Monocyte transcriptomic profile following EPA and DHA supplementation in men and women with low-grade chronic inflammation.

BACKGROUND: Recent data indicate considerable variability in response to very long chain omega-3 fatty acid supplementation on cardiovascular disease risk. This inconsistency may be due to differential effects of EPA vs DHA and/or sex-specific responses. METHODS: Sixteen subjects (eight men and eight women) 50-75 y and with low-grade chronic inflammation participated in a randomized controlled crossover trial comparing 3 g/d EPA, 3 g/d DHA, and placebo (3 g/d high oleic acid sunflower oil). Blood monocytes were isolated at the end of each phase for RNA-sequencing. RESULTS: Sex dimorphism in monocyte gene expression was observed, therefore, data for men and women were analyzed separately. 1088 genes were differentially expressed in men and 997 in women (p < 0.05). In both men and women, EPA and DHA repressed genes involved in protein turnover and mitochondrial energy metabolism, relative to placebo. In men only, EPA and DHA upregulated genes related to wound healing and PPARα activation. In women only, EPA and DHA activated genes related to ER stress response. Relative to DHA, EPA resulted in lower expression of genes involved in inflammatory processes in men, and lower expression of genes involved in ER stress response in women. CONCLUSIONS: EPA and DHA supplementation elicited both similar and differential effects on monocyte transcriptome, some of which were sex specific. The observed variability in response to EPA and DHA in men and women could in part explain the conflicting results from previous cardiovascular clinical trials using omega-3 fatty acids.

2021 Dietary Guidance to Improve Cardiovascular Health: A Scientific Statement From the American Heart Association.

Poor diet quality is strongly associated with elevated risk of cardiovascular disease morbidity and mortality. This scientific statement emphasizes the importance of dietary patterns beyond individual foods or nutrients, underscores the critical role of nutrition early in life, presents elements of heart-healthy dietary patterns, and highlights structural challenges that impede adherence to heart-healthy dietary patterns. Evidence-based dietary pattern guidance to promote cardiometabolic health includes the following: (1) adjust energy intake and expenditure to achieve and maintain a healthy body weight; (2) eat plenty and a variety of fruits and vegetables; (3) choose whole grain foods and products; (4) choose healthy sources of protein (mostly plants; regular intake of fish and seafood; low-fat or fat-free dairy products; and if meat or poultry is desired, choose lean cuts and unprocessed forms); (5) use liquid plant oils rather than tropical oils and partially hydrogenated fats; (6) choose minimally processed foods instead of ultra-processed foods; (7) minimize the intake of beverages and foods with added sugars; (8) choose and prepare foods with little or no salt; (9) if you do not drink alcohol, do not start; if you choose to drink alcohol, limit intake; and (10) adhere to this guidance regardless of where food is prepared or consumed. Challenges that impede adherence to heart-healthy dietary patterns include targeted marketing of unhealthy foods, neighborhood segregation, food and nutrition insecurity, and structural racism. Creating an environment that facilitates, rather than impedes, adherence to heart-healthy dietary patterns among all individuals is a public health imperative.

Serum Nonesterified Fatty Acids and Incident Stroke: The CHS.

Background Significant associations between total nonesterified fatty acid (NEFA) concentrations and incident stroke have been reported in some prospective cohort studies. We evaluated the associations between incident stroke and serum concentrations of nonesterified saturated, monounsaturated, polyunsaturated, and trans fatty acids. Methods and Results CHS (Cardiovascular Health Study) participants (N=2028) who were free of stroke at baseline (1996-1997) and had an archived fasting serum sample were included in this study. A total of 35 NEFAs were quantified using gas chromatography. Cox proportional hazards regression models were used to evaluate associations of 5 subclasses (nonesterified saturated, monounsaturated, omega (n)-6 polyunsaturated, n-3 polyunsaturated, and trans fatty acids) of NEFAs and individual NEFAs with incident stroke. Sensitivity analysis was conducted by excluding cases with hemorrhagic stroke (n=45). A total of 338 cases of incident stroke occurred during the median 10.5-year follow-up period. Total n-3 (hazard ratio [HR], 0.77 [95% CI, 0.61-0.97]) and n-6 (HR, 1.32 [95% CI, 1.01-1.73]) subclasses of NEFA were negatively and positively associated with incident stroke, respectively. Among individual NEFAs, dihomo-γ-linolenic acid (20:3n-6) was associated with higher risk (HR, 1.29 [95% CI, 1.02-1.63]), whereas cis-7-hexadecenoic acid (16:1n-9c) and arachidonic acid (20:4n-6) were associated with a lower risk (HR, 0.67 [95% CI, 0.47-0.97]; HR, 0.81 [95% CI. 0.65-1.00], respectively) of incident stroke per standard deviation increment. After the exclusion of cases with hemorrhagic stroke, these associations did not remain significant. Conclusions A total of 2 NEFA subclasses and 3 individual NEFAs were associated with incident stroke. Of these, the NEFA n-3 subclass and dihomo-γ-linolenic acid are diet derived and may be potential biomarkers for total stroke risk.

