Indian J Physio! Pharmacol 2001; 45 (1): 71-19

EFFECT OF CHYAWANPRASH AND VITAMIN C ON GLUCOSETOLERANCE AND LIPOPROTEIN PROFILE'

S. MANJUNATHA, A. K. JARYAL, R. L. BIJLANI-,U. SACHDEVA AND S. K. GUPTA--

Departments of ·Physiology and ··Pharmacology,All India Institute of Medical Sciences,New Delhi - 110 029

( Received on September 8, 2000 )

Abnract. : Chyawanprash is aD ancient. Indian die.tary supplementcontaining vitamin C (34 mgllOO g) derived from amla (Emblica officinal;").In addition, Chyawanprash also contains several othe:r herbal producu.The present atudy wu designed to compare the effects of vitamin C withthoae of Cbyawanprash. Ten normal healthy adult male volunteen (age20-32 years) participated in the 16-week study They were placed randomlyin either the Chyawanprasb group (0: 5) or vitamin C group (n "" 5). Thosein the former received 15 g/d of Chyawanpruh while those in the lallerreceived 500 mg/d vitanlin C during the first 8 weeks of tbe study. For thenext 8 weeks, no supplement was given. For each individual, an oral glucosetolerance teat was performed, and lipoprotein profile in peripheral serumsamples was determined at 0 weeks, 4 weeks, 8 weeks, 12 weeks nnd 16weeks.

In the Chyawanprash group, the 8 weeks Vs 0 weeks value (mean ± S.OJrespectively for variou8 indices which were significantly differentwere faating plasma glucose 000.2:t; 5.58 mg/dl va 116.2:t; 11.6 mg/dO,areR under 2-h pluma glucose curve (245.9:t 15,13 mg.dr 1 .h VB

280.8 ~ 37.09 mg.dl,l.h), HDL cholesterol (53.2:t; 4,56 mgldl VB

42.7 :t 7.11 mg/dl), LDL cholesterol (82.4 :t; 8.80 mg/dl vs 98.26:t; 12.07 mgldl), LOUHOL rstio (1.56:t; 0.28 vs 2.38:t; 0.63). In the Vitamin C group,only the LDLlHDL ratio was significantly lower at 8 weeks than at 0weeks (1.99:t; 0.44 VII 2.29:t 0.43). All the variablea that changedsignificantly were no longer significantly iiifferent from the 0 weeks valueat 16 weeks, Chyawaoprasb reduces postprandial glycemia in the oralglucoae toler....nce teat and reduces blood choleaterollevel to a significantlygreater exteat than vitamin C.

Key word.: Cbyawanprashglucose tolerance

vitamin Clipoprotein

ascorbic acidcholesterol

·CotTuponding Author:'This work w.. pretented at the 45th AnDual Conference or the Aaaoc:iation of Physiologist. and Pharmac:ologi$Laof India in December 1999 and publilhed .. ao abstract.

72 Manjunllthll ct nl

INTRODUCTION

Chyawanprash is an ancient IndianAyurvedic preparation, which has beenclaimed to have health promoting effectsand has been advocated for degenerativediseases, heart disease and diabetesmellitus (1). A few studies are availableon the anabolic effects of Chyawanprash(2-4). However, to our knowledge, there isno information about the effects ofChyawanprash on carbohydrate and lipidmetabolism.

A major constituent of Chyawanprash isamla (Emblica officilWlis) (about 7 gllOO g),which is a rich natural source of vitamin C.Extensive literature is available regardingthe functions of vitamin C as an antioxidant,its protective role in degenerative diseaseslike coronary artery disease and in agingand its role in human metabolism includingthat in lipid and glucose metabolism.Also vitamin C IS quite commonlyconsumed as a dietary supplement byhealthy persons as is Chyawanprash15-14).

