Omega-3 Fatty Acids In Prevention Research Articles

Active oils, comparator oils, and study populations as explanations for contrasting results of reduce-it vs. strength: copenhagen general population study mimicking trial designs

Background and Aims: We tested the hypothesis that conflicting results for the efficacy of high-dose, purified omega-3 fatty acids for prevention of atherosclerotic cardiovascular disease (ASCVD) in two randomized trials, REDUCE-IT and STRENGTH, can be explained by differences in active oil, comparator oil, and study population.

Prospective Evaluation of Clinico-Pathological Predictors of Postoperative Atrial Fibrillation: An Ancillary Study From the OPERA Trial.

Postoperative atrial fibrillation (POAF) occurs in 30% to 50% of patients undergoing cardiac surgery and is associated with increased morbidity and mortality. Prospective identification of structural/molecular changes in atrial myocardium that correlate with myocardial injury and precede and predict risk of POAF may identify new molecular pathways and targets for prevention of this common morbid complication. Right atrial appendage samples were prospectively collected during cardiac surgery from 239 patients enrolled in the OPERA trial (Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation), fixed in 10% buffered formalin, and embedded in paraffin for histology. We assessed general tissue morphology, cardiomyocyte diameters, myocytolysis (perinuclear myofibril loss), accumulation of perinuclear glycogen, interstitial fibrosis, and myocardial gap junction distribution. We also assayed NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT, CRP (C-reactive protein), and circulating oxidative stress biomarkers (F2-isoprostanes, F3-isoprostanes, isofurans) in plasma collected before, during, and 48 hours after surgery. POAF was defined as occurrence of postcardiac surgery atrial fibrillation or flutter of at least 30 seconds duration confirmed by rhythm strip or 12-lead ECG. The follow-up period for all arrhythmias was from surgery until hospital discharge or postoperative day 10. Thirty-five percent of patients experienced POAF. Compared with the non-POAF group, they were slightly older and more likely to have chronic obstructive pulmonary disease or heart failure. They also had a higher European System for Cardiac Operative Risk Evaluation and more often underwent valve surgery. No differences in left atrial size were observed between patients with POAF and patients without POAF. The extent of atrial interstitial fibrosis, cardiomyocyte myocytolysis, cardiomyocyte diameter, glycogen score or Cx43 distribution at the time of surgery was not significantly associated with incidence of POAF. None of these histopathologic abnormalities were correlated with levels of NT-proBNP, hs-cTnT, CRP, or oxidative stress biomarkers. In sinus rhythm patients undergoing cardiac surgery, histopathologic changes in the right atrial appendage do not predict POAF. They also do not correlate with biomarkers of cardiac function, inflammation, and oxidative stress. Graphic Abstract: A graphic abstract is available for this article.

New Areas of Interest: Is There a Role for Omega-3 Fatty Acid Supplementation in Patients With Diabetes and Cardiovascular Disease?

Summarize studies on omega-3 fatty acids in prevention of albuminuria in subjects with diabetes. Several small, short-term trials suggested benefit on albuminuria in subjects with diabetes; however, results were not definitive. Welty et al. showed that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 1year slowed progression of early-stage albuminuria in subjects with diabetes with clinical coronary artery disease on an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, the majority of whom had an albumin/creatinine ratio (ACR) < 30μg/mg. Moreover, significantly more (3-fold) subjects on EPA and DHA had a decrease in ACR compared to control, and three on EPA and DHA had a change in category from > 30μg/mg to < 30μg/mg, whereas no controls did. Potential mechanisms for benefit are discussed. These results suggest that there is benefit and perhaps even reversal of albuminuria with EPA and DHA at an early stage of disease in those with ACR < 30μg/mg and those with microalbuminuria (ACR > 30).

Fish Oil Supplementation Does Not Affect Cognitive Outcomes in Cardiac Surgery Patients in the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (OPERA) Trial

