Plasm
ahomocysteine
response
tofolicacid
intervention
inischaem
icheart
disease
patients:
implications
for
food
fortification
policy.
By
P.
TIG
HE
1,
M.
WA
RD
1,
H.
MCN
UL
TY
1,
O.
FIN
NE
GA
N2,
J.J.
ST
RA
IN1,
A.
DU
NN
E3,
A.M
.M
OL
LO
Y4
and
J.M
.S
CO
TT
4,
1NorthernIreland
CentreforDietandHealth,University
ofUlster,
Coleraine,
UK,BT521SA,
2Coronary
Care
Unit,
CausewayHospital,Coleraine,
UK,BT521HS,
3DepartmentofStatistics,
University
CollegeDublin,
Belfield,Dublin
4,RepublicofIreland
and
4DepartmentofBiochem
istry,
TrinityCollege,
Dublin,
RepublicofIreland
Food
fort
ifica
tion
wit
hfo
lic
acid
ispri
mar
ily
aim
edat
reduci
ng
neu
ral
tube
def
ects
,but
isal
soex
pec
ted
tohav
eso
me
ben
efit
inte
rms
of
CV
Dvia
ahom
ocy
stei
ne
(Hcy
)-lo
wer
ing
effe
ct.
One
rece
nt
met
a-
anal
ysi
shas
esti
mat
edth
ata
3mm
ol/
ldec
reas
ein
tota
lH
cy(t
Hcy
)co
nce
ntr
atio
ns
could
reduce
the
risk
of
IHD
by
16
%,
dee
p-v
ein
thro
mbosi
sby
25
%an
dst
roke
by
24
%(W
aldet
al.
2002).
Contr
over
sy
curr
entl
yex
ists
,how
ever
,re
gar
din
gth
edose
of
foli
cac
idre
quir
edto
achie
ve
opti
mal
Hcy
low
erin
gin
IHD
pat
ients
,w
ith
som
esu
gges
ting
that
the
dose
nec
essa
rym
aybe
ashig
has
0.8
mg
foli
cac
id/d
,w
hic
h
isunli
kel
yto
be
achie
vab
leth
rough
food
fort
ifica
tion
(Wal
det
al.
2001).
The
aim
of
the
pre
sent
study,
ther
efore
,w
asto
det
erm
ine
the
min
imum
effe
ctiv
edose
of
foli
cac
idre
quir
edto
achie
ve
asi
gnifi
cant
reduct
ion
intH
cyco
nce
ntr
atio
nin
IHD
pat
ients
.In
anat
tem
pt
tom
imic
food
fort
ifica
tion,
whic
hby
its
nat
ure
involv
esch
ronic
exposu
re,
the
dura
tion
of
the
inte
rven
tion
per
iod
was
26
wee
ks.
IHD
pat
ients
(n101)
wer
ere
cruit
edfr
om
the
coro
nar
yca
reunit
,C
ause
way
Hosp
ital
on
the
bas
is
of
hav
ing
pre
vio
usl
yhad
am
yoca
rdia
lin
farc
tion
(at
leas
t3
month
sbef
ore
com
men
cing
inte
rven
tion)
or
hav
ing
angin
adia
gnose
dby
elec
troca
rdio
gra
mch
anges
.T
he
pat
ients
wer
eth
enst
rati
fied
into
one
of
four
gro
ups
on
the
bas
isof
thei
rin
itia
lsc
reen
ing
tHcy
,to
rece
ive
eith
erpla
cebo,
0.2
,0.4
or
0.8
mg
foli
cac
id
dai
lyfo
r26
wee
ks.
Fas
ting
blo
od
sam
ple
s(2
0m
l)w
ere
coll
ecte
dat
bas
elin
ean
dpost
-inte
rven
tion
and
anal
yse
dfo
rtH
cy(I
mX
)an
dse
rum
fola
te(m
icro
bio
logic
alas
say).
The
stat
us
of
oth
erB
vit
amin
s
rele
van
tto
Hcy
met
aboli
smw
ere
asse
ssed
atbas
elin
ean
dal
lpat
ients
wer
efo
und
tobe
wit
hin
the
norm
alra
nge
(res
ult
snot
show
n).
Inte
rven
tion
gro
up...
Pla
cebo
(n22)
0.2
mg
(n22)
0.4
mg
(n26)
0.8
mg
(n31)
Med
ian
IQR
Med
ian
IQR
Med
ian
IQR
Med
ian
IQR
tHcy
(mm
ol/
l)P
re-i
nte
rven
tion
12.4
10.1
,17.0
12.1
9.4
,18.4
13.2
10.2
,16.2
13.1
10.7
,16.1
Post
-inte
rven
tion
11.6
10.4
,16.6
9.9
8.1
,15.1
10.7
9.0
,13.2
10.6
8.3
,12.3
Abso
lute
chan
ge
-0.4
a-1
.0,
0.6
-2.7
b-4
.0,-1
.9-2
.3b
-3.7
,-0
.4-2
.7b
-4.5
,-1
.3P
erce
nta
ge
chan
ge
-2.7
a-7
.3,
5.6
-22.0
b-2
7.7
,-8
.5-1
5.8
b-2
4.1
,-3
.6-1
9.5
b-3
1.2
,-1
0.8
Ser
um
fola
te(m
g/l
)P
re-i
nte
rven
tion
7.6
4.7
,11.1
6.4
4.4
,9.4
7.8
5.1
,9.5
7.3
5.2
,10.7
Post
-inte
rven
tion
6.7
4.2
,11.5
13.3
9.0
,16.3
25.0
16.1
,31.0
32.3
26.3
,38.6
Abso
lute
chan
ge
-1.1
a-1
.7,
1.4
4.8
b1.8
,10.2
13.3
c9.9
,21.4
25.8
d19.0
,31.4
Per
centa
ge
chan
ge
-8.8
a-2
6.8
,37.8
87.6
b45.1
,187.7
209.8
c92.7
,348.7
346.8
d167.1
,508.5
IQR
,in
terq
uar
tile
range.
a,b
,c,d
Med
ian
val
ues
wit
hunli
ke
super
scri
pt
lett
ers
are
signifi
cantl
ydif
fere
nt
(AN
OV
A)
(P
Folate
depletion
post-w
eaning
suppresses
large
tumours
inthe
Apc+/m
inmouse
intestine.
By
J.A
.M
CK
AY
1,
E.A
.W
ILL
IAM
S2
and
J.C
.M
AT
HE
RS
1,
1HumanNutritionResearchCentre,
School
ofClinicalMedicalSciences,
University
ofNew
castle
upon
Tyne,
UK,NE1
7RU
and
2Human
NutritionUnit,University
ofSheffield,NorthernGeneralHospital,Sheffield,UK,S57AU
Colo
rect
alca
nce
r(C
RC
)is
the
seco
nd
most
com
mon
cause
of
cance
rm
ort
alit
yin
the
Wes
tern
worl
d
(Houls
ton
&T
om
linso
n,
2001).
Alt
hough
gen
etic
def
ects
are
fundam
enta
lto
all
cance
rs,
ther
eis
stro
ng
evid
ence
that
much
var
iati
on
inC
RC
inci
den
ceis
attr
ibuta
ble
todie
t.S
ever
alm
icro
nutr
ients
appea
rto
modif
yC
RC
risk
wit
hac
cum
ula
ting
evid
ence
of
reduce
dri
skin
indiv
idual
sw
ith
hig
her
fola
tein
takes
(Choi
&M
ason,
2000).
Giv
enth
atfo
late
pla
ys
afu
ndam
enta
lro
lein
DN
Asy
nth
esis
and
met
hyla
tion
and
that
inad
equat
efo
late
stat
us
may
impai
rgen
om
icst
abil
ity,
we
hypoth
esis
edth
atfo
late
insu
ffici
ency
inutero
may
incr
ease
the
risk
of
tum
ori
gen
esis
,an
dth
atco
nti
nual
dep
leti
on
may
exac
erbat
eth
eef
fect
s.T
ote
st
this
hypoth
esis
,w
euse
dth
eApc+/min
mouse
model
whic
hhas
apoin
tm
uta
tion
atco
don
850
of
theApc
gen
ere
sult
ing
inm
ult
iple
inte
stin
altu
mours
(Mose
ret
al.
1998).
Muta
tions
inth
ehum
anAPC
gen
ear
e
causa
lfo
rfa
mil
ial
aden
om
atous
poly
posi
san
dar
eac
quir
edin
the
maj
ori
tyof
spora
dic
colo
nic
tum
ours
(Suet
al.