Western and heart healthy dietary patterns differentially affect the expression of genes associated with lipid metabolism, interferon signaling and inflammation in the jejunum of Ossabaw pigs.

Diet quality and statin therapy are established modulators of coronary artery disease (CAD) progression, but their effect on the gastrointestinal tract and subsequent sequelae that could affect CAD progression are relatively unexplored. To address this gap, Ossabaw pigs (N = 32) were randomly assigned to receive isocaloric amounts of a Western-type diet (WD; high in saturated fat, refined carbohydrate, and cholesterol, and low in fiber) or a heart healthy-type diet (HHD; high in unsaturated fat, whole grains, fruits and vegetables, supplemented with fish oil, and low in cholesterol), with or without atorvastatin, for 6 months. At the end of the study, RNA sequencing with 100 base pair single end reads on NextSeq 500 platform was conducted in isolated pig jejunal mucosa. A two-factor edgeR analysis revealed that the dietary patterns resulted in three differentially expressed genes related to lipid metabolism (SCD, FADS1, and SQLE). The expression of these genes was associated with cardiometabolic risk factors and atherosclerotic lesion severity. Subsequent gene enrichment analysis indicated the WD, compared to the HHD, resulted in higher interferon signaling and inflammation, with some of these genes being significantly associated with serum TNF-α and/or hsCRP concentrations, but not atherosclerotic lesion severity. No significant effect of atorvastatin therapy on gene expression, nor its interaction with dietary patterns, was identified. In conclusion, Western and heart healthy-type dietary patterns differentially affect the expression of genes associated with lipid metabolism, interferon signaling, and inflammation in the jejunum of Ossabaw pigs.

Colon transcriptome is modified by a dietary pattern/atorvastatin interaction in the Ossabaw pig.

Optimizing diet quality in conjunction with statin therapy is currently the most common approach for coronary artery disease (CAD) risk management. Although effects on the cardiovascular system have been extensively investigated, little is known about the effect of these interventions in the colon and subsequent associations with CAD progression. To address this gap, Ossabaw pigs were randomly allocated to receive, for a six-month period, isocaloric amounts of either a heart healthy-type diet (HHD; high in unrefined carbohydrate, unsaturated fat, fiber, supplemented with fish oil, and low in cholesterol) or a Western-type diet (WD; high in refined carbohydrate, saturated fat and cholesterol, and low in fiber), without or with atorvastatin therapy. At the end of the intervention period, colon samples were harvested, mucosa fraction isolated, and RNA sequenced. Gene differential expression and enrichment analyses indicated that dietary patterns and atorvastatin therapy differentially altered gene expression, with diet-statin interactions. Atorvastatin had a more profound effect on differential gene expression than diet. In pigs not receiving atorvastatin, the WD upregulated "LXR/RXR Activation" pathway compared to pigs fed the HHD. Enrichment analysis indicated that atorvastatin therapy lowered inflammatory status in the HHD-fed pigs, whereas it induced a colitis-like gene expression phenotype in the WD-fed pigs. No significant association was identified between gene expression phenotypes and severity of atherosclerotic lesions in the left anterior descending-left circumflex bifurcation artery. These data suggested diet quality modulated the response to atorvastatin therapy in colonic mucosa, and these effects were unrelated to atherosclerotic lesion development.

Perspective: Design and Conduct of Human Nutrition Randomized Controlled Trials.

