Partial replacement of saturated fatty acids (SFA) with unsaturated fatty acids is recommended to reduce cardiovascular disease (CVD) risk. Monounsaturated fatty acids (MUFA), including oleic acid, are associated with lower CVD risk. Measurement of flow-mediated dilation of the brachial artery (FMD) is the gold standard for measuring endothelial function and predicts CVD risk. This study examined the effect of partially replacing SFA with MUFA from conventional canola oil and high-oleic acid canola oil on FMD. Participants (n = 31) with an elevated waist circumference plus ≥1 additional metabolic syndrome criterion completed FMD measures as part of the Canola Oil Multi-Centre Intervention Trial 2 (COMIT-2), a multi-center, double-blind, three-period crossover, controlled feeding randomized trial. Diet periods were 6 weeks, separated by ≥4-week washouts. Experimental diets were provided during all feeding periods. Diets only differed by the fatty acid profile of the oils: canola oil (CO; 17.5% energy from MUFA, 9.2% polyunsaturated fatty acids (PUFA), 6.6% SFA), high-oleic acid canola oil (HOCO; 19.1% MUFA, 7.0% PUFA, 6.4% SFA), and a control oil blend (CON; 11% MUFA, 10% PUFA, 12% SFA). Multilevel models were used to examine the effect of the diets on FMD. No significant between-diet differences were observed for average brachial artery diameter (CO: 6.70 ± 0.15 mm, HOCO: 6.57 ± 0.15 mm, CON: 6.73 ± 0.14 mm; p = 0.72), peak brachial artery diameter (CO: 7.11 ± 0.15 mm, HOCO: 7.02 ± 0.15 mm, CON: 6.41 ± 0.48 mm; p = 0.80), or FMD (CO: 6.32 ± 0.51%, HOCO: 6.96 ± 0.49%, CON: 6.41 ± 0.48%; p = 0.81). Partial replacement of SFA with MUFA from CO and HOCO had no effect on FMD in participants with or at risk of metabolic syndrome.

Abstract Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.

Lipids and lipoproteins are major targets for cardiovascular disease (CVD) prevention. Findings from a limited number of clinical trials suggest diet-induced atherogenic lipoprotein lowering can be altered in the presence of chronic low-grade inflammation or insulin resistance. This review summarizes results from randomized controlled trials that have examined diet-induced changes in lipids/lipoproteins by inflammatory or insulin sensitivity status. In addition, mechanisms to explain these clinical observations are explored. Post hoc analyses of data from a limited number of randomized controlled trials suggest attenuation of diet-induced lipid/lipoprotein lowering in individuals with inflammation and/or insulin resistance. These findings are supported by experimental studies showing that inflammatory stimuli and hyperinsulinemia alter genes involved in endogenous cholesterol synthesis and cholesterol uptake, reduce cholesterol efflux, and increase fatty acid biosynthesis. Further a priori defined research is required to better characterize how chronic low-grade inflammation and insulin resistance modulate lipid and lipoprotein responsiveness to guide CVD risk reduction in individuals presenting with these phenotypes.

BACKGROUNDNovel oils high in monounsaturated fatty acids (MUFAs) and low in saturated fatty acids (SFAs) are an alternative to partially hydrogenated oils high in trans-unsaturated fatty acids. There is widespread use of high-MUFA oils across the food industry; however, limited knowledge of their cardiovascular impact exists.OBJECTIVESWe investigated the effects of diets containing canola oil, high-oleic acid canola oil (HOCO), and a control oil blend (diet formulated to emulate a Western fat profile) on lipids, lipoproteins, and apolipoproteins (apos), as secondary outcomes of the trial.METHODSIn a multi-center, double-blind, randomized, 3-period crossover, controlled feeding trial, men (n = 44) and women (n = 75) with a mean age of 44 y, mean body mass index (BMI; in kg/m2) of 31.7, and an increased waist circumference plus ≥1 metabolic syndrome criteria consumed prepared, weight-maintenance diets containing canola oil [17.5% MUFAs, 9.2% polyunsaturated fatty acids (PUFAs), 6.6% SFAs], HOCO (19.1% MUFAs, 7.0% PUFAs, 6.4% SFAs), or control oil (10.5% MUFAs, 10.0% PUFAs, 12.3% SFAs) for 6 wk with ≥4-wk washouts. Fasting serum lipids were assessed at baseline and 6 wk. Diet effects were examined using a repeated measures mixed model.RESULTSCompared with the control, canola and HOCO diets resulted in lower endpoint total cholesterol (TC; -4.2% and -3.4%; P < 0.0001), LDL cholesterol (-6.6% and -5.6%; P < 0.0001), apoB (-3.7% and -3.4%; P = 0.002), and non-HDL cholesterol (-4.5% and -4.0%; P = 0.001), with no differences between canola diets. The TC:HDL cholesterol and apoB:apoA1 ratios were lower after the HOCO diet than after the control diet (-3.7% and -3.4%, respectively). There were no diet effects on triglyceride, HDL cholesterol, or apoA1 concentrations.CONCLUSIONSHOCO, with increased MUFAs at the expense of decreased PUFAs, elicited beneficial effects on lipids and lipoproteins comparable to conventional canola oil and consistent with reduced cardiovascular disease risk in adults with central adiposity. This trial was registered at www.clinicaltrials.gov as NCT02029833.

