-IBIS-1.7.6-
tx
cardiovascular system
hypercholesterolemia
Botanicals
primary herbs
Allium cepa (Onion): lowers cholesterol (Sainani GS, et al. Jpn Heart J 1979 May;20(3):351-357. )
Allium sativum (Garlic): Despite a few, potentially flawed studies to the contrary, a wide range of research has demonstrated garlic's ability to reduce cholesterol levels. Reviews of all such research indicate that a 9-12% reduction of total serum cholesterol can typically be acheved using 600-900 mg of garlic over a periods of one to four months. Chewing one clove of raw garlic daily presents the most direct method of consuming the necessary levels. However, those who prefer an odorless, enteric-coated tablet, standardized for allicin content would need to take a daily total of 900 mg, containing 5000 mcg of allicin, to obtain the same effects. (Silagy C, Neil A. J R Coll Physicians Lond 1994 Jan-Feb;28(1):39-45; Steiner M, et alk. Am J Clin Nutr 1996 Dec;64(6):866-870; Orekhov AN, Grunwald J. Nutrition 1997 Jul-Aug;13(7-8):656-663; Sainani GS, et al. Jpn Heart J 1979 May;20(3):351-357; Yeh YY, Yeh SM. Lipids 1994 Mar;29(3):189-193.)
Commiphora mukul (guggalon gum): lowers LDL and VLDL, while it raises HDL. In a study comparing guggul with the drug clofibrate, researchers found greater reductions in average serum cholesterol (11% vs. 10%) with the guggul, while the gugul alone produced a 60% increase in HDL levels. The therapeutic dosage of guggul is usually based on the guggulsterone content. Clinical studies have found that 25 mg guggulsterone, three times daily, can be an effective therapeutic dose for elevated cholesterol levels, elevated triglycerides, or both. In a commercial preparation containing 5% guggulsterones the recommended dose would typically be 500 mg three times daily, with results to be expected over a period of three to six months. (Mester L, et al. Planta Med 1979 Dec;37(4):367-369; Satyavati GV, et al. Indian J Med Res 1969 Oct;57(10):1950-1962; Singh K, et al. Phytotherapy Research. 1997; 11(4):291-294; Singh RB, et al. Cardiovascular Drugs and Therapy. 1994; 8:659-664; Verma, Indian J Med Res 87: 356-360; Nityanand S, et al. J Assoc Physicians India 1989 May;37(5):323-328.)
Dioscorea villosa (Wild Yam): In one study looking at adrenal hormones, particularly DHEA, researchers found that DHEA and dioscorea significantly reduced serum lipid peroxidation, lowered serum triglycerides, phospholipid and increased HDL levels. For such purposes 2-3 ml of Dioscorea tincture, 3-4 times daily, or 1-2 capsules of dried root, three times per day, would provide the appropriate dose. (Araghiniknam M, et al. Life Sci 1996;59(11):PL147-157.)
Eleutherococcus senticosus (Siberian Ginseng): lowers cholesterol (Pizzorno, Murray V: EleuSe-4; Maslova LV, et al. Biull Eksp Biol Med 1993 Mar;115(3):269-271.)
CAUTION regarding possible interaction: There has been an anecdotal report of elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. (McRae S. CMAJ 1996 Aug 1;155(3):293-295.)
Panax ginseng: in hyperlipidemia: reduces total serum cholesterol, triglycerides and raises serum HDL-cholesterol levels; CAUTION: in Classical Chinese medicine the use of Panax ginseng would often be contraindicated in many cases involving hypertension, esp. with Fire Shih (Excess) and/or Yin Xu (Deficiency) (Lin SG, et al. Chung Kuo Yao Li Hsueh Pao 1993 Jul;14(4):314-316 ; Lei XL, et al. Am J Chin Med 1986;14(3-4):145-152; Pizzorno, Murray V: PanaxG-6; Han KH, et al. Am J Chin Med 1998;26(2):199-209.)
Vaccinium myrtillus: reduces serum cholesterol and triglyceride levels in primary dyslipidemia (Pizzorno, Murray V: VacMyr-3; Detre Z, et al. Clin Physiol Biochem 1986;4(2):143-149.)
complementary herbs
footnotes
[No author listed.] Garlic powder for hyperlipidemiaanalysis of recent negative results. Quart Rev Natural Med. Fall, 1998;187-189.
Agarwal RC, Singh SP, Saran RK, Das SK, Sinha N, Asthana OP, Gupta PP, Nityanand S, Dhawan BN, Agarwal SS. Clinical trial of gugulipid--a new hypolipidemic agent of plant origin in primary hyperlipidemia. Indian J Med Res 1986 Dec;84:626-634.
Araghiniknam M, Chung S, Nelson-White T, Eskelson C, Watson RR. Antioxidant activity of dioscorea and dehydroepiandrosterone (DHEA) in older humans. Life Sci 1996;59(11):PL147-157.
Abstract: Dioscorea is a yam steroid extract used in commercial steroid synthesis and consumed by people. DHEA is a steroid which declines with age, but without known activity. This study was designed to determine whether dioscorea supplementation could increase serum dehydroepiandrosterone sulfate (DHEAS) in humans and modulate lipid levels in older people. The subjects were selected volunteers aged 65-82 years. The serum DHEAS level, lipid peroxidation and lipid profile were assessed. Three weeks of dioscorea supplementation had no affect on serum DHEAS level. However DHEA intake of 85 mg/day increased serum DHEA levels 100.3%. DHEA and dioscorea significantly reduced serum lipid peroxidation, lowered serum triglycerides, phospholipid and increased HDL levels. Both DHEA and the steroid yam extract, dioscorea, have significant activities as antioxidant to modify serum lipid levels.