In the field of human nutrition, randomized controlled trials (RCTs) are considered the gold standard for establishing causal relations between exposure to nutrients, foods, or dietary patterns and prespecified outcome measures, such as body composition, biomarkers, or event rates. Evidence-based dietary guidance is frequently derived from systematic reviews and meta-analyses of these RCTs. Each decision made during the design and conduct of human nutrition RCTs will affect the utility and generalizability of the study results. Within the context of limited resources, the goal is to maximize the generalizability of the findings while producing the highest quality data and maintaining the highest levels of ethics and scientific integrity. The aim of this document is to discuss critical aspects of conducting human nutrition RCTs, including considerations for study design (parallel, crossover, factorial, cluster), institutional ethics approval (institutional review boards), recruitment and screening, intervention implementation, adherence and retention assessment, and statistical analyses considerations. Additional topics include distinguishing between efficacy and effectiveness, defining the research question(s), monitoring biomarker and outcome measures, and collecting and archiving data. Addressed are specific aspects of planning and conducting human nutrition RCTs, including types of interventions, inclusion/exclusion criteria, participant burden, randomization and blinding, trial initiation and monitoring, and the analysis plan.

EPA and DHA differentially modulate monocyte inflammatory response in subjects with chronic inflammation in part via plasma specialized pro-resolving lipid mediators: A randomized, double-blind, crossover study.

BACKGROUND AND AIMS: The independent effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on chronic inflammation through their downstream lipid mediators, including the specialized pro-resolving lipid mediators (SPM), remain unstudied. Therefore, we compared the effects of EPA and DHA supplementation on monocyte inflammatory response and plasma polyunsaturated fatty acids (PUFA) SPM lipidome. METHODS: After a 4-week lead-in phase (baseline), 9 men and 12 postmenopausal women (50-75 years) with chronic inflammation received two phases of 10-week supplementation with 3 g/day EPA and DHA in a random order, separated by a 10-week washout. RESULTS: Compared with baseline, EPA and DHA supplementation differently modulated LPS-stimulated monocyte cytokine expression. EPA lowered TNFA (p < 0.001) whereas DHA reduced TNFA (p < 0.001), IL6 (p < 0.02), MCP1 (p < 0.03), and IL10 (p < 0.01). DHA lowered IL10 expression relative to EPA (p = 0.03). Relative to baseline, EPA, but not DHA, decreased the ratios of TNFA/IL10 and MCP1/IL10 (both p < 0.01). EPA and DHA also significantly changed plasma PUFA SPM lipidome by replacing n-6 AA derivatives with their respective derivatives including 18-hydroxy-EPA (+5 fold by EPA) and 17- and 14-hydroxy-DHA (+3 folds by DHA). However, DHA showed a wider effect than EPA by also significantly increasing EPA derivatives and DPA-derived SPM at a greater expense of AA derivatives. Different groups of PUFA derivatives mediated the differential effects of EPA and DHA on monocyte cytokine expression. CONCLUSIONS: EPA and DHA had distinct effects on monocyte inflammatory response with a broader effect of DHA in attenuating pro-inflammatory cytokines. These differential effects were potentially mediated by different groups of PUFA derivatives, suggesting immunomodulatory activities of SPM and their intermediates.

Exploring the effect of vitamin D3 supplementation on surrogate biomarkers of cholesterol absorption and endogenous synthesis in patients with type 2 diabetes-randomized controlled trial.

BACKGROUND: Inverse associations have been reported between serum 25-hydroxyvitamin D [25(OH)D] and circulating cholesterol concentrations in observational studies. Postulated mechanisms include reduced bioavailability of intestinal cholesterol and alterations in endogenous cholesterol synthesis. OBJECTIVE: To explore the effect of daily supplementation with 4000 IU/d vitamin D3 for 24 wk on surrogate biomarkers of cholesterol absorption (campesterol and ß-sitosterol) and endogenous synthesis (lathosterol and desmosterol). METHODS: Ancillary study of The Vitamin D for Established Type 2 Diabetes (DDM2) trial. Patients with established type 2 diabetes (N = 127, 25-75 y, BMI 23-42 kg/m2) were randomly assigned to receive either 4000 IU vitamin D3 or placebo daily for 24 wk. Of participants without changes in cholesterol-lowering medications (n = 114), plasma surrogate cholesterol absorption and endogenous synthesis biomarker concentrations were measured and merged with available measures of serum LDL cholesterol and HDL cholesterol concentrations. RESULTS: At week 24, vitamin D3 supplementation significantly increased 25(OH)D concentrations (+21.5 ± 13.4 ng/mL) but not insulin secretion rates (primary outcome of the parent study) as reported previously. In this ancillary study there was no significant effect of vitamin D3 supplementation on serum cholesterol profile or surrogate biomarkers of cholesterol absorption and endogenous synthesis. Compared with participants not treated with cholesterol-lowering medications, those who were treated exhibited a greater reduction in plasma campesterol concentrations in the vitamin D3 but not placebo group (P-interaction = 0.011). Analyzing the data on the basis of cholesterol absorption status (hypo- versus hyperabsorbers) or cholesterol synthesis status (hypo- versus hypersynthesizers) did not alter these results. CONCLUSIONS: Vitamin D3 supplementation for 24 wk had no significant effect on surrogate biomarkers of cholesterol absorption or endogenous synthesis, consistent with the lack of effect on serum cholesterol profile. Vitamin D3 supplementation resulted in greater reduction in campesterol concentrations in participants not using compared with those using cholesterol-lowering medications. Further studies are required.This trial was registered at clinicaltrials.gov as NCT01736865.

