Controlled trial of fasting and one-year vegetarian - FX Mayr.
Transcription
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. 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Phimcy SD,Odin RS,Johnu SB, Holrncn RT' Rcductd arrhidomtc phospholipids eld dlolctcryl csrcs associattd with in AmJ Clin Nun 1990; 5l:38195' vegcarim dics in 22. Good RA. Nutritiort urd imrnunity-J Ch ltmwl l98l;lz7-ll. sm hws.