The effects of dietary weight loss with or without exercise training on liver enzymes in obese metabolic syndrome subjects.

AIM: Insulin resistance and visceral adiposity are predisposing factors for fatty liver disease. The main objectives of this study were (i) to compare the effects of caloric restriction (CR) alone or together with moderate-intensity aerobic exercise training (CR+EX) on liver enzymes, a surrogate marker of liver injury, in obese metabolic syndrome (MetS) subjects and (ii) to identify anthropometric, metabolic, cardiovascular and dietary predictors of changes in liver enzymes. METHODS: Sedentary men and women (n = 63), aged 55 ± 6 (s.d.) years with body mass index 32.7 ± 4.1 kg/m(2) and confirmed MetS, were randomized to 12-week CR, CR+EX or no treatment (Control). RESULTS: Weight loss averaged 7.6% in the CR and 9.1% in the CR+EX group (time effect, p < 0.001; group effect, p = 0.11); insulin sensitivity improved by 49 and 45%, respectively (both p < 0.001). Fitness (maximal oxygen consumption) increased by 19% in the CR+EX group only (p < 0.001). Alanine aminotransferase (ALT) levels decreased by 20% in the CR and 24% in the CR+EX group (time effect, both p < 0.001; group effect, p = 0.68); corresponding values for γ-glutamyltransferase (GGT) were -28 and -33%, respectively (time effect, both p < 0.001; group effect, p = 0.28). Reduction in abdominal fat mass (measured by DXA from L1 to L4) independently predicted ΔALT (r = 0.42, p = 0.005) and ΔGGT (r = 0.55, p < 0.001), whereas change in dietary saturated fat intake was independently associated with ΔALT (r = 0.35, p = 0.03). CONCLUSIONS: Reductions in central adiposity and saturated fat intake are key drivers of improvement in liver enzymes during lifestyle interventions. Exercise training did not confer significant incremental benefits in this study.

Circulating inflammatory and atherogenic biomarkers are not increased following single meals of dairy foods.

BACKGROUND/OBJECTIVES: Inflammation characterizes obesity and is nutritionally modifiable. The hypothesis of this study is that full-fat dairy foods influence circulating inflammatory and atherogenic biomarkers according to fermentation status. SUBJECTS/METHODS: Thirteen overweight subjects participated in five test meals. Single breakfasts containing control low-fat milk or 45 g fat from butter, cream, yoghurt or cheese were tested over 3 weeks. Plasmas obtained 3 and 6 h were later analyzed for inflammatory markers interleukin (IL)-6, IL-1ß, tumor necrosis factor-α and high-sensitive C-reactive protein, and atherogenesis-related markers monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. A 4-week study in 12 subjects compared the effects on these biomarkers of diets containing ≈50 g dairy fat daily as either butter, cream and ice cream (non-fermented) or cheese plus yoghurt (fermented) dairy foods. RESULTS: In single-meal study, one outlier subject showed marked increments in biomarkers, hence the following results apply to 12. Within group analysis includes significant falls at 3 h in four inflammatory markers after cream, butter and low fat, and three atherogenesis-related biomarkers after cream. Changes were few after cheese and yoghurt. By 6 h, most values returned to baseline. However, between group analysis showed no differences between the five meals. The 4-week study showed no significant differences in fasting biomarker concentrations between non-fermented and fermented dairy diets. CONCLUSIONS: Single high-fat meals containing sequentially four different full-fat dairy foods did not increase eight circulating biomarkers related to inflammation or atherogenesis. Among subjects, significant falls occurred at 3 h in inflammatory biomarkers after cream and butter but were not specific for full-fat dairy foods. We could not confirm the reported increments in inflammation after fat meals.

Dietary supplementation with chickpeas for at least 5 weeks results in small but significant reductions in serum total and low-density lipoprotein cholesterols in adult women and men.

