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,3 Nutrients2011 Nutrients 2011,3 , 1023-1041; doi:10.

3390/nu3121023

1024

?itamin is responsi)le "or a wide ran(e o" "unctions in t%e )od' and t%ese 3nown roles are e>pandin( as researc% in t%is "ield accumulates. 9%e disco&er' in 19=9 o" t%e nuclear &itamin receptor .? B1 "or 1,2;.0$1 2 stimulated a &ast amount o" researc% t%at to date %as collecti&el' ISSN 2072-6643 www.mdpi.com/journal/nutrients descri)ed t%e presence o" t%e ? B in at least 3C %uman tissues and or(ans @1A. 9%e ? B was "irst Review in t%e )one, 3idne' and (astrointestinal tract )ut since %as )een identi"ied in a di&erse ran(e descri)ed o" ot%er tissues includin( t%ose in t%e )rain, )reast, colon and prostate. 9%e ? B, a p%osp%oprotein, The Potential Role of Vitamin D Enhan e! "oo!# in Im$%o&in' "acilitates t%e &arious )iolo(ical "unctions o" calcitriol )' )indin( to t%e acti&e %ormone wit% %i(% Vitamin D Stat(# a""init' and re(ulatin( t%e e>pression o" (enes &ia Dinc "in(er-mediated 86 )indin( and proteinEprotein interactions @2A. 1-2 - +a'!alena Ste$ien 1-2 1 - Anne P/ N('ent 1 an! )o(i#e O*+ahon, hael 0i1ne, 9%e well esta)lis%ed "unctions o" &itamin - +i relate to ./ calcium a)sorption and %omeostasis, wit% 1-2- 3 )o%%aine 2%ennan t%e role "or &itamin in )one mineraliDation and )one %ealt% e>tensi&el' documented and lon( reco(nised, particularl' in relation to ric3ets and osteomalacia @3,4A. ?itamin , in tandem wit% 1 UC !nstitute o" #ood and $ealt%, Uni&ersit' Colle(e u)lin, *el"ield, u)lin 4, !reland, calcium, ma' also )e in&ol&ed in t%e pre&ention o" osteoporosis, "racture incidence and "alls, +-,ails: louise.oma%on'-ucd.ie ./.0.,.1; ma(dalena.stepien-ucd.ie .,.2.1; particularl' in older populations @;,=A. $owe&er, &itamin is no lon(er re(arded as just a calcaemic mi3e.(i)ne'-ucd.ie .,.4.5.1; anne.nu(ent-ucd.ie .6.7.8.1 %ormone as a result o" t%e widespread distri)ution o" t%e ? B and t%e "act t%at t%e conseFuences o" 2 UC Conwa' !nstitute, Uni&ersit' Colle(e u)lin, *el"ield, u)lin 4, !reland insu""icienc' %a&e )een s%own to e>tend )e'ond t%e a)o&e classic e""ects. 9%ou(% t%e e&idence is less ro)ust, is nows%ould implicated in a %ost o"+-,ail: ot%er diseases includin( psoriasis, multiple 3 6ut%or&itamin to w%om de"icienc' correspondence )e addressed; lorraine.)rennan-ucd.ie; sclerosis, in"lammator' )owel t'pe 1 and 2 dia)etes, %'pertension, cardio&ascular disease, t%e 9el.: :3;3-1-<1==<;9; #a>:disease, :3;3-1-<1==<01. meta)olic s'ndrome and &arious cancers @<,CA. 6 t%orou(% e>amination o" all t%ese "unctions is )e'ond Received: 2 November 2011; in and revised form: 23 / Accepted: 6Fualit' December 2011 / t%e scope o" t%e present re&iew t%e reader is November re"erred to 2011 a num)er o" (ood re&iews @<,9A. Publis ed: 16 December 2011 !n parallel wit% t%e (rowin( e&idence "or widespread action "or &itamin t%ere is ro)ust data demonstratin( t%at an increased &itamin status is lin3ed to si(ni"icant )ene"its in terms o" mor)idit' and mortalit' ris3 reduction. 6 recent re&iew demonstrated t%at an estimated 20G reduction o" (lo)al A1#t%a t4/ow &itamin inta3e and status %a&e )een reported worldwide and man' &itamin -sensiti&e disease mortalit' and up to 1<.=G o" all-cause mortalit' could )e ac%ie&ed )' studies %a&e su((ested t%at t%is low status ma' )e in&ol&ed in t%e de&elopment o" se&eral dou)lin( &itamin status @10A. !n 8ordic populations impro&ement o" &itamin status ma' decrease c%ronic diseases. 9%ere are a limited num)er o" natural dietar' sources o" &itamin t%e ris3 o" mortalit' "rom a num)er o" common diseases includin( cancer and cardio&ascular disease leadin( to a real need "or alternati&es to impro&e dietar' inta3e. +n%ancement o" "oods )etween 19 and 24G, dependin( on t%e countr' @10A. #or Canada, w%ic% s%ares a similar nort%erl' wit% &itamin is a possi)le mode "or ensurin( increased consumption and t%us impro&ed latitude, reductions o" 1=.1G were estimated @11A. 9%ese "indin(s corro)orate t%ose o" a num)er o" &itamin status. 9%e present re&iew e>amines studies in&esti(atin( e""ects o" &itamin ot%er studies t%at %a&e demonstrated t%at mortalit' is (reatest amon(st indi&iduals wit% t%e lowest en%anced "oods in %umans and t%e "easi)ilit' o" t%e approac% is discussed. &itamin status @12,13A. 9a3in( into account t%e multiple "unctions o" &itamin and t%e disease ris3-reduction potential, it 5e,6o%!#4&itamin ; 2;.0$1 ; en%anced "oods; "orti"ication %as )ecome e&ident t%at maintainin( an adeFuate status is important. ?itamin status is assessed )' measurin( t%e circulatin( "orm o" t%e &itamin .2;.0$1 1 in serum. 9%ere is muc% de)ate in t%e literature as to w%ic% cut-o""s to use "or de"inin( &itamin de"icienc'. $owe&er, recent researc% %as 1/ Int%o!( tion to increase t%e cut-o"" "or de"icienc' to ;0 nmol// ."rom 2; nmol//1. Concomitant lead in&esti(ators wit% t%is, serum concentrations o" <; nmol// or %i(%er %a&e )een esta)lis%ed as adeFuate le&els, wit% ?itamin (enerall' re"ers to two "at solu)le pro%ormones, er(ocalci"erol .&itamin 1 and 2 &alues in )etween indicatin( insu""icienc' @14E1=A. c%olecalci"erol .&itamin 1. ?itamin is produced )' certain in&erte)rates and "un(i w%ilst 3 2 +stimates o" (lo)al &itamin status indicate widespread inadeFuac', wit% se&ere %'po&itaminosis &itamin 3 is produced in t%e s3in o" &erte)rates, )ot% "ollowin( e>posure to ultra&iolet .U?1 most common in t%e ,iddle +ast and 2out% 6sia @1;A. +&en wit%in +urope, lar(e &ariance in serum radiation. !n(ested &itamin 2 and endo(enousl' produced 3 are con&erted to t%e )iolo(icall' acti&e concentrations e>ist )etween countries @1<A. 9%ou(% indi&iduals li&in( at %i(%er latitudes commonl' "orm, 1,2;-di%'dro>'&itamin @1,2;.0$1 2 A .calcitriol1 in t%e %uman )od'. e>%i)it low 2;.0$1 serum concentrations due to reduced U?* radiation, especiall' durin( winter mont%s @1CE20A, %i(% le&els o" inadeFuac' %a&e also )een "ound in 2out%ern +urope, particularl'

