Kirk EA; Sutherland P; Wang SA; Chait A; LeBoeuf RC
Department of Medicine and the Nutritional Sciences Program, University of Washington, Seattle, WA 98195, USA.
J Nutr (United States) Jun 1998, 128 (6) p954-9

Susceptibility to atherosclerosis is determined by a combination of genetic and environmental factors, including diet. Consumption of diets rich in soy protein has been claimed to protect against the development of atherosclerosis. Potential mechanisms include cholesterol lowering, inhibition of lipoprotein oxidation and inhibition of cell proliferation by soy proteins or isoflavones, such as genistein , that are present in soy . This study was designed to determine whether soy isoflavones confer protection against atherosclerosis in mice and whether they reduce serum cholesterol levels and lipoprotein oxidation. C57BL/6 and LDL receptor-deficient (LDLr-null) mice were fed soy protein-based, high fat diets with isoflavones present (IF+, 20.85 g/100 g protein, 0.027 g/100 g genistein , 0.009 g/100 g daidzein) or diets from which isoflavones , and possibly other components, had been extracted (IF-, 20.0 g/100 g protein, 0.002 g/100 g genistein , 0.001 g/100 g daidzein). Because LDLr-null mice develop extensive atherosclerosis and hypercholesterolemia after minimal time on a high fat diet, they were fed the diets for 6 wk, whereas C57BL/6 mice were fed the diets for 10 wk. Plasma cholesterol levels did not differ between LDLr-null mice fed IF- and those fed IF+, but were 30% lower in C57BL/6 mice fed the IF+ diet than in those fed the IF- diet. Susceptibility of LDL to oxidative modification, measured as the lag phase of conjugated diene formation in LDLr-null mice, was not altered by isoflavone consumption. All LDLr-null mice developed atherosclerosis, and the presence or deficiency of dietary isoflavones did not influence atherosclerotic lesion area. In contrast, atherosclerotic lesion area was significantly reduced in C57BL/6 mice fed IF+ compared with those fed IF-. Thus, this study demonstrates that although the isoflavone-containing diet resulted in a reduction in cholesterol levels in C57BL/6 mice, it had no effect on cholesterol levels or on susceptibility of LDL to oxidative modification in LDLr-null mice. Further, dietary isoflavones did not protect against the development of atherosclerosis in LDLr-null mice but did decrease atherosclerosis in C57BL/6 mice. These findings suggest that soy isoflavones might lower cholesterol levels by increasing LDL receptor activity, and the reduction in cholesterol may offer some protection against atherosclerosis.

Barnes S.
S. Barnes, Dept. of Pharmacology and Toxicology, University of Alabama, Birmingham, AL 35294 United States
Proceedings of the Society for Experimental Biology and Medicine (United States), 1998, 217/3 (386-392)

Soy is a unique dietary source of the isoflavones , genistein and daidzein. It has been part of the Southeast Asian diet for nearly five millenia, whereas consumption of soy in the United States and Western Europe has been limited to the 20th century. Heavy consumption of soy in Southeast Asian populations is associated with reduction in the rates of certain cancers end cardiovascular disease. Recent experimental evidence suggests that phytochemicals in soy are responsible for its beneficial effects, which may also include prevention of osteoporosis, a hereditary chronic nose bleed syndrome, and autoimmune diseases. Exposure of soy formula-fed infants to the potential estrogenizing effects of the isoflavones is limited by the first pass effect of the liver following the uptake of isoflavones from the gut. Several mechanisms of action of isoflavones have been proposed-both through estrogen-dependent and estrogen-independent pathways.

Brouillard R; George F; Fougerousse A
Laboratoire de Chimie des Polyphenols, Universite Louis Pasteur, Faculte de Chimie, Strasbourg, France.
Biofactors (Netherlands) 1997, 6 (4) p403-10

Over the past few years, it has been accepted that a moderate red wine consumption is a factor beneficial to human health. Indeed, people of France and Italy, the two major wine-producing European countries, eat a lot of fatty foods but suffer less from fatal heart strokes than people in North-America or in the northern regions of Europe, where wine is not consumed on a regular basis. For a time, ethanol was thought to be the "good" chemical species hiding behind what is known as the "French paradox". Researchers now have turned their investigations towards a family of natural substances called "polyphenols", which are only found in plants and are abundant in grapes . It is well known that these molecules behave as radical scavengers and antioxidants, and it has been demonstrated that they can protect cholesterol in the LDL species from oxidation, a process thought to be at the origin of many fatal heart attacks. However, taken one by one, it remains difficult to demonstrate which are the best polyphenols as far as their antioxidant activities are concerned. The main obstacle in that kind of research is not the design of the chemical and biological tests themselves, but surprisingly enough, the limited access to chemically pure and structurally elucidated polyphenolic compounds. In this article, particular attention will be paid to polyphenols of red wine made from Vitis vinifera cultivars. With respect to the "French paradox", we address the following question: are wine polyphenolic compounds identical to those found in grapes (skin, pulp and seed), or are there biochemical modifications specifically taking place on the native flavonoids when a wine ages? Indeed, structural changes occur during wine conservation, and one of the most studied of those changes concerns red wine colour evolution, called "wine ageing". As a wine ages, it has been demonstrated that the initially present grape pigments slowly turn into new more stable red pigments. That phenomenon goes on for weeks, months and years. Since grape and wine polyphenols are chemically distinct, their antioxidant activities cannot be the same. So, eating grapes might well lead to beneficial effects on human health, due to the variety and sometimes large amounts of their polyphenolic content. However, epidemiological surveys have focused on wines,not on grapes .... (35 Refs.)

Crist DM; Peake GT; Stackpole PJ
Clin Exp Pharmacol Physiol (England) Jul 1986, 13 (7) p513-8

Testosterone cypionate administration in weight-trained subjects reduced serum high-density lipoprotein cholesterol (HDL-C) levels without affecting the total cholesterol (Total-C)/HDL-C ratio. Nandrolone decanoate administration also reduced HDL-C levels, but elevated the Total-C/HDL-C ratio. These findings could not be attributed to changes in exercise patterns, dietary intake, or alcohol consumption. It is concluded that the synthetic androgen employed in this study produced a worsening of potential lipid-related risk factors for ischemic heart disease and that exogenous testosterone has a much less pronounced effect on such risk factors.

Ghafoorunissa
National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania, Hyderabad 500 007 India
Lipids (USA), 1996, 31/3 Suppl. (S287-S291)

To arrive at fat requirements for Indians, the contribution of invisible fat should be determined. Total lipids were extracted from common Indian foods, and their fatty acid compositions were determined. This data and information on intake of various foods were used to estimate the contents of 'invisible' fat and fatty acids in Indian diets. Taking into account World Health Organization (WHO) guidelines and the invisible fat intake of Indians, recommendations were made for lower and upper limits of visible fats. In the rural poor, the 'visible'-fat intakes are much lower than estimated minimum requirements. Therefore, to meet the energy needs of low income groups, particularly young children, visible-fat intakes must be increased to recommended levels. The urban high-income group, however, should reduce dietary fat. Data on intake of various fatty acids in total diet shows that even the recommended lower limit of oil can meet linoleic acid requirements. Intake of alpha-linolenic acid is low, however. Increase in dietary n-3 polyunsaturated fatty acid (PUFA) produces hypolipidemic, anti-inflammatory, and antithrombotic effects. Effects of n-3 PUFA on blood lipids, platelet fatty acid composition, and platelet aggregation were therefore investigated in Indian subjects consuming cereal based diets. Supplementation of fish oils (long-chain n-3 PUFA) as well as the use of rapeseed oil (alpha-linolenic acid) produced beneficial effects. Since the requirements of alpha-linolenic acid and/or long-chain n-3 PUFA are related to linoleic acid intake, use of more than one oil (correct choice) is recommended for providing a balanced intake of various fatty acids. Analysis of Indian food showed that some foods are good sources of alpha-linolenic acid. Regular consumption of these foods can also improve the quality of fat in Indian diets. Nonvegetarians, however, have the choice of eating fish to accomplish this.

Schoolfield D.J.; Behall K.M.; Kelsay J.L.; Prather E.S.; Clark W.M.; Reiser S.; Canary J.J.
Carbohydrate Nutrition Laboratory, Beltsville Human Nutrition Research Center, ARS, USDA, Beltsville, MD 20705 USA
Nutr. Res. (USA), 1990, 10/4 (367-378)

Diets high in fiber and oxalate may result in decreased mineral bioavailability. However, increased fiber intake can reduce risk factors for some diseases. Twelve men were fed diets containing 25 g or 5 g of neutral detergent fiber with 450 mg/day of oxalic acid for six weeks each in a crossover design to determine whether plasma minerals and other metabolites would be affected. High dietary oxalate levels were fed throughout the study. The fiber sources were fruit and vegetables or their juices and spinach was the source of oxalate. Five minerals and cholesterol , triglycerides, uric acid, glucose and urea nitrogen (BUN) were measured in fasting plasma and correlated with fecal oxalate, mineral intake and apparent mineral balance. Fiber level had no effect on the plasma constituents. Plasma inorganic phosphorus (P(i)) decreased (p = 0.002), while BUN, calcium and copper increased (p < 0.010), (p = 0.004), (p = 0.011) with time. BUN and P(i) changes which occurred may have been related to ingestion of high levels of oxalate for eighty-four days.

Sikand G; Kashyap ML; Yang I
Division of Cardiology, University of California-Irvine, Orange 92868-3298, USA.
J Am Diet Assoc (United States) Aug 1998, 98 (8) p889-94; quiz 895-6

This study was designed to evaluate whether medical nutrition therapy administered by registered dietitians could lead to a beneficial clinical and cost outcome in men with hypercholesterolemia. Ninety-five subjects participating in a cholesterol -lowering drug study took part in an 8-week nutrition intervention program before initiating treatment with a cholesterol -lowering medication, Patient records were reviewed via a retrospective chart review to determine plasma lipid levels at the beginning and end of the program and the number and length of sessions with a dietitian. Complete information was available for 74 subjects aged 60.8 n+/- 9.8 years (mean +/- SD). Medical nutrition therapy lowered total serum cholesterol levels 13% (P < .001), low-density lipoprotein cholesterol (LDL-C) 15% (P < .0001), triglyceride 11% (P < .05), and high-density lipoprotein- cholesterol (HDL-C) 4% (P < .05). Total dietitian intervention time was 144 +/- 21 minutes (range = 120 to 180 minutes) in 2.8 +/- 0.7 sessions (range = 2 to 4) during 6.81 +/- 0.7 weeks of medical nutrition therapy (range = 6 to 8 weeks). Analysis of covariance was conducted to examine whether mean change in LDL-C differed by number of dietitian visits. Results showed a marginal difference between the number of dietitian visits and change in LDL-C (f = 2.6, P < .084). However, the magnitude of LDL-C reduction was significantly higher with 4 dietitian visits (180 minutes) than with 2 visits (120 minutes) (21.9% vs 12.1%; P = .027). Lipid drug eligibility was obviated in 34 of 67 (51%) subjects per the National Cholesterol Treatment Program guidelines algorithm. The estimated annualized cost savings from the avoidance of lipid medications was $60,561.68. Therefore, we conclude that 3 or 4 individualized dietitian visits of 50 minutes each over 7 weeks are associated with a significant serum cholesterol reduction and a savings of health care dollars.

Borgia MC; Medici F
Universita Degli Studi di Roma La Sapienza, Italy.
Angiology (United States) May 1998, 49 (5) p339-48

In this review the indications for the available treatments for dyslipidemias in the prevention of coronary heart disease (CHD) are considered, and their efficacy according to the latest studies is analyzed. As data sources the authors used the main multicenter studies performed in the last twenty years to evaluate primary and secondary prevention of CHD by correcting dyslipidemias as well as the results of meta-analyses of these studies. All treatments considered were found effective in preventing CHD morbidity and mortality to some extent. In particular, the combination of diet with niacin or hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors seems to give the best results. These drugs induce a marked reduction of total and low-density lipoprotein (LDL) cholesterol and an increase of high-density lipoprotein (HDL) cholesterol concentrations. The use of diet, niacin , and HMG CoA reductase inhibitors reduces total as well as specific mortality. Treatment of dyslipidemia to prevent CHD depends on the pattern and severity of dyslipidemia, the presence of overt CHD, and the patient's response to diet. Pharmacologic treatment should be started only after dietary modifications have been tried and must be combined with diet. Drug side effects must also be considered, for they may affect patient compliance. High levels of total and LDL and low levels of HDL cholesterol are major risk factors for coronary atherosclerosis. Correcting lipid abnormalities can reduce the risk of development or progression of CHD. Diet and drugs are the main instruments available to normalize lipid levels. The choice of drug to combine with diet must be based on its specific effects on lipid metabolism, side effects, and efficacy in reducing CHD. (77 Refs.)

Tato F; Vega GL; Grundy SM
Department of Clinical Nutrition of the University of Texas Southwestern Medical Center and The Veterans Affairs Medical Center at Dallas, 75235-9052, USA.
Am J Cardiol (United States) Mar 15 1998, 81 (6) p805-7

Marked lowering of plasma total and low-density lipoprotein cholesterol levels that occur during treatment of dyslipidemia with pharmacologic doses of nicotinic acid result from hepatotoxicity. Therefore, a marked reduction in low-density lipoprotein may suggest generalized liver toxicity and drug treatment should be discontinued.

McKenney JM; McCormick LS; Weiss S; Koren M; Kafonek S; Black DM
Virginia Commonwealth University, Richmond, USA.
Am J Med (United States) Feb 1998, 104 (2) p137-43

BACKGROUND: To assess the lipid-lowering effects and safety of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia.

METHODS: We performed a randomized, open-label, parallel-design, active-controlled, study in eight centers in the United States. We enrolled 108 patients with total cholesterol (TC) of > or =200 mg/dL, serum triglycerides (TG) > or =200 and < or =800 mg/dL, and apolipoprotein B (apo B) > or =110 mg/dL. Patients were randomly assigned to receive atorvastatin 10 mg once daily (n=55) or immediate-release niacin 1 g three times daily for 12 weeks (n=53). Patients were stratified based on low-density lipoprotein cholesterol (LDL-C): Patients with LDL-C > or =135 mg/dL were considered to have combined hyperlipidemia and patients with LDL-C <135 mg/dL were considered to have isolated hypertriglyceridemia. The primary outcome measure was percent change from baseline in LDL-C. Other lipid levels were evaluated as secondary parameters.

RESULTS: Atorvastatin reduced LDL-C 30% and TC 26% from baseline, and increased high-density lipoprotein cholesterol (HDL-C) 4%. Total TG were reduced 17%. Niacin reduced LDL-C 2%, TC 7%, increased HDL-C 25%, and reduced total TG 29% from baseline. There was a significant difference in LDL-C reduction , the primary efficacy parameter, between the two treatment groups (P <0.05, favoring atorvastatin), as well as a significant difference in the improvement in HDL-C (P <0.05, favoring niacin). The effect of atorvastatin was relatively consistent between patients with combined hyperlipidemia and isolated hypertriglyceridemia, whereas there was more variability between these strata in the niacin treatment group. Atorvastatin was better tolerated than niacin .

CONCLUSION: Atorvastatin may allow patients with combined hyperlipidemia to be treated with monotherapy and offers an efficacious and well-tolerated alternative to niacin for the treatment of patients with isolated hypertriglyceridemia.

Brown BG; Zambon A; Poulin D; Rocha A; Maher VM; Davis JW; Albers JJ; Brunzell JD
Department of Medicine, University of Washington School of Medicine, Seattle 98195, USA.
Am J Cardiol (United States) Feb 26 1998, 81 (4A) p52B-59B

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. (20 Refs.)

Gotto A.M. Jr.
Dr. A.M. Gotto Jr., Weill Medical College, Olin Hall, 445 E. 69th Street, New York, NY 10021 United States
American Journal of Cardiology (United States), 1998, 82/9 A (22Q-25Q)

The data for an independent association between triglyceride concentrations and risk for coronary artery disease (CAD) are equivocal, unlike the data for low-density lipoprotein (LDL) cholesterol and high- density lipoprotein (HDL) cholesterol , which show strong, consistent, and opposing correlations with CAD risk. There is some evidence for triglyceride as an independent risk factor in certain subgroups, for example, women 50-69 years of age (Framingham Heart Study) and in patients with noninsulin- dependent diabetes. However, the evidence is stronger for triglyceride as a synergistic CAD risk factor. For example, patients with the 'lipid triad' of high LDL cholesterol , low HDL cholesterol , and high triglyceride accounted for most of the event reduction with lipid-lowering therapy in the Helsinki Heart Study. An important confounder of the correlation between triglyceride and CAD risk is the heterogeneity of triglyceride, rich lipoproteins: the larger triglyceride-rich particles are thought not to be associated with CAD risk, whereas the smaller (and denser) particles are believed to be atherogenic. At present, measurement of fasting triglyceride levels and triglyceride assessment in conjunction with LDL cholesterol and HDL cholesterol concentrations are the most practical methods of evaluating hypertriglyceridemia in CAD risk, although postprandial lipemia may prove a better indicator of atherogenicity. Management of hypertriglyceridemia should initially focus on nonpharmacologic therapy (i.e., diet, exercise, weight control, and alcohol reduction). In diabetic patients, meticulous glycemic control is also important. However, if this approach proves inadequate, there are several pharmacologic options. Fibrates may be effective in decreasing triglyceride and increasing HDL cholesterol . Nicotinic acid (niacin) has been shown to decrease triglyceride, increase HDL cholesterol , lower LDL cholesterol , and decrease lipoprotein(a); it also decreases fibrinogen. The statins appear to be effective in decreasing triglyceride and LDL cholesterol in hypertriglyceridemia; however, they do not normalize metabolism of apolipoprotein B, and HDL cholesterol may remain low. Therefore, combination with a fibrate or niacin may be appropriate. Attention to hypertriglyceridemia with respect to increased CAD risk represents an important step in assessing global risk for CAD development.

Kwiterovich P.O. Jr.
Dr. P.O. Kwiterovich Jr., Johns Hopkins Hospital, CMSC 604, 600 North Wolfe Street, Baltimore, MD 21287-3654 United States
American Journal of Cardiology (United States), 1998, 82/9 A (13Q-21Q)

Landmark clinical studies in the past 5 years that demonstrated diminished mortality and first coronary events following lowering of low- density lipoprotein (LDL) cholesterol stimulated considerable interest in the medical community. Yet, high-density lipoprotein (HDL) cholesterol , which transports circulating cholesterol to the liver for clearance, clearly also exerts antiatherogenic effects. The Framingham Heart Study produced compelling epidemiologic evidence indicating that a low level of HDL cholesterol was an independent predictor of coronary artery disease (CAD). Emerging experimental and clinical findings are, collectively, now furnishing a solid scientific foundation for this relation. First, the reverse cholesterol transport pathway-including the roles of nascent (pre-beta) HDL, apolipoprotein A-I, lecithin-cholesterol acyltransferase (LCAT), cholesteryl ester transport protein, and hepatic uptake of cholesteryl ester from HDL by liver-is better understood. For example, the identification of a hepatic HDL receptor, SR-BI, suggests a mechanism of delivery of cholesteryl ester to liver that differs from the receptor-mediated uptake of LDL. Second, apolipoprotein A-I, the major protein component of HDL, and 2 enzymes on HDL, paraoxonase and platelet-activating factor acetylhydrolase appear to diminish the formation of the highly atherogenic oxidized LDL. Third, lower levels of HDL cholesterol are associated in a dose-response fashion with the severity and number of angiographically documented atherosclerotic coronary arteries. Fourth, low HDL cholesterol predicts total mortality in patients with CAD and desirable total cholesterol levels (<200 mg/dL). Fifth, low HDL cholesterol concentrations appear to be associated with increased rates of restenosis after percutaneous transluminal coronary angioplasty. In terms of elevating HDL cholesterol , cessation of cigarette smoking, reduction to ideal body weight, and regular aerobic exercise all appear important. Most medications used to treat dyslipidemias will raise HDL cholesterol levels modestly; however, niacin appears to have the greatest potential to do so, and can increase HDL cholesterol up to 30%. Recognizing these data, the most recent report of the National Cholesterol Education Program identified low HDL cholesterol as a CAD risk factor and recommended that all healthy adults be screened for both total cholesterol and HDL cholesterol levels.

Yee H.S.; Fong N.T.
H.S. Yee, Pharmacy Service, Dept. of Veterans Affairs Med. Ctr., 4150 Clement St., San Francisco, CA 94121 United States
Annals of Pharmacotherapy (United States), 1998, 32/10 (1030-1043)

OBJECTIVE: To review the efficacy and safety of atorvastatin in the treatment of dyslipidemias.

DATA SOURCES: A MEDLINE search (January 1960- April 1998), Current Contents search, additional references listed in articles, and unpublished data obtained from the manufacturer were used to identify data from scientific literature. Studies evaluating atorvastatin (i.e., abstracts, clinical trials, proceedings, data on file with the manufacturer) were considered for inclusion.

STUDY SELECTION: English- language literature was reviewed to evaluate the pharmacology, pharmacokinetics, therapeutic use, and adverse effects of atorvastatin. Additional relevant citations were used in the introductory material and discussion.

DATA EXTRACTION: Open and controlled animal and human clinical studies published in English-language literature were reviewed and evaluated. Clinical trials selected for inclusion were limited to those in human subjects and included data from animals if human data were not available.

DATA SYNTHESIS: Atorvastatin is a recent hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia, mixed dyslipidemias, and homozygous familial hypercholesterolemia. In patients who have not met the low-density lipoprotein cholesterol (LDL-C) goal as recommended by the National Cholesterol Education Program Adult Treatment Panel II guidelines, atorvastatin 10-80 mg/d may be used as monotherapy or as an adjunct to other lipid-lowering agents and dietary modifications. In placebo-controlled clinical trials, atorvastatin 10-80 mg/d lowered LDL-C by 35-61% and triglyceride (TG) concentrations by 14-45%. In comparative trials, atorvastatin 10-80 mg/d showed a greater reduction of serum total cholesterol (TC), LDL-C, TG concentrations, and apolipoprotein B-100 (apo B) compared with pravastatin, simvastatin, or lovastatin. In comparison, currently available HMG-CoA reductase inhibitors (lovastatin, simvastatin, pravastatin, fluvastatin, cerivastatin) lower LDL-C concentrations by approximately 20- 40% and TG concentrations by approximately 10-30%. In pooled placebo- controlled clinical trials of up to a duration of 52 weeks, atorvastatin in dosages up to 80 mg/d appeared to be well tolerated. The most common adverse effect of atorvastatin was gastrointestinal upset. The incidence of elevated serum hepatic transaminases may be greater at higher dosages of atorvastatin. The risk of myopathy and/or rhabdomyolysis is increased when an HMG-CoA reductase inhibitor is taken concomitantly with cyclosporine, gemfibrozil, niacin , erythromycin, or azole antifungals.

CONCLUSIONS: Atorvastatin appears to reduce TC, LDL-C, TG concentrations, and apo B to a greater extent than do currently available HMG-CoA reductase inhibitors. Atorvastatin may be preferred in patients requiring greater than a 30% reduction in LDL-C or in patients with both elevated LDL-C and TG concentrations, which may obviate the need for combination lipid-lowering therapy. Adverse effects of atorvastatin appear to be similar to those of other HMG-CoA reductase inhibitors and should be routinely monitored. Long-term safety data (>1 y) on atorvastatin compared with other HMG-CoA reductase inhibitors are still needed. Cost-effectiveness studies comparing atorvastatin with other HMG-CoA reductase inhibitors remain a subject for further investigation. Published clinical studies evaluating the impact of atorvastatin on cardiovascular morbidity and mortality are still needed. Additionally, clinical studies evaluating the impact of lipid-lowering therapy in a larger number of women, the elderly (>70 y), and patients with diabetes for treatment of primary and secondary prevention of coronary heart disease are needed.

Hilleman D.E.; Seyedroubari A.
Dr. D.E. Hilleman, Department of Pharmacy Practice, Creighton University, Sch. Pharm./Allied Hlth. Professions, 2500 California Plaza, Omaha, NE 68178 United States
Cardiovascular Reviews and Reports (United States), 1998, 19/5 (32-48)

Atorvastatin is the fifth HMG-CoA reductase inhibitor approved for use in the U.S. The mechanism of action of atorvastatin appears to be similar to other agents in the class. Atorvastatin is metabolized by cytochrome P450 3A4 to several active metabolites. Approximately 70% of the lipid lowering effect of atorvastatin is attributed to its metabolites. Atorvastatin's efficacy is greater than that of other available HMG-CoA reductase inhibitors. At 10 mg/day, atorvastatin reduces LDL cholesterol by 39% and triglycerides by 19%. At the highest FDA approved dose of 80 mg/day, atorvastatin reduces LDL cholesterol by 60% and triglycerides by 37%. Atorvastatin 10 mg/day produces LDL cholesterol reductions that are similar to or greater than the LDL cholesterol reductions achieved with all doses up to 40 mg/day with the other HMG-CoA reductase inhibitors. Atorvastatin is associated with a very low incidence of dose-limiting side effects with a discontinuation rate of less than 2%. The most common side effects are constipation, flatulence, dyspepsia, and abdominal pain. In comparative trials against other HMG-CoA reductase inhibitors, no significant differences in the incidence of side effects were observed. As with other HMG-CoA reductase inhibitors, combined use of atorvastatin with erythromycin, cyclosporin, fibric acid derivatives, niacin , and azole antifungals increases the risk of myopathy. Atorvastatin represents a highly effective HMG-CoA reductase inhibitor that produces greater reductions in LDL cholesterol and triglycerides than other currently available agents in this class. Based on NCEP treatment guidelines in which predetermined LDL cholesterol levels are the goal of therapy, atorvastatin appears to fill a major void that exists with current therapy. For patients requiring a 40% or greater reduction in LDL cholesterol , atorvastatin is the only agent capable of such reductions. The major unresolved issue with atorvastatin is its unknown impact on cardiovascular morbidity and mortality.

Nieuwenhuys CM; Beguin S; Offermans RF; Emeis JJ; Hornstra G; Heemskerk JW
Department of Human Biology, University of Maastricht, The Netherlands.
C.Nieuwenhuys@hb.unimaas.nl
Arterioscler Thromb Vasc Biol (United States) Sep 1998, 18 (9) p1480-9

We investigated the effects of dietary polyunsaturated fatty acids (PUFAs) on blood lipids and processes that determine hemostatic potential: platelet activation, coagulation, and fibrinolysis. For 8 to 10 weeks, Wistar rats were fed a high-fat diet containing various amounts (2% to 16%) of n-3 PUFAs derived from fish oil (FO) or a diet enriched in n-6 PUFAs from sunflower seed oil (SO). Only the FO diets caused a reduction in mean platelet volume, platelet arachidonate level, and formation of thromboxane B2 by activated platelets, but neither of the diets had a measurable effect on platelet activation. The FO-rich diets decreased the plasma concentrations of triglycerides and cholesterol , whereas the SO diet reduced triglycerides only. Parameters of fibrinolysis and standard coagulation times, ie, activated partial thromboplastin time and prothrombin time, were only marginally influenced by these diets. In contrast, dietary FO, but not SO, led to decreased levels of the vitamin K-dependent coagulation factors prothrombin and factor VII, while the level of antithrombin III was unchanged. The endogenous thrombin potential (ETP) was measured with an assay developed to detect the hypocoagulable state of plasma. After activation with tissue factor and phospholipids, the ETP was reduced by 23% or more in plasma from animals fed a diet with >4% FO. No significant effect of the SO diet on ETP was observed. Control experiments with plasma from warfarin-treated rats indicated that the ETP was more sensitive to changes in prothrombin concentration than in factor VII concentration. Taken together, these results indicate that in rats, prolonged administration of n-3 but not n-6 PUFAs can lead to a hypocoagulable state of plasma through a reduced capacity of vitamin K-dependent thrombin generation, with unchanged thrombin inactivation by antithrombin III.

van Vlijmen BJ; Mensink RP; van 't Hof HB; Offermans RF; Hofker MH; Havekes LM
TNO Prevention and Health, Gaubius Laboratory, Leiden, The Netherlands.
J Lipid Res (United States) Jun 1998, 39 (6) p1181-8

Studying the effects of dietary fish oil on VLDL metabolism in humans is subject to both large intra- and interindividual variability. In the present study we therefore used hyperlipidemic apolipoprotein (APO) E*3-Leiden mice, which have impaired chylomicron and very low density lipoprotein (VLDL) remnant metabolism, to study the effects of dietary fish oil on serum lipids and VLDL kinetics under highly standardized conditions. For this, female APOE*3-Leiden mice were fed a fat- and cholesterol -containing diet supplemented with either 0, 3 or 6% w/w (i.e. 0, 6, or 12% of total energy) of fish oil . Fish oil -fed mice showed a significant dose-dependent decrease in serum cholesterol (up to -43%) and triglyceride levels (up to -60%), mainly due to a reduction of VLDL (-80%). LDL and HDL cholesterol levels were not affected by fish oil feeding. VLDL-apoB kinetic studies showed that fish oil feeding resulted in a significant 2-fold increase in VLDL-apoB fractional catabolic rate (FCR). Hepatic VLDL-apoB production was, however, not affected by fish oil feeding. VLDL-triglyceride turnover studies revealed that fish oil significantly decreased hepatic VLDL-triglyceride production rate (-60%). A significant increase in VLDL-triglyceride FCR was observed (+70%), which was not related to increased lipolytic activity. We conclude that APOE*3-Leiden mice are highly responsive to dietary fish oil . The observed strong reduction in serum very low density lipoprotein (VLDL) is primarily due to an effect of fish oil to decrease hepatic VLDL triglyceride production rate and to increase VLDL-apoB fractional catabolic rate.

