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Background: Drug interactions have been identified as a risk factor for muscle-related side effects in statin users., Objectives: The aim was to assess whether use of medications that inhibit cytochrome P450 (CYP450) isozymes, organic anion transporting polypeptide 1B1 (OATP1B1), or P-glycoprotein (P-gp) are associated with muscle-related symptoms among current and former statin users., Methods: Persons (n = 10,138) from the Understanding Statin Use in America and Gaps in Education (USAGE) internet survey were categorized about whether they ever reported new or worsening muscle pain while taking a statin (n = 2935) or ever stopped a statin because of muscle pain (n = 1516). Univariate and multivariate logistic regression models were used to assess associations between use of concomitant therapies that inhibit CYP450 isozymes, OATP1B1, P-gp, or a combination and muscle-related outcomes., Results: In multivariate analyses, concomitant use of a CYP450 inhibitor was associated with increased odds for new or worse muscle pain (odds ratio [OR] = 1.42; P < .001) or ever having stopped a statin because of muscle pain (OR = 1.28; P = .037). Concomitant use of medication known to inhibit both OATP1B1 and P-gp was also associated with increased odds (OR = 1.80; P = .030) of ever having stopped a statin because of muscle pain., Conclusions: Concomitant use of medication(s) that inhibit statin metabolism was associated with increased odds of new or worse muscle pain while taking a statin and having previously stopped a statin because of muscle symptoms. These data emphasize the importance of enhancing the capabilities of clinicians and health systems for identifying and reducing statin drug interactions., (Copyright © 2014 National Lipid Association. All rights reserved.)

Data from randomized controlled trials (RCTs) provide the strongest evidence for establishing relations between exposures, including dietary exposures, and health outcomes. However, not all diet and health outcome relations can be practically or ethically evaluated by using RCTs; therefore, many dietary recommendations are supported by evidence primarily from observational data, particularly those from prospective cohort studies. Although such evidence is of critical importance, limitations are often underappreciated by nutrition scientists and policymakers. This editorial review is intended to 1) highlight some of these limitations of observational evidence for diet-disease relations, including imprecise exposure quantification, collinearity among dietary exposures, displacement/substitution effects, healthy/unhealthy consumer bias, residual confounding, and effect modification; and 2) advocate for greater caution in the communication of dietary recommendations for which RCT evidence of clinical event reduction after dietary intervention is not available.

Background: A novel omega-3 formulation in free fatty acid form (OM3-FFA) has as much as 4-fold greater bioavailability than ethyl ester forms and reduces triglyceride (TG) levels in patients with severe hypertriglyceridemia., Objective: This study was designed to evaluate the efficacy of adding OM3-FFA (2 or 4 g/d) to statin therapy for lowering non-HDL-C and TG levels in subjects with persistent hypertriglyceridemia and at high risk for cardiovascular disease., Methods: In this double-blind, parallel-group study, 647 diet-stable patients with fasting TG levels ≥ 200 mg/dL and <500 mg/dL (treated with a maximally tolerated dose of statin or statin with ezetimibe) and at high risk for cardiovascular disease were randomized to 6 weeks of treatment with capsules of control (olive oil [OO]) 4 g/d, OM3-FFA 2 g/d (plus 2 g/d OO), or OM3-FFA 4 g/d. Assessments included fasting serum levels of lipids and apolipoproteins (apo); plasma concentrations of eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and arachidonic acid; and laboratory safety values and adverse events., Results: In the 627 subjects in the intention to treat sample, non-HDL-C levels were reduced with OM3-FFA 2 g/d and OM3-FFA 4 g/d (-3.9% and -6.9%, respectively) compared with OO (-0.9%) (both, P < 0.05), as were TG levels (-14.6% and -20.6%, respectively, vs -5.9%; both, P < 0.001). LDL-C levels increased with OM3-FFA 2 g/d (4.6%) compared with OO (1.1%) (P = 0.025) but not with OM3-FFA 4 g/d (1.3%). Total cholesterol and VLDL-C concentrations were reduced compared with OO with both OM3-FFA dosages, and the total cholesterol/HDL-C ratio and apo AI and apo B levels were significantly lowered with OM3-FFA 4 g/d only (all at least P < 0.05). Percent changes from baseline in HDL-C did not differ between OO and either OM3-FFA group. Plasma concentrations of docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid were significantly increased and arachidonic acid was significantly reduced in both OM3-FFA treatment groups compared with the OO responses (all, P < 0.001). Withdrawals related to treatment-emergent adverse events ranged from 0.9% with OO to 3.2% with OM3-FFA 4 g/d., Conclusions: OM3-FFA was well tolerated and lowered non-HDL-C and TG levels at both 2- and 4-g/d dosages in patients with persistent hypertriglyceridemia taking a statin, with the 4-g/d dosage providing incremental improvements compared with 2 g/d., (© 2013 Elsevier HS Journals, Inc. All rights reserved.)

Background: Consumption of soybean oil enriched with stearidonic acid was previously shown to increase eicosapentaenoic acid (EPA) in red blood cells (RBC)., Objective: This study was designed to evaluate the effect of stearidonic acid oil used as a food ingredient in baked products and beverages on the RBC fatty acid profile., Design: This was a randomized, double-blind, controlled, parallel-arm study., Participants: Healthy men and women 21 to 65 years of age were included., Intervention: Participants consumed either negative control (1.5 g/day high-oleic sunflower ethyl ester oil softgel capsules+foods containing 7 g/day high-oleic sunflower oil), positive control (1.5 g/day EPA oil ethyl ester softgel capsules+foods containing 7 g/day high-oleic sunflower oil), or active (1.5 g/day high-oleic sunflower ethyl ester oil softgel capsules+foods containing 7 g/day stearidonic acid soybean oil) for 12 weeks., Main Outcome Measures: RBC membrane fatty acid profile (at weeks 0, 2, 4, 6, 8, 10, and 12); fasting serum lipids (weeks -2, 0, 6, 10, and 12); and fasting plasma glucose and insulin (weeks -2, 0, 10, and 12) were assessed., Statistical Analyses Performed: A repeated measures analysis of covariance was used for continuous variables, and pair-wise comparisons between treatments were adjusted using a step-down Bonferroni method. Fisher's exact or χ(2) tests were used for categorical data., Results: RBC %EPA throughout the 12-week study were significantly different between all groups. Means at 12 weeks were 0.50%±0.03%, 2.17%±0.21%, and 0.85%±0.05% for control, EPA, and stearidonic acid, respectively. Other efficacy outcome measures were not significantly different among treatment groups., Conclusions: Consumption of stearidonic acid-enriched soybean oil incorporated into common foods increased RBC %EPA in healthy men and women. Stearidonic acid soybean oil, a sustainable and accessible source of long-chain n-3, can effectively be used to increase EPA in RBC., (Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

In this randomized, double-blind crossover trial, the digestive tolerance of a novel dietary fibre (fibermalt, an indigestible maltose alternan oligosaccharide) was assessed in healthy men and women. Twenty-nine subjects consumed 0 (control), 45 or 60 g of fibre in two doses per day for 2-week treatment periods, each separated by a 2-week washout. Results indicated no differences between treatments in composite gastrointestinal (GI) symptom scores (sum of six GI symptom ratings), individual GI symptoms (nausea, bloating, GI rumbling, gas/flatulence, abdominal pain, diarrhoea), bowel characteristics (frequency, faecal consistency, faecal hardness, straining, discomfort and incomplete evacuation) or average daily faecal output. The symptom scores were consistently low for each treatment period with means averaging below 1 out of a possible range of 0-12 for the composite score. The results of this study suggest that fibermalt is well tolerated at intakes up to 60 g of fibre per day.

