Failure of omega-3 polyunsaturated fatty acids in prevention of migraine: a double-blind study versus placebo

Omega-3 polyunsaturated fatty acids (OPFA) have beneficial effects on inflammatory reactions and production of cytokines. They decrease the release of 5HT by platelets and possess vasorelaxant activity. This led them to be tried in the prophylactic treatment of migraine. After 4 weeks of a single-blind placebo run-in period, patients were randomized and treated in double-blind condition by placebo or OPFA 6 g a day for 16 weeks, followed by a 4-week placebo run-out period. The intention to treat population included 196 patients. Those who received all four treatment periods included 96 patients taking OPFA and 87 taking placebo. The primary efficacy analysis was the number of migraine attacks during the last 4 weeks of treatment. During this period, the mean number of attacks was 1.20 +/- 1.40 in the OPFA group and 1.26 +/- 1.11 in the placebo group (NS). The total number of attacks during the 4-month period of the study was significantly different between groups: 7.05 in the placebo group, 5.95 in the OPFA group (P = 0.036). Mean intensity, mean duration of the attacks and rescue medication use, were not significantly different between the two groups. Except for a significant difference against OPFA for eructations, the tolerance was satisfying. Despite a run-in placebo period of 1 month, a very strong placebo effect was observed in this trial: 45% reduction of the attacks between run-in and 4-month treatment period (55% in the OPFA group, P = 0.058). Finally, this large study did not confirm two previous studies based on a small number of patients.     

The effects of omega-3 polyunsaturated fatty acids on cardiac rhythm: A critical reassessment

Although epidemiological studies provide strong evidence for an inverse relationship between omega-3 polyunsaturated fatty acids (n−3 PUFAs) and cardiac mortality, inconsistent and often conflicting results have been obtained from both animal studies and clinical prevention trials. Despite these heterogeneous results, some general conclusions can be drawn from these studies: 1) n-PUFAs have potent effects on ion channels and calcium regulatory proteins that vary depending on the route of administration. Circulating (acute administration) n−3 PUFAs affect ion channels directly while incorporation (long-term supplementation) of these lipids into cell membranes indirectly alter cardiac electrical activity via alteration of membrane properties. 2) n−3 PUFAs reduce baseline HR and increase HRV via alterations in intrinsic pacemaker rate rather than from changes in cardiac autonomic neural regulation. 3) n−3 PUFAs may be only effective if given before electrophysiological or structural remodeling has begun and have no efficacy against atrial fibrillation. 5) Despite initial encouraging results, more recent clinical prevention and animal studies have not only failed to reduce sudden cardiac death but actually increased mortality in angina patients and increased rather than decreased malignant arrhythmias in animal models of regional ischemia. 6) Given the inconsistent benefits reported in clinical and experimental studies and the potential adverse actions on cardiac rhythm noted during myocardial ischemia, n−3 PUFA must be prescribed with caution and generalized recommendations to increase fish intake or to take n−3 PUFA supplements need to be reconsidered.     

Celecoxib and omega-3 fatty acids alone and in combination with risperidone affect the behavior and brain biochemistry in amphetamine-induced model of schizophrenia

The implications of oxidative stress and neuro-inflammation in the pathogenesis of schizophrenia have been elucidated. Despite their effectiveness against positive symptoms of schizophrenia, antipsychotics have limited effectiveness against negative and cognitive symptoms and are associated with remarkable adverse effects. The use of celecoxib or omega-3 in schizophrenia may have beneficial effects. This study aimed to evaluate the possible efficacies of celecoxib, omega-3 or the combination of celecoxib + risperidone and omega-3+ risperidone compared to risperidone on the behavior and brain biochemistry in rats. In the present study, an amphetamine-induced model of schizophrenia in adult male rats was used to evaluate the effects of celecoxib, omega-3, celecoxib + risperidone and omega-3+ risperidone on the behavior of animals and on brain lipid peroxidation or tumor necrosis factor-alpha. In the water maze task, celecoxib, omega-3, celecoxib + risperidone, omega-3+ risperidone significantly decreased the latency time compared to amphetamine-treated group. Celecoxib, omega-3, celecoxib + risperidone, omega–3 + risperidone also significantly reversed the decreased spontaneous alternation induced by amphetamine in the Y-maze task. In the social interaction task, groups treated with celecoxib, omega-3, celecoxib + risperidone, omega-3+ risperidone spent less time to recognize foreign animals than animals in the amphetamine-treated group. Increased brain MDA and TNF-α levels due to amphetamine were significantly reduced in groups treated with celecoxib + risperidone or omega-3+ risperidone. The present findings showed that celecoxib or omega-3 can attenuate amphetamine- induced behavioral impairment and these effects may be associated with their ability to decrease lipid peroxidation and cytokine release. Celecoxib or omega-3 may be promising candidates as adjuvant therapy for schizophrenia.     

