Marine Omega-3 Research Articles

Circulating Marine and Vegetable Omega-3 at the Time of ST-Segment Elevation Myocardial Infarction and Incident Hard Clinical Endpoints

Abstract Objectives Dietary marine omega-3 eicosapentaenoic acid (EPA) is readily incorporated into cardiac cell membranes, partially replacing the omega-6 arachidonic acid (AA). Blood omega-3 is an objective marker of their intake over the last days. Increasing blood EPA at the time of a ST-segment elevation myocardial infarction (STEMI) relates to a smaller infarct size and preserved long-term left ventricular ejection fraction. We explored whether blood EPA at the time of STEMI also relates to a lower incidence of hard clinical endpoints. We also explored whether blood alpha-linolenic acid (ALA, the vegetable omega-3) modulates such association. Methods We prospectively included 944 consecutive patients treated with primary percutaneous coronary intervention in a single tertiary referral hospital. We determined fatty acids in serum phosphatidylcholine (PC) at 12 hours of evolution. The primary outcomes were cardiovascular disease-related hospital readmission and all-cause mortality after 3 years of follow-up. We constructed multivariable Cox proportional hazards models, calculating risk estimates as hazard ratios (HR). Results The mean age of the cohort was 61 years and 209 (22.1%) were women. During follow-up, 130 patients (13.8%) were readmitted for cardiovascular disease, and 108 (11.4%) died. After adjustment for known clinical predictors, multivariate analysis showed that EPA in serum PC at the time of STEMI inversely related to incident hospital readmission (HR, 0.74; 95% CI, 0.56–0.96; P = 0.024, for a 1 SD increase). Further adjustment for serum PC AA and ALA did not change the association. EPA in serum PC was found to be unrelated to 3-y total mortality. However, after including serum PC proportions of AA and ALA into the model, we observed a significantly decreased risk of mortality for ALA (HR, 0.65; 95% CI, 0.44–0.96; P = 0.030, for a 1 SD increase). Conclusions Increasing proportions of EPA and ALA in serum PC at the time of STEMI inversely relate to 3-y cardiovascular disease-hospital readmission and all-cause mortality, respectively. Dietary EPA and ALA act synergistically and are partners rather than competitors in improving prognosis in case of a STEMI. Funding Sources Instituto de Salud Carlos III, Spain; California Walnut Commission.

Vitamin D supplements and marine omega-3 fatty acids and development of advanced cancer.

1510 Background: Epidemiologic data suggest that vitamin D supplementation may reduce cancer mortality. We tested whether vitamin D and/or omega-3 supplementation reduces the incidence of advanced stage cancer at diagnosis or lethal cancer, and whether body mass index (BMI) modifies these associations. Methods: The VITamin D and OmegA-3 TriaL (VITAL) is a randomized, placebo-controlled, 2x2 factorial trial of vitamin D3 (cholecalciferol, 2000 IU/day) and marine omega-3 fatty acids (1 g/day) that enrolled men aged ≥50 years and women aged ≥55 years free of cancer and cardiovascular disease at baseline. For this particular analysis, the primary outcome is a composite of metastatic and fatal invasive total cancer. Secondary analyses included examination of BMI (<25, 25-<30, and >= 30 kg/m2) as effect modifiers of the observed associations. Results: VITAL randomized 25,871 participants, among whom 1,617 were diagnosed with invasive cancer over a median 5.3 year intervention period. No significant differences by treatment arm (vitamin D vs placebo: hazard ratio [HR]=0.96; 95% confidence interval, 0.88-1.06; p=0.47; omega-3 vs placebo; HR 1.03 [0.93-1.13]; p=0.56) were observed. However, a significant reduction in advanced cancers (metastatic or fatal) was found for those randomized to vitamin D, compared to placebo (226 assigned to vitamin D and 274 to placebo; HR 0.83 [0.69-0.99]; p=0.036). There was no difference by omega-3 assignment (246 assigned to omega-3 and 254 to placebo: HR 0.97 [0.81-1.15], p=0.72). When stratified by BMI, there was a significant reduction for the vitamin D arm in incident metastatic or fatal cancer among those with normal BMI (BMI<25: HR 0.62 [0.45-0.86], but not among those who were overweight or obese (BMI 25-<30: HR 0.89 [0.68-1.17]; BMI >=30: HR 1.05 [0.74-1.49]); p for interaction by BMI =0.03. There was no effect modification by BMI noted for the omega 3 arm. Conclusions: In a randomized clinical trial, supplementation with vitamin D, but not omega-3s, reduced incidence of advanced (metastatic or fatal) cancer in the overall cohort, with strongest risk reduction in normal weight individuals. Further research is needed to understand these findings. Clinical trial information: NCT01169259.

DHA Supplementation Attenuates MI-Induced LV Matrix Remodeling and Dysfunction in Mice.