nutrients

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amon( older populations @21,22A. !n t%e UH, estimates su((est t%at onl' 1CG and 24.1G o" women and men, respecti&el', %a&e adeFuate 2;.0$1 concentrations @19A. $i(%er 2;.0$1 le&els %a&e )een reported in Canada, w%ere 3;G o" t%e population %a&e le&els a)o&e <; nmol// @23A. !n t%e U2, ;C.4G and 2<G o" adults %a&e serum 2;.0$1 concentrations I;0 nmol// and I<; nmol//, respecti&el' @24,2;A. 2temmin( "rom t%e reports o" low le&els o" circulatin( 2;.0$1 , certain countries recommend an e>posure o" 10E1; min dail' o" suns%ine @2=,2<A. $owe&er, due to (eo(rap%ical, cultural and )e%a&ioural di""erences )etween populations, increased U?* radiation e>posure is not su""icient to maintain %ealt%' &itamin le&els, especiall' durin( winter. 9%ere"ore, optimal dietar' &itamin inta3e is crucial to maintain adeFuate &itamin status. 9%e recommendation "or &itamin inta3e di""ers )etween countries in +urope and ran(es "rom 0 to 1; J( "or di""erent population (roups @2CA. 6ccordin( to a recent report o" t%e !nstitute o" ,edicine, t%e B 6 "or &itamin s%ould )e 1; J(/da' "or c%ildren (reater t%an 1 'ear old and adults, and 20 J(/da' "or t%e elderl' @29A. 6s suc%, t%ere is a renewed interest in impro&in( dietar' inta3e in an e""ort to meet t%ese recommendations. 6dditionall', i" we are to counteract population le&el &itamin de"icienc' en%ancement o" dietar' inta3e is t%e onl' "easi)le mode. 9%e main o)jecti&e o" t%e present re&iew is to pro&ide an o&er&iew o" t%e &itamin containin( "oods a&aila)le, to include natural, "orti"ied and enric%ed sources. !t will descri)e t%e randomiDed controlled trials t%at %a&e )een per"ormed wit% &itamin en%anced "oods and t%e e""ecti&eness o" t%ese in raisin( serum 2;.0$1 le&els. 9%e current re(ulations (o&ernin( t%e addition o" &itamin to "oods in +urope will also )e outlined. 2/ "oo! Inta8e# an! So(% e# of Vitamin D 6 recent trans-+uropean e>amination o" nutrient inta3e patterns s%owed dietar' inta3es o" &itamin to di""er mar3edl' )etween countries. !nta3es were si(ni"icantl' %i(%er in 8ordic countries includin( 2weden, enmar3 and 8orwa' t%an in ,editerranean re(ions suc% as !tal' and #rance @30A. !nta3es o" less t%an 3.0 J(/da' and 2.0 J(/da' %a&e )een reported in !talian and 2panis% adults @31,32A. 0lder men in #inland %a&e some o" t%e %i(%est dietar' inta3es in +urope at 9.0 J(/da' @33A. Becent estimates "rom !reland re&ealed inta3es ran(in( "rom 3.9 J( to C.; J(/da' in adults, wit% an increase o)ser&ed wit% a(e @34A. !n t%e U2, mean dietar' consumption "or adults ran(es "rom 3.= to ;.= J(/da' @3;A, lower t%an t%e population mean o" ;.C J(/da' in Canada @3=A. !nta3es in 4apanese adults appear %i(%er, at I= J( o" &itamin per 1000 3ilocalories o" ener(' inta3e per da' @3<A. #oods t%at ma3e t%e %i(%est contri)ution to dietar' inta3es o" &itamin &ar' "rom countr' to countr' accordin( to %a)itual dietar' patterns. !n 8orwa', t%e predominant "ood sources are "is% and "ats @3CA, as is t%e case in #inland w%ere liFuid mil3 and dair' products also contri)ute si(ni"icantl' @33A. !n t%e UH, oil' "is% .24G1, "ollowed )' meat and meat products .22G1 and cereal and cereal products .21G1 contri)ute t%e %i(%est percenta(e to a&era(e dail' &itamin inta3es in adults @39A. #or !ris% adults, meat .30G1, "is% .12G1 and spreads .10G1 made t%e most si(ni"icant contri)utions o" all "ood (roups @34A. !n 2pain t%e main source is "is% w%ic% accounts "or =;G o" inta3e @31A. 9%is can )e contrasted wit% t%e U2 w%ere &itamin "orti"ied mil3 ma3es )' "ar t%e %i(%est contri)ution to inta3es .;CG in men, 39G in women1 @40A, "i(ures compara)le to t%ose o" Canada w%ere mil3 products account "or 49G o" dietar' &itamin inta3e @3=A. !n 4apan, t%e major sources o" dietar' &itamin

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inta3e are "is%/s%ell"is% .<9G1 and e((s .9G1 @41A, t%ou(% "is% consumption %as )een s%own to contri)ute I90G o" &itamin inta3e in an elderl' 4apanese co%ort @42A. 7eople are o"ten reliant on dietar' inta3e o" &itamin to satis"' t%eir reFuirements, %owe&er "oods naturall' ric% in &itamin are "ew in num)er and in man' cases not widel' consumed. 9a)le 1 illustrates t%e le&els o" &itamin (enerall' "ound in a num)er o" "ood sources as reported in "ood consumption data)ases and in t%e scienti"ic literature. 6s can )e seen in 9a)le 1, t%e ric%est sources include "is% li&er oils, oil' "is%, e(( 'ol3, and wild mus%rooms. $owe&er, e&en in t%ose "oods considered t%e ric%est sources o" &itamin , t%e le&els are %i(%l' &aria)le. #or e>ample, t%e content o" &itamin in "is% can &ar' si(ni"icantl' )ot% )etween and wit%in species and accordin( to w%et%er t%e' are wild or "armed; t%e &itamin content o" "armed salmon %as )een s%own to )e onl' appro>imatel' 2;G t%at o" wild salmon @43A. Ta1le 1/?itamin content o" selected "oods.

"oo! Vitamin D Content 9:';100 '< "i#h Cod li&er oil 210.0 @44AE2;0.0 @4;A 2almon, wild .7aci"ic1 13.1 @4;AE24.< @43A 2almon, wild .6tlantic1 ;.9 @44A 2almon, "armed K =.0 @43A $errin(, *altic, raw ;.<E1;.4 @4=A Hipper "illets, raw C.0 @44A ,ac3erel, raw C.C @44AE1=.1 @4;A 2ardines, canned in )rine 4.= @44A 9una, canned in oil =.< @4;A 6nc%o&', canned in oil 1.< @4;AE3.0 @44A Cod 9race @44AE2.= @43A 2ole 9race @44AE2.C @4;A +(#h%oom#= ,us%rooms, wild edi)le .!"nt "rellus tub"eformis 1 13.= @4=AE29.C @4<A ,us%rooms, c%anterelle ;.3 @4;AE14.2 @4CA ,us%rooms, w%ite )utton.A#"ricus bisporus1 0.2 @4;A ,us%rooms, w%ite )utton.A#"ricus bisporus1, U? irradiated 11.9 @49A Dai%, ,il3, w%ole, un"orti"ied 0.1 @4;A ,il3, "orti"ied 1.3 @4;AE2.0 @;0A C%eese, c%eddar 0.3 @44AE0.= @4;A Lo(%urt, plain 0.1 @4;A

Nutrients 2011,3 Ta1le 1/ !ont$ +eat an! E''# /i&er, )ee", raw *ee", ri) e'e stea3, raw 7or3, cured )acon, raw $am C%ic3en, )reast, raw 9ur3e', slices *utter +((, w%ole, raw +((, 'ol3, raw Ce%eal $%o!( t# *rea3"ast cereals, "orti"ied *read, "orti"ied M
K /e&els dependent on "eed;
M ?itamin

1027

1.2 @4;A 0.1 @4;A 1.= @4;A 0.< @4;AE1.1 @44A 0.1 @4;A 2.2 @44A 1.; @4;A 1.C @44AE2.0; @4;A 4.9 @44AE;.4 @4;A 2.CEC.3 @44A 3.0 @;1A
in t%e "orm o" &itamin
2

. 8ote: ?itamin

inta3es are

discussed in terms o" micro(rams .J (1 or !nternational Units .!U1. !n +urope J ( are most commonl' adopted as t%e measure o" &itamin . !n order to con&ert J( to !U multipl' )' 40.

#orti"ied "oods are t%ose to w%ic% one or more essential nutrients %a&e )een added, w%et%er or not it is normall' contained in t%e "ood, "or t%e purpose o" pre&entin( or correctin( a demonstrated de"icienc' @;2A. +nric%ed "oods are t%ose t%at %a&e nutrients t%at were ori(inall' lost durin( processin( restored and are sometimes considered interc%an(ea)l' wit% "orti"ied "oods @;3A. !t is also possi)le to en%ance animal products )' "eedin( animals &itamin supplemented "eed, t%ere)' increasin( t%e le&els o" &itamin present in t%e edi)le products. !n t%e current re&iew, unless ot%erwise stated, we will consider animal and non-animal "orti"ied "oods, and enric%ed "oods under t%e um)rella term o" &itamin -en%anced "oods. 6t present, t%e num)er and &ariet' o" &itamin "orti"ied "oods a&aila)le on t%e mar3et di""ers si(ni"icantl' )etween countries )ut most commonl' includes mil3, )rea3"ast cereals and mar(arines. 9%e relati&e de"icit o" &itamin "orti"ied "oods can )e partl' attri)uted to t%e countr'-speci"ic policies on "ood "orti"ication w%ic% are not 'et uni"ied. ,ost indi&idual countries %a&e t%eir own national policies, e&en wit%in +urope, w%ic% tend to limit t%e num)er or t'pe o" "oods t%at can )e "orti"ied, as will )e discussed later in t%e re&iew. +&en in t%ose countries w%ere &itamin "ood "orti"ication is mandator', current le&els o" "orti"ication in permitted "oods are li3el' inadeFuate to satis"' p%'siolo(ical reFuirements @;4A. #urt%ermore, t%e small num)er o" "oods a&aila)le is li3el' to %a&e limited impact on population dietar' inta3e. #or e>ample, certain population (roups are low consumers o" mil3, one o" t%e more commonl' "orti"ied "oods @40A. 6s suc%, w%ilst it is important t%at currentl' "orti"ied "oods continue to )e widel' a&aila)le and consumed, no&el met%ods "or producin( a wider &ariet' o" &itamin -ric% "oods are also increasin(l' sou(%t. !n recent 'ears, e&idence %as emer(ed demonstratin( &ia)le new met%ods "or en%ancement o" "oods wit% &itamin . #un(i can produce considera)le &itamin 2 le&els w%en e>posed to U?* li(%t t%rou(% t%e con&ersion o" natural er(osterol, t%e rate dependin( on t%e irradiation dose and temperature @;;,;=A. 9%e &itamin content in t%ese irradiated mus%rooms appears relati&el' sta)le w%en re"ri(erated @;<A and t%e retention o" &itamin in mus%rooms "ollowin( coo3in( and stora(e %as )een reported as %i(%,

