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CategoryType of trialParticipantsAgePreexisting diseasesCompoundDoseSummaryReferences
Blood

Summary of 2 open-label trials

24 patients

25 patients

NRangina pectoris EPL
  • Over a period of 14 days V.A.Almazov et al. administered infusions of 500 mg/day

  • 500 mg/d of intravenous  either as a single administration or for a period of 15 days
  • During this relatively short observation period they achieved a reduction in relative platelet aggregation by approx. 60 % in comparison with baseline values.
  • Both the rate of primary and secondary aggregation and the interval until the aggregation peaks were reached were clearly diminished.
  • Microscopic examination revealed a reduced number of aggregates and within them a reduced number of platelet conglomerates
  • A significant inhibition of platelet adhesion to glass as well as an inhibition of platelet aggregation also have been described by S.Coccheri et al 
  • Almazov V.A., V.S.Gurevich, E.I.Krasilnikova, B.B.Bondarenko: Effects of Lipostabil on blood lipids, platelet function and macrophage function in patients with ischaemic heart disease Lipostabil Symp. Moscow, Nov. 1984
  • Coccheri S., M.Alessandri, V.de Rosa:
    Platelets and contact activation of blood clotting. Influence of some aggregation inhibitors Acta Med. Scand. 190 (Suppl. 525) (1971) 253-256
BloodSummary of 2 open-label trialsNRNRischemic heart disease EPL
  • 10 days treatment with 1 g i.v. /d and 30 days of daily oral administration of 1.8 g of EPL 
  • Used the relative dispersion of light transmission fluctuations as a parameter and measured platelet aggregation by means of electron optical analyser.
  • Clearly reduced sensitivity of thrombocytes to ADP related to an inhibitory effect on the ADP-induced rise in Ca++ in the platelets.
  • The authors observed inhibition of PAF-induced platelet aggregation both in-vitro and in-vivo
  • These changes did not vary during the 3-month follow-up phase after EPL treatment.
  • Reduced platelet sensitivity towards substances provoking aggregation (e.g. collagen) became evident.
  • Fakhri,O., E.Popov, Z.Gabbasov, H.Kurdanov, I.Gavrilov:
    Effect of Lipostabil (Nattermann) on serum lipid levels, end platelet aggregation in patients with ICD and hyperlipoproteinemia 8th Int. Symp. on Atherosclerosis, Roma, Oct. 1988
  • Belousova, S.S., S.I.Bogoslovskaya, L.M.Silagina: Plasma lipoproteins and platelet function in patients with ischaemic heart disease treated with "essential" phospholipids Kardiologiya 25 (1985) 112-115
BloodSummary of 3 open-label trialsNRelderlycerebral insufficiency of the elderly EPLi.v. injections of 250 mg/d  over a period of 30 days 
  • 15 and 22 days after the beginning of treatment the spontaneous blood coagulation was found to decrease distinctly, while the thrombo-elastogram showed fibrinolytic activity to increase.
  • Hence the platelet-related disturbance of the coagulation balance was being checked. These findings were confirmed later by S.S. Belousova et al. 
  • Merchan, R., G.Dona: Microcirculation and haemorheology studies on polyunsaturated phosphatidyicholine (EPL; Lipostabil) in the agedClin. Trials J. 21 (1984) 517-525
  • Merchan, R., G.Dona, A.Ribeiro: Fosfatidilcolina polinsatura (EPL) e vasculopatie nell'anziono: studio capillaroscopico, emostaseologico ed emoreologico
    Acta Gerontol. 34 (1984) 242-253
  • Belousova, S.S., S.I.Bogoslovskaya, L.M.Silagina:
    Plasma lipoproteins and platelet function in patients with ischaemic heart disease treated with "essential" phospholipids Kardiologiya 25 (1985) 112-115
BloodSummary of open-label11NRNR EPL1.5 g  oral over 16 weeks
  • elevation in serum 6-keto- PGF1? (stable metabolite of the antiaggregatory and vasodilatory prostaglandin PGI2) which was particularly noticeable in the 8th week
  • a drop in thromboxane level (TXB2).
  • The significant reduction of the TXB2-/6-keto-PGF1? ratio was interpreted as a cytoprotective effect of EPL
  • Numano, Furuta, Mitani, Aoyagi, Maruyama, Yashima, Numano: The effect of EPL on platelet aggregation and prostanoid
BloodSummary of open-labelNRNRHealthy group & chronic occlusive CVD groupEPLsingle injection of 750 mg 
  • Improved filtration of RBC through an 8 u capillary filter
  • 15 and 45 minutes after the injection, both the filtration rate as well as the number of RBCs per mm of the filtrate were higher than initial values
  • When patients with chronic occlusive arterial disease were examined under similar test conditions, the highest number of filtered red blood cells was detected 60 min after e 30 min later counts almost equalled the initial values.
  • The exchange of membrane phospholipids containing saturated fatty acids with EPL was considered a possible cause for the facilitated filtration of RBC and their improved deformability
  • Ehrly, A.M., R.Blendin: Influence of essential phospholipids on the flow properties of the blood In: Phosphatidylcholine - Biochemical and Clinical Aspects of Essential Phospholipids (H. Peeters, Ed.) Springer Press, Berlin - Heidelberg - New York (1976) 228-236
BloodOpen-labelNRNRCoronary artery diseaseEPLi.v. injections of 500 mg of EPL and after that 1.8 g of EPL for 3 months.
  • confirmed an improved passage of red blood cells through microfilters and the normalization of RBC aggregation in their patient group.
  • cholesterol/phospholipid index of RBC membranes dropped by 28% to normal values.
  • normalization in hematocrit and blood viscosity and an associated statistically significant rise in capillary flow.
  • the favourable influence on rheological findings and on lipid parameters correlated with an improvement of the clinical picture: depending on the severity of the coronary condition involved, these favorable changes persisted for up to 12 months after withdrawing EPL
  • Blagosklonov, A.S., E.S.Nalivaiko, G.A.Bykov, Y.T.Kaminka, E.M. Khalilov: Hemosorption and essential phospholipids as part of combined treatment in coronary patients Kardiologiya 26 (1986) 35-38
BloodOpen-labelNRNRatherosclerosisEPL

4-week EPL therapy (1.5g/d orally)

250 mg/d of EPL for 4 weeks

  •  In addition to other parameters, again the index of red blood cell deformability was improved and blood viscosity reduced.
  • These findings were substantiated by the trial results of R.Merchan 
  • Yoritsune, M., T.Mozai: Effect of polyenylphosphstidylcholine on platelets and red blood cell function Gendai no Shinryo 22 (1980) 836-842; 
  • Merchan, R., G.Dona:Microcirculation and haemorheology studies on polyunsaturated phosphatidyicholine (EPL; Lipostabil) in the agedClin. Trials J. 21 (1984) 517-525
BloodOpen-labelNRNRliver cirrhosis, spur cell anemiaEPL2g of EPL/d over 5 days
  • According to their report, the cholesterol increase in RBC membranes following a reduction in LCAT activity provokes expansion and rigidity of the membranes with changes in RBC morphology in the form of uneven contours.
  • As a consequence of the EPL- related LCAT activation the cholesterol content in the RBC membranes was lowered and the cholesterol/phospholipid ratio decreased; at the same time membrane phospholipids were exchanged for EPL which increased the content of linoleic acids in the membranes.
  • Salvioli, G., R.Salati, G.Rioli, R.Lugli, P.Rivasi:
    Le anomalie morfologiche eritrocitarie in corso di colestasi (effetto della fosfatidilcolina polinsatura sulle 'spur cells')
    II Fegato 21 (1975) 5-25
  • Salvioli G. Changes of red cell and lipoprotein lipid composition after polyunsaturated phosphatidylcholine infusion in patients with liver cirrhosis Int. Conf. Atherosclerosis. (L.A. Carlson et al., Eds.) Raven Press, New York (1978) 545- 551
  • Salvioli G. Effect of polyunsaturated phosphatidylcholine infusion on lipoprotein and red cell lipid composition in patients with spur cell anemia Diab. Obes. Hyperlipidemias (V.Cupaldi et al., Eds.) Academic Press, New York (1978) 305-310
  • Salvioli, G., G.Rioli, R.Lugli. R.Salati: Membrane lipid composition of red blood cells in liver disease: regression of spur cell anaemia after infusion of polyunsaturated phosphatidylcholine Gut 19 (1978) 844-850
BloodSummary of open-label trial7NRHealthy EPL

10 g of EPL/d orally


  •  6 weeks after the onset of treatment there was a reduction in total lipid and cholesterol content, which was significant as compared with baseline values, while the phospholipid/total lipid ratio increased and
  • a higher rate of esterification with linoleic acid in platelet phospholipids was observed.
  • regarded this as an indication of an exchange of phospholipids between cell membranes and the plasma compartment
  • Galli, C, E.Tremoli, E.Giani, P.Maderna, G.Gianfranceschi, C.R.Sirtori: Oral polyunsaturated phosphatidylcholine reduces platelet lipid and cholesterol contents in healthy volunteers Lipids 20 (1985) 561-566
Bone fractureSummaryNRNRBone fractureNRNR
  • fewer fat particales in the urine of patients with large bone fractures and surgery of fractures when high doses of i.v. EPL were applied
Hupe, K., U.Blazycek H.-J.Gent, G.Kunz, B.Roth, B.Schwarte: Klinische und tierexperimentelle Untersuchungen zur Therapie der Fettembolie Bruns Beitr. klin. Chir. 219/1 (1971) 
CardiovascularSummary of open-label15NRasymptomatic atherosclerosisEPL2.7 g EPL/day for at least one year
  • 18 months study kept track of the size of plaques by means of a real-time scanner covering sections of the superficial femoral artery as well as the carotid, iliac and popliteal arteries.
  • at least 1 atheroma had been diagnosed at one of the sites mentioned.
  • At the end of the observation period of more than 12 months the majority of the initial plaque volumes tended to stagnate after a transient initial rise.
  • Larger initial volumes stagnated in most cases or showed a downward trend at the end of the 12-month observation
  • the tendency to regression was clearer in the total plaque volume and the femoral artery than at the carotid artery. 
  • Rudofsky, G., H.Hirche, M.Egle, Ch.Sohn, J.Ranft: 

