High-field 13C NMR Studies of certain normal and abnormal human plasma lipoproteins.

High-field (63.4 kilogauss) Fourier transform nuclear magnetic resonance spectroscopy 13C in natural abundance has been used to study the structural organization and molecular dynamics of constituent lipids of normal human very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). The same method was used to study the abnormal beta-VLDL of two type III hyperlipoproteinemia patients having markedly differing ratios of VLDL cholesterol to triglyceride (0.3 and 0.6, respectively). Resolution obtained at 63.4 kilogauss has made possible the assignment of several additional resonances of cholesterol ring carbon atoms, not resolved in earlier studies at lower fields, in the VLDL spectra. The rotational reorientation of the ring portion of cholesteryl esters in VLDL (normal) and beta-VLDL (abnormal) is not highly anisotropic and is similar to that for cholesteryl esters disolved in excess triolein. The rotations of cholesteryl esters in LDL are more highly anisotropic and significantly more restricted. The results suggest that the structural organization of the lipid components in beta-VLDL resembles that found in normal VLDL but differs significantly from that for normal LDL.

Radioimmunoassay of human apolipoprotein CII. A study in normal and hypertriglyceridemic subjects.

A specific, precise, and sensitive double-antibody radioimmunoassay for the measurement of human apolipoprotein CII (apoCII) was developed. ApoCII was labeled with (125)I (chloramine-T) and monospecific antibody was raised in rabbits. No appreciable cross-reactivity with apolipoproteins CI, CIII, AI, AII, low density lipoproteins, and lipoprotein-free plasma was observed. Lipoproteins containing apoCII displaced the standard curve in parallel. ApoCII measurement was not affected by pretreatment of plasma with tetramethylurea, ethanol-diethyl ether, or heating. Mean (+/-SE) plasma-immunoreactive apoCII in 47 normotriglyceridemic subjects was 51.8+/-3.2 mug/ml, generally comparable with previous estimates of its concentration by other methods. ApoCII levels in 9 subjects with type IIB lipoprotein pattern, 14 with the type IV lipoprotein pattern, and 5 with type V lipoprotein pattern were respectively, 89.9+/-4.6, 85.4+/-6.9, 132.8+/-21.0 mug/ml, all higher than normals (P < 0.001). Plasma apoCII and triglyceride concentrations correlated in normo- and hypertriglyceridemics (r = 0.36 and 0.58, P < 0.05). Plasma triglycerides correlated inversely with the fraction of total apoCII in very low density lipoprotein (VLDL)-free plasma (r = -0.75, P < 0.01). There was no correlation between plasma apoCII and high density lipoprotein cholesterol. In normotriglyceridemics, VLDL apoCII levels correlated with in vitro lipoprotein lipase (LPL) activator activities (r = 0.89, P < 0.01). In hypertriglyceridemic subjects the mean concentrations of apoCII per milligrams VLDL protein, LPL activator activity per milligrams VLDL protein, and LPL activator activity per micrograms VLDL apoCII were all lower than in normotriglyceridemics, P < 0.05. As plasma triglycerides and apoCII increase, apoCII is redistributed from high density lipoprotein to VLDL. However, the amount of apoCII per milligram VLDL protein and its LPL activator potency per milligram VLDL protein are reduced. These factors may contribute to impaired VLDL catabolism.

Metformin-diet ameliorates coronary heart disease risk factors and facilitates resumption of regular menses in adolescents with polycystic ovary syndrome.

BACKGROUND: In 35 adolescent females (17 +/- 2 years) with polycystic ovary syndrome (PCOS), median body mass index (BMI) 30.8 kg/m2, we assessed effeicacy of metformin-diet for 1 year for reduction of weight, insulin, HOMA insulin resistance (IR), cholesterol, triglycerides, and resumption of regular menses. METHODS: Calories (26% protein, 44% carbohydrate) were targeted to 1,500-1,800/day if BMI was <25 or to 1,200-1,500/day if BMI was > or = 25, along with 2,550 mg metformin. RESULTS: Median weight fell from 82.7 to 79.1 kg (p = 0.009), insulin 16.7 to 13.3 microU/ml (p <0.0001), HOMA IR 3.41 to 2.74 (p = 0.0004), total cholesterol 164 to 151 mg/dl (p = 0.002), and triglyceride 103 to 85 mg/dl (p = 0.006). The percentage of cycles with normal menses rose from a pre-treatment mean of 22% to 74%, p < 0.0001. CONCLUSIONS: In adolescents with PCOS, metformin-diet reduces weight, insulin, IR, cholesterol, and triglycerides, and facilitates resumption of regular menses.

