Hyperlipidemias: Lichtenstein AH

Gidding SS, Dennison BA, Birch LL, Daniels SR, Gillman MW, Gilman MW, Lichtenstein AH, Rattay KT, Steinberger J, Stettler N, Van Horn L, Anonymous00030, Anonymous00031. · No affiliation provided · Circulation. · Pubmed #16186441 links to  free full text

Abstract: Since the American Heart Association last presented nutrition guidelines for children, significant changes have occurred in the prevalence of cardiovascular risk factors and nutrition behaviors in children. Overweight has increased, whereas saturated fat and cholesterol intake have decreased, at least as percentage of total caloric intake. Better understanding of children's cardiovascular risk status and current diet is available from national survey data. New research on the efficacy of diet intervention in children has been published. Also, increasing attention has been paid to the importance of nutrition early in life, including the fetal milieu. This scientific statement summarizes current available information on cardiovascular nutrition in children and makes recommendations for both primordial and primary prevention of cardiovascular disease beginning at a young age.

Lichtenstein AH. · Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111, USA. · Curr Opin Clin Nutr Metab Care. · Pubmed #11844980 No free full text.

Abstract: Plant sterols have recently been recommended by the National Cholesterol Education Panel for use with the more traditional approaches of limiting saturated fat and cholesterol intakes, maintaining a healthy body weight and engaging in regular exercise, as a non-pharmacological approach to reduce low-density lipoprotein cholesterol levels. Recent data confirm the original observation that approximately 1.6 g of plant sterol esters per day results in a maximal low-density lipoprotein cholesterol lowering of approximately 10%. Few side-effects of plant sterols have been reported, with the exception of decreased levels of circulating carotenoids.

Santosa S, Demonty I, Lichtenstein AH, Jones PJ. · School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, QC, Canada. · Int J Obes (Lond). · Pubmed #17264848 No free full text.

Abstract: OBJECTIVE: To determine how moderate weight loss protocol through diet and exercise may affect changes in body composition, to determine the effects of weight loss on cholesterol metabolism and to examine the relationship between cholesterol metabolism and changes in body composition. DESIGN: Thirty-five otherwise healthy, hypercholesterolemic women completed a 24-week weight loss study. A 20% decrease in energy intake through diet and a 10% increase in energy expenditure by exercise were combined with motivational strategies to encourage weight loss. The diet was self-selected and comprised of 50-60% carbohydrates, 20% protein and <30% fat. RESULTS: Participants lost an average of 11.7+/-2.5 kg (P<0.001). Whole body and regional losses in tissue mass occurred after weight loss. After weight loss, cholesterol fractional synthesis rate (FSR) decreased (P=0.003) 3.86+/-9.33%, whereas rates of cholesterol absorption and turnover did not change (3.31+/-19.4%, P=0.32 and -0.01+/-6.20%, P=0.75, respectively). Changes in cholesterol turnover were positively correlated (r=0.44, P=0.01) with changes in FSR. Reductions in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were predictive (beta=-5.04, r=0.38; P=0.03, and beta=-147, r=0.40; P=0.03, respectively) of increases in cholesterol turnover. Losses in skeletal muscle (SM) and upper-body SM predicted (beta=6.82, r=0.36; P=0.04 and beta=14.7, r=0.41; P=0.01, respectively) decreases in cholesterol absorption. CONCLUSIONS: Decreases in cholesterol synthesis after moderate weight loss are not compensated for by changes in cholesterol absorption or turnover. Changes in regional body composition were associated with variations in cholesterol metabolism. Understanding how weight loss affects cholesterol metabolism will help identify more effective treatment routes for overweight individuals undergoing weight loss resulting in earlier and more intensive therapy for the associated dyslipidemia.

Goldin BR, Brauner E, Adlercreutz H, Ausman LM, Lichtenstein AH. · Department of Family Medicine and Community Medicine, Tufts University School of Medicine, Boston, MA 02111, USA. · Nutr Cancer. · Pubmed #15749623 No free full text.

