Gender-specific differences in the kinetics of nonfasting TRL, IDL, and LDL apolipoprotein B-100 in men and premenopausal women.

OBJECTIVE: To investigate mechanisms underlying gender differences in serum lipoprotein concentrations, the kinetic behavior of apoB-100 was assessed. METHODS AND RESULTS: Twenty subjects (<50 years; 12 men and 8 premenopausal women) were provided a Western diet for 4 to 6 weeks, after which the kinetics of apoB-100 in triglyceride-rich, intermediate-density, and low-density lipoprotein (TRL, IDL, and LDL) were determined in the fed state. Nonfasting plasma TC, LDL-C, and triglyceride concentrations were 23%, 34%, and 57% lower, respectively, in the women compared with men. Plasma TRL and LDL apoB 100 pool sizes were lower by 40% and 30%, respectively. These differences were accounted for by higher TRL and LDL apoB 100 fractional catabolic rates (FCR), rather than differences in production rates (PR). Plasma TRL-C and LDL-C were positively correlated with TRL and LDL apoB 100 concentrations and pool size, and negatively correlated with TRL and LDL apoB 100 FCR (women: r=-0.59, P<0.01 and r=-0.54, P<0.04, and men: r=-0.43, P<0.05 and r=-0.44, P<0.05). No significant associations were observed between plasma TRL-C and LDL-C and PR. CONCLUSIONS: These data suggest the mechanism for lower TRL-C and LDL-C concentrations in women was determined predominantly by higher TRL and LDL FCR rather than lower PR. This could explain, in part, the lower CVD risk in premenopausal women relative to men.

Effect of soy protein from differently processed products on cardiovascular disease risk factors and vascular endothelial function in hypercholesterolemic subjects.

BACKGROUND: The magnitude of the effect of soy protein on lipoprotein concentrations is variable. This discordance is likely attributable to the various forms of soy protein used and to unrecognized shifts in dietary fatty acid, cholesterol, and fiber. OBJECTIVE: The objective was to evaluate the effect of soybean processing as well as soy consumption relative to animal protein, independent of alterations in major dietary variables, on cardiovascular disease risk factors and vascular endothelial function. DESIGN: Twenty-eight hypercholesterolemic subjects (LDL cholesterol >/=3.36 mmol/L) aged >50 y consumed each of 4 diets for 6-wk periods according to a randomized crossover design. The diets [55% of energy as carbohydrate, 30% of energy as fat, and 15% of energy as protein-7.5% of energy as experimental protein (37.5 g/d)] were designed to contain products made from either whole soybeans, soyflour, or soymilk and were compared with a diet containing an equivalent amount of animal protein (meat, chicken, and dairy products). The cholesterol, fiber, and fatty acid profiles of the diets were equalized. All food and drink were provided, and body weight was maintained throughout the study. RESULTS: No significant differences in blood pressure, vascular endothelial function, or total cholesterol, VLDL-cholesterol, triacylglycerol, apolipoprotein B, or C-reactive protein concentrations were observed between the diets. Consumption of the soymilk diet resulted in a modest decrease (4%) in LDL-cholesterol concentrations compared with the animal-protein and soyflour diets (P < 0.05) and higher HDL-cholesterol (1%) and apolipoprotein A-I (2%) concentrations compared with the soybean and soyflour diets (P < 0.05). CONCLUSIONS: The results suggest that the consumption of differently processed soy-based products and different types of protein (animal and soy) has little clinical effect on cardiovascular disease risk factors, including peripheral endothelial function, when other major dietary variables are held constant.

Palm and partially hydrogenated soybean oils adversely alter lipoprotein profiles compared with soybean and canola oils in moderately hyperlipidemic subjects.

