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Effect of High-Dose Marine Omega-3 Fatty Acids on Atherosclerosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Sekikawa, A, Cui, C, Sugiyama, D, Fabio, A, Harris, WS, Zhang, X
Nutrients. 2019;11(11)
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This systematic review and meta-analysis reports that high dose omega 3 at a dose of 3g/day with 90% purity significantly slowed the progression of atherosclerosis and is a promising mechanism for reducing cardiovascular (CVD) incidents. The study reviewed 6 articles from 2016-2017 with a total of 693 participants, which met the criteria of omega 3 and a primary outcome on atherosclerosis. Only one trial was placebo controlled with the remaining five open-label trials with no placebo. Four of the trials were conducted in Japan using a highly purified EPA whilst the remaining trials used an EPA / DHA combination. The effect of high dose omega 3 was significant even after removing the two most influential studies. Preclinical studies in animal models show that Omega 3 slows atherosclerosis progression through various molecular mechanisms. In humans there is less conclusive evidence and observational studies report that dietary intake of Omega 3 has no significant correlation with coronary artery calcification, the measure used to assess atherosclerosis. The limitation of this study is that different technologies were used to assess atherosclerosis across the selected trials. However, the authors conclude that the anti-atherosclerotic properties of high-dose OM3 are one potential mechanism in reducing CVD risk.
Abstract
A recent randomized controlled trial (RCT), the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT), reported that high-dose marine omega-3 fatty acids (OM3) significantly reduce cardiovascular disease (CVD) outcomes, yet the mechanisms responsible for this benefit remain unknown. To test the hypothesis that high-dose OM3 is anti-atherosclerotic, we performed a systematic review and meta-analysis of RCT of high-dose OM3 on atherosclerosis. The protocol of this systematic review was registered with PROSPERO (CRD42019125566). PubMed, Embase, Cochran Central Register for Controlled Trials, and Clinicaltrials.gov databases were searched using the following criteria: adult participants, high-dose OM3 (defined as ≥3.0 g/day, or in Japan 1.8 g/day and purity ≥90%) as the intervention, changes in atherosclerosis as the outcome, and RCTs with an intervention duration of ≥6 months. A random-effects meta-analysis was used to pool estimates across studies. Among the 598 articles retrieved, six articles met our criteria. Four RCTs evaluated atherosclerosis in the coronary and two in the carotid arteries. High-dose OM3 significantly slowed the progression of atherosclerosis (standardized mean difference -1.97, 95% confidence interval -3.01, -0.94, p < 0.001). The results indicate that anti-atherosclerotic effect of high-dose OM3 is one potential mechanism in reducing CVD outcomes demonstrated in the REDUCE-IT trial.
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Effect of Fish Oil Supplementation on Hepatic and Visceral Fat in Overweight Men: A Randomized Controlled Trial.
Parker, HM, Cohn, JS, O'Connor, HT, Garg, ML, Caterson, ID, George, J, Johnson, NA
Nutrients. 2019;11(2)
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Being overweight increases the risk of the development of metabolic conditions such as non-alcoholic fatty liver disease (NAFLD). Omega-3 polyunsaturated fatty acid (PUFA) supplementation is recommended for prevention of chronic disease, and is thought to reduce liver fat, but there have been few randomised controlled trials that accurately measure liver fat. The aim of this double-blind randomised controlled trial was to assess the effect of 12 weeks of supplementation with omega-3 PUFA from fish oil on liver fat, liver tests, and body composition. Fifty healthy overweight men were given either fish oil (1,728 mg marine triglycerides, of which 588 mg EPA and 412 mg DHA, combined with 200 mg antioxidant, coenzyme Q10) or placebo (capsules containing 2g olive oil) daily for 12 weeks. Participants were assessed at the beginning of the study, and following 6 and 12 weeks of supplementation. At the start of the study, 16 (32%) participants met the criteria for NAFLD (>5.5% liver fat). There were no significant changes in liver fat, liver function or body composition in either of the groups over 12 weeks. When the researchers looked at the results for those participants with NAFLD at the start of the study, there were no significant changes here either. The authors concluded that omega-3 PUFA did not appear to be an effective agent for reducing liver fat in overweight men. The factors determining the health benefits of omega-3 PUFA supplementation on an individual level need to be clarified.