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at C=G and (reater @4=A. +&en a"ter = 'ears o" stora(e, dried mus%rooms appear to retain muc% o" t%eir &itamin content @4CA. 2uccess in terms o" &itamin en%ancement o" animal products %as )een seen wit% pi(s, "is% and %ens. !ncreasin( t%e dietar' &itamin 3 content o" pi(s diets can produce meat and li&er wit% %i(%er le&els o" &itamin @;C,;9A. 2imilarl', t%e le&els o" &itamin in "is% can )e 3 impro&ed t%rou(% t%e "eedin( o" &itamin 3 -ric% "eed, wit% I10G o" t%e dietar' content o" &itamin 3 retrie&ed in t%e w%ole "is% @=0A. 9%e &itamin content o" e((s can also )e sa"el' increased )' "eedin( %ens &itamin 3 -ric% diets. 9%e consumption o" one o" t%ese e((s could pro&ide up to 2.C J( o" &itamin , appro>imatel' 3 times t%at o" a t'pical e((, wit% scope "or increasin( t%is e&en "urt%er @=1,=2A. 9%e preser&ation o" &itamin 3 and 2;-%'dro>'&itamin 3 in e(( 'ol3 a"ter coo3in( is %i(% and onl' modestl' a""ected )' stora(e, wit% losses o" N10G in )ot% cases @4=A. /ittle wor3 %as )een done on modellin( t%e impact t%at t%e widespread introduction o" suc% en%anced "oods mi(%t %a&e on t%e &itamin inta3es o" populations. 9o assess t%e potential e""ecti&eness o" suc% e((s in increasin( &itamin inta3es, we simulated t%e increase t%at would result "rom t%e consumption o" en%anced e((s )' !ris% adults. *ased upon current estimated inta3es o" 112 ( o" e((s and e(( dis%es per wee3, t%e consumption o" e((s wit% a &itamin content o" 2.C J( versus 1.1 J( .per =0 ( e((1 would result in a wee3l' population inta3e o" ;.2 J( &itamin "rom e(( products versus t%e current estimated inta3e o" 2.1 J(. *' e>cludin( t%ose people t%at do not consume e(( products, inta3e increases "rom 4.2 J( to 10.C J( per wee3. #urt%er assessment o" t%e potential impact o" a ran(e o" &itamin en%anced "oods on population inta3es o" t%is &itamin is certainl' warranted. 9o t%is end we %a&e per"ormed "ood modellin( wor3 w%ic% will )e discussed in t%e section e>aminin( t%e re(ulation surroundin( t%e sale o" "oods en%anced wit% &itamin . 3/ "oo!# Enhan e! 6ith Vitamin D 6s outlined a)o&e, it is "easi)le to en%ance a &ariet' o" "oods wit% &itamin ; %owe&er, t%e )iolo(ical si(ni"icance o" consumption o" t%ese "oods needs to )e assessed. !n order to assess t%e e""icac' o" &itamin en%anced products in increasin( serum 2;.0$1 concentration, a num)er o" randomiDed controlled trials .BC9s1 %a&e )een conducted in recent 'ears. 9%e present re&iew "ocuses on t%e BC9s w%ic% pro&ided at least 10J( o" &itamin 2 or 3 eac% da' wit% "oods t%at were en%anced wit% &itamin @=3E<1A .9a)le 21. 6 literature searc% was conducted usin( t%e 7u),ed and ,edline data)ases up to ,a' 2011 "or studies in t%e +n(lis% lan(ua(e. He'words used included O&itamin P and "oods t%at could )e "orti"ied wit% &itamin , suc% as Oc%eeseP, O)readP, Ooran(e juiceP, O'o(urtP, OspreadsP and Omar(arineP, OcerealsP, and Omus%roomsP. !n (eneral, t%e majorit' o" t%e studies concentrated on mar3ers o" )one meta)olism as well as &itamin status and as a conseFuence most anal'sed serum 2;.0$1 , 79$ and calcium concentration; some included collection o" a t%ree da' "ood diar'. ,ost o" t%e inter&entions were t%ree to twel&e wee3s duration and were per"ormed durin( winter mont%s, w%en t%e cutaneous s'nt%esis o" &itamin is low and does not contri)ute to circulatin( le&els o" 2;.0$1 . 9wo out o" nine studies %ad a lon(er duration o" twent'-"our mont%s. 6cross t%e nine studies &olunteers were (enerall' %ealt%', representin( )ot% (enders and a(e (roups ran(in( "rom 1C to C< 'ears .9a)le 21.

Nutrients 2011,3 Ta1le 2/C%an(e in serum 2;.0$1 a"ter inta3e o" "oods en%anced wit% &itamin .
Dail, !o#e 9:'< "oo! #o(% e Refe%en e# &itamin D 9:' &itamin D;100 ' $%o!( t< C%ee et "l$, 2003 @=4A #orti"ied mil3 al' et "l$, 200= @=;A 20 J( .;.0 J(/100 (1 10 J( .2.2 J(/100 (1 24 mont%s ;0E=; 'ears, postmenopausal "emales nR 200 24 mont%s ;0EC< 'ears, am)ulator' communit'-li&in( .male1 nR 1=< 12 wee3s, 0cto)er-,arc% #orti"ied 'o(urt drin3 8i3oo'e% et "l$, 2011 @=CA 2; J( .;.0 J(/100 (1 30E=0 'ears, dia)etic su)jects ."astin( )lood (lucose R12= m(/d/1 nR 90 4o%nson et "l$, 200; @==A .stud' 11 #orti"ied c%eese Sa(ner et "l$, 200C @<1A 100 J( K .20C3.3 or 1=90.C J(/100 (1 KK C wee3s, 4anuar'E6pril 1CE=0 'ears, %ealt%' su)jects nR C0 1; J( .1< .= J(/100 (1 1. ?itamin 2. ?itamin
3 3

102?

Chan'e f%om D(%ation an! $o$(lation St(!, '%o($# 9$%o!( t $o%tion< 1a#eline of #e%(m 279O@<D 9A< 1. &itamin
3

: Ca-"orti"ied s3immed mil3

2;.0 Q 4.1 Q

2. Usual diet

1. ?itamin

: Ca-"orti"ied U$9 mil3, reduced "at

2. Usual diet

<.4 Q -19.9 Q

-"orti"ied 'o(urt drin3 : Ca-"orti"ied 'o(urt drin3

<;.0 =<.= -10.= -C.< 10.0 ;.= 12C.C 120.< 10=.; 111.0 -<.C
QQ

3 . 7lain 'o(urt drin3

2 winter mont%s 1. ?itamin 3 -"orti"ied process c%eese R=0 'ears, su)jects .total serum c%olesterol 2. 7lace)o process c%eese N240 m(/d/1 3 . 8o c%eese nR 110 1.?itamin 2. ?itamin 3. ?itamin 4. ?itamin
3

-"orti"ied re(ular "at c%eddar c%eese KKK

-"orti"ied reduced "at c%eddar c%eese 3 supplement to )e ta3en wit% "ood 3 supplement to )e ta3en wit%out "ood 3

;. 7lace)o re(ular "at c%eddar c%eese =. 7lace)o supplement

Nutrients 2011,3 Ta1le 2/ !ont$


9an(pric%aet "l$, 2003 @=9A .stud' 21 #orti"ied oran(e juice *iancuDDo et "l$, 2010 @=3A 2; J( .10.= J(/100 (1 11 wee3s, commenced in #e)ruar' 1CE<9 'ears, %ealt%' su)jects nR 10; 2; J( .10.4 J(/100 (1 12 wee3s, commenced in ,arc% 22E=0 'ears, %ealt%' su)jects nR 30 1. ?itamin
3

1030

: Ca-"orti"ied oran(e juice

1;0.0 4;.0 <1.; =<.1 42.9 =;.1 -C.= ;0.0 Q <=.< Q -2C.9 Q
QQQ =;.0

2. 7lace)o Ca-"orti"ied oran(e juice 1. ?itamin 2. ?itamin 3. ?itamin 4. ?itamin


3

oran(e juice T : place)o capsule

oran(e juice : place)o capsule 2 capsules : place)o oran(e juice 3

capsules : place)o oran(e juice 2 ;. 7lace)o capsule : place)o oran(e juice


2

U? en%anced mus% rooms

Ur)ain et "l$, 2011 @<0A

100 J( K .191.0 J(/100 (1 KK

3 wee3s : 2 wee3s "ollow up, 4anuar'E,arc% 1. ?itamin $ealt%' "emale and male N4; 'ears nR 2< 3 wee3s, #e)ruar'E,arc% 2;E4; 'ears, %ealt%' "emales .2;.0$1 N ;C.1 nmol//1 nR 41
Q

soup : place)o oran(e juice KKK


2

2. 7lace)o soup : &itamin 1. ?itamin 2. ?itamin

supplement in oran(e juice

3. 7lace)o soup : place)o oran(e juice


3

-"orti"ied w%eat )read .C; (1

#orti"ied )read 8atri 200= @=<A

et "l$,

10 J( .2<.3 J(/100 (1

-"orti"ied r'e )read 3

;9.0 Q QQ <C.0 Q QQ -1.2 QQQ

3. Be(ular w%eat )read : &itamin 3 supplement 4. Be(ular w%eat )read measurement at t%e end o" t%e inter&ention;
QQ

K eFui& alent to a dail' dose; KK in(ested in one wee3l' dose; KKK all portions ser&ed once a wee3;

com)ined place)o

(roups;Q QQestimated )aseline 2;.0$1 ; T all oran(e ju ice in t%is stud' contain ed 3;0 m( Ca/23=.= m/.