Pharmacology and therapeutics of omega-3 polyunsaturated fatty acids in chronic inflammatory disease

Omega-3 (n−3) polyunsaturated fatty acids (n−3 PUFAs) have well documented anti-inflammatory properties, and consequently therapeutic potential in chronic inflammatory diseases. Here we discuss the effects of n−3 PUFAs on various inflammatory pathways and how this leads to alterations in the function of inflammatory cells, most importantly endothelial cells and leukocytes. Strong evidence indicates n−3 PUFAs are beneficial as a dietary supplement in certain diseases such as rheumatoid arthritis; however for other conditions such as asthma, the data are less robust. A clearer understanding of the pharmacology of n−3 PUFAs will help to establish targets to modulate chronic inflammatory diseases.     

Biochemical and therapeutic effects of Omega-3 fatty acids in sickle cell disease

Sickle cell disease (SCD) is a hematologic disorder with complex pathophysiology that includes chronic hemolysis, vaso-occlusion and inflammation. Increased leukocyte-erythrocyte-endothelial interactions, due to upregulated expression of adhesion molecules and activated endothelium, are thought to play a primary role in initiation and progression of SCD vaso-occlusive crisis and end-organ damage. Several new pathophysiology-based therapeutic options for SCD are being developed, chiefly targeting the inflammatory pathways.Omega−3 fatty acids are polyunsaturated fatty acids that are known to have effects on diverse physiological processes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the principal biologically active omega-3 fatty acids. The therapeutic effects of DHA and EPA on chronic inflammatory disorders and cardiovascular diseases are well recognized. The therapeutic effects of omega-3 fatty acids are attributed to their anti-inflammatory and anti-thrombotic eicosanoids, and the novel class of EPA and DHA derived lipid mediators: resolvins, protectins and maresins.Blood cell membranes of patients with SCD have abnormal fatty acids composition characterized by high ratio of pro-inflammatory arachidonic acid (AA) to anti-inflammatory DHA and EPA (high omega-6/omega-3 ratio). In addition, experimental and clinical studies provide evidence that treatment with DHA does confer improvement in rheological properties of sickle RBC, inflammation and hemolysis. The clinical studies have shown improvements in VOC rate, markers of inflammation, adhesion, and hemolysis. In toto, the results of studies on the therapeutic effects of omega-3 fatty acids in SCD provide good body of evidence that omega-3 fatty acids could be a safe and effective treatment for SCD.     

The limited effect of omega-3 polyunsaturated fatty acids on cardiovascular risk in patients with impaired glucose metabolism: A meta-analysis

Objectives

The impacts of marine-derived n − 3 polyunsaturated fatty acids (n − 3 PUFAs) on cardiovascular risk are not well known. We conducted this meta-analysis to determine the effects of n − 3 PUFAs on cardiovascular outcomes and cardiovascular risk markers in patients with impaired glucose metabolism (IGM).

Design and methods

We searched PUBMED, EMBASE, The Cochrane Library and reference lists of relevant papers for high quality randomized controlled trials comparing dietary intake of n − 3 PUFAs with placebo in IGM patients. Data was extracted and quality assessed independently by two reviewers. Authors were contacted for missing information. Overall estimates were calculated using a random-effects model or a fixed-effects model, and the possibility of publication bias was examined using a funnel plot. Subgroup analyses were conducted to explore the association between the risk markers and study characteristics.