Background: Different fatty acids (FAs) can vary in their obesogenic effect, and genetic makeup can contribute to fat deposition in response to dietary FA composition. However, the antiobesogenic effects of the interactions between dietary MUFAs and genetics have scarcely been tested in intervention studies. Objective: We evaluated the overall (primary outcome) and genetically modulated (secondary outcome) response in body weight and fat mass to different levels of MUFA consumption. Methods: In the Canola Oil Multicenter Intervention Trial II, a randomized, crossover, isocaloric, controlled-feeding multicenter trial, 44 men and 71 women with a mean age of 44 y and an increased waist circumference (men similar to 108 cm and women similar to 102 cm) consumed each of 3 oils for 6 wk, separated by four 12-wk washout periods. Oils included 2 high-MUFA oils-conventional canola and high-oleic canola (< 7% SFAs, > 65% MUFAs)-and 1 low-MUFA/high-SFA oil blend (40.2% SFAs, 22.0% MUFAs). Body fatwas measured using DXA. Five candidate single-nucleotide polymorphisms (SNPs) were genotyped using qualitative PCR. Data were analyzed using a repeated measures mixed model. Results: No significant differences were observed in adiposity measures following the consumption of either highMUFA diet compared with the low-MUFA/high-SFA treatment. However, when stratified by genotype, 3 SNPs within lipoprotein lipase (LPL), adiponectin, and apoE genes influenced, separately, fat mass changes in response to treatment (n = 101). Mainly, the LPL rs13702-CC genotype was associated with lower visceral fat (high-MUFA: -216.2 +/- 58.6 g; low-MUFA: 17.2 +/- 81.1 g; P = 0.017) and android fat mass (high-MUFA: -267.3 +/- 76.4 g; low-MUFA: -21.7 +/- 102.2 g; P = 0.037) following average consumption of the 2 high-MUFA diets. Conclusions: Common variants in LPL, adiponectin, and apoE genes modulated body fat mass response to dietary MUFAs in an isocaloric diet in adults with abdominal obesity. These findings might eventually help in developing personalized dietary recommendations for weight control.

Three recent clinical trials have demonstrated the benefits of marine omega-3 fatty acids on cardiovascular disease end points. In the Vitamin D and Omega-3 Trial (VITAL), 840 mg/d of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) resulted in a 28% reduced risk for heart attacks, 50% reduced risk for fatal heart attacks, and 17% reduced risk for total coronary heart disease events. In the ASCEND trial (A Study of Cardiovascular Events in Diabetes), cardiovascular disease death was significantly reduced by 19% with 840 mg/d of EPA and DHA. However, the primary composite end points were not significantly reduced in either study. In REDUCE-IT (the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), there was a 25% decrease in the primary end point of major cardiovascular events with 4 g/d EPA (icosapent ethyl) in patients with elevated triglycerides (135-499 mg/dL) who also were taking a statin drug. For clinical practice, we now have compelling evidence of the cardiovascular benefits of omega-3 fatty acids. The findings of REDUCE-IT provide a strong rationale for prescribing icosapent ethyl for patients with hypertriglyceridemia who are on a statin. For primary prevention, the goal is to increase the population intake of omega-3 fatty acids to levels currently recommended, which translates to consuming at least one to two servings of fish/seafood per week. For individuals who prefer taking omega-3 fatty acid supplements, recent findings from clinical trials support the benefits for primary prevention.

