Omega-3 Supplements May Slow Memory Decline

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Six months of daily supplements of omega-3 increased the levels of two biomarkers of inflammation and nerve damage in the cerebrospinal fluid (CSF) of people with Alzheimer’s disease, according to a post-hoc analysis of data from the OmegAD clinical trial.

While these preliminary findings suggest that omega-3 supplements may be associated with higher inflammation and nerve damage, previous OmegAD data showed that patients with very mild cognitive decline saw their memory stabilize over six months, while those not given omega-3 experienced memory decline.

Notably, no cognitive benefits were observed among patients with greater cognitive impairment, suggesting that omega-3’s benefits may be limited to people with early stage disease and milder cognitive problems.

“We can see a difference in the results of the memory tests. Patients who were taking omega-3 supplements at an early stage of the disease scored better,” Yvonne Freund-Levi, MD, PhD, the study’s senior author of the Karolinska Institute, in Sweden, said in a press release.

“Even if this data isn’t enough for us to change our recommendations to patients at this time, it is an interesting material for researchers to build on,” added Freund-Levi, who also is a researcher in neuroscience at Örebro University.

Larger studies are needed to confirm these findings and clarify the therapeutic potential of omega-3 supplements in early stage Alzheimer’s.

The study, “Effects of Peroral Omega-3 Fatty Acid Supplementation on Cerebrospinal Fluid Biomarkers in Patients with Alzheimer’s Disease: A Randomized Controlled Trial — The OmegAD Study,” was published in the Journal of Alzheimer’s Disease.

Omega-3 is a polyunsaturated fatty acid, a type of healthy fat found in foods such as fatty fish (salmon, tuna, mackerel), walnuts, and some seeds. Omega-3 is key to cells’ structure and has been shown to help prevent heart disease.

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Previous studies in animal models suggested that omega-3 supplementation may have beneficial effects in cognitive function and reduce the levels of beta-amyloid — the protein that forms toxic clumps in Alzheimer’s — in a mouse model of the disease.

However, inconsistent findings have been reported in older adults and in Alzheimer’s patients.The OmegAD trial (NCT00211159), launched in 2005, evaluated the safety and effects of omega-3 supplements in cognitive function of 204 people with mild-to-moderate Alzheimer’s, enrolled at the Karolinska University Hospital Huddinge.

Participants were assigned randomly to receive either omega-3 (2.3 grams) or placebo supplements, once daily for six months, after which all were given daily omega-3 for six more months.

Cognitive function was assessed with the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) and the Mini-Mental State Examination (MMSE), which includes tests of orientation, attention, memory, language, and visual-spatial skills.

Previous results showed that after six months there were no differences in terms of cognitive function between the groups in the overall patient population.

However, significant group differences were found among a sub-group of 32 patients with very mild cognitive impairment (MMSE score higher than 27). Those on omega-3 had stable cognitive function throughout the study, while those on a placebo showed worse cognitive performance after six months, particularly in the memory domains of both measures (MMSE and ADAS-Cog).

Notably, this memory decline was arrested when patients switched from placebo to omega-3 supplements, suggesting that omega-3 prevents or slows memory decline in Alzheimer’s patients with mild cognitive impairment.

Now, Freund-Levi, one of the researchers involved in the OmegAD study, and colleagues conducted a post-hoc analysis of the trial data evaluating changes in the CSF levels of multiple disease-relevant biomarkers in a subset of participants.

Of note, a post-hoc analysis is normally focused on a particular subject of interest and performed after a trial has been completed.

The new analysis involved 33 participants: 18 initially assigned to omega-3 and 15 assigned to placebo. CSF samples (the liquid that surrounds the brain and spinal cord) were collected at the trial’s start and after six months of treatment. The levels of several biomarkers of Alzheimer’s, nerve cell damage, and inflammation were measured.

Results showed that while the levels of biomarkers were similar between groups at the study’s start, there was a small, but significant, increase in neurofilament light chain (NfL), a marker of nerve cell damage, and YKL-40, a marker of inflammation, in the omega-3 group after six months of treatment.

The levels of the other biomarkers, such as Alzheimer’s-associated beta-amyloid and tau protein, remained stable in the omega-3 group.

These preliminary findings suggest “a possible increase of inflammatory response and [nerve fiber] damage,” with omega-3 supplementation, but this raise in NfL and YKL-40 “did not correlate with MMSE score,” the researchers wrote, indicating no clinical link with the memory test results.

“We are cautious about giving recommendations, but we know that starting early is by far the best thing – it is difficult to influence the disease at a later stage,” Freund-Levi said. She added that given the evidence so far “the best piece of advice we have to offer at the moment is to be physically active and to include omega-3 in your diet – in the form of oily fish or as supplements.”

The researchers noted that changes in the levels of these biomarkers also can be analyzed in blood samples, meaning that future studies on biomarkers no longer will require spinal tap procedures to collect CSF samples.

“We have already tested this approach at Sahlgrenska University Hospital. Without a doubt, it is so much better for the patients,” Freund-Levi said.