Indian J Physiol Pharmacol 2001; 45(1)

With this background, the presentstudy has examined the effects ofingestion of 15 g per day of Chyawanprashon the glucose metabolism and lipidprofile in normal healthy volunteersand how this effect, if present,compares with that of 500 mg/d of

vitamin C.

METHODS

Subjects

The study was conducted on 10healthy young male volunteers. Thevolunteers were divided randomly intotwo groups of fjve volunteers each.The characteristics of the volunteersare given in Table I. The two groupswere well matched as seen in thetable. Subjects were enlisted for thestudy after they had given theirinformed written consent. The studywas also approved by the EthicsCommittee of All India Institute ofMedical Sciences, New Delhi.

TABLE I: Age and physical characteristics of volunteers

GrOllp

til=' 5)

"(n =5)

IAge (yJ HeighJ (m) Weight (kg) 8M! (hglm)

22.6:1:4.5 1.66::1:0.02 57.0:1:3.9 20.52:1:1.21

(19-28) 0.64-1.70} (51-61) (18.50-21.51)

28.6±2.07 1.69:1:0.03 61.4:1:7.6 21.28:1:1.76

(27-32) (1.65-1.75) (51-72) 08.73-23.51)

(All values lire lUean :t: standard deviation. Values in llarentheses arc ranges).

Indian J Physiol Pharmacol 2001: 45(1)

E%perimeatal desiga aad procedures

Group 1 received 15 g per dayChyawanprash (Dabur, lnclia) while groupn received 500 mg/day vitamin C (tabletCelin, Glaxo, India) as dietary supplementfor the first 8 wk of the study. During thenext 8 wk, neither group receivedany supplement. The subjects were followedup every 4 wk. Blood samples weredrawn before the start of the study (0 wk),at 4 wk. 8 wk. 12 wk and 16 wk for theestimation of fasting plasma glucose, glucosetolerance. serum lipid profile and plasmavitamin C levels. In addition to theseprincipal outcome measures, body weightwas recorded at 0 wk. 8 wk and 16 wk; andliver function tests and estimation of bloodurea were done at the beginning and at thec.nd of the study.

Oral glucose tolerance test wasperformed using the standard dose of75 g glucose dissolved in 300 ml of watergiven in the morning after an overnight fast.Besides a fasting venous blood sample, bloodsamples were also collected 0.5 h. 1.0 h,1.5 h nnd 2 h after ingestion of glucose.Plasma glucose levels were measured byglucose oxidase method (I5) usingcommercial kits (Rnnbaxy, India).

Serum cholesterol and its fractionsand serum triacylglycerol were determinedcolorimetrically by enzymatic method (16)using commercial kits (Randox. UK).

ChY8wanprash, Blood Glucose and Lipid Profile 73

Plasma vitamin C was also measuredcolorimetrically by tricarboxylic acidmethod (17).

Statistical analysis

The values at 4 wk, 8 wk, 12 wk and16 wk were compared with '0' wk values ofthe same group using Wilcoxon Signed Ranktest. The difference was consideredsignificant if the P value was less than 0.05.

For comparing the changes in the twogroups, first the '0' wk values of the twogroups were compared using WilcoxonRank Sum test. After verifying that '0' wkvalues were not significantly different,the percentage changes at 4 wk, 8 wk.12 wk and 16 wk were compared betweenthe groups using Wilcoxon Rank Sumtest. The groups were consideredsignificantly different if P value was lessthan 0.05.

RESULTS

None of the subjects had any majorcomplaints during the study. There was nosignificant change in the body weightdurin/:{ the study. The results of liverfunction tests and kidney function testswere found to be within normal limits bothat the beginning and at the end of the study.There was also no significant change in theplasma vitamjn C levels of the subjects ineither group (Table II).

