-IBIS-1.7.6-
tx
cardiovascular system
hypercholesterolemia
Nutrition

dietary guidelines

eating principles:
• low sugar
low fat diet of unsaturated fats
(Burr ML, Sweetnam PM. Am J Clin Nutr 1982;36:873-877; Resnicow K, et al. J Am Dietet Assoc 1991;91:447-453; Thorogood M, et al. Br Med J (Clin Res Ed) 1987;295:351-353; Ornish D, et al. Lancet 1990;336:129-133; Connor SL, Connor WE. Prev Med 1983;12:115-123; Edington JD, et al. Am J Clin Nutr 1989;50:58-62.)
• calorie percentages: 70% complex carbohydrates, protein 12-15%, fat 15-18%
• high fiber
• low cholesterol
• low Sodium/ Sodium-restricted diet
• vegetarian cleansing diet or short fasts
• see Materia Medica: Diet for Lowering Cholesterol, Fasting, General Sample Diet, General Guidelines for Eating, Sample Vegetarian Diet

therapeutic foods:
garlic, wheat germ, liquid chlorophyll, alfalfa sprouts, buckwheat, watercress, rice polishings, apple, celery, cherries (Ni, p. 120)
foods high in water-soluble fiber: flax seed, pectin, guar gum, oat bran (Anderson JW, Chen WJL. 1983; Bierenbaum ML, et al. J Am Coll Nutr 1993;12:501-504; Glore SR, et al. J Am Dietet Assoc 1994;94:425-436; Jenkins DJA, et al. Am J Clin Nutr 1999;69:395-402; Miettinen TA, Tarpila S. Clin Chim Acta 1977;79:471-477; Rimm EB, et al. JAMA 1996;275:447-451; Ripsin CM, et al. JAMA 1992;267:3317-3325.)
• onions, beans, legumes, soy, ginger, alfalfa, yogurt (Marz)
increase omega-3 and omega-6 fatty acids: vegetable, nut, seed oils, salmon, herring, mackerel, sardines, walnuts, flaxseed oil, evening primrose oil, black currant oil (Layne KS, et al. J Nutr 1996;126:2130-2140; Mantzioris E, et al. Am J Clin Nutr 1994;59:1304-1309; Harris WS. Am J Clin Nutr 1997;65(5 Suppl):1645S-1654S; Jenkins DJA, et al. Am J Clin Nutr 1999;69:395-402.)
Psyllium seed husks: 5-10 grams of psyllium per day can lower cholesterol levels by 5% and LDL cholesterol by 9%. (Davidson MH, et al. Am J Clin Nutr. 1998; 67(3):367-376; Wolever TM, et al. Am J Med Sci. 1994; 307(4):269-273; Olson BH, et al. J Nutr 1997;127:1973-1980.)
Red wine antioxidants: Ingestion of red wine by human volunteers significantly inhibited LDL oxidation; this effect was not seen after ingestion of grape juice. Research has found that both red wine and grape juice inhibited oxidation of low-density lipoprotein (LDL) in vitro. However, the antioxidant effect of red wine and grape juice appeared to be due to the flavonoids, not to ethanol or nonflavonoid phenolic compounds.
(Miyagi Y, et al. Am J Cardiol 1997;80:1627-1631.)
soy: Soy protein reduces both total and LDL cholesterol.
(Anderson JW, et al. N Engl J Med 1995;3333:276-282; Potter SM. Curr Opin Lipidol. 1996; 7(4):260-264.)

fresh juices:
• carrot and pineapple with honey
• liquid chlorophyll (Jensen, p. 51)
• parsley, alfalfa, and pineapple (Jensen, p. 51)
• carrot, celery, parsley, and spinach (Walker, p. 123)
• carrot and spinach (Walker, p. 123)
• carrot, beet, and celery (Walker, p. 123)
• celery, lettuce, and spinach (Walker, p. 123)
• asparagus and honey (Ni, p. 120)

avoid:
trans-fatty acids, hydrogenated oils (margarine, vegetable shortenings, imitation butter spreads, most commercial peanut butters), oxidized fats (deep fried foods, fast food, ghee, barbequed meats)
(Willett WC, et al. Lancet 1993;341:581-585; Khosla P, Hayes KC. J Am Coll Nutr 1996;15:235-239.)
refined, simple carbohydrates: sucrose, white flour, processed foods
(Yudkin J, et al. Br Med J 1980;281:1396; Liu K, et al. Arteriosclerosis 1982;2:221-227; Reiser S. Nutr Health 1985;3:203-216.)
alcohol, except possibly red wine: Even though two to three drinks per day may raise HDL cholesterol the overall effect on the liver, heart, blood pressure and other aspects of health indicate that alcohol use will increase the risk of heart disease for most people.
(Dai WS, et al. Am J Epidemiol 1985;122:620-627; Doll R, et al. Br Med J 1994;309:911-918; Hein HO, et al. Br Med J 1996;736-741; Hendriks HF, et al. Br Med J 1994;304:1003-1006; Marques-Vidal P, et al. Am J Epidemiol 1996;143:1089-1093; Rimm EB, et al. Br Med J 1996;312:731-736.)

lifestyle:
Reduce stress and maintain regular exercise: Stress reduction and regular exercise contribute to higher levels of HDL cholesterol and reduce the risk of heart disease. Individuals over 40 and those who have not been engaged in vigorous activity on a regular basis should consult with their physician and consider starting with less strenuous activities such as walking.
(N Engl J Med 1988;318:110-112; Jiang W, Babyak M, Krantz DS, et al. JAMA 1996;275:1651-1656; Lundberg U, et al. Psychosomatic Med 1989;51:113-122; McCann BS, et al. Psychosomatic Med 1990;52:97-108; Kawachi I, et al. Circulation 1996;94:2090-2095; Duncan JJ, et al. JAMA 1991;266:3295-3299; Pekkanen J, et al. Lancet 1987;1:1473-1477; Reaven PD, et al. J Am Geriatr Soc 1990;38:847-854; Willich SN, et al. N Engl J Med 1993;329:1684-1690.)

supplements

Vitamin B3: 100 mg of niacin, three times per day, working up to 6 g once daily (Monitor for POSSIBLE LIVER PROBLEMS) (Carlson, 1973; Brown WV. Postgrad Med 1995;98:185-193.); while niacin will lower cholesterol, niacinamide will not; the form recommended as safest and most effective: inositol hexaniacinate, 500 mg three times daily for two weeks, then 1,000 mg three times daily.
(Head KA. Alt Med Rev 1996;1:176-184; Murray M. Am J Natural Med 1995;2:9-12; Murray and Pizzorno, 1998, p. 354; Dorner Von G, et al. Arzneimittelforschung 1961;11:110-113.)
• Vitamin B5, specifically Pantethine significantly lowers serum cholesterol levels and increases HDL, 300 mg 3-4 times daily (Avogaro P, et al. Curr Ther Res 1983;33;488-493; Miccoli R, et al. Curr Ther Res 1984;36:545-549; Murray and Pizzorno, 1998, p. 354; Wittwer CT, et al. Atherosclerosis 1987 Nov;68(1-2):41-49; Binaghi P, et al. Minerva Med 1990 Jun;81(6):475-479. )
Vitamin B6 40 mg: helps lower homocysteine and hence risk of heart disease.
(Ubbink JB, et al. J Nutr 1994 Oct;124(10):1927-1933; Ubbink JB, et al. J Clin Invest 1996 Jul 1;98(1):177-184.)
Vitamin B12: (Ubbink JB, et al. J Nutr 1994 Oct;124(10):1927-1933)
Folate. 5 mg (Ubbink JB, et al. J Nutr 1994 Oct;124(10):1927-1933; Heinecke JW, et al. Biol Chem 1987 Jul 25;262(21):10098-10103.)
Vitamin C, 1-3 g per day: protects lipids in human plasma and low-density lipoprotein against oxidative damage. Some researchers have found that vitamin C can reduce cholesterol levels, specifically LDL levels, when elevated.
(Frei B. Am J Clin Nutr 1991 Dec;54(6 Suppl):1113S-1118S; Simon JA. J Am Coll Nutr 1992 Apr;11(2):107-125; Gatto LM, et al. J Am Coll Nutr 1996 Apr;15(2):154-158.)
Vitamin E, 400 IU per day: Apparently vitamin E can enhance HDL cholesterol, though not all studies have confirmed this effect. Researchers have also found that vitamin E can reduce the occurrence of damaged LDL cholesterol that is widely believed to play a key role in increasing the risk of heart disease. By whatever mechanism, vitamin E supplementation reduces the risk of heart disease with a daily dose of several hundred IU being strongly associated with a lower incidence of heart disease.
(Cloarec MJ, et al. Isr J Med Sci 1987 Aug;23(8):869-872; Kesaniemi YA, Grundy SM. Am J Clin Nutr 1982 Aug;36(2):224-228; Belcher JD, et al. Arterioscler Thromb 1993 Dec;13(12):1779-1189; Rimm EB, et al. N Engl J Med 1993 May 20;328(20):1450-1456; Stampfer MJ, et al. N Engl J Med 1993 May 20;328(20):1444-1449; Stephens NG, et al. Lancet 1996 Mar 23;347(9004):781-786.)
Calcium: Researchers have found that calcium supplementation can reduce cholesterol, apparently by binding fat and reducing its absorption. The doses usually used for this purpose range from 800-1000 mg per day.
(Bell L, et al. Arch Intern Med 1992 Dec;152(12):2441-2444; Denke MA, et al. J Nutr 1993 Jun;123(6):1047-1053; Yacowitz H, et al. BMJ 1965;1:1352-1354)
Chromium, 200 mcg per day (Roeback JR, et al. Ann Intern Med 1991 Dec 15;115(12):917-924; Press RI, et al. West J Med 1990 Jan;152(1):41-45; Riales R, Albrink MJ. Am J Clin Nutr 1981 Dec;34(12):2670-2678.)
Magnesium 500 mg per day (Davis WH, et al. Curr Ther Res 1984;36:341-346; Baxter GF, et al. Lancet 1996 Nov 23;348(9039):1424-1426; Galeone F, et al. Curr Ther Res 1983;34:383-390; Galloe AM, et al. BMJ 1993 Sep 4;307(6904):585-587; Djurhuus MS, et al. Diabetes Care 1999 Apr;22(4):546-554.)
• Selenium
• Molybdenum
• Zinc (Hooper, 1980)
• Copper 2 mg per day (Klevay, 1980)
L-carnitine, 3 g per day: may reduce serum cholesterol and increase HDL cholesterol
(Pola P, et al. Curr Ther Res 1980;27:208-216; Maebashi M, et al. Lancet Oct 14;2(8094):805-807; Davini P, et al. Drugs Exptl Clin Res 1992;18(8):355-365; Rossi CS, Siliprandi N. Johns Hopkins Med J 1982 Feb; 150(2):51-54.)
Artichoke Leaf (high-dose standardized extract): One six-week post-marketing surveillance study (PMS) in patients with non-specific digestive disorders found the extract to be an efficacious and safe phytopharmaceutical with clinically relevant spasmolytic, antiemetic, carminative and lipid-lowering characteristics.
(Fintelmann V. ZFA-Zeitschrift fur Allgemeinmedizen. 1996; 2:3-19.)
• Bromelain
Garlic (Allium sativum): 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 achieved 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.
(Holzgartner J, et al. Arzneim-Forsch Drug Res 1992;42:1473-1477; Silagy C, Neil A. J R Coll Physicians Lond 1994 Jan-Feb;28(1):39-45; Steiner M, et al. 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; Isaacsohn JL, et al. Arch Intern Med 1998;158:1189-1194; Lawson L.Quart Rev Natural Med. Fall 1998;185-186; McCrindle BW, et al. Arch Pediatr Adolesc Med 1998;152:1089-1094; Quart Rev Natural Med. Fall, 1998;187-189; Berthold HK, et al. JAMA 1998;279:1900-1902.)
Lecithin: can increase HDL cholesterol and lower LDL cholesterol.
(Childs MT, et al. Atherosclerosis 1981;38:217-228; Knuiman JT, et al. Am J Clin Nutr 1989;49:266-268;
Wilson TA, et al. Atherosclerosis 1998;140:147-153.)
• Maitake mushrooms: Research found ability to alter lipid metabolism by inhibiting both the accumulation of liver lipids and the elevation of serum lipids. (Nanba H, Kubo K. Alt Therap September 19961(5):62-66.)
Omega-3 fatty acids: EPA 5-10 g per day; most capsules are 300 mg EPA/DHA, but 500 mg are available; this equals 1.5-3.5 gms of EPA/DHA (Childs, 1990; Saynor, 1984.)
• Phosphatidyl ethanolamine (Kneimann, 1989.)
Quercitin protects LDL from damage. A diet high in quercetin, from foods such asapples, onions, and black tea, can help reduce the risk of heart disease. As a supplement, 35 mg per day or more will provide increased protection against heart disease.
(Ronzio RA. Townsend Letter Oct, 1996:34-35; Keli SO, et al. Arch Intern Med 1996 Mar 25;156(6):637-642; Knekt P, et al. BMJ 1996 Feb 24;312(7029):478-481; Hertog MG, et al. Lancet 1993 Oct 23;342(8878):1007-1011; Hertog MG, et al. Arch Intern Med 1995 Feb 27;155(4):381-386.)
• Rice bran oil: 3 g per day.
Royal Jelly: 50-100 mg per day may lowered serum cholesterol, especially when nicotine is a contributing factor.
(Abou-Hozaifa BM, et al. J Biomed Sci Ther 1993;9:35-44; Abou-Hozaifa BM, Badr El-Din NK. Saudi Med J 1995;16:337-342; Cho YT. Am Bee J 1977;117:36-39; Vittek J. Experientia 1995;51:927-935.)

