Support for zoom in, zoom out when user open an epub book. Chapters are listing. User can find the chapter immediately.Support for file connection. User can double click the epub file and open it.The viewer is also added to the right menu.
Several subsequent clinical trials, however, had largely null findings [53-55]. For example, the 2012 Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial included 12,536 patients who had diabetes or a high risk of diabetes and a high risk of cardiovascular events. Supplementation with 1 g/day omega-3s (375 mg DHA and 465 mg EPA) for about 6 years significantly lowered triglyceride levels but had no effect on risk of myocardial infarction, stroke, or death from cardiovascular causes in comparison with placebo [54]. Similarly, in the 2010 Alpha Omega Trial, low-dose EPA and DHA supplementation (150 mg DHA and 226 mg EPA daily, supplied in a margarine) for 40 months also failed to reduce the rate of major cardiovascular events in comparison with placebo among 4,837 older men and women who had previously experienced a myocardial infarction and were receiving antihypertensive, antithrombotic, and/or lipid-lowering medications [55].
Find My Font Pro 3.1 Rar.epub
ASCEND had similar findings [56]. After a mean follow-up of 7.4 years, the omega-3 supplement did not significantly affect the risk of a serious vascular event (composite of nonfatal myocardial infarction or stroke, transient ischemic attack, and cardiovascular death, excluding intracranial hemorrhage) or revascularization. However, omega-3 supplementation did significantly reduce the risk of cardiovascular death by 19% in comparison with placebo.
Possible reasons for conflicting findings: The omega-3 form, study population, background dietary omega-3 intakes, and use of statins and other cardioprotective therapies might explain some conflicting findings among studies [17,54,55,60-67]. In addition, dose probably plays a major role in the ability of omega-3 supplementation to confer significant benefits [60]. The REDUCE-IT findings suggest that a high daily dose of IPE, 4 g, is an effective adjunct to statin therapy in people with CVD or a high risk of CVD [58]. The daily dose of 1 g used in many studies of omega-3 dietary supplements might affect some CVD pathways [60] but has had no significant effect on the primary outcomes in several trials [54,56,57].
Recent reviews and meta-analyses: A 2019 systematic review and meta-analysis of 13 trials included ASCEND, VITAL, and REDUCE-IT (but not STRENGTH) and a total of 127,477 participants [62]. LC omega-3 doses ranged from 0.376 to 4 g/day, and the mean treatment duration was 5 years. The authors concluded that LC-omega-3 supplementation reduces the risk of myocardial infarction, coronary heart disease death, total coronary heart disease, CVD death, and total CVD, and the effects appear to be dose related. However, the findings showed no significant associations for risk of fatal and nonfatal stroke. The authors noted that REDUCE-IT reduced risk of stroke significantly [58], suggesting that a higher dose of omega-3s (4 g/day) might be needed to affect this outcome.
A 2020 Cochrane review of 86 randomized controlled trials published between 1968 and 2019 found that 0.5 g/day to more than 5 g/day LC omega-3s for 12 to 88 months in a total of 162,796 participants reduced serum triglyceride levels by about 15% and slightly decreased rates of cardiovascular mortality and coronary heart disease events [70]. However, the supplements did not affect all-cause mortality, cardiovascular events, stroke, or arrhythmia. The authors of several earlier meta-analyses and systematic reviews, as well as a 2016 report from the Agency for Healthcare Research and Quality, concluded that omega-3 supplements do not appear to significantly reduce the risk of most cardiovascular events [63-65,71-82]. Many of these analyses [63-65,76-81], however, but not all [75,82], did find that omega-3s reduce the risk of cardiac death.
To manage high triglyceride levels, the AHA concludes that 4 g/day prescription omega-3s (containing EPA plus DHA or EPA only) lower triglyceride levels when used alone or as adjuncts to other lipid-lowering medications [84]. Although this finding pertains to high-dose prescription omega-3s, an earlier analysis of 58 trials also revealed a dose-response relationship between lower-dose dietary and supplemental omega-3 intakes and triglyceride levels [85]. Each 1 g/day of LC omega-3 increase reduced triglyceride levels by 5.9 mg/dL, and the effect was stronger in people with higher baseline triglyceride levels.