Nutrients 2011,3

1031

!n t%e current literature t%e most commonl' used &e%icles "or &itamin "orti"ication are dair' products .mil3, c%eese and 'o(urt1. 9wo lon( term studies .24 mont%s1 used mil3 "orti"ied wit% &itamin 3 to deli&er 10 J( or (reater per da' @=4,=;A. !n )ot% studies, 2;.0$1 concentrations increased "or t%e supplemented (roup compared to )aseline; %owe&er, t%e relati&e increases &aried )etween t%e studies .2;.0G vs$<.4G1 w%ic% ma' )e as a result o" &er' di""erent stud' populations. !t s%ould )e noted t%at in t%e stud' )' al' and collea(ues a 20G decrease in serum 2;.0$1 was reported "or t%e control (roup. !n (eneral, compliance was (ood, wit% onl' a small num)er o" dropouts reported despite t%e necessit' to consume a lar(e &olume o" mil3 .400 m//da'1. *ot% studies concluded t%at &itamin was )ioa&aila)le and impro&ed 2;.0$1 status and mar3ers o" )one turno&er. 2imilarl', dail' inta3e o" 2; J( o" &itamin in a 'o(urt drin3 wit% or wit%out added 3 calcium si(ni"icantl' increased serum 2;.0$1 3 concentrations a"ter 12 wee3s )' <;.0G and =<.=G, respecti&el', compared to a decrease o" 10.=G in t%e control (roup. !n addition, t%e (l'caemic status in dia)etic patients was impro&ed @=CA. 6cceptance o" t%e drin3 was %i(% amon( &olunteers and no ad&erse e""ects were o)ser&ed. #orti"ication o" c%eese wit% &itamin %as )een e>amined in two separate ei(%t-wee3 studies s%owin( di&erse results. !n t%e stud' )' 4o%nson and collea(ues, consumption o" "orti"ied c%eese .1; J( &itamin 1 resulted in an C.<G decrease in t%eir serum 2;.0$1 @==A. 9%is was an une>pected "indin( t%at t%e aut%ors attri)ute to a %i(%er )aseline &alue o" 2;.0$1 in t%e supplemented (roup. 6dditionall' no c%an(es in serum 79$ were "ound. 9%e second stud' )' Sa(ner et "l$ s%owed an appro>imate 120G increase in serum 2;.0$1 concentration a"ter a wee3l' dose o" <00 J( &itamin "orti"ied c%eese @<1A. !n t%is stud' serum 79$ decreased and t%ere were no c%an(es in serum calcium concentration; additionall' no dropouts or ad&erse side e""ects o)ser&ed were reported. $owe&er, in t%e stud' )' 4o%nson and collea(ues t%ere were "i&e dropouts in t%e c%eese (roup: t%e reasons "or wit%drawal included (astrointestinal pro)lems, a disli3e "or t%e saltiness o" t%e c%eese and medical ad&ice @==A. !ndeed, as c%eese t'picall' contains relati&el' %i(% le&els o" salt and saturated "at, a portion siDe closer to t%at usuall' recommended "or c%eese .30 (1 rat%er t%an w%at was used )' 4o%nsonet "l. .C; (1 ma' %a&e )een more appropriate @==A. 0&erall, c%eese could )e a "easi)le "ood "or t%e impro&ement o" &itamin status, )ut a more realistic amount and &itamin dose s%ould )e used in "uture studies. 9o summarise, &itamin was )ioa&aila)le "rom all studied dair' products; en%anced mil3 and 'o(urt or a &er' %i(% wee3l' inta3e o" en%anced c%eese impro&ed &itamin status, w%ilst consumption o" 1; J( o" &itamin in c%eese was insu""icient to produce a si(ni"icant increase in serum 2;.0$1 . ue to lactose intolerance or low dair' product consumption in some countries, new "oods s%ould )e considered as possi)le &e%icles "or en%ancement wit% &itamin . 9wo BC9s usin( oran(e juice "orti"ied wit% 2; J( o" &itamin s%owed a positi&e e""ect on serum 2;.0$1 concentration @=3,=9A. !n t%e stud' o" 9an(pric%a et "l ., 2;.0$1 increased )' 1;0G a"ter 12 wee3s supplementation @=9A. 9%e second stud' reported t%at in(estion o" 2; J( &itamin and 3 "orti"ied oran(e juice "or 2 11 wee3s resulted in a rise in serum 2;.0$1 concentration )' =<.1G and <1.;G, respecti&el' @=3A. 2erum 79$ decreased onl' in t%e "irst stud', w%ile calcium concentration remained sta)le in )ot% inter&entions. 8o ad&erse e""ects were reported in eit%er stud'. 9%e "orti"ication o" oran(e juice wit% &itamin seems a promisin( met%od o" )oostin( serum 2;.0$1 concentration. $owe&er, replication o" t%e a)o&e studies usin( a dail' dose in line wit% t%e B 6 "or &itamin is warranted.

Nutrients 2011,3

1032

6not%er non-dair' &itamin en%anced product t%at %as recei&ed attention recentl' is mus%rooms. ?itamin 2 "rom wild (rown mus%rooms was well a)sor)ed and )ioa&aila)le in %umans @<2A. 9%is stud' used wild and not en%anced mus%rooms, and t%ere"ore %as not )een included in t%is re&iew t%at "ocuses on en%anced &itamin "oods. $owe&er, a recent paper %as in&esti(ated t%e e""ect o" a wee3l' dose o" <00 J( o" &itamin "rom &itamin 2 -en%anced mus%rooms in a soup @<0A and reported a ;0G increase in serum 2;.0$1 concentration. 9%ere were no c%an(es in serum 79$ and calcium concentration and no ad&erse e""ects were o)ser&ed. 6dditionall', t%e soup was well tolerated )' &olunteers. 9%e limitations o" t%is stud' include t%e low num)er o" su)jects and t%e %i(% &itamin dose in(ested wee3l'. 8onet%eless, t%is stud' demonstrated t%at &itamin "rom mus%rooms was )ioa&aila)le and s%ows promise as an alternati&e to supplements in maintainin( serum 2;.0$1 concentration. *read "orti"ied wit% &itamin could also ser&e as a (ood source o" &itamin due to its common consumption. 7romisin( results were o)tained "ollowin( dail' consumption o" 12; J( o" &itamin 3 en%anced )read "or 12 mont%s in older adults @<3A, %owe&er t%e details o" t%e stud' are not included in 9a)le 2 as it was a sin(le-arm desi(n. 9o date, onl' one BC9 %as in&esti(ated t%e e""ect o" supplementation o" w%eat and r'e )read wit% 10 J( o" &itamin 3 per dail' C; ( portion .eFui&alent to "our t%in slices1 @=<A. !n t%is stud' serum 2;.0$1 increased )' appro>imatel' =0G a"ter 3 wee3s in )ot% (roups t%at recei&ed "orti"ied )read. 8o di""erences in serum 79$ were "ound, w%ile calcium concentration decreased in t%e "orti"ied r'e )read (roup. 9%ree su)jects dropped out o" t%e stud' due to di""iculties wit% compliance. !n conclusion, "orti"ied )read increased serum 2;.0$1 concentration, wit% r'e and w%eat )read eFuall' e""ecti&e. #inall', t%e a"orementioned BC9s s%ow t%e potential o" a num)er o" &itamin en%anced "oods to increase &itamin status. 0&erall, "orti"ication was t%e principal strate(' adopted )ut t%e potential o" U? li(%t en%anced mus%rooms to )oost &itamin status was more recentl' e>plored. 6 comparison )etween t%e studies is di""icult to per"orm )ecause o" &aria)ilit' in t%e population c%aracteristics .i$e$, a(e, (ender1, dose o" &itamin pro&ided, inter&ention period and met%ods used "or 2;.0$1 determination @<4,<;A. 9%e majorit' o" t%e studies pro&ided a dail' suppl' o" t%e "oods w%ilst two used a wee3l' dose. $owe&er, t%e impact o" t%e "reFuenc' o" dose %as not )een studied in relation to an' o" t%e a)o&e "oods. Sit% respect to inta3e o" &itamin supplements it %as )een demonstrated t%at t%e "reFuenc' o" inta3e %as an impact on 2;.0$1 serum concentrations @<=A, illustratin( t%e imperati&e need to stud' t%is in t%e &itamin en%anced "oods. 0&erall, in t%e en%anced "ood a %i(%er dose was more e""ecti&e in increasin( 2;.0$1 concentration; %owe&er, "or s%ort term studies .3 wee3s1 t%e increase seemed to )e independent o" dose. 9%e majorit' o" t%e "oods in t%e selected BC9s were well tolerated )' t%e stud' su)jects. 6"ter t%e in(estion o" di""erent &itamin "orti"ied/enric%ed "oods, 79$ decreased or did not c%an(e, w%ile serum calcium concentration remained sta)le or in t%e case o" t%e r'e )read (roup decreased, %i(%li(%tin( no sa"et' ris3s wit% t%e use o" t%ese &itamin en%anced products. ,il3, 'o(urt, oran(e juice, mus%rooms and )read pro&ed to )e (ood matrices "or supplementation wit% &itamin at t%e le&el o" 10 J( .mil3, )read1, 2; J( .oran(e juice and 'o(urt1 or or 100 J( .mus%rooms1. ,ore studies are needed to assess t%e e""ecti&eness o" &itamin "orti"ied c%eese, wit% t%e use o" a more "easi)le ser&in( siDe. #inall', more BC9s, usin( t%ese "oods, s%ould )e conducted to in&esti(ate t%e lin3 )etween &itamin and ot%er disease mar3ers )e'ond t%ose related to )one %ealt% and &itamin status.