1992).
The
pre
sent
study
des
crib
esth
edev
elopm
ent
and
test
ing
of
am
odel
todis
tinguis
h
bet
wee
nth
eef
fect
sof
alte
ring
fola
tesu
pply
inutero
and
duri
ng
suck
lingv.
post
-wea
nin
gli
fe.
Fro
mm
atin
g(m
aleApc+/minf
emal
eC
57B
l6/J
),m
ice
wer
era
ndom
ised
toone
of
two
die
tsbas
ed
on
AIN
93A
(Ree
ves
etal.
1993),
nam
ely
die
tA
(contr
ol)
or
die
tB
(fola
tedep
lete
d)
(2an
d0.4
mg
fola
te/k
gre
spec
tivel
y)adlibitum
.A
tw
eanin
g,
off
spri
ng
wer
eas
signed
atra
ndom
toei
ther
die
tA
or
a
more
fola
te-d
eple
ted
die
t(d
iet
C;
0.2
6m
gfo
late
/kg).
This
resu
lted
info
ur
die
tgro
ups
from
wea
nin
g,
nam
ely
AA
,A
C
,B
A
,an
dB
C
.A
t10
wee
ks
post
-wea
nin
g,
mic
ew
ere
kil
led
for
asse
ssm
ent
of
inte
stin
altu
mour
num
ber
,lo
cati
on
and
size
.B
efore
anal
ysi
sby
AN
OV
A,
dat
aas
per
centa
ges
wer
ear
c
sine-
tran
sform
edw
hil
stfo
rpre
senta
tion
inth
efi
gure
bel
ow
,co
nven
tional
mea
ns
are
show
n.
020406080100
AC
Po
st-w
ean
ing
die
t
% of large tumours
*P
oo
led
SE
M =
4.9
n 34
n
36
Inth
ese
mic
em
ost
(96
%)
of
the
tum
ours
occ
urr
edin
the
smal
lin
test
ine
and
the
pre
sent
study
show
edth
atfe
edin
gth
efo
late
-dep
lete
ddie
tfr
om
wea
nin
gre
sult
edin
asi
gnifi
cantl
yre
duce
dper
centa
ge
of
larg
e(>
1m
mdia
met
er)
tum
ours
(*P=0
.039).
Inhum
anpat
ients
,la
rger
poly
ps
are
more
likel
yto
pro
gre
ssto
carc
inom
as.
Ther
ew
asno
det
ecta
ble
effe
ctof
mat
ernal
die
t.T
hes
ere
sult
ssu
gges
tth
atfo
late
supply
has
ast
ronger
infl
uen
ceon
the
pro
gre
ssio
nof
tum
our
dev
elopm
ent
(whic
hocc
urs
afte
rw
eanin
g)
(Shoem
aker
etal.
1997)
than
on
init
iati
on
inth
ism
odel
.
J.A
.M.
hold
sa
BB
SR
CR
esea
rch
Stu
den
tship
(01/A
1/D
/17951).
We
acknow
ledge
addit
ional
support
from
the
Worl
dC
ance
r
Res
earc
hF
und
(2001/3
7).
Choi
S-W
&M
ason
JB(2
000)JournalofNutrition130,
129
132.
Houls
ton
RS
&T
om
linso
nIP
M(2
001)Gastroenterology121,
282301.
Mose
rA
R,
Pit
ot
HC
&D
ove
WF
(1990)Science
247,
322324.
Ree
ves
PG
,N
iels
enF
H&
Fah
eyG
CJr
(1993)JournalofNutrition123,
1939
1951.
Shoem
aker
AR
,G
ould
KA
,L
uongo
C,
Mose
rA
R&
Dove
WF
(1997)Biochimicaet
BiophysicaActa1332
,F
25F
48.
Su
L-K
,K
inzl
erK
W,
Volg
elst
ein
B,
Pre
isin
ger
AC
,M
ose
rA
R,
Luongo
C,
Gould
KA
&D
ove
WF
(1992)Science
256,
668
670.
The
relationship
between
body
mass
index
and
Bvitamin
status.
By
M.A
.K
ER
R1,
M.B
.E.
LIV
ING
ST
ON
E1,
I.B
RA
DB
UR
Y1,
J.M
.S
CO
TT
2,
M.
WA
RD
1,
C.
J.B
AT
ES
3an
dH
.M
CN
UL
TY
1,
1Northern
Ireland
Centre
forDietand
Health,University
ofUlster,
Coleraine,
UK,BT52
1SA,
2DepartmentofBiochem
istry,
Trinity
College,
Dublin,Republic
ofIreland
and
3MRC
Human
NutritionResearch,Cambridge,
UK
Obes
ity
atth
est
art
of
pre
gnan
cyis
asso
ciat
edw
ith
incr
ease
dri
skof
man
yobst
etri
cco
mpli
cati
ons.
Les
s
wel
ldocu
men
ted
isth
eposi
tive
asso
ciat
ion
bet
wee
nm
ater
nal
BM
Ian
dri
skof
congen
ital
mal
form
atio
ns,
incl
udin
gneu
ral
tube
def
ects
(NT
D).
Ithas
bee
nsh
ow
nth
atco
mpar
edw
ith
non-o
bes
e
wom
en,
obes
ew
om
enar
eat
agre
ater
risk
of
anN
TD
affe
cted
pre
gnan
cy,
anef
fect
not
expla
ined
by
low
erdie
tary
fola
tein
take
or
non-u
seof
foli
cac
idsu
pple
men
tati
on
(Shaw
etal.
1996;
Wer
leret
al.
1996).
Itm
aybe
poss
ible
ther
efore
that
impai
red
stat
us
of
fola
tean
d/o
roth
erre
late
dB
vit
amin
s(B
12,
B6
and
ribofl
avin
)m
aybe
involv
edin
the
exce
ssof
NT
Dri
skam
ong
obes
ew
om
en,
or
that
afa
ctor
unre
late
dto
fola
tem
aybe
involv
ed.
Our
aim
was
toex
amin
eth
ere
lati
onsh
ipbet
wee
nB
MI,
fola
tean
d
rela
ted
Bvit
amin
san
dpla
sma
hom
ocy
stei
ne
(tH
cy,
afu
nct
ional
indic
ator
of
Bvit
amin
stat
us)
,usi
ng
blo
od
and
anth
ropom
etri
cdat
aco
llec
ted
aspar
tof
the
Offi
cefo
rN
atio
nal
Sta
tist
ics
Soci
alS
urv
ey
Div
isio
n(1
997)
Nat
ional
Die
tary
and
Nutr
itio
nS
urv
eyof
Young
Peo
ple
aged
418
yea
rs.
Var
iable
Age-
and
sex-a
dju
sted
per
centi
les*
P
98th
(n91)
Med
ian
IQR
Med
ian
IQR
Med
ian
IQR
Med
ian
IQR
BM
I(w
t/ht2
)15.0
a13.7
,16.0
17.9
b16.0
,19.8
22.3
c19.4
,24.8
27.4
d22.9
,29.8
0.0
00
Age
(yea
rs)
13.2
8.8
,15.9
11.6
8.3
,15.1
11.4
8.7
,15.8
12.1
9.7
,15.9
NS
S.B
12
(pm
ol/
l)326
ab
251,
448
370
a269,
508
342
a261,
452
286
b211,
366
0.0
00
RC
F(n
mol/
l)528
443,
680
569
451,
714
561
451,
688
524
422,
656
NS
SF
(nm
ol/
l)20.4
ab
13.7
,26.8
21.1
a15.2
,27.4
18.1
b12.9
,24.3
19.0
ab
12.9
,25.0
0.0
39
tHcy
(mm
ol/
l)7.1
5.9
,8.9
6.1
5.0
,7.9
6.7
5.3
,7.9
6.5
5.1
,8.3
NS
PL
P(n
mol/
l)50.1
a35.6
,65.4
57.4
b42.9
,76.3
53.8
ab
41.0
,70.9
59.2
ab
46.1
,71.3
0.0
42
EG
Rac
1.4
51.3
3,
1.5
31.4
21.3
2,
1.5
41.4
61.3
4,
1.5
81.4
31.3
4,
1.5
4N
S
IQR
,in
terq
uar
tile
range.
RC
F,
eryth
rocy
tefo
late
;S
F,
seru
mfo
late
;P
LP
,pla
sma
pyri
doxal
phosp
hat
e;E
GR
ac,
eryth
rocy
teglu
tath
ione
acti
vat
ion
coef
fici
ent.
a,b
,c,d
Med
ian
val
ues
wit
hunli
ke
subsc
ript
lett
ers
are
signifi
cantl
ydif
fere
nt
(AN
OV
A)
(P
Dietvariety
and
dietdiversity
ofpregnantand
lactating
women.
