Controlled trial of fasting and one-year vegetarian - FX Mayr.

Controlled trial of fasting and one-year vegetarian - FX Mayr.

THE LANCET
No 8772
Sarurday 12 October 1991
Vo1 338
Controlled trial of fasting and one-year vegetarian
diet in rheumatoid arthritis
JENS KIEr-DseN-KnecH MancanrrrnHAucEN
GrnrsrmN F. BoRancREvrNK EwN Laenul,r MoRrrN Erx*
I'p-rrpnMorunNxsr- KNurHovt OvsrrmFonne
Fasting is an effective treatment for rheumatoid
arthritis, but most patients relapse on reintroduction
of food. The effect of fasting followed by one year of
a vegetarian diet was assessed in a randomised,
single-blind controlled trial.
27 patiens were allocated to a four-rveek stay at a
health farm. After an initial 7-10 day subtotal fast,
they were put on an individually adjusted gluten-free
vegan diet for 3'5 months. The food was then
gradually changed to a lactovegetarian diet for the
remainder of the study. A control group of 26
patients stayed for four weeks at a convalescent
home, but ate an ordinary diet throughoutthe whole
study period. After four weeks at the health farm the
diet group showed a significant improvement in
number of tender joints, Ritchie's articular index,
number of swollen joints, pain score, duration of
morning stiffness,
grip
strength, erythrocyte
sedimentation rate, C-reactive protein, white blood
cell count, and a health assessment questionnaire
score. ln the control group, only pain score improved
significantly. The benefits in the diet group were still
present after one year, and evaluation of the whole
course showed significant adv6ntages for the diet
group in allmeasured indices.
This dietary regimen seems to be a useful
to conventional medical treatment of
supplement
rheumatoid arthritis.
Lancet 1 991 ; 338: 899-902.
lntroduction
Most general practitioners and rheumatologists
have
encountered patiens with rheumatoid arrhricis who claim
that their symptoms are all:r'iated by a special diet or by
simple elimination of certain iterns from the usual diet. Such
reports tend to be viewcd w:th scepticism. Only a few
anhriris patients havc convincing "fbod allergy"rr-3 and
clinical trials of "diet therapy" have yielded conllicting
results.tT Fasting, however, does reduce objeccive as well as
subjective indices of disease activiry in most paricnts with
rheumatoid arthritis.'EP
tVc have evaluated the eflect of a shon fasr fbllowed by
one year of individually adjusted vegeurian diet in patiena
with rheumatoid arftriris. The dietary regimeo rvas the one
used in a Norwegian health farm, slightly modified for the
clinical trial.
Patients and methods
Patients
53 padens with classic or definite rheumatoid arrhritis'o in
firnctional class lI or lllrt (45 womcn and 8 mcn) were enrollcd
Department of General Practice, University of
Oslo. 02O4 Oslo, Norway (J. Kjeldsen-Kragh, tro, Prof C. F.
Sorchgrevink, Mo, Prof E. Laerunr. MO); Oslo Sanitetsforening
Rheumatism Hospital, 0173 Oslo, Norway (M. Haugen, 8Sc, M.
Eek. Mo, Prol @. Fone, Mo); Medstat Research, PO Box 37.
2011 Stromrnen, Norway (P. Mowinkel, MSc); TonsSson
Rokreasjonsheim. 289O Etnedal, Norway (K. Hovi, Mo).
ADORESSES:
Corespondencc lo Dr J. Kjeldsen-Kragh, lnstitute 9t lmmunology end
Rheum3tology. National Hospital, Fredrikko Ovams gale 1, 0172 Oslo.
Norway.
'Dr
Iick dicd irr Ircbrury, 1991.
■‐
900
VOL 338:OCT 12,1991
LAN∝ T
TABLEト ーPAT:ENT CHARACTER:ST:CS AT ENTRY
Prln
p<o@'
5
Dir.ttloo ol
Age, yr
lwnl,!g
Mcan
3tllld.
2
p <
RsnSF
o.@ll
Ser
M
H..lth
F
qlaallonulrr
alraandt
Disease duration, yr
p<oOt!