Sorensen NS; Marckmann P; Hoy CE; van Duyvenvoorde W; Princen HM
Department of Biochemistry and Nutrition, Technical University of Denmark, Lyngby. ninas@mimer.be.dtu.dk
Am J Clin Nutr (United States) Aug 1998, 68 (2) p235-41

We investigated the effect of incorporating n-3 polyunsaturated fatty acids (PUFAs) into the diet on the lipid-class composition of LDLs, their size, and their susceptibility to oxidation. Forty-seven healthy volunteers incorporated 30 g sunflower-oil (SO) margarine/d into their habitual diet during a 3-wk run-in period and then used either SO or a fish -oil -enriched sunflower oil (FO) margarine for the following 4 wk. Plasma concentrations of total cholesterol , triacylglycerols, HDL cholesterol , LDL cholesterol , and apolipoproteins A-I and B did not differ significantly between the groups during intervention. The FO margarine increased the concentration of n-3 very-long-chain PUFAs in the LDL particles, showing 93% (P < or = 0.0001), 8% (P = 0.05), and 35% (P = < 0.0001) increases in eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid, respectively, in the FO group compared with 3%, 7%, and 7%, respectively, in the SO group during the intervention. The cholesterol content of the LDL particles increased in the FO group [total cholesterol : 6% (P = 0.008); cholesterol ester: 12% (P = 0.014)], although it was not significantly different from that in the control group, whereas the other lipid classes and the size of the LDL particles remained unchanged in both groups. A reduction in the alpha-tocopherol content in LDL (6%, P = 0.005) was observed in the FO group. Ex vivo oxidation of LDL induced with Cu2+ showed a significantly reduced lag time (from 91 to 86 min, P = 0.003) and lower maximum rate of oxidation (from 10.5 to 10.2 nmol x mg(-1) x min(-1), P = 0.003) after intake of the FO margarine. The results indicate that consumption of the FO compared with the SO margarine had no effect on LDL size and lipid composition and led to minor changes in LDL a-tocopherol content and oxidation resistance.

Corrigan FM; Horrobin DF; Skinner ER; Besson JA; Cooper MB
Argyll and Bute Hospital, Lochgilphead, UK.
Int J Biochem Cell Biol (England) Feb 1998, 30 (2) p197-207

The long-chain fatty acid composition of cholesterol esters, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI) from parahippocampal cortex of Alzheimer's disease (AD) patients and control subjects was examined. In general the PC fraction contained less polyunsaturated long-chain fatty acids than did PE, PS or PI. Of the n-6 polyunsaturated long-chain fatty acids, PI contained the greatest incorporation of these acids followed by PE. There were significant differences between controls and AD patients in total n-6 EFAs. Arachidonic acid (C20:4n-6) was the predominant fatty acid of this family found to be present. In AD, PE and PS showed a deficit of adrenic acid (C22:4n-6) content and PE also contained less arachidonic acid. In AD subjects, the cholesterol esters contained significantly less n-3 polyunsaturated fatty acids with, specifically, a reduction in alpha-linolenic acid. Acetyl CoA content of hippocampal cortex was greater in AD patients than in control subjects indicating either an increased extent of oxidative metabolism or a failure to utilise acetyl CoA for anabolic processes. Abnormal magnitude of oxidative processes could give rise to the biosynthesis of PE and PS species containing less n-6 polyunsaturated fatty acids than occurs in control subjects.

de Lorgeril M; Salen P; Martin JL; Monjaud I; Boucher P; Mamelle N
Laboratoire de Physiologie and GIP-Exercice, Centre Hospitalo-Universitaire de Saint-Etienne and School of Medicine, France.
Arch Intern Med (United States) Jun 8 1998, 158 (11) p1181-7

BACKGROUND: The Mediterranean dietary pattern is thought to reduce the risk of cancer in addition to being cardioprotective. However, no trial has been conducted so far to prove this belief.

METHODS: We compared overall survival and newly diagnosed cancer rate among 605 patients with coronary heart disease randomized in the Lyon Diet Heart Study and following either a cardioprotective Mediterranean-type diet or a control diet close to the step 1 American Heart Association prudent diet.

RESULTS: During a follow-up of 4 years, there were a total of 38 deaths (24 in controls vs 14 in the experimental group), including 25 cardiac deaths (19 vs 6) and 7 cancer deaths (4 vs 3), and 24 cancers (17 vs 7). Exclusion of early cancer diagnoses (within the first 24 months after entry into the trial) left a total of 14 cancers (12 vs 2). After adjustment for age, sex, smoking, leukocyte count, cholesterol level, and aspirin use, the reduction of risk in experimental subjects compared with control subjects was 56% (P=.03) for total deaths, 61% (P=.05) for cancers, and 56% (P=.01) for the combination of deaths and cancers. The intakes of fruits, vegetables, and cereals were significantly higher in experimental subjects, providing larger amounts of fiber and vitamin C (P<.05). The intakes of cholesterol and saturated and polyunsaturated fats were lower and those of oleic acid and omega - 3 fatty acids were higher (P<.001) in experimental subjects. Plasma levels of vitamins C and E (P<.05) and omega -3 fatty acids (P<.001), measured 2 months after randomization, were higher and those of omega-6 fatty acids were lower (P<.001) in experimental subjects.

CONCLUSIONS: This randomized trial suggests that patients following a cardioprotective Mediterranean diet have a prolonged survival and may also be protected against cancer. Further studies are warranted to confirm the data and to explore the role of the different lipids and fatty acids in this protection.

Fickova M; Hubert P; Cremel G; Leray C
Institute of Experimental Endocrinology, Slovak Academy of Sciences, 83306 Bratislava, Slovakia.
J Nutr (United States) Mar 1998, 128 (3) p512-9

The influence of dietary (n-3) compared with (n-6) polyunsatured fatty acids (PUFA) on the lipid composition and metabolism of adipocytes was evaluated in rats over a period of 1 week. Isocaloric diets comprised 16.3 g/100 g protein, 53.8 g/100 g carbohydrate and 21.4 g/100 g lipids, the latter containing either (n-3) PUFA (32.4 mol/100 mol) or (n-6) PUFA (37.8 mol/100 mol) but having identical contents of saturated, monounsaturated and total unsaturated fatty acids and identical polyunsaturated to saturated fatty acid ratios and double bond indexes. Despite comparable food intake, significantly smaller body weight increments and adipocyte size were observed in rats of the (n-3) diet group after feeding for 1 wk. Rats fed the (n-3) diet also had significantly lower concentrations of serum triglycerides, cholesterol and insulin compared with those fed the (n-6) diet, although levels of serum glucose and free fatty acids did not differ in the two dietary groups. In the (n-6) diet group, the (n-6) and (n-3) PUFA contents of plasma triglycerides, free fatty acids and phospholipids were 30-60% higher and 60-80% lower, respectively, than in the (n-3) diet group, whereas adipocyte plasma membrane phospholipids showed a significantly higher unsaturated to saturated fatty acid ratio and greater fluidity. Glycerol release in response to noradrenaline was significantly higher in the adipocytes of rats fed the (n-3) diet, whereas the antilipolytic effect of insulin generally did not differ in the two groups. Finally, insulin stimulated the transport of glucose and its incorporation into fatty acids to a lesser extent in adipocytes of (n-3) diet fed rats compared with (n-6) diet fed rats. This reduction in the metabolic effects of insulin in rats fed a (n-3) diet for 1 wk could be related to smaller numbers and a lower binding capacity of the insulin receptors on adipocytes and/or to a lesser degree of phosphorylation of the 95 kDa beta subunit of the receptor. In conclusion, dietary intake for 1 wk of (n-3) rather than (n-6) PUFA is sufficient to induce significant differences in the lipid composition and metabolic responses to insulin of rat adipocytes.

Brun J.F.; Khaled S.; Raynaud E.; Bouix D.; Micallef J.P.; Orsetti A.
J.F. Brun, Svc. d'Explor. Phys. Hormones Metab., CHRU de Montpellier, F-34059 Montpellier France
Clinical Hemorheology and Microcirculation (United States), 1998, 19/2 (89-104)

The life-extending effects of regular exercise are related to a decrease in both coronary and peripheral vascular morbidity, associated with some improvements in cardiovascular risk factors. A possible link between the beneficial metabolic and hemodynamic effects of exercise could be blood rheology, which is markedly affected by exercise. We propose here a description of the hemorheological effects of exercise as a triphasic phenomenon. Short-term effects of exercise are an increase in blood viscosity resulting from both fluid shifts and alterations of erythrocyte rheologic properties (rigidity and aggregability). Increased blood lactate, stress, and acute phase play a role in this process. Middle-term effects of regular exercise are a reversal of these acute effects with an increase in blood fluidity, explained by plasma volume expansion (autohemodilution) that lowers both plasma viscosity and hematocrit. Long-term effects further improve blood fluidity, parallel with the classical training-induced hormonal and metabolic alterations. While body composition, blood lipid pattern, and fibrinogen improve (thus decreasing plasma viscosity), erythrocyte metabolic and rheologic properties are modified, with a reduction in aggregability and rigidity. On the whole, these improvements reflect a reversal of the so- called 'insulin-resistance syndrome' induced by a sedentary lifestyle. Since impaired blood rheology has been demonstrated to be at risk for vascular diseases, the hemorheologic effects of exercise can be hypothesized to be a mechanism (or at least a marker) of risk reversal. This latter point requires further investigation. The physiological meaning of the tripbasic pattern of exercise-induced alterations of blood theology is uncompletely understood, but increased blood fluidity may improve several steps of oxygen transfer to muscle, as clearly demonstrated in hypoxic conditions. Increasing evidence emerges from the literature, that blood fluidity is a physiological determinant of fitness.

O'Brien T.; Nguyen T.T.; Zimmerman B.R.
Dr. T. O'Brien, Div. of Endocrinol., Metabol./Nutri., Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905 United States
Mayo Clinic Proceedings (United States), 1998, 73/10 (969-976)

The increased risk of coronary artery disease in subjects with diabetes mellitus can be partially explained by the lipoprotein abnormalities associated with diabetes mellitus. Hypertriglyceridemia and low levels of high-density lipoprotein are the most common lipid abnormalities. In type 1 diabetes mellitus, these abnormalities can usually be reversed with glycemic control. In contrast, in type 2 diabetes mellitus, although lipid values improve, abnormalities commonly persist even after optimal glycemic control has been achieved. Screening for dyslipidemia is recommended in subjects with diabetes mellitus. A goal of low-density lipoprotein cholesterol of less than 130 mg/dL and triglycerides lower than 200 mg/dL should be sought. Several secondary prevention trials, which included subjects with diabetes, have demonstrated the effectiveness of lowering low-density lipoprotein cholesterol in preventing death from coronary artery disease. The benefit of lowering triglycerides is less clear. Initial approaches to lowering the levels of lipids in subjects with diabetes mellitus should include glycemic control, diet, weight loss, and exercise. When goals are not met, the most common drugs used are hydroxymethylglutaryl coenzyme A reductase inhibitors or fibrates.

Jabbar M.A.; Zuhri-Yafi M.I.; Larrea J.
Dr. M.A. Jabbar, Department of Pediatrics, Hurley Medical Center, 1 Hurley Plaza, Flint, MI 48502 United States
Journal of the American College of Nutrition (United States), 1998, 17/5 (458-461)

Objective: To compare the short and long term effectiveness of fish oil , insulin, and gemfibrozil in a non-diabetic patient with severe hypertriglyceridemia.

Method: An adolescent male with hypertriglyceridemia (triglyceride level 4575 mg/dl) and abdominal pain was treated with the goal of immediate reduction and maintenance of triglyceride (TG) level below 1000 mg/dl. Fish oil , insulin and gemfibrozil were administered sequentially, in separate time blocks, for a duration of 3, 6, and 6 months, respectively.

Results: Fish oil took several weeks to lower TG level, and patient compliance during 3 months of therapy was inadequate. Insulin was effective in immediately lowering the TG level, but was unable to maintain the level below 1000 mg/dl. Gemfibrozil was ineffective in achieving the immediate reduction of TG level; however, it was adequate in maintaining the desired level in the long-term and patient compliance was better than with the fish oil .

Conclusion: In patients with risk of pancreatitis due to severe hypertriglyceridemia, immediate reduction of the triglyceride level is achievable by using a single dose of regular insulin (0.1 unit/kg, subcutaneous) while long-term maintenance therapy can be provided by gemfibrozil.

Seljeflot I.; Arnesen H.; Brude I.R.; nenseter M.S.; Drevon C.A.; Hjermann I.
I. Seljeflot, Medical Outpatient Clinic, Department of Medicine, Ulleval University Hospital, N-0407 Oslo Norway
European Journal of Clinical Investigation (United Kingdom), 1998, 28/8 (629-635)

Background. Increased expression of cell adhesion molecules and increased procoagulant activity of the vascular endothelium have been postulated to characterize dysfunctional endothelium. The cellular effects of n-3 fatty acids (n-3 FAs) and antioxidants are still not clarified.

Methods. In a randomized, factorial two-by-two design study, we have investigated 41 male smokers with hyperlipidaemia before and after 6 weeks of supplementation with either n-3 FAs (4.8 g daily) or placebo with the addition of antioxidants (1.50 mg of vitamin C, 75 mg of vitamin E and 15 mg of p-carotene daily) or placebo with regard to the effects on some endothelial cell markers: thrombomodulin (sTM), von Willebrand factor (vWF), tissue plasminogen activator antigen (tPAag) and soluble forms of the cell adhesion molecules E-selectin, P-selectin and vascular cell adhesion molecule 1 (VCAM-1).

Results. In the n-3 FA group, significant reductions in the plasma levels of vWF (P = 0.034) and sTM (P<0.001) were demonstrated compared with placebo, whereas increased levels were found for E-selectin (P = 0.001) and VCAM-1 (P = 0.010). In the antioxidant group, no differences in changes were noted for any of the variables.

Conclusion. The reduction in the levels of sTM and VWF with n-3 FA supplementation could indicate an improvement with regard to the haemostatic markers of endothelial dysfunction, whereas the simultaneous increase in the soluble forms of E-selectin and VCAM-1 may suggest an adverse effect on the inflammatory system. The antioxidants seem to be neutral in their effect on these endothelial cell markers in our study population of smokers. The interpretation of the soluble forms of these molecules are, however, still debatable.

Swahn E.; von Schenck H.; Olsson A.G.
Dr. E. Swahn, Department of Cardiology, Institution of Internal Medicine, University Hospital, S-581 85 Linkoping Sweden
Clinical Drug Investigation (New Zealand), 1998, 15/6 (473-482)

This study investigated whether an ethyl ester preparation of fish oil (omega-3) could normalise raised plasma concentrations of triglycerides, apolipoprotein CIII on apolipoprotein B-containing particles (LP CIII:B) found in patients with recent acute myocardial infarction. We also studied the effect of fish oil on antithrombin III levels. Out of 75 patients with a plasma triglyceride value less than or equal to 2.0 mmol/L, 22 normalised their triglycerides during diet and were therefore not randomised. The remaining patients were randomly assigned to 12 weeks' treatment with a daily dose of 4g omega-3 or placebo. Mean plasma triglyceride concentrations were reduced by 24% from 3.10 plus or minus 1.15 (SD) to 2.53 plus or minus 0.94 mmol/L (p < 0.001) on omega-3 (p < 0.001 vs placebo). The reduction was due to decreases in very low density lipoprotein concentrations. Total apolipoprotein CIII decreased significantly. This was due to reductions in LP CIII:non B concentrations, but the ratio LP CIII:non B/LP CIII:B was unaffected because of a slight insignificant decrease in LP CIII:B. The plasma triglyceride decreasing effect of omega-3 could therefore not be due to redistribution of CIII between lipoproteins. Low density lipoprotein (LDL) cholesterol increased significantly with omega-3 by 7%, and antithrombin III increased significantly with fish oil . In conclusion, omega-3 had a moderate plasma triglyceride lowering effect and increased LDL cholesterol slightly, while antithrombin III increased in patients with hypertriglyceridaemia who had recently experienced a myocardial infarction. Myocardial infarction starts via a thrombotic process at an atherosclerotic lesion in a coronary artery. Most patients developing this disease have an abnormal plasma lipoprotein pattern consisting of slightly raised triglycerides (TGs), moderately elevated total cholesterol , and low high density lipoprotein (HDL) cholesterol values predisposing to atherosclerosis. Hypertriglyceridaemia may be associated with a greater risk for thrombosis in postmyocardial infarction patients because of a reduced fibrinolytic capacity. The dyslipidaemia may also indicate an unfavourable distribution of plasma lipoprotein particles in patients with myocardial infarction. Dietary changes normalise the dyslipidaemia in some patients but are inadequate in others. In these latter patients pharmacological lipid-lowering treatment is necessary. The myocardial infarction patient with an athero-thrombogenic syndrome could theoretically therefore benefit from a pharmacological agent acting on both the thrombotic and lipidaemic pathophysiological pathways. The pharmacological potency of the omega -3 -fatty acids allows for this possibility. It has been known since the mid 1970s that omega -3 -fatty acids are effective in lowering plasma triglyceride concentrations. They also increase the concentration of HDL cholesterol slightly. Their effects on cholesterol have varied, with some studies showing increases and others decreases. These fatty acids also inhibit platelet aggregation. It was therefore of interest to expand the experience of this type of treatment to effects on plasma lipoprotein particle distribution. We also studied parameters of fibrinolysis since the literature shows diverging results of omega - 3 - fatty acids on these parameters. In the present study we tested a new compound, omega-3, an oil consisting of ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with the aim of normalising dyslipidaemia, and reducing the thrombotic tendency in a potentially important target population for such treatment, postmyocardial infarction patients. The high EPA and DHA concentration in omega-3 made a convenient intake of only four capsules daily possible. The design of the study followed the current guidelines for secondary prevention of ischaemic heart disease.

Sirtori C.R.; Crepaldi G.; Manzato E.; Mancini M.; Rivellese A.; Paoletti R.; Pazzucconi F.; Pamparana F.; Stragliotto E.
C.R. Sirtori, Center E. Grossi Paoletti, University of Milano, Milan Italy
Atherosclerosis (Ireland), 1998, 137/2 (419-427)

n-3 Fatty acids in the form of ethyl esters (EE) allow lower daily doses and improved compliance. Administration of n-3 fatty acids to patients with glucose intolerance has led to controversial findings, some studies indicating worsening of the disorder, others no effect, or an improvement. A total of 935 patients with hypertriglyceridemia, associated with additional cardiovascular risk factors, i.e. glucose intolerance, NIDDM and/or arterial hypertension were entered a double blind (DB) protocol lasting 6 months with n-3 BE versus placebo, followed by a further 6 months of open study (n = 868) on 2 g a day of n-3 EE. At the end of the DB period, triglyceridemia in the total group was reduced significantly more by n-3 EE, without alterations in glycemic parameters. In the 6 months open follow up, patients on n-3 EE with type IIB hyperlipoproteinemia showed a significant reduction of total cholesterol , both in cases with (- 4.15% vs. the 6 month levels) and without NIDDM (- 3.8%). HDL-cholesterol had an overall mean rise of 7.4%, maximal in type IV patients with (+9.1%) and without (+ 10.1%) NIDDM. No alterations in glycemic parameters were detected in treated patients. Administration of n-3 EE to patients with hypertriglyceridemia associated with NIDDM or impaired glucose tolerance appears safe and effective.

Abe Y.; El-Masri B.; Kimball K.T.; Pownall H.; Reilly C.F.; Osmundsen K.; Smith C.W.; Ballantyne C.M.
Dr. C.M. Ballantyne, Baylor College of Medicine, 6565 Fannin, MS A-601, Houston, TX 77030 United States
Arteriosclerosis, Thrombosis, and Vascular Biology (United States), 1998, 18/5 (723-731)

Hypertriglyceridemia may contribute to the development of atherosclerosis by increasing expression of cell adhesion molecules (CAMs). Although the cellular expression of CAMs is difficult to assess clinically, soluble forms of CAMs (sCAMs) are present in the circulation and may serve as markers for CAMs. In this study, we examined the association between sCAMs and other risk factors occurring with hypertriglyceridemia, the effect of triglyceride reduction on sCAM levels, and the role of soluble vascular cell adhesion molecule-1 (sVCAM-1) in monocyte adhesion in vitro. Compared with normal control subjects (n=20), patients with hypertriglyceridemia and low HDL (n=39) had significantly increased levels of soluble intercellular adhesion molecule-1 (sICAM-1) (316plus or minus28.8 versus 225plus or minus16.6 ng/mL), sVCAM-1 (743plus or minus52.2 versus 522plus or minus43.6 ng/mL), and soluble E-selectin (83plus or minus5.9 versus 49three-quarter.6 ng/ml). ANCOVA showed that the higher sCAM levels in patients occurred independently of diabetes mellitus and other risk factors. In 27 patients who received purified n-3 fatty acid (Omacor) 4 g/d for less than or equal to7 months, triglyceride level was reduced by 47plus or minus4.6%, sICAM-1 level was reduced by 9plus or minus3.4% (P=.02), and soluble E-selectin level was reduced by 16plus or minus3.2% (P<.0001), with the greatest reduction in diabetic patients. These results support previous in vitro data showing that disorders in triglyceride and HDL metabolism influence CAM expression and treatment with fish oils may alter vascular cell activation. In a parallel-plate flow chamber, recombinant sVCAM-1 at the concentration seen in patients significantly inhibited adhesion of monocytes to interleukin-1-stimulated cultured endothelial cells under conditions of flow by 27.5plus or minus7.2%. Thus, elevated sCAMs may negatively regulate monocyte adhesion.

Borthwick L.
Dr. L. Borthwick, Lister Hospital, Correy's Mill Lane, Stevenage SG1-4AB United Kingdom
Clinical Drug Investigation (New Zealand), 1998, 15/5 (397-404)

The objective of this study was to investigate the effects and tolerability of an omega-3 ethyl ester concentrate (Omacor (R)) on serum lipid concentrations in patients with hyperlipidaemia. A multicentre, double-blind, randomised, placebo-controlled trial was performed in the hospital and general practice setting. 84 patients with hyperlipidaemia were given a therapeutic lipid-lowering diet for 10 weeks. Of these, 55 patients were randomised to a 12-week treatment period. 47 patients completed the study and two patients withdrew because of adverse events. Randomised patients received omega-3 ethyl ester concentrate or corn oil (placebo), both administered at a dose of 2 g twice daily in soft gelatin capsules. Main outcome measures included changes in eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA) content of serum phospholipids, total serum triglycerides, total serum cholesterol , and high density lipoprotein (HDL) cholesterol between baseline (week 10) and the end of treatment (week 22). After 12 weeks of treatment, patients receiving the omega-3 ethyl ester concentrate showed a significant increase in the EPA/DHA content of serum phospholipids (p < 0.0001). No significant changes in serum phospholipids were observed in the patients given placebo. A mean [standard deviation (SD)] reduction in serum triglyceride of 28.3 (19.1)% (p = 0.0001) occurred in patients given the omega-3 ethyl ester concentrate. Patients receiving corn oil showed a nonsignificant mean (SD) increase in serum triglyceride of 9.1 (24.8)%. Therefore, a difference between the groups of 37.4% in favour of active treatment was found (p < 0.0001). Total serum cholesterol did not change significantly in either treatment group. Mean (SD) HDL cholesterol concentrations showed an increase of 0.9 (21.6)% in patients receiving omega-3 ethyl ester concentrate and 3.6 (24.3)% in the corn-oil group; however, neither increase was significant. In conclusion, omega-3 ethyl ester concentrate, 4 g/day, produced a significant reduction in mean serum triglyceride concentration in patients with hyperlipidaemia and was well tolerated.

Willumsen N.; Vaagenes H.; Holmsen H.; Berge R.K.
R.K. Berge, Department of Clinical Biology, Division of Biochemistry, University of Bergen, N-5021 Bergen Norway
Biochimica et Biophysica Acta - Biomembranes (Netherlands), 1998, 1369/2 (193-203)

A series of 2-substituted eicosapentaenoic acid (EPA) derivatives (as ethyl esters) have been synthesized and evaluated as hypolipidemic and antithrombotic agents in feeding experiments in rats. Repeated administration of purified 2-methyleicosapentaenoic acid and its deuterium analogues (all as ethyl esters) to rats resulted in a decrease in plasma triglycerides and high density lipoprotein cholesterol . The 2-methyl-EPA analogues were, apparently, four times more potent than EPA in inducing the triglyceride lowering effect. The 2-deuterium-2-methyl-EPA decreased plasma cholesterol level to similar 40%. A moderate enlargement of the liver was observed in 2-methyl-EPA treated rats. This was accompanied with an acute reduction in the liver content of triglycerides and a stimulation of peroxisomal beta-oxidation and fatty acyl-CoA oxidase activity. The results suggest that the triglyceride-lowering, effect of 2-methyl-EPA may be due to a reduced supply of fatty acids for hepatic triglyceride biosynthesis because of increased fatty acid oxidation. Platelet aggregation with ADP and A23187 was performed ex vivo in platelet-rich plasma, after administration of different doses of the EPA-derivatives for five days. EPA and 2,2-dideuterium EPA had no effect on ADP-induced aggregation, while 2-deuterium-, 2-methyl- and 2-deuterium-2-methyl EPA produced a biphasic effect, i.e. potentiation and inhibition at low (250 mg/day kg body weight) and higher doses (600-1300 mg/day kg body weight), respectively. A23187-induced platelet aggregation was affected in a similar way by feeding the 2-substituted EPA derivatives, except that 2-deuterium-2-methyl EPA had no effect relative to EPA itself and that the inhibition was far greater than that for ADP-induced aggregation (similar 100% inhibition with 600 mg 2-methyl-EPA/day kg body weight). The ranking order of the EPA-derivatives to affect platelet aggregation and to cause hypolipidemia was different, suggesting different mechanisms. Our observations suggest that the effects of the EPA derivatives on platelet aggregation could be related to the degree of bulkiness around C2 and that an asymmetric substitution at C2 caused inhibition of platelet aggregation while a symmetric substitution did not. It is suggested that the bulky, asymmetric derivatives inhibit platelet aggregation by altering platelet membrane phospholipid packing.

Bordia A; Verma SK; Srivastava KC
Department of Medicine, RNT Medical College, Udaipur, India.
Prostaglandins Leukot Essent Fatty Acids (Scotland) Apr 1998, 58 (4) p257-63

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.

Isaacsohn JL; Moser M; Stein EA; Dudley K; Davey JA; Liskov E; Black HR
The Christ Hospital Cardiovascular Research Center, Cincinnati, Ohio, USA.
ejlmarc@aol.com
Arch Intern Med (United States) Jun 8 1998, 158 (11) p1189-94

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.

Berthold HK; Sudhop T; von Bergmann K
Department of Clinical Pharmacology, University of Bonn, Germany.
berthold@uni-bonn.de
JAMA (United States) Jun 17 1998, 279 (23) p1900-2

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.

