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Omega-3 supplementation and cardiovascular disease: formulation-based systematic review and meta-analysis with trial sequential analysis.
Rizos, EC, Markozannes, G, Tsapas, A, Mantzoros, CS, Ntzani, EE
Heart (British Cardiac Society). 2021;(2):150-158
Abstract
BACKGROUND Omega-3 supplements are popular for cardiovascular disease (CVD) prevention. We aimed to assess the association between dose-specific omega-3 supplementation and CVD outcomes. DESIGN We included double-blind randomised clinical trials with duration ≥1 year assessing omega-3 supplementation and estimated the relative risk (RR) for all-cause mortality, cardiac death, sudden death, myocardial infarction and stroke. Primary analysis was a stratified random-effects meta-analysis by omega-3 dose in 4 a priori defined categories (<1, 1, 2, ≥3 of 1 g capsules/day). Complementary approaches were trial sequential analysis and sensitivity analyses for triglycerides, prevention setting, intention-to-treat analysis, eicosapentaenoic acid, sample size, statin use, study duration. RESULTS Seventeen studies (n=83 617) were included. Omega-3 supplementation as ≤1 capsule/day was not associated with any outcome under study; futility boundaries were crossed for all-cause mortality and cardiac death. For two capsules/day, we observed a statistically significant reduction of cardiac death (n=3, RR 0.55, 95% CI 0.33 to 0.90, I2=0%); for ≥3 capsules/day we observed a statistically significant reduction of cardiac death (n=3, RR 0.82, 95% CI 0.68 to 0.99, I2=0%), sudden death (n=1, RR 0.70, 95% CI 0.51 to 0.97) and stroke (n=2, RR 0.74, 95% CI 0.57 to 0.95, I2=0%). CONCLUSION Omega-3 supplementation at <2 1 g capsules/day showed no association with CVD outcomes; this seems unlikely to change from future research. Compared with the robust scientific evidence available for low doses, the evidence for higher doses (2-4 1 g capsules/day) is weak. The emerging postulated benefit from high-dose supplementation needs replication and further evaluation as to the precise formulation and indication.
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The effects of low-ratio n-6/n-3 PUFA on biomarkers of inflammation: a systematic review and meta-analysis.
Wei, Y, Meng, Y, Li, N, Wang, Q, Chen, L
Food & function. 2021;(1):30-40
Abstract
OBJECTIVE The purpose of the systematic review and meta-analysis was to determine if low-ratio n-6/n-3 long-chain polyunsaturated fatty acid (PUFA) supplementation affects serum inflammation markers based on the current studies. METHODS PubMed, Embase and The Cochrane library databases were systematically searched to find randomized controlled trials (RCTs) on the effect of low-ratio n-6/n-3 PUFA intervention on inflammation markers up to July 2020. Data were pooled using standardized mean difference (SMD) and 95% confidence intervals (95% CI), with P value ≦ 0.05 as statistical significance. RESULTS Thirty-one RCTs were included in the meta-analysis. The analysis indicated that increasing low-ratio n-6/n-3 PUFA supplementation decreased the level of tumor necrosis factor-α (TNF-α) (SMD = -0.270; 95% CI: -0.433, -0.106; P = 0.001) and interleukin 6 (IL-6) (SMD = -0.153; 95% CI: -0.260, -0.045; P = 0.005). There were no significant effects on C-reactive protein (CRP) (SMD = -0.027; 95% CI: -0.189: 0.135; P = 0.741). Subgroup analysis indicated that there was a significant reduction in TNF-α serum concentration in subjects from Asia (SMD: -0.367; 95% CI: -0.579, -0.155; P = 0.001) and in subjects with diseases (SMD: -0.281; 95% CI: -0.436, -0.127; P < 0.001). In the subgroup of the n-6/n-3 ratio ≦5, low-ratio n-6/n-3 PUFA supplementation could decrease the level of TNF-α (SMD: -0.335; 95% CI: -0.552, -0.119; P = 0.002). Serum IL-6 decreased significantly in patients from the Europe subgroup (SMD: -0.451; 95% CI: -0.688, -0.214; P < 0.001), but not in Asia (SMD: -0.034; 95% CI: -0.226, 0.157; P = 0.724), North America (SMD: -0.115; 95% CI: -0.274, 0.044; P = 0.157) and Oceania (SMD: 0.142; 95% CI: -0.557, 0.842; P = 0.690). CONCLUSION Low-ratio n-6/n-3 PUFA supplementation could decrease significantly the concentration of serum TNF-α and IL-6, but not decrease CRP concentration.
