'1'1.

11: first p i ~ r of
t the tjtlc of t,his pt~pcrmay be ,z rriis~~omel..
There is 110 gu;~l~ar
1tec tllut tlie rri:~ill points c.)f t]his disc.:ussio~lw e :~c:t,~ltllly
:d)out, :~rtcriosc:lerosis
or the p:~l-t,ic:ulurvariety labelled ut,hc:rosc:lert.,sis. 8illce t,licl pathological condition c:tliliot, he precisely c v : ~ l u ~ ~ lill
e dlife, :uld is :~11 l o o scldom verifird at, tl(::it,h,
it is proper t o 11::tvc t h e p:.i,t,hologist ill c:oxrirnuiiti of Iljs ow11 fieltl : ~ n dt,o st,:by
withill the lixriit,~of the f:.~r:t,son w1lic:li this disc~ussiot~
t~c:t,t~uIly
tlcpo~lds;lhclsc
arc t,lie I':LC.~,S
S C O II-oc:orded,
~,
:LI~(Ixneasu~-etlI)y the (:lit~i('i;~~i,
tli(: I)joclic~riist~
:1,11(1
the vital st:~listici;t~l.
~
set's of j terris: I ) '1'11(: first js thc
The f'nctts t,o i)(: disc:ussed Iir:r~: c o l i c c r ~t,liree
1)r.o:td c:ztego~.yof 1ic::trt di,wusc:, 01. disc:tsc:s, djngllosed hy t,he (:li l t i ~ i a ;is
~ l iillgi~lit
pec.toris, c:orolt:iry I-le,:~l.t,dise:~se, rriyoc:ar~di:~.li~lf'a~*cli(.)ll,
(:hr.ot~i(:~~lyo(:;~rdit,is,
tics it is ~.sr.elypossible
:1~1(1rr~yo(:al'djalOegcl icl'at,io~l.111 lio~pitala nd vit,sl st,:~t,is
tJodjf'fe1-clit,i:tt,ct;hcsc+c:le,z~.lys o it is c:olivcttic:~ltto group thcln, for. tlie plesent, p11rposc, as "dege~lernt~ivc
1lct:tr.l ciisc::~sc." h/ro~.eovcr,the1.c is rno1.e t,lian a suspic:ic)~l
that, l.hcy :dl, .ill f';tc:t,, sh:.~t.c:s ome c:oxnrnor) f:ict.or,s in basic: eliology, I)ut tlc1,ails
\votalcl he out. of p1:tc:c here. 2 ) 'I'lle sec:olid set of items c:ol~c.c~-~is
serum c:liolesterol
wlii(:h arc c~u~~~.ellt,Iy
t,o 1)e i~nportantlyrc:!:tt,ed
;i.~icl:illiod sul)st;~.~ic:cs
co~lsicte~*etl
i;o t,Iicr developmc~it,of' sorne, :tt l(:nst, of' t,hesc: c:o~~cIitio~ls
in man. r1 h c rc:l;tt,iol\sliip is ~)~'csrl~ri:~l)ly
t.111.ough the ntlhcro~ol~:rt,f,ic:
procfiess~ I I I t,hjs
~,
:~ssrlrnpt,io~t
is
n o t c:c:~l t,r:~lfor m y n ~ ~ g ~ ~6,. r3)
n cFi
t ~tlally,
~
t,lit:re is f,l~e~ ~ e l a t ~ i o ~ of
r s hthe
i ~ )die{,t,o
t,hct c*ol~~~:1it~1':.~t,io11
of (:holest,orol : i ~ ~ c:~,llietl
i
sul)~t,n.llc:cs
ill tht: sc:l,uln :111d t,o the
d(:a l h ~ . : ~ tof. c the :~clult, ~)oplllat,iotl.
LVIIJ~ t,t>escli:~\'~::i,11yt11i1ig t o d o 1vit~11p ~ l b l i cII(YLIth, C:IY;I 1 it "l~(:~v(:r
p111)lic
FOI.n?ariy dec:udos (,he ofiic:i:~l:ts ~zr(:ll :LS
h(::lItl-1," ~.eciuiresa lit,tlo c:otlsiclc:~*at.io~l.
t.he gcllel-:tl v i i : ~of'~t,hc slil)j(!c.t, of' " ~ ) i ~ l ) l i t1ic:alth"
:
flus 1)ccll t,liat i t :;hould I.)(; c:olii:c:~~t~~.:~t,(~.l
0 1 1 n f c \ v 1ri:tjol- rp~est,iortsol)\riously ~.ocluirillgorga~tiactcl:~ttelit,io~l
I)(:of ~~i(:(jic.:i~i(:-puI?li(~
s:~tiil:~t,ioti,
( ~ I i,~*ol
I
yolid the sc!o~)cof t,lie iiltli~ritlllalp~.ac*t,icae
of' y no^-t,:rlit,y :111(1c:ornrnu~~iof c!pidemjcs a t ~ ditlSer.t,i\rc tlisi::~ncs,~,c:c'o~.ci-liee~)i~ig
ties h(:~t.lt,h
st :I,~,IIS, id t,lie (~o~al*(xc:tio~~
oS l~e;alt~l~
l ~ : ~ z : ~ \\.l~e~*c:
~ ~ l , s ~ l i : i r ~peol)l(:
j~
(Y)IIg1.(:g:.:~t,(!,
as i l l sc:llools n ~ l df';~c~i;oric!s.
'I'ltcsc? limitckci ho~.jzo~is
:i.~.c. I I O \ \ . 1)cillg (:st,(-:~ldetl
i 11
\\,:i.ys. 14-j rst ? ~,II(:IY: is ge11e1*:1,1
p [ i l ) l i c iilsist(:~l(:(l
( , I I ; L ~ (:/'Sej~,t~s
011 :I /)r,o:~(j
fro^ I 1,
s l i o ~ ~ llw
d mucio t,o prevell t 01- clt!c~r~c;~.sc
t h(: ir)c:idc.llc.c:01' (111, $01 nls of illr~ctxs:l.iicl
~ t , i o ~Sec~oilcl,
~~tl
clis;\.l)ility, 1101. rnel.ely thost1 i , l ~ ; ~:I.IY:
. t , irli'c:c.ti\:e 01. e ) c ~ c ~ ~ ~ ~i~l l :ot-ij$~-t.
7

there js tI1(: r(:rtli~aLiont,llut progrc~sjrl both ~)reverl.t,ioll

:tlid r~l(:dicttl(:are dt:mul~du
ili(:roasc(l kl~o\vl(:dg(:whic:ki call olily corrle from research. 'l'his means ~-ese;trc:h
workers ailtl facilitjcs whosc cont~.il)ut,iollis l,o the corninoli good and \\rhos($
fillallcia1 s~lj)~)ort
must c:ome, someho\v, f roln thc: commuiiity. 'l'his just,ifies t,lle
g
1.y the
faclt, that a litrgc palst,of all our inc(3jr:al rcscarr!h is ~io\vb e i ~ ~supported
'I;. S. 13ut>lic:Hc::tlth S~:rvj(*e.
S o w on purely f i ~ i a i i ~ igro~llids
i~l
pi.1t~lichealth ac:t.ivit,ic:s, incaltltliI lg i.eset.~l.cki,
cnll~lotbe exprtilded i.iidcliliitel.y,psrtic!~xlarlywhen wc httve such ;L stiuggcring
c:ost for rnilit;:t~:ydefel~sc.l3ut the need for major. public! heultlh at,t,c:~~tio~i
is caleur
1~1ic:licvcltn.o cro~itlitioils(:xist: ,First, when tohcrc:LI-elarge ~lumbcrsof t,he populatiol~suffcrilig disat)ilit,y : ~ n ddeath frorn diseascs agailist, \\~kiichprivate: medic::il
pr:~(:t,ir:eis xnakilig litt,lc head\\la,y. And, scc:c,tld, who11 there is aily I'C:.LSOI~
to hop(:
t,llitt the jnc:idc:lice of thcse diseases may he al1,erc:d 1)y measures upplic:~tt)let,o
t,he g(:lic~*:~l
poplll:~tioll,(:VCII if these meusrll.cs are not, yet k~io\v~i.
Ilegenerative heart, tliseasc: flilfills thcse c:olldit,iol~s.T t is urlnec:ossar*yt,o cite
the mol~r~iful
f';~(:t,s:~11outthe gr~:tt11111nl)(:rsof persotiti, :t~i(lby 110 rne:tlis meroly
the: agc(1, ivlio alee:~fTt:cl,t,cd.A lid everyo1I(: must :admit; t,hat the prescllh p~*ac:ticc
mlicl pl-ogross of cliitg~losti~
:tll(l thera~.)euti(:
ruotlic!irle is llot solvi~igthe problem;
the proof in only too c;lcar. ill our vital stut,istic:s. It, is possi1)le to :trguc a1)out the
clelailed ac:curac:y of tlec~thc:crt.ific:at!ioll alld to poilit out the cllallgil~gage ;it,ruc:1,llre of 1;lle populat;iol1, 1)ut; no rntlt,tcr what; cl~lnlific:aCio~~s
slrd rcfi~lc:xnciilsof
;1,11:~1ysis
:ire :tppliccl, t l ~ gc~lerttl
:
f : ~ trcxnaills Ihc same. TI) tho past, t,hil.ly yc::.trs,
\vhic:h is us ~ : L I - :ASuc:c:cptul)lc I-C(:OI*~S~xf~erld,
the age-spc:c:ifi(: d(:at,h rutc frorxl
clege~~c:r;tt,ive
he:~rtcliseusc: i s cel.t,ai~ilynot tlcc+reasil~g.
li'or- rnalcs undw 70 yoars,
i l l fact,, it, is difficwlt to deny that therc: has 1)c:e11a st,e:.~dy
up~;.~,rd
1;1*~1id.
This is
p:trt,i~~~I:trly
striking ill vie\\' of Cho f;~(:tt,h;tt, the total age-speclific: dcakh ritt,c,
from all ot,he~.c::trlscs, i s :it.cv~dilyf:blling.
1he mc:re e>;ist,c?~loc
of' mi ulld(:sir:l,t~lcst;~t,c:of' ttiTuirs is 11o1,,ill itsolf, elio~lgh
re:Lsoli to derriu~~tl
u rnt~joreSSor-t t,o c:orrec:t, j 1,. Thc1.e musk also t)e some I-c;i,solito
t)clievc: that impl.ovemer~t,ia possi1)le. 111 t,hc pust,, u tlefeat>ist:~.ttit,~ide
al~olxt
h(3ul.t cIise;r.sc.:,p3l't,i('~litl'ly
degc:iiernt,ivo heal%disctasc, has I.)c:c:~i s rnajor lli~l&-:~~l(:(:
to effort, all() eve11 t.o c : t ~ t - t f f ~ lcollsidelh;bt,i~li.
l
131.11,it is 110\1~:~~)ur~dallt,]y
( ' ~ ~ Uthat
I(legenoralive lic:art, dist:i~scis 1)ot all ilievila1)le c:olisccpielloc-,x?of ::tgei~ig,t)(:gii\~~i~)g
i l l youth al\.tlpl'ogrcssil~gwith the years, il~dift'cre~lt!
ulikc to mot1ic:n.l c:ffor.ts ; L I I ( ~
improvc:rnell ls i 11 living c:o~ldit;io~~s.
r 7

The f'ac:t th:~1,the prc:st:~lt high tlentli r;tt,o froru tlcgenctrut,ivc: hc?:i,r.(.#
disct:l.se ill
the TTliit,ecl Si;a,tes is 11ot itlc:vitabl(: is easily sho\\rii l)y c.onlpi~~.isoi~
u-it.11 some
ot,licl. (*(.)[I 11tl.jes.'l'he ol)joc:toiol)xn::ty I)(: 1.tiscd t,liitt, c.ert,ific::~t,io~i
of spt:c,ific: c.uusc:s
of cle:~t,liis ~ ~ ovc:l*y
t , 19cliitt)lt: a.iid that; clifYe~.c:lit,c'1.i l,clniurn::ty ))e :tpplied i 1.1 clifSe~.c:lit,c+o~~i~t,l.ic?s.
'l'hc? fucbt, that ofic*iiil vit,::~]st,:tt;istic:s ilidi(*tltf(:
f 01% 1't8:.~I
y, f01'
~ h from ( L ~ ) ~ ' oClisei~s(:
~ i : ~ ~(*olt(aci\';:i,l)ly
8~~y
c:s:~mplo,olily a, small fi.:ic~t,iollof our ( l ~ a t ~ltt,(:
lrl2,jl IN: (:spli~i~~(xl
ill t,his I V : L ~ . J3ut t,klis oljjt:(*t,io~i
los(2s rrl11r11f o l ~ eif (1(?:11.11l*at,es
sys1,ern ~ L I Y : c~ornparetl.Phjrsic.i:.tlls
1'01.thc t,ot;~lof' :LII disc::l.ses of the cril.c*~lla~t.ol.y

120

ANCEL KEYS

may differ it1 thc desigllatjon of ki~ldsof heart, disease brrt there is much less doubt,
whcri it comes to ticc:idiilg wlict,her t h y have to do with hcart disensc in gerlerttl.
Tfie data iri 'l'ablc 1 c:ovcr tht: ugc rangc from 40 through ti4 years, probably
thc most sigllificalit, 25 yc:ars of life in regard to degcnerst,ive licsrt clisehve. Thrtjr
show higher dc:ath rates from the tot,ttl of ull ctauser in thc Ullit,cd States than
in Ttaly czud this ctisadvunt:~gcis Inore markcd \V~C:II deaths from iufectivc and
pa~.ssit,ic:tliseases aid from all forms of violerice are cxcludcd. The high death
rato frorn vjo1cnt:c i l l the TJrlitcd Stat,cs is more t,h,zn of'fset, by the high death
rate from t,ubc:rculosis ill It,aly. Wheli comparison is limited to deaths from all
forms of churdiovust:ular di~case,the T i . S. rat,es are far worse than those for
Italy. Finally, if only tlcge~icrd,iveheart disease is eonsidered, thc differcncbe
is tremendous. It \\.ill I)(: iiotic:ed, also, that thc U. S. malts farc much worso thsli
the TJ. S. fcmales ill thcst: comparisons. 'l'his is signific*antit1 view of thc fad
that thc inoid(tnce of dcge~lcrstivcheart, disease iri American rrien is much highcr
than i l l Amcricba~i\\.omell, psrtic:ularly hefore old age.
TA l31,l.C 1
Ilenth rates in IluZy (1948) as perrer~lugeso j corraspondircg rates i n Ihc 7J.S.A. (1949) for men
( M ) ar~tlwomert ( P ) i 7 ~three age fjroups for:
1) all causes, 2) :ill causos less irlfect,ivc: and parasitic diseases s11dviolence, 3) di~easesof
t,hc circulst,ory syslcrrl (C:ltcgory VIT i l l the 1ntern:rtion:~llist,), 4) dep;enarutivc he@
disasisc ( I ) .
.-

. . . . .

