Study Title:

DHA and Brain Inflammation in Alzheimer's Patients

Study Abstract

Objective
Little is known about the transfer of essential fatty acids (FAs) across the human blood–brain barrier (BBB) in adulthood. In this study we investigated whether oral supplementation with omega-3 (n-3) FAs would change the FA profile of the cerebrospinal fluid (CSF).

Methods
A total of 33 patients (18 receiving the n-3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double-blind, placebo-controlled randomised OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n-3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation.

Results
At 6 months, the n-3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n-3 FA levels (P < 0.01) whereas no changes were observed in the placebo group. Changes in CSF and plasma levels of EPA and docosapentaenoic acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin-1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers.

Conclusions
Oral supplementation with n-3 FAs conferred changes in the n-3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults.

From press release:

New research from Karolinska Institutet in Sweden shows that omega-3 fatty acids in dietary supplements can cross the blood brain barrier in people with Alzheimer's disease, affecting known markers for both the disease itself and inflammation. The findings are presented in the Journal of Internal Medicine, and strengthen the evidence that omega-3 may benefit certain forms of this seriously debilitating disease.

"Earlier population studies indicate that omega-3 can protect against Alzheimer's disease, which makes it interesting to study the effects of dietary supplements containing this group of fatty acids in patients who have already developed the disease," says the study's lead author Dr Yvonne Freund-Levi.

Omega-3 and other essential polyunsaturated fatty acids accumulate in the central nervous system (CNS) during gestation. It has been assumed that these acids are continually replaced throughout life, but little is known about how this occurs and whether changes in diet can affect the transport of important fatty acids across the blood-brain barrier. The blood-brain barrier serves to protect the brain from harmful chemicals existing naturally in the blood, but also blocks the delivery of drug substances to the brain.

Several diseases can affect the fatty acid profile of the CNS; in patients with Alzheimer's disease, for example, previous research has observed lower than normal brain concentrations of docosahexaenoic acid (DHA), an omega-3 fatty acid.

In the present study, part of the larger OmegAD project, scientists examined whether omega-3 dietary supplements change the fatty acid profile of the CNS in patients with mild Alzheimer's disease. Thirty-three patients participated in the study, 18 of whom received a daily omega-3 supplement and 15 a placebo for six months. The results show that the first group had higher levels of both DHA and eicosapentaenoic acid (EPA, another omega-3 fatty acid) in their cerebrospinal fluid (which surrounds the CNS) and blood. No such change was seen in the placebo group.

Moreover, they also found that levels of DHA correlated directly with the degree of change in Alzheimer's disease and inflammatory markers in the cerebrospinal fluid. Researchers in the field have long been interested in this link between Alzheimer's disease and inflammation, but attempts to treat the disease using traditional anti-inflammatory drugs have failed to produce any improvements in memory function.

"In animals, DHA dietary supplements can lead to an increase in DHA concentrations in the CNS," says Professor Jan Palmblad, who initiated the study. "Here we show that the same applies to humans, which suggests that omega-3 fatty acids in dietary supplements cross the blood-brain barrier. However, much work remains to be done before we know how these fatty acids can be used in the treatment of Alzheimer's disease to halt memory loss."

Study Information

Yvonne Freund Levi, Inger Vedin, Tommy Cederholm, Hans Basun, Gerd Faxén Irving, Maria Eriksdotter, Erik Hjorth, Marianne Schultzberg, Bengt Vessby, Lars-Olof Wahlund, Norman Salem, Jan Palmblad.
Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid (DHA)-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study
Journal of Internal Medicine
2013 November
Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.

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