Saturated fats and cardiovascular health: Current evidence and controversies.

A diet high in saturated fatty acids (SFA) is a suspected contributor to atherosclerotic cardiovascular disease (ASCVD) risk, in large part because of an effect to raise the low-density lipoprotein cholesterol (LDL-C) concentration. Most dietary guidance from health authorities advocates limiting intake of SFA, particularly for people with clinical ASCVD, dyslipidemia, or diabetes mellitus. However, recent reviews have highlighted controversies regarding SFA intake and cardiovascular health. This brief editorial commentary includes a discussion of the evidence regarding SFA intake and cardiovascular health, outlines gaps in the available evidence, and proposes tentative conclusions based on what is known today about SFA consumption and ASCVD risk. Results from observational studies demonstrate that dietary patterns with lower average intakes of SFA are associated with favorable cardiovascular outcomes. Additionally, although the number of randomized controlled trials testing the effects of reducing SFA intake on ASCVD outcomes is limited, the available evidence supports the view that replacing SFA with unsaturated fatty acids, particularly polyunsaturated fatty acids, may reduce ASCVD risk. Beyond raising LDL-C and atherogenic lipoprotein particle concentrations, higher intakes of SFA may influence pathways affecting inflammation, cardiac rhythm, hemostasis, apolipoprotein CIII production, and high-density lipoprotein function. However, the impacts of these effects on ASCVD risk remain uncertain. In the authors' view, the totality of the evidence supports the current recommendation to limit SFA intake to <10% of total daily energy for the general healthy population and further (e.g., to 5-6% of total daily energy) for patients with hypercholesterolemia.

Omega-3 fatty acid therapy for cardiovascular disease: justified or not?

PURPOSE OF REVIEW: To discuss the current evidence regarding the relationship between omega-3 fatty acid intake and atherosclerotic cardiovascular disease (ASCVD) risk. RECENT FINDINGS: Combined results from randomized controlled trials using low-dosage (≤1.8 g/day of ethyl esters) eicosapentaenoic acid (EPA) or EPA + docosahexaenoic acid (DHA) suggest a small benefit for reducing coronary heart disease risk. The Reduction of Cardiovascular Events with EPA-Intervention Trial (REDUCE-IT) that administered 4 g/day icosapent ethyl (IPE) to individuals on statin at high or very high ASCVD risk with elevated triglycerides demonstrated a 25% relative risk reduction in the composite primary endpoint (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization and unstable angina) for IPE vs. placebo, and a lower hazard for all prespecified individual endpoints other than total mortality. Several national organizations have recommended IPE for ASCVD risk reduction in populations aligning with REDUCE-IT; the Food and Drug Administration has approved IPE for ASCVD risk reduction. However, the Outcomes Study to Assess Statin Residual Risk Reduction with Epanova (EPA + DHA carboxylic acids) in High Cardiovascular Risk Patients with Hypertriglyceridemia was recently stopped for futility. SUMMARY: At present, the best available evidence for a role of omega-3 fatty acids in ASCVD risk reduction is for 4 g/day of IPE, as an adjunct to statin therapy, for patients with ASCVD or diabetes mellitus and elevated triglycerides.

Strategies to improve bioavailability of omega-3 fatty acids from ethyl ester concentrates.

PURPOSE OF REVIEW: To describe recent strategies that have been developed to enhance absorption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from dietary supplements. RECENT FINDINGS: The long-chain omega-3 fatty acids EPA and DHA have important physiologic functions, and numerous potential health benefits have been suggested by results from observational studies and randomized, controlled trials. EPA and DHA intakes in the average American diet are substantially below recommended levels. Dietary supplements are available for consumers wishing to increase their intakes, but many of these are in ethyl ester formulations from which EPA and DHA are poorly absorbed when consumed without a meal containing dietary fat. Technologies have been developed to enhance EPA and DHA absorption through in-situ emulsification, which facilitates bioavailability, even in the absence of a fat-containing meal. Findings from randomized controlled trials of absorption enhancers incorporated into omega-3 fatty acid supplements demonstrate that they can markedly improve the bioavailability of EPA and DHA. SUMMARY: The development of absorption enhancement technology to increase bioavailability of long-chain omega-3 fatty acids has important implications for studies on the health effects of dietary supplement and pharmaceutical products containing EPA and/or DHA.