Three recent clinical trials have demonstrated the benefits of marine omega-3 fatty acids on cardiovascular disease end points. In the Vitamin D and Omega-3 Trial (VITAL), 840 mg/d of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) resulted in a 28% reduced risk for heart attacks, 50% reduced risk for fatal heart attacks, and 17% reduced risk for total coronary heart disease events. In the ASCEND trial (A Study of Cardiovascular Events in Diabetes), cardiovascular disease death was significantly reduced by 19% with 840 mg/d of EPA and DHA. However, the primary composite end points were not significantly reduced in either study. In REDUCE-IT (the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial), there was a 25% decrease in the primary end point of major cardiovascular events with 4 g/d EPA (icosapent ethyl) in patients with elevated triglycerides (135-499 mg/dL) who also were taking a statin drug. For clinical practice, we now have compelling evidence of the cardiovascular benefits of omega-3 fatty acids. The findings of REDUCE-IT provide a strong rationale for prescribing icosapent ethyl for patients with hypertriglyceridemia who are on a statin. For primary prevention, the goal is to increase the population intake of omega-3 fatty acids to levels currently recommended, which translates to consuming at least one to two servings of fish/seafood per week. For individuals who prefer taking omega-3 fatty acid supplements, recent findings from clinical trials support the benefits for primary prevention. REVIEW METHODIST DEBAKEY CARDIOVASC J | 15 (3) 2019 JOURNAL.HOUSTONMETHODIST.ORG 172 a significant 19% reduction in the primary end point, whereas there was no reduction or individuals with higher baseline fish intake. For African Americans, there was a significant 77% reduction in heart attacks in the O3AEE group, a 49% reduction in the need for coronary revascularization, and a 53% reduction in total coronary heart disease. However, VITAL was considered a “null” study because the primary end point of composite major CV events was not significantly reduced (8% reduction, 95% CI, -20% to 6%). The primary end point was unaffected because it was a combination of three CV outcomes, including two that were not reduced by O3AEE treatment (total stroke and death from CVD) and one that was (total myocardial infarction). Thus, pooling them together produced an overall null effect. But should a failure to reduce the risk for stroke and death from CVD nullify the success in reducing rates of myocardial infarction (MI)? In our view, the problem is the convention requiring that the success or failure of a trial depends completely on the effect of the intervention on only one prespecified primary end point—to the exclusion of all other findings. In the case of VITAL, had total MI or coronary heart disease (CHD) been the predefined end point (which would have been reasonable given the long history of demonstrated benefits of omega-3 fatty acids in CVD, but which could not have been confidently foreseen when the trial was being designed), the findings of the study would have been positive. It is true that one cannot go on a fishing expedition for effects with significant p-values in such trials, but the finding of an effect on total CHD or MI should not be considered unexpected or exploratory in VITAL. Thus, despite the published conclusions and subsequent reporting in the media, we contend that this is a positive trial for omega-3 fatty acids, especially given the relatively low dose of EPA and DHA used (< 1 g/d), the fairly short follow-up period, and the focus on primary prevention. A Study of Cardiovascular Events in Diabetes (ASCEND) ASCEND was a 7-year RCT in the United Kingdom that tested the effects of EPA, DHA, and aspirin on CVD events in 15,480 patients with diabetes and no diagnosis of CVD (Table 1).5 The omega-3 product and dose were the same as in VITAL4—one capsule per day of O3AEE—and the placebo was a 1-gram capsule of olive oil. The effects of aspirin in this population were reported in a separate publication and can be summarized as reduced risk for CVD counterbalanced by an increased risk for major bleeding.7 ASCEND also was considered a null omega-3 trial because the primary end point—again, a composite of risk for nonfatal MI, nonfatal stroke, transient ischemic attacks, RANDOMIZED CONTROLLED TRIAL COUNTRY SAMPLE SIZE/SUBJECT TYPE YEARS OF FOLLOW-UP EPA+DHA DOSE FINDINGS ASCEND5 United Kingdom 15,480/patients with type 2 diabetes 7.4 840 mg Composite end point not significantly altered Risk for vascular death ↓ by 19% (95% CI, 1%-33%) VITAL4 United States 25,871/older adults without history of CVD or cancer 5.3 840 mg Composite end point not significantly altered Risk for heart attack ↓ by 28% (95% CI, 10%-41%) Risk for total CHD ↓ by 17% (95% CI, 3%-29%) REDUCE-IT6 International (11 countries) 8,179/statin-treated patients with median TG levels of 216 mg/dL and other CVD risk factors 4.9 3,600 mg (EPA only) Primary CVD end point ↓ by 26% Significant reductions in several secondary end points Table 1. Comparison of three major trials of omega-3 fatty acids reported in 2018. ASCEND: A Study of Cardiovascular Events in Diabetes; VITAL: Vitamin D and Omega-3 Trial; REDUCE-IT (the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial; CVD: cardiovascular disease; TG: triglycerides; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; CHD: coronary heart disease REVIEW METHODIST DEBAKEY CARDIOVASC J | 15 (3) 2019 JOURNAL.HOUSTONMETHODIST.ORG 173 and “vascular death” (including fatal CHD, fatal stroke, and death from other “vascular” causes, in other words, CVD death)—was only 3% lower in the omega-3 group and did not achieve statistical significance. However, as in VITAL, some components were affected and others were not. There was no effect of EPA and DHA on the first three outcomes, but CVD death was significantly reduced by 19%. This important benefit was largely overlooked in the publication, which concluded that their findings did not support the current recommendations for routine dietary supplementation with omega-3 fatty acids to prevent vascular events in patients with diabetes.5 As with VITAL, we take exception to this conclusion since the omega-3 fatty acids clearly provided an important benefit. The reduction in total CVD deaths should not be dismissed simply because this relatively low dose of omega-3 fatty acids did not reduce the risk for all possible CVD end points. In fact, a reduced risk of CV death tends to be the common denominator in most large studies of omega-3 supplementation.8,9 Reduction of Cardiovascular Events with Icosapent Ethyl– Intervention Trial (REDUCE-IT) As opposed to VITAL and ASCEND, REDUCE-IT used icosapent ethyl (IPE; brand name Vascepa, Amarin Corporation), which is EPA in ethyl ester form. Vascepa was the second FDA-approved omega-3 drug indicated for TG lowering.6 It differs from O3AEE that contain both EPA and DHA in the ethyl ester form. REDUCE-IT was designed to investigate whether IPE combined with statin therapy was superior to statin therapy alone when used to prevent long-term CV events in highrisk patients with mixed dyslipidemia. Over 8,000 patients at increased risk of CVD were followed for approximately 5 years (Table 1). Participants were required to have TG levels of 135 to 499 mg/dL as well as known CVD or diabetes and at least one other CV risk factor. Average low-density lipoprotein cholesterol was ∼75 mg/dL (on statins) and average TG levels were ∼216 mg/dL (normal is < 100 mg/dL). Participants were randomized to either 4 g/d IPE or a placebo. IPE significantly reduced CV events by 25%. The following outcomes were also significantly reduced with IPE treatment: • CV death, heart attack, or stroke in the secondary prevention population: 28% (P < .001) • CV death or nonfatal heart attack: 26% (P < .001) • Fatal or nonfatal heart attack: 31% (P < .001) • Urgent or emergent revascularization: 35% (P < .001) • CV death: 20% (P < .03) • Hospitalization or unstable angina: 32% (P < .002) • Fatal or nonfatal stroke: 28% (P < .01) • Total mortality, nonfatal heart attack, or nonfatal stroke: 23% (P < .001) Comparatively, IPE was a more effective add-on agent to statins for reducing adverse CVD outcomes in REDUCE-IT than virtually every hypolipidemic drug tested in the last 12 years, including but not limited to: evolocumab, alirocumab, ezetimibe, niacin, torcetrapib, anacetrapib, and evacetrapib.10-16 Additionally, it was safer and had fewer side effects than any of these other drugs. This is a strong refutation of the view that “fish oil does not work”—a conclusion that is based on studies providing approximately a quarter of the omega-3 dose used here.3,17 The fact that the 4 g/d dose of EPA in REDUCE-IT was remarkably effective strongly reinforces that dose is an important consideration. The outcomes from a larger study with a similar design as REDUCE-IT, the Statin Residual Risk Reduction with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia (STRENGTH) trial, which is using 4 g/day of EPA and DHA (as free fatty acids), are expected in late 2020 and will help to clarify this.18 WHY DID PREVIOUS OMEGA-3 STUDIES FAIL? Many trials have been conducted to assess the effects of long-chain omega-3 fatty acids on CV end points. Studies published prior to 2018 are described in Table 2.19-30 In general, early trials—including DART, GISSI-P, JELIS, and GISSI-HF— reported beneficial effects on CV outcomes,21-23 whereas more recent trials, such as Alpha Omega, OMEGA, SU.FOL.OM3, ORIGIN, AREDS2, and R&P, reported neutral effects.24-27,30 This discrepancy may be attributed to methodological limitations of later trials that biased results toward the null and confounded the interpretation of results. The limitations include short intervention duration, lengthy event-to-enrollment interval in seco

