Comments on "The effectiveness of intervention with omega-3 fatty acids, eicosapentaenoic and docosahexenoic acid in peripheral arterial disease: a systematic review and meta-analysis".

Fatty acids and bipolar disorder

Rationale for different formulations of omega-3 fatty acids leading to differences in residual cardiovascular risk reduction

The effectiveness of intervention with omega-3 fatty acids, eicosapentaenoic and docosahexenoic acid in peripheral arterial disease: a systematic review and meta-analysis.

Background: Urinary thromboxane B2 metabolites (TXB 2 ) are biomarkers of systemic thromboxane A2 (TXA 2 ) activity, an eicosanoid synthesized from arachidonic acid (AA) that is recognized to contribute to cardiovascular disease (CVD) independent of its platelet effects. The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), produce downstream molecules that can suppress TXA 2 . Whether circulating EPA+DHA or AA may influence TXB 2 levels or modify its association with incident CVD is unknown. Aims: To investigate the relations of circulating EPA, DHA, and AA to urinary TXB 2 and to assess whether these fatty acids may modify the association between TXB 2 and incident CVD. Methods: We studied 2,524 participants in the Framingham Heart Study Offspring/Omni cohorts, who were free of CVD at baseline, with measurements of urinary TXB 2 and circulating EPA, DHA, and AA. Incident CVD included a composite of coronary heart disease, stroke, peripheral artery disease, heart failure, and cardiovascular mortality. Hazard ratio (HR) and 95% confidence interval (CI) of the association between urinary TXB 2 (comparing high vs low using pre-determined cut-offs) and CVD, were calculated using multivariable-adjusted Cox models. We analyzed the cross-sectional relationship between circulating EPA, DHA, and AA with TXB 2 and assessed the relation between a per-1 standard deviation increment in TXB 2 and CVD stratified by tertiles of EPA+DHA or AA. Results: Among non-aspirin users, median TXB 2 decreased across tertiles of EPA (T3 vs T1: 3696 vs 4486 pg/mg creatinine) and DHA (T3 vs T1: 3670 vs 4497) ( P trend <0.0005 for each) ( Table 1 ). On the other hand, TXB 2 increased with higher AA (T3 vs T1: 4378 vs 3857 ( P trend =0.009). Similar trends were seen among aspirin users. After a median 12.9 years of follow-up, 428 incident CVD events occurred. Higher urinary TXB 2 was associated with incident CVD, with HR (95% CI) of 1.61 (1.19, 2.18) for aspirin non-users and 1.36 (1.02, 1.81) for users. Higher EPA+DHA or AA did not appear to modify the association between TXB 2 and incident CVD ( P interaction >0.05 for each). Conclusion: Urinary TXB 2 is associated with incident CVD after accounting for standard CVD risk factors. While circulating EPA and DHA are inversely related to TXB 2 , the association of TXB 2 with incident CVD is consistent across levels of EPA+DHA, suggesting likely separate biological pathways linking TXB 2 and omega-3 fatty acids with CVD development.

Since the original American Heart Association (AHA) Science Advisory was published in 1996,1 important new findings have been reported about the benefits of omega-3 fatty acids on cardiovascular disease (CVD). Omega-3 fatty acids are obtained from two dietary sources: seafood and certain nut and plant oils. Fish and fish oils contain the 20-carbon eicosapentaenoic acid (EPA) and the 22-carbon docosahexaenoic acid (DHA), whereas canola, walnut, soybean, and flaxseed oils contain the 18-carbon α-linolenic acid (ALA). ALA appears to be less potent than EPA and DHA. The evidence supporting the clinical benefits of omega-3 fatty acids derive from population studies and randomized, controlled trials, and new information has emerged regarding the mechanisms of action of these nutrients. These are outlined in a recent Scientific Statement, “Fish Consumption, Fish Oil, Omega-3 Fatty Acids and Cardiovascular Disease.”2 See page e20 Large-scale epidemiologic studies suggest that people at risk for coronary heart disease (CHD) benefit from consuming omega-3 fatty acids from plants and marine sources. Although the ideal amount to take is not firmly established, evidence from prospective secondary prevention studies suggests that intakes of EPA+DHA ranging from 0.5 …

Background: The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) exert antitumoral properties shown in several cancer types. DHA is found in abundance in the brain and is of importance in normal brain development and maintenance of function including cognitive functions. Medulloblastoma is the most common malignant CNS tumor of childhood. Intensive multimodal treatment is necessary including surgery, radiotherapy and chemotherapy. However, treatment often results in significant neurological sequelae and the risk of resistant relapses is still significant. The neuroprotective and antitumoral properties of omega-3 could therefore be of great benefit. Our aim was to investigate the effect of DHA and EPA on medulloblastoma in vitro and in vivo. Methods: In a panel of medulloblastoma cell lines the cytotoxic activity of DHA and EPA was studied using cell viability assays. The molecular mechanisms were characterized using cell- and molecular biology techniques. Mice with human medulloblastoma xenografts were treated with; DHA alone or with DHA and EPA for 30 days from time of tumor take while tumor growth was monitored. Control mice were fed with normal chow. The incorporation of fatty acids was analyzed in tumors, erythrocytes and brain tissue by LS-MS/MS. Results: DHA and EPA induced medulloblastoma cell toxicity with IC50 values ranging from 1.9 to 68 μM in six medulloblastoma cell lines. DHA reduced the prostaglandin E2 production, indicating a possible mechanism of action. In vivo, omega-3 supplementation resulted in significant reduction of tumor growth when established tumors were treated. DHA levels were increased in both tumor tissue and erythrocyte membrane compared to control. The in vivo treatment was non-toxic. Conclusions: DHA and EPA exert toxic effect on medulloblastoma cells in vitro and reduce tumor growth in vivo. These omega-3 fatty acids could therefore be good candidates for improving current therapy and at the same time protect healthy neurons from therapy-induced toxicity promoting cognitive function in survivors. Thus, omega-3 fatty acid supplementation has the potential of reducing tumor growth as well as reducing sequelae. Citation Format: Linda M. Ljungblad, John-Inge Johnsen, Malin Wickström, Per Kogner, Helena Gleissman. A novel approach to treat medulloblastoma: The omega-3 fatty acids DHA and EPA reduce medulloblastoma tumor growth in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3275. doi:10.1158/1538-7445.AM2015-3275

