F on ie s in Nu i ion 01 on ie sin.o g
Heal h bene i s and isks o
e men ed oods— he PIMENTO
ini ia i e
SmiljaTodo o ic
1, AsliAkpina
2, Rica doAssunção
3,
Co neliaBä
4, SimonaL.Ba a o
5, MuzeyyenBe kelKasikci
2,6,
Julie aDomínguez-Sobe anes
7, Vi o ioCapozzi
8,
PaulD.Co e
9, Eun-HeeDoo
10, Bu cuGündüzE gün
11,
Mus a aGuzel
12, Hay iyeS.Ha sa
13, Em eHas aoglu
14,
Ch is èleHumblo
15, Bah i Hyseni
16, MugeI.Hosoglu
17,
AlineIssa
18, Ba çınKa akaş-Budak
19, SibelKa akaya
20,
Ha unKesenkas
21, E hanKey an
22, Ib ahimE.Künili
23,
Ma y-LiisKü
24, Ma aLa anjo
25, Sand ineLouis
26,
FaniT.Man zou idou
27, An oniaMa alas
28, Bal asa Mayo
29,
Sand aMojso a
30, A ghyaMukhe jee
9, Anas asiosNikolaou
31,
Fa ihO akci
32, DianaPa eljšek
33, Gianca loPe one
34,
EugeniaPe zige
35,36, DushicaSan a
37, Tane Sa
38,
IsabelleSa a y-Auzeloux
39, Cla issaSchwab
40,
Małgo za aS a owicz
41, Ma koS ojano ić
42, MichailSy pas
43,
Jyo iP.Tamang
44, Ok ayYe likaya
21, Bi senYilmaz
45,46,
Jead anMalagon-Rojas
47, SeppoSalminen
48, JuanaF ias
49,
Ch is opheChassa d
39 and GuyVe gè es
35*
1 Ins i u e o Biological Resea ch Sinisa S anko ic, Na ional Ins i u e o Republic o Se bia, Uni e si y
o Belg ade, Belg ade, Se bia, 2 Depa men o Food Enginee ing, Manisa Celal Baya Uni e si y Facul y
o Enginee ing and Na u al Science, Manisa, Tü kiye, 3 Egas Moniz Cen e o In e disciplina y
Resea ch (CiiEM), Egas Moniz School o Heal h and Science, Almada, Po ugal, 4 Compe ence Di ision
Me hod De elopmen and Analy ics, Ag oscope, Be ne, Swi ze land, 5 Ins i u e o Sciences o Food
P oduc ion (ISPA), Na ional Resea ch Council (CNR), Ba i, I aly, 6 STLO, INRAE, Ins i u Ag o-Rennes
Ange s, Rennes, F ance, 7 Facul ad de Ingenie ía, Uni e sidad Paname icana, Aguascalien es, Mexico,
8 Depa men o Food Science, Uni e si y o Foggia, Foggia, I aly, 9 Depa men o Food Biosciences,
Teagasc Food Resea ch Cen e, Fe moy, I eland, 10 School o Li ing and En i onmen al Enginee ing,
Dongyang Mi ae Uni e si y, Seoul, Republic o Ko ea, 11 Bio echnology Resea ch Cen e , Field C ops
Cen al Resea ch Ins i u e, Anka a, Tü kiye, 12 Depa men o Food Enginee ing, Hi i Uni e si y,
Co um, Tü kiye, 13 Depa men o Food Enginee ing, Izmi Ins i u e o Technology, Izmi , Tü kiye,
14 Cumhu iye Uni e si y, Si as, Tü kiye, 15 F ench Na ional Resea ch Ins i u e o Sus ainable
De elopmen (IRD), Mon pellie , F ance, 16 Facul y o Food Technology, Uni e si y “Isa Bole ini”,
Mi o ica, Republic o Koso o, 17 Bio echnology Ins i u e, Gebze Technical Uni e si y, Kocaeli, Tü kiye,
18 Facul y o Nu sing and Heal h Sciences, No e Dame Uni e si y-Louaize, Zouk Mosbeh, Lebanon,
19 Depa men o Food Enginee ing, Akdeniz Uni e si y Facul y o Enginee ing, An alya, Tü kiye,
20 Depa men o Food Enginee ing, Facul y o Enginee ing, Ege Uni e si y, Izmi , Tü kiye,
21 Depa men o Dai y Technology, Facul y o Ag icul u e, Ege Uni e si y, Izmi , Tü kiye, 22 Depa men
o Food Hygiene and Technology, Facul y o Ve e ina y Medicine, Bu du Mehme Aki E soy
Uni e si y, Bu du , Tü kiye, 23 Depa men o Fishing and Fish P ocessing Technology, Facul y o Ma ine
Sciences and Technology, Canakkale Onsekiz Ma Uni e si y, Canakkale, Tü kiye, 24 ÄIO, Tallinn,
Es onia, 25 MED-Medi e anean Ins i u e o Ag icul u e, En i onmen and De elopmen -CHANGE-
Global Change and Sus ainabili y Ins i u e and Depa amen o de Medicina Ve e iná ia-Escola de
Ciências e Tecnologia (ECT), Uni e sidade de É o a, É o a, Po ugal, 26 Depa men o Physiology and
Biochemis y o Nu i ion, Max Rubne -Ins i u , Ka ls uhe, Ge many, 27 Labo a o y o Food Chemis y
and Technology, School o Chemis y, A is o le Uni e si y o Thessaloniki, Thessaloniki, G eece,
28 Depa men o Nu i ion and Die e ics, Ha okopio Uni e si y, A hens, G eece, 29 Depa amen o de
Mic obiología y Bioquímica, Ins i u o de P oduc os Lác eos de As u ias (IPLA), Consejo Supe io de
In es igaciones Cien í icas (CSIC), Villa iciosa, Spain, 30 Depa men o Food Sa e y and Ve e ina y
Public Heal h, Food Ins i u e, Facul y o Ve e ina y Medicine, Skopje, Ss. Cy il and Me hodius
Uni e si y, Skopje, No h Macedonia, 31 Depa men o Molecula Biology and Gene ics, Democ i us
OPEN ACCESS
EDITED BY
Ma ia João F aqueza,
Uni e si y o Lisbon, Po ugal
REVIEWED BY
Chia a De i giliis,
CREA (Consiglio pe la ice ca in ag icol u a e
l’analisi dell’economia ag a ia), I aly
Luis Pa a a a,
Uni e si y o T ás-os-Mon es and Al o Dou o,
Po ugal
*CORRESPONDENCE
Guy Ve gè es
guy. e ge [email p o ec ed]
RECEIVED 02 July 2024
ACCEPTED 14 Augus 2024
PUBLISHED 03 Sep embe 2024
CITATION
Todo o ic S, Akpina A, Assunção R, Bä C,
Ba a o SL, Be kel Kasikci M,
Domínguez-Sobe anes J, Capozzi V,
Co e PD, Doo E-H, Gündüz E gün B,
Guzel M, Ha sa HS, Has aoglu E, Humblo C,
Hyseni B, Hosoglu MI, Issa A,
Ka akaş-Budak B, Ka akaya S, Kesenkas H,
Key an E, Künili IE, Kü M-L, La anjo M,
Louis S, Man zou idou FT, Ma alas A, Mayo B,
Mojso a S, Mukhe jee A, Nikolaou A,
O akci F, Pa eljšek D, Pe one G, Pe zige E,
San a D, Sa T, Sa a y-Auzeloux I, Schwab C,
S a owicz M, S ojano ić M, Sy pas M,
Tamang JP, Ye likaya O, Yilmaz B,
Malagon-Rojas J, Salminen S, F ias J,
Chassa d C and Ve gè es G (2024) Heal h
bene i s and isks o e men ed oods— he
PIMENTO ini ia i e.
