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A randomized controlled trial to determine whether beta-hydroxy-beta-methylbutyrate and/or eicosapentaenoic acid improves diaphragm and quadriceps strength in critically Ill mechanically ventilated patients.
Supinski, GS, Netzel, PF, Westgate, PM, Schroder, EA, Wang, L, Callahan, LA
Critical care (London, England). 2021;(1):308
Abstract
BACKGROUND Intensive care unit acquired weakness is a serious problem, contributing to respiratory failure and reductions in ambulation. Currently, there is no pharmacological therapy for this condition. Studies indicate, however, that both beta-hydroxy-beta-methylbutyrate (HMB) and eicosapentaenoic acid (EPA) increase muscle function in patients with cancer and in older adults. The purpose of this study was to determine whether HMB and/or EPA administration would increase diaphragm and quadriceps strength in mechanically ventilated patients. METHODS Studies were performed on 83 mechanically ventilated patients who were recruited from the Medical Intensive Care Units at the University of Kentucky. Diaphragm strength was assessed as the trans-diaphragmatic pressure generated by supramaximal magnetic phrenic nerve stimulation (PdiTw). Quadriceps strength was assessed as leg force generated by supramaximal magnetic femoral nerve stimulation (QuadTw). Diaphragm and quadriceps thickness were assessed by ultrasound. Baseline measurements of muscle strength and size were performed, and patients were then randomized to one of four treatment groups (placebo, HMB 3 gm/day, EPA 2 gm/day and HMB plus EPA). Strength and size measurements were repeated 11 days after study entry. ANCOVA statistical testing was used to compare variables across the four experimental groups. RESULTS Treatments failed to increase the strength and thickness of either the diaphragm or quadriceps when compared to placebo. In addition, treatments also failed to decrease the duration of mechanical ventilation after study entry. CONCLUSIONS These results indicate that a 10-day course of HMB and/or EPA does not improve skeletal muscle strength in critically ill mechanically ventilated patients. These findings also confirm previous reports that diaphragm and leg strength in these patients are profoundly low. Additional studies will be needed to examine the effects of other anabolic agents and innovative forms of physical therapy. TRIAL REGISTRATION ClinicalTrials.gov, NCT01270516. Registered 5 January 2011, https://clinicaltrials.gov/ct2/show/NCT01270516?term=Supinski&draw=2&rank=4 .
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Secondary data analysis investigating effects of marine omega-3 fatty acids on circulating levels of leptin and adiponectin in older adults.
Rausch, JA, Gillespie, S, Orchard, T, Tan, A, McDaniel, JC
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102302
Abstract
BACKGROUND Higher leptin and lower adiponectin levels have been linked to progressing systemic inflammation and diseases of aging. Among older adults with obesity and an inflammatory conditions, we quantified effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on leptin, adiponectin, and the leptin-to-adiponectin ratio (LAR). We also examined associations among adipokine and cytokine levels. METHODS Using a randomized, double-blind, placebo-controlled design, participants (mean age 61.3 ± 2.1) received 1.5 g EPA + 1.0 g DHA (n = 14) or mineral oil (n = 18) daily. Plasma adipokine and cytokine levels were quantified by electrochemiluminescence at all study intervals. RESULTS While no between-group differences were detected, there was a reduction in the LAR (by 23%, p=.065) between weeks 4 and 8 among the EPA+DHA group. Adiponectin levels were negatively associated with IL-1β levels at week 4 (p=.02) and TNF-α levels at week 8 (p=.03). CONCLUSION Potential benefits of EPA+DHA supplementation among aging populations warrant further study.
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Secular Decreasing Trend in Plasma Eicosapentaenoic and Docosahexaenoic Acids among Patients with Acute Coronary Syndrome from 2011 to 2019: A Single Center Descriptive Study.