McGl
Glcbd
Rerrgt
Positivc
Ncgrtivc
Cunent medication
NSAID
C-ortioosrcrokts
Sulplsselzdttc
Cy@ttbdrugF
Nqrc
Alleeylintoletencet
F@d
Othc
1・
０■
PcnlillamLr
出福
ニュ
Antirnelrrial drugs
Gold
４ 一１
III
Rheumttoid lactot (lgM)
atxaamnl
P<omll
0-
unchn● ●●
脚
“
II
Cless
Class
３ ４ ６ ５ ０ ３ １ ０ ２ ３ ３ ６
Ｚ ３ ︲
︲
︲
︲
Functional cttegory
pく
oぼ
F露 ひ
types
rPatidrB om npo(ls.
k9
benrccn Jan l, 1987, md.Oct l, 1989. Thcy wcrt rccnrited rninly
fuough thc oupaticot dcparuncot of tbe Oslo Sanictsforstings
Rhcunratisrn Hcpital, uriich rcives paticots &,ocr tlrc whole of
Norway. All had acivc discasc, as dcdned by thc prcscoe of drrce
of tlrc folbwing four critcria: >3 swolleo inints; 26 tcodcr ioins;
momirg stiftrcss >45 min; crytbroqnc scdirnatadon ratc (ESR)
228 in dre lst hour. Further paticot dreractcristics rrc givcn in
table t.
Bdore indusirn, paticoa uing slow-acting alrtirbanmatic drugs
(SAARDs) or cytctatic dnrgs had o havc bccnon a stable dose for
at lcast 3 rnootlrs. C.ortiostcroid dosagc was not to a(c.d
7.5 rrrgl&ly F€dnisooc cquivdcnt and thc docc bad to hrvc bc€n
$ablc for 4 nnccks bdorc so'dy artry. Thc docc of non-srcmidal
anti-inllanrnaory drugs (NSAIDS) likcrvisc had o bavc bccn
stablc for at lcast 3 wcc*s. No drange in thc domge of SAARDs,
cytoctatb drugs, or corricrcroids (by moudr or by intra-anicular
inicction) nras allowcd during the sndy. Ifn ccssary, rhe dose of
NSAIDS and analgcsks could be drangpd. Patiens were asked not
ro usc orncgB-3 fatty acid supplanana othcr ttran cod livcr oil; thc
dosc of this had
o
bave bccn stablc for 6 wccks bcfore cntry and wlts
the samc throughout thc study pcrkd. Patieots using
sclcnium urd vitamin E supplcrrrcns wereelso tocootinuc wittt the
to be
kqt
samc do-sagp.
Design
Thc study was a l}'month prospcctive, single-blind, rsndornisd
trial, approvcd by the rcgiorul scicntific ethics omminec. By block
randomissdon,D wi*r 6 potients in cach block, 27 patients were
allocarcd to a dic group and 26 paticnts to a control group. The
paticnts startcd onc of thc hatrncnt rcgimas as son as possible
aftcr thcy had agrccd to perticiparc; in mct instanccs, tlrcy were
assernblcd in srnall goups who startcd the trid at the same time.
Thc rcsult of the randomisation was r.urknown to rhc patient until
thc first oramination was completcd.
Thc padents in drc diet group began their four week suy at a
healdr farm by fasting for 7-10 days. Dictary inuke during thc fast
consisted of hcrbal tcas, garlic, vcgctablc broth, dccocrion of
polztocs and parsley, and iuicc ocracrs from carrots, bccts, and
celery. No fruit iuiccs wcre allowed. Thc daily cnergy inukc during
the fast uaricd bctweco 800 and 1260 kf. After &e fast the patiens
rcintroduccrt a "ncrt" fmd itern cvery 2nd &y. !f drcy noticed an
incrcase in paiu, stiftrcss, or joint swdling within 2-48 h this itcrn
64
R.
r▼
・
T
,
1￢
.
.