F on . Nu . 11:1458536.
doi: 10.3389/ nu .2024.1458536
COPYRIGHT
© 2024 Todo o ic, Akpina , Assunção, Bä ,
Ba a o, Be kel Kasikci,
Domínguez-Sobe anes, Capozzi, Co e , Doo,
Gündüz E gün, Guzel, Ha sa, Has aoglu,
Humblo , Hyseni, Hosoglu, Issa,
Ka akaş-Budak, Ka akaya, Kesenkas, Key an,
Künili, Kü , La anjo, Louis, Man zou idou,
Ma alas, Mayo, Mojso a, Mukhe jee, Nikolaou,
O akci, Pa eljšek, Pe one, Pe zige , San a,
Sa , Sa a y-Auzeloux, Schwab, S a owicz,
S ojano ić, Sy pas, Tamang, Ye likaya, Yilmaz,
Malagon-Rojas, Salminen, F ias, Chassa d and
Ve gè es. This is an open-access a icle
dis ibu ed unde he e ms o he C ea i e
Commons A ibu ion License (CC BY). The
use, dis ibu ion o ep oduc ion in o he
o ums is pe mi ed, p o ided he o iginal
au ho (s) and he copy igh owne (s) a e
c edi ed and ha he o iginal publica ion in
his jou nal is ci ed, in acco dance wi h
accep ed academic p ac ice. No use,
dis ibu ion o ep oduc ion is pe mi ed
which does no comply wi h hese e ms.
TYPE Concep ual Analysis
PUBLISHED 03 Sep embe 2024
DOI 10.3389/ nu .2024.1458536
Todo o ic e al. 10.3389/ nu .2024.1458536
F on ie s in Nu i ion 02 on ie sin.o g
Uni e si y o Th ace, Alexand oupolis, G eece, 32 Food Enginee ing Depa men , Is anbul Technical
Uni e si y, Is anbul, Tü kiye, 33 Ins i u e o Dai y Science and P obio ics, Depa men o Animal Science,
Bio echnical Facul y, Uni e si y o Ljubljana, Domžale, Slo enia, 34 Consiglio Nazionale delle Rice che,
Is i u o di Scienze delle P oduzioni Alimen a i, Ba i, I aly, 35 Resea ch Di ision Mic obial Food Sys ems,
Ag oscope, Be ne, Swi ze land, 36 Depa men o Epidemiology and Heal h Sys ems, Cen e o
P ima y Ca e and Public Heal h (Unisan é), Uni e si y o Lausanne, Lausanne, Swi ze land, 37 Facul y o
Ag icul u al Sciences and Food, Ss. Cy il and Me hodius Uni e si y in Skopje, Skopje, No h
Macedonia, 38 Swedish Cen e o Resou ce Reco e y, Uni e si y o Bo ås, Bo ås, Sweden, 39 Human
Nu i ion Uni , INRAE, Uni e si é Cle mon -Au e gne, Cle mon -Fe and, F ance, 40 Depa men o
Biological and Chemical Enginee ing, Aa hus Uni e si y, Aa hus, Denma k, 41 Depa men o Chemis y
and Biodynamics o Food, Ins i u e o Animal Rep oduc ion and Food Resea ch o he Polish
Academy o Sciences, Olsz yn, Poland, 42 Facul y o Medicine, Uni e si y o Belg ade, Belg ade, Se bia,
43 Depa men o Food Science and Technology, Kaunas Uni e si y o Technology, Kaunas, Li huania,
44 Depa men o Mic obiology, School o Li e Sciences, Sikkim Uni e si y, Gang ok, India,
45 Depa men o Biological Sciences, Ta a Ins i u e o Fundamen al Resea ch, Hyde abad, India,
46 Depa men o Nu i ion and Die e ics, Facul y o Heal h Sciences, Çuku o a Uni e si y, Adana,
Tü kiye, 47 Ins i u o Nacional de Salud de Colombia, Bogo á, Colombia, 48 Func ional oods Fo um,
Facul y o Medicine, Uni e si y o Tu ku, Tu ku, Finland, 49 Depa men o Technological P ocesses and
Bio echnology, Ins i u e o Food Science, Technology and Nu i ion (ICTAN-CSIC), Mad id, Spain
Wo ldwide, e men ed oods (FF) a e ecognized as heal hy and sa e. Despi e
he apid inc ease o esea ch pape s, he e is a lack o sys ema ic e alua ion
o he heal h bene i s and isks o FF. The COST Ac ion CA20128 “P omo ing
inno a ion o e men ed oods” (PIMENTO) aims o p o ide a comp ehensi e
assessmen on he a ailable e idence by compiling a se o 16 e iews. Se en
e iews will co e clinical and biological endpoin s associa ed wi h majo
heal h indica o s ac oss se e al o gan sys ems, including he ca dio ascula ,
gas oin es inal, neu ological, immune, and skele al sys ems. Nine e iews will
add ess b oade biological ques ions associa ed wi h FF including bioac i e
compounds and i amin p oduc ion, nu ien bioa ailabili y and bioaccessibili y,
he ole o FF in heal hy die s and pe sonalized nu i ion, ood sa e y, egula o y
p ac ices, and inally, he heal h p ope ies o no el and e hnic FF. Fo each
ou come assessed in he e iews, an inno a i e app oach will beadop ed based
on EFSA’s published guidance o heal h claim submissions. In pa icula , each
e iew will be composed o h ee pa s: (1) a sys ema ic e iew o a ailable
human s udies; (2) a non-sys ema ic e iew o he mechanism o ac ion ela ed
o he clinical endpoin s measu ed by he human s udies iden i ied in pa 1; and
(3) a non-sys ema ic e iew o he cha ac e iza ion o he FF in es iga ed in he
human s udies iden i ied in pa 1. The e idence and esea ch gaps de i ed om
he e iews will besumma ized and published in he o m o a s a egic oad
map ha will pa e he way o u u e esea ch on FF.
KEYWORDS
e men ed oods, ood cha ac e iza ion, ood sa e y, unc ional claims, heal h bene i s,
heal h claims, mechanism o ac ion, sys ema ic e iew
In oduc ion
Need o coo dina ed esea ch on FF—
PIMENTO
The impac o ood sys ems on plane a y heal h is a socie al issue
o pa amoun impo ance eques ing a ansi ion owa ds mo e
sus ainable die s (1, 2). This ansi ion esona es wi h he g owing
consume demand o na u al and heal hie p oduc s a ailable a
a o dable p ices (3). On he o he hand, while a body o e idence
indica es he impo ance o die a y di e si y o human heal h (4),
biodi e si y is dec easing wo ldwide (5). In imes when die s a e
apidly changing owa ds highly p ocessed oods, he e is a c i ical
need o main ain and imp o e ood as a sou ce o di e se nu ien s as
well as bene icial mic obes (6, 7).
FF hold a s a egic place in all Eu opean die s due o he bene i s
hey o e in e ms o nu i ion, cul u al he i age, inno a ion,
sus ainabili y, and consume in e es . In pa icula , he po en ial o FF
as pa o he die o imp o ing human heal h has become highly
ele an (8, 9). FF can mee he demands ou lined abo e owing o hei
unique p ope ies (10), which include he p esence o li e
mic oo ganisms and mic obial me aboli es, i amins, and bioac i e
compounds as well as ex ended shel -li e. Howe e , o ully ealize
hei po en ial, he e is a need o coo dina ing he weal h o new
scien i ic e idence on FF eme ging om he s udies on ood
ecosys ems, sys emic app oaches o ood mic obiology, oodomics,
Todo o ic e al. 10.3389/ nu .2024.1458536
F on ie s in Nu i ion 03 on ie sin.o g
and nu igenomics as well as on he ole o he gu mic obio a and he
gas oin es inal (GI) ac in heal h and disease onse (9, 11). This
consolida ed knowledge and, he e o e, FF can beul ima ely in eg a ed
in o e ec i e public heal h and sus ainabili y policies (12).
PIMENTO is a Eu opean ini ia i e unded by he COST Ac ion
(CA20128) o add ess he needs indica ed abo e h ough esea ch on
FF. In pa icula , PIMENTO con ibu es o an open-access
iden i ica ion, s anda diza ion, and mapping o exis ing and po en ial
bene icial mic oo ganisms and communi ies. PIMENTO also
collec i ely ad ances he scien i ic e idence on he heal h e ec s o FF,
building a isk–bene i app oach and igh ly connec ing and cla i ying
he scien i ic e idence on he heal h-p omo ing p ope ies o
FF. Fu he mo e, PIMENTO con ibu es o he Eu opean G een Deal
s a egy “Fa m o Fo k” by enhancing esea ch and inno a ion on
e men a ion-based solu ions and p ocesses, imp o ing ood’s
nu i ional, s uc u al and unc ional p ope ies. Th ough i s mul i-
modal inno a i e app oach, PIMENTO no only esponds o he
expec a ions o di e en Eu opean communi ies o heal hy and
sus ainable ood p oduc s by boos ing he de elopmen o FF, bu also
places Eu ope as a leade in FF inno a ion wo ldwide.