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3.
Meta-Analysis Comparing the Effect of Combined Omega-3 + Statin Therapy Versus Statin Therapy Alone on Coronary Artery Plaques.
Fan, H, Zhou, J, Yuan, Z
The American journal of cardiology. 2021;:15-24
Abstract
Statin therapy plays an important role in stabilizing and regressing coronary artery plaques. Omega-3 supplements also have anti-inflammatory and antioxidant effects on coronary plaques. However, the effect of omega-3 supplementation on the basis of statin therapy on the stability and composition of plaques, is still unclear. We searched for randomized controlled trials published prior to November 2020 in the PubMed, Embase and Cochrane databases. Finally, eight studies using different imaging techniques to evaluate coronary atherosclerotic plaque, including optical coherence tomography (OCT), coronary CT angiography (cCTA) and intravascular ultrasound (IB-IVUS), met our inclusion criteria. We pooled data extracted from the included studies using the standardized mean difference (SMD) or mean difference (MD) of the random effects model. Compared with statin treatment alone, the combined treatment further delayed the progression of total plaque volume [SMD -0.36, 95% confidence interval (CI) -0.64 to -0.08, p = 0.01] and fiber content (SMD -0.40, 95% CI -0.68 to -0.13, p = 0.004). The plasma high-sensitivity C-reactive protein (hs-CRP) level of patients in the combination treatment group was significantly lower than that of the patients in the statin treatment group alone (SMD -0.30, 95% CI -0.59 to -0.01, p = 0.04). In addition, the combined use of omega-3 further increases the fibrous cap thickness (FCT) of the plaque with an MD of 29.45 μm. There were no significant differences in plasma high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), or lipid content in plaques between the two groups. Omega-3 combined with statins is superior to the statin treatment group in stabilizing and promoting coronary plaque regression and may help to further reduce the occurrence of cardiovascular events.
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Influence of n-3 fatty acid supplementation on inflammatory and oxidative stress markers in patients with polycystic ovary syndrome: a systematic review and meta-analysis.
Tosatti, JAG, Alves, MT, Cândido, AL, Reis, FM, Araújo, VE, Gomes, KB
The British journal of nutrition. 2021;(6):657-668
Abstract
Polycystic ovary syndrome (PCOS) is defined as a reproductive endocrine disease that results in a low-grade inflammatory and pro-oxidant state. Dietary factors, including n-3 fatty acids, may have a key role in improving metabolic disorders in PCOS patients. The present study aimed to investigate the influence of n-3 fatty acid supplementation on inflammatory and oxidative stress (OS) markers in patients with PCOS. A systematic literature search of Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus and Lilacs, until November 2019, was conducted. Randomised clinical trials that reported inflammatory and OS markers as endpoints in women with PCOS receiving n-3 fatty acid supplementation were included. The pooled estimates of the weighted mean differences (WMD) and the standard mean differences (SMD) were calculated. Random effects models were adopted to measure the pooled outcomes. Among the 323 studies retrieved, ten fulfilled the inclusion criteria for a meta-analysis. We founded a significant decrease in high-sensitivity C-reactive protein (hs-CRP) (SMD -0·29 (95 % CI -0·56, -0·02) mg/l) and an increase in adiponectin (WMD 1·42 (95 % CI 1·09, 1·76) ng/ml) concentrations in the intervention group when compared with the placebo group. No statistically significant results were found in the meta-analysis for visfatin, nitric oxide, GSH or malondialdehyde levels or total antioxidant capacity. The data suggest that supplementation of n-3 fatty acids could reduce the inflammatory state in women with PCOS, through a decrease in hs-CRP and an increase in adiponectin levels.
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5.
Effect of omega-3 fatty acids supplementation on cardio-metabolic and oxidative stress parameters in patients with chronic kidney disease: a systematic review and meta-analysis.