    Diagnosis and follow-up of preclinical atherosclerosis and the influence of medication - a preliminary communication

    In: 50th Anniversary of Phospholipid Research (EPL) (K.-J. Gundermann and R.Schumacher, Eda.) wbn Press, Bingen/Rhine (1990) 185-194

CardiovascularSummary of 4 open-label trialsNRNRECGEPLNR
  • an improvement of ECG findings could be achieved in many cases.
  • Among others, this was reflected in a dose-related reversal of pathologically changed terminal segments. 
  • S-T depressions were found to disappear; previously negative T-waves were reversed to positive. 
  • These favorable changes indicated a relief of stenocardiac complaints. Exercise tolerance as tested on the bicycle ergometer improved.
  • The phase until S-T depression occurred became longer, with the depressions themselves being less distinct
  • Almazov V.A., V.S.Gurevich, E.I.Krasilnikova, B.B.Bondarenko: Effects of Lipostabil on blood lipids, platelet function and macrophage function in patients with ischaemic heart disease Lipostabil Symp. Moscow, Nov. 1984
  • Almazov, V.A., I.S.Freidlin, E.I.Krasilnikova:
    The use of Lipostabil to control lipid metabolic disorders in coronary patients Kardiologiya 26 (1986) 39-42
  • Kukes, V.G., E.A.Senik, E.T.Gneushev, S.A.Potekaeva, N.M. Milovanova, F.M.Slavutskaya, V.P.Litvinova: The use of preparation "Essentiale" in patients with chronic ischaemic heart disease Kardiologiya (Moscow) 18 (1978) 70-82
  • Kukes, V.G:, E.A.Senik, E.N.Slavinskaya, T.A.Zolotova: On the mechanism of action of Lipostabil forte Lipostabil Symp. Moscow, Nov. 1988
CardiovascularSummary of open-label and RCTsNRNRAnginal attacksEPL

500 mg/day for 14 days

30 days on an oral daily dosage of 1.8 g

  • All authors reported a decrease in anginal attacks
  • 34 male patients suffering from ischaemic heart disease and angina pectoris (stages III and IV); they received 500 mg/d of intravenous EPL for a period of 14 days.
  • 20 of the 34 patients reported an absence of anginal attacks at the end of the first/beginning of the second week of treatment. The other 14 patients experienced a reduction of attacks from 8 to 10 within 24 h to 1 to 3 attacks within 24 h, with the severity decreasing as well. Daily nitro-consumption, therefore, could be reduced to 2 to 5 doses as well.
  • 42 patients with stable angina on exertion (stages II to IV) for  observed a 50% reduction in the nitro-consumption of her patients.
  • Corresponding results have already been described in a multicentre study comprising 507 patients 
  • the walking distance without stopping or requiring nitroglycerin was extended from 30-50 m to 3000 m.
  • In a controlled trial, geriatric patients with atherosclerosis suffered from fatigue, a decrease in vitality, disturbed sleep, a sensation of constriction in the heart region, retrosternal pain, palpitation.
  • On completion of the EPL treatment, 88 of 94 patients reported a decrease in complaints and an increase in vitality.
  • These changes were more pronounced after 2 months of treatment than after 1 month.
  • Almazov V.A., V.S.Gurevich, E.I.Krasilnikova, B.B.Bondarenko: Effects of Lipostabil on blood lipids, platelet function and macrophage function in patients with ischaemic heart disease Lipostabil Symp. Moscow, Nov. 1984
  • Almazov, V.A., I.S.Freidlin, E.I.Krasilnikova:The use of Lipostabil to control lipid metabolic disorders in coronary patients Kardiologiya 26 (1986) 39-42;
  • Kukes, V.G., E.A.Senik, E.T.Gneushev, S.A.Potekaeva, N.M. Milovanova, F.M.Slavutskaya, V.P.Litvinova:The use of preparation "Essentiale" in patients with chronic ischaemic heart disease Kardiologiya (Moscow) 18 (1978) 70-82;
  • Hevelke, G., Th.Högn, W.Haase, V.Böhlau: Ergebnisse einer multizentrischen Studie mit Lipostabil Med. Welt 31 (1980) 593-602
  • Idu, S.M., P.Popescu, E.A.Mihai, M.Muntesnu: Über die Wlrksamkeit "essentieller" Phospholipide bei der Behandlung der Atherosklerose Viata Medicala 17 (1970) 297-305
  • Itkina, L.D., E.Bogorad, G.M.Bulatova: The use of Lipostabil in geriatric practice Lipostabil Symp. Moscow, Nov. 1984
  • Nakajima, O.:Therapie von Angiopathia diabetica mit Hilfe von Lipostabil Research Report no. 842774 (1984)
  • Seki, H., R.Nakayama, Ch.Ibukiyama, Y.Higuchi, K.Anraku, M. Yoshimura: Effects of polyenephosphatidylcholine (EPL) against coronary sclerotic ischemic heart- diseases and arteriosclerosisGendai Iryo 6 (1977) 599-618
  • Serkova, V.K.:Dynamics of blood lipids, parameters of lipid peroxidation and energy metabolism in patients with ischaemic heart disease treated with Essentiale Klin. Med. 7 (1988) 91-95
  • Spesivtseva, V.G., V. I.Kalmykova, G.A.Golubyatnikova, T.V. Koroleva: Effect of Lipostabil forte on lipid metabolism and microcirculation in patients with diabetes mellitus and ischaemic heart disease Lipostabil Symp. Mocow, Nov. 1984
CardiovascularSummary of RCTNRNRPeripheral arterial diseaseEPL30-day treatment with 1.8 g/d of oral EPL
  • In a controlled study comprising healthy volunteers and patients in stages I + II as well as III + IV of the disease (according to Fontaine)  an improvement of blood flow in the muscles of the lower extremities after a 30-day treatment with 1.8 g/d of oral EPL was demonstrated
  • This increase concerned both reactive hyperaemia as well as blood supply at rest.
  • Flow velocity was raised as well, though slightly less in patients in stages III + IV due to longer collateral pathways
  • Klemm, J.:The treatment of arterial and venous circulatory disturbances with EPLIn: Phosphetidylcholine - Biochemical and Clinical Aspects of Essential Phospholipids (H. Peeters, Ed.), Springer Press, Berlin - Heidelberg - New York (1976) 237-243
CardiovascularSummary of open-label200 elderlyPeripheral arterial diseaseEPL

first 2 weeks, the patients received 1 g/d of intravenous EPL plus 1.35 g orally

500 mg/d of intravenous EPL plus 1.35 g orally for another 6 weeks

maintenance therapy of 1.35 g/d of oral EPL covering 18 months

  • oscillometric index as a measure of therapeutic success in occlusive vascular changes, using it to determine the patency of major vessels in 200 elderly male patients.
  • An improvement of the oscillometric index and the walking distance (from 0-200 m to 1500 m) was observed in 35 patients. The withdrawal of EPL resulted in a shortened walking distance
  • Luczak, S., R.Leutschaft:
Phospholipids; therapeutic use; pharmacodynamics Research Report no. 842762 (1984)
CardiovascularSummary of RCT (cross over)NRNRPeripheral arterial diseaseEPL1.8 g/day orally
  • compared high doses of EPL (1.8 g/d orally) on rheographic and oscillographic findings as compared with the influence of low doses of EPL (1.05 g/d orally) and placebo.
  • A dose-related, distinct increase in the oscillographic index ( > 0.8 mV) indicated improved vascular passage
  • Pristautz, H.:
Zum therapeutischen Wert der "essentiellen" Phospholipide Münch. Med. Wschr. 117 (1975) 583-586
CardiovascularSummary of RCT808NRPeripheral arterial diseaseEPL6 week EPL
  • In a comprehensive trial involving 808 patients, the above results were confirmed.
  • After a 6-week treatment with EPL, 198 patients with intermittent claudication and 505 with pain at rest reported complete relief.
  • Mean pain-free walking time was extended from 9.8 to 21.3 min on average
  • Hevelke, G., Th.Högn, W.Haase, V.Böhlau: Ergebnisse einer multizentrischen Studie mit Lipostabil Med. Welt 31 (1980) 593-602
CardiovascularSummary of open-label221NRFat embolismEPLNR
  • The studies covered 221 cases of fat embolism treated with EPL.
  • 202 patients recovered
  • 19 (8.6%) died
  • In the retrospective control groups, who had not received EPL, 58 out of the 83 patients with fat embolism died (70%) and 25 survived.
  • Even though the clinical trials presented here were conducted as open studies without controls or in retrospective comparison and a statistical analysis was not performed, the mere comparison of figures points to the life- saving and life-protecting action of EPL therapy.

CNSSummmary of open-label + RCTNRNRCerebral Circulatory DisordersEPL250 mg i.v. to 3 g orally, single-dose to up to 2-14 years
  • improves oxygen supply and consumption in the brain, cerebral blood flow, microcirculation, vessel resistance and blood coagulation, lipid values, anti-peroxidative processes, and subjective symptoms, such as headache, vertigo, concentration, fatigability, memory, speech and irritability.
  • The results on the reduction of the cerebral blood flow time of the open studies were confirmed by an RCT

CNSSummary of open-label + RCTNRNRMultiple SclerosisEPL

500 mg i.v. + 800 mg orally to 6-8 g orally.

duration of treatment of 5.7 to 23.8 years

  • Four publications are available, one of them being a double-blind trial.
  • The applied EPL doses ranged from 500 mg i.v. + 800 mg orally to 6-8 g orally.
  • In 2 studies i.v. EPL was given first, and then oral medication.
  • The duration of treatment of 5.7 to 23.8 years in the study by A.R.Borromei et al. is quite striking.
  • The results have been confirmed by the double-blind, long- term study of W.Autenrieth and I.Neu.