Abstract
Being overweight increases the risk of the development of metabolic conditions such as non-alcoholic fatty liver disease (NAFLD), which is itself an independent predictor of cardiovascular disease. Omega-3 polyunsaturated fatty acid (PUFA) supplementation is recommended for prevention of chronic disease, and is thought to reduce raised liver fat, yet there have been few randomized controlled trials with accurate measurement of liver fat. We assessed the effect of 12 weeks of supplementation with omega-3 PUFA from fish oil versus placebo on quantified liver fat, liver tests, and body composition including visceral adipose tissue (VAT) in a double-blind randomized controlled trial. Fifty apparently healthy overweight men (BMI 25.0⁻29.9 kg/m²; waist > 94 cm) were randomly allocated to consume fish oil (total daily dose: 1728 mg marine triglycerides, of which 588 mg EPA and 412 mg DHA, combined with 200 mg antioxidant, coenzyme Q10) or placebo (olive oil capsules) daily for 12 weeks. Liver fat was assessed using proton magnetic resonance spectroscopy. All outcomes were assessed at baseline and following 6 and 12 weeks of supplementation. Baseline liver fat was 4.6 ± 0.5% (range: 0.6 to 18.2%); 16 (32%) participants met the criteria for NAFLD (>5.5% liver fat). Repeated measures ANOVA revealed no significant time or group × time effect for fish oil versus placebo for liver fat, liver enzymes, anthropometry, or body composition including VAT (p > 0.05 for all), with similar finding for sub-analysis of participants with NAFLD. Omega-3 PUFA did not appear to be an effective agent for reducing liver fat in overweight men. The factors determining the health benefits of omega-3 PUFA supplementation on an individual level need to be clarified.
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Effect of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition on inflammatory and immune function in postoperative patients with gastrointestinal malignancy: A meta-analysis of randomized control trials in China.
Zhao, Y, Wang, C
Medicine. 2018;97(16):e0472
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Omega-3 polyunsaturated fatty acids (PUFAs) can have a beneficial effect on inflammation and immune function. This meta-analysis looked at the effectiveness of omega-3 PUFAs on inflammatory and immune function in patients with stomach or colorectal cancers, following surgery. 16 Chinese randomised controlled trials with over 1000 patients carried out between 2000 and 2017 were included in the analysis. The researchers found that the numbers of immune cells in the omega-3 group were significantly higher than those in the control group. The levels of antibodies in people given omega-3 were significantly higher than those in the control group. Inflammatory markers in the omega-3 group were significantly lower. Those given omega-3 were 64% less likely to experience post-surgical infections. The result of this meta-analysis confirmed that supplementing gastrointestinal cancer patients with omega-3 improves post-surgery indicators of immune function, reduces inflammation, and reduces infections related to surgery. The authors recommend that omega-3 should be added to the nutrition formula given to gastrointestinal cancer patients following surgery.
Abstract
BACKGROUND There are no consensus regarding the efficacy of omega-3polyunsaturated fatty acids (PUFAs) on inflammatory and immune function in postoperative patients with gastrointestinal malignancy. METHODS The literatures published randomized control trials (RCT) were searched in PubMed, Embase, Scopus, Cochrane Library, CNKI, Weipu, and Wanfang Databases. The immune efficacy outcomes of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition in patients with gastrointestinal malignancy were compared. RESULTS Sixteen RCTs involving 1008 patients (506 in the omega-3 group, 502 in the control group) were enrolled into the analysis. The results of meta-analysis: the cell immunity: The proportions of CD3, CD4, CD4/CD8 in the omega-3 group were significantly higher than those in the control group (CD3: WMD = 4.48; 95% CI, 3.34-5.62; P < .00001; I = 0%; CD4: WMD = 5.55; 95% CI, 4.75-6.34; P < .00001; I = 0%; CD4/CD8: WMD = .28; 95% CI, 0.13-0.44; P = .0004; I = 81%). In the humoral immunity: The levels of IgA, IgM and IgG in the omega-3 group were significantly higher than those in the control group (IgA: WMD = 0.31; 95% CI, 0.25-0.37; P < .00001; I = 0%; IgM: WMD = 0.12; 95% CI, 0.06-1.81; P < .00001; I = 0%; IgG: WMD = 1.19; 95% CI, 0.80-1.58; P < .00001; I = 0%). The count of lymphocyte in the omega-3 group was significantly higher than that in the control group (WMD = 0.22; 95% CI, 0.12-0.33; P < .0001; I = 40%). In the postoperative inflammatory cytokine: The levels of interleukin-6, tumor necrosis factor (TNF)-α and C-reactive protein in the omega-3 group were significantly lower than those in the control group (IL-6: WMD = -3.09; 95% CI, -3.91 to 2.27; P < .00001; I = 45%; TNF-α: WMD = -1.65; 95% CI, -2.05 to 1.25; P < .00001; I = 28%; CRP: WMD = -4.28; 95% CI, -5.26 to 3.30; P < .00001; I = 37%). The rate of postoperative infective complications in the omega-3 group was significantly lower than that in the control group (OR = 0.36; 95% CI, 0.20-0.66; P = .0008; I = 0%). CONCLUSION This meta-kanalysis confirmed that early intervention with Omega -3 fatty acid emulsion in gastrointestinal cancer can not only improve the postoperative indicators of immune function, reduce inflammatory reaction, and improve the postoperative curative effect but also improve the immune suppression induced by conventional PN or tumor. Therefore, postoperative patients with gastrointestinal cancer should add omega-3 unsaturated fatty acids in their PN formula. Further high-quality RCTs are needed to verify its efficacy.