AIM: To compare the effects of a chickpea-supplemented diet and those of a wheat-supplemented diet on human serum lipids and lipoproteins. METHODS: Forty-seven free-living adults participated in a randomized crossover weight maintenance dietary intervention involving two dietary periods, chickpea-supplemented and wheat-supplemented diets, each of at least 5 weeks duration. RESULTS: The serum total cholesterol and low-density lipoprotein cholesterol levels were significantly lower (both p < 0.01) by 3.9 and 4.6%, respectively, after the chickpea-supplemented diet as compared with the wheat-supplemented diet. Protein (0.9% of energy, p = 0.01) and monounsaturated fat (3.3% of total fat, p < 0.001) intakes were slightly but significantly lower and the carbohydrate intake significantly higher (1.7% of energy, p < 0.001) on the chickpea-supplemented diet as compared with the wheat-supplemented diet. Multivariate analyses suggested that the differences in serum lipids were mainly due to small differences in polyunsaturated fatty acid and dietary fibre contents between the two intervention diets. CONCLUSIONS: Inclusion of chickpeas in an intervention diet results in lower serum total and low-density lipoprotein cholesterol levels as compared with a wheat-supplemented diet.

Fish oils, phytosterols and weight loss in the regulation of lipoprotein transport in the metabolic syndrome: lessons from stable isotope tracer studies.

1. Dyslipoproteinaemia is a cardinal feature of the metabolic syndrome that accelerates atherosclerosis. It is characterized by high plasma concentrations of triglyceride-rich and apolipoprotein (apo) B-containing lipoproteins, with depressed concentrations of high-density lipoprotein (HDL). Dysregulation of lipoprotein metabolism in these subjects may be due to a combination of overproduction of very-low density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles and increased catabolism of HDL apoA-I particles. 2. Nutritional interventions may favourably alter lipoprotein transport in the metabolic syndrome. We review our collaborative studies, using stable isotopes and compartmental modelling, of the kinetic effects of fish oils, plant sterols (phytosterols) and weight reduction on the dyslipoproteinaemia in this disorder. 3. Fish oil supplementation diminished hepatic secretion of VLDL-apoB and enhanced conversion of VLDL to low-density lipoprotein (LDL)-apoB, without altering catabolism. 4. Plant sterols (phytosterols) did not have a significant effect on plasma concentrations of lipids and lipoprotein or the kinetics of apoB and apoA-I. 5. Modest weight reduction optimally decreased plasma triglyceride and LDL-cholesterol via reduction in hepatic apoB secretion and reciprocal upregulation of LDL catabolism. 6. The scope and potential of future studies using stable isotope tracers is discussed.

Dairy fat in cheese raises LDL cholesterol less than that in butter in mildly hypercholesterolaemic subjects.

OBJECTIVE: To determine whether dairy fat in cheese raises low-density lipoprotein (LDL) cholesterol as much as in butter, since epidemiology suggests a different impact on cardiovascular disease. DESIGN: A randomised crossover trial testing the daily consumption of 40 g dairy fat as butter or as matured cheddar cheese, each of 4 weeks duration, was preceded by and separated by 2-week periods when dietary fat was less saturated. SETTING: Free-living volunteers. SUBJECTS: A total of 14 men and five women of mean age 56+/-8 y, with mean total cholesterol of 5.6+/-0.8 mmol/l. MAIN OUTCOME MEASURES: Plasma cholesterol, LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triacylglycerol and glucose. RESULTS: Saturated fat intake was significantly lower during the run-in than during the cheese and butter periods. Mean lipid values did not differ significantly between the cheese and run-in periods, but total cholesterol and LDL-C were significantly higher with butter: total cholesterol (mmol/l): butter 6.1+/-0.7; run-in 5.6+/-0.8 (P < 0.05; ANOVA with Bonferroni adjustment); vs cheese 5.8+/-0.6 (P > 0.05); median LDL-C (mmol/l): butter 3.9 (3.5-4.1) vs run-in 3.4 (3.0-4.1) (P < 0.05; Tukey test); vs cheese 3.7 (3.3-3.9) (P > 0.05). Among 13 subjects whose initial LDL-C was >4 mmol/l, the difference between butter (4.4+/-0.3 mmol/l) and cheese (3.9+/-0.3 mmol/l) was significant (P = 0.014). HDL-C was highest with butter and triacylglycerol with cheese (neither was significant). CONCLUSION: A total of 40 g dairy fat eaten daily for 4 weeks as butter, but not as cheese, raised total and LDL cholesterol significantly compared with a diet containing significantly less saturated fat. Dietary advice regarding cheese consumption may require modification.