Results

Our meta-analysis included 19 studies, 24,788 patients. Compared with placebo, n − 3 PUFAs had no statistically significant reduce effect on cardiovascular mortality, major cardiovascular events, all-cause mortality or composite endpoint of all-cause mortality or hospitalization for cardiovascular cause, however it can significantly reduce the level of triglycerides (weighted mean difference [WMD] − 0.25 mmol/L; 95% CI − 0.37 to − 0.13: p < 0.001; 12 trials, 13,921 patients).

Conclusion

Marine-derived n − 3 polyunsaturated fatty acids have no protective effect on cardiovascular mortality, major cardiovascular events, all-cause mortality and composite endpoint of all-cause mortality or hospitalization for cardiovascular cause in IGM patients, but can reduce triglyceride level.     

Treatment of hypertriglyceridemia with omega-3 fatty acids: a systematic review

PURPOSE: To (a) critically appraise available randomized controlled trials (RCTs) addressing the efficacy of long-chain omega-3 fatty acids as secondary agents for prevention of hypertriglyceridemia and (b) make recommendations for clinical practice. DATA SOURCES: Two independent reviewers examined all RCTs from 1994 to 2003 identified in several databases, extracted data from each study, and used the previously tested Boyack and Lookinland Methodological Quality Index (MQI) to determine study quality. CONCLUSIONS: Ten studies reported long-chain omega-3 fatty acids to be effective in the treatment of hypertriglyceridemia. The average decrease in triglycerides was 29%, total cholesterol 11.6%, very low density lipoprotein (VLDL) 30.2%, and low-density lipoprotein (LDL) 32.5%. One study found LDLs to increase by 25%. The average increase in high-density lipoprotein was 10%. The overall average MQI score was 36% (range = 26% to 54%). Many of the RCTs had serious shortcomings, including short duration, lack of a power analysis, no intention-to-treat analysis, no report of blind assessment of outcome, and lack of dietary control as a confounding variable. IMPLICATIONS FOR PRACTICE: Overall study methodology was weak. Although the evidence supporting use of long-chain omega-3 fatty acids in the secondary prevention of hypertriglyceridemia is reasonably strong, until there are larger RCTs of better methodological quality, it is not recommended that practitioners treat hypertriglyceridemia with omega-3 fatty acid supplementation in lieu of lipid-lowering medications.     

Effect of omega-3 fatty acids supplementation on anthropometric indices in children and adolescents: A systematic review and meta-analysis of randomized controlled trials

• •Background Childhood obesity is a major public health problem with a global prevalence greater than 23 %. Omega-3 polyunsaturated fatty acids (omega-3 FAs) supplementation may improve anthropometric indices by increased energy expenditure, attenuated appetite, elevated adiponectin levels, though current evidence is still inconclusive.
• •Objective The aim of this systematic review was to conduct the first comprehensive meta-analysis of randomized controlled trials on the association between omega-3 FAs supplementation and anthropometric indices in children and adolescents.
• •Methods We performed an extensive online database search of the published literature using the SCOPUS, Web of Science, PubMed, EMBASE, and Cochrane library databases from the index date through April 2019. Six studies met inclusion criteria. Changes in anthropometric indices (weight, BMI and waist circumference) were extracted from each article. Statistical heterogeneity was assessed by calculating the I² statistic. We used the standardized mean difference (SMD) with 95 % confidence interval. The meta-analysis was performed based on a random effects model.
• •Results This meta-analysis demonstrated that omega-3 FAs supplementation had no effect on reducing body weight (SMD = -0.00, 95 % CI -0.26 to 0.25), BMI (SMD = -0.07, 95 % CI -0.32 to 0.17) and waist circumference (SMD = -0.16, 95 % CI -0.51 to 0.19).
• •Conclusions Omega-3 FAs supplementation did not change anthropometric indices in children and adolescents. Further large-scale studies with larger sample sizes in children and adolescents are needed to clarify the effects of omega-3 FAs.