Dosing/PK/PDOpen-label + RCTs1705NROralEPL700-2700 mg/day
  • 700-2700 mg n-1705 in 39 clinical trials on lipid metabolism disorders
  • Only undesired drug reactions affecting the gastrointestinal tract have been reported.
  • In 20 out of 1504 patients undergoing EPL therapy, and in 5 of 201 placebo-treated patients, complaints such as slight, unspecific gastric disorders, soft stool and diarrhea were observed;
  • The incidence of side-etfects in these clinical studies was 1.3%.
Göpfert, E.,K.J.Schlüter:
"Essentielle" Phospholipide (EPL) zur oralen Therapie von Fettstoffwechselstörungen
Research Röeport no 900135 (May 15, 1990)
Dosing/PK/PDSummaryNRNROralEPLNR
  • Abnormal values with respect to haematology, blood chemistry and urine analysis, or interactions with other substances have not been reported.
  • 7 spontaneous records were made in Germany between 1978 and 1989, 2 about stomach complaints and 2 about allergic reactions.
  • Three records about arrhythmias are from the time before 1988, when the formulation of Lipostabil still contained etophylline.
  • According to a rough estimation a total of 225 million daily doses of Lipostabil were sold in Germany between 1954 and 1989 (230).
  • No manifestations of intoxication or overdosing have been reported.
  • There are neither contraindications nor precautions to be observed in the administration of the preparation.
  • From the animal experiments on fertility and reproduction as well as from the hitherto obtained clinical results no restrictions for the application during pregnancy and lactation can be inferred

Dosing/PK/PD3499NRNRNR (fatty liver)EPLDoses of up to 5000 mg/day i.v. for periods of up to 3 months
  • evaluated in a total of 3,499 patients
  • Doses of up to 5000 mg/day for periods of up to 3 months, in some cases for longer periods, were administered
  • Diarrhea and abdominal complaints occurred only in 7 patients with fatty liver
Gundermann, K.-J., M.J.Parnham:
"Essential" phospholipids (EPL) for intravenous application in liver diseases Research Report no. 520852 (March 1991)
Dosing/PK/PDOpen-label30NRcirrhosisEPLi.v. application
  • increased intestinal movement was observed in 3 of 30 patients with cirrhosis of the liver
  • 1 patient complained of fever
Loginov, A.S., M.N.Markova: Prostaglandins in liver diseases Materia Medica Polona 11 (1979) 91-99
Dosing/PK/PDSummaryNRNRchronic hepatitisEPL1000 mg i.v.
  • One patient with chronic persisting hepatitis developed general weakness, nausea, tachycardia, reddening of the skin, and fever at the beginning of the therapy with 10 ml (1000 mg EPL i.v.)
  • the symptoms disappeared when the preparation was given as a slow drip infusion
Kravchenko, A.L.:
Effectiveness of the use of the preperation "Essentiale" in patients with viral hepatitis
Dosing/PK/PDSummaryNRNRchronic hepatitisEPLi.v. application
  • a patient with chronic active hepatitis complained of headache and chills with i.v. EPL therapy
Chisu, A., L.Marian, M.Nanulescu:
Die Behandlung der chroniachen Hepetitis bei Kindern mit Essentiale 303 (EPL) Research Report no. 841178 (1973)
Dosing/PK/PDSummaryNRNRliver diseaseEPLi.v. application
  • Six of 17 patients reported temporary pain after intravenous injection of EPL in another study
Pogromov, A.P., L.I.Otbinskaya, N.I.Antonenko, N.P.Gitel, A. Smolyanitsky, P.B.Verkhovskaya:
Use of Essentiale in the treatment of liver diseases
Klin. med. (Moecow) 10 (1978) 97-101
Dosing/PK/PDSummaryNRNRchronic hepatitisEPLi.v. application
  • Also in another study slight exacerbation of pain in the right hypochondrium was observed in 3 of 75 patients
Serebrina, L.A.:
Efficacy of Essentiale in the treatment of patients with active chronic hepatitis
Essentiale Conf. Kiev, Oct. 1981
Dosing/PK/PDSummaryNRNRcirrhosisEPLi.v. application
  • aggravated gingivitis in a patient with cirrhosis of the liver after intravenous EPL administration; the medication had to be discontinued
Martinez-Llinares,V., M.Valle-Lopez, M. Del Carmen, Ruiz Gonzales, J.Madrid Arrau:
Die Behandlung von Leberschäden mit Essentiale 303
25th Portugese-Spanish Congr. Adv. Sci., Sevilla, 23.-26. Nov. 1960
Dosing/PK/PDSummaryNRNRliver diseaseEPLi.v. application
  • Hypersensitivity reactions of the skin, finally, were reported in a total of 4 patients with liver disease 
Grebenev, A.L., K.I.Sirokova, V.S.Glocevskaja, M.V.Bogatkova, N.G.Pletneva, G.I.Klimenko, I.M.Lobastovs, L.P.Genja:
A trial of the clinical use of the product Essentiale in patients with chronic liver disease
Essentiale Symp. Moscow (1S77) 88-92; Wallnöfer, H.:
The treatment of hepatoses with "essential" phospholipids Essentiale Symp. Moscow (1977) 93-98
Dosing/PK/PDSummary3499NRNREPLi.v. application
  • in the existing study reports undesired drug reactions occurred in a total of 27 of 3,499 patients, i.e. an incidence of 0.77%.
  • Only in 5 of these cases, the medication had to be discontinued.
  • Dose reduction, slow injection or discontinuation of the preparation produced in all patients complete disappearance of the undesired symptoms.
  • The incidence of side-effects recorded in clinical studies is conclusive with the incidence of spontaneous records of undesired drug reactions made by doctors between 1979 and 1989. The incidence amounts to 0.0018% to 0.00056% of the used ampoules
Gundermann, K.-J., M.J.Parnham:
"Essential" phospholipids (EPL) for intravenous application in liver diseases Research Report no. 520852 (March 1991)
Dosing/PK/PDexpert recommended doseNRNRi.v. applicationEPL

i.v. application

oral

  • The Lipostabil and Essentiale products on the market have an EPL content of 175/250/300 mg in capsules, in the liquid form of 5%, (500 mg/10 ml), and in the parenterals of 5% (250 mg/5 ml, 500 mg/10 ml) and 10% (1000 mg/10 ml).
  • The recommended daily dosage is 3 times 1 to 2 capsules (= up to 1.8 g), and 1-2 - in severe cases up to 4 - ampoules for injection or infusion (= up to 4.0 g).

GallbladderSummary of open-labelNRNRGall bladder dysfunctionEPLNR
  •  EPL may inhibit cholesterol gall stone formation; linoleic acid deficiency in patients with gallstones was corrected 
  • biliary deoxycholic acid increased 

Salvioli, G., R.Lugli:Farmaci che influenzano la secrezione lipidica biliare Epat. 28 (1982 

Toouli, J., P.Jablonski, J.McK.Watts: Gallstone dissolution in man using cholic acid and lecithin Lancet II (1975 

GallbladderSummaryNRNRCholelithiasisEPLNR
  • combination of EPL and chenodeoxycholic acid was more effective in reducing lithogenic index and in reducing side effects of chenodeoxycholic acid
Stiehl, A., P.Czygan, R.Gtz, R.Raedsch, W.Fröhling:
Der Einfluß essentieller Phospholipide auf Gallezusammensetzung und Darmtätigkeit während der Behandlung mit Chenodeoxycholsäure
In: Verhandlungen der Deutschen Gesellschaft für Innere Medizin (B.Schlegel, Ed.) J.F.Bergmann Press, München (1978)
GallbladderSummary of DB-RCT8NRpost cholecystectomy EPLNR
  • Cholesterol content of bile decreased in relation to the EPL dose and the lithogenic index was reduced
Bron, B.: Bestimmung der Gallensekretion bei Menschen bei Verabreichung essentieller Phospholipide (Essahepan)
Research Report no. 0006/81 (Jan. 1981)
GastrointestinalSummary of open, randomized cross-over trial9NRHealthyEPL + indomethacin

Indomethacin (AmunoR) was administered p.o. at a dose of 50 mg either alone or in combinationwith 200 mg EPL.