The isoflavone metabolite dehydroequol produces vasodilatation in human resistance arteries via a nitric oxide-dependent mechanism.

BACKGROUND: Isoflavones (phytoestrogens) offer potential cardioprotective benefits. We recently reported on the vasodilatory activity of the isoflavone metabolite, dehydroequol, in rat isolated aortic ring preparations. In the current study, we examine the effect of this metabolite on the vascular haemodynamic profile in human forearm resistance arteries. METHODS AND RESULTS: Responses to brachial artery infusion of dehydroequol (0.1, 0.3, 1 and 3 micromol/min) in forearm resistance arteries were obtained in six healthy males. These were done, on two separate occasions, in the absence and presence of endogenous nitric oxide synthase inhibition using NG-monomethyl-L-arginine, with sufficient sodium nitroprusside to maintain vascular tone. Dehydroequol produced a dose-dependent increase in forearm blood flow from 2.44 +/- 0.37 (basal) to 5.25 +/- 1.07 mL/100 mL/min (P < 0.05) at dehydroequol 3 micromol/min. Responses to dehydroequol were significantly dampened with inhibition of endogenous nitric oxide synthase (at 3 micromol/min: % increase in forearm blood flow fell from 114.3 +/- 22.81 to 19.45 +/- 9.19; P < 0.01). CONCLUSION: This is the first report of dehydroequol, a metabolite derived from the isoflavone diadzein, demonstrating potent vasodilatory properties in human resistance arteries via a nitric oxide-dependent mechanism.

Post-prandial remnant lipids impair arterial compliance.

OBJECTIVES: We sought to examine the effects of plasma lipids, especially in remnants after a fat meal, on systemic arterial compliance (SAC), a newly recognized cardiovascular risk factor. BACKGROUND: Post-prandial remnants correlate with coronary heart disease events through mechanisms that may include vascular dysfunction, although the effect on SAC has not been studied. METHODS: Systemic arterial compliance was measured non-invasively over 6 h after a fat meal in 16 subjects with varying plasma triglyceride levels. Changes were related to rises in plasma lipids and remnant lipids. Systemic arterial compliance was measured in 20 subjects after a control low-fat meal. RESULTS: The fat meal induced increments in plasma triglyceride and remnant cholesterol and triglyceride (respectively +54%, 50% and 290% at 3 h, analysis of variance <0.001). Systemic arterial compliance fell at 3 h and 6 h by 25% and 27% (analysis of variance <0.001). Baseline SAC correlated significantly with all lipid concentrations at 0, 3 h and 6 h, but only with triglyceride on stepwise regression analysis. The SAC response to the low-fat meal was very small and not significant. CONCLUSIONS: This is the first demonstration of SAC becoming impaired after a fat meal. Remnant lipids and plasma total triglyceride appeared to contribute to the fall in SAC.

The vascular activity of some isoflavone metabolites: implications for a cardioprotective role.

Legume-derived isoflavones such as genistein, diadzein and equol have been associated with a reduction in risk of cardiovascular disease. In the current study, we explore the vascular activity of several isoflavone metabolites namely dihydrodaidzein, cis and trans-tetrahydrodaidzein and dehydroequol for potential cardioprotective properties. Rat isolated aortic rings were used. 17beta-oestradiol, equol, and all four of the metabolites studied significantly antagonized contractile responses to noradrenaline. The direct vasodilatory action of these compounds were examined and in contrast to 17beta-oestradiol, the vasodilatory effect of which was demonstrated to be endothelium independent, the dilatory action of all four compounds could be inhibited by endothelium denudation. Further, the dilatory action of both dihydrodaidzein and cis-tetrahydrodaidzein were inhibited by the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine (NOLA), by the soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and by 40 mM KCl. Dilatory responses to dehydroequol and trans-tetrahydrodaidzein, on the other hand, were inhibited by 40 mM KCL but not by NOLA nor ODQ. Finally, we examined the protective potential of these compounds in inhibiting endothelium damage by oxidized low density lipoprotein (ox-LDL). Trans-tetrahydrodaidzein was at least 10 fold more potent than 17beta-oestradiol in protecting against ox-LDL induced damage. We conclude that the isoflavone metabolites, dihydrodaidzein, cis- and trans-tetrahydrodaidzein and dehydroequol, may potentially represent a novel series of cardioprotective therapeutics.