TABLE II: Plasma vitamin C levels in the two groups

GroupOw,

Plasmo IJjlomin C fmgldlJ

4wk 8wk 1211Jk 16 wk

I (ChyAwanprash)II (VitAmin CJ

0.37:1:0.09

0.43:1:0.22

0.34:1:0.13

004l:t0.16

0.36:1:0.11

0.41.:1;0.25

0.34.:t0.09

0.39:1:0.24

0.30:1:0.14

0043:1:0.24

(All values Are mean :I: SD)

74 Manjunatha et a1

Glucose tolerance

The effects of Ohyawanprash onfasting plasma glucose and postprandialglucose levels during the glucose tolerancetest h~ve been tabulated in Table III.At at wk, there was a significantreduction in the fasting plasma gluco elevel, 0.5·h glucose level, 1 h glucose leveland area under 2-h plasma glucose curve(AUO) when compared to '0' wk value. tfterdiscontinuation of Ohyawanprash at at wk,the follow-up showed that the valuesreWfned close to baseline (0 wk) values by16 wk.

The effects of vitamin 0 on glucosetolerance have heen tabulated in Table IV.

lndian J Physiol Pharmacal 2001; 45(1)

The supplementation with vitamin 0 for awk did not lead to any significant changein glucose tolerance at 4 or a wk, but therewas a trend towards improvement inglucose tolerance. The valuet returned tobaseline (0 wk) levels by 16t wk.

Tbe percentage change in the~ndicators

of glucose tolerance at at wk inOhyawanprash group have been comparedwith the corresponding changes in thevitamin 0 group in Fig 1. A seen in thefigure, the percentage change in the plasmagluco e values at 0.5 h and 1 h and thearea under the 2-h plasma gluco e curve(AUO) are significantly greater in theOhyawanprash group than in the vitamin 0group.

TABLE III: Plasma glucose levels in Chyawanprash group.

Plasma glucose (mg Idl) AUC

No. of weeks (mg.dL- I• h)

Fasting 0.5 h 1 h 1.5 h 211

0 116.2±l1.6 164%10.12 153±28.68 127*26.78 119±29.03 280.8%37.09

4 103.4±7.92 142%19.78 130.4±16.1 118.2±5.8 111.4±8.56 249±18.39

8 100.2±5.58· 138.2±8.1· 125.9±9.2· 123.4*11.9 110.4±9.76 245.9%15.13·

12 99.4±15.61 144.2±18.68 127.8± 10.32 123.6±16.31 111.4±16.68 250.5±20.50

16 115±14.31 148.8±22.78 132.8±13.6 122.6±11.19 119.6±6.54 260.75±22.6

(AU values are mean ± SD; *P<O .05 compared to baseline value).

TABLE: IV Effect of Vitamin C on glucose tolerance.

Plasma glucQse (mg / dl) AUCNo. of weeks (mg.dL- I

. h)Fasting 0.5 h 1 II 1.5 h 2 Ii

0 99.4±19.5 112.2%28.11 112.2%17.92 100.8±9.09 95.2±7.46 211.2±31.03

4 97.6±13.22 114.6%22.7 112.6±15.74 103.8±12.49 97.4±10.89 214.25±30.7

8 92±4.3 112±19.74 109.2±9.62 100.4±l0.11 95.4±6.46 207.65±17.6

12 94.2±4.08 114.8±24.93 112.2±14.68 102.6±8.79 99±4.84 213.1±25.62

16 89.8±5.21 115±21.05 116.4:t!5.96 104.4±11.41 99.8%2.48 215.3±22.02

(All values are mean ± Sn)

Indian J Physiol Pharmacol 2001; 45(1)

5

Chyawanprash, Blood Glucose and Lipid Profile 75

Serum lipid profil

Fig. 1: Comparison of the effects of Chyawanprash andvitamin C on observations made during the oralgluco e tolerance test (OGTT) after 8 weeks ofsupplementation. FPG, fasting plasma glucose;0.5 h G, 1 h G, 1.5 h G and 2 h G, plasmaglucose 0.5 h, Ih, 1.5 hand 2 h respectivelyafter ingestioD of glucose during OGTT; AVC,ar a under the 2-h plasma glucose curve;chyaw, Chyawanprash; vit C, vitamin C.

i 0

! -5;;..2' ·10~u~

.20w..-.....- ....- ...- ...---.......FPG O.5hO 1hO 1.5hG 2hG AUC

CCHVAW

.VITC

The effects of Chyawanprash on erumlipid profile have been shown in Table V.