Fazelian, S, Moradi, F, Agah, S, Hoseini, A, Heydari, H, Morvaridzadeh, M, Omidi, A, Pizarro, AB, Ghafouri, A, Heshmati, J
BMC nephrology. 2021;(1):160
Abstract
BACKGROUND Omega-3 fatty acids (FAs) have been suggested as a beneficial supplement in chronic kidney disease (CKD) patients, but the results of randomized clinical trials (RCTs) are controversial. We conducted a systematic review and meta-analysis to evaluate all the RCTs about the impact of omega-3 FAs supplementation on cardiometabolic outcomes and oxidative stress parameters in patients with CKD. METHODS We performed a systematic database search in PubMed/MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central, up to May 2020. We included all placebo-controlled randomized trials that assessed the effect of omega-3 FAs supplementation on any cardiometabolic outcomes: blood pressure, total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) or triglycerides (TG) and oxidative stress parameters. Data were pooled using DerSimonian-Laird's random-effects model. RESULTS Finally, thirteen articles met the inclusion criteria for this review omega-3 FAs supplementation significantly decrease TC (SMD: -0.26; 95% CI: - 0.51, - 0.02; I2 = 52.7%), TG (SMD: -0.22; 95% CI: - 0.43, - 0.02; I2 = 36.0%) and Malondialdehyde (MDA) levels (SMD: -0.91; 95% CI: - 1.29, - 0.54; I2 = 00.0%) and also significantly increase superoxide dismutase (SOD) (SMD: 0.58; 95% CI: 0.27, 0.90; I2 = 00.0%) and Glutathione peroxidase (GPx) (SMD: 0.50; 95% CI: 0.14, 0.86; I2 = 00.0%) activities. However our results show that omega-3 FAs supplementation have no significant effects on HDL, LDL and blood pressure. Conclusion This systematic review and meta-analysis supports current evidence for the clinical benefit of omega-3 FAs intake to improve cardiometabolic parameters in CKD patients. However, well-designed RCTs still needed to provide a conclusive picture in this field.
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Effect of omega-3 fatty acids supplementation during childhood in preventing allergic disease: a systematic review and Meta-Analysis.
Zhang, Y, Lin, J, Zhou, R, Zheng, X, Dai, J
The Journal of asthma : official journal of the Association for the Care of Asthma. 2021;(4):523-536
Abstract
BACKGROUND Early omega-3 fatty acids exposure can influence early immune development and potentially prevent allergic disease. OBJECTIVES To review the effects of omega-3 fatty acids during childhood on allergic disease outcomes. METHODS We conducted searches of the PubMed, EMBASE and Cochrane Central Register of Controlled Trials and international trial registers (ClinicalTrials.gov and ISRCTN Registry) to September 30, 2018. We included randomized controlled trials (RCTs) and prospective cohort studies regarding the effect of omega-3 fatty acids during childhood on allergic disease outcomes. A total of 8 publications from 2 prospective cohort studies and 6 reports representing 5 unique RCTs were included. RESULTS The results of meta-analysis showed that omega-3 fatty acids during childhood did not appear to significantly alter the risk of any atopy (≤3 years old: RR 0.70, 95% CI 0.47 to 1.04, p = 0.08; > 3 years old: RR 0.98, 95% CI 0.82 to 1.16, p = 0.77), wheeze (≤3 years old: RR 0.82, 95% CI 0.54 to 1.26, p = 0.375; > 3 years old: RR 1.03, 95% CI 0.53 to 2.00, p = 0.929) and eczema (≤3 years old: RR 0.86, 95% CI 0.68 to 1.08, p = 0.20; > 3 years old: RR 0.90, 95% CI 0.60 to 1.35, p = 0.60). CONCLUSIONS There is limited evidence to support omega-3 fatty acids during childhood could reduce the risk of allergic disease.
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Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.
Harris, WS, Tintle, NL, Imamura, F, Qian, F, Korat, AVA, Marklund, M, Djoussé, L, Bassett, JK, Carmichael, PH, Chen, YY, et al
Nature communications. 2021;(1):2329
Abstract
The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.
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All-Cause Mortality and Cardiovascular Death between Statins and Omega-3 Supplementation: A Meta-Analysis and Network Meta-Analysis from 55 Randomized Controlled Trials.
