Abstract 397: Correlation Between the Whole Blood Omega-Score and Red Blood Cell Membrane Omega-3 Index in a Patient Population with Cardiovascular Disease Risk Factors Treated With a Unique Omega-3 Formulation

Background: Growing evidence supports the value of maintaining a diet rich in omega-3 polyunsaturated fatty acids (PUFA) to achieve longevity of cardiovascular health, and prevent sudden death. Omega-3 deficiency (OM3D) is highly prevalent in the US and contributes to 84,000 deaths/year. To identify patients at risk with OM3D, two laboratory tests are available, including the Omega-Score (OS - whole blood), as well as the Omega-3 Index (OI - red blood cell membrane), that measure omega-3 blood levels. Omega-Score or OI levels &lt;6.1% suggest OM3D. Here we report on the dietary omega-3 status of Canadians, including those with CVD risk factors, through a comparative analysis of the OS vs. OI both pre- and post-treatment with a unique omega-3 formulation. Methods: Open label study of 143 study subjects enrolled for baseline omega-3 deficiency assessment, of which 63 subjects were scheduled to receive a 4 g/day regimen of a highly purified (&gt;90%) omega-3 formulation (2720 mg/day of EPA + 440 mg/day of DHA), a ratio of 6:1 EPA:DHA (6:1 OM-3) for two weeks, and 31 subjects received 6:1 OM-3 for six weeks. Diagnostic evaluation of the OS, and OI was carried out at baseline, and every two weeks until the study completion. Results: The majority (84.5%) of subjects tested at baseline had OS levels &lt;6.1%. The baseline, mean OS and OI levels were 3.4% and 4.4% respectively (N=143). After six weeks of treatment, a significant improvement in the OS (120.6% increase, p&lt;0.0001), and OI (72.7% increase, p&lt;0.0001) was observed (N=31). Comparative analysis of the OS vs. the OI resulted in comparable values, with a greater baseline OI, but with near-identical resultant OS an OI levels after six weeks of treatment (7.5%, vs. 7.6% respectively). Conclusions: This study shows that both the OS and OI provide highly correlative results in the assessment of nutritional omega-3 deficiency, and response to treatment with 6:1 OM-3. </jats:p

Abstract 447: Treatment of Omega-3 Nutritional Deficiency Improves Cardiovascular Disease Risk Factors: Results of the Randomized, Double-Blind, Placebo-Controlled VASCAZEN-REVEAL Trial

Introduction Treatments with Omega-3 (OM3) formulations have been suggested to have cardio-protective effects. A strong association of high plasma OM3 levels has been correlated with reduced risk of sudden death and “risk quartiles” based upon OM3 levels, have been previously described. However, systematic studies describing the extent of OM3 deficiency, it’s correction by intervention, and improvement in CVD risk factors are lacking. Our study is the first to determine dietary levels of OM3 in plasma and in red blood cells using Omega-Score and Omega-3 Index diagnostics, improvement after treatment with a proprietary “&gt;90%-pure OM3 preparation with a 6:1 EPA (eicosapentaenoic acid): DHA (docosapentaenoic acid) ratio” (6:1-OM3), and the concomitant beneficial effects on CVD risk factors in patients with high triglycerides (TG 200-500mg/dL). Hypothesis CVD patients are nutritionally deficient in OM3 fatty acids, and through treatment with 6:1-OM3, such deficiency can be corrected, improving CVD risk factors. Methods A double blind, placebo-controlled study comprised of 110 subjects randomized and stratified by baseline TG levels (A: 90-199 mg/dL, and B: 200-500mg/dL). This report includes placebo (corn oil, n=54) and 6:1-OM3 treatment (&gt; 3g of EPA + DHA/day; n=56) groups at baseline and after 8 weeks of treatment. The primary endpoints were the change in the Omega-Score (OS) and Omega-3-Index (OI), with secondary endpoints including the change in serum TG, lipoprotein cholesterol (VLDL, LDL, HDL, ApoB, and subfractions), and hsCRP. Results 89% of screened CVD subjects (N=655) were nutritionally deficient in Omega-3. In group B subjects, a significant (p&lt;0.0001) increase in OS (121%) and OI (112%) was observed in treated subjects with a TG reduction of 48% (p=0.0005), VLDL-C reduction of 30% (p=0.0023) and HDL-C increase of 9% (p=0.0069) without significantly affecting LDL-C, ApoB or hsCRP levels. Conclusions This study confirms that omega-3 deficiency is prevalent with CVD, and that such a deficiency can be corrected with 6:1-OM3 resulting in a concomitant and significant placebo-corrected reduction in TG and VLDL, and increase in HDL-C in patients with high TG (200-500mg/dL), without adversely affecting LDL-C. </jats:sec

Abstract 20243: Differential Uptake of Omega-3 Polyunsaturated Fatty Acids in Trial Subjects Could Explain Variability of the Trials’ Outcome