As shown in Table V, total chole terollevel decreased gradually till 8th wk butthe decrease was not statisticallysignificant. The values returned closer tothe baseline (O-wk) values by 16th wk. Incase of HDL cholesterol levels, there was asignificant increa e in the levels at 4th wkand 8 th wk. But the value was nottatistically significantly different from the

'0' wk value at 12th wk and returned closeto the baseline (0 wk) level by 16th wk. The

TABLE V: Effect of Chyawanprash or. serum lipid profile.

Lipid fraction (mg / dl)No. ofweeks Total HDL LDL LDLJHDL Triacylglycerol

cholesterol cholesterol cholesterol (mgJdl)

0 174.6:1:10.4 42.7±7.17 98.26:1:12.07 2.38:1:0.63 168.3:1:13.97

4 168:1:9.59 52.5:1:6.54- 82.1:1:15.23 1.60:1:0.46- 167:1:35.16

8 167.8:1:5.16 53.2:1:4.56- 82.4:1:8.80- 1.56:1:0.28- 16hl0.07

12 170.6:1:7.02 46.9:1:6.82 90.78:1:9.15- 1.98:1:0.46 164.6:1:17.22

16 170:1:5.70 42.7±9.71 93.06:1:10.86 2.3hO.77 171.2:1:20.64

(All value are mean :I: SD; -P<O .05 compared to baseline value).

TABLE VI: Effect of vitamin C on serum lipid profile.

Lipid fraction (mg / dl)No. ofweek Total HDL LDL LDLJHDL Triacylglycerol

cholesterol cholesterol cholesterol (mgJdl)

0 190:1:14.81 47.4:1:7.3 106.24:1:10 2.29:1:0.43 181.8:1:18.79

4 189:1:22 48.4:1:8.23 105.4:1:16.52 2.23:1:0.50 176:1:23

8 186:1:19.64 51.3:1:8.36 99.7:1:16.81 1.99:1:0.44· 175:1:15.79

12 191.6:1:13.93 50.6:1:5.54 104.96:1:11.6 2.10:1:0.33- 180.2:1:16.84

16 195.8:1:16.72 47.2:1:6.87 111±l2.81 2.40:1:0.50 187.6:1:15.17

(AJI values are mean :I: SD; -P<O .05 compared to baseline value).

76 1anjun tha et al Indian J Physiol Pharmacol 2001; 45(1)

-4oJ..llll-_---_-IIIIIII--....LOl l..DlJHDL TRlGLY

DISCUSSIO

Comparison of the effects of Chyawanprash andvitamin C on serum lipid profile after 8 weeksof supplementation. Total CH, total chole terol;HDL, high density lipoprotein cholesterol; LDL,low density lipoprotein cholesterol; TRIGLY,triacylglycerols; chyaw, hyawanpra h; vit C,vitamin C

TOTAL HOLCH

Fig. 2.

Supplementation with Chyawanpra hfor a wk re ulted in a significant decrea ein the fasting plasma gluco e I vels.Also, in the oral gluco e tolerance test,

hyawanprash led to a ignificantimprov ment in glucose tolerance at ath wka compared to ba eline (0 wk). The effectis unlikely to be due to vitamin C becau ethe do e of Chyawanprash given in thestudy upplie only ahout 5 mg of vitaminC per day while even 500 mg of vitamin Cper day has not given a comparableimprovement in glucose tolerance. AsChyawanpra h is a complex mixture of manyingredients, a combined effect, which maybe additive or even multiplicative due tomutual interactions, would be the mostprobable and logical explanation of thieffect rather than anyone active principle.The aminoglycans and the flavonoidglyco ides, the active principles ofAsparagus racemosus have a significant

30

level at a th wk in Chyawanpra h group issignificantly greater than the corresponding

change in the vitamin C group.