Introduction: The short-chain fatty acids (SCFA) acetic acid, propionic acid, and butyric acid are microbial-produced metabolites that can influence host physiology through regulation of hepatic cholesterol metabolism. These biologically relevant gut metabolites may play a role in the hypocholesterolemic effects of select dietary components. The objective of this exploratory study was to determine the effects of diets that differ only in fatty acid composition on fecal SCFA levels and to assess their correlations with circulating lipids, lipoproteins, and apolipoproteins. Hypothesis: We assessed the hypothesis that dietary fat quality will differentially affect fecal SCFA and there will be significant associations between fecal SCFA levels and those of circulating total cholesterol, low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), and apolipoprotein (apo) B. Methods: In a double-blind, randomized, three period crossover, controlled feeding clinical trial, participants with ≥2 metabolic syndrome criteria (n=20) were provided with a weight maintenance, controlled feeding base diet plus conventional canola oil, high-oleic acid canola oil (HOCO), or a control oil (control diet formulated to represent a Western diet fatty acid profile) for 6 weeks followed by washout periods of ≥4 weeks. The macronutrient profiles of the diets were: canola diet [17.5% monounsaturated fatty acid (MUFA), 9.2% polyunsaturated fatty acid (PUFA), 6.6% saturated fatty acid (SFA)], HOCO diet (19.1% MUFA, 7.0% PUFA, 6.4% SFA), and control diet (10.5% MUFA, 10.0% PUFA, 12.3% SFA). Fecal and blood samples were collected at study enrollment and at the end of each diet. Results: After 6 weeks, a trend toward a treatment effect on endpoint fecal propionic acid was observed ( P =0.09), with a trend toward a higher concentration following the control compared to the canola diet ( P =0.09). Acetic acid was increased from baseline following the control diet ( P =0.04). After the control diet only, fecal levels of propionic acid were positively correlated with blood levels of LDL-C, non-HDL-C, and apo B (r=0.52 to 0.64, P =0.003 to 0.02), with a trend for total cholesterol (r=0.39, P =0.10), and acetic acid was positively correlated with LDL-C and apo B levels (r=0.48 to 0.49, P =0.03 to 0.04), with a trend for non-HDL-C (r=0.44, P =0.06). No significant correlations between fecal SCFA and lipids and lipoproteins were observed after the two canola oil-based diets. Conclusions: In conclusion, these data suggest that the adverse effects of a contemporary Western diet fatty acid profile on circulating lipid and lipoprotein parameters compared to diets higher in unsaturated fat and lower in SFA may be mediated by gut-derived SCFA.

