Cholesterol Articles and Abstracts

For medical practitioners and the general public - Cholesterol Journal Article Catalog.

Cholesterol Journal Articles



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A new cholesterol derivative suitable for transfecting certain type of cells in the presence of 10% serum
Sochanik, A., I. Kaida, et al. (2000), Cancer Gene Ther 7(4): 513-20.
Abstract: We developed a new cationic lipid suitable for use as a DNA carrier in the presence of 10% sera. The novel compound (abbreviated as Arg-Chol) contains cholesterol and a dipeptide consisting of glycine and sterically protected arginine. The efficiency of reporter gene transfection using liposomes based on this new reagent was compared with that of liposomes made with other cationic derivatives of cholesterol. Lipoplexes formulated with the newly synthesized lipid mediate in vitro transfection of B16(F10) murine melanoma cells in the presence of 10% sera more efficiently than in other cell lines and compared with other cholesterol derivatives studied.

A new comparison method of HDL-cholesterol measurement for evaluation of routine methods
Sakurabayashi, I. (2002), Rinsho Byori 50(3): 234-41.

A new feature on the cholesterol-lowering landscape
Rader, D. J. (2001), Nat Med 7(12): 1282-4.

A new fluorescent cholesterol derivative: structure and blood plasma analysis
Abubaker, M. A. and R. von Wandruszka (1992), Photochem Photobiol 56(2): 163-70.
Abstract: A fluorescent cholesterol derivative produced by reaction with gaseous HCl and zinc chloride in ethyl acetate is shown to be a chlorine substituted B-ring diene. The species forms relatively rapidly via an i-steroid rearrangement, requiring a temperature around 70 degrees C. A weak, possibly dimeric pi-allyl zinc complex exists in solution, leading to a red shift in the fluorescence emission. The application of the derivative to the determination of cholesterol in bovine plasma provides good sensitivity and precision and requires notably small sample volumes.

A new high-temperature transition of crystalline cholesterol in mixtures with phosphatidylserine
Epand, R. M., D. Bach, et al. (2001), Biophys J 81(3): 1511-20.
Abstract: Phosphatidylserine and cholesterol are two major components of the cytoplasmic leaflet of the plasma membrane. The arrangement of cholesterol is markedly affected by the presence of phosphatidylserine in model membranes. At relatively low mol fractions of cholesterol in phosphatidylserine, compared with other phospholipids, cholesterol crystallites are formed that exhibit both thermotropic phase transitions as well as diffraction of x-rays. In the present study we have observed and characterized a novel thermotropic transition occurring in mixtures of phosphatidylserine and cholesterol. This new transition is observed at 96 degrees C by differential scanning calorimetry (DSC), using a heating scan rate of 2 degrees C/min. Observation of the transition requires that the hydrated lipid mixture be incubated for several days, depending on the temperature of incubation. The rate of formation of the material exhibiting a transition at 96 degrees C is more rapid at higher incubation temperatures. At 37 degrees C the half-time of conversion is approximately 7 days. Concomitant with the appearance of the 96 degrees C peak the previously known transitions of cholesterol, occurring at approximately 38 degrees C and 75 degrees C on heating scans of freshly prepared suspensions, disappear. These two transitions correspond to the polymorphic transition of anhydrous cholesterol and to the dehydration of cholesterol monohydrate, respectively. The loss of the 75 degrees C peak takes a longer time than that of the 38 degrees C peak, indicating that anhydrous cholesterol first gets hydrated to the monohydrate form exhibiting a transition at 75 degrees C and subsequently is converted by additional time of incubation to an altered form of the monohydrate, showing a phase transition at 96 degrees C. After several weeks of incubation at 37 degrees C, only the form with a phase transition at 96 degrees C remains. If such a sample undergoes several successive heating and cooling cycles, the 96 degrees C peak disappears and the 38 degrees C transition reappears on heating. For samples of 1-palmitoyl-2-oleoyl phosphatidylserine or of 1-stearoyl-2-oleoyl phosphatidylserine having mol fractions of cholesterol between 0.4 and 0.7, the 38 degrees C transition that reappears after the melting of the 96 degrees C component generally has the same enthalpy as do freshly prepared samples. This demonstrates that, at least for these samples, the amount of anhydrous cholesterol crystallites formed is indeed a property of the lipid mixture. We have also examined variations in the method of preparation of the sample and find similar behavior in all cases, although there are quantitative differences. The 96 degrees C transition is partially reversible on cooling and reheating. This transition is also scan rate dependent, indicating that it is, at least in part, kinetically determined. The enthalpy of the 96 degrees C transition, after incubation of the sample for 3 weeks at 37 degrees C is dependent on the ratio of cholesterol to 1-palmitoyl-2-oleoyl phosphatidylserine or to 1-stearoyl-2-oleoyl phosphatidylserine, with the enthalpy per mole cholesterol increasing between cholesterol mol fractions of 0.2 and 0.5. Dimyristoyl phosphatidylserine at a 1:1 molar ratio with cholesterol, after incubation at 37 degrees C, exhibits a transition at 95 degrees C that reverses on cooling at 44 degrees C, instead of 60 degrees C, as observed with either 1-palmitoyl-2-oleoyl phosphatidylserine or 1-stearoyl-2-oleoyl phosphatidylserine. These findings along with the essential absence of the 96 degrees C transition in pure cholesterol or in cholesterol/phosphatidylcholine mixtures, indicates that the phospholipid affects the characteristics of the transition, and therefore the cholesterol crystallites must be in direct contact with the phospholipid and are not simply in the form of pure crystals of cholesterol. These observations are particularly important in view of recent observations of the presence of cholesterol crystals in biological systems.