.-.-,
..--.
.......
Scx... . . . . . . . : . . . . . . . . . . . . . . . . . : . . . . . . . . . . . . . .
.
.- . ,
," ..........

50-5-1

40-44
-.

............
1:

1. A11

91

1(K)

2.

ca,uses... . . . . . . . . . . . . . . . . . . . . .
1Sscl. infcct,ivo, violcnc:~.. . . . . . . . .

79

3. Circulatory systcrrl... . . . . . . . . . . . .

35

1logencr:ttivc heart,. . . . . . . . . . . . . . .

20

87
79
56

4.

-
.......

-...

--.,

ACE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

-.

M
..,.

...

60 64

.....-........

1;

88
83

75
73

5!1
48

28

.......

77
70
31
23

--

....

25

I:

97

06

67

66

The example of Italy is c:itod bec:ausc other cvideiicc frorn Tluly, to 11eprcsc11tetl
latex. i l l this: p:y)cr, is partic:ularly r.clt:va~lttoothc p1~oi)lcm.13ut Italy is not
pectuliar exc:cptlion. M e ~ l yot,hcr c:oul~tx.iexappe:-lr to have much Icss degenerative
11c:ert diseasc thall ill !,he 'TTllitecl St:at,cs. 'I'hcy certainly have lo\ver t,ott~ldeath
rates, as showil ill 1':~hlo2. It; mcty come as a shoc;k to I-oalizcthat,, acttuitlly, the
mol-tality r.c:c:o~.dof :~dults ill the litli tetl Sl;ntes is poorcr. t,ha~iin other c:omparal)lc
c.oullt,iies i l l the: Wcstjcrll World. Most of our i~lferioritysho~vtiill 'l'at)Je 2 is
ctxp1ic:tblc as u resill(; of :tll c:xcessive arnourlt of degcrtc?ra,t,ivt:heart discti~~e
in this
c:ou11t,l:y.
'Tho list, ill 7'rtbIc: 2 i~iclutlcsthc c:oulit,ries with good vjt,ul stat,ist,ic:s which arc
rcusonably c:omy)artd)le i l l ~.:tc:c, climat,e, (:.ult,ul.e, metlic:al sc~,vic!csarid vjlsl
st,atisl,ic!s. 'l'he omissioi 1s are 'Wcs(,en1 Ckrmany a1ict Fi l.il;t~id,I)C(::LIISC of major
populatioll sl~ift~s
alld
:l,lld ot,her cf'feclt;s from tohew:r, and l(:cla1ld, I,~~srtml)ourg
some c:olonies alld semi-i~ldepei~clelIt
states with vcly small populat,iolls. 01113'
p~\~ertyv-st,ric~Jie~~
I'ort.ugul sccrxls ljo I)(: :ti1 csyeptioll to thct ~-lllc
that, men it1 ot;hc:rh
W(!,sft ? r . ~ l( : O I I I ~ ~ . I * ~ , h~ Sn v p l,l\vp~.mc~r~f.a.1it.v
I'!.~.+.PS t.hn11 i n i:hrl l i ~ trrrJ
\ ; St.5f PS T4111.

Yort,~lgnl'sbud roc:ord is mainly explained by t~xberculosisand Tablc 3 stlows a

difyer~entpic:t,uro when deaths from jnfoc:tive discascts arltl violence are cxctllxded.
Ilctailed study of thu vital stat,istic,s of all these coulltries itldicates that the
differenc:cs (:om pared to t,hc I T . S., in trotal age-specific death r,zt,es c:olild be Jargcly
Th131,1!: 2

I6 co~t7~trics
with a total population of about 680 millions

Ileath ralcs, jrop~tall causes, i n

All valucs :ire for tho pcriod 1047-1949 and are expressed as pr.rcent,zgcs of t h e rates in
t h e United St:~l,csill 1.!)4!).
. -

...

ACE

....................................

..- - --.--- - .- .
..Sex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
....
. . . . . . .

Ausl,r;~lia. . . . . . .
.. . . . . . . . . . . .
13elgiurn . . . . . . . . . . . . . . . . . . . . . .
C:ln:~ti~~
.......................
llcnmark . . . . . . . . . . . . . . . . . . . . .
Nnglantl & Wales.. . . . . . . . . . . .
1'r:~noe. . . . . . . . . . . . . . . . . . . . . . . .
1rel:ind . . . . . . . . . . . . . . . . . . . . . . . .
Italy . . . . . . . . . . . . . . . . . . . . . . . . .
N(:t,hcrli~ntls. . . . . . . . . . . . . . . . . .
New Zealand. . . . . . . . . . . . . . . . . .
IYorw:~y. . . . . . . . . . . . . . . . . . . . . . .
I'ortugttl . . . . . . . . . . . . . . . . . . . . . .
Scotl:~nti. . . . . . . . . . . . . . . . . . . . . .
South Africa. . . . . . . . . . . . . . . . . .
Swcdcn . . . . . . . . . . . . . . . . . . . . . . .
Swit,zcrl:~nd. . . . . . . . . . . . . . . . . . .

Mean. . . . . . . . . . . . . . . . . . . . . . . . .
...

40-44
. .

75
00

-.

.-

---...-

-.

--

59

!I 1
80
!I 1

83

87
91
76
83

68

78

76

98
80
91
52
56
64
13!)
0.3
03
81
78
79.!)

100
78
I (K)
60
72
78

91

78

125

97
108
86
97
00.1

-..
. . .-

.... -- ....

.-

E'

... -- --.

M
..

Y2

84

94

101

96

88
83
91

70

100

93
93

88

91

88

97

89

63
09

65
'36
100
115
85
07
89.7

69
75
63
85
54

81

94
97

86
88
76

!I3

6iJ-64

..- - - -.
1.'

96
06

57
77
66
66

102
63
78
76. S

.-

50-54

68

103

107

104

(32

108

!14.6

99

07
94
68
88
82.7

.----. ..

......-.....

TAUJ.,k: 3

L)cc~thrc~lcs,per 1000, rr.,tron.q wen o j lhret: age gt-ortys i n I'orluyul (1950) and i n thc Ilnilcd
Stulcs (1949)
T,i~ics1 : ~ n d2 give lho rates fro111 all c::Luses of do:rth except infcctivc: :uid parssil,ic
disc:~scsa n d violcncc. 1,i11csY and 4 give tho tfc:~thr:tt,es fro111:ill disc:~scsof the circ:ulr~t;ory
system (Category V1.I i r I~:hc! 1nt.ernatiorl:rl '1,orlg rist or it,c?ms 2.4 :ulrl 25 i r ~t,ho A b r i d ~ o d
T,ist,).
.----,.
.
.. -- -
.
..........................................

10-44

.......

.
.. ...
, .......

...............-..

AGES .

50-54

1 . 1'ortug:ll. . . . . . . . . . . . . . . . . . . . . . . . . . . .

1.2

!I .O

2 . T J . S . A. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3 . 1'ort.ugnl.. . . . . . . . . . . . . . . . . . . . . . . . . . .
1. 1 J . S . A. . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.8
0.9
1 .X

11 .O

..

- ..-.-

-- -.

.-

. ,.-..- -. . --

1.8
5.0
.....

......

- -

60-04

.-

23.3

26.0

5.2

13 .!I

........

or wholly exp1uillc:tl hy di SI'~~CI~(!CSi ll L11(: death rates f rorn degcl lc:rut,ive h e u t ,

clisc:~se. -c;orollsr.y hewt tlisease, ztngirl;~pcc:torjs, c:hro~iicmyoc::i.~.tlit~is,
ulld rnyoc:ardia,l degent!rat,ioli.
W1i:~tis possil)Ie for t.he It;ali:i~is,and tho n'ol*wegia~is,lid l1h(:( ~ ; l l l i L ( ~ i ~ 1 1 ~ ,
:uld so 011, should 1)c posrible for Arneric!s~~s.
'I'htt dat,w,i l l rl':~l)lc2 :il.e tl c:hallc~~ge.

But, i ~ o \ \ :let, I I , ~~ ~ c \ ~ i:L

( :t'c\\f
\ v ( - ) u t , s t i ~ ~ ~f:~(:t,s
d i ~ l tg,l~:it~
l)(;ar 011 t,lw (ltl(!st,io~~
of' 1;llc
i t ~c.itlt\lic:eof' tl(:g:.e~jc.~.;l
t'i\,c: 1lc:art c1isc:~sc.'J'lic~sc:\\/ill poi11t the n.:i,v tc:, o~ic:jji30rnisi11gl i tic 01' alt ncsk 01 I :I. st:l.ics of pro1)le.m~1 x 1 1gi11gf I ' O I ~th(: (~~l(:st,ioli
of t,l~eI 'c'.(~I)JLllil,ioll of' tlic. t,e11de11cy
1.0 tlc:gcllel~:~,tivc
Ii(::~rt (~IS(>:LS(:i ll popul:~t,io1is i o t . 1 1 ~(I(:\ ~ e l o l ) ~ r1,i of'
(~~
;L ip1iysiologir:il 11ygi(:11(~
:iirnc:d at, p ~ . c \ ~ c l ~ t: , i o ~ i

1 ) 11 is :I f ' : i c a t , t l ~i i, (.011111:11.(:(1~ vt.1)

i he:~ll.hypclnsolisof flit: s:inlc3 :igt, j):~i r
1 :~,
]\.it 11 (l(:fj~ it,ei : L I I ~ ~ I I : 1I )(:1*I 01.i;;(11, ~\rtlo~ I : L \ ~ ( >stlrvivc:d 21. ~nyo(::l~*(Ii:~l
i~if':i,t~ai
i 011 1 , t ~I 1I I
I o l i ; ~ v (1)lood
~
sc11111i (*li:~l.:i(~t,t~t~izc(l
1))~ liigh (*liolesterola,ll(l (~;l-t,;~,i
11 I i ~ ) i ) p ~ . oI tI , ( > j

I:I,I>~(:I*

( ~ o ~ i ( ~ ~ ~ l l ~:i~ liigli
- ; ~ t j(o2 l1t~s~, ) ~ ~ ~ t , ( : i i j ~ - ~ ) ~
I ,~;~I )~s,i]
~
~j
,o
I~
i ,(~l:Lo ~ ~ ~ ) ~ (
1 )1~o~)ot,t,iot1
~
of'

the t,ol,;ll ~~l~t11~:st~c~rol

i l l I l l ( ; l ) ( > t , : I~i p ( . ) ] ~ t ~ o l , c :fl~:t(.t,io~i.
i~~

2) Tt, is :I, f:~c.tt,li:~t,,011 1.11('; L I ~ c I . : p(:~.sotl:i

~~(',
:\fllic.l c.cl \vit8litlia1)oic:s,
riiysc;cjc:rn:i,
:111(1 1 1 0 ~ ~ 1 i l ~t,e~ltl
o s i s t.o II:IV(S Iiig11 c*l~olcsl
ci,ol ;1,11(1 1'lii' 01~11~1'
SC'I.IIIII l)(;'('l.~li;il.j
f it's
tno~ltio~ic(l
:11)ov(:. A.rrio11g tl~~cs(:
l ) : i , t ~ i ( ~tl1(:1~!
~ ~ l s I F :l t~~igh
i ~ i ( ~ i ( l ( : ~ ~ ( f i ( kof : I I ~ C I X )
,:c<l(:t*osiea~lclclegetle~*:t.t,ivc.
Jicl:r 1.t d i:ie:l.sc..

