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Biomedical subjects

A H Lichtenstein

Publications and source records attributed to A H Lichtenstein.

At least 19 recordsLinked to original sources
PubMed2001

AHA Science Advisory. Stanol/sterol ester-containing foods and blood cholesterol levels. A statement for healthcare professionals from the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association.

Considerable attention in the recent past has focused on the potential benefits or adverse effects of butter versus different types of margarines, usually with respect to their relative content of polyunsaturated, saturated, and trans fatty acids, and the impact of these on low-density lipoprotein (LDL) cholesterol levels. Recently, a new class of margarines and other fat-derived products (eg, salad dressings, mayonnaise) containing plant-derived sterols that are intended for use to lower blood cholesterol levels have been introduced into the food supply. These products are being marketed as adjuncts to low-saturated-fat and low-cholesterol diets to maximize reductions in LDL cholesterol levels achievable by dietary means.

American Heart Association↗
PubMed2001

Human triglyceride-rich lipoprotein apo E kinetics and its relationship to LDL apo B-100 metabolism.

Apolipoprotein (apo) E is a multifunctional protein that can act as a ligand for lipoprotein receptors. The receptor-mediated clearance of the triglyceride-rich lipoproteins (TRL) chylomicrons and VLDL from plasma is, in part, dependent on apo E. Enrichment of VLDL with apo E is thought to enhance receptor-mediated clearance of VLDL resulting in a low rate of conversion of VLDL to LDL. However, the kinetic mechanism controlling the concentration of apo E in VLDL is not known. We conducted kinetic studies on apo E in the TRL fraction (d < 1.006 g/ml) and apo B-100 in the TRL and LDL (d = 1.019-1.063 g/ml) fractions to assess the kinetic determinants of apo E concentration in TRL and to determine the effects that TRL apo E production and clearance rates have on the production rate of LDL apo B-100. Nineteen males between the ages of 24 and 73 underwent a primed-constant infusion with deuterated leucine tracer in the constantly-fed state. Apo B-100 from TRL and LDL, and apo E from TRL were isolated and their tracer incorporation measured by gas chromatography/mass spectrometry. The residence time and production rates of each protein were determined from the kinetic data using the SAAM II modeling program. The residence time and production rate of TRL apo E were about one-half that of TRL apo B-100 (1.8 +/- 1.0 vs. 2.9 +/- 2.1 h and 14.5 +/- 11.0 vs. 27.6 +/- 17.3 mg/kg per day, respectively). The production rate of TRL apo E was weakly correlated with the production rate of TRL apo B-100 (r = 0.424, P = 0.07). Multiple regression analysis showed that the residence time of TRL apo B-100 and the relative TRL apo E production rate (relative to the TRL apo B100 production rate) were negatively associated with LDL apo B-100 production rate, accounting for 68% of its variability. We conclude that (1) the concentration of apo E in TRL is highly correlated to its production rate, suggesting that production rate regulates the TRL apo E concentration, and (2) individuals with a relatively short TRL apo B-100 residence time and those producing TRL with a relatively low apo E content have the highest LDL apo B-100 production rates.

Adult↗
PubMed2001

Human apolipoprotein A-IV metabolism within triglyceride-rich lipoproteins and plasma.

In order to investigate the metabolism of apo A-IV within TRL and plasma, we assessed TRL and plasma apo A-IV kinetics in 19 and 4 subjects, respectively, consuming an average US diet for a 6-week period. At the end of this diet study, each subject received a primed-constant infusion of deuterated leucine over a 15 h time period with hourly feeding, and blood samples were drawn at 10 time points. TRL was separated by ultracentrifugation. Apo A-IV was isolated by immunoprecipitation and/or SDS-PAGE. Apo A-IV concentrations were determined by immunoelectrophoresis. Stable isotope tracer/tracee ratios were measured by gas chromatography/mass spectrometry, and the data were analyzed by multicompartmental modeling. The mean concentrations of plasma and TRL apo A-IV during the isotope infusion period were 21.0+/-3.2 and 0.66+/-0.25 mg/dl, respectively, and these values were 11.5 and 30.5% higher than those of fasting samples. The mean TRL and plasma apo A-IV residence times (RT) were 1.97+/-0.57 and 2.71+/-0.65 days, and transport rates (TR) were 0.17+/-0.19 and 3.90+/-1.24 mg/kg per day, respectively. There were significant correlations between TRL apo A-IV concentrations and TR (r(2)=0.79, P<0.001), and between TRL apo A-IV pool size and TRL cholesterol levels (r(2)=0.29, P=0.02). Our data indicated that; (1) TRL apo A-IV has a RT of 1.97 days which is similar to that earlier reported for HDL apo A-IV; (2) Apo A-IV recirculates between TRL and other slowly turning over pools; (3) the primary determinant of TRL apo A-IV levels is its TR; and (4) there is no correlation between TRL apo A-IV and apo B48 fractional catabolism in TRL.