A new HMG-CoA reductase inhibitor, pitavastatin remarkably retards the progression of high cholesterol induced atherosclerosis in rabbits
Hayashi, T., P. J. Rani, et al. (2004), Atherosclerosis 176(2): 255-63.
Abstract: BACKGROUND: The remarkable anti-atherosclerotic effects of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor have not been demonstrated in diet induced severe hyperlipidemia in rabbit model. OBJECTIVE: We have investigated the effect of pitavastatin, a newly developed statin, on atherosclerosis in rabbits. METHODS AND RESULTS: Oophorectomized female NZW rabbits were fed 0.3% cholesterol chow for 12 weeks with or without pitavastatin (0.1mg/kg per day) (Gp.NK and HCD). The level of serum cholesterol was decreased in Gp.NK compared with Gp.HCD (772.8 +/- 70.2 versus 1056.9 +/- 108.3 mg/d), whereas no significant alterations were observed in triglyceride and HDL-cholesterol. NO dependent response stimulated by acetylcholine and calcium ionophore A23187 and tone related basal NO response induced by N(G)-monomethyl-l-arginine acetate were all improved by pitavastatin treatment. Pitavastatin treatment increased the level of cyclic GMP in the aorta of cholesterol fed rabbits. In the aorta, the expression of eNOS mRNA was significantly up regulated and O(2)(-) production was slightly reduced in Gp.NK animals. Atherosclerotic area was significantly decreased in aortic arch and thoracic aorta from Gp.NK compared with those from Gp.HCD (15.1 +/- 5.3 versus 41.9 +/- 10.2%, 3.1 +/- 1.1versus 7.9 +/- 1.2% in Gp.NK and Gp.HCD aortic arch and thoracic aorta). Anti-macrophage staining area, the MMP1 or 2 and the nitrotyrosine positive area were decreased in Gp.NK. CONCLUSION: Pitavastatin retards the progression of atherosclerosis formation and it improves NO bioavailability by eNOS up-regulation and decrease of O(2)(-).

A new in vitro assay of cholesterol adsorption by food and microbial polysaccharides
Soh, H. S., C. S. Kim, et al. (2003), J Med Food 6(3): 225-30.
Abstract: The adsorption of total cholesterol by polysaccharides was measured in vitro by enzymatic reactions, including the polysaccharide precipitation procedure. Total cholesterol adsorption capacities, in a mixture of polysaccharide and total cholesterol, were compared for apple pectin, gelrite gellan gum, xanthan gum, high-methoxyl pectin, citrus pectin, high-viscous alginate, low-viscous alginate, dextran, and zooglan. Acidic polysaccharides such as pectins, alginate, and xanthan gum at concentrations of 0.1% (wt/vol) were able to adsorb over 90% of the total cholesterol when dissolved in distilled water, sodium acetate buffer (pH 4.6), or sodium phosphate buffer (pH 7.0). However, total cholesterol adsorptions by gellan and zooglan were dependent upon the salt concentration and pH value, which decreased cholesterol adsorption in the following order by degree: distilled water, acidic pH, and alkaline pH. In particular, total cholesterol adsorption of zooglan was greatly decreased by the addition of sodium chloride. With 0.1% (wt/vol) polysaccharide dissolved in distilled water, the adsorption capacities of alginate, pectins, gellan gum, xanthan gum, and zooglan were 2.9, 2.88, 2.5, 2.9, and 2.4 mg/dL, respectively. However, 0.2% of zooglan was able to completely adsorb the cholesterol (3 mg/dL), whereas dextran did not adsorb cholesterol at all, producing no precipitate with hexadecyltrimethylammonium bromide.