Objective Myocardial ischemia and reperfusion (I/R) injury is associated with oxidative stress and inflammation, leading to scar development and malfunction. The marine omega-3 fatty acids (ω-3 FA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are mediating cardioprotection and improving clinical outcomes in patients with heart disease. Therefore, we tested the hypothesis that docosahexaenoic acid (DHA) supplementation prior to LAD occlusion-induced myocardial injury (MI) confers cardioprotection in mice. Methods C57BL/6N mice were placed on DHA or control diets (CD) beginning 7 d prior to 60 min LAD occlusion-induced MI or sham surgery. The expression of inflammatory mediators was measured via RT-qPCR. Besides FACS analysis for macrophage quantification and subtype evaluation, macrophage accumulation as well as collagen deposition was quantified in histological sections. Cardiac function was assessed using a pressure-volume catheter for up to 14 d. Results DHA supplementation significantly attenuated the induction of peroxisome proliferator-activated receptor-α (PPAR-α) (2.3 ± 0.4 CD vs. 1.4 ± 0.3 DHA) after LAD occlusion. Furthermore, TNF-α (4.0 ± 0.6 CD vs. 1.5 ± 0.2 DHA), IL-1β (60.7 ± 7.0 CD vs. 11.6 ± 1.9 DHA), and IL-10 (223.8 ± 62.1 CD vs. 135.5 ± 38.5 DHA) mRNA expression increase was diminished in DHA-supplemented mice after 72 h reperfusion. These changes were accompanied by a less prominent switch in α/β myosin heavy chain isoforms. Chemokine mRNA expression was stronger initiated (CCL2 6 h: 32.8 ± 11.5 CD vs. 78.8 ± 13.6 DHA) but terminated earlier (CCL2 72 h: 39.5 ± 7.8 CD vs. 8.2 ± 1.9 DHA; CCL3 72 h: 794.3 ± 270.9 CD vs. 258.2 ± 57.8 DHA) in DHA supplementation compared to CD mice after LAD occlusion. Correspondingly, DHA supplementation was associated with a stronger increase of predominantly alternatively activated Ly6C-positive macrophage phenotype, being associated with less collagen deposition and better LV function (EF 14 d: 17.6 ± 2.6 CD vs. 31.4 ± 1.5 DHA). Conclusion Our data indicate that DHA supplementation mediates cardioprotection from MI via modulation of the inflammatory response with timely and attenuated remodeling. DHA seems to attenuate MI-induced cardiomyocyte injury partly by transient PPAR-α downregulation, diminishing the need for antioxidant mechanisms including mitochondrial function, or α- to β-MHC isoform switch.

Marine Omega-3 (N-3) Fatty Acids for Cardiovascular Health: An Update for 2020.

The omega-3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found in seafood (especially fatty fish), supplements and concentrated pharmaceutical preparations. Long-term prospective cohort studies consistently demonstrate an association between higher intakes of fish, fatty fish and marine n-3 fatty acids (EPA + DHA) or higher levels of EPA and DHA in the body and lower risk of developing cardiovascular disease (CVD), especially coronary heart disease (CHD) and myocardial infarction (MI), and cardiovascular mortality in the general population. This cardioprotective effect of EPA and DHA is most likely due to the beneficial modulation of a number of known risk factors for CVD, such as blood lipids, blood pressure, heart rate and heart rate variability, platelet aggregation, endothelial function, and inflammation. Evidence for primary prevention of CVD through randomised controlled trials (RCTs) is relatively weak. In high-risk patients, especially in the secondary prevention setting (e.g., post-MI), a number of large RCTs support the use of EPA + DHA (or EPA alone) as confirmed through a recent meta-analysis. This review presents some of the key studies that have investigated EPA and DHA in the primary and secondary prevention of CVD, describes potential mechanisms for their cardioprotective effect, and evaluates the more recently published RCTs in the context of existing scientific literature.

Abstract TP433: Effect of Vitamin D and Marine Omega-3 Fatty Acid Supplements on Stroke Outcomes