Klipstein-Grobusch K; Kroke A; Voss S; Boeing H
Deutsches Institut fur Ernahrungsforschung, Abteilung Epidemiologie.
Z Ernahrungswiss (Germany) Mar 1998, 37 (1) p38-46

Differences in dietary habits and lifestyle factors associated with a high dietary intake of fruit and vegetables are discussed and used to explain the disparity between results of observational epidemiologic studies consistently showing antioxidative vitamins to exert a protective effect on chronic diseases, and intervention studies so far not confirming this association. Within the scope of the "Brandenburger Ernahrungs- und Krebsstudie", the East German contribution to the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined whether study participants using supplements on a regular basis--minerals, vitamins, protein formulation, bran/linseed, fiber, yeast or garlic pills--differed from those who did not report use of supplements according to selected lifestyle factors and dietary intake of vitamins, minerals, fiber, cholesterol , and fat from food. The study sample consisted of 10,522 participants (4,500 men and 6,022 women) aged 35-65 years enrolled in the cohort from January 1995 to July 1996. Regular intake of one or more supplements during the past year was reported by 32.6% of women and 25.5% of men. Vitamin supplements were used by 18.8% of the women and 15.8% of the men. Figures for minerals were 14.2% for women and 8.6% for men, respectively. Garlic pills were taken regularly by 9.7% of men and 9.3% of women. Prevalence of supplement use was generally higher in women and was more pronounced in elderly participants. The most frequently used combinations were vitamin and mineral supplements, followed by a combination of garlic and either vitamin or mineral supplements. Increased use of supplements was significantly associated with higher level of education attained, regular engagement in sporting activities, health complaints, and dietary change during the previous year. No association between use of supplements and smoking status nor elevated alcohol consumption was observed. Body mass index above 30 was significantly related to increased intake of garlic pills, and in women to significantly increased use of vitamin and mineral supplements. For both men and women, age-adjusted consumption of fruit and vegetables and intake of vitamins, minerals, and fiber from food was higher for participants using mineral but also vitamin supplements compared to those who did not use these supplements. For the cohort of the "Brandenburger Ernahrungs- und Krebsstudie" we observed on the one hand that age, gender, and health-conscious lifestyle factors were related to supplement use. On the other hand presence of subjective health complaints was related to supplement use, especially for use of vitamins and minerals. Participants, who regularly consumed minerals and vitamins were also shown to have a higher intake of foods and nutrients considered to exert an antioxidative effect.

Orekhov AN; Tertov VV
Institute of Experimental Cardiology, Russian Academy of Medical Sciences, Moscow, Russia.
Lipids (United States) Oct 1997, 32 (10) p1055-60

In the present study, the mechanism of the in vitro effect of garlic powder extract (GPE) on lipid content of cultured human aortic cells was investigated. The addition of GPE abolished atherogenic blood serum-induced accumulation of free cholesterol , triglycerides, and cholesteryl esters in smooth muscle cells derived from uninvolved (normal) intima. In cells isolated from atherosclerotic plaque, GPE lowered these lipids. GPE inhibited lipid synthesis both in normal and atherosclerotic cells. It inhibited acyl-CoA:cholesterol acyltransferase activity that participates in the cholesteryl ester formation and stimulated cholesteryl ester hydrolase that degrades cholesteryl esters. This may explain the lipid reduction caused by GPE in atherosclerotic cells. GPE inhibited the uptake of modified low density lipoprotein and degradation of lipoprotein-derived cholesteryl esters, thus considerably reducing the intracellular accumulation of cholesteryl esters. This suggests the mechanism responsible for the prevention of lipid accumulation in aortic cells caused by atherogenic blood serum.

Morcos NC
Division of Cardiology, University of California, Irvine 92717, USA.
J Natl Med Assoc (United States) Oct 1997, 89 (10) p673-8

Fish consumption has been shown to influence epidemiology of heart disease, and garlic has been shown to influence triglyceride levels. This study was undertaken to evaluate the effect of fish oil and garlic combinations as a dietary supplement on the lipid subfractions. Forty consecutive subjects with lipid profile abnormalities were enrolled in a single-blind, placebo-controlled crossover study. Each subject received placebo for 1 month and fish oil (1800 mg of eicosapentanoic acid [EPA] + 1200 mg of docosahexanoic acid) with garlic powder (1200 mg) capsules daily for 1 month. Lipid fractionation was performed prior to study initiation, after the placebo period, and after the intervention period. Subjects all had cholesterol levels > 200. Subjects were instructed to maintain their usual diets. Supplementation for 1 month resulted in an 11% decrease in cholesterol , a 34% decrease in triglyceride, and a 10% decrease in low-density lipoprotein (LDL) levels, as well as a 19% decrease in cholesterol /high-density lipoprotein (HDL) risk. Although not significant, there was a trend toward increase in HDL. There was no significant placebo effect. These results suggest that in addition to the known anticoagulant and antioxidant properties of both fish oil and garlic , the combination causes favorable shifts in the lipid subfractions within 1 month. Triglycerides are affected to the largest extent. The cholesterol lowering and improvement in lipid/HDL risk ratios suggests that these combinations may have antiatherosclerotic properties and may protect against the development of coronary artery disease.

Adler AJ; Holub BJ
Department of Human Biology, University of Guelph, Canada.
Am J Clin Nutr (United States) Feb 1997, 65 (2) p445-50

This study examined the effects of garlic and fish-oil supplementation (alone and in combination) on fasting serum lipids and lipoproteins in hypercholesterolemic subjects. After an initial run-in phase, 50 male subjects with moderate hypercholesterolemia were randomly assigned for 12 wk to one of four groups: 1) 900 mg garlic placebo/d + 12 g oil placebo/d; 2) 900 mg garlic /d + 12 g oil placebo/d; 3) 900 mg garlic placebo/d + 12 g fish oil/d, providing 3.6 g n-3 fatty acids/d; and 4) 900 mg garlic /d + 12 g fish oil/d. In the placebo group, mean serum total cholesterol , low-density-lipoprotein cholesterol (LDL-C), and triacylglycerols were not significantly changed in relation to baseline. Mean group total cholesterol concentrations were significantly lower with garlic +fish oil (-12.2%) and with garlic (-11.5%) after 12 wk but not with fish oil alone. Mean LDL-C concentrations were reduced with garlic +fish oil (-9.5%) and with garlic (-14.2%) but were raised with fish oil (+8.5%). Mean triacylglycerol concentrations were reduced with garlic +fish oil (-34.3%) and fish oil alone (-37.3%). The garlic groups (with and without fish oil) had significantly lower ratios of total cholesterol to high-density-lipoprotein cholesterol (HDL-C) and LDL-C to HDL-C. In summary, garlic supplementation significantly decreased both total cholesterol and LDL-C whereas fish-oil supplementation significantly decreased triacylglycerol concentrations and increased LDL-C concentrations in hypercholesterolemic men. The combination of garlic and fish oil reversed the moderate fish-oil-induced rise in LDL-C. Coadministration of garlic with fish oil was well-tolerated and had a beneficial effect on serum lipid and lipoprotein concentrations by providing a combined lowering of total cholesterol , LDL-C, and triacylglycerol concentrations as well as the ratios of total cholesterol to HDL-C and LDL-C to HDL-C.

Neil HA; Silagy CA; Lancaster T; Hodgeman J; Vos K; Moore JW; Jones L; Cahill J; Fowler GH
Department of Public Health and Primary Care, University of Oxford.
J R Coll Physicians Lond (England) Jul-Aug 1996, 30 (4) p329-34

OBJECTIVE: To determine the effect of 900 mg/day of dried garlic powder (standardised to 1.3% allicin) in reducing total cholesterol .

DESIGN: Double-blind, randomised six-month parallel trial.

SUBJECTS: 115 individuals with a repeat total cholesterol concentration of 6.0-8.5 mmol/l and low-density lipoprotein (LDL) cholesterol of 3.5 mmol/l or above after six weeks of dietary advice.

INTERVENTION: The active treatment group received dried garlic tablets (standardised to 1.3% allicin) at a dosage of 300 mg three times daily. The control group received a matching placebo.

OUTCOME MEASURES: Primary end-point: total cholesterol concentration; secondary end-points: concentrations of LDL and high-density lipoprotein cholesterol , apolipoproteins (apo) A1 and B, and triglycerides.

RESULTS: There were no significant differences between the groups receiving garlic and placebo in the mean concentrations of serum lipids, lipoproteins or apo A1 or B, by analysis either on intention-to-treat or treatment received. In a meta-analysis which included the results from this trial, garlic was associated with a mean reduction in total cholesterol of -0.65 mmol/l (95% confidence intervals: -0.53 to -0.76).

CONCLUSIONS: In this trial, garlic was less effective in reducing total cholesterol than suggested by previous meta-analyses. Possible explanations are publication bias, overestimation of treatment effects in trials with inadequate concealment of treatment allocation, or a type 2 error. We conclude that meta-analyses should be interpreted critically and with particular caution if the constituent trials are small.

Kwon BM; Nam JY; Lee SH; Jeong TS; Kim YK; Bok SH
Korea Research Institute of Bioscience & Biotechnology, Taejon.
Chem Pharm Bull (Tokyo) (Japan) Feb 1996, 44 (2) p444-5

We have isolated cholesteryl ester transfer protein (CETP) inhibitors from the extract of Korean Panax ginseng C. A. Meyer roots and identified them as polyacetylene analogs. These compounds inhibit human CETP with IC50 values of around 20-35 mg/ml.

Steiner M; Khan AH; Holbert D; Lin RI
Memorial Hospital of Rhode Island, Pawtucket, USA
Steiner@Brody.med.ecu.edu
Am J Clin Nutr (United States) Dec 1996, 64 (6) p866-70

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.

Goldberg AC
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
J Nutr (United States) Mar 1995, 125 (3 Suppl) p675S-678S

Dietary therapy is the first step in the treatment of hyperlipidemia. However, some patients are unable to lower their cholesterol concentrations to a desirable range with diet alone. For primary prevention of coronary artery disease, physicians and patients often wish to avoid pharmacologic therapy of elevated cholesterol concentrations. The use of adjuncts to diet such as soluble fibers, garlic and soy protein may allow target lipid concentrations to be reached without the use of drugs. Soy protein incorporated into a low-fat diet can reduce cholesterol and LDL- cholesterol concentrations. The main obstacles to greater use of soy protein in the therapy of hyperlipidemia include lack of knowledge by physicians and patients of its effects and lack of availability of easily used products. Although soy products such as tofu and soymilk are available in many stores, consumers may be unaware of their presence and uses. Without the publication of articles in mainstream medical journals on the cholesterol -lowering effects of soy protein, few physicians are likely to know of possible uses. Readily available packaged products, recipes and cookbooks also will be necessary to make incorporation of soy protein into the American diet a reality. (30 Refs.)

Ali M; Thomson M
Department of Biochemistry, Faculty of Science, Kuwait University, Safat, Kuwait.
Prostaglandins Leukot Essent Fatty Acids (Scotland) Sep 1995, 53 (3) p211-2

The effect of the consumption of a fresh clove of garlic on platelet thromboxane production was examined. A group of male volunteers in the age range 40-50 years participated in the study. Each volunteer consumed one clove (approximately 3 g) of fresh garlic daily for a period of 16 weeks. Each participant served as his own control. Thromboxane B2 (TXB2, a stable metabolite of thromboxane A2), cholesterol and glucose were determined in serum obtained after blood clotting. After 26 weeks of garlic consumption, there was an approximately 20% reduction of serum cholesterol and about 80% reduction in serum thromboxane. No change in the level of serum glucose was observed. Thus, it appears that small amounts of fresh garlic consumed over a long period of time may be beneficial in the prevention of thrombosis.

Simons LA; Balasubramaniam S; von Konigsmark M; Parfitt A; Simons J; Peters W
University of New South Wales Lipid Research Department, St Vincent's Hospital, Darlinghurst, Australia.
Atherosclerosis (Ireland) Mar 1995, 113 (2) p219-25

The ingestion of garlic has been reported to have many cardiovascular effects, including a reduction in plasma cholesterol concentration and the susceptibility of LDL to oxidation. A double-blind, placebo-controlled, randomised crossover study was conducted in subjects with mild to moderate hypercholesterolaemia who were subject to strict dietary supervision and assessment. After a baseline dietary period of 28 days, subjects took Kwai garlic powder tablets 300 mg three times daily or matching placebo for 12 weeks, followed by 28 days washout, followed by a 12 weeks crossover on the alternative preparation. In the analysis hypercholesterolaemia was defined as those subjects in the range 5.5-8.05 mmol/l. Three subjects were withdrawn, one allocated to garlic and complaining of garlic body odour, one using placebo having intercurrent health problems, and one with a baseline cholesterol below 5.5 mmol/l, yielding analysable results in 28 subjects. Comparing the period on garlic with that on placebo, there were no significant differences in plasma cholesterol , LDL cholesterol , HDL cholesterol , plasma triglycerides, lipoprotein(a) concentrations, or blood pressure. Mean LDL cholesterol concentration was 4.64 +/- 0.52 mmol/l on garlic and 4.60 +/- 0.59 mmol/l on placebo. There was no demonstrable effect of garlic on oxidisability of LDL, on the ratio of plasma lathosterol/ cholesterol (a measure of cholesterol synthesis), nor on LDL receptor expression in lymphocytes. This study found no demonstrable effect of garlic ingestion on lipids and lipoproteins.

Orekhov AN; Tertov VV; Sobenin IA; Pivovarova EM
Institute of Experimental Cardiology, Russian Academy of Medical Sciences, Moscow.
Ann Med (England) Feb 1995, 27 (1) p63-5

Direct anti-atherosclerosis-related effects of garlic were studied using cell culture. An aqueous extract from garlic powder (GPE) was added to smooth muscle cells cultured from atherosclerotic plaques of human aorta. During a 24-hour incubation, GPE significantly reduced the level of cholesteryl esters and free cholesterol in these cultured cells and inhibited their proliferative activity. In addition, GPE significantly reduced cholesterol accumulation and inhibited cell proliferation stimulated by blood serum taken from patients with angiographically assessed coronary atherosclerosis, i.e. GPE reduced atherogenic manifestations of patients' serum. Garlic effect on blood atherogenicity of patients with coronary atherosclerosis has also been studied ex vivo. Following a 24-hour incubation with cultured cells, patients' blood serum caused an increase of total cell cholesterol . Blood serum taken 2 hours after an oral administration of 300 mg garlic powder tablet caused substantially less cholesterol accumulation in cultured cells. This suggests that garlic powder manifests direct anti-atherogenic-related action not only in vitro but also in vivo.

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Gore JM; Dalen JE
University of Massachusetts Medical School, Worcester.
JAMA (United States) Jun 1 1994, 271 (21) p1660-1

The GUSTO angiographic trial helps to confirm the open artery theory. Cholesterol levels in US adults continue to decrease. The consumption of one-half to one clove of garlic per day reduces cholesterol levels by approximately 9%.

Silagy C; Neil A
Department of Public Health and Primary Care, University of Oxford.
J R Coll Physicians Lond (England) Jan-Feb 1994, 28 (1) p39-45

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).(ABSTRACT TRUNCATED AT 250 WORDS)

Kenzelmann R; Kade F
Institute for Clinical Research, Gumlingen Switzerland.
Arzneimittelforschung (Germany) Sep 1993, 43 (9) p978-81

The efficacy of a garlic -ginkgo combination product (Allium plus) was analyzed in a randomized placebo-controlled double-blind study under extreme dietary conditions. The Christmas/New Year's season was chosen for this 2 months lasting investigation analyzing whether the known cholesterol lowering effect of garlic was even effective during the period of the year with the most cholesterol -rich meals. 43 patients with elevated total cholesterol levels ranging between 230-390 mg/dl completed the study. There were no significant changes of the total cholesterol values in both treatment groups. Nevertheless the analysis of improvement or deterioration of total cholesterol values revealed a clear difference between verum and placebo. 20% of the patients in the placebo group showed an improvement of their total cholesterol level, while there was a significant greater improvement rate of 35% in the verum group (p < 0.05). The responders of the verum group showed a reduction in the total cholesterol values from 298.5 +/- 53.8 to 293.0 +/- 56.4 mg/dl after 1 month and a total reduction of 10.4% after 2 months to 267.6 +/- 44.4 mg/dl. The difference after 2 months of treatment was significantly different from the starting value (p < 0.05). After the 2 months treatment phase there was a 2 weeks wash-out period. During this period the total cholesterol value returned to 293.5 +/- 90.1 mg/dl showing the effectiveness of garlic treatment, but indicating the need for a continuous long-term therapy.

Elwood PC; Beswick AD; O'Brien JR; Yarnell JW; Layzell JC; Limb ES
MRC Epidemiology Unit, Llandough Hospital, Penarth, South Glamorgan.
Blood Coagul Fibrinolysis (England) Aug 1993, 4 (4) p529-36

Inter-relationships between fibrinogen, platelets and other haemostatic factors were examined in 1030 men aged 55-99 years. Fasting blood was taken and used for cell counts, platelet counts and platelet parameters, aggregation of platelets to ADP by a whole blood method and a filter test of platelet activation. Plasma fibrinogen, von Willebrand factor, factor VII and plasma viscosity were measured by standard methods. A stressed bleeding time was conducted on the forearm of the arm not used for venepuncture. Variability within the laboratory and short-term intra-subject variation were examined and found to be acceptably small. The effect of age on the tests was modest, except for von Willebrand factor which increased by about 50% of a SD for every 10 years of age. Cholesterol and triglyceride levels had small effects on the platelet tests and a large effect on factor VII. A number of dietary and life-style determinants were examined: smokers had increased levels of fibrinogen, viscosity and white cell count and reduced bleeding times. Alcohol drinkers showed reduced platelet activity and have lower levels of fibrinogen, von Willebrand factor and white cell count. Men who took fish oil capsules had substantially increased bleeding times and lower levels of von Willebrand factor and men who took capsules containing an extract of garlic showed reduced platelet retention in the filter test.

Warshafsky S; Kamer RS; Sivak SL
Department of Medicine, New York Medical College, Valhalla 10595.
Ann Intern Med (United States) Oct 1 1993, 119 (7 Pt 1) p599-605

OBJECTIVE: To assess the size and consistency of garlic 's effect on total serum cholesterol in persons with cholesterol levels greater than 5.17 mmol/L (200 mg/dL).

DATA SOURCES: Clinical trials were identified by a computerized literature search of MEDLINE and by an assessment of the bibliographies of published studies and reviews.

STUDY SELECTION: Trials were selected if they were randomized and placebo-controlled and if at least 75% of their patients had cholesterol levels greater than 5.17 mmol/L (200 mg/dL). Studies were excluded if they did not provide enough data to compute effect size. Five of 28 studies were selected for review.

DATA EXTRACTION: Details of study design, patient characteristics, interventions, duration of therapy, and cholesterol measurements were extracted by one author and were verified by another.

DATA SYNTHESIS: Study quality was evaluated by multiple reviewers using a closed-ended questionnaire. Patients treated with garlic consistently showed a greater decrease in total cholesterol levels compared with those receiving placebo. Meta-analysis of homogeneous trials estimated a net cholesterol decrease attributable to garlic of 0.59 mmol/L (95% CI, 0.44 to 0.74) (23 mg/dL [CI, 17 to 29]) (P < 0.001).

CONCLUSIONS: Meta-analysis of the controlled trials of garlic to reduce hypercholesterolemia showed a significant reduction in total cholesterol levels. The best available evidence suggests that garlic, in an amount approximating one half to one clove per day, decreased total serum cholesterol levels by about 9% in the groups of patients studied.

Kiesewetter H; Jung F; Jung EM; Blume J; Mrowietz C; Birk A; Koscielny J; Wenzel E
Abteilung fur Klinische Hamostaseologie und Transfusionsmedizin, Universitat des Saarlandes, Homburg/Saar.
Clin Investig (Germany) May 1993, 71 (5) p383-6

For the first time, a weak clinical efficacy of a 12-week therapy with garlic powder (daily dose, 800 mg) is demonstrated in patients with peripheral arterial occlusive disease stage II. The increase in walking distance in the verum group by 46 m (from 161.0 +/- 65.1 to 207.1 +/- 85.0 m) was significantly higher (P < 0.05) than in the placebo group (by 31 m, from 172.0 +/- 60.9 to 203.1 +/- 72.8). Both groups received physical therapy twice a week. The diastolic blood pressure, spontaneous thrombocyte aggregation, plasma viscosity, and cholesterol concentration also decreased significantly. Body weight was maintained. It is quite interesting that the garlic -specific increase in walking distance did not appear to occur until the 5th week of treatment, connected with a simultaneous decrease in spontaneous thrombocyte aggregation. Therefore, garlic may be an appropriate agent especially for the long-term treatment of an incipient intermittent claudication.

Jain AK; Vargas R; Gotzkowsky S; McMahon FG
Clinical Research Center, New Orleans, Louisiana 70112.
Am J Med (United States) Jun 1993, 94 (6) p632-5

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.

Auer W; Eiber A; Hertkorn E; Hoehfeld E; Koehrle U; Lorenz A; Mader F; Merx W; Otto G; Schmid-Otto B; et al
Incorporated Society, Nittendorf, West Germany.
Br J Clin Pract Suppl (England) Aug 1990, 69 p3-6

Forty-seven non-hospitalised patients with mild hypertension took part in a randomised, placebo-controlled, double-blind trial conducted by 11 general practitioners. The patients who were admitted had diastolic blood pressures between 95 and 104 mmHg after a two-week acclimatization phase. The patients then took either a preparation of garlic powder (Kwai) or a placebo of identical appearance for 12 weeks. Blood pressure and plasma lipids were monitored during treatment after four, eight and 12 weeks. Significant differences between the placebo and the drug group were found during the course of therapy. For example, the supine diastolic blood pressure in the group having garlic treatment fell from 102 to 91 mmHg after eight weeks (p less than 0.05) and to 89 mmHg after 12 weeks (p less than 0.01). The serum cholesterol and triglycerides were also significantly reduced after eight and 12 weeks of treatment. In the placebo group, on the other hand, no significant changes occurred.

Vorberg G; Schneider B
University of Hannover, West Germany.
Br J Clin Pract Suppl (England) Aug 1990, 69 p7-11

A double-blind study of 40 hypercholesterolaemic out-patients was carried out over a period of four months to examine the effects of a garlic powder preparation*. The drug group received 900 mg garlic powder per day, equivalent to 2,700 mg of fresh garlic . During the therapy, the drug group showed significantly lower total cholesterol, triglycerides and blood pressure than those of the placebo group. In addition, results of a self-evaluation questionnaire indicated that patients in the drug group had a greater feeling of 'well-being'.

Brosche T; Platt D; Dorner H
Chair of Internal Medicine-Gerontology, University of Erlangen-Nuremberg, West Germany.
Br J Clin Pract Suppl (England) Aug 1990, 69 p12-9

This study evaluated the effect of a dried garlic powder preparation, standardised to 1.3% alliin, on the composition of plasma lipoproteins and erythrocyte membranes. Forty volunteers, aged 70 years and over, took 600 mg of garlic powder per day for three months. In participants with initially normal plasma cholesterol levels (CH less than 200 mg/dl; n = 11) after three months of garlic tablet administration, little or no change in CH values was registered, as for most of the other parameters. In contrast, in volunteers with initially elevated CH levels (CH greater than 200 mg/dl, n = 29), the CH levels were reduced by -7.7% (p less than 0.001). This reduction took place primarily in the esterified cholesterol fraction (-12%, p less than 0.001), whereas free cholesterol concentrations were not altered significantly. Triglycerides (-15.9%, p less than 0.05) and plasma choline phospholipids (-4.6%, p less than 0.01) were also reduced. No change of the plasma LDL-CH to HDL-CH ratio was observed in this group. Based on the weight of lyophilised, haemoglobin-free erythrocytes, the mean membrane concentration of phospholipids and cholesterol in the total cohort (n = 40) increased by 5.7% (p less than 0.001) and 6.1% (p less than 0.01), respectively. These increases were more pronounced the lower the body mass indices (kg/m2) were, and the longer the duration of garlic administration was. The molar ratio of membrane phospholipids to cholesterol remained unchanged. The results are discussed with regard to a possible role of the garlic -induced membrane effects in the plasma lipid-lowering potency of garlic and preparations made from it.

Holzgartner H; Schmidt U; Kuhn U
Arbeits- und Forschungsgemeinschaft fur Arzneimittel-Sicherheit e.V., Cologne, Fed. Rep. of Germany.
Arzneimittelforschung (Germany) Dec 1992, 42 (12) p1473-7

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.

Rotzsch W; Richter V; Rassoul F; Walper A
Institut fur Klinische Chemie und Laboratoriumsdiagnostik, Universitat Leipzig.
Arzneimittelforschung (Germany) Oct 1992, 42 (10) p1223-7

Postprandial Lipaemia under Treatment with Allium sativum/Controlled double-blind study in healthy volunteers with reduced HDL2-cholesterol levels. The effectiveness of a standardized garlic powder preparation (Sapec, Kwai) on alimentary hypertriglyceridaemia after intake of a standardized fatty test meal containing 100 g butter was analyzed in a randomized placebo-controlled double-blind study. 24 volunteers with HDL2- cholesterol concentrations in plasma of less than 10 mg/dl (men) respectively 15 mg/dl (women) participated in the study. The volunteers received 3 times 1 tablet daily over a period of 6 weeks equivalent to a daily dosage of 900 mg garlic powder in the active treated group. Control measurements were made on the 1st, 22nd and 43rd day of treatment and 0, 3 and 5 h after intake of the meal. The postprandial increase of triglycerides was clearly reduced under garlic medication as compared to placebo treatment. The determined AUC-values for the triglycerides were up to 35% lower in the garlic group compared to the placebo group. The regular intake of the garlic preparation over the period of 6 weeks showed a significant lowering of the fasting values of triglycerides in comparison to placebo. Under garlic medication HDL2- cholesterol increased more than under placebo in tendency.

Gadkari JV; Joshi VD
Department of Physiology, L. T. M. Medical College, Sion, Bombay, Maharashtra.
J Postgrad Med (India) Jul 1991, 37 (3) p128-31

The effect of raw garlic on serum cholesterol, fibrinolytic activity and clotting time was studied in 50 medical students of the age group of 17 to 22 years before and after feeding raw garlic . All pre-experimental values ranged within normal limits. The volunteers were then divided into experimental and control groups. The subjects of the experimental group were given 10 gm of raw garlic daily after breakfast for two months. Fasting blood samples of all the subjects were investigated after two months. In the control group, there was no significant change in any of the above parameters. In the experimental group, there was a significant decrease in serum cholesterol and an increase in clotting time and fibrinolytic activity. Hence, garlic may be an useful agent in prevention of thromboembolic phenomenon.

Kiesewetter H; Jung F; Pindur G; Jung EM; Mrowietz C; Wenzel E
Department of Clinical Hemostasiology and Transfusion Medicine, University of the Saarland, Homburg.
Int J Clin Pharmacol Ther Toxicol (Germany) Apr 1991, 29 (4) p151-5

Significant positive effects could be achieved in a placebo-controlled double-blind study through the administration of 800 mg of garlic powder over a period of four weeks. Spontaneous thrombocyte aggregation disappeared, the microcirculation of the skin increased by 47.6% (from 0.63 +/- 0.13 to 0.93 +/- 0.22 mm/s), plasma viscosity decreased by 3.2% (from 1.25 +/- 0.34 to 1.21 +/- 0.43 mPas), diastolic blood pressure by 9.5% (from 74 +/- 9 to 67 +/- 5 mmHg), and blood glucose concentration by 11.6% (from 89.4 +/- 8.8 to 79.0 +/- 11.9 mg/dl). The vascular protection of garlic as atherosclerosis prevention by influencing the mentioned risk parameters for cardiovascular diseases must be pointed out. Especially interesting is the thrombocyte aggregation inhibiting effect. Thus, the application of garlic may be useful in case of acetylsalicyclic acid intolerance.

Brosche T; Platt D
Lehrstuhl fur Innere Medizin-Gerontologie, Universitat Erlangen-Nurnberg.
Fortschr Med (Germany) Dec 20 1990, 108 (36) p703-6

Garlic (Allium sativum L.) is a commonplace drug. It is now available in the form of dragees made of garlic powder, standardized to 1.3% alliin. The lipid-lowering potential of such preparations has not been reviewed yet. In 7 out of 8 studies, including over 500 patients, a daily dose of 0.6 g to 0.9 g garlic powder reduced plasma cholesterol and triglyceride levels by 5 to 20 percent. The metabolic mechanisms of these reductions are not known. (0 Refs.)

Mader FH
Study Group on Phytotherapy of the German Association of General Practitioners, Nittendorf.
Arzneimittelforschung (Germany) Oct 1990, 40 (10) p1111-6

In a multicentric placebo-controlled randomised study the effect of standardized garlic -powder tablets (Kwai, Sapec) in the treatment of hyperlipidaemia was investigated. A total of 261 patients of 30 general practitioners in West Germany with total cholesterol and/or triglyceride values more than 200 mg/dl (mostly hyperlipoproteinaemia type II a/II b) took part in the study. Patients were randomly allocated to take tablets containing a total of 800 mg garlic powder (standardized to 1.3% of alliin content) daily or the same number of placebo tablets for 16 weeks (monthly controlled). 221 patients were used for statistical analysis of total cholesterol and 219 patients for the analysis of triglyceride values. Mean serum cholesterol levels dropped in the verum group from 266 to 235 mg/dl (i.e. 12%) during the 4 month treatment period, mean triglyceride values fell in the verum group from 226 to 188 mg/dl (i.e. 17%). The best cholesterol lowering effects were seen in the patients with initial total cholesterol values between 250-300 mg/dl. The difference between the verum and placebo group was highly significant (p less than 0.001). A mild garlic smell was observed in up to 21% of the verum group and up to 9% in the placebo group. Only one of the patients left the study for this reason. Standardized garlic tablets have been shown to be effective in the treatment of hyperlipidaemia by lowering total cholesterol values by an average of 12% and triglyceride values by an average of 17%.