A new labeling approach using stable isotopes to study in vivo plasma cholesterol metabolism in humans
Ouguerram, K., M. Krempf, et al. (2002), Metabolism 51(1): 5-11.
Abstract: A method to study reverse cholesterol transport in humans was developed using stable isotopes and kinetic analysis. Three normolipidemic subjects received simultaneous intravenous infusions of deuterated leucine and (13)C-acetate for 14 and 8 hours, respectively. Deuterium enrichment was measured in protein-bound leucine in apolipoproteins (apo) B-100 and A-I (using gas chromatography coupled with mass spectrometry GCMS) and (13)C-enrichment in unesterified cholesterol and cholesteryl ester (using gas chromatography coupled to isotope ratio mass spectrometry GC-C-IRMS) in very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) during the tracer infusion. Curves were analyzed using multicompartmental analysis. This protocol is suitable to quantify the different processes involved in reverse cholesterol transport (RCT) in humans, including cholesterol esterification, transfer of cholesteryl ester from HDL towards apo B-100-containing lipoproteins, and the contribution of VLDL, LDL, and HDL in the final steps of RCT. In agreement with previous data from kinetic analysis of radiotracer experiments, our results suggest that in fasting normolipidemic subjects the major fraction of cholesteryl ester enters plasma through esterification in HDL (more than 95%). The major fraction of cholesteryl ester disappears through apo B-100-containing lipoproteins (VLDL and LDL) catabolism (mean of 82%) rather than through removal from HDL (mean of 18% with approximately an equal part for apo AI-dependent and independent catabolism, respectively, 7% and 11%). We conclude that this protocol could be applied to study the modulation of these processes by nutrition, diseases, or pharmacologic treatments.

A new LC/APCI-MS method for the determination of cholesterol oxidation products in food
Raith, K., C. Brenner, et al. (2005), J Chromatogr A 1067(1-2): 207-11.
Abstract: Cholesterol oxidation products (COPs) can be formed in the body or in animal foods from cholesterol during food processing. A new method for the extraction and quantification of cholesterol, 7-ketocholesterol, cholestane-3beta-5alpha-6beta-triol, 25-hydroxycholesterol, 5,6alpha-epoxycholesterol, and 7beta-hydroxycholesterol by means of reversed-phase LC/atmospheric pressure chemical ionization mass spectrometry is presented. A baseline separation of all COPs was achieved, allowing a separate quantification also for isobaric compounds. The limits of detection were 15-30 ng/mL, quantification was performed from 100 ng/mL to 10 microg/mL with RSD < 2%. The method was applied successfully to the determination of cholesterol and COPs in processed foods such as pork, beef, chicken, and egg.

A new liquid homogeneous assay for HDL cholesterol determination evaluated in seven laboratories in Europe and the United States
Nauck, M., M. S. Graziani, et al. (1999), Clin Chem Lab Med 37(11-12): 1067-76.
Abstract: We evaluated a new liquid homogeneous assay for the direct measurement of high density lipoprotein cholesterol (HDL-C Plus) in seven laboratories. The assay includes two reagents which can be readily used in most available clinical chemistry analyzers. The total CVs of the new method were below 4.6% and the bias in relation to the designated comparison method was below 3.9%. The total error ranged between 4 to 7%. HDL-C values determined by this method were in good agreement with those obtained by the old homogeneous assay using lyophilized reagents, and other homogeneous and precipitation assays (0.944 < r < 0.996). The assay was linear up to at least 3.89 mmol/l HDL-C. Hemoglobin did not interfere, whereas in icteric samples slight deviations were observed. Lipemia up to 11.3 to 22.6 mmol/l triglycerides did not interfere with this homogeneous HDL-C assay. In samples of patients with paraproteinemia, discrepant results were seen. This liquid homogeneous HDL-C assay was easy to handle and produced similar results in all laboratories participating in this study. This method will enable clinical laboratories to reliably measure HDL-C for risk assessment of coronary heart disease.