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Fish consumption, fish oil supplements and risk of atherosclerosis in the Tromsø study.
Johnsen, SH, Jacobsen, BK, Brækkan, SK, Hansen, JB, Mathiesen, EB
Nutrition journal. 2018;17(1):56
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The importance of omega-3 fatty acids from fatty fish is frequently highlighted as a protective measure against artery plaque formation, and therefore protective against heart disease. The prospective, cross-sectional study of 3,900 individuals aimed to assess the impact of fish consumption or fish oil supplementation on artery plaque formation over a 7-year period. Using food frequency questionnaires, blood serum measures of fats and ultrasound imaging, the authors found no statistically significant association between fatty fish intake or fish oil supplements and artery plaque formation. Those who ate fish more than 3 times per week were found to have an increased risk of plaque formation when compared to those who ate less. Lean fish intake was associated with lower plaque formation however, and total fish consumption was inversely associated with triglyceride levels. The authors highlight some limitations of the study. They found that those who ate more fish tended to be older, male, smokers and have high inflammatory markers such as CRP. The cooking method used for the fish was also not assessed. Frying fish has been shown in other studies to affect the oils and their positive health benefits and could affect the results of this study. The authors conclude that the beneficial effects of fish consumption on artery plaque formation could be due to mechanisms other than omega-3 fat intake.
Abstract
BACKGROUND Whether long-chain n-3 PUFAs of marine origin have an anti-atherogenic effect in the general population has hardly been studied. In this population-based study, we hypothesized that fatty fish and fish oil intake protect against development of novel atherosclerotic plaques and is associated with reduced plaque size. METHODS We obtained questionnaire-based information on fish consumption and carotid ultrasonography from 3900 persons aged 45-74 years. The questionnaires were validated by measuring serum concentrations of PUFAs and triglycerides in a subgroup. At follow-up seven years later, 2983 (76%) went through a second ultrasound scanning. Logistic regression and general linear models were used to analyze the outcome (plaque presence and plaque area) as a function of fish consumption, including analyses stratified on fish oil supplements. RESULTS At baseline, lean fish intake < 1 time/week vs. 1-1.9 times/week was associated with risk of plaque (OR 1.34, 95% CI 1.03-1.76). Fatty fish intake and use of fish oil supplements were not statistically significantly associated with atherosclerosis at baseline. In persons without plaque at baseline, total fish consumption ≥3 times/week vs. 1-1.9 times/week was associated with risk of novel plaque (OR 1.32, 95% CI 1.01-1.73) and larger plaque area (1.76 mm2 vs. 1.46 mm2, p = 0.02) at follow-up. Adjustments for use of fish oil supplements had no impact on the associations, and no interactions were seen between total, fatty or lean fish consumption and fish oil intake. CONCLUSIONS We found no protective effect of fatty fish eating or fish oil supplements on atherosclerotic plaque formation or plaque area in a general population. Lean fish consumption was associated with a reduced risk for plaque in cross-sectional analysis, suggesting that the beneficial effects of fish consumption on atherosclerosis may be mediated through other mechanisms than n-3 PUFAs.
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Association between cognitive function and supplementation with omega-3 PUFAs and other nutrients in ≥ 75 years old patients: A randomized multicenter study.
