mg o be be ine chlo ide), RYR (200 mg, o which 3 mg o monacolin K), policosanol
(10 mg), olic acid (0.2 mg), CoQ10 (2.0 mg) and as axan hin (0.5 mg).
Pos - ma ke ing in o ma ion was collec ed in a olun a y nu i igilance sys em es ablished by he manu ac u ing com-
pany (Meda Pha ma SpA, a Via is Company, Monza, I aly) om 1 Oc obe 2004 o 31 Decembe 2019. This sys em cap u ed
cases o suspec ed ad e se e ec s spon aneously epo ed by consume s, heal hca e p o essionals o heal h au ho i ies,
ega dless o causali y. A o al o 542 no i ica ions/cases epo ing on 855 ad e se e en s we e ecei ed ela ed o he use
o A molipid® (s anda d) and A molipid® Plus (enhanced). The numbe o musculoskele al ad e se e en s (% o he o al)
was 148 (17.3%), and he numbe o hepa ic ad e se e en s was 26 (3%). Se ious ad e se e en s occu ed in nine cases, wo
ela ed o habdomyolysis and se en o se ious hepa i is.
One case o habdomyolysis occu ed in an elde ly woman who ook A molipid® Plus (enhanced) while using se aline
and osu as a in. The second case was a consume (unknown sex) wi h a his o y o habdomyolysis in esponse o sim as-
a in who de eloped habdomyolysis equi ing hospi alisa ion a e s a ing A molipid® Plus (enhanced). The au ho s claim
ha , in bo h cases, he labelling wa nings agains concomi an use o RYR supplemen s and o he s a ins wi hou medical
supe ision we e no espec ed by he consume s. As o he se en cases o se ious hepa i is, causali y was assessed as
p obable (in wo cases), possible (in wo cases) and unlikely (in h ee cases) by he epo e based on he WHO- UMC sys em
c i e ia (WHO,2018).
The au ho s (Banach e al.,2021) calcula ed he o al epo ing a e o ad e se e en s and se ious ad e se e en s no i-
ied in ela ion o he consump ion o A molipid® (s anda d) and A molipid® Plus (enhanced) by es ima ing he numbe o
exposed consume s based on he numbe o able s manu ac u ed o e 15 yea s, assuming a consump ion o one able
pe day o 1 yea (n = 2,287,449). The o al epo ing a e (numbe o cases among o al consume s) was 0.0374% o any
18314732, 2025, 2, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9276 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [13/05/2025]. 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
16 o 17
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MONACOLINS FROM RED YEAST RICE PLACED UNDER UNION SCRUTINY
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h ps:// www. mhlw. go. jp/ s / seisa kuni sui e/ bunya/ kenkou_ i you/ shoku hin/ daie o/ index_ 00005. h ml
Newman, C. B., P eiss, D., Tobe , J. A., Jacobson, T. A., Page, R. L., 2nd, Golds ein, L. B., Chin, C., Tannock, L. R., Mille , M., Raghu ee , G., Duell, P. B., B in on,
E. A., Pollak, A., B aun, L. T., Wel y, F. K., & Ame ican Hea Associa ion Clinical Lipidology, Lipop o ein, Me abolism and Th ombosis Commi ee, a
Join Commi ee o he Council on A he oscle osis, Th ombosis and Vascula Biology and Council on Li es yle and Ca diome abolic Heal h; Council
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No a a, G. D., & Banach, M. (2024). The impac o ed yeas Rice ex ac use on he occu ence o muscle symp oms and li e dys unc ion: An upda e om
he ad e se e en epo ing sys ems and a ailable me a- analyses. Nu ien s, 16(3), 444. h ps:// doi. o g/ 10. 3390/ nu160 30444
Peng, D., Fong, A., & an Pel , A. (2017). O iginal esea ch. Ame ican Jou nal o Nu sing, 117(8), 46–54. h ps:// doi. o g/ 10. 1097/ 01. naj. 00005 21973. 38717. 2e
Pe e slund, P., Dahl Ch is ensen, H., U bahnke, J., & Cappeln, A. V. (2020). Røde gæ is som o mode å sag il aku ny e- og le e s ig . Ugesk i o Laege ,
182(13), V02190107. h p:// ugesk i e . dk/ iden skab/ ode- gae is- som- o mo de - a sag - il- aku - ny e- og- le e s ig
P asad, G. V., Wong, T., Meli on, G., & Bhaloo, S. (2002). Rhabdomyolysis due o ed yeas ice (Monascus pu pu eus) in a enal ansplan ecipien .