Cognitive decline has been reported following cardiac surgery, leading to great interest in interventions to minimize its occurrence. Long-chain n-3 (ω-3) polyunsaturated fatty acids (PUFAs) have been associated with less cognitive decline in observational studies, yet no trials have tested the effects of n-3 PUFAs on cognitive decline after surgery. We sought to determine whether perioperative n-3 PUFA supplementation reduces postoperative cognitive decline in patients postcardiac surgery. The study comprised a randomized, double-blind, placebo-controlled, multicenter, clinical trial conducted on cardiac surgery recipients at 9 tertiary care medical centers across the United States. Patients were randomly assigned to receive fish oil (1-g capsules containing ≥840 mg n-3 PUFAs as ethyl esters) or placebo, with preoperative loading of 8-10 g over 2-5 d followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first. Global cognition was assessed using in-person testing over 30 d with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (primary outcome), Mini-Mental State Exam (secondary outcome), and Trails A and B (secondary outcome) tests. All end points were prespecified. Statistical methods were employed, including descriptive statistics, logistic regression, and various sensitivity analyses. A total of 320 US patients were enrolled in the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (OPERA) Cognitive Trial (OCT), a substudy of OPERA. The median age was 62 y (IQR 53, 70 y). No differences in global cognition were observed between placebo and fish oil groups at day 30 (P = 0.32) for the primary outcome, a composite neuropsychological RBANS score. The population demonstrated resolution of initial 4-d cognitive decline back to baseline function by 30 d on the RBANS. Perioperative supplementation with n-3 PUFAs in cardiac surgical patients did not influence cognition ≤30 d after discharge. Modern anesthetic, surgical, and postoperative care may be mitigating previously observed long-term declines in cognitive function following cardiac surgery. This trial was registered at clinicaltrials.gov as NCT00970489.

Omega-3 fatty acids in prevention of diabetic retinopathy.

To review the competence of Omega-3 fatty acids in restricting the progression, thereby leading to prevention of diabetic retinopathy. Owing to their anti-inflammatory and anti-angiogenic properties, Omega-3 fatty acids alleviate major aetiological agents. These fatty acids are renowned for their beneficial effects in various cardiovascular and other disorders; however, their potential to prevent the progression of diabetic retinopathy remains least explored. Utilizing this potential, we may develop effective prophylactic agents which markedly inhibit the advent of retinal angiogenesis and prevent the apoptosis of retinal endothelial and neuronal cells, thereby averting retinal degeneration, hence safeguarding diabetic patients from this sight-threatening complication.

Effects of Omega-3 Fatty Acids in Prevention of Early Preterm Delivery

Abstract Objective Preterm birth continues to be the one of the leading causes of infant deaths worldwide. There is a need for effective, easily available, safe and acceptable interventions to prevent preterm delivery, especially before 34 weeks of gestation. Omega-3 fatty acids such as EPA (eicosapentanoic acid) and DHA (docosahexanoic acid) are available as over the counter nutritional supplements, and are taken by women to improve pregnancy outcomes, without any clear recommendations. We undertook a systematic review to assess the effects of omega-3 fatty acids on early ( Methods We searched MEDLINE, EMBASE and Cochrane Library from inception to 2014 without any language restrictions. Study selection, quality assessment and data extraction were done by two independent reviewers. Results were summarized as relative risks and 95% confidence intervals for dichotomous outcomes and mean differences for continuous outcomes. Results Of the nine included trials (5980 women), six (4193 women) evaluated the effects of omega-3 fatty acids on early preterm delivery. The risk of early preterm delivery was reduced by 58% (RR 0.42; 95% CI 0.27–0.66; I2 = 0%; p = 0.0002) and any preterm delivery by 17% (RR 0.83; 95% CI 0.70–0.98; I2 = 0%; p = 0.03) with the intervention. There was a significant increase in the mean gestational age by 1.95 weeks (95% CI 0.42–3.48 weeks; I2 = 0.47; p = 0.01) and mean birth weight by 122.1 g (95% CI 47.4–196.8; I2 = 0.84; p = 0.001) in the intervention group compared to the controls. Subgroup analysis showed no significant differences in the effects between the groups according to the risk status, dose and timing of the intervention. Conclusion Omega-3 fatty acids are effective in preventing early and any preterm delivery. The intervention is simple and easily available and has the potential to influence population based strategies in the prevention of preterm birth.

Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic review and meta-analysis of randomized studies