  • The absorption of indomethacin was slightly retarded in combination with EPL
Löhr, J.P., K.-J.Johannes, H.Habel, K.Kesselring:
Randomized clinical trial in healthy volunteers on the bioavailability of indomethacin
Research Report no. 0048/80 (July 16, 1980)
GastrointestinalSummary open-label20NRdrug-induced GI complaintsEPL + gastrointestinal irritation provoking agent5 days with GI irritation agent and then 4x450 mg EPL with the agent for 10 days
  • Variables of effectiveness included 7 subjective parameters (hiccup, heartburn, epigastric distress, loss of appetite, nausea/vomiting, feeling of fullness, constipation) associated with mucosal damage in the upper gastrointestinal tract. Semiquantitative assessment was based on symptom intensity.
  • 18 out of the 20 patients registered an improvement of symptoms with EPL treatment. 15 of them were very much better. Therapeutic benefits noticed most by the patients were relief from pain and nausea and improved evacuation of the stomach and bowels. As a rule, the favourable effect occurred during the first days of treatment and was complete in about a week
Schulz, V.:
Relative bioavailability of Phospholipon 100 (500 mg) + diclofenac (50 mg) in comparison with 50 mg VoltarenR in 8 healthy volunteers Research Report no. 0036/86 (June 5, 1986)
GastrointestinalSummary Open-label11 female and 9 male 44-79rheumatoid arthritis and NSAID-induced epigastric complaintsEPL + NSAID2.7 g EPL average period of 13.7 days + usual NSAID
  • 11 female and 9 male patients with rheumatoid arthritis and NSAID-induced epigastric complaints, aged 44-79 years, were given in another open clinical study a daily dose of 2.7 g EPL for an average period of 13.7 days, in addition to their medication consisting of indomethacin, diclofenac, piroxicam, ASA and tiaprofenic acid or phenylbutazone
  • During this period subjective complaints could be reduced by 65% on an average.
  • Pre-treatment and post-treatment gastroscopies, in some cases biopsies, were performed in 13 patients with a mean time interval of 23 days. In 80% of cases an improvement or even complete healing was observed.
Horsch A., K.-J.Gundermann, K.-J.Johannes:
Reduction of non-steroidal anti-rheumatic drugs induced gastric disturbances by Pospholipon 100 - open pilot study
Research Report no. 0035/86 (June 6, 1986)
Gastrointestinal Summary Open-label19
piroxicam-induced gastrointestinal disturbancesEPL + piroxicam2 x 450 mg EPL) 3 times daily 1 hour before meals, concurrently with piroxicam
  • The investigators noted clear improvement in 15 out of 19 patients whose symptoms disappeared completely or nearly so.
  • EPL was assessed as very good by the patients. Subjective improvement generally occurred after a few days (< 4).
  • Four patients reported normal bowel evacuation with EPL
Appelboom, Th.:
Relief of piroxicam-induced gastrointestinal disturbances by Phospholipon 100 Research Report no. 0054/84 (June 1, 1984)
GastrointestinalSummary Open-label30
3 Gl side-effects related to the administration of diclofenacEPL + diclofenac (75-150 mg/day)10 minutes prior to diclofenac in 3 different diclofenac:EPL ratios: 1:1, 1:3 and 1:10 wt/wt
  •  The diclofenac dose varied between 75 mg and 150 mg/day.
  • The degree (low, mild, moderate, severe) of Gl disturbances was assessed before and at each visit for approx. 1-3 weeks, and the therapeutic effect was evaluated at the end of treatment.
  • EPL relieved from all symptoms in 5 of 12 patients at the low 1:1 dose, in 4 of 8 at the mean 1:3 dose, and in 8 out of 10 at the high dose
Appelboom, Th., K.J.Gundermann:
Inhibition of diclofenac-induced gastrointestinal disturbances by polyenephosphatidylcholine (PhospholiponR 100; PPC) Gastro-Entero-Hepatologie, Progr. and Abstr. 18th Congr. Eur. Assoc. Gastroenterol. Endosc. (1986) 44
GastrointestinalSummary Open-labelNRNRGI-induced gastric side effectsEPL + NSAIDNR
  • EPL caused no reduction of the effectiveness of diclofenac.
Dettmer, N.:
Phospholipon 100 (Phosphatidylcholine) in patients with diclofenac-induced gastrointestinal disturbances
Research Report no. 0001/86 (Dec. 9, 1985);
408 Lemmel, E.:
P 0415/1/01 (Phospholipon 100 + Diclofenac) open, uncontrolled study by patients with diclofenac-induced gastrointestinal disturbances
Research Report no. 0051/86 (June 30, 1986)
GastrointestinalSummary Case-control41 children (25 male, 16 femaleaged 6-15 yearschildren with peptic ulcer diseaseEssentiale3x1 capsule daily for 3-4 weeks on an in-patient level and for another 2-3 months on an out-patient 
  • received as basic treatment: diet, antacids, sedatives and spasmolytics
  • 19 of them were treated additionally with Essentiale (3x1 capsule daily) for 3-4 weeks on an in-patient level and for another 2-3 months on an out-patient level. The remaining 22 patients served as control.
  • In the Essentiale group pain, dyspeptic and astenovegetative symptoms disappeared.
  • The concentration of pepsin in the gastric juice fell significantly, whereas in the control group the proteolytic activity remained elevated.
  • The activity of lipid peroxidation was normalized with Essentiale only and corresponded to the values in healthy children.
  • The rate of recidivation was reduced by the factor of 1.7 in comparison with the control group
Zhukova, E.A., N.N.Kulik,I.A.Pereslegina:
The use of Essentiale in combined treatment of children with duodenal ulceration In: Proc. of the Lithuanian Scient. Conf. with the Participation of the All- Union Scient. Soc. of Gastroenterologists, Vilnius, Sept. 22-23, 1988
GestationSummary Case series47NRvomitingEPL

1-4 injections

250 mg i.v. every other day

  •  in 39 patients, symptoms disappeared after 1-2 injections
  • in the remaining 8 patients, 3-4 injections were necessary
Mücke, H.G.:
The treatment of vomiting in pregnancy with Essentiale Der Landarzl 39 (1963
GestationSummary Case series7NRvomitingEssentialeinjection 250 mg/day
  • nausea and vomiting subsided after the first essentiale injection 250 mg/day.
  • At the end of 8 days, the patient was free of all symtpoms.
  • Another 6 patients with less pronounced symtoms also obtained positive results
Hartel, J.:
Kasuistischer Beitrag zum Thema Hyperemesis gravidarum Ärztl. Praxis 17 (1965)
GestationSummaryNRNRvomitingEPL1 g/day
  • could not confirm a positive effect, depsite increasing dose up to 1 g/day
Jaisle, F.:
Die Phoaphatide und ihre Wirkung während der Schwangerschaft und bei Geburtsbeginn
Z. Geburtsh. Gyn. 163 (1965)
GestationSummary Case series52NRPreeclampsiaEPL500 mg/day i.v.
  • rapid disappearance of edema, liver and kidney function normalized, diuresis normalized in an average of 7 days of treatment - 500 mg/day i.v. 
Bottiglioni, F., R.Tirelli:
"Essentielle" Phospholipide in der Therapie der Spätgestosen Ärztl. Praxis 20 (1968)
GestationSummary Case series42NRPreeclampsiaEPL2 essentiale amp. or 6 capsules daily for 10-15 days
  •  perinatal mortality was reduced and no icterus was seen
Therapeutische Anwendung von EPL und Gestanon zur Leberenzym-Induktion und zur Abwendung des Sätgestose-Risikos
Essentiale Symp., Cavtat/Yugoslavia (1974)
GestationSummary Case seriesn=37
PreeclampsiaEssentiale forte3-6 capsules per day for 7 days
  • total protein and albumin increased, serum transaminases fell to within normal ranges and subjective well-being of the patients improved quickly 
Kovacevic, M., S.Gavric:
EPL-Substanz (Essentiale) in der Therapie der Spätgestosen Essentiale Symp., Cavtat/Yugoslavia (1974)
GestationSummaryNRNRPreeclampsiaNRNR
  • normalization of pathological lipid values and increased utilization of lipids by the fetus
Ailamazyan, E.K.:
Effect of exogenous phospholipids on lipid metabolism parameters in pregnant women with late toxemia and in their neonates
Akush. Ginekol. (1983
GestationSummary Case controln=50NRPreeclampsiaNR1 g/day for 10 days
  • compared to a group that received glutathionine, B12 and UDP glucose 
  • 46 patients presented with no symptoms after 10 days and the remaining 4 after 15 days compared to the control group in which 40 patients were free of symptoms after 10 days and the remaining 10 after 22 days
Rendina, G.M., G.Maselli, D.Patrono:
La fosfatidilcolina polinsatura nella terepia delle gestosi II Policlinico 84 {1971
GestationSummary Case control

52


NRPreeclampsiaEPL1.8 g oral /day
  • lipid peroxidation was inhibited with EPL, with values almost reaching the level of the controls 
Kurbanova, F.R.:
Peroxidation of lipids in pregnant women with hepatitis and its correction with Essentisle
Med. Zh. UZB 61 (1990) 59
GestationSummary Case controln=549 NRPreeclampsiaEssentialeNE
  • 153 treated with Essentiale - confirmed antioxidative effect and fetal hypoxia 
Ailamazyan, E.K.:
Antioxidants in the combined therapy of late toxicoses and chronic fetal hypoxia Akush. Ginekol. (1991) 30-34
GestationSummary 13 trials n= 684NRPreeclampsiaEPLNR
  • combination of EPL and vitamin E were most effective in reducing lipid peroxidation in n=145 preeclamptic patients
Shalina, R.l., I.B.Kusch, V.P.Oreshkina, O.A.Azizova, A.V. Kozlov, O.M.Panasenko:
Antioxidants as a part of combined treatment of patients with late gestosis Akusherstvo i ginekologiya 65 (1989)
HepaticSummaryNRNRchemicalsNRNR
  • favourable results, in chronic intoxification improved uptake and secretory functions of liver

HepaticSummary Open-labeln= 380NRanti -TB meds liver dysfunctionEPLNR
  • concomitant administration of EPL delayed hepatic injury (60 days vs 30 days)
  • the number of patients with elevated AST/ALT was less
  • clinical symptoms were milder
Djuric-Milosavijevic et al., Polyunsaturated phosphatidylcholine (EPL) used to prevent hepatic lesions during the treatment of tuberculosis
HepaticSummary Case seriesn=42 NRanti TB medsEPLNR
  • 5/42 showed mild liver function disorders
Hirose et al. The prophylactic effects of polyene phosphatidylcholines (EPL) on liver disorders induced by antitubercular drugs (rifampicin, isoniazid). 1982
HepaticSummaryNRNRliver dysfunction due to anti TB medsEssentialeNR
  • were able to resume treatment with TB meds without further liver deterioration
Insanov et al.Essentiale in the comprehensive treatment of patients with pulmonary tuberculosis and impaired liver function.1986
HepaticSummary RCT

n=17 Tx

n=150 controls

NRanti TB medsEPLNR
  • all 17 maintained normal AST/ALT values vs elevations in 63% of control group
Kuntz, 1991 "Essentielle" Phospholipide in der Hepatologie - 50 Jahre experimentelle und klinishe Erfahrung (book)
HepaticSummary RCTn= 120 NRanti TB medsEssentiale forteNR
  • 16% vs 38.5% elevated AST
  • 25% vs. 8.2% ALT
  • decreased GGT in treated group, 2.5 times more likely to experience elevation of transaminase
Marpaung et al.Tuberculostatic combination treatment with INH/RMP/EMB and administration of Essentiale forte for the prevention of liver damage. 1993
HepaticSummary 8 Open-label trialsNRNRanti TB medsNRNR
  • decreased liver cell necrosis