A new liquid homogeneous assay for the determination of HDL-cholesterol. A comparison to precipitation with phosphotungstic acid/MgCl2 and a lyophilized homogeneous assay
Nauck, M., I. Neumann, et al. (1999), Clin Chem Lab Med 37(5): 537-43.
Abstract: We evaluated a new ready to use liquid assay for the homogeneous determination of HDL-cholesterol (HDL-C; Merck, Darmstadt, Germany) in comparison to phosphotungstic acid precipitation and a homogeneous assay, based on sulfated alpha-cyclodextrin and polyethylene glycol-modified enzymes (Roche Diagnostics/Boehringer Mannheim, Germany). The new liquid homogeneous HDL-C assay had inter-assay coefficients' of variation of less than 2.1%. The method is linear up to at least 3.11 mmol/I HDL-C, but even at 4.40 mmol/I the deviation from the expected value is less than 5%. Spinking experiments with low density lipoproteins and very low density lipoproteins proved that the new assay was specific for high density lipoproteins up to cholesterol associated with low density lipoproteins (LDL-C) and very low density lipoproteins (VLDL)-triglyceride concentrations of 18.13 and 22.60 mmol/l, respectively. Free fatty acids above 2mmol/l did not interfere. Icteric samples with bilirubin concentrations between 170 and 400 micromol/l did not show any systematic deviation compared to the precipitation procedure. In addition, serum hemoglobin concentrations up to 7.0 mmol/l and ascorbic acid up to 3000 micromol/l did not interfere with the HDL-C assay. An intermethod comparison including 120 samples revealed good agreement of the liquid HDL-C assay and the precipitation procedure (y = 0.943x + 0.074 mmol/l; r = 0.992). The new homogeneous HDL-C assay is thus precise, comparable and robust. Due to its ease of handling this assay will significantly facilitate attempts to include the differentiation between HDL-C and LDL-C in the routine screening for cardiovascular risk factors and in the monitoring of lipid lowering therapy.

A new method for the rapid measurement of cholesterol crystallization in model biles using a spectrophotometric microplate reader
Somjen, G. J., Y. Ringel, et al. (1997), J Lipid Res 38(5): 1048-52.
Abstract: Measurements of the cholesterol crystal observation time, and particularly the crystal growth rate in model biles, are important in biliary pathophysiology. The aim of this study was to develop a semi-automated method permitting multiple, simultaneous, and precise measurements of the crystal growth rate in model biles. Incubated model biles were mixed with a high concentration of NaTDC to solubilize non-crystalline turbidity and spectrophotometric measurements were performed. In parallel, samples were observed by light microscopy. The absorbance correlated linearly with the crystal mass and permitted quantitation of the crystal growth rate. Polarized light microscopy was more sensitive than spectrophotometry for determining the initial crystal observation time, while spectrophotometry was more precise and quantitative for measuring the crystal growth rate.

A new method of estimating cost effectiveness of cholesterol reduction therapy for prevention of heart disease
Kinlay, S., D. O'Connell, et al. (1994), Pharmacoeconomics 5(3): 238-48.
Abstract: The purpose of this study was to demonstrate a new method of estimating the cost effectiveness of interventions that lower blood cholesterol levels in the prevention of coronary heart disease (CHD) at the community level. The participants in the study were 67 651 men aged 35 to 64 years in the Lower Hunter region of New South Wales, Australia. Census data, risk factor profiles and CHD event rates from community surveillance, plus costs in 1988-1989 Australian dollars, were used as inputs to a computer program that used a logistic equation. The output estimated the CHD events avoided and the cost effectiveness of an intervention that identified and treated men with cholesterol levels greater than 6.5 mmol/L with dietary modification and cholestyramine. The cost of implementation of the intervention was $A50.1 million to prevent 104 CHD events. The cost-effectiveness ratio was $A482 224 per CHD event avoided (SD = $A24 761) and the direct medical costs avoided were approximately $A500 000 over a 5-year period ($A4535.07 per CHD event avoided). Drug acquisition costs contributed substantially (88%) to the total costs of interventions that rely on screening to identify individuals with high cholesterol for intensive treatment.