Kleijnen J; Knipschild P; ter Riet G
Department of Epidemiology/Health Care Research, University of Limburg, Maastricht, The Netherlands.
Br J Clin Pharmacol (England) Nov 1989, 28 (5) p535-44

1. Claims for beneficial effects on cholesterol levels, fibrinolytic activity, and platelet aggregation are attributed both to fresh garlic and onions (or their extracts) and to commercially available preparations.

2. Regarding fresh garlic, the claims have been confirmed, but so far only at very high dosages.

3. For onions and commercially available supplements contradictory results have been reported.

4. All published trials showed severe methodological shortcomings. Some trials were not randomized and/or not blinded whilst this was possible, and in only one of every three studies more than 25 patients participated in each treatment group. In no trial was prognostic comparability of the treatment and the control groups ascertained. At the moment there is inadequate scientific justification for garlic supplementation. (39 Refs.)

Harenberg J; Giese C; Zimmermann R
First Medical Department, Klinikum Mannheim, University of Heidelberg, F.R.G.
Atherosclerosis (Netherlands) Dec 1988, 74 (3) p247-9

The effects of intake of dried garlic on blood coagulation, fibrinolysis, platelet aggregation, serum cholesterol levels, and blood pressure were studied in 20 patients with hyperlipoproteinemia over a period of four weeks. Fibrinogen and fibrinopeptide A significantly decreased by 10%. Streptokinase activated plasminogen and fibrinopeptide B beta 15-42 significantly increased by about 10%. Serum cholesterol levels significantly decreased by 10%. Systolic and diastolic blood pressure decreased. ADP and collagen induced platelet aggregation were not influenced.

Luley C; Lehmann-Leo W; Moller B; Martin T; Schwartzkopff W
Arzneimittelforschung (Germany, West) Apr 1986, 36 (4) p766-8

The effects of dried garlic on blood lipids, apolipoproteins and blood coagulation parameters in hyperlipemic patients were studies in two controlled, randomized, double-blind studies. Both studies comprised placebo and therapy periods of 6 weeks each. The doses administered were 3 X 198 mg in Study I (34 patients) and 3 X 450 mg in Study II (51 patients). In both studies, the following serum parameters were measured every 3 weeks: total cholesterol, HDL (high density lipoprotein)- and LDL (low density lipoprotein)- cholesterol, triglycerides and several safety parameters. In addition, apolipoproteins A and B, euglobulin lysis time, fibrin split products, prothrombin time, whole blood coagulation time and fibrinogen levels were determined in the second study only. The results indicated that neither dosage of dried garlic showed any significant effect on any of the parameters measured. It is therefore concluded that, if there is any effect of garlic on the parameters measured, it is not apparent when using a dried preparation in the dosage studied.

Petkov V
J Ethnopharmacol (Switzerland) Feb 1986, 15 (2) p121-32

Some data about the use of medicinal plants in Bulgarian traditional medicine in the Middle Ages and in modern times are presented and the results of 40-year-long experimental-pharmacological investigations on many medicinal plants used in Bulgarian traditional medicine are reviewed. In-depth discussion is presented on the investigations of garlic (Allium sativum L.), a plant widely used by Bulgarian people for treating different diseases. Data from studies on a large number of plants used for treatment of hypertension, infectious diseases and as diuretic and spasmolytic remedies are summarized. (51 Refs.)

Bakhsh R; Chughtai MI
Nahrung (Germany, East) 1984, 28 (2) p159-63

Human subjects were used for a garlic experiment. The subjects were given a fat-rich diet for 7 days and on the 8th day the fasting blood was analyzed for serum cholesterol, serum triglycerides, serum total lipids and serum glucose. The human subjects were then given a fat-rich diet with 40 g of garlic for 7 days and on the 15th day the fasting blood was analyzed for the above investigations. On a fat-rich diet the serum cholesterol, serum triglycerides and serum total lipids were significantly increased as compared to normally fed diet. When 40 g of garlic was substituted in fat-rich diet for 7 days, the garlic significantly reduced the serum cholesterol and serum triglycerides.

Ernst E
MMW Munch Med Wochenschr (Germany, West) Oct 9 1981, 123 (41) p1537-8

Garlic has had a firm place in folk medicine since ancient times. More recent results are summarized here which show that extracts of the plant have an antimicrobial action, they are capable of lowering blood cholesterol and of reducing secondary vascular changes. They raise fibrinolytic activity and inhibit thrombocyte aggregation. Therefore the plant contains highly active therapeutic principles which appear to be particularly suitable for prophylaxis of arteriosclerosis.

Hase J; Kobashi K; Mitsui K; Namba T; Yoshizaki M; Tomimori T
J Pharmacobiodyn (Japan) Nov 1981, 4 (11) p833-7

Chikusetsusaponin IV and V, whose genin is oleanolic acid, exhibited weak hemolytic activities. Removal of glucose residue at position 29 of chikusetsusaponin V by partial hydrolysis increased the activity more than 30-fold. Methylation of the carboxyl group at position 28 increased the activity furthermore by about 10-fold, showing HD50 value of 3.77 microM. On the other hand, removal of the sugar chain at position 3 of chickusetsusaponin V by partial hydrolysis completely lost the activity. These facts suggest that the sugar chain at position 3 of oleanolic acid is essential but that at position 29 is pernicious for the activity. The cytolytic agents, whose target has been regarded as membrane cholesterol, were inactivated not only by cholesterol but also by sapogenins such as oleanolic acid, gitogenin and hederagenin. Among saponins tested, akebia saponin B and C were inactivated by cholesterol, but not by the genins, probably because their affinities for the genins are too low to form complexes.

Arora RC; Arora S; Gupta RK
Atherosclerosis (Netherlands) Oct 1981, 40 (2) p175-9

The hypocholesterolemic and fibrinolysis-enhancing properties of garlic were assessed in patients with ischemic heart disease (IHD) and in healthy control subjects. The peak of blood fibrinolytic activity (BFA) achieved at the 4th week of garlic therapy was not sustained despite its continuous use and returned to about the pre-garlic values at the 12th week. Garlic withdrawal did not cause any further change in BFA. Under the same conditions serum total cholesterol (STC) values did not show any significant change. Both of the foregoing features were observed in the IHD as well as in the control group. Garlic therapy for 12 weeks did not cause any appreciable changes in serum triglyceride, beta-lipoprotein, plasma fibrinogen levels or coagulation time in either IHD or control subjects. The evidence cited above does not appear to substantiate the prevalent popular belief in the efficacy of garlic in the management of IHD either as a hypocholesterolemic or as a fibrinolytic agent.

Arora RC; Arora S
Atherosclerosis (Netherlands) Jul 1981, 39 (4) p447-52

The effect of clofibrate on the same subjects in similar test conditions were used as a control to verify the alleged beneficial effects from garlic and onion on alimentary hyperlipemia in normals and in cases with ischemic heart disease. The results showed that clofibrate checked the fat-induced (a) rises of serum triglyceride and plasma fibrinogen, and (b) falls of coagulation time (CT) and blood fibrinolytic activity (BFA). Only garlic had a clofibrate-like effect on CT but both garlic and onion checked the postprandial fall of BFA. Clofibrate, however, increased BFA even above the fasting level. Serum cholesterol and beta-lipoprotein were not appreciably affected by fat with or without any drug. Thus, surprisingly, the so-called beneficial effects of garlic and onion were not seen in subjects who had shown significant changes after clofibrate.

Bhushan S; Sharma SP; Singh SP; Agrawal S; Indrayan A; Seth P
Indian J Physiol Pharmacol (India) Jul-Sep 1979, 23 (3) p211-4

The effect of raw garlic on normal blood cholesterol level in males of the age group of 18-35 years was studied. The subjects, who never ingested garlic before, were given 10 g of garlic daily with their diet for two months. Fasting blood samples were investigated in respect of cholesterol before and after two months of garlic intake. Initially the blood cholesterol level ranged between 160-250 mg% which decreased significantly in all the subjects of experimental group after two months of ingestion of garlic . The slight decrease or increase in the blood cholesterol level of control group was not significant. The raw garlic can be advocated for daily ingestion in order to lower one's blood cholesterol level even if it is within normal limits.

Bordia A; Bansal HC; Arora SK; Singh SV
Atherosclerosis (Netherlands) Jan-Feb 1975, 21 (1) p15-9

Summary: The effect of garlic and onion on alimentary hyperlipemia, induced by feeding 100 g butter, has been studied in 10 healthy subjects. The freshly extracted juice of 50 g of garlic or onion, as well as an equivalent amount of their ether-extracted essential oils, was administered randomly on four different days during a one-week period. Garlic and onion have a significant protective action against fat-induced increases in serum cholesterol and plasma fibrinogen and decreases in coagulation time and fibrinolytic activity. The essential oil fraction, which contains all the taste and odour, exactly duplicated the beneficial effects of whole garlic and onion. It is, therefore, concluded that the active principle of garlic and onion is the essential oil, which chemically is a combination of sulphur-containing compounds, mainly allyl propyl disulphide and diallyl disulphide.

McCrindle B.W.; Helden E.; Conner W.T.
Dr. B.W. McCrindle, Hospital for Sick Children, 555 University Ave, Toronto, Ont. M5G 1X8 Canada
Archives of Pediatrics and Adolescent Medicine (United States), 1998, 152/11 (1089-1094)

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 Phanna, 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%]) 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.

Zink T.; Chaffin J.
Dr. T. Zink, Univ. of Cincinnati Coll. of Med., Cincinnati, OH United States
American Family Physician (United States), 1998, 58/5 (1133-1140)

Patients who self-medicare with herbs for preventive and therapeutic purposes may assume that these products are safe because they are 'natural,' but some products cause adverse effects or have the potential to interact with prescription medications. The United States lacks a regulatory system for herbal products. Although only limited research on herbs has been published, St John's wort shows promise as a treatment for depression. Ginkgo biloba extract is possibly effective for cerebrovascular insufficiency and dementia. Feverfew is used extensively in Canada for migraine prophylaxis but needs more rigorous study. Ephedrine has been regulated by many states because its misuse has been associated with several deaths. Echinacea is being tried as an agent for immune stimulation, and garlic is under study for cholesterol -lowering properties, but both require more study. Physicians should educate themselves and their patients about the efficacy and adverse interactions of herbal agents and the limitations of our present knowledge of them.

Steiner M.; Lin R.S.
Dr. M. Steiner, Division of Hematology/Oncology, East Carolina University, School of Medicine, Greenville, NC 27858-4354 United States
Journal of Cardiovascular Pharmacology (United States), 1998, 31/6 (904-908)

Garlic and some of its organosulfur components have been found to be potent inhibitors of platelet aggregation in vitro. Demonstration of their efficacy in vivo, however, especially when administered over extended periods, is sparse. We recently performed a 10-month study comparing the effect of aged garlic extract (AGE) with placebo on the lipid profiles of moderately hypercholesterolemic men. In the course of the intervention trial, we examined platelet functions and susceptibility of lipoproteins to oxidation in a subgroup of this study population. Study subjects supplemented with 7.2 AGE per day showed a significant reduction of epinephrine- and, to a lesser degree, collagen-induced platelet aggregation but failed to demonstrate an inhibition of adenosine diphosphate (ADP)-induced aggregation. Platelet adhesion to fibrinogen, measured in a laminar flow chamber at moderately high shear rate, was reduced by similar30% in subjects taking AGE compared with placebo supplement. A trend toward decreased susceptibility of lipoproteins to oxidation also was noted during AGE administration compared with the placebo period. We conclude that the beneficial effect of garlic preparations on lipids and blood pressure extends also to platelet function, thus providing a wider potential protection of the cardiovascular system.

Gilbert L.
L. Gilbert, HealthFocus, Inc., P.O. Box 7174, Des Moines, IA 50309-3117 United States
Journal of Nutraceuticals, Functional and Medical Foods (United States), 1997, 1/3 (5-21)

Major demographic and psychographic shifts in the consumer market are directing the next stage evolution of healthy products, sharpening the marketing focus on healthy products that offer specific functional health benefits to an aging population of increasingly savvy consumers. Because functional food opportunities are largely consumer-driven, understanding consumer interests and motivations is key to successfully negotiating market opportunities for functional foods, beverages and supplements. The HealthFocus survey identifies the functional food concerns of key population segments for companies marketing functional products who need to identify and profile the most appropriate target groups.

Masley S.C.
Dr. S.C. Masley, Group Health Coop. of Puget Sound, Olympia, WA United States
American Family Physician (United States), 1998, 57/6 (1299-1306)

Nearly one half of Americans die of cardiovascular disease. The morbidity and mortality associated with coronary artery disease is strongly related to abnormal lipid levels, oxidation of lipids and intra-arterial clot formation. Nutrition powerfully influences each of these factors. There is growing evidence that patients can improve lipid levels and decrease the rate of cardiovascular events by 'adding' specific foods to their diets and switching from saturated and polyunsaturated to monounsaturated fats and n-3 fatty acids. Appropriate dietary changes decrease arteriosclerotic plaque formation, improve endothelial vasomotor dynamics, reduce oxidation of low- density lipoproteins and enhance thrombolytic activity. Brief discussions between physicians and patients can influence patients' food choices. Changes in diet can reduce the premature mortality and morbidity associated with coronary artery disease.

Merat A.; Fallahzadeh M.
A. Merat, Department of Biochemistry, School of Medicine, Shiraz Univ. of Med. Sci., Shiraz Iran
Iranian Journal of Medical Sciences (Iran), 1996, 21/3-4 (141-146)

Triglyceride, total cholesterol, HDL cholesterol, LDL cholesterol, lipoprotein (a), free fatty acids and glucose levels were measured in the serum or plasma of 86 normal male human subjects, aged 25 to 50 years, before and after one month of garlic powder consumption (one 400 mg garlic tablet, 3 times daily). Levels of total cholesterol, LDL cholesterol and triglycerides were significantly decreased after garlic consumption (by 10.7%, 11.5% and 14.2% respectively, p < 0.05). Furthermore, this decrease was significantly greater (p < 0.05) for initial cholesterol levels of > 200 mg/dl and triglyceride levels of > 150 mg/dl/(14.7% and 15% respectively), and less pronounced for cholesterol levels of less than or equal to200 mg/dl and triglyceride levels of less than or equal to150 mg/dl/(7.3% and 6% respectively). The reduction in LDL cholesterol was also significantly greater (p < 0.05) for initial levels of > 135 mg/dl/(16.7%)as compared with levels of less than or equal to135 mg/dl/(10.0%). No significant differences existed in the levels of glucose, free fatty acids, lipoprotein (a) and HDL cholesterol measured before and after consumption of garlic . Measurements of cholesterol and triglycerides were also carried out in 15 normal male rats, weighing 250 to 300g, after receiving a diet containing 2.5% garlic powder for 10 days. Total cholesterol and triglyceride levels were significantly lower (p < 0.05) in these rats as compared to a control group receiving regular stock powder without garlic . The specific activity of HMGCoA reductase in the liver microsomal fraction of 12 normal male rats receiving the garlic powder (2.5% of the diet) for 10 days, was also significantly decreased (p < 0.05) as compared to a control group on the stock diet without garlic .

Graubaum H.-J.; Metzner C.; Scheider B.
TC Biomed, Abt Umweltmedizin, Etkar-Andre-Str. 8, 12619 Berlin Germany
Therapiewoche (Germany), 1996, 46/25 (1421-1425)

In a randomized, double-blind, clinically-controlled study, BNK 04, a combination of active ingredients containing ginseng, hawthorn, and micronized mixed polled as its main ingredients, was administered to 18 stressed and untrained patients (test group: 9 female, 9 male subjects; mean age = 56,9 years) for 40 days (first treatment phase). A significant increase in physical performance (p < 103) as compared to the control group (10 female, 8 male patients; mean age = 59,2 years) was detected by means of bicycle ergometry. The difference between groups was 20,0%, expressed as the Watt-minute product (Delta = 207 W x min). Sixteen patients of the test group underwent a second treatment phase with BNK 04 (single-blind) following a 4-week washout phase, during which patients received placebo. At the onset of the second treatment phase, physical performance continued to be significantly increased (p = 0,008) compared to baseline (11,7%). At the end of treatment, the enhancement of physical performance was 20,6% combpared to baseline (p = 0,006). Adverse drug reactions were not observed. These results demonstrate the conditioning effect on physical performance of the active ingredient combination, BNK 04, upon repeated administration.

Ramon Gimenez J.R.; Alonso M.B.; Rubio S.; Ramon B.M.; Plaza Celemin L.; Mostaza J.M.; Lozano I.F.; Fernandez J.M.; Marquez-Montes J.
Gral. Rodrigo, 1, 28003 Madrid Spain
Clinica Cardiovascular (Spain), 1996, 14/2 (29-38)

High levels of cholesterol and Low Density Lipoproteins (LDL) in plasma are related to high risk to develop Coronary Heart Disease (CHD). LDL-chosterol is a primary ingredient of the atherosclerotic plaque; its accumulation in the subendothelial space is due to peroxidative reactions. Natural antioxidants such as carotenes, polyphenolic flavonoids, vitamin E and C show defensive properties against lipid peroxidation, hence it is possible to apply these molecules in clinical therapy in the prevention of the CHD. On the other hand, alcohol, and special red wine, as well as the intake of selenium can afford a cardioprotective effect. Blood cholesterol reduction, dietary and/or due to pharmacological interventions, could modulate lipid peroxidation through a decreased production of O2.-, pivotal step in the peroxidative chain of reactions. The importance of other dietary components (fresh fruits, nuts, garlic and other vegetables as well as olive oil) have been analyzed to assess its influence and protective action in the prevention of CHD.

Reuter H.D.
Siebengebirgsallee 24, 50939 Koln Germany
Zeitschrift fur Phytotherapie (Germany), 1996, 17/1 (13-25)

The reports of the satellite symposium 'International Garlic Research' presented recent results of garlic research. Pharmacological investigations showed that the vessel-dilatating effect of garlic powder extracts, allicin and ajoen is mediated by opening K+-channels and by membrane hyperpolarization. It could be shown that garlic powder directly affects cholesterol -accumulation by LDL and that there exists an inverse correlation between LDL-atherogenicity and sialic acid content of LDL. By garlic powder in hyperlipidemic patients the decreased sialic acid level could be normalized. Garlic constituents influence cholesterol biosynthesis on several levels. With respect to the late steps of cholesterol biosynthesis the inhibition of lanosterol 14-demethylase by allicin and ajoene was most important. Garlic also influences nitric oxide metabolism by increasing the blood levels of NO. Insufficient synthesis of NO in the blood may result in hypertension, angina pectoris and impotentia. A metaanalysis of clinical trials with garlic powder preparations proves their effects on blood pressure and lipid levels. A comparative trial of the effects of garlic powder and garlic oil bas shown, that powder preparations have a stronger lipid-lowering effect than oil-preparations, while blood pressure is affected by powder preparations only. Another study showed that supplementation of a fish oil medication with garlic abolishes the fish-oil-induced increase of LDL-cholesterol levels and lowers the LDL-cholesterol levels. Finally the preliminary evaluation of an epidemiological study indicates that there are hints of a decreased stiffness of the aorta in humans with regular intake of a garlic powder preparation while another trial reveals a significant reduction of the extention of atheromateous plaques by garlic powder.

Schiewe F.P.; Hein T.
Naturheilverfahren, Zorgiebelstr. 10-12, 50767 Koln Germany
Zeitschrift fur Phytotherapie (Germany), 1995, 16/6 (343-348)

The lipid lowering effect of an enteric coated garlic /cyclodextrine preparation (Tegra (R)) was investigated. 97 patients with known primary hyperlipidaemia (serum levels of total cholesterol exceeding 260 mg/100 ml) took part in this trial. Patients received 10 mg/day of essential garlic oil obtained by steam distillation of garlic . The trial was carried out of 3 months and for 6 months in those cases in which the aim of the treatment (reduction of serum levels of total cholesterol to values less than 260 mg/100 ml) had not been reached after 3 months. Most of the patients did not alter their diet, though they were advised to do so. In 28 of 97 patients the treatment was successful after 3 months. The total cholesterol (TC) decreased by 7.8% from 287 to 264 mg/100 ml in the mean, the triglycerides (TG) by 2.2% from 205 to 180 mg/100 ml, the low-density lipoprotein cholesterol (LDL-C) by 10.2% from 207 to 186 mg/100 ml. The high-density lipoprotein cholesterol (HDL-C) increased by 10% from 38.8 to 42.6 mg/100 ml. Continuing the trial for a further three months in 69 patients resulted in an overall reduction of TC by 14.1% to 246 mg/100 ml, of TG by 20.2% to 164 mg/100 ml, and of LDL-C by 18.8% to 168 mg/100 ml. HDL-C values in the same time increased by 17.6% to 45.6 mg/100 ml. All changes were statistically significant (p < 0.001). The aim of the treatment was reached by 90% of the patients (87 of 97). All patients had a reduction of TC, TG and LDL-C and an increase in HDL-C. No severe side effects were observed. The results of the study demonstrate the efficacy of essential garlic oil/beta-cyclodextrine complexes in the treatment of hyperlipidaemia.

Agarwal K.C.
Dept. of Mol. Pharm./Biotechnology, Brown University School of Medicine, Providence, RI 02912 USA
Medicinal Research Reviews (USA), 1996, 16/1 (111-124)

Most studies on garlic during the past 15 years have been primarily in the fields of cardiovascular and cancer research. Cardiovascular studies have been mainly related to atherosclerosis, where effects were examined on serum cholesterol, LDL, HDL, and triglycerides. Although the studies were not consistent in relation to the dosage, standardization of garlic preparations, and period of treatment, most findings suggest that garlic decreases cholesterol and triglycerides levels in patients with increased levels of these lipids. Lowering of serum lipids by garlic ingestion may decrease the atherosclerosis process. The other major beneficial effect of garlic is due to its antithrombotic actions. This field of garlic research has been extensively studied. Garlic extracts and several garlic constituents demonstrate significant antithrombotic actions both in vitro and in vivo systems. Allicin and adenosine are the most potent antiplatelet constituents of garlic because of their in vitro effects. Since both allicin and adenosine are rapidly metabolized in human blood and other tissues, it is doubtful that these compounds contribute to any antithrombotic actions in the body. In addition, ajoene also seems not to be an active antiplatelet principle, because it is not naturally present in garlic, garlic powders, or other commercial garlic preparations. Only a small amount of ajoene can be found in garlic oil-macerates; however, ajoene is being developed as a drug for treatment of thromboembolic disorders. Recent findings on the identification of potent enzyme inhibiting activities of adenosine deaminase and cyclic AMP phosphodiesterase in garlic extracts are interesting, and may have a significant role in the pharmacological actions in the body. Presence of such enzyme inhibitors in garlic may perhaps explain several clinical effects in the body, including the antithrombotic, vasodilatory, and anticancer actions. Epidemiological studies have suggested that garlic plays a significant role in the reduction of deaths caused by malignant diseases. This had led many investigators to examine garlic and garlic constituents for their antitumor and cytotoxic actions both in vitro and in laboratory animals. The data from these investigations suggest that garlic contains several potentially important agents that possess antitumor and anticarcinogenic properties. In summary, the epidemiological, clinical, and laboratory data have proved that garlic contains many biologically and pharmacologically important compounds, which are beneficial to human health from cardiovascular, neoplastic, and several other diseases. Numerous studies are in progress all over the world to develop effective and odorless garlic preparations, as well as to isolate the active principles that may be therapeutically useful.

Abarquez R.F. Jr.
Philippine Heart Center, East Avenue, Quezon City Philippines
Philippine Journal of Internal Medicine (Philippines), 1995, 33/2 (33-35)

As of 1990 the Philippines is 2nd to Indonesia in hypertensive-related mortality. To reverse this trend, hypertension control strategies involve health provider and client perceptions of the issues. A recent Philippine Society of Hypertension (PSH) survey which included pooled historical data of 25,427 respondents showed 15% clinical practice hypertension prevalence. Most initial work-up includes ECG, urinalysis, cholesterol and sugar blood levels and chest x-ray examinations. Antihypertensive monotherapy preferences were calcium antagonists (25%), betablockers (8%), and diuretics (7%). Client awareness of being hypertensive is 52% with only 23% admitting good BP control. Almost 60% are asymptomatic at hypertension discovery. Role of diabetes, pregnancy, renal and eye problems in hypertension obtained low perception. Use of garlic and cleansing diet were perceived to be beneficial in BP control despite lack of documentation. Antihypertensive medication compliance was 33% in industrial patients compared to 51% in the general population. From this pooled survey data, programs and strategies will emerge in order to control the hypertension epidemic. A clear message seems obvious - it is wrong to assume that a patient understands a doctor's explanation readily.

Larner A.J.
University of Cambridge, Department of Anatomy, Downing Street, Cambridge CB2 3DY United Kingdom
Medical Hypotheses (United Kingdom), 1995, 44/4 (295-297)

The efficacy of garlic as a lipid-lowering agent is being increasingly recognized, but the biochemical mechanisms underlying this action are currently unknown. It is proposed that organic tellurium compounds, which are found in high concentration in fresh garlic buds, may contribute to this action by inhibiting squalene epoxidase, the penultimate enzyme in the synthetic pathway of cholesterol . Weanling rats fed a diet rich in tellurium develop a demyelinating polyneuropathy due to inhibition of this enzyme in peripheral nerves. Chronic exposure to small amounts of tellurium found in garlic might reduce endogenous cholesterol production through inhibition of hepatic squalene epoxidase and so reduce cholesterol levels. Tellurium may also contribute to the characteristic odour of garlic since the most obvious clinical sign of tellurium poisoning is a garlic -like odour.

Walper A.; Rassoul F.; Purschwitz K.; Schulz V.
Lichtwer Pharma GmbH, Wallenroder Strasse 8-10, D-13435 Berlin Germany
Med. Welt (Germany), 1994, 45/7-8 (327-323)

Within a primary lipid screening including 9251 persons a group of 8001 subjects (65% women, 35% men) with a serum level of 221 -300 mg/dl total cholesterol are recommended a diet with low fat and cholesterol content during 6-8 weeks. The 'nonresponder' received by continuous diet 600 mg/die of Allium sativum. After the period with diet alone the mean serum cholesterol level decrease was 3 mg/dl, after the next weeks with additional application of garlic powder a decrease of 6 mg/dl was measured. Short time dietary recommendations alone are not as succesful as a diet connected with application of standardized garlic powder. With a good compliance the effect of diet on serum cholesterol level is supported by phytotherapy.

Rosenson R.S.; Frauenheim W.A.; Tangney C.C.
Department of Medicine and Pathology, Preventive Cardiology Center, Rush University, Chicago, IL USA
Dis. Mon. (USA), 1994, 40/8 (373-462)

Dyslipidemias in patients with coronary heart disease confer a greater risk of ischemic cardiac events than comparable dyslipidemias in people free of disease. A major dyslipidemia can be diagnosed in more than 80% of patients with established premature coronary heart disease. These dyslipidemias constitute not only elevations of low-density lipoprotein cholesterol (hypercholesterolemia) but also indicate abnormalities in the metabolism of triglyceride-rich lipoproteins, high-density lipoproteins, and lipoprotein(a). Clinical trials have demonstrated that therapy to lower low- density lipoprotein levels can delay angiographic progression of coronary stenoses and reduce recurrent cardiac event rates. These clinical benefits from low-density lipoprotein cholesterol lowering may occur as early as 6 to 12 months after initiation of therapy. Intervention strategies for dyslipidemias are directed toward lowering the low-density lipoprotein cholesterol fraction to 90 to 100 mg/dl. This approach begins with dietary modification, weight loss, smoking cessation, and aerobic exercise. Patients with hypercholesterolemia refractory to nonpharmacologic intervention require lipid-lowering agents. The choice of lipid-lowering medications is influenced by concomitant abnormalities of lipoprotein metabolism, such as hypertriglyceridemia or hypoalphalipoproteinemia. Treatment of primary dyslipidemias other than hypercholesterolemia may be warranted in the presence of other cardiac risk factors; however, a broader spectrum of clinical trial data is needed to support or refute this contention.