By
I.B
LO
SS
FE
LD
,C
.A.
MA
RT
INan
dC
.M.
DE
LA
HU
NT
Y,DepartmentofFoodandNutritionalSciences,University
College
Cork,Cork,RepublicofIreland
Ther
eis
evid
ence
that
the
moth
ers
die
tduri
ng
pre
gnan
cyan
dth
efi
rst
few
month
saf
ter
bir
thw
hen
bre
ast-
feed
ing
can
hav
elo
ng-t
erm
effe
cts
on
the
infa
nt
sdie
tary
hab
its
and
eati
ng
beh
avio
ur,
whic
hca
n
affe
ctth
efu
ture
hea
lth
and
wel
lbei
ng
(Sull
ivan
&B
irch
,1994;
Men
nel
laet
al.
2001).
Hum
anin
fants
exper
ience
avar
iety
of
flav
ours
bef
ore
wea
nin
gbec
ause
som
eof
the
flav
ours
consu
med
by
the
moth
er
are
tran
smit
ted
toth
eam
nio
tic
fluid
and
late
rto
the
moth
ers
mil
k.
To
dat
e,m
ost
studie
son
die
tvar
iety
and
die
tqual
ity
of
pre
gnan
tan
dla
ctat
ing
wom
enhav
efo
cuse
don
die
tary
adeq
uac
yan
dth
ere
lati
onsh
ip
of
the
mat
ernal
die
tan
dbir
thoutc
om
e.
The
purp
ose
of
the
pre
sent
study
was
toch
arac
teri
seth
em
oth
ers
die
tin
term
sof
die
tvar
iety
and
die
tdiv
ersi
tyto
form
abas
isto
study
the
link
bet
wee
nth
em
oth
ers
die
tan
dth
ech
ilds
pre
fere
nce
s
for
foods
and
flav
ours
inla
ter
studie
s.T
he
pre
sent
study
ispar
tof
alo
ngit
udin
alpro
ject
inves
tigat
ing
the
dev
elopm
ent
of
senso
rypre
fere
nce
san
dea
ting
beh
avio
ur
inin
fants
up
toth
eag
eof
18
month
s.N
inet
y-
thre
ew
om
enan
dth
eir
infa
nts
par
tici
pat
ein
this
pro
ject
,but
only
dat
afr
om
eighty
-nin
em
oth
ers
is
report
edher
e,as
4m
oth
ers
did
not
com
ple
teth
ese
cond
dia
ry.
The
expec
tant
moth
ers
wer
ere
cruit
ed
from
ante
nat
alcl
asse
sin
the
thre
em
ater
nit
yhosp
ital
sin
Cork
.M
ost
of
the
moth
ers
expec
ted
thei
rfi
rst
chil
d(5
5.4
%).
The
maj
ori
tyof
the
wom
enw
ere
bet
wee
n30
and
34
yea
rsat
the
tim
eof
recr
uit
men
t,
rangin
gfr
om
18
to44
yea
rs.
Die
tary
info
rmat
ion
from
the
moth
ers
was
coll
ecte
dduri
ng
thei
rla
st
trim
este
rof
pre
gnan
cy(m
ean
35.0
4(r
ange
2440)
wee
ks
of
pre
gnan
cy)
and
agai
nat
2m
onth
s
post
nat
ally
usi
ng
7d
die
tary
reco
rds.
Adie
tvar
iety
score
(DV
S)
and
adie
tdiv
ersi
tysc
ore
(DD
S)
wer
e
calc
ula
ted
for
each
wom
anfo
rth
etw
oti
me
poin
ts.
The
DV
Sis
defi
ned
asth
eto
tal
num
ber
of
food
item
s
consu
med
over
7d
wher
eas
the
DD
Sco
unts
the
num
ber
of
food
gro
ups
consu
med
by
each
moth
er.
Furt
her
more
,m
oth
ers
food
neo
phobia
score
san
dvar
iety
-see
kin
gbeh
avio
ur
wer
eca
lcula
ted.
Die
tvar
iety
was
the
sam
efo
rpre
gnan
cyan
dla
ctat
ion,
(mea
nsc
ore=4
3.9
;ra
ngin
gfr
om
18
to
61)
wher
eas
DD
Sduri
ng
pre
gnan
cyw
ere
signifi
cantl
yhig
her
than
duri
ng
lact
atio
n(m
ean
score=0
.76
and
0.6
9re
spec
tivel
y,
p
Acomparisonofvitamin
Dintakedata
from
afood-frequency
questionnairewitha14ddietary
history
and
vitamin
Dstatusin
threeIrish
female
population
groups.
By
A.
CO
LL
INS
,M
.M.
OB
RIE
N,
T.R
.H
ILL
,A
.F
LY
NN
,K
.D.
CA
SH
MA
Nan
dM
.K
IEL
Y,DepartmentofFood
and
NutritionalSciences,University
CollegeCork,Cork,RepublicofIreland
Hil
let
al.
(2004)
show
edth
atdie
tary
inta
kes
of
vit
amin
Dar
elo
win
Iris
had
ult
s(a
ged
18
to64
yea
rs)
and
sugges
ted
that
inth
eab
sence
of
skin
bio
synth
esis
of
vit
amin
Din
win
tert
ime,
asi
gnifi
cant
pro
port
ion
of
the
Iris
had
ult
popula
tion
may
ben
efit
from
addit
ional
inta
kes
.A
svit
amin
Dis
pre
sent
in
few
foods,
itis
esse
nti
alto
hav
ea
reli
able
tool
tom
easu
redie
tary
inta
kes
and
food
sourc
es,
soth
at
pote
nti
ally
effe
ctiv
est
rate
gie
sto
incr
ease
the
supply
of
vit
amin
Din
the
die
tca
nbe
iden
tifi
ed.
Inth
epre
sent
study,
asi
xty
-nin
e-it
emfo
od-f
requen
cyques
tionnai
re(F
FQ
)w
asdev
eloped
usi
ng
the
foods
that
suppli
ed95
%vit
amin
Din
takes
mea
sure
din
the
Nort
h/S
outh
Irel
and
Food
Consu
mpti
on
Surv
ey(I
rish
Univ
ersi
ties
Nutr
itio
nA
llia
nce
,2001).
Vit
amin
Din
take
dat
afr
om
the
FF
Qw
ere
com
par
edw
ith
dat
afr
om
adet
aile
ddie
tary
his
tory
(DH
),w
hic
hes
tim
ated
hab
itual
vit
amin
Din
takes
duri
ng
aty
pic
al14
dper
iod.
One
hundre
dan
dtw
enty
appar
entl
yhea
lthy
free
-liv
ing
Iris
hfe
mal
esw
ere
recr
uit
edfr
om
the
Cork
regio
n.
Subje
cts
wer
efr
om
thre
eag
egro
ups
(1113
yea
rs,
50
64
yea
rs,
6575
yea
rs).
Eac
hsu
bje
ct
com
ple
ted
the
FF
Qan
dD
H,
whic
hw
ere
adm
inis
tere
dby
the
sam
ere
sear
cher
,on
two
separ
ate
occ
asio
ns
wit
hin
1m
onth
of
each
oth
er.
Food
port
ion
size
sw
ere
esti
mat
edusi
ng
aphoto
gra
phic
food
atla
s
(Min
istr
yof
Agri
cult
ure
,F
isher
ies
and
Food,
1997).
The
vit
amin
Dfo
od
com
posi
tion
dat
aw
ere
obta
ined
from
McC
ance
andWiddowsonstheCompositionofFoods
(Holl
andet
al.
1991)
and
rece
ntl
ypubli
shed
vit
amin
Dval
ues
(Hil
let
al.
2004).
Fas
ting
seru
mle
vel
sof
25-h
ydro
xyvit
amin
D(2
5(O
H)D
)w
ere
det
erm
ined
usi
ng
anen
zym
eim
munoas
say
(ID
SL
td,
Bold
on,
Tyne
and
Wea
r,U
K)
inth
ew
om
enag
ed
bet
wee
n50
and
70
yea
rsan
dby
HP
LC
inth
egir
lsan
dth
ew
om
en>7
0yea
rs.
Est
imat
esof
vit
amin
Din
take
should
alw
ays
spec
ify
nutr
itio
nal
supple
men
tuse
and
the
clea
r
dif
fere
nce
sin
the
inta
ke
val
ues
that
incl
uded
(WS
)an
dex
cluded
(NS
)su
pple
men
tsar
esh
ow
nin
the
Tab
le.