Phytosterols and cholesterol in malignant and benign breast tumors.

Tissue phytosterol and cholesterol levels in 10 benign and 8 malignant breast tumors were quantitated to reexamine the hypothesis that malignant tumors had distinctive phytosterol content. Phytosterols were present in 9 of 10 benign and 7 of 8 malignant breast tumors. Mean (+/- S.E.) cholesterol, campesterol, stigmasterol, and beta-sitosterol in malignant and benign tumors (microgram/g wet weight) did not significantly differ (p greater than 0.1): (formula: see text) In the malignant tumors, tissue cholesterol correlated with campesterol (r = 0.97) and beta-sitosterol (r = 0.97) (p less than 0.01), but not stigmasterol (r = -0.06). In benign tumors, tissue cholesterol correlated with campesterol (r = 0.43), stigmasterol (r = 0.64), and beta-sitosterol (r = 0.94), with p less than 0.01 for the latter two. Phytosterols were present in four samples of normal breast tissue with mean (+/- S.E.) campesterol, stigmasterol, and beta-sitosterol (2 +/- 0.8, 15 +/- 9, 7 +/- 5 microgram/g wet weight) slightly but not significantly lower than in benign and malignant breast tumors, p greater than 0.1. The comparability of tissue phytosterols in benign and malignant breast tumors and in normal breast tissue appears to render unlikely and putative etiological relationship between phytosterols and breast carcinoma.

Exchange of phospholipids between unilamellar vesicles of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine and plasma very low density lipoproteins.

Purified phosphatidylcholine exchange protein from bovine liver was used to exchange [14C]dipalmitoyl phosphatidylcholine from sonicated vesicles to human plasma very low density lipoproteins (VLDL). The exchange of [14C]-dipalmitoyl phosphatidylcholine for VLDL phospholipids was temperature dependent and linear with respect to time and amount of exchange protein. In the absence of the exchange protein, less than 10% of the [14C]dipalmitoyl phosphatidylcholine was transferred. At an initial weight ratio of [14C]-dipalmitoyl phosphatidylcholine vesicles to VLDL phospholipid (1.2 mg) of 2.2, the exchange protein (14 microgram) replaced 55% of the VLDL phospholipids with [14C]dipalmitoyl phosphatidylcholine in 15 min; VLDL protein and cholesterol content were unaltered. From these studies we conclude that the exchange protein is a useful method to alter the phospholipid composition of VLDL under conditions such that there is minimal perturbation of the lipoprotein.

Amaurosis fugax: associations with heritable thrombophilia.

The aim of this study was to prospectively assess associations between amaurosis fugax, inherited thrombophilia, and acquired thrombophilia. Thrombophilia and hypofibrinolysis were studied in 11 cases (eight women, three men; all white) with amaurosis fugax, 57 +/- 17 years old, selected by the absence of abnormal brain magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), magnetic resonance venography (MRV), ipsilateral internal carotid artery plaque, atrial fibrillation, or cardiac thrombus. Cases were compared to 78 healthy adult white controls (53 +/- 18 years old) for serologic measures, and by polymerase chain reaction to 248 healthy white controls (78 adults, 170 children) for gene mutations. All 11 cases had one or more familial thrombophilic coagulation disorder including one heterozygous for the G1691A factor V Leiden mutation, two with low free protein S, four with high factor VIII, three with resistance to activated protein C, three homozygous for the C677T methylenetetrahydrofolate reductase (MTHFR) mutation, two compound C677T-A1298C MTHFR heterozygotes, and three with hypofibrinolytic 4G4G homozygosity for the PAI-1 gene. The case with factor VIII of 160% had two other thrombophilias (compound MTHFR C677T-A1298C heterozygosity, resistance to activated protein C), and hypofibrinolytic high Lp(a). Thrombophilic C677T MTHFR homozygosity or compound C677T-A1298C heterozygosity was present in five of 10 (50%) cases vs. 30 of 248 (12%) controls, Fisher's p (p(f)) = .005. Thrombophilic factor VIII was high in four of 10 (40%) cases vs. 0 of 38 controls, p(f) = .001. Thrombophilic hyperestrogenemia in five of the eight women (four exogenous estrogen, one pregnant) may have interacted with inherited thrombophilia-hypofibrinolysis, promoting thrombus formation. In cases selected by the absence of abnormal brain magnetic resonance imaging, significant ipsilateral internal carotid artery plaque, atrial fibrillation, or cardiac thrombus, we speculate that amaurosis fugax can be caused by reversible (by anticoagulation) retinal artery thrombi associated with heritable thrombophilia and/or hypofibrinolysis, often augmented by estrogen-driven acquired thrombophilia.