Abstract: Consumption of soy protein has been associated with altered risk of developing endocrine-regulated cancers. This study was designed to assess the independent effect of soy relative to animal protein and soy-derived isoflavones on circulating estrogen and androgen concentrations in postmenopausal women and older men. Forty-two subjects (> 50 yr) with low-density lipoprotein cholesterol levels of > or = 3.36 mmol/l were fed each of 4 diets in randomized order for 6 wk/phase. All food and drink were provided. Diets contained 25 g soy or common sources of animal protein/4.2 MJ containing trace or 50 mg isoflavones/4.2 MJ. At the end of each diet phase, concentrations of estrone sulfate, estrone, estradiol, testosterone, androstendione, dihydrotestosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were measured. In postmenopausal women, concentrations of estrone were higher and its precursor, dehydroepiandrosterone, lower after consuming the soy compared with animal protein diets (P = 0.0396 and 0.0374, respectively). There was no significant effect of isoflavones on any of the hormones measured. In older men, dehydroepiandrosterone sulfate concentrations were lower after consuming the isoflavone (P = 0.0106) and higher after soy, compared with the animal protein diets (P = 0.0118). These data suggest that relatively large amounts of soy protein or soy-derived isoflavones had modest and limited sex-specific effects on circulating hormone levels.

Matthan NR, Welty FK, Barrett PH, Harausz C, Dolnikowski GG, Parks JS, Eckel RH, Schaefer EJ, Lichtenstein AH. · Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston Mass 02111, USA. · Arterioscler Thromb Vasc Biol. · Pubmed #15087307 links to  free full text

Abstract: OBJECTIVE: To determine mechanisms contributing to decreased high-density lipoprotein cholesterol (HDL-C) and increased low-density lipoprotein cholesterol (LDL-C) concentrations associated with hydrogenated fat intake, kinetic studies of apoA-I, apoB-100, and apoB-48 were conducted using stable isotopes. METHODS AND RESULTS: Eight postmenopausal hypercholesterolemic women were provided in random order with 3 diets for 5-week periods. Two-thirds of the fat was soybean oil (unsaturated fat), stick margarine (hydrogenated fat), or butter (saturated fat). Total and LDL-C levels were highest after the saturated diet (P<0.05; saturated versus unsaturated) whereas HDL-C levels were lowest after the hydrogenated diet (P<0.05; hydrogenated versus saturated). Plasma apoA-I levels and pool size (PS) were lower, whereas apoA-I fractional catabolic rate (FCR) was higher after the hydrogenated relative to the saturated diet (P<0.05). LDL apoB-100 levels and PS were significantly higher, whereas LDL apoB-100 FCR was lower with the saturated and hydrogenated relative to the unsaturated diet. There was no significant difference among diets in apoA-I or B-100 production rates or apoB-48 kinetic parameters. HDL-C concentrations were negatively associated with apoA-I FCR (r=-0.56, P=0.03) and LDL-C concentrations were negatively correlated with LDL apoB-100 FCR (r=-0.48, P=0.05). CONCLUSIONS: The mechanism for the adverse lipoprotein profile observed with hydrogenated fat intake is determined in part by increased apoA-I and decreased LDL apoB-100 catabolism.

Wang Y, Jones PJ, Ausman LM, Lichtenstein AH. · School of Dietetics and Human Nutrition, Macdonald Campus of McGill University, Ste-Anne-de-Bellevue, QE, Canada H9X 3V. · Atherosclerosis. · Pubmed #15064101 No free full text.

