| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| A conjugated equine estrogen with differential effects on uterine weight and plasma cholesterol in the rat Washburn, S. A., M. R. Adams, et al. (1993), Am J Obstet Gynecol 169(2 Pt 1): 251-4; discussion 254-6. Abstract: OBJECTIVE: Our purpose was to determine the effect of Premarin (conjugated estrogens) and three of its component estrogens on uterine weight and plasma cholesterol concentrations in surgically menopausal female rats. STUDY DESIGN: A randomized trial of Premarin and three component estrogens--estrone sulfate, 17 alpha-estradiol sulfate, and 17 alpha-dihydroequilenin sulfate--in female rats after oophorectomy. RESULTS: High-dose Premarin and high- and middle-dose estrone sulfate significantly increased uterine weight relative to untreated controls (high-dose Premarin, 243.34 +/- 0.15 mg; high-dose estrone sulfate, 376.1 +/- 9.36 mg; middle-dose estrone sulfate, 249.0 +/- 6.34 mg; untreated controls, 124.63 +/- 3.17 mg; for all, p < 0.05). 17 alpha-Dihydroequilenin sulfate had no effect on uterine weight relative to controls. All 17 alpha-dihydroequilenin sulfate doses markedly reduced total plasma cholesterol concentrations versus controls (34.02 +/- 3.44 mg/dl, 32.49 +/- 1.08 mg/dl, and 71.55 +/- 5.16 mg/dl vs 90.44 +/- 1.06 mg/dl; for all, p < 0.02). 17 alpha-Dihydroequilenin sulfate had a more pronounced effect on low- or very-low-density lipoprotein cholesterol than total plasma cholesterol or high-density lipoprotein cholesterol concentrations. CONCLUSIONS: 17 alpha-Dihydroequilenin sulfate reduced total plasma cholesterol concentrations without inducing uterine growth in rats after oophorectomy. |
| A convenient conversion chart for obtaining serum LDL-cholesterol values Ishihara, N. (1995), Kurume Med J 42(2): 129-32. Abstract: I devised a convenient conversion chart to obtain the LDL-cholesterol value from the measured total cholesterol, HDL-cholesterol and triglyceride values without calculations. The principles and the practical use of the chart are described. Its application to the development of slide calculators that allow direct reading of LDL-cholesterol value is also discussed. |
| A convenient synthesis of 7 alpha-hydroxycholest-4-en-3-one by the hydroxypropyl-beta-cyclodextrin-facilitated cholesterol oxidase oxidation of 3 beta,7 alpha-cholest-5-ene-3,7-diol Alexander, D. L. and J. F. Fisher (1995), Steroids 60(3): 290-4. Abstract: The initial biosynthetic conversions of cholesterol to the bile acids involve sequential 7 alpha-hydroxylation (catalyzed by cholesterol 7 alpha-hydroxylase) followed by C-3 oxidation and concomitant double bond migration (to a delta 4-configuration, catalyzed by 3 beta-delta 5-C27-steroid oxidoreductase) to provide 7 alpha-hydroxycholest-4-en-3-one. A straightforward, and economical, preparation (on a 0.1 g scale) of this pivotal biosynthetic intermediate has been devised. Reduction of 3 beta-(benzoyloxy)-cholest-5-en-7-one with LiB(sec-butyl)3H provided a 4:1 mixture, respectively, of the 7 alpha- and 7 beta-hydroxy diastereomers, which were separated chromatographically. Solvolytic removal of the C-3 benzoyl group gave 3 beta,7 alpha-cholest-5-ene-3,7-diol. A suspension of the 1:1 (v/v) complex (formed by mutual dissolution in MeOH, followed by evaporation of the solvent) of this diol with hydroxypropyl-beta-cyclodextrin, at a concentration of 1 mg mL-1 (in neutral phosphate buffer), was converted by Brevibacterium sp cholesterol oxidase (0.25 U mg-1 of substrate) and catalase (70 U mg-1 of substrate, to recover O2 from the H2O2 produced by the enzymatic oxidation) to a suspension of 7 alpha-hydroxycholest-4-en-3-one and the hydroxypropyl-beta-cyclodextrin. The yield for the enzymatic conversion was in excess of 90%. A much poorer and less reproducible yield (< 20%) was seen in the absence of the hydroxypropyl-beta-cyclodextrin. Routine extraction of this aqueous suspension, and chromatographic purification (85:15 CHCl3/acetone v/v on silica) of the residue, gave pure 7 alpha-hydroxycholest-4-en-3-one in 68% isolated yield. This route is a significant improvement, in terms of reaction scale and convenience, over the previous procedures for the preparation of this steroid. |