Azizov AP. [Effects of eleutherococcus, elton, leuzea, and leveton on the blood coagulation system during training in athletes]. Eksp Klin Farmakol 1997 Sep-Oct;60(5):58-60. [Article in Russian]
Abstract: Comparative study was conducted of formal preparations of tinctures of eleutherococcus and leuzea and the newly developed preparations Elton and Leveton containing, respectively, eleutherosids and ecdisten. Intensive physical activity of high-class athletes leads to increase of blood coagulation expressed in shortening of the thromboelastogram r and K intervals and increased activity of the proth rombin complex according to Quick, and increased activity of factors II, VII, X, XIII, and fibrinolysis. The concentration of fibrinogen increases. A 20-day course of eleuthrococcus tincture causes a decrease in the blood coagulation potential and activity of the blood coagulation factors induced by intensive training of the athletes. Twenty-day treatment with the new broad-spectrum adaptogens Elton and Leveton causes a more marked reduction of the coagulation potential in athl etes. The activity of the factors and fibrinolys are normalized in this case. The indicated shifts are accompanied with increase of working capacity and rehabilitation of the athletes.
Baldwa VS, Bhasin V, Ranka PC, Mathur KM. Effects of Commiphora Mukul (Guggul) in experimentally induced hyperlipemia and atherosclerosis. J Assoc Physicians India 1981 Jan;29(1):13-17.
Berthold HK, Sudhop T, von Bergmann K. Effect of a garlic oil preparation on serum lipoproteins and cholesterol metabolism: a randomized controlled trial. JAMA 1998 Jun 17;279(23):1900-1902.
Abstract: CONTEXT: Garlic-containing drugs have been used in the treatment of hypercholesterolemia even though their efficacy is not generally established. Little is known about the mechanisms of action of the possible effects on cholesterol in humans. OBJECTIVE: To estimate the hypocholesterolemic effect of garlic oil and to investigate the possible mechanism of action. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Outpatient lipid clinic. PATIENTS: We investigated 25 patients (mean age, 58 years) with moderate hypercholesterolemia. INTERVENTION: Steam-distilled garlic oil preparation (5 mg twice a day) vs placebo each for 12 weeks with wash-out periods of 4 weeks. MAIN OUTCOME MEASURES: Serum lipoprotein concentrations, cholesterol absorption, and cholesterol synthesis. RESULTS: Baseline lipoprotein profiles were (mean [SD]): total cholesterol, 7.53 (0.75) mmol/L (291 [29] mg/dL); low-density lipoprotein cholesterol (LDL-C), 5.35 (0.78) mmol/L (207 [30] mg/dL); high-density lipoprotein cholesterol (HDL-C), 1.50 (0.41) mmol/L (58 [16] mg/dL); and triglycerides, 1.45 (0.73) mmol/L (127 [64] mg/ dL). Lipoprotein levels were virtually unchanged at the end of both treatment periods (mean difference [95% confidence interval]): total cholesterol, 0.085 (-0.201 to 0.372) mmol/L (3.3 [-7.8 to 14.4] mg/dL), P=.54; LDL-C, 0.001 (-0.242 to 0.245) mmol/L (0.04 [-9.4 to 9.5] mg/dL), P=.99; HDL-C, 0.050 (-0.028 to 0.128) mmol/L (1.9 [-1.1 to 4.9] mg/dL), P=.20; triglycerides, 0.047 (-0.229 to 0.135) mmol/L (4.2 [-20.3 to 12.0]) mg/dL, P=.60. Cholesterol absorption (37.5% [10.5%] vs 38.3% [10.7%0], P=.58), cholesterol synthesis (12.7 [6.5] vs 13.4 [6.6] mg/kg of body weight per day, P=.64), mevalonic acid excretion (192 [66] vs 187 [66] microg/d, P=.78), and changes in the ratio of lathosterol to cholesterol in serum (4.4% [24.3%] vs 10.6% [21.1%], P=.62) were not different in garlic and placebo treatment. CONCLUSIONS: The commercial garlic oil preparation investigated had no influence on serum lipoproteins, cholesterol absorption, or cholesterol synthesis. Garlic therapy for treatment of hypercholesterolemia cannot be recommended on the basis of this study.
Note: This study has been widely criticized as irrelevant to standard practice as the dosages and form used are not those usually recommended.
Bordia A, Verma SK, Srivastava KC. Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids 1998 Apr;58(4):257-263.
Abstract: Thirty patients with coronary artery disease (CAD) were administered garlic (study group) while another 30 patients received the placebo (control group). Various risk parameters were determined at 1.5 and 3 months of garlic administration. Garlic, administered in a daily dose of 2 x 2 capsules (each capsule containing ethyl acetate extract from 1 g peeled and crushed raw garlic), reduced significantly total serum cholesterol and triglycerides, and increased significantly HDL-cholesterol and fibrinolytic activity. There was no effect on the fibrinogen and glucose levels. In vitro effects of the garlic oil on platelet aggregation (PAg) and eicosanoid metabolism were examined; it inhibited PAg induced by several platelet agonists, and also platelet thromboxane formation. Two important paraffinic polysulphides - diallyl disulphide (DADS) and diallyl trisulphide (DATS) - derived from garlic and are usual constituents of garlic oil, showed antiplatelet activity, and also inhibited platelet thromboxane formation. In this respect DATS was more potent than DADS. The nature of inhibition of PAg by DATS was found to be reversible.
Chen CF, Chen SM, Lin MT, Chow SY. In vivo and in vitro studies on the mechanism of cardiovascular effects of Wu-Chu-Yu (Evodiae fructus). Am J Chin Med 1981 Spring;9(1):39-47.
Abstract: The effects of the Chinese herb Wu-Chu-Yu (Evodiae fructus) on the cardiovascular function were assessed in anesthetized cats, conscious rats, and isolated preparations of rat aortic strip and auricle. In anesthetized cats, intravenous administration of alcohol-water crude extracts of Wu-Chu-Yu (0.03-0.24 g/kg) produced a dose-dependent hypertension and an increased contractile force of nictitating membrane which lasted for more than 5 min in higher doses. Phentolamine, but not tetraethylammonium antagonized hypertension and the increased contractile force of nictitating membrane induced by Wu-Chu-Yu. In conscious rats, hypertension was also observed by intraperitoneal administration of Wu-Chu-Yu (6 g/kg). Bilateral nephrectomy, administration of phentolamine or propranolol, all significantly decreased the hypertensive effect of Wu-Chu-Yu. Pretreatment with reserpine 24 hours in advance did not change the pressor effect of the crude extract. In aortic strip preparations, Wu-Chu-Yu caused the increase of contractile force, and the dose-response curve was parallel shift to the right in the presence of phentolamine. In auricle preparations, Wu-Chu-Yu produced positive inotropic and positive chronotropic effects, and the presence of propranolol changed the slope of Wu-Chu-Yu's dose-inotropic effect curve and reversed the chronotropic effect from positive to negative. Both in vivo and in vitro results suggested that alpha and beta adrenoceptors were directly involved in the cardiovascular effects of Wu-Chu-Yu.