Introduction: Low serum 25-hydroxyvitamin D (25(OH)D) and low marine omega-3 fatty acid (n-3) intake are associated with increased stroke risk in observational studies. Among stroke patients, low serum 25(OH)D at admission predicts poor outcomes and animal studies suggest that higher n-3 intake may diminish brain damage in ischemic stroke. However, few studies have examined effects of vitamin D or n-3 supplements on stroke outcomes. Hypothesis: We hypothesized that vitamin D (cholecalciferol, 2,000 IU/day) or n-3 (840 mg/day of EPA/DHA [ratio of 1.3:1]) supplementation initiated prior to stroke would reduce risk of functional limitations or physical disability after stroke compared to placebo. Methods: We used data from the completed VITamin D and OmegA-3 TriaL (VITAL) which randomized 25,871 men aged ≥50 years and women aged ≥55 years without cardiovascular disease or cancer at baseline and followed them for incident events over 5.3 years. Individuals experiencing a stroke were mailed a questionnaire to assess functional limitations (with the physical performance scale adapted from Nagi) and physical disability (with the modified Katz Activities of Daily Living and Rosow-Breslau Functional Health scales). We used logistic regression to analyze associations between randomized treatment assignments and limitations on each scale. Results: 290 individuals experienced their first stroke during the trial (including 42 fatal strokes). 197 stroke survivors completed the stroke outcomes questionnaire a mean of 1.6 years after diagnosis. We observed no associations between randomized treatment to vitamin D and functional limitations (odds ratio (OR)=1.01, 95% confidence interval (CI): 0.52, 1.97) or physical disability on the Rosow-Breslau (OR=1.03, 95% CI: 0.31, 3.42) or Katz (OR=0.92, 95% CI: 0.50, 1.67) scales. Although not statistically significant, those randomized to n-3 had lower risk of functional limitations (OR=0.55, 95% CI: 0.28, 1.09) and physical disability on the Katz scale (OR=0.32, 95% CI: 0.50, 1.67) but not on the Rosow-Breslau scale (OR=1.03, 95% CI: 0.31, 3.42). Conclusion: Supplementation with vitamin D or omega-3 fatty acids prior to stroke did not result in significantly improved outcomes after stroke among older individuals.

Adipose tatty acid composition and gene expression in obesity, and response to chronic marine omega-3 fatty acid supplementation.

AbstractIntroduction:Obesity is an excess of adipose tissue (AT) and is linked with increased inflammation that enhances risk of type-2 diabetes and cardiovascular disease. The BIOCLAIMS study assessed the effect of obesity on AT fatty acid composition and gene expression, and the responses of these to chronic omega-3 FA supplementation.Materials and methods:AT biopsies were collected pre- and post-12 week supplementation with 1.1 g EPA + 0.8 g DHA/day or corn oil. The composition of FA in the total lipid extract of AT from 37 normal-weight and 44 obese subjects was assessed by gas chromatography, whole AT transcriptome from 10 normal-weight and 10 obese subjects was assessed by RNA-Sequencing, and selected gene expression in AT of 27 normal-weight and 38 obese subjects was assessed by qRT-PCR.Results:789 AT genes were differentially expressed (623 upregulated, 175 downregulated) in obesity compared to normal-weight (FC > 2, P < 0.05). Differentially expressed genes included EGFL6, MMP-7 and -9, 5-LOX, WNT3 and WNT10B, DACT2, CNR1, SLC27A2 and PLA2G7, and were associated with immune and inflammatory response, cell proliferation, activation and movement, Wnt signalling, remodelling and expansion, and lipid incorporation and degradation.Chronic supplementation with EPA + DHA increased the concentration of AT EPA, DPA and DHA in normal-weight subjects (P < 0.01), and EPA in obese subjects (P = 0.006). EPA + DHA modulated the expression of 26 genes (14 upregulated, 12 downregulated) in normal-weight subjects and 7 genes (3 upregulated, 5 downregulated) in obese subjects (FC > 2, P < 0.05). Of note, EPA + DHA downregulated IGLV1-44, IGLV1-51, PROK2, and TREM1 in normal weight subjects (P < 0.05), and IGLV1-44, IGLV1-47, DACT2 and IDO1 obese subjects (P < 0.05). Genes of note upregulated by EPA + DHA included KCNH2, GCGR, SLC36A2 and FOXC2 in normal-weight subjects, and MAB21L1, LRRTM4, and COX-2, in obese subjects. Differentially expressed genes were associated with a decrease in complement activation and immunoglobulin secretion, negative regulation of cell proliferation, and positive regulation of remodelling, amino acid and glucose transport, and COX pathway metabolite synthesis.Discussion:These data indicate an altered AT transcription profile and gene expression in obesity suggesting enhanced immune and inflammatory response, tissue expansion and remodelling, and changes to lipid metabolism, as well as dysregulation in response to supplementary EPA + DHA at a gene expression level. EPA + DHA are able to modulate AT gene expression predominantly associated with reducing immune response, but obesity may involve resistance to the effects on tissue remodelling and nutrient transport.