ω-6 Polyunsaturated Fatty Acids and Cardiometabolic Health: Current Evidence, Controversies, and Research Gaps.

The 2015 Dietary Guidelines for Americans recommend limiting the intake of saturated fatty acids (SFAs) to <10% of energy/d and replacing dietary SFAs with unsaturated fatty acids. A Presidential Advisory from the American Heart Association recently released its evaluation of the relation between dietary fats and cardiovascular disease (CVD), and also recommended a shift from SFAs to unsaturated fatty acids, especially polyunsaturated fatty acids (PUFAs), in conjunction with a healthy dietary pattern. However, the suggestion to increase the intake of PUFAs in general, and omega-6 (n-6) PUFAs in particular, continues to be controversial. This review was undertaken to provide an overview of the evidence and controversies regarding the effects of ω-6 PUFAs on cardiometabolic health, with emphasis on risks and risk factors for CVD (coronary heart disease and stroke) and type 2 diabetes mellitus (T2D). Results from observational studies show that higher intake of ω-6 PUFAs, when compared with SFAs or carbohydrate, is associated with lower risks for CVD events (10-30%), CVD and total mortality (10-40%), and T2D (20-50%). Findings from intervention studies on cardiometabolic risk factors suggest that ω-6 PUFAs reduce concentrations of LDL cholesterol and non-HDL cholesterol in a dose-dependent manner compared with dietary carbohydrate, and have a neutral effect on blood pressure. Despite the concern that ω-6 fatty acids increase inflammation, current evidence from studies in humans does not support this view. In conclusion, these findings support current recommendations to emphasize consumption of ω-6 PUFAs as a replacement of SFAs; additional randomized controlled trials with cardiometabolic disease outcomes will help to more clearly define the benefits and risks of this policy.

Corn Oil Lowers Plasma Cholesterol Compared with Coconut Oil in Adults with Above-Desirable Levels of Cholesterol in a Randomized Crossover Trial.

Background: Few trials have examined the effects of coconut oil consumption in comparison with polyunsaturated fatty acid-rich oils such as corn oil. Objective: This trial assessed the effects of consuming foods made with corn oil compared with coconut oil on lipids, glucose homeostasis, and inflammation. Methods: This was a preliminary randomized crossover study of men (n = 12) and women (n = 13) with a mean age of 45.2 y, mean body mass index (in kg/m2) of 27.7, fasting LDL cholesterol ≥115 mg/dL and <190 mg/dL, and triglycerides (TGs) ≤375 mg/dL. Subjects consumed muffins and rolls providing 4 tablespoons (∼54 g) per day of corn oil or coconut oil as part of their habitual diets for 4 wk, with a 3-wk washout between conditions. Fasting plasma lipids and high-sensitivity C-reactive protein (hs-CRP) and glucose metabolism were assessed via an intravenous glucose tolerance test at baseline and 15 and 29 d of treatment. Responses were compared between treatments by ANCOVA. Results: Median baseline concentrations of LDL cholesterol, non-HDL cholesterol, total cholesterol (total-C), HDL cholesterol, total-C:HDL cholesterol, and TGs were 123, 144, 188, 46.0, 4.21, and 92.5 mg/dL, respectively. Changes from baseline for corn oil and coconut oil conditions, respectively, were: LDL cholesterol (primary outcome; -2.7% compared with +4.6%), non-HDL cholesterol (-3.0% compared with +5.8%), total-C (-0.5% compared with +7.1%), HDL cholesterol (+5.4% compared with +6.5%), total-C:HDL cholesterol (-4.3% compared with -3.3%), and TGs (-2.1% compared with +6.0%). Non-HDL cholesterol responses were significantly different between corn and coconut oil conditions (P = 0.034); differences between conditions in total-C and LDL cholesterol approached significance (both P = 0.06). Responses for hs-CRP and carbohydrate homeostasis parameters did not differ significantly between diet conditions. Conclusions: When incorporated into the habitual diet, consumption of foods providing ∼54 g of corn oil/d produced a more favorable plasma lipid profile than did coconut oil in adults with elevated cholesterol. This trial was registered at clinicaltrials.gov as NCT03202654.

Omega-3 Fatty Acid Supplementation and Cardiovascular Disease Risk: Glass Half Full or Time to Nail the Coffin Shut?