Dalvi SS, Nayak VK, Pohujani SM, Desai NK, Kshirsagar NA, Gupta KC. Effect of gugulipid on bioavailability of diltiazem and propranolol. J Assoc Physicians India 1994 Jun;42(6):454-455.
Abstract: The effect of single oral dose of 1 gm gugulipid was studied on bioavailability of single oral dose of propranolol (40 mg) and diltiazem (60 mg) in 10 and 7 normal healthy male volunteers respectively. It was a randomised within group crossover study. Blood samples were collected at hourly intervals upto 8 hrs. Gugulipid significantly reduced (P < .01) peak plasma concentration (Cmax) and area under curve (AUC 0-8 hrs) of both the drugs in normal volunteers. Such interaction in patients receiving propanolol or diltiazem with gugulipid may lead to diminished efficacy or nonresponsiveness due to significant reduction in bioavailability.
Detre Z, Jellinek H, Miskulin M, Robert AM. Studies on vascular permeability in hypertension: action of anthocyanosides. Clin Physiol Biochem 1986;4(2):143-149.
Abstract: The initial phase of renal hypertension induced by ligature of the abdominal aorta was accompanied by a transient increase in vascular permeability. This permeability increase has not the same intensity in all parts of the organism: it is greater in the skin and in the aorta wall than in the brain vessels. Treatment of rats with a flavonoid-type drug (anthocyanosides of Vaccinium myrtillus) for 12 days before the induction of hypertension kept the blood-brain barrier permeability normal and limited the increase in vascular permeability in the skin and the aorta wall. As previously demonstrated, the collagens of the blood vessel walls play an important role in the control of vascular permeability. Interaction of these collagens with the drug may be partly responsible for the protection against the permeability-increasing action of hypertension observed in the treated animals.
Efendy JL, Simmons DL, Campbell GR, Campbell JH. The effect of the aged garlic extract, 'Kyolic', on the development of experimental atherosclerosis. Atherosclerosis 1997 Jul 11;132(1):37-42.
Abstract: The aged garlic extract 'Kyolic' lowers serum cholesterol levels in humans and experimental animals and thus is presumed to have a protective effect against atherosclerosis. However, to date no studies have examined the effect of this substance on the actual development of the disease. In the present study, the right carotid artery of 24 rabbits was de-endothelialized by balloon catheterisation in order to produce a myointimal thickening. After 2 weeks the rabbits were randomly assigned to four groups: Group I received a standard diet; Group II received the standard diet supplemented with 800 microl/kg body weight/day 'Kyolic'; Group III received a 1% cholesterol supplemented standard diet; and Group IV received a 1% cholesterol supplemented standard diet plus 'Kyolic'. After 6 weeks, the cholesterol diet caused a 6-fold increase in serum cholesterol level (Group III; 6.4 +/- 0.6 mmol/l) compared to normal diet (Group I; 1.2 +/- 0.4 mmol/l) (P < 0.05) with only a minor, non-significant reduction seen by the addition of 'Kyolic' (Group IV; 6.2 +/- 0.7 mmol/l). Group III rabbits developed fatty streak lesions covering approximately 70 +/- 8% of the surface area of the thoracic aorta, which was significantly reduced to 25 +/- 3% in the 'Kyolic'-treated Group IV. No lesions were present in Groups I and II. The hypercholesterolaemic diet caused an increase in aortic arch cholesterol (2.1 +/- 0.1 mg cholesterol/g tissue) which was significantly reduced by 'Kyolic' supplementation (1.7 +/- 0.2 mg cholesterol/g tissue) (P < 0.05). 'Kyolic' significantly inhibited the development of thickened, lipid-filled lesions in the pre-formed neointimas produced by balloon-catheter injury of the right carotid artery in cholesterol-fed rabbits (intima as percent of artery wall, Group III 42.6 +/- 6.5% versus Group IV 23.8 +/- 2.3%, P < 0.01), but had little effect in rabbits on a standard diet (Group II 18.4 +/- 5.0% versus Group I 16.7 +/- 2.0%). In vitro studies showed that 'Kyolic' has a direct effect on inhibition of smooth muscle proliferation. In conclusion, 'Kyolic' treatment reduces fatty streak development, vessel wall cholesterol accumulation and the development of fibro fatty plaques in neointimas of cholesterol-fed rabbits, thus providing protection against the onset of atherosclerosis.
Fintelmann V. Antidyspeptic and lipid-lowering effect of artichoke leaf extract. Zeitschirfit fur Allgemeinmed 1996;72:1-19.
Gopal K, Saran RK, Nityanand S, Gupta PP, Hasan M, Das SK, Sinha N, Agarwal SS. Clinical trial of ethyl acetate extract of gum gugulu (gugulipid) in primary hyperlipidemia. J Assoc Physicians India 1986 Apr;34(4):249-251.
Hammond TG, Whitworth JA. Adverse reactions to ginseng. Med J Aust 1981 May 2;1(9):492. (Letter)
Han KH, Choe SC, Kim HS, Sohn DW, Nam KY, Oh BH, Lee MM, Park YB, Choi YS, Seo JD, Lee YW. Effect of red ginseng on blood pressure in patients with essential hypertension and white coat hypertension. Am J Chin Med 1998;26(2):199-209.