Effects of simvastatin on hepatic cholesterol metabolism, bile lithogenicity and bile acid hydrophobicity in patients with gallstones.

BACKGROUND AND AIMS: There is limited information available on the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on hepatic and biliary cholesterol metabolism in patients with gallstones. The aims of this study were to determine the effect of simvastatin on the regulatory elements of cholesterol metabolism that determine the concentrations of cholesterol in plasma and bile. METHODS: Thirty-one gallstone patients were enrolled in the study; 17 were treated with 20 mg simvastatin daily for 3 weeks prior to cholecystectomy and 14 served as controls. Samples of blood, liver, gall-bladder bile and bile from the common bile duct (CBD) were collected and analysed. RESULTS: The plasma cholesterol (-30%), triacylglycerol (-23%) and low-density lipoprotein (LDL) cholesterol (-42%) concentrations were significantly lowered by simvastatin treatment, as was the plasma lathosterol: cholesterol (-70%), which reflects whole-body cholesterol synthesis. Despite these changes, the hepatic LDL receptor protein and LDL receptor activity in circulating mononuclear cells were similar in both groups. There were no differences in the plasma phytosterol: cholesterol, which reflects the intestinal cholesterol absorption capacity or in the activity of hepatic acyl-coenzyme A: cholesterol acyltransferase. There were however, lower cholesterol concentrations in CBD (-68%) and gall bladder (-41%) bile, and decreased lithogenic (-47%) and bile acid hydrophobicity (-22%) indices of CBD bile in the simvastatin group. CONCLUSIONS: These data indicate that simvastatin reduced plasma and biliary cholesterol levels primarily by reducing cholesterol synthesis. The reduction in CBD bile lithogenicity and bile acid hydrophobicity by simvastatin suggests that this agent may be useful for people who have early stages of cholesterol gallstone development and in whom a choleretic effect is required.

Diet high in monounsaturated fat does not have a different effect on arterial elasticity than a low-fat, high-carbohydrate diet.

OBJECTIVE: To compare the effects of a modified-fat diet high in monounsaturated fat, and a low-fat/high-carbohydrate diet on arterial elasticity. DESIGN: Randomized crossover design; each diet period was 1 month and a 2-week wash out period occurred in between. SUBJECTS/SETTING: Thirty healthy, free-living, nonsmoking men and women were recruited from the Melbourne, Australia, metropolitan region of Australia. Men were aged 35 to 55 years and postmenopausal women were aged 50 to 60 years and were not taking hormone replacement therapy. Twenty-eight subjects completed the study. INTERVENTION: Two diets of equal energy value: a modified-fat diet and a low-fat/high-carbohydrate diet; the modified-fat diet had 3 times more energy from monounsaturated fat. MAIN OUTCOME MEASURES: Arterial elasticity and serum lipoprotein concentrations. STATISTICAL ANALYSIS: The general linear model was used to investigate overall effect and any carryover or order effects. Paired t test and the general linear model were used to compare the results from the 2 diet periods. RESULTS: High-density lipoprotein cholesterol concentration was significantly higher on the modified-fat diet than on the low-fat/low-carbohydrate diet. Arterial elasticity and concentrations of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were not significantly different on the 2 diets. APPLICATIONS/CONCLUSIONS: There is no evidence to favor a diet high in monounsaturated fat over a low-fat/high-carbohydrate diet because of an effect on arterial elasticity. Other changes in diet may be needed to cause a beneficial effect on arterial elasticity.