Baleztena, J, Ruiz-Canela, M, Sayon-Orea, C, Pardo, M, Añorbe, T, Gost, JI, Gomez, C, Ilarregui, B, Bes-Rastrollo, M
PloS one. 2018;13(3):e0193568
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Nutrition may play an important role in the prevention of dementia. The aim of this study was to evaluate the effect of a multinutrient supplementation rich in omega-3 fatty acids on the cognitive function of adults aged 75 years and over with either no, or mild, cognitive impairment. Participants were given either a multinutrient capsule (each containing DHA 250 mg, EPA 40 mg, vitamin E 5 mg, phosphatidylserine 15 mg, tryptophan 95 mg, vitamin B 12 5 μg, folate 250 μg and ginkgo biloba 60 mg) or a placebo, three times a day for one year. Supplementation with the multinutrient did not improve overall cognitive function in the group. However, it did result in an improvement in memory in a sub-group of older people who were previously well nourished, but not in those with worse nutritional status.
Abstract
A few studies have assessed the association between omega-3 polyunsaturated fatty acids (n-3 PUFA) and cognitive impairment (CI) in very old adults. The aim of this study was to evaluate the effect of a multinutrient supplementation rich in n-3 PUFA on the cognitive function in an institutionalized ≥75-year-old population without CI or with mild cognitive impairment (MCI). A multicenter placebo-controlled double-blind randomized trial was conducted between 2012 and 2013. Cognitive function was assessed at baseline and after one year using 4 neuropsychological tests. Nutritional status was assessed using Mini Nutritional Assessment (MNA). Interaction between Mini-Mental State Examination (MMSE) score and nutritional status were analyzed using linear regression models. A total of 99 participants were randomized to receive placebo or pills rich in n-3 PUFA. After 1-year follow-up, both groups decreased their MMSE score (-1.18, SD:0. 53 and -0.82, SD:0. 63, p = 0.67 for the control and the intervention group respectively). The memory subscale of the MMSE showed an improvement (+0.26, SD:0.18) in the intervention group against a worsening in the control group (-0.11, SD: 0.14; p = 0.09 for differences between groups). Patients at intervention group with normal nutritional status (MNA ≥24) showed an improvement in the MMSE (+1.03, p = 0.025 for differences between 1-y and baseline measurements) against a worsening in the group with malnutrition (MNA<24) (-0.4, p = 0.886 for differences between 1-y and baseline; p of interaction p = 0.05). Supplementation with n-3 PUFA did not show an improvement in the global cognitive function in institutionalized elderly people without CI or with MCI. They only suggest an apparent improvement in memory loss if previously they were well nourished.
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Effects of krill oil and lean and fatty fish on cardiovascular risk markers: a randomised controlled trial.
Rundblad, A, Holven, KB, Bruheim, I, Myhrstad, MC, Ulven, SM
Journal of nutritional science. 2018;7:e3
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Fish consumption and supplementation with omega-3 rich fish oil has been shown to reduce the risk of cardiovascular disease. Krill oil is becoming a popular choice of fish oil for supplementation however few studies have investigated its health benefits. This small (n=36) double blind, randomised controlled trial aimed to assess the different impacts of 8-week consumption of either: krill oil supplements (4g oil daily); 3 fish meals per week (2 oily fish, one lean fish); or placebo of sunflower oil (4g oil daily), on cardiovascular risk markers. The results showed significant positive changes to blood glucose, lipids, phospholipids and cholesterol markers for the krill oil group, compared to the fish group and placebo. Vitamin D levels increased significantly in the fish consumption group compared to krill oil and placebo. Plasma levels of omega-3 fatty acids increased for both the krill oil group and fish consumption group. The authors conclude that krill oil supplementation and fish consumption both have positive health effects in relation to cardiovascular disease and larger studies of longer duration are needed.