凪
諮智
:
Fig l―Clinica:indices.
of
lhe m€an for lhe diet group:
Mean and standard enor of th€ nrean for the conttol
The standard enors ol the mean lor global
aigsssment were too small to be d€pided on the tigute. Th€ p values refer
Mean and standa.d enor
--{-.
group:
-----6-----.
to orerall group difterence. iunpaired t-tesl of rhe endpoint ttlues.
tRepeated-measures ANOVA on the .anks. IANACOVA. tRepeated
nreasurcsANOVA
was omittcd from the dict for at lcast 7 days. If sympoms were
cxaccrbatcd on rcintroduction of ttris food itcm, it was e<cludcd
&qn the dict for thc rcst of the snrdy pcriod. Dudng thc first 3'5
moorhs the patians wcre as&cd not to qlt food Olat conteincd
gtuten, mcatr'6slt, cggs, dairy produas, rclincd sugar' or citrus
fruis. Salt, strong spioc, and prcscn ativ6 werc avoidcdJikdris€
doholic bcvcragcs, tc:I, and @fee. After tttis Pcriod thc paticra
were allowed to rcinooducc milk' other dairy products, and glutcn
conaining foods in thc way dcscribcd abovc. Thepaticnts who did
rr;t usc cod liver oil sulplernented ttre diet with vitamin D during
the 6rst 4 months.
At rhc hcalth farm the patients, who were instructcd by the seff
and the dictitian (MH), kcpt a diary rcponing dl fod and liquid
intake. During ttrc rest of the sn dy period they recorded all lbod
itcrns rcinoodued and any worscning of symptons subscqucnt to
rcinooduction.
The ptiens in thc control group had a four wcck stay at a
onvalescent home and were askd to eat ordinary mixd fmd
throughoutdre study. At the onvalesccnt homethcy kepta diary of
their food intakc and thercaficr they made a <ieailed recold of fmd
intakc onc day a weck (the day bcing varicd). Both groups werc
offcred physiother"apy thrce rimes a wer:k during the stay at thc
healdr ferm or convdcscent horne.
Clinicat and dietary assettments
All
clinical examinadons rvere done by a single physicisn
0. K. K.), who did not know *rc group to wtuch padins had b<r:r
allocated (they were csked not to divulgc it). Eraminatiors v;ere
901
THE LANCE´
「
VOL 338:OCr 12,1991
TABLE‖ ― DROP‐ OUTS
Time atter recruitment
Drop+uts
in
'I'murrot
rclatcd
diet group
Not tr€atrnmt r€lated
Drop-outs
Tratmcnt
in
cnntrol group
Not
Results
34 patiens completd the trial, and table It lists the
fordmp-outs. During ttte study period,5 patien$ in
1st mo 4rh mo 7th mc
reasons
the diet group reduoed and
lt
l
露
rclatcd
increased the consumption
of
consumption of rhese drugs.
After
related
tetrnat
I
NSAIDs; in the control group 3 patients reduced their
I
mondr at *re heal*r farm patients
strowed
in the number of tender ioints (p<0'0002), in
Ritctrie's ardcular index (p<0'0004), in the number of
swolen ioints (p <0'04), in pain (p <0'0001), in duration of
decreases
0
0
.Could nor 6pa with rhe disr.
twhMrown dG to flare-up ot a.thritis slmptm.
tom ol tho patienb witMrawn beaue ol skts-ellcts ol auramfim; lhe olhs wG
morning stiffitess (p<0'0002), and in ESR (p<0'002),
Greactive protein @<0'005), white blood c€ll @unt
b<0.0001), and platelet count (p<0'006). In ttre same
ofld€d tot l i)int rcplacmsnt.
lwithd.awn bcau$ they wm otlsod lotal joint replacment.
period they had an increase in grip strength (p < 0'0005) and
on healtS assessment questionnaire (p<0.0001).
These gains were rnaintained tt'oughout t5e year (figs I and
doneatbaseline,afterfourweeksetttrehealthfarm/convalescent s@re
home, and thereafter every 3 months. The patients recorded
dreir
pein(l0crnviiualanaloguescale)anddurationofmomingstiftress;
and, for gradiog of funcdonal ability, ttrey filted in
-- -r
-:r-e-r:--'Tt
. p".i*o in the control group showed a decrease in
'-13,i
asscssment questionnaire.s At the second and subsequent clinical
paln
ttreir stay in fhe Convdesccnt home
evaluarions the patients recorded their overall gfoUaf as.str"*t
ry.re -after
ompared with itut at entry to the snrdy (scored as muctr bctter, tt <0_'02)r but none of the ottrer indices improved
beacr, unclarged, worse, and much *ors.). Joit t -,-t included significandy, and at the end of the study they had
deteriorated.