T ansplan a ion, 74(8), 1200–1201. h ps:// doi. o g/ 10. 1097/ 00007 890- 20021 0270- 00028
Radaelli, G., Sausen, G., Cesa, C. C., San os, F. S., Po al, V. L., Neyelo , J. L., & Pellanda, L. C. (2018). S a in ea men s and dosages in child en wi h amilial
hype choles e olemia: Me a- analysis. A qui os B asilei os de Ca diologia, 111(6), 810–821. h ps:// doi. o g/ 10. 5935/ abc. 20180180
Righe i, L., Dall'As a, C., & B uni, R. (2021). Risk assessmen o RYR ood supplemen s: Pe cep ion s. eali y. F on ie s in Nu i ion, 8, 792529. h ps:// doi.
o g/ 10. 3389/ nu . 2021. 792529
Rigillo, G., Baini, G., B uni, R., Puja, G., Mi aldi, E., Pani, L., Tascedda, F., & Biagi, M. (2025). Red yeas Rice o lo as a in? A compa a i e e alua ion o sa e y
and e icacy h ough a mul i ace ed app oach. Phy o he apy Resea ch: PTR, 39(1), 264–281. h ps:// doi. o g/ 10. 1002/ p . 8371
Roselle, H., Eka an, A., Tzeng, J., Sapienza, M., & Koche , J. (2008). Symp oma ic hepa i is associa ed wi h he use o he bal ed yeas Rice. Annals o
In e nal Medicine, 149(7), 516–517. h ps:// doi. o g/ 10. 7326/ 0003- 4819- 149- 7- 20081 0070- 00021
San os, S., Gomes, S., Ca alho, I., Boni o, I., & Ca mo, C. (2023). Rhabdomyolysis ela ed o ed yeas Rice inges ion. Cu eus, 15, e33532. h ps:// doi. o g/
10. 7759/ cu eus. 33532
Shang, Q., Liu, Z., Chen, K., Xu, H., & Liu, J. (2012). A sys ema ic e iew o xuezhikang, an ex ac om ed yeas ice, o co ona y hea disease compli-
ca ed by dyslipidemia. E idence- Bbased Complemen a y and Al e na i e Medicine, 2012, 636547. h ps:// doi. o g/ 10. 1155/ 2012/ 636547
SIFITLab Labo a o io d'analisi di Siena, Uni e si à degli S udi di Siena, Fondazione E. Mach. (2018a). Linea guida anali ica pe il iso osso e men a o.
Feb ua y 2018.
SIFITLab Labo a o io d'analisi di Siena, Uni e si à degli S udi di Siena, Fondazione E. Mach. (2018b). Analy ical guideline o ed yeas ice. English e -
sion. Feb ua y 2018.
Sil a, L. J. G., Pe ei a, A. M. P. T., Pena, A., & Lino, C. M. (2021). Ci inin in oods and supplemen s: A e iew o occu ence and analy ical me hodologies.
Foods (Basel, Swi ze land), 10(1), 14. h ps:// doi. o g/ 10. 3390/ oods 10010014
SmPC (Summa y o P oduc Cha ac e is ic) o lo as a in. (online). h ps:// m i. c s- m p. eu/ downl oad/ DK_H_ 0744_ 001_ Final SPC. pd
Tsian as, K., Tsiaka, T., Kou o sios, G., Siapi, E., Ze akis, G. I., Kaloge opoulos, N., & Zoumpoulakis, P. (2021). On he iden i ica ion and quan i ica ion o e -
go hioneine and lo as a in in a ious mush oom species: Asse s and challenges o di e en analy ical app oaches. Molecules (Basel, Swi ze land),
26(7), 1832. h ps:// doi. o g/ 10. 3390/ molec ules2 6071832
Vi iello, A., Izzo, L., Cas aldo, L., d'Angelo, I., Unga o, F., Mi o, A., Ri ieni, A., & Quaglia, F. (2023). The ques ionable quali y p o ile o ood supplemen s: The
case o ed yeas Rice ma ke ed p oduc s. Foods (Basel, Swi ze land), 12(11), 2142. h ps:// doi. o g/ 10. 3390/ oods 12112142
Wen , F. A. F. C. (1895). Monascus pu pu eus, le Champignon de l'Ang- Quac, une nou elle Thélébolée. Annales Ddes Ssciences Nna u elles, Bo anique, 1,
1–18.