3 ) 11,is :i, f':i,~:t~

t,ll:~t,i11 : I I ~ ~ I ~ I : L I e x l ) c ~ ~ i i ~ it(l;l~o~~lI~,~sIiP : I > ; I I I , ~ ~s~l(:li
:;,
:i,k, 11igI1

1 I ? I Y ) ~ ( l j ~ i ,: ~ 1, 1 ( 1t~Iiyr(,)ic~
~ l i ] ~ l ) ~ ' ( ? > i\\,lli(.lt
~ i o t ~ ,])I.O(IIL(~(> 111gl1
I(:\-(>ls
01 i ~ ~ i o ] ( ~ s l: !, I( I~(~] ~ o l
n l l i c ~ t ls ~iI)st:t~lc.es
i l l I he s c t * ~ ~ l:II.(~
r i , also ~ ) ~ ~ i ) c l l ~of
r ~:LIt I 11t~i~os1~11:r.osis.
\;(~

I j Tl, is ;I f':~(:t,t,ltxt, :I.l r l : ~ , i o ~~, ~ I ~ : ~ t ~01'~ {~I ) ( ~

> : I~( ~ lI I ~
I ~ I~, I )~S ~ ~* I (~~ I ;~i IOsI~ ,l~,, (iis
; I~,I,IIo

J~~
I ) I ~ ~ I I (oj'
Y ~: t , l ~ t ~ o t ~ :1,nlo11111,s
n ~ : ~ , l 01' (~liolest
e1.01i 11 t 1 l : ~ i ':1r1( > r y .r l ' l ~ ( i: I ~ ~ I I ~ ~ I ~ ; ~I : S I ~ I ~ ~ I ~ O ~
~ I ~ : I I~:olisisls
~ I I , : o f 40 l.,o 70 I W I . ( ~ ~ ~
t t~,l - t o l ~ ~ s It
t,~
is~t1\1
i~o
I ,JI.> I I ~~
I~
) IJ~
I )I,~ I It h;1!
: I I )~II (I I~
I:;~
I
:I/]of i11is ~~11i)lcsl(;t~ol
I S (loi~i\*(~(d
S ~ O I I I1 11(1 l)loo(l. 'I'll(: ( ~ I I I ) I ( J F , ~ ~ ( ~ I .i Il Il ~ i
1)IIIIII I
i l o c : ~ 11ot crsisi. :ts :t, sinlplc: s o l ~ l ~ i o
01'i ~1 ' 1 ~ ~:111i1
1
clsiel. i.holcst,c~~-ol;
i t i.) c , : ~ ~ , t , i c , ( l i l l
1111 0 I ) I , I ~ ) I , ( > ~(I ~I o ~ ~ - t ~ ~ l c ~ x ~ : s .
( d l ~ o l o : - ;

i ( 8

)I,

the hizarrc ~ i t u a t ~ i oofi ~the alloxan diabetic rabbit fed cliorrnous arnoul~tsof
cholesterol (2) has uxly c:ouliterpart ill man.
'I'wo years ago, total cholestcr.01 and the Sf 10-20 fractioli in tlic scrurn wcrc
compared (3, 4). It nras co11cluded, from suitable mathemat.ic.:al aiiulysis, that
jmportaiit differelice l)ct\\~ccliS f 10-20 alld
thcrc was theii 110 evidence for
c:l-iolcstcl.ol rncasurcrncrlts as cievices to diff~rciitiat~c
t)ct,\vc:cll (4,linic:ally healt,hy
people and patients \\:it11 definite c:orollary disease and tha.t neither measure nras
act:eptat)ly reliable in tiet~liligwith illtiividuals. Morc rcvcllt c:vidc~lc.etc~idst.o
col1fir.m the p~:opriet,y of t;liesc: (:or lc:l usiol~s.
,Jo~lesalld co-\\rorkers (2) have preselltcd rlcw data, this time 011 ttic: Sf12-20
fruc:t,ion, and 1iavct rtrguccl for it,s supc:rior.it,y to total (:holesterol measurement
from compnrisons mr~di!on 550 mcu, illc:luding l 5 f i me11 who had wrvived myoc:artlial ilifarctioli. l'hc w~lxlysjsof thc data sho\vs, act,ually, that; there was 110
st.i~t,ist.ic.nllysigl~ifi(:tllit,(iiffcr(:11(*(:I)c;t,we(:i1 the Sf 12-20
the choleste1.01
hetweeli "iiormuls" and "irlfarc:t,s" in tho
messuremelits ill the discr.imj~l:~tjo~~
331 Iri(:ll frorn 41 to 50 ycars of agc:, though, if we accept cerlail~:rssumptiol~s,
ill thc 219 mcli from 51 L o (iO yc:~rsof agc the Sf12-20 xrioasurcrnellt mtty havc:
:tclhieved sorncwhtlt t)et,t,crdisttrimi~ltlti.on.
l'l-ic c:omput:~tio~l
made by Jo~iesci a1 (2) ttssrrmes that the r.elt.ztiol~shipis
r.t:c:t,ili~loa~*,
that is who11t,hc Sf12 20 or t,hc c:llolesl;erol level is tlouhled the degree
of itssoc:j:~t,iorlwith illfarc:t,iol~also tends to be doul)letl alitl so (.)II 111) alld (low11
t,he sc::lle. 'l'here is I I O evidei1c:e that i,his assrnuption is propcr and thc: c:omput,a,tiolls of I~jser-ialc:orrclat,ior~c:oeflicticn ts may, therefore, bc illvalid.
Hut,, for t,hc momc~it,,let, 11s :~ccept,t,l.ic?ass~mpt~ion
atld ask h.ow good is the
c:omputctl (1isc:rimi11:~tiol1.'l'he most fttvorablc ~~csults
o t)t,ained wit11 the S r
12-20 rneasureme~~
t. \\rerc.: wi t,h t;he younger rneli where s biscrial c:orrclat,iou c:oolfic:iclit, of r = O.(i2 & 0.07 ol>tailictl l)ct,wccllthc: prttsc:nc:e of' illfarction and the
coilc:cnt~.ut,iwof Sf12-20 i l l the scrurn. .Totlc:s cL a1 (2) argue that the relatio~ishi~
\vould be eve11 (!loser.with idctully perfect methods :.itid that t h (:orl-(:l:it,ioll
~
tlwy
f oulid is ''stitelirla,t,ed" I)y errors in measlircmc:ll t,. lio\vcvc:l., we itre ctor1c:el.lled
about \vh:~t, t;o t:spec*t \vil,h l;hc itc:t,ual methocis f i t hnlltl a ~ i dthis is itldiva1,c:d
from t,hc: :~(:t,llal<:orrt:lat,io~i
(tocfK(~i(:lit,of O.fi2. Wl1:~tdoes this meall ill t,crms of
protlicat,i~ig~vhicth l~lootlscome froin c.liliic:ally hc:ult,hy r r i t : ~ ~ ?'I'his is readily all.-;wereti i l l t;errns of' t,be jlldex of forecasling efhc*iellc.y.'l'sl)l(: 4 srcrnmarizes data
ot I t,h: forcc:ast,i~lgcl1ic:icllc:y ir I t,l-iisrc:g:ird.
'l'he jiides of for.c?c*ast;j~lg
c:fi ic*ic:llc*yshows the; pc,rc:clit,agc1)y whictll it is possible
1.0 r-ctlr.~c.c:
the elB1.ol.t:h:l,t. \vollld pl-evail if \ve tric:d to predict, i l l the :~bseilc.eof ally
~ ~ o r r ~ ~ c l r tl'hc
t , i o ~c:orrclttt,ioli
.
(1ocflic.ic:tlt of O.(.i2 means all illtics of fort:(~:~st;i~ig
::ff c.icllc*yof al)out, 21 pel- c.el)t,.(,~ollsitler1000 rnotl, half of' whom a1.e c ~ l i ~ l i c . a , I I ~
ll(:aI ttiy, t,hc ot,l~:rs1)ojt ~ gvj(,t,ilns ol' ~r~yo(::~~r~li:~,l
iilf';~~*t~t~io~l.
M(:r(:ly gi\-(;11a list
of 1000 c.otlc? liamcs a11t:li,hc i~lforrnst,io~)
that hidf of these pert;zill 1.0 me11 \vi t,h
jilf':~~.('t.s,
g~t:ss\\-ol.k
t h e eff'ort t,o c.l::bssif'y(,hem \\-oul(lI)(: purcly r~t~ldorri
itl~dt.lict
result \ v o ~ ~ l bc
t l 500 cAorrcc.tclia,g~losc:sttl~tl300 er.ro1.s. 13111 if Sf 12-20 rr1easul.c.mcllts \\.c;lscrnatlc tho rost11t ror~ltlhc: irnp~.ovedby ~nakillg2 1 pe1' (4~111.f'ewe~.el6I-OI-S; o~lc:c.o\lltl h o l ) ( ~
f 'ol ollly 3!)5 ch~.r.ol.s
j~l~t.ei~tl
of 500.

121

ANCEL KEYS

I t is illuminating t,o apply this to zt more realistic situatiorl as i l l the last c!olumn
of Table 4. Take the problem of diagnosing the trend toward infarc:tion before
the infarction occurs or the likelihood that a given individual is specifically
threatened. If one out of 10 persor~spresenting themselves for tcst i s actually ,qo
thrcatencd and if such thrc?atencd persons are really iderlt,icttl in regard to blood
chemistry wjth the me11 who have had inf:~rets,the likelihood of deciding which is
which, and therefore of being ablc to give the right advicc, would t)e onc chance
j11 ten t)y sheer random guess\vork. With the aid of the Sf 12-20 measurcmeut
with men aged 41 to 50 years, the tliag~lost,ic:ian'sjudgement would be improved
by 21 pcr cc:nt; he would make 21 per ccnt less than 9 errors out of 10. This is
almost exactly the samc result zts would be cxpected with tot.al cholestcrol xneasurements from the data of ('lertler el a1 (5, 6) in men ulider 50,but ,Jolies et a1
(2) arc it littlc less suc!cessful with cholt!sterol. It siiould be ot)served that .Jones

L)iscriminalz'on liel~oeenhealthy men and patients wilh eoronnrg rlisease (in/ut.cts)

b?/ 1~111-nccnlrijugalnnd tutu1 cho2csterol measurements
"r" = biscrjal oorrelation coeficicnt ;"Index" = irltfex of forec:~stingefficiency;rel:ttivc
value (R.el. Val.) indicnt2csthe chance of assigning :L correct di:tgnosis to fi mctn with coro11:1,rydisease in LZ 1)opu131ioni n which it is known tl1:~t10 pcr cent of the mcrl havc coron:wy
discase. I1;~t:tin lir~es2 : ~ n d7 from I(eya (3, 4) .zft,crGertler et :~1. (ti, 6) :tnd Gofm:tn et ~tl.
(7) ; lines 3-6 from .Jones at al. @).

__.

.
. .

.
.
-.----

ITEM

I.

- . -1. No Lest or ~neasurcn~er~f,.

...........

__ _

.-

lNDU

.
.
-

R.11..
VAL.

2. S f 10-20, 51-,50 yrs.. . . . . . . . . . . . . . . . . .

3. 8 r 1%.20, 41-50 y rs. . . . . . . . . . . . . . . . . .

4 . S f 12-20, 51-60 yrs.. . . . . . . . . . . . . . . . .

5. Cholesterol, 41-50 yrs.. . . . . . . . . . . . . .

6. Cholesterol, 51-60 yrs.. . . . . . . . . . . . . .

7. Cholesterol, 31-50 yrs.. . . . . . . . . . . . . .

8. 1de:il test. . . . . . . . . . . . . . . . . . . . . . . . . .

- . - -,

*-

- .-

.- . .

... -- . .

et al (2) report Ear better results with the Sr 1.2-20 mct:tsurc:rne~lt, Iharl werc: oht.uirietl l>y<;ofrn:~n cl nl (7) with thc 81 10--20~ncasurt:me~it(3, 4).

It, secxns prol)tll)le that; something like this disappoilltjng situatio~lwill (:ontil~uet,o I)(: the cusc with :ill of the i t,c:ms of blood alialysjs r low pt.oposec1 or which
may bc proposcd to i~ldicttt,c:the development of atherosc!lerosis ~tndtho cjt~liger
of aoroll:),ry diseuso :tnd infttrctio~i.1 101~(c:ouldit be otherwise? A singlc sumplo
of 1,lood ~.cp~.c:sc:llt,s
o n l y a partic:ulal. moment but the pat,hologic:al, proc:oss is the
of the opc:r:itio~ls of the blood fac:Lor (or fsc:tol-s) over many mo~lt,hs,
~*esult,;tt~t;
years or dec::zdcs, plus all tho othw facttors which may he c*oncer~~ed
-t;hc in(Iividu:bl7~
pc:culinritics of blood flow, tirt,c:rial \vall and otklc:r fac:t,orsyet urtk~iow~~.
Rut this great, Ijmitatiol-1for ilidjvitlual c:lirlicsl applic:rttdoii should 1101, prc~rc:~it,
~.(:c*ogl~it,ion
of the favt that statistit:ally, dealing wilb groups of people, thc
mcasul.emc~ilt,of' any :trld all of tho items - -t,otal cholc:stel,ol, gianh molec:uJ,t:s, ett.
:..
.. ...C........, f ....- 1..s:-.. ....... a...:
....4.. ..t d l . , ..-.,I-.. ..r A t? A , .
:

.... L : l Q . .

..1.

.-

1,.