     

Omega-3 polyunsaturated fatty acids and cardiovascular disease: an emphasis on omega-3-acid ethyl esters 90 for the treatment of hypertriglyceridemia

A number of epidemiological/observational studies, as well as large-scale randomized intervention studies, have been conducted to provide evidence for the efficacy of ω-3 fatty acids against atherosclerotic diseases. Currently, ω-3 fatty acids are commercially available in many parts of the world containing the same active ingredients as Lotriga^® (ω-3-acid ethyl esters 90 [O3AE highly concentrated ω-3 fatty acid ethyl esters, consisting of eicosapentaenoic acid-ethyl ester and docosahexaenoic acid-ethyl ester [EPA-E/DHA-E]). A recent head-to-head comparative study of O3AEE90 versus EPA-E demonstrated that O3AEE90 4g/day led to a significantly greater reduction in triglycerides (TG) than EPA-E 1.8g/day and that O3AEE90 2g/day produced comparable effects on TG to those with EPA-E 1.8g/day. While both agents were shown to be useful in lowering TG, the hallmark feature of O3AEE90, that is, the presence of the DHA-E component versus its absence in EPA-E, needs to be further examined for its clinical implications.     

Atorvastatin and omega-3 fatty acids protect against activation of the coagulation system in patients with combined hyperlipemia

Summary. Activation of factor (F)VII by tissue factor may represent a critical event during plaque rupture in acute coronary syndromes. Patients with combined hyperlipemia are at high risk for developing coronary heart disease and their tendency to thrombosis may be accelerated during postprandial hyperlipemia. In the present double‐blind, placebo‐controlled parallel study, 42 patients with combined hyperlipemia and serum triglycerides between 2.0 and 15.0 mmol L^?1 and serum cholesterol >5.3 mmol L^?1 at the end of a 3‐month dietary run‐in period were treated with atorvastatin at 10 mg day^?1 for at least 10 weeks. During the last 5 weeks the patients were randomized into two groups receiving 1.68 g day^?1 omega‐3 fatty acids (ω‐3 FA) or placebo (corn oil). The fasting levels of FVII antigen (FVII‐Ag) and FVII coagulant activity (FVII:C) were high compared with healthy males. The fasting levels of activated FVII (FVIIa) and FVII‐Ag correlated both to serum triglycerides and apolipoprotein A1 (apoA1). FVIIa and FVII:C increased during postprandial hyperlipemia. This increase of FVIIa correlated to the fasting triglyceride and apoA1 levels, but not to the degree of postprandial hypertriglyceridemia. The concentrations of fasting FVIIa in these patients were reduced in parallel with a reduction of fasting triglycerides by treatment with atorvastatin + placebo. This treatment also reduced the postprandial level of FVIIa. ω‐3 FA in addition to atorvastatin further reduced FVIIa concentrations, fasting and postprandially, and also significantly reduced FVII:C and FVII‐Ag during postprandial hyperlipemia. Prothrombin fragment 1 + 2 (F1 + 2) increased during postprandial hyperlipemia. This increase was significantly reduced after treatment with atorvastatin plus ω‐3 FA. The increase of F1 + 2 measured as incremental area under the curve (iAUC) during postprandial hyperlipemia correlated to the fasting levels of FVIIa, FVII:C and FVII‐Ag and also to the levels of these factors during postprandial lipemia. In conclusion, patients with combined hyperlipemia are at risk for activation of the coagulation system, particularly during postprandial lipemia. This activation may be significantly reduced by statins and ω‐3 FA.     

Effects of combination treatment with policosanol and omega-3 fatty acids on platelet aggregation: A randomized, double-blind clinical study

Background:

Policosanol is a mixture of long-chain primary aliphatic alcoholspurified from sugar cane wax that has cholesterol lowering and antiplatelet effects. Omega-3 fatty acids (FA) have triglyceride lowering and antiplatelet effects. Combination treatment with policosanol and omega-3 FA (Ω23FA) has been associated with significant inhibition of platelet aggregation in rabbits compared with either drug alone.