Objective: This randomized, placebo-controlled, crossover trial assessed the lipid-altering efficacy of a softgel capsule dietary supplement, providing esterified plant sterols/stanols 1.8 g/d, in 28 participants (≈ 75% women) with primary hypercholesterolemia (fasting low-density lipoprotein cholesterol [LDL-C] levels ≥ 130 and <220 mg/dL), a mean age of 58.4 y, and a mean body mass index of 27.9 kg/m(2)., Methods: After a 5-wk National Cholesterol Education Program (NCEP) Therapeutic Lifestyle Changes (TLC) diet and a single-blinded placebo lead-in, subjects received double-blinded placebo or sterol/stanol softgel capsules for 6 wk and then crossed over to the opposite product for 6 wk while continuing the TLC diet. Fasting lipids were assessed in duplicate at the end of the diet lead-in (baseline) and the end of each treatment., Results: The mean baseline lipid concentrations (milligrams per deciliter) were 223 for total cholesterol (TC), 179 for non-high-density lipoprotein cholesterol (non-HDL-C), 154 for low-density lipoprotein cholesterol, 44 for HDL-C, 125 for triacylglycerols, and 5.2 for TC/HDL-C. Differences from the control responses (plant sterol/stanol minus control) in the per-protocol sample were significant (P < 0.05) for LDL-C (-9.2%), non-HDL-C (-9.0%), TC (-7.4%), TC/HDL-C (-5.4%), and triacylglycerols (-9.1%). The HDL-C responses were not significantly different between treatments., Conclusion: The incorporation of softgel capsules providing esterified plant sterols/stanols 1.8 g/d into the NCEP TLC diet produced favorable changes in atherogenic lipoprotein cholesterol levels in these subjects with hypercholesterolemia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background/objectives: Elevated oxidized low-density lipoprotein (OxLDL) may promote inflammation, and is associated with increased risk of atherosclerotic coronary heart disease and worsening complications of diabetes mellitus. The primary objective of this study was to evaluate the efficacy of chitin-glucan (CG), alone and in combination with a potentially anti-inflammatory olive oil (OO) extract, for reducing OxLDL in subjects with borderline to high LDL cholesterol (LDL-C) levels., Subjects/methods: This 6-week, randomized, double-blind, placebo-controlled study of a novel, insoluble fiber derived from the Aspergillus niger mycelium, CG, evaluated 130 subjects free of diabetes mellitus with fasting LDL-C 3.37-4.92 mmol/l and glucose ≤ 6.94 mmol/l. Participants were randomly assigned to receive CG (4.5 g/day; n=33), CG (1.5 g/day; n=32), CG (1.5 g/day) plus OO extract (135 mg/day; n=30), or matching placebo (n=35)., Results: Administration of 4.5 g/day CG for 6 weeks significantly reduced OxLDL compared with placebo (P=0.035). At the end of study, CG was associated with lower LDL-C levels relative to placebo, although this difference was statistically significant only for the CG 1.5 g/day group (P=0.019). CG did not significantly affect high-density lipoprotein cholesterol, triglycerides, glucose, insulin or F2-isoprostane levels. Adverse events did not substantively differ between treatments and placebo., Conclusions: In this 6-week study, CG (4.5 g/day) reduced OxLDL, an effect that might affect the risk for atherosclerosis.

A group of academic and industry experts in the fields of nutrition, cardiology, epidemiology, food science, bone health, and integrative medicine examined the data on the relationship between calcium supplement use and risk of cardiovascular events, with an emphasis on 4 of the Bradford Hill criteria for causal inference: strength, consistency, dose-response, and biological plausibility. Results from 2 epidemiological studies and a meta-analysis of randomized, controlled clinical trials, including a subgroup analysis from the Women's Health Initiative, have prompted concern about a potential association between calcium supplement use and a small increase in the risk of adverse cardiovascular events. However, a number of issues with the studies, such as inadequate compliance with the intervention, use of nontrial calcium supplements, potential bias in event ascertainment, and lack of information on and adjustment for known cardiovascular risk determinants, suggest that bias and confounding cannot be excluded as explanations for the reported associations. Findings from other cohort studies also suggest no detrimental effect of calcium from diet or supplements, with or without vitamin D, on cardiovascular disease risk. In addition, little evidence exists for plausible biological mechanisms to link calcium supplement use with adverse cardiovascular outcomes. The authors do not believe that the evidence presented to date regarding the hypothesized relationship between calcium supplement use and increased cardiovascular disease risk is sufficient to warrant a change in the Institute of Medicine recommendations, which advocate use of supplements to promote optimal bone health in individuals who do not obtain recommended intakes of calcium through dietary sources.

Objective: We assessed whether a wheat bran extract containing arabino-xylan-oligosaccharide (AXOS) elicited a prebiotic effect and influenced other physiologic parameters when consumed in ready-to-eat cereal at two dose levels., Methods: This double-blind, randomized, controlled, crossover trial evaluated the effects of consuming AXOS at 0 (control), 2.2, or 4.8 g/d as part of ready-to-eat cereal for 3 wk in 55 healthy men and women. Fecal microbial levels, postprandial serum ferulic acid concentrations, and other physiologic parameters were assessed at the beginning and end of each condition., Results: The median bifidobacteria content of stool samples (log₁₀/grams of dry weight [DW]) was found to be higher in the subjects consuming the 4.8-g/d dose (10.03) than in those consuming 2.2 g/d (9.93) and control (9.84, P < 0.001). No significant changes in the populations of other fecal microbes were observed, indicating a selective increase in fecal bifidobacteria. Postprandial ferulic acid was measured at 120 min at the start and end of each 3-wk treatment period in subjects at least 50 y old (n = 37) and increased in a dose-dependent manner (end-of-treatment values 0.007, 0.050, and 0.069 μg/mL for the control, AXOS 2.2 g/d, and AXOS 4.8 g/d conditions, respectively, P for trend < 0.001)., Conclusion: These results indicate that AXOS has prebiotic properties, selectively increasing fecal bifidobacteria, and increases postprandial ferulic acid concentrations in a dose-dependent manner in healthy men and women., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Previous reports have shown that metabolic syndrome and some metabolic syndrome components are associated with serum 25-hydroxyvitamin D [25(OH)D]., Methods: Using the National Health and Nutrition Examination Surveys (NHANES), 2003-2006, we evaluated the associations of vitamin D intake (n=3543) and vitamin D status [25(OH)D; n=3529], with the prevalence of metabolic syndrome and its components in adults 20 years and older. Exclusion criteria included nonfasted subjects, those pregnant and/or lactating, and, for intake analyses, those with unreliable 24-h recall records. Subjects were separately classified into quartiles of vitamin D intake (both including and excluding supplements) and serum 25(OH)D. Logistic regression was used to determine odds ratios (OR) for metabolic syndrome after adjusting for multiple confounders., Results: Those in the highest quartile of serum 25(OH)D had 60% lower odds for metabolic syndrome as compared to those in the lowest quartile [OR=0.40; 95% confidence interval (CI) 0.27, 0.59]. Elevated waist circumference (OR=0.57; 95% CI 0.39, 0.84), low high-density lipoprotein cholesterol (HDL-C) (OR=0.54; 95% CI 0.39, 0.75), and high homeostasis model assessment of insulin resistance (HOMA-IR) (OR=0.40; 95% CI 0.29, 0.55) were the main components associated with serum 25(OH)D. Compared with the lowest vitamin D intake quartile (excluding supplements), those in the highest intake quartile had 28% lower odds for metabolic syndrome (OR=0.72; 95% CI 0.58, 0.90). No components of metabolic syndrome were significantly associated with dietary intake of vitamin D with supplements included or excluded., Conclusions: We conclude that higher 25(OH)D, and, to a lesser degree, greater dietary vitamin D intake, are associated with reduced prevalence of metabolic syndrome.

A severe elevation in triglycerides (TG; ≥500 mg/dL) increases the risk for pancreatitis. TG levels ≥200 mg/dL are associated with a greater risk of atherosclerotic coronary heart disease (CHD). However, no outcomes trials exist to assess the efficacy of TG lowering for preventing pancreatitis in patients with severe hypertriglyceridemia. Similarly, no completed prospective outcomes trial exists to support or refute a reduction in CHD risk resulting from lipid-altering therapy in patients specifically selected for the presence of hypertriglyceridemia. This review examines the available evidence for the use of statins, omega-3 fatty acids, fibrates, and niacin in the management of hypertriglyceridemic patients. Results from CHD outcomes trials support statins as the first-line lipid-altering drug therapy to reduce CHD in hypercholesterolemic patients, and subgroup analyses suggest statins are efficacious in hypertriglyceridemic patients with fasting TG levels <500 mg/dL. Omega-3 fatty acids and fibrates are reasonable first drug options for patients with TG ≥500 mg/dL and often are used to lower TG levels with the objective of reducing pancreatitis risk, although a statin or niacin may also be reasonable options. Combination lipid drug therapy may be needed to achieve both low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals for CHD prevention in patients with elevated TG levels, particularly those with TG ≥500 mg/dL. Additional clinical outcomes data are needed to provide a more evidence-based rationale for clinical lipid management of hypertriglyceridemic patients., (Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Purpose: Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels contribute to cardiovascular disease risk and can be effectively treated with fenofibric acid. A trial is under way to evaluate the effect of once-daily fenofibric acid or placebo on carotid intima-media thickness (CIMT) progression in patients with controlled low-density lipoprotein cholesterol (LDL-C) levels achieved through atorvastatin treatment, but with high TG and low HDL-C levels., Methods: In this multicenter, double-blind study, 682 patients were randomized to once-daily delayed-release capsules of choline fenofibrate 135 mg (fenofibric acid [Trilipix(®); Abbott, North Chicago, IL]) or placebo plus atorvastatin treatment after a 2- to 10-week diet and atorvastatin run-in period. Key inclusion criteria included age ≥45 years; posterior-wall common CIMT ≥0.7 mm on at least one side at baseline; fasting results of TG ≥150 mg/dL, and HDL-C ≤45 mg/dL for men or HDL-C ≤55 mg/dL for women at screening while receiving atorvastatin; controlled LDL-C; and known coronary heart disease (CHD) or a CHD risk equivalent. The primary efficacy variable is the rate of change from baseline through week 104 in the mean posterior-wall intima-media thickness of the common carotid arteries (composite value of left and right sides)., Conclusions: This trial is the first to examine the effect of fenofibric acid on CIMT and the first CIMT trial to select patients with controlled LDL-C and elevated TG and low HDL-C as inclusion criteria. Also, this trial will prospectively evaluate the effect of treatment on LDL particles and address shortcomings of previous CIMT trials.