Supplementation with Seabuckthorn Oil Augmented in 16:1n-7t Increases Serum Trans-Palmitoleic Acid in Metabolically Healthy Adults: A Randomized Crossover Dose-Escalation Study.

BACKGROUND: In animal models cis-palmitoleic acid (9-hexadecenoic acid; 16:1n-7c), a lipokine, improves insulin sensitivity, inflammation, and lipoprotein profiles; in humans trans-palmitoleic acid (16:1n-7t) has been associated with lower incidence of type 2 diabetes. The response to dose-escalation of supplements containing cis- and trans-palmitoleic acid has not been evaluated. OBJECTIVES: We examined dose-escalation effects of oral supplementation with seabuckthorn oil and seabuckthorn oil augmented in 16:1n-7t on serum phospholipid fatty acids (PLFAs). METHODS: Thirteen participants (7 women and 6 men; age 48 ± 16 y, BMI 30.4 ± 3.7 kg/m2) participated in a randomized, double-blind, crossover, dose-escalation trial of unmodified seabuckthorn oils relatively high in 16:1n-7c (380, 760, and 1520 mg 16:1n-7c/d) and seabuckthorn oils augmented in 16:1n-7t (120, 240, and 480 mg 16:1n-7t/d). Each of the 3 escalation doses was provided for 3 wk, with a 4-wk washout period between the 2 supplements. At the end of each dose period, fasting blood samples were used to determine the primary outcomes (serum concentrations of the PLFAs 16:1n-7t and 16:1n-7c) and the secondary outcomes (glucose homeostasis, serum lipids, and clinical measures). Trends across doses were evaluated using linear regression. RESULTS: Compared with baseline, supplementation with seabuckthorn oil augmented in 16:1n-7t increased phospholipid 16:1n-7t by 26.6% at the highest dose (P = 0.0343). Supplementation with unmodified seabuckthorn oil resulted in a positive trend across the dose-escalations (P-trend = 0.0199). No significant effects of either supplement were identified on blood glucose, insulin, lipids, or other clinical measures, although this dosing study was not powered to detect such effects. No carryover or adverse effects were observed. CONCLUSIONS: Supplementation with seabuckthorn oil augmented in 16:1n-7t and unmodified seabuckthorn oil moderately increased concentrations of their corresponding PLFAs in metabolically healthy adults, supporting the use of supplementation with these fatty acids to test potential clinical effects in humans.This trial was registered at clinicaltrials.gov as NCT02311790.

Dietary Fat and Cardiovascular Disease: Ebb and Flow Over the Last Half Century.

Dietary modification has been the cornerstone of cardiovascular disease (CVD) prevention since the middle of the last century when the American Heart Association (AHA) first issued recommendations. For the vast majority of that time the focus has been on saturated fat, with or without concomitant guidance for total or unsaturated fat. Over the past few years there has been a renewed debate about the relation between dietary saturated fat and CVD risk, prompted by a series of systematic reviews that have come to what appears to be different conclusions. This triggered a robust discourse about this controversy in the media that in turn has led to confusion in the general public. The genesis of the different conclusions among the systematic reviews has been identified in several studies on the basis of isocaloric substitution analyses. When the data were analyzed on the basis of polyunsaturated fat replacing saturated fat, there was a positive relation between dietary saturated fat and CVD. When the data were analyzed on the basis of carbohydrate replacing saturated fat, there was a null relation between dietary saturated fat and CVD. When the substitution macronutrient was not taken into consideration, the differential effects of the macronutrient substitution went unrecognized and the relations judged as null. The lack of distinction among substituted macronutrients accounted for much of what appeared to be discrepancies. Dietary guidance consistent with replacing foods high in saturated fat with foods high in unsaturated fat, first recommended more than 50 y ago, remains appropriate to this day.