Inta
kes
wer
esi
gnifi
cantl
ydif
fere
nt
(P
Evaluation
of
adietary
checklist
toassess
fruit
and
vegetable
consumption.
By
A.C
.
HA
RD
CA
ST
LE
2,
R.
SA
ND
ISO
N1,
S.A
.N
EW
3,
D.M
.R
EID
1,2
and
H.M
.M
ACD
ON
AL
D1,2
,1OsteoporosisResearch
Unit,University
ofAberdeen,WoolmanhillHospital,
Aberdeen,UK,AB25
1LD,
2DepartmentofMedicineandTherapeutics,University
ofAberdeen,Aberdeen,UK,AB252ZD
and
3CentreforNutritionandFoodSafety,SchoolofBiomedicalandLifeSciences,
University
of
Surrey,Guildford,UK,GU27XH
Ther
ear
ea
var
iety
of
met
hodolo
gie
sav
aila
ble
for
the
asse
ssm
ent
of
die
tary
inta
ke.
The
use
of
any
met
hod
should
be
consi
der
edw
ith
resp
ect
toit
sval
idit
yan
dre
pro
duci
bil
ity,
espec
iall
ygiv
enth
atdie
tary
val
idat
ion
studie
sdo
not
com
par
ea
met
hod
wit
hth
eab
solu
tetr
uth
,but
use
aco
mpar
ison
of
one
tech
niq
ue
whic
hhas
dif
fere
nt
lim
itat
ions
toth
atof
anoth
er(W
ille
tt,
1990).
The
aim
of
the
pre
sent
study
was
toev
aluat
eth
euse
of
adie
tary
chec
kli
stfo
ras
sess
men
tof
fruit
and
veg
etab
leco
nsu
mpti
on
whic
his
quic
kto
com
ple
tean
dan
alyse
,in
com
par
ison
wit
han
esti
mat
edport
ion
size
food
dia
ryw
hic
hpla
ces
a
gre
ater
burd
enon
par
tici
pan
tsan
dre
sear
cher
ssi
nce
they
are
more
tim
eco
nsu
min
gto
anal
yse
.
The
subje
cts
wer
ew
om
en(m
ean
age
59.6
2.1
yea
rs)
who
had
bee
nre
cruit
edin
1990
3
aspar
t
of
the
Aber
dee
nP
rosp
ecti
ve
Ost
eoporo
sis
Scr
eenin
gS
tudy,
the
maj
ori
tyof
whom
retu
rned
in
19972000
for
ase
cond
vis
it.
Asu
bse
t(n
279)
was
recr
uit
edin
2003
topar
tici
pat
ein
a2-y
ear
inte
rven
tion
study.
Die
tary
inta
ke
was
asse
ssed
usi
ng
the
EP
ICfo
od
dia
ry(M
cKeo
wnet
al.
2001)
and
a
3d
fruit
and
veg
etab
ledie
tary
chec
kli
st.
The
food
dia
ryw
asco
mple
ted
for
aper
iod
of
4d
(incl
udin
gone
wee
ken
dday
)an
dw
asan
alyse
dusi
ng
Win
Die
tsco
mpute
rpro
gra
m(R
ober
tG
ord
on
Univ
ersi
ty,
Sco
tlan
d).
The
one-
pag
ech
eckli
stw
asan
alyse
dusi
ng
stan
dar
dfo
od
port
ion
size
s.W
eighte
dkap
pa
(Kw
)
was
use
das
am
easu
reof
cross
-cla
ssifi
cati
on.
Com
par
isons
infr
uit
and
veg
etab
lein
takes
bet
wee
nth
efo
od
dia
ryan
dch
eckli
star
esh
ow
nin
the
Tab
le.
Tota
lfr
uit
incl
uded
tinned
and
dri
edfr
uit
s;ro
ot
veg
etab
les
incl
uded
bee
troot
and
oth
erro
ots
(excl
udin
gpota
toes
);an
dgre
enan
dco
loure
dveg
etab
les
incl
uded
sala
ds,
tom
atoes
,onio
ns
and
pep
per
s.
Food
gro
up
Food
dia
ryC
hec
kli
stC
om
par
ison
Med
ian
(g/d
)R
ange
(g/d
)%
Eat
ing
each
gro
up
Med
ian
(g/d
)R
ange
(g/d
)%
Eat
ing
each
gro
up
Corr
ect
clas
sifi
cati
on
Mis
clas
sifi
cati
on
>one
quar
tile
Kw
Fru
itju
ice
38
0480
53.4
83
01167
58.7
53.0
19.7
0.4
6F
resh
fruit
185
0848
95.5
322
02670
99.0
39.0
19.0
0.3
3T
ota
lfr
uit
251
0848
97.6
452
02670
99.3
38.2
20.4
0.3
1G
reen
and
colo
ure
dveg
etab
les
80
309
98.3
144
01445
99.0
33.3
21.9
0.2
5
Root
veg
etab
les
80
153
54.5
20
0180
69.0
34.8
30.8
0.2
0T
ota
lveg
etab
les
130
0440
98.6
191
171502
99.6
34.8
25.4
0.2
3
One-
thir
dof
the
subje
cts
report
edea
ting
the
reco
mm
ended
five
port
ions
of
fruit
and
veg
etab
les/
d
inth
edia
ries
,an
d69.6
%re
port
edth
isin
thei
rch
eckli
sts.
Of
the
par
tici
pan
ts,
11.8
%re
port
edea
ting
tw
oport
ions
of
100
gof
fruit
per
dby
the
chec
kli
st,
and
38
%re
port
edth
isin
the
food
dia
ry.
More
subje
cts
report
edea
tingt
wo
port
ions
of
veg
etab
les/
d(5
3.4
%in
the
chec
kli
stan
d74.6
%in
the
dia
ry).
Fai
rag
reem
ent
was
found
inth
eas
sess
men
tof
fruit
and
veg
etab
lein
take
bet
wee
nth
etw
ote
chniq
ues
(Kw>0
.20)
(Alt
man
,1991)
wit
hgre
ater
mis
clas
sifi
cati
ons
bei
ng
found
for
the
veg
etab
legro
ups
com
par
edw
ith
the
fruit
gro
ups,
whic
hm
aybe
expla
ined
inpar
tby
the
over
-est
imat
ion
of
par
ticu
lar
item
s(f
or
exam
ple
,onio
ns,
pep
per
s)in
the
chec
kli
st.
Alt
hough
furt
her
eval
uat
ion
of
the
die
tary
chec
kli
st
isre
quir
edan
dit
suse
should
be
trea
ted
wit
hso
me
cauti
on,
par
ticu
larl
yw
ith
resp
ect
toport
ion
size
s,it
is
ause
ful
tool
for
the
rapid
asse
ssm
ent
of
fruit
and
veg
etab
lein
take.
This
work
was
funded
by
the
Food
Sta
ndar
ds
Agen
cy.
Any
vie
ws
expre
ssed
are
the
auth
ors
ow
n.
Alt
man
DG
(1991)PracticalStatisticsforMedicalResearch
,pp.
404409.
London:
Chap
man
and
Hal
l.M
cKeo
wn
NM
,D
ayN
E,
Wel
chA
A,
Runsw
ick
SA
,L
uben
RN
,M
ull
igan
AA
,M
cTag
gar
tA
&B
ingham
SA
(2001)American
JournalofClinicalNutrition74,
188196.
Wil
lett
WC
(1990)NutritionalEpidem
iology,
pp.
127132.
Oxfo
rd:
Oxfo
rdU
niv
ersi
tyP
ress
.
Factors
associatedwithcompliance
withthepopulationgoals
forintakes
offruit
andvegetables
anddietary
fibre
inIrishadults.
By
M.
CO
SG
RO
VE
,M
.M.
OB
RIE
N,
M.A
.G
AL
VIN
,A
.F
LY
NN
and
M.
KIE
LY
,DepartmentofFood
and
NutritionalSciences,
University
College
Cork,Cork,
RepublicofIreland
Usi
ng
dat
afr
om
the
Nort
h/S
outh
Irel
and
Food
Consu
mpti
on
Surv
ey(N
SIF
CS
)(I
rish
Univ
ersi
ties
Nutr
itio
nA
llia
nce
,2001),
Gal
vin
etal.
(2001)
and
OB
rien
etal.