Background: Limited consumption of red meat, including beef, is one of many often-suggested strategies to reduce the risk of coronary heart disease (CHD). However, the role that beef consumption specifically plays in promoting adverse changes in the cardiovascular risk factor profile is unclear., Objective: A meta-analysis of randomized, controlled, clinical trials (RCTs) was conducted to evaluate the effects of beef, independent of other red and processed meats, compared with poultry and/or fish consumption, on lipoprotein lipids., Methods: RCTs published from 1950 to 2010 were considered for inclusion. Studies were included if they reported fasting lipoprotein lipid changes after beef and poultry/fish consumption by subjects free of chronic disease. A total of 124 RCTs were identified, and 8 studies involving 406 subjects met the prespecified entry criteria and were included in the analysis., Results: Relative to the baseline diet, mean ± standard error changes (in mg/dL) after beef versus poultry/fish consumption, respectively, were -8.1 ± 2.8 vs. -6.2 ± 3.1 for total cholesterol (P = .630), -8.2 ± 4.2 vs. -8.9 ± 4.4 for low-density lipoprotein cholesterol (P = .905), -2.3 ± 1.0 vs. -1.9 ± 0.8 for high-density lipoprotein cholesterol (P = .762), and -8.1 ± 3.6 vs. -12.9 ± 4.0 mg/dL for triacylglycerols (P = .367)., Conclusion: Changes in the fasting lipid profile were not significantly different with beef consumption compared with those with poultry and/or fish consumption. Inclusion of lean beef in the diet increases the variety of available food choices, which may improve long-term adherence with dietary recommendations for lipid management., (Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Consumption of 400 μg folic acid per day from fortified foods and/or supplements, plus food folate from a varied diet is recommended for women of childbearing potential to reduce the risk for neural tube defects during fetal development. This randomized crossover study was designed to evaluate the bioavailability of folic acid from a multivitamin softgel capsule vs a folic acid tablet in 16 premenopausal women (18 to 45 years of age). Participants were randomly assigned to receive a single dose of ∼1,000 μg folic acid in two tablets or ∼1,000 μg folic acid in a multivitamin softgel capsule, and then crossed over to receive the other study product ∼1 week later. Products were administered with a low-folate breakfast. Blood samples were collected predose (0 hour) and 1, 2, 3, 4, 6, and 8 hours post-dose for serum folate analysis. Repeated measures analysis of variance was used to compare responses between treatments. Data from the two sequence groups (n=8 per sequence) were pooled. Mean serum folate total and net incremental areas under the curve (AUC(0-8 hours)) were not significantly different between tablets and softgel capsule (AUC(0-8 hours) 214.9±11.2 hours×ng/mL [487±25.4 hours×nmol/L] and 191.6±13.3 hours×ng/mL [434.2±30.1 hours×nmol/L]; net incremental AUC(0-8 hours) 117.3±8.5 hours×ng/mL [265.8±19.3 hours×nmol/L] and 105.8±12.5 hours×ng/mL [239.7±28.3 hours×nmol/L], respectively), nor was maximum folate concentration (45.1±2.5 ng/mL [102.2±5.7 nmol/L] and 42.5±3.8 ng/mL [96.3±8.6 nmol/L], respectively). Time to peak folate concentration was significantly (P<0.001) delayed for the softgel capsule vs tablet (3.9±0.3 vs 1.7±0.2 hours, respectively). In conclusion, apparent bioavailability of folic acid was similar for the folic acid tablets and a multivitamin softgel capsule., (Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Research dating back to the 1950s reported an association between the consumption of saturated fatty acids (SFAs) and risk of coronary heart disease. Recent epidemiological evidence, however, challenges these findings. It is well accepted that the consumption of SFAs increases low-density lipoprotein cholesterol (LDL-C), whereas carbohydrates, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) do not. High-density lipoprotein (HDL)-C increases with SFA intake. Among individuals who are insulin resistant, a low-fat, high-carbohydrate diet typically has an adverse effect on lipid profiles (in addition to decreasing HDL-C, it also increases triglyceride and LDL particle concentrations). Consequently, a moderate fat diet in which unsaturated fatty acids replace SFAs and carbohydrates are not augmented is advised to lower LDL-C; compared with a low-fat diet, a moderate-fat diet will lower triglycerides and increase HDL-C. Now, there is some new evidence that is questioning the health benefits of even MUFAs and PUFAs. In addition, in a few recent studies investigators have also failed to demonstrate expected cardiovascular benefits of marine-derived omega-3 fatty acids. To clarify the clinical pros and cons of dietary fats, the National Lipid Association held a fatty acid symposium at the 2011 National Lipid Association Scientific Sessions. During these sessions, the science regarding the effects of different fatty acid classes on coronary heart disease risk was reviewed., (Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

The consumption of EPA and DHA has been associated with reduced risk for cardiovascular disease morbidity and mortality. Mean intakes of EPA and DHA in the United States and elsewhere are below levels recommended by health authorities. The main non-marine source of dietary (n-3) fatty acids (α-linolenic acid) is poorly converted to EPA in humans. Stearidonic acid (SDA) is a non-marine fatty acid that appears to be more readily converted to EPA in humans. Results from previous studies suggested that SDA, relative to EPA, increases RBC EPA, with reported efficiencies ranging from ~16 to 30%. A recently published, randomized, single-blind, controlled, parallel group study in healthy men and women characterized the relationships between intakes of SDA and EPA and EPA enrichment of RBC membranes over a 12-wk period. %EPA in RBC membranes was greater after EPA (0.44, 1.3, or 2.7 g/d, respectively) and SDA (1.3, 2.6, or 5.2 g/d, respectively) consumption compared to a safflower control (all P < 0.02). Based on quadratic response surface models, for EPA intakes of 0.25, 0.50, and 0.89 g/d, SDA intakes of 0.61, 1.89, and 5.32 g/d, respectively, would be required to produce equivalent values for RBC %EPA, translating to relative efficiencies of 41.0, 26.5, and 16.7%. Thus, dietary SDA over a range of intakes increases RBC %EPA, with declining relative efficiency as SDA intake increases.

Objective: The purpose of this randomized, controlled, parallel group study was to characterize the relationships between dosages of stearidonic acid (SDA) and eicosapentaenoic acid (EPA), and incorporation of EPA into red blood cell (RBC) membranes over time., Methods: Healthy subjects (n=131) received capsules with placebo (safflower oil), SDA (0.43, 1.3, 2.6, or 5.2 g/d) or EPA (0.44, 1.3, or 2.7 g/d) for 12 weeks. RBC fatty acids were analyzed biweekly., Results: RBC %EPA increased in all EPA and SDA groups (p<0.02 vs. control) except the 0.43 g/d SDA group (p=0.187). For theoretical intakes of EPA of 0.25, 0.5, and 0.89 g/d, the amounts of SDA needed to achieve equivalent RBC EPA enrichment were 0.61, 1.89, and 5.32 g/d (conversion efficiencies of 41%, 26%, and 17%), respectively., Conclusions: SDA increased RBC %EPA in a dosage and time-dependent manner at intakes as low as 1.3 g/d., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: Progression of carotid intima-media thickness (CIMT) is a surrogate indicator for the early stages of atherosclerosis., Methods: The study investigated relationships between baseline lipoprotein cholesterol, triglyceride (TG), and apolipoprotein (Apo) B levels assessed with density gradient ultracentrifugation (DGU) and progression of posterior wall common CIMT in men (45-75 years of age) and women (55-74 years of age) in the control arm of a clinical trial. Participants had baseline posterior wall CIMT 0.7-2.0 mm, without significant stenosis. CIMT was assessed using B-mode ultrasound at baseline, and 12 and ~18 months. A DGU cholesterol panel that assessed the major lipoprotein classes and subclasses, plus triglycerides, lipoprotein (a) cholesterol, low-density lipoprotein (LDL) peak time (inversely related to LDL particle density), and Apo B were performed on fasting baseline samples. Apo B was also measured using an enzyme linked immunosorbent assay., Results: Baseline CIMT was inversely associated (P < 0.001) with CIMT progression. After adjustment for baseline CIMT, significant predictors of posterior wall CIMT progression in linear regression analyses included LDL peak time (inverse, P = 0.045), total high-density lipoprotein cholesterol (HDL-C) (inverse, P = 0.001), HDL(2)-C (inverse, P = 0.005), HDL(3)-C (inverse, P = 0.003), very low-density lipoprotein (VLDL)-C (P = 0.037), and VLDL(1+2)-C (P = 0.016)., Conclusion: These data indicate that DGU-derived indicators of the "atherogenic lipoprotein phenotype," including increased TG-rich lipoprotein cholesterol, lower HDL-C and HDL-C subfractions, and a greater proportion of LDL-C carried by more dense LDL particles, are associated with CIMT progression in men and women at moderate risk for coronary heart disease.