AHRQ report: In 2016, AHRQ published a review on the effects of omega-3 fatty acids on child and maternal health [99]. This comprehensive report evaluated the findings from 95 randomized controlled trials and 48 prospective longitudinal studies and nested case-control studies. Most studies examined the effects of fish oil supplements or other DHA and EPA combinations in pregnant or breastfeeding women or of infant formula fortified with DHA plus arachidonic acid, an omega-6. The authors concluded that, except for small beneficial effects on infant birth weight and length of gestation, omega-3 supplementation or fortification has no consistent effects on infant health outcomes.
Although the findings from the Prostate Cancer Prevention Trial and the SELECT trial suggest that higher LC omega-3 intakes might increase prostate cancer risk, some scientists have questioned the significance of these findings [113]. They have noted, for example, that in the SELECT trial [15], the difference in the omega-3 levels in the men with and without prostate cancer was very small and of questionable physiological significance. Other scientists have pointed out that localized (even high-grade) prostate cancers usually progress slowly and are common on autopsy in men who have died from other causes, suggesting that prostate cancer mortality is a more critical endpoint than prostate cancer incidence [114]. Finally, desaturation enzymes that convert ALA into EPA and DHA can be upregulated in some cancer cells, suggesting the possibility that it was the disease that raised the omega-3 levels, not the omega-3 levels that raised the disease risk [12].
A number of systematic reviews and meta-analyses of prospective studies of the effects of fish intakes, omega-3 intakes, and omega-3 blood levels on prostate cancer risk have had inconsistent findings as well. For example, circulating levels of EPA, but not DHA, were positively associated with prostate cancer risk in a meta-analysis of 5,098 men with prostate cancer and 6,649 men without prostate cancer from seven studies [117]. Another meta-analysis of 12 studies that included 4,516 men with prostate cancer and 5,728 men without prostate cancer found that high serum levels of these LC omega-3s were positively associated with high-grade disease [118]. In other analyses, dietary intakes of LC omega-3s had no effect on prostate cancer risk [120], whereas fish consumption decreased prostate cancer mortality but had no effect on prostate cancer incidence [120]. A 2015 meta-analysis found no significant associations between dietary intakes or blood levels of LC omega-3s and total prostate cancer risk [121]. The authors noted that most dietary-intake studies included in their meta-analysis found inverse associations, whereas biomarker studies of blood levels of these fatty acids found positive associations.
A systematic review and meta-analysis of 9 prospective cohort and 10 case-control studies did not find an association between fish or LC-omega-3 intakes and risk of pancreatic cancer [128]. Similarly, systematic reviews and meta-analyses have not found significant associations between fish consumption and risk of gastric or esophageal cancers [129,130].
These findings, combined with other epidemiological evidence, formed the basis for the AREDS2 clinical trial that examined whether adding 350 mg DHA and 650 mg EPA to the AREDS formulation further reduced the risk of progression to advanced AMD [155]. The results showed that EPA and DHA did not provide any additional benefits after a median follow-up of 5 years. These findings are in line with those from a Cochrane review [156] that included the results from AREDS2 and the Nutritional AMD Treatment 2 study [157], a 3-year randomized clinical trial of LC omega-3 supplements (840 mg/day DHA and 270 mg/day EPA) in patients with early age-related maculopathy and neovascular AMD. The Cochrane review authors concluded that LC omega-3 supplementation for up to 5 years in people with AMD does not reduce the risk of progression to advanced AMD or of moderate to severe vision loss.
Reviews and meta-analyses of studies that assessed whether fish oil and LC omega-3s are beneficial for RA have had inconsistent findings [9,168-171]. Some suggest that they do not significantly affect the clinical symptoms of RA but do reduce the amounts of NSAIDs and corticosteroids that patients need [169,170]. Others indicate that LC omega-3s reduce joint swelling and pain, morning stiffness, and number of painful joints in addition to reducing NSAID use [9,168,171]. Some researchers suggest that differences in findings could be due in part to whether patient-determined use of NSAIDs is considered a measure of pain [9].
Findings to date suggest that LC omega-3s may be helpful as an adjunctive treatment to pharmacotherapy for ameliorating the symptoms of RA [9,171]. However, more research is needed to confirm this finding.
Depression: A 2016 meta-analysis of 26 studies found a 17% lower risk of depression with higher fish intake [174]. However, a 2015 Cochrane review of 26 studies found insufficient evidence to determine whether omega-3s (1,000 to 6,600 mg/day EPA, DHA, and/or other omega-3s) are beneficial for major depressive disorder in adults [175]. The authors did find a small-to-modest beneficial effect on depressive symptoms, but they concluded that this effect was not clinically significant. 2ff7e9595c
Comments