| A correlation between membrane cholesterol level, cell adhesion and tumourigenicity of polyoma virus transformed cells Kaur, T., P. Gopalakrishna, et al. (2004), Mol Cell Biochem 265(1-2): 85-95. Abstract: We have investigated the implications of the rise in membrane cholesterol levels on several in vitro and in vivo properties of polyoma virus transformed rat fibroblasts (PyF), with a special emphasis on alpha5beta1 integrin functions. We show that increased membrane cholesterol causes the PyF cells to change their shape and become more bipolar in appearance. These cells also show significantly higher adhesion to the cell-binding domain of fibronectin, increased localization of alpha5beta1 integrin and talin molecules in focal adhesions and a more robust actin cytoskeleton organization. PyF cells with increased membrane cholesterol show reduced growth in vitro and tumours caused by these cells in nude mice are slow growing. These changes in the growth properties of PyF cells are reversible when the cholesterol levels of PyF cells become normal. Our results suggest that changes in membrane cholesterol levels influence the growth and morphological properties of transformed cells, which can be exploited in controlling the growth of tumours in vivo. |
| A cost-effectiveness model of alternative statins to achieve target LDL-cholesterol levels Maclaine, G. D. and H. Patel (2001), Int J Clin Pract 55(4): 243-9. Abstract: An economic model was developed to estimate the relative cost-effectiveness of alternative HMG-CoA reductase inhibitors (statins)--atorvastatin, cerivastatin, fluvastatin, pravastatin and simvastatin--to achieve target low-density lipoprotein cholesterol (LDL-C) levels in a population of secondary CHD prevention patients. By using a cholesterol target as the endpoint of interest and a dose titration approach, the model assumes that the statins demonstrate a class effect through cholesterol lowering. The model was used to estimate the proportion of patients achieving target LDL-C levels (< 3 mmol/l) under each scenario tested. Total costs and incremental cost-effectiveness relative to no treatment and to the lowest cost option were estimated for each scenario. Total costs were highest for pravastatin and lowest for cerivastatin. Compared with no treatment, the incremental cost per patient treated to target LDL-C varied between 383 Pounds (atorvastatin) and 1213 Pounds (pravastatin). Incremental cost-effectiveness ratios in comparison with the lowest cost treatment (cerivastatin) were 141 Pounds per additional patient achieving target LDL-C with atorvastatin, and 275 Pounds with simvastatin. Fluvastatin and pravastatin were both less effective and more expensive than the lowest cost therapy. Although cerivastatin was associated with lowest expected costs, therapy with atorvastatin achieved the lowest cost-effectiveness ratios. Hence atorvastatin would allow the largest number of patients to be treated to target LDL-C within a fixed drug budget. Choosing between drug therapies on the basis of price alone may be misleading if the effectiveness of therapies varies. |
| A critical analysis of the role of cholesterol in atherogenesis Sloop, G. D. (1999), Atherosclerosis 142(2): 265-8. Abstract: Serum hypercholesterolemia is theorized to accelerate atherogenesis by augmenting cholesterol accumulation (insudation) in the arterial intima. The author views this theory as an example of what the noted philosopher of science Imre Lakatos called 'degenerative science', because data have forced several modifications of the theory. Although the theory that some fraction of intimal cholesterol causes atherosclerosis is not yet disproved, the author favors the hypothesis that serum hypercholesterolemia accelerates atherogenesis and contributes to symptomatic atherosclerosis by increasing blood viscosity and the mechanical fragility of atherosclerotic plaques, making them vulnerable to rupture and thrombosis. |
| A cross-sectional study of endogenous tissue plasminogen activator, total cholesterol, HDL cholesterol, and apolipoproteins A-I, A-II, and B-100 Ridker, P. M., D. E. Vaughan, et al. (1993), Arterioscler Thromb 13(11): 1587-92. Abstract: Elevated levels of endogenous tissue-type plasminogen activator (t-PA) appear to be a marker for preclinical atherosclerosis. At present, however, data describing potential relations between plasma t-PA level and established lipid risk factors for coronary atherosclerosis are sparse. To explore these potential relations, we measured plasma levels of t-PA antigen (t-PA:ag) in 633 apparently healthy men in the Physicians' Health Study as well as total cholesterol, high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, HDL3 cholesterol, and apolipoproteins A-I, A-II, and B-100. Overall, plasma t-PA:ag levels were inversely correlated with HDL cholesterol (r = -.1616, P <.0005), HDL2 cholesterol (r = -.1632, P <.0005), and HDL3 cholesterol (r = -.0927, P =.019). In stratified analyses, the inverse association between t-PA:ag and HDL cholesterol was present among frequent (P trend =.002) and infrequent (P trend =.004) consumers of alcohol as well as among the subgroups of frequent exercisers (P trend <.001), men in the lower half of body mass index (P trend =.001), and nonsmokers (P trend <.001). In contrast, there was no association between t-PA:ag and total cholesterol (r =.0219, P =.58), whereas relations of t-PA:ag with apolipoproteins A-I, A-II, and B-100 were minimal and of borderline significance. These data indicate that plasma levels of endogenous t-PA:ag are inversely related to HDL cholesterol as well as HDL2 and HDL3 cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) |
| A cross-sectional study on relationships between daily physical activity and concentration of serum cholesterol and body mass index in fifth grade elementary schoolchildren and their parents Miyanishi, K., H. Toyoshima, et al. (1993), Nippon Koshu Eisei Zasshi 40(6): 451-8. Abstract: The purpose of this study was to estimate the effects of daily physical activity on serum total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C), body mass index (BMI) and atherogenic index (AI) in 240 fifth grade schoolchildren, their 174 fathers and 212 mothers. Information on daily physical activity was obtained by inquiry with a questionnaire and was also measured directly with a device sensing acceleration of physical movement. In schoolchildren, effect of physical activity on TC, HDL-C and AI was not apparent, but that on BMI was shown. In adult men, HDL-C differed by job classification and increased as the degree of physical labor increased from desk work to light and heavy work. Strength of physical activity using the quotient of total amount of measured physical activity divided by body weight had a significant positive correlation with serum HDL-C (r = 0.20, p < 0.05) and significant negative correlation with AI (r = -0.18, p < 0.05) in adult men. In adult women, daily physical activity did not have a significant correlation to TC, HDL-C, AI or BMI. These results appear to suggest that the effect of daily physical activity on serum cholesterol, AI, BMI of schoolchildren and adult women was smaller than that for adult men. |
| A cytochemical study of glycocalyx and the membrane cholesterol of rat glomerular podocytes Nishi, S., H. Ozawa, et al. (1990), Arch Histol Cytol 53(4): 371-9. Abstract: In order to elucidate the cytochemical properties of rat podocyte's membranes, the authors studied the constituents and distribution of glycocalyx and membrane cholesterol. Chromic-phosphotungstic acid (Cr-PTA) stain combined with enzyme digestive tests was used for the glycocalyx analysis. A digitonin fixation method was applied for the detection of membrane cholesterol. On the whole surface of podocytes, glycocalyx showed a strongly positive reaction to Cr-PTA. In normal rats, the reactivity on the urinary surface above the slit membrane of the podocyte foot processes was decreased after treatments with neuraminidase, hyaluronidase and heparitinase. The reactivity on the basal surface below the slit membrane disappeared only after treatment with chondroitinase ABC. In Puromycin Aminonucleoside nephrosis (PAN) rats, the foot processes were effaced extensively. Though a highly positive reactivity of Cr-PTA was observed on the urinary surface of the podocytes, the basal surface reacted weakly. The positive reaction of the urinary surface was not affected by the treatments with neuraminidase, hyaluronidase and heparitinase, but the weak reaction of the basal surface disappeared completely through chondroitinase ABC treatment. The distribution of membrane cholesterol was clearly revealed by the digitonin fixation method, showing digitonin cholesterol complexes of localized trilamellar structures. In normal rat podocytes the complexes were found on the urinary surface, with only a few on the basal surface. In PAN rats the complexes were seldom noticed either on the urinary or basal surfaces. The heterogeneous distribution of glycocalyx and membrane cholesterol seen in normal rat podocytes are changed remarkably under nephrotic condition. |