Purpose of Review: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been attributed with several health benefits, including triglyceride lowering and cardiovascular disease risk reduction. This review focuses on new prescription omega-3 fatty acid products in development and recently published data regarding omega-3 fatty acid effects on arrhythmias, heart failure, and platelet inactivation., Recent Findings: A free fatty acid form of n-3 PUFA was found to produce a four-fold higher area under the plasma n-3 PUFA curve than prescription omega-3-acid ethyl esters in patients on a low-fat diet. Eicosapentaenoic acid ethyl esters reduced triglyceride without significantly elevating LDL cholesterol in patients with severe hypertriglyceridemia and in those with mixed dyslipidemia. Recent investigations of n-3 PUFA effects on ventricular and atrial arrhythmias, including studies in patients with implanted defibrillators, failed to demonstrate a significant benefit. However, increased fatty fish or n-3 PUFA consumption was associated with a lower rate of hospitalization in heart failure patients. A further important finding was potentiation of the antiplatelet response when n-3 PUFAs were added to aspirin + clopidogrel., Summary: Although n-3 PUFA therapy continues to show promise in the prevention and management of cardiovascular diseases, further research is necessary to more fully elucidate its role in specific disorders.

Background: Prescription omega-3-acid ethyl esters (POM3) reduce triglycerides (TG) and very low-density lipoprotein cholesterol and increase high-density lipoprotein cholesterol (HDL-C) in patients with hypertriglyceridemia., Objective: To examine the effects of POM3 plus atorvastatin versus placebo plus atorvastatin on lipoprotein particle concentrations and sizes, apolipoprotein (Apo) CIII, and lipoprotein-associated phospholipase A(2) mass in subjects with mixed dyslipidemia., Methods: After a 4-week diet lead in, men and women with non-HDL-C >160 mg/dL and TG 250-599 mg/dL, while taking no lipid-altering drugs, received double-blind 4 g/d POM3 (n = 118) or placebo (n = 119) with open-label atorvastatin 10 mg/d for 8 weeks, followed by escalation to 20 mg/d atorvastatin for 4 weeks, then 40 mg/d atorvastatin for 4 weeks., Results: Total low-density lipoprotein particle (LDL-P) concentration decreased significantly from baseline, and the reductions did not differ between the POM3 and placebo groups (-659.7 vs -624.4 nmol/L, P = .181). With POM3, compared with placebo, small LDL-P concentration decreased (P = .026), large LDL-P concentration increased (P < .001), mean LDL-P size increased (P = .001), a larger fraction of subjects switched from LDL subclass pattern B to A, and Apo CIII and lipoprotein-associated phospholipase A(2) levels were reduced (P < .001). The incremental effects of POM3 were similar across atorvastatin doses for most variables., Conclusion: This analysis supports the view that LDL-P concentration is not increased by POM3 plus atorvastatin, relative to atorvastatin monotherapy, and is associated with potentially favorable shifts in LDL-P subfractions, Apo CIII and lipoprotein-associated phospholipase A(2) in mixed dyslipidemia., (Copyright © 2011 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

The National Cholesterol Education Program Adult Treatment Panel guidelines have established low-density lipoprotein cholesterol (LDL-C) treatment goals, and secondary non-high-density lipoprotein (HDL)-C treatment goals for persons with hypertriglyceridemia. The use of lipid-lowering therapies, particularly statins, to achieve these goals has reduced cardiovascular disease (CVD) morbidity and mortality; however, significant residual risk for events remains. This, combined with the rising prevalence of obesity, which has shifted the risk profile of the population toward patients in whom LDL-C is less predictive of CVD events (metabolic syndrome, low HDL-C, elevated triglycerides), has increased interest in the clinical use of inflammatory and lipid biomarker assessments. Furthermore, the cost effectiveness of pharmacological intervention for both the initiation of therapy and the intensification of therapy has been enhanced by the availability of a variety of generic statins. This report describes the consensus view of an expert panel convened by the National Lipid Association to evaluate the use of selected biomarkers [C-reactive protein, lipoprotein-associated phospholipase A(2), apolipoprotein B, LDL particle concentration, lipoprotein(a), and LDL and HDL subfractions] to improve risk assessment, or to adjust therapy. These panel recommendations are intended to provide practical advice to clinicians who wrestle with the challenges of identifying the patients who are most likely to benefit from therapy, or intensification of therapy, to provide the optimum protection from CV risk., (Copyright © 2011 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Treatment with prescription omega-3-acid ethyl esters (POM3) reduces triglycerides (TG) and TG-rich lipoprotein particles, but has been associated with increased fasting glucose (2-6mg/dL). This double-blind, randomized, controlled crossover trial in 19 men and women with hypertriglyceridemia (fasting TG ≥150 and ≤499mg/dL) examined lipid responses and indices of insulin sensitivity and secretion following a liquid meal tolerance test. Six weeks treatment with POM3 vs. corn oil resulted in significant lower mean fasting (-50.1mg/dL, p<0.001) and postprandial TG (-76.1mg/dL, p<0.001), higher mean fasting glucose (2.8mg/dL, p=0.062), reduced mean disposition index (2.1 vs. 2.4, p=0.037), and no change in the median Matsuda composite insulin sensitivity index (3.3 vs. 3.2, p=0.959). These results suggest that POM3 slightly reduces pancreatic β-cell responsiveness to plasma glucose elevation, which may contribute to the rise in fasting glucose sometimes observed with POM3., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Previous work suggests a positive correlation between intraabdominal adipose tissue and high-sensitivity C-reactive protein (hsCRP). We sought to further explore the relationships between body fat mass/distribution and hsCRP levels in sedentary overweight and obese men and women., Methods: Body composition and abdominal fat areas were measured using dual-energy X-ray absorptiometry and abdominal computed tomography, respectively. Concentrations of hsCRP were measured in serum by nephelometry., Results: Values for hsCRP were 3.2 ± 0.3 mg/L and 4.8 ± 0.6 mg/L in men and women, respectively. Fat mass was nonsignificantly (P=0.09) higher in women (38.8 ± 1.0 kg) than men (36.2 ± 1.1 kg). Abdominal visceral adipose tissue (VAT) area was greater in men than women (104.5 ± 5.7 vs. 59.6 ± 4.3 cm(2), P<0.001) whereas women had greater abdominal subcutaneous adipose tissue (SAT) area compared to men (334.6 ± 11.6 vs. 285.0 ± 13.4 cm(2), P<0.01). Significant associations were present between hsCRP concentrations (natural log transformed) and total fat mass (r=0.502, P<0.01), VAT (r=0.241, P<0.05), and SAT (r=0.418, P<0.01) in men, whereas a significant association for women was found only for total fat mass (r=0.359, P<0.01). Multiple regression analyses showed that men and women had similar concentrations of hsCRP for a given age and fat mass. In both men and women, neither VAT nor SAT area independently predicted hsCRP when included individually or separately in models with age and fat mass., Conclusions: Results suggest that whole body fat mass, but not abdominal fat distribution, is associated with hsCRP concentrations in overweight and obese men and women.

Background: A liquid meal tolerance test (LMTT) has been proposed as a useful alternative to more labor-intensive methods of assessing insulin sensitivity and secretion., Objective: This substudy, conducted at the conclusion of a randomized, double-blind crossover trial, compared insulin sensitivity indices from a LMTT (Matsuda insulin sensitivity index [MISI] and LMTT disposition index [LMTT-DI]) with indices derived from minimal model analysis of results from the insulin-modified intravenous glucose tolerance test (IVGTT) (insulin sensitivity index [S(I)] and disposition index [DI])., Results: Participants included men (n = 16) and women (n = 8) without diabetes but with increased abdominal adiposity (waist circumference ≥102 cm and ≥89 cm, respectively) and mean age of 48.9 years. The correlation between S(I) and the MISI was 0.776 (P < 0.0001). The respective associations between S(I) and MISI with waist circumference (r = -0.445 and -0.554, both P < 0.05) and body mass index were similar (r = -0.500 and -0.539, P < 0.05). The correlation between DI and LMTT-DI was 0.604 (P = 0.002)., Conclusions: These results indicate that indices of insulin sensitivity and secretion derived from the LMTT correlate well with those from the insulin-modified IVGTT with minimal model analysis, suggesting that they may be useful for application in clinical and population studies of glucose homeostasis.