Abstract: The objective of this study is to evaluate the changes of diurnal blood pressure pattern after 8 weeks of red ginseng medication (4.5 g/day) by 24 hour ambulatory blood pressure monitoring. In 26 subjects with essential hypertension, 24 hour mean systolic blood pressure decreased significantly (p = 0.03) while diastolic blood pressure only showed a tendency of decline (p = 0.17). The decrease in pressures were observed at daytime (8 A.M.-6 P.M.) and dawn (5 A.M.-7 A.M.). In 8 subjects with white coat hypertension, no significant blood pressure change was observed. We suggest that red ginseng might be useful as a relatively safe medication adjuvant to current antihypertensive medications.
Heckers H, Dittmar K, Schmahl FW, Huth K. Inefficiency of cynarin as therapeutic regimen in familial type II hyperlipoproteinemia. Atherosclerosis 1977; 26:249-253.
Holzgartner H, Schmidt U, Kuhn U. Comparison of the efficacy and tolerance of a garlic preparation vs. bezafibrate. Arzneimittelforschung 1992 Dec;42(12):1473-1477.
Abstract: The efficacy and tolerance of a garlic preparation (Sapec, Kwai) was investigated in a randomized double-blind study vs. bezafibrate. This multi-centre study was conducted in 5 general medical practices and involved 98 patients with primary hyperlipoproteinaemia. The daily doses of the active substances were 900 mg of garlic powder (standardized as to 1.3% alliin) and 600 mg of bezafibrate, respectively. The pre-phase with placebo lasted 6 weeks, the treatment period covered 12 weeks. All patients were advised to observe a low-fat "step-1 diet" for the duration of the study. The 98 case report forms allowed the statistical evaluation of total cholesterol, HDL cholesterol and triglyceride levels for 94 patients, and of LDL cholesterol values for 92 patients. In the course of the treatment both study medications caused a statistically highly significant reduction in total cholesterol, in LDL cholesterol and triglycerides, and an increase in HDL cholesterol. However, there was no significant difference in the efficacies of both medication groups. Side effects were mentioned by 5 patients each in both treatment groups, none of which led to the withdrawal of the patients. Concerning the garlic preparation, there was no correlation between the perception of garlic odour and the influence on the cholesterol level.
Isaacsohn JL, Moser M, Stein EA, Dudley K, Davey JA, Liskov E, Black HR. Garlic powder and plasma lipids and lipoproteins: a multicenter, randomized, placebo-controlled trial. Arch Intern Med 1998 Jun 8;158(11):1189-1194.
Abstract: BACKGROUND: Garlic powder tablets have been reported to lower serum cholesterol levels. There is widespread belief among the general public that garlic powder tablets aid in controlling cholesterol levels. However, much of the prior data demonstrating the cholesterol-lowering effect of garlic tablets involved studies that were inadequately controlled. OBJECTIVE: To determine the lipid-lowering effect of garlic powder tablets in patients with hypercholesterolemia. METHODS: This was a randomized, double-blind, placebo-controlled, 12-week, parallel treatment study carried out in 2 outpatient lipid clinics. Entry into the study after 8 weeks of diet stabilization required a mean low-density lipoprotein cholesterol level on 2 visits of 4.1 mmol/L (160 mg/dL) or lower and a triglyceride level of 4.0 mmol/L (350 mg/dL) or lower. The active treatment arm received tablets containing 300 mg of garlic powder (Kwai) 3 times per day, given with meals (total, 900 mg/d). This is equivalent to approximately 2.7 g or approximately 1 clove of fresh garlic per day. The placebo arm received an identical-looking tablet, also given 3 times per day with meals. The main outcome measures included levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol after 12 weeks of treatment. RESULTS: Twenty-eight patients (43% male; mean +/- SD age, 58 +/- 14 years) received garlic powder treatment and 22 (68% male; mean +/- SD age, 57 +/- 13 years) received placebo treatment. There were no significant lipid or lipoprotein changes in either the placebo- or garlic-treated groups and no significant difference between changes in the placebo-treated group compared with changes in the garlic-treated patients. CONCLUSION: Garlic powder (900 mg/d) treatment for 12 weeks was ineffective in lowering cholesterol levels in patients with hypercholesterolemia.
Jain AK, Vargas R, Gotzkowsky S, McMahon FG. Can garlic reduce levels of serum lipids? A controlled clinical study. Am J Med 1993 Jun;94(6):632-635.
Abstract: PURPOSE: To assess the effects of standardized garlic powder tablets on serum lipids and lipoproteins, glucose, and blood pressure. SUBJECTS AND METHODS: Forty-two healthy adults (19 men, 23 women), mean age of 52 +/- 12 years, with a serum total cholesterol (TC) level of greater than or equal to 220 mg/dL received, in a randomized, double-blind fashion, either 300 mg three times a day of standardized garlic powder in tablet form or placebo. Diets and physical activity were unchanged. This study was conducted in an outpatient, clinical research unit. RESULTS: The baseline serum TC level of 262 +/- 34 mg/dL was reduced to 247 +/- 40 mg/dL (p < 0.01) after 12 weeks of standard garlic treatment. Corresponding values for placebo were 276 +/- 34 mg/dL before and 274 +/- 29 mg/dL after placebo treatment. Low-density lipoprotein cholesterol (LDL-C) was reduced by 11% by garlic treatment and 3% by placebo (p < 0.05). There were no significant changes in high-density lipoprotein cholesterol, triglycerides, serum glucose, blood pressure, and other monitored parameters. CONCLUSIONS: Treatment with standardized garlic 900 mg/d produced a significantly greater reduction in serum TC and LDL-C than placebo. The garlic formulation was well tolerated without any odor problems.
Kaloeva ZD. [Effect of the glycosides of Eleutherococcus senticosus on the hemodynamic indices of children with hypotensive states]. Farmakol Toksikol 1986 Sep-Oct;49(5):73. [Article in Russian]
Abstract: Efficacy of extractum eleutherococci fluidum in children aged 7-10 years with a stable stage of neurocirculatory hypotension was shown. A positive dynamics of subjective evidence, a statistically significant elevation of levels of systolic and diastolic pressures low before treatment and an increase of total peripheral resistance were noted.
