Nutrition interventions for adults with dyslipidemia: A Clinical Perspective from the National Lipid Association.

Lifestyle habits can have a profound impact on atherosclerotic cardiovascular disease (ASCVD) risk. The National Lipid Association previously published recommendations for lifestyle therapies to manage dyslipidemia. This Clinical Perspective provides an update with a focus on nutrition interventions for the three most common dyslipidemias in adults: 1) low-density lipoprotein cholesterol (LDL-C) elevation; 2) triglyceride (TG) elevation, including severe hypertriglyceridemia with chylomicronemia; and 3) combined dyslipidemia, with elevations in both LDL-C and TG levels. Lowering LDL-C and non-high-density lipoprotein cholesterol are the primary objectives for reducing ASCVD risk. With severe TG elevation (≥500 mg/dL), the primary objective is to prevent pancreatitis and ASCVD risk reduction is secondary. Nutrition interventions that lower LDL-C levels include reducing cholesterol-raising fatty acids and dietary cholesterol, as well as increasing intakes of unsaturated fatty acids, plant proteins, viscous fibers, and reducing adiposity for patients with overweight or obesity. Selected dietary supplements may be employed as dietary adjuncts. Nutrition interventions for all patients with elevated TG levels include restricting intakes of alcohol, added sugars, and refined starches. Additional lifestyle factors that reduce TG levels are participating in daily physical activity and reducing adiposity in patients with overweight or obesity. For patients with severe hypertriglyceridemia, an individualized approach is essential. Nutrition interventions for addressing concurrent elevations in LDL-C and TG include a combination of the strategies described for lowering LDL-C and TG. A multidisciplinary approach is recommended to facilitate success in making and sustaining dietary changes and the assistance of a registered dietitian nutritionist is highly recommended.

A Head-to-Head Comparison of a Free Fatty Acid Formulation of Omega-3 Pentaenoic Acids Versus Icosapent Ethyl in Adults With Hypertriglyceridemia: The ENHANCE-IT Study.

Background MAT9001 is an omega-3 free fatty acid (FFA) formulation containing mainly eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). Compared with icosapent ethyl (EPA-ethyl esters [EE]), EPA+DPA-FFA previously showed enhanced triglyceride lowering and higher plasma EPA when both were administered once daily with a very-low fat diet. This trial compared pharmacodynamic responses and plasma omega-3 levels following twice daily dosing, with meals, of EPA+DPA-FFA and EPA-EE in hypertriglyceridemic subjects consuming a Therapeutic Lifestyle Changes diet. Methods and Results This open-label, randomized, 2-way crossover trial, with 28-day treatment periods separated by ≥28-day washout, was conducted at 8 US centers and included 100 subjects with fasting triglycerides 1.70 to 5.64 mmol/L (150-499 mg/dL) (median 2.31 mmol/L [204 mg/dL]; 57% women, average age 60.3 years). The primary end point was least squares geometric mean percent change from baseline plasma triglycerides. In the 94 subjects with analyzable data for both treatment periods, EPA+DPA-FFA and EPA-EE reduced least squares geometric mean triglycerides from baseline: 20.9% and 18.3%, respectively (P=not significant). EPA+DPA-FFA reduced least squares geometric mean high-sensitivity C-reactive protein by 5.8%; EPA-EE increased high-sensitivity C-reactive protein by 8.5% (P=0.034). EPA+DPA-FFA increased least squares geometric mean plasma EPA, DPA, and total omega-3 (EPA+docosahexaenoic acid+DPA) concentrations by 848%, 177%, and 205%, respectively, compared with corresponding changes with EPA-EE of 692%, 140%, and 165% (all P<0.001). EPA+DPA-FFA increased docosahexaenoic acid by 1.7%; EPA-EE decreased docosahexaenoic acid by 3.3% (P=0.011). Lipoprotein cholesterol and apolipoprotein responses did not differ between treatments. Conclusions EPA+DPA-FFA raised plasma EPA, DPA, and total omega-3 significantly more than did EPA-EE. EPA+DPA-FFA also reduced triglycerides and high-sensitivity C-reactive protein without increasing low-density lipoprotein cholesterol. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04177680.

Effectiveness of a Novel ω-3 Krill Oil Agent in Patients With Severe Hypertriglyceridemia: A Randomized Clinical Trial.