ObjectivePreterm birth continues to be the one of the leading causes of infant deaths worldwide. There is a need for effective, easily available, safe and acceptable interventions to prevent preterm delivery, especially before 34 weeks of gestation. Omega-3 fatty acids such as EPA (eicosapentanoic acid) and DHA (docosahexanoic acid) are available as over the counter nutritional supplements, and are taken by women to improve pregnancy outcomes, without any clear recommendations. We undertook a systematic review to assess the effects of omega-3 fatty acids on early (<34 weeks) and any (<37 weeks) preterm delivery. MethodsWe searched MEDLINE, EMBASE and Cochrane Library from inception to 2014 without any language restrictions. Study selection, quality assessment and data extraction were done by two independent reviewers. Results were summarized as relative risks and 95% confidence intervals for dichotomous outcomes and mean differences for continuous outcomes. ResultsOf the nine included trials (5980 women), six (4193 women) evaluated the effects of omega-3 fatty acids on early preterm delivery. The risk of early preterm delivery was reduced by 58% (RR 0.42; 95% CI 0.27–0.66; I2=0%; p=0.0002) and any preterm delivery by 17% (RR 0.83; 95% CI 0.70–0.98; I2=0%; p=0.03) with the intervention. There was a significant increase in the mean gestational age by 1.95 weeks (95% CI 0.42–3.48 weeks; I2=0.47; p=0.01) and mean birth weight by 122.1g (95% CI 47.4–196.8; I2=0.84; p=0.001) in the intervention group compared to the controls. Subgroup analysis showed no significant differences in the effects between the groups according to the risk status, dose and timing of the intervention. ConclusionOmega-3 fatty acids are effective in preventing early and any preterm delivery. The intervention is simple and easily available and has the potential to influence population based strategies in the prevention of preterm birth.

Update on the Vitamin D and OmegA-3 trial (VITAL)

Despite continued appreciation of the potential role of vitamin D and omega-3 fatty acids in the prevention of cancer and cardiovascular disease (CVD), there remain no completed large-scale, randomized trials of these agents for the primary prevention of cancer or CVD in a population that has not been selected on the basis of elevated risk. The VITamin D and OmegA-3 TriaL (VITAL) is a 2×2 factorial randomized, double-blind, placebo-controlled trial of the benefits and risks of vitamin D (vitamin D3 [cholecalciferol], 2000IU/d) and marine omega-3 fatty acids (Omacor® fish oil, a 1g/d) in the primary prevention of cancer and CVD among 25,875 men and women, aged ≥50 and ≥55 years, respectively. Randomization began in November 2011 and was completed in March 2014. This report will describe the rationale for the trial and currently available randomized trial data, summarize related ongoing large-scale trials, and provide a brief overview of study design, and an update on randomization milestones, racial/ethnic diversity, biorepository activities, in-depth phenotyping of a subcohort, and ancillary studies.

Circulating cardiac biomarkers and postoperative atrial fibrillation in the OPERA trial.

Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and predicts increased morbidity and mortality. Identification of patients at high risk of POAF with the help of circulating biomarkers may enable early preventive treatment but data are limited, especially in contemporary surgical patients. Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured at enrollment, on the morning of cardiac surgery, at end surgery, and 2 days postsurgery in 562 patients undergoing cardiac surgery, randomized to perioperative supplementation with oral fish oil or placebo in the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation trial (OPERA). The primary endpoint was incident POAF lasting ≥ 30 s, centrally adjudicated and confirmed electrocardiographically. Higher levels of NT-proBNP and hs-cTnT before surgery were associated with older age, renal or cardiac dysfunction and EuroSCORE. NT-proBNP peaked on postoperative day 2 (2172 [1238-3758] ng/L, median [Q1-Q3]), while hs-cTnT peaked at the end of surgery (373 [188-660] ng/L). Fish oil supplementation did not alter the time course of the cardiac biomarkers (P > 0.05). Concentrations of NT-proBNP or hs-cTnT, on the morning of surgery, or changes in their level between morning of surgery and postsurgery, were not significantly associated with POAF after adjustment for clinical and surgical characteristics. Among patients undergoing cardiac surgery, NT-proBNP and hs-cTnT are related to clinical and surgical characteristics, have different perioperative time courses but are not independently associated with risk of POAF.

Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of dementia and the most common neurodegenerative disease in the elderly. Furthermore, AD has provided the most positive indication to support the fact that inflammation contributes to neurodegenerative disease. The exact etiology of AD is unknown, but environmental and genetic factors are thought to contribute, such as advancing age, family history, presence of chronic diseases such as cardiovascular disease (CVD) and diabetes, and poor diet and lifestyle. It is hypothesised that early prevention or management of inflammation could delay the onset or reduce the symptoms of AD. Normal physiological changes to the brain with ageing include depletion of long chain omega-3 fatty acids and brains of AD patients have lower docosahexaenoic acid (DHA) levels. DHA supplementation can reduce markers of inflammation. This review specifically focusses on the evidence in humans from epidemiological, dietary intervention, and supplementation studies, which supports the role of long chain omega-3 fatty acids in the prevention or delay of cognitive decline in AD in its early stages. Longer term trials with long chain omega-3 supplementation in early stage AD are warranted. We also highlight the importance of overall quality and composition of the diet to protect against AD and dementia.