Lawson L. Garlic oil for hypercholesterolemia - negative results. Quart Rev Natural Med. Fall 1998;185-186.
Lei XL, Chiou GC. Cardiovascular pharmacology of Panax notoginseng (Burk) F.H. Chen and Salvia miltiorrhiza. Am J Chin Med 1986;14(3-4):145-152.
Abstract: The cardiovascular pharmacology of two Chinese herbs, Salvia miltiorrhiza (SM) and Panax notoginseng (Burk) F. H. Chen (PNG) were studied both in vivo and in vitro. Extracts of both herbs suppressed systemic blood pressure in albino rats and rabbits, an effect which was blocked or reversed by atropine, propranolol, and chlorpheniramine plus cimetidine. This reversed hypertension was blocked by phenoxybenzamine. These results indicate that these herbs have multiple effector sites in the cardiovascular system. This could be due to an increased utilization of extracellular calcium ions since the activity of SM on isolated blood vessels of rabbits was enhanced by 2 mM Ca++. The effects of aqueous extract of SM and purified active principles of SM (tanshinones) on rat and rabbit blood vessels in vitro were very similar both qualitatively and quantitatively. Both caused vasodilation of coronary arteries at all concentrations tested but induced vasodilation of renal, mesenteric and femoral arteries only at low concentrations. At higher concentrations, vasoconstriction was induced in these vessels. These results indicate that an economical decoction of SM is as efficacious as the more expensive isolated tanshinones. Both SM and PNG would be useful as antianginal agents since they dilate coronary vessels. Their use in hypertension is questionable since they induce both vasodilation and vasoconstriction depending on dose and target vessel.
Lin SG, Zheng XL, Chen QY, Sun JJ. Effect of Panax notoginseng saponins on increased proliferation of cultured aortic smooth muscle cells stimulated by hypercholesterolemic serum. Chung Kuo Yao Li Hsueh Pao 1993 Jul;14(4):314-316.
Abstract: Panax notoginseng saponins (PNS) was extracted from a Chinese herb medicine. After preparation of cultured aortic smooth muscle cell (SMC) from primary aortic explants, the cytotoxicity of hypercholesterolemic serum (HCS) for cultured cells was determined by trypan blue exclusion test, and [3H]thymidine incorporation and cell numbers were counted at the same time. The results showed that HCS (0.5 mg cholesterol.ml-1) increased the incorporation of [3H]thymidine into cultured cells (3722 +/- 440 vs 1655 +/- 288 dpm/microgram cell proteins, P < 0.01), stimulated the proliferation of SMC [(6.5 +/- 1.5) x 10(5) vs (4.3 +/- 1.2) x 10(5) cells/plate, P < 0.01], and that high concentration HCS (final cholesterol concentration 2 mg.ml-1) was cytotoxic to the cultured cells. PNS (100 and 400 micrograms.ml-1) decreased the incorporation of [3H]thymidine into SMC in culture with or without HCS (1292 +/- 260 and 982 +/- 314 or 4111 +/- 886 and 2361 +/- 751 dpm/microgram cell protein), and inhibited the proliferation of the cultured cells [(3.3 +/- 0.7) x 10(5) and (2.9 +/- 0.7) x 10(5) or (4.7 +/- 1.4) x 10(5) and (4.1 +/- 1.2) x 10(5) cells/plate). We conclude that PNS can inhibit the proliferation of aortic SMC stimulated by HCS. These results also suggest that HCS may play an atherogenic role in the arterial wall and that PNS may prevent atherosclerosis and inhibit progression of the atherosclerotic lesions by interfering with the proliferation of arterial SMC.
Liu SY, Xu YY, Zhu JY. [The effects of Salvia miltiorrhizae Bge and Ligustrazine on thromboxane A2 and prostacyclin in pregnancy induced hypertension]. Chung Hua Fu Chan Ko Tsa Chih 1994 Nov;29(11):648-50, 697. [Article in Chinese]
Abstract: The clinical efficiency and mechanism of traditional Chinese medicinal herb Salvia Miltiorrhizae Bge (SMB) and Ligustrazine (L) on pregnancy induced hypertension (PIH) were studied in 30 patients. Before and after the administration of SMB and L, the following parameters: mean arterial pressure (MAP), proteinuria, levels of Thromboxane A2 (TXA2) and Prostacyclin (PGI2) were observed. TXA2 and PGI2 were measured by their stable hydration products Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) by an established radioimmunoassay. The results of treatment were compared with the base line values and showed as follows: MAP and proteinuria decreased significantly (P < 0.05); no marked difference existed in TXB2; the level of 6-keto-PGF1 alpha increased significantly (P < 0.05); the rate of TXB2/6-keto-PGF1 alpha decreased significantly (P < 0.05). The results suggested that SMB and L can invigorate blood circulation by decreasing vasoconstriction.
Maslova LV, Lishmanov IuB, Maslov LN. [Cardioprotective effects of adaptogens of plant origin]. Biull Eksp Biol Med 1993 Mar;115(3):269-271. [Article in Russian]
Abstract: The experiments performed on emotional--painful stress model in rats demonstrated cardioprotective activity of adaptogens of vegetable origin (rodiolae, eleutherococcus, levsea, p-tyrosol). Preliminary injection of rodiolae extract was found to prevent stress--induced increase in cAMP level and cGMP content decrease in heart. We can conclude that adaptogens cardioprotective effect may be the drugs to prevent stressor change in cyclic nucleotides level in myocardium.
McCrindle BW, Helden E, Conner WT. Garlic extract therapy in children with hypercholesterolemia. Arch Pediatr Adolesc Med 1998 Nov;152(11):1089-1094.
