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Interest in the potential cardiovascular (CV) benefits of omega-3 polyunsaturated fatty acids (Ω-3) began in the 1940s and was amplified by a subsequent landmark trial showing reduced CV disease (CVD) risk following acute myocardial infarction. Since that time, however, much controversy has circulated due to discordant results among several studies and even meta-analyses. Then, in 2018, three more large, randomized trials were released—these too with discordant findings regarding the overall benefits of Ω-3 therapy. Interestingly, the trial that used a higher dose (4 g/day highly purified eicosapentaenoic acid (EPA)) found a remarkable, statistically significant reduction in CVD events. It was proposed that insufficient Ω-3 dosing (<1 g/day EPA and docosahexaenoic acid (DHA)), as well as patients aggressively treated with multiple other effective medical therapies, may explain the conflicting results of Ω-3 therapy in controlled trials. We have thus reviewed the current evidence regarding Ω-3 and CV health, put forth potential reasoning for discrepant results in the literature, highlighted critical concepts such as measuring blood levels of Ω-3 with a dedicated Ω-3 index and addressed current recommendations as suggested by health care professional societies and recent significant scientific data.

Gastrointestinal toxicity (GIT) is a debilitating side effect of Irinotecan (CPT-11) and limits its clinical utility. Gut dysbiosis has been shown to mediate this side effect of CPT-11 by increasing gut bacterial β-glucuronidase (GUSB) activity and impairing the intestinal mucosal barrier (IMB). We have recently shown the opposing effects of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) on the gut microbiome. We hypothesized that elevated levels of tissue n-3 PUFA with a decreased n-6/n-3 PUFA ratio would reduce CPT-11-induced GIT and associated changes in the gut microbiome. Using a unique transgenic mouse (FAT-1) model combined with dietary supplementation experiments, we demonstrate that an elevated tissue n-3 PUFA status with a decreased n-6/n-3 PUFA ratio significantly reduces CPT-11-induced weight loss, bloody diarrhea, gut pathological changes, and mortality. Gut microbiome analysis by 16S rRNA gene sequencing and QIIME2 revealed that improvements in GIT were associated with the reduction in the CPT-11-induced increase in both GUSB-producing bacteria (e.g., Enterobacteriaceae) and GUSB enzyme activity, decrease in IMB-maintaining bacteria (e.g., Bifidobacterium), IMB dysfunction and systemic endotoxemia. These results uncover a host–microbiome interaction approach to the management of drug-induced gut toxicity. The prevention of CPT-11-induced gut microbiome changes by decreasing the tissue n-6/n-3 PUFA ratio could be a novel strategy to prevent chemotherapy-induced GIT.

Deficiency of omega 3 fatty acids may be linked to autism spectrum disorder (ASD). Evidence about the potential therapeutic effects of supplementation of omega 3 fatty acids is lacking in ASD patients. We searched major electronic databases from inception to June 21, 2017, for randomized clinical trials, which compared treatment outcomes between supplementation of omega 3 fatty acids and placebo in patients with ASD. An exploratory random-effects meta-analysis of the included studies was undertaken. Six trials were included (n=194). Meta-analysis showed that supplementation of omega 3 fatty acids improved hyperactivity (difference in means =-2.692, 95% confidence interval [CI] =-5.364 to -0.020, =0.048, studies =4, n=109), lethargy (difference in means =-1.969, 95% CI =-3.566 to -0.372, =0.016, studies =4, n=109), and stereotypy (difference in means =-1.071, 95% CI =-2.114 to -0.029, =0.044, studies =4, n=109). No significant differences emerged between supplementation of omega 3 fatty acids and placebo in global assessment of functioning (n=169) or social responsiveness (n=97). Our preliminary meta-analysis suggests that supplementation of omega 3 fatty acids may improve hyperactivity, lethargy, and stereotypy in ASD patients. However, the number of studies was limited and the overall effects were small, precluding definitive conclusions. Future large-scale randomized clinical trials are needed to confirm or refute our findings.

Attention-deficit hyperactivity disorder (ADHD) is a complex disorder in terms of etiology, clinical presentation, and treatment outcome. Pharmacological and psychological interventions are recommended as primary treatments in ADHD; however, other nonpharmacological intervention such as a dietary supplementation with omega-3 polyunsaturated fatty acids (ω-3 PUFAs) has emerged as an attractive option. The objective of the present study was to assess whether dietary supplementation with highly concentrated ω-3 docosahexaenoic acid (DHA) triglyceride may improve symptoms in ADHD. A 6-month prospective double-blind placebo-controlled randomized clinical trial was designed in 66 patients with ADHD, aged between 6 and 18 years. Participants in the experimental group received a combination of ω-3 fatty acids (DHA 1,000 mg, eicosapentaenoic acid 90 mg, and docosapentaenoic acid 150 mg). Instruments included d2-test, AULA Nesplora, EDAH scales, and abbreviated Conner's Rating Scale. In the cognitive test, between-group differences were not found, but within-group differences were of a greater magnitude in the DHA group. Between-group differences in favor of the DHA arm were observed in behavioral measures, which were already detected after 3 months of treatment. Results were not changed when adjusted by ADHD medication. This study provides further evidence of the beneficial effect of supplementation with ω-3 DHA in the management of ADHD.