Abstract 12364: Circulating Cardiac and Inflammatory Biomarkers to Predict Post-Operative Atrial Fibrillation in the OPERA Trial

Objectives: Post-operative atrial fibrillation (POAF) is a common complication after cardiac surgery and predicts increased morbidity and mortality. Identification of patients at high risk of POAF with the help of circulating biomarkers may enable early preventive treatment but data are limited, especially in contemporary surgical patients. Methods: Plasma concentrations of N-terminal probrain natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin T (hs-cTnT) and C-reactive protein (hsCRP) were measured at enrollment, on the morning of cardiac surgery, at end-surgery, and 2 days post-surgery in 562 patients undergoing cardiac surgery, randomized to perioperative supplementation with oral fish oil or placebo in the international clinical trial Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation trial (OPERA). The primary endpoint was incident POAF lasting ≥ 30 seconds, centrally adjudicated and confirmed electrocardiographically. Results: Higher levels of NT-proBNP and hs-cTnT before surgery were associated with older age, renal or cardiac dysfunction and higher EuroSCORE, while hsCRP correlated positively with BMI. NT-proBNP (2172 [1238-3758] ng/L) and hsCRP (118 [75-165] mg/L) peaked on post-operative day 2, while hs-cTnT peaked at the end of surgery (373 [188-660] ng/L). Fish oil supplementation did not alter the time course of the cardiac or inflammatory biomarkers. Concentrations of the 3 biomarkers, on the morning of surgery, or changes in their level between morning of surgery and post-surgery, were not significantly associated with POAF after adjustment for clinical and surgical characteristics. Conclusions: Among patients undergoing cardiac surgery, cardiac markers are related to clinical and surgical characteristics, have different perioperative time courses but do not help in predicting the risk of POAF.

Abstract P357: Omega-3 Fatty Acid Biomarkers and Coronary Heart Disease: a Pooling Project of 17 Cohort Studies

Background: Recent trials have raised questions about the role of seafood-derived long-chain omega-3 fatty acids for prevention of CHD; and evidence linking intermediate-chain omega-3 fatty acids to CHD remains weak. Methods: We developed a global consortium of 17 prospective (cohort or nested case-control) and retrospective studies having circulating or tissue biomarker measures of eicosapentaenoic (EPA; 20:5n-3), docosapentaenoic (DPA; 22:5n-3), docosahexaenoic acid (DHA; 22:6n-3), and α-linolenic acid (ALA; 18:3n-3). Each study ascertained CHD risk, including total CHD, nonfatal MI, and/or fatal CHD. Associations of each omega-3 fatty acid biomarker with CHD were evaluated within each cohort using standardized models, exposures, outcomes, and covariates across studies. Omega-3 fatty acid levels were analyzed continuously (per SD) and categorically (quintiles), and study-specific estimates were centrally pooled using fixed effects meta-analysis. Results: Current findings (Oct 2013) were based on 13 of 17 participating studies, including 7105 total CHD, 4926 nonfatal MI, and 2466 fatal CHD events. In both continuous and categorical multivariable-adjusted analyses, each omega-3 biomarker was inversely associated with fatal CHD. For each 1 SD unit increment, ALA was associated with 9% lower risk [HR 0.91 (95% CI 0.84-0.99)]; EPA, with 8% lower risk [HR 0.92 (95% CI 0.85-1.00)]; DPA, with 8% lower risk [HR: 0.92 (0.87-0.98)]; and DHA, with 9% lower risk [HR: 0.91 (0.86-0.96)] (Figure). Associations with total CHD and nonfatal MI were generally weaker and non-significant, except for EPA and nonfatal MI [HR: 0.93 (0.89-0.98)] and DHA and nonfatal MI [HR: 0.95 (0.91-0.99)]. Conclusions: Based on all available studies from around the world, both long and intermediate-chain omega-3 fatty acids, measured using objective biomarkers, are associated with lower risk of fatal CHD. These findings support potential benefit of omega-3 fatty acids for reducing CHD death.

Omega-3 Fatty Acids for Prevention of Breast Cancer: an Update and the State of the Science

The quantity and makeup of dietary fat intake are known to impact human health. Use of Omega-3 (ω-3) polyunsaturated fatty acid (PUFA) supplements has gained increasing attention for a variety of purported health benefits, including cancer prevention. Preclinical evidence has been encouraging and recent studies have expanded our understanding of the mechanisms by which ω-3 PUFAs may protect against breast cancer. However, epidemiologic studies have yielded mixed results. Recent population studies have attempted to delineate factors that may influence the effects of ω-3 PUFAs such as total fat intake and the ratio of ω-3 to ω-6 PUFA intake. Several clinical trials, including some currently ongoing, are investigating novel strategies that favorably alter endogenous fatty acid profiles in an effort to develop clinically feasible prevention methods. Identification of well-defined subpopulations that are most likely to benefit from a targeted prevention approach will likely be crucial in this effort.