HepaticSummary controlled studyn=94childrenmalnutritionessentialeNR
  • disappearance of fat deposits and restoration of livers cells and organelles 

HepaticOpen-labeln=4046.1obesity with NAFLDEPL vs diet0.6 g EPL po tid vs 20 diet only for 3 months.
  • 14/19 patients improved ultrasonography vs 3/20 in the control group
  • 6 normalized totally
  • EPL vs control: more frequent normalization of AST, AP, y-GT, and serum and urine bilirubin

HepaticSummary Case reportsn=47NRMushroom poisoningEssentialeNR
  • 3/24 died when treatment was initiated within 2 days
  • 7/10 died when treatment was initiated 3-4 days after disease onset
  • shortening of duration of liver abnormalities

HepaticSummary9 clinical trialsNRAcute viral hepatitisEssentialeNR
  • earlier improvement of symptoms such as dyspepsia, pressure, tension, fullness nausea epigastric pain
  • AST ALT total protein, bilirubin AP returned to normal more rapidly
  • earlier regeneration of the liver, shorter hospitalization, less progression to chronicity
  • DB-RCT - 15/30 HBsAg not detectable after 30 days vs. 7/30 in the control group
  • n=56 treated with EPL 12-60 days showed better histology ; earlier return to normal n=25/25/100 control 

HepaticSummary67 studies2245Chronic hepatitisEPLNR
  • DB-RCT n=17/17 - the treated group showed improvements on liver biopsy
  • 2 week Tx increased LCAT activity to normal
  • decreased in transaminase, increased albumin in Tx group
  • significant improvement in clinical symptoms (n=58) after 3 months
  • trend to improved biochemical values 4,8,12 weeks; the worse the values initially, the better with treatment
  • reduction of transaminases by 50 Units
  • 6 months EPL - 4/6 Tx group had improved histology, 3/4 placebo showed more pathology
  • DB-RCT - n=20 decreased portal infiltration associated with a decrease in inflammatory activity
  • n=14 treatment 11.2 months compared to control group with vitamins - reductions in AST/ALT, inflammation in the liver lobules, necrosis

HepaticSummaryNRNRCirrhosisEPLNR
  • plasma prostaglandins increased, and a trend towards normal bilirubin, AST/ALT, GGT
  • disappearance of the HBsAg in 5/8 Tx vs 1/7 controls after 3 months
  • improvement in treatment group liver function
  • n=24 - free phenols and ammonia reduced 1-2 hours after EPL injection
  • n=27 - EPL orally 8 months, decrease in blood ammonia, AST/ALT, GLDH and SDH activities in serum, interpreted as an improvemet in oxidative processes and detox capacity of the liver 
  • n=81 - EPL 6 months, amelioration of liver function parameters, increased serum albumin level, reduction in ALT, globulin levels
  • n=25 - improved wellbeing, nearly all biochemical parameters were in normal range
  • open label n=30 - marked improvement in clinical and biochemical findings, IgA decreased to normal

Loginov, A.S., M.N.Markova, N.V.Fedorova, R.A.Pilenitsyna, S.S.Derzhavins: The role of endogenous prostaglandins in disorders of lipid metabolism in patients with chronic liver diseases In: Actual Problems of Gastroenterology. Collected Scientific Works (Ministry of Public Health of the USSR, Ed.) Moscow, Vol. 1, No. 12 (1980)

Fassati, P., J.Horejsi, M.Fassati, Z.Jezkova, J.Spizek: The effect of essential choline phospholipids on HBsAg and on certain biochemical tests in cirrhosis of the liver Cas. Lek. ces. 120 (1981)

Müting, D., P.Dohn, J.Reikowski: The action of intravenous and oral administration of high doses of essential phospholipids on protein and lipid metabolism and on enzyme activities in chronic liver disease Verh. Dtsch. Ges. inn. Med. 78 (1972

etera, V., V.Prokop:The compensated cirrhosis of the liver. Therapeutic experience with EssentialeR forte Therapiewoche 36 (1986) 

Pogromov, A.P., L.I.Otbinskaya, N.I.Antonenko, N.P.Gitel, A. Smolyanitsky, P.B.Verkhovskaya: Use of Essentiale in the treatment of liver diseases Klin. med. (Moecow) 10 (1978)

HepaticSummaryNRNRHepatic ComaNRNR
  • good results
  • n=35/55 EPL continuous drip, reduction in ammonia, AST, AP, 18/35 awoke vs 7/20 control 
  • severe liver insufficiency, 3 g EPL i.v. 8-16 days, 7/10 showed clear improvement, after a 4 week observation, 9/10 were still alive, stabilized and recompensated
  • n=50 fulminant hepatitis open clinical trial, 2-4 amp. Essentiale 500-1000 mg/day over 14 days - significantly improved survival rate and time with essentiale

Rottini, E., F.Bazzanella, G.Marri, A.Venerando:
Zur Behandlung verschiedener Formen von Leberinsuffizienz mit "essentiellen" Phospholipiden
Med. Monatsschr. 17 (1963

Sakai, Y., T.Sekihara, M.Sano: The intravenous treatment of hepatic coma and cirrhosis with Essentiale 303 Therap. Umschau 19 (1962)

Davcev, P., V.Serafimovski: Eigene Erfahrungen mit Essentiale bei der Behandlung des Leberkomas Essentiale Symp. Leningrad, Nov. 1982

Kuntz, E.:The "essential" phospholipids in hepatology - 50 years of experimental and clinical experiences In: 50th Anniversary of Phospholipid Research (EPL) (K.-J. Gundermann and R.Schumacher, Eds.) Wbn Press, Bingen/Rhine 1990 

Xian, Ch.: Essentiale-Injektionslösung bei fulminanter Hepatitis Publication in preparation

HepaticSummaryn=714NRRegenerationNRNR
  • 18 trials (5 open, 8 single-blind, 5 DB) n=714 increase of albumin, regenerative activity of hepatocytes 

KidneySummaryNRchildrenGlomerulonephritisEPLi.v. + oral
  • controlled study n=49, children 25 received essentiale i.v. for 10 days and oral EPL for 20 days at 2-2.5 mg/kg -  renal and extrarenal manifestations of disease disappeared significnatly earlier, symptoms of intoxication were reduced, blood pressure normalized, hepatomegaly and hematuria, proteinuria, hypoalbuminemia, leukocytosis disappeared, stabilization of the renal excretion of phospholipids 
Petrushina, A.D., V.J.Krylov, G.B.Moreva, V.A.Zhmurov, A.N. Durygin: Essentiale forte in comprehensive treatment of glomerulonephritis in children Pediatriya (Russ.) (1987 
KidneySummaryNRNRRenal insufficiencyEPLi.v. and oral
  • n=19 -  5 day iv EPL 1000 mg and 750 mg orally followed by 1500 mg/day over 10 days orally - significant rise in creatinine clearance, urea and sodium clearance. 5 patients complete clinical remission including normalized BP; 3 more patients showed clear improvements and only 2 remained unchanged. 
  • decreased nitrogen and BP in 2 nephrosclerotic patients
  • single i.v. administration of 250 mg EPL n=12, patients without renal disease, all except one  increased GFR, renal plasma flow and renal blood flow 30 min after administration.
  • improved GFR after a single dose or oral EPL 2 g , 22 patients, creatinine clearance increased and serum creatinine fell 
  • positive effects on hyperlipidemia provoked by renal disorders
  • increased osmotic resistance of erythrocytes of patients with renal insufficiency

Jacyszyn, K., W.Kornaszewski, H.Paluszynska:Eseentielle Phosphoiipide in der Behandlung der Niereninsuffizienz Das Deutsche Gesundheitswesen 21 (1966) 

Martinez Llinares, V.: Diagnostische und therapeutische Bedeutung des Lipidstoffwechsels Ärztl. Praxis 13 (1961 

Mainieri, L, A. de Lutterotti: Azione favorevole dei fosfolipidi essenziati per via venosa sulla funzionalita renale- studiata per mezzo delle clearances Rivista di Patologia e Clinica 18 (1963

Deibert, K., R.Juchems: Erhöhung der glomerulären Filtration durch Phoepholipide Münch. Med. Wschr. 108 (1966) 

Pupita, F., C.Gagna: Treatment of arteriosclerosis with "essential" phospholipids Med. Monatsschr. 23 (1969) 514-515; Moriya, K. et al.:

Clinical effect of EPL on hyperlipemia Gendai no Shinryo 21 (1979;Kukes, V.G:, E.A.Senik, E.N.Slavinskaya, T.A.Zolotova: On the mechanism of action of Lipostabil forte

Lipostabil Symp. Moscow, Nov. 1985; DobiAsovA, M., J.StribrnA, K.Matousovic:

Effect of polyenoic phoSpholipid therapy on lecithin cholesterol acyltrAnsferase activity in the human serum

Physiologia Bohemoslovaca 37 (1988); Kirsten, R., B.Heintz, K.Nelson, G.Oremek: Reduction of hyperlipidemia with 3-sn-polyenylphosphatidylcholine in dialysis patients intern. J. Clin. Pharmacol. Therapy Toxicol. 27 (1989) 

