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Garlic as a phytogenic lipid-lowering drug - A review of clinical trails with standardized garlic powder preparations
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.

Effect of an odor-modified garlic preparation on blood lipids
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.

Oral guar gum treatment of intrahepatic cholestasis and pruritus in pregnant women: effects on serum cholestanol and other non- cholesterol sterols.
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.

Increasing amounts of dietary fiber provided by foods normalizes physiologic response of the large bowel without altering calcium balance or fecal steroid excretion.
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).

[The use of dietary fiber as natural enterosorbents in diseases of the hepatobiliary system]
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.

Validity and reproducibility of a food frequency questionnaire to assess dietary intake of women living in Mexico City.
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.

Oxidized LDL promotes vascular endothelial cell pinocytosis via a prooxidation mechanism.
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.

[Dietary fibers in diet therapy]
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.

Definition of healthy eating in the Spanish adult population: a national sample in a pan-European survey.
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'.

Dietary sources of nutrients among US adults, 1989 to 1991.
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.

Fruit consumption, fitness, and cardiovascular health in female adolescents: the Penn State Young Women's Health Study.
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.
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.

Zinc absorption, mineral balance, and blood lipids in women consuming controlled lactoovovegetarian and omnivorous diets for 8 wk.
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.

Long-term effects of consuming foods containing psyllium seed husk on serum lipids in subjects with hypercholesterolemia.
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
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.

Decreased serum total cholesterol concentration is associated with high intake of soy products in Japanese men and women.
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.

Cholesterol , phospholipid, and protein changes in focal opacities in the human eye lens.
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.

A low-viscosity soluble- fiber fruit juice supplement fails to lower cholesterol in hypercholesterolemic men and women
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.

Food and nutrient intake of premenopausal female vegetarians and omnivores in Finland
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.

Functional food science and the cardiovascular system
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.

Lipid- and glucose-lowering efficacy of Plantago Psyllium in type II diabetes
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.

Impact of neuroendocrine activation on coronary artery disease
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.

Fruit and vegetable intake in young children
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.

Whole flaxseed consumption lowers serum LDL- cholesterol and lipoprotein(a) concentrations in postmenopausal women
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.

The potential role of soluble fibre in the treatment of hypercholesterolaemia
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.

Nutrition and coronary heart disease
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.

Distribution and synthesis of apolipoprotein J in the atherosclerotic aorta
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.

Dietary fiber , the evolution of the human diet and coronary heart disease
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.

Managing hypercholesterolaemia: What role for dietary fibre?
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.

Human fatty acid synthesis is reduced after the substitution of dietary starch for sugar
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.

LDL oxidation: therapeutic perspectives.
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.)

Influence of vitamin C status on ethanol metabolism in guinea-pigs.
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.

Dietary antioxidants inhibit development of fatty streak lesions in the LDL receptor-deficient mouse.
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.

Vitamin E combined with selenium inhibits atherosclerosis in hypercholesterolemic rabbits independently of effects on plasma cholesterol concentrations.
Schwenke DC; Behr SR
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1072, USA.
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.

Regulation of apolipoprotein B-containing lipoproteins by vitamin C level and dietary fat saturation in guinea pigs.
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).

The nutritional health of New Zealand vegetarian and non-vegetarian Seventh-day Adventists: selected vitamin, mineral and lipid levels.
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.

Characteristics of survey participants with and without a telephone: findings from the third National Health and Nutrition Examination Survey.
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.

Low-density lipoprotein oxidation and vitamins E and C in sustained and white-coat hypertension.
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.
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.

Citrus fruit supplementation reduces lipoprotein oxidation in young men ingesting a diet high in saturated fat: presumptive evidence for an interaction between vitamins C and E in vivo.
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.

Diet, antioxidant status, and smoking habits in French men
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.

Vitamin C supplementation restores the impaired vitamin E status of guinea pigs fed oxidized frying oil.
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.

Antioxidant vitamins and coronary artery disease risk in South African males
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.

Nutrient losses and gains during frying: A review
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.

Vitamins E plus C and interacting conutrients required for optimal health
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.

Hypolipidemic effects of synthetic gugulsterones in normal rats and assessment of its long-term toxicity at cellular levels in various organs.
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.

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 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.

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

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.

Reduction of cholesterol and Lp(a) and regression of coronary artery disease: A case study
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).

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 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.

Nicotinic acid treatment shifts the fibrinolytic balance favourably and decreases plasma fibrinogen in hypertriglyceridaemic men
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.

Clinical trial experience with extended-release niacin (Niaspan): dose-escalation study.
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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