WHO (Wo ld Heal h O ganiza ion). (2018). The use o he WHO- UMC sys em o s anda dised case causali y assessmen . Uppsala Moni o ing Cen e. h ps://
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Woo, J. J. (2007). Ad e se e en moni o ing and mul i i amin- mul imine al die a y supplemen s. The Ame ican Jou nal o Clinical Nu i ion, 85(1), 323S–
324S. h ps:// doi. o g/ 10. 1093/ ajcn/ 85.1. 323S
How o ci e his a icle: EFSA NDA Panel (EFSA Panel on Nu i ion, No el Foods and Food Alle gens), Tu ck, D.,
Bohn, T., Cáma a, M., Cas enmille , J., De Henauw, S., Hi sch- E ns , K. I., Jos, Á., Mangelsdo , I., McNul y, B., Naska, A.,
Pen ie a, K., Siani, A., Thies, F., Ma ije ić, L., Ma inez, S. V., & Maciuk, A. (2025). Scien i ic Opinion on addi ional
scien i ic da a ela ed o he sa e y o monacolins om ed yeas ice submi ed pu suan o A icle 8(4) o
Regula ion (EC) No 1925/2006. EFSA Jou nal, 23(2), e9276. h ps://doi.o g/10.2903/j.e sa.2025.9276
18314732, 2025, 2, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9276 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [13/05/2025]. 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
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17 o 17
MONACOLINS FROM RED YEAST RICE PLACED UNDER UNION SCRUTINY
APPENDIX A
Documen a ion as p o ided o EFSA
SISTE:
Banach, M., & No a a, G. D. (2023). Rhabdomyolysis o Se e e Acu e Hepa i is Associa ed wi h he Use o Red Yeas Rice Ex ac s: an Upda e om he
Ad e se E en Repo ing Sys ems. Cu en A he oscle osis Repo s, 25(11), 879–888. h ps:// doi. o g/ 10. 1007/ s1188 3- 023- 01157 - 4
Cice o, A. F. G., Pa izia Uboldi, Be e a, G., Fede ica Fogacci, G andi, E., S ecla, M., & No a a, G. D. (2024). E ec s o low- dose monacolin K on he ci cu-
la ing p o eome in indi iduals wi h subop imal choles e olaemia: A andomised clinical ial. MedRxi (Cold Sp ing Ha bo Labo a o y). h ps:// doi.
o g/ 10. 1101/ 2024. 06. 19. 24309106
No a a, G. D., & Banach, M. (2024). The Impac o Red Yeas Rice Ex ac Use on he Occu ence o Muscle Symp oms and Li e Dys unc ion: An Upda e
om he Ad e se E en Repo ing Sys ems and A ailable Me a- Analyses. Nu ien s, 16(3), 444. h ps:// doi. o g/ 10. 3390/ nu160 30444
EHPM:
EHPM (Eu opean Fede a ion o Associa ions o Heal h P oduc Manu ac u e s).(2024). Final epo o he EHPM Alliance o a Nu i igilance Sys em o
Food Supplemen s Pilo P ojec : Red Yeas Rice. Unpublished epo .
Rigillo, G., Baini, G., B uni, R., Puja, G., Mi aldi, E., Pani, L., Tascedda, F., & Biagi, M. (2025). Red Yeas Rice o Lo as a in? A Compa a i e E alua ion o Sa e y
and E icacy Th ough a Mul i ace ed App oach. Phy o he apy Resea ch: PTR, h ps:// doi. o g/ 10. 1002/ p . 8371
Linneus Consul ing Se ices:
Linneus Consul ing se ices.(2024). Fondazione Toscana Li e Sciences: Moni o ing o Fe men ed Red Yeas Rice (RYR) ood supplemen s. Repo _
EFSA_180624. Unpublished epo .
SUPPLEMENTARY_MATERIALS_TOT.pd .
Hyloba es Consul ing s l:
AFEPADI (Asociación Española de Complemen os Alimen icios).(2024). Monacolins in Red Yeas Rice, submission unde a icle 8, pa . 4 o Reg. (EC) No
1925/2006 demons a ing he sa e y o monacolins om ungal species, including monacolins om Red Yeas Rice. Unpublished epo .
AFEPADI20240703MonacolinRe e encesP o ided.pd .
Ala cón, J., Aguila, S., A ancibia- A ila, P., Fuen es, O., Zamo ano- Ponce, E., & He nández, M. (2003). P oduc ion and pu i ica ion o s a ins om Pleu o us
os ea us (Basidiomyce es) s ains. Zei sch i u Na u o schung. C, Jou nal o biosciences, 58(1–2), 62–64. h ps:// doi. o g/ 10. 1515/ znc- 2003- 1- 211
Bel án, D., F u os- Lisón, M. D., Espín, J. C., & Ga cía- Villalba, R. (2019). Re- examining he ole o he gu mic obio a in he con e sion o he lipid- lowe ing
s a in monacolin K (lo as a in) in o i s ac i e β- hyd oxy acid me aboli e. Food & Func ion, 10(4), 1787–1791. h ps:// doi. o g/ 10. 1039/ c8 o0 2594k
Duong, H., & Bajaj, T. (2023). Lo as a in. S a Pea ls. A ailable om: h ps:// www. ncbi. nlm. nih. go / books/ NBK54 0994/
Fio en ino, R., & Chia elli, F. (2023). S a ins in Child en, an Upda e. In e na ional Jou nal o Molecula Sciences, 24(2), 1366. h ps:// doi. o g/ 10. 3390/ ijms2
4021366
Haja R. (2011). S a ins: Pas and p esen . Hea Views: The O icial Jou nal o he Gul Hea Associa ion, 12(3), 121–127. h ps:// doi. o g/ 10. 4103/ 1995- 705X.