Adipose tissue fatty acid and lipid mediator composition in obesity and response to chronic marine omega-3 fatty acid supplementation

AbstractIntroduction:Obesity is an excess of adipose tissue (AT) and is linked with increased inflammation that enhances risk of type-2 diabetes and cardiovascular disease. The BIOCLAIMS study assessed the fatty acid (FA) and lipid mediator composition in normal weight and obese individuals, and their response to chronic omega-3 FA supplementation.Materials and methods:AT biopsies were collected pre- and post-12 week supplementation with 1.1 g EPA + 0.8 g DHA/day or corn oil. The composition of FA in the total lipid extract (TLE) of AT from 37 normal weight and 44 obese subjects was assessed by gas chromatography (GC) and the concentration of lipid mediators in AT TLE of 36 normal weight and 45 obese subjects by coupled GC-mass spectrometry.Results:AT of obese subjects had higher concentrations of arachidonic acid (AA), EPA, DPA, PGF2α, arachidonoylethanolamine (AEA), and eicosapentaenoylethanolamine (EPEA) than that of normal weight subjects (P < 0.05). Obese subjects also had and lower concentrations of mediators derived from linoleic and α-linolenic acids, DHA-derived mediators including RvD2 and hydroxydocosahexaenoic acids (HDHAs), AA-derived mediators including lipoxin-B4, hepoxilin-A3, 11,12-dihydroxyeicosatetrienoic acid (DHET), and 6-keto-PGF1α, and the FA ethanolamine of myristic acid and glycerol ester of palmitic acid (P < 0.05 all) than normal weight subjects.Chronic supplementation with EPA + DHA increased the concentration of EPA (P = 0.006) and EPA-derived lipid mediators including dihydroxyeicosatetrienoic acids, EPEA, and EPA-glycerol ester (P < 0.05), and increased the concentration of DHA (P < 0.001), docosahexaenoylethanolamine, and 8-, 11-, 14-, and 16-HDHA (P < 0.05). Chronic supplementation with EPA + DHA also decreased the concentration 4-, 17-, and 20-HDHA, and AA-derived lipid mediators including DHETs, AEA, and LTs in normal weight subjects (P < 0.05), and decreased 2-AG in obese subjects (P < 0.05).Discussion:These data indicate altered lipid signalling in AT in obesity (at baseline) suggesting dysregulation of adipose tissue expansion and inflammatory signalling, including lack of self-resolution, as well as dysregulation in the utilization of supplementary EPA + DHA for synthesis of anti-inflammatory lipid mediators. EPA + DHA are able to modulate synthesis of EPA-, DHA- and AA-derived lipid mediators but obesity may involve resistance to these effects particularly in endocannabinoid synthesis.

Modulation of the Liver Protein Carbonylome by the Combined Effect of Marine Omega-3 PUFAs and Grape Polyphenols Supplementation in Rats Fed an Obesogenic High Fat and High Sucrose Diet.

Diet-induced obesity has been linked to metabolic disorders such as cardiovascular diseases and type 2 diabetes. A factor linking diet to metabolic disorders is oxidative stress, which can damage biomolecules, especially proteins. The present study was designed to investigate the effect of marine omega-3 polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) and their combination with grape seed polyphenols (GSE) on carbonyl-modified proteins from plasma and liver in Wistar Kyoto rats fed an obesogenic diet, namely high-fat and high-sucrose (HFHS) diet. A proteomics approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labelling of protein carbonyls, visualization of FTSC-labelled protein on 1-DE or 2-DE gels, and protein identification by MS/MS was used for the protein oxidation assessment. Results showed the efficiency of the combination of both bioactive compounds in decreasing the total protein carbonylation induced by HFHS diet in both plasma and liver. The analysis of carbonylated protein targets, also referred to as the ‘carbonylome’, revealed an individual response of liver proteins to supplements and a modulatory effect on specific metabolic pathways and processes due to, at least in part, the control exerted by the supplements on the liver protein carbonylome. This investigation highlights the additive effect of dietary fish oils and grape seed polyphenols in modulating in vivo oxidative damage of proteins induced by the consumption of HFHS diets.

Can mesopelagic mixed layers be used as feed sources for salmon aquaculture?

Salmon aquaculture is in great need of good quality balanced protein and lipid sources, particularly marine omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA), to sustain a further development of the industry. One possibility is to harvest mesopelagic marine layers. Therefore, the current project analysed mesopelagic hauls from three cruises (November 2015 to October 2016) collected from the inner fjord systems around Bergen and in open-waters off Tromsø and Ålesund, Norway. Jellyfish, krill, shrimps and small amounts of the mesopelagic fish, Maurolicus muelleri and Benthosema glaciale, dominated the mixed mesopelagic hauls. Lipid content ranged between 35-40% of dry matter with two samples from autumn being 21 and 13%, with the latter haul being almost exclusively krill. In contrast, M. muelleri and B. glaciale had lipid contents of around 54 and 47% respectively. Overall, lipid was a relatively good source of marine n-3 LC-PUFA, EPA and DHA, being in the range of 15–20% of fatty acids which increased in lean samples. However, many of the trawl hauls contained wax esters (7 out of 9 hauls), equivalent to 40% or more of the lipid, with B. glaciale containing almost 90% wax esters of lipid. This presents a challenge if used in salmon diets, as their utilisation is limited. Protein contents ranged between 45-50%, increasing in lean samples. The essential amino acid content was well above the requirements for Atlantic salmon (Salmo salar) with B. glaciale generally containing higher levels compared to M. muelleri. Leucine, lysine and valine levels were particularly high. Hauls from open-waters contained mixtures of amphipods resulting in cadmium levels exceeding the maximum allowable level in feedstuffs. Arsenic levels were high or borderline. Reducing crustacean mix in hauls appear to be the only option to reduce these levels, whereas mesopelagic fish contained low levels of all heavy metals. In summary, the mesopelagic layer contains protein and lipid sources that could supply raw materials to the salmon aquaculture industry. However, high levels of wax esters, cadmium and arsenic needs to be addressed.