Abstract: OBJECTIVE: To determine whether garlic extract therapy is efficacious and safe in children with hypercholesterolemia. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: Specialized pediatric lipid disorders ambulatory clinic. PARTICIPANTS: Thirty pediatric patients, aged 8 to 18 years, who had familial hyperlipidemia and a minimum fasting total cholesterol level greater than 4.8 mmol/L (> 185 mg/dL). INTERVENTION: An 8-week course of a commercially available garlic extract (Kwai [Lichtwer Pharma, Berlin, Germany], 300 mg, 3 times a day) or an identical placebo. MAIN OUTCOME MEASURES: Absolute and relative changes in fasting lipid profile parameters. RESULTS: The groups were equivalent at baseline and compliance was similar in the 2 groups (P = .45). There was no significant relative attributable effect of garlic extract on fasting total cholesterol (+0.6% [95% confidence interval, -5.8% to +6.9%1) or low-density lipoprotein cholesterol (-0.5% [95% confidence interval, -8.7% to +7.6%]). The lower limits of the confidence intervals did not include -10%, the minimum relative attributable effect believed to be clinically important. Likewise, no significant effect was seen on the levels of high-density lipoprotein, triglycerides, apolipoprotein B-100, lipoprotein (a), fibrinogen, homocysteine, or blood pressure. There was a small effect on apolipoprotein A-I (+10.0% [95% confidence interval, +1.2% to +16.5%] P=.03). There were no differences in adverse effects between groups. CONCLUSION: Garlic extract therapy has no significant effect on cardiovascular risk factors in pediatric patients with familial hyperlipidemia.
McRae S. Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. CMAJ 1996 Aug 1;155(3):293-295.
Abstract: A 74-year-old man taking a constant dose of digoxin for many years was found to have an elevated serum digoxin level with no signs of toxic effects. Common causes of elevated serum digoxin were ruled out, and the patient's digoxin level remained high after digoxin therapy was stopped. The patient then revealed that he was taking Siberian ginseng, a popular herbal remedy. The patient stopped taking ginseng, and the serum digoxin level soon returned to an acceptable level. The digoxin therapy was resumed. The patient resumed taking ginseng several months later, and the serum digoxin level again rose. Digoxin therapy was maintained at a constant daily dose, the ginseng was stopped once more, and the serum digoxin levels again returned to within the therapeutic range. It is unclear whether some component of the ginseng was converted to digoxin in vivo, interfered with digoxin elimination or caused a false serum assay result. The author cautions physicians to be alert to the potential for herbal remedies to interact with prescribed medications and to affect biochemical analyses.
Mester L, Mester M, Nityanand S. Inhibition of platelet aggregation by "guggulu" steroids. Planta Med 1979 Dec;37(4):367-369.
Miller AL. Botanical influences on cardiovascular disease. Altern Med Rev 1998 Dec;3(6):422-431. (Review)
Abstract: Several botanicals, including Crataegus oxycantha, Terminalia arjuna, Inula racemosa, and Astragalus membranaceus, have been found to have therapeutic benefit for the treatment of cardiovascular disease. Crataegus oxycantha has been used traditionally as a cardiac tonic and current uses include treatment for angina, hypertension, arrhythmias, and congestive heart failure. Animal studies have also indicated that Crataegus extracts may also have potential use as anti-ischemic and lipid-lowering agents. The bark of the Terminalia arjuna tree has a long history of use as a cardiac tonic as well, and has been indicated in the treatment of coronary artery disease, heart failure, hypercholesterolemia and for relief of anginal pain. Additionally, it has been found to have antibacterial and antimutagenic properties. Inula racemosa, also known as Pushkarmoola, is another traditional Ayurvedic botanical that has potential cardioprotective benefit. In human trials, a combination of Inula racemosa and Commiphora mukul was shown to be superior to nitroglycerin in reducing the chest pain and dyspnea associated with angina. Astragalus membranaceus, a Chinese herb, is often used as a "Qi tonifier" and has been studied for its therapeutic benefit in treatment of ischemic heart disease, myocardial infarction, heart failure, and relief of anginal pain. Clinical studies have indicated that its in vitro antioxidant activity is the mechanism by which it affords its cardioprotective benefit.
Nielsen AS. [Hypertension caused by ginseng tablets]? Ugeskr Laeger 1988 Feb 8;150(6):377. [Article in Danish] (Letter)
Nityanand S, Srivastava JS, Asthana OP. Clinical trials with gugulipid. A new hypolipidaemic agent. J Assoc Physicians India 1989 May;37(5):323-328.
Abstract: Multicentric clinical trials of the efficacy of gugulipid conducted at Bombay, Bangalore, Delhi, Jaipur, Lucknow, Nagpur and Varanasi have been reported. Two hundred and five patients completed 12 week open trial with gugulipid in a dose of 500 mg tds after 8 week diet and placebo therapy. One patient showed gastrointestinal symptoms which did not necessitate withdrawal of the drug. A significant lowering of serum cholesterol (av. 23.6%) and serum triglycerides (av. 22.6%) was observed in 70-80% patients Double-blind, crossover study was completed in 125 patients with gugulipid therapy and in 108 patients with clofibrate therapy. Two patients had flu-like syndrome with clofibrate and opted out from the study. With gugulipid the average fall in serum cholesterol and triglycerides was 11 and 16.8% respectively and with clofibrate 10 and 21.6% respectively. The lipid lowering effect of both drugs became evident 3-4 week after starting the drug and had no relationship with age, sex, and concomitant drug intake. Hypercholesterolaemic patients responded better to gugulipid therapy than hypertriglyceridaemic patients who responded better to clofibrate therapy. In mixed hyperlipidaemic patients response to both drugs was comparable. HDL-cholesterol was increased in 60% cases who responded to gugulipid therapy. Clofibrate had no effect on HDL-cholesterol. A significant decrease in LDL-cholesterol was observed in the responder group to both drugs.
Olson BH, Anderson SM, Becker MP, et al. Psyllium-enriched cereals lower blood total cholesterol and LDL cholesterol, but not HDL cholesterol, in hypercholesterolemic adults: Results of a meta-analysis. J Nutr 1997;127:1973-1980.
Orekhov AN, Grunwald J. Effects of garlic on atherosclerosis. Nutrition 1997 Jul-Aug;13(7-8):656-663.