Importance: Intense interest exists in novel ω-3 formulations with high bioavailability to reduce blood triglyceride (TG) levels. Objective: To determine the phase 3 efficacy and safety of a naturally derived krill oil with eicosapentaenoic acid and docosahexaenoic acid as both phospholipid esters (PLs) and free fatty acids (FFAs) (ω-3-PL/FFA [CaPre]), measured by fasting TG levels and other lipid parameters in severe hypertriglyceridemia. Design, Setting, and Participants: This study pooled the results of 2 identical randomized, double-blind, placebo-controlled trials. TRILOGY 1 (Study of CaPre in Lowering Very High Triglycerides) enrolled participants at 71 US centers from January 23, 2018, to November 20, 2019; TRILOGY 2 enrolled participants at 93 US, Canadian, and Mexican centers from April 6, 2018, to January 9, 2020. Patients with fasting TG levels from 500 to 1500 mg/dL, with or without stable treatment with statins, fibrates, or other agents to lower cholesterol levels, were eligible to participate. Interventions: Randomization (2.5:1.0) to ω-3-PL/FFA, 4 g/d, vs placebo (cornstarch) for 26 weeks. Main Outcomes and Measures: The primary outcome was the mean percentage of change in TG levels at 12 weeks; persistence at 26 weeks was the key secondary outcome. Other prespecified secondary outcomes were effects on levels of non-high-density lipoprotein cholesterol (non-HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), HDL-C, and low-density lipoprotein cholesterol (LDL-C); safety and tolerability; and TG level changes in prespecified subgroups. Results: A total of 520 patients were randomized, with a mean (SD) age of 54.9 (11.2) years (339 men [65.2%]), mean (SD) body mass index of 31.5 (5.1), and baseline mean (SD) TG level of 701 (222) mg/dL. Two hundred fifty-six patients (49.2%) were of Hispanic or Latino ethnicity; 275 (52.9%) had diabetes; and 248 (47.7%) were receiving statins. In the intention-to-treat analysis, TG levels were reduced by 26.0% (95% CI, 20.5%-31.5%) in the ω-3-PL/FFA group and 15.1% (95% CI, 6.6%-23.5%) in the placebo group at 12 weeks (mean treatment difference, -10.9% [95% CI, -20.4% to -1.5%]; P = .02), with reductions persisting at 26 weeks (mean treatment difference, -12.7% [95% CI, -23.1% to -2.4%]; P = .02). Compared with placebo, ω-3-PL/FFA had no significant effect at 12 weeks on mean treatment differences for non-HDL-C (-3.2% [95% CI, -8.0% to 1.6%]; P = .18), VLDL-C (-3.8% [95% CI, -12.2% to 4.7%]; P = .38), HDL-C (0.7% [95% CI, -3.7% to 5.1%]; P = .77), or LDL-C (4.5% [95% CI, -5.9% to 14.8%]; P = .40) levels; corresponding differences at 26 weeks were -5.8% (95% CI, -11.3% to -0.3%; P = .04) for non-HDL-C levels, -9.1% (95% CI, -21.5% to 3.2%; P = .15) for VLDL-C levels, 1.9% (95% CI, -4.8% to 8.6%; P = .57) for HDL-C levels, and 6.3% (95% CI, -12.4% to 25.0%; P = .51) for LDL-C levels. Effects on the primary end point did not vary significantly by age, sex, race and ethnicity, country, qualifying TG level, diabetes, or fibrate use but tended to be larger among patients taking statins or cholesterol absorption inhibitors at baseline (mean treatment difference, -19.5% [95% CI, -34.5% to -4.6%]; P = .08 for interaction) and with lower (less than median) baseline blood eicosapentaenoic acid plus docosahexaenoic acid levels (-19.5% [95% CI, -33.8% to -5.3%]; P = .08 for interaction). ω-3-PL/FFA was well tolerated, with a safety profile similar to that of placebo. Conclusions and Relevance: This study found that ω-3 -PL/FFA, a novel krill oil-derived ω-3 formulation, reduced TG levels and was safe and well tolerated in patients with severe hypertriglyceridemia. Trial Registration: ClinicalTrials.gov Identifiers: NCT03398005 and NCT03361501.