Familial hyperalphalipoproteinemia.

A 26-member kindred had the newly recognized heritable hyperlipoproteinemia, familial hyperalphalipoproteinemia. In affected family members, hyperalphalipoproteinemia was not secondary to any diseases, drugs, or industrial exposures known to elevate alpha-lipoprotein (high-density) cholesterol (C-HDL) levels. Hyperalphalipoproteinemia was transmitted vertically through three generations. There were five matings of hyperalphalipoproteinemic to normal individuals, with 25 offspring. The ratio of offspring with elevated C-HDL levels to those with normal C-HDL levels was 12:13 (0.923), a ratio not significantly different from 1 (x2 equals 0.04), the ratio predicted for an autosomal dominant trait. In affected kindred members, levels of total plasma cholesterol were slightly elevated, those of low density lipoprotein cholesterol were normal to low, those of triglyceride were normal, and those of C-HDL were consistently elevated. Affected subjects were healthy, without xanthomata, and had no unique physical or neurological features.

Improvement in symptoms of depression and in an index of life stressors accompany treatment of severe hypertriglyceridemia.

In 14 men and nine women referred because of severe primary hypertriglyceridemia, our specific aim in a 54-week single-blind treatment (Rx) period was to determine whether triglyceride (TG) lowering with a Type V diet and Lopid would lead to improvement in symptoms of depression, improvement in an index of life stressors, change in locus of control index, and improved cognition, as serially tested by Beck (BDI), Hassles (HAS) and HAS intensity indices, Locus of Control index, and the Folstein Mini-Mental status exam. On Rx, median TG fell 47%, total cholesterol (TC) fell 15%, and HDLC rose 19% (all p < or = 0.001). BDI fell at all nine Rx visits (p < or = 0.001), a major reduction in a test of depressive symptoms. The HAS score also fell at all nine visits (p < or = 0.05 - < or = 0.001). Comparing pre-Rx baseline BDI vs BDI at 30 and 54 weeks on Rx, there was a major shift towards absence or amelioration of depressive symptoms (chi 2= 5.9, p = 0.016). On Rx, the greater the percent reduction in TG, the greater the percent fall in BDI (r = 0.47, p < or = 0.05); the greater the percent reduction in TC, the greater the percent fall in HAS (r = 0.41, p < or = 0.05). Improvement in the BDI and HAS accompanied treatment of severe hypertriglyceridemia, possibly by virtue of improved cerebral perfusion and oxygenation. There may be a reversible causal relationship between high TG and symptoms of depression.

Short term study of sucrose polyester a nonabsorbable fat-like material as a dietary agent for lowering plasma cholesterol.

The efficacy, safety, and acceptability of sucrose polyester (SPE), a fat-like material that is neither digested nor absorbed, were assessed in 13 normal and seven hypercholesterolemic subjects for its potential as a cholesterol-lowering agent. Addition or substitution of SPE for culinary fats in the diets of the normocholesterolemic individuals produced a mean reduction of total and low-density lipoprotein cholesterol of 14 and 17%, respectively (P less than 0.001), despite the daily ingestion of a diet containing 800 mg of cholesterol and of dietary fat with a P/S ratio of 0.4. Total and low-density lipoprotein cholesterol were not significantly reduced by similar 10-day feeding periods of SPE in seven subjects with familial hypercholesterolemia. High-density lipoprotein cholesterol and triglycerides were not changed in normal or hypercholesterolemic subject receiving SPE. Plasma vitamin A and E levels were reduced by 10 and 21% (p less than 0.02 and less than 0.001) in both normal and hypercholesterolemic subjects on SPE. These returned to the basal levels when SPE consumption was discontinued. SPE was recovered quantitatively (greater than 97%) in the stools, with the last measurable SPE being found day 3 to 5 after cessation of SPE intake. Despite recovery of 50 g or more of unhydrolyzed SPE in stools during SPE feeding, there was no clinical or chemical steatorrhea. On subtracting SPE's input to total stool fatty acids, it was found that "non-SPE" fatty acids in the stool had not increased during SPE feeding, SPE was easily incorporated into routine foodstuffs in addition to, or in substitution for, conventional dietary fats. On the basis of this short term evaluation in humans and other investigations with the rat and dog. SPE appears to have potential as a cholesterol-lowering agent.