Marine omega-3 (n-3) phospholipids: A comprehensive review of their properties, sources, bioavailability, and relation to brain health.

For several decades, there has been considerable interest in marine-derived long chain n-3 fatty acids (n-3 LCPUFAs) due to their outstanding health benefits. n-3 LCPUFAs can be found in nature either in triglycerides (TAGs) or in phospholipid (PL) form. From brain health point of view, PL n-3 is more bioavailable and potent compared to n-3 in TAG form, as only PL n-3 is able to cross the blood-brain barrier and can be involved in brain biochemical reactions. However, PL n-3 has been ignored in the fish oil industry and frequently removed as an impurity during degumming processes. As a result, PL products derived from marine sources are very limited compared to TAG products. Commercially, PLs are being used in pharmaceutical industries as drug carriers, in food manufacturing as emulsifiers and in cosmetic industries as skin care agents, but most of the PLs used in these applications are produced from vegetable sources that contain less (without EPA, DPA, and DHA) or sometimes no n-3 LCPUFAs. This review provides a comprehensive account of the properties, structures, and major sources of marine PLs, and provides focussed discussion of their relationship to brain health. Epidemiological, laboratory, and clinical studies on n-3 LCPUFAs enriched PLs using different model systems in relation to brain and mental health that have been published over the past few years are discussed in detail.

Effects of One Year of Vitamin D and Marine Omega-3 Fatty Acid Supplementation on Biomarkers of Systemic Inflammation in Older US Adults.

Observational studies suggest vitamin D and marine ω-3 fatty acid (n-3 FA) supplements are associated with lower systemic inflammation. However, past trials have been inconsistent. The randomized, double-blind, placebo-controlled VITamin D and OmegA-3 TriaL (VITAL) tested vitamin D (2000 IU/day) and/or n-3 FA (1 g/day) supplementation in a 2 × 2 factorial design among women ≥55 and men ≥50 years of age. We assessed changes in interleukin (IL)-6, tumor necrosis factor receptor 2 (TNFR2), and high-sensitivity C-reactive protein (hsCRP) concentrations from baseline to 1 year among participants randomized to vitamin D + n-3 FA (392), vitamin D (392), n-3 FA (392), or placebo only (385). Geometric means and percent changes were compared, adjusting for baseline factors. Baseline characteristics were well balanced. In the active arms, 25-OH vitamin D rose 39% and n-3 FA rose 55% vs minimal change in placebo arms. Neither supplement reduced biomarkers at 1 year. Vitamin D resulted in 8.2% higher IL-6 (95% CI, 1.5%-15.3%; adjusted P = 0.02), but TNFR2 and hsCRP did not. Among 784 receiving vitamin D, hsCRP increased 35.7% (7.8%-70.9%) in those with low (<20 ng/mL) but not with higher baseline serum 25(OH) vitamin D [0.45% (-8.9% to 10.8%); P interaction = 0.02]. Among 777 randomized to n-3 FA, hsCRP declined [-10.5% (-20.4% to 0.8%)] in those with baseline low (<1.5 servings/week), but not with higher fish intake [6.4% (95% CI, -7.11% to 21.8%); P interaction = 0.06]. In this large sample from a population-based randomized controlled trial, neither vitamin D nor n-3 FA supplementation over 1 year decreased these biomarkers of inflammation. NCT01169259; NCT01351805.

Effect of High-Dose Marine Omega-3 Fatty Acids on Atherosclerosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

A recent randomized controlled trial (RCT), the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT), reported that high-dose marine omega-3 fatty acids (OM3) significantly reduce cardiovascular disease (CVD) outcomes, yet the mechanisms responsible for this benefit remain unknown. To test the hypothesis that high-dose OM3 is anti-atherosclerotic, we performed a systematic review and meta-analysis of RCT of high-dose OM3 on atherosclerosis. The protocol of this systematic review was registered with PROSPERO (CRD42019125566). PubMed, Embase, Cochran Central Register for Controlled Trials, and Clinicaltrials.gov databases were searched using the following criteria: adult participants, high-dose OM3 (defined as ≥3.0 g/day, or in Japan 1.8 g/day and purity ≥90%) as the intervention, changes in atherosclerosis as the outcome, and RCTs with an intervention duration of ≥6 months. A random-effects meta-analysis was used to pool estimates across studies. Among the 598 articles retrieved, six articles met our criteria. Four RCTs evaluated atherosclerosis in the coronary and two in the carotid arteries. High-dose OM3 significantly slowed the progression of atherosclerosis (standardized mean difference −1.97, 95% confidence interval −3.01, −0.94, p < 0.001). The results indicate that anti-atherosclerotic effect of high-dose OM3 is one potential mechanism in reducing CVD outcomes demonstrated in the REDUCE-IT trial.