Adult↗
PubMed2001

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Cardiovascular Diseases↗
PubMed2001

Association of sex, adiposity, and diet with HDL subclasses in middle-aged Chinese.

BACKGROUND: There is limited information regarding the associations of lifestyle factors and sex with HDL subclasses containing apolipoprotein (apo) A-I (Lp A-I) and both apo A-I and apo A-II (Lp A-I:A-II). OBJECTIVE: We sought to examine the relations between 2 major HDL subclasses and sex, menopausal status, nutrient intakes, and adiposity. DESIGN: We conducted interviews and measured blood variables in 409 government employees aged 40-59 y in Taiwan. RESULTS: Women (n = 203) had significantly higher concentrations of HDL cholesterol, Lp A-I, and Lp A-I:A-II than did men (n = 206). Postmenopausal women (n = 72) had higher concentrations of HDL cholesterol, Lp A-I, and Lp A-I:A-II than did premenopausal women (n = 131). Body mass index and waist-to-hip ratio were strong predictors of and exerted an independent additive effect on Lp A-I concentrations in both men and women. However, body adiposity was associated with Lp A-I:A-II concentrations only in men. Waist-to-hip ratio was an independent determinant of Lp A-I but not of Lp A-I:A-II in men and postmenopausal women after adjustment for age, body mass index, smoking, and diet. Although there were relatively weak associations between dietary factors and both HDL subclasses (r = 0.01-0.26) in men and women according to bivariate analyses, multiple regression models showed that total fat, saturated fat, and cholesterol intakes were significantly correlated with HDL cholesterol and both Lp A-I and Lp A-I:A-II in men, but not in women. CONCLUSION: Our data suggest that body adiposity and dietary fat consumption affect 2 major HDL subclasses differently depending on subject sex and menopausal status.

Adipose Tissue↗
PubMed2001

Effects of a National Cholesterol Education Program Step II Diet on apolipoprotein A-IV metabolism within triacylglycerol-rich lipoproteins and plasma.

BACKGROUND: Apolipoprotein (apo) A-IV is a major component of triacylglycerol-rich lipoprotein (TRL) apolipoproteins. OBJECTIVE: We investigated the effects of dietary saturated fat and cholesterol restriction on the metabolism of TRL and plasma apo A-IV. DESIGN: We assessed TRL and plasma apo A-IV kinetics in 16 and 4 subjects, respectively, consuming an average US (baseline) diet for 6 wk and a National Cholesterol Education Program Step II diet for 24 wk, respectively. At the end of each diet period, all subjects received a primed, constant infusion of deuterated leucine for 15 h with hourly feeding. Ratios of stable-isotope tracer to tracee were measured by using gas chromatography-mass spectrometry, and kinetic data were modeled by using SAAM II. RESULTS: Mean apo A-IV concentrations during the isotope infusion period were 6.9 +/- 2.6 mg/L in TRL and 2.2 +/- 3.2 mg/L in plasma with the baseline diet; these values were 37.7% (P < 0.001) and 19.4% (P < 0.01) lower with the Step II diet. Similar changes were observed in the fasting state between the 2 diets. The mean apo A-IV secretion rate decreased significantly from baseline by 59.6% in TRLs and by 40.2% in plasma. Significant correlations were observed between TRL apo A-IV concentrations and the secretion rate (r = 0.94, P < 0.001) and between TRL apo A-IV pool size and TRL-cholesterol concentrations (r = 0.48, P < 0.01). CONCLUSIONS: Our data indicate that the National Cholesterol Education Program Step II diet significantly decreases TRL and plasma apo A-IV concentrations compared with the average US diet and that this decrease is due to a decreased secretion rate.