Nutrients 2011,3 4/ Vitamin D2 an! D 3 2ioa&aila1ilit,

1033

Until relati&el' recentl' it was widel' )elie&ed, )ased upon anti-rac%itic "indin(s, t%at &itamin 2 and 3 were eFuipotent and could )e considered interc%an(ea)l'. $owe&er, e&idence is accumulatin( to su((est t%e two "orms ma' &ar' in t%eir )ioe""icac' and t%e importance o" t%is must )e considered w%en discussin( potential "ood matrices. 6 num)er o" recent studies addressin( t%e potenc' o" t%e two calci"erols %a&e "ound 3 to )e more e""ecti&e in raisin( serum 2;.0$1 le&els. !n a (roup o" &itamin insu""icient %ip "racture patients, a dail' capsule o" 2; J( was more e""ecti&e t%an an 3 eFual dose o" 2 in increasin( total serum 2;.0$1 @<<A. 6lso in older populations, 1; J( dail' or 12;0 J( mont%l' o" capsular &itamin 3 increased serum 2;.0$1 more e""icientl' t%an an eFual dose o" 2 @<CA, as %as also )een s%own wit% a sin(le <;00 J( dose o" oral or intramuscular 3 @<9A. 9%e increased a)ilit' o" a wee3l' capsule o" 12;0 J( o" 3 "or 12 wee3s to maintain serum 2;.0$1 w%en compared wit% eFuimolar 2 %as also )een s%ownin %ealt%' adults @C0A. 9%ese "indin(s support t%ose o" a num)er o" earlier studies also addressin( t%is topic @C1,C2A. 9%e a)o&e "indin(s were not replicated in a num)er o" recent studies in w%ic% and 3 were 2 "ound to )e eFuall' e""ecti&e in increasin( serum 2;.0$1 w%en administered to %ealt%' adults as capsules @=3,C3A or in oran(e juice @=3A "or 11 wee3s, or in a %i(%-dose liFuid suspension to &itamin de"icient in"ants "or = wee3s @C4A. espite t%is, t%e (eneral consensus t%at is )e(innin( to emer(e is t%at &itamin 3 is t%e more potent "orm. $owe&er, it is di""icult to directl' compare t%e results o" t%e discussed studies (i&en t%e man' con"oundin( "actors )etween t%em. ,ost nota)le in t%is re(ard are t%e di""erent met%ods emplo'ed to anal'De serum 2;.0$1 , t%e di""erin( )aseline serum le&els, t%e &ariance in a(e (roups studied, t%e doses administered, and t%e duration o" supplementation. 0&erall, more studies speci"icall' desi(ned to address t%is Fuestion are needed )e"ore t%e results can )e translated into a pu)lic %ealt% messa(e. 7/ Re'(lation S(%%o(n!in' the Sale of "oo!# Enhan e! 6ith Vitamin D #rom a re(ulator' perspecti&e, t%e &itamin en%anced "oods mentioned in t%is re&iew %a&e t'picall' "allen into two cate(ories .i1 "orti"ied "oods and .ii1 "oods t%at %a&e used tec%nolo(ies to en%ance naturall' occurrin( &itamin le&els. $owe&er, prior to sale on a commercial scale, t%ere are a series o" steps w%ic% potential manu"acturers must consider. 5lo)all' t%ese can &ar' dependin( on t%e re(ion .e.(., +urope, U21 and also )etween countries .e.(., wit% respect to "orti"ication policies1. 9%is re&iew will now )rie"l' outline some o" t%e re(ulations t%at must )e considered in t%e +U. #or "orti"ied "oods, addition o" )ot% er(ocalci"erol and c%olecalci"erol is permitted )ut consideration must )e (i&en to dietar' inta3e "rom ot%er sources and sa"e upper le&els o" inta3e )e"ore a(reein( on t%e le&els o" addition @C;A. 6t present t%e !0, %as de"ined 100 J(/da' as an upper le&el "or &itamin inta3e @29A. Be(ardin( "oods w%ic% e>ploit new tec%nolo(ies to en%ance naturall' occurrin( le&els .as in t%e case o" &itamin en%anced mus%rooms, w%ic% were irradiated )' U? li(%t1, i" t%e' are not currentl' widel' consumed wit%in t%e +U, t%e' would )e considered as a Ono&el "oodP and su)ject to appro&al as Osa"e "or useP )' t%e competent aut%orit' in t%e applicant countr' and also in ot%er ,em)er 2tates @C=A.

Nutrients 2011,3

1034

9%erea"ter, )ot% cate(ories o" "ood are su)ject to (eneral "ood law la)ellin(. Currentl', in t%e +U &itamins and minerals can )e declared on "ood onl' i" t%e' are present in a Osi(ni"icantP amount, i$e$, R1;G o" Becommended ail' 6llowance .B 61 @C<A. 6ccordin( to current le(islation in relation to &itamin , "ood containin( R0.<; J( &itamin /100 ( .100 m/1 product can )e claimed as a OsourceP o" &itamin , w%ereas to )e declared as O%i(%P in &itamin , it %as to contain at least twice t%e &alue o" a OsourceP o" &itamin , i$e$, R1.; J(/100 ( .100 m/1 or 30G B 6 @CC,C9A. #or t%ose manu"acturers w%o wis% to ma3e "urt%er nutrition and %ealt% claims, speci"ic procedures and conditions "or use are applica)le to eac% claim and are outlined in t%e appropriate re(ulations @CCA. !n )rie", t%ere are t%ree cate(ories o" permitted %ealt% claims .i1 article 13 (eneral "unction claims; .ii1 article 13.; claims )ased on newl' de&eloped scienti"ic e&idence; and .iii1 article 14 claims re"errin( to t%e reduction o" a ris3 "actor in t%e de&elopment o" a disease and c%ildrenUs de&elopment and %ealt%. Currentl', appro&ed &itamin %ealt% claims relate to &itamin and )one and teet% %ealt%, a)sorption and utilisation o" calcium and p%osp%orus, normal "unction o" t%e immune s'stem, cell di&ision, normal (rowt% and de&elopment o" )one in c%ildren, as well as claims re"errin( to t%e relations%ip )etween calcium and &itamin and t%e reduction o" )one loss in elderl' women @90E94A. $owe&er, i" a &itamin -en%anced product wis%es to )ear an' o" t%e a)o&e claims, it must con"orm to t%e a"orementioned conditions "or use and to as 'et unspeci"ied nutrient pro"iles @C<,CCA. 6s mentioned, we conducted "ood modellin( to simulate t%e inta3e o" &itamin "rom en%anced "oods in t%e !ris% adult population. !nitiall' t%e e""ect o" consumption o" oran(e juice en%anced wit% 10.; J( &itamin per 100 ( on mean dail' inta3es was in&esti(ated. Consumption o" suc% oran(e juice would increase mean inta3es o" &itamin "rom 4.< J( to <.9 J( per da'. !n anot%er simulation desi(ned to mimic mandator' "orti"ication policies, in tandem wit% t%e oran(e juice, mil3 was en%anced at a conser&ati&e le&el o" 1 J(/100 (. !n t%is scenario inta3es increased to 9.9 J(/da', %owe&er, it also resulted in 1G o" t%e population consumin( I;0 J( &itamin , t%ere)' reiteratin( t%e need to )e co(nisant o" e>treme consumers. 0n t%e ot%er %and, an' mandator' "orti"ication policies would need to )e aware o" non-consumers o" t%e particular en%anced "ood (roup: to t%is end it ma' )e prudent to introduce "orti"ication at low le&els in a num)er o" "oods. 6/ Con l(#ion# 0&erall, t%e e&idence t%at en%anced &itamin "oods can impro&e &itamin status is con&incin(. 6 ran(e o" en%anced "oods were s%own to )e e""ecti&e in increasin( circulatin( 2;.0$1 concentrations wit% no si(ns o" ad&erse e""ects. #urt%er researc% and de&elopment in suc% "oods is warranted as t%e' %a&e t%e potential to pro&ide a means to address t%e &itamin de"icienc' pandemic. A 8no6le!'ment# Se would li3e to ac3nowled(e ,ona(%an ,us%rooms "or support o" researc% in our la)oratories. Confli t of Inte%e#t 9%e aut%ors declare no con"lict o" interest.

Nutrients 2011,3 Refe%en e#

1037

1. 8orman, 6.S.; *ouillon, B. ?itamin nutritional polic' needs a &ision "or t%e "uture. %&p$ 'iol$ (ed$ )("*wood+ 2010, 23,, 1034E104;. 2. $aussler, ,.B.; $aussler, C.6.; 4urut3a, 7.S.; 9%ompson, 7. .; $sie%, 4.C.; Bemus, /.2.; 2elDnic3, 2.$.; S%it"ield, 5.H. 9%e &itamin %ormone and its nuclear receptor: ,olecular actions and disease states. -$ %ndocrinol$ 1??7, 1,..2uppl.1, 2;<E2<3. 3. $ess, 6.#.; Un(er, /.4. 9%e cure o" in"antile ric3ets )' sunli(%t. -A(A 1?22, /0, 29E31. 4. *%an, 6.; Bao, 6. .; Bao, .2. 0steomalacia as a result o" &itamin de"icienc'. %ndocrinol$ (et"b$ !lin$ N$ Am$ 2010, 31, 321E331. ;. 6&enell, 6.; 5illespie, S.4.; 5illespie, /. .; 0UConnell, . ?itamin and &itamin analo(ues "or pre&entin( "ractures associated wit% in&olutional and post-menopausal osteoporosis. !oc r"ne D"t"b"se 2*st$ Rev$ 200?, C 00022<. =. /ips, 7.; *ouillon, B.; &an 2c%oor, 8.,.; ?andersc%ueren, .; ?ersc%ueren, 2.; Huc%u3, 8.; ,ilisen, H.; *oonen, 2. Beducin( "racture ris3 wit% calcium and &itamin !lin$ . %ndocrinol$ )3&f$+ 2010, /3, 2<<E2C;. <. $olic3, ,.#. ?itamin : +&olutionar', p%'siolo(ical and %ealt% perspecti&es. !urr$ Dru# 4"r#ets 2011, 12, 4E1C. C. C%u, H.4.; /ai, +.C.; Lao, V.7.; W%an(, $.S.; /au, S.L.; #u, V.$.; /u, C. .; 2%i, 4.; C%en(, 2.X. ?itamin analo(ues in c%emopre&ention o" %epatocellular carcinoma a"ter resection or a)lationYa s'stematic re&iew and meta-anal'sis. Asi"n -$ 2ur#$ 2010, 33, 120E12=. 9. W%an(, $./.; Su, 4. Bole o" &itamin in immune responses and autoimmune diseases, wit% emp%asis on its role in multiple sclerosis. Neurosci$ 'ull$ 2010, 26, 44;E4;4. 10. 5rant, S.*. 6n estimate o" t%e (lo)al reduction in mortalit' rates t%rou(% dou)lin( &itamin le&els. %ur$ -$ !lin$ Nutr$ 2011, 6,, 101=E102=. 11. 5rant, S.*.; 2c%wal"en)er(, 5.H.; 5enuis, 2.4.; S%itin(, 2.4. 6n estimate o" t%e economic )urden and premature deat%s due to &itamin de"icienc' in Canada. (ol$ Nutr$ 5ood Res$ 2010, ,., 11<2E11C1. 12. 5inde, 6.6.; 2cra((, B.; 2c%wartD, B.2.; Camar(o, C.6. 7rospecti&e stud' o" serum 2;-%'dro>'&itamin le&el, cardio&ascular disease mortalit', and all-cause mortalit' in older U2 adults. -$ Am$ 6eri"tr$ 2oc$ 200?, ,/, 1;9;E1=03. 13. o)ni(, $.; 7ilD, 2.; 2c%arna(l, $.; Benner, S.; 2eel%orst, U.; SellnitD, *.; Hin3eldei, 4.; *oe%m, *.0.; Sei%rauc%, 5.; ,aerD, S. !ndependent association o" low seru m 2;-%'dro>'&itamin and 1,2;-di%'dro>'&itamin le&els wit% all-cause and cardio&ascular mortalit'. Arc $ 7ntern$ (ed$ 200>, 160, 1340E1349. 14. $olic3, ,.#.; C%en, 9.C. ?itamin de"icienc': 6 worldwide pro)lem wit% %ealt% conseFuences. Am$ -$ !lin$ Nutr$ 200>, 0/, 10C02E10C=2. 1;. ,it%al, 6.; Sa%l, .6.; *onjour, 4.7.; *urc3%ardt, 7.; awson-$u(%es, *.; +isman, 4.6.; +l-$ajj #ulei%an, 5.; 4osse, B.5.; /ips, 7.; ,orales-9orres, 4. 5lo)al &itamin status and determinants o" %'po&itaminosis .3steoporos$ 7nt$200?, 20, 1C0<E1C20.