Abstract: To examine the effects of protein source and isoflavones on triglyceride (TG) fatty acid (TGFA) and cholesterol biosynthesis, subjects (>50 years, LDL cholesterol >130 mg/dl) underwent a four-phase randomized cross-over feeding trial. Diets contained either isolated soy protein or common sources of animal protein (25 g/1000 kcal), without or with isoflavones (49 mg/1000 kcal) and were each fed for 6 weeks. Blood samples from 20 hyperlipidemic subjects (6M, 14F, 62 +/- 9 years, BMI 26 +/- 3 kg/m(2), LDL cholesterol >160 mg/dl after feeding animal protein without isoflavones) were selected to measure TGFA fractional synthetic rate (TGFA-FSR) and free cholesterol fractional synthetic rate (FC-FSR) over 24h as deuterium oxide uptake into TGFA and free cholesterol. Soy protein reduced TG by 12.4% (P < 0.0001), total cholesterol by 4.4% (P < 0.001), and LDL cholesterol by 5.7% (P = 0.003) compared to animal protein. The TGFA-FSR was reduced by 13.3% (P = 0.018) and FC-FSR was increased by 7.6% (P = 0.017) after the soy protein relative to the animal protein. Isoflavones had no significant effect on TG and TGFA-FSR. Isoflavones reduced total cholesterol levels by 3.1% (P = 0.009) but had no significant effect on LDL, HDL cholesterol levels, or FC-FSR. These data demonstrate that dietary protein type modulates circulating TG and cholesterol levels in hypercholesterolemic individuals by distinct mechanisms.

Desroches S, Mauger JF, Ausman LM, Lichtenstein AH, Lamarche B. · Institute on Nutraceuticals and Functional Foods, Laval University, Ste-Foy, Québec, Canada. · J Nutr. · Pubmed #14988449 links to  free full text

Abstract: We assessed the independent effect of soy protein relative to animal protein and of isoflavones on various electrophoretic characteristics of LDL particles. LDL particles were characterized by polyacrylamide gradient gel electrophoresis in 36 moderately hypercholesterolemic men and women (LDL cholesterol > 3.36 mmol/L). All subjects consumed in random order each of the four diets (soy protein depleted of isoflavones, soy protein enriched in isoflavones, animal protein with no added isoflavones, and animal protein with added isoflavones) for 6 wk. Consumption of soy protein was associated with a larger LDL peak particle size relative to animal protein (P < 0.01). Soy protein also decreased the cholesterol levels in LDL < 25.5 nm by 12.3% (P < 0.001) and increased cholesterol levels in LDL > 26.0 nm by 14.3% (P < 0.05) relative to animal protein. Isoflavones did not affect these LDL particle characteristics. Soy protein shifted LDL particle distribution to a less atherogenic pattern and this effect is independent of soy's isoflavone component.

Han SN, Leka LS, Lichtenstein AH, Ausman LM, Meydani SN. · Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. · J Lipid Res. · Pubmed #12951363 links to  free full text

Abstract: Hypercholesterolemia is a risk factor for coronary heart disease (CHD) and also could contribute to impaired immune response. The National Cholesterol Education Program Expert Panel recommends a therapeutic lifestyle change (TLC) diet to reduce the risk for CHD. We investigated the effects of changing from a high-fat Western diet to a low-fat diet in accordance with a TLC diet on immune functions of older adults with hypercholesterolemia to determine whether improving the lipid profile via dietary intervention would have beneficial effects on immune functions. In a double-blind study, 18 subjects consumed both a Western diet (38% fat) and a TLC diet (28% fat) for 32 days in a randomized order. Measures of cellular immune responses, including delayed-type hypersensitivity (DTH) response, in vitro lymphocyte proliferation, and interleukin (IL)-2 production, and production of proinflammatory mediators, including tumor necrosis factor-alpha, IL-6, IL-1beta, and prostaglandin E2, were determined. DTH response and lymphocyte proliferative response increased significantly (29% and 27%, respectively) after consumption of a TLC diet. Our results indicate that consumption of a TLC diet enhances T cell-mediated immune functions in older adults with elevated cholesterol level. This might be a clinically important benefit, considering the decline of T cell-mediated immune functions with aging and evidence of impaired immune function associated with hypercholesterolemia.