Dietary patterns influence epicardial adipose tissue fatty acid composition and inflammatory gene expression in the Ossabaw pig.

Epicardial adipose tissue (EAT) inflammation is implicated in the development and progression of coronary atherosclerosis. Dietary saturated and polyunsaturated fatty acids (SFAs and PUFA) can influence adipose tissue inflammation. We investigated the influence of dietary patterns, with emphasis on dietary fat type, and statin therapy, on EAT fatty acid (FA) composition and inflammatory gene expression. Thirty-two Ossabaw pigs were fed isocaloric amounts of a Heart Healthy (high in unsaturated fat) or Western (high in saturated fat) diets +/- atorvastatin for 6 months. EAT FA composition reflected dietary fat composition. There was no significant effect of atorvastatin on EAT FA composition. Total and long-chain SFAs were positively associated with inflammatory signaling (TLR2) and a gene involved in lipid mediator biosynthesis (PTGS2) (P<.0003). Medium-chain SFAs capric and lauric acids were negatively associated with IL-6 (all P<.0003). N-6 and n-3 PUFAs were positively associated with anti-inflammatory signaling genes (PPARG, FFAR4 and ADIPOQ) and long-chain n-3 PUFAs were positively associated with a gene involved in lipid mediator biosynthesis (ALOX5) (all P<.0003). These data indicate that dietary patterns, differing in fat type, influence EAT FA composition. Associations between EAT SFAs, PUFAs, and expression of genes related to inflammation provide a link between dietary quality and EAT inflammation.

Theoretical Food and Nutrient Composition of Whole-Food Plant-Based and Vegan Diets Compared to Current Dietary Recommendations.

Public interest in popular diets is increasing, in particular whole-food plant-based (WFPB) and vegan diets. Whether these diets, as theoretically implemented, meet current food-based and nutrient-based recommendations has not been evaluated in detail. Self-identified WFPB and vegan diet followers in the Adhering to Dietary Approaches for Personal Taste (ADAPT) Feasibility Survey reported their most frequently used sources of information on nutrition and cooking. Thirty representative days of meal plans were created for each diet. Weighted mean food group and nutrient levels were calculated using the Nutrition Data System for Research (NDSR) and data were compared to DRIs and/or USDA Dietary Guidelines/MyPlate meal plan recommendations. The calculated HEI-2015 scores were 88 out of 100 for both WFPB and vegan meal plans. Because of similar nutrient composition, only WFPB results are presented. In comparison to MyPlate, WFPB meal plans provide more total vegetables (180%), green leafy vegetables (238%), legumes (460%), whole fruit (100%), whole grains (132%), and less refined grains (-74%). Fiber level exceeds the adequate intakes (AI) across all age groups. WFPB meal plans failed to meet the Recommended Dietary Allowances (RDA)s for vitamin B12 and D without supplementation, as well as the RDA for calcium for women aged 51⁻70. Individuals who adhere to WFBP meal plans would have higher overall dietary quality as defined by the HEI-2015 score as compared to typical US intakes with the exceptions of calcium for older women and vitamins B12 and D without supplementation. Future research should compare actual self-reported dietary intakes to theoretical targets.

Dietary Supplementation With Medium-Chain Triglycerides Reduces Candida Gastrointestinal Colonization in Preterm Infants.

BACKGROUND: Candida is an important cause of infections in premature infants. Gastrointestinal colonization with Candida is a common site of entry for disseminated disease. The objective of this study was to determine whether a dietary supplement of medium-chain triglycerides (MCTs) reduces Candida colonization in preterm infants. METHODS: Preterm infants with Candida colonization (n = 12) receiving enteral feedings of either infant formula (n = 5) or breast milk (n = 7) were randomized to MCT supplementation (n = 8) or no supplementation (n = 4). Daily stool samples were collected to determine fungal burden during a 3-week study period. Infants in the MCT group received supplementation during 1 week of the study period. The primary outcome was fungal burden during the supplementation period as compared with the periods before and after supplementation. RESULTS: Supplementation of MCT led to a marked increase in MCT intake relative to unsupplemented breast milk or formula as measured by capric acid content. In the treatment group, there was a significant reduction in fungal burden during the supplementation period as compared with the period before supplementation (rate ratio, 0.15; P = 0.02), with a significant increase after supplementation was stopped (rate ratio, 61; P < 0.001). Fungal burden in the control group did not show similar changes. CONCLUSIONS: Dietary supplementation with MCT may be an effective method to reduce Candida colonization in preterm infants.