..... 20~i 10

OJ o~jii:~~=iII

~ -10to ~ _

<1 -20;1'.-30.,r----

LDL cholesterol level wa significantly lowerthan the '0' wk values by a th wk. Thisdecrease was maintained even at 12 wk. Butthe value r turnei close to the ba eline(0 wk) level by 16t wk. Th ratio of LDLchole terol to HDL chole terol decreasedsignificantly by 4th wk and continued to besitnificantly lower than the '0' wk value atat wk. But as in the case of other variable,the ratio returned to the baselin (0 wk)value by 16th wk. The total triachlglycerollevel decrea ed marginally by at wk butthe decrease w not tati ticallyignificant.

The effect of vitamin C supplementationon erum lipid profile have been shown inTable VI. As seen in the Table, th re was amargin 1 progre ive decrease in the valuesof total chol terol, LDL cholesterol andtotal triacylglycerol at 4th and a th wk butit wa not tati tically ignificant. Thevalues return d very close to the baseline(0 wk) values by 16 th wk. The HDLcholesterol level increa ed marginally butnot significantly till the at wk andreturn d v r1 clo e to the baseline (O-wk)values by 16t wk. But as een in Table VI,the LDL chole terol to HDL cholesterol ratiowa significantly lower at a th wk than at'0' wk. Thi decrea e was maintained till12

th wk. But by 16thwk, the value returtJ.edto the baselin (0 wk) value.

The percentage changes in the serum lipidprofile at atli: wk in Chyawanprash grouphave been compared with the corre pondingchanges in the vit.amin C group in Fig 2. Aeen in the figure, the trend of changes is

similar in the two groups but the changeare omewhat more in Chyawanpra h group.But only the decrease in LDL chole terol

_,_....._~_I ..l I O,..._on.......... _ ......... ....- n

l\1POf1~c ad:JTit The 1'81.1" aJUI fihnocoateat of •••,. of tbe herb could be

pon.,ble (or th low r ab rpilon ofIha • wbach LD turn. reduc," the ~IYa!mic

...p'..... tl J D. with low .1yc.~lc mde:z

.1 IlDpro..." 10Dr t nD &Iuc tol ranee.91. The debydro••corbtc aCld· ..aaDoid

coQJu 1 and navonold which are uongAno,oJ:ldanLs. may al.o be partlv respon iblefor lh effect. The amino ocld. pI' cnl could.1.0 b" prarlly respon .ble by inducing1ft uhnumic rupoou (20). All lbc factorsput tocetbel' rould b h.ylnl' YllcorgisticffKl, wweb lDight be the nu of better

,Iuc tolU&Dce see.a with b,awanprasb.-uppl mt.nUliOD

h I CO.UDOal,. Id that by wanpruh•• H .ade...nble (or r Oil haY-i!lgd.ab te .elluQ bee••n ( I hirbrar hydrate Derosei ('ODt a\ But thed.aJl d ( Chy.....aprub Uftd 1Il this

tud ~ 15 &Id b... onl,. 12. ue .. 12 g orR I"ry small qUaIltlty t Y mealFurther. '-IDU this quantity or .ugar in

hyowanpn h is n ocilJ,t~ with (at, fibreend protem, its glycemic re'l)on'e will bemnrkNlly attenuated (21). In rnet, it hasbuon uluwrvl.'d in a preliminnry st.udy withthru(l NtDDM palients thot thtdr glucoseloll,tRne improved wlLh daily IngeJJtion of16 C' orChyowanpra..h (or wk tM nJuna-th.S, unpublit:bed data)