» drug-related therapeutics:
• Calcium should also be supplemented due to decreased absorption of Vitamin D with patient using colestipol or cholestyramine (see below)

» drug interactions:
Colestipol (Colestid) interferes with absorption of iron, folate, and vitamins A, D, K and E.
Cholestyramine (Questran, Cholybar) interferes with absorption of Iron, Folate, and Vitamins A, D, K and E.


footnotes

[No author listed.] A perspective on type A behavior and coronary disease. N Engl J Med 1988;318:110-112. (Review)

[No author listed] Garlic powder for hyperlipidemia - analysis of recent negative results. Quart Rev Natural Med. Fall, 1998;187-189.

[No author listed] Inositol hexaniacinate. Altern Med Rev 1998 Jun;3(3):222-223.

[No author listed.] Regular or decaf? Coffee consumption and serum lipoproteins. Nutr Rev 1992;50:175-178. (Review)

Abou-Hozaifa BM, Badr El-Din NK. Royal jelly, a possible agent to reduce the nicotine-induced atherogenic lipoprotein profile. Saudi Med J 1995;16:337-342.

Abou-Hozaifa BM, Roston AAH, El-Nokaly FA. Effects of royal jelly and honey on serum lipids and lipoprotein cholesterol in rats fed cholesterol-enriched diet. J Biomed Sci Ther 1993;9:35-44.

Albert CM, Manson JE, O’Donnoell C, et al. Fish consumption and the risk of sudden death in the Physicians’ Health Study. Circulation 1996;94 (suppl 1):I-578. (Abstract)

Anderson JW, Chen WJL. Legumes and their soluble fiber: effect on cholesterol-rich lipoproteins. In: Unconventional Sources of Dietary Fiber, ed, I Furda, Washington, DC: American Chemical Society, 1983.

Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. 1995;3333:276-282.

Aneiros E, Calderson B, Más R, et al. Effect of successive dose increases of policosanol on the lipid profile and tolerability of treatment. Curr Ther Res 1993;54:304-312.

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.

Arsenio L, Caronna S, Lateana M, Magnati G, Strata A, Zammarchi G. [Hyperlipidemia, diabetes and atherosclerosis: efficacy of treatment with pantethine]. Acta Biomed Ateneo Parmense 1984;55(1):25-42. [Article in Italian]
Abstract: The hypolipidemizing effects of Pantethine were investigated by the Authors in 37 hypercholesterolemic and/or hypertriglyceridemic patients. Of these, 21 were also diabetic, in a satisfying glucidic compensation, in order to verify the action of this drug also in this metabolic condition. The study was carried out for three months and during this period the patients were given Pantethine at the dose of 600 mg/die orally. At the 30th, the 60th, the 90th day of treatment the
following parameters were controlled: cholesterolemia, HDL cholesterol, apolipoproteins A and B, triglyceridemia, systolic and diastolic arterial pressure, uricemia, body weight. Thirty days after suspending the treatment, the parameters were controlled again to detect a possible "rebound" effect. The results were analyzed on the whole case-record, subdividing the patients in dislipidemic and diabetic-dislipidemic, and on the basis of the Fredrickson's classification. Pantethine induced in all groups a quick and progressive decrease of cholesterolemia, triglyceridemia, LDL cholesterol and Apolipoproteins B with increased HDL cholesterol and Apolipoproteins A. After suspending the treatment, there is a clear inversion of the state of these parameters. The Authors conclude that the present work shows that Pantethine, a natural and atoxic substance, an important component of Coenzyme A, is efficacious in determining a clear tendency towards normalization of the lipidic values.

Ascherio A, Rimm EG, Stampfer MJ, et al. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med 1995;332:977-982.

Avogaro P, Bittolo-Bon G, Pais M, Taroni GC.Effect of a new niacin derivative (nicotinic hexaester of D-glucitol) on type IIA, IIB and IV hyperlipoproteinemia in man. Pharmacol Res Commun 1977 Jun;9(6):599-606.

Avogaro P, Bon B, Fusello M. Effect of pantethine on lipids, lipoproteins and apolipoproteins in man. Curr Ther Res 1983;33;488-493.

Baggio G, Pagnan A, Muraca M, et al. Olive-oil-enriched diet: effect on serum lipoprotein levels and biliary cholesterol saturation. Am J Clin Nutr 1988;47:960-964.

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.

Baxter GF, Sumeray MS, Walker JM. Infarct size and magnesium: insights into LIMIT-2 and ISIS-4 from experimental studies. Lancet 1996 Nov 23;348(9039):1424-1426.

Belcher JD, Balla J, Balla G, Jacobs DR Jr, Gross M, Jacob HS, Vercellotti GM. Vitamin E, LDL, and endothelium. Brief oral vitamin supplementation prevents oxidized LDL-mediated vascular injury in vitro. Arterioscler Thromb 1993 Dec;13(12):1779-1189.
Abstract: In previously reported in vitro studies, we found that heme, a physiologically widespread hydrophobic iron compound, can rapidly generate oxidized low-density lipoprotein (LDL), which then becomes cytotoxic to cultured vascular endothelial cells; both LDL oxidation and endothelial cytotoxicity were inhibited by incubation with exogenous alpha-tocopherol (vitamin E) or ascorbic acid (vitamin C). Seeking relevance to in vivo conditions, we performed a study in which 10 human volunteers were given daily antioxidant supplements of 800 IU of DL-alpha-tocopherol acetate alone or in combination with 1000 mg of ascorbic acid for 2 weeks. LDL resistance to heme oxidation ex vivo, as measured by the lag time for conjugated-diene formation, increased by as much as threefold from a mean +/- SD of 58 +/- 11 to 104 +/- 18 minutes (P < .001); LDL alpha-tocopherol increased from 11 +/- 2 to 26 +/- 6 molecules per LDL particle (P < .001); and most impressively, cytotoxicity to porcine aortic endothelial cells incubated with LDL conditioned with heme plus H2O2 or with copper was completely prevented (cytotoxicity before supplementation was 42 +/- 12%, decreasing after supplementation to 3 +/- 2%, P < .001). These measurements reverted to their presupplement levels within 2 weeks after participants stopped taking antioxidant supplements and were reproduced in 4 subjects taking 800 IU of DL-alpha-tocopherol acetate supplements alone but not in the same subjects taking 1000 mg ascorbic acid supplements alone. In conclusion, oral vitamin E supplementation increases LDL alpha-tocopherol content, increases LDL resistance to oxidation, and decreases the
cytotoxicity of oxidized LDL to cultured vascular endothelial cells.

Bell L, Halstenson CE, Halstenson CJ, Macres M, Keane WF. Cholesterol-lowering effects of calcium carbonate in patients with mild to moderate hypercholesterolemia. Arch Intern Med 1992 Dec;152(12):2441-2444.
Abstract: BACKGROUND--In recent years, several authors have noted that oral calcium treatment was associated with a reduction in serum cholesterol level. METHODS--Calcium carbonate was examined for its ability to lower serum cholesterol levels in hypercholesterolemic patients. Fifty-six patients with mild to moderate hypercholesterolemia were examined in this randomized, double-blind, placebo-controlled crossover study. Patients were treated with a low-fat, low-cholesterol diet targeted at the American Heart Association Step-1 diet for 8 weeks before and while receiving placebo or calcium carbonate (9.98 mmol [400 mg] of elemental calcium) three times daily with meals for 6 weeks. Patients were then crossed over to the alternate treatment for an additional 6-week period. RESULTS--Compared with placebo, calcium carbonate achieved a 4.4% reduction in the low-density lipoprotein cholesterol level, and a 4.1% increase in the high-density lipoprotein cholesterol level. The ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol significantly decreased by 6.5% with calcium carbonate treatment. Calcium carbonate treatment did not significantly affect blood pressure or serum levels of triglycerides,lipoprotein Apo B, or calcium. Relative urinary saturation ratios of calcium oxalate levels were unchanged during calcium carbonate therapy. Compliance with diet and treatment was excellent and no significant adverse effects were noted. CONCLUSIONS--Thus, calcium carbonate was a modestly effective and well-tolerated adjunct to diet in the management of mild to moderate hypercholesterolemia in this clinical study.

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.

Bierenbaum ML, Reichstein R, Watkins TR. Reducing atherogenic risk in hyperlipemic humans with flaxseed supplementation: a preliminary report. J Am Coll Nutr 1993;12:501-504.

Binaghi P, Cellina G, Lo Cicero G, Bruschi F, Porcaro E, Penotti M. [Evaluation of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal age]. Minerva Med 1990 Jun;81(6):475-479. [Article in Italian]
Abstract: Cardiovascular diseases are the main cause of death also in women. Their incidence, rapidly growing in the peri-menopausal period, is related to serum levels of total cholesterol and its LDL fraction. It was also shown that the peroxidation of LDL is an additional factor in the genesis of atherosclerotic vascular disease. As long-term treatments with synthetic lipid-lowering drugs may cause undesirable side effects, while pantethine is known to be well tolerated, we treated 24 hypercholesterolemic women (total serum cholesterol greater than or equal to 240 mg/dl), in perimenopausal age (range: 45-55 years, mean +/- SD = 51.6 +/- 2.4) with 900 mg/day of pantethine. This is a precursor of coenzyme A, with an antiperoxidation effect in vivo, and our aim was to confirm its lipid lowering activity in this particular type of patients. After 16 weeks of treatment, significant reductions of total cholesterol, LDL-cholesterol and LDL-C/HDL-C ratio could be observed. No remarkable changes of the main laboratory parameters (fasting blood sugar, B.U.N., creatinine, uric acid) were seen. Efficacy percentages of the treatment were about 80%. None of the patients complained of adverse reactions due to the treatment with pantethine. In conclusion, we suggest that pantethine should be considered in the long-term treatment of lipid derangements occurring in the perimenopausal age.