Santos MS, Lichtenstein AH, Leka LS, Goldin B, Schaefer EJ, Meydani SN. · Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, USA. · J Am Coll Nutr. · Pubmed #12672714 links to  free full text

Abstract: OBJECTIVE: The immunologic effects of isocaloric reduced- and low-fat diets and a voluntary calorie-restricted low-fat diet resulting in weight loss were compared to the immunologic effects of an average American diet in hyperlipidemic individuals. METHODS: Ten hyperlipidemic subjects were studied during three six-week weight maintenance phases: baseline (BL) [35% fat [14% saturated fat (SFA), 13% monounsaturated fat (MUFA), 8% polyunsaturated fat (PUFA)] and 147 mg cholesterol (C)/1000 kcal], reduced-fat (RF) [26% fat (4% SFA, 11% MUFA, 11% PUFA) and 45 mg C/1000 kcal], and low-fat (LF) [15% fat (5% SFA, 5% MUFA, 3% PUFA) and 35 mg C/1000 kcal] diets followed by 12-week, low-fat calorie reduced phase (LFCR). RESULTS: During the last phase, the subjects' weight significantly decreased (p = 0.005). Cholesterol levels were significantly reduced during all phases, compared to BL diet (p < 0.05). Delayed-type hypersensitivity (DTH) was assessed using Multi-test CMI. Maximum induration diameters were 22.7, 25.4, 30.5, 34.5 mm for BL, RF, LF and LFCR diets, respectively. Subjects on the LFCR diets had significantly higher DTH compared to the BL diet (p = 0.005). No significant effect of diet was observed on lymphocyte proliferation or interleukin (IL)-1, IL-2 and prostaglandin (PG) E(2) production. CONCLUSIONS: These data suggest that low-fat diets (15% energy), under conditions which result in weight loss, do not compromise and may enhance the immune response of middle-aged and elderly hyperlipidemic subjects. The results of this study provide support for the hypothesis that moderate caloric restriction in humans may have a beneficial effect on cell-mediated immunity such as those reported in calorie-restricted rodents.

Lichtenstein AH, Jalbert SM, Adlercreutz H, Goldin BR, Rasmussen H, Schaefer EJ, Ausman LM. · Cardiovascular Nutrition Laboratory and Lipid Metabolism Laboratory, JM HNRC Human Nutrition Research Center on Aging at Tufts University, Boston, Mass 02111, USA. · Arterioscler Thromb Vasc Biol. · Pubmed #12426215 links to  free full text

Abstract: 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.

Han SN, Leka LS, Lichtenstein AH, Ausman LM, Schaefer EJ, Meydani SN. · Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. · J Lipid Res. · Pubmed #11893781 links to  free full text

Abstract: Consumption of diets high in hydrogenated fat/trans fatty acids has been shown to have an adverse affect on lipoprotein profiles with respect to cardiovascular disease risk. Dietary fat and cholesterol play an important role in the regulation of immune and inflammatory responses shown to be involved in atherogenesis. We investigated the effects of diets containing hydrogenated fat on cellular immune response and production of inflammatory cytokines in human subjects with moderately elevated cholesterol levels (LDL cholesterol >130 mg/dl). In a double blind cross-over study, 19 subjects consumed three diets, 30% of calories as fat, of which two thirds were provided as soybean oil, soybean oil-based stick margarine, or butter for 32 days, each in a randomized order. Production of proinflammatory mediators, prostaglandin (PG)E(2), interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha); delayed type hypersensitivity (DTH) response, in vitro lymphocyte proliferation, and production of IL-2 were determined. Production of IL-6 and TNF-alpha was significantly higher after consumption of stick margarine diet compared with soybean oil diet. IL-1beta and TNF-alpha production correlated positively with ratios of total cholesterol to HDL cholesterol (r = 0.499, P < 0.001 and r = 0.291, P = 0.04, respectively). There was no significant difference in DTH response, lymphocyte proliferation, or levels of IL-2 and PGE(2) produced among three groups. Our results indicate that consumption of a diet high in hydrogenated fat does not adversely affect cellular immunity but increases production of inflammatory cytokines that have been associated with the pathophysiology of atherosclerosis.