Effects of alcohol ingestion on lipids and lipoproteins in normal men: isocaloric metabolic studies.

To investigate metabolic relationships between alcohol ingestion and fasting plasma high density lipoprotein cholesterol (C-HDL) and triglycerides, seven young normal males were assessed with isocaloric substitution of alcohol for carbohydrate in the diet. For a 5-week study period, an isocaloric low cholesterol diet containing 20% of the calories as protein, 40% as fat, and 40% as carbohydrate, with < 300 mg cholesterol per day, P/S 1.5/1, was ingested. In weeks 2 and 3, 35 and 53 g/day of 100 proof Vodka were ingested, with isocaloric substitution of alcohol for dietary carbohydrate during these study weeks. In week 5, 1.35 g/day of lecithin linoleate was added to assess another putative nutritional approach to increasing C-HDL levels. By two-way analysis of variance and Scheffe's paired t tests, there were no significant differences in either C-HDL or triglyceride levels for any of the five metabolic diet, alcohol substitution diet periods; additionally, there were no significant effects of lecithin on plasma lipids or lipoproteins. The general question asked, "Does alcohol affect C-HDL levels?" is answered negatively for isocaloric alcohol substitution, on a cholesterol-poor, high P/S, and relatively carbohydrate restricted diet, for a 2-week period of moderate alcohol intake. Alcohol's effect on C-HDL and triglyceride probably involves an interaction with total calories, and perhaps with dietary composition (cholesterol, saturated fat, carbohydrate content), as well as the amount of ethanol ingested, and duration of intake.

Influence of polyunsaturated and saturated fats on plasma lipids and lipoproteins in man.

The effects of varying polyunsaturated/saturated (P/S) fat ratios on the plasma levels of lipids, lipoproteins, and apolipoprotein A-I were assessed in six normal healthy subjects (three males, three females) with a particular focus on the P/S ratio which would offer optimal concentrations of both low-(LDL) and high-density lipoproteins (HDL). The isocaloric experimental diets contained 40% of calories as carbohydrate, 40% fat, and 20% protein; dietary cholesterol was 400 mg/day. The P/S ratio for the diets was 0.4, 1.0, or 2.0. Each diet was sequentially consumed for periods of 2 wk each. At the end of each 2-wk study period, plasma lipid, apolipoprotein A-I, and LDL and HDL cholesterol concentrations were determined; HDL were fractionated by zonal ultracentrifugation and lipid and protein composition determined. Compared to the P/S = 0.4 diet, mean plasma total cholesterol fell by approximately 6 and 12% on the P/S = 1.0 or P/S = 2.0 diets, respectively; plasma concentrations of LDL-cholesterol, HDL-cholesterol, and apolipoprotein A-I were also decreased on the polyunsaturated fat diets. The mean +/- SEM concentration (mg/dl) of HDL-cholesterol was 49.0 +/- 5.2 (P/S = 0.4), 44.0 +/- 3.8, (P/S = 1.0) and 41.0 +/- 3.7 (P/S = 2.0). As a result of a reduction in both LDL- and HDL-cholesterol on the polyunsaturate-rich diets, the ratios of HDL-cholesterol to plasma total cholesterol and HDL- to LDL-cholesterol were not significantly changed on the three diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Parent-child nutrient intake interrelationships in school children ages 6 to 19: the Princeton School District Study.