Objective:

The aim of this study was to investigate the effects of combination treatment with Ω3FA (1 g/d) and policosanol (Ω3FA+Poli) compared with Ω3FA (1 g/d) plus placebo (Ω3FA+Pla) on platelet aggregation in human patients with hypercholesterolemia.

Methods:

This randomized, double-blind, clinical study at the Surgical Medical Research Center (Havana City, Cuba) recruited outpatients from lipid clinics, with some atherosclerotic risk factors. Outpatients of both sexes aged 20 to 75 years with serum total cholesterol (TC) levels ≥5 and <6 mmol/L were eligible to enroll. They were included in the study at the end of a 4-week diet stabilization period if their platelet aggregation to arachidonic acid (AA) was ≥50% and serum TC level remained ≥5 mmol/L. Patients were then evenly randomized to receive Ω3FA (1 g/d) + placebo or Ω3FA (1 g/d) + policosanol (10 mg/d) to be taken PO with the evening meal for 21 days. Treatment was assigned according to a randomization code using balanced blocks and a 1:1 allocation ratio. Inhibition of platelet aggregation to AA was the primary efficacy variable, while effects on platelet aggregation to collagen and epinephrine and on lipid profile were secondary variables. Drug compliance and adverse events (AEs) were monitored. Tolerability was assessed using physical examinations and laboratory test results.

Results:

Sixty-four subjects were initially enrolled. Fifty-four patients (30 women, 24 men; mean [SD] age, 58.4 [12] years, [range, 40-70 years]) met the inclusion criteria and were randomized to treatment; 2 groups of 27. After 21 days, platelet aggregation to AA was significantly inhibited in the 2 groups. Ω3FA+Poli inhibited platelet aggregation to all agonists by ≥20%. Platelet aggregation to AA 1.0 and 1.5 mM was inhibited with combination treatment (39.6% and 33.9%, respectively; both P < 0.001 vs baseline; P < 0.001 and P < 0.01, respectively, vs Ω3FA+Pla) and with Ω3FA+Pla (11.0% and 13.3%; both, P < 0.001). Combination treatment was more effective in inhibiting platelet aggregation to AA 1.0 and 1.5 mM in 28.6% (P < 0.001) and 20.6% (P < 0.01), respectively. Platelet aggregation to collagen 1 μg/mL was significantly inhibited with combination treatment and with Ω3FA+Pla compared with baseline (43.2% and 15.1%, respectively; both, P < 0.001), but the effects of combination treatment were significantly greater (P < 0.01). Platelet aggregation to epinephrine 0.1 mM was inhibited with Ω3FA+Poli and Ω3FA+Pla (34.8% and 20.1%; both, P < 0.001), with similar results for both groups. Bleeding time did not change significantly for either group and Ω3FA+Pla did not significantly change the lipid profile. Combination treatment did significantly reduce levels of low-density lipoprotein cholesterol (LDL-C) (17.4%; P < 0.001 vs baseline, P < 0.05 vs Ω3FA+Pla) and TC (10.1%; P < 0.001 vs baseline, P < 0.05 vs Ω3FA+Pla), increase high-density lipoprotein cholesterol (HDL-C) levels (18.0%; P < 0.001 vs baseline), but did not significantly change triglyceride levels. Three patients (2 from the Ω3FA+Poli group and 1 from the Ω3FA+Pla group) withdrew from the trial, though none were due to AEs. Two patients receiving combination treatment reported mild AEs (headache). All treatments were well tolerated.

Conclusions:

In these patients, policosanol (10 mg/d) administered concomitantly with Ω3FA (1 g/d) enhanced the inhibition of platelet aggregation to AA and collagen, but not to epinephrine, compared with Ω3FA+Pla, without significantly affecting bleeding time. Concomitant treatment was also associated with reduced levels of LDL-C and TC and raised HDL-C levels. All treatments were well tolerated.     