Background The purpose of this review is to examine the effect of Omega-3 Fatty acids on mortality, morbidity, and adverse events in patients with acute myocardial infarction (AMI). Methods Data Sources: MEDLINE, EMBASE, and the Cochrane Library through May 2018. Study Selection: Randomized Controlled trials (RCT). Certainty of evidence was assessed with the GRADE system. Interventions: omega 3 fatty acids against placebo or no treatment. Primary and secondary outcomes: All-cause death, cardiovascular death, new AMI, stroke, need for therapeutic angioplasty or By-pass, new diagnosis of cancer and incidence of adverse events. Results For the efficacy endpoints we included 10 RCT (24,414 patients). Omega 3 fatty acids probably make little or no difference to all-cause mortality (4 studies 9141 patients RR 1.06 - CI95% 0.90 to 1.27, moderate certainty), cardiovascular mortality (3 studies 4304 patients RR 0.93 - CI95% 0.63 to 1.37, moderate certainty), new AMI (RR 1.24 CI95% 0.71 to 2.14 - moderate certainty), any cardiovascular event (RR 0.95 95%CI 0.86 to 1.05; low certainty due to risk of bias and imprecision), and stroke (RR 1.2 95%CCI 0,66–2,19 - moderate certainty). Regarding adverse events, we are uncertain if Omega 3 fatty acids improve/reduce non severe adverse events (RR 1.39 95% CI 0.36 to 5.34; very low certainty). There is probably little or no difference in the outcome suspension due to adverse events (RR 1.19 CI 95% 0.97 to 1.47; moderate certainty). Conclusions For adult patients with AMI, omega 3 fatty-acids probably yield no benefit to patient important outcomes.

Background Nut butter-based Ready to Use Supplemental Foods (RUSF) are an effective way to add nutrients and calories to diets of malnourished and food insecure populations. The RUSF formulations have been further modified to add micronutrients including iron and folic acid needed during pregnancy and lactation. Because docosahexaenoic acid (DHA, C22:6 n-3) enhances fetal development and birth outcomes, it has been suggested that perhaps RUSF formulations for pregnancy should also include this Omega 3 fatty acid. The goal of the present study was to gain an understanding of Zambian women’s knowledge of nutritional needs in pregnancy through structured focus group discussions, and to formulate and determine the acceptability of a RUSF with DHA. Methods Structured focus group sessions were conducted among women attending an antenatal clinic at the University Teaching Hospitals in Lusaka, Zambia. Dietary and nutrition knowledge was surveyed through structured dialogue that was recorded by audio and transcribed verbatim. An RUSF containing 400 mg DHA from fish oil in 50 g RUSF was designed and assessed for fatty acid content and product stability. Participants then sampled the RUSF-DHA, provided feedback on taste, and were surveyed about willingness to consume the novel formula using a standardized hedonic instrument. Results The participants’ knowledge of foods recommended for use in pregnancy included fruits, vegetables, meat, and fish. Most women reported eating fish at least once per week, although the specific type of fish varied. Most did not have prior knowledge of the importance of consuming fish during pregnancy or that some fish types were more nutritional than others as they included omega 3 fatty acids. The participants were uniformly accepting of the RUSF-DHA for the purpose of enhancing birth and developmental outcomes, but were critical of the aroma in hedonic testing. Conclusions Women were committed to consuming a healthy diet that would impact the outcome of pregnancy, and were receptive to advice on the importance of consuming foods such as fish as a source of DHA. The RUSF-DHA formulation was acceptable due to the potential benefits for the developing infant, however, the fishy odor may be limiting for long-term daily use.