Lichtenstein AH, Ausman LM, Jalbert SM, Vilella-Bach M, Jauhiainen M, McGladdery S, Erkkilä AT, Ehnholm C, Frohlich J, Schaefer EJ. · Cardiovascular Nutrition Research Program and Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA. · J Lipid Res. · Pubmed #11861668 links to  free full text

Abstract: 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.

Matthan NR, Cianflone K, Lichtenstein AH, Ausman LM, Jauhiainen M, Jones PJ. · Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. · J Lipid Res. · Pubmed #11714853 links to  free full text

Abstract: 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.

Matthan NR, Raeini-Sarjaz M, Lichtenstein AH, Ausman LM, Jones PJ. · School of Dietetics and Human Nutrition, McGill University, Macdonald Campus, Ste-Anne-de-Bellevue, Quebec, Canada. · Lipids. · Pubmed #11026626 No free full text.

Abstract: 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.

Matthan NR, Ausman LM, Lichtenstein AH, Jones PJ. · School of Dietetics and Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Québec, Canada H9X 3V9. · J Lipid Res. · Pubmed #10787444 links to  free full text

Abstract: To determine mechanisms by which hydrogenated fat influences plasma lipid levels, 14 women (65;-71 yrs with LDL-C >/= 130 mg. dl(-)(1)) consumed, for 5-week periods each, a baseline (BL) diet (39% kcal fat, 164 mg chol. 1000 kcal(-)(1)) and reduced fat diets (30% kcal) where two-thirds of the fat was either soybean oil (SO), low trans squeeze (SQM), medium trans tub (TM), or high trans stick (SM) margarines, or butter (BT). Plasma lipid levels were analyzed at the end of each phase. Fractional synthesis rates (FSR) in pools/day (p. d(-)(1)) and absolute synthesis rates (ASR) in grams/day (g. d(-)(1)) of free cholesterol (FC) were measured using the deuterium incorporation methodology. Plasma total (P < 0.01) and low density lipoprotein (P < 0.05) cholesterol levels increased with increasing degree of hydrogenation or saturated fat intake. High density lipoprotein cholesterol levels (P < 0.05) were lowest on the SM diet when compared to the BT diet. Low trans SQM (0.081 +/- 0.019 p. d(-)(1)) and medium trans TM (0.086 +/- 0.029 p. d(-)(1)) diets elicited responses similar to the SO (0.078 +/- 0.024 p. d(-)(1)) diet, whereas high trans SM (0.053 +/- 0.029 p. d(-)(1)) diet mimicked the BT (0.062 +/- 0.017 p. d(-)(1)) and high fat BL (0.053 +/- 0.023 p. d(-)(1)) diet in its suppression (P < 0.05) of FSR-FC. ASR-FC, which is an approximation of the daily production of newly synthesized cholesterol, showed a trend similar to the FSR-FC data. These results indicate that reduced synthesis is not responsible for the higher plasma TC levels seen with consumption of the SM, BT, and BL diets, and suggest that another mechanism, possibly impairment of the catabolic pathway of cholesterol, is involved.

Schwab US, Ausman LM, Vogel S, Li Z, Lammi-Keefe CJ, Goldin BR, Ordovas JM, Schaefer EJ, Lichtenstein AH. · Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston 02111, USA. · Atherosclerosis. · Pubmed #10704618 No free full text.

Abstract: 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.

Mascioli EA, McLennan CE, Schaefer EJ, Lichtenstein AH, Høy CE, Christensen MS, Bistrian BR. · Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts, USA. · Lipids. · Pubmed #10574652 No free full text.