Inno a i e s a egy o e alua e he
heal h bene i s and isks o FF
In line wi h PIMENTO’s mission Wo king G oup3 o PIMENTO
(PIMENTO WG3) aims a e alua ing he heal h bene i s and isks o
FF. Compa ed o o he componen s o he human die , FF add a
unique dimension o he ela ionship be ween die and heal h because
his ca ego y o oods con ains e men a i e mic oo ganisms and hei
e men a ion p oduc s in addi ion o he mac o- and mic onu ien s
classically s udied by nu i ionis s. Al hough nu i ion science is an
in e disciplina y ield, published esea ch epo s a e o en
cha ac e ized by a limi ed scope, esul ing in a lack o holis ic
assessmen o he complex a ay o elemen s ha cha ac e ize he
in e ac ion o ood componen s wi h he human body. This
agmen ed app oach o nu i ion esea ch makes i di icul o
objec i ely cha ac e ize he heal h p ope ies o die s, oods, o
nu ien s. A p agma ic, ye inno a i e app oach o he academic
sec o o ackle he heal h p ope ies o die s is o use he “Eu opean
Food Sa e y Au ho i y” (EFSA) heal h claim guidelines (13, 14). The
EFSA guidance equi es no only ha he esul s o human s udies a e
sys ema ically epo ed and e alua ed bu also an assessmen o he
p ope ies o a ood o ing edien o which he e ec is claimed. This
cha ac e iza ion comp ises in o ma ion on he composi ion and
s abili y o he ac i e compounds in he ood o in e es . Fu he mo e,
EFSA asks o addi ional da a on he mechanism o ac ion o
bep o ided, de i ed om in i o o animal models. The mechanis ic
da a should becomplemen ed by in o ma ion abou he bioa ailabili y
and bioaccessibili y o he ac i e compounds.
Al hough e men ed oods a e di e se, unde lying mechanisms
con ibu ing o hei po en ial impac on heal h migh besimila . A
ha monized and sys ema ic e iew on he scien i ic e idence o he
heal h p ope ies o FF can hus lead o he iden i ica ion o common
unc ional p ope ies. PIMENTO WG3 will e alua e he heal h
p ope ies o FF by ollowing an inno a i e app oach ha will
bebased on he compila ion o a se ies o e iews based on he EFSA
guidance o heal h claims. This s a egy includes he h ee pilla s
human s udies, p oduc cha ac e is ics, and mechanism o ac ion as
well as wo complemen a y opics closely associa ed wi h FF, i.e., ood
sa e y and he in e ac ion be ween FF and gu mic obio a.
In May 2022, a wo kshop was held in Belg ade o de ine he
unc ional hema ic a eas ha he PIMENTO COST Ac ion should
in es iga e. A se ies o 16 hema ic a eas co e ing he mos ele an
heal h indica o s in key o gan sys ems we e selec ed. These hema ic
a eas we e o ganized in o wo g oups acco ding o whe he hey could
be e iewed in close alignmen wi h he EFSA guidance. Se en “EFSA
p ojec s” (E1-E7) we e de ined, co e ing he ollowing clinical a eas:
GI heal h (E1), alle gy (E2), immuni y (E3), me abolic heal h (E4),
ca dio ascula heal h (E5), bone heal h (E6), and cogni i e heal h
(E7). Nine “Sa elli e p ojec s” (S1-S9) we e also o med, co e ing
impo an opics on FF ha a e less amenable o adap a ion o he
EFSA guidance: bioac i e compounds (S1), i amin p oduc ion (S2),
nu ien bioa ailabili y and bioaccessibili y (S3), e hnic oods (S4),
heal hy die s (S5), pe sonalized nu i ion (S6), ood sa e y (S7), no el
oods (S8), and byp oduc s o e men a ion (S9).
Following his ini ial phase, a i s ound o li e a u e analyses was
conduc ed o de ine a speci ic esea ch ques ion o each o he opics.
These ques ions should be sys ema ically add essed o assess he
a ailable e idence and iden i y knowledge gaps o ocus u u e
esea ch. The inal e iew ques ions a e p esen ed in Table1. As he
p elimina y wo k p og essed, he e iew p ocess became inc easingly
ha monized and he dis inc ion be ween he wo ca ego ies o e iews
blu ed so ha he 16 e iews we e no longe e e ed o as EFSA o
Sa elli e e iews. Finally, a gene ic s udy p o ocol (PIMENTO-SP;
Supplemen a y File 1) was de eloped based on he PROSPERO
guidance o sys ema ic e iews (13, 15) and u he adap ed o
in eg a e he non-sys ema ic pa s o he e iews. In addi ion, a
gene ic sea ch s a egy o he li e a u e in PubMed, Scopus, and he
Coch ane Lib a y Cen al (PIMENTO-LS) was de eloped o
sys ema ically sea ch o human s udies epo ing on he heal h e ec s
o FF (Supplemen a y File 2). PIMENTO-SP and PIMENTO-LS
o ms will beused as a amewo k o he con en o each e iew and
adap ed acco ding o he speci ics o he biological o clinical
endpoin s being add essed.
A summa y o he aims and me hodology o each o he 16
e iews unde p epa a ion is p esen ed in he ollowing sec ions.
Al hough he sec ions below ocus hei esea ch summa y on he
analysis o he human clinical s udies, each o he 16 p ojec s will also
add ess he non-sys ema ic pa s discussed abo e. Speci ic s udy
p o ocols we e p epa ed o each e iew and we e deposi ed in he
Open Science F amewo k (OSF). In addi ion o he e iew plans, he
s udy p o ocols documen he names and ins i u es o he
e iewing eams.
Resea ch ques ions add essed by he
PIMENTO WG3 e iews
Gas oin es inal heal h
In ecen yea s, FF ha e been he ocus o a esu gence in in e es
among he gene al public, p ima ily owing o hei pu po ed heal h
bene i s. Indeed, g owing e idence shows ha FF posi i ely modula es
GI heal h h ough di e se mechanisms, including he po en ial
p obio ic e ec o hei cons i uen mic obes, educ ion o
Todo o ic e al. 10.3389/ nu .2024.1458536
F on ie s in Nu i ion 04 on ie sin.o g
an i-nu ien s, and bioac i i y o no el compounds p oduced du ing
e men a ion, among o he s (16). Conce ning he o me , i is no able
ha se e al p obio ic mic obes, which a e o en closely ela ed o
hose ound in FF (17, 18), ha e been shown o bebene icial in he
managemen o GI symp oms in di e en popula ions, such as
p egnan women, a hle es, and pa ien s wi h i i able bowel synd ome
(IBS) and neu odegene a i e diso de s (19–22). Howe e , despi e his
g owing body o e idence, a sys ema ic e iew o he impac o FF
consump ion on GI discom o and GI unc ions, such as de eca ion,
in heal hy adul s has no been conduc ed.
This sys ema ic e iew will add ess he ollowing ques ion: “Does
consump ion o e men ed oods ha e a bene icial e ec on
gas oin es inal discom o and no mal de eca ion in a heal hy adul
popula ion?” To answe his esea ch ques ion, wewill in es iga e he
e ec o FF consump ion on GI discom o and de eca ion as guided
by he “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 ense
agains pa hogenic mic oo ganisms” (23). Acco ding o EFSA,
symp oms associa ed wi h GI discom o include abdominal pain,
c amps, bloa ing, s aining, bo bo ygmi ( umbling) and a sensa ion
o incomple e e acua ion, along wi h excessi e in es inal gas
accumula ion. Reducing GI discom o is conside ed an indica o o
imp o ed GI unc ion and, hence, a bene icial physiological e ec
(23). Simila ly, main enance o no mal de eca ion is ega ded as a
bene icial physiological e ec o he gene al popula ion, gi en ha i
does no esul in dia hea. The e o e, he e iew will addi ionally
in es iga e he e ec o FF consump ion on de eca ion in he con ex
o main enance o acili a ion o no mal de eca ion h ough one o
mo e o he ollowing means: imp o ed equency o bowel
mo emen s, inc eased ecal bulk, imp o ing s ool consis ency, o
dec easing ansi ime.
