Trial reportEBioMedicine2020
Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial.
Trial report in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02541929 (Fish Oil Brain Delivery Study), which is not on this map. Cited by 71 papers, 7 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Fish Oil Brain Delivery Study
Who cites it
71 citing papers in PubMed, 7 syntheses or guidelines pooled it, 124 citations in OpenAlex.
- Nutritional supplements and cognition in healthy aging and mild cognitive impairment patients: a systematic review and network meta-analysis.The journal of prevention of Alzheimer's disease · 2026Pooled it
- A systematic review and dose response meta analysis of Omega 3 supplementation on cognitive function.Scientific reports · 2025Pooled it
- Effects of Different Proportions of DHA and ARA on Cognitive Development in Infants: A Meta-Analysis.Nutrients · 2025Pooled it
- The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose-response meta-analysis.BMC medicine · 2024Pooled it
- Pooled it
- Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer's Disease and MCI: A Review.International journal of molecular sciences · 2023Pooled it
- Pooled it
- CNS target engagement of high-dose DHA supplementation in older adults at risk for dementia: a randomised, double-blind, placebo-controlled trial.EBioMedicine · 2026Trial
- The effects of docosahexaenoic acid supplementation on cognition and well-being in mild cognitive impairment: A 12-month randomised controlled trial.International journal of geriatric psychiatry · 2022Trial
- Bioavailability of Orally Administered Active Lipid Compounds from four Different Greenshell™ Mussel Formats.Marine drugs · 2020Trial
- Food-Derived Omega-3 Fatty Acids and Cognitive Aging: Integrating Nutritional Neuroscience and Geroscience.Nutrients · 2026Review
- Integrated metabolomics and genetic analyses reveal loss of protective docosahexaenoic acid as a key driver linking ultra-processed food to Crohn's disease risk.medRxiv : the preprint server for health sciences · 2026Article
- Cetoleic acid and other long-chain unsaturated fatty acids as neuroprotective nutraceuticals.Lipids in health and disease · 2026Review
- FADS1 contributes to anesthesia/surgery-induced cognitive impairment by aggravating omega-6 fatty acid metabolic disruption in aged mice.Journal of neuroinflammation · 2026Article
- Scientific Opinion on the tolerable upper intake level for supplemental docosahexaenoic acid.EFSA journal. European Food Safety Authority · 2026Article
- Gut-brain health effects of PREbiotics in older adults with suspected COgnitive DEcline: design of the PRECODE randomised placebo-controlled trial.Frontiers in nutrition · 2026Article
- Marine-derived PUFAs and peptides for aging-related memory deficits: processing methods, pharmacokinetics, mechanistic insights, and clinical application.Frontiers in nutrition · 2026Review
- Development of potent, selective cPLAnpj drug discovery · 2026Article
- Advancements in non-pharmaceutical interventions for Alzheimer's disease management: an update review.Frontiers in aging neuroscience · 2026Review
- Influence of APOE4 Genotypes on Nutrient-Cognition Relationship in Taiwanese Older Adults: Longitudinal Findings from the HALST.Nutrients · 2025Observational
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPast clinical trials of docosahexaenoic Acid (DHA) supplements for the prevention of Alzheimer's disease (AD) dementia have used lower doses and have been largely negative. We hypothesized that larger doses of DHA are needed for adequate brain bioavailability and that APOE4 is associated with reduced delivery of DHA and eicosapentaenoic acid (EPA) to the brain before the onset of cognitive impairment.
methods33 individuals were provided with a vitamin B complex (1 mg vitamin B12, 100 mg of vitamin B6 and 800 mcg of folic acid per day) and randomized to 2,152 mg of DHA per day or placebo over 6 months. 26 individuals completed both lumbar punctures and MRIs, and 29 completed cognitive assessments at baseline and 6 months. The primary outcome was the change in CSF DHA. Secondary outcomes included changes in CSF EPA levels, MRI hippocampal volume and entorhinal thickness; exploratory outcomes were measures of cognition.
findingsA 28% increase in CSF DHA and 43% increase in CSF EPA were observed in the DHA treatment arm compared to placebo (mean difference for DHA (95% CI): 0.08 µg/mL (0.05, 0.10), p<0.0001; mean difference for EPA: 0.008 µg/mL (0.004, 0.011), p<0.0001). The increase in CSF EPA in non-APOE4 carriers after supplementation was three times greater than APOE4 carriers. The change in brain volumes and cognitive scores did not differ between groups.
interpretationDementia prevention trials using omega-3 supplementation doses equal or lower to 1 g per day may have reduced brain effects, particularly in APOE4 carriers.
trial registrationNCT02541929.
fundingHNY was supported by R01AG055770, R01AG054434, R01AG067063 from the National Institute of Aging and NIRG-15-361854 from the Alzheimer's Association, and MGH by the L. K. Whittier Foundation. This work was also supported by P50AG05142 (HCC) from the National Institutes of Health. Funders had no role in study design, data collection, data analysis, interpretation, or writing of the report.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.