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.

Bower B. Women take un-type A behavior to heart. Sci News 1993;144:244.

Brown BG, Zambon A, Poulin D, Rocha A, Maher VM, Davis JW, Albers JJ, Brunzell JD. Use of niacin, statins, and resins in patients with combined hyperlipidemia. Am J Cardiol 1998 Feb 26;81(4A):52B-59B.
Abstract: Patients in the original Familial Atherosclerosis Treatment Study (FATS) cohort were subgrouped into those with triglyceride levels < or = 120 mg/dL (n = 26) and those with triglyceride levels > or = 190 mg/dL (n = 40). Their therapeutic responses to niacin plus colestipol, lovastatin plus colestipol, colestipol alone, or placebo were determined. Therapeutic response was also determined in the same 2 triglyceride subgroups (n = 12 and n = 27, respectively) of patients selected for low levels of high-density lipoprotein (HDL) cholesterol and coronary artery disease. These triglyceride criteria were chosen to identify patient subgroups with high likelihood of "pattern A" (normal-size low-density lipoprotein [LDL] particles and triglyceride < or = 120 mg/dL) or "pattern B" (small dense LDL and triglyceride > or = 190 mg/dL). Our findings in these small patient subgroups are consistent with the emerging understanding that coronary artery disease patients presenting with high triglyceride levels have lower HDL-C, smaller less buoyant LDL-C, and greater very low-density lipoprotein (VLDL) cholesterol and VLDL apolipoprotein B, and are more responsive to therapy as assessed by an increase in HDL-C and reduction in triglycerides, VLDL-C, and VLDL apolipoprotein B. In the FATS high-triglyceride subgroup with these characteristics, a tendency toward greater therapeutic improvement in coronary stenosis severity was observed among those treated with either of the 2 forms of intensive cholesterol-lowering therapy. This improvement is associated with therapeutic reduction of LDL-C and elevation of HDL-C, but also appears to be associated with drug-induced improvement in LDL buoyancy.

Brown WV. Niacin for lipid disorders. Indications, effectiveness, and safety. Postgrad Med 1995 Aug;98(2):185-9, 192-193.
Abstract: Niacin can be very effective and safe in lowering low-density lipoprotein cholesterol and triglyceride levels and also in increasing high-density lipoprotein cholesterol levels. In combination with other lipid-lowering drugs (eg, bile acid sequestrants), it has reduced the incidence of cardiovascular events and stopped the progression of coronary artery lesions. It may be the most cost-effective lipid-lowering agent currently available. At lower doses, sustained-release forms of niacin may also improve patient compliance.

Burr ML, Sweetnam PM. Vegetarianism, dietary fiber and mortality. Am J Clin Nutr 1982;36:873-877.

Carrol KK, Kurowska EM. Soy consumption and cholesterol reduction: Review of animal and human studies. J Nutr 1995;125:594S-597S. (Review)

Castano G, Canetti M, Moreira M, et al. Efficacy and tolerability of policosanol in elderly patients with type II hypercholesterolemia: A 12-month study. Curr Ther Res 1995;56:819-823.

Castano G, Tula L, Canetti M, et al. Effects of policosanol in hypertensive patients with type II hypercholesterolemia. Curr Ther Res 1996;57:691-695.

Childs MT, Bowlin JA, Ogilvie JT, et al. The contrasting effects of a dietary soya lecithin product and corn oil on lipoprotein lipids in normolipidemic and familial hypercholesterolemic subjects. Atherosclerosis 1981;38:217-228.

Cho YT. Studies on royal jelly and abnormal cholesterol and triglycerides. Am Bee J 1977;117:36-39.

Cloarec MJ, Perdriset GM, Lamberdiere FA, Colas-Belcour JF, Sauzieres JP, Neufeld HN, Goldbourt U. Alpha-tocopherol: effect on plasma lipoproteins in hypercholesterolemic patients. Isr J Med Sci 1987 Aug;23(8):869-872.
Abstract: This study was designed to examine the hypothesis that dl-alpha-tocopheryl acetate (vitamin E) increases the level of high-density lipoprotein cholesterol (HDLC) with a concomitant decrease of the ratio of total cholesterol/HDLC and a resultant amelioration of the coronary risk profile. Vitamin E (500 IU/day) or placebo were administered under double-blind randomized allocation to 69 hypercholesterolemic patients for 3 months. Sixty patients completed the study (30 in the active treatment group and 30 in the placebo group). Vitamin E raised the mean level of HDLC from 1.39 +/- 0.38 (SD) to 1.58 +/- 0.41 mmol, a 13.6% increase. This increase significantly (P less than 0.05) exceeded a parallel smaller increase of only 0.05 mmol (3.8%) in the placebo group. As total cholesterol (TC) declined by similar proportions in the vitamin E (7.8%) and placebo (9.4%) groups, a concomitant reduction of 23% in the TC/HDLC ratio was achieved in the vitamin E group, significantly exceeding a 9.1% reduction under placebo. Significant beneficial effects were noted on apolipoprotein (Apo) A (which rose) and Apo B (which declined). An increase of Apo A/Apo B ratio by 17.9% was observed only in the vitamin E group. These results suggest that the oral administration of vitamin E (500 IU/day) is beneficial in hyperlipoproteinemia and offers a potential tool for treating the increased coronary heart disease risk.

Connor SL, Connor WE. The importance of dietary cholesterol in coronary heart disease. Prev Med 1983;12:115-23. (Review)

Dai WS, Laporte RE, Hom DL, et al. Alcohol consumption and high density lipoprotein cholesterol concentration among alcoholics. Am J Epidemiol 1985;122:620-627.

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.

Davidson MH, Maki KC, Kong JC, Dugan LD, Torri SA, Hall HA, Drennan KB, Anderson SM, Fulgoni VL, Saldanha LG, Olson BH. Long-Term Effects of Consuming Foods Containing Psyllium Seed Husk on Serum Lipids in Subjects with Hypercholesterolemia. Am J Clin Nutr. 1998; 67(3):367-376.
Abstract: The effects of consuming foods containing 0 (control), 3.4, 6.8, or 10.2 g psyllium seed husk (PSH)/d for 24 wk on the serum lipid profile were assessed in this randomized, double-blind controlled study. Men and women (n = 286) with LDL-cholesterol concentrations between 3.36 and 5.68 mmol/L (130 and 220 mg/dL) were randomly assigned to one of four treatment groups after following a low-fat diet for > or = 8 wk. At week 24, LDL cholesterol was 3% above baseline in the control group. In the group consuming 10.2 g PSH/d, LDL cholesterol remained below baseline during treatment, with a value 5.3% below that of the control group at week 24 (P < 0.05 compared with the control group). No significant differences were observed in HDL cholesterol or triacylglycerol. Although modest, the effect of 10.2 g PSH/d on LDL cholesterol (relative to the control) persisted throughout the 24-wk treatment period, indicating potential for long-term benefit.

Davini P, Bigalli A, Lamanna F, Boem A. Controlled study on L-carnitine therapeutic efficacy in post-infarction. Drugs Exptl Clin Res 1992;18(8):355-365.
Abstract: A controlled study was carried out on 160 patients of both sexes (age between 39 and 86 years) discharged from the Cardiology Department of the Santa Chiara Hospital, Pisa, with a diagnosis of recent myocardial infarction. L-carnitine was randomly administered to 81 patients at an oral dose of g 4/die for 12 months, in addition to the pharmacological treatment generally used. For the whole period of 12 months, these patients showed, in comparison with the controls, an improvement in heart rate (p < 0.005), systolic arterial pressure (p < 0.005) and diastolic arterial pressure (NS); a decrease of anginal attacks (p < 0.005), of rhythm disorders (NS) and of clinical signs of impaired myocardial contractility (NS), and a clear improvement in the lipid pattern (p < 0.005). The above changes were accompanied by a lower mortality in the treated group (1.2%, p < 0.005), while in the control group there was a mortality of 12.5%. Furthermore, in the control group there was a definite prevalence of deaths caused by reinfarction and sudden death. On the basis of these results, it is concluded that L-carnitine represents an effective treatment in post-infarction ischaemic cardiopathy, since it can improve the clinical evolution of this pathological condition as well as the patient's quality of life and life expectancy.

Davis WH, Leary WP, Reyes AJ, Olhaberry JV. Monotherapy with magnesium increases abnormally low high density lipoprotein cholesterol: a clinical assay. Curr Ther Res 1984;36:341-346.

de Roos NM, Schouten G, Katan MB. Yoghurt enriched with Lactobacillus acidophilus does not lower blood lipids in healthy men and women with normal to borderline high serum cholesterol levels. Eur J Clin Nutr 1999;53:277-280.

Denke MA, Fox MM, Schulte MC. Short-term dietary calcium fortification increases fecal saturated fat content and reduces serum lipids in men. J Nutr 1993 Jun;123(6):1047-1053.
Abstract: The effect of dietary calcium on fecal fatty acid excretion and serum lipids was tested in a randomized, single-blind metabolic study in 13 healthy men with moderate hypercholesterolemia. A low calcium base diet containing 34% of energy from fat, 13% from saturated fatty acids, 240 mg cholesterol/d and 410 mg Ca/d was compared with a fortified version in which calcium citrate malate was added to orange juice, (550 mg) muffins (750 mg), and two tablets (500 mg) for a total calcium intake of 2200 mg/d. Fecal collections (72 h, d 8, 9, 10) and blood from fasting subjects for lipids and lipoproteins (d 9, 10, 11) were obtained. The percentage of dietary saturated fat excreted per day increased from 6 to 13% with calcium fortification. There was no change in fecal bile acid excretion. The high Ca diet significantly reduced total cholesterol 6% (5.99 to 5.66 mmol/L), LDL cholesterol 11% (4.13 to 3.67 mmol/L), and apolipoprotein B concentrations 7% when compared with the low Ca diet (P < 0.05). There was no change in HDL cholesterol or apolipoprotein A1 concentrations. Urinary calcium excretion increased from 146 to 230 mg/d when the high Ca diet was consumed. Calcium fortification was effective in lowering total and LDL cholesterol concentrations and may be an effective adjunct to cholesterol-lowering diet therapy.

Denke MA, Grundy SM. Comparison of effects of lauric acid and palmitic acid on plasma lipids and lipoproteins. Am J Clin Nutr 1992;56:895-898.

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.

Djurhuus MS, Henriksen JE, Klitgaard NA, Blaabjerg O, Thye-Ronn P, Altura BM, Altura BT, Beck-Nielsen H. Effect of moderate improvement in metabolic control on magnesium and lipid concentrations in patients with type 1 diabetes. Diabetes Care 1999 Apr;22(4):546-54.
Abstract: OBJECTIVE: To evaluate the effect of clinically obtainable improvements in metabolic control in patients with type 1 diabetes on biochemical cardiovascular risk factors. RESEARCH DESIGN AND METHODS: Blood and 24-h urinary samples were obtained from 49 patients with type 1 diabetes before and after a run-in period and after 3 months of intervention, with frequent adjustment of insulin dosage according to measured blood glucose concentrations. RESULTS: The intervention caused a mean insulin dosage increment of 10%, a 20% decrease in fasting plasma glucose concentration, a 10% decrease in albumin corrected serum fructosamine, and a somewhat lesser decrease in HbAlc.A 14% decrease in the renal excretion of magnesium (Mg) was observed, but without a change in average serum Mg concentration. Serum HDL cholesterol increased 4%, and serum triglycerides decreased 10% as an average. Looking at individual patients, the decrease in serum triglycerides correlated with both the change in serum total Mg concentration and with the increase in insulin dosage. Using the change in serum total Mg concentration and in insulin dosage as independent variables in a multiple regression analysis, the coefficient of correlation with the decrease in serum triglycerides was 0.52. CONCLUSIONS: Moderate but clinically obtainable improvement of metabolic control in patients with type 1 diabetes seems to reduce the loss of Mg, increase serum HDL cholesterol, and decrease serum triglycerides. The decrease in serum triglycerides was associated with the change in serum total Mg concentration. These reductions in Mg loss and serum triglycerides might reduce the risk of developing cardiovascular disease in patients with type 1 diabetes.