BACKGROUND: Partially hydrogenated fat has an unfavorable effect on cardiovascular disease risk. Palm oil is a potential substitute because of favorable physical characteristics. OBJECTIVE: We assessed the effect of palm oil on lipoprotein profiles compared with the effects of both partially hydrogenated fat and oils high in monounsaturated or polyunsaturated fatty acids. DESIGN: Fifteen volunteers aged > or =50 y with LDL cholesterol > or =130 mg/dL were provided with food for each of 4 diets (35 d/phase) varying in type of fat (partially hydrogenated soybean, soybean, palm, or canola; two-thirds fat, 20% of energy). Plasma fatty acid profiles, lipids, lipoproteins, apolipoprotein A-I, apolipoprotein B, lipoprotein(a), glucose, insulin, HDL subfractions, and indicators of lipoprotein metabolism (HDL-cholesterol fractional esterification rate, cholesteryl ester transfer protein, phospholipid transfer protein, and paraoxonase activities) were measured at the end of each phase. RESULTS: Plasma fatty acid profiles reflected the main source of dietary fat. Partially hydrogenated soybean and palm oils resulted in higher LDL-cholesterol concentrations than did soybean (12% and 14%, respectively; P < 0.05) and canola (16% and 18%; P < 0.05) oils. Apolipoprotein B (P < 0.05) and A-I (P < 0.05) concentrations mirrored the pattern of LDL- and HDL-cholesterol concentrations, respectively. No significant effect on the total-to-HDL cholesterol ratio was observed for palm oil compared with the other dietary fats. HDL3 cholesterol was higher after palm oil than after partially hydrogenated and soybean oils (P < 0.05). Differences in measures of glucose and HDL intravascular processing attributable to dietary fat were small. CONCLUSION: Palm and partially hydrogenated soybean oils, compared with soybean and canola oils, adversely altered the lipoprotein profile in moderately hyperlipidemic subjects without significantly affecting HDL intravascular processing markers.

Novel soybean oils with different fatty acid profiles alter cardiovascular disease risk factors in moderately hyperlipidemic subjects.

BACKGROUND: A variety of soybean oils were developed with improved oxidative stability and functional characteristics for use as alternatives to partially hydrogenated fat. OBJECTIVE: The objective was to assess the effect of selectively bred and genetically modified soybean oils with altered fatty acid profiles, relative to common soybean and partially hydrogenated soybean oils, on cardiovascular disease risk factors. DESIGN: Thirty subjects (16 women and 14 men) aged >50 y with LDL-cholesterol concentrations >130 mg/dL at screening consumed 5 experimental diets in random order for 35 d each. Diets contained the same foods and provided 30% of energy as fat, of which two-thirds was either soybean oil (SO), low-saturated fatty acid soybean oil (LoSFA-SO), high-oleic acid soybean oil (HiOleic-SO), low-alpha-linolenic acid soybean oil (LoALA-SO), or partially hydrogenated soybean oil (Hydrog-SO). RESULTS: Plasma phospholipid patterns reflected the predominant fat in the diet. LDL-cholesterol concentrations were 3.66 +/- 0.67(b), 3.53 +/- 0.77(b), 3.70 +/- 0.66(b), 3.71 +/- 0.64(a,b), and 3.92 +/- 0.70(a) mol/L; HDL-cholesterol concentrations were 1.32 +/- 0.32(a,b), 1.32 +/- 0.35(b), 1.36 +/- 0.33(a), 1.32 +/- 0.33(b), and 1.32 +/- 0.32(a,b) mol/L for the SO, LoSFA-SO, HiOleic-SO, LoALA-SO, and Hydrog-SO diets, respectively (values with different superscript letters are significantly different, P < 0.05). No significant effects were observed on VLDL-cholesterol, triacylglycerol, lipoprotein(a), and C-reactive protein concentrations or on ratios of LDL cholesterol to apolipoprotein B (apo B) and HDL cholesterol to apo A-I. Total cholesterol:HDL cholesterol was lower after subjects consumed the unhydrogenated soybean oils than after they consumed the Hydrog-SO diet. CONCLUSIONS: All varieties of soybean oils resulted in more favorable lipoprotein profiles than did the partially hydrogenated form. These soybean oils may provide a viable option for reformulation of products to reduce the content of trans fatty acids.

TRL, IDL, and LDL apolipoprotein B-100 and HDL apolipoprotein A-I kinetics as a function of age and menopausal status.