Tea Consumption and Longitudinal Change in High-Density Lipoprotein Cholesterol Concentration in Chinese Adults.

BACKGROUND: The relation between tea consumption and age-related changes in high-density lipoprotein cholesterol (HDL-C) concentrations remains unclear, and longitudinal human data are limited. The aim of current study was to examine the relation between tea intake and longitudinal change in HDL-C concentrations. METHODS AND RESULTS: Baseline (2006) tea consumption was assessed via a questionnaire, and plasma HDL-C concentrations were measured in 2006, 2008, 2010, and 2012 among 80 182 individuals (49±12 years of age) who did not have cardiovascular diseases or cancer, or did not use cholesterol-lowering agents both at baseline (2006) and during the follow-up period (2006-2012). The associations between baseline tea consumption and rate of change in HDL-C concentrations were examined using generalized estimating equation models. Tea consumption was inversely associated with a decreased rate of HDL-C concentrations (P-trend <0.0001) in the fully adjusted model. The adjusted mean difference in the HDL-C decreased rate was 0.010 (95% confidence interval, 0.008, 0.012) mmol/L per year for tea consumers versus nonconsumers (never or less than once/month group). Interactions between tea consumption and age, sex, lifestyle scores, and metabolic syndrome (all P-interaction <0.0001) were identified. The associations between greater tea consumption and slower decrease in HDL-C concentrations were more pronounced in men, individuals aged 60 or older, individuals with a lower lifestyle score, and individuals with metabolic syndrome (all P-trend <0.0001). CONCLUSIONS: Tea consumption was associated with slower age-related decreases in HDL-C concentrations during 6 years of follow-up. CLINICAL TRIAL REGISTRATION: URL: www.chictr.org. Unique identifier: ChiCTR-TNRC-11001489.

Medical Nutrition Education, Training, and Competencies to Advance Guideline-Based Diet Counseling by Physicians: A Science Advisory From the American Heart Association.

Growing scientific evidence of the benefits of heart-healthy dietary patterns and of the massive public health and economic burdens attributed to obesity and poor diet quality have triggered national calls to increase diet counseling in outpatients with atherosclerotic cardiovascular disease or risk factors. However, despite evidence that physicians are willing to undertake this task and are viewed as credible sources of diet information, they engage patients in diet counseling at less than desirable rates and cite insufficient knowledge and training as barriers. These data align with evidence of large and persistent gaps in medical nutrition education and training in the United States. Now, major reforms in undergraduate and graduate medical education designed to incorporate advances in the science of learning and to better prepare physicians for 21st century healthcare delivery are providing a new impetus and novel ways to expand medical nutrition education and training. This science advisory reviews gaps in undergraduate and graduate medical education in nutrition in the United States, summarizes reforms that support and facilitate more robust nutrition education and training, and outlines new opportunities for accomplishing this goal via multidimensional curricula, pedagogies, technologies, and competency-based assessments. Real-world examples of efforts to improve undergraduate and graduate medical education in nutrition by integrating formal learning with practical, experiential, inquiry-driven, interprofessional, and population health management activities are provided. The authors conclude that enhancing physician education and training in nutrition, as well as increasing collaborative nutrition care delivery by 21st century health systems, will reduce the health and economic burdens from atherosclerotic cardiovascular disease to a degree not previously realized.

Seafood Long-Chain n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease: A Science Advisory From the American Heart Association.

