Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial
Arellanes IC, Choe N, Solomon V, He X, Kavin B, Martinez AE, Kono N, Buennagel DP, Hazra N, Kim G, D'Orazio LM, McCleary C, Sagare A, Zlokovic BV, Hodis HN, Mack WJ, Chui HC, Harrington MG, Braskie MN, Schneider LS, Yassine HN
EBioMedicine · 111 citations
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- National Institute on Aging
- Government
- National Center for Advancing Translational Sciences
- Government
- NIA NIH HHS
- Government
- NCATS NIH HHS
- Grants
- National Institute on Aging (R01 AG055770); National Institute on Aging (P50 AG005142); National Institute on Aging (P30-AG066530); National Institute on Aging (R01AG067063); National Center for Advancing Translational Sciences (UL1‐TR‐001855); National Institute on Aging (R21 AG056518); National Institute on Aging (R01 AG054434)
Based on 4 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2020-07-17 · EBioMedicine · vol. 59 · p. 102883
- Publisher
- Elsevier BV
- Cited
- 134 citations · more than 99% of similar papers · 8.2× the field average
- Impact
- Top 10% most cited in its field
- References
- 63 works
- Access
- Open access (journal) · CC-BY-NC-ND
- Research areas
- Fatty Acid Research and Health · Antioxidant Activity and Oxidative Stress · Diet and metabolism studies
- Keywords
- Docosahexaenoic acid, Medicine, Eicosapentaenoic acid, Placebo, Internal medicine, Vitamin D and neurology, Randomized controlled trial, Gastroenterology, Physiology, Endocrinology, Polyunsaturated fatty acid, Fatty acid, Pathology, Biology, Biochemistry
- MeSH
- brain, humans, alzheimer disease, docosahexaenoic acids, treatment outcome, cognition, genotype, dietary supplements, aged, aged, 80 and over, middle aged, female, male, apolipoprotein e4
21 authors
From US
- Isabella C. ArellanesKeck Hospital of USC
- Nicholas ChoeKeck Hospital of USC
- Victoria A. SolomonKeck Hospital of USC
- Xulei HeKeck Hospital of USC
- Brian KavinKeck Hospital of USC
- Ashley E. MartinezKeck Hospital of USC
Abstract
Background
Past 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.
Methods
33 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.
Findings
A 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.
Interpretation
Dementia 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 registration
NCT02541929.
Funding
HNY 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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
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