Abstract: The objective of this study was to determine if the positional structure of dietary triacylglycerol affected lipidemic responses. Thirty healthy adults (16 men and 14 postmenopausal women) with low-density lipoprotein cholesterol (LDL-C) concentrations >3.37 mM (130 mg/dL) enrolled in a prospective, single-blind, cross-over outpatient clinical trial that consisted of two 5-wk dietary phases. After baseline screening, subjects were instructed to follow individualized meal plans (weight maintenance diets with 36% of total energy from fat, half of which was from a test oil) and randomized to receive either butter (B) or an interesterified mixture (IM) of butter, medium-chain triacylglycerol (MCT), and safflower oils. Blood drawn during weeks 5 and 10 of feeding was analyzed for total cholesterol (TC), high density lipoprotein cholesterol (HDL-C),LDL-C, and triacylglycerols (TAG). Mean plasma levels of TC (B, 6.98+/-1.06 mM; IM, 7.09+/-1.20 mM), HDL-C (B,1.30+/-0.35 mM; IM, 1.29+/-0.34 mM), and LDL-C (B, 4.91+/-0.95 mM; IM, 4.92+/-1.10 mM) were not significantly different between the two dietary treatments. Mean TAG levels were higher for the interesterified B-MCT mixture (B, 1.75+/-0.72 mM; IM, 1.96+/-0.86 mM, P < 0.05). We conclude that an IM of B, MCT, and safflower oils as compared to native B has no appreciable effect on plasma cholesterol concentrations but is associated with a modest rise in plasma TAG.

Lamon-Fava S, Diffenderfer MR, Barrett PH, Buchsbaum A, Nyaku M, Horvath KV, Asztalos BF, Otokozawa S, Ai M, Matthan NR, Lichtenstein AH, Dolnikowski GG, Schaefer EJ. · Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. · Arterioscler Thromb Vasc Biol. · Pubmed #18566298 No free full text.

Abstract: OBJECTIVE: Extended-release niacin effectively lowers plasma TG levels and raises plasma high-density lipoprotein (HDL) cholesterol levels, but the mechanisms responsible for these effects are unclear. METHODS AND RESULTS: We examined the effects of extended-release niacin (2 g/d) and extended-release niacin (2 g/d) plus lovastatin (40 mg/d), relative to placebo, on the kinetics of apolipoprotein (apo) A-I and apoA-II in HDL, apoB-100 in TG-rich lipoproteins (TRL), intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), and apoB-48 in TRL in 5 men with combined hyperlipidemia. Niacin significantly increased HDL cholesterol and apoA-I concentrations, associated with a significant increase in apoA-I production rate (PR) and no change in fractional catabolic rate (FCR). Plasma TRL apoB-100 levels were significantly lowered by niacin, accompanied by a trend toward an increase in FCR and no change in PR. Niacin treatment significantly increased TRL apoB-48 FCR but had no effect on apoB-48 PR. No effects of niacin on concentrations or kinetic parameters of IDL and LDL apoB-100 and HDL apoA-II were noted. The addition of lovastatin to niacin promoted a lowering in LDL apoB-100 attributable to increased LDL apoB-100 FCR. CONCLUSIONS: Niacin treatment was associated with significant increases in HDL apoA-I concentrations and production, as well as enhanced clearance of TRL apoB-100 and apoB-48.

Santosa S, Demonty I, Lichtenstein AH, Cianflone K, Jones PJ. · School of Dietetics and Human Nutrition, McGill University, Montreal, Canada. · J Am Coll Nutr. · Pubmed #17634170 links to  free full text