A new molecular defect in the lecithin: cholesterol acyltransferase (LCAT) gene associated with fish eye disease
Contacos, C., D. R. Sullivan, et al. (1996), J Lipid Res 37(1): 35-44.
Abstract: We report a new genetic defect in the lecithin:cholesterol acyltransferase (LCAT) gene associated with classical clinical and biochemical features of fish eye disease. The 63-year-old Australian female proband also suffers from non-insulin-dependent (type II) diabetes mellitus. She presented with corneal opacities, markedly reduced HDL-cholesterol (0.1 mmol/L; < 10% of normal controls), and elevated plasma triglycerides. The presence of diabetes did not explain the lipoprotein profile, which differed markedly in comparison to two female hypertriglyceridemic diabetic subjects. Cholesterol esterification in HDL-like particles was minimal but plasma cholesterol esterification was maintained due to LCAT activity in non-HDL-containing lipoprotein fractions. DNA sequence analysis of the proband's LCAT gene showed two C to T transitions resulting in the substitution of Thr123 with Ile and Tyr144 with Cys. Allele-specific PCR amplification procedures were used to confirm the presence of the mutations in this proband and to screen for additional carriers in her family. Three first degree relatives (mother, brother, son) were heterozygous for the Thr123 --> Ile mutation and her daughter had the Tyr144 --> Cys mutation. Apart from a reduction in HDL-cholesterol levels to half the normal concentration and a 20% reduction in apoA-I levels, their plasma lipids were unremarkable. The proband's son and daughter were further investigated. Both had normal cholesterol esterification rates in plasma and VLDL/LDL-depleted plasma, but reduced LCAT activity (50% that of normal). Thus, the biochemical and phenotypic expression for fish eye disease in the heterozygote subjects was similar, irrespective of the underlying LCAT mutation.

A new on-line dual enzymatic method for simultaneous quantification of cholesterol and triglycerides in lipoproteins by HPLC
Usui, S., Y. Hara, et al. (2002), J Lipid Res 43(5): 805-14.
Abstract: We describe an on-line dual detection method using HPLC for lipoprotein analysis that allows simultaneous determination of cholesterol and triglyceride profiles from a single injection of sample. Two different gel permeation columns, TSKgel LipopropakXL and Superose 6HR, were applied to the dual detection system, evaluating analytical performance of the proposed method and the columns by analyzing serum samples from human and nonhuman subjects. Both TSK and Superose columns produced good within-day imprecision values less than 4.7% for cholesterol and 4.2% for triglyceride determination. Linear regression analysis showed the results from the Superose column (y) correlated well with those from the TSK column (x): y = 0.969x + 5.44 (r = 0.990) for total cholesterol (mg/dl), y = 1.08x - 11.14 (r = 0.985) for total triglycerides (mg/dl), and y = 1.093x - 0.06 (r = 0.978) for the ratios of triglycerides to cholesterol (mg/mg). Furthermore, the cholesterol and triglyceride profiles elucidated the differences in the resolution ability of the columns, which have not been apparent from a single lipid profile. We conclude that the dual detection concept with proper choice of column and enzymic reagents specific to the objectives of the particular study can facilitate studies of lipoprotein metabolism.

A new pectin-based material for selective LDL-cholesterol removal
Lewinska, D., S. Rosinski, et al. (1994), Artif Organs 18(3): 217-22.
Abstract: A new material, natural polysaccharide-pectin, was tested for removal of human blood lipoproteins. Pectin was prepared in a granular form with the help of the specifically designed gelification device and tested in batch sorption experiments in vitro for removal of total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C) from human plasma. Pectin granules removed 40% of TC, 45% of LDL-C, and 36% of HDL-C on average with respect to the initial amounts whereas corresponding values for LA-40 Kanegafuchi adsorbent were 69%, 81%, and 33% in the same experimental conditions (shaking 1 g of sorbent sample with 2 ml of plasma).

A new precipitation method with magnetic separation for high-density-lipoprotein cholesterol assay
Iida, S., S. Osawa, et al. (1994), Clin Chim Acta 228(2): 133-42.
Abstract: We describe a new precipitation method for high-density-lipoprotein cholesterol quantitation. The new method uses magnetic force instead of centrifugal force to separate high-density-lipoprotein from other lipoproteins that are fractioned with a precipitating reagent. The reagents used for the new method are the same as those for the conventional method except that magnetizable particles are included in the former. The magnetizable particles are used without any modifications. The correlation between the new and the centrifuge methods with dextran sulfate-magnesium chloride, sodium phosphotungstate-magnesium chloride and polyethylene glycol 6,000 were satisfactory (r = 0.990, 0.997 and 0.997, respectively). The new method, which can be combined with any precipitating reagents used in conventional methods, is very simple to perform and does not need any special equipment.