| A cytolysin, theta-toxin, preferentially binds to membrane cholesterol surrounded by phospholipids with 18-carbon hydrocarbon chains in cholesterol-rich region Ohno-Iwashita, Y., M. Iwamoto, et al. (1991), J Biochem (Tokyo) 110(3): 369-75. Abstract: We have previously suggested the existence of two distinctive states of cholesterol in erythrocyte and lymphoma cell membranes as revealed by high- and low-affinity binding sites for theta-toxin of Clostridium perfringens Ohno-Iwashita, Y., Iwamoto, M., Mitsui, K., Ando, S., & Nagai, Y. (1988) Eur. J. Biochem. 176, 95-101; Ohno-Iwashita, Y., Iwamoto, M., Ando, S., Mitsui, K., & Iwashita, S. (1990) Biochim. Biophys. Acta 1023, 441-448. To understand factor(s) which determine membrane cholesterol heterogeneity, we analyzed toxin binding to large unilamellar liposomes composed of cholesterol and phospholipids (phosphatidylcholine/phosphatidylglycerol = 82:18, mol/mol). Liposomes containing phospholipids with 18-carbon hydrocarbon chains at both positions 1 and 2 of the glycerol have both high- and low-affinity toxin-binding sites with Kd values similar to those of intact erythrocytes, whereas liposomes with hydrocarbon chains containing 16 or fewer carbons at either position 1 or 2 have only low-affinity toxin-binding sites. The cholesterol/phospholipid ratio, in addition to the length of phospholipid hydrocarbon chain, also determines the number of toxin-binding sites, indicating that at least these two factors determine the topology of membrane cholesterol by creating distinctively different affinity sites for the toxin. Since theta-toxin binding detects specific populations of membrane cholesterol that are not detectable by the measurements of susceptibility to cholesterol oxidase and cholesterol desorption from membranes, the toxin could provide a unique probe for studying the organization of cholesterol in membranes. |
| A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis Cooper, M. K., C. A. Wassif, et al. (2003), Nat Genet 33(4): 508-13. Abstract: Smith-Lemli-Opitz syndrome (SLOS), desmosterolosis and lathosterolosis are human syndromes caused by defects in the final stages of cholesterol biosynthesis. Many of the developmental malformations in these syndromes occur in tissues and structures whose embryonic patterning depends on signaling by the Hedgehog (Hh) family of secreted proteins. Here we report that response to the Hh signal is compromised in mutant cells from mouse models of SLOS and lathosterolosis and in normal cells pharmacologically depleted of sterols. We show that decreasing levels of cellular sterols correlate with diminishing responsiveness to the Hh signal. This diminished response occurs at sterol levels sufficient for normal autoprocessing of Hh protein, which requires cholesterol as cofactor and covalent adduct. We further find that sterol depletion affects the activity of Smoothened (Smo), an essential component of the Hh signal transduction apparatus. |
| A deuterium NMR and steady-state fluorescence anisotropy study of the effects of cholesterol on the lipid membrane-disordering actions of ethanol Johnson, D. A., C. F. Valenzuela, et al. (1992), Biochem Pharmacol 44(4): 769-74. Abstract: We examined the effects of cholesterol on the membrane-disordering action of ethanol by using deuterium nuclear magnetic resonance (2H-NMR) and fluorescence spectroscopy. Specifically, the effects of ethanol were measured on the 2H-NMR spectra of di(perdeuteropalmitoyl)phosphatidylcholine (DPPC-d62) and on the steady-state emission anisotropy of diphenylhexatriene (DPH) incorporated into hydrated egg phosphatidylcholine (eggPC)/cholesterol dispersions. Analysis of the 2H-NMR spectra of DPPC-d62 incorporated into eggPC liposomes showed that the addition of cholesterol up to 30 mol% enhanced the ability of ethanol to disorder methylene groups all along the phospholipid acyl chains. This effect was somewhat greater toward the terminal methyl groups. However, above 30 mol% cholesterol, the bilayer-disordering action of ethanol on both the upper and lower portions of the acyl chains decreased to an apparent constant change up to the highest cholesterol content examined (50 mol%). Analysis of the fluorescence anisotropy of DPH, on the other hand, suggested that cholesterol attenuated the ability of ethanol to disorder the bilayers, which is in agreement with a previous EPR study Chin and Goldstein, Mol Pharmacol 19: 425-431, 1981. Re-analysis of our previous fluorescence anisotropy results with DPH incorporated into dispersions of brain-lipid extracts as a percent change Johnson et al., Mol Pharmacol 15: 739-746, 1979 indicated that the chemical composition of the lipid bilayers also affects the apparent ability of cholesterol to modulate the membrane-disordering action of ethanol, because the addition of cholesterol to brain-lipid extracts had no significant effect on the membrane-disordering action of ethanol. Given the greater likelihood that the 2H-NMR probes accurately monitor bulk phospholipid properties, some caution is required in the analysis of the membrane-disordering actions of drugs using EPR and fluorescence spectroscopy. |