Peleshchuk, A.P., N.Y.Melman, V.M.Arishchenko, G.G.Nikulina, L.P.Musienko: Effect of Essentiale on the lipid metabolism of patients with chronic renal failure Vrach Delo 2 (1983) 

Dewailly, P., E.Lepoutre, M.Zandecki, W.Alrifai, G.Sezille: Effets "in vitro" d'une dispersion aqueuse de phospholipides essentiels sur la resistance osmotique des hematies dans I'insuffisance renale Lille Medical 23 (1978 

KidneySummaryNRNRNephrotic syndromeNRNR
  • n=9 nephrotic syndrome - 330-700 mg EPL daily, edema was reduced, diuresis increased by 64%, albumin increased, serum cholesterol reduced and serum lipids reduced by an average of 33% 
Priscu, R., E.Manolescu, S.Sichitiu: On our experience with administration of "essential" phospholipids (EPL) in children
Symp. "Essentiale in Paediatrica" Moscow, Feb. 1980 
KidneySummaryNRNRElectrolyte metabolismNRNR
  • n=20 10 mL of 10% phospholipid - phosphate and potassium excretion diminished, fall in magnesium levels
  • 3x2 capsules Essentiale daily (1050 mg) n=15 fatty liver/5 healthy control - both groups increased sodium and chlorine excretion
  • phospholipids + diuretics leads to a further increase in sodium uresis and potassium retention
  • 3 day application of i.v. EPL on renal function in healthy volunteers, chronic renal insufficiency, cirrhosis and cardiac insufficiency - 3.5 mg/kg bw over 90 min - some patients received aspirin - increase in renal plasma flow, GFR and sodium and water excretion, which was reversed by aspirin.

Mertz, D.P., G.Schettler, Bohring: ber Wirkungen einer Cholin-Phospholipid-Reinstfraktion auf den Mineralhaushalt des Menschen Klin. Wochenschr. 38 (1960) 

Juchems, R., W.Gross:Zur Wirkung von Cholinphosphstiden auf die Elektrolytausscheidung bei histologisch gesicherten Fettlebern Gastroenterologia 107 (Suppl.) (1967) 

Juchems, R., W.Gross: Über eine kaliumretinierende Wirkung von Phospholipiden bei Leberkranken Intern. Conf. on "Extra-Hepatic Pethology end Livel", Montecatini Termo (Oct. 1969)

Bernardi, P., A.Mezzetti, V.Tomassetti, A.Andalo: Effetti sulla funzionalita renale di un prodotto ricco di ac. grassi polinsaturi: risultati ottenuti in soggetti sani Clin. Dietol. 9 (1982) 291-302

Bernardi, P., L.Bestagli, F.Pecoraro, C.Adani, M.Cavazza, C. Minelli, A.Danieli: Effetti di un prodotto ricco di acidi grassi polinasaturi (EPL - Nattermann) sulla funzionalita renale nel soggetto sano ed in varie condizioni patologiche Clin. Dietol. 10 (1983) 63-90

Bernardi, P., F.Ghezzi, L.Bastagli, R.Grimaldi, M.Cavazza, C. Minelli, F.Fontana, C.Clo, C.Ventura, M.Capelli: Effects of polyunsaturated fatty acids and prostaglandin synthesis on rerial function Prostaglandins, Leukotrienes and Medicine 22 (1986)

KidneySummaryNRNRChronic peritoneal dialysisNRNR
  • EPL in the dialysis fluid, i.v., or oral, all restored ultrafiltration in patients with low ultrafiltration - 
  • results were not confirmed with oral 800 mg/day
  • increased ultrafiltration even in normal peritoneum

Di Paolo, N., U.Buoncristiani, L.Capotondo, E.Gaggiotti, M. de Mia, P.Rossi, E.Sansoni, M.Bernini:
Phosphatidylcholine and peritoneal transport during peritoneal dialysis
Nephron 44 (1986)

De Vecci, A., C.Castelnovo, L.Guerra, A.Scalamogna: Phosphatidylcholine administration in continuous ambulatory peritoneal dialysis (CAPD) patients with reduced ultrafiltration Peritoneal Dial. Int. 9 (1989

Dombros, N.V., E.Balaskas, N.Savidis, A.Tourkantonis, K. Sombolas: Phosphatidylcholine increases ultrafiltration in continious ambulatory peritoneal dialysis function.In: Ambulatory Peritoneal Dialysis (Avram, M.M., Girodano, C., Eds.) Plenum Press, New York (1990) 

KidneySummaryNRNRGlomerulonephritisNRNR
  • n=11 - 6 day treatment 1000 mg EPL i.v. daily, 6/9 patients showed a reduction of edema, serum albumin increased by 35%, total cholesterol and total lipids fell by 13.7% and 17.2% resp. 
Jacyszyn, K., R.Szymanski: Phospholipide in der Therapie der chronischen Glomerulonephritis mit nephrotischem
Syndrom
Med. Monatsschr. 15 (1961) 
LipidsSummaryNRNRRenal insufficiencyNRNR
  • increased LCAT activity, increased HDL which persisted 3 months after end of treatment, decreased TG during treatment period 
DobiAsovA, M., J.StribrnA, K.Matousovic:
Effect of polyenoic phoSpholipid therapy on lecithin cholesterol acyltrAnsferase activity in the human serum
Physiologia Bohemoslovaca 37 (1988)
LipidsSummaryn=1160NRhyperlipidemiaEPLi.v. + oral
  • reduction of LDL cholesterol ranging from 10  to 31% of mean initial values. The extent of reduction was determined by the type of hyperlipoproteinaemia involved, the homogenicity of the case material, the EPL dosages as well as the duration
  • double-blind trials against placebo with oral doses of 2.7 g EPL/d or of 1.8 g EPL/d resp.; already on the 14th or 21st day of treatment  registered a drop in LDL cholesterol of 12% and 20 %, respectively.
  • In a controlled cross-over study mean reductions of 25.8 % in the initial LDL cholesterol levels were obtained within a 2-month therapy period
  • treatment period of up to 218 days M.Murakami and H. Sekimoto  achieved average reductions of 25.5%
  • mean reduction of pathological initial values of 27.9% within 120 days 
  • reductions of LDL cholesterol, viz. 34.1% after 42 days

Dewailly, P., S.Moulin, J.P.Rouget, G.Sezille, J.Jaillard: Wirkungen des Polyenylphosphatidylcholins auf Lipoproteine bei Patienten mit HypercholesterinämieMed. Welt 36 (1985) 367-369

Horsch, A.K., I.Majolk, C.C.Heuck, E.Göpfert: Influence of polyenphosphatidylcholine (PPC) on serum lipids of patients with hyperlipoproteinemis VASA 15 (1986) 251-256

Arsenio, L. P.Bodria, G.Magnati, A.Strata: Studio dell'attivita terapeutica della fosfatidilcolina in diabetici con sssociata iperdislipidemia Clin. Ter. 114 (1985) 117-127

Murakami, M., H.Sekimoto: Klinische Erfahrungen mit EPL  Research Report no. 840745 (1984)

Saba, P., F.Galeone, F.Salvadorini, E.Pagliai, G.Guidi, A. Scalabrigo: Effects of soybean polyunsaturated phosphatidylcholine (LipoetabilR ) on hyperlipoproteinemia Cuur. Therap. Res. 24 (1978) 299-306

LipidsSummaryNRNRHDL-CNRi.v. + oral
  • Within 1 to 3 months of treatment with EPL, the HDL cholesterol of the patient groups investigated improved by 1.5 to 2-fold.
  • H.Izumi et al observed an increase In HDL cholesterol from 13.4 ± 1.3% to 20 ± 2.3% of total lipoproteine (normal range) when subjecting diabetic patients to a 12-month oral treatment with 1.5g of EPL daily
  • The increase rates obtained for HDL cholesterol as compared with initial levels ranged between 10 and 45% with values above 20% being the most frequently described. It was obvious that low initial levels of HDL cholesterol were raised, while high initial values were hardly influenced or remained normal throughout treatment
  • 15 studies cited

Belousova, S.S., S.I.Bogoslovskaya, L.M.Silagina:
Plasma lipoproteins and platelet function in patients with ischaemic heart disease treated with "essential" phospholipids Kardiologiya 25 (1985) 112-115

Izumi, H.: Effect of polyenephoephstidylcholine on abnormality of lipid metabolism in diabetic patients
11. Proceed. Jap. Atheroscl. Soc., Tokyo 1979

Nakamura, H., Y.Ebata, A.Tonomo, Y.Hata, H.Shigematsa, T. Hara, T.Takeuchi, Y.Umetada: Effect of EPL capsule on serum lipid level - double blind test - Jap. J. New. Rem. Clin. 22 (1973) 1565-1574

Stankovic, D., I.Zulic, J.Grujic-Vesic, B.Nikulin, J. Stankovic: Effects of "essential" phospholipids in controlling and preventing hyperlipemia in young and middle-aged persons Medicinski Arhiv 28 (1974) 287-296

Thurnherr, A.: Klinische Erfahrungen in der Therapie der Arteriosklerose Therapiewoche 7 (1956) 116-118

LipidsSummaryNRNRLDL/HDL ratioNRi.v. + oral
  • This ratio was found to decrease from 4.3 to 2.8 in an open study including 14 patients who received a 4-week course of treatment with intravenous EPL injections of 0.5 to 1g/d;  decreased by 24% 
  • A reduction of the LDL-/HDL- cholesterol ratio from 5.6 to 3.7 was observed under double-blind conditions

Goto, Y., H.Nakamura:
Gaschromatographische Untrersuchungen des Lipidstoffwechsels und seine Beeinflussung durch LipostabilPraxis 55 (1966) 1235-1237

Tomasevic, M.: Lipostabil forte in 1he control of hyperlipidemia in diabetic patients Liposiabil Symp. Moscow, Nov. 1984

Kirsten, R., B.Heintz, K.Nelson, G.Oremek:
Reduction of hyperlipidemia with 3-sn polyenylphosphatidylcholine in dialysis patients intern.