(2003)
show
edth
atin
takes
of
fruit
and
veg
etab
les
and
die
tary
fibre
(DF
)ar
elo
win
Iris
had
ult
s.T
he
NS
IFC
Ses
tim
ated
hab
itual
food
and
bev
erag
ein
takes
usi
ng
a7
dfo
od
dia
ryin
1379
random
lyse
lect
edad
ult
s,ag
ed18
64
yea
rs.
Usi
ng
the
food
consu
mpti
on
dat
aco
nst
ruct
edby
list
ing
each
food
asco
nsu
med
incl
udin
gport
ion
wei
ght
and
nutr
ients
obta
ined
per
port
ion,
the
pre
sent
study
des
crib
esdie
tary
hab
its
that
bes
tdif
fere
nti
ate
com
pli
ers
and
non-c
om
pli
ers
wit
hboth
of
the
popula
tion
goal
sfo
rin
takes
of
fruit
and
veg
etab
les
(400
g)
and
DF
(>25
g).
Fru
itan
dveg
etab
lein
takes
are
bas
edfr
om
dis
cret
eport
ions
and
com
posi
tedis
hes
.B
inar
y
logis
tic
regre
ssio
nan
alysi
sid
enti
fied
food-r
elat
edfa
ctors
that
pre
dic
ted
the
likel
ihood
of
bei
ng
a
mem
ber
of
the
com
pli
ers
gro
up.
Pre
dic
tors
BS
EP
Incr
emen
tO
R*
95
%C
Ifo
rO
R
Ener
gy
(excl
udin
gal
cohol)
(MJ)
1.8
88
0.4
57
0.0
00
0.8
08.1
23.4
9,
18.4
1V
eget
able
s(i
ncl
udin
gca
rrots
)(g
/d)
0.0
91
0.0
18
0.0
00
21.6
53.0
62.2
4,
3.8
8F
ruit
(incl
udin
gap
ple
s)(g
/d)
0.0
82
0.0
20
0.0
00
19.9
82.7
21.9
0,
3.5
3C
itru
sfr
uit
(g/d
)0.0
88
0.0
17
0.0
00
14.6
12.3
71.8
6,
2.8
9S
alad
veg
etab
les
(incl
udin
gto
mat
oes
)(g
/d)
0.1
20
0.0
37
0.0
01
10.3
82.3
71.5
4,
3.2
1F
ruit
juic
e(g
/d)
0.0
60
0.0
11
0.0
00
21.2
82.3
41.8
5,
2.8
4B
anan
as(g
/d)
0.0
76
0.0
15
0.0
00
14.8
02.2
11.7
4,
2.6
8W
hole
mea
lbre
ad(g
/d)
0.0
72
0.0
15
0.0
00
14.1
42.0
91.6
5,
2.5
3P
eas
and
bea
ns
(g/d
)0.1
40
0.0
27
0.0
00
6.6
02.0
71.6
7,
2.4
8G
reen
veg
etab
les
(g/d
)0.1
15
0.0
27
0.0
00
5.4
21.7
51.4
0,
2.1
0W
hit
ebre
ad(g
/d)
0.0
31
0.0
10
0.0
02
22.1
81.7
21.2
6,
2.1
7C
onfe
ctio
ner
y(i
ncl
udin
gch
oco
late
)(g
/d)
-0.0
43
0.0
20
0.0
36
4.3
40.7
70.5
6,
0.9
8C
arbonat
edbev
erag
es(g
/d)
-0.0
08
0.0
03
0.0
10
29.2
30.7
70.5
9,
0.9
5B
utt
eran
dsp
read
ing
fats
(g/d
)-0
.064
0.0
27
0.0
16
4.8
60.6
30.3
2,
0.9
3
*T
he
odds
rati
o(O
R)
was
bas
edon
a10
%in
crem
ent
inth
em
edia
ndai
lyfo
od
ener
gy
inta
ke
and
a33
%in
crem
ent
inth
em
edia
ndai
lyfo
od
inta
ke
(g)
inco
nsu
mer
sonly
.
Of
the
Iris
had
ult
s,45
%w
ere
com
pli
ers
(of
whic
h53
%w
ere
men
and
47
%w
om
en)
whil
e23
%
(of
whic
h28
%w
ere
men
and
72
%w
om
en)
wer
enon-c
om
pli
ers
wit
hboth
of
the
popula
tion
goal
sfo
r
fruit
and
veg
etab
les
and
DF
inta
kes
.F
ood
ener
gy
was
asi
gnifi
cant
(P
Sizedoes
notmatter:validationofamicro-m
ethodforadipose
tissuebiopsy
formeasurementof
fatty
acid
composition.
By
F.F
.M.
CH
ON
G,
A.S
.T.
BIC
KE
RT
ON
,B
.A.
FIE
LD
ING
and
K.N
.
FR
AY
N,Oxford
CentreforDiabetes,Endocrinologyand
Metabolism
,ChurchillHospital,
Oxford,
UK,OX37LJ
The
fatt
yac
idco
mposi
tion
of
subcu
taneo
us
adip
ose
tiss
ue
(AT
)obta
ined
usi
ng
the
met
hods
of
Hir
sch
etal.
(1960)
and
Bey
nen
&K
atan
(1985)
for
AT
sam
pli
ng
hav
ebee
nsh
ow
nto
refl
ect
the
long-t
erm
die
tary
inta
ke
of
fatt
yac
ids
inin
terv
enti
onal
and
cross
-sec
tional
studie
s(G
arla
ndet
al.
1998).
The
min
imum
requir
emen
tof
the
bio
psy
nee
dle
is1.5
mm
dia
met
er(1
9-g
auge
(19G
)fo
r
Hir
schs
met
hod
and
17G
for
Bey
nen
sm
ethod)
soth
atsm
all,
but
vis
ible
,am
ounts
of
AT
can
be
coll
ecte
dfo
rfa
tty
acid
anal
ysi
s(B
eynen
&K
atan
,1985).
We
hypoth
esis
edth
atfa
tty
acid
anal
ysi
sca
n
be
carr
ied
out
wit
hev
ensm
alle
ram
ounts
of
AT
and
we
sought
todev
elop
ale
ssin
vas
ive
met
hod
of
bio
psy
.
We
per
form
edtw
oA
Tbio
psi
eson
ten
norm
al,
hea
lthy
subje
cts
under
loca
lan
aest
hes
ia.
The
firs
t
bio
psy
was
taken
usi
ng
an18G
nee
dle
and
syri
nge
from
one
side
of
the
abdom
enan
duse
ddir
ectl
yfo
r
lipid
extr
acti
on.
The
oth
erbio
psy
was
taken
usi
ng
a21G
butt
erfl
ynee
dle
that
was
par
tof
aV
acuta
iner
blo
od
coll
ecti
on
syst
em,
anal
ogous
toB
eynen
sm
ethod.
AT
was
init
iall
ynot
clea
rly
vis
ible
inth
e
tubin
gof
the
21G
nee
dle
.W
hen
flush
edw
ith
sali
ne
(3m
l)in
toa
gla
sstu
be
and
centr
ifuged
(1000
rpm
,
1m
in),
gli
sten
ing
fat
glo
bule
sw
ere
seen
on
the
surf
ace.
Thes
ew
ere
aspir
ated
and
use
dfo
rli
pid
extr
acti
on.
Tw
ofu
rther
layer
s(e
ach
appro
xim
atel
y0.5
ml)
wer
eth
enas
pir
ated
and
use
dfo
rli
pid
extr
acti
on.
Fat
tyac
idco
mposi
tion
of
the
lipid
extr
acts
was
anal
yse
dby
GC
.N
obru
ises
wer
ese
enusi
ng
the
21G
nee
dle
,co
mpar
edw
ith
vis
ible
blu
e-bla
ckm
arks
by
the
18G
nee
dle
afte
r24
h.
Fat
tyac
id(g
/100
g)...
14
:016
:016
:1n-7
18
:018
:1n
-918
:2n-6
20
:1n
-920
:4n-6
20
:5n
-322
:6n-3
21G
(n10)
Mea
n2.6
621.7
15.4
73.4
449.8
413.0
50.7
00.2
90.2
30.1
0S
EM
0.1
90.3
90.3
20.3
90.6
10.5
40.1
00.0
60.1
40.0
418G
(n10)
Mea
n2.7
822.0
25.2
23.6
149.9
912.8
80.6
80.3
10.1
10.1
1S
EM
0.2
40.5
30.2
70.4
50.4
80.5
50.1
20.0
50.0
50.0
4
The
fatt
yac
idco
mposi
tion
of
AT
taken
usi
ng
the
18G
nee
dle
and
the
21G
nee
dle
are
ver
y
sim
ilar
(P=0
.6usi
ng
repea
ted
mea
sure
san
alysi
s),
pro
vin
gth
atonly
ver
yti
ny
amounts
of
AT
are
nee
ded
toan
alyse
fatt
yac
idco
mposi
tion.