Interrelationships between nutrient intakes (dietary cholesterol, total carbohydrate, saturated and polyunsaturated fat, and total calories) of parents and children were examined in 294 families (60 black, 234 white) which included at least one parent and one child in the Princeton School survey of parents and their children, ages 6 to 19. The nutrient data were collected by means of the standardized Lipid Research Clinics' collaborative 24-hr dietary recall; simple correlations and analysis of covariance were used to assess parent-child nutrient intake (per kg body weight) relationships. There were significant positive simple correlations between nutrient intake of parents and children for total carbohydrate (r = 0.28, P < 0.0001), saturated fat (r = 0.15, P < 0.01), polyunsaturated fat (r = 0.19, P < 0.001), and calories (r = 0.24, P < 0.0001); parents' intake of cholesterol did not correlate with that of their children (r = 0.004, P > 0.1). By analysis of covariance with adjustment for sex, race, age, and recall group, the parent-child association of cholesterol intake was significant (P = 0.001), and the remaining parent-child nutrient intake relationships were congruent with those observed by simple correlations. The proportion of variation of the children's nutrient intake accounted for by parental nutrient intake varied from a low of 23% for parent-child cholesterol intakes (all parents-all children) to a high of 97% for carbohydrate intake in black fathers over age 40 and their children. The multiple Rs2 for black parents-black children for nutrient intakes were higher than those for white parents-white children for carbohydrate, saturated fat, and calories. Close parent child nutrient interrelationships not only suggest that a considerable portion of lipid-lipoprotein variability may be nutritionally-environmentally determined, but may contribute to clustering of coronary heart disease risk factors in families.

The substitution of sucrose polyester for dietary fat in obese, hypercholesterolemic outpatients.

Our aim was to determine the effects of the substitution of sucrose polyester (SPE) for dietary fat in a 16-week outpatient study in 36 obese subjects with primary hypercholesterolemia. The subjects were randomized into three groups who followed a 16-week treatment period where all subjects received hypocaloric diets which provided approximately 7 kcal/lb body weight, a polyunsaturated/saturated (P/S) fat ratio of 0.9, and 180 mg cholesterol/day. The percentages of calories as fat in the 3 groups were as follows: a low fat diet group (n = 12) received 27% of dietary calories as fat, a low fat plus SPE group (n = 13) received 25% of calories as fat plus 27 g SPE/day as a bread spread and salad dressing, and a third group (placebo, n = 11) received 37% of calories as fat with a 27 g/day conventional fat placebo (bread spread and salad dressing). Mean weight loss from baseline in the 16 week treatment period was 2.6, 3.9, and 3.4% respectively in the placebo, diet, and SPE groups, p less than .05 for each group, without significant differences between the groups. There was a mean reduction of low density lipoprotein cholesterol (LDL-C) of 16% in the SPE group (p less than .05), more than twice the reductions in the placebo and diet groups, 5% and 6%, respectively. There was a mean 20% reduction in the SPE group in triglyceride and very low density lipoprotein cholesterol (p less than .05), compared to 7 and 10% reductions in the placebo and diet groups respectively. The degree of weight loss was correlated with the degree of reduction in LDL-C in the low fat diet group, and in the low fat diet group plus SPE (r = 0.59 for both groups). Without confounding by different levels of dietary cholesterol or P/S, SPE induced significant reductions in LDL-C in hypercholesterolemic obese subjects beyond the effects of weight loss alone. The effects of SPE were significantly greater than those achieved by the use of a diet which severely limited conventional dietary fat intake (to 40 g/day). SPE in the form of a bread spread and a salad dressing is a practical formulation for outpatient hypocholesterolemic low fat diets and provides the lubricity and organoleptic benefits of authentic foods without the dense caloric content of digestible fats.

Sucrose polyester: substitution for dietary fats in hypocaloric diets in the treatment of familial hypercholesterolemia.

In five obese women heterozygous for familial hypercholesterolemia, we assessed the combination of weight loss and sucrose polyester (SPE) in lowering low-density lipoprotein cholesterol (LDLC). After a 10-day basal hypocaloric (1426 cal/day), 270 mg cholesterol, P/S 1.2:1 diet, an average of 36 g of dietary fat/day was replaced by 36 g of an 80/20 SPE-hydrogenated palm oil mixture, providing 30 g SPE for 30 days; during the SPE substitution period mean dietary cholesterol and P/S were unchanged, mean caloric intake was 1104 cal/day. During the hypocaloric basal diet, mean weight fell 1.2 kg, p less than 0.02, total plasma cholesterol fell 8% from 358 +/- 46 to 330 +/- 47 mg/dl, p less than 0.01, LDLC fell 4% from 264 +/- 37 to 254 +/- 44 mg/dl, p greater than 0.1, and mean high-density lipoprotein cholesterol fell 11%, from 52 +/- 4 to 46 +/- 4, p less than 0.05. Over the 30-day SPE substitution, mean cholesterol fell 20% from 330 +/- 47 at the end of the basal diet to 265 +/- 42 mg/dl, p less than 0.001; mean LDLC fell 23%, from 254 +/- 44 to 195 +/- 41 mg/dl (p less than 0.01); weight fell 4%, p less than 0.01, from 91 +/- 7 to 87 +/- 7 kg, and mean high-density lipoprotein cholesterol fell 11% from 46 +/- 4 to 41 +/- 2, p less than 0.05. Hypocaloric removal of dietary fat by SPE, an artificial fat with culinary properties of conventional dietary fats, effectively reduces LDLC (by 23%) in familial hypercholesterolemia subjects, with additive effects of SPE and weight loss.