Doll R, Peto AR, Hall E, et al. Mortality in relation to consumption of alcohol: 13 years’ observations on male British doctors. Br Med J 1994;309:911-18.

Dorner Von G, Fisher FW, Zur Beinflussung der Serumlipide und -lipoproteine durch den Hexanicotinsaureester des m- Inositol. Arzneimittelforschung 1961;11:110-113.

Dreon DM, Fernstrom HA, Williams PT, Krauss RM. A very-low-fat diet is not associated with improved lipoprotein profiles in men with a predominance of large, low-density lipoproteins. Am J Clin Nutr 1999;69:411-418.

Duncan JJ, Gordon NF, Scott CB. Women walking for health and fitness - how much is enough? JAMA 1991;266:3295-3299.

Dwyer JH, Rieger-Ndakorerwa GE, Semmer NK, et al. Low-level cigarette smoking and longitudinal change in serum cholesterol among adolescents. JAMA 1988;2857-2862.

Edelstein SL, Barrett-Connor EL, Wingard DL, Cohn BA. Increased meal frequency associated with decreased cholesterol concentrations; Rancho Bernardo, CA, 1984-1987. Am J Clin Nutr 1992;55:664-669.

Edington JD, Geekie M, Carter R, et al. Serum lipid response to dietary cholesterol in subjects fed a low-fat, high-fiber diet. Am J Clin Nutr 1989;50:58-62.

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 Effects of Artichoke Leaf Extract - Results of Clinical Studies into the Efficacy and Tolerance of Hepar-SL® forte Involving 553 Patients. ZFA-Zeitschrift fur Allgemeinmedizen. 1996; 2:3-19.
Abstract: Artichoke leaf extracts (AK) have choleretic, lipid-lowering and hepatoprotective effects. Within the framework of an indicated ambulatory routine therapy, the efficacy and tolerance of high-dose standardized Hepar-SL® forte as AE was investigated in a six-week post-marketing surveillance study (PMS) in patients with non-specific digestive disorders (n=553), by symptom evaluation both through the physician and the patient. This was a prospective, structured, prescription-epidemiological multicenter study with exploratory character as part of the phase IV research program. It was evaluated by descriptive-statistical means. The PMS study involved 52 ambulatory centers. The average patient age was 54.7 years old. The age group distribution was as follows: < 30 years, 3.8%, 30-39 years, 14.7%, 40-49 years, 20.4%, 50-59 years, 17.6%, 60 years and older, 43.5%. 42% were men and 58% were women. The average duration of application was 43.5 days. The most prominent diagnoses were dyspeptic discomforts, functional bile duct discomforts and obstipation. The major clinical picture was that of chronic disorders; the symptoms had been present on average for 155 weeks prior to inclusion in the study. The average total daily dose was 4.75 capsules Hepar-SL® forte (1 capsule contains 320 mg of high-dose, standardized, aqueous dry extract of artichoke leaves [Extr. Cynarae scol. e fol. aquos. sicc.] (3.8-5.5:1). The preparation was typically administered three times daily (1 to 2 capsules). A distorting influence of concomitant medication and diseases was not found. Relative to their severity on inclusion in the PMS study, the observed symptoms regressed after six weeks of treatment on average by 70.5%; the most pronounced regression was found for vomiting (88.3%), nausea (82.4%), abdominal pain (76.2%), loss of appetite (72.3%), obstipation (71.0%), flatulence (68.2%), meteorism (66.0%) and fat intolerance (58.8%). In 85% of patients the global therapeutic efficacy of Hepar-SL® forte was judged by the physicians as excellent or good, in 12% as moderate and in 3% as insufficient or minimal. In spite of the relatively short duration of therapy, sample averaging showed an 11.5% reduction in serum cholesterol from initially 264.24 mg/dl to 233.91 mg/dl (n=302; p<O.OO1). Serum trigylcerides were similarly reduced from initially 214.97 mg/dl to 188.07 mg/dl, corresponding to a decrease of 12.5%. This lowering of lipid levels is in agreement with the results of other relevant clinical studies and the recently established inhibitory effect of the artichoke leaf extract used in this study on cholesterol biosynthesis. During the surveillance study mild adverse events [flatulence (n=5), weakness (n=1), hunger feelings (n=1)] were noticed in seven cases, corresponding to a total adverse effect rate of 1.3%. The PMS study confirms the well-known excellent tolerance of Hepar-SL® forte and the high therapeutic safety of AE preparations documented in the professional literature. The results of this PMS study show the extract to be an efficacious and safe phytopharmaceutical with clinically relevant spasmolytic, antiemetic, carminative and lipid-lowering characteristics which should have a good chance to be of significance in the prevention of arteriosclerosis.

Frei B. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage. Am J Clin Nutr 1991 Dec;54(6 Suppl):1113S-1118S.
Abstract: We exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.

Friedman M, Theresen CE, Gill JJ, et al. Alteration of type A behavior and reduction in cardiac recurrences in postmyocardial infarction patients. Am Heart J 1984;108:237-248.

Galeone F, Scalabrino A, Giuntoli F, et al. The lipid-lowering effect of pantethine in hyperlipidemic patients: a clinical investigation. Curr Ther Res 1983;34:383-90.

Galloe AM, Rasmussen HS, Jorgensen LN, Aurup P, Balslov S, Cintin C, Graudal N, McNair P. Influence of oral magnesium supplementation on cardiac events among survivors of an acute myocardial infarction. BMJ 1993 Sep 4;307(6904):585-587.
Abstract: OBJECTIVE--To investigate the effect of long term oral magnesium treatment on incidence of cardiac events among survivors of an acute myocardial infarction. DESIGN--Double blind, placebo controlled parallel study in which patients were randomised to treatment or placebo. SETTING--Two coronary care units and corresponding outpatient clinics. SUBJECTS--468 survivors of an acute myocardial infarction (289 men and 178 women) aged 31-92. INTERVENTIONS--One tablet of 15 mmol magnesium hydroxide or placebo daily for one year. MAIN OUTCOME MEASURES--Incidences of reinfarction, sudden death, and coronary artery bypass grafting in one year. RESULTS--There was no significant difference between treatment and placebo groups in the incidence of each of the three cardiac events, but when the events were combined and drop outs were excluded from calculations there was a significantly higher incidence of events in the treatment group (56/167 v 33/153; relative risk 1.55 (95% confidence interval 1.07 to 2.25); p = 0.02). When the timing of events was incorporated by means of a Kaplan-Meier plot the treatment group showed a significantly higher incidence of events whether drop outs were included or excluded (p < 0.025). CONCLUSION--Long term oral treatment with 15 mmol magnesium daily doses not reduce the incidence of cardiac events in survivors of an acute myocardial infarction and, indeed, seems to increase the risk of developing a cardiac event. Consequently, this treatment cannot be recommended as secondary prophylaxis for such patients.

Galloe AM, Graudal NA. [Magnesium treatment of patients with acute myocardial infarction. A meta-analysis]. Ugeskr Laeger 1995 Jan 23;157(4):437-440. [Article in Danish]
Abstract: The object of the study was to investigate the effect of intravenous magnesium in acute myocardial infarction. It was carried out as an overview of available randomized trials in which patients were allocated to receive either magnesium or placebo, the trials having taken place in the coronary care units of several hospitals. The subjects were 2438 patients with acute myocardial infarction in nine blind randomized trials combined in a meta-analysis and 54,822 patients in one unblinded randomized multi-centre trial. The main outcome measure was the relative chance of survival and relative chance of avoiding ventricular tachyarrhythmia. In the meta-analysis, the relative chance of survival was significantly increased in the magnesium group (RR = 1.049, 95% CI = 1.020-1.078, p < 0.0007). Hypothetically 25 papers with a mean of 271 patients and an RR of 1.0 should be included to make the result insignificant. The relative chance of avoiding ventricular tachyarrhythmia was not significantly increased in the magnesium group (RR = 1.041, 95% CI = 0.996-1.089, p = 0.07). The risk of accepting the null hypothesis (RR = 1.0) if the alternative hypothesis (RR = 1.041) is correct is 0,58 (the type 2 error). There was no effect on survival in the multi-centre study (RR = 0.996). It is concluded that intravenous treatment with magnesium increases survival in patients with acute myocardial infarction by 4.9% in nine blind trials, but has no effect in a large open multi-centre study.

Gatto LM, Hallen GK, Brown AJ, Samman S. Ascorbic acid induces a favorable lipoprotein profile in women. J Am Coll Nutr 1996 Apr;15(2):154-158.
Abstract: OBJECTIVES: The aim of this study was to determine the effect of ascorbic acid (AA) supplements on plasma lipids and lipoproteins in healthy, young women. METHODS: Ten women were recruited to participate in a randomized double-blind cross-over trial and supplemented with 1000 mg AA daily for 4 weeks, followed by placebo, and vice versa. RESULTS: Plasma AA concentrations were significantly higher at 2 weeks (p < 0.0001) and at 4 weeks (p < 0.001), compared with baseline. Plasma AA levels appeared to peak after 2 weeks of supplementation. Plasma concentrations of LDL-C were found to be 16% lower at 4 weeks compared with baseline (p < 0.05) and although HDL-C levels did not change significantly with AA supplementation, the change in HDL-C was positively associated with the change in plasma AA (p < 0.05). Significant decreases were observed in the total cholesterol (TC) to HDL-C at 2 weeks and LDL-C to HDL-C ratios at 2 and 4 weeks supplementation (p < 0.05). CONCLUSIONS: Our findings agree with those from epidemiological studies and suggest that increases in AA intake may favorably alter the lipoprotein profile in young women.

Glore SR, Van Treeck D, Knehans AW, Guild M. Soluble fiber and serum lipids: a literature review. J Am Dietet Assoc 1994;94:425-436.

Glueck CJ, Taylor HL, Jacobs D, et al. Plasma high-density lipoprotein cholesterol: association with measurements of body mass: the Lipid Research Clinics Program Prevalence Study. Circulation 1980;62 (Suppl IV):IV-62-69.

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.

Grundy SM, Ahrens EH Jr, Davignon J. The interaction of cholesterol absorption and cholesterol synthesis in man. J Lipid Res 1969;10:304-315. (Review)

Grundy SM. Monounsaturated fatty acids and cholesterol metabolism: implications for dietary recommendations. J Nutr 1989;119:529-533. (Review)

Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997;65(5 Suppl):1645S-1654S. (Review)

Head KA. Inositol hexaniacinate: A safer alternative to niacin. Alt Med Rev 1996;1:176-184. (Review)
Abstract: Niacin has long been prescribed for the treatment of various cardiovascular conditions, particularly the hyperlipidemias. It has been proven effective at lowering VLDL, LDL, total cholesterol and triglyceride levels while raising HDL levels. The side effects of niacin which may occur at the dosages often required for therapeutic efficacy, ranging from flushing and pruritus to hepatoxicity and impaired glucose tolerance, often prove troubling for both patient and practitioner. The need for a safer approach to niacin supplementation has resulted in the investigation of niacin esters. One of the most widely studied of these is inositol hexaniacinate (IHN). In numerous trials it has been found to be virtually free of the side effects associated with conventional niacin therapy. Extensive research has found IHN to be effective in the treatment of hyperlipidemia, Raynaud's disease and intermittent claudication. A number of other conditions which respond favorably to niacin therapy such as hypertension, diabetes, dysmennorhea and alcoholism bear further investigation.