Prevention of sudden cardiac death with omega-3 fatty acids in patients with coronary heart disease: A meta-analysis of randomized controlled trials

Aim. To systematically review trials concerning the effects of omega-3 fatty acids on sudden cardiac death (SCD), cardiac death, and all-cause mortality in coronary heart disease (CHD) patients.

Methods. PubMed, Embase, and the Cochrane database (1966–2007) were searched. We identified randomized controlled trials that compared dietary or supplementary intake of omega-3 fatty acids with control diet or placebo in CHD patients. Eligible studies had at least 6 months of follow-up data, and cited SCD as an end-point. Two reviewers independently assessed methodological quality. Meta-analysis of relative risk was carried out using the random effect model.

Results. Eight trials were identified, comprising 20,997 patients. In patients with prior myocardial infarction (MI), omega-3 fatty acids reduced relative risk (RR) of SCD (RR = 0.43; 95% CI: 0.20–0.91). In patients with angina, omega-3 fatty acids increased RR of SCD (RR = 1.39; 95% CI: 1.01–1.92). Overall, RR for cardiac death and all-cause mortality were 0.71 (95% CI: 0.50–1.00) and 0.77 (95% CI: 0.58–1.01), respectively.

Conclusions. Dietary supplementation with omega-3 fatty acids reduces the incidence of sudden cardiac death in patients with MI, but may have adverse effects in angina patients.     

Effect of omega-3 supplements on plasma apolipoprotein C-III concentrations: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Apolipoprotein C-III (apo C-III) is a key regulator of triglycerides metabolism. The aim of this meta-analysis was to assess the effect of fish omega-3 polyunsaturated fatty acids (PUFAs) on apo C-III levels.

Methods: Randomized placebo-controlled trials investigating the impact of omega-3 on apo C-III levels were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar. A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on glycemic parameters.

Results: This meta-analysis comprising 2062 subjects showed a significant reduction of apo C-III concentrations following treatment with omega-3 (WMD: ?22.18?mg/L, 95% confidence interval: ?31.61, ?12.75, p?<?.001; I²: 88.24%). Subgroup analysis showed a significant reduction of plasma apo C-III concentrations by eicosapentaenoic acid (EPA) ethyl esters but not omega-3 carboxylic acids or omega-3 ethyl esters. There was a greater apo C-III reduction with only EPA as compared with supplements containing EPA and docosahexaenoic acid (DHA) or only DHA. A positive association between the apo C-III-lowering effect of omega-3 with baseline apo C-III concentrations and treatment duration was found.

Conclusions: This meta-analysis has shown that omega-3 PUFAs might significantly decrease apo C-III.

• Key messages

• Omega-3 PUFA supplements significantly reduce apo C-III plasma levels, particularly in hypertriglyceridemic patients when applied in appropriate dose (more than 2?g/day)

• Triglyceride (TG)-lowering effect is achieved via peroxisome proliferator-activated receptors α

• Further studies should address the effect of omega-3 PUFAs alone or with other lipid-lowering drugs in order to provide a final answer whether apo C-III could be an important target for prevention of cardiovascular disease

• New apo C-III antisense oligonucleotide drug (Volanesorsen) showed to be promising in decreasing elevated TGs by reducing levels of apo C-III mRNA

     

Distal procto-colitis and n-3 polyunsaturated fatty acids: the mechanism(s) of natural cytotoxicity inhibition