Incomplete Conflicts of Interest Disclosures in: Fish Oil and Postoperative Atrial Fibrillation: The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) Randomized Trial

Incomplete Conflicts of Interest Disclosures in: Fish Oil and Postoperative Atrial Fibrillation: The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) Randomized Trial

Fish Oil and Postoperative Atrial Fibrillation: The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial: Mozaffarian D, Marchioli R, Macchia A, et al. JAMA 2012;308:2001–11.

Fish Oil and Postoperative Atrial Fibrillation: The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial: Mozaffarian D, Marchioli R, Macchia A, et al. JAMA 2012;308:2001–11.

AHA 2012: Prevention a key focus of meeting

The American Heart Association (AHA) Scientific Sessions 2012 brought together leading experts from around the world to discuss successes and new initiatives aimed at reducing the burden of cardiovascular disease (CVD). A key focus of the meeting was on treatments aimed at preventing cardiovascular events. In addition, the meeting discussed the efficacy of novel therapies and safety of marketed treatments. A review of select late-breaking trials and other presentations will be covered in this article.

Fish Oil and Postoperative Atrial Fibrillation

Postoperative atrial fibrillation or flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results. To determine whether perioperative n-3-PUFA supplementation reduces postoperative AF. The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first. Occurrence of postoperative AF lasting longer than 30 seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events. At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = .74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P = .73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events. In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00970489.

Do Omega-3 Fatty Acids Have a Role in Prevention of Cardiovascular Disease?

As often the case within scientific research, the answer is not as straightforward as the question. In contradistinction to earlier data, recently published studies have been negative, and thus raised the question of whether supplementation with omega-3 fatty acids for prevention of cardiovascular disease is now passe. Some background knowledge is necessary to appreciate this perplexing and controversial topic.

EP News: Clinical

Kowey et al (JAMA 2010;[EPub ahead of print], PMID 21078810) evaluated omega-3 fatty acids for prevention of atrial fibrillation (AF) in a prospective, randomized, double-blind, placebo-controlled, parallel-group multicenter trial. A total of 663 outpatients with paroxysmal (n = 542) or persistent (n = 121) AF, with no structural heart disease, and in normal sinus rhythm at baseline were randomized to omega-3 (8 g/day) or placebo for the first 7 days, then omega-3 (4 g/day) or placebo thereafter through week 24. The primary endpoint was first symptomatic recurrence of AF. Secondary analyses included first recurrence in the persistent stratum and both strata combined. There was no difference between treatment groups for recurrence of symptomatic AF in the paroxysmal stratum (P = .26), in the persistent stratum (P = .09), and in both strata combined (P = .08). Other secondary endpoints were supportive of the primary result. A total of 5% of patients receiving placebo and 4% of those receiving prescription omega-3 discontinued due to adverse events. Eicosapentaenoic and docosahexaenoic acid blood levels were significantly higher in the prescription group than in the placebo group at weeks 4 and 24. The authors conclude that omega-3 compared with placebo did not reduce AF over 6 months.

Potential Effects of Omega-3 Fatty Acid Supplements in the Prevention of Type 2 Diabetes: A Critical Appraisal of Data from Randomized Clinical Trials

Emerging evidence has suggested favorable effects of marine omega-3 fatty acids on glucose homeostasis, lipid metabolism, endothelial function, and chronic inflammation, which could contribute individually or synergistically to the development of type 2 diabetes (T2D). With increasing prevalence of use of fish oil supplements and increasing fortification of the food supply with marine omega-3 fatty acids in the general population, it will be critically important to assess the overall balance of benefits and risks of omega-3 fatty acid supplements on glucose tolerance and diabetes. This article aims to summarize the evidence from available randomized clinical trials on the potential effects of fish oil and/or omega-3 fatty acid supplements among both nondiabetic and diabetic participants. Overall, the evidence for the beneficial or deleterious effects of fish oil supplements on insulin sensitivity has been inconsistent, with limited randomized trial data involving small trials of short duration. However, dietary recommendation of taking omega-3 fatty acids for prevention of T2D or diabetic complications may ultimately only be resolvable by definitive data from future large-scale clinical trials that include T2D as a primary outcome in a general