There has been a great deal of controversy in recent years about the potential role of dietary supplementation with long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) in the prevention of cardiovascular disease (CVD). Four recent meta-analyses have been published that evaluated randomized, controlled trial (RCT) data from studies that assessed the effects of supplemental n-3 PUFA intake on CVD endpoints. The authors of those reports reached disparate conclusions. This review explores the reasons informed experts have drawn different conclusions from the evidence, and addresses implications for future investigation. Although RCT data accumulated to date have failed to provide unequivocal evidence of CVD risk reduction with n-3 PUFA supplementation, many studies were limited by design issues, including low dosage, no assessment of n-3 status, and absence of a clear biological target or pathophysiologic hypothesis for the intervention. The most promising evidence supports n-3 PUFA supplementation for prevention of cardiac death. Two ongoing trials have enrolled high cardiovascular risk subjects with hypertriglyceridemia and are administering larger dosages of n-3 PUFA than employed in previous RCTs. These are expected to clarify the potential role of long-chain n-3 PUFA supplementation in CVD risk management.

Assessing Cardiovascular Disease Risk and Responses to Preventive Therapies in Clinical Practice.

PURPOSE OF REVIEW: The aims of this review are to provide perspective on evaluation of relative and absolute cardiovascular disease (CVD) risk reductions for assessing the efficacy of preventive therapies and to summarize methods for evaluation of CVD risk in clinical practice. RECENT FINDINGS: Major CVD risk factors can be used to stratify patients into risk categories. Results from recent trials reinforce the view that benefits of preventive therapies will be greatest in those with the highest absolute risk and in those with the most severe disturbance in the risk factor targeted. In evaluating clinical utility, it is necessary to assess the impact of an intervention on both relative and absolute risk. Quantitative risk scoring using major CVD risk factors is effective for identifying those at low, moderate, and high CVD risk. When there is uncertainty about the appropriate treatment strategy, additional testing may be used to refine risk assessment. This may include measurement of inflammatory markers, subclinical indicators of atherosclerosis (e.g., coronary artery calcium and ankle brachial index), urinary albumin/creatinine ratio, and the level of lipoprotein (a). The benefit of a preventive therapy will generally be the greatest in those with the highest absolute risk and in those with the most severe disturbance in the risk factor targeted. Quantitative risk scoring with major CVD risk factors can be supplemented with additional testing for refinement of risk assessment in patients for whom decisions about pharmacotherapy, or the intensity of therapy, for risk factor modification are uncertain.

Effects of n-3 fatty acid treatment on monocyte phenotypes in humans with hypertriglyceridemia.

BACKGROUND: Hypertriglyceridemia increases risk for atherosclerotic cardiovascular disease and may contribute to atherosclerosis by changing circulating monocyte phenotypes. High-dose n-3 polyunsaturated fatty acids reduce blood triglyceride levels. Effects of triglyceride-lowering therapy on monocyte phenotypes are not well known. OBJECTIVE: We examined effects of n-3 polyunsaturated fatty acid treatments (eicosapentaenoic acid [EPA] plus docosapentaenoic acid [MAT9001] vs EPA ethyl esters [EPA-EE]) on monocyte phenotypes in individuals with hypertriglyceridemia. METHODS: Individuals with triglycerides 200 to 400 mg/dL were recruited. Subjects received 2 treatments in randomized order for 14 days each: MAT9001 and EPA-EE, at 4 g/d. At 2 days before the start of, and on the last day of, each treatment, nile red staining for lipids and phenotypes of each monocyte subset were examined by flow cytometry after an overnight fast and postprandially after a high-fat meal. RESULTS: Treatment with MAT9001 or EPA-EE reduced fasting triglyceride levels and decreased proportions of intermediate monocytes. Only MAT9001 decreased postprandial blood triglyceride levels, lowered fasting nile red levels, indicating less lipid in classical and intermediate monocytes, and reduced postprandial CD11c levels on nonclassical monocytes. MAT9001 and EPA-EE each reduced fasting and postprandial CD11c and CD36 levels on classical and intermediate monocytes and postprandial CCR5 levels on intermediate and nonclassical monocytes, with no significant differences between the 2 treatments. CONCLUSIONS: Treatment with MAT9001 in individuals with hypertriglyceridemia reduced fasting nile red staining for lipids in classical and intermediate monocytes. MAT9001 and EPA-EE each improved fasting and postprandial monocyte phenotypes, which could potentially help to protect against atherosclerosis.