Introduction: Identifying dietary interventions for cardiometabolic disease prevention in individuals with metabolic syndrome is relevant to a significant portion of the population. Numerous studies have investigated the effects of canola oil on cardiovascular disease risk; however, no studies have compared canola oil diets to a control diet with a fatty acid composition characteristic of Western intakes in individuals with metabolic syndrome risk factors. The objectives of this study were to evaluate effects of canola oil, high-oleic acid canola oil (HOCO), and a control oil (blend of butter, safflower, coconut, and flaxseed oils formulated to represent a Western diet fatty acid profile) on lipids, lipoproteins, and apolipoproteins. Hypothesis: We tested the hypothesis that the two canola oil diets would elicit beneficial effects on the total lipid/lipoprotein profile compared to the Western (control oil) diet. Methods: In a multi-center, double blind, randomized, three-period crossover, controlled feeding clinical trial, 119 individuals with an increased waist circumference plus at least one additional metabolic syndrome risk factor consumed prepared isocaloric, weight maintenance diets containing canola oil [17.5% E from monounsaturated fatty acids (MUFA), 9.2% polyunsaturated fatty acids (PUFA), 6.6% saturated fatty acids (SFA)], HOCO (19.1% E from MUFA, 7.0% PUFA, 6.4% SFA), or control oil (11% E from MUFA, 10% PUFA, 12% SFA) for six-weeks each separated by 4-12 week washouts. The differences at the end of 42 days of feeding were tested. Results: The canola oil and HOCO resulted in lower endpoint total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), the TC: high-density lipoprotein-cholesterol (HDL-C) ratio, apolipoprotein (apo) B, the apoB: apoA1 ratio, and non-HDL-C compared to control oil ( P <0.0001 for treatment effect), with no differences between HOCO and canola oil for these parameters. Endpoint apoA1 did not significantly differ between the two canola oils and control, but was higher after the HOCO compared to canola oil (1.46 ± 0.02 g/L vs. 1.43 ± 0.02 g/L, P = 0.0462). There were no differences among the three diets in endpoint triglycerides or HDL-C. Conclusions: Incorporating canola or high-oleic acid canola oils into the diet improves blood lipids and lipoproteins compared to a contemporary Western diet in individuals with at least two criteria for metabolic syndrome.