Adult↗
PubMed2001

Effects of a hydrogenated form of vitamin K on bone formation and resorption.

BACKGROUND: Hydrogenation of vegetable oils affects blood lipid and lipoprotein concentrations. However, little is known about the effects of hydrogenation on other components, such as vitamin K. Low phylloquinone (vitamin K1) intake is a potential risk factor for bone fracture, although the mechanisms of this are unknown. OBJECTIVE: The objective was to compare the biological effects of phylloquinone and its hydrogenated form, dihydrophylloquinone, on vitamin K status and markers of bone formation and resorption. DESIGN: In a randomized crossover study in a metabolic unit, 15 young adults were fed a phylloquinone-restricted diet (10 microg/d) for 15 d followed by 10 d of repletion (200 microg/d) with either phylloquinone or dihydrophylloquinone. RESULTS: There was an increase and subsequent decrease in measures of bone formation (P = 0.002) and resorption (P = 0.08) after dietary phylloquinone restriction and repletion, respectively. In comparison with phylloquinone, dihydrophylloquinone was less absorbed and had no measurable biological effect on measures of bone formation and resorption. CONCLUSION: Hydrogenation of plant oils appears to decrease the absorption and biological effect of vitamin K in bone.

Adult↗
PubMed2001

An oat-containing hypocaloric diet reduces systolic blood pressure and improves lipid profile beyond effects of weight loss in men and women.

Hypertension, dyslipidemia and overweight contribute substantially to cardiovascular disease risk. One of the most effective methods for improving high blood pressure and lipid profiles is loss of excess weight. Other recommendations for reducing cardiovascular risk include changes in dietary micronutrient, macronutrient and fiber intakes. To better define a diet for reduction in cardiovascular risk, 43 adults (body mass index 26.4 +/- 3.3, range 20.5-33.9 kg/m(2)) participated in an 8-wk study to determine the effects of two diets on weight, blood pressure, lipids and insulin sensitivity. For 2 wk, weight was maintained and all subjects consumed a control diet. For the next 6 wk, subjects consumed one of two hypocaloric diets (maintenance energy minus 4.2 MJ/d): the control diet (n = 21) or a diet containing oats [45 g/(4.2 MJ dietary energy. d), n = 22]. There was no significant difference between groups in changes in weight loss (control -4.0 +/- 1.1 kg, oats -3.9 +/- 1.6 kg, P = 0.8). The oats diet resulted in greater decreases in mean systolic blood pressure (oats -6 +/- 7 mm Hg, control -1 +/- 10 mm Hg, P = 0.026), whereas diastolic blood pressure change did not differ between the two groups (oats -4 +/- 6 mm Hg, control -3 +/- 5 mm Hg, P = 0.8). The oat diet resulted in significantly greater decreases in total cholesterol (oats -0.87 +/- 0.47 mmol/L, control -0.34 +/- 0.5 mmol/L, P = 0.003) and LDL cholesterol (oats -0.6 +/- 0.41 mmol/L, control -0.2 +/- 0.41mmol/L, P = 0.008). In summary, a hypocaloric diet containing oats consumed over 6 wk resulted in greater improvements in systolic blood pressure and lipid profile than did a hypocaloric diet without oats.

Adult↗
PubMed2001

Impact of hydrogenated fat on high density lipoprotein subfractions and metabolism.