Corn oil improves the plasma lipoprotein lipid profile compared with extra-virgin olive oil consumption in men and women with elevated cholesterol: results from a randomized controlled feeding trial.

BACKGROUND: Restricted intakes of saturated and trans-fatty acids is emphasized in heart-healthy diets, and replacement with poly- and monounsaturated fatty acids is encouraged. OBJECTIVE: To compare the effects of polyunsaturated fatty acid-rich corn oil (CO) and monounsaturated fatty acid-rich extra-virgin olive oil (EVOO) on plasma lipids in men and women (N = 54) with fasting low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and <200 mg/dL and triglycerides (TG) ≤350 mg/dL. METHODS: In a double-blind, randomized, crossover design (21-day treatments, 21-day washout between), 4 tablespoons/day CO or EVOO were provided in 3 servings study product/day (muffin, roll, yogurt) as part of a weight-maintenance diet (∼35% fat, <10% saturated fat, <300 mg cholesterol). Subjects ate breakfast at the clinic every weekday throughout the study. Lunches, dinners, and snacks (and breakfasts on weekends) were provided for consumption away from the clinic. RESULTS: Baseline mean (standard error) lipids in mg/dL were: LDL-C 153.3 (3.5), total cholesterol (total-C) 225.7 (3.9), non-high-density lipoprotein (non-HDL)-C 178.3 (3.7), HDL-C 47.4 (1.7), total-C/HDL-C 5.0 (0.2), and TG 124.8 (7.2). CO resulted in significantly larger least-squares mean % changes (all P < .001 vs EVOO) from baseline in LDL-C -10.9 vs -3.5, total-C -8.2 vs -1.8, non-HDL-C -9.3 vs -1.6, and total-C/HDL-C -4.4 vs 0.5. TG rose a smaller amount with CO, 3.5 vs 13.0% with EVOO (P = .007). HDL-C responses were not significantly different between conditions (-3.4 vs -1.7%). CONCLUSION: Consumption of CO in a weight-maintenance, low saturated fat and cholesterol diet resulted in more favorable changes in LDL-C and other atherogenic lipids vs EVOO.

A new, microalgal DHA- and EPA-containing oil lowers triacylglycerols in adults with mild-to-moderate hypertriglyceridemia.

In this double-blind, parallel trial, 93 healthy adults with hypertriglyceridemia (triacylglycerols [TAG] 150-499 mg/dL) were randomized to receive either a nutritional oil derived from marine algae (DHA-O; 2.4 g/day docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA] in a 2.7:1 ratio), fish oil (FO; 2.0 g/day DHA and EPA in a 0.7:1 ratio), or a corn oil/soy oil control as 4-1g softgel capsules/day with meals for 14 weeks; and were instructed to maintain their habitual diet. Percent changes from baseline for DHA-O, FO, and control, respectively, were TAG (-18.9, -22.9, 3.5; p<0.001 DHA-O and FO vs. control), low-density lipoprotein cholesterol (4.6, 6.8, -0.6; p<0.05 DHA-O and FO vs. control), and high-density lipoprotein cholesterol (4.3, 6.9, 0.6; p<0.05 FO vs. control). This study demonstrated that ingestion of microalgal DHA-O providing 2.4 g/day DHA+EPA lowered TAG levels to a degree that was not different from that of a standard fish oil product, and that was significantly more than for a corn oil/soy oil control.

Lipid effects of a dietary supplement softgel capsule containing plant sterols/stanols in primary hypercholesterolemia.

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.

Treatment options for the management of hypertriglyceridemia: strategies based on the best-available evidence.

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.

Absorption of folic acid from a softgel capsule compared to a standard tablet.

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.

Lipid-altering effects of a dietary supplement tablet containing free plant sterols and stanols in men and women with primary hypercholesterolaemia: a randomized, placebo-controlled crossover trial.