Background: A relationship of regular fish consumption with lowered incidence of cardiovascular disease (CVD) has been appreciated for decades. However, preparations from fish oils, showed mixed results in recent meta-analyses and have raised some doubts on the efficacy of omega-3 polyunsaturated fatty acids (ω-3 PUFA) for management of CVD. Some of these reports suffer from inclusion of studies with ill-defined patient populations, varying PUFA doses, purity, and formulation, while others have patients on drug milieu or have employed placebo that could have undermine the trial outcome. Very few studies have determined ω-3 PUFA levels pre &amp; post treatment. In this report, we are the first to describe heterogeneity of Omega 3 uptake among trial subjects that could have contributed to the inconsistencies of results. Methods: In VASCAZEN-REVEAL trials, 54 subjects with normal to high blood triglycerides levels (TG 90-500mg/dl) and with ω-3 PUFA deficiency (Omega-Score™, OS, blood levels of eicosapentaenoic (EPA)+docosahexaenoic (DHA) +docosapentaenoic acid (DPA) of &lt;6.1% of total blood fatty acids) were provided 4g/day of 6:1 EPA/DHA formulation (&gt;90% purity) for 8 weeks. Changes in the OS levels pre-and post treatment along with individual fatty acids including arachidonic (AA) were determined and desaturation enzymes activities were calculated. Results: Based upon post-treatment increases in the blood levels of OS, weak (WR), intermediate (IR) and strong (SR) responders were identified. Conclusion: This is the first report to show differential effect of Omega-3 on trial subjects and warrants caution in the interpretation of trial data without identifying the responders. </jats:p

Abstract 589: Correction of Long-Chain Omega-3 Fatty Acid Deficiency With a Unique Omega-3 Formulation is Associated With a Significant Reduction in Atherogenic Index of Plasma in Hypertriglyceridemic Patients: Results of the VASCAZEN-REVEAL Trial

Background: A large number of studies have suggested that the triglyceride/high density lipoprotein cholesterol (TG/HDL-C)) ratio provides useful information about atherogenicity of plasma (AIP) and that a higher ratio has been linked to increased incidence of myocardial infarction. Others have suggested the use of AIP (log ratio of molar concentrations of TG to HDL-C) as a significant predictor of cardiovascular risk and to identify insulin resistant individuals at high cardio-metabolic risk. In this report, we analyzed data from the VASCAZEN-REVEAL trial to investigate if the correction of Omega-3 fatty acid deficiency with a unique Omega-3 formulation (referred to as 6:1 OM-3) in 6:1 ratio of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids affects TG/HDL-C and AIP indices in hypertriglyceridemic subjects. Methods: A double blind, placebo-controlled study of 42 ambulatory cardiovascular subjects with elevated baseline TG levels (200-500mg/dL) were treated with either placebo (corn oil, 4g/day, n=22) or with 6:1 OM-3 (4g/day; n=20) for 8 weeks. Primary endpoint: Correction of OM-3 deficiency by determining changes in the Omega Score (OS, constituting blood concentration of EPA, DHA and DPA-docosapentaenoic acids). Secondary endpoints: changes in the serum lipid profile including TG and HDL-C. Results: Eight weeks of treatment with 6:1 OM-3 resulted in a significant increase in placebo adjusted median OS (+120.8%, p&lt;0.0001) with concomitant reduction in TG/HDL (-50.3%, p=0.0005), AIP (-46.9%, p&lt; 0.0006) and in AA (arachidonic acid): EPA (-86.6%, p&lt;0.0001) ratios. No significant changes in OS (-2.0% p= 0.5519), TG/HDL (+4.72%, p=0.5233), AIP (+2.43%, p=0.8119) or in AA/EPA (11.3%, p=0.6780) ratios were observed in placebo. Treatment with 6:1 OM-3 also resulted in a significant increase in placebo adjusted median levels of HDL-C (+9.1%, p=0.0069), a significant decrease in VLDL-C (-30.2%, p=0.0023) and with no significant changes in LDL-C (+11.3, p=0.1164). Conclusions: This study shows that 6:1 OM-3 is effective in correcting OM-3 deficiency in hypertriglyceridemic patients and that this correction is strongly associated with significant decreases in TG/HDL ratio and in AIP- an emerging predictor of cardiovascular risk. </jats:p

TRPV1+ Sensory Neurons Control β Cell Stress and Islet Inflammation in Autoimmune Diabetes

SummaryIn type 1 diabetes, T cell-mediated death of pancreatic β cells produces insulin deficiency. However, what attracts or restricts broadly autoreactive lymphocyte pools to the pancreas remains unclear. We report that TRPV1+ pancreatic sensory neurons control islet inflammation and insulin resistance. Eliminating these neurons in diabetes-prone NOD mice prevents insulitis and diabetes, despite systemic persistence of pathogenic T cell pools. Insulin resistance and β cell stress of prediabetic NOD mice are prevented when TRPV1+ neurons are eliminated. TRPV1NOD, localized to the Idd4.1 diabetes-risk locus, is a hypofunctional mutant, mediating depressed neurogenic inflammation. Delivering the neuropeptide substance P by intra-arterial injection into the NOD pancreas reverses abnormal insulin resistance, insulitis, and diabetes for weeks. Concordantly, insulin sensitivity is enhanced in trpv1−/− mice, whereas insulitis/diabetes-resistant NODxB6Idd4-congenic mice, carrying wild-type TRPV1, show restored TRPV1 function and insulin sensitivity. Our data uncover a fundamental role for insulin-responsive TRPV1+ sensory neurons in β cell function and diabetes pathoetiology

Additional file 1 of TRPV1 Gates Tissue Access and Sustains Pathogenicity in Autoimmune Encephalitis

Supplementary material, approximately 2.03 MB