Abstract
Fish consumption and supplementation with n-3 fatty acids reduce CVD risk. Krill oil is an alternative source of marine n-3 fatty acids and few studies have investigated its health effects. Thus, we compared krill oil supplementation with the intake of fish with similar amounts of n-3 fatty acids on different cardiovascular risk markers. In an 8-week randomised parallel study, thirty-six healthy subjects aged 18-70 years with fasting serum TAG between 1·3 and 4·0 mmol/l were randomised to receive either fish, krill oil or control oil. In the fish group, subjects consumed lean and fatty fish, according to dietary guidelines. The krill and control group received eight capsules per d containing 4 g oil per d. The weekly intake of marine n-3 fatty acids from fish given in the fish group and from krill oil in the krill group were 4103 and 4654 mg, respectively. Fasting serum TAG did not change between the groups. The level of total lipids (P = 0·007), phospholipids (P = 0·015), cholesterol (P = 0·009), cholesteryl esters (P = 0·022) and non-esterified cholesterol (P = 0·002) in the smallest VLDL subclass increased significantly in response to krill oil supplementation. Blood glucose decreased significantly (P = 0·024) in the krill group and vitamin D increased significantly in the fish group (P = 0·024). Furthermore, plasma levels of marine n-3 fatty acids increased significantly in the fish and krill groups compared with the control (all P ≤ 0·0003). In conclusion, supplementation with krill oil and intake of fish result in health-beneficial effects. Although only krill oil reduced fasting glucose, fish provide health-beneficial nutrients, including vitamin D.
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Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial.
Phelan, N, O'Connor, A, Kyaw Tun, T, Correia, N, Boran, G, Roche, HM, Gibney, J
The American journal of clinical nutrition. 2011;93(3):652-62
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5-10% of women of reproductive age are thought to be affected by polycystic ovary syndrome (PCOS). Women with PCOS don’t ovulate and have high levels of androgens (‘male’ hormones) such as testosterone. Dietary changes are often recommended for women with PCOS, yet the optimal diet for managing the condition has not been defined. Long-chain polyunsaturated fatty acids (PUFAs), in particular omega-3s, may influence various aspects of metabolic health in ways that are beneficial for women with PCOS. The objectives of this study were to determine the link between PUFAs and hormonal aspects of PCOS, to investigate the effects of omega-3 supplementation, and to support the findings with cellular studies. Participants were given 4 mg of either omega-3 supplementation or an olive oil placebo every day for 6 weeks. There was a 6-week rest period, after which the women crossed over to receive the alternative treatment for a further 6 weeks. Women who had higher levels of circulating androgens at the start of the study tended to have both higher omega-6 levels and omega-6:omega-3 ratios. After taking omega-3 supplements, testosterone levels were significantly reduced, particularly in those women who experienced more substantial falls in the ratio of omega-6:omega-3. Alongside this, the researchers found that ovarian cells sourced from cows increased production of androgens when treated with omega-6, but not omega-3. The authors concluded that supplementation with omega-3 PUFAs improves hormonal balance in women with PCOS.
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is characterized by an adverse metabolic profile. Although dietary changes are advocated, optimal nutritional management remains uncertain. Polyunsaturated fatty acids (PUFAs), particularly long-chain (LC) n-3 (omega-3) PUFAs, improve metabolic health, but their therapeutic potential in PCOS is unknown. OBJECTIVES We aimed to determine the associations between plasma PUFAs and metabolic and hormonal aspects of PCOS to investigate the efficacy of LC n-3 PUFA supplementation and to support the findings with mechanistic cellular studies. DESIGN We selected a cross-sectional PCOS cohort (n = 104) and conducted a principal component analysis on plasma fatty acid profiles. Effects of LC n-3 PUFA supplementation on fasting and postprandial metabolic and hormonal markers were determined in PCOS subjects (n = 22) by a randomized, crossover, placebo-controlled intervention. Direct effects of n-6 (omega-6) compared with n-3 PUFAs on steroidogenesis were investigated in primary bovine theca cells. RESULTS Cross-sectional data showed that a greater plasma n-6 PUFA concentration and n-6:n-3 PUFA ratio were associated with higher circulating androgens and that plasma LC n-3 PUFA status was associated with a less atherogenic lipid profile. LC n-3 PUFA supplementation reduced plasma bioavailable testosterone concentrations (P < 0.05), with the greatest reductions in subjects who exhibited greater reductions in plasma n-6:n-3 PUFA ratios. The treatment of bovine theca cells with n-6 rather than with n-3 PUFAs up-regulated androstenedione secretion (P < 0.05). CONCLUSIONS Cross-sectional data suggest that PUFAs modulated hormonal and lipid profiles and that supplementation with LC n-3 PUFAs improves androgenic profiles in PCOS. In bovine theca cells, arachidonic acid modulated androstenedione secretion, which suggests an indirect effect of n-3 PUFAs through the displacement of or increased competition with n-6 PUFAs. This trial was registered at clinicaltrials.gov as NCT01189669.