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1=. W%an(, B.; 8au(%ton, .7. ?itamin in %ealt% and disease: Current perspecti&es. Nutr$ -$ 2010, 1, =;. 1<. /ips, 7. ?itamin status and nutrition in europe and asia. -$ 2teroid 'ioc em$ (ol$ 'iol$ 2007, 103, =20E=2;. 1C. $ill, 9.B.; #l'nn, 6.; Hiel', ,.; Cas%man, H. . 7re&alence o" su)optimal &itamin status in 'oun(, adult and elderl' !ris% su)jects. 7r$ (ed$ -$ 2006, 11, 4CE49. 19. 6t%erton, H.; *err', .4.; 7arsons, 9.; ,ac"arlane, 5.4.; 7ower, C.; $'pponen, +. ?itamin and c%ronic widespread pain in a w%ite middle-a(ed )ritis% population: +&idence "rom a cross-sectional population sur&e'. Ann$ R eum$ Dis$200?, 60, C1<EC22. 20. $ill, 9.; Collins, 6.; 0U*rien, ,.; Hiel', ,.; #l'nn, 6.; Cas%man, H. . ?itamin inta3e and status in !ris% postmenopausal women. %ur$ -$ !lin$ Nutr$ 2007, ,1, 404E410. 21. /apatsanis, .; ,oulas, 6.; C%ole&as, ?.; 2ou3a3os, 7.; 7apadopoulou, W./.; C%alla, 6. ?itamin : 6 necessit' "or c%ildren and adolescents in 5reece. !"lcif$ 4issue 7nt$ 2007, //, 34CE3;;. 22. !saia, 5.; 5ior(ino, B.; Bini, 5.*.; *e&ilacFua, ,.; ,au(eri, .; 6dami, 2. 7re&alence o" %'po&itaminosis in elderl' women in !tal': Clinical conseFuences and ris3 "actors.3steoporos$ 7nt$ 2003, 1., ;<<E;C2. 23. /an(lois, H.; 5reene-#inestone, /.; /ittle, 4.; $idiro(lou, 8.; S%itin(, 2. ?itamin status o" Canadians as measured in t%e 200< to 2009 Canadian %ealt% measures sur&e'. 8e"lt Rep$ 2010, 21, 4<E;;. 24. /oo3er, 6.C.; 7"ei""er, C.,.; /ac%er, .6.; 2c%leic%er, B./.; 7icciano, ,.#.; Letle', +.6. 2erum 2;-%'dro>'&itamin status o" t%e us population: 19CCE1994 compared wit% 2000E2004. Am$ -$ !lin$ Nutr$ 200>, 00, 1;19E1;2<. 2;. #orrest, H.L.W.; 2tu%ldre%er, S./. 7re&alence and correlates o" &itamin de"icienc' in U2 adults. Nutr$ Res$ 2011, 31, 4CE;4. 2=. 6s%well, ,.; 2tone, +.,.; 2tolte, $.; Cas%man, H. .; ,acdonald, $.; /an%am-8ew, 2.; $iom, 2.; Se)), 6.; #raser, . UH "ood standards a(enc' wor3s%op report: 6n in&esti(ation o" t%e relati&e contri)utions o" diet and sunli(%t to &itamin status.'r$ -$ Nutr$ 2010, 10., =03E=11. 2<. ,iller, 5. Report from t e ! "ir of t e 2cottis 5ood Advisor* !ommittee ; !n"o10/12/03; #ood 2tandards 6(enc': /ondon, UH, 2010. 2C. oets, +./.; de Sit, /.2.; %onu3s%e-Butten, B.6.; Ca&elaars, 6.+.; Baats, ,.,.; 9imotije&ic, /.; *rDoDows3a, 6.; Sijn%o&en, 9.,.; 7a&lo&ic, ,.; 9otland, 9.$.; et "l$ Current micronutrient recommendations in +urope: 9owards understandin( t%eir di""erences and similarities. %ur$ -$ Nutr$ 200>, ./, 21<E240. 29. !nstitute o" ,edicine. Diet"r* Reference 7nt"9es for !"lcium "nd :it"min D ; 9%e 8ational 6cademies 7ress: Sas%in(ton, C, U26, 2011. 30. #reislin(, $.; #a%e', ,.9.; ,os3al, 6.; 0c3e, ,.C.; #errari, 7.; 4ena), ,.; 8orat, 9.; 8as3a, 6.; Selc%, 6.6.; 8a&arro, C.; et "l$ Be(ion-speci"ic nutrient inta3e patterns e>%i)it a (eo(rap%ical (radient wit%in and )etween +uropean countries. -$ Nutr$ 2010, 1.0, 12C0E12C=. 31. 2erra-,ajem, /.; Bi)as-*ar)a, /.; 2al&ador, 5.; 4o&er, /.; Baido, *.; 8(o, 4.; 7lasencia, 6. 9rends in ener(' and nutrient inta3e and ris3 o" inadeFuate inta3es in Catalonia, 2pain .1992E20031. Public 8e"lt Nutr$ 2007, 10, 13;4E13=<.

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32. 2ette, 2.; /e onne, C.; 7iccinelli, B.; 6rcella, .; 9urrini, 6.; /eclercF, C. 9%e t%ird !talian national "ood consumption sur&e', !8B68-2C6! 200;E0=Y7art 1: 8utrient inta3es in !tal'. Nutr$ (et"b$ !"rdiov"sc$ Dis$ 2011, 21, 922E932. 33. 4 e N"tion"l 5indiet 200/ 2urve* ; 7aturi, ,., 9apanainen, $., Beini&uo, $., 7ietinen, 7., +ds.; 8ational 7u)lic $ealt% !nstitute: $elsin3i, #inland, 200C. 34. !ris% Uni&ersities 8utrition 6lliance. N"tion"l Adult Nutrition 2urve* ; !ris% Uni&ersities 8utrition 6lliance: u)lin, !reland, 2011. 3;. *aile', B./.; odd, H.S.; 5oldman, 4.6.; 5a%c%e, 4.4.; w'er, 4.9.; ,os%"e(%, 6.4.; 2empos, C.9.; 7icciano, ,.#. +stimation o" total usual calcium and &itamin inta3es in t%e United 2tates.-$ Nutr$ 2010, 1.0, C1<EC22. 3=. ?atanparast, $.; Cal&o, ,.2.; 5reen, 9.4.; S%itin(, 2.4. espite mandator' "orti"ication o" staple "oods, &itamin inta3es o" Canadian c%ildren and adults are inadeFuate. -$ 2teroid 'ioc em$ (ol$ 'iol$ 2010, 121, 301E303. 3<. 8anri, 6.; #oo, /.$.; 8a3amura, H.; $ori, 6.; 7oudel-9andu3ar, H.; ,atsus%ita, L.; ,iDoue, 9. 2erum 2;-%'dro>'&itamin concentrations and season-speci"ic correlates in 4apanese adults. -$ %pidemiol$ 2011, 21, 34=E3;3. 3C. Cal&o, ,.2.; S%itin(, 2.4.; *arton, C.8. ?itamin inta3e: 6 (lo)al perspecti&e o" current status. -$ Nutr$ 2007, 13,, 310E31=. 39. $enderson, /.; !r&in(, H.; 5re(or', 4.; *ates, C.4.; 7rentice, 6.; 7er3s, 4.; 2wan, 5.; #arron, ,. 4 e N"tion"l Diet "nd Nutrition 2urve*: Adults A#ed 11 to 6. ;e"rs<:it"min "nd (iner"l 7nt"9e "nd =rin"r* An"l*sis; 0""ice "or 8ational 2tatistics: 8ewport, UH, 2003; ?olume 3. 40. 7ar3, L.H.; *arton, C.8.; Cal&o, ,.2. ietar' contri)utions to serum 2;.0$1 &itamin le&els @2;.0$1 A di""er in )lac3 and w%ite adults in t%e United 2tates: Besults "rom 8$68+2 !!!. -$ 'one (iner$ Res$2001, 16, #2C1. 41. Hen3'u3ai, H.+.4. 4 e N"tion"l 8e"lt "nd Nutrition 2urve* in -"p"n ; aiic%i-s%uppan: 9o3'o, 4apan, 2010. 42. 8a3amura, H.; 8as%imoto, ,.; 03uda, L.; 0ta, 9.; Lamamoto, ,. #is% as a major source o" &itamin in t%e 4apanese diet. Nutrition 2002, 10, 41;E41=. 43. /u, W.; C%en, 9.C.; W%an(, 6.; 7ersons, H.2.; Ho%n, 8.; *er3owitD, B.; ,artinello, 2.; $olic3, ,.#. 6n e&aluation o" t%e &itamin 3 content in "is%: !s t%e &itamin content adeFuate to satis"' t%e dietar' reFuirement "or &itamin Z -$ 2teroid 'ioc em$ (ol$ 'iol$ 2007, 103, =42E=44. 44. #ood 2tandards 6(enc'. (cc"nce "nd >iddowson?s t e !omposition of 5oods 2i&t 2umm"r* %dition , =t% re&ised ed.; Bo'al 2ociet' o" C%emistr': Cam)rid(e, UH, 2002. 4;. U.2. epartment o" 6(riculture 6.B.2. U2 6 national nutrient data)ase "or standard re"erence. 6&aila)le online: %ttp://www.ars.usda.(o&/nutrientdata .accessed on 1; 0cto)er 20111. 4=. ,attila, 7.; Bon3ainen, B.; /e%i3oinen, H.; 7iironen, ?. +""ect o" %ouse%old coo3in( on t%e &itamin content in "is%, e((s, and wild mus%rooms. -$ 5ood !ompos$ An"l$1???, 12, 1;3E1=0. 4<. ,attila, 7.$.; 7iironen, ?.!.; Uusirau&a, +.4.; Hoi&istoinen, 7.+. ?itamin- contents in edi)le mus%rooms.-$ A#ric$ 5ood ! em$1??4, .2, 2449E24;3. 4C. Ban(el-Castro, 4.!.; 2ta""as, 6.; anell, +. 9%e er(ocalci"erol content o" dried pi(mented and al)ino !"nt "rellus cib"rius"ruit )odies. (*col$ Res$2002, 106, <0E<3.

