Omega-3 fatty acids

Findings:

Genetically predicted total omega-3 fatty acids were found to reduce the odds of Major Depressive Disorder (MDD) (OR 0.96 per SD), with the strongest association observed for eicosapentaenoic acid (EPA) (OR 0.92). The effect remained robust after accounting for correlated lipids using Multivariable MR. Colocalization analyses suggested a shared causal variant, although potential genomic confounding or pleiotropy could not be fully excluded.

Participants:

Genetic data from large human cohorts: UK Biobank (UKBB, n = 115,078), Psychiatric Genomics Consortium (PGC) MDD GWAS (n = 430,775; cases = 116,209; controls = 314,566), PGC recurrent depression (rMDD) GWAS (n = 80,933; cases = 17,451; controls = 62,482), and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, n = 8866).

Study Quality Assessment:

Mendelian randomization study (two-sample MR). Utilizes large GWAS datasets (UKBB, PGC, CHARGE) with specified sample sizes. Methods mentioned: Multivariable MR (MVMR), genetic colocalization analyses, 'Leave-one-out' analyses. Potential limitations acknowledged: 'genomic confounding could not be fully excluded', 'pleiotropic mechanisms cannot be ruled out'. Conflict of interest statement: 'The authors declare no competing interests.'

All Effects:

Authors:

Abdalaziz M Alsubaie, Ibrahim M Dighriri

Findings:

Ingestion of omega-3 fatty acids was found to increase learning, memory, cognitive well-being, and blood flow in the brain. Omega-3 treatments were reported as advantageous, well-tolerated, and low-risk, potentially benefiting lonelier people, the elderly, and those with lower dietary omega-3 intake or lower baseline levels.

Participants:

Systematic review included 9 RCTs with a total of 1319 participants (591 men, 728 women), mean age 45. Individual studies included adult males and females across various age ranges (e.g., 20-29, 30-54, 50-75, 61-72, 20-80) and specific groups like healthy adults, elderly volunteers, lonelier individuals, and those with low baseline DHA or low episodic memory.

Dosage:

Included studies used various daily dosages, e.g., 300mg omega-3, 900mg DHA, 1g fish oil, 2g fish oil, 1.25g omega-3, 2.5g omega-3, 2.2g fish oil/omega-3. Administration periods mentioned include 12 weeks, 24 weeks, 26 weeks, 4 months, 6 months. FDA recommendation mentioned: consume no more than 3g/day total omega-3, with supplements delivering no more than 2g/day.

Study Quality Assessment:

Systematic review of 9 Randomized Clinical Trials (RCTs) published in English between 2010-2022. Quality assessed using Cochrane Collaboration bias assessment tool: all trials used appropriate randomization protocols, six used allocation concealment, all were double-blind, outcome evaluation was appropriately blinded in eight RCTs, one trial had unclear bias due to insufficient outcome data, all used acceptable selective reporting, and seven had low risk of other bias. Limitations acknowledged: potential confounding effects of other nutrients/vitamins not assessed in included studies; review limited to nine articles found via three databases.

All Effects:

Findings:

Evidence from multiple RCTs showed that turmeric and curcuminoids significantly lowered blood triglycerides (TG), total cholesterol (TC), and LDL cholesterol, and increased HDL cholesterol in adults with metabolic diseases. However, findings should be interpreted cautiously due to significant heterogeneity between studies.

Participants:

Adults with metabolic diseases

Study Quality Assessment:

Systematic review and meta-analysis of Randomized Controlled Trials (RCTs). Searched multiple English and Chinese databases (Web of Science, PubMed, Ovid, Scopus, Cochrane Library, Wanfang Data, China National Knowledge Infrastructure). Used random-effects models with inverse-variance. Reported mean difference with 95% CIs. Acknowledged limitation: significant heterogeneity between included studies (I2 > 50%).