Relative to saturated fatty acids, trans-fatty acids/hydrogenated fat-enriched diets have been reported to increase low density lipoprotein (LDL) cholesterol levels and either decrease or have no effect on high density lipoprotein (HDL) cholesterol levels. To better understand the effect of trans-fatty acids/hydrogenated fat on HDL cholesterol levels and metabolism, 36 subjects (female, n = 18; male, n = 18) were provided with each of three diets containing, as the major sources of fat, vegetable oil-based semiliquid margarine, traditional stick margarine, or butter for 35-day periods. LDL cholesterol levels were 155 +/- 27, 168 +/- 30, and 177 +/- 32 mg/dl after subjects followed the semiliquid margarine, stick margarine, and butter-enriched diets, respectively. HDL cholesterol levels were 43 +/- 10, 42 +/- 9, and 45 +/- 10 mg/dl, respectively. Dietary response in apolipoprotein (apo) A-I levels was similar to that in HDL cholesterol levels. HDL(2) cholesterol levels were 12 +/- 7, 11 +/- 6, and 14 +/- 7 mg/dl, respectively. There was virtually no effect of dietary fat on HDL3 cholesterol levels. The dietary perturbations had a larger effect on particles containing apoA-I only (Lp A-I) than apoA-I and A-II (Lp A-I/A-II). Cholesterol ester transfer protein (CETP) activity was 13.28 +/- 5.76, 15.74 +/- 5.41, and 14.35 +/- 4.77 mmol x h(-1) x ml(-1), respectively. Differences in CETP, phospholipid transfer protein activity, or the fractional esterification rate of cholesterol in HDL did not account for the differences observed in HDL cholesterol levels. These data suggest that the saturated fatty acid component, rather than the trans- or polyunsaturated fatty acid component, of the diets was the putative factor in modulating HDL cholesterol response.

Aged↗
PubMed2001

Hydrogenated fat consumption affects acylation-stimulating protein levels and cholesterol esterification rates in moderately hypercholesterolemic women.

To determine whether hydrogenated fat consumption alters triglyceride metabolism and cholesterol esterification rates, 14 women (65-71 years of age) were provided with each of four diets for 5-week periods according to a randomized cross-over design. The experimental diets contained either soybean oil (SO), low trans squeeze (SQM), medium trans tub (TM), or high trans stick (SM) margarines. Triglyceride uptake by adipose tissue was determined by measuring plasma acylation-stimulating protein (ASP), FFA, glucose, and insulin levels, while rates of transfer and esterification rate of newly synthesized cholesterol (ER) were derived by using plasma CETP levels and the deuterium incorporation methodology. Plasma ASP levels were lowest (P < 0.05) in subjects on the SM diet (33.4 +/- 12.7 nM) compared with the SO (48.7 +/- 17.0 nM) and SQM (50.7 +/- 15.7 nM) diets. Conversely, FFA were highest (P < 0.05) on the SM diet (0.86 +/- 0.45 mM) relative to all the other diets. No differences were observed in plasma glucose and insulin levels among diets. A trend toward higher CETP levels after consumption of the SM diet was observed. However, the ER was lowest (P < 0.05) after the SM (0.111 +/- 0.062 g x day(-1)) diet and highest after consumption of the SQM (0.216 +/- 0.123 g x day(-1)) diet. In addition, ASP levels were negatively correlated with FFA (r = -0.63, P < 0.05), LDL cholesterol (r = -0.56, P < 0.05), and TG (r = -0.41, P < 0.05), whereas FFA was positively correlated with apolipoprotein B-containing lipoproteins (r = 0.58 and 0.47, for VLDL and LDL cholesterol, P < 0.05), and negatively correlated with HDL cholesterol (r = -0.51, P < 0.05). The ER was found to positively correlate with HDL cholesterol and HDL2 subfraction (r = 0.53 and 0.45, respectively, P < 0.05). Taken together, these data demonstrate that the alterations in circulating lipid levels, commonly observed with consumption of hydrogenated fat-rich diets, can be explained in part by changes in ASP activity as well as newly synthesized cholesterol ER.

Blood Proteins↗
PubMed2000

Deuterium uptake and plasma cholesterol precursor levels correspond as methods for measurement of endogenous cholesterol synthesis in hypercholesterolemic women.