Fish oil and cardiovascular disease: lipids and arterial function.

n-3 Fatty acids have been shown to modify several key risk factors for cardiovascular disease. However, it is not clear whether the apparent protection against cardiovascular disease is directly related to antiatherogenic functions of these fatty acids or is mediated through their modification of the risk factors through mechanisms not directly related to lipids. A major question concerns the importance of lipid modification, which is a potent outcome of fish-oil supplementation. On balance, lipid modification is likely to represent a significant antiatherogenic factor. The benefits include increased HDL(2)-cholesterol concentrations, reduced triacylglycerol-rich lipoprotein concentrations, reduced postprandial lipemia, and reduced remnant concentrations. In contrast, LDL-cholesterol concentrations have often been noted to rise and the potential of increased oxidizability of LDLs is potentially adverse with lipid modification, but this potential can be overcome with vitamin E supplementation. The characteristic lipid changes and the underlying mechanisms are reviewed. Additional benefits of fish oils include improved endothelial function and better arterial compliance (elasticity). Future trials will be needed to determine minimum effective dosages of eicosapentaenoic and docosahexaenoic acids over lengthy periods and to show cardiovascular disease reduction through intervention.

Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women.

The possibility that the heightened cardiovascular risk associated with the menopause can be reduced by increasing dietary isoflavone intake was tested in 17 women by measuring arterial compliance, an index of the elasticity of large arteries such as the thoracic aorta. Compliance diminishes with age and menopause. An initial 3- to 4-week run-in period and a 5-week placebo period were followed by two 5-week periods of active treatment with 40 mg and then 80 mg isoflavones derived from red clover containing genistein, daidzein, biochanin, and formononetin in 14 and 13 women, respectively, with 3 others serving as placebo controls throughout. Arterial compliance, measured by ultrasound as a pressure (carotid artery) and volume (outflow into aorta) relationship, was determined after each period; plasma lipids were measured twice during each period. Urinary output of isoflavones was also determined. Arterial compliance rose by 23% relative to that during the placebo period with the 80-mg isoflavone dose and slightly less with the 40-mg dose (mean +/- SEM: placebo, .197 +/- .015; 40 mg, .237 +/- 0.007; 80 mg, .244 +/- .014). In the three women receiving continuous placebo, compliance was .16 +/- .022, similar to that during the run-in period for the remaining subjects (.17 +/- .021) [corrected]. ANOVA showed a significant (P = < 0.001) difference between treatments; by Bonferroni multiple comparisons and by paired t test, differences were significant between placebo and 40- and 80-mg isoflavone doses (by paired t test: P = 0.039 for placebo vs. 40 mg; P = 0.018 for placebo vs. 80 mg). Plasma lipids were not significantly affected. An important cardiovascular risk factor, arterial compliance, which diminishes with menopause, was significantly improved with red clover isoflavones. As diminished compliance leads to systolic hypertension and may increase left ventricular work, the findings indicate a potential new therapeutic approach for improved cardiovascular function after menopause.

Effects of menopause and hormone replacement therapy on plasma lipids, lipoproteins and LDL-receptor activity.