The objective of the present trial was to assess the effects of vitamin D supplementation on serum 25-hydroxyvitamin D [25(OH)D] and high-density lipoprotein cholesterol (HDL-C) in subjects with high waist circumference. Subjects were randomly assigned a daily multivitamin and mineral (MVM) supplement or a MVM supplement plus vitamin D 1,200 IU/day (MVM+D) for 8 weeks. There was a significant difference in mean change for 25(OH)D between the MVM and MVM+D treatment groups ( - 1.2 ± 2.5 nmol/l vs. 11.7 ± 3.0 nmol/l, respectively; P = 0.003). Vitamin D 1,200 IU/day did not increase 25(OH)D to a desirable level ( ≥ 75 nmol/l) in 61% of participants. There were no significant changes in cardiovascular disease risk markers. Thus, vitamin D supplementation with 1,200 IU/day was insufficient to achieve desirable serum 25(OH)D in most participants and did not affect cardiovascular disease risk markers.

Background: The rate of carotid intima media thickness (CIMT) progression has been widely used in clinical trials as a surrogate marker for subclinical atherosclerosis., Objective: The aim of this study was to investigate relationships between coronary heart disease (CHD) risk markers and progression of CIMT in patients at moderate CHD risk., Methods: Participants included men (45-75 years) and women (55-74 years) in the control arm of a clinical trial. All had at least one major CHD risk factor and baseline posterior wall CIMT 0.7-2.0 mm, without significant stenosis. Posterior (n = 134) and anterior wall (in a subset, n = 72) CIMT were assessed with B-mode ultrasound at baseline and 12 and ∼18 months. Fasting lipoprotein lipid, apolipoprotein (Apo), inflammatory, and oxidative stress markers were evaluated., Results: Baseline CIMT was inversely associated (P < .001) with CIMT progression. After adjustment for baseline CIMT, significant predictors of anterior wall CIMT progression in linear regression analyses included glucose (P = .044), high-density lipoprotein cholesterol (HDL-C, inverse, P = .006), triglycerides (TG, P = .006), and ratios of total cholesterol (TC)/HDL-C (P = .013), TG/HDL-C (P = .005), and Apo B/HDL-C (P = .021). Posterior wall CIMT progressed on average, whereas anterior wall CIMT regressed (0.0078 vs -0.0164 mm/year, P = .014). Significant baseline CIMT-adjusted predictors of posterior wall CIMT progression included TC (P = .028), low-density lipoprotein-C (P = .035), non-HDL-C (P = .004), TG (P = .016), Apo B (P = .005), and ratios of TC/HDL-C (P < .001), TG/HDL-C (P = .015), Apo B/Apo AI (P = .012) and Apo B/HDL-C (P = .004)., Conclusion: The strongest predictors for CIMT progression in anterior and posterior walls were lower baseline CIMT, increased TG, and elevated ratios, including TC/HDL-C, TG/HDL-C and Apo B/HDL-C., (Copyright © 2011 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

This double-blind, randomized crossover study investigated the effects of 6 weeks of treatment with prescription omega-3-acid ethyl esters (POM3, 4 g/day) versus placebo (soy oil) on low-density lipoprotein cholesterol (LDL-C) and other aspects of the fasting lipid profile in 31 men and women with primary, isolated hypercholesterolemia (LDL-C 130-220 mg/dL and triglycerides less than 150 mg/dL while free of lipid-altering therapies). Mean ± standard error of the mean baseline concentrations of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein cholesterol, and triglycerides were 229 ± 3, 146 ± 3, 60 ± 2, 23 ± 2, and 113 ± 8 mg/dL, respectively. POM3 produced a modest increase from baseline in LDL-C (3.4%) versus the placebo response (-0.7%, P = 0.010). Significant changes (P < 0.05) for POM3 (placebo-corrected) were observed for very-low-density lipoprotein cholesterol (-18.8%), triglycerides (-18.7%), and HDL-C (3.3%). Nuclear magnetic resonance-determined very-low-density lipoprotein particle concentration and size and HDL particle concentration decreased significantly more with POM3 versus placebo, whereas LDL and HDL particle sizes increased significantly more with POM3 versus placebo. Total cholesterol, non-HDL-C, apolipoproteins A1 and B, and LDL particle concentration responses did not differ between treatments. These results did not confirm the hypothesis that POM3 treatment would lower LDL-C in primary, isolated hypercholesterolemia. Effects on other variables were consistent with prior results in mixed dyslipidemia.

Objective: To compare tolerability of colesevelam hydrochloride powder versus a cholesterol-lowering equivalent dose of generic cholestyramine powder, each mixed in water, by means of the validated Bile Acid Sequestrant Acceptability (BASA) Scale., Methods: We conducted a randomized, single-blind, single-visit, single-site study, comparing doses of 2 different bile acid sequestrant powders for oral suspension that produce similar cholesterol lowering: colesevelam hydrochloride (3.75 g) and generic cholestyramine (12 g), each mixed in a transparent cup with tap water., Results: The study sample consisted of 42 participants-12 men and 30 women. The study subjects were non-Hispanic white (64%) or black (36%), with a mean age of 50 years and a mean body mass index of 32.2 kg/m2. The components of the BASA Scale included taste, texture, appearance, and mixability. Colesevelam hydrochloride and cholestyramine did not differ significantly when assessed by both the unweighted and the weighted global BASA Scale. Although study participants indicated that the colorless or whitish colesevelam hydrochloride powder tasted better (P<.0001), they thought that the orange-colored cholestyramine had a more appealing appearance (P<.0001). Regarding the potential for taking the drug "for the rest of your life," 71.4% of study participants rated taste as "very important," and 11.9% rated appearance as "very important.", Conclusion: Although study participants thought that the orange-colored generic cholestyramine powder had a better appearance, they also reported that colesevelam hydrochloride for oral suspension tasted better. A minority of study participants thought appearance was "very important"; a substantial majority thought taste was "very important" for potential long-term compliance.

We have previously shown that krill oil (KO), more efficiently than fish oil, was able to downregulate the endocannabinoid system in different tissues of obese zucker rats.We therefore aimed at investigating whether an intake of 2 g/d of either KO or menhaden oil (MO), which provides 309 mg/d of EPA/DHA 2:1 and 390 mg/d of EPA/DHA 1:1 respectively, or olive oil (OO) for four weeks, is able to modify plasma endocannabinoids in overweight and obese subjects.The results confirmed data in the literature describing increased levels of endocannabinoids in overweight and obese with respect to normo-weight subjects. KO, but not MO or OO, was able to significantly decrease 2-arachidonoylglycerol (2-AG), although only in obese subjects. In addition, the decrease of 2-AG was correlated to the plasma n-6/n-3 phospholipid long chain polyunsaturated fatty acid (LCPUFA) ratio. These data show for the first time in humans that relatively low doses of LCPUFA n-3 as KO can significantly decrease plasma 2-AG levels in obese subjects in relation to decrease of plasma phospholipid n-6/n-3 LCPUFA ratio. This effect is not linked to changes of metabolic syndrome parameters but is most likely due to a decrease of 2-AG biosynthesis caused by the replacement of 2-AG ultimate precursor, arachidonic acid, with n-3 PUFAs, as previously described in obese Zucker rats.