The Effect of Multi-Vitamin/Multi-Mineral Supplementation on Nutritional Status in Older Adults Receiving Drug Therapies: A Double-Blind, Placebo-Controlled Trial.

Polypharmacy regimens may increase the susceptibility of older adults to micronutrient inadequacy and deficiency via impairment of nutritional status. We hypothesized that a multi-vitamin-mineral supplement (MVMS) could improve nutritional status in older adults prescribed diuretics, metformin, and/or proton pump inhibitors (PPIs). We conducted a randomized, double-blind, placebo controlled, parallel clinical trial in which eligible subjects were instructed to consume either a MVMS or placebo for 16 wk. Fasting blood was collected at baseline, 8, and 16 wk and the status of selected vitamins and minerals determined. Thirty-five and 19 men and women aged 45-75 yrs in the in MVMS and placebo arms, respectively, completed the trial. The mean total number of medications among the three drug classes taken by participants did not differ between two groups. The status of vitamins B1, B12, C and folate and calcium, copper, magnesium and zinc at baseline were within normal ranges. The MVMS group had a greater change in nutrient status after 16 wk compared to the placebo group for serum folate (7.5 vs. -1.6 ng/mL, p < 0.0001), vitamin B12 (159.2 vs. -33.9 pg/mL, p = 0.007), and plasma vitamin C (0.2 vs. 0.0 mg/dL, p = 0.004). Other measured vitamins and minerals were not significantly changed during the intervention. In conclusion, the status of vitamins B12, C and folate improved with MVMS but remained within normal ranges in older adults taking diuretics, metformin, and/or PPIs.

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.

National Lipid Association Scientific Statement on the use of icosapent ethyl in statin-treated patients with elevated triglycerides and high or very-high ASCVD risk.

Representatives from the National Lipid Association (NLA) participated in the development of the 2018 American Heart Association/American College of Cardiology/Multisociety Guideline on the Management of Blood Cholesterol, which reaffirmed that lifestyle changes and statin treatment are therapeutic cornerstones for atherosclerotic cardiovascular disease (ASCVD) risk reduction. It also updated prior recommendations to incorporate newer data demonstrating ASCVD risk reduction with ezetimibe and proprotein convertase subtilisin kexin type 9 inhibitors as adjuncts to statin therapy for patients at high and very-high ASCVD risk. The 2018 Guideline was finalized shortly before full results were available from a randomized, placebo-controlled cardiovascular outcomes trial [Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT)] that examined the effects of icosapent ethyl (IPE) 4 g/d on major adverse cardiovascular events in selected high- or very high-risk, statin-treated patients with elevated triglycerides. The primary outcome variable of first major adverse cardiovascular event (cardiovascular death, myocardial infarction, stroke, coronary revascularization and hospitalization for unstable angina) was reduced by 25% (95% confidence interval 17%-32%, P < .001). REDUCE-IT served as the primary basis for the NLA's review of evidence for the use of IPE for ASCVD risk reduction. Based on this review, the NLA position is that for patients aged ≥45 years with clinical ASCVD, or aged ≥50 years with diabetes mellitus requiring medication plus ≥1 additional risk factor, with fasting triglycerides 135 to 499 mg/dL on high-intensity or maximally tolerated statin therapy (±ezetimibe), treatment with IPE is recommended for ASCVD risk reduction (evidence rating: class I; evidence level: B-R).

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.

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.

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.

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.

Spearmint Extract Improves Working Memory in Men and Women with Age-Associated Memory Impairment.

OBJECTIVE: The purpose of this study was to investigate the effects of supplementation with a spearmint (Mentha spicata L.) extract, high in polyphenols including rosmarinic acid, on cognitive performance, sleep, and mood in individuals with age-associated memory impairment (AAMI). DESIGN: Subjects with AAMI (N = 90; 67% female; age = 59.4 ± 0.6 years) were randomly assigned (n = 30/group) to consume 900, 600, or 0 mg/day (two capsules, once daily) spearmint extract for 90 days, in this double-blind, placebo-controlled trial. Assessments were completed for cognition (days 0, 45, and 90), sleep (days 0 and 90), and mood (days 0 and 90) by using the Cognitive Drug Research (CDR) System™, Leeds Sleep Evaluation Questionnaire (LSEQ), and Profile of Mood States (POMS™), respectively. RESULTS: Quality of working memory and spatial working memory accuracy improved after supplementation with 900 mg/day spearmint extract by 15% (p = 0.0469) and 9% (p = 0.0456), respectively, versus placebo. Subjects consuming 900 mg/day spearmint extract reported improvement in their ability to fall asleep, relative to subjects consuming placebo (p = 0.0046). Overall treatment effects were evident for vigor-activity (p = 0.0399), total mood disturbance (p = 0.0374), and alertness and behavior following wakefulness (p = 0.0415), with trends observed for improvements after spearmint supplementation relative to placebo. CONCLUSIONS: These results suggest that the distinct spearmint extract may be a beneficial nutritional intervention for cognitive health in older subjects with AAMI.

