Food and Behaviour Research

Donate Log In

Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial.

Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J. (2006) Arch Neurol 63(10): 1402-8. 

Web URL: View this and related abstracts via PubMed here


BACKGROUND: Epidemiologic and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids, for example, docosahexaenoic acid and eicosapentaenoic acid, may prevent Alzheimer disease (AD).

OBJECTIVE: To determine effects of dietary omega-3 fatty acid supplementation on cognitive functions in patients with mild to moderate AD.

DESIGN: Randomized, double-blind, placebo-controlled clinical trial.

PARTICIPANTS: Two hundred four patients with AD (age range (mean +/- SD), 74 +/- 9 years) whose conditions were stable while receiving acetylcholine esterase inhibitor treatment and who had a Mini-Mental State Examination (MMSE) score of 15 points or more were randomized to daily intake of 1.7 g of docosahexaenoic acid and 0.6 g of eicosapentaenoic acid (omega-3 fatty acid-treated group) or placebo for 6 months, after which all received omega-3 fatty acid supplementation for 6 months more.

MAIN OUTCOME MEASURES: The primary outcome was cognition measured with the MMSE and the cognitive portion of the Alzheimer Disease Assessment Scale. The secondary outcome was global function as assessed with the Clinical Dementia Rating Scale; safety and tolerability of omega-3 fatty acid supplementation; and blood pressure determinations.

RESULTS: One hundred seventy-four patients fulfilled the trial. At baseline, mean values for the Clinical Dementia Rating Scale, MMSE, and cognitive portion of the Alzheimer Disease Assessment Scale in the 2 randomized groups were similar. At 6 months, the decline in cognitive functions as assessed by the latter 2 scales did not differ between the groups. However, in a subgroup (n = 32) with very mild cognitive dysfunction (MMSE >27 points), a significant (P<.05) reduction in MMSE decline rate was observed in the omega-3 fatty acid-treated group compared with the placebo group. A similar arrest in decline rate was observed between 6 and 12 months in this placebo subgroup when receiving omega-3 fatty acid supplementation. The omega-3 fatty acid treatment was safe and well tolerated.

CONCLUSIONS: Administration of omega-3 fatty acid in patients with mild to moderate AD did not delay the rate of cognitive decline according to the MMSE or the cognitive portion of the Alzheimer Disease Assessment Scale. However, positive effects were observed in a small group of patients with very mild AD (MMSE >27 points).


204 patients with mild to moderate Alzheimer's Disease were randomly allocated to receive either a food supplement containing the main omega-3 fatty acids found in fish oils - DHA and EPA - or placebo capsules for 6 months. They were then followed up, and their cognitive function re-assessed using a standardised rating scale for dementia.

In a subgroup of 32 patients with only mild cognitive impairment, their rate of decline in cognitive function was significantly reduced if they received omega-3 rather than placebo. There were no discernible differences, however, between the two treatment groups as a whole.


This is the first clinical trial to investigate whether dietary supplementation with EPA and DHA - the long-chain omega-3 found in fish oils - could help in the management of mild to moderate Alzheimer's disease.

While no benefits were found for the group as a whole, there appeared to be a significant slowing of the rate of cognitive decline in those patients whose cognitive problems were still mild at the outset - suggesting further investigations are warranted.


A pioneering clinical trial of B vitamins for Age-related Cognitive Decline and Dementia found significant benefits from supplementation over a 2-year period with Vitamins B6, B12 and folate.

However, it was later found that only those participants with good initial Omega-3 status showed benefits from the B vitamins - and other evidence had already shown that omega-3 and B vitamins work synergistically together to support brain development and function. See:

This discovery led to a re-investigation of data from this very early trial of omega-3 for dementia - to see if B vitamin status might have influenced the results. (This was assessed via measures that had been taken of a toxic substance called homocysteine, which builds up when Vitamins B6, B12 and/or folate are lacking).

Results of this re-analysis of the original data found that any benefits of omega-3 supplementation in slowing cognitive decline did indeed depend on patients' B vitamin status. Effects of omega-3 were greater for those with lower homocysteine (indicating higher lvels of B6, B12 and folate) See:

These findings add to the existing evidence that there are important synergies between long-chain omega-3 and B vitamins for brain health - such that neither can work optimally without the other.

To date, the vast majority of clinical trials of either omega-3 or B vitamins have supplemented only one or the other, without considering their potential interactions.  This may help to explain some of the inconsistencies in their findings - and future trials now need to take these nutrient synergies and interactions into account.