De A. Santos O.S.; Grunwald J.
Lichtwer Pharma GmbH, Drewitzer Strasse 10, 1000 Berlin 28 Germany
Br. J. Clin. Res. (United Kingdom), 1993, 4/- (37-44)

In a double blind, placebo controlled randomised study the effects of a standardised garlic powder tablet (Kwai(*), Lichtwer Pharma) on blood lipids and blood pressure was investigated. A total of 52 out-patients with total cholesterol values over 6.5 mmol/l took part in the study. Patients were randomly allocated to take tablets containing a total of 900 mg garlic powder (standardised to 1.3% alliin) daily or the same number of placebo tablets for six months. All patients were advised to follow a low fat/ cholesterol diet. Blood lipids were measured at baseline and after three and six months treatment. Blood pressure and well-being were assessed in monthly intervals. The baseline mean for serum total cholesterol of 6.92 mmol/l was reduced to 6.31 mmol/l after six months of garlic powder tablet treatment. Corresponding values for placebo were 7.05 mmol/l before and 6.74 mmol/l after placebo treatment. The difference between active treatment and placebo is statistically significant (p < 0.05). The mean values for low density lipoprotein cholesterol (LDL-C) was reduced by nearly 10% by garlic and by 6% by placebo. Mean systolic blood pressure (SBP) remained unchanged in the placebo group and was reduced in the active treated group by 17% from 145 to 120 mmHg (p < 0.001). Mean diastolic blood pressure (DBP) remained unchanged in the placebo group and was reduced in the active treated group from 90 mmHg to 80 mmHg (p < 0.01). The differences between active and placebo treatment were significant after two months of treatment for DBP and after four months for SBP. Well-being, as analysed by a five-point score system, remained unchanged in the placebo group and was improved in the active treated group by 20% (p < 0.001).

Phelps S.; Harris W.S.
Lipid Laboratory, KU Medical Center, 3800 Cambridge St., Kansas City, KS 66160 USA
Lipids (USA), 1993, 28/5 (475-477)

Interventions which make serum lipoproteins less susceptible to oxidation may be antiatherogenic. The antioxidant properties of garlic which have been demonstrated in vitro led us to investigate the effects of garlic supplements on lipoprotein oxidation susceptibility in humans. Ten healthy volunteers were given 600 mg/d of garlic powder (6 tablets of Kwai (R)) for two weeks in a placebo-controlled, randomized, double-blind crossover trial. We found that although serum lipid and lipoprotein levels were not lowered in this short time period, the ex vivo susceptibility of apolipoprotein B-containing lipoproteins to oxidation was significantly decreased (-34%). Because garlic has been reported to beneficially affect serum lipid levels, platelet function, fibrinolysis and blood pressure, this additional effect of retarding lipoprotein oxidation may contribute to the potential antiatherosclerotic effect of garlic .

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Brosche T.; Platt D.
Lehrstuhl fur Innere Medizin - Gerontologie der Universitat, Heimerichstrasse 58, W-8500 Nurnberg 90 Germany, Federal Republic of
Fortschr. Med. (Germany, Federal Republic of), 1990, 108/36 (49-54)

Garlic (Allium sativum L.) is a commonplace drug. It is now available in the form of dragees made of garlic powder, standardized to 1.3% alliin. The lipid-lowering potential of such preparations has not been reviewed yet. In 7 out of 8 studies, including over 500 patients, a daily dose of 0.6 g to 0.9 g garlic powder reduced plasma cholesterol and triglyceride levels by 5 to 20 percent. The metabolic mechanisms of these reductions are not known.

Lau B.H.S.; Lam F.; Wang-Cheng R.
Department of Microbiology, School of Medicine, Loma Linda University, Loma Linda, CA 92350 USA
Nutr. Res. (USA), 1987, 7/2 (139-149)

The effect of an odor-modified liquid garlic extract on blood lipids was evaluated in human subjects over a six month period. Lowering of cholesterol , triglycerides, low density and very low density lipoproteins (LDL, VLDL) with rise of high density lipoprotein (HDL) was observed in the majority of subjects who took garlic extract; the effect was clearly more significant than with subjects taking placebo. Garlic extract did not significantly influence the levels of cholesterol and triglycerides in subjects whose initial cholesterol levels were relatively low. Of special interest was the initial rise of cholesterol , triglycerides, and LDL/VLDL with garlic supplementation, suggesting possible mobilization of tissue lipids into the circulation during this phase of garlic ingestion. This study confirms previous reports of lowering cholesterol and triglycerides using various garlic preparations. Furthermore, it suggests that odor-modified garlic extract may be used in conjunction with dietary modification for control of hyperlipidemia.

Gylling H; Riikonen S; Nikkila K; Savonius H; Miettinen TA
Department of Medicine, University of Helsinki, Finland.
Eur J Clin Invest (England) May 1998, 28 (5) p359-63

BACKGROUND: Our aim was to investigate whether intestinal binding of bile acids by guar gum, a dietary fibre, relieves cholestasis and pruritus in intrahepatic cholestasis of pregnancy.

METHODS: Forty-eight pregnant women with cholestasis and pruritus were randomized double-blind to guar gum and placebo until the time of delivery, and 20 healthy pregnant women were used as control subjects. The pruritus score and serum bile acids, lipids and non-cholesterol sterols were measured at baseline, at least 2 weeks after treatment, just before delivery and up to 4 weeks after delivery.

RESULTS: The increase in serum bile acids and worsening of pruritus were prevented by guar gum in relation to placebo (P < 0.05). Serum cholesterol was unchanged, but increased cholesterol precursor sterol values suggested that cholesterol synthesis was increased by guar gum. Serum cholestanol proportion, an indicator of cholestasis, was related to pruritus but was unaffected by guar gum.

CONCLUSION: We conclude that in intrahepatic cholestasis of pregnancy and pruritus, guar gum treatment is beneficial in relieving pruritus, even although indicators of cholestasis are only partially reduced.

Haack VS; Chesters JG; Vollendorf NW; Story JA; Marlett JA
Department of Nutritional Sciences, University of Wisconsin-Madison, 53706, USA.
Am J Clin Nutr (United States) Sep 1998, 68 (3) p615-22

Nine healthy, young men consumed constant diets to determine selected large-bowel, serum cholesterol and triacylglycerol, and calcium balance responses to 3 amounts of fiber provided by a mixture of fruit, vegetables, and grains. The diets, each consumed for 1 mo, contained 16, 30, and 42 g total fiber /d, of which 2.9, 4.8, and 7.7 g, respectively, was soluble. Mean daily wet and dry stool weights increased with each fiber addition. The first fiber addition increased defecation frequency and decreased fecal pH, bile acid concentration, and neutral steroid concentration; the second addition had no further effect. Mean weight of each defecation and stool moisture did not increase and serum cholesterol and triacylglycerol concentrations, calcium balance, and gastrointestinal transit time did not decrease as fiber intake increased. We conclude that 1) fiber provided by a mixed-food diet increases stool weight as effectively as does wheat or oat bran; 2) even high amounts of dietary fiber do not change transit time or defecation frequency if they are already approximately 1 and 2-3 d, respectively; 3) food patterns consistent with the food pyramid and incorporating legumes and whole grains are necessary to achieve recommended fiber intakes of 20-35 g/d, even if energy intake is > 12.55 MJ (3000 kcal); 4) soluble fiber provided by a mixture of whole foods has no effect on serum cholesterol concentrations or output of fecal bile acids; and 5) mixed-food fiber has little effect on calcium balance when calcium intakes are high (> or = 1.5 g/d).

Berezovs'kyi VIa; Lytova IH; Dynnyk OB; Korychens'kyi OM; Pavlyk IV
Lik Sprava (Ukraine) Mar-Apr 1998, (2) p80-2

Intensity was studied of sorption of cholesterol , bile acids, and phospholipids by cereals food fibre in samples of vesicular and hepatic bile. Intensive absorption has been shown of these fractions by food fibres. Clinical observation over 92 patients with chronic noncalculous cholecystitis confirmed the beneficial effect of cereals food fibre.

Hernandez-Avila M; Romieu I; Parra S; Hernandez-Avila J; Madrigal H; Willett W
Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Mexico.
Salud Publica Mex (Mexico) Mar-Apr 1998, 40 (2) p133-40

OBJECTIVE: To assess the reproducibility and validity of a 116 item semi-quantitative food frequency questionnaire (FFQ), designed to assess the relation between dietary intake and chronic diseases.

MATERIAL AND METHODS: To test the reproducibility of the FFQ questionnaire, the FFQ was administered twice to 134 women residing in Mexico City at an interval of approximately one year; to assess the validity we compared results obtained by the FFQs with those obtained by four 4-day 24-hour recalls at three month intervals. Validity and reproducibility were evaluated using regression analysis and Pearson and intraclass correlation coefficients of log-e and calorie-adjusted nutrient scores.

RESULTS: Mean values for intake of most nutrients assessed by the two food frequency questionnaires were similar. However, means for the 24-hr recall were significantly lower. Intraclass correlation coefficients for nutrient intakes, assessed by questionnaires, administered one year apart, ranged from 0.38 for cholesterol to 0.54 for crude fiber. Correlation coefficients between energy-adjusted nutrient intakes, measured by diet recalls, and the first FFQ ranged from 0.12 for polyunsaturated fatty acids to 0.67 for saturated fatty acids. Regression coefficients between 24-hr recall and FFQ,s were all significant were significant for all nutrients, except for polyunsaturated fat, folic acid, vitamin E and Zinc.

CONCLUSIONS: These data indicate that this semi-quantitative FFQ is reproducible and provides a useful estimate by which to categorize individuals by level of past nutrient intake. However, its application outside Mexico City or in different age and gender populations will require additional modifications and validation efforts.

Chow SE; Lee RS; Shih SH; Chen JK
Department of Biology, National Taiwan Normal University, Taipei.
FASEB J (United States) Jul 1998, 12 (10) p823-30

Human low density lipoprotein (LDL) is prepared in the presence of antioxidants and is oxidized to different levels (measured by thiobarbituric acid reactive substance) with copper ion. The effects of unoxidized LDL and oxidized LDL (ox-LDL) on stress fiber formation, cell membrane ruffling, and pinocytosis (measured by [14C]sucrose uptake) in cultured human umbilical cord vein endothelial cells (EC) are compared. We show that at a concentration range of 100 to 200 microg cholesterol /ml, both unoxidized LDL and ox-LDL promote EC elongation and stress fiber formation, but the effect by the latter is more prominent when compared at the same dose range. In addition, ox-LDL also induces EC membrane ruffling and promotes pinocytosis. These effects are positively correlated with the extent of LDL oxidation and depend on the dose of ox-LDL. Ox-LDL-promoted membrane ruffling and pinocytosis are effectively blocked by brief preexposure of the cells to antioxidants. In contrast, stress fiber formation is not affected by antioxidant pretreatment. Although unoxidized LDL also promotes [14C]sucrose uptake, it is less potent than ox-LDL and significantly higher concentrations are required to produce a detectable effect. Unlike ox-LDL, unoxidized LDL-enhanced pinocytosis is not accompanied by the appearance of membrane ruffling; therefore, they may act via different mechanisms. Elevated pinocytosis may increase transcytotic activity of the endothelium, leading to an increased influx of plasma components such as LDL into the subendothelial space.

Pogozheva AV
Vopr Pitan (Russia) 1998, (1) p39-42

Dietary fibers belong to the group of polymeric compounds with different chemical origin. They play an important part in functioning of number of organs and body systems and in the first place influence upon the function of large intestine. Having ability to retain water, they accelerate an intestine transit and peristalsis of large intestine, and are the stool forming factor. Dietary fibers adsorb many bile acids, metabolites, toxins and electrolytes and promote detoxification of organism. Due to ionchange properties dietary fibers are capable to remove ions of heavy metals and radionuclides. Dietary fibers render positive action during the functional diseases of large intestine, reduce blood cholesterol concentration, have hypolipidemic effect and can be used for prophylactic and therapy of cardiovascular and other diseases.

Martinez-Gonzalez MA; Lopez-Azpiazu I; Kearney J; Kearney M; Gibney M; Martinez JA
Department of Epidemiology and Public Health, University of Navarra, Pamplona, Spain.
Public Health (England) Mar 1998, 112 (2) p95-101

A national survey was carried out to find out how the Spanish adult population defined 'healthy eating'. Consumers were asked to describe in their own words what 'healthy eating' means to them. The sample included 1009 Spanish subjects over 15 y of age selected by a multietapic procedure. This study belongs to the Spanish partnership in a pan-European survey about attitudes to food, nutrition and health coordinated by the Institute of European Food Studies of Dublin. The results were shown as the percentages of the sample who gave one of the five most frequently mentioned descriptions ('more vegetables', 'balanced diet', 'more fruit', 'less fat' and 'more fish') and the distribution of responses by age, sex, region, socio-economic level and education level. A multivariable logistic regression model was fitted to assess the characteristics independently related to the use of the definition 'balance and variety' for healthy eating. The majority of the Spanish people defined 'healthy eating' as a diet with 'more vegetables' as the main description. Other descriptions commonly mentioned were 'less fat', 'more fruit', 'more fish', and 'more lean meat'. A higher age was associated with a lower likelihood of mentioning the concept of balanced diet. A higher educational level was also independently and strongly related to a higher prevalence of this definition. Differences between men and women showed only borderline significance. Our results suggest the need to improve nutritional education about fiber, low fat and cholesterol. It would be interesting to develop strategies in Spain to educate people on a definition of 'healthy eating' based upon 'balance and variety'.

Subar AF; Krebs-Smith SM; Cook A; Kahle LL
National Cancer Institute, Applied Research Branch, Bethesda, Md. 20892-7344, USA.
J Am Diet Assoc (United States) May 1998, 98 (5) p537-47

OBJECTIVE: To identify major food sources of 27 nutrients and dietary constituents for US adults.

DESIGN: Single 24-hour dietary recalls were used to assess intakes. From 3,970 individual foods reported, 112 groups were created on the basis of similarities in nutrient content or use. Food mixtures were disaggregated using the US Department of Agriculture (USDA) food grouping system.

SUBJECTS/SETTING: A nationally representative sample of adults aged 19 years or older (n = 10,638) from USDA's 1989-91 Continuing Survey of Food Intakes by Individuals.

ANALYSES PERFORMED: For each of 27 dietary components, the contribution of each food group to intake was obtained by summing the amount provided by the food group for all respondents and dividing by total intake from all food groups for all respondents.

RESULTS: This article updates previous work and is, to the authors' knowledge the first to provide such data for carotenes, vitamin B-12, magnesium, and copper. Beef, yeast bread, poultry, cheese, and milk were among the top 10 sources of energy, fat, and protein. The following other major sources also contributed more than 2% to energy intakes: carbohydrate: yeast bread, soft drinks/soda, cakes/cookies/ quick breads/doughnuts, sugars/syrups/jams, potatoes (white), ready-to-eat cereal, and pasta; protein: pasta; and fat: margarine, salad dressings/mayonnaise, and cakes/ cookies/quick breads/doughnuts. Ready-to-eat cereals, primarily because of fortification, were among the top 10 food sources for 18 of 27 nutrients.

APPLICATIONS/CONCLUSIONS: These analyses are the most current regarding food sources of nutrients and, because of disaggregation of mixtures, provide a truer picture of contributions of each food group.

Lloyd T; Chinchilli VM; Rollings N; Kieselhorst K; Tregea DF; Henderson NA; Sinoway LI
Department of Obstetrics and Gynecology, The College of Medicine and University Hospitals, The Pennsylvania State University at The Milton S Hershey Medical Center, Hershey 17033, USA.
tlloyd@psuhmc.hmc.psu.edu
Am J Clin Nutr (United States) Apr 1998, 67 (4) p624-30

The objective of this study was to compare the relations among nutrient intake, fitness, serum antioxidants, and cardiolipoprotein profiles in female adolescents. The study design was a cross-sectional analysis of the Penn State Young Women's Health Study. The present study was performed with the entire cohort (n = 86) when they were 17.1+/-0.5 y (x+/-SD) of age. Primary measurements included cardiolipoprotein indexes, serum antioxidants, nutrient intakes, aerobic fitness, and percentage body fat. The cohort was stratified by estimated maximal oxygen uptake (VO2max) measurements and by percentage body fat. The fifth quintile by estimated VO2max had significantly lower percentage body fat, higher athletic scores, higher fruit intake, lower total serum cholesterol , and lower ratios of total serum cholesterol to HDL cholesterol than members of the first quintile. When the members of the first and fifth quintiles by percentage body fat were compared, the first quintile had significantly lower weight, lower body mass index, higher estimated VO2max, higher athletic scores, lower ratios of total serum cholesterol to HDL cholesterol , and higher fruit, carbohydrate, and fiber intakes. Correlation analyses performed with the data for the entire cohort showed fruit consumption to be positively correlated with estimated VO2max, and predicted VO2max to be positively correlated with circulating beta-carotene and alpha-tocopherol. This study provided evidence that the positive associations of exercise and fruit consumption with cardiovascular health apply to female adolescents as well as to adults.

Hunt JR; Matthys LA; Johnson LK
US Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, ND 58202-9034, USA.
Am J Clin Nutr (United States) Mar 1998, 67 (3) p421-30

Zinc absorption, mineral balance, and blood lipid concentrations were measured in 21 women aged 33 +/- 7 y (range: 20-42 y) consuming controlled lactoovovegetarian and nonvegetarian diets for 8 wk each in a crossover design. The lactoovovegetarian and nonvegetarian diets, respectively, provided (by analysis) 973 and 995 mg Ca, 1.8 and 1.3 mg Cu, 367 and 260 mg Mg, 5.9 and 2.5 mg Mn, 1457 and 1667 mg P, 9.1 and 11.1 mg Zn, and (by calculation) 40 and 16 g dietary fiber , 2.5 and 0.8 mmol phytic acid, molar ratios of phytate to Zn of 14 and 5, and millimolar ratios of (phytate x Ca) to Zn of 344 and 111. Dietary zinc absorption was measured by extrinsic isotopic labeling and whole-body counting. Plasma cholesterol , cholesterol fractions, and lipoproteins were reduced 7-12% with the lactoovovegetarian diet, consistent with predictions based on dietary cholesterol and fat. Blood pressure was unaffected. Calcium, copper, magnesium, and phosphorus balances were not different between diets; manganese balance tended to be greater with the lactoovovegetarian diet (P < 0.07). The lactoovovegetarian diet was associated with a 21% reduction in absorptive efficiency that, together with a 14% reduction in dietary zinc, reduced the amount of zinc absorbed by 35% (2.4 compared with 3.7 mg/d) and reduced plasma zinc by 5% within the normal range. Zinc balance was maintained with both diets. Although there is a greater risk of zinc deficiency in persons consuming lactoovovegetarian compared with omnivorous diets, with inclusion of whole grains and legumes zinc requirements can be met and zinc balance maintained.

Davidson MH; Maki KC; Kong JC; Dugan LD; Torri SA; Hall HA; Drennan KB; Anderson SM; Fulgoni VL; Saldanha LG; Olson BH
Chicago Center for Clinical Research, IL 60610, USA
mdavidson@cccr.com
Am J Clin Nutr (United States) Mar 1998, 67 (3) p367-76

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.

Nagata C; Takatsuka N; Kurisu Y; Shimizu H
Department of Public Health, Gifu University School of Medicine, Gifu 500, Japan.
J Nutr (United States) Feb 1998, 128 (2) p209-13

The relationship between soy product intake and serum total cholesterol concentration was examined in 1242 men and 3596 women who participated in an annual health check-up program in Takayama City, Japan, provided by the municipality in 1992. The intake of soy products and various foods and nutrients was assessed by a semiquantitative food-frequency questionnaire. Blood samples were collected from fasting subjects to measure the serum total cholesterol concentration. A significant trend (P for trend = 0. 0001) was observed for decreasing total cholesterol concentration with an increasing intake of soy products in men after controlling for age, smoking status and intake of total energy, total protein and total fat. This negative trend (P for trend = 0.0001) was also noted in women after controlling for age, menopausal status, body mass index and intake of total energy and vitamin C. An additional adjustment for physical activity, coffee and tea consumption, and intake of cholesterol , carbohydrates, fiber and vitamin E did not change the results. These data suggest a role for soy products in human cholesterol homeostasis.

Duindam JJ; Vrensen GF; Otto C; Greve J
Department of Morphology, The Netherlands Ophthalmic Research Institute, Amsterdam.
Invest Ophthalmol Vis Sci (United States) Jan 1998, 39 (1) p94-103

PURPOSE: Focal opacities are signs of early cataractogenesis in the human lens. They progress slowly over a lifetime and may be precursors of mature cataracts. The authors analyzed changes in proteins, phospholipids, and cholesterol in these opacities using in situ techniques: Raman microspectroscopy, filipin cytochemistry for cholesterol , and transmission electron microscopy (TEM).

METHODS: Human lenses with verified focal opacities were fixed in 1% paraformaldehyde. Slabs with opacities were analyzed using confocal Raman spectroscopy, then filipin Raman analysis of cholesterol , and finally TEM.

RESULTS: Compared with normal fibers, opacities consistently showed elevated levels of cholesterol and aliphatic chains, increased phospholipid acyl chain disorder, and changes in phospholipid lateral packing. Disulfide bridges of specific geometry (trans-gauche-trans) were found. Although protein content was unchanged, compared with normal fibers, aromatic amino acid content was significantly lower. The hydrophobicity of tyrosine residues showed a significant decrease, and a change in the tryptophan indole ring angle was found. The changes were abrupt and sharply delineated focal opacities. TEM confirmed this sharp boundary and showed that the opacities were densely packed with vesicles of varying size and electron density embedded in a homogenous matrix.

CONCLUSIONS: The Raman and TEM analyses of opacities showed that early cataractogenic events led to disruption of fiber membranes, formation of vesicles from the membrane constituents, and protein changes. The aberrant morphology of the membranes enveloping the focal opacities may have segregated the affected fibers from the surrounding normal tissue, thus explaining the stationary or slowly progressing character of these opacities.

Davidson M.H.; Dugan L.D.; Stocki J.; Dicklin M.R.; Maki K.C.; Coletta F. ; Cotter R.; McLeod M.; Hoersten K.
M.H. Davidson, Chicago Center for Clinical Research, Chicago, IL 60610 United States
Journal of Nutrition (United States), 1998, 128/11 (1927-1932)

This study was designed to determine whether a soluble dietary fiber supplement containing gum arabic and pectin in apple juice would lower serum lipids in 110 hypercholesterolemic men and women. Subjects were stabilized on an American Heart Association Phase I Diet for 8 wk. Those with elevated low density lipoprotein cholesterol levels, despite dietary modification, continued to follow the diet and were randomly assigned to receive 720 mL/d of apple juice containing 0 (control), 5, 9 or 15 g of gum arabic and pectin (4:1 ratio) for 12 wk, followed by a 6-wk apple juice-only washout phase. Serum lipid profiles, body weight and 3-day diet records were collected at 3- wk intervals. No significant differences among groups were observed in serum lipid responses during treatment or washout. During the treatment phase, mean serum total cholesterol and triglyceride concentrations increased by 3.5 and 28.5%, respectively (all groups combined, P < 0.0001). The high density lipoprotein cholesterol level did not change significantly from baseline in any group. During washout, mean total cholesterol concentration rose by an additional 2.4% (P < 0.05) compared with the value at the end of the treatment period, suggesting that the apple juice used to deliver the fiber supplement may have contributed to the adverse changes observed in the serum lipid profile. These findings do not support the hypothesized hypocholesterolemic effect of the gum arabic/pectin (4:1) mixture studied, but do underline the importance of selecting appropriate vehicles for delivery of dietary fiber mixtures.

Outila T.; Karkkainen M.; Seppanen R.; Lamberg-Allardt C.
Dr. C. Lamberg-Allardt, Dept. of Applied Chem./Microbiology, Division of Nutrition, University of Helsinki, PO Box 27, FIN-00014 Helsinki Finland
Scandinavian Journal of Nutrition/Naringsforskning (Sweden), 1998, 42/3 (98-103)

We have investigated the food and nutrient intake of five demi-vegans, six lacto-vegetarians and fourteen omnivores, all females and aged 22-45 years, collecting a total of 42 dietary records per person in 2-day periods during one year. The yearly mean intakes of cereals, vegetables, fruits and berries, dietary fibre and vitamin C were higher and that of sugar, eggs, saturated fat and cholesterol lower in the vegetarians than in the omnivores. The intake of iron was higher in the vegetarians, but their serum ferritin levels were lower throughout the year than in the omnivores indicating lower iron status in vegetarians. The vegetarian diets provided practically no vitamin D, which was reflected in a low serum 25-hydroxyvitamin-D concentration during spring, but during summer concentrations increased to the adequate level. Furthermore, the mean iodine intake of vegetarians using minor amounts of dairy products was below the recommended level. Thus, the vegetarians had lower cholesterol , saturated fat and higher carbohydrates and fibre intakes than omnivores. However, seven of the eleven vegetarians were iron deficient throughout the year and six had serum 25-hydroxyvitamin-D concentrations below reference values in the winter.

Hornstra G.; Barth C.A.; Galli C.; Mensink R.P.; Mutanen M.; Riemersma R.A.; Roberfroid M.; Salminen K.; Vansant G.; Verschuren P.M.
Dr. G. Hornstra, Department of Human Biology, Maastricht University, PO Box 616, NL-6200 MD, Maastricht Netherlands
British Journal of Nutrition (United Kingdom), 1998, 80/Suppl. 1 (S113-S146)

Cardiovascular disease has a multifactorial aetiology, as is illustrated by the existence of numerous risk indicators, many of which can be influenced by dietary means. It should be recalled, however, that only after a cause-and-effect relationship has been established between the disease and a given risk indicator (called a risk factor in that case), can modifying this factor be expected to affect disease morbidity and mortality. In this paper, effects of diet on cardiovascular risk are reviewed, with special emphasis on modification of the plasma lipoprotein profile and of hypertension. In addition, dietary influences on arterial thrombotic processes, immunological interactions, insulin resistance and hyperhomocysteinaemia are discussed. Dietary lipids are able to affect lipoprotein metabolism in a significant way, thereby modifying the risk of cardiovascular disease. However, more research is required concerning the possible interactions between the various dietary fatty acids, and between fatty acids and dietary cholesterol. In addition, more studies are needed with respect to the possible importance of the postprandial state. Although in the aetiology of hypertension the genetic component is definitely stronger than environmental factors, some benefit in terms of the development and coronary complications of atherosclerosis in hypertensive patients can be expected from fatty acids such as alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid. This particularly holds for those subjects where the hypertensive mechanism involves the formation of thromboxane A2 and/or alpha1-adrenergic activities. However, large-scale trials are required to test this contention. Certain aspects of blood platelet function, blood coagulability, and fibrinolytic activity are associated with cardiovascular risk, but causality has been insufficiently proven. Nonetheless, well-designed intervention studies should be initiated to further evaluate such promising dietary components as the various n-3 and n-6 fatty acids and their combination, antioxidants, fibre, etc. for their effect on processes participating in arterial thrombus formation. Long-chain polyenes of the n-3 family and antioxidants can modify the activity of immunocompetent cells, but we are at an early stage of examining the role of immune function on the development of atherosclerotic plaques. Actually, there is little, if any, evidence that dietary modulation of immune system responses of cells participating in atherogenesis exerts beneficial effects. Although it seems feasible to modulate insulin sensitivity and subsequent cardiovascular risk factors by decreasing the total amount of dietary fat and increasing the proportion of polyunsaturated fatty acids, additional studies on the efficacy of specific fatty acids, dietary fibre, and low-energy diets, as well as on the mechanisms involved are required to understand the real function of these dietary components. Finally, dietary supplements containing folate and vitamins B6 and/or B12 should be tested for their potential to reduce cardiovascular risk by lowering the plasma level of homocysteine.

Rodriguez-Moran M.; Guerrero-Romero F.; Lazcano-Burciaga G.
Dr. F. Guerrero-Romero, Siqueiros 225 esq, Durango CP 34000 Mexico
Journal of Diabetes and its Complications (United States), 1998, 12/5 (273-278)

The beneficial effect of dietary fiber in the management of type II diabetes is still controversial and has not been totally demonstrated. The purpose of this study was to determine the plasma-lowering effects of 5 g t.i.d. of Plantago Psyllium, as an adjunct to dietary therapy, on lipid and glucose levels, in patients with type II diabetes. Patients were randomly selected from an outpatient clinic of primary care to participate in a double-blind placebo-controlled study in which Plantago Psyllium or placebo was given in combination with a low fat diet. One hundred twenty-five subjects were included in the study that consisted in a 6-week period of diet counseling followed by a 6-week treatment period. Fasting plasma glucose, total plasma cholesterol , LDL cholesterol , HDL cholesterol and triglyceride levels were measured every 2 weeks. The test products (Psyllium or placebo) were supplied to subjects in identically labeled foil packets containing a 5-g dose of product, to consume three doses per day (of 5 g each one), before regular meals. There was an excellent tolerance to Psyllium, without significant adverse effects. No significant changes were observed in the patient's weight for both groups (not significant). Fasting plasma glucose, total cholesterol , LDL cholesterol , and triglycerides levels, showed a significant reduction (p < 0.05), whereas HDL cholesterol increased significantly (p < 0.01) following Psyllium treatment. Our results show that 5 g t.i.d. of Psyllium is useful, as an adjunct to dietary therapy, in patients with type II diabetes, to reduce plasma lipid and glucose levels, resolving the compliance conflict associated with the ingest of a great amount of fiber in customary diet.