Changes in plasma lipid and lipoprotein fractions after alteration in dietary cholesterol, polyunsaturated, saturated, and total fat in free-living normal and hypercholesterolemic children.

To assess the effects of dietary cholesterol and the amount and type of fat on plasma lipid and lipoproteins, nutrient intakes were altered sequentially over 15 months in 11 normal children and 12 children with heterozygous familial hypercholesterolemia. After a 3-month base-line assessment period, on an ad libitum diet, the following diets were given sequentially for three months each: dietary cholesterol greater than 450 mg/day, total fat less than 35% of total calories, and polyunsaturated fat to saturated fat ratio (P/S) greater than 1.5 (diet 1); dietary cholesterol less than 160 mg/day, total fat less than 35% total calories and P/S greater than 1.5 (diet 2); dietary cholesterol less than 160 mg/day, total fat 40% total calories P/S = 1 (diet 3), and dietary cholesterol greater than 450 mg/day total fat greater than 40% total calories, P/S less than 0.04 (diet 4). In normal and familial hypercholesterolemic children the high dietary P/S ratio lowered total and low-density lipoprotein cholesterol in the presence of high dietary cholesterol; sharp reductions in dietary cholesterol lowered the total and low-density lipoprotein cholesterol slightly in familial hypercholesterolemia subjects when P/S was high. High-density lipoprotein cholesterol was not affected by large changes in dietary cholesterol or amount or type of fat. Sustained dietary alteration which significantly lowers total and low-density lipoprotein cholesterol with commercially available products is achievable and practical in free-living children.

Dietary and other correlates of changes in total and low density lipoprotein cholesterol in hypercholesterolemic men: the lipid research clinics coronary primary prevention trial.

Correlates of changes in total (TOTAL-C) and low density lipoprotein cholesterol (LDL-C) were examined in the 3806 hypercholesterolemic men of the Lipid Research Clinics Coronary Primary Prevention Trial. These correlates included changes in weight, dietary and alcohol intake, plasma glucose and thyroxine, cigarette smoking, packet count, lipid-lowering drugs other than cholestyramine, and antihypertensive drugs. In both placebo plus diet and cholestyramine plus diet treatment groups, decreases in Quetelet index and in saturated fat and cholesterol intake and increases in polyunsaturated fat intake were consistently associated with reductions in TOTAL-C and in LDL-C. In the cholestyramine group, plasma glucose and smoking were predictors of increased TOTAL-C and LDL-C; age and packet count were predictors of decreased TOTAL-C and LDL-C. Diuretic use was associated with increases in TOTAL-C in both groups and with increases in LDL-C in the cholestyramine group.

Effect of sucrose polyester on fecal bile acid excretion and composition in normal men.

The effects of sucrose polyester (SPE) (a nonabsorbable mixture of hex-a, hepta,- and octa-fatty acid esters of sucrose with physical properties similar to those of common dietary fats) on fecal bile acid excretion and composition were assessed in 24 healthy, nonobese, normolipemic male volunteers, in a 40-day, inpatient, metabolic balance study. Isocaloric diets provided either 800, 300, or less than 50 mg of cholesterol/day (P/S ratios respectively 0.4, 1.0, and 1.5). After diet-only perids of 10 days (for the 800 and 300 mg cholesterol regimens), and 21 days (for the 50 mg diet), the diets were continued for 30 days, with addition of SPE to diets over three successive treatment periods of 10 days each, with 8, 16, and 35 g of liquid SPE/day, or 15, 30, and 50 g SPE/day in a SPE-hydrogenated palm oil mix. On both the liquid SPE and SPE-hydrogenated palm oil mix, there were no significant changes in fecal bile acid excretion as a function of dietary SPE, at any level of cholesterol intake, P > 0.1. In most subjects SPE changed fecal bile acid composition; lithocholic acid was decreased, and in most instances this was accompanied by the appearance and increase in chenodeoxycholic acid. In one subject, both deoxycholic and 3 beta, 12 alpha-dihydroxycholanic acid were reduced, with an accompanying increase in cholic acid. The hypocholesterolemic effect of SPE appears to be mediated through its reduction of intestinal absorption of cholesterol, not through effects on bile acid excretion.