BACKGROUND: Altered natural killer (NK) and lymphokine-activated killer (LAK) cell activities have been reported with ulcerative colitis (UC). Previously, we have shown that in patients with UC, the n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), specifically inhibit natural cytotoxicity with clinical improvement in disease activity. The aim of this study therefore was to evaluate the possible mechanism(s) involved in this inhibition, and in particular the alteration of production of interleukin 2 (IL2) and the arachidonic acid metabolite leukotriene B4 (LTB4), both known to modulate NK cell activity. MATERIALS AND METHODS: Each patient with procto-colitis received either fish oil extract (EPA 3.2 g, DHA 2.4 g; n = 9) or placebo (n = 9) daily for 6 months. Monthly assessment included disease activity using clinical and sigmoidoscopic scores. Peripheral blood mononuclear (PBMN) cells were isolated and NK cell cytotoxic activity in vitro was measured. Monthly serum samples were analysed for LTB4, IL2 and soluble IL2 receptors (sIL2R). RESULTS: The n-3 PUFAs group had significantly reduced NK cell activity, compared with the placebo group (P < 0.05, Mann-Whitney U-test). In the n-3 PUFA group, incubation of PBMN cells for 72 h with recombinant interleukin 2 (rIL2) reversed the NK inhibition. In patients with active proctocolitis, serum levels of LTB4 correlated positively with NK cell cytotoxicity (r = 0.873, P < 0.05, Kendall's correlation coefficient). After six months of n-3 PUFAs supplementation, serum levels of LTB4 were undetectable with concurrent significant reduction in NK cell cytotoxic activity. The latter was associated with significant reduction of serum IL2 and sIL2R levels (P < 0.05). CONCLUSION: This study has demonstrated both evidence of suppression of immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFAs supplementation. This may have important implications for therapy in patients with UC.     

Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: A randomized trial

Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches. After a 4-week preintervention phase, ambulatory patients with chronic daily headache undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention. Clinical outcomes included the Headache Impact Test (HIT-6, primary clinical outcome), Headache Days per month, and Headache Hours per day. Biochemical outcomes included the erythrocyte n-6 in highly unsaturated fatty acids (HUFA) score (primary biochemical outcome) and bioactive n-3 and n-6 derivatives. Fifty-six of 67 patients completed the intervention. Both groups achieved targeted intakes of n-3 and n-6 fatty acids. In intention-to-treat analysis, the H3-L6 intervention produced significantly greater improvement in the HIT-6 score (−7.5 vs −2.1; P < 0.001) and the number of Headache Days per month (−8.8 vs −4.0; P = 0.02), compared to the L6 group. The H3-L6 intervention also produced significantly greater reductions in Headache Hours per day (−4.6 vs −1.2; P = 0.01) and the n-6 in HUFA score (−21.0 vs −4.0%; P < 0.001), and greater increases in antinociceptive n-3 pathway markers 18-hydroxy-eicosapentaenoic acid (+118.4 vs +61.1%; P < 0.001) and 17-hydroxy-docosahexaenoic acid (+170.2 vs +27.2; P < 0.001). A dietary intervention increasing n-3 and reducing n-6 fatty acids reduced headache pain, altered antinociceptive lipid mediators, and improved quality-of-life in this population.     

Targeted nano-delivery of novel omega-3 conjugate against hepatocellular carcinoma: Regulating COX-2/bcl-2 expression in an animal model

The present approach enumerates the effectiveness of tuftsin tagged nano-liposome for the cytosolic transport of 2,6-di-isopropylphenol-linolenic acid conjugate against liver cancer in mice. Initially, the conjugate in its free form was examined for anticancer potential on HepG2 liver cancer cells. Induction of apoptosis and suppression of migration and adhesion of HepG2 cells confirmed the effectiveness of conjugate as an anticancer agent. After this, role of the conjugate entrapped in a nano-carrier was evaluated in animal model. The nano-formulation comprising of conjugate bearing tuftsin tagged liposome was firsly characterized and then its therapeutic effect was determined. The nano-formulation had 100–130 nm size nanoparticles and showed sustained release of the conjugate in the surrounding milieu. The nano-formulation distinctly reduced the expression of COX-2, an important molecule that is vastly expressed in hepatocellular carcinoma. The utilization of in-house engineered nano-formulation was also successful in significantly up-regulating Bax and down-regulating bcl-2 gene expression eventually helping in better survival of treated mice. Histopathological analysis also revealed positive recovery of the general architecture and the violent death of cancer cells by apoptosis at tumor specific site. The site specific delivery of conjugate entrapped in tuftsin tagged liposomes was highly safe as well as efficaceous. Nano-formulation based approach showed a visible chemotherapeutic effect on liver cancer progression in experimental mice thereby making it a potential candidate for treatment of liver cancer in clinical settings.