OSF link o s udy p o ocol: PIMENTO-SP-E1.
Alle gies
Food alle gy (FA) is an abno mal eac ion o he immune sys em
a e exposu e o speci ic oods, which is a se ious ood sa e y and public
heal h p oblem wo ldwide. Cu en ly, ood alle gies a ec up o 10% o
child en and 2–3% o adul s and appea o beinc easing in p e alence
ac oss he wo ld (24). Based on he immunological mechanisms
in ol ed, FA may beclassi ied as (1) IgE-media ed, he mos well-
unde s ood o m, which is caused by IgE an ibodies agains ood
an igens; (2) non-IgE-media ed, in which he immune esponse is
hough o ac mainly h ough cell-media ed mechanisms; (3) o mixed,
in which bo h IgE-media ed and cell-media ed immunological
mechanisms a e in ol ed (25). The IgE-media ed alle gies occu mos
equen ly in he i s yea s o li e and may lead o u ica ia, angioedema,
o al alle gic synd ome, hini is, o acu e as hma and anaphylaxis, while
cu aneous, espi a o y, o GI eac ions cha ac e ize non-IgE alle gies.
The mechanism o ac ion o FA usually occu s in wo di e en
phases: a sensi iza ion phase and an elici a ion phase, wi h he la e
TABLE1 O e iew o he hema ic a eas and e iew ques ions add essed by PIMENTO WG3.
Re iew numbe and
hema ic a ea
Resea ch ques ion
E1. Gas oin es inal heal h Does consump ion o e men ed oods ha e a bene icial e ec on gas oin es inal discom o and no mal de eca ion in a heal hy adul
popula ion?
E2. Alle gies Wha is he e ec o he consump ion o e men ed ood on he de elopmen o ood alle gic symp oms in he ood alle gic popula ion
and a popula ion a high isk o ood alle gy?
E3. Immuni y Can consump ion o e men ed oods aid in p e en ion o bac e ial aginosis and/o ul o aginal candidiasis?
E4. Me abolic heal h Does e men ed oods consump ion help o educe pos p andial glucose esponse o main ain as ing blood glucose concen a ions o
insulin sensi i i y in heal hy o p ediabe ic adul s?
E5. Ca dio ascula heal h Does consump ion o e men ed dai y p oduc s impac blood lipids in heal hy adul s?
E6. Bone heal h Wha is he e ec o consuming e men ed oods on he bone heal h o heal hy adul s and adul s wi h os eopo osis and os eopenia?
E7. Cogni i e heal h Does he consump ion o oods e men ed wi h Lac obacillus sp. and/o Bi idobac e ium sp. ha e a bene icial e ec on cogni i e
pe o mance in a heal hy adul popula ion, including adul s wi h mild cogni i e impai men ?
S1. Bioac i e compounds Wha compounds de i ed om ood e men a ion a e associa ed wi h e ec s on clinical endpoin s in human s udies?
S2. P oduc ion o i amins Does he consump ion o e men ed oods, o i ied in i amin by e men a ion, con ibu es o i amin co e age o a heal hy popula ion o
o a i amin-de icien popula ion?
S3. Bioa ailabili y and
bioaccessibili y o nu ien s
Does sou dough and egula b ead e men a ion inc ease i on bioa ailabili y, abso p ion, and s a us in humans?
S4. E hnic oods Wha a e he heal h e ec s o e hnic e men ed oods?
S5. Heal hy die s Wha is he impac o e men ed oods consump ion on mo ali y isk?
S6. Pe sonalized nu i ion Does he impac o e men ed oods on di e en heal h ou comes depend on speci ic cha ac e is ics o popula ion g oups, and,
consequen ly, can e men ed oods beused in ailo ed nu i ional s a egies?
S7. Food sa e y Wha a e he main mic obiological and chemical haza ds posed by e men ed oods and hei associa ed isks?
S8. No el e men ed oods Wha a e he heal h e ec o no el e men ed oods?
S9. Food byp oduc s Wha a e he heal h e ec o e men ed whey?
E1–E7 e e o each o he se en “EFSA p ojec s.” S1–S9 e e o each o he nine “Sa elli e p ojec s.”
Todo o ic e al. 10.3389/ nu .2024.1458536
F on ie s in Nu i ion 05 on ie sin.o g
esul ing in clinical symp oms o alle gic disease (26). Sensi iza ion is
he phase du ing which immunological p iming o he inducing
alle gen occu s, associa ed wi h he e olu ion o a Th2-biased immune
esponse. I he sensi ized subjec is subsequen ly exposed o a
su icien amoun o he inducing ood alle gen, an alle gic eac ion
may beelici ed, esul ing in he clinical mani es a ions desc ibed abo e.
Food p ocessing can impac he IgE-binding p ope ies o ood
p o eins’ an igenic si es and hei abili y o elici alle gic eac ions (27).
Compa ed o o he ood p ocessing echniques, ood e men a ion has
shown unique ad an ages in educing he alle genici y o oods; hus,
i may ep esen a new end in p e en ing ood-induced alle gies in
child and adul popula ions. Fo example, consuming ully ma u ed
Pa migiano Reggiano cheese seems o inhibi he IgE binding o milk
alle gens and bewell ole a ed by a subse o cow’s milk alle gic
pa ien s (28). In he same way, he consump ion o e men ed dai y
p oduc s appea s o beassocia ed wi h educed as hma and a opic
de ma i is in child en bo n by caesa ean sec ion and a ec ed by FA
(29). Simila ly, whea -based swee baked goods wi h glu en deg aded
by sou dough e men a ion seem o bewell ole a ed by pa ien s
a ec ed by coeliac disease (30).
Al hough he consump ion o FF migh bean e ec i e way o
educe he se e i y o alle gic eac ions, a sys ema ic e iew is needed
o e alua e he e idence mo e objec i ely. This e iew will hus add ess
he ollowing ques ion: “Wha is he e ec o he consump ion o
e men ed ood on he de elopmen o ood alle gic symp oms in he ood
alle gic popula ion and a popula ion a high isk o ood alle gy?”
OSF link o s udy p o ocol: PIMENTO-SP-E2.
Immuni y
Human clinical s udies on immuni y in es iga e a b oad a ay o
opics, some being add essed in o he PIMENTO WG3 e iews (e.g.,
alle gy, gu heal h). Wi h ega d o pa hogenic diseases, immuni y
e e s o he sa egua ding o heal h h ough he p e en ion o
dysbiosis. This highligh s he impo ance o main aining a balance o
commensal mic oo ganisms o sus ain immune unc ion.
As ue o o he pa s o he human body, he composi ion o he
communi y o mic obial esiden s in luences a balanced immune
esponse in he emale geni al sys em. Bac e ial aginosis (BV) and
ul o aginal candidiasis (VVC) a e he mos common pa hogenic
condi ions in women ha no only cause discom o bu also esul in
inc eased suscep ibili y o o he in ec ions o isk o obs e ic
complica ions (31). Con en ional he apies o BV and VVC in ol e
o al and opical applica ion o an imic obial agen s wi h a high isk o
ecu ence (32). Bo h condi ions a ise when he na u al mic obio a is
dis u bed. Inc easing he p opo ion o lac obacilli and dec easing he
p opo ion o po en ially pa hogenic bac e ia o yeas s in he agina
hus becomes he a ge o p e en ion and ea men o
bo h condi ions.
Clinical s udies ha e demons a ed he e icacy o o al
adminis a ion o speci ic p obio ics (33), ye he mechanism o
ansloca ion emains o beelucida ed. A ew human s udies sugges
he bene icial e ec s o he consump ion o FF o he p e en ion and
ea men o agini is. Howe e , clinical sciences and ood sciences
ake a dis inc app oach o using bac e ia, wi h he o me ocusing on
e icacy s udies in ol ing p obio ic s ains as supplemen s and he
la e employing he same s ains as cul u e o ganisms o e men ood
ma ices. This sys ema ic e iew aims o add ess his gap and ocus on
he po en ial ole o FF in he die o modula e agini is by answe ing
he ques ion: “Can consump ion o e men ed oods p e en bac e ial
aginosis o ul o aginal candidiasis?”