Ritr*rie's anicular indocrr' the number of ioints that werc tcnder or
painful on movement, and the number of swollen ioina. Three
!(/hen tlre two groups were compard by t-test after 13
dcrcrminatiors of grip socngth werc made for cactr hand with
months, repeated measures AI.IOVA, and ANACOVA, a
Vigorimetcd (Martin, Tuttlingeri, Ccrrtany). S"Td$
satistically significant improvcrnerit wns scen in ttre diet
calailrtionswcremadeonthesumofthemediansofbdTS..t] gtoup ror at fiai* excepi plarelet ount and haernoglobin
the clinical consultation neither padent nor physician had acccss to
7--: --- .;. ;
(rrgs I.anO Z)' 5OtIl gfOUpS qetenOtirteq SllgnUy wltlr respect
thc results from caflier visits--€.ccpt pin scorcs frorn thc prwious
-t
a to radiograp-h sore, and in this rcspect they did not differ at
visit, whidr wcre strown to paticnts. At baseline au p"tens
trani, wrist, and forefoot radiographs takco and ttrcsc wcre done the end Ofthe trial.
The diet grcup lost more weight than the control group
againinpaderrswhocompletedthcstudy.Thcpairsofradiographs
were cornpared as dcscribcd by I-arsen ct
al.ts
Haarroglobin, ESR, platclet ount, white blood ell ount,
Grcactiveprocin,andscrumalbuminweremeasuredinitialyan!
at each clinical evduaticn. Food inEkc was asscscd bcfore,studl
cntry, at thc time of cadr clinical cvduation, and by tclcphonc
(oncc)
:.';--'
evaluauoilt. lnlal(c was asscsscd ttom ztFhour
rccalts by usc of hourhold mcasurcm€nts. Encrgr and ;"k";
nutrients werc calcrrlated by mcans of the FIBER software package
oct\,v,een curucal
and stroweda biggerdrop in haernoglobin (though the lauer
wasnotsigfrificant).Albumindidnotdrangesigfrificandyin
eit6er group. During the period on vegan dietthe patients
116a Artcutry in meeting some of their-essential nutritional
_ ^ _ , - ;^^::'^ .
needs desprte advice from *re dietidan. However, when *re
diet was switdted to lacrovegetarian thesc problerns were
besed'oo the Norwegian food composition able.!6
:1∞
ξ
５
５
３３
︲ｍ ２ ” ”
︲¨２
Statistical analysis
tVithin-group differences at fixed time poina wcre tested b.y
paircd t-tcsts. Howevcr, for duradon of moming stifftress, grip
L,
"",.u|
,. I i1--
sucngth,andC-rcactiveproteinther0/iloxonsigned-rar*rcstwas
,.r1
uscdrmainlybccauseoftheprescneofoutliers.Repcatedmeasures
r2l
ANOVA was used for tcsting overall group differcnces,tt Because .9
‐ao
oF signiflmt baseline direren∝ 関品通 the tw。
regard o dre healh ass€ssrnent questionnaire s@re:rn
analysiswith
"ups
:""@{
2511rう
of
;;l \
:
I
I
: ー
-
rl
H.omoerobrn
-
[
c''...dlv.
・ 11:T鵠
¨・I… ……1 … …
・ ´‐
品
`…
l,
,{<
2ol
1・
I
covariane(ANA@VA)wasdonefordrisvariablc.,"al.IAe;Vl
ff
--q----, t
was also performed on weight, platclet count, and white blood cell - roe,r o.^
: {￨ぽ
¨
¨
¨
‐
一
∞unt minly be‐ usc J baseline difF― ces betw― the"ups, 窮 I卜 ‐
.:.¨ ″
」
nrrI.tct
:
.