To assess the validity of two techniques used to measure human cholesterol synthesis, the rate of uptake of deuterium (D) into plasma free cholesterol (FC), and plasma cholesterol precursor (squalene, lanosterol, desmosterol and lathosterol) levels were compared in 14 women [65-71 yr with low density lipoprotein-cholesterol (LDL-C) > or = 3.36 mmol x L(-1)]. Subjects consumed each of six diets for 5-wk periods according to a randomized crossover design. The experimental diets included a baseline diet (39% energy as fat, 164 mg chol x 4.2 MJ(-1)) and five reduced-fat diets (30% of energy as fat), where two-thirds of the fat was either soybean oil; squeeze, tub or stick margarines; or butter. Fractional and absolute synthesis rates (FSR and ASR) of FC were determined using the deuterium incorporation (DI) method, while cholesterol precursor levels were measured using gas-liquid chromatography. Data were pooled across diets for each variable and correlation coefficients were calculated to determine if associations were present. There was good agreement among levels of the various cholesterol precursors. In addition, FSR in pools/d (p x d(-1)) and ASR in grams/d (g x d(-1)) were strongly associated with lathosterol (r= 0.72 and 0.71, P= 0.0001), desmosterol (r= 0.75 and 0.75, P = 0.0001), lanosterol (r = 0.67 and 0.67), and squalene (r = 0.69 and 0.68) when levels of the precursors were expressed as micromol x mmol(-1) C. Significant but lower correlations were observed between the D uptake and plasma cholesterol precursor levels when the latter were expressed in absolute amounts (micromol x L(-1)). The wide range of fatty acid profiles of the experimental diets did not influence the degree of association between methods. In conclusion, the DI method and levels of some cholesterol precursors correspond as methods for shortterm measurement of cholesterol synthesis.

Aged↗
PubMed2000

Dietary cholesterol increases the susceptibility of low density lipoprotein to oxidative modification.

Evidence suggests that oxidative modification of low density lipoprotein (LDL) occurs in vivo, increasing the atherogenecity of the particle. A total of 13 subjects (age range 46-78 years) with an LDL cholesterol concentration >3.36 mmol/l consumed each of four diets for 32-day periods. The diets contained 30% energy as fat of which 2/3 was either corn oil or beef tallow with and without 115 mg/4.2 MJ of supplemental cholesterol in the form of cooked egg yolk. The susceptibility of LDL to oxidation was assessed during a challenge with hemin and hydrogen peroxide, and results are expressed as lag time to oxidation in minutes. Addition of moderate amounts of cholesterol to either the corn oil or beef tallow enriched diet resulted in increased susceptibility of LDL to oxidation (decreased lag time): 69+/-22 min versus 96+/-24 min in the corn oil diet with versus without supplemental cholesterol, respectively, P = 0.006; 82+/-20 min versus 96+/-26 min in the beef tallow diet with versus without supplemental cholesterol, respectively, P = 0.025. A stepwise equation indicated that as plasma oleic acid concentrations increased and/or linoleic acid concentrations decreased, lag time increased (decreased susceptibility to oxidation), whereas as dietary cholesterol concentrations increased, lag time decreased (increased susceptibility to oxidation). In conclusion, these data suggest that addition of a moderate amount of dietary cholesterol to a reduced fat diet rich in polyunsaturated or saturated fatty acids increased the in vitro susceptibility of LDL to oxidation.

Aged↗
PubMed2000

Relationship of dietary fat to glucose metabolism.

The relationship between dietary fat and glucose metabolism has been recognized for at least 60 years. In experimental animals, high fat diets result in impaired glucose tolerance. This impairment is associated with decreased basal and insulin-stimulated glucose metabolism. Impaired insulin binding and/or glucose transporters has been related to changes in the fatty acid composition of the membrane induced by dietary fat modification. In humans, high-fat diets, independent of fatty acid profile, have been reported to result in decreased insulin sensitivity. Saturated fat, relative to monounsaturated and polyunsaturated fat, appears to be more deleterious with respect to fat-induced insulin insensitivity. Some of the adverse effects induced by fat feeding can be ameliorated with omega-3 fatty acid. Epidemiological data in humans suggest that subjects with higher intakes of fat are more prone to develop disturbances in glucose metabolism, type 2 diabetes or impaired glucose tolerance, than subjects with lower intakes of fat. Inconsistencies in the data may be attributable to clustering of high intakes of dietary fat (especially animal fat) with obesity and inactivity. Metabolic studies suggest that higher-fat diets containing a higher proportion of unsaturated fat result in better measures of glucose metabolism than high-carbohydrate diet. Clearly, the area of dietary fat and glucose metabolism has yet to be fully elucidated.

Animals↗