Swedberg K.B.
Dr. K.B. Swedberg, Department of Medicine, Sahlgrenska Univ. Hospital/Ostra, S-41685 Goteborg Sweden
American Journal of Cardiology (United States), 1998, 82/6 A (8H-14H)

Several independent predictors of the risk of atherosclerosis are known including plasma cholesterol concentration, cigarette smoking, elevated blood pressure, as well as genetic factors such as non-insulin-dependent diabetes and plasma fibrinogen. Also known are the 3 major elements of the pathogenesis of atherosclerosis, involving modification of endothelial function, changes in vascular tone, and clinical sequelae of hyperplasia of smooth muscle cells in the intima of the affected blood vessels. This article further examines vasoconstrictor/vasodilator balance, the role of angiotensin II, and the significant role played by the endothelium in the complex events and interactions that occur both with smooth muscle cells and platelets. Clinical evidence of endothelial dysfunction in coronary artery disease is presented. The importance of the association of the progression of coronary artery disease with signs of neuroendocrine activation, the relation of endothelin-1 to mechanisms of neuroendocrine activation, and how the counteraction of this activation may have beneficial effects on disease progression are discussed.

Dennison B.A.; Rockwell H.L.; Baker S.L.
Dr. B.A. Dennison, Mary Imogene Bassett Research Inst., One Atwell Road, Cooperstown, NY 13326-1394 United States
Journal of the American College of Nutrition (United States), 1998, 17/4 (371-378)

Background: Current recommendations call for most Americans, 2 years of age and over, to eat more fruits and vegetables.

Objective: To determine, in a sample of healthy children, the extent to which young children's diets include the recommended numbers of fruit and vegetable servings per day.

Design: Cross-sectional study?

Setting: A general primary care health center in upstate New York.

Participants: One-hundred-sixteen 2-year-old children and 107 5-year-old children, who were scheduled for a non-acute visit, and their parent/primary caretaker (PPC) were recruited between 1992 and 1993.

Measurements: For 168 children (94 2-year-old children and 74 5-year-old children), mean dietary intakes were calculated from 7 days of written dietary records, entered and analyzed using the Minnesota Nutrition Data System. The numbers of fruit and vegetable servings/day were calculated according to USDA definitions of serving sizes.

Results: The 2-year-old children consumed the same amounts of fruits, 100% fruit juice, and total fruits and vegetables as the 5-year-old children (0.8 and 0.7 fruit servings/day, 1.0 and 0.8 juice servings/day, and 2.2 and 2.1 total fruit and vegetable servings/day, respectively). Fruit juice accounted for 54% of all fruit servings consumed and 42% of all fruit and vegetable servings consumed. Total fruit consumption (fruits plus juice) was correlated with carbohydrate intake (R=0.46), and inversely correlated with total fat and saturated fat intakes (R= -0.48 and R= -0.36, respectively, both p<0.0001) and with cholesterol intake (R= -0.21, p<0.01). Citrus fruit and juice consumption was strongly correlated with vitamin C intake (R=0.56, p<0.0001). Total vegetable consumption was strongly correlated with beta-carotene and vitamin A intakes (R=0.63 and R=0.32, respectively, both p<0.0001). Total fruit and vegetable consumption correlated with intakes of beta-carotene, vitamin A, vitamin C, fiber , and potassium (R=0.55, R=0.31, R=0.56, R=0.58, and R=0.66, respectively, all p<0.0001). Forty percent of 2-year old children and 50% of 5-year-old children consumed <2 servings/day of fruits and vegetables. Ninety-five percent of children consuming less than or equal to2 servings/day of fruits and vegetables met the RDA for vitamin C vs. 50% of those consuming <2 servings/day (p<0.001).

Conclusions: In this study, preschool-aged children consumed, on average, about 80% of the recommended fruit servings/day, but only 25% of the recommended vegetable servings/day. Low intakes of fruits and vegetables were associated with inadequate intakes of vitamin A, vitamin C, and dietary fiber , in addition to high intakes of total fat and saturated fat.

Arjmandi B.H.; Khan D.A.; Juma S.; Drum M.L.; Venkatesh S.; Sohn E.; Wei L.; Derman R.
Dr. B.H. Arjmandi, Department of Nutritional Sciences, 425 Human Environmental Sciences, Oklahoma State University, Stillwater, OK 74078-6141 United States
Nutrition Research (United States), 1998, 18/7 (1203-1214)

We conducted a double-blind cross-over study to compare the effects of whole flaxseed and sunflower seed, as part of the daily diet, on the lipid profile of postmenopausal women. During two 6-wk periods, thirty-eight mild, moderate, or severely (5.85-9.05 mmol/L) hypercholesterolemic postmenopausal women were randomly assigned to one of the two regimens: flaxseed or sunflower seed. The subjects were provided with 38 g of either treatment in the forms of breads and muffins. The first treatment period lasted six weeks and was followed by a two-wk washout phase. After the washout phase, subjects switched regimens and treatments continued for another 6 weeks. Blood samples were collected at baseline, 6, 8, and 14th wk of the study periods. Significant (p<0.01) reductions in total cholesterol were observed for both treatments (6.9 and 5.5% for flaxseed and sunflower seed, respectively). However only flaxseed regimen was able to significantly (p<0.001) lower LDL- cholesterol (14.7%). Serum HDL- cholesterol and triglyceride concentrations were unaffected by either of the treatments. Most interestingly, lipoprotein(a) [Lp(a) ], a strong predictor of cardiovascular disease, concentrations were significantly (p<0.05) lowered by the flaxseed treatment (7.4% compared to baseline values). Regression analyses showed the strongest association between age and both total and LDL- cholesterol concentrations. Among the dietary variables, total and soluble fiber intakes were negatively correlated with serum total and LDL-cholesterol concentrations. The cholesterol lowering effects of flaxseed and sunflower seed may be due to the activity of single or multiple components, including alpha-linolenic or linoleic acids, total and soluble fiber , and non-protein constituents present in these seeds.

Coats A.J.S.
A.J.S. Coats, Department of Cardiology, Royal Brompton Hospital, London SW3 6NP United Kingdom
Postgraduate Medical Journal (United Kingdom), 1998, 74/873 (391-394)

The three major modifiable coronary risk factors are smoking, hypertension, and hypercolesterolaemia. Serum cholesterol levels are above the desirable level of 5.2 mmol/l in 79% of men and 65% of women aged between 35 and 50 years and thus are an important target for intervention. In this paper, the role of nonpharmacological intervention with soluble fibre in treating mild to moderate primary hypercholesterolaemia is reviewed. Evidence from controlled studies shows that soluble fibre can be effective in lowering cholesterol by clinically significant amounts. It is stressed, however, that risk factors for coronary heart disease are interactive and attention is shifting to addressing multiple rather that individual factors.

Pandya D.P.
Dr. D.P. Pandya, 16 Lilian St., Edison, NJ 08817 United States
Comprehensive Therapy (United States), 1998, 24/4 (198-204)

Modification of the nutritional risk factors, along with moderate amount of fiber content in food, fresh fruits and vegetables, necessary mineral supplements, smoking reduction and routine physical exercise, is an important strategy for the prevention and reduction of adverse outcome in coronary heart disease.

Ishikawa Y.; Akasaka Y.; Ishii T.; Komiyama K.; Masuda S.; Asuwa N.; Choi- Miura N.-H.; Tomita M.
Dr. Y. Ishikawa, Department of Pathology, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8450 Japan
Arteriosclerosis, Thrombosis, and Vascular Biology (United States), 1998, 18/4 (665-672)

The distribution of apolipoprotein (apo) J during the development of atherosclerosis in the human aorta was evaluated by immununohistochemical observation, together with the other apolipoprotein A-I, A-II, B, C-III, and E. Although apoJ was never observed in the normal aorta (ie, without any intimal lesions or intimal thickening), it was distributed not only in the intima but also in the media of aortas with diffuse, intimal thickening or atherosclerotic lesions. Double immunostaining with antibodies for apoJ and alpha-smooth muscle actin revealed apoJ deposition in smooth muscle cells (SMCs) or the aortic stroma in the vicinity of SMCs. The extent of apoJ distribution in the aortic wall increased with the degree of atherosclerosis development. In addition, the distribution pattern of apoJ was very similar to that of apoA-I and E. In situ hybridization with human apoJ cDNA demonstrated intense signals in cells scattered within the subendothelial space and medial SMCs of the aorta with advanced atherosclerosis but not in those of the normal aorta without intimal thickening. Furthermore, reverse transcriptase-polymerase chain reaction of the cultured human aortic SMCs revealed apoJ mRNA expression in these cells. The results indicate that apoJ in the aortic wall originates from not only apoJ circulated in the plasma but also apoJ produced by SMCs in the aortic wall. Considering the similarities of the distribution between apoJ and apo-A-I or E, we hypothesize that apoJ possibly has a protective role against human atherosclerosis by its involvement with cholesterol transport from the aortic wall to the liver.

Jenkins D.J.A.; Kendall C.W.C.; Ransom T.P.P.
Dr. D.J.A. Jenkins, Clinical Nutrition, St. Michael's Hospital/Dept. of Med., University of Toronto, Toronto, Ont. M5S 3E2 United Kingdom
Nutrition Research (United States), 1998, 18/4 (633-652)

Speculation on the evolution of the human diet together with comparative studies with the diet of other primates suggest that the human gastrointestinal tract and metabolism are adapted to high fiber diets. Epidemiological studies support a negative association between dietary fiber intake and risk of coronary heart diseases (CHD). For the most part, the association has been with insoluble fiber , especially wheat bran. However, viscous fiber sources are likely to play a role since they reduce lipid rink factors for CHD including total and low-density-lipoprotein cholesterol and apolipoprotein B by increasing fecal bile acid losses. In addition, soluble fiber may reduce the rate of nutrient absorption so altering chylomicron synthesis and reducing postprandial glucose and insulin levels and other risk factors for CHD. There is also evidence that soma insoluble fibers might alter serum lipids and improve carbohydrate tolerance but these phenomena need to be confirmed and other mechanisms explored including improved clothing and thrombolytic factors and increased antioxidant status. Epidemiology, clinical and laboratory studies support increased consumption of high fiber foods as part of the strategy to reduce the risk of CHD.

Poulter N.R.
Prof. N.R. Poulter, Cardiovascular Studies Unit, Dept. of Clin. Pharmacol./Therapeut., Imperial College School of Medicine, St Mary's, London W2 1PG United Kingdom
British Journal of Cardiology (United Kingdom), 1998, 5/3 (156-163)

Although there is now general agreement that lowering blood cholesterol levels brings about a reduction in the incidence of coronary heart disease (CHD), there is no consensus as to how and on whom lipid lowering should be attempted. With millions of people likely to benefit from cholesterol lowering, many of them with no overt signs or symptoms of CHD, managing hypercholesterolaemia needs to be effective, inexpensive, and highly acceptable to patients. This review looks briefly at the need to manage hypercholesterolaemia, and then considers the methods available for management. In particular, it explores the potential role of the addition of soluble fibre to the diet.

Hudgins L.C.; Seidman C.E.; Diakun J.; Hirsch J.
L.C. Hudgins, Lab. of Human Behavior and Metabol., Rockefeller University, 1230 York Avenue, New York, NY 10021 United States
American Journal of Clinical Nutrition (United States), 1998, 67/4 (631-639)

Using new nonisotopic and isotopic methods, we showed previously that fatty acid synthesis was markedly stimulated in weight-stable normal volunteers by a very-low-fat formula diet with 10% of energy as fat and 75% as short glucose polymers. In this study, we determined whether fatty acid synthesis was equally stimulated by a very-low-fat solid diet made with foods consumed typically. Four normal volunteers consumed the same very-low-fat formula diet for 25 d and then an isoenergetic solid food diet with 10% of energy as fat and 75% as starch, simple sugars, and fiber for 25 d. To measure fatty acid synthesis, the fatty acid compositions of the diets were matched to the composition of each subject's adipose tissue and compared with the composition of VLDL-triacylglycerol. In all subjects, the large increases in newly formed palmitate and decreases in linoleate in VLDL-triacylglycerol were quickly reversed by the solid food diet, and the fraction of de novo synthesized fatty acids in fasting VLDL-triacylglycerol decreased from 30- 54% to 0-1%. In a second group of subjects, the stimulation of fatty acid synthesis by the formula diet with 75% glucose polymers was similarly reduced by a formula diet with amounts of fat, starch, and sugar chosen to mimic those of the solid food diet, but persisted after the addition of fiber or a diet with 75% sugar. In conclusion, an increase in fatty acid synthesis and palmitate-rich, linoleate-poor VLDL-triacylglycerol induced by very-low-fat, high-sugar diets may be reduced by the substitution of dietary starch for sugar with potentially beneficial effects on cardiovascular health.

Heller FR; Descamps O; Hondekijn JC
Department of Internal Medicine, Hopital de Jolimont, Belgium.
Atherosclerosis (Ireland) Apr 1998, 137 Suppl pS25-31

The peroxidation step of lipid transormation is considered to be essential in the pathogenesis of atherosclerosis. Although data concerning the mechanisms by which lipid peroxidation occurs in vivo are scarce, several lines of evidence suggest that some endogenous and exogenous compounds with antioxidant activity could have some beneficial effects in the prevention of atherosclerosis. Ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) act as the most important hydrophilic and lipophilic antioxidants, respectively in vivo. Accordingly, animal and human studies suggest that these compounds may have some preventive effect against the development of clinical coronary heart disease. Many plant phenols and flavonoids may be important dietary antioxidants and it has been speculated that these compounds in red wine or in the Mediterranean diet could explain the 'French paradox'. Several studies show that antioxidants such as probucol and butylated hydroxytoluene can inhibit development of atherosclerotic lesions in Watanabe and cholesterol -fed rabbits. Some drugs such as beta-blockers, calcium antagonists, hypolipodemic drugs,...appear to have at least in vitro antioxidant effects but the clinical relevance of these properties remains unkonwn. Moreover, some interventions aimed to decrease the LDL-oxidative susceptibility have not been shown to attenuate atherogenesis when cholesterol levels remain markedly elevated. (55 Refs.)

Ginter E; Zloch Z; Ondreicka R
Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic.
Physiol Res (Czech Republic) 1998, 47 (2) p137-41

Guinea-pigs were maintained for 5 weeks on a diet containing three different concentrations of vitamin C : a) traces (none added), b) medium (0.05% w/w) and high (0.5% w/w). Twenty-four hours before killing the animals received one i.p. dose of 3 g ethanol per kg body weight (a model of short-term acute intoxication). In a parallel experiment which lasted 5 weeks, the animals were treated every week with two i.p. doses of 1 g ethanol per kg body weight followed by the final acute intoxication (3g ethanol/kg) (a model of long-term chronic alcoholization). In both experiments, the guinea-pigs with the highest tissue concentration of vitamin C proved to have significantly decreased residual levels of ethanol and acetaldehyde in the liver and the brain, a decreased activity of alanine- and aspartate aminoacyl transferases in the serum and decreased contents of triacylglycerols and cholesterol in the serum and liver in comparison with the vitamin C -unsupplemented group. The regression curve expressing vitamin C levels versus residual ethanol and acetaldehyde concentrations in the liver confirmed the highly significant negative correlation between them. Administration of the guinea-pigs with large amounts of vitamin C appears to accelerate ethanol and acetaldehyde metabolism and reduce some of their adverse health effects.

Crawford RS; Kirk EA; Rosenfeld ME; LeBoeuf RC; Chait A
Department of Medicine, University of Washington, Seattle 98195-6426, USA.
Arterioscler Thromb Vasc Biol (United States) Sep 1998, 18 (9) p1506-13

Oxidized low density lipoprotein (LDL) promotes atherogenesis. Although pharmacological antioxidants such as probucol inhibit both LDL oxidation and atherosclerosis in hyperlipidemic animals, the effects of natural antioxidants such as vitamin E are inconclusive. To further determine the effects of supplemental dietary antioxidants in vivo, we evaluated whether combined dietary antioxidants (0.1% vitamin E, 0.5% beta-carotene, and 0.05% vitamin C) inhibit LDL oxidation and fatty streak lesion development in homozygous LDL receptor-null (LDLR-/-) mice fed a high-fat, high- cholesterol diet. An additional group of mice were fed black tea, which has been shown to inhibit LDL oxidation in vitro. After receiving a high-fat, high- cholesterol diet for 8 weeks, the combined antioxidant-supplemented (antioxidant) group (n=18), tea group (n=19), and control group (n=17) had equivalent plasma cholesterol levels. LDL oxidation, as measured by the lag phase of conjugated diene formation, was markedly inhibited in the antioxidant group compared with the tea or control groups [mean lag phases=143+/-7 (antioxidant), 100+/-5 (tea), and 84+/-4 (control) minutes; P<0.0001 antioxidant versus tea or control]. The cross-sectional surface area of fatty streak lesions in the aortic sinus was reduced by 60% in the antioxidant group compared with both the tea and control groups (P<0.0001 antioxidant versus tea or control). There was no difference in lesion area between tea and control groups. Although both LDL oxidation and atherosclerosis were significantly inhibited in the antioxidant group, no correlation between lag phase values and lesion size was observed among individual animals. Furthermore, black tea did not inhibit fatty streak development in LDLR-/- mice. These data suggest that combined natural dietary antioxidants inhibit both LDL oxidation and atherogenesis in animals with elevated LDL but that inhibition of LDL oxidation alone may not prevent the development of atherosclerosis.

Schwenke DC; Behr SR
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1072, USA.
schwenke@bgsm.edu
Circ Res (United States) Aug 24 1998, 83 (4) p366-77

Several antioxidants inhibit atherosclerosis. This study investigated the hypothesis that combining vitamin E, a lipophilic antioxidant, with vitamin C , a hydrophilic antioxidant, and/or selenium, a cofactor of peroxidases that detoxify lipid peroxides, would inhibit atherosclerosis more effectively than vitamin E alone. We also considered whether regional variation in inhibition of atherosclerosis by antioxidants would be associated with regional variation in aortic lipophilic antioxidants. Rabbits were fed an atherogenic diet (control) or an atherogenic diet supplemented with vitamin E, vitamins E and C, vitamin E+selenium, vitamins E and C+selenium, or probucol (positive control). Supplements were as follows: vitamin E, 146 IU/d; vitamin C , 791 mg/d; selenium, 22 microg/d; or probucol, 406 mg/d. Vitamin C did not influence atherosclerosis. After 22 weeks of treatment, rank order of aortic atherosclerosis was control>vitamin E (with or without vitamin C )>vitamin E+selenium (with or without vitamin C)>probucol. Antioxidant treatment reduced aortic cholesterol concentrations 21% to 56%, 29% to 86%, and 19% to 75% for the aortic arch, descending thoracic aorta, and abdominal aorta, respectively (P<0.025 to P<0.0003 by ANOVA), with slightly greatly reductions for areas of atherosclerotic lesions. Some treatments reduced plasma cholesterol concentrations, but none altered the distribution of cholesterol among lipoproteins. Corrected for differences in plasma cholesterol concentrations, aortic cholesterol concentrations were reduced up to 72% (P<0.02) by the antioxidant treatments, with equal reductions by vitamin E+selenium and by probucol. Aortic alpha-tocopherol standardized by aortic cholesterol as a measure of aortic lipids was lower in the abdominal aorta than in the aortic arch of rabbits not given alpha-tocopherol and increased relatively more in the abdominal aorta than in the aortic arch with alpha-tocopherol supplementation. The results of this study suggest that vitamin E+ selenium inhibited atherosclerosis as effectively as an equally hypocholesterolemic dose of probucol by a mechanism(s) that is in part independent of effects on plasma and lipoprotein cholesterol concentrations. The tendency for greater efficacy of antioxidant treatments in the abdominal aorta than aortic arch may relate to the lower concentrations of alpha-tocopherol in the abdominal aorta of unsupplemented rabbits.

Montano CE; Fernandez ML; McNamara DJ
Department of Nutritional Sciences and Interdisciplinary Nutritional Science Program, University of Arizona, Tucson, USA.
Metabolism (United States) Jul 1998, 47 (7) p883-91

Effects of suboptimal and adequate vitamin C , with varying dietary fat saturation, on hepatic cholesterol and plasma lipoprotein concentrations and metabolism were studied in guinea pigs fed 15% (wt/wt) fat/0.04% cholesterol diets. Fat mixtures were either 49% saturated (SFA) (24% lauric acid) or 53% polyunsaturated fatty acid (PUFA) linoleic acid with vitamin C at 50 (suboptimal) or 500 (adequate) mg/kg diet. Guinea pigs fed suboptimal vitamin C had 15% lower hepatic active 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and 25% lower low-density lipoprotein (LDL; apolipoprotein [apo] B/E) receptor number, 20% higher acyl-CoA:cholesterol acyltransferase (ACAT) activity, 28% higher triacylglycerol (TAG) and cholesteryl ester concentrations, and increased very-low-density lipopoprotein (VLDL) apo B secretion rates in comparison to animals fed adequate vitamin C. Intake of suboptimal vitamin C lowered plasma high-density lipoprotein (HDL) cholesterol concentrations by 45% and increased plasma TAG, total and VLDL/LDL cholesterol , and cholesteryl ester transfer protein (CETP) activity by 40%, 50%, and 30%, respectively. The hyperlipidemic effects of suboptimal vitamin C were more pronounced with intake of the SFA diet. These data demonstrate that low vitamin C intake results in a pattern of changes in whole-body cholesterol and lipoprotein metabolism that are related to increased risk of cardiovascular disease (CVD).

Harman SK; Parnell WR
Department of Human Nutrition, University of Otago, Dunedin.
N Z Med J (New Zealand) Mar 27 1998, 111 (1062) p91-4

AIM: To determine whether adult non-vegetarian Seventh-day Adventists differ in selected nutrition related health aspects from adult vegetarian Seventh-day Adventists.

METHODS: One hundred and forty-one Seventh-day Adventist church members responded to a general health questionnaire. Forty-seven sex and age matched subjects (23 non-vegetarians and 24 vegetarians) were selected for further investigation. Blood lipids, serum vitamin B12, folate, haemoglobin and ferritin levels were measured along with stature, weight and blood pressure. A quantitative 7-day diet record was also completed.

RESULTS: Body mass index was similar between the non-vegetarian and vegetarian groups but diastolic blood pressure was higher for non-vegetarian than vegetarian males. Even though the dietary vitamin B12 intake was significantly lower (p < 0.01) in the vegetarian group both vegetarians and non-vegetarians recorded similar serum vitamin B12 levels. The vegetarian and non-vegetarian groups had similar haemoglobin concentrations. While dietary iron intake was higher in the female vegetarian group, though predominantly in the non-haem form, the difference was not significant. Low serum ferritin levels were found in both female dietary groups even though the vegetarian group had a significantly (p < 0.05) higher vitamin C intake. Blood lipid levels were similar in the two diet groups even though the vegetarian group had a lower percentage energy contribution from total and saturated fat (p < 0.01) and consumed significantly less cholesterol.

CONCLUSION: Both non-vegetarian and vegetarian Seventh-day Adventists appear likely to enjoy a lower risk of nutrition related chronic degenerative disease than the average New Zealander and have a satisfactory iron and vitamin B12 status.

Ford ES
Division of Nutrition, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.
J Clin Epidemiol (England) Jan 1998, 51 (1) p55-60

This study examines the potential coverage bias in telephone surveys. Data were analyzed from the first phase of the third National Health and Nutrition and Examination Survey conducted from 1988 to 1991. In that survey, 10,120 persons 17 years and older were interviewed and 9034 were examined. About 2.7% of respondents reported not having a telephone. Differences in demographic and lifestyle variables, but not physiological or anthropometric variables, existed between persons with a telephone and those without one. Respondents without a telephone were more likely to report that an impairment or health problems limited their work or activities. Compared with respondents with a telephone, those without one were more likely to be current smokers, to be less physically active, to never have had their blood pressure checked or have had it checked more than 5 years ago, and to never have had their cholesterol checked. Based on data from a 24-hour dietary recall, persons without a telephone consumed less vitamin A, vitamin C , vitamin E, and carotene than did respondents with a telephone. However, prevalence estimates of health characteristics obtained from telephone surveys in populations with high telephone coverage are unlikely to be seriously affected by coverage bias nor are conclusions of comparisons involving populations with low telephone coverage.

Pierdomenico SD; Costantini F; Bucci A; De Cesare D; Cuccurullo F; Mezzetti A
Centro per lo Studio dell'Ipertensione Arteriosa, delle Dislipidemie e dell'Arteriosclerosi, Dipartimento di Medicina e Scienze dell'Invecchiamento, University G. D'Annunzio, Chieti, Italy.
pierdomenico@unich.it
Hypertension (United States) Feb 1998, 31 (2) p621-6

Low-density lipoprotein oxidation and antioxidant vitamins E and C were investigated in white-coat hypertension in comparison with sustained hypertension and normotension. We selected 21 sustained hypertensive subjects, 21 white-coat hypertensive subjects, and 21 normotensive subjects matched for gender, age, and body mass index. White-coat hypertension was defined as clinical hypertension and daytime ambulatory blood pressure <139/90 (subjects were also reclassified using 134/90 and 135/85 mm Hg as cutoff points for daytime blood pressure). Blood samples were drawn for lipid profile determination, assessment of fluorescent products of lipid peroxidation in native LDL, evaluation of susceptibility to LDL oxidation in vitro (lag phase and propagation rate), and determination of LDL vitamin E and plasma vitamins E and C contents. Compared with sustained hypertensive subjects, white-coat hypertensives had significantly lower fluorescent products of lipid peroxidation (15.4+/-3.4 versus 10.2+/-3 units of relative fluorescence/mg LDL protein, P<.05), longer lag phase (54+/-10 versus 88+/-10 minutes, P<.05), lower propagation rate (8.2+/-2.5 versus 5.95+/-2.1 nmol diene/min per mg LDL cholesterol , P<.05), higher LDL vitamin E content (8.3+/-1.1 versus 10.1+/-1.8 nmol/mg LDL cholesterol , P<.05), and plasma vitamin C content (40+/-13 versus 57+9 micromol/L, P<. 05). No significant difference was observed between white-coat hypertensive and normotensive subjects. The results did not change after reclassification of subjects. Our data show that white-coat hypertensive subjects do not show an enhanced propensity to LDL oxidation or reduction in antioxidant vitamins. Given the role of LDL oxidation in the development of atherosclerosis and that of vitamin E and C in protecting against it, these findings suggest that white-coat hypertension per se carries a low atherogenic risk.

Harats D; Chevion S; Nahir M; Norman Y; Sagee O; Berry EM
Lipid Research Laboratory, Sheba Hospital, Tel Hashomer, Israel.
Am J Clin Nutr (United States) Feb 1998, 67 (2) p240-5

To determine the effects of vitamin C on cardiovascular risk factors, we studied dietary vitamin C enrichment in 36 healthy male students consuming a diet high in saturated fatty acids. After a 1-mo run-in period during which the subjects consumed approximately 50 mg ascorbic acid/d (low-C diet), half of the subjects were randomly assigned to receive 500 mg ascorbic acid/d for an additional 2 mo (high-C diet). Plasma ascorbic acid increased from 13.5 micromol/L with the low-C diet to 51.7 micromol/L with the high-C diet. Plasma cholesterol increased slightly with the high-C diet, but not above baseline concentrations. This increase was offset by an increase in the lag period of in vitro LDL oxidation, which correlated with plasma ascorbic acid concentrations (r = 0.735, P = 0.0012). Lipoprotein vitamin E concentrations were unchanged with the two diets. There were no effects on concentrations of fibrinogen or factor VII. The fact that ascorbic acid reduced the in vitro susceptibility of lipoproteins to oxidation provides presumptive evidence for an interaction between aqueous and lipophilic antioxidants (vitamins C and E) in maintaining the integrity of LDL particles.