Heckers H, Dittmar K, Schmahl FW, Huth K. Inefficiency of cynarin as therapeutic regimen in familial type II hyperlipoproteinemia. Atherosclerosis 1977; 26:249-253.

Hein HO, Suadicani P, Gyntelberg F. Alcohol consumption, serum low density lipoprotein cholesterol concentration, and risk of ischaemic heart disease: six year follow up in the Copenhagen male study. Br Med J 1996;736-741.

Heinecke JW, Rosen H, Suzuki LA, Chait A. The role of sulfur-containing amino acids in superoxide production and modification of low density lipoprotein by arterial smooth muscle cells. Biol Chem 1987 Jul 25;262(21):10098-10103.
Abstract: Extracellular superoxide (O2-.) was detected in cultures of monkey arterial smooth muscle cells as measured by the superoxide dismutase-inhibitable reduction of cytochrome c and acetylated cytochrome c. Reduction of cytochrome c by these cells required L-cystine in the incubation medium. A variety of other sulfur-containing amino acids, including D-cystine, L-cystathionine, L-methionine, and djenkolic acid did not support O2-. generation when present at concentrations equimolar to L-cystine. At millimolar concentrations, the chelators EDTA and diethylene triamine penta-acetic acid inhibited O2-. production by smooth muscle cells. This effect was maximal when the chelator was present at the same concentration as the sum of the Ca2+ and Mg2+ in the medium, suggesting a role for these cations in O2-. generation by cells. Modification of low density lipoprotein (LDL) by arterial smooth muscle cells, as assessed by changes in lipid peroxide content, mobility on agarose gel electrophoresis, and apoprotein B fragmentation, was also L-cystine-dependent. LDL modification also required micromolar concentrations of the transition metal ion Cu(II) or Fe(III) and was inhibited by superoxide dismutase. LDL modified by smooth muscle cells in the presence of L-cystine and Cu(II) was taken up and degraded less well than native LDL by human skin fibroblasts, suggesting that recognition by the LDL receptor was lost. In contrast, LDL modified by smooth muscle cells was taken up and degraded to a greater degree than native LDL by mouse peritoneal macrophages, consistent with recognition by the scavenger receptor. These results indicate that monkey arterial smooth muscle cells produce O2-. and modify LDL by an L-cystine-dependent process. This may involve reduction of cystine to a thiol, possibly cysteine or a cysteine-containing peptide such as glutathione. Sulfur-containing amino acids may play a role in atherogenesis by supporting cell-mediated generation of reactive oxygen species and modification of lipoprotein to a form recognized by the scavenger receptor.

Hendriks HF, Veenstra J, Wierik EJMV, Schaafsma G, Kluft C. Effect of moderate dose of alcohol with evening meal on fibrinolytic factors. Br Med J 1994;304:1003-1006.

Hendriks HFJ, Westrate JA, van Vliet T, Meijer GW. Spreads enriched with three different levels of vegetable oil sterols and the degree of cholesterol lowering in normocholesterolaemic and mildly hypercholesterolaemic subjects. Eur J Clin Nutr 1999;53:319-327.

Hepner G, Fried R, St Jeor S, et al. Hypocholesterolemic effect of yogurt and milk. Am J Clin Nutr 1979;19-24.

Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 1993 Oct 23;342(8878):1007-1011.
Abstract: Flavonoids are polyphenolic antioxidants naturally present in vegetables, fruits, and beverages such as tea and wine. In vitro, flavonoids inhibit oxidation of low-density lipoprotein and reduce thrombotic tendency, but their effects on atherosclerotic complications in human beings are unknown. We measured the content in various foods of the flavonoids quercetin, kaempferol, myricetin, apigenin, and luteolin. We then assessed the flavonoid intake of 805 men aged 65-84 years in 1985 by a cross-check dietary history; the men were then followed up for 5 years. Mean baseline flavonoid intake was 25.9 mg daily. The major sources of intake were tea (61%), onions (13%), and apples (10%). Between 1985 and 1990, 43 men died of coronary heart disease. Fatal or non-fatal myocardial infarction occurred in 38 of 693 men with no history of myocardial infarction at baseline. Flavonoid intake (analysed in tertiles) was significantly inversely associated with mortality from coronary heart disease (p for trend = 0.015) and showed an inverse relation with incidence of myocardial infarction, which was of borderline significance (p for trend = 0.08). The relative risk of coronary heart disease mortality in the highest versus the lowest tertile of flavonoid intake was 0.42 (95% CI 0.20-0.88). After adjustment for age, body-mass index, smoking, serum total and high-density-lipoprotein cholesterol, blood pressure, physical activity, coffee consumption, and intake of energy, vitamin C, vitamin E, beta-carotene, and dietary fibre, the risk was still significant (0.32 [0.15-0.71]). Intakes of tea, onions, and apples were also inversely related to coronary heart disease mortality, but these associations were weaker. Flavonoids in regularly consumed foods may reduce the risk of death from coronary heart disease in elderly men.

Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 1995 Feb 27;155(4):381-386.
Abstract: OBJECTIVE: To determine whether flavonoid intake explains differences in mortality rates from chronic diseases between populations. DESIGN: Cross-cultural correlation study. SETTING/PARTICIPANTS: Sixteen cohorts of the Seven Countries Study in whom flavonoid intake at baseline around 1960 was estimated by flavonoid analysis of equivalent food composites that represented the average diet in the cohorts. MAIN OUTCOME MEASURES: Mortality from coronary heart disease, cancer (various sites), and all causes in the 16 cohorts after 25 years of follow-up. RESULTS: Average intake of antioxidant flavonoids was inversely associated with mortality from coronary heart disease and explained about 25% of the variance in coronary heart disease rates in the 16 cohorts. In multivariate analysis, intake of saturated fat (73%; P = 0.0001), flavonoid intake (8%, P = .01), and percentage of smokers per cohort (9%; P = .03) explained together, independent of intake of alcohol and antioxidant vitamins, 90% of the variance in coronary heart disease rates. Flavonoid intake was not independently associated with mortality from other causes. CONCLUSIONS: Average flavonoid intake may partly contribute to differences in coronary heart disease mortality across populations, but it does not seem to be an important determinant of cancer mortality.

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.

Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983;67:968-977.

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.

Izuka K, Murata K, Nakazawa K, et al. Effects of chondroitin sulfates on serum lipids and hexosamines in atherosclerotic patients: With special reference to thrombus formation time. Jpn Heart J 1968;9:453-460.

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.

Jenkins DJA, Kendall CWC, Vidgen E, et al. Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. Am J Clin Nutr 1999;69:395-402.

Jenkins DJA, Khan A, Kenkins AL, et al. Effect of nibbling versus gorging on cardiovascular risk factors: serum uric acid and blood lipids. Metabolism 1995;44:549-555.

Jiang W, Babyak M, Krantz DS, et al. Mental stress-induced myocardial ischemia and cardiac events. JAMA 1996;275:1651-1656.

Kawachi I, Sparrow D, Spiro II A, et al. A prospective study of anger and coronary heart disease. Circulation 1996;94:2090-2095.

Keli SO, Hertog MG, Feskens EJ, Kromhout D. Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study. Arch Intern Med 1996 Mar 25;156(6):637-642.
Abstract: BACKGROUND: Epidemiological studies suggested that consumption of fruit and vegetables may protect against stroke. The hypothesis that dietary antioxidant vitamins and flavonoids account for this observation is investigated in a prospective study. METHODS: A cohort of 552 men aged 50 to 69 years was examined in 1970 and followed up for 15 years. Mean nutrient and food intake was calculated from cross-check dietary histories taken in 1960, 1965, and 1970. The association between antioxidants, selected foods, and stroke incidence was assessed by Cox proportional hazards regression analysis. Adjustment was made for confounding by age, systolic blood pressure, serum cholesterol, cigarette smoking, energy intake, and consumption of fish and alcohol. RESULTS: Forty-two cases of first fatal or nonfatal stroke were documented. Dietary flavonoids (mainly quercetin) were inversely associated with stroke incidence after adjustment for potential confounders, including antioxidant vitamins. The relative risk (RR) of the highest vs the lowest quartile of flavonoid intake ( > or = 28.6 mg/d vs <18.3 mg/d) was 0.27 (95% confidence interval [CI], 0.11 to 0.70). A lower stroke risk was also observed for the highest quartile of beta-carotene intake (RR, 0.54; 95% CI, 0.22 to 1.33). The intake of vitamin C and vitamin E was not associated with stroke risk. Black tea contributed about 70% to flavonoid intake. The RR for a daily consumption of 4.7 cups or more of tea vs less than 2.6 cups of tea was 0.31 (95% CI, 0.12 to 0.84). CONCLUSION: The habitual intake of flavonoids and their major source (tea) may protect against stroke.

Kesaniemi YA, Grundy SM. Lack of effect of tocopherol on plasma lipids and lipoproteins in man. Am J Clin Nutr 1982 Aug;36(2):224-228.
Abstract: The influence of D,L-alpha-tocopherol (vitamin E) on the plasma total and very low-density lipoprotein, low density lipoprotein, and high-density lipoprotein cholesterol and triglyceride was studied in one normolipidemic and four hypertriglyceridemic subjects. Overall vitamin E caused no decrease in plasma total, very low-density and low-density lipoprotein cholesterol and triglyceride concentrations and no increase in high-density lipoprotein cholesterol level. D,L-alpha-Tocopherol does not seem to have any consistent effect on plasma lipids and lipoproteins in these patients.

Keys A, ed. Coronary heart disease in seven countries. Circulation 1970;41(suppl q):I1-211.

Khosla P, Hayes KC. Dietary trans-monounsaturated fatty acids negatively impact plasma lipids in humans: critical review of the evidence. J Am Coll Nutr 1996;15:235-239.

Khosla S, Laddu A, Ehrenpreis S, Somberg JC. Cardiovascular effects of nicotine: relation to deleterious effects of cigarette smoking. Am Heart J 1994;127:1669-1671. (Review)

Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ 1996 Feb 24;312(7029):478-481.
Abstract: OBJECTIVE: To study the association between dietary intake of flavonoids and subsequent coronary mortality. DESIGN: A cohort study based on data collected at the Finnish mobile clinic health examination survey from 1967-72 and followed up until 1992. SETTINGS: 30 communities from different parts of Finland. SUBJECTS: 5133 Finnish men and women aged 30-69 years and free from heart disease at baseline. MAIN OUTCOME MEASURE: Dietary intake of flavonoids, total mortality, and coronary mortality. RESULTS: In women a significant inverse gradient was observed between dietary intake of flavonoids and total and coronary mortality. The relative risks between highest and lowest quarters of flavonoid intake adjusted for age, smoking, serum cholesterol concentration, blood pressure, and body mass index were 0.69 (95% confidence interval 0.53 to 0.90) and 0.54 (0.33 to 0.87) for total and coronary mortality, respectively. The corresponding values for men were 0.76 (0.63 to 0.93) and 0.78 (0.56 to 1.08), respectively. Adjustment for intake of antioxidant vitamins and fatty acids weakened the associations for women; the relative risks for coronary heart disease were 0.73 (0.41 to 1.32) and 0.67 (0.44 to 1.00) in women and men, respectively. Intakes of onions and apples, the main dietary sources of flavonoids, presented similar associations. The relative risks for coronary mortality between highest and lowest quarters of apple intake were 0.57 (0.36 to 0.91) and 0.81 (0.61 to 1.09) for women and men, respectively. The corresponding values for onions were 0.50 (0.30 to 0.82) and 0.74 (0.53 to 1.02), respectively. CONCLUSIONS: The results suggest that people with very low intakes of flavonoids have higher risks of coronary disease.