OBJECTIVE: To determine mechanisms contributing to the altered lipoprotein profile associated with aging and menopause, apolipoprotein B-100 (apoB-100) and apoA-I kinetic behavior was assessed. METHODS AND RESULTS: Eight premenopausal (25+/-3 years) and 16 postmenopausal (65+/-6 years) women consumed for 6 weeks a standardized Western diet, at the end of which a primed-constant infusion of deuterated leucine was administered in the fed state to determine the kinetic behavior of triglyceride-rich lipoprotein (TRL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) apoB-100, and high-density lipoprotein (HDL) apoA-I. Data were fit to a multicompartmental model using SAAM II to calculate fractional catabolic rate (FCR) and production rate (PR). Total cholesterol, LDL cholesterol (LDL-C), TRL-C, and triglyceride levels were higher (50%, 55%, 130%, and 232%, respectively) in the postmenopausal compared with the premenopausal women, whereas HDL-C levels were similar. Plasma TRL, IDL, and LDL-apoB-100 levels and pool sizes (PS) were significantly higher in the postmenopausal than premenopausal women. These differences were accounted for by lower TRL, IDL, and LDL apoB-100 FCR (P<0.05), with no difference in PR. There was no significant difference between groups in HDL-C levels or apoA-I kinetic parameters. Plasma TRL-C concentrations were negatively correlated with TRL apoB-100 FCR (r=-0.46; P<0.05) and positively correlated with PR (r=0.62; P<0.01). Plasma LDL-C concentrations were negatively correlated with LDL apoB-100 FCR (r=-0.70; P<0.001) but not PR. CONCLUSIONS: The mechanism for the increase in TRL and LDL apoB-100 PS observed in the postmenopausal women was determined predominantly by decreased TRL and LDL catabolism rather than increased production. No differences were observed in HDL apoA-I kinetics between groups.

Lipoprotein response to diets high in soy or animal protein with and without isoflavones in moderately hypercholesterolemic subjects.

OBJECTIVE: The objective of this study was to assess the independent effect of soy relative to common sources of animal protein and soy-derived isoflavones on blood lipids. METHODS AND RESULTS: Forty-two subjects with LDL cholesterol levels > or =3.36 mmol/L were fed each of four diets in randomized order for 6 weeks per phase. Diets contained a minimum of 25 g animal protein or isolated soy protein/4.2 MJ, with each containing trace amounts or 50 mg of isoflavones/4.2 MJ. Soy protein had a modest effect on total, LDL and HDL cholesterol, and triglyceride concentrations (-2%, P=0.017; -2%, P=0.042; +3%; P=0.034, -11%, P<0.001, respectively). Soy protein had no significant effect on plasma lipids in individuals with LDL cholesterol <4.14 mmol/L and significantly reduced total and LDL cholesterol and triglyceride concentrations in individuals with LDL cholesterol > or =4.14 mmol/L (-4%, P=0.001; -5%, P=0.003; -15%, P<0.001, respectively). No significant effect of isoflavones on plasma lipid levels was observed either constituent to the soy protein or supplemental to the animal protein. CONCLUSIONS: Although potentially helpful when used to displace products containing animal fat from the diet, the regular intake of relatively high levels of soy protein (>50 g/day) had only a modest effect on blood cholesterol levels and only in subjects with elevated LDL cholesterol levels (> or =4.14 mmol/L). Soy-derived isoflavones had no significant effect.

Effect of different forms of dietary hydrogenated fats on LDL particle size.

BACKGROUND: Dietary trans fatty acids (FAs), which are formed during the process of hydrogenating vegetable oil, are known to increase plasma LDL-cholesterol concentrations. However, their effect on LDL particle size has yet to be investigated. OBJECTIVE: We investigated the effect of trans FA consumption on the electrophoretic characteristics of LDL particles. DESIGN: Eighteen women and 18 men each consumed 5 experimental diets in random order for 35-d periods. Fat represented 30% of total energy intake in each diet, with two-thirds of the fat in the form of semiliquid margarine (0.6 g trans FAs/100 g fat), soft margarine (9.4 g trans FAs/100 g fat), shortening (13.6 g trans FAs/100 g fat), stick margarine (26.1 g trans FAs/100 g fat), or butter, which was low in trans FAs (2.6 g trans FAs/100 g fat) but rich in saturated fat. LDL particle size and distribution were characterized by nondenaturing, 2-16% polyacrylamide gradient gel electrophoresis. RESULTS: Relative to the LDL particle size observed after consumption of the butter-enriched diet, LDL particle size decreased significantly and in a dose-dependent fashion with increasing amounts of dietary trans FAs (P < 0.001). Cholesterol concentrations in large (> 260 A) and medium-sized (255-260 A) LDL particles also increased proportionately to the amount of trans FAs in the diet. CONCLUSION: Consumption of dietary trans FAs is associated with a deleterious increase in small, dense LDL, which further reinforces the importance of promoting diets low in trans FAs to favorably affect the lipoprotein profile.