. uppl.... atation with b. awanprashb CJWII rnou.rahl~ .a CIa rum hpldprofil _ell B ... It Ir thenw. • ',luric.at increa la RDLell rot and decn:u 1.0 LD L chol lerola ca.p nd to ba .I1D. \' :alu Thesee(li u beam. more pronou nald b the th

wk and p.nlsud •••D ~ _lit anerdl nhnuLDI h,...anpraah The ben ficial

n of ClI..J1Iwanp on hpld prarLie is.. t lakely bto due to th co.blned Mrec.tor nral chemIcal The phyto terols,_bu::h are preae:nt I.D th Cbya.anprash..com with choleslerol r. r b IrptJOD atIn tlnalmueo&a and an U D to dl!c:l"l!aSec..hol rol ab rptlO:D (22) Th non-starchpoly..«b.and like lalactomannan couldfurthe.r deere ae tbe cbolellLerol absorption..The .aponins, steroidal or trltcrpenoidamphiphlllr clycoaid 8 ar not absorbedrrom tbe IDtesline but preciplta cholesteroland Interfere with mlCt."1I rormaLlon byt."ahanc.:LDI the blnd.t.nc of bit ("ld to fibre,

hlch In tura dKn!!:. ea dl l ry ch"t terol.b orpl' D (23). Reduction ID C'bol lerol

b rplion and 1IICTU.a 10 (ee 1 bale saltun lI. a due to bind.loc bv dl tar)' fibn1u. tic dftort. lac.-.....d ft'Ca1 bile

It ••c:reUOD reel l.bt:ar e:.at robepatirctrnll u • ...-Iuc.b in tDrll IA the needfor tI It )'llt.h - of btl. aaI yalhesisor bll ..h.• usa: up chol t rol. therebyreduClD, IU level 10 th bl f2·U. ThetannIn p~nt ar known to rt"duCt' the

ctlvlty or digestive o:r.ym wbac..h couldbE' re pon.lble (or both decrcut'd digestionnnd ohlorpliun of lipids PM \\foil nil glucose(23). COllsfdoring Lho fncL Lhlll nil thesechornicolK ore present in hynwunptllllh andlh pOlllibiliLy of synergistic inlt'rnct.ionamoncthem ~lves, it it: n(lt reolly .urprisingthaI byawanprash h.. a bc.on fie. I effectan (jpld prom .

11. I cOlIDlIDoaly d that lh b ..e ofCbyaW1lJlp II. 6ltrr tel nft d t.uller.

b.ich 1 aD animal Cat. of _hich.. A.lUratPC! aad th (1.1 Cby. DDp:ra.sh

...a,. ralS. blood chole ter t Flut there.aIOJOI 3 'I of lDonooo lurat d dpolyun .lu",~ (a'" 10 c:h would ~-jbly

counler Ct the effect of aturatedr.... econdt,.. and more Importantly.

78 Manjunatlul et al

Chyawanprash contains 5% fat. Therefore15 g/d of Chyawanprash would provide only0.75 gld of fat. This quantity of fat in theform of ghee in a mixed diet is unlikely tohave any appreciable effect on blood lipidprofile.

On the other hand, supplementationwith vitamin C did not result in anysignificant hchange i~ glucose toleranceeither at 4t wk or 8t wk although therewas a trend towards improved glucosetolerance. A significant reduction in bloodglucose values following Lv. injection of65 mg/kg L-ascorbic acid in rats was shownby Cheng et al (25). In human volunteers,Paolisso et al (26) demonstrated a reductionin fasting plasma glucose levels following avitamin C supplement of 500 mg twice daily.These findings have been supported bydemographic studies (27). The discrepancybetween these studies and the present studymay be due to the fact that the amount ofvitamin C in this study was 500 mg/day nndduration was 8 wk, both of which are lesscompared to the above study by Paolisso etal (26) who had used a higher dose for alonger duration (l000 mg/d for 6 months).

Vitamin C supplementation had afavourable effect on serum lipid profile.Although there was a trend towards gradualdecrease in LOL-cholesterol ag increase inHDL-cholesterol levels till 8t wk it wasstatistically not significant. However, theLDL·cholesterollliOL cholesterol ratio wassignificantly less at wk 8 compared to thebaseline (0 wk) values. The change persistedtill the 12th wk. In a previous study, Cernaet al (9) had shown similar results but inaddition there was a significant decrease inLDL-cholesterol and increase in HDL·cholesterol. In another study, Jacques etal (10) had shown an increase in HDL-

Indian J PhYliol PhlU'macol 2001; 45(.1)

cholesterol levels. The more pronouncedeffects in these studies than in thepresent study could possibly be becauseCerna et al (9) conducted the study onhyperlipidemic subjects where there is agreater scope for possible reductionand Jacques et al (10) used a higher dose(l g/day) of vitamin C for a much longertime (8 months). In the present study, thesubjects were healthy normolipidemicvolunt.eers and the amount of vitamin Cgiven was 500 mg/day for only 8 wk.

When the effects of Chyawanprash werecompared to those of vitamin C it was foundthat only Chyawanprash improved theglucose tolerance and Chyawanprashwas more effective than vitamin C inimproving the blood lipid profile. Keepingin view the doses given vitamin C couldhave made only a minor contribution to theeffects of Chyawanprash. It seems that theeffects of Chyawanprash are due to thepresence, and possible interaction, of manysubstances.

Further studies are required foridentifying individual effects of theconstituents of Chyawanprash separatelyand/or in combination. Also, in this study,only the effects on glucose and lipidmetabolism have been studied. Studies arealso required on the effect of Chyawanprashon antioxidant status, immunity and variousdegenerative diseases.

ACKNOWLEDGMENTS

The authors would like to acknowledgethe financial assistance provided by DaburResearch Foundation, India and thefacilities provided by the Defence Instituteof Physiology and Allied Sciences forestimation of vitamin C.

1

REFEREJ-

1 t

I" ....uta. r ....., E G.ndM', &ae:yaaue~ ., tMal ch,'.,,-na .. __ ./ cz...Cu. el.. __.... liH. It 4

Jl I"f~.,•••l.. r l'\. Wadb.... Nair K..K......"' •••r.. 1.4Ua,.. A •••ual .rlabe,.tor,. tech,"quea .'11.'1•••1 , ••",.r, ofN.,,,,,,,". II,drrolNd 19 . 124&11$

1 ADd..,.... JW ht Shlla Mil, 01.- JA, 8Mb la,ItMM At" .r-del "aden Nulnu". I. n...llh ~D'M .. lI.lt...re. Wlll~ ••d Wllkill •• I.... ,,_ I I 1

11 OJA .....erTM& .., a....... n.c..J. ".1 Al.... r.at,. &L~ ... ,,-.a; '-Cl .....

~~.._.... • 4; t lie 4wt. ... J a... N-.fTI ••

'--u ..AI' ..

'11 A n.&u- MG. S..,.•..aridI .......... La &.- rb-- ...

1..'.··.... • , , , ./, ;,..J"-,..alI _U

tt J_ ...In Ku'-- S. 18 s~ O~ .lit,.Shih 111 It-. AC fUa r. NutnlJ•• ID

nuUit .~. O..~... Balll•• r•. Wllha•• aadWII.UIC. W f'dIUoa 1999 17- •

23. J"nldll" OJA W.ln'!!r TMS, ."'nAlnll AL In ShiteME, OIlun JA, ShJk. M. Ito.. A lEd.). ModuDNutrilioll In 1"*Dllh !\%" Ollflll .... Ihllilnore,Wlllhllll. nml Wllklllll; 9 udltloll IOU9;079-098.

24 LIIVll II hI CIA. SIIUllllrlh:h liP. lohcblllllul ofchol".lt'rol d.Prtl.I.IlI ..rr.c.l.rpeclin In chlJlull!ntlrid r.~ J N.tr 1966. 8 ' 209-~ 14

2.5 caw.., JT UIIlllh elMDo SC, TNI CL L-a_lIIac arid'r....c... hyPOC1fc-eaia ••d b,ptonDoul ... La.... Uwow"; rala J "Mr. "h,..... II ~ 41...

K P..U... a ..Il.. v Val,. VU"~I. GGa A ...-.•••_ ... Aa. • 'e\'lnKdUe M OOooflle , Jht.aMlx ....Mfiu~ ~ 'Vl-laaa C...... _ , , ._ .lA-CeIl.. In$.... ~

n, LI ~~ • LT ....,-.I s.-c.... ~.P.... u-" .... A L t_DDtrta;L::c:---n ..'.,.aJa-lac... '- .....~,.. wIou_ A JO ,.... -•• aC" .- 0.-10 ..t.rt..t u.. l' -.u:-­..... b ........ c:..n 1"'--1 II. 111

U. T.......... o.w...'_,_ ........ r ~

......... ,...n.s.M.... ,'u'•••, -

... C k.. ICL'/CJia,..,. 1 US...

....111 .s..,t ru 0 , t.. Cia'''' , "'-- .....

ll,.pnl#ri ~ .. II J:a ........'" I.for ....1.AaUI ('; C_ \ .... In:.!, 34441- "'4

to JacqU4'" I". Sul~", 51 Pnroafl Olt "UD.' .I.Scb.lr., f.;J El'TII!CI of "lleDlln r lupplsmtlQtationon IIPOprlllil!ln cholesterol, lpollpoJl'Olflln andIrlc1yc"rh.lfl eonunlrftllolll An,. E/lll/nfllwl 1995;0: !III-nO

ll. Prfllfll'n,,11l Nt Depeodlln(fI of 1IIIIIIlI stlilles ofpentos. phluphalll qcltll on \'It,,,nlll C mt!lnbollatQto eonPKIlv. Il,.utI paLhololJ' Vppr IJltd ICJum1992. S 41-44

U Dallea lUI "~uad&rS. Cub.nUl R.! \I.hla· K M...... A A1unll ,. 0.. "11."_ .ram- '''-'- La n 1IC ..:t<I'1II....-... 6aqa. I 27. ":6-10

1I ~ .. I .at' ,.u.......... _ ..--..,11 ...... .t .t __,..... n,....... ........... ef _ , -.aa It...... t.-....... ~..-lar J & Ir .,1IIt'k­t •

It C"'a H uek IIIl C ,. K Wa....\; ..Pl._ ...... .. ,,' ,..-C WllaaIaE..... .. ,Iii

...,~. r,_ ra' w , ..Had • I. ,all••u• ..,..,.......~ 6.r H.." J I 15.

-I

I Qanib _ ••~A~s.a.t ""_apr

~ SIt.ar..- P\' )Cl;

U. .......... TS Cl,,.. -..,-aU ... -...blllr.,..'~.I"" J ..J"llal1m. 1. 11.14

J T,"", TL rtIIIIur ~. PlIa.. 10 \ .,... SP,N••~aN PK.~ EJfKt.r C"tJ'.....praaJa _...bunn..... J /fa "'.7 Sui t til. 125

• Vu•• MO, Slach RU. Udu..- KN .'hrsl.toe-cai.sIMI.., .... aad ••t.bohC' Ilud .... on lh••trec.r.. .rra.., •• IMf.p, 18 acel perMO? J Ifn IN lIaiI.n. ~ 1 t 1

I A W.c-tlho U, 8u.~.,. 0 TlI*...,;oUI .... .tnu-aC Aft r,..1UJ,nd BMIt... 44., .. ~., ......._.~.,................ -n-,.......... ,J • ~'1dI

lMI III II

, a &acIu<I L............ '- ~ ...• IL\ ..AC