The
com
posi
tion
of
the
nex
tla
yer
aspir
ated
was
also
sim
ilar
(res
ult
s
not
show
n),
but
the
thir
dla
yer
show
eda
fatt
yac
idco
mposi
tion
rese
mbli
ng
that
of
phosp
holi
pid
s(f
or
exam
ple
,20
:2,
1.7
7g/1
00
g;
20
:4,
4g/1
00
g).
We
concl
ude
that
was
hin
gw
ith
sali
ne
and
centr
ifugat
ion
effe
ctiv
ely
separ
ated
AT
tria
cylg
lyce
rol
from
blo
od
conta
min
atio
n.
The
impli
cati
on
of
the
pre
sent
study
isth
atit
isunnec
essa
ryfo
rsu
bje
cts
tounder
go
unco
mfo
rtab
lean
din
vas
ive
met
hods
of
sam
pli
ng
toobta
inA
Tfo
rfa
tty
acid
anal
ysi
s.T
his
met
hod
of
sam
pli
ng
isea
syan
dsi
mil
arto
aro
uti
ne
ven
epunct
ure
,al
low
ing
appli
cati
on
on
ala
rge
scal
e.
Bey
nen
AC
&K
atan
MB
(1985)AmericanJournalofClinicalNutrition42,
317322.
Gar
land
M,
Sac
ks
FM
,C
old
itz
GA
,R
imm
EB
,S
ampso
nL
A,
Wil
let
WC
&H
unte
rD
J(1
998)AmericanJournalofClinical
Nutrition67,
2530.
Hir
sch
J,F
arquhar
JW,
Ahre
ns
EH
Jr,
Pet
erso
nM
L&
Sto
ffel
W(1
960)AmericanJournalofClinicalNutrition8,
499
511.
Deleteriouseffectsofskippingbreakfast
onlipid
andcarbohydrate
metabolism
inleanhealthy
women.
By
H.R
.F
AR
SH
CH
I1,
M.A
.T
AY
LO
R1
and
I.A
.M
AC
DO
NA
LD
1,SchoolofBiomedical
Sciences,Queens
MedicalCentre,
Nottingham,UK,NG72UH
Bre
akfa
stco
nsu
mpti
on
appea
rsto
hav
edec
lined
inth
ela
stfe
wdec
ades
(Hai
nes
etal.
1996)
and
eati
ng
bre
akfa
st,
espec
iall
yce
real
,is
asso
ciat
edw
ith
alo
wer
risk
of
obes
ity
(Cho
etal.
2003).
Ser
um
chole
ster
ol
conce
ntr
atio
nis
report
edto
be
low
erin
adult
sea
ting
bre
akfa
st(E
B)
and
hig
her
among
those
not
(Sta
nto
n&
Kea
st,
1989).
No
study,
toour
know
ledge,
has
inves
tigat
edth
eef
fect
of
skip
pin
g
bre
akfa
st(S
B)
on
var
ious
aspec
tof
ener
gy
met
aboli
sm.
Thus,
the
pre
sent
study
eval
uat
edth
eef
fect
of
EB
or
SB
on
adult
ener
gy,
carb
ohydra
tean
dli
pid
met
aboli
sm.
Ten
hea
lthy
wom
en(B
MI
23.2
( SD
1.4
)kg/m
2)
wer
ere
cruit
edaf
ter
giv
ing
info
rmed
conse
nt.
Eac
hsu
bje
ctpar
tici
pat
edin
ara
ndom
ised
cross
-over
tria
lw
hic
hen
com
pas
sed
two
14
din
terv
enti
on
per
iods;
EB
inone
of
them
and
SB
inth
eoth
erw
ith
a2-w
eek
was
hout
per
iod
bet
wee
n.
InE
B,
subje
cts
wer
eas
ked
toco
nsu
me
apac
kof
whole
gra
ince
real
(Kel
loggs
,U
K,
45
g)
wit
h200
ml
sem
i-sk
imm
ed
mil
kbet
wee
n07.0
0an
d08.0
0hours
and
eat
ach
oco
late
bar
(Nes
tle,
48
g)
at10.3
011.0
0hours
.T
hen
,
they
consu
med
four
furt
her
mea
lsof
sim
ilar
conte
nt
tousu
alin
the
rest
of
the
day
atpre
det
erm
ined
tim
esev
ery
day
for
2w
eeks.
InS
B,
subje
cts
consu
med
the
choco
late
at10.3
011.0
0hours
,an
dth
enhad
the
cere
alan
dse
mi-
skim
med
mil
kat
12.0
012.3
0hours
.T
hen
,th
eyco
nsu
med
four
furt
her
mea
lsof
sim
ilar
conte
nt
tousu
alas
for
EB
.S
ubje
cts
consu
med
thei
rnorm
aldie
tfo
ra
2-w
eek
was
hout
per
iod
bet
wee
nth
etw
oin
terv
enti
on
per
iods.
Subje
cts
reco
rded
thei
rfo
od
inta
ke
on
3d
duri
ng
each
inte
rven
tion,
and
cam
eto
the
labora
tory
afte
ran
over
nig
ht
fast
atth
est
art
and
end
of
each
inte
rven
tion
per
iod
and
thei
rw
eight
and
anth
ropom
etri
cvar
iable
sw
ere
mea
sure
d.
Blo
od
sam
ple
sw
ere
taken
for
glu
cose
,li
pid
san
din
suli
nbef
ore
and
for
3h
afte
ra
test
mea
l(m
ilk
shak
eco
nta
inin
g30
kJ/
kg,
50
%
carb
ohydra
te).
RM
Rw
asm
easu
red
by
indir
ect
calo
rim
etry
bef
ore
and
afte
rth
ete
stm
eal.
Rep
eate
d-
mea
sure
sA
NO
VA
,an
dpai
redt
test
sw
ere
use
dfo
rth
est
atis
tica
lco
mpar
isons.
SB
was
asso
ciat
edw
ith
hig
her
fast
ing
tota
lch
ole
ster
ol
(3.4
( SD
0.4
)co
mpar
edw
ith
3.1
(SD
0.4
)
mm
ol/
laf
ter
EB
;P
Dietary
advice
for
prevention
oftype
2diabetes
mellitusin
adults.
By
H.J
.M
OO
RE
1,
C.D
.
SU
MM
ER
BE
LL
1,
L.
HO
OP
ER
2,
V.J
.A
SH
TO
N1,
P.
JOH
NS
TO
NE
3an
dP
.K
OP
EL
MA
N4,
1University
ofTeesside,
Middlesbrough,UK,TS13BA,
2University
ofManchester,
Manchester,
UK,M156FH,
3DepartmentofHealth,Leeds,UK,LS14USand
4University
ofLondon,London,UK,E12AD
The
chan
gin
gof
die
tary
hab
its
may
less
enth
ech
ance
of
dev
elopin
gty
pe
2dia
bet
es.
Giv
enth
e
pre
val
ence
and
the
pote
nti
ally
seri
ous
cost
sof
the
dis
ease
,it
isim
port
ant
toes
tabli
shw
hic
hty
pe
of
die
tary
advic
e,ei
ther
alone
or
inco
mbin
atio
nw
ith
oth
erin
terv
enti
ons
(the
addit
ion
of
exer
cise
,
beh
avio
ura
lap
pro
aches
and
alte
rnat
ive
trea
tmen
ts),
ism
ost
effe
ctiv
ein
pre
ven
ting
dev
elopm
ent
of
the
dis
ease
. The
pre
sent
syst
emat
icre
vie
was
sess
esth
eef
fect
of
type
and
freq
uen
cyof
dif
fere
nt
types
of
die
tary
advic
eto
all
adult
son
morb
idit
y,
wei
ght,
qual
ity
of
life
,to
tal
mort
alit
yan
dm
easu
res
of
dia
bet
ic
contr
ol.
We
sear
ched
The
Coch
rane
Lib
rary
,M
ED
LIN
E,
EM
BA
SE
,C
INA
HL
,A
ME
D,
bib
liogra
phie
s
and
conta
cted
rele
van
tex
per
ts.
All
random
ised
contr
oll
edtr
ials
,of
12
month
sor
longer
,w
her
edie
tary
advic
ew
asth
em
ain
inte
rven
tion
inad
ult
sw
ere
incl
uded
.