Marangon K; Herbeth B; Lecomte E; Paul-Dauphin A; Grolier P; Chancerelle Y; Artur Y; Siest G
Centre de Medecine Preventive, Vandoeuvre-les-Nancy, France.
Am J Clin Nutr (United States) Feb 1998, 67 (2) p231-9

The aim of this study was to assess the association between smoking, food consumption, and antioxidant vitamin intake and plasma indexes of oxidative stress and antioxidant defenses in French adults. Food and nutrient intakes of 459 healthy men aged 23-57 y were estimated by the diet history method and analyzed by smoking status. Plasma alpha-tocopherol, ascorbic acid, and carotenoids were measured as antioxidants and malondialdehyde, protein Schiff bases, and autoantibodies against malondialdehyde-protein adducts as oxidative stress indexes. Smokers ate less fruit and vegetables than nonsmokers, leading to lower vitamin E, vitamin C , and carotene intakes, even after adjustment for age, education, and marital status. Unlike vitamin E, plasma ascorbic acid and beta-carotene concentrations were reduced in smokers compared with nonsmokers and were inversely related to cigarette consumption. This difference remained significant after adjustment for alcohol and dietary intakes. Among the measured oxidative stress indexes, only Schiff base concentration was positively related to the number of cigarettes smoked. In our sample of French men, smoking had an adverse effect on antioxidant status; vitamin intakes were reduced in smokers and plasma antioxidant indexes were altered independently of dietary intakes. As in other countries, in France smokers require particular attention in terms of public health intervention.

Liu JF; Lee YW
School of Nutrition and Health Science, Taipei Medical College, Taipei, Taiwan, R.O.C.
J Nutr (United States) Jan 1998, 128 (1) p116-22

To investigate the effect of dietary oxidized frying oil (OFO) on tissue retention of vitamin C , and to explore the effect of vitamin C supplementation on tissue vitamin E concentrations and lipid peroxidation, male weanling guinea pigs were divided into four groups. Guinea pigs were fed 15% OFO diets supplemented with vitamin C at 300, 600 or 1500 mg/kg diet. Control animals were fed a diet containing 15% fresh untreated soybean oil with 300 mg/kg of vitamin C. After 60 d of feeding, body weight gain, food intake, feed efficiency and plasma triglyceride concentration were significantly lower in guinea pigs fed OFO diets than in controls (P < 0.05). However, plasma cholesterol concentration was highest in guinea pigs fed the OFO diet supplemented with 300 mg/kg vitamin C. Increasing vitamin C in OFO diets significantly reduced plasma cholesterol concentration. Plasma and tissue vitamins C and E concentrations were significantly lower in the OFO-fed guinea pigs receiving 300 mg/kg vitamin C than in controls. Greater levels of supplemental vitamin C increased tissue vitamins C and E. Guinea pigs fed OFO diets had significantly higher tissue levels of thiobarbituric acid reactive substances (TBARS) (P < 0.05) than controls. Our results demonstrated that OFO feeding, which impaired alpha-tocopherol retention and increased TBARS, could be alleviated somewhat by vitamin C supplementation.

Delport R.; Ubbink J.B.; Human J.A.; Becker P.J; Myburgh D.P.; Hayward Vermaak W.J.
R. Delport, Department of Chemical Pathology, Faculty of Medicine, University of Pretoria, PO Box 2034, Pretoria 0001 South Africa
Clinica Chimica Acta (Netherlands), 1998, 278/1 (55-60)

Decreased antioxidant-vitamin nutritional status may increase lipid peroxidation and susceptibility of low-density lipoprotein (LDL) to oxidative modification. The aim of this study was to evaluate the vitamin nutritional status of coronary artery disease (CAD) patients and to assess the risk of CAD related to each individual antioxidant vitamin. The study was performed as a case-control study with 41 patients with angiographically demonstrated CAD and 41 apparently healthy age- and smoking status-matched controls. Plasma vitamin E, C and A concentrations were significantly decreased in CAD patients compared with controls (p<0.001) after correcting for significant covariates. Per quartile decrease in vitamin A and E concentrations was associated with increased risk of CAD, even after adjusting for CAD risk factors, while per quartile decrease in vitamin C concentrations was not associated with significant CAD risk after adjusting for CAD risk factors. Decreased vitamin A and E concentrations are independently associated with increased risk of CAD independent from other CAD risk factors in white male South Africans and dietary intervention strategies are advocated. Copyright (C) 1998 Elsevier Science B.V.

Fillion L.; Henry C.J.K.
C.J.K. Henry, School Biological Molecular Sciences, Oxford Brookes University, Gipsy Lane, Headington, Oxford OX3 0BP United Kingdom
International Journal of Food Sciences and Nutrition (United Kingdom), 1998, 49/2 (157-168)

Recent consumer interest in 'healthy eating' has raised awareness to limit the consumption of fat and fatty foods. What are the relative nutritional advantages and disadvantages of consuming fried foods? Are all fried foods bad for you? A review on macro- and micronutrients losses and gains during frying is presented here. Frying has little or no impact on the protein or mineral content of fried food, whereas the dietary fibre content of potatoes is increased after frying due to the formation of resistant starch. Moreover, the high temperature and short transit time of the frying process cause less loss of heat labile vitamins than other types of cooking. For example, vitamin C concentrations of French fried potatoes are as high as in raw potatoes, and thiamine is well retained in fried potato products as well as in fried pork meat. The nutritive value of the frying media is also important to take into consideration and therefore losses of nutrients from the frying oil are also discussed. Although some unsaturated fatty acids and antioxidant vitamins are lost due to oxidation, fried foods are generally a good source of vitamin E. It is true that some fat is inevitably taken up by the food being fried, contributing to an increased energy density. However, this also results in highly palatable foods with a high nutritional content. It is concluded that fried foods certainly have a place in our diets.

Gey K.F.
Dr. K.F. Gey, Dept. Chemistry/Molecular Biology, University of Berne, Buhlstrasse 28, CH-3000 Berne 9 Switzerland
BioFactors (Netherlands), 1998, 7/1-2 (113-174)

Antioxidants are crucial components of fruit/vegetable-rich diets preventing cardiovascular disease (CVD) and cancer: - plasma vitamins C, E, carotenoids from diet correlate prevalence of CVD and cancer inversely, low levels predict an increased risk of individuals which is potentiated by combined inadequacy (e.g., vitamins C+E, C+carotene, A+carotene); - self-prescribed rectification of vitamins C and E at adequacy of other micronutrients reduce forthcoming CVD, of vitamins A, C, E, carotene and conutrients also cancer; - randomized exclusive supplementation of beta-carotene plus or minus vitamin A or E lack benefits except prostate cancer reduction by vitamin E, and overall cancer reduction by selenium; - randomized intervention with synchronous rectification of vitamins A+C+E+B + minerals reduces CVD and counteracts precancerous lesions; - high vitamin E supplements reveal potentials in secondary CVD prevention. Plasma values desirable for primary prevention: less than or equal to30 micromol/l lipid-standardized vitamin E alpha-tocopherol/cholesterol less than or equal to 5.0 micromol/mmol); less than or equal to 50 micromol/l vitamin C aiming at vitamin C /vitamin E ratio >1.3-1.5; less than or equal to 0.4 micromol/l beta- (less than or equal to 0.5 micromol/l alpha+beta-) carotene. Conclusions: - in CVD vitamin E acts as first risk discriminator, vitamin C as second one; - optimal health requires synchronously optimized vitamins C+E, A, carotenoids and vegetable conutrients.

Far SR; Master HE; Billimoria FR; Sane RT
Dept. of Biochemistry, L.T.M. Medical College, Sion, Bombay.
Indian J Med Sci (India) Mar 1996, 50 (3) p63-7

Synthetic gugulsterones when administered to rats for a period of 3 weeks in dose of 5.0 mg/kg body weight/day caused a reduction in levels of total cholesterol by 30%, LDL-chol. by 40%, Tg by 40%. VLDL-chol. by 40% and HDL-chol. by 35%. The drug when administered to rats for a period of 16 weeks with increasing dose upto 1150 mg/kg body weight/day, reduced VLDL-chol. and Tg. by 55% and 50% respectively (P < 0.001) and LDL-chol by 33% (P < 0.05), whereas HDL-chol. was increased by 25% (P < 0.001). Histopathological studies on liver, spleen, intestine, lung, kidney, stomach and adrenal gland revealed drug related changes in a few animals upon exposure to high dose of the drug.

Sheela CG; Augusti KT
Department of Bio-Chemistry, University of Kerala, Thiruvananthapuram, India.
Indian J Exp Biol (India) Oct 1995, 33 (10) p749-51

S-allyl cysteine sulfoxide, isolated from garlic, A. sativum, is more or less as active as gugulipid in controlling hypercholestermia, obesity and derangement of enzyme activities in cholesterol diet fed rats. The beneficial effects of the drugs are partly due to their inhibitory effects on transaminases, alkaline phosphatase, lipogenic enzymes and HMG CoA reductase and partly due to their stimulatory effects on plasma lecithin- cholesterol acyl transferase lipolytic enzymes and fecal excretion of sterols and bile acids.

Sheela CG; Augusti KT
Department of Biochemistry, University of Kerala, India.
Indian J Exp Biol (India) May 1995, 33 (5) p337-41

Cholesterol containing diet significantly increased not only the body weight, but also the weight of liver and adipose tissue of rats. This is accompanied by a significant increase in blood lipids, atherogenic index and lipid peroxidation and a significant decrease in reduced glutathione level, superoxide dismutase and catalase activities in tissues. Treatment with S-allyl cysteine sulphoxide reverses the deleterious effects of cholesterol diet significantly and almost as effectively as gugulipid.

Nityanand S; Srivastava JS; Asthana OP
J Assoc Physicians India (India) May 1989, 37 (5) p323-8

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.

Katz E.A.
190 W. Surry Rd,Keene, NH 03431 United States
Journal of Orthomolecular Medicine (Canada) 1996, 11/3 (173-179)

Data in the literature suggests that elevated Lp(a) contributes to coronary artery disease. This case study documents the use of ascorbic acid, amino acids lysine and proline, an ayurvedic herb gum gugulu , pure crystaline niacin, and guar gum in lowering Lp(a). These natural substances were well tolerated and each lowered Lp(a) significantly. In this study (32 months duration) one of the above mentioned substances and/or an increase or change in dosage was given approximately every two months to a 62 year old female with extremely elevated familial Lp(a). Blood lipids were drawn and results were recorded before changes were made. At the end of 32 months Lp(a) was reduced by 81 points or 63%. Significant regression of coronary artery blockages was documented by a Board Certified Cardiologist who analyzed two angiograms performed one and half years apart, the latter performed 19 months after the study began. It was also observed that Lp(a) decreased directly in relation to the decrease in LDL. Research with clinical studies is recommended to test the efficacy of the above-mentioned nutritional substances in lowering Lp(a) and in both lessening the risk of coronary artery disease and in regressing already existing disease. This is especially crucial for those families with a strong history of familial coronary artery disease and elevated Lp(a).

Ghatak A.; Asthana O.P.
Division of Clinical, Experimental Medicine, Central Drug Research Institute, P.O. Box No. 173,Lucknow - 226 001 India
Indian Journal of Pharmacology (India) 1995, 27/1 (14-29)

Hyperlipoproteinemias cause atherosclerosis which is a major cause of death in the developed world and is also now becoming a major cause of morbidity and mortality in India, especially with changing lifestyles and increasing stress and food habits shifting towards the 'fast food' era. If is extremely important to understand the risk factors, the criteria for starting treatment, the efficacy and safety profile of drugs for hyperlipoproteinemia and the drugs which are available for pharmacotherapy especially in the Indian perspective. The significant contributions of Central Drug Research Institute, Lucknow in developing potent lipid lowering drugs like Gugulipid an already marketed product and a new synthetic drug coded as compound 80/574 in the early phase of clinical trials have been specially discussed in this article. At present it is recommended that for mild to moderate hyperlipoproteinemia Gugulipid would be an extremely cost effective indigenous choice and with the further development of the new CDRI compound 80/574 even moderate to severe hyperlipoproteinemia would be manageable. The other alternatives like Gemfibrozil though highly effective for moderate to severe hyperlipoproteinemia are extremely expensive and have other side effects and only very few can afford to take it on long term basis in India.

Johansson JO; Egberg N; Asplund Carlson A; Carlson LA
Research Centre of General Medicine, NVSO, Karolinska Hospital, Stockholm, Sweden
J Cardiovasc Risk, 1997 Jun, 4:3, 165-71

BACKGROUND: Nicotinic acid in gram doses decreases cholesterol and triglyceride concentrations in plasma, but the effect on haemostatic function is not known.

METHODS: Twenty-three men with hypertriglyceridaemia were treated with 4 g nicotinic acid daily for 6 weeks. Tests for haemostatic function and serum lipoproteins were performed before and at the end of the period of treatment.

RESULTS: Treatment with nicotinic acid had the expected effect on lipoprotein concentrations: it reduced the serum concentrations of triglyceride and the three major density fractions of triglyceride (very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL)). The VLDL cholesterol concentration was reduced, but that of HDL cholesterol was increased (all P<0.0001). The lipoprotein(a) (Lp(a)) concentration decreased significantly (P<0.01). The total fibrinolytic activity was increased by nicotinic acid treatment as indicated by decreases in plasminogen activator inhibitor-1 activity from 34.3 to 23.8 U/ml (P<0.01) and in alpha2-antiplasmin activity from 1.10 to 0.97 U/ml (P<0.01). The plasma fibrinogen concentration decreased from 3.55 to 3.01 U/ml (P<0.01). Multvariate analysis showed that the changes in alpha2-antiplasmin and Lp(a) concentrations could explain 53% of the change in plasma fibrinogen, suggesting that increased plasmin mobilization could be responsible for the decrease in plasma fibrinogen.

CONCLUSION: This study of hypertriglyceridaemic men has shown that long-term treatment with nicotinic acid not only corrects serum lipoprotein abnormalities, but also reduces the fibrinogen concentration in plasma and stimulates fibrinolysis.

Goldberg AC
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Am J Cardiol, 1998 Dec 17, 82:12A, 35U-38U; discussion 39U-41U

Niacin is a useful lipid-modifying drug because it (1) decreases low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and lipoprotein(a), and (2) raises high-density lipoprotein (HDL) cholesterol. Its use tends to be limited by side effects and inconvenient dosing regimens. The availability of an extended-release preparation (Niaspan-which has safety and efficacy similar to immediate-release niacin but which can be given once a day) provides an opportunity to increase the use of this effective lipid-modifying agent. To study the safety and efficacy of escalating doses of extended-release niacin, hyperlipidemic patients were randomly assigned to placebo or Niaspan. A forced dose-titration was done with the dosage increasing by 500 mg every 4 weeks to a maximum of 3,000 mg/day. Niaspan showed dose-related changes in total, LDL, and HDL cholesterol levels, triglycerides, cholesterol/HDL ratio, and lipoprotein(a). At a dosage of 2,000 mg/day, total cholesterol decreased by 12.1%, LDL cholesterol by 16.7%, triglycerides by 34.5%, and lipoprotein(a) by 23.6%; HDL cholesterol increased by 25.8%. Flushing was the most commonly reported side effect; flushing episodes tended to decrease with time despite an increasing dose of niacin. Of the reported side effects, only pruritus and rash were significantly different between the 2 groups. Aspartate aminotransferase, lactate dehydrogenase, and uric acid increased in a dose-dependent fashion, but fasting blood sugar increased by about 5% across most dosages. Two subjects had aspartate aminotransferase levels greater than twice the upper limit of normal, but there were no subjects in whom transaminases increased to 3 times the upper limit of normal. Women tended to have a greater LDL cholesterol response to the medication and also experienced more side effects, especially at higher dosages. Thus, the use of lower dosages of niacin may be desirable in women. The results of this dose-escalation study show beneficial effects of Niaspan on the entire lipid profile. At the maximum recommended dosage of 2,000 mg/day, all lipid and lipoprotein levels changed in desirable directions. Side effects (other than flushing) and blood chemistries were comparable to those seen with immediate-release niacin.

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Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats

Babu PS; Srinivasan K
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, India.
Molecular and Cellular Biochemistry (Netherlands), 1997, 166/1-2 (169-175)

Streptozotocin-induced diabetic rats were maintained on 0.5% curcumin containing diet for 8 weeks. Blood cholesterol was lowered significantly by dietary curcumin in these diabetic animals. Cholesterol decrease was exclusively from LDL-VLDL fraction. Significant decrease in blood triglyceride and phospholipids was also brought about by dietary curcumin in diabetic rats. In a parallel study, wherein diabetic animals were maintained on a high cholesterol diet, the extents of hypercholesterolemia and phospholipidemia were still higher compared to those maintained on control diet. Curcumin exhibited lowering of cholesterol and phospholipid in these animals also. Liver cholesterol, triglyceride and phospholipid contents were emin showed a distinct tendency to counter these changes in lipid fractions of liver. This effect of curcumin was also seen in diabetic animals maintained on high cholesterol diet. Dietary curcumin also showed significant countering of renal cholesterol and triglycerides elevated in diabetic rats. In order to understand the mechanism of hypocholesterolemic action of dietary curcumin, activities of hepatic cholesterol-7a-hydroxylase and HMG CoA reductase were measured. Hepatic cholesterol-7a-hydroxylase activity was markedly higher in curcumin fed diabetic animals suggesting a higher rate of cholesterol catabolism.

Effects of S-allyl cysteine sulfoxide isolated from Allium sativum Linn and gugulipid on some enzymes and fecal excretions of bile acids and sterols in cholesterol fed rats

Sheela C.G.; Augusti K.T.
Founder General Secretary, Kerala Academy of Sciences, Medical College, Thiruvananthapuram 695 011 India
Indian Journal of Experimental Biology (India), 1995, 33/10 (749-751)

S-allyl cysteine sulfoxide, isolated from garlic, A. sativum, is more or less as active as gugulipid in controlling hypercholesterolemia, obesity and derangement of enzyme activities in cholesterol diet fed rats. The beneficial effects of the drugs are partly due to their inhibitory effects on transaminases, alkaline phosphatase, lipogenic enzymes and HMG CoA reductase and partly due to their stimulatory effects on plasma lecithin-cholesterol acyl transferase lipolytic enzymes and fecal excretion of sterols and bile acids.

Antiperoxide effects of S-allyl cysteine sulphoxide isolated from Allium sativum Linn and gugulipid in cholesterol diet fed rats

Sheela C.G.; Augusti K.T.
Kerala Academy of Sciences, Jai Nagar, Thiruvananthapuram 695 011 India
Indian Journal of Experimental Biology (India), 1995, 33/5 (337-341)

Cholesterol containing diet significantly increased not only the body weight, but also the weight of liver and adipose tissue of rats. This is accompanied by a significant increase in blood lipids, atherogenic index and lipid peroxidation and a significant decrease in reduced glutathione level, superoxide dismutase and catalase activities in tissues. Treatment with S-allyl cysteine sulphoxide reverses the deleterious effects of cholesterol diet significantly and almost as effectively as gugulipid.

Recent trends in hyperlipoproteinemias and its pharmacotherapy

Ghatak A.; Asthana O.P.
Division of Clinical, Experimental Medicine, Central Drug Research Institute, P.O. Box No. 173, Lucknow - 226 001 India
Indian Journal of Pharmacology (India), 1995, 27/1 (14-29)

Hyperlipoproteinemias cause atherosclerosis which is a major cause of death in the developed world and is also now becoming a major cause of morbidity and mortality in India, especially with changing lifestyles and increasing stress and food habits shifting towards the 'fast food' era. If is extremely important to understand the risk factors, the criteria for starting treatment, the efficacy and safety profile of drugs for hyperlipoproteinemia and the drugs which are available for pharmacotherapy especially in the Indian perspective. The significant contributions of Central Drug Research Institute, Lucknow in developing potent lipid lowering drugs like Gugulipid an already marketed product and a new synthetic drug coded as compound 80/574 in the early phase of clinical trials have been specially discussed in this article. At present it is recommended that for mild to moderate hyperlipoproteinemia Gugulipid would be an extremely cost effective indigenous choice and with the further development of the new CDRI compound 80/574 even moderate to severe hyperlimia would be manageable. The other alternatives like Gemfibrozil though highly effective for moderate to severe hyperlipoproteinemia are extremely expensive and have other side effects and only very few can afford to take it on long term basis in India.

Cholesterol biosynthesis inhibitory component from Zingiber officinale Roscoe

Tanabe M; Chen YD; Saito K; Kano Y
Nagakura Pharmaceutical Company Ltd., Osaka, Japan.
Chem Pharm Bull (Tokyo) (Japan) Apr 1993, 41 (4) p710-3

We previously reported on the isolation and identification of (E)-8 beta,17-epoxylabd-12-ene-15,16-dial (ZT) from ginger (rhizome of Zingiber officinale Roscoe, Zingiberaceae). In this paper, the pharmacological effects of ZT are reported. The experimental mouse hypercholesterolemia induced by Triton WR-1339 was treated after oral administration of ZT. In homogenated rat liver with ZT, cholesterol biosynthesis was decreased. In addition, the same activity was observed in the homogenated rat liver which was resected after the oral administration of ZT. According to the results of general pharmacological screening, no remarkable activity of ZT was observed except for an inhibitory effect on the cholesterol biosynthesis.

Effect of psyllium in hypercholesterolemia at two monounsaturated fatty acid intakes.

Jenkins DJ; Wolever TM; Vidgen E; Kendall CW; Ransom TP; Mehling CC; Mueller S; Cunnane SC; O'Connell NC; Setchell KD; Lau H; Teitel JM; Garvey MB; Fulgoni V 3rd; Connelly PW; Patten R; Corey PN
Clinical Nutrition and Risk Factor Modification Center, J Alick Little Core Lipid Laboratory, St Michael's Hospital, Toronto, Ontario, Canada.
tina.perera@utoronto.ca
Am J Clin Nutr (United States) May 1997, 65 (5) p1524-33

We performed two studies to determine whether the lipid-lowering effect of viscous soluble fiber was modified by monounsaturated fatty acid (MUFA). First, psyllium (1.4 g/MJ) was compared with wheat bran (control) in 1-mo metabolic diets by using a randomized crossover design (n = 32 hyperlipidemic subjects). The background diet contained approximately 6% of energy as MUFA (20% of total fat). The second study (n = 27 hyperlipidemic subjects) was similar to the first but the background diet contained approximately 12% MUFA (29% of total fat) because of the addition of canola oil. At both fat intakes, psyllium resulted in significant reductions in total, low-density-lipoprotein (LDL), and high-density-lipoprotein (HDL) cholesterol compared with the wheat bran control. For the psyllium diet at 6% compared with 12% MUFA, the decreases in LDL cholesterol were 12.3 +/- 1.5% (P < 0.001) and 15.3 +/- 2.4% (P < 0.001), respectively. With the higher-MUFA diet triacylglycerol fell significantly over the control phase (16.6 +/- 5.5%, P = 0.006) and the ratio of LDL to HDL cholesterol fell significantly over the psyllium phase (7.3 +/- 2.8%, P = 0.015). Psyllium and MUFA intakes were negatively related to the percentage change in the ratio of LDL to HDL cholesterol (r = -0.34, P = 0.019 and r = -0.44, P = 0.002, respectively). Chenodeoxycholate synthesis rate increased (30 +/- 13%, P = 0.038) with the psyllium diet in the 12 subjects in whom this was assessed. We conclude that psyllium lowered LDL- and HDL-cholesterol concentrations similarly at both MUFA intakes. However, there may be some advantage in combining soluble fiber and MUFA to reduce the ratio of LDL to HDL cholesterol.

Wheat bread supplemented with depolymerized guar gum reduces the plasma cholesterol concentration in hypercholesterolemic human subjects.

Blake DE; Hamblett CJ; Frost PG; Judd PA; Ellis PR
Division of Life Sciences, King's College London, United Kingdom.
Am J Clin Nutr (United States) Jan 1997, 65 (1) p107-13

Recent human studies have shown that the physiologic effects of guar gum are not diminished by partial depolymerization of its galactomannan fraction. We evaluated the effect of depolymerized guar galactomannan on fasting plasma cholesterol and triacylglycerol concentrations in healthy volunteers with moderately raised plasma cholesterol concentrations (range: 5.2-8.0 mmol/L). This study was designed as a randomized, double-blind crossover of two 3-wk feeding periods separated by a 4-wk washout period. Control and guar wheat breads were prepared by a commercial bread-making process. Subjects (n = 11) were asked to replace their normal bread with that provided, receiving control bread for one 3-wk period and guar bread for the other period, without altering their baseline diet. Subjects recorded their intake of foods for 6 consecutive days on three occasions during the study. Fasting venous blood samples (10 mL) were taken from subjects on two consecutive mornings at the start and end of each feeding period. No significant changes in body weight or dietary intake were recorded in the control and guar bread periods. There was a significant reduction (10%) in total plasma cholesterol concentration after the guar treatment (P < 0.001), mainly because of a reduction in the low-density-lipoprotein-cholesterol fraction. No changes in plasma high-density-lipoprotein-cholesterol or triacylglycerol concentrations were seen. The cholesterol-lowering effect of partially depolymerized guar gum appears to be of a magnitude similar to that of high-molecular-weight guar gum used in earlier studies.

Eicosapentaenoic acid, but not docosahexaenoic acid, increases mitochondrial fatty acid oxidation and upregulates 2,4-dienoyl-CoA reductase gene expression in rats.

Willumsen N; Vaagenes H; Lie O; Rustan AC; Berge RK
University of Bergen, Department of Clinical Biology, Haukeland Hospital, Norway.
Lipids (United States) Jun 1996, 31 (6) p579-92

The aim of the present study was to investigate whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) was responsible for the triglyceride-lowering effect of fish oil. In rats fed a single dose of EPA as ethyl ester (EPA-EE), the plasma concentration of triglycerides was decreased at 8 h after acute administration. This was accompanied by an increased hepatic fatty acid oxidation and mitochondrial 2,4-dienoyl-CoA reductase activity. The steady-state level of 2,4-dienoyl-CoA reductase mRNA increased in parallel with the enzyme activity. An increased hepatic long-chain acyl-CoA content, but a reduced amount of hepatic malonyl-CoA, was obtained at 8 h after acute EPA-EE treatment. On EPA-EE supplementation, both EPA (20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3) increased in the liver, whereas the hepatic DHA (22:6n-3) concentration was unchanged. On DHA-EE supplementation retroconversion to EPA occurred. No statistically significant differences were found, however, for mitochondrial enzyme activities, malonyl-CoA, long-chain acyl-CoA, plasma lipid levels, and the amount of cellular fatty acids between DHA-EE treated rats and their controls at any time point studied. In cultured rat hepatocytes, the oxidation of [1-14C]palmitic acid was reduced by DHA, whereas it was stimulated by EPA. In the in vivo studies, the activities of phosphatidate phosphohydrolase and acetyl-CoA carboxylase were unaffected after acute EPA-EE and DHA-EE administration, but the fatty acyl-CoA oxidase, the rate-limiting enzyme in peroxisomal fatty acid oxidation, was increased after feeding these n-3 fatty acids. The hypocholesterolemic properties of EPA-EE may be due to decreased 3-hydroxy-3-methylglutaryl-CoA reductase activity. Furthermore, replacement of the ordinary fatty acids, i.e., the monoenes (16:1n-7, 18:1n-7, and 18:1n-9) with EPA and some conversion to DPA concomitant with increased fatty acid oxidation is probably the mechanism leading to changed fatty acid composition. In contrast, DHA does not stimulate fatty acid oxidation and, consequently, no such displacement mechanism operates. In conclusion, we have obtained evidence that EPA, and not DHA, is the fatty acid primarily responsible for the triglyceride-lowering effect of fish oil in rats.

Dose-response characteristics of cholesterol-lowering drug therapies: implications for treatment.

Schectman G; Hiatt J
Division of General Internal Medicine, Medical College of Wisconsin, Froedtert Lutheran Memorial Hospital, Milwaukee 53226, USA.
Ann Intern Med (United States) Dec 15 1996, 125 (12) p990-1000

PURPOSE: To develop an optimal treatment strategy that reduces low-density lipoprotein (LDL) cholesterol levels and improves adherence to therapy by reviewing clinical trials that define the dose-response characteristics for 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), bile acid sequestrants, and niacin.

DATA SOURCES: Data were obtained from a MEDLINE search of the English-language literature published from 1975 through November 1995 and from an extensive bibliography review.

STUDY SELECTION: Controlled, clinical trials were reviewed if they evaluated 1) the effectiveness and toxicity of one LDL cholesterol-lowering agent (statins, bile acid sequestrants, or niacin, at two or more doses) or 2) monotherapy with two LDL cholesterol-lowering agents at defined doses used alone and in combination. Studies that had fewer than 10 patients in a treatment group or that selected patients on the basis of previous response to therapy were not included.