Serum 25-hydroxyvitamin D in the VITamin D and OmegA-3 TriaL (VITAL): Clinical and demographic characteristics associated with baseline and change with randomized vitamin D treatment

BackgroundThe VITamin D and OmegA-3 TriaL (VITAL) is a completed randomized, placebo-controlled trial of vitamin D3 (2000 IU/day) and marine omega-3 (1 g/day) supplements in the primary prevention of cancer and cardiovascular disease. Here we examine baseline and change in 25-hydroxyvitamin D (25(OH)D) and related biomarkers with randomized treatment and by clinical factors. MethodsBaseline 25(OH)D was measured in 15,804 participants (mean age 68 years.; 50.8% women; 15.7% African Americans) and in 1660 1-year follow-up samples using liquid chromatography-tandem mass spectrometry and chemiluminescence. Calcium and parathyroid hormone (iPTH) were measured by chemiluminescence and spectrophotometry respectively. ResultsMean baseline total 25(OH)D (ng/mL ± SD) was 30.8 ± 10.0 ng/mL, and correlated inversely with iPTH (r = −0.28), p < .001. After adjusting for clinical factors, 25(OH)D (ng/mL ± SE) was lower in men vs women (29.7 ± 0.30 vs 31.4 ± 0.30, p < .0001) and in African Americans vs whites (27.9 ± 0.29 vs 32.5 ± 0.22, p < .0001). It was also lower with increasing BMI, smoking, and latitude, and varied by season. Mean 1-year 25(OH)D increased by 11.9 ng/mL in the active group and decreased by 0.7 ng/mL in placebo. The largest increases were noted among individuals with low baseline and African Americans. Results were similar for chemiluminescent immunoassay. Mean calcium was unchanged, and iPTH decreased with treatment. ConclusionIn VITAL, baseline 25(OH)D varied by clinical subgroups, was lower in men and African Americans. Concentrations increased with vitamin D supplementation, with the greatest increases in those with lower baseline 25(OH)D. The seasonal trends in 25(OH)D, iPTH, and calcium may be relevant when interpreting 25(OH)D levels for clinical treatment decisions.Clinical Trial Registration: VITAL ClinicalTrials.gov number NCT01169259.

Current level of fish and omega-3 fatty acid intakes and risk of Type 2 diabetes in China

Whether fish and marine omega-3 polyunsaturated fatty acid (PUFA) intakes are linked to type 2 diabetes (T2D) risk remains unclear in China. We aimed to assess the long-term associations in a nationwide cohort. Overall 15,100 Chinese adults, aged ≥20 years, were included from China Health and Nutrition Survey. The cumulative averages of fish and marine omega-3 PUFA intakes were evaluated based on 3-day 24-h records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of T2D risk. Overall 1017 T2D cases were documented over a median of 14 years of follow-up. Compared with non-fish consumers, low and moderate fish consumption were associated with higher T2D risk whereas high fish consumption was not associated. Multivariable-adjusted HRs (95% CIs) for low and moderate fish consumption were 1.43 (1.09, 1.86) and 1.42 (1.07, 1.85) respectively in men, and were 1.58 (1.22, 2.02) and 1.39 (1.08, 1.83) respectively in women. In meat substitution analyses, low and moderate fish consumption was related to 55% and 69% higher T2D risk for men, and was associated with 68% and 54% higher T2D risk for women, respectively. Fried but not non-fried fish intake was associated with higher T2D risk. Intake of marine omega-3 PUFAs was dose-dependently associated with higher T2D risk for both men and women (P-trend<0.001). Overall low and moderate intakes of fish, especially fried fish, and marine omega-3 PUFAs were associated with higher T2D risk. Current level of fish and marine omega-3 PUFA consumption is not protective against T2D incidence among Chinese people.