Abstract: This review discusses the use of garlic and garlic preparations as agents for prevention and treatment of atherosclerosis and atherosclerosis-related diseases. Garlic indirectly effects atherosclerosis by reduction of hyperlipidemia, hypertension, and probably diabetes mellitus and prevents thrombus formation. In addition, in animal models, garlic causes direct antiatherogenic (preventive) and antiatherosclerotic (causing regression) effects at the level of artery wall. Garlic's direct effect on atherosclerosis may be explained by its capacity to reduce lipid content in arterial cells and to prevent intracellular lipid accumulation. This effect, in turn, is accompanied by other atherosclerotic manifestations, i.e., stimulation of cell proliferation and extracellular matrix synthesis. Clinical trials are currently being carried out to reveal the possible effect of garlic therapy on human atherosclerosis. Positive results of these trials may open a new era in the use of garlic for prevention and treatment of many atherosclerosis-related diseases. (Review)
Sainani GS, Desai DB, Natu MN, Katrodia KM, Valame VP, Sainani PG. Onion, garlic, and experimental atherosclerosis. Jpn Heart J 1979 May;20(3):351-357.
Abstract: Forty-two healthy male albino rabbits weighing around 1 Kg were divided into 4 groups. Group I (8)- fed on normal stock diet, Group II (8)- fed on stock diet plus cholesterol (0.5 gm in 5 ml of olive oil). Group III (15)- received stock diet plus cholesterol plus garlic (0.25 gm) juice. Group IV (11)- received stock diet plus cholesterol plus onion (2.5 gm) juice. The animals were closely observed and followed for 16 weeks. Approximately every 4 weeks, blood samples were collected for estimation of various parameters (S. cholesterol, S. triglycerides, S. lipoproteins, S. phospolipids, and fibrinolytic activity). At the end of experiment, animals were sacrificed and degree of aortic atherosclerosis was graded (grade 0 to 4) in different groups and compared. Experimental study revealed that both garlic and onion (garlic more than onion) had significant effect in inhibiting the rise in S. cholesterol, S. triglycerides, S. beta lipoproteins, and S. phospolipids and significant effect in enhancing the fibrinolytic activity. The beta: alpha ratio was altered favourably and the ratio was kept close to normal. As regards the degree of aortic atherosclerosis as seen on post mortem, it was significantly less in garlic and onion group when compared with pure cholesterol group.
Satyavati GV, Dwarakanath C, Tripathi SN. Experimental studies on the hypocholesterolemic effect of Commiphora mukul. Engl. (Guggul). Indian J Med Res 1969 Oct;57(10):1950-1962.
Siegel RK. Ginseng abuse syndrome. Problems with the panacea. JAMA 1979 Apr 13;241(15):1614-1615.
Siegel RK. Ginseng and high blood pressure. JAMA 1980 Jan 4;243(1):32. (Letter)
Silagy C, Neil A. Garlic as a lipid lowering agent--a meta-analysis. J R Coll Physicians Lond 1994 Jan-Feb;28(1):39-45.
Abstract: Garlic supplements may have an important role to play in the treatment of hypercholesterolaemia. To determine the effect of garlic on serum lipids and lipoproteins relative to placebo and other lipid lowering agents, a systematic review, including meta-analysis, was undertaken of published and unpublished randomised controlled trials of garlic preparations of at least four weeks' duration. Studies were identified by a search of MEDLINE and the ALTERNATIVE MEDICINE electronic databases, from references listed in primary and review articles, and through direct contact with garlic manufacturers. Sixteen trials, with data from 952 subjects, were included in the analyses. Many of the trials had methodological shortcomings. The pooled mean difference in the absolute change (from baseline to final measurement in mmol/l) of total serum cholesterol, triglycerides, and high-density lipoprotein (HDL)-cholesterol was compared between subjects treated with garlic therapy against those treated with placebo or other agents. The mean difference in reduction of total cholesterol between garlic-treated subjects and those receiving placebo (or avoiding garlic in their diet) was -0.77 mmol/l (95% CI: -0.65, -0.89 mmol/l). These changes represent a 12% reduction with garlic therapy beyond the final levels achieved with placebo alone. The reduction was evident after one month of therapy and persisted for at least six months. In the dried garlic powders, in which the allicin content is standardised, there was no significant difference in the size of the reduction across the dose range of 600-900 mg daily. Dried garlic powder preparations also significantly lowered serum triglyceride by 0.31 mmol/l compared to placebo (95% CI: -0.14, -0.49).
Singh K, Chander R, Kapoor NK. Guggulsterone, a Potent Hypolipidaemic, Prevents Oxidation of Low Density. Phytotherapy Research. 1997; 11(4):291-294.
Abstract: The oxidation of low-density lipoprotein (LDL) induced by Cu+2 caused marked oxidative changes in the lipid and protein, constituents of this lipoprotein in vitro. Guggulsterone (present in the oleogum resin of Commiphora wightii) prevented the generation of lipid peroxides measured as thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes. This compound protected LDL against depletion of lipid constituents such as cholesterol, cholesterol esters, triglycerides [triacylglycerols] and phospholipids as well as inhibiting the conversion of cholesterol into oxygenated cholesterols. Oxidized LDL containing less apoprotein B with a high protein carbonyl value was more electronegative as evidenced by the increase in relative electrophoretic mobility (REM) on agarose gel. Guggulsterone significantly protected LDL apoprotein as measured by reversal of REM after oxidation. The protective action of guggulsterone may be due to its free radical scavenging property as this compound significantly inhibited the generation of hydroxyl radicals in a non-enzymic system.
Singh RB, Niaz MA, Ghosh S. Hypolipidemic and Antioxidant Effects of Commiphora Mukul as an Adjunct to Dietary Therapy in Patients with Hypercholesterolemia. Cardiovascular Drugs and Therapy. 1994; 8:659-664.