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49. ,ontere' ,us%rooms ,us%room nutritional c%art. 6&aila)le online: %ttp://www. montere'mus%rooms.com/wp-content/uploads/2011/0=/mus%room-nutritional-c%art.(i" .accessed on 1; 0cto)er 20111. ;0. 6&onmore S%ole super mil3. 6&aila)le online: %ttp://www.a&onmoresupermil3.ie/ran(e/ w%olesupermil3.%tml .accessed on 1; 0cto)er 20111. ;1. Sonder)read 8utritional "acts. 6&aila)le online: %ttp://www.wonder)read.com/Q/products/ w%ite[)reads/classic[w%ite .accessed on 1; 0cto)er 20111 ;2. #60/S$0. !ode& Aliment"rius , 2nd ed.; #60/S$0: Boma, !tal', 1994; ?olume 4. ;3. U2 #ood and ru( 6dministration. 9itle 21: #ood and ru( 6dministration. !n !ode of 5eder"l Re#ul"tions ; U2 5o&ernment 7rintin( 0""ice: Sas%in(ton, C, U26, 2004; ?olume 2, pp. 100E1=9. ;4. /e%tonen-?eromaa, ,.; ,ottonen, 9.; /eino, 6.; $einonen, 0.4.; Bauta&a, +.; ?ii3ari, 4. 7rospecti&e stud' on "ood "orti"ication wit% &itamin amon( adolescent "emales in #inland: ,inor e""ects. 'r$ -$ Nutr$ 200>, 100, 41CE423. ;;. Ho, 4.6.; /ee, *.$.; /ee, 4.2.; 7ar3, $.4. +""ect o" U?-* e>posure on t%e concentration o" &itamin 2 in sliced s%iita3e mus%room . @entinus edodes1 and w%ite )utton mus%room .A#"ricus bisporus 1. -$ A#ric$ 5ood ! em$ 200>, ,6, 3=<1E3=<4. ;=. Ho''alamudi, 2.B.; 4eon(, 2.C.; 2on(, C.$.; C%o, H.L.; 7an(, 5. ?itamin "ormation and 2 )ioa&aila)ilit' "rom A#"ricus bisporus )utton mus%rooms treated wit% ultra&iolet irradiation. -$ A#ric$ 5ood ! em$200?, ,/, 33;1E33;;. ;<. Bo)erts, 4.2.; 9eic%ert, 6.; ,c$u(%, 9.$. ?itamin "ormation "rom post-%ar&est U?-* 2 treatment o" mus%rooms . A#"ricus bisporus1 and retention durin( stora(e. -$ A#ric$ 5ood ! em$ 200>, ,6, 4;41E4;44. ;C. Sil)orn, *.2.; Hert%, C.B.; 0wsle', S.#.; 4ones, S.B.; #ro)is%, /.9. !mpro&in( por3 Fualit' )' "eedin( supranutritional concentrations o" &itamin 3 . -$ Anim$ 2ci$2004, 02, 21CE224. ;9. 4a3o)sen, 4.; ,ari)o, $.; *'sted, 6.; 2ommer, $.,.; $els, 0. 2;-%'dro>'&itamin a""ects 3 &itamin status similar to &itamin in pi(sY)ut t%e meat produced %as a lower content o" 3 &itamin . 'r$ -$ Nutr$ 2007, 10, 90CE913. =0. 5ra"", !.+.; $\!e, 2.; 9otland, 5.H.; /ie, \. 9%ree di""erent le&els o" dietar' &itamin "ed to 3 "irst-"eedin( "r' o" 6tlantic salmon . 2"lmo s"l"r/.1: +""ect on (rowt%, mortalit', calcium content and )one "ormation.AAu"c$ Nutr$ 2002, 0, 103E111. =1. ,attila, 7.; ?alaja, 4.; Bossow, /.; ?enalainen, +.; 9upasela, 9. +""ect o" &itamin - and 2 -enric%ed diets on e(( &itamin content, production, and )ird condition durin( an entire 3 production period. Poult$ 2ci$ 2004, 03, 433E440. =2. ,attila, 7.; /e%i3oinen, H.; Hiis3inen, 9.; 7iironen, ?. C%olecalci"erol and 2;-%'dro>'c%olecalci"erol content o" c%ic3en e(( 'ol3 as a""ected )' t%e c%olecalci"erol content o" "eed. -$ A#ric$ 5ood ! em$ 1???, ./, 40C9E4092. =3. *iancuDDo, B.,.; Loun(, 6.; *i)uld, .; Cai, ,.$.; Sinter, ,.B.; Hlein, +.H.; 6meri, 6.; BeitD, B.; 2alame%, S.; C%en, 9.C.; et "l$ #orti"ication o" oran(e juice wit% &itamin or &itamin 3 is as 2 e""ecti&e as an oral supplement in maintainin( &itamin status in adults. Am$ -$ !lin$ Nutr$ 2010, 11, 1=21E1=2=.

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=4. C%ee, S.2.; 2uria%, 6.B.; C%an, 2.7.; Waitun, L.; C%an, L.,. 9%e e""ect o" mil3 supplementation on )one mineral densit' in postmenopausal C%inese women in ,ala'sia.3steoporos$ 7nt$ 2003, 1., C2CEC34. =;. al', B.,.; *rown, ,.; *ass, 2.; Hu3uljan, 2.; 8owson, C. Calcium- and &itamin -"orti"ied 3 mil3 reduces )one loss at clinicall' rele&ant s3eletal sites in older men: 6 2-'ear randomiDed controlled trial. -$ 'one (iner$ Res$2006, 21, 39<E40;. ==. 4o%nson, 4./.; ,istr', ?.?.; ?u3o&ic%, ,. .; $o(ie-/orenDen, 9.; $ollis, *.S.; 2pec3er, *./. *ioa&aila)ilit' o" &itamin "rom "orti"ied process c%eese and e""ects on &itamin status in t%e elderl'. -$ D"ir* 2ci$ 2007, 00, 229;E2301. =<. 8atri, 6.,.; 2alo, 7.; ?i3stedt, 9.; 7alssa, 6.; $uttunen, ,.; Har33ainen, ,.U.; 2alo&aara, $.; 7iironen, ?.; 4a3o)sen, 4.; /am)er(-6llardt, C.4. *read "orti"ied wit% c%olecalci"erol increases t%e serum 2;-%'dro>'&itamin concentration in women as e""ecti&el' as a c%olecalci"erol supplement.-$ Nutr$ 2006, 136, 123E12<. =C. 8i3oo'e%, *.; 8e'estani, 9.B.; #ar&id, ,.; 6la&i-,ajd, $.; $ous%iarrad, 6.; Hala'i, 6.; 2%ariatDade%, 8.; 5%ara&i, 6.; $era&i"ard, 2.; 9a'e)inejad, 8.; et "l$ ail' consumption o" &itamin - or &itamin : calcium-"orti"ied 'o(urt drin3 impro&ed (l'cemic control in patients wit% t'pe 2 dia)etes: 6 randomiDed clinical trial.Am$ -$ !lin$ Nutr$ 2011, 13, <=4E<<1. =9. 9an(pric%a, ?.; Hout3ia, 7.; Bie3e, 2.,.; C%en, 9.C.; 7ereD, 6.6.; $olic3, ,.#. #orti"ication o" oran(e juice wit% &itamin : 6 no&el approac% "or en%ancin( &itamin nutritional %ealt%. Am$ -$ !lin$ Nutr$ 2003, //, 14<CE14C3. <0. Ur)ain, 7.; 2in(ler, #.; !%orst, 5.; *iesals3i, $.H.; *ertD, $. *ioa&aila)ilit' o" &itamin "r om 2 U?-*-irradiated )utton mus%rooms in %ealt%' adults de"icient in serum 2;-%'dro>'&itamin : 6 randomiDed controlled trial. %ur$ -$ !lin$ Nutr$ 2011, 6,, 9=;E9<1. <1. Sa(ner, .; 2id%om, 5.; S%itin(, 2.4.; Bousseau, .; ?iet%, B. 9%e )ioa&aila)ilit' o" &itamin "rom "orti"ied c%eeses and supplements is eFui&alent in adults. -$ Nutr$ 200>, 130, 13=;E13<1. <2. 0utila, 9.6.; ,attila, 7.$.; 7iironen, ?.!.; /am)er(-6llardt, C.4. *ioa&aila)ilit' o" &itamin "rom wild edi)le mus%rooms .!"nt "rellus tub"eformis 1 as measured wit% a %uman )ioassa'. Am$ -$ !lin$ Nutr$ 1???, 61, 9;E9C. <3. ,ocanu, ?.; 2titt, 7.6.; Costan, 6.B.; ?oroniuc, 0.; W)ranca, +.; /uca, ?.; ?iet%, B. /on(-term e""ects o" (i&in( nursin( %ome residents )read "orti"ied wit% 12; J( .;000 !U1 &itamin per 3 dail' ser&in(. Am$ -$ !lin$ Nutr$ 200?, 01, 1132E113<. <4. /ai, 4.H.; /ucas, B.,.; *an3s, +.; 7onson)', 6./. ?aria)ilit' in &itamin assa's impairs clinical assessment o" &itamin status. 7ntern$ (ed$ -$ 2011, doi:10.1111/j.144;-;994.2011.024<1.>. <;. 2nellman, 5.; ,el%us, $.; 5ede)or(, B.; *')er(, /.; *er(lund, /.; Sernrot%, /.; ,ic%aelsson, H. eterminin( &itamin status: 6 comparison )etween commerciall' a&aila)le assa's.P@o2 3ne 2010, ,, e11;;;. <=. C%el, ?.; Sijn%o&en, $.6.; 2mit, 4.$.; 0oms, ,.; /ips, 7. +""icac' o" di""erent doses and time inter&als o" oral &itamin supplementation wit% or wit%out calcium in elderl' nursin( %ome residents.3steoporos$ 7nt$ 200>, 11, ==3E=<1.