Knuiman JT, Beynen AC, Katan MB. Lecithin intake and serum cholesterol. Am J Clin Nutr 1989;49:266-268.

Kromhout D, Bosschieter EB, Coulander CdL, The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985;312:1205-1209.

Kromhout D, Menotti A, Bloemberg B, et al. Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: the Seven Countries Study. Prev Med 1995;24:308-315.

Kumar PD. The role of coconut and coconut oil in coronary heart disease in Kerala, south India. Trop Doct 1997;27:215-217.

Lawson LD, Ransom DK, Hughes BG. Inhibition of whole blood platelet-aggregation by compounds in garlic clove extracts and commercial garlic products. Thrombosis Res. 1992;65:141-156.

Lawson LD. Garlic oil for hypercholesterolemia - negative results. Quart Rev Natural Med. Fall 1998;185-186.

Lawson LD. Garlic powder for hyperlipidemia-analysis of recent negative results. Quart Rev Natural Med. Fall, 1998;187-189.

Layne KS, Goh YK, Jumpsen JA, et al. Normal subjects consuming physiological levels of 18:3(n-3) and 20:5(n-3) from flaxseed or fish oils have characteristic differences in plasma lipid and lipoprotein fatty acid levels. J Nutr 1996;126:2130-2140.

Lees AM, Mok HYI, Lee RS, et al. Plant sterols as cholesterol-lowering agents: Clinical trials in patients with hypercholesterolemia and studies of sterol balance. Atheroscler 1977;28:325-338.

Levy Y, Maor I, Presser D, Aviram M. Consumption of eggs with meals increases the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation. Ann Nutr Metabol 1996;40:243-251.

Liu K, Stamler J, Trevisan M, Moss D. Dietary lipids, sugar, fiber, and mortality from coronary heart disease. Bivariate analysis of international data. Arteriosclerosis 1982;2:221-227.

Liusov VA, Zimin IU. Experimental rational and trial of therapeutic use of bee raising product in cardiovascular diseases. Kardiologia 1983;23:105-109. [Article in Russian].

Lundberg U, Hedman M, Melin B, Frankenhaeuser M. Type A Behavior in healthy males and females as related to physiological reactivity and blood lipids. Psychosomatic Med 1989;51:113-122.

Maebashi M, Kawamura N, Sato M, Imamura A, Yoshinaga K. Lipid-lowering effect of carnitine in patients with type-IV hyperlipoproteinaemia. Lancet Oct 14;2(8094):805-807.
Abstract: Serum-lipid concentrations were determined in patients with type-IV hyperlipoproteinaemia treated with 900 mg/day oral DL-carnitine chloride. Serum-triglyceride was significantly reduced and concentrations continued to decline as carnitine administration continued. Total and esterified cholesterol concentrations did not change. Intravenous infusion of carnitine produced the same effects. The results suggest that carnitine is of value in the therapy of type-IV hyperliproteinaemia. Increased oxidation of free fatty acids in the tissues seems to account for the effects of carnitine on serum-lipid concentrations.

Maezaki Y, Tsuji K, Nakagawa Y, et al. Hypocholesterolemic effect of chitosan in adult males. Biosci Biotech Biochem 1993;57:1439-1444.

Mansell P, Reckless JPD. Garlic - effects on serum lipids, blood pressure, coagulation, platelet aggregation, and vasodilatation. Br Med J 1991;303:379-380. (Editorial)

Mantzioris E, James MJ, Bibson RA, Cleland LG. Dietary substitution with an alpha-linolenic acid-rich vegetable oil increases eicosapentaenoic acid concentrations in tissues. Am J Clin Nutr 1994;59:1304-1309.

Marques-Vidal P, Ducimetiere P, Evans A, et al. Alcohol consumption and myocardial infarction: a case-control study in France and northern Ireland. Am J Epidemiol 1996;143:1089-1093.

McCann BS, Warnick R, Knopp RH. Changes in plasma lipids and dietary intake accompanying shifts in perceived workload and stress. Psychosomatic Med 1990;52:97-108.

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.

Mendis S, Kumarasunderam R. The effect of daily consumption of coconut fat and soya-bean fat on plasma lipids and lipoproteins of young normolipidaemic men. Br J Nutr 1990;63:547-552.

Menendez R, Arruzazabala L, Mas R, et al. Cholesterol-lowering effect of policosanol on rabbits with hypercholesterolaemia induced by a wheat starch-casein diet. Br J Nutr 1997;77:923-932.

Miccoli R, Marchetti P, Sampietro T, et al. Effects of pantethine on lipids and apolipoproteins in hypercholesterolemic diabetic and non diabetic patients. Curr Ther Res 1984;36:545-549.

Miettinen TA, Tarpila S. Effect of pectin on serum cholesterol, fecal bile acids and biliary lipids in normolipidemic and hyperlipidemic individuals. Clin Chim Acta 1977;79:471-477.

Miyagi Y, Miwa K, Inoue H. Inhibition of human low-density lipoprotein oxidation by flavonoids in red wine and grape juice. Am J Cardiol 1997 Dec 15;80(12):1627-1631.
Abstract: In the presence of red wine or grape juice, low-density lipoprotein was significantly resistant to oxidation; the biological activity of flavonoids, but not ethanol or nonflavonoid phenolic compounds, appeared to contribute to the antioxidant properties of red wine and grape juice. A significant antioxidant activity was also confirmed in low-density lipoprotein from humans after ingesting red wine but not grape juice, suggesting that flavonoids in red wine can be absorbed from the intestine more efficiently than those in grape juice.

Murray M, Pizzorno J. Encyclopedia of Natural Medicine, Revised Second Edition. Prima Publishing: Rocklin, CA, 1998.

Murray M. Lipid-lowering drugs vs. Inositol hexaniacinate. Am J Natural Med 1995;2:9-12. (Review)

Nakazawa K, Murata K. Comparative study of the effects of chondroitin sulfate isomers on atherosclerotic subjects. ZFA 1979;34:153-159.

Nanba H, Kubo K. The Effect of Maitake Mushroms on Liver and Serum Lipids. Alternative Therapies September 19961(5):62-66.

Nestel PJ, Pomeroy SE, Sasahara T, et al. Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidizability. Arterioscler Thromb Vasc Biol 1997;17:1163-1170.

Newman HAI, Leighton RF, Lanese RR, Freedland NA. Serum chromium and angiographically determined coronary artery disease. Clin Chem 1978;541-544.

Nityanand S, Srivastava JS, Asthana OP. Clinical trials with Gugulipid - A new hypolipidemic agent. J Assoc Phys India 1989; 37:323-328.
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.

Nozue T, Kobayashi A, Uemasu F, et al. Magnesium status, serum HDL cholesterol, and apolipoprotein A-1 levels. J Pediatr Gastroenterol Nutr 1995;20:316-318.

Nyboe J, Jensen G, Appleyard M, Schnohr P. Smoking and the risk of first acute myocardial infarction. Am Heart J 1991;122:438.

Nygärd O, Refsum H, Velanb PM, et al. Coffee consumption and plasma total homocysteine: The Hordaland Homocysteine Study. Am J Clin Nutr 1997;65:136-143.

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. (Review)
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.

Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet 1990;336:129-133.

Pekkanen J, Marti B, Nissinen A, Tuomilehto J. Reduction of premature mortality by high physical activity: a 20-year follow-up of middle-aged Finnish men. Lancet 1987;1:1473-1477.

Pelletier X, Belbraouet S, Mirabel D, et al. A diet moderately enriched in phytosterols lowers plasma cholesterol concentrations in normocholesterolemic humans. Ann Nutr Metab 1995;39:291-295.

Pola P, Savi L, Grilli M, et al. Carnitine in the therapy of dyslipidemic patients. Curr Ther Res 1980;27:208-216.

Pons P, Rodríquez M, Mas R, et al. One-year efficacy and safety of policosanol in patients with type II hypercholesterolemia. Curr Ther Res 1994;55:1084-1092.

Potter SM. Overview of proposed mechanisms for the hypocholesterolemic effect of soy. J Nutr 1995;606S-611S. (Review)

Potter SM. Soy Protein and Serum Lipids. Curr Opin Lipidol. 1996; 7(4):260-264.
Abstract: Evidence exists indicating that substitution of soy for animal protein reduces both total and LDL-cholesterol concentrations in humans. There are a number of biologically active compounds associated with soy protein; however, the precise mechanism and the component(s) of soy responsible have not been fully established. Some studies suggest that, when soy protein is fed, cholesterol absorption or bile acid reabsorption, or both, is impaired. This is observed in some animal species such as rabbits and rats but not in humans, nor when amino acids replace intact soy protein. Other workers have proposed that changes in endocrine status are responsible, however, this again has not been observed in humans. Increases in LDL receptor activity in both animals and humans have been reported after ingestion of soy protein or various extracts of soy, or both. Furthermore, the soybean isoflavone genistein may inhibit lesion and thrombus formation via inhibition of second messengers.)

Press RI, Geller J, Evans GW. The effect of chromium picolinate on serum cholesterol and apolipoprotein fractions in human subjects. West J Med 1990 Jan;152(1):41-45.
Abstract: Chromium has been implicated as a cofactor in the maintenance of normal lipid and carbohydrate metabolism. A deficiency of chromium results from diets low in biologically available chromium. Picolinic acid, a metabolite of tryptophan, forms stable complexes with transitional metal ions, which results in an improved bioavailability of the metal ion chromium. To determine whether or not chromium picolinate is effective in humans, 28 volunteer subjects were given either chromium tripicolinate (3.8 micromol [200 micrograms] chromium) or a placebo daily for 42 days in a double-blind crossover study. A 14-day period off capsules was used between treatments. Levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B, the principal protein of the LDL fraction, decreased significantly while the subjects were ingesting chromium picolinate. The concentration of apolipoprotein A-I, the principal protein of the high-density lipoprotein (HDL) fraction, increased substantially during treatment with chromium picolinate. The HDL-cholesterol level was elevated slightly but not significantly during ingestion of chromium picolinate. Only apolipoprotein B, of the variables measured, was altered significantly during supplementation with the placebo. These observations show that chromium picolinate is efficacious in lowering blood lipids in humans.

Raloff J. Oxidized lipids: a key to heart disease? Sci News 1985;127:278.

Reaven PD, McPhillips JB, Barrett-Connor EL, Criqui MH. Leisure time exercise and lipid and lipoprotein levels in an older population. J Am Geriatr Soc 1990;38:847-854.

Reiser S. Effect of dietary sugars on metabolic risk factors associated with heart disease. Nutr Health 1985;3:203-216.

Resnicow K, Barone J, Engle A, et al. Diet and serum lipids in vegan vegetarians: a model for risk reduction. J Am Dietet Assoc 1991;91:447-453.