-.,.I.

attempts a t jiidividual diagnosis or prognosis but they havc high predictivct significance for groups, cvcn quite snlall groups. In about 96 out; of 100 samples of
only 10 coronary patients the average measurement would be higher than thc
average for clinically healthy men (Tat~lc4, lines 3, 4, 7). Other things being
equal, there seems to be rio clout)t that high serum levels of cholcstcrol, etc., are
undesirable and the higher thc valucs the more undesirat>lethey arc. Hence there
is evcry justification for devoting great effort to discovering what determirles
the level in man and how that level may t)c controlled.
CllOLESTEltOL IN TIlE DINT AND IN 'I'HE 13LOOD

Because of the limitations of both space arid data the rcrnaitinder of this discussion is restricted to the tots~lcholesterol conc:cntration in the blood serum. The
serum cholesterol level is thc resultant of scveral factors. All animals, illcluding
mall, ~yrithcsizecholestcrol, rnnirlly in the liver, and eliminate it in thc bile arid
by chemical degradation. Tf there is cholesterol iri the food it may be absorbed and
so eriter the balance picture. 13ut whcn exogenous cholesterol is supplicd the
synthesis in thc livcr is suppressed (8,9, '10).Some animals, such as the rubbit.
and the chicken, have little or 110 dictary experierlce with cholcstctrol aftcr weaning or hatching aild have little capacity to tlcstroy or otherwise eliminate j t when
they are fed large amounts. Others, like t,hc rat, the dog anti man, havc much
greatcr ability to handle c*holcst,eroland are relatively unslfcc:ted by dietary
admirlistrntion.
The attempt to cxtrnpolstc to man the findings from cholesterol experiments
with ra1)bits and chjckens can lead to sbsurtliticts. Thc typical rabbit experiment
involvcs a diet, c:o~lt,aining2 per cent added cholcstcrol, or some 6 mg. of cholesterol per Calorie. 'l'his mcarls 15 grams of cholesterol in a human diet of 3000
Calories, an arnount ahout ten times higher thall it is possibb to attaili in any
habitual diet of ordinary human foods and fifteen or twenty timrts what is (:onsidered n high-cholcstorol diet for man (11). And it must be emphasized again
that marl is very different from the I-abbit and t,hc c:hicken in his melabolism of
choleslerol.
I ri marl and animals only a portiou of orally i tlgested cholcstcrol is al)sort)~(l.
From esperimcnt,~with <?I4 labelled cholesterol ill tho rat (12) and 113 labelled
c:holcsterol in man (13) it seems ~)rol)al)l(:
that somethirlg likc 20 to 50 per cent
of cholcstcrol iilgcsted i n a fat vehicale ia sbsort)c?d from the gut. 13ut sn(:h absort)od c:holesterol does iiot simply add to the cholesterol a1rc:ady prcsent in thc
t~loodand the tot,:~Ioolic:c:llt,rat,ioxl in l,h< blood rises vcry little, eve11 with massive doses.
From 20 csperime~ltswith youiig mctn i~lgcatillg5 to 12 grams of (:holesterol
in a fat-rich meal it was fou~idtho mrtxirnurn rise in thc t~loodcoiicentr.ation occurred from 3 to 10 hours liltel. but the vsluc at 4 hours was a t or ~l(:;trthe pc:sk.
111Table 5 are the sll~nmarizcddata from esperirncrits or1 73 clinically healthy
men ~vhowere givt:ii a breakfast of toast
t)ut,t,t:rand coffcc wit,l-1c:rc::Lrn aild
scl.ambled eggs in which 10 grams of pure c~hol(:st,crol\Irere c~nulsificd.'L'hc? rncarl
risc of 3.!)5 mg. pel. 100 ml. of serum (*orrespondsto : L I ~ilicl.ease of a't~o~it
250

126

ANCE;L KEYS

mg. ill the total (:irculat,ing blood or less than 3 per cerrt of tho i ~ ~ ~ e scholested
tel.ol. &forcover, ill 18 t o 30 hours thc serum level no loligcr sklowvs any trace of
such a s i ~ ~ gmassive
le
doso.

Continueti foc?ditl.gof rnuu with diets contai~~i.ng

20
or more grams of added
cholesterol daily c:ventually produces a rise in thc scrurn level of elderly xnon
(Id), bnt this is trivittl c;ompareci ~viththe change in rabbits or c:hic:kens fed an
ecluivalent amount. 'l71e tluta summarized in 'rat)lc (5 show how greatly mail differs from othcr a ~ ~ i r nspc?c:icts,
t~l
particularly the ra111)it and the chicken. I t will
also
observed that man on t~l.1ordinary diet has a higher c:onccntratjon of
cholestcrol in the serum th.an the other ar~jmalslisted as well as othcr animals
sttltlicd on normal diot,s; tlicsct irlclude the (:at, (:ow,goat, guinea pig, horse, and
mouse.
Hor1ic:k a ~ ~I-Tavel
tl
(19) observed that the maximum effect of dietary cholesterol j11 the rat is ac:hicvc:d by dicts contaitiniug al.ountl 3 mg. of cholestt:rol por
Caloric?ttrlcl that further increasing this massive dose to heroic proportions has 110
effect on t,hc 1)lootl.The tlstu w~ggcstthis rnay 1)etrue of man tklso. Tn any casc, thc
Meuns nnrl standard deviutz'ons jor sclbum total cholcslcrol concenlralions, in mg. per 100 nd.,

i7~73 h<eallhyyoung nrcn l(;.fo~earr.d 4 hours njtsr in,!jcslion of 10.7 grarris o j cholestcrol in

a fat-rich breakjast

..... - . . -. -. . .
.mAF:

-.....

..

'I3efol.e ingcsLion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chungc after ingest,ion. . . . . . . . . . . . . . . . . . . . . . .

......

-...........

216.85
+3 .!I5

S.U.

.- ..

A36.22

kll .09

problenr is not what may be the result of trernel~dousdoses over limited timc so
~nuc:l-las the effect of prolonged ingt!stliotl of far rnore motlcrate amounts.
111 the United Stat,c:s differcrit, pc:rsonx havc:: greatly differellt htibits in regt1r.d
to diet:~r.yc:hol(:stcrol. Some persoils never drink milk, eat c , rrs
~ c , or (:o11~11nle
tnor(:
than millute mounts of l,utt,c:r, ice c:rearn, c:hc:c:sc or fat rricat. Others, ho\vc:vc~~,
regulltrly c;o~lsumeseveral. eggs a day and use large a~riou~lt~s
of meat :tnd dairy
products. 'l'he rallgc: cllc:ou11telct;1ill a populatioi~sample may I)(: from less t hall
100 mg. to us muc:ll
1 ggm. of (:Iiol~~t(Tol
ill t,hc tl~ilydiet. I3ut sx1,e1~~ivo
surveys
of the serum c:holest,arol c~llcentrat~lqn
i l l ilrlvjdua1.s of difT(:rilig cholcstt:rol
i~t,ali(:
c.:ol~sisLently.fail to show u rclatiih~I)ct,~rcoiit,hesc vlzriables.
Our surveys on c:'lil~ic:allyhealthy me 1 of the upper eco~lornic:1)r:tc:kot ill the
r i
1\\rill (:ittics have (:overed scvc:rzil hund *cd rni:li ill c:at:I.i of five sl~ccesuivcyoitrs.
Each yeax. wc liuvc: ot)tuillctl ~lcgativeresu I ts sjrnilslstro thowt rcpor tctl for the
filxt yc:aa. (25) and ctolllirxned by othcrs (6, 20). Perhaps the most sigl~ific:ttlitfiliciings arc those obtaj 11ed on xncu persist,cnt,ly ost~~crnc t,l.lcir dietary cholcstlc:rol
1l:tl)its a11c1o11 me11 1 1 r 1 1 0 (!hanged their die1,al.y c:liolcstc~.olirltakcs. T:hle 7 givc:s
:L summary of tdrct tiat,a 011 (i3 middlc-sgctl me11 \\rho were persishen t;ly i?st,rc~nc.
ill
thcir dietary c:holcst,erol 1lul)itb wh~11
stutlicd over :z pcrioti of ~ w oyears. It in
cal(t;l.~. t.h:tt, the mc:11 who \\-ereal\va,ys shove khc: 8Otll pt:l.c:o~lt,il(:
i l l tIict,:~rycholcsA - .

terol (lid 1101, at. ally lime, h:,~vch i g h - sc:rurn values than the me11 who wc1.c al\vays I)olo\\~th(: 20th p(:r(~.~tlt,ilo
oC i~ttilce.
'1'al)le 7 also gives 1-1 summary of tlic da1,a 01) 4.0 men who made rnt/l.kct-l ch:~~~g,.cs
i l l thcir diet,:zry (*holesterol iiit~lk(:s,i l k wine (rases bec.ause of i~lteredtlomcstic
st,i~t,us,i l l ot,hersi 11 u c:onsc:ious effort t o chatigc thc cholcst,crol in.tak(:. Pl.ixnal*ily,
thcse mcli c:huiigcd their. c1i~t~ar.y
huhits ~vjl,hregard to eggs and changed fl-om
TA13T115 6
-+lcnn sf:r.rrmclr,olc,s~crolrcsponscs to choleslcrol feedz'ny in diJ'er.e*I

specic.s

Thc dict:~r~'
~h01cstcr01V:LIIICS ;LI.(: rough :~~prosirn:~t,ions
to c~l:tl)lc1;hcm all to Ijc cs-.
~)rc:snctl011 1,ha s:mc SCILIC of mg. of chol(:st.c:rol per t1ict:~ryCalorie. References (referring tto
I i11e ~\umI)crs) : 1, 10, 11-(~001i : L I I ~T1lo1r~so11
(1 5) ; 2, 3-&?8t,t:11 : L I I ~Silk)o\\-itz
~
(lo) ;
3 , 5 --lCocll):~rtl,U ol(:~~c:
:.~ntiKalz (17) ; 6-S1:;unlor and Matz (18); 7, 8-liorlick tirltl 1I:~rvcl
(I!)) ; 9-Rpcrry i~11c1Stoy:~i101'f(20) ; 12-G.recllt)crg : L I I ( ~Rinchurt (21 ) ; I3 .. ,Moses (22) ;
14.---Stcillcr(23) ; 1.5,J 6 , :17-Messinger., 1'orows:twska : L I I ~SIOCIC
(14) ;18 -0ltey :~ndSten,:~rt
(24).
.....

. .

-.

...

--

-.

IIUIIAlltlN,

'X

CII AXGE

Final

...- .-.

. . . . .

149
(145)*
141"
(100)
(100)
116
(59)*
(.FA)*
59
70
$6
175
2212

J.6
5-8

25
J. 5
5-15
22
22
?
4

5
29
16

235
254

6
7
0
r1.t

-.I1 050

+200

+580

550
J 69

-1- 450

+30

+dl6

+10s

113*
12!)*
163
222
27 1
218
223

$139

+I76

+217

I.JX2

2!!

"slight."

-t1s

272
287
276
167

238
154

1.
. . . - -. .-

1720
4-30*
(35!)*
J 30

+1:3

+lti

+8

* Wtlole bloo(l.

t (~hol~:st,crol
i n dricrl egg yolk, ~,owdcrfctl. This ])owtlcr :11so ~)l.ovidctl: ~ l ) o l ~20
i.
~ 1 1 1o
. l'
.,

. .,

. . . . . -... --.. --.......

. .

10 Mr..

-. . . . . . . .
Colrtrol

WEEKS
---

I.. Jl:J)l)it . . . . . . . . . . . . . . . . . . . .
2. 1l:~l)l)it.
...................
3. Il:~l)bit,.. . . . . . . . . . . . . . . . . . .
4. Clliclc.. . . . . . . . . . . . . . . . . . . .
5. Chick. . . . . . . . . . . . . . . . . . . . .
6. C h i c k . . . . . . . . . . . . . . . . . . . . .
7. lht,.. . . . . . . . . . . . . . . . . . . . . .
8. 1t:lt... . . . . . . . . . . . . . . . . . . . .
9. lt:~l#.
......................
10. It.:1t... . . . . . . . . . . . . . . . . . . . .
11. (;uiuo:~Pig. . . . . . . . . . . . . . . .
12. Monkc.v. . . . . . . . . . . . . . . . . . .
13. M a t ) . . . . . . . . . . . . . . . . . . . . . . .
14. M;LII... . . . . . . . . . . . . . . . . . . . .
15. M:LII... . . . . . . . . . . . . . . . . . . . .
16. M : L I .~.. . . . . . . . . . . . . . . .
.. . .
17. M:LII..
.....................
18. M:LII.. . . . . . . . . . . . . . . . . . . . . .

MC. P):Y

.......

..

...-.-......

l(!(:il~llit i .
r

I)ut,ti(:l. atld Jat-d (.(I vaaatoai)lofats, (avice versa. I he rcsrult was 1:trgc :c!.hsl~gci l l
cholest.c~.oli lit:tke wi t,h lit,tle ox. 11o ( * ~ : L I I ~i lcl (:alorics, i11 tot,al p~,ol,(:i~.~s
ox. i l l f;ot.:tl
fa1.s s11(1ti.)(:I ~otfy\\:cight,s \\:crc p1':~(:ti(:ally~:o~.~stallt,.
Hcri: agi~ill,US i l l the s~~l.vc:ys
of moll oli c!o~lst,ailt,dic:t,s, t,her.e \\I:LS110 t,~.ac:c:of a11c:lTc:c:t oil the serum coi~cc!~i.l~i.al,iotl of total c:holeste~.ol.
111thc c:ol.llaseof this wo1.k jt wax poswit)l(: t,o ~ t ~ ~17
i d11101.1
y who, t,hough (:lilii(~;~lly
\\:(:11,chhu~lgc:clto 21 lo\v-c~hol(:st8~:rol
tlic:t, witohmoclerate restl*ic~tioiiof all fxt,s. R l o s t
of t,hcsc! rnoll \vc?lSrtf ollo~vj~lg
the :~civicr.eo f thcil. pct~-sollalphysic!iutts who :id\-oc::zt,c:d

]0w-(:holcst,(:rt,I dit:t~;tnd

ftlt

rc:strjction for all xniddlc-aged mcli. Prior to thc

.diet ahallge the mcall aild sl:t~ldartlerror of the serum total cholerterol concelltrstioll was 242.2 rt 14.0. Aftw 3 to 7 moliths on t,hc: restrictecl dict the valrics
werc 229.9 & $1.9. l'hough this diff'erel~ceis not statistically very irnprcssivc, it,
\\rasimporta,nt in thc (lcsigu of the systematic: cxpcrjments to 1)c rncllt,iolled 1)elow.