Purpose of Review This review summarizes recent developments in nutrition and cardiovascular disease (CVD) prevention. Recent Findings Contemporary dietary guidance recommends healthy dietary patterns with emphasis on food-based recommendations because the totality of the diet (i.e., the combinations and quantities of foods and nutrients consumed) is an important determinant of health. In many guidelines, recommendations are still made for saturated fat, added sugar, sodium, and dietary cholesterol because these are over-consumed by many people and are related to chronic disease development. Epidemiological research illustrates the importance of considering the total diet and the interrelatedness of nutrients in a dietary pattern. Traditionally, epidemiological research focused on individual nutrients in isolation, which can result in erroneous conclusions. An example of this, which has led to substantial controversy, is the evidence from studies evaluating the association between saturated fat and CVD without considering the replacement nutrient. Another controversial topic is the relationship between dietary cholesterol and CVD, which is confounded by saturated fat intake. Finally, the totality of evidence shows that high sodium intake is associated with greater CVD risk; however, some epidemiological research has suggested that a low-sodium intake is detrimental, which has caused some controversy. Overall, this reductionist approach has led to a debate about recommendations for saturated fat, cholesterol, and sodium. However, if approaches that accounted for the interrelatedness of nutrients had been taken, it is likely that there would be less controversy about these nutrients. To encourage dietary pattern-based approaches and consideration of total intake, dietary guidelines should emphasize food-based recommendations that meet nutrient targets. Thus, nutrient targets should underpin food-based dietary guidelines, and recommended dietary patterns should comply with nutrient-based targets. Summary The evidence reviewed shows that it is imperative to consider total dietary patterns for CVD prevention. Dietary guidance should be aligned with nutrient targets and recommendations should be food and dietary pattern based.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake is well below the amount recommended by the 2015-2020 Dietary Guidelines for Americans (0.25 g/day), supporting the need for alternative dietary sources. Stearidonic acid (SDA)-enriched soybeans were bioengineered to endogenously synthesize SDA, which can be readily metabolized to EPA in humans; thus, incorporating the derived SDA-enriched soybean oil into the food supply is a potential strategy to increase EPA. We performed a dietary modeling exercise using National Health and Nutrition Examination Survey 2003-2008 repeat 24-h dietary recall data (n = 24,621) to estimate the potential contribution of SDA-enriched oils to total long-chain n-3 fatty acid intake (defined as EPA + DHA + EPA-equivalents) following two hypothetical scenarios: (1) replacement of regular soybean oil with SDA soybean oil and (2) replacement of four common vegetable oils (corn, canola, cottonseed, and soybean) with respective SDA-modified varieties. Estimated median daily intakes increased from 0.11 to 0.16 g/day post-replacement of regular soybean oil with SDA-modified soybean oil, and to 0.21 g/day post-replacement of four oils with SDA-modified oil; the corresponding mean intakes were 0.17, 0.27, and 0.44 g/day, respectively. The percent of the population who met the 0.25 g/day recommendation increased from at least 10% to at least 30% and 40% in scenarios 1 and 2, respectively. Additional strategies are needed to ensure the majority of the US population achieve EPA and DHA recommendations, and should be assessed using methods designed to estimate the distribution of usual intake of these episodically consumed nutrients.