OSF link o s udy p o ocol: PIMENTO-SP-E3.
Me abolic heal h
Type 2 diabe es (T2D) is one o he majo diseases among
me abolic diso de s. The p e alence o T2D is ising wo ldwide and
ep esen s a signi ican bu den o he heal hca e sys em (34). The
Wo ld Heal h O ganiza ion (WHO) de ines diabe es as a condi ion
wi h ele a ed as ing plasma glucose and ele a ed pos p andial plasma
glucose in he o al glucose ole ance es (35). T2D is o en
cha ac e ized by insulin esis ance and hype insulinemia, which
con ibu es o he disease de elopmen .
Se e al s udies e iew he e ec o speci ic FF, pa icula ly
e men ed milk, on glycaemia pa ame e s, among o he heal h
ou comes. O he e iews conside se e al kinds o e men ed oods
bu include di e en s udies independen ly o he heal h s a us o he
pa icipan s (36–38). In his con ex , a sys ema ic e iew o he e ec s
o consump ion o di e en FF on glucose homeos asis in a heal hy
popula ion is, o ou knowledge, missing. By conduc ing a sys ema ic
sea ch o human s udies, his sys ema ic e iew aims o assess whe he
egula FF consump ion posi i ely impac s T2D me abolic isk ac o s
in heal hy adul s wi hou medica ion, including pa icipan s wi h
p ediabe es and obesi y. The main ou comes will include glucose and
insulin homeos asis pa ame e s, such as he main enance o no mal
as ing blood glucose le els o a pos p andial glucose esponse. The
e iew will add ess he ollowing ques ion: “Does e men ed oods
consump ion help o educe pos p andial glucose esponse o main ain
as ing blood glucose concen a ions o insulin sensi i i y in heal hy o
p ediabe ic adul s?”
OSF link o s udy p o ocol: PIMENTO-SP-E4.
Ca dio ascula heal h
Ca dio ascula diseases (CVD) emain he leading cause o
mo bidi y and mo ali y wo ldwide, wi h signi ican con ibu ion o
loss o heal h and excessi e heal hca e cos s (39). No iceably, dea hs
om CVD nea ly doubled om 12.1 million in 1990 o 20.5 million
in 2021, accoun ing o 32% o all dea hs. O e h ee-qua e s o CVD
dea hs ake place in low- and middle-income coun ies (40). Die has
a signi ican impac bo h on disease pa hogenesis and p e en ion.
Al hough se e al coho s udies ha e examined he associa ion o
objec i e endpoin s (e.g., CVD incidence o mo ali y) wi h e men ed
dai y oods in ake, he esul s emained unclea , as sugges ed by null
o in e se associa ions (38, 41).
Speci ic blood lipids, such as lipop o eins and iglyce ides, a e
isk ac o s o CVD (42). Al hough e men ed dai y p oduc s a e an
impo an pa o he die wo ldwide, he impac o hei consump ion
on blood lipid p o ile in heal hy adul s is unclea . This e iew aims o
add ess whe he e men ed dai y p oduc consump ion can impac
he blood lipid p o ile in heal hy adul s. Among all e men ed ood
g oups, e men ed dai y p oduc s may p o ide he bes scien i ic
e idence o a posi i e impac o e men ed oods on ca dio ascula

Todo o ic e al. 10.3389/ nu .2024.1458536
F on ie s in Nu i ion 06 on ie sin.o g
heal h h ough hei ac ion on ci cula o y lipids. In addi ion,
e men ed dai y p oduc s a e ela i ely well cha ac e ized and
bioac i e compounds ha e been iden i ied ha may media e hei
impac on ca diome abolic heal h (43). The ocus on e men ed dai y
p oduc s is hus mo i a ed by hei po en ial o p o ide key elemen s
in his e iew, which will co e all h ee elemen s o he e iewing
s a egy, namely human s udies, p oduc cha ac e is ics, and
mechanism o ac ion. All human s udies wi h adul s wi hou
medica ion and disease will beconside ed. The p ima y ou come
in es iga ed will be he blood lipid p o ile, which includes o al
choles e ol, HDL-c, LDL-c, iglyce ides, o hei combina ion.
Seconda y ou comes will include blood glucose and insulin le els,
hs-CRP, TNF-alpha, IL-1, IL-6, blood p essu e, and an h opome ic
measu emen s, including body mass index (BMI). The e iew will
add ess he ollowing ques ion: “Does consump ion o e men ed dai y
p oduc s impac blood lipids in heal hy adul s?”
OSF link o s udy p o ocol: PIMENTO-SP-E5.
Bone heal h
Bones unde go con inuous emodeling and epai , and hei
p ope unc ion elies on he in ake o essen ial die a y nu ien s, wi h
calcium being o pa amoun impo ance (44). Calcium consump ion
alone is insu icien o main ain bone heal h unless i is e icien ly
abso bed. Many ac o s, such as age, heal h s a us, o p egnancy, may
in luence abso p ion. Fu he , die a y calcium is abso bed in he small
in es ine in i s ionized o m (Ca
2+
). This p ocess depends on he
in es inal pH, a ac o modula ed by die as he pH o he chyme
apidly ises du ing he diges ion p ocess as i en e s he small
in es ine, po en ially hinde ing he abso p ion o ions (45).
FF ha e ga ne ed subs an ial a en ion as po en ial die a y
in e en ions agains os eopenia and os eopo osis (46, 47). As o milk
o igin, dai y p oduc s a e excellen sou ces o calcium (48). The low pH
ound in mos dai y FF could delay he neu aliza ion o chyme, hus
p olonging calcium ioniza ion and enhancing i s abso p ion. In plan -
based oods, he abso p ion o calcium (and o he mine als) can
bead e sely a ec ed by an i-nu i ional ac o s such as oxala es and
phy a es, whose le els can be educed by e men a ion (49). Some o he
me aboli es esul ing om he e men a ion p ocesses also possess he
po en ial o modula e he physiology o cells, including bone cells.
Associa ion s udies ha e highligh ed he signi ican ole o i amins in
main aining bone heal h, including i amin D, i amin K, and B-g oup
i amins (50). FF s ands ou as a po en ially ich sou ce o bo h i amin
K (menaquinones) and B-g oup i amins (such as ibo la in and ola e).
These i amins a e p oduced by e men a i e mic oo ganisms,
pa icula ly hose in he lac ic acid bac e ia (LAB) g oup. Addi ionally,
FF could modula e he gu mic obio a, eme ging as a ac o in bone
homeos asis and he pa hogenesis o os eopo osis (51).
In ligh o hese insigh s, a sys ema ic e iew will beconduc ed o
comp ehensi ely e alua e he exis ing scien i ic e idence on he e ec
o FF consump ion on bone heal h. The e idence will bed awn om
andomized clinical ials (RCT) and obse a ional s udies in ol ing
heal hy adul s and adul s diagnosed wi h ei he os eopo osis o
os eopenia. The cen al esea ch ques ion guiding his e iew is:
“Wha is he e ec o consuming e men ed oods on he bone heal h o
heal hy adul s and adul s wi h os eopo osis and os eopenia?”
OSF link o s udy p o ocol: PIMENTO-SP-E6.
Cogni i e heal h
In oday’s pe o mance-o ien ed wo ld, whe e li espan is
ex ending and, as a esul , he heal h bu den on he olde popula ion
is inc easing, main aining cogni i e heal h h oughou li e in o old age
is c i ical. In ecen yea s, esea ch on he mic obio a-gu -b ain axis
has p o ided insigh s in o he e ec s o gu mic obio a on cogni i e
heal h. As a esul , he e ec s o consuming FF con aining bene icial
mic obes has become an ac i e a ea o esea ch.