Abstract LB-249: Marine omega-3 fatty acid supplementation and risk of colorectal adenomas and serrated polyps: A randomized placebo-controlled trial

Abstract BACKGROUND Marine omega-3 fatty acid (MO3FA) has been suggested to protect against colorectal cancer. However, the chemopreventive effect of MO3FA on precursors of colorectal cancer remains unclear. METHODS We assessed the effect of MO3FA supplementation on risk of conventional adenomas and serrated polyps, the two distinct subtypes of precursors of colorectal cancer, within the VITamin D and OmegA-3 TriaL (VITAL), a randomized, placebo-controlled, two-by-two factorial trial of MO3FA (1 g per day [460 mg EPA and 380 mg DHA]) and vitamin D3 (2000 IU per day) supplements among 25,871 Americans aged 50 years or older (including 5,106 blacks). Although regular screening endoscopy was not protocol-mandated during the study period, prior colonoscopy/sigmoidoscopy and other risk factors were well balanced by treatment group at baseline. When participants reported a diagnosis of polyp on the annual follow-up questionnaire, we requested permission to obtain endoscopic and pathologic records to confirm the diagnosis and extract the histopathologic information. Serrated polyps included hyperplastic polyps and mixed/serrated adenomas (traditional and sessile types). We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) in relation to MO3FA treatment using logistic regression, after adjusting for age, sex, vitamin D treatment assignment, and use of endoscopy. We also performed subgroup analyses according to polyp features and participants’ characteristics. RESULTS During a median follow-up of 5.3 years, we documented 296 cases of colorectal adenomas in the intervention group and 306 in the control groups (multivariable OR=0.97, 95% CI, 0.83-1.14); and 178 and 170 cases of serrated polyps in the two groups, respectively (OR=1.05, 95% CI, 0.85-1.30). Similar null association was found for advanced adenomas (advanced histology or ≥10 mm) or high-risk serrated polyps (located in the proximal colon or ≥10 mm), or polyp subgroups according to size, location, multiplicity, or histology. When stratified by race/ethnicity, we found that MO3FA treatment was associated with lower risk of adenomas (OR=0.53, 95% CI, 0.31-0.91) and serrated polyps (OR=0.54, 95% CI, 0.27-1.10) in African Americans, whereas no association was found in non-Hispanic whites or other racial/ethnic groups (P for interaction=0.06 for adenomas and 0.15 for serrated polyps). No interaction was detected with other demographic factors, colorectal cancer risk factors, endoscopic use, baseline fish intake, or plasma MO3FA levels. CONCLUSIONS Supplementation with marine omega-3 fatty acids at a dose of 1 g per day was not associated with risk of colorectal premalignant lesions. A potential benefit among African Americans requires further confirmation. Citation Format: Mingyang Song, I-Min Lee, JoAnn E. Manson, Julie E. Buring, Rimma Dushkes, David Gordon, Joseph Walter, Kana Wu, Andrew T. Chan, Shuji Ogino, Charles S. Fuchs, Jeffrey A. Meyerhardt, Edward L. Giovannucci. Marine omega-3 fatty acid supplementation and risk of colorectal adenomas and serrated polyps: A randomized placebo-controlled trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-249.

Recent Clinical Trials Shed New Light on the Cardiovascular Benefits of Omega-3 Fatty Acids.

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.

Positive Associations of Dietary Marine Omega-3 Polyunsaturated Fatty Acids with Lung Function: A Meta-analysis (P18-087-19)

ObjectivesOur previous study found positive associations between plasma levels of the omega-3 polyunsaturated fatty acids (n-3 PUFAs), specifically docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA), and lung function, especially in current smokers. Given that plasma n-3 PUFA concentrations are driven by dietary intake, we extended our prior findings to a larger sample by studying dietary n-3 PUFAs, including DHA, DPA, eicosapentanoic acid (EPA), and alpha-linolenic acid (ALA), and fish intake. MethodsNine cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N = 37,077 black and white participants) contributed dietary intake and lung function data. In each cohort and each ancestry, separately, associations of dietary n-3 PUFA/fish intake with lung function were estimated in linear regression models. Models were extended to test for n-3 PUFA/fish × smoking status interaction. Fixed-effects meta-analysis was used to generate summarized effect estimates across the cohorts and ancestries. ResultsDietary DPA, DHA, EPA, and fish intake were positively associated with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). ALA had little to no association with these lung function parameters. Associations were similar for black and white participants, and consistent in direction and magnitude across most cohorts. For all participants, 1 standard deviation (SD) higher intake of DPA (∼30 mg/d), DHA (∼200 mg/d), and EPA (∼150 mg/d) were associated with 12–16 mL higher FEV1 and 10–15 mL higher FVC. The effect estimates for fish were in the same direction but smaller in magnitude. Smoking modified the associations of DHA and EPA with FEV1 and FVC; 1 SD higher intake of DHA and EPA were associated with 28–32 mL higher FEV1 and 24–25 mL higher FVC in current smokers, 17–21 mL higher FEV1 and 7–12 mL higher FVC in former smokers, and little to no association in never smokers. ConclusionsDietary DHA, DPA, and EPA, but not ALA, are positively associated with FEV1 and FVC, corroborating our previous findings for plasma n-3 PUFAs. This large cross-sectional meta-analysis shows that diets rich in marine n-3 PUFAs are associated with higher lung function, especially for current and former smokers. Funding SourcesNational Institutes of Health, NHLBI and NIDDK.