Fourt
een
arti
cles
report
ing
nin
etr
ials
wer
ein
cluded
.V
ario
us
die
tary
appro
aches
wer
e
consi
der
ed.
Tw
otr
ials
com
par
edth
eusu
aldie
tary
hab
its
wit
ha
low
-fat
die
t.S
ixst
udie
sco
mpar
ed
die
tary
advic
ew
ith
die
tary
advic
eplu
sex
erci
sean
done
oth
erst
udy
looked
atdie
tary
advic
ev.
die
tary
advic
eplu
sa
beh
avio
ura
lap
pro
ach.
The
studie
sal
lm
easu
red
wei
ght
and
gly
caem
icco
ntr
ol
alth
ough
not
all
studie
sre
port
edth
ese
outc
om
es.
Four
studie
sre
port
edth
enum
ber
of
par
tici
pan
tsw
ho
dev
eloped
dia
bet
esan
donly
two
studie
sre
port
edm
ort
alit
y.
Oth
eroutc
om
esm
easu
red
inth
ese
studie
sin
cluded
blo
od
pre
ssure
,se
rum
chole
ster
ol
(incl
udin
gL
DL
-an
dH
DL
-chole
ster
ol)
,se
rum
tria
cylg
lyce
rols
,
max
imal
exer
cise
capac
ity
and
com
pli
ance
.
Usi
ng
exer
cise
asan
adju
nct
todie
tary
advic
eap
pea
rsto
impro
ve
fast
ing
pla
sma
glu
cose
at12
month
sin
norm
ogly
caem
icin
div
idual
s.D
ieta
ryad
vic
eplu
sex
erci
se,
asco
mpar
edw
ith
die
tary
advic
e
alone,
was
asso
ciat
edw
ith
ast
atis
tica
lly
signifi
cant
mea
n(p
oole
dw
eighte
dm
ean
dif
fere
nce
)dec
reas
ein
fast
ing
pla
sma
glu
cose
of
0.2
(95
%C
I0.1
,0.3
)m
mol/
lat
the
12-m
onth
foll
ow
-up.
Thre
est
udie
s(T
orj
esen
etal.
1997;
Win
get
al.
1998;
Tuom
ileh
toet
al.
2001)
contr
ibute
ddat
a
toth
ism
eta-
anal
ysi
s.T
he
adopti
on
of
regula
rex
erci
seis
agood
way
topro
mote
bet
ter
gly
caem
ic
contr
ol
inad
ult
s.
Torj
esen
PA
,B
irkel
and
KI,
Ander
ssen
SA
,H
jerm
ann
I,H
olm
eI
&U
rdal
P(1
997)Diabetes
Care
20,
26
31.
Tuom
ileh
toJ,
Lin
dst
rom
J,E
rikss
on
JG,
Val
leT
T,
Ham
alai
nen
H,
Ilan
ne-
Par
ikka
P,
Kei
nan
en-K
iukaa
nnie
mi
S,
Laa
kso
M,
Louher
anta
A,
Ras
tas
M,
Sal
min
enV
,A
unola
S,
Cep
aiti
sZ
,M
olt
chan
ov
V,
Hak
um
aki
M,
Man
nel
inM
,M
arti
kkal
aV
,S
undval
lJ
&U
usi
tupa
M(2
001)New
EnglandJournalofMedicine344,
13431350.
Win
gR
R,
Ven
dit
tiE
,Ja
kic
icJM
,P
oll
eyB
A&
Lan
gW
(1998)Diabetes
Care
21,
350
359.
Dietary
advice
for
treatm
entoftype
2diabetes
mellitusin
adults.
By
H.J
.M
OO
RE
1,
C.D
.
SU
MM
ER
BE
LL
1,
L.
HO
OP
ER
2,
K.
CR
UIC
KS
HA
NK
2,
A.
VY
AS
2,
P.
JOH
NS
TO
NE
3,
V.J
.
AS
HT
ON
1an
dP
.K
OP
EL
MA
N1,
1University
ofTeesside,
Middlesbrough,UK,TS13BA,
2University
ofManchester,
Manchester,
UK,M15
6FH,
3DepartmentofHealth,Leeds,
UK,LS1
4US
and
4University
ofLondon,London,UK,E12AD
Whil
ein
itia
ldie
tary
man
agem
ent
imm
edia
tely
afte
rfo
rmal
dia
gnosi
sis
ana
ccep
ted
corn
erst
one
of
trea
tmen
tof
type
2dia
bet
esm
elli
tus,
afo
rmal
and
syst
emat
icover
vie
wof
its
effi
cacy
and
met
hod
of
del
iver
yis
not
curr
entl
yav
aila
ble
.
The
pre
sent
Coch
rane
syst
emat
icre
vie
was
sess
esth
eef
fect
of
type
and
freq
uen
cyof
dif
fere
nt
types
of
die
tary
advic
eto
all
adult
sw
ith
type
2dia
bet
eson
wei
ght,
mea
sure
sof
dia
bet
icco
ntr
ol,
morb
idit
y,
tota
lm
ort
alit
yan
dqual
ity
of
life
.
We
sear
ched
The
Coch
rane
Lib
rary
,M
ED
LIN
E,
EM
BA
SE
,C
INA
HL
,A
ME
D,
bib
liogra
phie
s
and
conta
cted
rele
van
tex
per
ts.
All
random
ised
contr
oll
edtr
ials
,of
6m
onth
sor
longer
,w
her
edie
tary
advic
ew
asth
em
ain
inte
rven
tion
inad
ult
sw
ith
type
2dia
bet
esm
elli
tus
wer
ein
cluded
.
Thir
ty-s
ixar
ticl
esre
port
ing
eighte
entr
ials
wer
ein
cluded
.V
ario
us
die
tary
appro
aches
wer
e
consi
der
ed.
Nin
est
udie
sco
mpar
eddie
tary
advic
ew
ith
anoth
erdie
t.S
ixst
udie
sco
mpar
eddie
tary
advic
e
wit
hdie
tary
advic
eplu
sex
erci
sean
dth
ree
oth
erst
udie
slo
oked
atdie
tary
advic
ev.
die
tary
advic
eplu
s
beh
avio
ura
lap
pro
aches
.T
he
studie
sal
lm
easu
red
wei
ght
and
gly
caem
icco
ntr
ol
alth
ough
not
all
studie
s
report
edth
ese
outc
om
es.
Oth
eroutc
om
esm
easu
red
inth
ese
studie
sin
cluded
mort
alit
y,
blo
od
pre
ssure
,
seru
mch
ole
ster
ol
(incl
udin
gL
DL
-an
dH
DL
-chole
ster
ol)
,se
rum
tria
cylg
lyce
rols
,m
axim
alex
erci
se
capac
ity
and
com
pli
ance
.
Usi
ng
exer
cise
asan
adju
nct
todie
tary
advic
eap
pea
rsto
impro
ve
gly
cate
dH
bat
6an
d12
month
sin
indiv
idual
sw
ith
type
2dia
bet
es.
Ther
ew
ere
smal
l,yet
signifi
cant
chan
ges
ingly
cate
dH
bin
the
four
(Uusi
tupaet
al.
1996;
Agurs
-Coll
inset
al.
1997;
Lig
tenber
get
al.
1997;
Sam
aras
etal.
1997)
and
thre
e(W
inget
al.
1988;
Uusi
tupaet
al.
1996;
Sam
aras
etal.
1997)
studie
sth
atco
ntr
ibute
ddat
ato
thes
ean
alyse
s.
Die
tary
advic
eplu
sex
erci
sew
asas
soci
ated
wit
ha
stat
isti
call
ysi
gnifi
cant
mea
n(p
oole
d
wei
ghte
dm
ean
dif
fere
nce
)dec
reas
ein
gly
cate
dH
bof
0.9
(95
%C
I0.4
,1.3
)%at
6m
onth
san
dof
1.0
(95
%C
I0.4
,1.5
)%at
12
month
s.T
he
adopti
on
of
regula
rex
erci
seis
agood
way
topro
mote
bet
ter
gly
caem
icco
ntr
ol
inty
pe
2dia
bet
icpat
ients
.
Agurs
-Coll
ins
TD
,K
um
anyik
aS
K,
Ten
Hav
eT
R&
Adam
s-C
ampbel
lL
L(1
997)Diabetes
Care
20,
15031511.
Lig
tenber
gP
C,
Hoek
stra
JB,
Bol
E,
Zonder
land
ML
&E
rkel
ens
DW
(1997)ClinicalScience
93
,127135.