Influence of hydrogenated fat and butter on CVD risk factors: remnant-like particles, glucose and insulin, blood pressure and C-reactive protein.

Dietary trans fatty acids/partially-hydrogenated fat has been associated with increased risk of developing cardiovascular disease (CVD), possibly greater than predicted from changes in lipoprotein levels. To explore this issue further potential risk factors were assessed in subjects provided with each of six diets in randomized order containing as the major source of fat: soybean oil, semi-liquid margarine, soft margarine, shortening, traditional stick margarine or butter. Plasma fatty acid profiles reflected diet, with triglyceride and phospholipid subfractions affected to a greater extent than cholesteryl ester. Non-fasting LDL-cholesterol levels were 144+/-27, 141+/-27, 146+/-26, 148+/-30, 151+/-29 and 165+/-31 mg/dl (P<0.001) and total cholesterol/HDL-cholesterol ratios were 5.50+/-1.25, 5.54+/-1.50, 5.69+/-1.29, 5.82+/-1.40, 6.11+/-1.30 and 5.94+/-1.43 (P=0.011), respectively, whereas other lipoprotein levels were not significantly different. Remnant-like particles levels were unaffected by dietary fat, either in the fasting or non-fasting state. Differences in fasting insulin and glucose levels were small and would not be predicted to have a large impact on glucose homeostasis. There was no significant effect of dietary fat type on C-reactive protein levels or blood pressure. These data suggest that, as previously demonstrated, the major CVD risk factor adversely affected by dietary trans fatty acids/partially-hydrogenated fat is LDL-cholesterol levels and total cholesterol/HDL-cholesterol ratios.

Plasma transport of vitamin K in men using deuterium-labeled collard greens.

The plasma transport of stable isotope-labeled phylloquinone at physiologic doses from food was studied. A single bolus of 100 g (396 +/- 28 microg phylloquinone) deuterium-labeled collard greens was fed with a breakfast containing 24 g fat to 5 men (26 to 71 years). Eleven blood samples were obtained over 216 hours. Phylloquinone concentrations in plasma and lipoprotein subfractions were measured using high-performance liquid chromatography (HPLC), and the ion abundances of deuterated and endogenous phylloquinone were determined using gas chromatography/mass spectrometry (GC/MS). Plasma total phylloquinone concentrations peaked at 6 to 9 hours (10.51 +/- 4.38 to 8.30 +/- 4.64 nmol/L) and returned to baseline by 24 hours (1.26 +/- 0.38 nmol/L). The triglyceride-rich lipoprotein (TRL) fraction was the major carrier of phylloquinone; low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions contained smaller amounts. Maximum enrichment of plasma and TRL phylloquinone with deuterium (88% and 89%, respectively) was reached at 6 hours, respectively; t(1/2) was 22.8 hours (n = 3). Deuterated-phylloquinone was not detectable in plasma or TRL fraction at 72 hours. These results suggest rapid uptake and transport of physiologic doses of phylloquinone.

Efficacy of a Therapeutic Lifestyle Change/Step 2 diet in moderately hypercholesterolemic middle-aged and elderly female and male subjects.

Lifestyle modification to decrease cardiovascular disease (CVD) risk has recently been reaffirmed by both the National Cholesterol Education Program and American Heart Association (AHA). Using a randomized crossover design, the Therapeutic Lifestyle Change (TLC)/Step 2 diet relative to a typical Western diet was assessed in 36 moderately hypercholesterolemic subjects in a clinical setting under isoweight conditions. Mean lipoprotein and apolipoprotein levels (fasting and non-fasting), fatty acid profiles, parameters of HDL metabolism, and glucose homeostasis were determined. Relative to the Western diet, the TLC/Step 2 diet resulted in 11% and 7% lower LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C), respectively, with no significant change in TG levels or total cholesterol-HDL-C ratio. Similar responses were observed in the non-fasting state. Linoleic (18:2n-6c) and alpha-linolenic (18:3n-3) acids increased at the expense of oleic acid (18:1n-9c) in the cholesteryl ester, TG, and phospholipid subfractions. The dietary changes had no significant effect on fractional esterification rate of HDL, phospholipid transfer protein (PLTP), or cholesterol ester transfer protein activities, or glucose and insulin levels. Female and male subjects responded similarly. The TLC/Step 2 diet resulted in a decrease in some CVD risk factors and no apparent adverse effects in others.