The American Heart Association recommends consuming fish (particularly oily fish) at least two times per week, which would provide ≈ 0.5 g/day of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) for cardiovascular disease risk reduction. Previous analyses indicate that this recommendation is not being met; however, few studies have assessed different ethnicities, subpopulations requiring additional n-3 fatty acid intake (i.e., children and pregnant and/or lactating women), or deciles of intake. Data from the National Health and Nutrition Examination Survey 2003–2008 was used to assess n-3 fatty acid intake from foods and supplements in the US population, according to age, sex, and ethnicity. A unique “EPA equivalents” factor, which accounts for potential conversion of shorter-chain n-3 fatty acids, was used to calculate total long-chain n-3 fatty acid intake. Data are reported for 24,621 individuals. More than 90% consumed less than the recommended 0.5 g/day from food sources (median = 0.11 g/day; mean = 0.17 g/day). Among the top 15% of n-3 fatty acid consumers, fish was the largest dietary contributor (71.2%). Intake was highest in men aged 20 years or more, and lowest in children and women who are or may become pregnant and/or are lactating. Among ethnicities, intake was lowest in Mexican-Americans. Only 6.2% of the total population reported n-3 fatty acid supplement use, and this did not alter median daily intake. Additional strategies are needed to increase awareness of health benefits (particularly among Mexican-Americans and women of childbearing age) and promote consumption of oily fish or alternative dietary sources to meet current recommendations.

The fatty acid ethanolamide oleoylethanolamide (OEA) is an endogenous lipid mediator derived from the monounsaturated fatty acid, oleic acid. OEA is synthesized from membrane glycerophospholipids and is a high-affinity agonist of the nuclear transcription factor peroxisome proliferator-activated receptor α (PPAR-α). Dietary intake of oleic acid elevates circulating levels of OEA in humans by increasing substrate availability for OEA biosynthesis. Numerous clinical studies demonstrate a beneficial relationship between high-oleic acid diets and body composition, with emerging evidence to suggest OEA may mediate this response through modulation of lipid metabolism and energy intake. OEA exposure has been shown to stimulate fatty acid uptake, lipolysis, and β-oxidation, and also promote food intake control. Future research on high-oleic acid diets and body composition is warranted to confirm these outcomes and elucidate the underlying mechanisms by which oleic acid exerts its biological effects. These findings have significant practical implications, as the oleic acid-derived OEA molecule may be a promising therapeutic agent for weight management and obesity treatment.

Early secondary prevention trials of fish and omega-3 polyunsaturated fatty acid (PUFA) capsules reported beneficial effects on cardiovascular disease (CVD) outcomes, including all-cause mortality and sudden cardiac death. These clinical findings, as well as observational and experimental data, demonstrated that omega-3 PUFAs reduced the risk of coronary outcomes and overall mortality and were the basis for recommendations made in the early 2000s to increase omega-3 PUFA intake. In the last 6 years, however, results from both primary and secondary prevention trials have generally failed to show a beneficial effect of omega-3 PUFA supplementation, bringing current recommendations into question. Several possible reasons for these null findings have been proposed, including short treatment periods, relatively low doses of omega-3 PUFAs, small sample sizes, higher background omega-3 intakes, and the concurrent use of modern pharmacotherapy for CVD prevention. At least one of these caveats is being assessed in major clinical trials, with two omega-3 PUFA pharmacological agents being tested at doses of 4 g/day (instead of the more common <1 g/day). These null findings, however, do not necessarily mean that omega-3 PUFAs “are ineffective” in general, only that they were not effective in the context in which they were tested. Accordingly, higher intakes of omega-3 PUFAs, either from fatty fish or from supplements, if continued for decades (as the epidemiological data support) are likely to contribute towards lower risk for CVD. At this time, evidence supports the consumption of a healthy dietary pattern with at least two servings per week of fatty fish. Omega-3 PUFA supplementation is a reasonable alternative for those who do not consume fish, although fish is the preferred source of omega-3 PUFAs because it also provides additional nutrients, some of which are often under-consumed.

