Six months of daily omega-3 supplementation increased 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 results suggest that omega-3 supplements may be linked to higher levels of inflammation and nerve damage, previous OmegAD data showed that memory stabilized over six months in patients with very slight cognitive decline, while those who did not receive omega-3s experienced amnesia.
Notably, no cognitive benefits were seen in patients with more severe cognitive impairment, suggesting that omega-3 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 taking omega-3 supplements early in the disease had better results, ”said Yvonne Freund-Levi, MD, PhD, lead author of the study from the Karolinska Institute in Sweden, in a press release.
“Even if we do not currently have enough data to change our recommendations for patients, it is an interesting material for researchers to build on,” added Freund-Levi, who also conducts neuroscience research at Örebro University.
Larger studies are needed to confirm these results and to clarify the therapeutic potential of omega-3 supplements in early-stage Alzheimer’s disease.
The study, “Effects of Oral 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 like oily fish (salmon, tuna, mackerel), walnuts, and some seeds. Omega-3 is the key to cell structure and has been shown to help prevent heart disease.
Previous studies in animal models suggested that omega-3 supplementation could have beneficial effects on cognitive function and lower levels of beta amyloid – the protein that forms toxic clumps in Alzheimer’s disease – in a mouse model of the disease.
However, conflicting results have been reported in older adults and in Alzheimer’s patients. The OmegAD study (NCT00211159), launched in 2005, examined the safety and effects of omega-3 dietary supplements on the cognitive function of 204 people with mild to moderate Alzheimer’s disease. enrolled at Karolinska University Hospital Huddinge.
Participants were randomly given either omega-3 (2.3 grams) or placebo supplements once daily for six months, followed by omega-3 daily for six months.
Cognitive function was assessed using the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) and the Mini-Mental State Examination (MMSE), which includes orientation, attention, memory, language and visuospatial skills.
Previous results showed that after six months there were no differences in cognitive function between groups in the overall patient population.
However, significant group differences were found in a subgroup of 32 patients with very mild cognitive impairment (MMSE score higher than 27). Those who received omega-3 had stable cognitive function throughout the study, while those who received a placebo showed poorer cognitive performance after six months, especially in the memory ranges of both measures (MMSE and ADAS-Cog).
Notably, this memory loss stopped when patients switched from placebo to omega-3 supplements, suggesting that omega-3 prevents or slows memory loss in Alzheimer’s patients with mild cognitive impairment.
Freund-Levi, one of the researchers involved in the OmegAD study, and colleagues now carried out a post-hoc analysis of the study data, in which changes in the CSF levels of several disease-related biomarkers were assessed in a subset of participants.
It should be noted that post hoc analysis usually focuses on a specific topic of interest and is done after a study is complete.
The new analysis included 33 participants: 18 were initially assigned to omega-3s and 15 to placebo. CSF samples (the fluid that surrounds the brain and spinal cord) were collected at the start of the study and after six months of treatment. The levels of several biomarkers for Alzheimer’s, nerve cell damage, and inflammation were measured.
The results showed that biomarker levels were similar between the groups at the start of the study, but 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 amyloid beta and tau protein, remained stable in the omega-3 group.
These preliminary results suggest “a possible increase in the inflammatory response and” [nerve fiber] Harm “with omega-3 supplementation, but this increase in NfL and YKL-40” did not correlate with the MMSE score, “the researchers wrote, showing no clinical association with the results of the memory test.
“We are reluctant to make recommendations, but we know that starting early is by far the best – it is difficult to influence the disease later,” says Freund-Levi. She added that, given what we know so far, “the best advice we can offer right now is to be physically active and include omega-3s in your diet – in the form of oily fish or as a dietary supplement”.
The researchers found that changes in the levels of these biomarkers can also be analyzed in blood samples, meaning that future studies on biomarkers will no longer require a spinal tap to collect CSF samples.
“We have already tested this approach at the Sahlgrenska University Hospital. Without a doubt, it’s so much better for the patients, ”said Freund-Levi.