- Email: [email protected]
Effect of dried garlic on blood coagulation, fibrinolysis, platelet aggregation and serum cholesterol levels in patients with hyperlipoproteinemia
Atherarclerosis, 74 (1988) X7-249
blishers Ireland, Ltd.
ATH 04235
ote
cal Clinic, University
First Medical Department, ~i~nik~rn Mannheim, and Third
ofIleidelberg
(F.R. 6.)
(Retiscd, received 21 June,
he effects of in
oagulation; Fi
olysis; Platelet a
ation;
ark
Garlic has been shown to lower fasting serum cholesterol values [I], to diminish alimentary increase of cholesterol and triglyceride values [5], to decrease fibrinogen lev fibrinolytic activity [3].
Corrcspndence to: &iv.-Doz. Dr. medl. J. kuenberg, 1. Medizinische Klinik, Klinikum Mannheim, UniversitSt Hddelberg, Theodor-Kutzer-Ufer, D-6800 Mannheim, F.R.G.
0021-9150/88/$03.50
fibrin.
0 1988 Elsevier Scientific Publishers Ireland, Ltd.
The present paper describes the effect Of
248
garlic on these and other blood coagulation and fibrinolysis parameters and reinvestigates the effect on collagen induced platelet aggregation, plasma cholesterol and blood pressure in patients with hyperlipoproteinemia. Methods Thz study was performed in a group of 20 out-patients with hyperlipoproteinemia (5 patients
with hyperlipoproteinemia type IV and 15 patients between with hypercholesterolemia type IIb) 36 and 71 years (mean 53.3 years). Inclusion criteria were plasma cholesterol levels between 250 vels between 170 and tri and coronary artery and All P disease, and 67 had experienced myocardial infarction 6 to 18 months earlier. Six patients were nermotensive upon treatment with antihypertensive drugs, 3 diabetic patients were treated with oral antidiabetics. No patient took drugs interfering with lipid metabolism, coagulation or fibrinolysis system or platelet function. The individual medication was not changed during the study. No et. Patients received 600 patient had fat lowe oated pills (3 times 200 mg dried garlic as su mg daily) over a pen of 4 weeks. The dose ce the metabolic at 50 OC temperature; Ilium sativum (Lichtwer fore, and 2 and 4
.
A 1.1. mm wide needle was placed in vein with minimal venous occlu-
The following parameters were determined: serum cholesterol, serum total triglycerides (enzymatic tests, r Mannheim GmbH, F.RG.) high density lipoprotein (HDL)cholesterol (enzymatically after precipitation of very low
and low density lipoproteins (LDL) with phosphotungstic acid, Boehringer Mannheim), LDLcholesterol (after calculation according to the Friedewald formula if triglycerides were e 400 mg/dl), blood pressure, hematocrit, and platelet count (Hemalog S, Technicon), prothrombin time (Men and Dade, Munich, F.R.G.), activated partial thromboplastin time ring Werke factor VIII antithrombin III activity (S 2238 chromogenic substrate method, Kabi Vitrum AB, Munich, F.R.G.), anti-factor Xa activity (S 2222 method), fibrinopeptide A (7), streptokinase-activated tiplasmin activity (fluorogenic , Merz and Dade, Munich, induced (8), 10m5 mol 4 (PF4 and platelet Enzygnost Elisatest, Behringwerke AG, Marburg, F.R.G.). The Wilcoxon r test was used for evaluation. The values determined 2 an after onset of treatment were compared to those before treatment. The descriptive levels of significance were P < 0.05 or P s 0.01. Data are express as mean and SD.
All patients completed the study. The cholesterol levels dropped significantly from 277 mg% to 258 mg% (P < 0.01) (Table 1). Serum HDLcholesterol, serum LDL-cholesterol and serum triglyceride levels did not change during medication. The prothrombin time decreased during medication, but did not reach statistical significance. Fibrinogen significantly decreased by 10 333 mg% to 299 mg% (P < 0.01). Values fo factor VIII activity, factor Xa inhibition, and antithrombin III activity remained uuchanged. FpA values were elevated to 2.19 ng/ml f 1.04 ng/ml compared to healthy persons (1.0 f 0.7 ng/ml) (12,17) before treatment. FpA values significantly decreased to 1.19 ng/ml in these patients upon intake of garlic (P -z 0.01). Streptokinase activated plas cantly increased from 2.51 to 2.88 W/ml (P < 0.01). The FpB p15-42 significantly increased from
TABLE 1
LEVELS, IBEFO& AND DURING INTA IN 20 PATIENTS WITH HYP I~PRG~INEMIA Values are means f SD.
prothrombin time which, however,
Variable Cholesterol (mg%)
before treatment after 2 weeks
277.90* 45.13 267.35 f 53.21 258.30 k 40.68
before treatment
333.25 f
Fibrinupeptide A Ou/~)
before treatment
2.19* 2. 1.