95070
Hylo2024SignedLe e .pd .
Lachenmeie , D. W., Monakho a, Y. B., Kuballa, T., Löbell- Beh ends, S., Maixne , S., Kohl- Himmelsehe , M., Waldne , A., & S e en, C. (2012). NMR e alua-
ion o o al s a in con en and HMG- CoA educ ase inhibi ion in ed yeas ice (Monascus spp.) ood supplemen s. Chinese Medicine, 7, 8. h ps://
doi. o g/ 10. 1186/ 1749- 8546- 7- 8.
López Sánchez, P., de Nijs, M., Spanje , M., Pie i, A., Be uzzi, T., S a ski, A., Pos upolski, J., Cas ella i, M., & Ho ós, M. (2017). Gene a ion o occu ence
da a on ci inin in ood. EFSA Suppo ing Publica ions, 14(2), A icle 1177E. h ps:// doi. o g/ 10. 2903/ sp. e sa. 2017. EN- 1177
Radaelli, G., Sausen, G., Cesa, C. C., San os, F. S., Po al, V. L., Neyelo , J. L., & Pellanda, L. C. (2018). S a in T ea men s and Dosages In Child en Wi h Familial
Hype choles e olemia: Me a- Analysis. A qui os b asilei os de ca diologia, 111(6), 810–821. h ps:// doi. o g/ 10. 5935/ abc. 20180180
Righe i, L., Dall'As a, C., & B uni, R. (2021). Risk Assessmen o RYR Food Supplemen s: Pe cep ion s. Reali y. F on ie s in Nu i ion, 8, 792529. h ps:// doi.
o g/ 10. 3389/ nu . 2021. 792529
Shang, Q., Liu, Z., Chen, K., Xu, H., & Liu, J. (2012). A sys ema ic e iew o xuezhikang, an ex ac om ed yeas ice, o co ona y hea disease compli-
ca ed by dyslipidemia. E idence- Based Complemen a y and Al e na i e Medicine: eCAM, 2012, 636547. h ps:// doi. o g/ 10. 1155/ 2012/ 636547
SIFITLab Labo a o io d'analisi di Siena, Uni e si à degli S udi di Siena, Fondazione E. Mach. (2018). Linea guida anali ica pe il iso osso e men a o.
Feb ua y 2018.
SIFITLab Labo a o io d'analisi di Siena, Uni e si à degli S udi di Siena, Fondazione E. Mach. (2018). Analy ical guideline o ed yeas ice. English e sion.
Feb ua y 2018.
Sil a, L. J. G., Pe ei a, A. M. P. T., Pena, A., & Lino, C. M. (2021). Ci inin in oods and supplemen s: A e iew o occu ence and analy ical me hodologies.
Foods (Basel, Swi ze land), 10(1), 14. h ps:// doi. o g/ 10. 3390/ oods 10010014
Tsian as, K., Tsiaka, T., Kou o sios, G., Siapi, E., Ze akis, G. I., Kaloge opoulos, N., & Zoumpoulakis, P. (2021). On he Iden i ica ion and Quan i ica ion
o E go hioneine and Lo as a in in Va ious Mush oom Species: Asse s and Challenges o Di e en Analy ical App oaches. Molecules (Basel,
Swi ze land), 26(7), 1832. h ps:// doi. o g/ 10. 3390/ molec ules2 6071832
Vi iello, A., Izzo, L., Cas aldo, L., d'Angelo, I., Unga o, F., Mi o, A., Ri ieni, A., & Quaglia, F. (2023). The Ques ionable Quali y P o ile o Food Supplemen s:
The Case o Red Yeas Rice Ma ke ed P oduc s. Foods (Basel, Swi ze land), 12(11), 2142. h ps:// doi. o g/ 10. 3390/ oods 12112142
Wen , F.A.F.C. (1895). Monascus pu pu eus, le Champignon de l'Ang- Quac, une nou elle Thélébolée. Annales des Sciences Na u elles Bo anique, 1, 1–18.
The EFSA Jou nal is a publica ion o he Eu opean Food Sa e y
Au ho i y, a Eu opean agency unded by he Eu opean Union
18314732, 2025, 2, Downloaded om h ps://e sa.onlinelib a y.wiley.com/doi/10.2903/j.e sa.2025.9276 by Readcube (Lab i a Inc.), Wiley Online Lib a y on [13/05/2025]. 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