Sam
aras
K,
Ash
wel
lS
,M
ackin
tosh
AM
,F
leury
AC
,C
ampbel
lL
V&
Chis
holm
DJ
(1997)Diabetes
ResearchandClinical
Practice37,
121128.
Uusi
tupa
M,
Lai
tinen
J,S
iito
nen
O,
Van
nin
enE
&P
yora
laK
(1996)AnnalsofMedicine28,
445449.
Win
gR
R,
Epst
ein
LH
,P
ater
nost
ro-B
ayle
sM
,K
risk
aA
,N
ow
alk
MP
&G
oodin
gW
(1988)Diabetologia
31
,902
909.
Vol. 63 Meeting of 58 July 2004 57A
Investigationinto
theeffectsofinitiatinginsulintherapyin
type2diabetes.
By
R.M
.B
AR
RA
TT
1,
H.
TR
UB
Y1,
D.J
.M
ILL
WA
RD
1an
dG
.S.
FR
OS
T2,
1CentreforNutritionandFoodSafety,Schoolof
Biomedicaland
MolecularSciences,
University
ofSurrey,Guildford,Surrey,UK,GU2
7XH
and
2NutritionandDieteticDepartment,Hammersm
ithHospitals
NHSTrust,DuCaneRoad,London,UK,
W120HS
Sin
ceth
epubli
cati
on
of
the
UK
Pro
spec
tive
Dia
bet
esS
tudy
(Unit
edK
ingdom
Pro
spec
tive
Dia
bet
es
Stu
dy
(UK
PD
S)
Gro
up,
1995)
insu
lin
ther
apy
isbei
ng
use
dea
rlie
ran
dm
ore
exte
nsi
vel
yin
the
trea
tmen
t
of
type
2dia
bet
esm
elli
tus
(type
2D
M).
Insu
lin
ther
apy
undoubte
dly
impro
ves
gly
caem
icco
ntr
ol
and
reduce
sth
eri
skof
mic
rovas
cula
rco
mpli
cati
ons.
How
ever
,it
has
not
bee
nsh
ow
nto
signifi
cantl
yim
pac
t
or
reduce
mac
rovas
cula
rco
mpli
cati
ons
(UK
PD
SG
roup
1998).
Iatr
ogen
icw
eight
gai
naf
ter
init
iati
ng
insu
lin
isa
com
mon
pro
ble
m,
whic
hm
ayim
pac
tfu
rther
on
the
risk
of
mac
rovas
cula
rco
mpli
cati
ons
(Rea
ven
,2002).
The
pre
sent
study
aim
edto
inves
tigat
ech
anges
inbody
wei
ght
foll
ow
ing
the
intr
oduct
ion
of
insu
lin
ther
apy
inad
ult
sw
ith
type
2D
Man
dto
det
erm
ine
the
infl
uen
ceth
atth
isch
ange
intr
eatm
ent
has
on
lipid
met
aboli
sm,
body
com
posi
tion
and
CH
Dri
sk.
An
inte
nsi
ve
die
teti
cw
eight-
man
agem
ent
inte
rven
tion
was
also
test
edto
det
erm
ine
whet
her
wei
ght
gai
nca
nbe
min
imis
edan
d
outc
om
eopti
mis
edin
this
noto
riousl
ydif
ficu
lt-t
o-t
reat
gro
up.
Subje
cts
wit
hty
pe
2D
Mhav
ebee
nre
cruit
edduri
ng
the
tran
siti
on
per
iod
toin
suli
nth
erap
y(
4
wee
ks
of
init
iati
ng
insu
lin).
As
subje
cts
are
recr
uit
ed(t
arget
num
ber
n74)
they
are
random
lyas
signed
to
eith
erth
eco
ntr
ol
or
inte
rven
tion
gro
up.
The
contr
ol
gro
up
wil
lco
nti
nue
wit
hst
andar
dca
re,
whil
eth
e
inte
rven
tion
gro
up
wil
lfo
llow
adie
titi
an-l
edin
tensi
ve
wei
ght-
man
agem
ent
pro
gra
mm
e.A
sub-c
ohort
from
each
gro
up
wil
lhav
em
agnet
icre
sonan
ceim
agin
gsc
ans
com
ple
ted
tom
easu
rebody
fat
dep
osi
tion
and
musc
lean
dli
ver
tria
cylg
lyce
rols
,an
dpost
pra
ndia
lst
udie
sw
ill
be
carr
ied
out
todem
onst
rate
chan
ges
inli
pid
han
dli
ng.
All
mea
sure
men
tsar
eco
mple
ted
atbas
elin
ean
den
dpoin
t(6
month
);th
en
inte
r-an
din
tra-
gro
up
anal
ysi
sw
ill
be
under
taken
.
Curr
entl
yhal
fof
the
tota
lnum
ber
of
pat
ients
hav
ebee
nre
cruit
ed(5
7%
mal
e,43
%fe
mal
e)an
d
12
pat
ients
(16
%)
hav
eco
mple
ted
the
study;
thes
enum
ber
sar
eco
nti
nual
lyin
crea
sing.
Init
ial
anal
ysi
s
indic
ates
that
ther
eis
aw
ide
var
iabil
ity
inw
eight
chan
ge
and
oth
erbio
chem
ical
mar
ker
sfo
llow
ing
the
init
iati
on
of
insu
lin.
Of
those
that
hav
eco
mple
ted,
the
init
ial
mea
nB
MI
was
34.7
(SD
4.3
,ra
nge
29.7
44.6
)kg/m
2,
mea
nin
gth
atal
lpat
ients
,ex
cept
one,
wer
ecl
inic
ally
obes
e.T
he
mea
nH
bA
1c
at
bas
elin
ew
as10.0
1(S
D1.7
7,
range
7.8
12.5
)%
and
aten
dpoin
t,af
ter
6m
onth
s,w
as10.1
0(S
D1.7
4,
range
8.5
12.4
)%
,w
hic
hac
tual
lyin
dic
ates
aw
ors
enin
gin
gly
caem
icco
ntr
ol
atth
isst
age.
The
wei
ght
chan
ge
of
those
inth
eco
ntr
ol
gro
up
hav
era
nged
from-1
.9to
+8.3
kg
(mea
n+3
.52
kg).
For
those
inth
e
inte
rven
tion
gro
up
the
chan
ge
inw
eight
has
ranged
from
-1.6
TO
+2.5
kg
(mea
n+0
.43
kg).
Ther
efore
,
init
iall
yit
appea
rsth
atan
inte
nsi
ve
die
teti
cin
terv
enti
on
can,
on
aver
age,
pre
ven
tso
me
wei
ght
gai
n
foll
ow
ing
the
init
iati
on
of
insu
lin
ther
apy.
Itis
anti
cipat
edth
atas
addit
ional
pat
ients
com
ple
teth
est
udy
the
resu
lts
wil
lin
dic
ate
more
com
pre
hen
sivel
yth
eri
sks
and
ben
efits
of
insu
lin
ther
apy
inty
pe
2D
Man
d
revea
lw
het
her
inte
nsi
ve
die
teti
cin
put
atth
isti
me
isof
signifi
cant
advan
tage.
Unit
edK
ingdon
Pro
spec
tive
Dia
bet
esS
tudy
Gro
up
(1998)Lancet352,
837853.
Rea
ven
GM
(2002)Diabetes,ObesityandMetabolism
4,
Suppl.
1,
S13S
18.
Unit
edK
ingdom
Pro
spec
tive
Dia
bet
esS
tudy
Gro
up
(1995)BMJ310,
8388.
Cis-9,trans-11
conjugated
linoleic
acid
(CLA)im
proves
metabolicand
molecularmarkersof
insulinsensitivityin
adipose
tissueandliver.
By
F.
MO
LO
NE
Y,
E.
NO
ON
E,
M.J
.G
IBN
EY
and
H.M
.R
OC
HE
,NutrigenomicsResearchGroup,DepartmentofClinicalMedicine,
TrinityCentrefor
HealthSciences,StJamess
Hospital,Dublin8,RepublicofIreland
Conju
gat
eddie
onic
der
ivat
ives
of
linole
icac
idar
ea
mix
ture
of
geo
met
ric
and
posi
tional
isom
ers
of
linole
icac
id.
The
effe
cts
of
CL
Aon
glu
cose
and
insu
lin
met
aboli
smhav
eyie
lded
contr
over
sial
resu
lts.
Fee
din
ga
ble
nd
of
CL
Ais
om
ers
(trans-
10,cis-
12
CL
Aan
dcis-
9,trans-
11
CL
A;