1.09 1.10 O.B1
Streptokinaseactivated plasminogen (U/ml)
before treatment after 2 weeks after 4 weeks
2.51* 2.53f 2.88&
0. 0.66 0.71
Fibrinopeptide B/3 15-42 (ng/ml)
before treatment after 2 weeks after 4 weeks
17.10f 18.75 f 24.30 f
6.73 8.54 12.70
89.90
17.1 to 24.3 ng/ml (P < 0.01). a2-antiplasmin activity remained unchanged.
eaves fibrin in b
1 Ernst, E., Cardiovascular effects of garlic (A&urn suriuum):
3
count, IO-’ mol A treatment period. The mean systolic blo pressure decreased from 136.5 to 125.5 mm and the mean diastolic blood pressure dec from 86.0 to 81.0 g (P < 0.01) without changes in heart mm rate/min. iscussion
The present investigation confirms earlier results which have shown a cholesterol levels [1] and fibri well as systolic and diastok patients with hyperlipoprotein of dried garlic. The specific assays for fibrin formation use our study demonstrate that enhanced fibrin for-
4 5
6
7
8
9
a review, Pbarmatherapeutica, 5 (1987) 83. nsal, W.C.. Arora, SK. and Singh, S.V., Effmt of the essential oils in garlic ami onion on alimentary hyperlipemia, Athero Bordia, AK., Joshi, Sanadhya, Y.K. and Effect of essential oi ic on serum fibrindyti in patients with coronary artery disease, Atherosclerosis, 28 (1977) 155. Ariga, T., Qsihira, S. and Tamada, T., inhibitor in garlic, Lance& i (1981) 150. Luley, C., Lehman-Leo, W., Mtiller, Schartzkopff. W., Lack of efficacy of dried garlic in patients with hyperlipoproteinemia, Arzneimittelforschung, 36 (1986) 766. Nossel, H.L., Wasser, J., Kaplan, K.L., La Gamma, KS., Yudelman, I. and Canfield, R.E., Sequence of fibrinogen proteolysis and platelet release after intrauterine infusion of hypertonic saline, J. Clin. Invest., 64 (1979) 1371. Hare&erg, J., Hepp, G. and Schmidt-Gayk, H., Fibrinopeptide A in human plasma. Evaluation of a new radioimmunoassay technique on microtiter-plates, Thromb. Res., 15 (1979) 513. Kudryk, B., Robinson, B., Netre, C., M. alld Blomb%ck, B., Measuremen fibrinogen/fibrin fragments containing the quence, Thromb. Res., 26 (198 Haeenberg, J., Waas, R. and Zi of fibrinopeptide A in patients Thromb. Haemostas., 4: (19Bl) 282.
blishers Ireland, Ltd.
ATH 04235
ote
cal Clinic, University
First Medical Department, ~i~nik~rn Mannheim, and Third
ofIleidelberg
(F.R. 6.)
(Retiscd, received 21 June,
he effects of in
oagulation; Fi
olysis; Platelet a
ation;
ark
Garlic has been shown to lower fasting serum cholesterol values [I], to diminish alimentary increase of cholesterol and triglyceride values [5], to decrease fibrinogen lev fibrinolytic activity [3].
Corrcspndence to: &iv.-Doz. Dr. medl. J. kuenberg, 1. Medizinische Klinik, Klinikum Mannheim, UniversitSt Hddelberg, Theodor-Kutzer-Ufer, D-6800 Mannheim, F.R.G.
0021-9150/88/$03.50
fibrin.
0 1988 Elsevier Scientific Publishers Ireland, Ltd.
The present paper describes the effect Of
248
garlic on these and other blood coagulation and fibrinolysis parameters and reinvestigates the effect on collagen induced platelet aggregation, plasma cholesterol and blood pressure in patients with hyperlipoproteinemia. Methods Thz study was performed in a group of 20 out-patients with hyperlipoproteinemia (5 patients
with hyperlipoproteinemia type IV and 15 patients between with hypercholesterolemia type IIb) 36 and 71 years (mean 53.3 years). Inclusion criteria were plasma cholesterol levels between 250 vels between 170 and tri and coronary artery and All P disease, and 67 had experienced myocardial infarction 6 to 18 months earlier. Six patients were nermotensive upon treatment with antihypertensive drugs, 3 diabetic patients were treated with oral antidiabetics. No patient took drugs interfering with lipid metabolism, coagulation or fibrinolysis system or platelet function. The individual medication was not changed during the study. No et. Patients received 600 patient had fat lowe oated pills (3 times 200 mg dried garlic as su mg daily) over a pen of 4 weeks. The dose ce the metabolic at 50 OC temperature; Ilium sativum (Lichtwer fore, and 2 and 4
.