Okada, T, Miyoshi, T, Doi, M, Seiyama, K, Takagi, W, Sogo, M, Nosaka, K, Takahashi, M, Okawa, K, Ito, H
Nutrients. 2021;(1)
Abstract
Despite intensive lipid-lowering interventions, patients treated with statins develop atherosclerotic cardiovascular disease (ASCVD), and these patients have an increased risk of developing recurrent cardiovascular events during follow-up. Therefore, there is a need to focus on the residual risks in patients in statin therapy to further reduce ASCVD. The aim of this study was to retrospectively investigate the 10-year trend (2011-2019) regarding changes in polyunsaturated fatty acids (PUFAs) in patients with acute coronary syndrome (ACS) in a single center. We included 686 men and 203 women with ACS admitted to Kagawa Prefectural Central Hospital. Plasma PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-γ-linolenic acid (DGLA), were measured at admission for suspected ACS. A secular decreasing trend in the levels of EPA and DHA and the EPA/AA ratio, but not of AA and DGLA, was observed. The analyses based on age (>70 or <70 years) and sex showed that the decreasing trend in the levels of EPA and DHA did not depend on age and remained significant only in men. Further studies are needed to obtain robust evidence to justify that the administration of n-3 PUFA contributes to the secondary prevention of ACS.
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Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation: A Randomized Clinical Trial.
Albert, CM, Cook, NR, Pester, J, Moorthy, MV, Ridge, C, Danik, JS, Gencer, B, Siddiqi, HK, Ng, C, Gibson, H, et al
JAMA. 2021;(11):1061-1073
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Abstract
IMPORTANCE Atrial fibrillation (AF) is the most common heart rhythm disturbance, continues to increase in incidence, and results in significant morbidity and mortality. The marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D have been reported to have both benefits and risks with respect to incident AF, but large-scale, long-term randomized trial data are lacking. OBJECTIVE To test the effects of long-term administration of marine omega-3 fatty acids and vitamin D on incident AF. DESIGN, SETTING, AND PARTICIPANTS An ancillary study of a 2 × 2 factorial randomized clinical trial involving 25 119 women and men aged 50 years or older without prior cardiovascular disease, cancer, or AF. Participants were recruited directly by mail between November 2011 and March 2014 from all 50 US states and were followed up until December 31, 2017. INTERVENTIONS Participants were randomized to receive EPA-DHA (460 mg/d of EPA and 380 mg/d of DHA) and vitamin D3 (2000 IU/d) (n = 6272 analyzed); EPA-DHA and placebo (n = 6270 analyzed); vitamin D3 and placebo (n = 6281 analyzed); or 2 placebos (n = 6296 analyzed). MAIN OUTCOMES AND MEASURES The primary outcome was incident AF confirmed by medical record review. RESULTS Among the 25 119 participants who were randomized and included in the analysis (mean age, 66.7 years; 50.8% women), 24 127 (96.1%) completed the trial. Over a median 5.3 years of treatment and follow-up, the primary end point of incident AF occurred in 900 participants (3.6% of study population). For the EPA-DHA vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.24; P = .19). For the vitamin D3 vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.25; P = .19). There was no evidence for interaction between the 2 study agents (P = .39). CONCLUSIONS AND RELEVANCE Among adults aged 50 years or older, treatment with EPA-DHA or vitamin D3, compared with placebo, resulted in no significant difference in the risk of incident AF over a median follow-up of more than 5 years. The findings do not support the use of either agent for the primary prevention of incident AF. TRIAL REGISTRATION ClinicalTrials.gov Identifiers: NCT02178410; NCT01169259.
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Body surface area-based omega-3 fatty acids supplementation strongly correlates to blood concentrations in children.
Ljungblad, L, Gleissman, H, Hedberg, G, Wickström, M, Eissler, N, Pickova, J, Johnsen, JI, Tedroff, K, Strandvik, B, Kogner, P
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102285
Abstract
Omega-3 fatty acids have been suggested as a complement in cancer treatment, but doses are not established. We performed a dose-finding study in 33 children in remission from cancer. Participants were allocated to a body surface area (BSA) adjusted dose (mg/m2) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (40:60), ranging 233-3448 mg/m2 daily for 90 days. Fatty acid concentration in plasma phospholipids and red blood cells were determined by GC. Supplementation was well tolerated and correlated strongly with blood ω3-fatty acid concentrations and EPA showed the highest increase. Using the ω3-index disregards docosapentaenoic acid (DPA), which increased 30-43% in our study motivating an EDD-index (∑EPA,DPA,DHA). The ratio between arachidonic acid and EPA or DHA showed negative exponential trends. Dose per BSA enabled an individualized omega-3 supplementation decreasing the variation referred to interindividual differences. Based on our results, we suggest a dose of 1500 mg/m2 BSA for further studies.