All Effects:

Findings:

Preclinical and observational studies suggest low EPA/DHA intake is linked to suboptimal brain development, increased Alzheimer's risk, and potentially poorer cognitive functioning in mid-life adults. Raising intake among healthy adults may improve some aspects of cognitive performance (memory, psychomotor speed, attention, response inhibition reported sporadically in RCTs). However, the review concludes that evidence from Randomized Clinical Trials (RCTs) is currently sparse, weak, preliminary, inconsistent, and does not demonstrate robust benefits, leaving key questions about clinical significance, dosage, timing, and specific cognitive domains unanswered.

Participants:

Review summarizes studies involving infants, children (e.g., 6-10 year-olds, some 'marginally nourished' or low SES), adolescents (e.g., N=4000 Swedish males 15-18), mid-life adults (e.g., N=54-280 healthy adults aged 18-70, N=55 for MRI, U.S. military servicemembers, some with depressive symptoms), and elderly adults (>55 years, some healthy, some with MCI, N=1111 post-menopausal women, N=2300 older adults for imaging). Preclinical studies involved rats and non-human primates. The review focuses primarily on cognitive performance in generally healthy mid-life adults.

Dosage:

Review discusses various dosages. Typical US intake <200mg/day EPA+DHA. RCTs in mid-life adults used doses ranging from ~500mg to 2400mg/day EPA+DHA combined (e.g., 1740mg EPA+250mg DHA; 1600mg EPA+800mg DHA; 630mg EPA+850mg DHA; 1160mg DHA+160mg EPA; 450mg DHA+90mg EPA; 300mg EPA+200mg DHA) for 4-26 weeks. Elderly RCTs used 80-2300mg/day; studies <800mg/day generally found no treatment effects. Dose-response relationships remain unclear.

Study Quality Assessment:

Review discusses evidence from preclinical studies (rodents, non-human primates, cell culture), observational studies (cross-sectional, prospective, case-control, cohort studies using dietary questionnaires or blood biomarkers like plasma/RBC/serum phospholipids), and Randomized Clinical Trials (RCTs, often placebo-controlled using olive oil/sunflower oil, some double-blind). Methods mentioned include neuropsychological testing, MRI, magnetic resonance spectroscopy (MRS), functional near IR spectroscopy (fNIRS), IQ tests. Limitations acknowledged for observational studies (confounding) and RCTs (sparse evidence, small sample sizes [e.g., N=10-70 in some elderly trials, N=49-228 in mid-life trials], short durations [4-26 weeks], unclear clinical significance/dose-response/time course, potential unblinding due to side effects like 'fishy belching', placebo choice issues [olive oil criticized], inconsistent recruitment criteria regarding baseline intake, high drop-out rate in one trial [23%]). Funding source disclosure provided (NIH funding, one past grant from Isodi Natura acknowledged for separate study).

All Effects:

Findings:

The meta-analysis found an overall beneficial effect of omega-3 PUFAs on depression symptoms (SMD = -0.28, P = 0.004). Formulations with EPA ≥ 60% (including EPA-pure) at dosages ≤1 g/d showed clinical benefits compared to placebo, whereas DHA-pure and DHA-major formulations did not. Current evidence supports beneficial effects on depression for omega-3 PUFAs with EPA ≥ 60% at a dosage of ≤1 g/d.

Participants:

N=2160 participants (from 26 studies analyzed)

Dosage:

Beneficial effects observed with EPA ≥ 60% formulations at an EPA dosage ≤1 g/d.

Study Quality Assessment:

Meta-analysis of double-blind randomized placebo-controlled trials (RCTs). N=26 studies, N=2160 participants. Methods included systematic bibliographic search (PubMed, EMBASE), RevMan 5.3 and R 3.4.3 for analysis, fixed- or random-effects models based on Q-test, sensitivity analysis, funnel plot and Egger's linear regression analysis for publication bias. Conflict of interest statement: Authors declare no conflict of interest.

All Effects: