Milan Fiala, Ramesh C Halder, Bien Sagong, Olivia Ross, James Sayre, Verna Porter, Dale E Bredesen
Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2015;29(7):2681-9
PMID: 25805829
The build-up of a protein fragment, beta-amyloid, in the brains of individuals with Alzheimer’s disease (AD) has been the focus of experimental therapeutics however, no significant impacts from medication have been achieved to date. This open label study of 21 individuals, with either pre-mild cognitive decline, mild cognitive decline (MCD) or AD, measured the effects of 4-17 months supplementation with omega-3 fatty acids (1000mg DHA, 1000mg EPA plus antioxidants, Vitamin D and resveratrol) on beta-amyloid breakdown, changes to inflammatory gene expression and measures of cognitive function (mini-mental state examination questionnaire). The study found significant increases in beta-amyloid breakdown with omega-3 supplementation in patients with pre-MCI or MCI but not in patients with AD. Cognitive function was also affected by supplementation and appeared to be stabilised. The authors call for this work to be followed up with randomised clinical trials.
We investigated the effects of 4-17 month supplementation with ω-3 fatty acids and antioxidants (Smartfish drink; Smartfish AS, Oslo, Norway) in 12 patients with minor cognitive impairment (MCI) [minimental state examination (MMSE) ≥19], 2 patients with pre-MCI (normal MMSE), and 7 patients with Alzheimer disease (AD) (MMSE <19). We measured the phagocytosis of amyloid-β 1-42 (Aβ) by flow cytometry and microscopy, the transcription of inflammatory genes by RT-PCR, the production of resolvin D1 (RvD1) by enzyme immunoassay, and the cognitive status by MMSE. In patients with MCI and pre-MCI, phagocytosis of Aβ by monocytes increased from 530 to 1306 mean fluorescence intensity units (P = 0.016). The increase in patients with AD was not significant (N.S.). The lipidic mediator RvD1, which stimulates Aβ phagocytosis in vitro, increased in macrophages in 80% of patients with MCI and pre-MCI (mean increase 9.95 pg/ml) (N.S.). Transcription of inflammatory genes' mRNAs was increased in a subgroup of patients with low transcription at baseline, whereas it was not significantly changed in patients with high transcription at baseline. The mean MMSE score of patients with MCI and pre-MCI was 25.9 at baseline and 25.7 after 4-17 months (N.S.). Our study is the first to show significant immune and biochemical effects of ω-3 fatty acids with antioxidants in patients with MCI. Cognitive benefits of ω-3 supplementation in patients with MCI should be tested in a clinical trial.
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