Abstract: The effects of the administration of 50 mg of guggulipid or placebo capsules twice daily for 24 weeks were compared as adjuncts to a fruit- and vegetable-enriched prudent diet in the management of 61 patients with hypereholesterolemia (31 in the guggulipid group and 30 in the placebo group) in a randomized, double-blind fashion. Guggulipid decreased the total cholesterol level by 11.7%, the low density lipoprotein cholesterol (LDL) by 12.5%, triglycerides by 12.0%, and the total cholesterol/high density lipoprotein (HDL) cholesterol ratio by 11.1% from the postdiet levels, whereas the levels were unchanged in the placebo group. The NDL cholesterol level showed no changes in the two groups. The lipid peroxides, indicating oxidative stress, declined 33.3% in the guggulipid group without any decrease in the placebo group. The compliance of patients was greater than 96%. The combined effect of diet and guggulipid at 36 weeks was as great as the reported lipid-lowering effect of modern drugs. After a washout period of another 12 weeks, changes in blood lipoproteins were reversed in the guggulipid group without such changes in the placebo group. Side effects of guggulipid were headache, mild nausea, eructation, and hiccup in a few patients.
Sumiyoshi H. [New pharmacological activities of garlic and its constituents]. Nippon Yakurigaku Zasshi 1997 Oct;110 Suppl 1:93P-97P. [Article in Japanese]
Abstract: According to the recent pharmacological findings, garlic is a preventive rather than therapeutic. Epidemiological studies in China, Italy and USA showed the inverse relationship between stomach and colon cancer incidences and dietary garlic intake. Anti-carcinogenic activities of garlic and its constituents including sulfides and S-allyl cysteine, have been demonstrated using several animal models. Garlic preparations has been also shown to lower serum cholesterol and triglyceride levels, which are major risk factors of cardiovascular diseases, through inhibition of their bio-synthesis in the liver, and to inhibit oxidation of low density lipoprotein. Furthermore, in vitro and in vivo studies have revealed that aged garlic extract stimulated immune functions, such as proliferation of lymphocyte, cytokine release, NK activity and phagocytosis. More recently, aged garlic extract has been demonstrated to prolong life span of senescence accelerated mice and prevent brain atrophy. Manufacturing processes significantly affect chemical constituents in garlic preparations. Different forms contain different phytochemicals and may have different effects and toxicities. For example, aged garlic extract inhibited t-BuOOH-induced oxidation, whereas raw garlic stimulated the oxidation. Although garlic has been used as a condiment and folklore for a long time, it has been noted to cause adverse reactions, such as stomach ulcer and anemia. Among the garlic preparations, only aged garlic extract has been proven to be safe through toxicological studies. Thus, aged garlic extract could be the most promising garlic preparation for disease prevention.
Steiner M, Khan AH, Holbert D, Lin RI. A double-blind crossover study in moderately hypercholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids. Am J Clin Nutr 1996 Dec;64(6):866-870.
Abstract: A double-blind crossover study comparing the effect of aged garlic extract with a placebo on blood lipids was performed in a group of 41 moderately hypercholesterolemic men [cholesterol concentrations 5.7-7.5 mmol/L (220-290 mg/dL)]. After a 4-wk baseline period, during which the subjects were advised to adhere to a National Cholesterol Education Program Step I diet, they were started on 7.2 g aged garlic extract per day or an equivalent amount of placebo as a dietary supplement for a period of 6 mo, then switched to the other supplement for an additional 4 mo. Blood lipids, blood counts, thyroid and liver function measures, body weight, and blood pressure were followed over the entire study period. The major findings were a maximal reduction in total serum cholesterol of 6.1% or 7.0% in comparison with the average concentration during the placebo administration or baseline evaluation period, respectively. Low-density-lipoprotein cholesterol was also decreased by aged garlic extract, 4% when compared with average baseline values and 4.6% in comparison with placebo period concentrations. In addition, there was a 5.5% decrease in systolic blood pressure and a modest reduction of diastolic blood pressure in response to aged garlic extract. We conclude that dietary supplementation with aged garlic extract has beneficial effects on the lipid profile and blood pressure of moderately hypercholesterolemic subjects.
Tripathi SN, Upadhyay BN. A clinical trial of Commiphora mukul in the patients of iscaemic heart disease. J Molec Cell Cardiol 1978. 10 (suppl 1): 124.
Verma SK, Bordia A. Effect of Commiphora mukul (gum guggulu) in patients of hyperlipidemia with special reference to HDL-cholesterol. Indian J Med Res 1988 Apr;87:356-360.
Yeh YY, Yeh SM. Garlic reduces plasma lipids by inhibiting hepatic cholesterol and triacylglycerol synthesis. Lipids 1994 Mar;29(3):189-193.
Abstract: Prompted by the reported hypolipidemic activity of garlic, the present study was undertaken to elucidate the mechanism(s) underlying the cholesterol-lowering effects of garlic. Rat hepatocytes in primary culture were used to determine the short-term effects of garlic preparations on [1-14C]acetate and [2-3H]glycerol incorporation into cholesterol, fatty acids and glycerol lipids. When compared with the control group, cells treated with a high concentration of garlic extracts [i.e., petroleum ether- (PEF), methanol- (MEF) and water-extractable (WEF) fractions from fresh garlic] showed decreased rates of [1-14C]acetate incorporation into cholesterol (by 37-64%) and into fatty acids (by 28-64%). Kyolic containing S-allyl cysteine and organosulfur compounds inhibited cholesterogenesis in a concentration dependent manner with a maximum inhibition of 87% at 0.4 mM. At this concentration, Kyolic decreased [1-14C]acetate incorporation into fatty acids by 67%. S-allyl cysteine at 2.0 and 4.0 mM inhibited cholesterogenesis by 20-25%. PEF, MEF and WEF depressed the rates of [2-3H]glycerol incorporation into triacylglycerol, diacylglycerol and phospholipids in the presence of acetate, but not in the presence of oleate. The results suggest that the hypocholesterolemic effect of garlic stems, in part, from decreased hepatic cholesterogenesis, whereas the triacylglycerol-lowering effect appears to be due to inhibition of fatty acid synthesis. Primary hepatocyte cultures as used in the present study have been proven useful as tools for screening the anticholesterogenic properties of garlic principles.