Means and ~ t a ~ ~ ( errors

j ( ~ r dj ~ SrC ~ ~ I I ~IolaE
T ? . cholesto.od, in nlg. per 100 7td., i n clinically hcaltl~y
middle-ngcd nLer,, lrlnlched as lo age, v ~ i t h trbitually diJerent cholesterol inlakcs
The diet,:~ryint:tkcs rlrc: indicat,r:d 1 ) the
~ percent,ilc ranks of Lhc: Inen in the t,ot,:ti s:~rnj)le
of 300 men of t,hc upper e c o l l o n ~ I)r:~c:lict
i~
i n tthc Twin Cities.
..-.

I
NO. MEN

-- . . Intake Perccritile
.. .-

00
I0
60

17
-

45
.-.

Intake Pcrccntilc

Sct-urn Conc.
.--

35
51
23
.

- . . .- .,..

--

SECOND YEAR*

FIWST Y ~ A R

--

..-.. .-

-.

214.7 5.0
240.6 f 8.8
250.1
7.1
259.7 & 8.3
.

. --

- --

. ..-..

Serum Conc.

---..- -. -. .. - . - ...

!I0

246.0 =t6.7

10

211.0 & 10.3

250.3 & 6 . 7

252.5 + 10.2

25
70
-..--

..

--...--.. . - . ..

* Corrcct(>dfor incrc:tscd r~g(:froln ( I i ~ t t i~ l f~<(:YsC l f 111. (30).

I,i]<eolll(:rs (27, 28) \re had c:o~isist,erltlyo1)scrvod a markcd dcc:r(:asc: in t,hc

serurn c:holcsterol c:ollcetlt,rt~tionill hypertei~sivepat,icrlt,s when treatsd I)y srll)sisterlce o11 t,hc rice fruit diet; (29). St,uclic:s werc: tallenmade oli 21 11~1.lnot;ensivc
xnon befon: alltl drlrilig otle rnoiith 's S I ~ ~ ) S ~ S ~ C IOI I(I: Cit modified rice-fruit diet ill
which salt W ; ~ Sallowctd as well :ts the sui)slit,utioll of pot,at,ocsfor sorne of the rice.
The result,s :ire su~nrn:~rized
ill 'r:hlc: 8. This dictt,, (:oiltai!ling 11 o c:holost,erol and
extremely Jit,tl(:fat.- -.a,l)out;I t,o 1.5 pc:~.(:elll of the tola1 ctalorics. --immeclialely
iilitiitt;cs a tlec:Iilie i l l serurn cllolesterol so that; i l l 3 weeks the uver.:ige is ;~)~oi.it,
70 pel- cent of t,llc:v:~111(:0 1 1 all ortliliary frcc: did, (30).
Mort: prolollRc(i (:xperirnollt,s were can.ict:l o u t oll p1iysic:ully hc:~lt,hysc:llizo~lhrellicme11 ill all jsol:~tetl rnet,ai)olisrn t t ~ ~ i l d i lat
~ gthe 1 1 a s t , j 1 1( ~M~i l ~ ~ l e s o ~ ; ~ )
St,at,eHospitjs,l.111 t,he firstseries of expcrimcili;~21 rnon were stnclicd ill c!ollak)~~.itof u moiith o:~ch
t,ioil \vit,h I>r. ,J. '1'. Atldel-son, for eight rnonlhs of :.~It,erl~:tt,ions
or) six ctjet,s of c:orlst,:ll~t,c:ttlol-ie,~)rot,ciii,miilcral a ~ l dvitalnil1 c:olit,cnt,i)ut di.fTcri n g j11 cholest,c:rol %lidill t,ot:tl f a t (:~xlt~(:llt,.
The l)it~i(:diet w:ts it modified ricefruil,(Ii(tt,simjlar. t o t,h:~t:~rl(:llt,io~led
also soin(: egg \vliit,(:s,
d)ove t ~ l l t ;colll;ail~il~g
fat-frcc: 111.r:ada,r~tl1)oiJc:dgrceil veget:it)les, to ~vhjch\vt!rc :~ddedveget,:~,t)lefats or
sugu~.
tl.~ldjc!lly t,oIceepc:ulorics coii~t~al~t,.
'l'hc: c:liolcst,ci.ol w:ts atltl(:d ill the Sol-rn of
c:gg yolks, (,he fat; c:ollLellt, of tlic:sc sul)st,jt~itjilgfor :LI~ oclr~ivalellt:~moiiritof
fal,. Tllc: Inell p,.oc!ceded through t,hcsc alt,cl.nat,iollsi l l diff(:rcttlt,ordet~so
veget;~.t)le
possiI)l(! c:llnlllJ:~t,ivc(:(Tec:t,s of p:trt,ic:uIttl. d ieG seclueiictes worc elimi~la.t.~ed
i i 1 tho
:vel-:l.gesel.rlm c!hallges sliowl~ill '1'aI)le !I.
Tal)lc !) c.lc:t~.ly shows a pro~lou~lc'cd
cfTc:c.t of dic:t,ary (vcgctJ)l(:) fat, :md I lo
signific.u~~t.
eSf(:c.t,of c:holest,s~.oli l l t,llc i.itllg:.(:0 1.0 (j5O mg. pol' clay. C:ornp:ll.iso~l

of the scxurn choleslerol vslutw 111thc third ml(i in the fo~lrt~h

wecks 01)eaah diel
dist~losedrlo sig1iific:ant dif'ferellcct, jr~dicati~ig
that thc diet effect wits sul~st,ar~tially
clomp1etc.d ill 3 ~vceks.Collc~ordu~~t
results ill studics on 3 mcll have t,ct?ll reported by IIiidreth et a1 (32).
Further evj(ittxlce on thesc cluestiolls wtis ol)t,r~illedi l l an experimel~tof 32
weeks' duration on 20 xc~hixophre~~ic:
mcll similar t,o those rno~ltiolledatlove
(31). The xneli, rttllgilig from 27 to 4(i ycars old, were paired of?' i l l 2 groups
matched 2s lo agc, relative body \\-eight, me~ltitldiagnosis a11d ha1,itual 11hysic:al
:~cat~ivity.
l ' \ \ r o diets were devised, t)ot,h providing 3400 C:alories, I10 gm. of proTAUI,II; 8
L(iel.tcnlLola1 choleslerol concentrdiolc, i n w~y.per 100 ~ILZ.,
bejore und ajtc+r.? ~useksoj,~c~/)sisfer~~e
on (L tnodijied rice -fruit diet

Mcsn v:~lucsin 21 ~~c)r~not.ci~sivc

rnon, :~gcd22 to 45, grouped :~c:cordingt o thc: co~lt~rol

l en with marked idiojt;~thichygcrscrunl concentr:~t,ion,the 1:~stgroult inclutling s c v ~ r a m
cholestc~.olemi:~.
--
.

NO. OF MEN
... -- .

........

.-...............

20

417

252

33
35

in ~n!l.per IOU
aubsistertce f o r 4 ?ueeks on conlrolled diets

.
.
.
-..... -...................

S C ~ ~ O I1ol~Z
L
choLe~le1~01
concentralion,

w r , (;M.U A ~ L Y
...................................
72
15

--

..-. . - .

..-.

...

- .-

All E s p t s . .. . . . . . . . . . .

.---.

--.

...

-.
.----

.....

........

-21

0
.-.

-46
-41
,--

.
P
.
.

-.

i.n, 21 ?)Len r~jlcr

~ 1 . 1 . EXITS.

-27

-24

-63

...

rrll.,

114

.........

- tj4
-61

600
..

......

1GO

'%I

.......

160

.....

.......

%0()

CIIOL. MQ./J)AY

....

CIIANGX IN

.. ,

- - -.

230

--

.....

APTB:lf

7
7

dlcan chan!les in
.-

..

ICI;.l?ORE

. . . -.

I
o
I

....

....,.....

........

...

--

....

teiils a l ~ d700 mg. of chol(:ster-ol but ill on(: (high fat) there were 1:10 g ~ n o. f fat
alld ill thc other (modcrate fat) thelac were 70 gm. of fats. In t)oth diets th(: fats
wcrc 90 per ccrlt from si~irnult~rld10 pel. c:r:tlt from vegctul.)le xourceu. Orle group
c:hal~getlfrom the high to t,hc model-ut,c:fat, dict, a ~ l din 4 wecks there was n meall
dec~.eaacof 21 mg. of c!holest,crol per 100 ml. of serum. 'l'hc other group made the
revers(: dietary change czl~(.i
the result, was a mean increase of '2'7 mg. of c:holestcrol
pels 100 ml. of sel-urn.C:oilt,iuuetl sut)~istel~c:c
on l;hc:se contl-oileddiets for 32 weeks
ctuusecl rio sigllificallt, furlher change i l l the scrum :tud Chc difSerc11c:e bet:\\-eelltthe
serum (,holesterol values oil the two diets \i7a..mai~ltailleci.
111 all of t,hc: st,udiesme11tiolic:d itbovc t,he sul)jccts, like the gelic!ral pol)ulutt.ioliof.'
the ( !~lit,edKl.at.es, 1i;~dli\-cd n.11 t,lieilhli\.os 1.0 the t..imc: of ~l!u(.ly
011 c1ieI;s rbe1a,-

tively high ill both t o l d fats a l ~ dcholesterol, alld t,lic experinlelltal fitlclillgx refer
o~ilyt,o relatively short pcl.iods of ehange from this life-lollg pattern. 111 order t,o
discover relat,ioliships wilh grossly djfterent life-lollg diets studic:~w:rc nlade 011
c1iliic:ally heal thy me11ill other coul~trics.
I he st.andard of cornp:viyoll for such studies are the 1.esu11~s
o11 I492 c*lirtically
heal thy mcll ill Mjlillcsoi,u w surnrnarized ill rl':~t)le10 (33). TIicsc stal~d:irdsare
r etropolitail areas i l l t l ~ IJ~iit~cd
t
Stgates(34).
:~Isovalid, app;tro~itly,for o t h ~ m
The age trelltl, most* c~learlyshow11 ill t,hc c:olurnr~sof per<:e~lt:tgesin Table
10, is strikitig slid sl~ggeststhe: age t,rcnd c:ornmol~lyo1)scrvcd it1 the i~lcidel~c:e
of coronary artery discuse. 111 the follo\vil~gc o m p a r i s ~ ~wit11
~ s men ill other c:oullt,ric:s this age trc~idis of part,i(:ular int,c:rebt.
r'l

r r ~ ~ 3 10
~ , ~ c
No~.rrml" ou111.c.sjar. Ihc total cholesterol concenlralz'on, i n ~ I L ! , .7 ~ : 1r00 ml. oj so?cnz,jar

c b i ~ ~ i c c i healthy
lb~

rrben irc M i n ~ ~ e s o l a
T11o (1:tt:~r(:for
1492 nien g:~ir~f~illy
o<:(:~ll)i(;(l
irl ~ 1 0 1 1 - 1 1 ~ i t t l~rorlc
~ i ~ l i l l l,ii(: 11~:1,ropoli
t ~ r
: L ~ B : L of M i ~ ~ ~ i e a p o:~tld
l i s St,. l':tul. Means : ~ n ds(,:tntl;lrd dcvi:l.l,ions (S.D.), :tnd m c a ~ l sos])I.CSSC~~its ~ ) ( : ~ c o I ~ ~of
~ :tL, l~i ~(111(::~11
:s
i ~ ilgc
t 25. T1ic:sc: vi~lucsrcfcr l,o xric::isurcrno~il,susing
re:lc:(;jon with t,hc 13lool. cstr:~c:bof 1)loods clr:~wni r ~l,he 1)assl
thr: Li(:l)(:r1rl:~lln-J3~r~l1i~~d
sts:tt8e;for c:tus:tl I)looci s:~mplesthe vitlues should be incre:tseci by a!)out#5 per cent*.Wi t,lr t.lic
Sl~crry-Schocxihaixric:r
rnc!i;hod t,11(: v:t.lucs sl~oul(1
IN: :~l)out5 per cetlI Iowc:r, (33).
I1

..... -..- ... . . . . .

....
AGE

. .

.....

%!

M E A N S . 1).

AGE

..

173 + 31
18.1 Z t 34
1!)5
40

$14
100
3.06
100

211) & 39
236 rt- 37

119

+
200 + 4 3

128

60
55
BO
65
70
76

M K A N S. 11.

--

218 f 45
266 f 48
253
84
237
34
2'25 & 42
212 tit- 37

...- ...

-.