| A diet containing myristoleic plus palmitoleic acids elevates plasma cholesterol in young growing swine Smith, D. R., D. A. Knabe, et al. (1996), Lipids 31(8): 849-58. Abstract: The objective of this study was to test the effect of a novel fatty acid mixture, enriched with myristoleic and palmitoleic acids, on plasma lipoprotein cholesterol concentrations. Weanling pigs were assigned to one of six groups and each group received a diet differing in fatty acid composition. Diets were fed for 35 days and contained 10 g added cornstarch/100 g (to provide baseline data) or 10 g added fatty acids/100 g. For those diets containing added fatty acids, extracted lipids contained 36% myristoleic plus palmitoleic acid combined (14:1/16:1 diet), 52% palmitic acid (16:0 diet), 51% stearic acid (18:0 diet), 47% oleic acid (18:1 diet), or 38% linoleic acid (18:2 diet). With the exception of the cornstarch diet, all diets contained approximately 30% myristic acid. There were no significant differences in weight gain across treatment groups (P = 0.22). All diets caused a significant increase in triglycerides and in total, low density lipoprotein, high density lipoprotein, and very low density lipoprotein cholesterol. The increase in total plasma cholesterol from pretreatment values was greatest in pigs fed the 14:1/16:1 and 18:1 diets. However, the increase in low density lipoprotein cholesterol from the pretreatment concentration was greatest in the 14:1/16:1-fed pigs. Increases in very low density lipoprotein cholesterol above pretreatment concentrations were lowest in 16:0-fed pigs and greatest in 18:1-fed pigs. Dietary fatty acids elicited changes in plasma fatty acids which generally were reflective of the diets, although the 18:0 diet did not alter plasma fatty acid concentrations and the 16:0 diet increased plasma 16:0 only at the end of the study. These results demonstrated that the combination of myristoleic plus palmitoleic acids increased plasma cholesterol in young pigs, suggesting that fatty acid chain length, rather than degree of unsaturation, is primarily responsible for the effects of fatty acids on circulating lipoprotein cholesterol concentrations. |
| A diet moderately enriched in phytosterols lowers plasma cholesterol concentrations in normocholesterolemic humans Pelletier, X., S. Belbraouet, et al. (1995), Ann Nutr Metab 39(5): 291-5. Abstract: Twelve normolipidic healthy human subjects were fed a diet with or without additional soybean phytosterols for 4 weeks in a crossover design. The order of the treatments was randomized. Phytosterols were added to the diet blended in butter. The dietary ratio cholesterol:phytosterols was 0.7 during the control period (436 mg cholesterol/day and 29 mg phytosterols/day) and 1.88 during the phytosterols period (410 mg cholesterol/day and 740 mg phytosterols/day). Blood cholesterol was 10% lower after subjects consumed the phytosterol-enriched diet than when they consumed the control diet (p < 0.001), which was due to a 15% LDL cholesterol decrease (p < 0.001). The HDL cholesterol:LDL cholesterol ratio was markedly enhanced (+25%) (p < 0.01). These findings suggest that a significant lowering of plasma total and LDL cholesterol can be effected by a modest dietary intake of soybean phytosterols. |
| A diet rich in high-oleic-acid sunflower oil favorably alters low-density lipoprotein cholesterol, triglycerides, and factor VII coagulant activity Allman-Farinelli, M. A., K. Gomes, et al. (2005), J Am Diet Assoc 105(7): 1071-9. Abstract: OBJECTIVE: To compare concentrations of factor VII coagulant activity (factor VIIc), fibrinogen, plasminogen activator inhibitor-1, and blood lipids on a saturated fat-rich diet with one rich in monounsaturated fat. DESIGN: Subjects were randomly allocated to two groups. The study design was an ABB/BAA extra-period crossover. One group consumed a diet rich in saturated fatty acid (SFA) with fat making up 20.8% of total energy, for 5 weeks and then one rich in monounsaturated fatty acid (MUFA), with fat making up 20.3% of total energy for 10 weeks. The other group consumed the MUFA diet for 5 weeks followed by the SFA diet for 10 weeks. SUBJECTS/SETTING: Men