Abstract: OBJECTIVE: The objectives of this study were to determine 1) whether the extent of weight loss is predictive of the degree of changes in hormone and lipid levels; 2) the interactions between energy regulating hormones after weight loss through an energy deficit/exercise protocol diet and exercise; 3) whether initial metabolic parameters are indicative of the extent of weight loss. METHODS: Thirty-five hyperlipidemic females (BMI 28-39 kg/m2) 35-60 years old participated in a six month weight loss trial. Weight loss resulted from a diet and exercise program that when combined produced a 30% energy deficit. Fasting plasma taken during 2 wk stabilization periods at the beginning and end of the study was analysed for lipids, hormone and glucose levels. RESULTS: Average weight loss was 11.7 +/- 2.5 kg (p < 0.0001). TC, LDL-C, and triacylglycerols decreased 9.3 +/- 9.5% (p < 0.0001), 7.4 +/- 12.2% (p < 0.001), and 26.8 +/- 19.6% (p < 0.05), respectively, while HDL-C increased (p < 0.05) by 8.2 +/- 16.3%. Leptin levels declined (p < 0.001) 48.9 +/- 16.0% and ghrelin levels rose (p < 0.001) 21.2 +/- 26.7%. While overall levels of adiponectin did not differ, individual values changed such that weight loss predicted increases in adiponectin levels. Though initial weight did not predict weight loss, baseline lipid and insulin levels positively predicted weight loss. CONCLUSION: Initial metabolic parameters may be predictors of weight loss. Beneficial effects of weight loss as achieved through diet and exercise on measured parameters indicate moderate weight loss reduces key risk factors of cardiovascular disease in overweight individuals.

Matthan NR, Jalbert SM, Ausman LM, Kuvin JT, Karas RH, Lichtenstein AH. · Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. · Am J Clin Nutr. · Pubmed #17413093 links to  free full text

Abstract: 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.

Lichtenstein AH, Matthan NR, Jalbert SM, Resteghini NA, Schaefer EJ, Ausman LM. · Cardiovascular Nutrition Laboratory and the Lipid Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA. · Am J Clin Nutr. · Pubmed #16960162 links to  free full text

Abstract: 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.

Vega-López S, Ausman LM, Jalbert SM, Erkkilä AT, Lichtenstein AH. · Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. · Am J Clin Nutr. · Pubmed #16825681 links to  free full text

Abstract: 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.

AbuMweis SS, Vanstone CA, Ebine N, Kassis A, Ausman LM, Jones PJ, Lichtenstein AH. · School of Dietetics and Human Nutrition, McGill University, Montréal, Quebec, Canada. · J Nutr. · Pubmed #16549466 links to  free full text

Abstract: Recommendations for decreasing the risk of developing cardiovascular disease include increasing the intake of plant sterols and fish oil. The cholesterol-lowering action of plant sterols, when provided in a fish-oil fatty acids vehicle, remains to be investigated in humans. A randomized, crossover-feeding, single-blind trial was conducted in 30 subjects with mild-to-moderate hypercholesterolemia to study the effects on plasma lipids of 2 novel forms of plant sterols: those combined with, or esterified to, fish-oil fatty acids. The treatments were margarine (control), free plant sterols, plant sterols esterified to fatty acids from sunflower oil, plant sterols esterified to very long-chained fatty acids from fish oil, and plant sterols combined with the same amount of very long-chained fatty acids from fish oil. Each sterol-containing food (1.0-1.8 g plant sterols/d) was consumed for 29 d as a single dose with breakfast under staff supervision. Compared with the control treatment, none of the plant sterol preparations reduced plasma total cholesterol or LDL cholesterol, triacylglycerol, apolipoprotein A-I, apolipoprotein B, lipoprotein (a), or C-reactive protein concentration. Relative to the control phase, all plant sterols treatment increased the plasma HDL cholesterol concentration (P < 0.05) by approximately 8%. In conclusion, because standard forms of plant sterols did not reduce plasma cholesterol concentrations, the efficacy of the new formulation of plant sterols cannot be confirmed from the present study design, where plant sterols were given as a single morning dose.