Background: Previous research shows that informal caregivers of individuals with a memory disorder experience financial strain, declining physical health, and psychological distress. Various resources and services have been developed to address and/or prevent these potential outcomes, yet caregivers continue to be negatively affected by the demands of caregiving. We hypothesize that better identification and clarification of concrete patient and caregiver needs will aid in the modification and improvement of the available resources. The purpose of this study is to determine the psychosocial needs of the cognitively impaired population and their caregivers. Methods: A one-page Needs Assessment was created to address areas of potential concern for the individual with a memory disorder and the caregiver. This assessment was administered during visits to an outpatient clinic in Philadelphia. Results: A total of 204 Needs Assessments were collected. The significant needs found in our study cohort include sleep, exercise, clinical trials, education, and assistance with ADLs and IADLs. Conclusions: This study satisfied the initial identification of caregiver and patient needs; now each must be explored further to determine how to successfully meet such needs. If the primary needs of the patient can be met by a focused service, the caregiver will no longer be the sole provider of meeting the specific need. This will decrease the involved role of the caregiver, maximize patient homecare, minimize caregiver stress, and increase the quality of life for both the patient and caregiver.

OBJECTIVE: The purpose of this study is to systematically assess gender differences in dementia caregiver risk. The following questions are of interest: Are there gender differences in dementia caregiver risks; Is there an association between sex roles and caregiver risk; Are there gender differences in the challenges dementia caregivers' face; What are specific considerations for a gender integrated intervention for dementia caregivers? BACKGROUND: Health outcomes for patients with dementia are dependent upon informal caregivers. The quality of life and well-being of the caregiver must be at an optimum level in order to provide the best care. Compared to other disease states, dementia caregivers experience greater dependency, provide more extensive assistance and provide care for a longer time period. With disease progression, caregivers often experience increased emotional stress, depression, health impairments, and financial loss. Gender is an important contextual factor that influences the stress response, coping and access to resources. Beyond positing that differences exist in caregiver risk, there is a dearth of current research that explores the role of gender in these processes. DESIGN/METHODS: A mixed methods cross-sectional research design was used to assess the role of gender in dementia caregiver risks, experiences and challenges. The quantitative component includes self-administration of a questionnaire in clinical and community samples. The questionnaire assesses six risk domains: depression, burden, behaviors, support network, safety, and management strategies. The qualitative component includes an analysis of a gender activity and discussion in dementia caregiver support groups. RESULTS: Preliminary data for this study indicates a trend toward significant gender differences in the risk domains of management strategies, behaviors, and support network. Final analysis of 300 caregivers of dementia patients and a subset participating in the qualitative component will be discussed. CONCLUSIONS: The results support the need for development of gender focused caregiver interventions for both clinic and community settings. Study Supported by: Does Not Apply

Medical care professionals must not only identify and address the underlying neurological abnormalities of memory disorder patients, but also evaluate the psychosocial needs to maximize patient homecare and minimize caregiver stress. The use of a “Needs Assessment” aids in understanding a patient/caregiver's concerns and can identify areas of need over time. A one page questionnaire was developed to assess the needs of cognitively impaired Memory Program patients in the Neurology Department of an academic center. The questionnaire addressed the care network, living situation, mobility, safety, physical state, level of independence, and available resources and services. Demographics, health data, and MMSE scores were also obtained. 200 questionnaires were administered at the patient's appointment, completed by the patient and caregiver. 95.2% of patients lived at home, and almost universally expressed a desire to remain there. 69.8% of patients had a caregiver; 49.5% were spouses and 45.5% were other family members. 17.3% of patients received additional help, such as a home health aide or home nurse. 20.6% of patients' were independent with ADLs, 70.1% required some assistance, and 9.3% were completely dependent. 49.5% of caregivers were interested in a caregiver education program. Of those interested, 45% preferred access to an online class, while 35% favored in person sessions. The greatest areas of perceived need were exercise/nutrition programs and clinical trial information. An overwhelming majority of patients live at home with caregivers and are not receiving help from outside sources. This suggests that there is a patient /family commitment to keep cognitively impaired individuals at home. There is need for online and face-to-face caregiver training to optimize safety and function, and to decrease caregiver stress. These findings support the notion that there is a national need to allocate energy and resources to Alzheimer's care.