and women aged 35 to 69 years who were nonsmokers with no chronic illness and not on any medication were recruited to participate. Eighteen subjects were recruited and 15 (5 men, 10 women) completed the community-based study. INTERVENTION: Blood was sampled at the beginning and end point of each 5-week diet period for analysis of coagulation and fibrinolysis factors and blood lipids. Subjects kept 3-day food diaries twice during each of the three diet periods and were weighed on each visit for blood collection. Analysis of plasma fatty acids was used to indicate dietary compliance. MAIN OUTCOME MEASURES: Differences in fasting factor VIIc, fibrinogen, plasminogen activator inhibitor-1, insulin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoproteins A-1 and B, and plasma oleic acid levels while receiving the SFA diet vs MUFA diet. STATISTICAL ANALYSIS: A general linear model allowing for the ABB/BAA extra-period crossover, was used for each of the outcome measures. RESULTS: Factor VIIc was lower on the MUFA diet (P <.05) but fibrinogen and insulin concentrations and plasminogen activator inhibitor-1 activity did not differ between diets. Low-density lipoprotein cholesterol (P <.001) and triglyceride (P <.01) levels were lower on the MUFA diet compared with the SFA diet. A significant increase in both plasma phospholipid and neutral lipid oleic acid (P <.0001) occurred on the MUFA diet. CONCLUSIONS: Substitution of foods rich in saturated fat with foods rich in high-oleic-acid sunflower oil and margarine has favorable outcomes on blood lipids and factor VIIc. This oil presents another useful source of MUFA for diets aimed at prevention of heart disease. |
| A diet rich in monounsaturated rapeseed oil reduces the lipoprotein cholesterol concentration and increases the relative content of n-3 fatty acids in serum in hyperlipidemic subjects Gustafsson, I. B., B. Vessby, et al. (1994), Am J Clin Nutr 59(3): 667-74. Abstract: The effects of 3 wk on a diet rich in monounsaturated rapeseed oil were compared with those of a diet containing sunflower oil within a lipid-lowering diet. Ninety-five subjects with moderate hyperlipoproteinemia were randomly assigned to one of the two well-controlled diets prepared at the hospital kitchen. Total serum, low-density- and high-density-lipoprotein cholesterol concentrations decreased by 15%, 16%, and 11% (P < 0.001), respectively, on the rapeseed oil diet and by 16%, 14%, and 13% (P < 0.001) on the sunflower oil diet. Serum triglycerides decreased more markedly (by 29%, P < 0.001) on the sunflower oil than on the rapeseed oil diet (14%, P < 0.01). The n-3 fatty acids (20:5 and 22:5) in the serum phospholipids increased significantly on the rapeseed oil diet but decreased on the sunflower oil diet. There was an increase in the alpha-tocopherol concentrations after both diets. The findings indicate that low erucic acid rapeseed oil can replace oils and fats rich in polyunsaturated fatty acids in a lipid-lowering diet. |
| A dietary portfolio approach to cholesterol reduction: combined effects of plant sterols, vegetable proteins, and viscous fibers in hypercholesterolemia Jenkins, D. J., C. W. Kendall, et al. (2002), Metabolism 51(12): 1596-604. Abstract: Plant sterols, soy proteins, and viscous fibers are advised for cholesterol reduction but their combined effect has never been tested. We therefore assessed their combined effect on blood lipids in hyperlipidemic subjects who were already consuming a low-saturated fat, low-cholesterol diet before starting the study. The test (combination) diet was 1 month in duration and was very low in saturated fat and high in plant sterols (1 g/1,000 kcal), soy protein (23 g/1,000 kcal), and viscous fibers (9 g/1,000 kcal) obtained from foods available in supermarkets and health food stores. One subject also completed 2 further diet periods: a low-fat control diet and a control diet plus 20 mg/d lovastatin. Fasting blood lipids, blood pressure, and body weight were measured prior to and at weekly intervals during the study. The combination diet was rated as acceptable and very filling. The diet reduced low-density lipoprotein (LDL)-cholesterol by 29.0% +/- 2.7% (P <.001) and the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol by 26.5% +/- 3.4% (P <.001). Near maximal reductions were seen by week 2. In the subject who took Mevacor and control diets each for 4 weeks, the reduction in LDL:HDL-cholesterol on Mevacor was similar to the combination diet. We conclude that acceptable diets of foods from supermarkets and health food stores that contain recognized cholesterol-lowering dietary components in combination (a dietary portfolio) may be as effective as the starting dose of older first-line drugs in managing hypercholesterolemia. |