Welty FK, Lichtenstein AH, Barrett PH, Dolnikowski GG, Schaefer EJ. · Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center at Tufts University, 711 Washington St, Boston, MA 02111, USA. · Arterioscler Thromb Vasc Biol. · Pubmed #15242863 links to  free full text

Abstract: OBJECTIVE: Our purpose was to determine the relationship between apolipoprotein (apo) A-I and apoB-48 and apoB-100 metabolism in moderately hypercholesterolemic humans. METHODS AND RESULTS: The kinetics of apoA-I within high-density lipoprotein (HDL), apoB-48 and apoB-100 within triglyceride-rich lipoproteins, and apoB-100 within intermediate-density lipoprotein and low density-lipoprotein (LDL) were examined with a primed constant infusion of [5,5,5-(2)H(3)] leucine in the fed state (hourly feeding) in 23 subjects after consumption of a 36% total fat diet. Lipoproteins were isolated by ultracentrifugation; apolipoproteins by SDS-PAGE gels; and isotope enrichment assessed by gas chromatograph/mass spectrometry. Kinetic parameters were calculated by multicompartmental modeling of the data with SAAM II. ApoA-I production rate (PR) was correlated with LDL apoB-100 pool size (PS; r=0.49; P=0.017) and LDL cholesterol (r=0.61; P=0.002), whereas apoA-I fractional catabolic rate (FCR) was inversely correlated with apoB-48 FCR (r=-0.40; P=0.05) but not with very low-density lipoprotein apoB-100 FCR. CONCLUSIONS: Two links exist between apoA-I and apoB kinetics: 1) when LDL apoB-100 PS is high, there is increased apoA-I PR; and 2) delayed chylomicron remnant clearance (represented by apoB-48 FCR) is associated with enhanced apoA-I FCR, a finding indicating that alterations in intestinal lipoproteins may be more important in determining HDL cholesterol levels than changes in liver lipoproteins. Using stable isotopes in humans, 2 links were observed between apoA-I and apoB kinetics: (1) when LDL apoB-100 PS is high, there is increased apoA-I PR; and (2) delayed chylomicron remnant clearance is associated with enhanced apoA-I FCR, indicating that alterations in intestinal lipoproteins may be more important in determining HDL-C levels than changes in liver lipoprotein particles.

Li Z, Otvos JD, Lamon-Fava S, Carrasco WV, Lichtenstein AH, McNamara JR, Ordovas JM, Schaefer EJ. · Lipid Metabolism Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. · J Nutr. · Pubmed #14608054 links to  free full text

Abstract: A diet restricted in saturated fat and cholesterol is recommended for subjects with elevated LDL cholesterol concentrations before and during drug therapy. Gender differences in lipoprotein subspecies response to such diets have not been studied in detail. We examined the effects of a diet low in total fat, saturated fat and cholesterol (Therapeutic Lifestyle Changes, TLC, diet: 26% of energy as fat, 4% as saturated fat, and 45 mg cholesterol/4.2 MJ), compared with an average American diet (AAD: 35% of energy as fat, 14% as saturated fat, and 147 mg cholesterol/4.2 MJ), on plasma lipoprotein subspecies in men and women. Each diet period lasted 6 wk. Body weight was kept constant during each diet period. Men (n = 19) and postmenopausal women (n = 14) >40 y old with moderate hypercholesterolemia participated in this study. Plasma lipoprotein concentrations were assessed by standardized methodology, and lipoprotein sizes were determined by gradient gel electrophoresis and NMR spectroscopy. The TLC diet resulted in greater reductions in total cholesterol and plasma apolipoprotein B concentrations in men than in women (-19% vs. -12%, P < 0.05, and -18% vs. -9%, P < 0.05, respectively). Postprandial triacylglycerol and LpAI:AII concentrations were reduced in men, but not in women (-15% vs. 8%, P < 0.05, and -9% vs. -2%, respectively, P < 0.05). Similar decreases in LpAI concentrations and LDL and HDL particle size were observed in men and women. These data are consistent with the concept that middle aged/elderly men may have a more favorable lipoprotein response to a low fat, low cholesterol diet than postmenopausal women.