Consump ion o FF may a ec he cen al ne ous sys em
unc ion, al hough he mechanisms unde lying he e ec o FF on
cogni i e pe o mance a e s ill unknown. Th ee non-exclusi e
hypo heses ha e been p oposed ega ding he bene icial e ec s o
e men a ion on b ain heal h, each elying on da a de i ed p ima ily
om p obio ic s udies (52). Fi s , e men a ion modula es he
p oduc ion and bioa ailabili y o compounds such as bioac i e
pep ides and phy ochemicals (53). Among hese, sho -chain a y
acids (SCFA) posi i ely in luence he hos ’s me abolism h ough hei
e ec on he cen al ne ous and he immune sys ems (54). The second
hypo hesis is ocused on he neu obiology o he s ess esponse
h ough he associa ion o he hypo halamic–pi ui a y–ad enal (HPA)
axis and he gu mic obio a: p obio ic adminis a ion appea s o
imp o e cogni i e unc ion by no malizing he HPA ac i i y and
educing sys emic in lamma ion (55). The hi d hypo hesis sugges s
ha FF may con ol he elease o neu o ansmi e s and hus a ec
cogni i e pe o mance. Taken oge he , he abili y o bac e ia o al e
he chemical composi ion o oods and, upon consump ion, he
composi ion o he gu mic obio a communi y may accoun o he
bene icial e ec s o FF on human cogni i e pe o mance.
In his con ex , he p obio ic p ope ies o Bi idobac e ium sp. and
Lac obacillus sp. ha e ecen ly a ac ed a en ion, as se e al s ains
ha e been epo ed o ha e bene icial e ec s on cogni i e abili ies (52).
Bioac i e compounds syn hesized by hese bac e ia ha may di ec ly
o indi ec ly a ec cogni i e pe o mance, include neu o ansmi e s
(e.g., gamma-aminobu y ic acid (GABA), se o onin), SCFA (e.g.,
bu y a e, ace a e), pep ides, and i amins (56). As hese bac e ial
species a e commonly p esen in FF, a sys ema ic li e a u e e iew will
beconduc ed o e alua e he cogni i e pe o mance o humans who
consume hese ood p oduc s. This e iew will hus add ess he
ques ion: “Does he consump ion o oods e men ed wi h Lac obacillus
sp. and/o Bi idobac e ium sp. ha e a bene icial e ec on cogni i e
pe o mance in a heal hy adul popula ion, including adul s wi h mild
cogni i e impai men ?”
OSF link o s udy p o ocol: PIMENTO-SP-E7.
Bioac i e compounds
Bioac i e compounds, such as polyphenols, pep ides,
exopolysaccha ides, conjuga ed linoleic acid (CLA), o i amins, a e
p esen in oods ac oss all ood g oups and co e a b oad ange o
biological ac i i ies, such as an ioxidan , an i-in lamma o y,
an imic obial, and an ihype ensi e e ec s (57). Food e men a ion
o e s a unique oppo uni y o inc ease he concen a ion o bioac i e
compounds in oods (58, 59). Many publica ions highligh he ole o
e men a ion in p oducing bioac i e molecules, po en ially explaining
he bene icial e ec s o FF in ake on di e en aspec s o heal h (60–
63). Howe e , e idence linking hese bioac i e compounds in FF o
Todo o ic e al. 10.3389/ nu .2024.1458536
F on ie s in Nu i ion 07 on ie sin.o g
hei e ec on clinical endpoin s in human s udies is sca ce and has
no been sys ema ically add essed.
This sys ema ic na a i e e iew aims a ca aloguing compounds
in FF o which e idence o bioac i i y has been epo ed in human
s udies by add essing he ollowing esea ch ques ion: “Wha
compounds de i ed om ood e men a ion a e associa ed wi h e ec s
on clinical endpoin s in human s udies?” This ques ion will beanswe ed
by sea ching all human s udies, speci ically in es iga ing he po en ial
ole o one o se e al bioac i e compounds p esen in FF on clinical
ou comes. A ca alogue o he FF, o which an associa ion be ween he
bioac i e compounds and clinical endpoin s has been epo ed, will
bees ablished.
OSF link o s udy p o ocol: PIMENTO-SP-S1.
P oduc ion o i amins
Vi amins a e essen ial mic onu ien s equi ed o many i al
human unc ions. The human body canno syn hesize mos i amins
due o i s limi ed biosyn he ic capaci y and equi es ex e nal p o ision
h ough he die . Despi e he p esence o i amins in a wide ange o
oods, de iciencies emain high in many con ex s, leading o heal h
p oblems speci ic o each i amin (64). Fo example, i amin A
de iciency esul s in isual impai men , ail y, and inc eased mo ali y
isk, while i amin B9 ( ola e) can lead o neu al ube de ec s in he
o sp ing. Con en ional ea men and p e en ion app oaches, such
as supplemen a ion and o i ica ion, ha e no always p o en e ec i e
and may ha e undesi able side e ec s (64, 65).
FF ha e he po en ial o p o ide a ange o heal h bene i s,
including i amin syn hesis (66). The scien i ic li e a u e also epo s
on he possibili y o inc easing i amin le els in he gene al popula ion
by consuming FF na u ally en iched in i amins as an al e na i e
die a y app oach o o i ica ion o supplemen a ion (67, 68). Thus,
his sys ema ic na a i e e iew aims o in es iga e i consuming oods
en iched in i amins h ough e men a ion con ibu es o he i amin
needs o a heal hy popula ion wi h a ying i amin s a us. The speci ic
esea ch ques ion will be: “Does he consump ion o e men ed oods,
o i ied in i amin by e men a ion, con ibu es o i amin co e age o
a heal hy popula ion o o a i amin-de icien popula ion?” In he
human s udies included in he e iew, he p ima y ou come o in e es
will be he i amin s a us in he s udy pa icipan s assessed in ela ion
o FF consump ion, while he seconda y ou come will be he i amin
con en in FF.
OSF link o s udy p o ocol: PIMENTO-SP-S2.
Bioa ailabili y and bioaccessibili y o
nu ien s
Mic onu ien de iciencies a e an ala ming global heal h p oblem.
In pa icula , i on de iciency anemia a ec s a la ge pa o he wo ld’s
popula ion, mainly child en and p egnan women, and is conside ed
one o he leading con ibu o s o he global disease bu den (69). Since
he e is no physiological mechanism o exc e ion, he i on balance in
he human body is only con olled by abso p ion (70). Phy a e,
polyphenols, calcium, asco bic acid, and muscle issue a e die a y
ac o s ha ha e been epea edly shown o a ec i on abso p ion in
se e al s udies (71, 72).
E idence sugges s ha e men a ion signi ican ly imp o es he
bioa ailabili y o i on in oods, and especially o plan -based oods
such as ce eals and legumes, which o en se e as impo an sou ces
o i on in many die s (73). Sou dough and yeas -lea ened b eads a e
s aple oods p oduced in many pa s o he wo ld. Fe men a ion can
enhance he bioa ailabili y o non-hem i on in sou dough b ead (74)
h ough a ious mechanisms, such as educing phy a e le els,
inc easing acidi y, and gene a ing o ganic acids.
The p ima y pu pose o his sys ema ic e iew is o
comp ehensi ely examine he a ailable clinical s udies ha assessed
he associa ion be ween e men ed sou dough and yeas -lea ened
b ead and i on bioa ailabili y, abso p ion, and s a us in human
subjec s. This e iew will add ess he ollowing ques ion: “Does
sou dough and egula b ead e men a ion inc ease i on bioa ailabili y,
abso p ion, and s a us in humans?” The sea ch s a egy and inclusion
c i e ia will bede e mined a p io i. Mo e speci ically, all ypes o
sou dough and yeas -lea ened b ead, p epa ed om ce eal lou (s)
ha may o may no ha e been p e iously o i ied will beconside ed
exposu e o in e en ion. The ou comes o in e es will include i on-
ela ed bioma ke s (i.e., hemoglobin, hema oc i , se um i on, se um
e i in, se um ans e in ecep o , o al i on-binding capaci y, o i on
iso ope abso p ion). O e all, he e iew is an icipa ed o con ibu e o
a be e unde s anding o he impac o e men a ion on i on
bioa ailabili y in hese s aple ood p oduc s.
OSF link o s udy p o ocol: PIMENTO-SP-S3.