To date, treatment of hypertriglyceridemia with long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been investigated solely in fasting and postprandial subjects. However, non-fasting triacylglycerols are more strongly associated with risk of cardiovascular disease. The objective of this study was to investigate the effect of long-chain n-3 PUFA on non-fasting triacylglycerol levels and to compare the effects of n-3 PUFA formulated as acylglycerol (AG-PUFA) or ethyl esters (EE-PUFA). The study was a double-blinded randomized placebo-controlled interventional trial, and included 120 subjects with non-fasting plasma triacylglycerol levels of 1.7–5.65 mmol/L (150–500 mg/dL). The participants received approximately 3 g/day of AG-PUFA, EE-PUFA, or placebo for a period of eight weeks. The levels of non-fasting plasma triacylglycerols decreased 28 % in the AG-PUFA group and 22 % in the EE-PUFA group ( P  < 0.001 vs. placebo), with no significant difference between the two groups. The triacylglycerol lowering effect was evident after four weeks, and was inversely correlated with the omega-3 index (EPA + DHA content in erythrocyte membranes). The omega-3 index increased 63.2 % in the AG-PUFA group and 58.5 % in the EE-PUFA group ( P  < 0.001). Overall, the heart rate in the AG-PUFA group decreased by three beats per minute ( P  = 0.045). High-density lipoprotein (HDL) cholesterol increased in the AG-PUFA group ( P  < 0.001). Neither total nor non-HDL cholesterol changed in any group. Lipoprotein-associated phospholipase A2 (LpPLA2) decreased in the EE-PUFA group ( P  = 0.001). No serious adverse events were observed. Supplementation with long-chain n-3 PUFA lowered non-fasting triacylglycerol levels, suggestive of a reduction in cardiovascular risk. Regardless of the different effects on heart rate, HDL, and LpPLA2 that were observed, compared to placebo, AG-PUFA, and EE-PUFA are equally effective in reducing non-fasting triacylglycerol levels.

Background The Omega‐3 Index is a test that measures the amount of the long‐chain omega‐3 polyunsaturated fatty acids (n‐3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in red blood cell membranes, which is expressed as a percentage of all fatty acids. However, alpha‐linolenic acid (ALA) from flaxseed oil, which is a short‐chain n‐3 PUFA, is often promoted in pet feed as a n‐3 source, implicitly assuming it is an effective precursor of EPA and DHA. Objective This study was aimed to compare the effect of supplementation with a plant‐based short‐chain n‐3 PUFA source (flaxseed oil, FSO) with a marine long‐chain n‐3 PUFA source (astaxanthin krill oil, AKO) to increase the Omega‐3 Index in dogs. Methods Ten adult Alaskan Huskies of both genders were supplemented daily with 1,155 mg of EPA/DHA from AKO, whereas another 10 dogs received 1,068 mg ALA from flaxseed oil for 6 weeks. Fatty acid and Omega‐3 Index measurements of the two groups were taken after 0, 3 and 6 weeks for comparison. Results The EPA and DHA concentrations increased significantly only in the dogs fed with AKO resulting in a significant increase in mean Omega‐3 Index, from 1.68% at baseline to 2.7% after 6 weeks of supplementation (p < .0001). On the contrary, both EPA and DHA concentrations decreased significantly in the dogs fed with FSO, which led to a significant decrease in mean Omega‐3 Index from 1.6% at baseline to 0.96% at study end (p < .0001). Conclusions The results showed that supplementation of AKO from Antarctic krill led to a significant increase in the Omega‐3 Index in comparison to FSO in dogs. This suggests that preformed marine EPA and DHA sources are needed in dog feeds, as the dietary requirements proposed by feed industry organizations are not met with conversion from short‐chain n‐3 fatty acids. This study investigated supplementation of two different omega‐3 fatty acid sources i.e. plant (flaxseed oil, FSO) versus marine (astaxanthin krill oil, AKO) to compare the effects of short‐ versus long‐chain polyunsaturated fatty acids (PUFAs) on the Omega‐3 Index in dogs. The results suggest that preformed marine EPA and DHA sources are needed in dog feeds, as the dietary requirements are not met with conversion from equal dosage of the short‐chain omega‐3 PUFA precursor, ALA from flaxseed oil.

The dietary recommendation encourages reducing saturated fatty acids (SFA) in diet and replacing them with polyunsaturated fatty acids (PUFAs) n–3 (omega–3) and n–6 (omega–6) to decrease the risk of metabolic disturbances. Consequently, excessive n–6 PUFAs content and high n–6/n–3 ratio are found in Western-type diet. The importance of a dietary n–6/n–3 ratio to prevent chronic diseases is linked with anti-inflammatory functions of linolenic acid (ALA, 18:3n–3) and longer-chain n–3 PUFAs. Thus, this review provides an overview of the role of oxylipins derived from n–3 PUFAs and oxylipins formed from n–6 PUFAs on inflammation. Evidence of PUFAs’ role in carcinogenesis was also discussed. In vitro studies, animal cancer models and epidemiological studies demonstrate that these two PUFA groups have different effects on the cell growth, proliferation and progression of neoplastic lesions.

Long chain omega-3 fatty acids (omega-3 FAs) supplements have been shown to exert beneficial effects in patients with epilepsy through elevation of seizure thresholds and dampening of inflammatory responses. In this triple blind randomized, placebo-controlled parallel group trial of omega-3 FA supplementation, 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA) as well as placebo capsules were administered twice a day in 50 patients with refractory seizure during a 16-week period respectively. Seizure frequency and duration were reduced after completion of the treatment in the supplement group. The supplementation resulted in a significant decrease in TNF-α and IL-6 concentrations. Further studies are needed to compare different omega-3 FA compositions and determine the most effective dose and treatment duration as well as the long term benefits of this supplementation.