Neu, I.S., A.Schrader: Encephalomyelitis disseminata (multiple Sklerose) In: Neurologische und psychiatrische Therapie (K.A. Flügel, Ed.), Perimed Press, München (1987) 181-190

Spigai, C.: Enflu der "essentiellen" Phospholipide auf den Lipidspiegel Med. Heute 1a (1970) 197-198

Sznajderman, M.: Hyperlipoproteinämie Typ II
Z. Allg. Med. 61 (1985) 391-393

LipidsSummaryNRNRhyperlipidemiaEPLoral + i.v.
  • During a 6-week treatment period 80 patients with hyperlipoproteinaemia received 1.05g of oral EPL/d
  • another study included 45 patients who were given 1.8g/d of oral EPL for a period of three weeks.
  • In the treatment groups the activity of LPL increased by 25% and 40%, repectively, while no change was observed in the control groups.
  • V.G.Kukes et al, who had administered 1,8 g/d of EPL to 55 patients over a period of 30 to 50 days, also reported a significant increase (p < 0.001) in the activity of heparin-dependent lipolytic enzymes. The stimulation of lipoprotein lipase was most noticeable when initial values were low.

Zulic, I., D.Stankovic, N.Mulabegovic, K.Valjevac, D.Serdarevic: The influence of a hypolipaemic agent on serum lipid levels in manual and office workers
Medicinski Arhiv 23 (1978) 3-6

Zulic, I., M.Ivanc, E.Stankovic, M.Kapidzic:
Reactivation of serum lipase by means of essential phospholipids Medicinski Arhiv 35 (1981) 127-129

Zulic, I., M.Tomasevic, M.Kadic:
Effects and mechanism of action of "essential" phospholipids Medicinski Arhiv 39 (1985) 11-16

Kukes, V.G., E.A.Senik, E.T.Gneushev, S.A.Potekaeva, N.M. Milovanova, F.M.Slavutskaya, V.P.Litvinova:
The use of preparation "Essentiale" in patients with chronic ischaemic heart disease
Kardiologiya (Moscow) 18 (1978) 70-82

Kukes, V.G:, E.A.Senik, E.N.Slavinskaya, T.A.Zolotova: On the mechanism of action of Lipostabil forte
Lipostabil Symp. Moscow, Nov. 1985

LungSummaryn=270.8-3 yearsPneumoniaEssentialeNR
  • For 7-12 days treated 27 children, aged 0.8 to 3 years, suffering from acute pneumonia with a combination of Essentiale and Dimephosphon (Soviet product, vasodilator with phospholipase-inhibiting properties). The authors saw the origin of the pathology and the associated hypoxia in the lack of surfactant (i.e. of phosphatidylcholine), in reduced capillary circulation in the lungs and in the membrane damages caused by raised lipid peroxidation and phospholipase activity and subsequent phospholipid deficiency.
  • In contrast to standard treatment, the additional combination treatment led to a shortened duration of the disease, to improved oxygen uptake and to a normalization of the surfactant composition
Vainberg M.M., L.A.Nikulin:
The use of dimephosphon and Essentiale in treatment for acute suppurative destructive pneumonia in children
Voprosi Okhrania Materinstva i Detstva 32 (1987) 11-14
LungSummary4 trialsNRPneumoniaEssentialeNR
  • Further studies into acute pneumonia with Essentiale alone confirm that EPL is able to reduce lipid peroxidation and phospholipase activities with simultaneous increase of the PC/lyso-PC ratio.
  • These biochemical changes were associated with an improvement of the pathological picture, and with a shortened duration of the disease

Kawata, S., A. Chitranukroh, J.S.Owen, N.Mclntyre:
Membrane lipid changes in erythrocytes, liver and kidney in acute and chronic experimental liver disease in rats
Biochim. Biophys. Acta 896 (1987) 26-34

Khalilov, E.N., T.I. Torkhovskaya: Aktivierung des Cholesterin-Riicktransportes durch Lipostabil
In: "Essentielle" Phospholipide in der Therspie der Atherosklerose (B.B. Bondarenko, Ed.) Leningrad (1989) 36-44

Kotenko T.B., M.G. Chukhlovina, S.A.Lekomtseva:
Disorders of lipid metabolism in broncho-pulmonary pathology in children First All-Union Congress of Diseases of the Respiratory System, Kiev, October 9-12, 1990, abstract no. 110

Kozhevnikov, Yu.N., M.V. Gorbunova, S.P.Moiseenko, O.V. Pavlova: Determinants of Essentiale efficacy in the treatment of pneumonia in the newborn First All-Union Congress of Diseases of the Respiratory System, Kiev, October 9- 12, 1990, abstract no. 732

LungSummary2 trialsNRChronic Lung DiseaseEssentialeNR
  • in patients with chronic lung disease (n=54) a 4-week Essentiale therapy the cholesterol/phospholipid ratio was found to have decreased and erythrocyte flexibility to have increased.
  • reduced azotemia (n=104) and increased effects of antibiotics

Aleksandrov, O.V., S.S.Markin: Development of atherosclerosis in patients with lung diseases Kardiologiya 23 (1983) 94-97

Seri, I.: The place of essential cholinphospholipid in the therapy of nonspecific lung disease
Pneumonologia Hungarica 31 (1978) 19-25

PregnancySummaryNRNRSurfact deficiencyEssentialeNR
  • In pregnant women showing an IRDS risk for the baby  found in gestation weeks 28-31 reduced phospholipid levels (particulary of phosphatidylcholine, but also of sphingomyelin and phosphatidylethanolamine) in the blood of mother and fetus and in the placenta, caused by surfactant deficiency.
  • Unlike the conventional prevention therapy with glucocorticoids, thyroxine, ethyl alcohol etc., involving the risk of side- effects, these women received a substitution treatment with Essentiale.
  • The phospholipid values, especially phosphatidylcholine were found to have increased again in both mother and fetus, and reached normal levels.
  • Also the values of the hormones favouring the surfactant synthesis in the fetus (oestriol, oestradiol and placental lactogen) increased
Stepankovskaya, G.K., V.A.Tovstanovskaya:
Antenatal prevention of the respiratory disorders syndrome in premature babies by the use of Essentiale
Proceedings of the Dnepropetrovskaya Province Scientific and Clinical Conference of Obstetricians-Gynaecologists and Urologists, Dnepropetrovsk (1988) 41-44
RiskSummaryNRNROxidation/storageEPLNR
  • There is no risk that oxygen autoxidizes the polyunsaturated fatty acids during storage after the manufacturing process: G.-Sh. Wu et al. (752) showed that 1 Mol ?-tocopherol is enough to efficiently protect 2,000-20,000 Mol linoleic acid from oxidation with atmospheric oxygen.
  • To substitute the naturally present vitamin E, which is lost during manufacturing, 0.3% - tocopherol is added to the EPL during the production process. This quantity guarantees sufficient protection of the unsaturated fatty acids in the phospholipids.

Skin conditionsSummaryNRNRPsoriasisNRNR
  • oral EPL administration for 1-5 months in 4 patients with psoriasis vulgaris. Whereas 1 patient did not respond to the therapy, the other 3 showed improved clinical symptoms already 2-3 weeks after the beginning of therapy. After 4 months the skin manifestations disappeared completely in 2 of them, and were considerably improved in the 3rd patient
  • J.Borowski (69) who treated besides psoriatics (n=15) also patients with neurodermitis and seborrhoic eczema with EPL, partly over 2 years, increased the dose to 2.3 - 4 g EPL/day. Recidivations occurring in 10 of the 15 patients during the observation period were described by the author as very little pronounced.
  • marked trends towards healing of the skin eruptions already after 2-3 months of oral plus parenteral application of EPL (n=26); in some cases the eruptions were reduced so that only minor plaques could still be seen.

  • Another EPL therapy alleviated quickly the 5 cases of recidivation another group of 327 patients with psoriasis over 5 years. The treatment consisted of a combination of keratolytic ointments, diet, sun bathing, and oral/parenteral EPL administration. At the end of the 5- year observation period 291 of the 327 patients had no recidivations for 1-4 years. In the remaining 36 patients recidivations were little pronounced and disappeared quickly when the medication was repeated

  • improvement of liver function parameters, improved cell membrane structure and function, and a reduction of the hyperproliferation of epidermic cells.
  • significantly improved by the treatment with Esaentiale forte (1)%>

    With EPL therapy he observed a decreasing tendency for the values of palmitic acid (p < 0.05), palmitoleic acid (p < 0.001), oleic acid (p < 0.05) and docosohexaenoic acid (p < 0.01); these values approached the normal range, whereas the mean value of linoleic acid increased significantly (p < 0.05) without however reaching normal The author presumed that deficiency states of linoleic and linolenic acid might be at the origin of the syndrome which is characterized by a general lack of polyunsaturated fatty acids in the organism. It appears that psoriatic patients present a disturbed synthesis of arachidonic acid from linoleic acid.