Kim, J, Hoang, T, Kim, JM, Bu, SY, Choi, JH, Park, E, Lee, SM, Park, E, Min, JY, Lee, IS, et al
Nutrients. 2020;(10)
Abstract
Statins and omega-3 supplementation have shown potential benefits in preventing cardiovascular disease (CVD), but their comparative effects on mortality outcomes, in addition to primary and secondary prevention and mixed population, have not been investigated. This study aimed to examine the effect of statins and omega-3 supplementation and indirectly compare the effects of statin use and omega-3 fatty acids on all-cause mortality and CVD death. We included randomized controlled trials (RCTs) from meta-analyses published until December 2019. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to indirectly compare the effect of statin use versus omega-3 supplementation in a frequentist network meta-analysis. In total, 55 RCTs were included in the final analysis. Compared with placebo, statins were significantly associated with a decreased the risk of all-cause mortality (RR = 0.90, 95% CI = 0.86-0.94) and CVD death (RR = 0.86, 95% CI = 0.80-0.92), while omega-3 supplementation showed a borderline effect on all-cause mortality (RR = 0.97, 95% CI = 0.94-1.01) but were significantly associated with a reduced risk of CVD death (RR = 0.92, 95% CI = 0.87-0.98) in the meta-analysis. The network meta-analysis found that all-cause mortality was significantly different between statin use and omega-3 supplementation for overall population (RR = 0.91, 95% CI = 0.85-0.98), but borderline for primary prevention and mixed population and nonsignificant for secondary prevention. Furthermore, there were borderline differences between statin use and omega-3 supplementation in CVD death in the total population (RR = 0.92, 95% CI = 0.82-1.04) and primary prevention (RR = 0.85, 95% CI = 0.68-1.05), but nonsignificant differences in secondary prevention (RR = 0.97, 95% CI = 0.66-1.43) and mixed population (RR = 0.92, 95% CI = 0.75-1.14). To summarize, statin use might be associated with a lower risk of all-cause mortality than omega-3 supplementation. Future direct comparisons between statin use and omega-3 supplementation are required to confirm the findings.
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Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation on Non-Alcoholic Fatty Liver: A Systematic Review and Meta-Analysis.
Lee, CH, Fu, Y, Yang, SJ, Chi, CC
Nutrients. 2020;(9)
Abstract
(1) Aim: Non-alcoholic fatty liver disease (NAFLD) is a prevalent disease worldwide. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) bear anti-inflammatory action and can ameliorate hyperlipidemia. We wish to appraise the effects of n-3 PUFAs supplement on NAFLD. (2) Methods: We searched CENTRAL, Embase, and MEDLINE on 29 March 2020 for randomized control trials (RCTs) on the effects of n-3 PUFAs supplementation in treating NAFLD. The Cochrane Collaboration's tool was used to assess the risk of bias of included RCTs. (3) Results: We included 22 RCTs with 1366 participants. The risk of bias of included RCTs was generally low or unclear. n-3 PUFAs supplementation significantly reduced liver fat compared with placebo (pooled risk ratio 1.52; 95% confidence interval (CI) 1.09 to 2.13). n-3 PUFAs supplementation also significantly improved the levels of triglyceride, total cholesterol, high-density lipoprotein, and body-mass index, with pooled mean difference and 95% CI being -28.57 (-40.81 to -16.33), -7.82 (-14.86 to -0.79), 3.55 (1.38 to 5.73), and -0.46 (-0.84 to -0.08), respectively. (4) Conclusions: The current evidence supports the effects of n-3 PUFAs supplementation in improving fatty liver. n-3 PUFAs supplementation may also improve blood lipid levels and obesity.
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10.
Omega-3 PUFA intake and the risk of digestive system cancers: A meta-analysis of observational studies.
Wang, J, Zhang, Y, Zhao, L
Medicine. 2020;(19):e20119
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Abstract
BACKGROUND A growing number of epidemiological studies have suggested a possible association between long-chain omega-3 polyunsaturated fatty acid (PUFA) intake and the risk of cancers, but the results have been inconsistent. We aimed to conduct a meta-analysis to assess the association of omega-3 PUFA consumption with digestive system cancers. METHODS Relevant observational studies were identified through a comprehensive search of PubMed, Embase, and the Web of Science through December 2019 and by reviewing the references of the retrieved articles. The relative risks (RRs) of digestive system cancers associated with omega-3 PUFA intake were estimated using a random-effect model and were stratified by region, sex, study design, type of omega-3 PUFAs, smoking status, alcohol consumption, BMI, and physical activity. RESULTS Twenty-five studies (8 case-control studies and 17 cohort studies) involving 1,247,271 participants and 23,173 patients with digestive system cancers were included in this analysis. The risk of digestive system cancers decreased by 17% in individuals who consumed omega-3 PUFAs (RR = 0.83, 95% confidence interval (CI), 0.76-0.91). The risk estimates of digestive system cancers varied by cancer sites, study location, study design, type of omega-3 PUFAs, and other confounders (smoking, alcohol consumption, body mass index, and physical activity). Visual inspection of funnel plots and the Begg's and Egger's tests revealed no evidence of publication bias. CONCLUSION The findings show that omega-3 PUFAs should be as a healthy dietary component for the prevention of digestive system cancers. Cancer incidence decreases with increasing omega-3 PUFAs intake for most digestive system cancer sites. The relation between omega-3 PUFAs and digestive system cancers RR is similar among different populations.