Riales R, Albrink MJ. Effect of chromium chloride supplementation on glucose tolerance and serum lipids including high-density lipoprotein of adult men. Am J Clin Nutr 1981 Dec;34(12):2670-2678.
Abstract: Chromium deficiency may cause insulin resistance, hyperinsulinemia, impaired glucose tolerance, and hyperlipidemia, recovered by chromium supplementation. The effect of chromium supplementation on serum lipids and glucose tolerance was tested in a double-blind 12-wk study of 23 healthy adult men aged 31 to 60 yr. Either 200 micrograms trivalent chromium in 5 ml water (Cr) or 5 ml plain water (W) was ingested daily 5 days each week. Half the subjects volunteered for glucose tolerance tests with insulin levels. At 12 wk high-density lipoprotein cholesterol increased in the Cr group from 35 to 39 mg/dl (p less than 0.05) but did not change in the water group (34 mg/dl). The largest increase in high-density lipoprotein cholesterol and decreases in insulin and glucose were found in those subjects having normal glucose levels together with elevated insulin levels at base-line. The data are thus consistent with the hypothesis that Cr supplementation raises high-density lipoprotein cholesterol and improves insulin sensitivity in those with evidence of insulin resistance but normal glucose tolerance.

Rimm EB, Ascherio A, Giovannucci E, et al. Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men. JAMA 1996;275:447-451.

Rimm EB, Katan MB, Aschario A, et al. Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann Intern Med 1996;125:384-389.

Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits? Br Med J 1996;312:731-736. (Review)

Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993 May 20;328(20):1450-1456.
Abstract: BACKGROUND. The oxidative modification of low-density lipoproteins increases their incorporation into the arterial intima, an essential step in atherogenesis. Although dietary antioxidants, such as vitamin C, carotene, and vitamin E, have been hypothesized to prevent coronary heart disease, prospective epidemiologic data are sparse. METHODS. In 1986, 39,910 U.S. male health professionals 40 to 75 years of age who were free of diagnosed coronary heart disease, diabetes, and hypercholesterolemia completed detailed dietary questionnaires that assessed their usual intake of vitamin C, carotene, and vitamin E in addition to other nutrients. During four years of follow-up, we documented 667 cases of coronary disease. RESULTS. After controlling for age and several coronary risk factors, we observed a lower risk of coronary disease among men with higher intakes of vitamin E (P for trend = 0.003). For men consuming more than 60 IU per day of vitamin E, the multivariate relative risk was 0.64 (95 percent confidence interval, 0.49 to 0.83) as compared with those consuming less than 7.5 IU per day. As compared with men who did not take vitamin E supplements, men who took at least 100 IU per day for at least two years had a multivariate relative risk of coronary disease of 0.63 (95 percent confidence interval, 0.47 to 0.84). Carotene intake was not associated with a lower risk of coronary disease among those who had never smoked, but it was inversely associated with the risk among current smokers (relative risk, 0.30; 95 percent confidence interval, 0.11 to 0.82) and former smokers (relative risk, 0.60; 95 percent confidence interval, 0.38 to 0.94). In contrast, a high intake of vitamin C was not associated with a lower risk of coronary disease. CONCLUSIONS. These data do not prove a causal relation, but they provide evidence of an association between a high intake of vitamin E and a lower risk of coronary heart disease in men. Public policy recommendations with regard to the use of vitamin E supplements should await the results of additional studies.

Roeback JR Jr, Hla KM, Chambless LE, Fletcher RH. Effects of chromium supplementation on serum high-density lipoprotein cholesterol levels in men taking beta-blockers. A randomized, controlled trial. Ann Intern Med 1991 Dec 15;115(12):917-924.
Abstract: OBJECTIVE: To determine the efficacy of glucose tolerance factor (GTF)-chromium for increasing serum levels of high-density lipoprotein (HDL) cholesterol in patients taking beta-blockers. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Mixed primary and referral-based outpatient clinic at a university-affiliated VA Medical Center. PATIENTS: Referred sample of 72 men receiving beta-blockers, mainly for hypertension. Sixty-three patients (88%) completed the study. INTERVENTIONS: Current medications, including beta-blockers, were continued. During the 8-week treatment phase, patients in the chromium group received a total daily dose of 600 micrograms of biologically active chromium divided into three equal doses; control patients received a placebo of identical appearance and taste. MEASUREMENTS: Serum levels of total cholesterol and HDL cholesterol were measured. MAIN RESULTS: Mean baseline levels of HDL and total cholesterol (+/- SD) were 0.93 +/- 0.28 mmol/L and 6.0 +/- 1.0 mmol/L (36 +/- 11.1 mg/dL and 232 +/- 38.5 mg/dL), respectively. The difference between groups in adjusted mean change in HDL cholesterol levels, accounting for baseline HDL cholesterol levels, age, weight change, and baseline total cholesterol levels, was 0.15 mmol/L (5.8 mg/dL) (P = 0.01) with a 95% Cl showing that the treatment effect was greater than +0.04 mmol/L (+1.4 mg/dL). Mean total cholesterol, triglycerides and body weight did not change significantly during treatment for either group. Compliance as measured by pill count was 85%, and few side effects were reported. Two months after the end of treatment, the between-group difference in adjusted mean change from baseline to end of post-treatment follow-up was -0.003 mmol/L (-0.1 mg/dL). CONCLUSION: Two months of chromium supplementation resulted in a clinically useful increase in HDL cholesterol levels in men taking beta-blockers.

Ripsin CM, Keenan JM, Jacobs DR, et al. Oat products and lipid lowering - a meta-analysis. JAMA 1992;267:3317-3325.

Roeback JR, Hla KM, Chambless LE, Fletcher RH. Effects of chromium supplementation on serum high-density lipoprotein cholesterol levels in men taking beta-blockers. Ann Intern Med 1991;115:917-924.

Ronzio RA. Antioxidants, nutraceuticals and functional foods. Townsend Letter for Doctors and Patients. Oct, 1996:34-35. (Review)

Rosmarin PC, Applegate WB, Somes GW. Coffee consumption and serum lipids: a randomized, crossover clinical trial. Am J Med 1990;88:349-356.

Rossi CS, Siliprandi N. Effect of carnitine on serum HDL-cholesterol: report of two cases. Johns Hopkins Med J 1982 Feb; 150(2):51-54.
Abstract: In two otherwise normal male subjects selected for normal serum cholesterol and triglycerides but low serum high-density lipoprotein (HDL) levels, oral administration of 1 g per day of L-carnitine over a period of 10-15 weeks caused a substantial increase in high-density lipoprotein levels, as well as a decrease in serum triglycerides. The ratio of HDL-cholesterol to total cholesterol increased, but this change was not due to an obligatory lowering of total cholesterol. Possible mechanisms of the carnitine effect are discussed. Since elevated high-density lipoprotein levels significantly reduce the risk of arteriosclerotic cardiovascular disease, this action of carnitine deserves further study.

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.

Santos MJ, Lopez-Jurado M, Llopis J, et al. Influence of dietary supplementation with fish on plasma total cholesterol and lipoprotein cholesterol fractions in patients with coronary heart disease. J Nutr Med 1992;3:107-115.

Shekelle RB, Stamler J. Dietary cholesterol and ischaemic heart disease. Lancet 1989;i:1177-1179.

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).

Simon JA. Vitamin C and cardiovascular disease: a review. J Am Coll Nutr 1992 Apr;11(2):107-125. (Review)
Abstract: Vitamin C functions as a regulator of the catabolism of cholesterol to bile acids in the guinea pig and has been demonstrated to be an important factor in lipid regulation of the guinea pig, rabbit and rat. Correlation studies in humans have shown an inverse relationship between vitamin C intake and cardiovascular disease mortality. Observational and experimental studies in humans have yielded inconsistent results, but taken together indicate that for individuals with high total cholesterol concentrations, greater than or equal to 5.20 mmol/L (200 mg/dl) and less than full tissue saturation, increasing the concentration of vitamin C may have a salutary effect on total cholesterol. Vitamin C's effect on promoting the production and inhibiting the degradation of prostacyclin is reviewed, as are implications of these findings regarding thrombosis and atherogenesis. Evidence indicative of a protective effect on lipid peroxidation by vitamin C is examined. Analysis of the literature regarding groups at high risk for coronary heart disease reveals that men, the elderly, smokers, diabetics, hypertensives and perhaps oral estrogen-containing contraceptive users have lowered plasma vitamin C levels. Evidence linking vitamin C to human cardiovascular disease is largely circumstantial, but taken in total, is suggestive of an association. Further examination of the relationship between vitamin C and cardiovascular disease is warranted.

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.

Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993 May 20;328(20):1444-1449.
Abstract: BACKGROUND. Interest in the antioxidant vitamin E as a possible protective nutrient against coronary disease has intensified with the recognition that oxidized low-density lipoprotein may be involved in atherogenesis. METHODS. In 1980, 87,245 female nurses 34 to 59 years of age who were free of diagnosed cardiovascular disease and cancer completed dietary questionnaires that assessed their consumption of a wide range of nutrients, including vitamin E. During follow-up of up to eight years (679,485 person-years) that was 97 percent complete, we documented 552 cases of major coronary disease (437 nonfatal myocardial infarctions and 115 deaths due to coronary disease). RESULTS. As compared with women in the lowest fifth of the cohort with respect to vitamin E intake, those in the top fifth had a relative risk of major coronary disease of 0.66 (95 percent confidence interval, 0.50 to 0.87) after adjustment for age and smoking. Further adjustment for a variety of other coronary risk factors and nutrients, including other antioxidants, had little effect on the results. Most of the variability in intake and reduction in risk was attributable to vitamin E consumed as supplements. Women who took vitamin E supplements for short periods had little apparent benefit, but those who took them for more than two years had a relative risk of major coronary disease of 0.59 (95 percent confidence interval, 0.38 to 0.91) after adjustment for age, smoking status, risk factors for coronary disease, and use of other antioxidant nutrients (including multi-vitamins). CONCLUSIONS. Although these prospective data do not prove a cause-and-effect relation, they suggest that among middle-aged women the use of vitamin E supplements is associated with a reduced risk of coronary heart disease. Randomized trials of vitamin E in the primary and secondary prevention of coronary disease are being conducted; public policy recommendations about the widespread use of vitamin E should await the results of these trials.

Stampfer MJ, Rimm EB. Epidemiologic evidence for vitamin E in prevention of cardiovascular disease. Am J Clin Nutr 1995 Dec;62(6 Suppl):1365S-1369S.
Abstract: Ecologic studies of vitamin E have shown that regions with relatively low dietary vitamin E tend to have higher rates of coronary heart disease (CHD), but it is difficult to adjust for other risk factors. Cross-sectional studies in individuals have yielded conflicting results, as have prospective studies based on stored blood samples. Two large prospective studies found that persons who had used vitamin E supplements for > or = 2 y had approximately 40% lower rates of CHD. Short durations and doses of < 100 IU/d had no significant effect. The effect of dietary vitamin E was modest and nonsignificant. Adjustment for a wide array of other coronary risk factors had little effect on the findings, which were specific for vitamin E and not other supplements. The only large, randomized trial found no material reduction in CHD risk for 50 IU vitamin E/d. The epidemiologic evidence suggests that high doses of vitamin E may reduce the risk of CHD.

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.

Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study. Lancet 1996 Mar 23;347(9004):781-786.
Abstract: BACKGROUND: Vitamin E (alpha-tocopherol) is thought to have a role in prevention of atherosclerosis, through inhibition of oxidation of low-density lipoprotein. Some epidemiological studies have shown an association between high dietary intake or high serum concentrations of alpha-tocopherol and lower rates of ischaemic heart disease. We tested the hypothesis that treatment with a high dose of alpha-tocopherol would reduce subsequent risk of myocardial infarction (MI) and cardiovascular death in patients with established ischaemic heart disease. METHODS: In this double-blind, placebo-controlled study with stratified randomisation, 2002 patients with angiographically proven coronary atherosclerosis were enrolled and followed up for a median of 510 days (range 3-981). 1035 patients were assigned alpha-tocopherol (capsules containing 800 IU daily for first 546 patients; 400 IU daily for remainder); 967 received identical placebo capsules. The primary endpoints were a combination of cardiovascular death and non-fatal MI as well as non-fatal MI alone. FINDINGS: Plasma alpha-tocopherol concentrations (measured in subsets of patients) rose in the actively treated group (from baseline mean 34.2 micromol/L to 51.1 micromol/L with 400 IU daily and 64.5 micromol/L with 800 IU daily) but did not change in the placebo group. Alpha-tocopherol treatment significantly reduced the risk of the primary trial endpoint of cardiovascular death and non-fatal MI (41 vs 64 events; relative risk 0.53 [95% Cl 0.34-0.83; p=0.005). The beneficial effects on this composite endpoint were due to a significant reduction in the risk of non-fatal MI (14 vs 41; 0.23 [0.11-0.47]; p=0.005); however, there was a non-significant excess of cardiovascular deaths in the alpha-tocopherol group (27 vs 23; 1.18 [0.62-2.27]; p=0.61). All-cause mortality was 36 of 1035 alpha-tocopherol-treated patients and 27 of 967 placebo recipients. INTERPRETATION: We conclude that in patients with angiographically proven symptomatic coronary atherosclerosis, alpha-tocopherol treatment substantially reduces the rate of non-fatal MI, with beneficial effects apparent after 1 year of treatment. The effect of alpha-tocopherol treatment on cardiovascular deaths requires further study.

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.

Superko HR, Bortz WM, Albers JJ, Wood PJ. Lipoprotein and apolipoprotein changes during a controlled trial of caffeinated and decaffeinated coffee drinking in men. Circulation 1989;80:II-86.

Tell GS, Evans GW, Folsom AR, et al. Dietary fat intake and carotid artery wall thickness: the atherosclerosis risk in communities (ARIC) study. Am J Epidemiol 1994;139:979-989.

Thorogood M, Carter R, Benfield L, et al. Plasma lipids and lipoprotein cholesterol concentrations in people with different diets in Britain. Br Med J (Clin Res Ed) 1987;295:351-353.

Ubbink JB. The role of vitamins in the pathogenesis and treatment of hyperhomocyst(e)inaemia. J Inherit Metab Dis 1997 Jun;20(2):316-325.
Abstract: The relation between vitamin nutritional status and circulating plasma homocyst(e)ine concentrations is reviewed. Several studies have shown that plasma concentrations of folate, vitamin B12 and pyridoxal 5'-phosphate are inversely associated with plasma total homocyst(e)ine concentrations. Of the three vitamins mentioned above, folate is the most powerful homocyst(e)ine lowering agent and a daily supplement of 0.65 mg/day is sufficient to normalize moderate hyperhomocyst(e)inaemia in most individuals with normal renal function. In patients with severe renal failure, high doses of folate are required to treat hyperhomocyst(e)inaemia. Folic acid is ineffective in reducing plasma total homocyst(e)ine concentrations in patients with a vitamin B12 deficiency. Vitamin B6 supplementation has no effect on fasting plasma total homocyst(e)ine concentrations, but attenuates the post-methionine load plasma homocyst(e)ine peak. At least one report has shown that some individuals appear to be unable to maintain plasma total homocyst(e)ine concentrations in the normal reference range by a dietary intake of folic acid only. Long-term vitamin supplementation may be indicated in these individuals. However, the clinical benefit of vitamin supplementation has not yet been demonstrated and controlled trials are urgently required.

Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R, Vermaak WJ.
The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Invest 1996 Jul 1;98(1):177-184.
Abstract: Homocysteine, an atherogenic amino acid, is either remethylated to methionine or metabolized to cysteine by the transsulfuration pathway. The biochemical conversion of homocysteine to cysteine is dependent upon two consecutive, vitamin B-6-dependent reactions. To study the effect of a selective vitamin B-6 deficiency on transsulfuration, we performed oral methionine load tests on 22 vitamin B-6-deficient asthma patients treated with theophylline (a vitamin B-6 antagonist) and 24 age- and sex-matched controls with a normal vitamin B-6 status. Both groups had normal circulating vitamin B-12 and folate concentrations. Methionine loading resulted in significantly higher increases in circulating total homocyst(e)ine (P < 0.01) and cystathionine (P < 0.05) concentrations in vitamin B-6-deficient patients compared with controls. 6 wk of vitamin B-6 supplementation (20 mg/d) significantly (P < 0.05) reduced post-methionine load increases in circulating total homocyst(e)ine concentrations in deficient subjects, but had no significant effect on the increase in total homocyst(e)ine concentrations in controls. The increases in post-methionine load circulating cystathionine concentrations were significantly (P < 0.01) reduced in both groups after vitamin supplementation. It is concluded that a vitamin B-6 deficiency may contribute to impaired transsulfuration and an abnormal methionine load test, which is associated with
premature vascular disease.

Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ, Delport R, Potgieter HC. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994 Oct;124(10):1927-1933.
Abstract: We have previously shown that a modest vitamin supplement containing folic acid, vitamin B-12 and vitamin B-6 is effective in reducing elevated plasma homocysteine concentrations. The effect of supplementation of the individual vitamins on moderate hyperhomocysteinemia has now been investigated in a placebo-controlled study. One hundred men with hyperhomocysteinemia were randomly assigned to five groups and treated with a daily dose of placebo, folic acid (0.65 mg), vitamin B-12 (0.4 mg), vitamin B-6 (10 mg) or a combination of the three vitamins for 6 wk. Folic acid supplementation reduced plasma homocysteine concentrations by 41.7% (P < 0.001), whereas the daily vitamin B-12 supplement lowered homocysteine concentrations by 14.8% (P < 0.01). The daily pyridoxine dose did not reduce significantly plasma homocysteine concentrations. The combination of the three vitamins reduced circulating homocysteine concentrations by 49.8%, which was not significantly different (P = 0.48) from the reduction achieved by folate supplementation alone. Our results indicate that folate deficiency may be an important cause of hyperhomocysteinemia in the general population.

Urgert R, Schulz AGM, Katan MB. Effects of cafestol and kahweol from coffee grounds on serum lipids and serum liver enzymes in humans. Am J Clin Nutr 1995;61:149-154.

Vittek J. Effect of royal jelly on serum lipids in experimental animals and humans with atherosclerosis. Experientia 1995;51:927-935.

Wang MM, Fox EA, Stoecker BJ, et al. Serum cholesterol of adults supplemented with brewer’s yeast or chromium chloride. Nutr Res 1989;9:989-998.

Warshafsky S, Kamer RS, Sivak SL. Effect of garlic on total serum cholesterol - a meta-analysis. Ann Intern Med 1993;119:599-605.

Willett WC, Stampfer MJ, Manson JE, et al. Intake of trans fatty acids and risk of coronary heart disease among women. Lancet 1993;341:581-585.

Williams CL, Bollella M, Spark A, Puder D. Soluble fiber enhances the hypocholesterolemic effect of the Step I diet in childhood. J Am Coll Nutr 1995;14:251-257.

Willich SN, Lewis M, Lowel H, et al. Physical exertion as a trigger of acute myocardial infarction. N Engl J Med 1993;329:1684-1690.

Wilson TA, Meservey CM, Nicolosi. Soy lecithin reduces plasma lipoprotein cholesterol and early atherogenesis in hypercholesterolemic monkeys and hamsters: beyond linoleate. Atherosclerosis 1998;140:147-153.

Wittwer CT, Graves CP, Peterson MA, Jorgensen E, Wilson DE, Thoene JG, Wyse BW, Windham CT, Hansen RG. Pantethine lipomodulation: evidence for cysteamine mediation in vitro and in vivo. Atherosclerosis 1987 Nov;68(1-2):41-49.
Abstract: Recent human studies suggest rapid in vivo hydrolysis of the lipid-lowering drug, pantethine, to the vitamin pantothenic acid and the small aminothiol compound, cysteamine. To test whether the active agent is a hydrolysis product, we repeated three experimental models of pantethine's effect with pantothenate and cysteamine. In vitro experiments with human fetal fibroblasts showed equivalent modulation of cholesterol and methyl sterol synthesis by pantethine, cysteamine, or cystamine (the disulfide of cysteamine), but pantothenate had no effect. Similarly, in vivo experiments with 0.5% cholesterol-fed rabbits showed oral pantethine or equimolar cystamine significantly lowered plasma cholesterol, while pantothenate, cystine, and 2-hydroxyethyl disulfide did not. Lastly, diabetic male rats (40 mg/kg streptozotocin) fed 0.1% pantethine and lower plasma free fatty acids after 2 weeks than controls, an effect not seen with pantothenate and largely duplicated by cystamine. The efficacy of pantethine has previously been attributed to altered vitamin metabolism and increased coenzyme A concentration. Pantethine did increase CoA levels 45% in rat liver homogenates while equivalent amounts of cystamine or pantothenate did not. However, a causal relationship between CoA levels and pantethine's action as a hypolipemic agent has never been shown. At least in 3 independent experimental models, the lipomodulating effect of pantethine appears instead to be mediated by the hydrolysis product cysteamine.

Wolever TM, Jenkins DJ, Mueller S, Patten R, Relle LK, Boctor D, Ransom TP, Chao ES, McMillan K, Fulgoni V 3rd. Psyllium Reduces Blood Lipids in Men and Women with Hyperlipidemia. Am J Med Sci. 1994; 307(4):269-273.
Abstract: To see if a modest amount of soluble fiber reduced blood lipids in subjects with hyperlipidemia who were on a low-fat diet, 42 subjects (21 men, 21 women) consuming an American Heart Association step 2 diet took two servings of breakfast cereal daily for two 2-week periods in a randomized crossover trial. There were two types of test cereals, each providing 6.7 g psyllium fiber daily, and two types of wheat bran control cereals, matched for available carbohydrate and total fiber. Half the subjects tested each type of cereal, and the results were pooled because the psyllium cereals had similar effects on serum cholesterol levels. Comparing values at the end of 2 weeks, psyllium reduced serum total (6.33 +/- 0.12 mmol/L versus 6.76 +/- 0.12 mmol/L, p < 0.001), low-density lipoprotein (LDL; 4.36 +/- 0.11 mmol/L versus 4.73 +/- 0.12 mmol/L, p < 0.001) and high-density lipoprotein cholesterol levels (HDL; 1.10 +/- 0.05 mmol/L versus 1.14 +/- 0.05 mmol/L, p < 0. 05) and the LDL/HDL cholesterol ratio (4.27 +/- 0.20 versus 4.48 +/- 0.22, p < 0.02) with no effect on triglycerides. There was no significant interaction between the effects of treatment and sex for any of the blood lipid variables. Women tended to have greater decreases in total, LDL, and HDL cholesterol levels than men, but the percent decrease in LDL/HDL ratio on psyllium was similar in men, 4.9%, and women, 4.7%. It is concluded that 6.7 g of psyllium fiber daily, with a low-fat diet, reduces serum cholesterol levels in both men and women with hyperlipidemia.

Wood PD, Stefanick ML, Dreon DM, et al. Changes in plasma lipids and lipoproteins in overweight men during weight loss through dieting as compared with exercise. N Engl J Med 1988;319:1173-1179.

Yacowitz H, Fleischman AI, Bierenbaum ML. Effects of oral calcium upon serum lipids in man. BMJ 1965;1:1352-1354.

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.

Yudkin J, Kang SS, Bruckdorfer KR. Effects of high dietary sugar. Br Med J 1980;281:1396.

Zock PL, de Vries JHM, Katan MB. Impact of myristic acid versus palmitic acid on serum lipid and lipoprotein levels in healthy women and men. Arterioscler Thromb 1994;14:567-575.

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