A new probability mapping method to describe the development of atherosclerotic lesions in cholesterol-fed rabbits
Ivey, J., M. R. Roach, et al. (1995), Atherosclerosis 115(1): 73-84.
Abstract: A new probability mapping method was developed to quantify the size and location of lesions near aortic orifices. The precise location of any part of the lesion could be compared between rabbits. Colour photographs of lesions were projected onto a digitizing tablet, and coded as lesion or non-lesion. Next the orifices were warped onto a standard orifice, and then the lesion mapped to maintain the original length and angular location of the lesion from the edge of the orifice. This method, unlike the previously used polar mapping method, excludes neither absent lesions nor ones which surround more than one orifice. In contrast to other probability mapping methods it warps the orifice rather than the artery wall containing the lesion, and so is easier to use for correlation with histological studies. The eventual aim is to use the probability maps as a tool to estimate the age of various positions of the lesion and to identify areas for histological sampling. The method was used to describe the distribution of lesions in 21 rabbits fed a diet with cholesterol levels declining from 0.5% during the first week, to 0.25% during the next two weeks, to 0.125% for weeks 3-10, to 0.1% for weeks 11-24. This feeding protocol produces fatty lesions which are transformed into fibro-fatty and fibrous lesions with time.

A new reality: achieving cholesterol-lowering goals in clinical practice
Gaw, A. (2002), Atheroscler Suppl 2(4): 5-8; discussion 8-11.
Abstract: Physicians often fail to achieve recommended low-density lipoprotein (LDL) cholesterol goals for their patients using lipid-lowering therapies in the primary care setting. A variety of factors may contribute to this failure, including inadequate effectiveness of lipid-lowering drugs in reducing LDL cholesterol at commonly used doses. In the Lipid Assessment Treatment Project (L-TAP), for example, the success rates for lipid-regulating therapies and treatments according to National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II) LDL cholesterol goals were 43% for bile acid sequestrants, 39% for niacin, 32% for gemfibrozil, 28% for psyllium fiber, 40% for statins, and 40% for combination therapy. Rosuvastatin is a new statin that has been shown to achieve significantly greater reductions in LDL cholesterol compared with pravastatin, simvastatin, and atorvastatin in primary hypercholesterolemia and enabled greater proportions of patients to achieve LDL cholesterol goals. Similarly, rosuvastatin proved superior to atorvastatin in lowering LDL cholesterol in patients with familial hypercholesterolemia, with more patients achieving LDL cholesterol goals. Data from these trials suggest that rosuvastatin is as safe and well tolerated as other statins. The availability of lipid-lowering drugs with greater LDL cholesterol-lowering effects could simplify the approach to coronary heart disease risk reduction in primary care.

A new relationship between total/high density lipoprotein cholesterol and polyunsaturated fatty acids
Siguel, E. (1996), Lipids 31 Suppl: S51-6.
Abstract: Dietary and plasma fatty acids have been linked to total cholesterol but not to the ratio of total/high-density lipoprotein cholesterol (TC/HDLC). To evaluate the relationship between dietary and plasma levels of polyunsaturated fatty acids (PUFA) and TC/HDLC, we analyzed cross-sectional and longitudinal data using 519 plasma samples (50% men, 50% women) from subjects participating in the Framingham Heart Study and results from a study feeding diets rich in either n-6 linoleic acid or n-3 alpha-linolenic acid with or without fish oil supplements (n-3 derivatives). Values of TC/HDLC are inversely related to the percent of plasma PUFA when both variables are measured at the same time in different subjects, R = 0.82, P < 0.000001. PUFA in phospholipids increase in response to increased dietary intake of different PUFA, either n-3 or n-6 or fish oils. There was a highly significant inverse relationship between TC/HDLC and the percent of PUFA in phospholipids, R = 0.97, P < 0.001. The relationship was similar regardless of the source and type of dietary fatty acids. A similar relationship existed when only the baseline points were considered. When plasma PUFA % increases, either in response to a diet high in PUFA or across different subjects, TC/HDLC ratios decline. Evaluation of plasma fatty acid profiles and increased balanced dietary intake of PUFA to bring fatty acid profiles of subjects with low PUFA plasma levels closer to the profile of a healthy reference group is an effective approach to reduce high TC/HDLC. Reductions of more than 50% in TC/HDLC appear feasible with dietary modification alone. Further research, into fatty acid metabolic activity may determine the biochemical basis of common dyslipidemias.


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