DATA EXTRACTION: Trials were reviewed for overall methodology, inclusion and exclusion criteria, sources of bias, and outcomes.

DATA SYNTHESIS: Dose-response relations for bile acid sequestrants and statins are nonlinear, and most of their LDL cholesterol-lowering effects can be obtained with lower doses. The few dose-response studies of niacin that have been done suggest that most of niacin's high-density lipoprotein cholesterol-increasing effect can also be achieved with relatively low doses, but higher doses are needed to substantially reduce LDL cholesterol levels. If bile acid sequestrants or niacin are added to statin therapy, the effect of combined therapy on LDL cholesterol levels is additive.

CONCLUSION: The nonlinear dose-response relation of statins, bile acid sequestrants, and niacin and their additive LDL cholesterol-lowering effect when used together suggest a strategy for treating hypercholesterolemia that may optimize effectiveness while minimizing adverse effects and cost. (72 Refs.)

Soy protein concentrate and isolated soy protein similarly lower blood serum cholesterol but differently affect thyroid hormones in hamsters.

Potter SM; Pertile J; Berber-Jimenez MD
Department of Food Science and Human Nutrition, University of Illinois at Urbana/Champaign, IL 61801, USA.
J Nutr (United States) Aug 1996, 126 (8) p2007-11

There is a wide variation in the hypocholesterolemic response to ingestion of soy protein in humans. One possible explanation is that the different soy protein preparations used contain different spectra of biologically active components. This could affect a number of indices including thyroid hormone status. An increased level of thyroxine has been proposed as an underlying mechanism of the hypocholesterolemic effect of soy protein. The objective of this study was to determine if serum cholesterol and thyroid hormone concentrations differed because of feeding soy protein from different sources. Twenty-nine male weanling golden Syrian hamsters were fed rations containing 25 g/100 g protein from either isolated soy protein (ISP), soy protein concentrate (SPC) or casein for 35 d. Serum total cholesterol concentrations were lower in hamsters fed ISP and SPC compared with those fed casein (P < 0.05). No differences in cholesterol concentrations were observed in lipoprotein fractions. Serum thyroxine and free thyroxine were greater only in hamsters fed ISP than in those fed casein (P < 0.05), whereas triiodothyronine concentrations were higher in casein-fed than in SPC-fed hamsters (P < 0.05). Results indicate that protein from ISP and SPC are both effective in lowering blood cholesterol concentrations, whereas only ISP increases thyroxine concentrations. Therefore, it appears unlikely that modulation of thyroid hormone status is responsible for the cholesterol-lowering effect of soy protein.

Ascorbate administration to normal and cholesterol-fed rats inhibits in vitro TBARS formation in serum and liver homogenates.

Santillo M; Mondola P; Milone A; Gioielli A; Bifulco M
Dipartimento di Neuroscienze e della Comunicazione Interumana, Sezione Fisiologia, Universita di Napoli, Italy.
Life Sci (England) 1996, 58 (14) p1101-8

We have recently shown that ascorbate has a hypocholesterolemic and hypotriglyceridemic effect on rats fed a diet enriched with 1.5% cholesterol and 25% hydrogenated coconut oil (Nath diet). In this study we evaluated the effect of intraperitoneal ascorbate administration on susceptibility to lipoperoxidation either in rats fed standard or Nath diet. In normal rats ascorbate treatment decreased (p<0.05) the susceptibility to lipoperoxidation induced by incubation of serum for 24 hours with 2.2 mM Cu++, without altering the normal serum fatty acid profile. In rats fed Nath diet we observed a reduced susceptibility of serum to CU++-induced lipoperoxidation (36%), according with their low levels of serum unsaturated fatty acids (40% less than rats fed standard diet). In these animals ascorbate administration affects serum fatty acid profile leading to a decrease of S/U ratio from 1.6 to 1.2 without significantly modifying the susceptibility of serum to lipoperoxidation. Moreover, the production of spontaneous lipid peroxides in liver homogenates, measured as TBARS levels, was strongly inhibited by ascorbate (p<0.01) in rats fed either standard or Nath diet. These data indicate that ascorbate administration exerts an antioxidant effect and that in hypercholesterolemic rats, in addition to a lipid lowering effect, ascorbate exerts a protective role against the peroxidative damage of lipids.

Cholesterol-lowering effect of soyabean lecithin in normolipidaemic rats by stimulation of biliary lipid secretion.

Polichetti E; Diaconescu N; De La Porte PL; Malli L; Portugal H; Pauli AM ; Lafont H; Tuchweber B; Yousef I; Chanussot F
INSERM U130 and Laboratoire Central, Hopital Sainte Marguerite, Marseille, France.
Br J Nutr (England) Mar 1996, 75 (3) p471-8

The purpose of the present study was to assess the role of the liver in the plasma-cholesterol-lowering effect of soyabean lecithin. Normolipidaemic rats were fed on lecithin-enriched or control diets with the same amount of protein. The lecithin diets contained 200 g/kg high-fat commercial semi-purified soyabean lecithin (230 g/kg total lipids as soyabean phosphatidylcholine) or 200 g/kg high-fat purified soyabean lecithin (930 g/kg total lipids as soyabean phosphatidylcholine). The control diets were a lowfat diet (40 g fat/kg) and a high-fat triacylglycerol-rich diet (200 g fat/kg). The high-fat diets were isoenergetic. The cholesterol-lowering effect of the lecithin-enriched diets was associated with significantly lower levels of plasma total- and HDL-cholesterol and significantly higher levels of bile phosphatidylcholine (PC), bile salts and cholesterol. These findings suggest that the liver plays a major role in the reduction of plasma cholesterol, the increased biliary lipid being provided by both HDL and the hepatic microsomal pools of PC and cholesterol.

Comparison of pravastatin with crystalline nicotinic acid monotherapy in treatment of combined hyperlipidemia.

Mostaza JM; Schulz I; Vega GL; Grundy SM
Veterans Affairs Medical Center, Department of Clinical Nutrition, Center for Human Nutrition of the University of Texas Southwestern Medical Center at Dallas, 75235-9052, USA.
Am J Cardiol (United States) May 1 1997, 79 (9) p1298-301

Pravastatin treatment of combined hyperlipidemia lowers low-density lipoprotein effectively; nicotinic acid lowers remnant cholesterol and raises high-density lipoprotein. A combination of these 2 drugs may be indicated for optimal treatment of lipoprotein abnormalities in combined hyperlipidemia.

"Isolated" low high-density lipoprotein cholesterol.

Wilt VM; Gums JG
Department of Pharmacy Practice, University of Florida, Gainesville 32164, USA.
Ann Pharmacother (United States) Jan 1997, 31 (1) p89-97

OBJECTIVE: To present information on the function, structure, and importance of high-density lipoprotein cholesterol (HDL-C) and to evaluate the current literature regarding the controversy of managing patients with an "isolated" low HDL-C concentration.

DATA SOURCE: A MEDLINE search was performed (1966-June 1996) to identify English-language clinical and review articles pertaining to HDL-C. Some articles were identified through the bibliography of selected articles.

STUDY SECTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion.

DATA EXTRACTION: Important historical lipid studies, recent review articles, and clinical trials involving therapy for HDL-C were evaluated.

DATA SYNTHESIS: The structure, function, and measurement of HDL-C and the state of an isolated low HDL-C are discussed for background. Lifestyle modification measures to increase HDL-C, medications to avoid, estrogen replacement, and lipid-altering agents used to raise an isolated low HDL-C are presented.

CONCLUSIONS: An isolated low HDL-C concentration poses a risk for coronary heart disease. The management of this state is controversial. The first step in management is in agreement with experts and includes lifestyle modification (e.g., weight reduction, diet, smoking cessation, aerobic exercise). Estrogen replacement therapy and discontinuance of drugs that secondarily lower HDL-C are additional treatment options. The use of lipid-altering agents has been used in some patients. Nicotinic acid appears to be an effective agent for an isolated low HDL-C. A large clinical trial evaluating the effect of treating an isolated low HDL-C for primary and secondary prevention of coronary events is needed. (65 Refs.)

Effect of a combination of gemfibrozil and niacin on lipid levels.

Spencer GA; Wirebaugh S; Whitney EJ
Department of General Internal Medicine, Wilford Hall Medical Center, Lackland AFB, Texas 78236-5300, USA.
J Clin Pharmacol (United States) Aug 1996, 36 (8) p696-700

To determine the effect of the combination of niacin and gemfibrozil on the lipid profile, a retrospective review was conducted of 161 patients who were prescribed a combination of gemfibrozil and niacin for 6 to 12 months at a community-based lipid clinic. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, ratio of total cholesterol to HDL, alanine aminotransferase (ALT), and weight were measured at entry to the clinic, 2 months after dietary instruction, during single-agent therapy, and during combination therapy. Mean doses of niacin and gemfibrozil were 1,229 mg/day and 1,200 mg/day, respectively. Patient weight decreased significantly after dietary instruction and after institution of combination therapy. There were no significant changes in ALT levels with either single-agent therapy or with combination therapy. The combination of niacin and gemfibrozil produced marked and significant changes in lipid levels: total cholesterol and LDL decreased by 14%, HDL increased by 24%, the ratio of total cholesterol to HDL decreased by 30%, and triglycerides decreased by 52%. The combination of niacin and gemfibrozil in the setting of dietary instruction has a marked beneficial effect on serum lipid levels, and was most effective in patients with initial levels of HDL < 40 mg/dL, triglycerides > 250 mg/dL, and LDL > 160 mg/dL. No episodes of ALT elevation or symptomatic myositis were seen.

New developments in the use of niacin for treatment of hyperlipidemia: new considerations in the use of an old drug.

Crouse JR 3rd
Bowman Gray School of Medicine, Winston Salem, North Carolina 27157, USA.
Coron Artery Dis (United States) Apr 1996, 7 (4) p321-6

Niacin has been used for many years to treat hyperlipidemia. It has been shown to reduce coronary death and non-fatal myocardial infarction and, in a separate analysis of long-term (15-year) follow-up, all cause mortality. It reduces total cholesterol, low density lipoprotein cholesterol (LDL-C) and triglycerides and increases high density lipoprotein cholesterol (HDL-C). Sustained-release niacin may be associated with more dramatic changes in LDL-C and triglyceride, whereas the short acting preparation causes greater increases in HDL-C. The increase of HDL-C occurs at a lower dose (1500 mg/day) than the reduction of LDL-C (> 1500 mg/day). Niacin also favorably influences other lipid parameters including lipoprotein(a) [Lp(a)], alimentary lipemia, familial defective apolipoprotein B-100 and small dense LDL. Combination of niacin with a bile acid sequestrant or a reductase inhibitor represents a powerful lipid-altering regimen. Whereas the reductase inhibitors and bile acid binding resins primarily affect LDL-C, the combined therapy has a synergistic effect to reduce LDL-C and, in addition, the niacin reduces triglycerides and increases HDL-C. The major drawback in the use of niacin is associated side effects (flushing and palpitations) and toxicity (worsening of diabetes control, exacerbation of peptic ulcer disease, gout, hepatitis). Niacin has a long history of use as a lipid lowering agent and has several attractive features. Unfortunately, the side effect profile of this agent warrants its use only in patients with marked dyslipidemia in whom side effects and potential toxicity are closely monitored. (47 Refs.)

Effect of supplementary antioxidant vitamin intake on carotid arterial wall intima-media thickness in a controlled clinical trial of cholesterol lowering.

Azen SP; Qian D; Mack WJ; Sevanian A; Selzer RH; Liu CR; Liu CH; Hodis HN
Statistical Consultation and Research Center, University of Southern California, Los Angeles 90033, USA.
Circulation (United States) Nov 15 1996, 94 (10) p2369-72

BACKGROUND: There is accumulating experimental, epidemiological, and clinical evidence of an association between anti-oxidant vitamin intake and reduced risk of coronary heart disease. Using data from the Cholesterol Lowering Atherosclerosis Study (CLAS), we explored the association of self-selected supplementary antioxidant vitamin intake on the rate of progression of early preintrusive atherosclerosis.

METHODS AND RESULTS: CLAS was an arterial imaging trial in which nonsmoking 40- to 59-year-old men with previous coronary artery bypass graft surgery were randomized to colestipol/niacin plus diet or placebo plus diet. The rate of progression of early preintrusive atherosclerosis was determined in 146 subjects using high-resolution B-mode ultrasound quantification of the distal common carotid artery far wall intima-media thickness (IMT). From the nutritional supplement database, 22 subjects had an on-trial average supplementary vitamin E intake of > or = 100 IU per day (high users) and 29 subjects had an average on-trial supplementary vitamin C intake of > or = 250 mg per day (high users). Within the placebo group, less carotid IMT progression was found for high supplementary vitamin E users when compared with low vitamin E users (0.008 versus 0.023 mm/y, P = .03). No effect of vitamin E within the drug group was found. No effect of vitamin C within the drug or placebo group was found.

CONCLUSIONS: Supplementary vitamin E intake appears to be effective in reducing the progression of atherosclerosis in subjects not treated with lipid-lowering drugs while the process is still confined to the arterial wall (early preintrusive atherosclerosis).

Lipid management: current diet and drug treatment options.

Stone NJ
Northwestern University Medical School and the Lipid Research and Education Fund, Chicago, Illinois, USA.
Am J Med (United States) Oct 8 1996, 101 (4A) p4A40S-48S; discussion 48S-49S

Diet and drug therapy are two of the principal approaches to lipid management. The aim of both is to reduce low-density-lipoprotein (LDL) cholesterol to goal levels established by the National Cholesterol Education Program Expert Panel in its second report, based on a patient's short-term risk of a coronary event. In prescribing diet therapy, it is important to determine patients' willingness to initiate and adhere to dietary modifications, their skill at reading nutritional labels, adapting recipes, and ordering "heart-healthy" foods when eating out. Diet therapy should be directed at modifying dietary factors known to adversely influence blood cholesterol-saturated fats, cholesterol, and obesity. Diet therapy (with exercise) is not always adequate. High risk individuals with no overt coronary artery disease but with >/=2 risk factors, as well as patients with coronary artery disease, are potential candidates for drug therapy, depending on their LDL cholesterol levels. The "statins" are the drug of choice for patients with coronary disease and elevated LDL cholesterol or familial LDL-cholesterol abnormalities. These drugs increase high-density-lipoprotein (HDL) cholesterol and reduce LDL cholesterol, coronary artery disease, and total mortality. Bile acid resins lower LDL cholesterol and are often used to augment the effects of the statins and niacin. Niacin is particularly useful in the management of patients with combined hyperlipidemia and low HDL cholesterol levels. Gemfibrozil is effective in familial dysbetalipoproteinemia and is the drug of choice for patients with severely elevated serum triglycerides. (74 Refs.)

Clinical trial of wax-matrix sustained-release niacin in a Russian population with hypercholesterolemia.

Aronov DM; Keenan JM; Akhmedzhanov NM; Perova NV; Oganov RY; Kiseleva NY
National Research Centre for Preventive Medicine, Moscow, Russia.
Arch Fam Med (United States) Nov-Dec 1996, 5 (10) p567-75

OBJECTIVE: To assess the clinical effectiveness and tolerability of wax-matrix, controlled-release nicotinic acid (CNA) in persons with hypercholesterolemia.

DESIGN: Randomized, double-blind, placebo controlled, crossover trial.

SETTING: Ambulatory clinic at an academic cardiology center in Moscow, Russia.

PATIENTS: A volunteer sample of 135 men and women, aged 20 to 70 years, with hypercholesterolemia greater than 5.82 mmol/L (225 mg/dL) (70th-95th percentile for age and sex) who otherwise met study inclusion and exclusion criteria, were initially recruited into the study. Cholesterol levels were reduced to less than 5.82 mmol/L (225 mg/dL) in 46 subjects who participated in the initial diet intervention and were excluded from the drug intervention. Eighty-nine subjects were randomized into the clinical trial; 4 subjects (4.5%) dropped out of the study because of intolerance of CNA.

INTERVENTION: Eight weeks of diet alone (American Heart Association Step I Diet) was followed by randomization to 2 treatment groups (1500 mg/d CNA [ENDURACIN] or placebo) for 2 months followed by a crossover of treatments for 2 months, followed by all subjects taking 2000 mg/d of CNA for 2 months.

MAIN OUTCOME MEASURES: Significant improvements in baseline measures for total serum cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were observed after initial diet (TC, 6%; LDL-C, 6%; P < .001, t test), after 1500 mg/d CNA (TC, 14%; LDL-C, 18%; P < .001, t test), and after 2000 mg/d CNA (TC, 16%; LDL-C, 21%; P < .001, t test). Triglyceride, high-density lipoprotein cholesterol, and lipoprotein(a) levels also improved. No serious toxic reactions were encountered, and 4 subjects withdrew from the study because of intolerance of cutaneous and gastrointestinal adverse effects.

CONCLUSION: Wax-matrix CNA is an effective and well-tolerated pharmacological treatment for hypercholesterolemia.

Combination therapy with low-dose lovastatin and niacin is as effective as higher-dose lovastatin.

Gardner SF; Schneider EF; Granberry MC; Carter IR
Department of Pharmacy Practice, University of Arkansas for Medical Sciences, Little Rock, USA.
Pharmacotherapy (United States) May-Jun 1996, 16 (3) p419-23

STUDY OBJECTIVES. To determine if low-dose lovastatin in combination with niacin causes a greater percentage reduction in low-density lipoprotein (LDL) cholesterol than lovastatin alone, and to determine if the combination increases the risk of serious adverse effects. design. Prospective, randomized, open-label, clinical trial. setting. Family medicine clinic of a university-affiliated hospital. Patients. Patients with fasting LDL cholesterol concentrations of at least 150 mg/dl after 4 weeks of dietary stabilization and washout of any cholesterol-lowering drugs.

INTERVENTIONS. Twenty-eight patients received lovastatin 20 mg/day for 4 weeks after dietary stabilization and washout. If LDL cholesterol remained above 130 mg/dl (100 mg/dl in patients with coronary artery disease), they were randomized to receive either lovastatin 40 mg/day or a combination of lovastatin 20 mg/day and niacin 500 mg 3 times/day.

MEASUREMENTS AND MAIN RESULTS. There was no difference in actual or percentage reductions of LDL cholesterol, total cholesterol, and triglycerides between the groups. A greater increase in high-density lipoprotein (HDL) cholesterol occurred with combination therapy (p = 0.024). There was no difference in liver function tests, glucose, or uric acid between the therapies. Based on drug-acquisition cost, combination therapy is approximately 40% less expensive than monotherapy.

CONCLUSION. Low-dose niacin plus low-dose lovastatin was as effective as higher-dose lovastatin in lowering total cholesterol, LDL cholesterol, and triglyceride levels. The combination may offer benefit in raising HDL cholesterol levels.

Fluvastatin in combination with other lipid-lowering agents.

Jokubaitis LA
Cardiovascular Clinical Research, Sandoz Research Institute, East Hanover, NJ 07936, USA.
Br J Clin Pract Symp Suppl (England) Jan 1996, 77A p28-32

Fluvastatin, a new synthetic inhibitor of HMGCoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, has been studied in several models to examine its effects when used in combination with other lipid-modifying agents such as derivatives of fibric acid (bezafibrate), resins (cholestyramine), and niacin. The combination of fluvastatin with bezafibrate has been studied in a double-blind trial involving patients with well-documented familial hypercholesterolaemia. Fluvastatin 40 mg/day, combined with either bezafibrate 400 mg/day or cholestyramine 8 g/day, resulted in reductions in levels of low-density lipoprotein cholesterol (LDL-C), these being indistinguishable between the groups; however, significantly greater increases in levels of high-density lipoprotein cholesterol (21.3%) and reductions in levels of triglycerides (25.1%) were seen with the fluvastatin-bezafibrate combination. No notable increases were seen in levels of serum creatine kinase, aspartate aminotransferase, or alanine aminotransferase, and no cases of myopathy were observed. In a study model that examined low-dose combinations of fluvastatin with cholestyramine, reductions in levels of LDL-C of 15.8% and 19.3% were seen with fluvastatin 10 mg and 20 mg, respectively. After an 8-week interval in which a daily dosage of cholestyramine 8 g was added, from baseline, reductions of 26.3% in the 10 mg fluvastatin-cholestyramine group and 31.2% in the 20 mg fluvastatin-cholestyramine group were observed, whereas the placebo-cholestyramine group displayed a reduction of 14.9%. Doubling the resin dosage to 16 g/day for the final 8 weeks of the study provided little additional benefit. Myotoxicity has been observed when lovastatin is coadministered with niacin, and so the combination of niacin with fluvastatin has also been studied to examine the possibility of this effect occurring. Patients were randomised to either fluvastatin 20 mg or placebo for 6 weeks, after which time open-label niacin was administered to all patients and titrated to a final dosage of 3 g/day. After 6 weeks, fluvastatin produced a 20.8% reduction in LDL-C levels from baseline. When combined with niacin, a 43.7% reduction was noted at the week 15 endpoint, against the 26.5% reduction seen with niacin monotherapy. The combination was well tolerated, with no reports of myopathy or of significant elevations in creatine kinase or liver transaminase levels. Combinations of fluvastatin with a variety of other agents have been shown to have significant effects on lipid profiles, with no evidence to date of clinically remarkable safety findings. Thus, the use of combination therapies may result in optimal management of patients with moderately severe hypercholesterolaemia and mixed dyslipidaemic profiles. (4 Refs.)

Clinical trials with gugulipid. A new hypolipidaemic agent

Nityanand S; Srivastava JS; Asthana OP
J Assoc Physicians India (India) May 1989, 37 (5) p323-8

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.

Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia

Singh RB; Niaz MA; Ghosh S
Heart Research Laboratory, Medical Hospital and Research Centre, Moradabad, India.
Cardiovasc Drugs Ther (United States) Aug 1994, 8 (4) p659-64

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 hypercholesterolemia (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 HDL 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.

Beneficial effects of Allium sativum (garlic), Allium cepa and Commiphora mukul on experimental hyperlipidemia and atherosclerosis--a comparative evaluation.

Lata S; Saxena KK; Bhasin V; Saxena RS; Kumar A; Srivastava VK
Department of Pharmacology, L. L. R. M. Medical College, Meerut, Uttar Pradesh.
J Postgrad Med (India) Jul 1991, 37 (3) p132-5

Oral administration of petroleum ether extract of Allium sativum, Allium cepa and ethylacetate extract of Commiphora mukul in albino rats significantly prevented rise in serum cholesterol and serum triglyceride level, caused by atherogenic diet. All the three agents were also found to confer significant protection against atherogenic diet induced atherosclerosis.

Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets

Srivastava K.C.; Bordia A.; Verma S.K.
Department of Medicine, R.N.T. Medical College, Udaipur India
Prostaglandins Leukotrienes and Essential Fatty Acids (United Kingdom), 1995, 52/4 (223-227)

In traditional medicine, Ayurveda, several spices and herbs are held to possess medicinal properties. Earlier we have reported that extracts from several spices, including turmeric, inhibit platelet aggregation and modulate eicosanoid biosynthesis. Due to their eicosanoid-modulating property, it was suggested that the spices may serve to provide clues to drugs directed to arachidonic acid (AA) pathway enzymes as pharmacological targets. Curcumin, a major component of turmeric, inhibited platelet aggregation induced by arachidonate, adrenaline and collagen. This compound inhibited thromboxane B2 (TXB2) production from exogenous (14C) arachidonate in washed platelets with a concomitant increase in the formation of 12-lipoxygenase products. Moreover, curcumin inhibited the incorporation of (14C)AA into platelet phospholipids and inhibited the deacylation of AA-labelled phospholipids (liberation of free AA) on stimulation with calcium ionophore A23187. Curcumin's anti-inflammatory property may, in part, be explained by its effects on eicosanoid biosynthesis.

Influence of capsaicin, eugenol, curcumin and ferulic acid on sucrose-induced hypertriglyceridemia in rats

Srinivasan M.R.; Satyanarayana M.N.
Biochemistry Section, Department of Food Chemistry, Central Food Technological Research Institute, Mysore-570 013 India
Nutr. Rep. Int. (USA), 1988, 38/3 (571-581)

The spice active principles, capsaicin, eugenol curcumin and 'ferulic acid' a common plant constituent were found to counter many of the metabolic changes caused by a high sucrose diet fed to rats. The compounds tested at high and low levels were mostly found to lower or tend to lower liver weight, liver triglycerides, free fatty acids, phospholipids, serum total, VLDL+LDL and HDL triglycerides, VLDL+LDL cholesterol, free fatty acids and also elevate serum total and HDL cholesterol.

Inhibitory effect of curcumin, an anti-inflammatory agent, on vascular smooth muscle cell proliferation

Huang H.-C.; Jan T.-R.; Yeh S.-F.
Department of Pharmacology, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Taipei Taiwan
Eur. J. Pharmacol. (Netherlands), 1992, 221/2-3 (381-384)

The effects of curcumin, an anti-inflammatory agent from Curcuma longa, on the proliferation of blood mononuclear cells and vascular smooth muscle cells were studied. Proliferative responses were determined from the uptake of tritiated thymidine. In human peripheral blood mononuclear cells, curcumin dose dependently inhibited the responses to phytohemagglutinin and mixed lymphocyte reaction at the dose ranges of 10-6 to 3 x 10-5 and 3 x 10-6 to 3 x 10-5 M, respectively. Curcumin (10-6 to 10-4 M) dose dependently inhibited the proliferation of rabbit vascular smooth muscle cells stimulated by fetal calf serum. Curcumin had a greater inhibitory effect on platelet-derived growth factor-stimulated proliferation than on serum-stimulated proliferation. Cinnamic acid, coumaric acid and ferulic acid were much less effective than curcumin as inhibitors of serum-induced smooth muscle cell proliferation, suggesting that the cinnamic acid and ferulic acid moieties alone are not sufficient for activity, and that the characteristics of the diferuloylmethane molecule itself are necessary for activity. Curcumin may be useful as a new template for the development of better remedies for the prevention of the pathological changes of atherosclerosis and restenosis.

Polyphenols as cancer chemopreventive agents.

Stoner GD; Mukhtar H
Department of Preventive Medicine, Ohio State University, Columbus OH 43210 USA.
J Cell Biochem Suppl (United States) 1995, 22 p169-80

This article summarizes available data on the chemopreventive efficacies of tea polyphenols, curcumin and ellagic acid in various model systems. Emphasis is placed upon the anticarcinogenic activity of these polyphenols and their proposed mechanism(s) of action. Tea is grown in about 30 countries and, next to water, is the most widely consumed beverage in the world. Tea is manufactured as either green, black, or oolong; black tea represents approximately 80% of tea products. Epidemiological studies, though inconclusive, suggest a protective effect of tea consumption on human cancer. Experimental studies of the antimutagenic and anticarcinogenic effects of tea have been conducted principally with green tea polyphenols (GTPs). GTPs exhibit antimutagenic activity in vitro, and they inhibit carcinogen-induced skin, lung, forestomach, esophagus, duodenum and colon tumors in rodents. In addition, GTPs inhibit TPA-induced skin tumor promotion in mice. Although several GTPs possess anticarcinogenic activity, the most active is (-)-epigallocatechin-3-gallat e (EGCG), the major constituent in the GTP fraction. Several mechanisms appear to be responsible for the tumor-inhibitory properties of GTPs, including enhancement of antioxidant (glutathione peroxidase, catalase and quinone reductase) and phase II (glutathione-S-transferase) enzyme activities; inhibition of chemically induced lipid peroxidation; inhibition of irradiation- and TPA-induced epidermal ornithine decarboxylase (ODC) and cyclooxygenase activities; inhibition of protein kinase C and cellular proliferation; antiinflammatory activity; and enhancement of gap junction intercellular communication. Curcumin is the yellow coloring agent in the spice tumeric. It exhibits antimutagenic activity in the Ames Salmonella test and has anticarcinogenic activity, inhibiting chemically induced preneoplastic lesions in the breast and colon and neoplastic lesions in the skin, forestomach, duodenum and colon of rodents. In addition, curcumin inhibits TPA-induced skin tumor promotion in mice. The mechanisms for the anticarcinogenic effects of curcumin are similar to those of the GTPs. Curcumin enhances glutathione content and glutathione-S-transferase activity in liver; and it inhibits lipid peroxidation and arachidonic acid metabolism in mouse skin, protein kinase C activity in TPA-treated NIH 3T3 cells, chemically induced ODC and tyrosine protein kinase activities in rat colon, and 8-hydroxyguanosine formation in mouse fibroblasts. Ellagic acid is a polyphenol found abundantly in various fruits, nuts and vegetables. Ellagic acid is active in antimutagenesis assays, and has been shown to inhibit chemically induced cancer in the lung, liver, skin and esophagus of rodents, and TPA-induced tumor promotion in mouse skin.