Green tea catechins (GTC) are polyphenolic compounds present in the unfermented dried leaves of the plant, Camellia sinensis. Results from a number of randomized, controlled intervention trials have shown that consumption of GTC (270 mg to 1200 mg/day) may reduce body weight and fat. There are several proposed mechanisms whereby GTC may influence body weight and composition. The predominating hypothesis is that GTC influences sympathetic nervous system (SNS) activity, increasing energy expenditure and promoting the oxidation of fat. Caffeine, naturally present in green tea, also influences SNS activity, and may act synergistically with GTC to increase energy expenditure and fat oxidation. Other potential mechanisms include modifications in appetite, up-regulation of enzymes involved in hepatic fat oxidation, and decreased nutrient absorption. This article reviews the evidence for each of these purported mechanisms, with particular reference to studies in humans., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Soy protein (SP) and low-fat dairy product consumption have been suggested to have hypocholesterolemic effects, although the responsible mechanisms are poorly understood., Objective: This randomized, controlled, parallel arm trial evaluated the effects of an insoluble fraction of SP and total milk proteins (TMPs) with high calcium content on the fasting lipid profile. It also assessed the potential contributions of increased excretion of bile acids and neutral sterols to their lipid-altering effects., Methods: Subjects with hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] 100-199 mg/dL) followed the Therapeutic Lifestyle Changes diet for 4 weeks, followed by a 2-week lead-in with 3.75 g/d colesevelam HCl. Individuals with LDL-C lowering of ≥5.0% with colesevelam HCl were randomly assigned to one of two groups after a 3-week washout: 1) 25 g/d of an insoluble fraction of partially hydrolyzed SP or 2) 25 g/d TMP., Results: Both SP and TMP reduced atherogenic lipoproteins, as indicated by changes in total cholesterol (-7.4% and -3.6%), LDL-C (-10.9% and -5.9%), nonhigh-density lipoprotein cholesterol (-10.8% and -3.9%), and apolipoprotein B (-9.7% and -2.4%), respectively (P < .05 for between group differences except LDL-C, P = .085). No significant increases were observed in either group for fecal bile acids or neutral sterols., Conclusion: These results confirm that SP consumption exerts a hypocholesterolemic effect and indicate that TMP elicits a less pronounced response. However, these findings do not support the hypothesis that increased bile acid excretion is an important contributor to the hypocholesterolemic effects of either protein source., (Copyright © 2010 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: The objective of this investigation was to evaluate the test-retest repeatability of insulin sensitivity and secretion indices derived from liquid meal tolerance tests (MTTs) in subjects with normal fasting glucose (NFG) (n = 20), impaired fasting glucose (IFG) (n = 20), or type 2 diabetes mellitus (n = 38)., Methods: The Matsuda Index of insulin sensitivity and a Disposition Index (the product of the Matsuda Index and the ratio of the total areas under the curves for glucose and insulin from 0 to 120 min) were assessed in two standard liquid MTTs, separated by approximately 1 week., Results: Mean ±SD Matsuda Index values were 14.2±7.6, 8.8 ± 4.7, and 6.3±4.0, and Disposition Index values were 1,009.6 ±355.5, 671.4± 249.0, and 201.8 ±101.3 for NFG, IFG, and diabetes, respectively (all P < 0.05 except Matsuda Index for IFG vs. diabetes, P = 0.241). Differences between tests in subjects with NFG, IFG, and diabetes, respectively, were -0.2 ± 3.6 (coefficient of variation for the method error, 17.9%), 0.2±3.2 (26.1%), and 0.1±3.0 (34.1%) for the Matsuda Index and 16.5±225.8 (16.1%), 13.3±221.6 (23.1%), and 15.2±79.4 (28.1%) for the Disposition Index., Conclusions: The Matsuda and Disposition indices derived from liquid MTTs appropriately ranked categories of fasting glucose tolerance and have repeatability profiles suggesting potential usefulness in population studies and moderately sized clinical trials requiring repeated measurements.

Aims: The primary objective of this study was to validate a novel Bile Acid Sequestrant Acceptability (BASA) Scale intended to assess the acceptability and/or tolerability of bile acid sequestrant (BAS) beverage preparations. A secondary objective was to assess the utility of weightings based on subjective clinical importance for the BASA scale individual components and its composite score., Methods: This was a randomised, single-blind, single site, controlled study of oral administration of 4 g of orange-flavoured generic cholestyramine powder, 12 g of orange-flavoured generic cholestyramine powder and an orange-flavoured sweetened control drink powder, each mixed with water., Results: The study sample included 42 subjects; 26 men and 16 women. Participants were non-Hispanic white (76.2%) or black/African American (23.8%), with a mean age of 51.4 years and body mass index of 30.1 kg/m(2). The components of the BASA scale were taste, texture, appearance and mixability; the possible total BASA scores ranged being 4-20; the higher the BASA scale score, the better the acceptability/tolerability. Composite BASA scale scores were significantly lower for the 4 g (mean BASA score = 10.3) and 12 g (mean BASA score = 9.4) cholestyramine compared with the control drink powder (mean BASA score = 16.7) (p < 0.001). BASA scale scores did not significantly differ between the 4 and 12 g of cholestyramine. (p = 0.215). Weighting of the components did not materially alter the results. Findings for the individual components of the BASA scale were similar to the composite values., Conclusion: The BASA scale effectively distinguished between an orange-flavoured BAS powder and a commercial orange-flavour control powder.

Background: Well-controlled studies have demonstrated that inpatient hyperglycemia is an indicator of poor clinical outcomes, but the use of diabetes-specific enteral formulas in hospitalized patients remains a topic of great debate., Methods: In two different protocols, postprandial glycemia and insulinemia were measured in 22 subjects with diabetes fed a diabetes-specific or standard formula (protocol 1). Continuous glucose monitoring was used to assess glucose levels in 12 enterally fed patients with diabetes receiving the standard formula followed by the diabetes-specific formula continuously for 5 days each (protocol 2). End points included postprandial glycemia and insulinemia, glycemic variability (mean amplitude of glycemic excursions [MAGE]), mean glucose, and insulin use., Results: In the postprandial response protocol, the diabetes-specific formula resulted in lower positive areas under the postprandial curve (P < 0.001) and peak glucose (P < 0.001) and insulin (P = 0.017) levels. In the protocol using continuous glucose monitoring, glycemic variability (as measured by MAGE) was lower with continuous administration of the diabetes-specific than the standard formula (64.6 +/- 6.8 mg/dL vs. 110.6 +/-15.3 mg/dL, P = 0.003). Also, administration of the diabetes-specific formula resulted in lower mean glucose concentrations during feeding (171.1 +/- 16.1 vs. 202.1 +/- 17.4 mg/dL, P = 0.024) and insulin requirements (7.8 +/- 2.3 vs. 10.9 +/- 3.3 units/day, P = 0.039) than the standard formula., Conclusions: Relative to the standard formula, the diabetes-specific formula reduced postprandial glycemia, mean glucose, glycemic variability, and short-acting insulin requirements. These results suggest potential clinical usefulness of a diabetes-specific enteral formula for minimizing glycemic excursions in hospitalized patients.

The present post hoc analysis of data from the COMBination of prescription Omega-3 with Simvastatin (COMBOS) study investigated the predictors of the low-density lipoprotein (LDL) cholesterol response to prescription omega-3 acid ethyl ester (P-OM3) therapy in men and women with high (200 to 499 mg/dl) triglycerides during diet plus simvastatin therapy. Subjects (n = 256 randomized) received double-blind P-OM3 4 g/day or placebo for 8 weeks combined with diet and open-label simvastatin 40 mg/day. The percentage of changes from baseline (with diet plus simvastatin) in lipids was evaluated by tertiles of baseline LDL cholesterol and triglyceride concentrations. The baseline LDL cholesterol tertile was a significant predictor of the LDL cholesterol response (p = 0.022 for the treatment by baseline tertile interaction). The median LDL cholesterol response in the P-OM3 group was +9.5% (first tertile, <80.4 mg/dl), -0.9% (second tertile), and -6.4% (third tertile, > or =99.0 mg/dl). Non-high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride responses did not vary significantly by baseline LDL cholesterol tertile. The reductions in very-low-density lipoprotein cholesterol concentrations were greater than the increases in LDL cholesterol, where present, resulting in a net decrease in the concentration of cholesterol carried by atherogenic particles (non-high-density lipoprotein cholesterol) in all baseline LDL cholesterol tertiles. In conclusion, these results suggest that the increase in LDL cholesterol that occurred with the addition of P-OM3 to simvastatin therapy in subjects with mixed dyslipidemia was confined predominantly to those with low LDL cholesterol levels while receiving simvastatin monotherapy., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: Assess the long-term efficacy and safety of prescription omega-3-acid ethyl esters (P-OM3) coadministered with simvastatin in an extension of the Combination of Prescription Omega-3 Plus Simvastatin (COMBOS) trial., Methods: COMBOS included hypertriglyceridemic patients (triglyceride [TG] >or=200 mg/dL and <500 mg/dL or >or=2.26 mmol/L and <5.64 mmol/L) with low density lipoprotein cholesterol (LDL-C) level no greater than 10% above the National Cholesterol Education Program, Adult Treatment Panel III treatment goal. After an 8-week lead-in phase with simvastatin 40 mg/day (which continued throughout the trial), subjects were randomized to 8 weeks of P-OM3 4 g/day or placebo. Completers were eligible to participate in a 24-month extension study. Those who received placebo + simvastatin in COMBOS switched to open-label P-OM3 + simvastatin ('Switchers'); those who received P-OM3 + simvastatin during COMBOS continued the same regimen (open-label) in the extension phase ('Non-switchers'). The primary endpoint was the difference between Non-switchers and Switchers in median percent change in non-high-density lipoprotein-cholesterol (non-HDL-C) from COMBOS end of treatment to Month 4 of the extension phase., Results: At Month 4 from COMBOS end of treatment, non-HDL-C was reduced by a median of 9.4% in Switchers and increased by 0.9% in Non-switchers (p < 0.001). For the total population (combined Non-switcher + Switcher population), the median percent change from COMBOS baseline to Months 4, 12, and 24 was -8.3%, -7.3%, and -8.9%, respectively (all p < 0.001). This extension study revealed no unexpected safety findings. A limitation of this study was a gap between completion of COMBOS and enrollment in the extension phase for some patients; however, a post-hoc non-HDL-C sensitivity analysis performed at the 4-month primary endpoint revealed no influence of gap on study results., Conclusions: In this 24-month extension study, P-OM3 was generally well tolerated, and produced sustained reductions in non-HDL-C levels in simvastatin-treated patients with TG levels between 200 and 500 mg/dL (2.26 mmol/L and 5.64 mmol/L)., Clinical Trial Registry Number: NCT00903409.