Provider recommendations for patient-reported muscle symptoms on statin therapy: Insights from the Understanding Statin Use in America and Gaps in Patient Education survey.

BACKGROUND: Statin-associated muscle symptoms are reported by 10% to 29% of patients in clinical practice and are a major determinant of statin nonadherence, discontinuation, and switching. Little is known about what advice patients receive from their providers when dealing with these symptoms. OBJECTIVE: The objective of the study was to assess patient's reports of provider advice when experiencing new or worsened muscle symptoms while taking a statin. METHODS: Data were analyzed from the Understanding Statin Use in America and Gaps in Education survey, a self-administered internet-based survey of 10,138 adults with a reported history of high cholesterol and statin use. RESULTS: Of the respondents, 60% of former statin users (n = 1220) reported ever experiencing new or worsened muscle pain on a statin, in contrast to 25% of current users (n = 8918; P < .001). Former statin users reported stopping more statins because of muscle symptoms (mean ± standard deviation, 2.2 ± 1.7) compared with current users (mean 1.6 ± 1.5, P < .0001). For those with muscle-related symptoms while on a statin, participants reported that providers most often suggested switching to another statin (33.8%), stopping the statin (15.9%), continuing the statin with further monitoring of muscle symptoms (12.2%), reducing the statin dose (9.8%), or getting a blood test for signs of muscle damage (9.2%). A lower percentage were advised to add either vitamin D (7.0%) or coenzyme Q10 (5.8%), or to switch to nonstatin therapy (6.1%) or red yeast rice (2.6%). CONCLUSIONS: This study highlights patient experience with statin-associated muscle symptoms and the strategies recommended by providers in managing these symptoms. More research is needed to develop patient-centric and evidence-based approaches to managing statin-associated muscle symptoms, which is especially important in light of recent data showing increased cardiovascular risk among those who discontinue statin therapy.

Mono- and diglycerides improve lutein absorption in healthy adults: a randomised, double-blind, cross-over, single-dose study.

With the association between increased carotenoid intake and lower risk of chronic diseases, the absorption of lutein from the diet becomes an important factor in its delivery and physiological action. The primary objective of this study was to gain an understanding of how a new formulation technology (mixture of mono- and diglycerides (MDG)), affected lutein absorption. Subjects (n 24) were randomised in a cross-over, double-blind study to receive a single dose of 6 mg lutein (FloraGLO 20 %) provided as capsules containing either high-oleic safflower (SAF) oil or a MDG oil. Subjects receiving a single dose of lutein in MDG showed a significantly greater change from baseline (0 h) to 4, 6, 8, 12, 24, 48 and 336 h (P<0·05) and baseline adjusted AUC for plasma lutein at 48 and 336 h (P<0·001) as compared with subjects given lutein in SAF. Analysis of the 48 h absorption kinetics of lutein showed that the time to peak level of lutein (12 h) was the same for SAF and MDG groups, but the change in plasma lutein at 12 and 48 h were 129 and 320 % higher, respectively, for MDG compared with SAF. This difference continued as the adjusted AUC 0-48 and 0-336 h for the MDG group was 232 and 900 % higher, respectively, v. SAF. The study data show that by changing the lipid that is combined with a lutein supplement results in significant increases in lutein absorption in healthy adults.

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.

Use of supplemental long-chain omega-3 fatty acids and risk for cardiac death: An updated meta-analysis and review of research gaps.