A cross-sectional study of ninety six women was conducted to examine the effect of menopause and hormone replacement therapy (HRT) on plasma lipids, lipoproteins and oxidation of low density lipoproteins. The sample consisted of 26 premenopausal women, 26 postmenopausal women taking no replacement hormones and 43 postmenopausal women on hormone replacement therapy. Postmenopausal women not taking replacement hormones had significantly higher plasma cholesterol, low density lipoprotein (LDL) cholesterol and lipoprotein[a] (Lp[a]) levels compared to premenopausal women or postmenopausal women on HRT [6.00 +/- 0.15, 5.36 +/- 0.17 (P < 0.01), 5.63 +/- 0.13 (P < 0.05) mmol/l, respectively for total cholesterol; 4.13 +/- 0.15, 3.64 +/- 0.15 (P < 0.05), 3.82 +/- 0.12 (P < 0.05) mmol/l, respectively for LDL-cholesterol; 48.19 +/- 9.90, 26.59 +/- 5.53 (P < 0.03), 25.12 +/- 4.62 (P < 0.03) mg/dl, respectively for Lp[a]]. The differences in LDL cholesterol concentrations were inversely related to changes in LDL receptor activity (r = -0.27, P < 0.01). HRT use was found to be associated with a significantly smaller LDL particle size. Plasma triglyceride was significantly higher in women on HRT (1.16 +/- 0.07 mmol/l) than in the premenopausal group (0.96 +/- 0.07) or postmenopausal group not using HRT (0.87 +/- 0.06). There were no differences in LDL oxidation between the groups when LDL was oxidised in the presence of copper. Nor was there any difference in the uptake of copper-oxidised or macrophage-modified LDL into J774 macrophages. These results confirm the effect of menopause and exogenous hormones on plasma lipids and lipoproteins, and suggest that HRT modifies the activity of the LDL receptor. Hormone replacement did not appear to protect LDL from oxidation.

Relationship between plasma insulin and erythrocyte fatty acid composition.

Insulin resistance is an important condition which underlies much of the coronary artery disease in affluent societies. We have related insulin resistance, as assessed by fasting plasma insulin, to erythrocyte membrane composition in 54 healthy men and women on a low fat diet. We found a inverse relationship (r = -0.41, P = 0.002) between fasting plasma insulin and the percentage of arachidonic acid in erythrocyte fatty acids. An inverse relationship of similar strength was found with total n-6 fatty acids and a positive relationship was found with the percentage of saturated fatty acids (r = 0.39, P < 0.01). No relationship was found with n-3 fatty acids. We would suggest that n-6 fatty acids, and in particular arachidonic acid, modify the membrane environment of the insulin receptor (or the glucose transporters) so that lower levels of insulin are required for glucose homeostasis.

Effect of a stearic acid-rich, structured triacylglycerol on plasma lipid concentrations.

BACKGROUND: Structured lipids are being incorporated into foods to reduce their energy value. One such lipid is rich in stearic acid. OBJECTIVE: The objective of this study was to compare the effects on plasma lipids of a stearic acid-rich triacylglycerol and a fat rich in palmitic acid in hypercholesterolemic subjects. DESIGN: Fifteen subjects with an average plasma cholesterol concentration of 6.13 +/- 0.80 mmol/L initially ate a low-fat diet for 2 wk (run-in period), followed in random order and blinded fashion by 2 high-fat diets (for 5 wk each) containing foods derived from margarines rich either in palmitic acid or in the structured, stearic acid-rich triacylglycerol. RESULTS: Plasma cholesterol concentrations with the low-fat, the stearic acid-rich, and the palmitic acid-rich diets were not significantly different (5.35 +/- 0.83, 5.41 +/- 0.78, and 5.52 +/- 0.68 mmol/L, respectively) but were significantly lower (P < 0.001) than those measured during the habitual diet period (ie, 2 wk before the study began). Neither HDL cholesterol nor plasma triacylglycerol differed significantly among the 3 study diets. CONCLUSION: A similar increase in the intake of stearic and palmitic acids (differing by approximately 5% of total energy) to ensure a high fat intake resulted in plasma total and LDL-cholesterol concentrations that did not differ significantly from concentrations measured during a period of low-fat intake.

Arterial compliance, blood pressure, plasma leptin, and plasma lipids in women are improved with weight reduction equally with a meat-based diet and a plant-based diet.