| A dietary portfolio: maximal reduction of low-density lipoprotein cholesterol with diet Kendall, C. W. and D. J. Jenkins (2004), Curr Atheroscler Rep 6(6): 492-8. Abstract: Over the past two decades, cholesterol-lowering drugs have proven to be effective and have been found to significantly reduce the risk of coronary heart disease (CHD). However, diet and lifestyle factors are still recognized as the first line of intervention for CHD risk reduction by the National Cholesterol Education Program and the American Heart Association, which now advocate use of viscous fibers and plant sterols, and soy protein and nuts, respectively. In a series of metabolically controlled studies, we have combined these four cholesterol-lowering dietary components in the same diet (ie, a dietary portfolio of cholesterol-lowering foods) in an attempt to maximize low-density lipoprotein cholesterol reduction. We have found that the portfolio diet reduced low-density lipoprotein cholesterol by approximately 30% and produced clinically significant reductions in CHD risk. These reductions were the same as found with a starting dose of a first-generation statin drug. |
| A dietitian-delivered group nutrition program leads to reductions in dietary fat, serum cholesterol, and body weight: the Worcester Area Trial for Counseling in Hyperlipidemia (WATCH) Hebert, J. R., C. B. Ebbeling, et al. (1999), J Am Diet Assoc 99(5): 544-52. Abstract: OBJECTIVE: To assess the effectiveness of a dietitian-based nutrition counseling and education program for patients with hyperlipidemia. DESIGN: A 4-session program implemented as a complement to a randomized physician-delivered intervention. SUBJECTS/SETTING: From 12 practice sites of the Fallon Clinic, 1,162 subjects with hyperlipidemia were recruited, 645 of whom had data sufficient for our primary analyses. INTERVENTION: Two individual and 2 group sessions conducted over 6 weeks. MAIN OUTCOME MEASURES: Total and saturated fat levels; serum low-density lipoprotein cholesterol levels; and body weight, measured at baseline and after 1 year. STATISTICAL ANALYSES: Multiple linear regression was used to evaluate changes in outcome measures. RESULTS: After 1 year, there were significant reductions in outcome measures for subjects attending 3 or 4 nutrition sessions vs subjects attending fewer than 3 sessions or those never referred to a nutrition session. Reductions (mean +/- standard error) in saturated fat (measured as percent of energy) were 2.7 +/- 0.5%, 2.1 +/- 0.5%, and 0.3 +/- 0.1%, respectively. These reductions correspond to roughly a 22% relative change from baseline in those attending 3 or 4 sessions. Corollary reductions were observed for total fat (measured as percent of energy): 8.2 +/- 1.4%, 5.0 +/- 1.4%, and 0.7 +/- 0.4%; low-density lipoprotein cholesterol: 0.48 +/- 0.11 mmol/L, 0.13 +/- 0.11 mmol/L, and 0.02 +/- 0.03 mmol/L; and body weight: 4.5 +/- 0.9 kg, 2.1 +/- 0.8 kg, and 1.1 +/- 0.2 kg. The specified changes were additive to those of the physician-delivered intervention. APPLICATIONS/CONCLUSIONS: This investigation provides empirical data demonstrating the effectiveness of a dietitian-delivered intervention in the care of patients with hyperlipidemia. |
| A DNA polymorphism for lecithin:cholesterol acyltransferase (LCAT) is associated with high density lipoprotein cholesterol concentrations in baboons Kammerer, C. M., J. E. Hixson, et al. (1993), Atherosclerosis 98(2): 153-63. Abstract: We investigated the effects of a polymorphic PvuII site in the gene for lecithin:cholesterol acyltransferase (LCAT) on serum high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) concentrations in a population of 750 pedigreed baboons. We also tested for genotype by diet interactions using data on HDL-C and apo A-I concentrations on two diets (chow and high-cholesterol, saturated fat). A significant (P < 0.001) association between the LCAT genotypes and HDL-C levels was observed. On both diets, animals homozygous for the less common allele had HDL-C levels that averaged 18-19% lower than animals homozygous for the more common allele. HDL-C levels of the heterozygotes were intermediate. The LCAT RFLP accounted for approximately 5% of the variation in HDL-C levels on the two diets. We observed no strong evidence for an LCAT genotype by diet interaction effect. |