BACKGROUND: Randomized controlled trials (RCTs) assessing use of long-chain omega-3 polyunsaturated fatty acids (LC-OM3), primarily eicosapentaenoic acid, and/or docosahexaenoic acid have shown mixed results. OBJECTIVE: The objectives of the study were to update and further explore the available RCT data regarding LC-OM3 supplementation and risk for cardiac death and to propose testable hypotheses for the mixed results obtained in RCTs regarding supplemental LC-OM3 use and cardiac risk. METHODS: A literature search was conducted using PubMed and Ovid/MEDLINE for RCTs assessing LC-OM3 supplements or pharmaceuticals with intervention periods of at least 6 months and reporting on the outcome of cardiac death. Meta-analysis was used to compare cumulative frequencies of cardiac death events between the LC-OM3 and control groups, including sensitivity and subset analyses. RESULTS: Fourteen RCTs were identified for the primary analysis (71,899 subjects). In the LC-OM3 arms, 1613 cardiac deaths were recorded (4.48% of subjects), compared with 1746 cardiac deaths in the control groups (4.87% of subjects). The pooled relative risk estimate showed an 8.0% (95% confidence interval 1.6%, 13.9%, P = .015) lower risk in the LC-OM3 arms vs controls. Subset analyses showed numerically larger effects (12.9%-29.1% lower risks, all P < .05) in subsets of RCTs with eicosapentaenoic acid + docosahexaenoic acid dosages >1 g/d and higher risk samples (secondary prevention, baseline mean or median triglycerides ≥150 mg/dL, low-density lipoprotein cholesterol ≥130 mg/dL, statin use <40% of subjects). Heterogeneity was low (I2 ≤ 15.5%, P > .05) for the primary and subset analyses. CONCLUSION: LC-OM3 supplementation is associated with a modest reduction in cardiac death.

Replacement of Refined Starches and Added Sugars with Egg Protein and Unsaturated Fats Increases Insulin Sensitivity and Lowers Triglycerides in Overweight or Obese Adults with Elevated Triglycerides.

Background: Hypertriglyceridemia is a common condition in the United States and is often associated with other metabolic disturbances, including insulin resistance, metabolic syndrome, and a predominance of small dense LDL particles.Objective: The objective of this trial was to evaluate the effects of a combination of egg protein (Epro) and unsaturated fatty acids (UFAs) substituted for refined starches and added sugars on insulin sensitivity (primary outcome) and other cardiometabolic health markers in overweight or obese adults with elevated triglyceride (TG) concentrations.Methods: Subjects with elevated TG concentrations were given test foods prepared by using Epro powder (∼8% of energy) and vegetable oil (∼8% of energy; Epro and UFA condition) or test foods prepared by using refined starch and sugar (∼16% of energy; carbohydrate condition) in a randomized, double-blind, controlled-feeding, crossover trial (3 wk/condition, 2-wk washout). The Matsuda insulin sensitivity index (MISI), fasting lipids, and other cardiometabolic health markers were assessed at baseline and the end of each diet condition. Responses were compared by using repeated-measures ANCOVA.Results: Twenty-five participants [11 men, 14 women; mean ± SEM: age, 46.3 ± 2.4 y; body mass index (in kg/m2), 31.8 ± 1.0] with a median (interquartile range limits) fasting serum TG concentration of 173 mg/dL (159, 228 mg/dL) completed the trial. The MISI value increased 18.1% ± 8.7% from baseline during the Epro and UFA condition and decreased 5.7% ± 6.2% from baseline during the carbohydrate condition (P < 0.001). The disposition index increased 23.8% ± 20.8% during the Epro and UFA condition compared with a decrease of 16.3% ± 18.8% during carbohydrate (P = 0.042) and LDL peak particle size increased 0.12 nm (-0.12, 0.28 nm) with Epro and UFA compared with a decrease of 0.15 nm (-0.33, 0.12 nm) with carbohydrate (P = 0.019). TG and VLDL cholesterol concentrations were lowered by 18.5% (-35.7%, -6.9%) and 18.6% (-34.8%, -7.4%), respectively, after the Epro and UFA condition and by 2.5% (-13.4%, 17.0%) and 3.6% (-12.5%, 16.2%), respectively, after the carbohydrate diet condition (P < 0.002).Conclusions: The replacement of refined carbohydrates with a combination of Epro and UFA increased the MISI value and altered several markers of cardiometabolic health in overweight or obese adults with elevated TG concentrations. This trial was registered at clinicaltrials.gov as NCT02924558.