r
after
.".1 tf
--1-I
inspcctionofthesorefromthcpreviousvisitthismeasuremeorwas";.1 Y-l _--ldepcrtdent; hencc, an unpaired t-test for the eodpoint values was ,o,,
.""";"""""';..'.......;.....'....; l:.?lt:.:if
pcrformed.Thisrestwasalsousedtoevatua*ra.ioer"philJ- 't-' "'
:l I t
I P'oooo't
For ANOVA models the reaunem factor was regarded as fixed
dthough these were not significant. Since pain was scored
1樹
whilst the time and patient facton were assumcd to be random. For
all tcsts inspection and arulysis of thcC『
residuals was carried out
u淵
for
鮒 掘 ・ 1ぽ 嵩淋
樵 こ
sucngrh, and C-rcactive prorein were non-normal. Since no
._=L=… 」:
』
"Jノ
、、-]-_, --f_ =:…
iil ; :
performcd
a
suitable transformations werc found, thc ANOVA was
on the ranks rather than on the values thernselves, thus yielding
large sample p va.lue.r7
The principle of intention to ucat has bccn followcd *uoughout
*ris triar.', For drop+us unrelared ro uearncnr
the lastobserved value, and for treawrent-relared dmp-ou6 we used
minimum varuc extraporadon. p varrres berow 0.05 *.r.
*.
significant.
3ll
--
: .
or
I
Fig
t
ro
,
lt雲 1・
I
I
13
ffi
2-Laboratory values.
o,ofr"iJ il::|"ff"::""'j""#"'"'#T"ilJ'';::l-lrtf"i,l;;;i;,
:':'tlXT::A
..s;;;J; :'-;;$ ;.'-: ;;;",,t1"
oo*o"iIT"':H ;'"r::ffil^%3V^
_ _'-
-
measures ANOVA. NS = nor sisnificant.
eliminated (Flaugen
et al, unpublished).
,Uftn*
voL
'THEI.ANCET
902
*t"
M, Kieldsen-Kragh
J, Skakkeback
reduction could orplain only
N'
i-pau.rrt*,,
statisticat calculations were done only for
338:
OgI'12' l99l
a small part, of the
and ttre overall conclusion remained the
same.
gecause of the nature of the study, in rvhidr participants
we
had to be reoeptive to e:<tensive dranges in the diet'
with
those
of
arc
typical
patients
these
cannot te ,*"-tlot
oadens who completed the study (dropous o<cluded), the
iri"Apd conclusions rernained the same (dau not strown)'
Discussion
Alttrough most patients with rhetrmatoid arttritis benefit
from a stron period of fasting,"t nearly dl relapse on
rcintroduction of food. IVe have now shown that the
improvernent can be susained by ur individually adjusted
dt.t""y regimen. These resuls orroborate the findings of
Darli:n$on et al6 and Beri et aP who likewise used an
indiviJnally adiusted diet. In those two trials, howwer, the
study pcriod was onlY 3 months.
Sin; it is impossible to carry out double-blind trials of
diet treatrnent, we had to ctroose a single-blind design'
Panicipana had to be wiling to be randomised to either
gro.rpihot"..to, most of thern hoped t9 be randomised to
O. &.t group, so we must consider ttre possibility of a
negative pt"""Uo ("nocebo") effect in *re control goup as
*Ju r" it o.Uo eifect in ttre diet group. ITe ttrink that sudr
effects "are wrlikely to account for all the improverneot seen
in the diet group. If it was only a maner of placebo/noebo
effect, one-would expect the difference between the two
groups to diminish wittr time and to be negligible after 13
i,""it t. Furthermorc, one would etrpect the gains to be
mainly in ttre subiecdve and serniobiective indiq rather
tlran in ESR, C-reactive protein, white blood cell ount, and
numbcr of swollen iorgs.
That an individually adjusted diet reduces disease activity
dlerry or intolerance is involved to some
aegra in the pathogenesis of rheurnatoid artlritis' About
rtreumatoia ar*uitis. Nevertheless we have shown that in
can
some patients a zubstantial reduction in discase activiry
U""Ui"i""a UV fasting followed by an individually adjusted
ai"l. Desplte the diffiorlties of covering essential
first4 months we donotbelieve
G; dttt regim€o carries a heal*r risk' On ttre ontrary, it
r..rttr to bi a useful supplemeot to the ordinary medical
".g.*in ioi iotot ttoat duringtlre
treatrnent.
