Fish oil

Authors:

Dean Sherzai

Participants:

Humans during the period of neurodevelopment: from fetal development to adolescence.

Study Quality Assessment:

Systematic review evaluating articles published between 2000 and 2022.

Findings:

This systematic review concludes that while basic research suggests multiple cardioprotective mechanisms for fish oil (ω-3 PUFAs like EPA and DHA), clinical evidence from numerous studies (RCTs, meta-analyses) regarding its efficacy in preventing or treating cardiovascular diseases (hypertension, CHD, AF, HF) is inconsistent and controversial. Potential benefits appear influenced by dose, formulation (EPA vs. EPA+DHA), patient population, baseline ω-3 status, and background therapy, with high doses (>1 g/d) potentially increasing atrial fibrillation risk. Further research is needed to clarify optimal use and mechanisms.

Participants:

Systematic review discussing studies involving in vitro/in vivo models (e.g., rats, mice) and diverse human populations including healthy subjects, individuals with CVD risk factors (hypertension, dyslipidemia, diabetes, obesity), patients with established CVD (CHD, MI, AF, HF), specific groups (children, pregnant women, elderly), and post-surgical/procedural patients (CABG, PCI, cardioversion).

Dosage:

Discusses a wide range of dosages from reviewed studies: low dose (≤1 g/day, e.g., 400mg, 840mg, 1g) and high dose (>1 g/day, e.g., 1.8g, 2g, 2.4g, 3.6g, 4g, up to 10g loading dose). Mentions specific formulations (purified EPA like icosapent ethyl, EPA+DHA combinations as ethyl esters or carboxylic acids) and ratios (e.g., EPA:DHA 6:1, 1:1, 1:2, <1). Notes potential dose-dependent effects (e.g., BP reduction, AF risk, biomarker changes), but optimal dose remains undefined.

Study Quality Assessment:

Systematic review summarizing evidence from basic research (in vivo/in vitro), Randomized Controlled Trials (RCTs), cohort studies (prospective, cross-sectional), and meta-analyses. Discusses methodological factors influencing results of cited studies, including dosage (low: ≤1 g/d vs. high: >1 g/d), formulation (EPA vs. EPA+DHA, ethyl ester vs. carboxylic acid), placebo type (mineral oil, corn oil, olive oil), baseline ω-3 levels, background medical therapy (e.g., statins, antiplatelets), study duration, and specific methods (e.g., 24h BP monitoring, plaque imaging). Acknowledges controversial results and limitations in the evidence base. Funding source for the review is mentioned.

All Effects:

Findings:

Daily supplementation with 2.3 g DHA-rich fish oil for 18 months did not maintain or improve cognitive performance in cognitively healthy older adults. A small negative main effect was observed on psychomotor speed, and treatment effects differed by sex and APOE-ε4 status on some cognitive domains. Treatment was also associated with increased perceived cognitive mistakes and increased oxidative stress.

Participants:

Cognitively healthy Australian community-dwelling adults (aged 65-90 y), N=403 randomly assigned, N=390 analyzed (intervention n=194, control n=196).

Dosage:

1720 mg DHA and 600 mg eicosapentaenoic acid (total 2.3 g DHA-rich fish oil) daily for 18 months.

Study Quality Assessment:

18-month randomized, double-blind, placebo-controlled, parallel-group trial. Permuted-block randomization stratified by age. Cognitive assessments conducted at baseline and every 6 months. Primary analyses used latent growth curve models. Secondary outcomes included self-reported well-being/functioning, blood pressure, biomarkers (n-3 LC PUFAs, lipids, glucose metabolism, inflammation, oxidative stress, DNA damage), and Mini-Mental State Examination. Sample size N=390 analyzed. Trial registered (ACTRN12607000278437).

All Effects:

Findings:

Three meta-analyses from 2006-2007 reported a significant benefit of omega-3 fatty acids for treating depressed mood, with a modest effect size (0.13-0.61).

Study Quality Assessment:

Information derived from three meta-analyses (2006-2007). These meta-analyses noted a large degree of heterogeneity between studies and evidence of publication bias.

Findings:

Omega-3 PUFA supplementation (EPA/DHA 5:1 ratio) showed neuroprotective effects in the retinas of both Opa1enu/+ and wild-type mice. This included increased retinal ganglion cell and ON axonal densities, reduced apoptosis (decreased Caspase-3 and Bax expression), and decreased activation of inflammatory microglia and astrocytes. Neuroprotection did not appear related to oxidative stress inhibition (no change in SOD-2 expression).

Participants:

Animal model: Eight-month-old mice (Opa1enu/+ and wild-type strains), n=20 per group.

Dosage:

EPA and docosahexaenoic acid (DHA) in a 5:1 ratio administered by daily gavage for 4 months. Dosage was adjusted based on maintaining a blood arachidonic acid (AA) to eicosapentaenoic acid (EPA) ratio (AA/EPA) between 1.0-1.5.

Study Quality Assessment:

Study design involved four groups (n=20/group). Methods included daily gavage administration, blood level monitoring (AA/EPA ratio), gas chromatography for fatty acid levels, histological examination of retina and optic nerve (ON), Western blotting, and immunohistochemistry. Funding source mentioned: Research Support, Non-U.S. Gov't.

All Effects: