Progress in Medicine, Vol. 14, No.7, page 1972-1976, 1994. Research Report Effect of mycoproteins intake on serum lipids of healthy subjects Haruo Nakamura, Toshitsugu Ishikawa, Masahiko Akanuma, Masato Nishivaki, Tsuyoshi Yamashita, Koji Tomiyasu, Hiroshi Yoshida, Eisuke Nishio, Koji Hosoai, Hideki Shiga, Katsumi Hayashi, Kei Nakajima, Toshimitsu Ito, Kenji Higashi, Masato Ayaori, Yukihiro Takahashi and Emiko Miyajima The First Department of Internal Medicine the Uniformed (Defense Force) Medical College Introduction Serum cholesterol of the Japanese is increasing as a whole in recent years; approximately 50% of the Japanese females above 50 to 60 years old have serum cholesterol more than 220 mg/dl, a value which is closely associated with the pathogenesis of various vascular diseases. Accordingly, there is much concern that the occurrence of atherosclerotic diseases such as angina pectoris and cardiac infarction can be hardly prevented in the future”. From this point of view, more attention to the change of life style including diet and exercise is recommended and the diet and functionalism of nutrition are being focused. 1In 1984, Udall et al.?) studied tolerance and nutritional value of mycoproteins in humans, and suggested a possibility of serum lipid lowering effect. This work was substantiated in 1990 by Turnbull et. al.», demonstrating that 17 male and female healthy subjects who took normal diet supplemented with 49 g/day of mycoproteins had a 13% decrease in total cholesterol, 9% decrease in cholesterol of low density lipoprotein (LDL) and 12% increase in cholesterol of high density lipoprotein (HDL). In 1992, the same group has reported the follow-up results of the @-week trial with average 26.9 g/day of mycoproteins’. The report described the decrease both in total cholesterol (37 mg/dl) and LDI-cholesterol (33 mg/dl). In this report, we describe changes of serum lipids in 15 healthy males by the intakes of 18 g/day and 24 g/day mycoproteins in a form of cookies (or chips).Subject and Methods Subjects were 15 male medical doctors in The First Department of Internal Medicine, the Uniformed (Defense Force) Medical College, 25 to 60 years old (average 3319 years old), who had no apparent diseases requiring treatments and took no drugs in constant use. The subjects were randomly divided into two groups; one group (8 subjects) received 18 g/day of mycoproteins and the other (7 subjects) 24 g/day. Mycoproteins used have been developed by Zeneca Company, and was supplied by Otsuka Pharmaceutics. The mycoproteins was given in a form of cookies (or chips) in order not to leave residues. The mycoproteins contain rich proteins and dietary filers as listed in Table 1-1. Test diet composition containing mycoproteins is listed in Table 1-2. It contains good amino acids as well as a relatively high level of linoleic acid. The compositions of amino acids and fatty acids are shown in Table 2. ‘The subjects were instructed to take mycoproteins without changing daily diet, and requested not to change their body weights. Before the treatment, 4 weeks and 8 weeks after the treatment, blood samples were collected from fasting subjects in the morning to determine serum cholesterol and triglycerides levels by the enzyme method, HDL, cholesterol by the precipitation method followed by the enzyme method. LDL-cholesterol levels were calculated according to the Friedewald’s formula. Levels ofphospholipid and free fatty acids were assayed by the enzyme method, and apoprotein concentrations were measured by the turbidimetric method of immunoprecipitates. Results Average age, changes in body weights and body mass indexes (BMI) of the 2 groups, 18 g/day and 24 g/day respectively, are shown in Table 3. Changes in body weights and BMI during the treatment were not significant. Table 4 showed values of total serum cholesterol, triglycerides and HDL-cholesterol before the treatment. The concentrations of serum lipids were within a normal range, and there was no significant statistical difference between the two groups. Table 5 demonstrates changes in levels of serum cholesterol, LDL-cholesterol and HDL-cholesterol. The treatment was discontinued for 2 weeks following 8-week treatment. These results are also shown in Table 5. the total cholesterol level in 18 g/day group was not changed even after &-week treatment, while 24 g/day group had a sign of slight decrease. However, the decrease was not statistically significant. 24 g/day treatment also showed a slight decrease in LDL-cholesterol. With regard to HDL cholesterol levels, no changes were found in both groups. Fig. 1 shows decreases of total serum cholesterol levels in both 18 g/day and 24 g/day groups by limiting the subjects withtotal serum cholesterol levels of more than 190 ng/dl. There was no significant decrease of total serum cholesterol levels after the treatment in 18 g/day group, whereas 24 g/day group had a significant decrease at week 4 and 8 after the treatment. With regard to LDL-cholesterol levels, subjects with the pretreatment levels above 120 mg/dl in 24 g/day group had a significant decrease at week 4 after the treatment. Changes in levels of serum triglycerides and phospholipid are shown in Table 6. Although 15% and 17% decreases were found in 18 g/day and 24 g/day group respectively, no statistical significance was observed. However, the decrease by the treatment as a whole was 16% and was statistically significant. There was a tendency for phospholipid levels to decrease slightly after the treatment, but no statistical significance was found. Free fatty acids were found to show up-ward trend after the treatment. Table 7 summarizes changes in levels of major apoproteins. Although apoprotein A-1 tended to decrease in both groups, there was no significant difference. Apoprotein B also showed a tendency to decrease, but no statistical difference was found. Apoproteins E had no significant changes in both groups. It should be noted that there was a significant correlation between changes of LDL-cholesterol level and apoprotein B level (x?=0.279, p<0.05). Therefore, it indicates that LDL-cholesterolwould be closely related with apoprotein B. Discussion Although the intake of mycoprotein chips on healthy males have suggested only slight effects, it clearly shoved the effect of reducing serun cholesterol and triglycerides levels: 24 g/day intake of mycoproteins significantly decreased total cholesterol in subjects with cholesterol levels above 190 mg/dl, as compared with corresponding subjects in 18 g/day group. our finding that there was a significant correlation between LDL change and apoprotein B change levels, supported the usefulness of mycoproteins. The composition of mycoproteins could suggest some possible mechanisms of its effects. First, mycoproteins contain a relatively high level of linoleic acid. since the total amount of polyunsaturated fatty acids in 24 g mycoproteins is approximately 1.0 to 1.2 g, such a small amount of polyunsaturated fatty acids should be hardly effective. Secondly, protein might have a relevance. Proteins as soy bean proteins have shown to stimulate catabolism of cholesterol® and activation of LDL receptors®, Mycoproteins contain more lysine and less arginine as compared with soy bean protein. Therefore, the composition of the amino acids might hardly contribute to lowing effect on serum cholesterol”, Thirdly, the effect may come from a relatively high content of fibers. Although the effect of fibers including chitins and p-glucans should needfurther investigation, we suggest that the major effect of mycoproteins observed in our present study would be due to fibers. Those points, as mentioned in the above, for the mechanism of mycoproteins effect should be clarified on account of hypercholesterolemia cases. There was no particular case that implicated side effects. Conclusion When 15 healthy males took 18 g/day and 24 g/day of mycoproteins under the conditions in which their diet styles were not altered, levels of serum cholesterol and triglycerides tended to decrease. Especially, subjects in 24 g/day group with total serum cholesterol level above 190 mg/dl had a significant decrease in these levels. The major effect of mycoproteins is assumed to be related with the presence of dietary fibers, and the usefulness of mycoproteins mainly in hypercholesterolemia cases needs further investigation. A part of this work has been presented-at the 15th International Meeting of Nutrition, held at Aderade, Australia, on September 28, 1993. eee Reference 1) Report from the study group on circulation diseases, the Minister of Welfare, Japan, 1993 2) Udall, J.N., Lo, C.W., Young, V.R., Scrimshaw, N.S.: The3) 4) 5) 6) 7 tolerance and nutritional value of two microfungal foods in human subjects, Am.J.Clin.Nutr. 40:258-292, 1984 Turnbull, W.H., Leeds, A.R., Edwards, G.D.: Effect of mycoprotein on blood lipids. Am.J.Clin.Nutr. 52:646-650, 1990 Mycoprotein Turnbull, W.H., Leeds, A.R., Edwards, D.G reduces blood lipids in free-living subjects. Am.d.Clin.Nutr. 55:415-419, 1992 Sugano, M., Yamada, ¥., Yoshida, K., Hashimoto, ¥., Matsuo, T., Kimoto, M.: The hypocholesterolermic action of the undigested fraction of soybean protein in rats. Atherosclerosis 72:115-122, 1988 Sirtori, C.R., Descovich, G., Noseda, G.: Textered soy protein and serum cholesterol. Lancet 1: 149-152, 1980 Kritchevsky, D.: Dietary protein and atherosclerosis. Atherosclerosis 49:209-210, 1983Table 1-1.Composition of mycoproteins (MCP) (dry weight %) proteins, lipids, carbohydrate, fibers, ash content, water and others. Table 1-2.content of a test diet with mnycoproteins (MCP) Table 2. Table 3. Table 4. Table 5. Table 6. Table 7. Fig. 1. Fig. 2. McP-dry content, MCP-dry g amount , MCP-wet equivalent amount, wheat flour, granulated sugar caramel pigment, energy/day. amino acid and fatty acid composition of nycoproteins. Age, and changes in body weight and BMI. Serun lipids level before the treatment. changes in serum cholesterol. Changes in triglycerides and phospholipid. Changes in apoproteins. changes of total cholesterol in subjects with total cholesterol levels above 190 mg/dl. Correlation between LDL change and apoprotein change.Table 1-1 Composition of mycoproteins (MCP) (dry weight ) proteins 47.0 (8) lipids 10.5 carbohydrate 10.9 fibers 26.5 ash content 3.4 water and others 1.7 Table 1-2 Content of a test diet with mycoproteins (MCP) MCP-24 g group _| MCP-18 g group MCP-dry content 508 37.5% McP-dry g amount, 24.4g 18.39 MCP-set equivalent 95.69 71.79 amount wheat flour 23.4g 30.3g granulated sugar 2.5¢ 2.5 caramel pigment 0.39 0.49 energy/day 17Skeal 178kcalTable 2 Amino acid and fatty acid composition of mycoproteins A_A Composition (% FA Composition (% Arg Lys His Phe tyr Leu Tle Met val Ala sly Pro Glu ser thr Asp trp cys Ciao Cr6.0 Cie: Creo Cin Or SuUUNn AB aaNUMEUsNeSs Com ubbebdaese Table 3. Age, and changes in body weight and BMI [ Wei ight kg) Age - ow aw aw Total |32.949.2 |72,5£10.3 73.249.9 73.329.7 18g | 33.3412.1/73.6£7.1 73.946.9 73.946.7 24g | 32.427.5 | 71.3413.5 72.3413.1 72.6412.9 gable 4 Serum lipids level before the treatment 48.9416.8 43,748.21 178.3425.7 117.5+42.6 188.0415.5 _145.9+50.7 18g/day 24g/day (Mean+s.D. »mg/dl)Table 5. Changes in serum cholesterol ow aw 8w +2W Total (15) 182.8421.4 177.1417.2 179.6£17.3 179.722.0 18g (8) 178.3425.7 175.1£19.4 179.4+21.4 = 178.0£26.1 dg (7) 188.0£15.5 179.4415.4 179.9412.9 181,6+18.0 LDL-Cholesterol Total (15) 110.2418.2 104.9416.4 112.1419.5 112.8£18.8 “Ts (8) 105.9421.0 103.7420.2 111.924.8 110.023.7 2g (7) MIS1EM.4 106.4412.1 112.4+13.0 115.912.3 HDL-Cholesterol Total (15) 46.5413,3 47.4413.5 45.6413.3 45.6412.8 18g (8) 48.9416.8 50.1416.7 47.6416.3 48.1415.0 24g (7) 43.728. 44.349.0 43.349.4 42.7410.1 (MeanS.D., mg/d?) 208, 200 195, g I alee Piss err A + p<0.05 175, a ae =*p<0.0) no 16s ow) (aw) (ew) Fig. 1. Changes of total cholesterol in subjects with total cholesterol levels above 190 mg/dl Table 6, Changes in triglycerides and phospholipid ow aw aw +2W Triglyceride Total (15) 190,7247.1 124,0452.2 109,5429,0° 106.5428.0 18 (8) U17.5£42.6 106.8462.0 99.5232.6 99.4:434.7 2g (7) M45.9450.7 143.7431.8 121.0:20.8 114.617.0 Phospholipids Total (15) —200.3425.5 195.3422.0 192.4418.4 194.1:426.7 1g (8) —200.032.2 193.6:24.0 196.0221.2 189.4:£26.8 24g (7) 200.7£17,6 197.121.2 188.3:15,1 199,6:427.5 (Mean+S.D., mg/d) *p<0.05 uTable 7. Changes in apoproteins aw Apolipoprotein A-I Total (15) —-125.726.0 119.7%20.8 118.7420.8 18g (8) 131,3432.5 123.0422.7 120.5+21.5 24g (7) 119,4216.1 116.0419.4 116,6421.5 Apolipoprotein B Total (15) 94.1412.0 91.9212.5 89.849.1 _, 18g (8) 90.1+13.0 86.6211.1 87.1410,1 Mg (7) 98.79.5 98.0411.9 92.97.38 Apolipoprotein E Total (15) 4.4411 4,740.9 4,241.1 1g (8) 4,641.2 4,841.0 441.3 24g (7) 4.2+1.0 4.60.9 3,940.8 (MeanS.D., mg/dl) y=0.365x-+4.598,/7=0.279 (p<0.05) 15: Po ~20- —r =30 -25 20-15-10 5 0 5S 10 15 2 ALOLys Fig. 2. Correlation between LDL change and apoprotein changeProg. Med 14: 1972~1976, 1994 vAa7OF AYRES EH BML MT OR ea ite =| BM the ‘uF & 8k eR Me wR OM RE we Me RK Ris ERR aeoE BAAD RINT LAF OUR, SAI EHO MIE Boe OEHIHE NT, NISO~ OO PULDMDGIE. MAPA HE ENE E 47220 med eo TH. SRS, Comm ERE ANRC Ee EO IRE nim G11) TRE OHEMREN TOS”. SORMLTL, RU, Bae Ens4 7294 RADE BARE ENTE, ZOHTO REIS. KROVEYTENTH), MAMA RME NS & at, FTI. 1988 Udall 6 AONE BMEHE, RRM E OHA S NS. LAR BE OU Fon THE Turnbull 62 £ > T1990%%, ITI RRA AE BKC IT OF yiog/ DE ARCH L, BMTR IE AF OW NHK, Mle RAG (LDL SLAF OAM AS GEL, BRE Y RI (HDL) 2 AF BNE DMM IO BSE EL THB ZMih, WEI, MANAG ET, BIT ST OFA YEG, 96/T, 8 MINN MODNLHLA TERE a vA FO —wissImg/d!. LDL* DL AF OTB mg/Al MID Ma THs, SB, NDAs, Wade Ro Te SUTIN ISG, 118g, BLUMEN STO YET YR (Fy DEB HOR L, Mit T DRE Ae FL Nakamura TP lshikawa, M.Akanuma, M.Nishiwaki. T. Yamashita, K.Ton wie He TEA an Mf RRM * ko oH & ‘ei RN TTR Rin) YLAS AF Y(MCP)OAER A ME%) Rant 47,0056) Cae 10.5 a oF 10.9 | ‘Sethi 26.5 | RF 34 I ah ft La HULOT, CEEOMMESEDOTARY, ARES BIR SERS DELS AEE — PFE WLS ~ 600 OF SERIE 9M) OBE, HHI KS RS Be RTM 4 eSATA B, ASMMEMIHIE DECAY, 1 B18 OTF ST OFA YEH SUES I), 1 A2eg IMT BTR T IAD E Lt MMA 27 OFA viz, ZENECAUTIMSE SALIDTHRMEL IRE, 772 -(F 7 POKBEL, MRO~O ETM, 2B, 24 BT OFA VOMMIZ, I~ eC a BEVRRICHA TR, TERIURLEMRRAL MAREN 2OLE CHE ROT S / MHI ER URQUME, RIERLTAY, AMOT ETE BEE UI, HARI we Hass, MRERERORGIERA SEG, 7437 DFA EMM SET MRT SLE IC, MME 60. Yoshida. E. Nishio. K.Hlosoai, W.Shige, K-llayashi, K.Nakaiima, T.lto, K.lligashi, M-Ayaori, ¥.Takahashi, E. Miyajima { MmILFEASERT— 9 = 18201972) ~Rl v¢a7aF4 vor ism, Beet Rie? v4a7074 r(MCP)IRNRRARAER MCP-2ig | _NCP-itg BF BA Composition) FA Comacston(®4) | MCP-dry © ft 30% 37.8% Arg ee Cure bt jos 84 Cue BE MCP-dry g & 24 dg 18.3 His 27 Cut o8 | MCP-wer HUR| 96.60 The Phe 48 Cue a3 | ry 23.49 30.38 tr ae a ae K — Ls a7 wr tt | ea 2 5e 2.Se He 5.3 Cus a6 fF AoA noe Oe Oe Met 22 EaneH/8 | Wkeal Vitel | va ba \ Ala 65 | ay ar i Pro 44 Gi 20 ‘Ser 50 | Thr 3.4 | As 10.3 { os 16 | os os | Ho MAORM, HEL OMORE Weight) Bail | age on | | ww aww a, Tora [2.9292 [asi0.s 12298 TadedT ig [38.32.1|73.627.1 79.9268 72.936.7 nig [227.5 [32183 7292101 BkSeeo ss CMAseh, IRA. 4 Wik, SMR REMMI MHILAF OMA, RYTY ASA KEMIE, HDL=2 FA FO 18 HARE ANG PIRI AEAEET WEL, LDL3 LAF Owls, Priedewald ot (SCARBE L 22, MIRBSL As & USHARIERRE EB BEBE, TA RU a HES 9 TINE Lt aw a FLTC, Log ARLES OA, Dag MINE 7 talons Wi, (FIL EU BMI(Body Mass Inde orate LCS, MMM OEE, BMI DMNA TL thos SAMMI MITIEA LATO, bY TID 4K, HDL-D LAF OWE HA RL TAS. 18g IRIIRE, 2a ITER ea iE TERR FRAT A TIN ROBB SATOH, Rt BmROOANRAS Lag/day 178.5: 2.6 W9r168 | Npléwy 188.0515 5.9450.7 7281 | (Mean 8.0. nea RS kMiha LAF O—m, LDL-2vaze—n MDL-avAro-womieemt, 8 MINIM, 2 RRM yk TBD, SL Gee TT BL BILAFO—Mmis, [Sg MilhPATIs 8 MRI HERBS AK, Dlg REIN CHR BR LOS, LL AROSE TIE ete fe, LOL: AV AF OM MHMIL NT &, Ug MERZ eA SMPOMME MTHS, HDL-2 v AF o =i OUT, HERE LER K RMB SATOLU, AHABI LAF OM MMANIME/AL HLL MULE 16311973) —Progress in Medicine Vol.1¢ No.1 1884.7 Rs gmaLaro-noORt HDL-Cholesterol_ - Bus nts vr ’ a = [ ++p<0.1 oa Si a RE bye St ow ‘TrinWveeride Total (5) 190.7247. We (8) 117.5#42.6 | te C7) 148.9450.7 Phospholioids Total (i 200.3425. We (8) 200,0492.2 20. WT, 18g, Ug IRATRETS Oi & AN LRA HERLTAS. 18g MRAP D9 TLIO BN HACIA ALT eons Ug MACS ABR, BMRA ORD MBDSATOS, LDL-3 LAF OM mii uC 6 Hila WOme/al IERIE UTA BE, Udy IIIA T. ABALAROMDE BTS, 124.0:52.2 109,529.0° 106.528.0 105.862,0 99.5232.6 99.4434.7 143,7231.8 121.0420.8 U4.6217.0 195,9222.0 192.4218.4 194.1226.7 | 193.621.0 195.0221.2 189.4226. 197-1421.2 188.915.1 199.627.5 (Mean =S.D. mg/ad AMY TU LEE PREC MRORICE, BE IRL THB, 18g IRMBETIS, 24g RUBE ION MOE ELEM TO SHEN TLOMSUAET: eebots, LBL, BCH S EL OME THEM RECO TOS, MAMI THR, UNE TH tA" DIRE ER Sa, HEAROMMTR Hoe, MUI VARIG BIA RL THB. 1497) ~RD 7tEaoRe Apolipeprotein A-l Total (15) 125.726.0 119,720.8 118.7420.8 18g (8) 191.3432.5 123.0222.7 120.5221.5, 2g (7) 9.44162 116.0219.4 116.6421.5 Apolipoprotein B Total (15) 94,1212.0 91.9412.5 89.849.1 Te (8) 90.1H13.0 86.6111 87.1210.1 2g (7) 98,729.5 98.0211.9 27.3 Apolipoprotein E Total (15) Agel 4,720.9 Ig (8) 46412 48210 ag 7) 1.0 (isanzS.D. mg/ed Y= 0.26544 4,698,1"0.219 (B<0.05) = ‘R Beta TOF ty Ha? Ch, LETH Sm, MAMI, ith PERFORM, bY TVET RAMPS EMSS DTABIEMBD HA, HII LAF O—widae 8% 0 me RI FAL ASTRIRATUEL & (ou: Eine hen, TRRBBEOWT L, FIRMME & Ena Tie es 6 8D ‘AUDLe LoL oats: raHRaBOR CR ERTHRAOQMERLTHS, THE ROM, HANTH), TTEAREOY SOMMVASREA H — ELTSUAFO-ORIEITEDIIEN, LDL AE BASRTHS, LAL, CREORIIH Prot 190mg/d/ LE APA THS. 18e/ Birt L2ie/ AE FROMPMBBERTOS. SH LDL MRE iE, TRA Boy Ribas ROM A Les E LA OHMEE RAT SLME BL HHS. ZOBMEMRAEYASCIPL ITF OFA LD MUMLDH, ROM MANATEE SNS, 1 Did, I / IRR RAEN BO a 3 m6 Dig 21S STAGE, 871.0~1.2g RE Th LORRI AT Ahie Lieieea ee pte HiGHOO TEMA AGNTOS, PA ET ORLY BRDO Mie — MAINE BB TE ABR, ABOSACIEL Re NYRR TREE debi, SHubM TA Foie Rou CEA LES COM, oka TREBEL OWT, MMMMRE CET MOR — a, LMIIMATI RT OMIA SI. ARES BROS ATH, th, TREA BOR OB (eAE oft (F=0,219, p<0.05) BN THY, LDL-IVAFO Fi chem We TRROB SHRM L THB Se EHR ta, ft, ma UBT M EMME ST BIRIED MAE ELDL-DUAF OL _UDTRHSNE THAI A, GUMAIHMELT FOE CARON 2, MAI ES LDLME SIS, WL TIL AF OMIM BWM GOERS THBEBLBNTOS, Wo R94 Tatu T, HHS BME Boa BEL (LD BLE mote, 165 (1975) ~Progress in Medicine Vol.14 No.7 1984.7 BYE LP ORBBE. ROKER CORRE TBM UOT ITOT EMAL, Mi BURP OW, RUT VEST FONE ME IB Fe, ISRO LAF O—NANGOMg/Al LDINTL2, 99 5 OS 2dg/ BRIAR HOO Fo wENZ & NLT, ZEAE, MEL ES UDLIESRAM, + BR LAF Om MAO hts(s = OATHS HERE FOLENHS I ‘ISLES BIN » 23707 & (19990F 9 MBE AMO METER L A RRONT THERE x 1) MSMR MAT IATE, 19998 2 3 4 =188(1976) ~ Udall J.N.. Lo.C.W.. Young.V.R.. Scrimshaw N.S. The tolerance and nutritional value of ‘wo microfungal foods in human subjects.Am.J Clin. Nutr. 40 258-282, 1984 ‘Turnbull, W.H., Leeds. A-R.. Edwards.G.D. Effect of mycoprotein on blood lipids.Am.1 Clin. Nutr. 52 645-650. 1990 Turnbull, W.H., Leeds, A.R., Edwards, D.C. Mycoprotein reduces blood lipids in free - living subjects.Am,J.Clin, Nutr. $5 415-419, 1992 Sugano, M., Yamada... Yoshida... Hashimoto: Y., Matsuo.T., Kimoto,M. ! The hypocholestero: lermic action of the undigested fraction of sor ‘bean protein in rats. Atherosclerosis 12 113- 122, 1988 Sirtori.C.R., Descovich.G... Noseda.G. : Textered soy protein and serum cholesterol. Lancet 1 149-152, 1980 Kritchevsky.D. : Dietary protein and atherosclero: sis. Atherosclerosis 48 °20%-210. 1983CHOLESTEROL LOWERING EFFECT OF MYCOPROTEIN : CLINICAL TESTS bY | |\—|_———Fest Inake Period Dose- Completion |——Presentation—| Contribution} —— ~ 1: 26th Atherosclerosis oR Dose Finding Test Hyper | 4g Symposium at Yokohama] PROGRESS e cholesterolemia Mid Nov. 94.06.09-10 IN sti KAA 1| (Double Blind) z 12g 194 [2 xh Intemational | MC P-1 patients PL Atherosclerosis MEDICINE 4 weeks Symposium at Montreal (Ptanned) : Be 94.10.09-14 PROGRESS prot Long Term Health: IN 'y t cnpnrtaal 2) oe Tt | Votunteer | 748 | 94.06.29 em fe {Safety - QOL) 18g 93.09.26 - 10.1. | Vol.14No.7 8 weeks MC P-2A P1972-76 1994 Hyper- 7 Long Term cholesterolemia DE : atient: PROGRESS 3) _ Safety Test ae fe | 248 |end oF Now oS IN fomm)” | (Safety - QOL) | famitial 18g ‘94 MEDICINE MC P-2B patients) (Planned) 8 weeks BRSKET-940926 ox