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Effects of n-3 EPA and DHA supplementation on fat free mass and physical performance in elderly. A systematic review and meta-analysis of randomized clinical trial.
Rondanelli, M, Perna, S, Riva, A, Petrangolini, G, Di Paolo, E, Gasparri, C
Mechanisms of ageing and development. 2021;:111476
Abstract
The most studied n-3 polyunsaturated fatty acids (n-3 PUFAs) are eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), and their intake seem to have a positive effect on skeletal muscle. This systematic review and meta-analysis aims to investigate the effect of n-3 EPA and DHA supplementation on fat free mass, and on different indexes of physical performance in the elderly. Eligible studies included RCT studies that investigated EPA and DHA intervention. Random-effects models have been used in order to estimate pooled effect sizes, the mean differences, and 95 % CIs. Findings from 14 studies (n = 2220 participants) lasting from 6 to 144 weeks have been summarized in this article. The meta-analyzed mean differences for random effects showed that daily n-3 EPA + DHA supplementation (from 0.7 g to 3.36 g) decreases the time of Time Up and Go (TUG) test of -0.28 s (CI 95 %-0.43, -0.13;). No statistically significant effects on physical performance indicators, such as 4-meter Walking Test, Chair Rise Test and Handgrip Strength, have been found. The fat free mass follows an improvement trend of +0.30 kg (CI 95 % -0.39, 0.99) but not statistically significant. N-3 EPA + DHA supplementation could be a promising strategy in order to enhance muscle quality and prevent or treat frailty.
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Aspirin and omega-3 fatty acid status interact in the prevention of cardiovascular diseases in Framingham Heart Study.
Block, RC, Shearer, GC, Holub, A, Tu, XM, Mousa, S, Brenna, JT, Harris, WS, Tintle, N
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102283
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BACKGROUND The roles of omega-3 (n3) fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and low-dose aspirin in the primary prevention of ischemic cardiovascular disease (CVD) are controversial. Since omega-3 (n3) fatty acids and aspirin affect cyclooxygenase activity in platelets, there could be a clinically-relevant effect of aspirin combined with a particular n3 fatty acid level present in each individual. METHODS RBC EPA+DHA, arachidonic acid (AA) and docosapentaenoic acid (DPA) were measured in 2500 participants without known CVD in the Framingham Heart Study. We then tested for interactions with reported aspirin use (1004 reported use and 1494 did not) on CVD outcomes. The median follow-up was 7.2 years. RESULTS Having RBC EPA+DHA in the second quintile (4.2-4.9% of total fatty acids) was associated with significantly reduced risk for future CVD events (relative to the first quintile, <4.2%) in those who did not take aspirin (HR 0.54 (0.30, 0.98)), but in those reporting aspirin use, risk was significantly increased (HR 2.16 (1.19, 3.92)) in this quintile. This interaction remained significant when adjusting for confounders. Significant interactions were also present for coronary heart disease and stroke outcomes using the same quintiles. Similar findings were present for EPA and DHA alone but not for DPA and AA. CONCLUSIONS There is a complex interaction between aspirin use and RBC EPA+DHA levels on CVD outcomes. This suggests that aspirin use may be beneficial in one omega-3 environment but harmful in another, implying that a personalized approach to both aspirin use and omega-3 supplementation may be needed.
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Dietary Reference Intakes based on chronic disease endpoints: outcomes from a case study workshop for omega 3's EPA and DHA.