Are All Fish Equally Close to the Heart?–Reply

Chronic administration of docosahexaenoic acid or eicosapentaenoic acid, but not arachidonic acid, alone or in combination with uridine, increases brain phosphatide and synaptic protein levels in gerbils

Docosahexaenoic Acid Alleviates Atopic Dermatitis in Mice by Generating T Regulatory Cells and M2 Macrophages

Relation Between Red Blood Cell Omega-3 Fatty Acid Index and Bleeding During Acute Myocardial Infarction

Background: Evidence from observational studies and randomized trials suggest a favorable role of omega-3 fatty acids on cardiovascular outcomes. However, whether omega-3 fatty acids may reduce the incidence of peripheral artery disease (PAD) is not known. Aims: We prospectively evaluated blood and adipose tissue levels of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and the sum of EPA and DHA, with respect to incident PAD. Methods: We included 11 prospective studies from a global consortium up to May 2023 with measurements of ALA, EPA, DPA, or DHA (as a % of total fatty acids) in blood or adipose tissue among adults (age≥18), who were free of coronary artery disease, stroke, and PAD at baseline, and assessed incident PAD events. Each cohort conducted de novo individual-level analyses with a prespecified analytical plan and harmonized definitions for exposures, outcomes, covariates (including demographics, cardiovascular risk factors, medication use, and omega-6 fatty acid levels), and subgroups. Pooled hazard ratios (HRs) were calculated using inverse-variance weighted meta-analysis. Results: Among 142,316 participants from North America, Europe, and Australia followed for a weighted median of 13.7 years (range of median follow-up: 9.8 to 26.2 years), 1,842 incident cases of PAD were ascertained. In multivariable-adjusted pooled analysis, very long-chain EPA, DPA, DHA, and EPA+DHA each associated with lower PAD incidence, with HRs (95% CI) per interquintile range of 0.79 (0.69, 0.91), 0.80 (0.68, 0.95), 0.74 (0.64, 0.85), and 0.79 (0.69, 0.90), respectively ( P <0.01 for each) ( Figure 1 ). Long-chain ALA was not associated with PAD, 1.14 (0.98, 1.33). Heterogeneity between studies was low to moderate ( I 2\ ranging from 0% to 57%). Results were broadly consistent in prespecified subgroups by age, sex, smoking status, prevalent diabetes, and biomarker lipid fraction. Conclusion: In this large international consortium, objective levels of very long-chain, but not long-chain, omega-3 fatty acids inversely associated with incident PAD. Our data suggest a protective role for very long-chain omega-3 fatty acids in the development of PAD, supporting the need for further mechanistic studies and appropriately powered randomized controlled trials.

Intake of total omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid and risk of coronary heart disease in the Spanish EPIC cohort study

The differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on seizure frequency in patients with drug-resistant epilepsy — A randomized, double-blind, placebo-controlled trial

Essential fatty acids have long been identified as possible oncogenic factors. Existing reports suggest omega-6 (omega-6) essential fatty acids (EFA) as pro-oncogenic and omega-3 (omega-3) EFA as anti-oncogenic factors. The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells while the omega-6 fatty acids induces growth of these cells in animal models and cell lines. In order to explore likely mechanisms for the modulation of breast cancer cell growth by omega-3 and omega-6 fatty acids, we examined the effects of arachidonic acid (AA), linoleic acid (LA), EPA and DHA on human breast cancer cell lines using cDNA microarrays and quantitative polymerase chain reaction. MDA-MB-231, MDA-MB-435s, MCF-7 and HCC2218 cell lines were treated with the selected fatty acids for 6 and 24 h. Microarray analysis of gene expression profiles in the breast cancer cells treated with both classes of fatty acids discerned essential differences among the two classes at the earlier time point. The differential effects of omega-3 and omega-6 fatty acids on the breast cancer cells were lessened at the late time point. Data mining and statistical analyses identified genes that were differentially expressed between breast cancer cells treated with omega-3 and omega-6 fatty acids. Ontological investigations have associated those genes to a broad spectrum of biological functions, including cellular nutrition, cell division, cell proliferation, metastasis and transcription factors etc., and thus presented an important pool of biomarkers for the differential effect of omega-3 and omega-6EFAs.

Tissue Omega-6/Omega-3 Fatty Acid Ratio and Risk for Coronary Artery Disease