111cvmp:trisolr wit,h 1.11(: I111i1,cdSt,atcs thc: diet ill (:rc::tt, l3rj tail) is ilitcrest,i~~g.
Thc :ivcrn:Lgef : ~ tc.ollsumpt,io~lill Hrit,aiu is high, though lot, so high a,s ill thc
TJ1titt.d Stutoc:s(:tl)ollt 1 1 pelb(:ell{,lo\vel ill I3rjt:iiil) :111d the putte1.111v:zs i ~ o irnt
~Oltrit~ltlly
d11r.iI ~gWOI-It1W:tr Tr and st~l)se(li~e~lt.
~ht~11gcd
y(:ars. 13ut t h : ;tv(:ri~gc
c.holester.01itlt,uke is rn11c.h lowcr as ili(;li(:at,c(if>yt , h fit(:{)
~ i,hat,the per cupjt,;~
C~IIbrirnpt,ioll of eggs, rnu:tt, :tilt1 nlilk, ;is pt!rt:cr~t,agesof that, i l l ttlic: I Jrlit,c:d St,ut,c:s,is,
resp~x*t,iv(:ly,
32, 68, ; L I ) ( ~ 7 1 (fleorn Nj~,tio~~:il
lj'oo(1 13:~1a~i(*e
J):~t,afor J!bj!~-50,
su~.,~lied
t)y the NILIr-it,iorl 1)ivisio~~,
Foocl a11c;lAgric:ulkire ()~.gsliiz:~tioll
of t,he
ll~iit~ctd
?I':l,tiol~s).
111tho sy~.i~lg
of .I!)fiO it. 1va.x ~)ossil)l~
t,o stfi~(1y
4.8 ('li~lic~ally
he:zltlhy me11 (:Inployctl i l l Sloug11,a si~l)ri~.t)
of .T.,ot~doll,:t~ldt,ht:so 40 to 55 year-old rncli, t,ogct.hcr
\\-it h llle s:trripl(: of 44 heitlthy yo1111gcrmc11 strldic(1ill I , O I I ~ C ):II Ife\v mu11 111s 111-0vior~sly(35) u1.e c~ompa~-c:d
\\*it,llt,llct R/[i~.lll(:sot,arrl(w j l l rl':~41)l(?I I .
'I'heee .Er~glisllmell,t.lltft~,clol~Eorrnc:losely t,o the Milllic:sot,a st,u~idards111lt tollis
doc!? r ~ o lrncturl t,hk~1,
1
131l f f l
t~nd~I.lr~erj(~al~
poy)~~lat~ior~s
:tlVoidol)t.ic:al ill t,hc:ec

respects. The men studietl ill Lolldoll are not a 1,xzlessrnple becttlusc, for ollc thirlg,
their fat illtake was somewhat highor t,ha~ithe natioilal aver:lgc. A careful study
made by the Ministry of Health of fuotl actually catcn tjy the me11 a t Slough
gavc un average of 35.4 per ceilt, of calories from fat,s. Silir:c fat wastagc is I1ec:css ~ r i l ycoi~sidcrablebctweell n:tajl purchase and actual cao~lsumption,the retail
averngc for thesc lrleil might, correspond to somethilig like 38 pcr cent, of calories
from fats, as (*ornpnrcdwjth a ilatio~lalaverage for I3ritai11of 34.8. For cornparjson, the retail avttritge for Mii~lleapolisin the winter of 1948 \\.as 41.1 pcr
cent of t,otal caloric:^ as fats (data supplied from the IT. S. I>cpartmel~tof Agri-

Me:~iis,i n mg. per 100 rril., :~(Ijust~ed

10 I~ttst~l
condiLions, t!>gct.herwith percc~itngesof l;he
n~calrs:kt :tge 25 i n Englantl :i.nd c)f the mcuns f o r eq,u:~l:rgcs in Minrlcsot,n.
... -

,.---.--

- ,.

....

-.

MEAN

.-

.-

'%,
OF

-....

VALUE

----

Age '2.5

....

(31;
104
123
129

%
' , OP
........

. .-

20
30
40
50
..

MEAN

AOP:

-. .

.. .- ..

.--. ......

Age 25

204

113
107

21!)
21 8

116
115

176

..

.. .-

.-

OF

. . . ,.. ..

....

~Minncsots
.......

1 OR

00
104
1.01

VACOE OF

.
-- ..........

..

......

Minnesota
.-......

102
105
100
XX

..-- ....

....

.-

culture by Dl.. I':st,hcr lq. Phipard), thr: intakc value bcillg perhil,ps S(i to 38 per
cent.
The imporlant point st)ont the tluta from Ellglalld is that, with similar t,otal
Cat ilttakes, thc serum c:holest,erol val~ic?sare also c:losely similar. to thosc in
Mi~\riesota.But the choIest,crol .il~takcof thcst: E~.rglishmc~l
was ~ i o m
t uch mo1.c;
men, owing t,o t,l.ic: st.~.iol,r:~t,io~ljllg',
~iti(rc1(3.10,
thtul half t,l.lat of t,ho ~Minliesot~a
of eggs, k)ui;tel-alld msat,s; rntz~.gariileand cooking fats arc: abulltlan t ill I31.it,ai11.
111Naples, Italy, sirnjl;tl. stlidic:~were c:ar.rjed out 011 83 cli~~ic:ally
hcalthy me11
the tljet, proved t!o l . ~ ?identical
(:overing thc age rallge 20 tto 51i (3(i). IJIh':~~plt:s
\\:il,h the ltaliail 11aI,jo11:~1
tLv(:rage .for the pcrc:cl~t,ugeof t;ot8alcalories supplietl
about half the I?. S. (allti Mi ~ ~ ~ i e s o1cvc.d.
ta)
by f:lt,s. 20 pel*c!el.rt,. .a1111t,Ile~.efo~.c:
S c ~ u mc*t~olcst,t:~.ol
cIt~t,a;we sllm~n:~i-iz~d
i n Tt~,l)l(:12.

'l'he picture js not dilfcrcilt from that ill the E I L ~ ~ ~t.hrough

H ~ I ~agc
C I30~ h u t
therc:after the age trend does not co~ltirlrleas ill Et~glatldor the IJnit,cd States.
From age 40 t o agt: 50 in Mjrlnesottt there is 3 mc?:ui rise of 20 mg. ;iu Naples there
is a fall of 1 mg. Stat,istit:al analysis, Inoreover, shows these djffercnces to t)c
highly sig~lific:ant.

REGRESSION EQUATIONS

260-

240 V)

E
0

,220 -m

/'

w 200
m
t-

,d'

Poor
Workingmen

I
/

-.
f.

//

180

- ,/'

1/20

I
50

40

30

1
60

AGE

li'rc;. 1. ltcl:tt,ionship of serum total cliolesterol corrccntrstion to ugc in a1inic:tlly liesltliy

in Madrid. The lines show tho Ic:~st,-sclut~rcs
Spa~ii:~~.ds
regressloll equntip~isfor the nga
ranges covcrcd by t,hasc lincs, the points being the means for cach age scrlcs.

Means, i n m g. .. .pr:r 100 rril., :~djust,edto basit1 contlitions, tc~got~her

wjt h perccnti~gcsof Llic
means :it, : I ~ C25 and of 1 . 1 1 ~me:~ns for ec1u:ll ngcs i l l Milinesot,:\.

-.

........

..
....

I(;(I

...--

'g, of Value of
....

Agc 25

$1I.
100
114
105

1!)!I

20!)
.I !I7

--- .

. . . . -..-.....-

RICH MEN

............

. . . . .-

Mean

- -.

.....

POOR MEN

Mean

Minncsotx

05

102

0.5

7!)

I n M.atlrid, Syaiii, simil.ar st,~idjeswere maclc oli 55 poor xncll h:~hituttllyslways oli ;t lo\\r-fat diet; (ahout 22 por c:cr~to f (dories frotn fats) and 57 pl-ospcrorls
professiotial xncm 011 a diet, sirnj1:tl. to tllat, ea%.cn1)y \vcalt,hy xneii ill the IJ~iit,ed
low-c:alorje
i
diet, as i~idic::tt,ctl110th I)y
States. l.'ho -poor men, Inoreover, wcrc ~ I ;I.
the t l i e t ~ ys[uavey :uid 1)y the body \vcights and ~neasurelnerllsof skillfol(1s.
r.3.

<.

1.

1.

-7.

'l'hc: prosperous profctssioiisl Inen i i i Mntlrid are ilot much diffctret t f16om thc

Mi~illcsotastar~da~ds,

though
thcy tend to be high st a11 ages, but they are j i i
great c:o~ltrastto tllc: poor Madrilenos, espcc:ially after 30 years of age. l'ai~le13
sumin;~rizc:sthe d:lt:l from Madrid it1 a form similar t,o that, used j ~ T
i ables 11
alld 12.
'J'11J0

FACTOR OF 1tP:l~A'l'IVlC OIIESITY

Thc: f'c~l.egoj~~g
a~lalysisemphasizes the role of the total dietary fats ill determi11i11gt,hc: sc:i.um ctholcst,orol concel~trutioxt.The cluestio~lmay I)(: askcd, however, us ti) the role of total ctaloric I)slunc:e, pal-titularly ill view of the very low
serum val uos ill the ~~iic~crnour-ished
poor moll i 11 Mad rid. I-iowcvc:r, it, set:rns that
relative obesit,y is 11ot the major factor, short, of rc:al underliutrjtio~l,who11 t,ho
I ~lnesotaare collsidercd. The meall relat,ivc:
Inc:11 ill England, ill N aplcs and ~ I Mi
t,age of thc R1cdic:al-Actuaritll sf ai~dardsfor height allti
bcdy wejght,s, as pc~<c:on
age used ill th(: T71liled 8tatcs wcre as follows: Min~lesota103, Naples 105,
1;;11g1:~11(l
04. 111 spi1,e of thc relative lear~r~css
of the Englishmen, thoir scrum (:oncentrittions werc not lower than t,hc Mi~lliesotans.And tllc: Neapolitall serum (:oilcerit,l.rttior~sdiffcr, aft-er agc: 30, from thc Mitlxlc:sota values
spitc of I,he fact
!hey were a t,rifl(: fatter- thail thc Minneeotans.
Thoso I':tt!ts are iri liarrno~~y
with our fi~ldirlgsin Mintleeota where we have
studied the c!orrolat,io~lbetwecn sc:rum cholesterol and r.elczl;ivc! ot)c:sity. There is
a positive c:orrelstio~~
hut, it is small ~ I mctl
I
of equal a.g(:s in (,he ge~lernlpopulution. (25). Ilowovor, chronic severc undcrtlutrjtion is almost always sssoctiat,ctd
with 1o\v Serilxn crholesterol eorlc:cntrat,io~~s
(34, 37). 'I'his m:*y 1)c iri part 1)ecauue
tho fat ctontelit of t,l-lo diel in such CUS(:S
slways low. We have c:olleist,cntIy
fourltl i~~c:rcrtsc:dvalues irl ~rlcxlwhen they werc: act,ively gai~lingweight. from
sirnplc ovcreatillg. In simple fastji~gthe usual tendency for the serum c:hole8terol
to rise Inay rcflcct the fact that the fasting man is primarily me!,sbolixi~igfat,;
in a selise the11 hc is oil n high-fat diet (34).
T11K Dl J c r A N D MORTAIAI'I'T

All toll(:dst,it summarized herc suggest an importal~tc:Iiaitl of reltltiol~shctween the tot,31 fat (!olite~~l
of t,hc di(:t, (or the proportio~lof fat, c:alo~'iesof the
total rnc:taboljzed), the c:hol(:st,erol (slid Iipoprotejn) colicc:rit,ratioii i l l t,hc t)lood,
the tlevelopmoiit, of stheroslerosis, and the mort,aljt.y from dcgcrlei+ativeheart
diseuse:. 'l'hc vital stat,ist;ic:s data for 1taly ('l'able I ) clearly fit this patt,ern.
I t is ~~~~fol*l;unrtt;e
thiit vital statist,ic:s data arc: ]lot avsila1)lc: for*Sp:ijri t)lit perhaps t,hosc: frotn I'o~.tugal (Tal~lc3) may scrvc to jndicat,c what may l)e the case
in Spaill where the diet, is similar. 'l'hcrc: seems to t)c no doul~tthat, c!ororisi-y disc : ~ ( : arld myoc:ardial ii~f:~rc:t,ion
are r~ot,common ill Spaill. This is agreed hy t.hc
local dot:tors s ~ l dis c:oi~firmedby s sesrc:h through the public hospit,a1s. hit j t is
also of i~lt,c:rc:st;that thc Icadi~lgfsshior~ablephysictians do ilot lu(tli cases a.monlr;
their ric.h pat,ie~itsalld tell of marly relal,i~rcsa t ~ dcolleaguc:~1vJ1.ohttvc dictd froln
oc:c:ulsi o~ls,
So far i t has I)c:eli possi1)lc t,o get fully c:ornpal*aI)ledietary aiicl vitd st;atist~ic~s
Figurc 2 gives u surnm:~)-yfor mcxl of l\vo age ranges. 'I'his
ciut,s from f i c~orl~itl.jes.

is for "dcgei~erat,.iveheart disease" as defiiietf hcrc to moan c:orollary tlisea,se,

allgilla pe(:t>oris,iufarc:tio11, c:lironic rnyoc:arditis aild myocardial degeilel.ut,iolI ,

i .e. c*w,tegories93 alltl 94 ill t,hc .I !I38 Rcvisioll of the Tnterilational I,ist, a ~ c:at,c~ d
gorics 420 and 422 in t,ho 1948 Ttevisioil (1). Almost the same relatioil holds, 1nol.c:over, if the tot:nl dcaths from all hcsrt tliseabo zLro plotted against fd c~ttloriesr.~s
a pcrc!elit,ag(;c:of thc: t,ot,al. ?.'his is hc:c:ause of the domjil:-l~lceof these c:i~tcgol*ios
ill tlic caardiac: t,oi;xl at, these ages. Obviously tlie relatioil S ~ I O \ Y I I i l l ITjg. 2 is t,oo
regular and too marked t;o be ex plaitled oil the groul.ltfs of possi hlc c1ifTerent:es
Whc:t,hctr or ~lot,c*liolesbet\\:eei~count~.iesjii the chriter.is for death c:ert,ific.at,iol~.
DEGENERATIVE HEART DISEASE

1948-49, M E N

"I

AGE
55 - 59

10

20

30

40

FAT CAL. as % o f T O T A L

I'JG.
2. Mortalitjr fro~riclcgcncrat,ivc hc:w-t disease (:):~t,egol.ies9 3 i ~ n d94 in {,ticlicvision
of 1938, c::~te~ories
1.20 ancl 422 i n the Rcvisior~of 1048, 1ntc:rn:~tion:d Ilist. Natiou:~lvi(.:~l
sto:~.tjist,ics
fro111 ofi-i~i:.~l
sour(:cs. FIL~,
(::~lori(:s:LS1)erc:entage of total calorics cslcul~t~otl
from
natiori:il food t)al:mce cl:~t:i for I!)4!) supplied by l.he Nubri1,ioll Division, 1Caoc.l :mrl Agric:ult,ure C)rg,zniznl,ion of (,hc TJ11it;cd Naf,iorls.