Blood pressure lowering in elderly subjects: a double-blind crossover study of omega-3 and omega-6 fatty acids.

In 46 elderly (aged greater than or equal to 60 y) hypertensive subjects with entry systolic blood pressure (SBP) greater than or equal to 160 or diastolic blood pressure (DBP) greater than or equal to 90 mm Hg, our specific aim in a randomized, double-blind, crossover study (two 8-wk treatment periods separated by a 3-wk washout) was to compare blood pressure-lowering effects of 9 g fish oil/d [omega-3 (n-3) fatty acid] vs 9 g corn oil/d [omega-6 (n-6) fatty acid]. After a 4-wk baseline period, 22 subjects were randomly assigned to receive fish oil and 24 to receive corn oil. For both 8-wk treatments there were no between-group differences in the change in blood pressure. There was a treatment difference for standing DBP when baseline values were compared with those after treatment 2; DBP decreased by 5.1 mm Hg in the fish-oil group vs 0.72 mm Hg in the corn-oil group (P = 0.024). Within groups during the first treatment, both fish oil and corn oil lowered all four blood pressure measures (P less than 0.05); blood pressures were not further lowered during the second treatment compared with the washout period. There were no significant between-group differences in laboratory safety tests or categorical side effects. Fish oil lowered triglycerides by 0.47 mmol/L (P less than 0.001). In elderly subjects, diet plus both omega-3 and omega-6 supplements (9 g/d) safely and effectively lower SBP and DBP.

Alimentary lipemia: plasma high-density lipoproteins and apolipoproteins CII and CIII in healthy subjects.

Three healthy male and three female inpatient volunteers consumed isocaloric diets for 4 wk. At weekly intervals, a fatty meal (100 g fat) was consumed by each fasting subject and blood drawn at 2 h intervals for 12 h. Of the four oral fat loads, two contained saturated fat (polyunsaturated/saturated fat ratio = 0.34) and two contained unsaturated fat (polyunsaturated/saturated fat = 2.21). The magnitude of alimentary lipemia, expressed as area under the plasma triglyceride curve, was 3- to 4-fold higher in males than females. Alimentary lipemia was inversely related to the subjects' fasting plasma high-density lipoprotein (HDL)-cholesterol, HDL apolipoprotein (apo) CIII and directly related to plasma triglycerides. The P/S ratios of the daily diet or the fat meal did not significantly influence the plasma triglyceride curve. After fat intake, mean (+/- SEM) plasma total apoCII and CIII fell to 54 +/- 20% and 73 +/- 5% of base-line, respectively, at 12 h in five of six subjects. After oral fat, an initial fall and a subsequent rise in apoCII and CIII in HDL was associated with reciprocal changes in apoC concentrations in very low-density lipoproteins. We speculate from the data that 1) plasma HDL and their apoC concentrations are important determinants of chylomicron clearance and 2) transfer of apoCs from HDL to triglyceride-rich lipoproteins in the early phase of fat absorption does not result in the total recycling of apoCs from these lipoproteins to HDL during the late phase of alimentary lipemia.

A double-blind, placebo-controlled study of sucrose polyester in hypercholesterolemic outpatients.

Sucrose polyester (SPE) was studied in a double-blind, placebo-controlled trial in 91 outpatients with primary hypercholesterolemia. All patients maintained an isocaloric diet with cholesterol intake of 400 mg/day and a polyunsaturated to saturated fat ratio of 0.8 to 1.2 for the duration of the study. The study sequence consisted of a diet lead-in period, a first 8-wk treatment period, a 4-wk washout period, and a second 8-wk treatment period. Subjects were randomly assigned to six groups that differed by SPE dose (8, 16, and 32 g/day) and by the treatment period in which either SPE or an olive oil placebo was given in a bread spread formulation. Compared to placebo, the 8, 16, and 32 g/day doses of SPE decreased low-density lipoprotein cholesterol by 2%, 4% (p less than 0.05), and 5% (p less than 0.05) respectively, without changing high-density lipoprotein cholesterol. On SPE, 14/91 (15%) of the subjects experienced a decrease in low-density lipoprotein cholesterol greater than or equal to 10%, while only 2/91 (2%) showed this decrease with placebo.