KageyamaKageyama, R., Y.Morita:
Therapeutische Ertahrungen mit Lipostabil bei einigen Hauterkrankheiten Fortschr. Med. 77 (1959) 411-412, R., Y.Morita:

Borowski, J.: Lipostabil und Essentiale bei verschiedenen Dermatosen unter besonderer Berücksichtigung der Psoriasis Med. und Ernährung 6 (1964) 124-126

Giss, G.: Psoriasis vulgsris und die EPL-Substanz - aetiologische Betrachtungen und therapeutische Ertahrungen Der Prakt. Arzt 21 (1967) 1008-1017

Mashkilleyson, A.L., Yu.I.Golousenko, M.A.Gomberg E.N. Bocharova Treatment of psoriasis with a combination of PUVA and Essentiale forte (Es-PUVA) Dtsch. Dermatol. 38 (1990) 1318-1319

Abramovich, A.I.: Effect of Essentiale on the serum fatty acid spectrum in patients with psoriasis Metabolic aspects of dermatology and venerology, Gorki/USSR (1984) 35-39

Abramovich, A.I.: The use of Essentiale in the treatment of patients with psoriasis Vestnik Dermatol. Venerol. 7 (1984) 54-56

Abramovich, A.I.: The clinical significance of dislipidemia in psoriasis patients Acta Derm. Venerol. 146 (Suppl) (1989) 216

LipidsSummaryNRNRhypertriglyceridemia and healthyEPLoral + i.v.
  • Moderately elevated initial levels of neutral fats in serum however fell from 195 ± 56 mg/dl to mean levels of 146 ± 38 mg/dl (approx. 25%), and from 198 ± 26.4 mg/dl to 134 ± 15.8 mg/dl (p < 0.001) in diabetics after 2 months oral treatment with 1.5 g EPL/d
  • 4 weeks treatment with FPL led to a marked reduction both in the patient group with high initial values (lowered from 274 ± 21 mg/dl to 116 ± 8 mg/dl) as well as in the group with only moderately Increased baseline values (decrease from 201 ± 11 mg/dl to 94 ± 32 mg/dl)
  • In a double-blind trial with patients on a standardized diet mean values had dropped from 353.7 mg/dl to 276.2 mg/dl (-21.9%) after only 14 days.
  • In a further study including patients with coronary heart disease and angina pectoris, the investigators reported a mean decrease in serum triglycerides of 23% after 14 days of intravenous EPL injections of 1 g daily.
  • In a controlled study over 3 months T.Luther et al. administered 1.4 g of oral EPL/d to patients after myocardial infarction. The mean decrease in serum triglycerldes reached 24% after 4 weeks and 46% after 12 weeks.
  • increased LCAT activity 

Seki, H., R.Nakayama, Ch.Ibukiyama, Y.Higuchi, K.Anraku, M. Yoshimura: Effects of polyenephosphatidylcholine (EPL) against coronary sclerotic ischemic heart- diseases and arteriosclerosis Gendai Iryo 6 (1977) 599-61

Izumi, H.: Effect of polyenephoephstidylcholine on abnormality of lipid metabolism in diabetic patients
11. Proceed. Jap. Atheroscl. Soc., Tokyo 1979

Grebenev, A.L., S.S.Katsev, V.S.Golochevskaya, L.P.Geniya: Lipostabil in the treatment of hyperlipidemia and the possibility of its correcting effect on liver function Lipostabil Symp. Moscow, Nov. 1984, 47-48

Horsch, A.K., I.Majolk, C.C.Heuck, E.Göpfert: Influence of polyenphosphatidylcholine (PPC) on serum lipids of patients with hyperlipoproteinemis VASA 15 (1986) 251-256

Almazov V.A., V.S.Gurevich, E.I.Krasilnikova, B.B.Bondarenko: Effects of Lipostabil on blood lipids, platelet function and macrophage function in patients with ischaemic heart disease Lipostabil Symp. Moscow, Nov. 1984

Luther, T., F.Liebold, W.Helbig: Beeinflussung von Hämodynamik und Serumlipiden durch Training, Oxyfedrin und Lipostabil bei Patienten mit Zuatand nach Myokardinfarkt Inn. Med. 26 (1971) 508-515

LipidsSummaryn=3836NRhyperlipidemiaEPLoral/i.v.
  • average reduction between 12-19% 
  • 15 clinical trials 8.8 to 28.2% duration of 1-12 months of treatment
  • 9-20 days of i.v. EPL caused a reduction of total serum cholesterol of approx. 13%; After an initial 2-week intravenous administration of 1g of EPL/dH. Peeters et al. even registered a slight rise in serum cholesterol values when therapy was continued orally on 1.8 g EPL/d, though they did not return to Initial levels.
  • simultaneous administration of EPL capsules and solution for injection led to a pronounced decrease in cholesterol ; the author had introduced treatment on a dosage scheme of 250 mg i.v. + 875 mg orally and observed a further, though markedly slower decrease in cholesterol concentrations when continuing treatment on oral EPL 
  • Under oral treatment (1.05 to 2.7 g of EPl/d) successful lowering of total cholesterol obviously depended on basal values at the onset of therapy: starting from moderately elevated total cholesterol levels (up to approx. 400 mg/dl) the reduction became all the more noticeable, the higher initial levels had been
  • 1.8g of oral EPL/d led to mean reductions of total cholesterol by 12.7 % already within 14 days of treatment. After another 4 weeks reduction of initial values totalled 18.9%
  • After oral EPL treatment over 3-4 (to 16) weeks, mean rates of cholesterol reduction in another 4 studies that were either controlled against a diet, double-blind, controlled against placebo or were open, ranged from 12 to 25% as compared with initial values

Fasoli, A.:Clinical evaluation of polyenephosphatidylcholine (PPC) - effects on the serum lipid and lipoprotein patterns - In: Therap. Select. Risk/Benefit Assess. Hypolipid. Drugs (G. Ricci, R.Paoletti, Pocchiari, Poggiolini, Eds.) Raven Press, New York (1982

Blaton, V., F.Sateway, D.Vandamme, B.Decercq, H.Peeters: Effect of polyunsaturated phosphatildylcholine on human types II and IV hyperlipoproteinemiasArtery 2 (1976)

Blaton, V.H.: L'influence des acides grae poly-insatures sur les lipides et les lipoproteines plasmatiquesBull. Soc. Pharm. Lille (1980)

Caruzzo, C., L.Enrico-Bena, R.Camaghi: Variazioni delle frazioni lipidiche del siero di aterosclerotici indotte dello fosfatidilcholino Minerva Med. 60 (1969) 1643-1652

Peeters, H., V.Blaton, B.Declercq, D.Vandamme: The Effect of essential phospholipids on the lipid and fatty acid pattern of lipoproteins in type II patients4. Int. Symp. Drugs Affect Lipid Metab. Philadelphia, September 1971;

Peeters, H., V.Blaton, F.Soetewey, B.Declercq, V.Vandamme: Wirkung der "essentiellen" Phospholipide auf Plasmalipide und Fettsäuren beim Typ II der Hyperlipoproteinämie M7nch. Med. Wschr. 115 (19?3) 1358-1362;

Peeters, H., B.Declercq, V.Blaton: The effects of PU-PC on the fatty acid moiety of the plasma lipoproteins 17th Int. Conf. Biochem. Lipids, University Milan, Sept. 1974;

Peeters, H., D.Vandamme, V.Blaton: Longitudinal effect of polyunsaturated phosphatidylcholine on the human hyperlipoproteinaemia 5th Int. Symp. Drugs Affect. Lipid Metabol., Milan, Sept. 1974

Petruzzi, E., C.Chiostri: Analisi gas-cromatogratica delle varie frazioni lipidiche del siero e funzionalita piasrinica in soggetti diabetici con complicanze vascolari 5. Nat. Congr. Ital. Soc. Diabetol., March 1974

Andresen, P.: Die Behandlung von arteriosklerotischen Kreislaufstörungen und Hyperlipämien mit Phosphatidylcholin Therap. Umschau 22 (1965) 614-622

Hevelke, G., Th.Högn, W.Haase, V.Böhlau: Ergebnisse einer multizentrischen Studie mit Lipostabil Med. Welt 31 (1980) 593-602

Itkina, L.D., E.Bogorad, G.M.Bulatova: The use of Lipostabil in geriatric practice Lipostabil Symp. Moscow, Nov. 1984

Kasper, H., O.Krennrich: Der Einfluß von Phosphatiden auf den Stoffwechsel von Vitamin A und Carotin Z. gesamte exp. Med. 139 (1965) 644-650 Drugs Affect Lipid Metab. Philadelphia, September 1971;

Popescu, P., S.M.Idu, A.Mihail, X.Petrescu, N.Mihai:The effect of essential phospholipids in the long-term treatment of hyperlipoproteinaemia types II and IV Viata Medicala 25 (1978) 255-258

Seki, H., R.Nakayama, Ch.Ibukiyama, Y.Higuchi, K.Anraku, M. Yoshimura: Effects of polyenephosphatidylcholine (EPL) against coronary sclerotic ischemic heart- diseases and arteriosclerosis Gendai Iryo 6 (1977) 599-618

Shimizu, N., S.Sakajiri: Effects of EPL capsules on lipid in diabetic (part II) Jap. J. New Rem. Clin. 22 (1973) 2277-2283; Uemura, K.J.: Clinical experiences on polyenyl-2-phosphatidylcholine (EPL) Jap. J. New Rem. Clin. 22 (1973) 1583-1597

Horsch, A.K., I.Majolk, C.C.Heuck, E.Göpfert: Influence of polyenphosphatidylcholine (PPC) on serum lipids of patients with hyperlipoproteinemis VASA 15 (1986) 251-256

Casellas Bernat, G., L.Riera de Barcia, M.Alou, S.Solivellas, A.Casellas Bernat: Dislipemias y fosfatidilcolina insaturada Clin. Med. 15 (1975) 90-95;

Skoreps, J., P.Mares, H.Todorovicova:Die Wirkung von Polyen-Phospholipid auf den Cholesterin-Stoffwechsel bei Arteriosklerotikern Cas. lek. Ces. 113 (1974) 784-786;

Tomasevic, M.: Lipostabil forte in 1he control of hyperlipidemia in diabetic patients Liposiabil Symp. Moscow, Nov. 1984

Yasugi, T., M.Iijima, T.Kinoshita, S.Harada, H.Matsumoto, K.Sugita, H.Takeshita, M.Saijo, T.Shimizu, E.Sassa, M.Tomita, M.Kobari, I.Kobayashi, Y.Seto, H.Konno, K.Hoshino: Effects of EPL on serum lipid Jap. J. New Rem. Clin. 22 (1973) 691-693