The dietary transition and its association with cardiometabolic mortality among Chinese adults, 1982–2012: a cross-sectional population-based study

Few studies have used nationally representative data to describe dietary trends and the related cardiometabolic mortality burden in China. Thus, we aimed to characterise the trends in disease-related dietary factors as well as their associated disease burden among Chinese adults from 1982 to 2012. For this cross-sectional population-based study, we analysed a nationally representative sample of 204 802 adults aged 20 years or older, using data from the 1982, 1992, 2002, and 2010-12 China National Nutrition Surveys (CNNS). We did a comparative risk assessment, in which the effects of suboptimal intakes of 12 dietary factors, individually and collectively, on cardiometabolic mortality were estimated by calculating the population attributable fraction (PAF) to estimate the proportional reduction in cardiometabolic deaths that would occur if exposure to each dietary risk factor was reduced to an alternative optimal level. The overall PAF of mortality from cardiovascular disease and type 2 diabetes that was associated with suboptimal dietary quality was 62·2% in 1982, 57·9% in 1992, 56·2% in 2002, and 51·0% in 2010-12, which accounted for 21·6% of total mortality in China in 1982, 16·6% in 1992, 17·6% in 2002, and 20·8% in 2010-12. The estimated number of cardiometabolic deaths associated with suboptimal dietary intakes was 1·07 million in 1982, 0·93 million in 1992, 1·18 million in 2002, and 1·51 million in 2010-12. Of all 12 dietary factors examined, high sodium intake (17·3%), low fruit consumption (11·5%), and low marine omega-3 fatty acids (9·7%) were associated with the largest numbers of estimated cardiometabolic deaths in 2010-12. We observed an improvement in several dietary factors in China in the past few decades. However, current intakes of these dietary factors remain suboptimal. Poor diet quality is estimated to be associated with a substantial proportion of deaths from heart disease, stroke, and type 2 diabetes in China. Ministry of Health, China, and Ministry of Science and Technology, China.

Effects of Marine Omega-3 Fatty Acids on Cardiovascular Outcomes in Patients with Ischemic Heart Disease: A Meta-Analysis*

Effects of Marine Omega-3 Fatty Acids on Cardiovascular Outcomes in Patients with Ischemic Heart Disease: A Meta-Analysis*

Differences in peripheral blood mononuclear cell gene expression and triglyceride composition in lipoprotein subclasses in plasma triglyceride responders and non-responders to omega-3 supplementation

BackgroundIntake of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduces fasting triglyceride (TG) levels and may thereby lower cardiovascular disease risk. However, there are large inter-individual differences in the TG-lowering effect of omega-3 supplementation. Genotype differences partly explain this variation, but gene-environment interactions leading to gene expression differences may also be important. In this study, we aimed to investigate baseline differences and differences in the change in peripheral blood mononuclear cell (PBMC) gene expression and lipoprotein subclass TG levels between TG responders and non-responders to omega-3 fatty acid supplementation.MethodsIn a previous randomized controlled trial, healthy normotriglyceridemic subjects (n = 35, 71% women) received 1.6 g EPA + DHA/day for 7 weeks. In this exploratory sub-study, we defined TG responders as subjects having a TG reduction beyond the 20% day-to-day variation and non-responders as having a TG change between − 20% and + 20% after omega-3 supplementation. PBMC gene expression was measured using microarray, and lipoprotein subclasses were measured using nuclear magnetic resonance spectroscopy.ResultsEight subjects were defined as responders with a median TG reduction of 37%, and 16 subjects were defined as non-responders with a median TG change of 0%. At baseline, responders had higher TG levels in two of four high-density lipoprotein (HDL) subclasses and 909 gene transcripts (p ≤ 0.05) were differentially expressed compared to non-responders. During the intervention, the plasma TG reduction among responders was reflected in TG reductions in four of six different very low-density lipoprotein subclasses and three of four different HDL subclasses. Compared to non-responders, the expression of 454 transcripts was differentially altered in responders (p ≤ 0.05). Pathway analyses revealed that responders had altered signaling pathways related to development and immune function. In addition, two of the top 10 enriched pathways in responders compared to non-responders were related to lysophosphatidic acid signaling.ConclusionTG responders and non-responders to omega-3 supplementation have different lipoprotein subclass and PBMC gene expression profiles at baseline and different lipoprotein subclass and PBMC gene expression responses to omega-3 supplementation. These gene expression differences may partially explain the variability in TG response observed after omega-3 supplementation.Graphical abstractBased on free images from Servier Medical Art (Creative Commons Attribution License) and image from www.colourbox.com.