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<<. 5lendennin(, 7.; C%ew, 5.9.; 2e'mour, $.,.; 5illett, ,.4.; 5oldswain, 7.B.; !nderjeet%, C.6.; ?asi3aran, 2. .; 9aranto, ,.; ,us3, 6.6.; #raser, S. . 2erum 2;-%'dro>'&itamin le&els in &itamin -insu""icient %ip "racture patients a"ter supplementation wit% er(ocalci"erol and c%olecalci"erol. 'one 200?, .,, C<0EC<;. <C. *in3le', 8.; 5emar, .; +n(el3e, 4.; 5an(non, B.; Bamamurt%', B.; Hrue(er, .; reDner, ,.H. +&aluation o" er(ocalci"erol or c%olecalci"erol dosin(, 1=00 !U dail' or ;0,000 !U mont%l' in older adults. -$ !lin$ %ndocrinol$ (et"b$ 2011, 16, 9C1E9CC. <9. Boma(noli, +.; ,ascia, ,./.; Cipriani, C.; #assino, ?.; ,aDDei, #.; U+rasmo, +.; Carne&ale, ?.; 2cillitani, 6.; ,inisola, 2. 2%ort and lon(-term &ariations in serum calciotropic %ormones a"ter a sin(le &er' lar(e dose o" er(ocalci"erol .&itamin 2 1 or c%olecalci"erol .&itamin 3 1 in t%e elderl'. -$ !lin$ %ndocrinol$ (et"b$ 200>, 13, 301;E3020. C0. $eane', B.7.; Bec3er, B.B.; 5rote, 4.; $orst, B./.; 6rmas, /.6. ?itamin 3 is more potent t%an &itamin 2 in %umans. -$ !lin$ %ndocrinol$ (et"b$ 2010, 16, +44<E+4;2. C1. 6rmas, /.6.5.; $ollis, *.S.; $eane', B.7. ?itamin 2 is muc% less e""ecti&e t%an &itamin 3 in %umans.-$ !lin$ %ndocrinol$ (et"b$ 2004, 01, ;3C<E;391. C2. /e&entis, 7.; Hiel', 7. . 9%e tolera)ilit' and )ioc%emical e""ects o" %i(%-dose )olus &itamin 2 and 3 supplementation in patients wit% &itamin insu""icienc'. 2c"nd$ -$ R eum"tol$200?, 30, 149E1;3. C3. $olic3, ,.#.; *iancuDDo, B.,.; C%en, 9.C.; Hlein, +.H.; Loun(, 6.; *i)uld, .; BeitD, B.; 2alame%, S.; 6meri, 6.; 9annen)aum, 6. . ?itamin is as e""ecti&e as &itamin in 2 3 maintainin( circulatin( concentrations o" 2;-%'dro>'&itamin . -$ !lin$ %ndocrinol$ (et"b$ 200>, 13, =<<E=C1. C4. 5ordon, C.,.; Silliams, 6./.; #eldman, $.6.; ,a', 4.; 2inclair, /.; ?asFueD, 6.; Co>, 4.+. 9reatment o" %'po&itaminosis in in"ants and toddlers. -$ !lin$ %ndocrinol$ (et"b$ 200>, 13, 2<1=E2<21. C;. !ommission Re#ul"tion )%!+ No 11/0/2001 of 30 November 2001 Amendin# Directive 2002/.6/%! of t e %urope"n P"rli"ment "nd of !ouncil "nd Re#ul"tion )%!+ No 112,/2006 of t e %urope"n P"rli"ment "nd of t e !ouncil "s Re#"rds t e @ists of :it"min "nd (iner"ls "nd 4 eir 5orms t "t !"n 'e Added to 5oodsB 7ncludin# 5ood 2upplements; 0""icial 4ournal o" t%e +uropean Union / 314; +uropean Union: /u>em)our(, /u>em)our(, 2009. C=. Re#ul"tion )%!+ No 2,0/1/ of t e %urope"n P"rli"ment "nd of t e !ouncil of 2/ -"nu"r* 111/ !oncernin# Novel 5oods "nd Novel 5ood 7n#redients ; 0""icial 4ournal o" t%e +uropean Union / 043; +uropean Union: /u>em)our(, /u>em)our(, 199<. C<. !ouncil Directive 10/.16/%%! on Nutrition @"bellin# for 5oodstuffs )10/.16/%%!+ "s Amended b* !ommission Directives 2003/120/%! "nd 2000/100/%! ; 0""icial 4ournal o" t%e +uropean Union / 2<=; +uropean Union: /u>em)our(, /u>em)our(, 1990. CC. Re#ul"tion )%!+ No 112./2006 of t e %urope"n P"rli"ment "nd of t e !ouncil of 20 December 2006 on Nutrition "nd 8e"lt !l"ims ("de on 5oods "s Amended b* Re#ul"tion )%!+ No 10//2000 "nd Re#ul"tion )%!+ No 101/2000 ; 0""icial 4ournal o" t%e +uropean Union 04 / 404; +uropean Union: /u>em)our(, /u>em)our(, 200=.

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C9. 6nne> 1. !n !ommission Directive 2000/100/%! of 20 3ctober 2000 Amendin# !ouncil Directive 10/.16/%%! on Nutrition @"bellin# for 5oodstuffs "s Re#"rds Recommended D"il* Allow"ncesB %ner#* !onversion 5"ctors "nd Definitions ; 0""icial 4ournal o" t%e +uropean Union 04 / 2C;; +uropean Union: /u>em)our(, /u>em)our(, 200C. 90. +#26 7anel on ietetic 7roducts, 8utrition and 6ller(ies .8 61. 2cienti"ic opinion on t%e su)stantiation o" %ealt% claims related to &itamin and maintenance o" )one and teet% .! 1;0, 1;1, 1;C1, a)sorption and utilisation o" calcium and p%osp%orus and maintenance o" normal )lood calcium concentrations .! 1;2, 1;<1, cell di&ision .! 1;31, and t%'roid "unction .! 1;=1 pursuant to article 13.11 o" re(ulation .+C1 8o 1924/200=. %52A -$ 200?, /, doi:10.2903/j.e"sa.2009.122<. 91. +#26 7anel on ietetic 7roducts, 8utrition and 6ller(ies .8 61. 2cienti"ic opinion on t%e su)stantiation o" %ealt% claims related to &itamin and normal "unction o" t%e immune s'stem and in"lammator' response .! 1;4, 1;91, maintenance o" normal muscle "unction .! 1;;1 and maintenance o" normal cardio&ascular "unction .! 1;91 pursuant to article 13.11 o" re(ulation .+C1 8o 1924/200=. %52A -$ 2010, 0, doi:10.2903/j.e"sa.2010.14=C. 92. +#26 7anel on ietetic 7roducts, 8utrition and 6ller(ies .8 61. ?itamin and )one (rowt%Y2cienti"ic su)stantiation o" a %ealt% claim related to &itamin and )one (rowt% pursuant to 6rticle 14 o" Be(ulation .+C1 8o 1924/200=1Y2cienti"ic 0pinion o" t%e 7anel on ietetic 7roducts, 8utrition and 6ller(ies.%52A -$ 200>, 6, doi:10.2903/j.e"sa.200C.C2<. 93. +#26 7anel on ietetic 7roducts, 8utrition and 6ller(ies .8 61. 2cienti"ic opinion in relation to t%e aut%orisation procedure "or %ealt% claims on calcium and &itamin and t%e reduction o" t%e ris3 o" osteoporotic "ractures )' reducin( )one loss pursuant to article 14 o" re(ulation .+C1 8o 1924/200=. %52A -$ 2010, 0, doi:10.2903/j.e"sa.2010.1=09. 94. +#26 7anel on ietetic 7roducts, 8utrition and 6ller(ies .8 61. Calcium : &itamin 3 c%ewin( ta)lets and )one lossY2cienti"ic su)stantiation o" a %ealt% claim related to calcium plus &itamin 3 c%ewin( ta)lets and reduction o" t%e ris3 o" osteoporotic "ractures )' reducin( )one loss pursuant to 6rticle 14 o" Be(ulation .+C1 8o 1924/200=Y2cienti"ic 0pinion o" t%e 7anel on ietetic 7roducts, 8utrition and 6ller(ies. %52A -$ 200?, /, doi:10.2903/j.e"sa.2009.11C0. ] 2011 )' t%e aut%ors; licensee , 7!, *asel, 2witDerland. 9%is article is an open access article distri)uted under t%e terms and conditions o" t%e Creati&e Commons 6ttri)ution license .%ttp://creati&ecommons.or(/licenses/)'/3.0/1.

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