Since the 2002 American Heart Association scientific statement "Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease," evidence from observational and experimental studies and from randomized controlled trials continues to emerge to further substantiate the beneficial effects of seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease. A recent American Heart Association science advisory addressed the specific effect of n-3 polyunsaturated fatty acid supplementation on clinical cardiovascular events. This American Heart Association science advisory extends that review and offers further support to include n-3 polyunsaturated fatty acids from seafood consumption. Several potential mechanisms have been investigated, including antiarrhythmic, anti-inflammatory, hematologic, and endothelial, although for most, longer-term dietary trials of seafood are warranted to substantiate the benefit of seafood as a replacement for other important sources of macronutrients. The present science advisory reviews this evidence and makes a suggestion in the context of the 2015-2020 Dietary Guidelines for Americans and in consideration of other constituents of seafood and the impact on sustainability. We conclude that 1 to 2 seafood meals per week be included to reduce the risk of congestive heart failure, coronary heart disease, ischemic stroke, and sudden cardiac death, especially when seafood replaces the intake of less healthy foods.

Omega-3 Fatty Acids and Cardiovascular Disease: Summary of the 2016 Agency of Healthcare Research and Quality Evidence Review.

We summarize the 2016 update of the 2004 Agency of Healthcare Research and Quality's evidence review of omega-3 fatty acids and cardiovascular disease (CVD). The overall findings for the effects of marine oil supplements on intermediate CVD outcomes remain largely unchanged. There is high strength of evidence, based on numerous trials, of no significant effects of marine oils on systolic or diastolic blood pressures, but there are small, yet statistically significant increases in high density lipoprotein and low density lipoprotein cholesterol concentrations. The clinical significance of these small changes, particularly in combination, is unclear. The strongest effect of marine oils is on triglyceride concentrations. Across studies, this effect was dose-dependent and related to studies' mean baseline triglyceride concentration. In observational studies, there is low strength of evidence that increased marine oil intake lowers ischemic stroke risk. Among randomized controlled trials and observational studies, there is evidence of variable strength of no association with increased marine oil intake and lower CVD event risk. Evidence regarding alpha-linolenic acid intake is sparser. There is moderate strength of evidence of no effect on blood pressure or lipoprotein concentrations and low strength of evidence of no association with coronary heart disease, atrial fibrillation and congestive heart failure.

Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association.

Multiple randomized controlled trials (RCTs) have assessed the effects of supplementation with eicosapentaenoic acid plus docosahexaenoic acid (omega-3 polyunsaturated fatty acids, commonly called fish oils) on the occurrence of clinical cardiovascular diseases. Although the effects of supplementation for the primary prevention of clinical cardiovascular events in the general population have not been examined, RCTs have assessed the role of supplementation in secondary prevention among patients with diabetes mellitus and prediabetes, patients at high risk of cardiovascular disease, and those with prevalent coronary heart disease. In this scientific advisory, we take a clinical approach and focus on common indications for omega-3 polyunsaturated fatty acid supplements related to the prevention of clinical cardiovascular events. We limited the scope of our review to large RCTs of supplementation with major clinical cardiovascular disease end points; meta-analyses were considered secondarily. We discuss the features of available RCTs and provide the rationale for our recommendations. We then use existing American Heart Association criteria to assess the strength of the recommendation and the level of evidence. On the basis of our review of the cumulative evidence from RCTs designed to assess the effect of omega-3 polyunsaturated fatty acid supplementation on clinical cardiovascular events, we update prior recommendations for patients with prevalent coronary heart disease, and we offer recommendations, when data are available, for patients with other clinical indications, including patients with diabetes mellitus and prediabetes and those with high risk of cardiovascular disease, stroke, heart failure, and atrial fibrillation.

Dietary supplements and disease prevention - a global overview.

Dietary supplements are widely used and offer the potential to improve health if appropriately targeted to those in need. Inadequate nutrition and micronutrient deficiencies are prevalent conditions that adversely affect global health. Although improvements in diet quality are essential to address these issues, dietary supplements and/or food fortification could help meet requirements for individuals at risk of deficiencies. For example, supplementation with vitamin A and iron in developing countries, where women of reproductive age, infants and children often have deficiencies; with folic acid among women of reproductive age and during pregnancy; with vitamin D among infants and children; and with calcium and vitamin D to ensure bone health among adults aged ≥65 years. Intense debate surrounds the benefits of individual high-dose micronutrient supplementation among well-nourished individuals because the alleged beneficial effects on chronic diseases are not consistently supported. Daily low-dose multivitamin supplementation has been linked to reductions in the incidence of cancer and cataracts, especially among men. Baseline nutrition is an important consideration in supplementation that is likely to modify its effects. Here, we provide a detailed summary of dietary supplements and health outcomes in both developing and developed countries to help guide decisions about dietary supplement recommendations.