This randomized, placebo-controlled, crossover trial assessed the lipid-altering efficacy of a dietary supplement (tablet form) providing 1.8 g/day free (non-esterified) plant sterols and stanols versus placebo for 6 weeks as part of a therapeutic lifestyle changes (TLC) diet in 32 men and women with primary hypercholesterolaemia. Mean ± SE baseline (end of a 5-week TLC diet lead-in) lipid concentrations (mmol/l) were total cholesterol (TC), 5.88 ± 0.08; non-high-density lipoprotein cholesterol (non-HDL-C), 4.71 ± 0.09; low-density lipoprotein cholesterol (LDL-C), 4.02 ± 0.08; HDL-C, 1.17 ± 0.06 and triglycerides (TGs), 1.51 ± 0.12. Differences from control in responses (plant sterol/stanol - control) were significant (p < 0.05) for LDL-C ( - 4.9%), non-HDL-C ( - 3.6%) and TC ( - 2.8%). HDL-C and TG responses were not significantly different between treatment conditions. These results indicate that 1.8 g/day free plant sterols/stanols administered in a tablet produced favourable lipoprotein lipid changes in men and women with hypercholesterolaemia.

Predictors of anterior and posterior wall carotid intima media thickness progression in men and women at moderate risk of coronary heart disease.

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.

Effects of prescription omega-3-acid ethyl esters on fasting lipid profile in subjects with primary hypercholesterolemia.

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.

Baseline lipoprotein lipids and low-density lipoprotein cholesterol response to prescription omega-3 acid ethyl ester added to Simvastatin therapy.

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.

Effects of consumption of pomegranate juice on carotid intima-media thickness in men and women at moderate risk for coronary heart disease.

This randomized, double-blind, parallel trial assessed the influence of pomegranate juice consumption on anterior and posterior carotid intima-media thickness (CIMT) progression rates in subjects at moderate risk for coronary heart disease. Subjects were men (45 to 74 years old) and women (55 to 74 years old) with > or =1 major coronary heart disease risk factor and baseline posterior wall CIMT 0.7 to 2.0 mm, without significant stenosis. Participants consumed 240 ml/day of pomegranate juice (n = 146) or a control beverage (n = 143) for up to 18 months. No significant difference in overall CIMT progression rate was observed between pomegranate juice and control treatments. In exploratory analyses, in subjects in the most adverse tertiles for baseline serum lipid peroxides, triglycerides (TGs), high-density lipoprotein (HDL) cholesterol, TGs/HDL cholesterol, total cholesterol/HDL cholesterol, and apolipoprotein-B100, those in the pomegranate juice group had significantly less anterior wall and/or composite CIMT progression versus control subjects. In conclusion, these results suggest that in subjects at moderate coronary heart disease risk, pomegranate juice consumption had no significant effect on overall CIMT progression rate but may have slowed CIMT progression in subjects with increased oxidative stress and disturbances in the TG-rich lipoprotein/HDL axis.

Effects of adding prescription omega-3 acid ethyl esters to simvastatin (20 mg/day) on lipids and lipoprotein particles in men and women with mixed dyslipidemia.

Prescription omega-3 acid ethyl esters (P-OM3) are commonly used for treatment of very high triglyceride levels, often in combination with a statin, to lower persistent hypertriglyceridemia. This randomized, crossover trial evaluated 6 weeks of combination therapy with simvastatin 20 mg/day plus P-OM3 4 g/day or placebo in 39 men and women (average age 58 years) with a triglyceride concentration 200 to 600 mg/dl and non-high-density lipoprotein (non-HDL) cholesterol greater than their National Cholesterol Education Program treatment goals after a 5-week diet lead-in. Non-HDL cholesterol decreased from baseline (209 mg/dl) by 40% for P-OM3 + simvastatin compared with 34% for placebo + simvastatin (p <0.001). Favorable changes for P-OM3 + simvastatin versus placebo + simvastatin were also observed for very low-density lipoprotein (VLDL) cholesterol (-42% vs -22%), triglyceride (-44% vs -29%), total cholesterol (-31% vs -26%), HDL cholesterol (+16% vs +11%), apolipoprotein B (-32% vs -28%), total cholesterol:HDL cholesterol ratio (-39% vs -33%), triglyceride:HDL cholesterol ratio (-51% vs -37%), and systolic (-5.0 vs 0.3 mm Hg) and diastolic (-3.3 vs -1.8 mm Hg) blood pressures (p <0.05 for all). VLDL particle concentration and size decreased and LDL particle size increased significantly more with P-OM3 + simvastatin than with placebo + simvastatin (all p <0.05). Changes in LDL cholesterol, LDL particle concentration, HDL particle size and concentration, and apolipoprotein A-I did not differ significantly between treatments. In conclusion, P-OM3 + simvastatin appears to be a useful therapeutic option for the management of mixed dyslipidemia.