Objective: Weight loss and consumption of viscous fibers both lower low-density lipoprotein (LDL) cholesterol levels. We evaluated whether or not a whole-grain, ready-to-eat (RTE) oat cereal containing viscous fiber, as part of a dietary program for weight loss, lowers LDL cholesterol levels and improves other cardiovascular disease risk markers more than a dietary program alone., Design: Randomized, parallel-arm, controlled trial., Subjects/setting: Free-living, overweight and obese adults (N=204, body mass index 25 to 45) with baseline LDL cholesterol levels 130 to 200 mg/dL (3.4 to 5.2 mmol/L) were randomized; 144 were included in the main analysis of participants who completed the trial without significant protocol violations., Intervention: Two portions per day of whole-grain RTE oat cereal (3 g/day oat b-glucan) or energy-matched low-fiber foods (control), as part of a reduced energy ( approximately 500 kcal/day deficit) dietary program that encouraged limiting consumption of foods high in energy and fat, portion control, and regular physical activity., Main Outcome Measures: Fasting lipoprotein levels, waist circumference, triceps skinfold thickness, and body weight were measured at baseline and weeks 4, 8, 10, and 12., Results: LDL cholesterol level was reduced significantly more with whole-grain RTE oat cereal vs control (-8.7+/-1.0 vs -4.3+/-1.1%, P=0.005). Total cholesterol (-5.4+/-0.8 vs -2.9+/-0.9%, P=0.038) and non-high-density lipoprotein-cholesterol (-6.3+/-1.0 vs -3.3+/-1.1%, P=0.046) were also lowered significantly more with whole-grain RTE oat cereal, whereas high-density lipoprotein and triglyceride responses did not differ between groups. Weight loss was not different between groups (-2.2+/-0.3 vs -1.7+/-0.3 kg, P=0.325), but waist circumference decreased more (-3.3+/-0.4 vs -1.9+/-0.4 cm, P=0.012) with whole-grain RTE oat cereal. Larger reductions in LDL, total, and non-high-density lipoprotein cholesterol levels and waist circumference were evident as early as week 4 in the whole-grain RTE oat cereal group., Conclusions: Consumption of a whole-grain RTE oat cereal as part of a dietary program for weight loss had favorable effects on fasting lipid levels and waist circumference., (Copyright 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.)

Background: Prescription omega-3-acid ethyl esters (P-OM3) often are used for hypertriglyceridemic patients receiving statin therapy who have residual increases in atherogenic lipoprotein lipid levels. To date, limited information has been published regarding the effects of omega-3 fatty acid consumption on lipoprotein particle concentrations., Objective: We evaluated the effects of adding P-OM3 4g/d to an ongoing regimen of simvastatin 40mg/d on lipoprotein particles (P) in subjects with hypertriglyceridemia., Methods: Data were analyzed from the multicenter, randomized, double-blind, placebo-controlled Combination of Prescription Omega-3s with Simvastatin (COMBOS) study. After an 8-week simvastatin lead-in, 254 subjects received P-OM3 (n=122) or placebo (n=132) for an additional 8 weeks. Nuclear magnetic resonance spectroscopy was used to assess lipoprotein concentrations and sizes. Remnant-like particle cholesterol, apolipoprotein (Apo) CIII, Apo AI, and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels also were measured., Results: Compared with placebo, P-OM3 reduced mean very-low-density lipoprotein (VLDL-P) size and increased low-density lipoprotein particle (LDL-P) size (P < .006 for both) without altering high-density lipoprotein particle (HDL-P) size. P-OM3 did not significantly change total VLDL-P or LDL-P concentrations relative to placebo, but large VLDL-P and intermediate-density lipoprotein particle (IDL-P) concentrations were lowered (P < .01 for both), and the large LDL-P concentration was increased (P < .0001). HDL-P concentration was reduced (P < .0001) as the result of a decrease in medium HDL-P. Remnant-like particle cholesterol, Apo CIII, and Lp-PLA(2) concentrations were reduced compared with placebo (all P < .003)., Conclusions: P-OM3 induces changes in sizes, concentrations, and compositions of lipoproteins that may have relevance for the atherothrombotic process.

Antarctic krill, also known as Euphausia superba, is a marine crustacean rich in both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We tested the hypothesis that krill oil would increase plasma concentrations of EPA and DHA without adversely affecting indicators of safety, tolerability, or selected metabolic parameters. In this randomized, double-blind parallel arm trial, overweight and obese men and women (N = 76) were randomly assigned to receive double-blind capsules containing 2 g/d of krill oil, menhaden oil, or control (olive) oil for 4 weeks. Results showed that plasma EPA and DHA concentrations increased significantly more (P < .001) in the krill oil (178.4 +/- 38.7 and 90.2 +/- 40.3 micromol/L, respectively) and menhaden oil (131.8 +/- 28.0 and 149.9 +/- 30.4 micromol/L, respectively) groups than in the control group (2.9 +/- 13.8 and -1.1 +/- 32.4 micromol/L, respectively). Systolic blood pressure declined significantly more (P < .05) in the menhaden oil (-2.2 +/- 2.0 mm Hg) group than in the control group (3.3 +/- 1.5 mm Hg), and the response in the krill oil group (-0.8 +/- 1.4 mm Hg) did not differ from the other 2 treatments. Blood urea nitrogen declined in the krill oil group as compared with the menhaden oil group (P < .006). No significant differences for other safety variables were noted, including adverse events. In conclusion, 4 weeks of krill oil supplementation increased plasma EPA and DHA and was well tolerated, with no indication of adverse effects on safety parameters.

Background: Prescription omega-3-acid ethyl ester (P-OM3; Lovaza) therapy is indicated for treating very high triglyceride levels (>or= 500 mg/dL) at a dose of 4 g/day. The caloric content associated with each 1-g capsule of P-OM3 is approximately 11 Cal (Cal = kilocalories) - approximately 9 Cal from the oil in the capsule that contains omega-3 fat and approximately 2 Cal attributed to the components of the capsule shell. Thus, the 4-g/day dose contributes approximately 44 Cal/day, with approximately 36 Cal/day derived from the oil., Methods: This analysis evaluated 167 dyslipidemic (triglycerides: >or= 500 mg/dL and < 1300 mg/dL), overweight/obese (body mass index [BMI] >or= 25 kg/m(2) and

Background/rationale: Treatment of severe hypertriglyceridemia is indicated to reduce the risk of pancreatitis in patients with triglyceride (TG) levels > or =500 mg/dL. Hypertriglyceridemia is also a risk factor for atherosclerotic coronary heart disease. Prescription omega-3 fatty acids (P-OM3) and fenofibrate (FENO) are among the most effective lipid-altering agents that reduce TG levels. Given that some patients may not achieve optimal TG levels with a single agent, we hypothesized that concomitant use of P-OM3 or addition of P-OM3 to FENO would result in a TG reduction greater than that with FENO alone., Methods: This randomized, 8-week, double-blind, placebo-controlled study was designed to compare the safety and efficacy of P-OM3 4 g QD plus concomitant FENO 130 mg with FENO 130 mg QD plus placebo in subjects with very high TG levels (> or =500 mg/dL). Subjects who completed the double-blind study were given the option to continue into an open-label, 8-week extension study, wherein they all received P-OM3 4 g plus FENO 130 mg QD. On completion of the first extension study, subjects were eligible to continue into an open-label 24-month extension of the treatment with P-OM3 4 g plus FENO 130 mg QD., Results: Concomitant P-OM3 + FENO (n = 81) and FENO monotherapy (n = 82) reduced median TG values from 649.5 to 267.5 mg/dL (60.8%) and from 669.3 to 310 mg/dL (53.8%), respectively (P = 0.059). When subjects who had received 8 weeks of stable FENO monotherapy were given P-OM3 during the 8-week, open-label extension study (n = 58), TG levels were reduced 17.5% (P = 0.003) over the course of the extension. The second extension phase was terminated early (n = 93)-not because of a safety signal but because of the lack of a substantial incremental change in the primary endpoint lipid values above that reached in either the original study or the first extension in subjects receiving the combination of fenofibrate and P-OM3., Conclusions: Both FENO monotherapy and P-OM3 + FENO significantly reduced TGs in subjects with very high TGs, with a trend to greater reduction in the P-OM3 + FENO group. The addition of P-OM3 to stable FENO therapy in the same subjects in an open-label extension study resulted in a statistically significant reduction in TG levels. Subjects who received P-OM3 + FENO for 16 weeks and subjects in which P-OM3 was added to FENO monotherapy during the open-label phase of the study did not differ in their final lipid responses. In the second open-label extension, within the combined group taking P-OM3 and FENO, analysis of change from the second extension baseline to end of treatment revealed no clinically important change.