tc:rol, etc., :ire jilvolvc:d, it, must be c:oncludetf that dietary fat somc:ho\v is asso(1i;~teci\vit,h c:al-disc: tiisease mort,alit,y, at least ill rniddle age.
'I'hcl~is other Impi.c:ssivt: r:videlicte t,o (,his same effeat,. Worltl War 1I I)~.ough
.. t.
wjllllit diot,ary alterations ill m:ttly arctss s ~ i da rc:di~c:t,io~l
i l l diet,ttry fat, \\?as p~.ornjiicil t for sevol-a1yoare i l l lallds c:ollcluc:~.c:d I)y (;cl.many. I11 Norway, the p~rblic:
lo~lg:.~ft,e~.
(,he,nat,io~l:tl(iiet:~~*y
chailge t)c:git11I;her.e was a marked r.ic?c~litle
i l l m01.t,:zlit,y fleorn c:il*crulat,ol.y d.isc:ttsc, pai.tic:ularly from art~c:~.ioscrlcrot~i(~
heit1.t disc:ase
(38). At, fil-st,t,llis c*li:~,lige
i l l mortitlit,y \\:as:~ttl~il)ut~ccl
t;o :ireduc:t,ioil i l l dictitry
c+holcst,ctrol(:3!)), but; clot,ail(:d allalysis iildic*i~t.es
t>h:~,ta rctltic~tiol~
i l l Iiot,:tI tliet,:~i-y

DISCTJBSION

'I'ho ul.gumeiit itnd evidcrlcc: assembled hcre makc a c:oiisistcn t, pic turc which
holds promisc 01 a prevelitive hygiolle but m a ~ i ytict,ails arc 1ac:Iting. The rnec~h;illism of t h e ac:tiol.i of thc diet on the blood c!hol(:st!erol couoclltrutio~lhas ~iot.
really I)cct11esamillcd. 'l'his is url jrnport,ttnt part of Lhc blood cholcst,erol level
(41.). Wo shoul(l like to kllow how, apart from dietary peculiaritics, hyperc.:holc*s.tcrolemi:~t,elids to ruli ill families (42, 43, 4.2). Morctover, thcrc: is much ~-casollto
believc! t,h:tt other factors hesides the: 1)lood c:ouc:eilt,rat,io~lare irnporta~ltj11 t;hc
erct~~al
devcloprneiit of arterjosc:lerot,ic! hcart discasc. Why are rneil t.lll(1\vo~n(:nSO
differellt, 1111 ti1 well t)cyolld thc femslc reprocIuc:t,ive iAg(t range, ill susc:ept,ibj li t,y?
So f a r the blood sfiudies have heen made mostly 011 men but a t least to ago 30
or a lit,tle older. there seerns t,o be 110 differe1x:e i l l the t~loodadequt~tctooac:c:ouli!?
lor the scs difTerei~cei n c:orolisry djseaec i~lcitlc~lc:e
ill tho TTiiiteci rSt,ates.
ltcc:ogllit,ioli of all those limii,atiolls should riot iiit,crfere with the ailitlysis of
t h : iac:ts ~io\va t haiitl. It may hc hopeti that effort,sto diseovct*: I I I ~too~ ~ ~ i d e l ' ~ t r & ~ l d
mer:ha~lismswill t)e pursuttd vigoro[laly. 'l'hore is, klowever, obvjously a f r u i t f ~ ~ l

t'nl culot.ies a s a percenluge oj the lolal calories in. lhc

U ,AS. Nelz'on,al joorl srspply

si,t~cc!
1910
Co~nl)utccll)y Dr. 14:. l'llil):.~rcl from offic:i:~Id i ~ t of
: ~ t h c iJ. S. I)c!l):trtment,of Agricult.ut-e.

field for c:pjdemiologic!aI rescarc:h :I* yot scarr:c:ly touc.lit!d. Alld it, is ]lot too so011
to tlctgill the ;.l,pplicratioll,I)y educ::~,t,iol~ul
Inc:Ltlls, of t:pidemiologicaI fi~ldi~lgs.
'I'he pl.ctsc:llt. high love1 of fat ill lhc Amel.ir:ull diet did 11ol al\va.y,s prevail alld
t ui11.(:lated t,o tlic: jlltlic:at,ioli that, c:orLoliarydisease is i~lc!re:~,sthis f w t milsy~ i o be
i11gi l l this clou~itl.y.Table 1 1 shows t,hc average fat ctalories sts :I porc:e~itagcof the
1lat~io11ti.1
f'oocl clalorie supply f'rsorn 1!)10 (the begi~~~lillg
of r(?li;iblc (1at,tt) t,hro[lgh
1!)50. 111 thc! past 4.0 years thct c:oiltrik)uLio~lof fats t,o the totpalxxlet,:tf,olisrn ill lhc
Il'~litedSt at,c:s lltls risc~i1)y ~nol.c,t,haii 25 per
ill th(: past 20 Y(:;LI.S t , h ~rise
has t)(t(:11 i~lmost13 p(fr celit,. 1'11 the fi~c:t, of a11 the evid(:rlc:e, is this sii.,uat,ioilcicsir:~l)lc? 01ie mR,y sc:l.iout;ly 2tsk whct,hc:r tho cu~~reiit,
~lut,l.itiolial:11ld: dieietic:
tcu:hi I I i l~l tjhjx c:oun lry is as c:ompl(:tely 011 t,he right, txack as somc ~n:tysuppose.
Comp1et.c ilidifr'crelic*et,o the amou~rbof the f:~f;ill (,he cliot, is t8hc!atlit,lldc c1u~*~.ciit~ly
c:sp~.eshcdby hot,h t,c:cthr~j(.n.lmid p o ~ ) ~ iI~ooks
l ~ r 2~11d;trt.i(*lesO I I diet.

Fi.orn f,klc: st,;itist#ic:sof t,be 17.8. T)epart,rnent of A.g~.ir:~rlt,u~-e

it is c.le:ir

t,hut, tht
1)iggcst c.o~ltl.it,l~t~or
t,o t,hc f::~t,sill t,hc Arneric:all diot is fatasttiltl oils as s~lc*h,
es,
allti
c:lrldillg l)uttel., ~vhichctornprise i(i.5 per (:(:11tof tht: t;otal. h l c s t . ~poulirry
lish c:ornt)illccl rnake a pool. seco~itlat 22.1 per celil.. Ally at,10111~t~
10 rctduce the!
lot,a.l i'xt. i11t:tlce must., t,ht!r,, l)egi;ll~
n-it:h c~ookiligf'a,t.sulici, oils.

Thc m;tt,erial disc118scd thove covers too largo a field to be summarized except
ill t,c!rms of thc collctlusions which emerge from it,. These are:
1) Compared with othcr c:ou~~trie,.;
where records arc c:ornpat'able, the totit1
age-specjfia death rata over most of the sp:~11of adult life is excessively high jli
thc 'lJnited States nlid this Arrictr.ic:a~li~lferiorjt~y
is mo1.t: rnsl.k(:d with rrlell t h a ~ i
with \vomcli.
2) The excessive death rat;c of adults i ~ rthe Unit,cd Stat,es is al;trit)utal)le to
a11 exc:eusi\fe mor.t:ilit,y froxn "degerlerative" hcurt disease--c:orollary djsertse,
rt~~giris
pec:t,oris, myoclul.dia1 ilifarctioli, chroliic.:myocardi t,is slid myoc:arclial tlcgoricrz~t,io~i.
These c:o~iditiolls( : ~ ~ ~ t)o
i ~ i(:lt:arly
o t ~ sepsratetl j ~ ivital statistic:^ and
probably sharc: somc: clornrnorl features jn basic utiology.
3) Tho c:onc:entrat,jol~of t,ot!al cholesterol in the blood swum bears all imporet m t rclat,ioliship to the developme~it~
of athorosc:lerosis slid its seque1:tc: and
rc?latcd c:liilic:al coliditiolis. Similar rc:lationships exist, with the co~~cer~tratio~is
of
c:ertajl~"gis~it 1no1t:c:ules" (Sf10-20, Sf 12-20) arid of certain lipoprotciil f ractiolis sepural)l(: 1)y prcc:ipitatioli methods.
4) Messul*emerits of total cholcstcrol and of Sf .12-,20 palatic:lesi l l the serum
afford highly rqigliifi(:arit diffen:~~t;iatio~~
betwccri groups of lneli who arc (1li11ic::~lly
liaalthy and groups of me11 who havo or are likely to tlcvolop (:OI~OIIGI'Y11ear.t djsease. 'l'hcre irq rlo i m y o r t a ~ dif'fere~we
~t
het,~vcc~i
the (:holesterol a11d t,ho St I2 -20
mensurement,s i l l tlhis rcgard, parl;ic:ul:trly with mcli ])(!foreold :tgc.
5) 'l'hasc: xnensuremcn.ts of total cholcst,c:rol or of Sf 12-20 c:o~~ceii
tlsatioris ill
the serbumhave very Iit,t,le pr:tc:t,ic.:al vulrre for. j~ldividualdiagriosis or prc.)griosis,
the jr~tlexof forccast,il~gcfIic:ic:~ic:yheinf; of the ordt:r oE 20 pelnce~it,.
6) Thc tot,al c:holester'ol c:orlc:elitrat,ion i l l the serum of mall is su1)stalltjully
illdepeiide~it of thc tii ct,t~ryc:holostc:r*ol i r i take over tho wliole Ianligcof possi I~le
humall diets,
7) 'l'he t,ot,i~lc:hol(:storol cotlce~itt~at~iol~
ill ttic serum of' mcll hal)itiittlly 011
tliet,~c:hs~':~ct,el'ist,ic:
of t,hc 'Il~iit,ctdSlates chaliges dircc:tly witti changcs ill t,he
total fitt c:o~itentof the diet. 'l'hc rcsporlsc: lo
the new tlict 1)cgitlsin a few days
i~li(.ireiti~hes:1. licw pl;~t,oauill ;L few weeks, this llcw plutettu beilig rolut,ivoly
st,al.)lefol. a t 10:~stsov(:ral irlollt;hs. '1'bel.e is no ilidicatio~lof' a, diffcrouc:(?it1 ur~irnal
versus vegeta1)le fat iri evokjrlg t,hc wrum response.
8) C:omp,zrjso~.io f mcll from populatiolls always livillg O I L difTercrit urnotr~~t,~
of
totel fat ilitakf: it~di(::ttesthat ~ I yol~th
I
t,o th(! early t,hirt,ic:sl;he serum (:holest;el.ol c!onc!eni;ratioli is re1::~tivclyilidopetldent of t1.1edictt il there js c:~loric: suffii:ie~ic!y.Brit; from the thirties thrwigh t,hc fifties the scrrlxri c:o~lc:er~tritt,io~~
js
ilicl*susiliglydepelldclit oli t,hc arriou~ltof total fatlj i l tho diet.
I.)) Thc c.liffercrit, agc-specific death rates of men 40 to fi3 years old f'rorn degenelmrttivt:hc:art c1ist:asc ill dift'eibeilt r:olilit,rics arc! dil~ec+t1ly
15ol:~tedto the c1if'ft:re~ic:esi n thosc c:o1111
tries ill the ~)~*opo~bt,io~i
of the totr~lc:t~lorittsderiv.ed 1'1.om
toot8ttl
fatis. 'l'he ~~elxtionship
i l l t,ho c.:~st: of \ \ r o ~ ~is~rnric~li
e t ~ loss (!leals.
10) %'or tho 40 yit:~rs of rctc.01.d~nvnil:tble, the proport,io~~
of S;t c.:slorios i l l the
l,ofsrtl.4rric?rj i food c:orlsumptiori has st,o~~dily
iiic:rc:ased. 0 1 r t,l.ic1)asisof' c~ompsl*i-

with other courltries at prcselit this risc in fat ~ o r i s ~ r n p t i omight

ri
be predictcd to be associated with a n iricrcasc of the order of 50 to 100 per cent in
mortality f r o m d c g c ~ i e r n t i v ehcart discasc for mcll aged 40 to 05. U. S. vital
statistics are, in fact, compatible with this prediction.
11) Thc f a c t s arid relationships jlitlict~tedhcre are of such importalice as to
w s r r t ~ n at large exte~>siorl
of this type of epidemiological resear.c:h. It is diflicbult to
escztpc t h o c:oiiclusio~lthat public hc:tlth programs nlrxst t,ake cognizance of the
iriformstiotl already at hand.
soils

ACKNOWLEDGMENT

It is a pleas~irt:t o a(:knowledgo my g r e a t obligatiol~lor help i n gettiug sul>jects

and f o r 1abor::~tol.yspttce a n d facj1it;jes l o Drs. I I . M. Siilcl:~ir, 11. H. M;~gce,
K. It. I3rtttlsby, Austili Eaggc:r, D. I31lgc:l and Madr:linc 'Kectc:li i r ~E~lgl:tnd,to
Professors G i n o I3crgnmi a~ltd1i'errllcc:ic.) tli Lorciixo a n d Drs. Flsrniliio E'jdanztt,
Vicerizo Scardi a ~ A.
~ ddel Vecchio j.11 Naples, Iltttly, a n d to I'rofessors Ch~rlos
.Jimc~lcxDiaz, Fra11c:ist:o Grande a11c1J1r.s. Fralicisco V~V:LI~CO,
M i ~ i o ~I'ala~ios:
i,
merchant,^, Segovia a ~ i dParic:~ilic!si l l Spain. Dr. .J. T. A n d c r s o ~ lprovicled a b l e
~011:~1)or:tti01~
ill M i ~ ~ ~ i o n p o My
l i s . wife, Mrs. Margarof, M. Iccys, pcrformc:d m a n y
of the 1)loocI aiialyscs in 14lr1glar1(1, lt~llyslid Spain. Fig. I is r c ~ ) r o ( I ~ ~ cheecrIe by
permissjo~lof the 'Edit,ors of Voldiny, publislled in the Netllerlt-lllds.