E hnic e men ed oods
Acco ding o he Uni ed Na ions, he wo ld popula ion may
inc ease o 9.7 billion in he nex i e decades (75). The al eady
exis ing p oblem o inadequa e access o nu i ious ood o e e yone
will be u he exace ba ed. I is also p ojec ed ha in 2030, o e 670
million people will be expe iencing hunge . Finding al e na i e
solu ions o ensu e a heal hy ood en i onmen o e e yone is hus o
pa amoun impo ance.
E hnic FF can bede ined as oods o igina ing om he he i age
and cul u e o an e hnic g oup o people who use hei e hno-
mic obiological knowledge o ood e men a ion (76) wi h local
ing edien s om plan o animal sou ces (77). E hnic FF a e o en
a isanal and hus a isk o disappea ing oge he wi h he di e si y
o na i e mic oo ganisms used in hei p oduc ion due o u baniza ion
and changing ood habi s (76).
The scien i ic li e a u e sugges s ha consuming e hnic FF like
koumiss, kimchi, and doenjang may posi i ely a ec heal h,
including imp o emen s in hema ological and biochemical ac o s.
E hnic FF may educe iglyce ides and choles e ol le els, inc ease
high-densi y lipop o ein (HDL) choles e ol, imp o e blood
glucose con ol and, consequen ly, imp o e heal h and well-being
(78–81). While speci ic e hnic FF like na o, kinema, kimchi,
empeh, and pulque ha e ecei ed subs an ial a en ion in esea ch,
many o he e hnic FF a e neglec ed despi e hei po en ial
heal h bene i s.
Rega dless o he wide a ie y o e hnic FF p oduced and
consumed wo ldwide (76, 82), a comp ehensi e e iew examining
he heal h bene i s and po en ial isks associa ed wi h hese oods has
ye o be conduc ed. This na a i e sys ema ic e iew will hus
add ess he ollowing ques ion: “Wha a e he heal h e ec s o e hnic
Todo o ic e al. 10.3389/ nu .2024.1458536
F on ie s in Nu i ion 08 on ie sin.o g
e men ed oods?” In answe ing he e iew ques ion, a lis o e hnic
FF based on published li e a u e will be i s compiled (76, 82),
ollowed by iden i ying clinical s udies associa ing he consump ion
o e hnic FF wi h clinical endpoin s i espec i e o he heal h
condi ion s udied. Addi ional in o ma ion on he cha ac e is ics o
he e hnic FF, including hei egion o o igin, will also bep esen ed.
OSF link o s udy p o ocol: PIMENTO-SP-S4.
Heal hy die s
Die composi ion is one o he mos impo an de e minan s o
mo ali y isk (83). Fe men ed dai y p oduc s and o he FF a e cu en ly
being s udied o hei po en ial heal h e ec s in nume ous clinical
s udies, e alua ing he e ec s o FF on ch onic disease isk ac o s,
immune sys em pe o mance, and cogni i e unc ion. Howe e , only a
ew s udies ha e ocused on he ela ionship be ween FF consump ion
and li e expec ancy o mo ali y (17). The e o e, his e iew aims o
e alua e he e idence on he associa ion be ween he consump ion o FF
and mo ali y isk in ee-li ing popula ions and answe he ques ion:
“Wha is he impac o e men ed oods consump ion on mo ali y isk?”
A sys ema ic e iew o he li e a u e, inco po a ing a me a-
analysis i a signi ican numbe o pe inen human s udies a e
a ailable, will beunde aken. The e alua ion will ocus on coho
s udies wi h he p ima y objec i e o unco e ing he impac o die s,
including FF, on mo ali y. Mo ali y a e, mo ali y isk, and dea h
a e will beex ac ed as p ima y ou comes o his e iew. Con ounding
ac o s such as demog aphic da a, li e quali y indices, gene al heal h
s a us, die quali y, alcoholic d ink consump ion and smoking habi s,
as well as ch onic mo bidi y de eloped du ing he epo ed s udy, will
beconside ed. Suppo ing e idence will bede i ed om s udies ha
examined he bene icial heal h e ec s o e men ed oods and he
p obable unde lying mechanisms o ac ion, wi h po en ial ad e se
e ec s also being no ed (84).
The indings o his s udy will in o m u u e esea ch on he ole
o FF in heal hy die s. Finally, i is expec ed o highligh he need o
mo e de ailed inclusion o FF in na ional and Eu opean die a y
guidelines and popula ion nu i ion su eys.
OSF link o s udy p o ocol: PIMENTO-SP-S5.
Pe sonalized nu i ion
The gu mic obio a has ecen ly been iden i ied as a pe son-
speci ic ac o de e mining a iable me abolic esponse o die a y
in ake (85). In e es ingly, he e men a ion o ood by echnological
mic oo ganisms and he ans o ma ion o inges ed nu ien s by he
gu mic obio a sha e common enzyma ic eac ions (86). Taken
oge he , hese analogies sugges ha die a y e men ed oods could
also modula e he in e -indi idual a iabili y in esponse o ood
in ake (87, 88). This sys ema ic na a i e e iew aims o de e mine
whe he heal h ou comes in esponse o FF show a signi ican in e -
pe sonal a iabili y. I heal h ou comes a y be ween indi iduals, FF
can beconside ed as po en ial le e s in pe sonalized o p ecision
nu i ion s a egies. Acco ding o he ecen Food Fo um o he
Na ional Academies o Sciences, Enginee ing, and Medicine (89),
human a iabili y in esponse o ood can be ega ded as a basis o
de eloping pe sonalized nu i ion and a ge ed nu i ional guidelines.
To his end, human s udies (all popula ions s udied) ha include
sho - o long- e m nu i ional o die a y e alua ions will becollec ed
sys ema ically. The e iew will hus ocus on s udies epo ing a iable
heal h esponses ollowing he consump ion o FF, which could
bea ibu ed o well-de ined o ye - o-be-de ined cha ac e is ics o
popula ions. Addi ionally, conside ing ha he ield is ela i ely no el
and explo a o y, e iews o o he ypes o publica ions (e.g., epo s,
posi ion pape s) in which die a y FF a e discussed in ela ion o
pe sonalized o p ecision nu i ion will also beincluded. Pa icula
emphasis will begi en o ac o s ha may explain a a iable heal h
esponse: (1) popula ions (e.g., gende , age, loca ion, physical ac i i y),
(2) heal h s a us (global o speci ic ma ke s, wi h pa icula ocus on gu
mic obio a composi ion o unc ion), (3) e alua ion o he die s and
supplemen a ions, including he de ailed desc ip ion o FF (e.g., ype,
nu i ional composi ion, ma ix desc ip ion). This wo k will bea i s
s ep owa ds e alua ing he easibili y o using FF in ailo ed nu i ional
s a egies. This e iew will add ess he ollowing ques ion: “Does he
impac o e men ed oods on di e en heal h ou comes depend on speci ic
cha ac e is ics o popula ion g oups, and, consequen ly, can e men ed
oods beused in ailo ed nu i ional s a egies?”
OSF link o s udy p o ocol: PIMENTO-SP-S6.
Food sa e y
Foodbo ne diseases a e illnesses ha esul om consuming
con amina ed ood. Clinical signs and symp oms di e depending on
he cause o haza d in ol ed (90). Food sa e y is a high-p io i y opic,
conside ing ha su icien amoun s o sa e, sus ainably-p oduced ood
mus besecu ed o a g owing wo ld popula ion o comply wi h
Sus ainable De elopmen Goal 12 o he 2030 Agenda o he Uni ed
Na ions (91). Fe men a ion is one o he oldes adi ional p ocesses
o achie ing sa e ood p oduc ion (92); howe e , enewed in e es in
FF equi es e-examining hei sa e y. This sys ema ic na a i e e iew
will ask he ques ion: “Wha a e he main mic obiological and chemical
haza ds posed by e men ed oods and hei associa ed isks?” In o he
wo ds, a e e men ed oods sa e o humans?
A sys ema ic e iew o he scien i ic li e a u e will bepe o med
o add ess his ques ion. Repo s associa ing he occu ence o ood
haza ds o mic obiological and/o chemical o igin wi h he
consump ion o FF by he gene al popula ion, including ulne able
g oups (such as, p egnan and b eas eeding women, child en, and
elde ly), will becompiled wi hou limi a ion by age o gende . In
addi ion o p esen ing he illnesses associa ed wi h FF consump ion,
he e iew will p o ide scien i ic e idence on 1) he occu ence
(le els/magni ude, equency) o haza ds associa ed wi h he
consump ion o e men ed oods; 2) he associa ed isks o exposu e,
aking in o accoun hei p obabili y and se e i y; and 3) he epo ed
ou b eaks as well as he ex en o which he diseases occu (93).