Obesity, strongly associated with the risk for coronary heart disease (CHD), is becoming increasingly prevalent. This study was designed to establish first whether systemic arterial compliance (SAC), an index of arterial function, is improved with weight loss and second, whether cardiovascular risk factors that improve with weight loss are reduced equally with lean meat or with an equivalent amount of plant protein in the diet. Thirty-six women, mostly overweight or obese, aged 40+/-9 years, were allocated nonrandomly to a 16-week parallel-design trial of two equienergetic diets designed to lead to weight loss, with one arm of the study emphasizing red meat and the other soybeans as the major protein source. Body weight, waist and hip circumference, and plasma lipids, glucose, insulin, and leptin levels were measured, and SAC was calculated from ultrasound measurement of aortic flow velocity and aortic root driving pressure. Subjects lost weight (9% of body weight in 16 weeks) and showed decreased plasma total and low-density lipoprotein (LDL) cholesterol (12% and 14%, P < .0001, respectively), triacylglycerol (17%, P < .05), and leptin (24%, P < .01) concentrations. However, lipoprotein(a) [Lp(a)] levels did not change significantly. Mean arterial pressure (MAP) decreased 7% and SAC increased 28% (P < .001 for both). However, only the decrease in arterial pressure correlated significantly with the reduction in the waist to hip ratio (WHR), and the improvement in SAC correlated inversely with the blood pressure reduction (P < .001 for both). Further, weight loss and the metabolic benefits of weight loss occurred equally with the meat-based and plant-based diets. We conclude that moderate weight loss in women leads to a substantial reduction in the cardiovascular risk, including SAC.

LDL particle size and LDL and HDL cholesterol changes with dietary fat and cholesterol in healthy subjects.

We have conducted a dietary trial in 54 men and 51 women with a wide range of fasting cholesterol values to examine the use of low density lipoprotein (LDL) particle size to predict the lipoprotein response to dietary fat and cholesterol. After a 2-week low fat period, subjects were given two liquid supplements in addition to their low fat diet for 3 weeks each, one containing 31-40 g of fat and 650-845 mg of cholesterol, the other fat free. LDL particle type was determined by 3-15% gradient gel electrophoresis. On multiple regression, LDL type was independently related to plasma triglyceride (P < 0.001), waist circumference (P < 0.01), and high density lipoprotein (HDL) (P < 0.001) accounting for 56% of the variance in LDL type in the whole group. Change in LDL cholesterol with dietary fat and cholesterol was unrelated to LDL particle size in either men or women. However, change in HDL cholesterol in men was strongly related to LDL particle type (r = -0.52, P = 0.001) and change in HDL2 cholesterol in women was related to LDL particle type (r = -0.40, P < 0.01). In conclusion, we are unable to confirm the finding that LDL particle type can predict changes in LDL cholesterol following changes in dietary fat intake. However, LDL particle type can independently predict changes in HDL cholesterol in men and accounts for 27% of the variance.

Control of the forearm microcirculation: interactions with measures of obesity and noradrenaline kinetics.

1. Obesity influences the responsiveness of the microcirculation; constriction is augmented probably reflecting heightened sympathetic nervous activity. 2. The responsiveness of the microcirculation in the forearm to constriction and dilation was therefore examined in 14 men and women with varying degrees of abdominal adiposity, to determine the potential effects of sympathetic nervous activity and adiposity on flow. Changes in basal blood flow were measured by venous occlusion plethysmography during intra-arterial infusions of noradrenaline, acetylcholine and sodium nitroprusside and after temporary ischaemia. Total body noradrenaline spillover was also measured, as an index of sympathetic neuronal activity. 3. Parameters of obesity were found to influence the responsiveness of the microcirculation. Changes in vascular resistance with noradrenaline (100 ng/min) were positively correlated with body weight, body mass index and waist circumference (r=0.63, P=0.02), whereas waist circumference was negatively correlated with post-ischaemia vasodilatation (r=-0.76, P=0.002). Acetylcholine-induced vasodilatation was inversely related to body mass index (r=-0.53, P=0.053). 4. Basal blood flow did not correlate with adiposity. Furthermore, vasodilatation with 800 ng/min sodium nitroprusside was inversely correlated with total body noradrenaline spillover (r=-0. 77, P<0.001); and changes in flows with noradrenaline (constriction) and post-ischaemia (dilation) were inversely related (r=-0.56, P=0. 035). 5. These findings, taken together, are consistent with increased local sympathetic neuronal responsiveness and diminished nitric-oxide-mediated dilation in the forearm vasculature with increasing body adiposity.