Background/objectives: Consumption of hydroxypropylmethylcellulose (HPMC), a viscous dietary fiber, lowers total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). However, HPMC had not previously been studied in individuals receiving lipid drug therapy., Subjects/methods: This randomized, double-blind crossover trial examined the lipid effects of HPMC in subjects with hypercholesterolemia on statin therapy. Men (n=5) and women (n=8) with LDL-C> or =2.59 mmol/l after at least 4 weeks of stable-dose statin therapy, and a mean age of 58.6 years, were enrolled. Subjects received twice daily doses of either 2.5 g HPMC or control, delivered in a lemonade beverage for 4 weeks, then crossed over to receive the opposite treatment for an additional 4 weeks., Results: Mean baseline concentrations of TC, non-high-density lipoprotein cholesterol (non-HDL-C), LDL-C, HDL-C, triglyceride (TG), TC/HDL-C ratio and apolipoprotein (Apo) B were 4.95, 3.63, 3.03, 1.33, 1.30 and 3.89 mmol/l and 1.00 g/l, respectively. HPMC consumption resulted in significantly larger reductions (P<0.01 vs control for all) in TC (-10.9 vs -3.5%), non-HDL-C (-12.8 vs -2.9%), LDL-C (-15.7 vs -5.1%), TC/HDL-C ratio (-5.3 vs +1.3%) and Apo B (-8.7 vs -3.9%). There were no differences between treatments for changes in HDL-C (-5.2 vs -4.3%) or TG (+3.9 vs +8.9%)., Conclusions: These results support the view that HPMC is an effective adjunct to statin therapy for further lowering atherogenic lipids and lipoproteins in men and women with primary hypercholesterolemia.

Background: Low vitamin D status has been associated with markers of cardiovascular disease risk., Objective: This cross-sectional study assessed the relationships between serum 25-hydroxyvitamin D [25(OH)D] and selected markers for cardiovascular disease risk, including metabolic syndrome and its components, in adult men and women., Methods: Fasting blood samples, anthropometric measurements, and blood pressure were assessed in 257 men and women. Dietary intake was assessed with food frequency and dietary supplement questionnaires., Results: Total vitamin D intake and that from dietary supplements were significantly associated with increasing serum 25(OH)D tertile (both P < .001). Mean±SEM serum high-density lipoprotein cholesterol (HDL-C) increased in a graded fashion (P < .001) from the lowest (48.4±1.8mg/dL) to the highest (62.3±2.1mg/dL) 25(OH)D tertile. The relationship between 25(OH)D and HDL-C remained significant (P < .001) after adjustment for established determinants of the HDL-C, with each 10-ng/mL increase in 25(OH)D associated with a 4.2-mg/dL increase in HDL-C concentration. Serum triglycerides (P=.008), waist circumference (P < .001), and body mass index (P < .001) showed graded, inverse relationships with 25(OH)D tertile, and the prevalence of metabolic syndrome decreased significantly from the lowest to the highest 25(OH)D tertile (31%, 14%, and 10%, respectively, P for trend=.001)., Conclusions: Lower serum 25(OH)D is associated with the metabolic syndrome and adverse values for some metabolic syndrome risk factors, particularly the HDL-C concentration. Research is warranted to assess whether increasing vitamin D intake will improve the metabolic cardiovascular risk factor profile.

Objective: We assessed the ability of novel lipid structures including medium-chain triacylglycerols (MCTs) and 1,3-diacylglycerol (DG) oil to lower postprandial triacylglycerol (TG) elevation and increase hepatic fat oxidation when substituted for dietary TG, which may be useful in the prevention and treatment of obesity and other related metabolic conditions, such as dyslipidemias., Methods: This double-blind, randomized, crossover trial evaluated the effects of an oral fat load containing DG or MCTs compared with equivalent intakes of long-chain triacylglycerols (LCTs) on the postprandial metabolic responses of insulin-resistant men and women (n = 36). Each subject consumed a single oral fat load on each test day. The fat loads were delivered in milkshakes that contained 30 g of one of the three test oils., Results: The postprandial TG incremental area under the curve after MCT was 73% lower, and that for DG was 22% lower, compared with the response after LCT oil. The incremental area under the curve values for chylomicron TG were reduced versus LCT by 89% and 28%, respectively, in the MCT and DG conditions. Compared with the LCT treatment, beta-hydroxybutyrate concentration was increased after MCT oil, but not after DG., Conclusion: These results indicate that dietary DG decreased postprandial triglyceridemia compared with LCT, but to a lesser extent than MCT.

Background: To provide an initial evaluation of insulin sensitivity and secretion indices derived from a standard liquid meal tolerance test protocol in subjects with normal (NFG), impaired fasting glucose (IFG) or type 2 diabetes mellitus., Methods: Areas under the curve (AUC) for glucose, insulin and C-peptide from pre-meal to 120 min after consumption of a liquid meal were calculated, as were homeostasis model assessments of insulin resistance (HOMA2-IR) and the Matsuda index of insulin sensitivity., Results: Subjects with NFG (n = 19), IFG (n = 19), and diabetes (n = 35) had mean +/- SEM HOMA2-IR values of 1.0 +/- 0.1, 1.6 +/- 0.2 and 2.5 +/- 0.3 and Matsuda insulin sensitivity index values of 15.6 +/- 2.0, 8.8 +/- 1.2 and 6.0 +/- 0.6, respectively. The log-transformed values for these variables were highly correlated overall and within each fasting glucose category (r = -0.91 to -0.94, all p < 0.001). Values for the product of the insulin/glucose AUC ratio and the Matsuda index, an indicator of the ability of the pancreas to match insulin secretion to the degree of insulin resistance, were 995.6 +/- 80.7 (NFG), 684.0 +/- 57.3 (IFG) and 188.3 +/- 16.1 (diabetes) and discriminated significantly between fasting glucose categories (p < 0.001 for each comparison)., Conclusion: These results provide initial evidence to support the usefulness of a standard liquid meal tolerance test for evaluation of insulin secretion and sensitivity in clinical and population studies.

Background: Hydroxypropylmethylcellulose (HPMC), a viscous, soluble dietary fiber, has been shown to be efficacious for lowering total and low-density lipoprotein cholesterol (LDL-C) concentrations. The relative effects of various dosages and viscosities of HPMC have not been fully evaluated., Objective: To examine the lipid-altering effects of several formulations of HPMC., Methods: In this randomized, double-blind pilot study, 165 men and women with primary hypercholesterolemia consumed a control product (snack bar or drink mix) or an HPMC-containing test bar or drink for 4 weeks. HPMC-containing products delivered 3, 5, or 10g of HPMC of low, moderate, moderately high, or high viscosity (9 HPMC groups, each with ∼15 subjects)., Results: Data from drink and bar groups were combined because there was no evidence of a vehicle effect. The resulting analysis included data from the control and 6 HPMC dose and viscosity combinations. All HPMC groups showed LDL-C reductions ranging from 6.1 to 13.3% (P < .05 vs. baseline for 6 of the 7 groups), compared with a nonsignificant reduction (1.9%) in the control group. Changes in total and non-high-density lipoprotein cholesterol paralleled those for LDL-C. Concentrations of high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and high-sensitivity C-reactive protein were not significantly altered., Conclusion: This pilot study provides preliminary evidence to support the efficacy of various formulations of HPMC for reducing cholesterol carried by atherogenic particles in men and women with primary hypercholesterolemia. Additional research will be required to more clearly define the roles of viscosity and dosage on the lipid-altering effects of HPMC.