OSF link o s udy p o ocol: PIMENTO-SP-S7.
No el oods
Fe men a ion con e s unc ional p ope ies o ood ha migh
con ibu e o human heal h (94). Th ough a a ional choice o aw
ma e ial and s a e cul u e, no el FF wi h imp o ed unc ional
p ope ies ha posi i ely impac heal h can begene a ed (12, 67, 95).
Todo o ic e al. 10.3389/ nu .2024.1458536
F on ie s in Nu i ion 09 on ie sin.o g
These no el FF can bep oduced using ei he a new species as a s a e
cul u e, a new aw ma e ial, o a combina ion o bo h. The Eu opean
Commission de ines oods as no el i hey “had no been consumed
o a signi ican deg ee by humans in he EU be o e 15 May 1997.”
In e es ingly, he cu en lis o no el oods includes one e men ed
p oduc , namely e men ed whea ge m ex ac (96).
This sys ema ic na a i e e iew aims o e alua e he scien i ic
e idence on whe he no el FF con e heal h bene i s o consume s.
The esea ch ques ion add essed by his e iew will hus be: “Wha a e
he heal h e ec s o no el e men ed oods?” The lis o FF de eloped in
he li e a u e sea ch s ing PIMENTO-LS will becombined wi h
keywo ds ela ing o “no el ood” and sea ched in combina ion wi h
human s udies. S udies ela ed o “ e men ed whea ge m ex ac ” will
also beincluded. Gi en ha his e iew lea es he in es iga ed heal h
condi ions open, all p ima y and seconda y endpoin s epo ed by he
publica ions will be ex ac ed and e alua ed. The e idence o
po en ial heal h bene i s o speci ic no el FF will bediscussed in ligh
o he signi icance and ele ance o he epo ed endpoin s. The e iew
will iden i y esea ch gaps ha should os e u u e s udies o p omo e
inno a ion on no el FF and, e en ually, hei consump ion (12).
OSF link o s udy p o ocol: PIMENTO-SP-S8.
Food by-p oduc s
The inc easing p essu e on socie y o p oduce sus ainable ood
sys ems has highligh ed he impo ance o minimizing was e and
making be e nu i ional use o by-p oduc s (97, 98). Whey, eleased in
la ge amoun s in he dai y p ocessing indus y, is an impo an milk
by-p oduc ich in p o eins, lac ose, mine als and i amins (99). The
nu ien composi ion o whey, pa icula ly lac ose and p o eins, makes
i a sui able sou ce o e men a ion by mic oo ganisms. When
e men ed by Lac obacillaceae and Bi idobac e ium, whey can be u ned
in o a p oduc wi h appealing ex u e and senso y p ope ies (100). One
o he mos impo an bene icial heal h e ec s o e men ed why is i
en ichmen in bioac i e compounds compa ed o non- e men ed whey.
Indeed, in i o and animal s udies indica e ha whey e men a ion
migh inc ease i s an ioxida i e p ope ies (101). Se e al human s udies
epo ed using whey as a p obio ic ca ie o imp o e amino acid
abso p ion in physically ac i e males (102) o educe ood alle gies (103,
104). Cu en ly, no clea o e iew is a ailable on he po en ial heal h-
p omo ing e ec s o whey e men ed by adi ional me hods, e.g.,
spon aneous e men a ion o he addi ion o mic oo ganisms as s a e s.
This sys ema ic na a i e e iew will hus add ess he ollowing
ques ion: “Wha a e he heal h e ec s o e men ed whey?”
Thus, his e iew aims o p o ide an o e iew on exis ing
li e a u e on he p oduc ion, iden i ica ion, and unc ional p ope ies
o e men ed whey p oduc s. All human s udies wi h e men ed whey
as pa o hei nu i ional in ake assessmen will be included.
I espec i e o he a ge ed heal h condi ions, he p ima y and
seconda y endpoin s will be ex ac ed and analyzed o hei
signi icance and clinical ele ance. Special a en ion will begi en o
cha ac e iza ion o he nu i ional p ope ies o e men ed whey and
di e en ia ing i om un e men ed whey o which p obio ics we e
added. The e iew will iden i y esea ch gaps ha should os e u u e
s udies and p omo e inno a ion on e men ed whey and, e en ually,
he consump ion o e men ed whey p oduc s bene icial o heal h.
OSF link o s udy p o ocol: PIMENTO-SP-S9.
Discussion
Towa ds a s a egic esea ch oadmap on
he unc ionali y o FF
A ood company ha aims a ma ke ing a ood p oduc by
claiming a speci ic heal h p ope y, needs o documen , and
e en ually g ade, he s eng h o he a ailable scien i ic e idence o
he in ended claim based on guidelines es ablished by egula o y
au ho i ies such as he EFSA (13, 14). The body o e idence ha
should be p o ided o a success ul claim encompasses he
sys ema ic e iewing o well designed, conduc ed, analyzed, and
epo ed human s udies (105). In pa icula , he PICO c i e ia
(Popula ion, In e en ion, Con ol, Ou come) should be me ,
meaning ha he cha ac e is ics o he en olled pa icipan s, he
in es iga ed die a y componen s, he con ol, and he measu ed
clinical endpoin s should bein line wi h he esea ch ques ion
unde lying he claim. Fu he mo e, quali a i ely good human
s udies should a oid he isk o bias a ising om me hodological
laws along he s udy wo k low, including andomiza ion bias,
missing da a, o selec i e epo ing. In addi ion, he die a y
componen s in es iga ed should bewell cha ac e ized wi h espec
o hei composi ion, s abili y, and sa e y. Finally, human s udies
epo ing associa ions be ween die a y in ake and clinical endpoin s
should becomplemen ed wi h da a (in i o, animal, human) on he
in ol ed mechanism(s) o ac ion in o de o mo e he scien i ic
e idence om associa i e o causa i e.
Whe eas hese egula o y guidelines p ima ily aim a p o ec ing
consume s, hei ole in p omo ing inno a ion o he indus y is also
ecognized, al hough hei e icacy has been deba ed (106–109). The
ood and nu i ion esea ch communi y could make use o egula o y
guidelines (13, 14) and guidance o sys ema ic e iewing o human
s udies (105) o imp o e he e ec i eness o i s p e-compe i i e
esea ch. Independen ly om hei impac on inno a ion, hese
guidelines p o ide aluable in o ma ion o esea che s on design o
s udies ha , when conduc ed and analyzed p ope ly, will signi ican ly
con ibu e o he u u e e alua ion o he impac o die a y
componen s on heal h.
The U.S. Food and D ug Adminis a ion (FDA) ecen ly
announced a quali ied heal h claim on yoghu and diabe es, which
s a es “Ea ing yogu egula ly may educe he isk o ype 2 diabe es
acco ding o limi ed scien i ic e idence” (110). This claim is in e es ing
in he amewo k o his concep ual a icle o se e al easons. Fi s ly,
al hough submi ed o he FDA by he p i a e sec o , he ood p oduc
e alua ed by he FDA is a gene ic yoghu . In ha ega d, mos o he
da a used o suppo he claim, in pa icula human s udies, was
p oduced by he academic esea ch communi y, illus a ing he ole
o public esea ch in p o iding scien i ic e idence o he impac o
ood on heal h, in his pa icula case on he con ibu ion o yoghu
o he educ ion o ype 2 diabe es isk. On he o he hand, he
esea che s ha ing conduc ed hese s udies did ce ainly no
speci ically design hem o bepa o he FDA heal h claim! Indeed,
among he 66 human s udies published on yoghu and diabe es (20
in e en ion s udies, 46 obse a ion s udies) only 28 obse a ion
s udies we e e ained by he FDA. In pa icula , all o he in e en ion
s udies we e excluded as hey we e no su icien ly con olled o
p o ide use ul in o ma ion o assessmen o his pa icula heal h
claim. Also, isk o bias, e.g., due o imp ope baseline dis ibu ion o