1. World lIc:~~lt,l~i
0rg:~riiz:~tion.
M:tnuaI of the Irit,cr~iat,ion:llSttll,istic::~lC i ~ s s i f c a . t i oof~ ~
.I)iseases, Jnjurics anti Causes of Ilenth. Sixth Itevision of tJlc Jntern:ttion:.~l
Lists of 1)isc:~scsand C:tuscs of I)c:~th,Adopt;ccI 1948. Vol. 1. W.II.O., Geneva,
1918.
2. JONES,11. U., (>OI'MAN,
3. W., I J r ~ ~ ) ( : r F.
t i ~T.,
~ , LYON,T . 1'., (::ILAIIAM, L). M.,
Sn-t~sowrcn,I{., A N I ) NICIIOI,~,
A. V.: 1,ipoproteins ill At,l~erosclerosis.Alner. ,I.
Mcd., 11 : 358, 1951.
3. 1ih:~s,
A . : "Gi:~nt Molcculcs" :in(] Cholest,crol i r i itcl:lt,io~~
t,o At,l~c:rosc:lerosis.13ull.
J o h n s Iioj,ki~isHoap., 88: 473, 1961.
1.. I(I.:Ys, A. : Cholcstel-01, "Giant Moleculcs," ancl Atherosclerosis. J . Grncr. Med. Assoc.,
147: 1514, 1951..
5. ( ~ E R T L I M.
S R M.,
,
G A I ~ S.
N ,M., A N ] ) L E R M A N
J.:, The Int,crrcl:~t,ionsliipoC Sorr~rnC:holcsterol, Cl~oIc:sf,crolEsters, ar~cl I'hospholipids in Ilcaltli :~.ntl in (:oron:lry
Artery 1)iscusc. Circulation, 2: 205,1!)60.
6 . (';P:RTI,~R,
M. M., GARN,S. M., A N D WIIITX, P. D.: Diet, S B ~ U(~ilolestcrol
I ~
: ~ n t lCoronary Artery Ilisease. Circuli~t~ion,
2 : 606, 1950.

'7. COP'A.IAX,
J . W., .JONES,11. Ij., I,INI)OREN,
F. T., J,YON,T. J'., ICI,I,IC)'I"I-, H . A . ,
A N I )
S~nrsowlc~z,
13.: Rloocl I,i~)icls: I I I ~ I HUII~:LII
At,I~(:ros(:I(:~~~sis.
C'!ircul:tt4ion, 2 : 161 ,
1950.
8. S ( ! ~ ~ o i s r \ l r . r ~Irt n. ~
AN
~ Ie) ~I ,~ H I . ~ I I SI?.:
( : ISytlthesis
~,
i~nclI)est,ruct.io~iof Cllolesl(?rol i l l the?
0rg:~nism.J. 13iol. Chcm., 103 : 439, 193.3.
9. ( ; O I I I ~ I ) , It. G . : JJi1)idMet,ak)olis~n: L I ~ Atl~esosclerosis.Arii(:r. $1.B!l.~ii., 'I I : 20!); 1!)61.
10. I'lt~n.,~,x,I . I)., .Jtt., S(:HNP;';I.I)WH,
14. S.,A N I ) IIINKELMAN,
1.3. T.: ll.(?I:it.ic)nshil)sHetween
t.hc IJc!v(:ls of I)ict;:~ry,Livc:r :111(1 Scrum C:hotesterol :111(1 Ilol):l.t.i(:C:liolest,erol
Sj~j>thcsis.
(.:irculution, 6 : 407; I!)=.
11. .I<KYs, A . : H i i n l : ~.4t~li~1~os(;l(:ro~is
~~
:~ri(lt,li(? Diett. CjrcilI:i,tio~~,
5 : 115: l!M.
12. C I I , \ ~ K ~ 1.
F PI,.,
, 1ji.00~1,
I3., ~ I J J ~ ~ ; I I S , I ~ I M.
~ : ~ ND.,
,
'I<J\-.~.SI~,
J . I.., ~ I I - : I ~ H . AW.
I { IO
) I. ,~ ,

ANCEL ICEYS

DAUHEN,
W. C:., AND EASTITAM,
J. F.: C1'-Cllolcsterol. 1. Lymphatic Tr:trt~port
of Absorbed Cholcstcrol-4-C14. J. Biol. Chern., 194: 407,1952.
13. Blccs, M. W.,
~ < I Z H . I W ~ ~I).,
E VCOT~MAN,
B K Y , I)., GOFMAN,
J. W.,JONES,
H. H., J J ~ ~ ~ ) ~ ~ m ~ ,
I". T., IIYDE,
G., A N D LYON,T. P.: Observations on the Fstc of Ingeutctl Cholesterol in Man. (:irculat8ior~,6 : 359, 1952.
14. MESSIN(:EH,W. J . , ~'OHOSOWSKA, Y., A N D SI'EEI..,
J. M.: l3ffect of lcceding Egg YolIt
nrld Chole~t~erol
on Serum Cholesterol Levels. Arch. Internal Mcd., 86: 1.80,19,50.
15. COOK,R. F. AND THOMSON,
Ji. 0.: The Absorption of F>.L~
and
of Choleslerol in t h e
Itat, Cuinca-pig snd Itabbit. Quart. ,J, Exp. I'hysiol., 36: 61, 1951.

16. ICESTEN, IT. D. AND SILBOWITZ,

It.: Expcrinle~~t,aI
A t h ~ r o s ~ l ~and
r o ~Soya
i ~ Lecithin.
Proc. Soc. Exl). Hiol. 8 Med., 49: 71, 1942.
17. I~ODBARD,
S., BOT,FNE,C., A N D I<A'I~z,L. N. : IIyj)er~:holestcrernj:~
znd Athc:rornatosis
in Chicks on a Restricfted Jliet Corit;si~lingCl~olcstcrol.Circulation, 4: 43, 1!)51.
18. STAMI~ER,
J. AND
KATZ,L . N. : Prudu~ti011
of 3;xperimcnt:~lCholest,crol-induccd Athcrosclerosis in Chicks with Mirlim:~lIlypercholcstcrolcmia and Orgitrt T,ipidosis.
CirculatAon, 2 : 705, 1950.
10. I I o n ~ r c L.
~ , A N D JI AVCL,L. : Thc Effect of Fccding Propylthiourscil :tnd Cholest,crol
011 the Bloocl Cholcstarol a11d Artori:~I.Intima in the Itat. J . Lab. &L Clin. Med.,
33: 1029, 1948.
20. SI~IRKY,
W. M. A N D S'OYANOIW,
V. A.: Effc:cts on Long Continued Cholesterol I+'cedil~g
in Itats. ,J. Nutrition, !I: 131,1935.
21. CRXENRERG,
11. 1). AND ~ ~ J N B I T A R JT ., I?.: l'lr~~111~.
Cholesterol Levels of Cholesterol
Fed Control : ~ n dl'yridoxi~leDeficielit Monkcys. I'roc. Soc. Exper. niol. & Mcd.,
76: 580, 1051.
22. M o m s , C.: Ilie1,nry Choicutcrol and Athoroselcrosis. Amcr. .I, Med, Sci., 224: 212,
1952.
23.
A. : Cholesterol Metal:,olism and Artcriosclarosis. Anier. J . Mnd.,6: 117, 1!)49.
24. OKEY, It. A N J ) S ~ W A K I).:
T , Diet ntld Blood Chole~teroli n Norrnal Wornon. J . Hiol.
Ctlem., '30 : 717, 1!938.
26. J~EYS,A.: The l'hysiology of the Individual as an Appro:lch to a Morc Qunntit,at,ivo
Biology of M:m. lped. S'roo., 8: 523, 1949.
26. WIT~KINSON,
C. I!., JR., I~LL:CIIA,
I?:., A N D I~ICIMUR,
A . : Is Thcre a 1tel:~tioriI3etwc:en
Diet :tnd Blood C:l~olesteroi?Arch. I n l . Med., 85: 389, 1.950.
27. I<MMI~NEH,
W.: 'l'ront,ment

of IIy~)ert,ensiveV:iscular

Disc:bt;c. with Itice Diet. A~ncr.J .

Mcd., 4: 545, 1948.

28. %HWARTZ,
W. B. AND M R R I ~
J.SI<.:
, Nit,rogcli

lij:tlar~(:e~ t u d i e son Kenipllcr liicc?

nict,. J . Clil-I. Jnves., 27 : 406, 1948.
20. CHAPMAN,
( 2 , B., GIBBONS,
T.,ANI,)
I~~ENSCHEI,,
A , : T h c JSffect

of the 1Cicc-Fruit, Djcl,

on thc Composition of the .Body. New J'Cngland J . Med., 243: 890, 1050.

30. KEYS,,4., .MI(:KB;I.MEN,

(I.,MII,LER,
1d. V. O., AN]) ~ ~ I I A P M A Nc.
, n. : Thr: Rc:lnt,ion in
M:LI~
Hct,wc:et~Chol(:stlcrol J,evels in thc Ilict :uld in thc Blood. Scie~ice,112: 79,
1050.
31. ANUEHSON,
J . T. A N I ) KEYS,A.: Dietary Ic~tt:ultl Scrunl C:holcst,crol. I4'cd. 1'1-oc., in
presu.
32. IJTLDRETII,
X.A., MEI,I,INLLO~PF,
S. M., RLALK,
G1. W . , A N D HII,I)HETH,
I).
M.: Tile ICfft:ct,
Circu1:~of Veget,:~blcF a t ingestion or1 Hunian Serum I:holest.cl.ol C:once~.~tr:~tiorl.

tion, 3: 641, 1951.

33. KEYS,
A., MIC!KI+:I,SE:N,
O., MILI~ER,
13. V.
C ) . , ZIAYY:S, 1C. It., A N D T O D I )It.
, 1,.: The
Concentr:~tior~
of CI~olc~t~crol
in thc
13lood Serum of NorrnaI M:ln : ~ n d1t.s Ilclation

To Age. -7. Clin. Invest,., 29: 1347, 1960.

34. ~(EYS,I\.,I ~ R O Z EJ.,

K ,J~ENS(:HEI.,
A,, MICKEI~SEN,
O., AN11 ?'AY s,O#t, H. 1,. : The ljiology
of 1Ium:ln St:~rv:ttio11.2 Vols: Min~icsol.rtl'r-esa, Mirioe:~polis,1950.
35. ' ~ ' A , ~ N P : I ~.T., 31.:7'hc 1tel:ttioti 13etwccn Serum C:holesterol
: ~ n dI't~ysiquci n 1-Ieallhy
Yo11n.g Men. J. Physiol., 115: 371, 1951.

ATHEROSCLEROSIS

139

36. I i s ~ sA.,
, FIDANZA,
F., SCARDI,V., A N D BF;H(:A~II,
G.: The Trend of Serum Cholesterol
1,evels with Age. l.ancet, 2Ci3; 20'3,1952.
37. IIORST,W.: neitrag xum T~ipoidstoffwechselbei Chronischer Untern:ihrung. I<lir~.
Wscher., 28: 184, 1950.
:j8. S~I*H$M,
A. A N I ) JENSEN,A .
It.: Mol-t:~lityfrom C:ircul:rtory 1)isc:rses i n IVorw:ry 1940-45.
I,ancet, 260 : 126, !!I51 .

39. Mar,hmos, H.: Thc Itr:lat,ion of Nutrition to IIcalth. A ,E;tatibt,ir:~l

St U ~ oVf the W:tr
time on Arteriosclerosis, C~:irdiosclerosis, Tuberculosis and Dinbetes. act:^
Med. Sc:~nd.Suppl., 245: 137, 1050.
40. Prrrx~,,A . : Cllolestcrol Studies. 11. Ilietary Cholesterol and Atherobclcrcssis. Sctlrld J .
Clin. and I ~ a b .Invest,., 4 : 122, 1952.
M., A N D J ~ O S ~ S N M A11.
N , H . : Review: 011 thc It~gulatio11of
41. UYERS, S. O., FRIEDMAK,
I3lood Cholcst,crol. M(~t,aI)olism,
1: 479, ]!IS.
42. BOAS,1':. P. A N D ADI,ERSREH(:,
I). : 1':~rrlili:~lI ~ y ~ ) ~ r ( ~ l i o l ~ ~ t(Xantbomntosis)
crernia
and
Atherosclerosis. J. Mt,. Sir~ztiIIosp., 12 : 84,1945-1946.
4 3 . ~ I T , K I N S O N , C. F., .JK., I ~ A U I )11:.
, A., A N D FLIEGBLMAN,
M. T.: Essenti:rl F:~milial
IIypc:rchol~stcrt:~ni:~.
Atln. I n t . Med., 29 : 676, 1948.
44. Ar~r,lcnsrtl;.,nc;,
I). : IIy1)crcholest erc~rli:~
wi t11 Predisposihon to Atherosclerosis. A n I n
Iriborrl 1i;rrc)r of Lipid R/I(.t,al)olism.Amer. J. Med., 11 : 600, 1952.