S7c echowlcdgic frtancial suppon from the Norw-cgian
Vorncn's l\rblic
HJO e**i"U*, thc Andcrs Jahrc's Fund for Promotion of Sciene'
iiu.dr r.en v, Gt"o. H"ttio L,cgacv, Eckbo's t'cgaq' md Nvcomed
iit Gt
elso thank tfrc Dcparuncot of Clinical^Ch<nistry'
i.pt,A, Oslo, and the hboratorics at thc Rcd Cross Clinic' Oslo'
eS, O.:i.. !7e
ii"tt*r i
Rhcunsdsrn Hospirel for analysis of thc blood
J-A," Orf. S"rri i"f.rcnings
study'
s."npG, ,na Cut"ttrild Wft Mikkclscn for hcr assistgrcc in thc
REFERENCES
I.
Parkc AL, Hughcs GRV. Rharnatoid rrthritis and food:
Mcdl l98l;UI2tA274'
Z. p""G-nS,
-
Si-.ta RM, !?cbetct EM' Food-induccd
- l"tt"t*futy
*26.
ertluitis oracsbatod by
a casc
snrdy'
8r
(allctgic) ardrritis'
milk''{rrfinhi Rlun l*6;29:
:. prtt"O RS. Food indued ('eltcrgiC') arrhritis: dinical md scologic
I
stttdica.t R raa,4tol l99O; 11: 29144
L, Lasson L, Lindstr6m FD' Effccts of fasting and
hcrovcgea;n dict m rhcunratoid ardrids' Sod I Rbwtot 1979;
S"Ofa""t-
8:249-55.
RL, Kae P, Kowsti B' I-onglcy S' Firuric S' Dict
&erapy for rharmsroid erthritis. lrdnas Rlun 1983;26t462-71'
LG, Rrnrscy N!9, Mansfrcld IR. Pleccboontloucd' blind
tt"ai of aia".y -rttpulaticr thcrepy in rhumetoid erthrirjs' Lawt
1986; i:23,G38.
5. P.nush RS, Cancr
suggesB that food
6.
D.din;;
half of ttre patieots in *re present sntdy reported some kind
of allergy or intolerane. In a questionnaire based suweyre
?.
Bcii D, Malaviya AN, Shatdilya R, Singh RR. Effcct of diaary
we found that onethird of patiens wittr rhzumatoid
arthritis had experierrced aggravation of arthritis symptoms
after intake ofcertain food iterns. In a double-blind {bod
clullenge snrdy, Panush3 reported deterioration in 3 of 15
patiena with rheumatoid arduitii who daimd to have fmd
altergf/intolerance and he estimated tlrat sudr a condition
might be found in 57o of patiena with rheumatoid anbritis.
tt is aimcutt for the patient to recogrrise ill-cffects from
iterns ttrat are consumed every day, so the proportion of
patiens with food dlergy/intolerance might be higher than
banustr suggess.
In the present study, fircd dlergy/
intolerance was suspectd in l0 (37%) of the 27 patieoa in
the diet group. Food allergy/intolerane, however,
is
unlikely rc explain the improvernent in all the patiens who
ctunged their diet. Interest has been drarvn to dietary fatty
acids and treir ability to modulate ttre inflammatory
process.a A switdr to vegearian diet causes an ocensive
dunge of the profile of ttre fatry acids of te serum
phospholipids.zr These dranges may favour production of
pro*aglandins and leukotrienes with less inllammatory
activiry.
Ve know ttrat malnutrition suppresses immunityz and
*rat ceauneot with immunosuppressive dnrgs is one of the
most effrcient means of reducing disease activiry in
rheumatoid anhritis. The diet group lost more weight than
*re conrrol group, though albumin @ncentrations showed
no differencc. To evaluate rvhe*rer the improvernent was
ANACOVA
was done
values werc
approximately rhe same as we obrained wittr ttre ordinary
solely due to the weight reduction, an
with weight reduction as a covariate. All p
repeated measures ANOVA. Theref,ore,
the
weight
rcstrictiots on discasc activity in rharnatoid anhritis' r{rar Rhaon Dt
19ll8l'41t69-72.
Tnng L, Vcnizclos N, Pelmbhd J. Nartrophil functions md
8. Udan
ainicat pcrforrngre gftcr total fasting in paticnts with rhornetoid
gnhritis. ,{rr R tatr
l9B3; 42: 4}51.
9. Hefsu6rn I, RirucraB, GyllcnfrzmnrcrH, Pdmblad J' Harms-Ringdahl
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