Racey, M, MacFarlane, A, Carlson, SE, Stark, KD, Plourde, M, Field, CJ, Yates, AA, Wells, G, Grantham, A, Bazinet, RP, et al
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2021;(5):530-539
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Given the focus on developing Dietary Reference Intakes (DRIs) based on chronic disease risk reduction and recent research for omega-3 long chain PUFA since the last DRI review, the Canadian Nutrition Society convened a panel of stakeholders for a 1-day workshop in late 2019. Attendees discussed the new NASEM guidelines for establishing DRI values based on chronic disease risk endpoints and the strength of current evidence for EPA and DHA as it relates to the new guidelines. Novelty: Summarizes evidence and expert opinions regarding the potential for reviewing DRI values for EPA and DHA and cardiovascular disease risk and early development.
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Effects of dietary eicosapentaenoic acid and docosahexaenoic acid supplementation on metabolic syndrome: A systematic review and meta-analysis of data from 33 randomized controlled trials.
Zhang, HJ, Gao, X, Guo, XF, Li, KL, Li, S, Sinclair, AJ, Li, D
Clinical nutrition (Edinburgh, Scotland). 2021;(7):4538-4550
Abstract
BACKGROUND & AIMS Previous randomized controlled trials (RCTs) have compared the effects of pure preparations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in reducing metabolic syndrome (MetS) risk factors, but the results were inconsistent. The present study aimed to clarify whether EPA and DHA have differential effects on MetS features in humans. METHODS A systematic literature search was conducted in CNKI, PubMed, Embase and Scopus updated to February 2021. The mean changes in the characteristics of MetS were calculated as weighted mean differences by using a random-effects model. Thirty-three RCTs were included. RESULTS The results showed that both EPA and DHA were effective at lowering serum triglycerides (TG) levels. EPA supplementation decreased the serum levels of total cholesterol (TC) (WMD = -0.24 mmol/L; 95% CI, -0.43, -0.05 mmol/L), TG (WMD = -0.77 mmol/L; 95% CI, -1.54, -0.00 mmol/L) and low density lipoprotein-cholesterol (LDL-C) (WMD = -0.13 mmol/L; 95% CI, -0.25, -0.01 mmol/L), while DHA increased the serum levels of TC (WMD = 0.14 mmol/L; 95% CI, 0.03, 0.25 mmol/L), LDL-C (WMD = 0.26 mmol/L; 95% CI, 0.15, 0.38 mmol/L) and high density lipoprotein-cholesterol (HDL-C) (WMD = 0.07 mmol/L; 95% CI, 0.04, 0.09 mmol/L). Moreover, DHA increased the serum levels of insulin compared with EPA, especially in subgroups whose mean age was <60 years (0.43 mU/L; 95% CI: 0.04, 0.81 mU/L) and duration of DHA supplementation < 3 months (0.39 mU/L; 95% CI: 0.01, 0.77 mU/L). CONCLUSIONS The present meta-analysis provides evidence that EPA and DHA have different effects on risk factors of MetS.
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High Variability in Erythrocyte, Plasma and Whole Blood EPA and DHA Levels in Response to Supplementation.
Sparkes, C, Sinclair, AJ, Gibson, RA, Else, PL, Meyer, BJ
Nutrients. 2020;(4)
Abstract
(1) Aim: the aim of this secondary analysis was to report the variability in response to n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation in erythrocytes, plasma and whole blood of a previously published dose response study. (2) Methods: a randomized, double-blind, placebo-controlled trial of parallel design was conducted, whereby pre-menopausal women were randomly assigned to consume 0, 0.35, 0.7 or 1 g/day of supplemental eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Fasted blood samples were taken at baseline and after eight weeks intervention. Erythrocyte, plasma and whole blood fatty acids were extracted using the method of Lepage and Roy and analysed using gas chromatography. (3) Results: There were significant increases in EPA plus DHA levels in the 0.7 g and 1 g dose groups, with the highest increase with the 1 g dose notably: in erythrocytes (from 5.69% to 7.59%), plasma (from 2.94% to 5.48%) and in whole blood (from 3.81% to 6.03%). There was high variability in response to the supplement in erythrocytes, plasma and whole blood across the different doses. (4) Conclusion: there is high individual variability in n-3 LCPUFA levels in response to n-3 LCPUFA supplementation, which should be taken into account in clinical trials using n-3 LCPUFA supplements.