A 1.1. mm wide needle was placed in vein with minimal venous occlu-
The following parameters were determined: serum cholesterol, serum total triglycerides (enzymatic tests, r Mannheim GmbH, F.RG.) high density lipoprotein (HDL)cholesterol (enzymatically after precipitation of very low
and low density lipoproteins (LDL) with phosphotungstic acid, Boehringer Mannheim), LDLcholesterol (after calculation according to the Friedewald formula if triglycerides were e 400 mg/dl), blood pressure, hematocrit, and platelet count (Hemalog S, Technicon), prothrombin time (Men and Dade, Munich, F.R.G.), activated partial thromboplastin time ring Werke factor VIII antithrombin III activity (S 2238 chromogenic substrate method, Kabi Vitrum AB, Munich, F.R.G.), anti-factor Xa activity (S 2222 method), fibrinopeptide A (7), streptokinase-activated tiplasmin activity (fluorogenic , Merz and Dade, Munich, induced (8), 10m5 mol 4 (PF4 and platelet Enzygnost Elisatest, Behringwerke AG, Marburg, F.R.G.). The Wilcoxon r test was used for evaluation. The values determined 2 an after onset of treatment were compared to those before treatment. The descriptive levels of significance were P < 0.05 or P s 0.01. Data are express as mean and SD.
All patients completed the study. The cholesterol levels dropped significantly from 277 mg% to 258 mg% (P < 0.01) (Table 1). Serum HDLcholesterol, serum LDL-cholesterol and serum triglyceride levels did not change during medication. The prothrombin time decreased during medication, but did not reach statistical significance. Fibrinogen significantly decreased by 10 333 mg% to 299 mg% (P < 0.01). Values fo factor VIII activity, factor Xa inhibition, and antithrombin III activity remained uuchanged. FpA values were elevated to 2.19 ng/ml f 1.04 ng/ml compared to healthy persons (1.0 f 0.7 ng/ml) (12,17) before treatment. FpA values significantly decreased to 1.19 ng/ml in these patients upon intake of garlic (P -z 0.01). Streptokinase activated plas cantly increased from 2.51 to 2.88 W/ml (P < 0.01). The FpB p15-42 significantly increased from
TABLE 1
LEVELS, IBEFO& AND DURING INTA IN 20 PATIENTS WITH HYP I~PRG~INEMIA Values are means f SD.
prothrombin time which, however,
Variable Cholesterol (mg%)
before treatment after 2 weeks
277.90* 45.13 267.35 f 53.21 258.30 k 40.68
before treatment
333.25 f
Fibrinupeptide A Ou/~)
before treatment
2.19* 2. 1.
1.09 1.10 O.B1
Streptokinaseactivated plasminogen (U/ml)
before treatment after 2 weeks after 4 weeks
2.51* 2.53f 2.88&
0. 0.66 0.71
Fibrinopeptide B/3 15-42 (ng/ml)
before treatment after 2 weeks after 4 weeks
17.10f 18.75 f 24.30 f
6.73 8.54 12.70
89.90
17.1 to 24.3 ng/ml (P < 0.01). a2-antiplasmin activity remained unchanged.
eaves fibrin in b
1 Ernst, E., Cardiovascular effects of garlic (A&urn suriuum):
3
count, IO-’ mol A treatment period. The mean systolic blo pressure decreased from 136.5 to 125.5 mm and the mean diastolic blood pressure dec from 86.0 to 81.0 g (P < 0.01) without changes in heart mm rate/min. iscussion
The present investigation confirms earlier results which have shown a cholesterol levels [1] and fibri well as systolic and diastok patients with hyperlipoprotein of dried garlic. The specific assays for fibrin formation use our study demonstrate that enhanced fibrin for-
4 5
6
7
8
9
a review, Pbarmatherapeutica, 5 (1987) 83. nsal, W.C.. Arora, SK. and Singh, S.V., Effmt of the essential oils in garlic ami onion on alimentary hyperlipemia, Athero Bordia, AK., Joshi, Sanadhya, Y.K. and Effect of essential oi ic on serum fibrindyti in patients with coronary artery disease, Atherosclerosis, 28 (1977) 155. Ariga, T., Qsihira, S. and Tamada, T., inhibitor in garlic, Lance& i (1981) 150. Luley, C., Lehman-Leo, W., Mtiller, Schartzkopff. W., Lack of efficacy of dried garlic in patients with hyperlipoproteinemia, Arzneimittelforschung, 36 (1986) 766. Nossel, H.L., Wasser, J., Kaplan, K.L., La Gamma, KS., Yudelman, I. and Canfield, R.E., Sequence of fibrinogen proteolysis and platelet release after intrauterine infusion of hypertonic saline, J. Clin. Invest., 64 (1979) 1371. Hare&erg, J., Hepp, G. and Schmidt-Gayk, H., Fibrinopeptide A in human plasma. Evaluation of a new radioimmunoassay technique on microtiter-plates, Thromb. Res., 15 (1979) 513. Kudryk, B., Robinson, B., Netre, C., M. alld Blomb%ck, B., Measuremen fibrinogen/fibrin fragments containing the quence, Thromb. Res., 26 (198 Haeenberg, J., Waas, R. and Zi of fibrinopeptide A in patients Thromb. Haemostas., 4: (19Bl) 282.