13 October 2006. The results of the first randomized, double-blind, placebo-controlled clinical trial of omega-3 fatty acid supplements for the treatment of Alzheimer disease show no effect on the mental decline in patients with mild to moderate AD. The disappointing results cast a glimmer of hope, however, for the small number of subjects with very mild AD who showed a significant slowing of disease progression during 6 months of treatment. The work, from Jan Palmblad and colleagues at the Karolinska Institute in Stockholm, is published in the October Archives of Neurology.
Epidemiological evidence ties intake of fish, rich in the omega-3 polyunsaturated fatty acids docosohexaenoic acid (DHA) and eicosapentaenoic acid (EPA), to a lower risk of Alzheimer disease (see ARF related news story). DHA helps maintain synapses and reduce amyloid burden in mice (see ARF related news story; Calon et al., 2005; and Lim et al., 2005), and influences the activation of AKT, an important survival pathway for neurons (see ARF related news story). More importantly, people with lower serum levels of this fatty acid may have an increased risk for AD (see Kyle et al., 1999).
To look for a therapeutic effect of omega-3 fats, the researchers, led by first author Yvonne Freund-Levi, randomized 204 AD patients to receive DHA/EPA capsules (for a total dose of 1,720 mg DHA/600 mg EPA) or placebo for 6 months. After the treatment period, all the subjects received open label omega-3 for another 6 months. The treatment was well tolerated, and 174 people finished the trial. The researchers found no difference in cognitive decline between the treated and placebo groups over the 6 or 12 months as measured by the Mini-Mental State Exam and the cognitive portion of the Alzheimer Disease Assessment Scale (ADAS-Cog).
Thinking that omega-3 fats might selectively affect early events in AD, the researchers performed a post hoc analysis of subgroups of patients, dividing them according to MMSE scores. In the group of 32 patients with the most mild AD (MMSE >27, Clinical Dementia Rating Score 0.5-1), omega-3 supplementation stopped the decline in MMSE scores. Even with the small number of subjects, the results reach statistical significance. In addition, the very mild cases in the placebo group also showed a statistically significant slowing of decline when they were switched to treatment for second half of the study.
These results support the idea that omega-3 fatty acids, particularly DHA, might be useful in preventing AD. This would be consistent with epidemiological studies, which show that fish consumption lowers the risk of developing dementia. But the current findings are based on very few patients treated for a short time; longer, larger trials will be necessary to confirm the findings. Likewise, more studies will be needed to find out if DHA acts mainly as an anti-inflammatory agent, or has a different, perhaps direct effect on neurons.
“These findings cannot serve as a basis for general recommendations for treatment of AD with dietary DHA-rich fish oil preparations,” the authors write. “However, studies in larger cohorts with mild cognitive impairment, including those at risk for AD, are needed to further explore the possibility that omega-3 fatty acids might be beneficial in halting initial progression of the disease.” Given that the treatment appears safe and was well tolerated, that may be a pill some folks are willing to swallow.—Pat McCaffrey.
Freund-Levi Y, Eriksdotter-Jönhagen M, Cederholm T, Basun H, Faxén-Irving G, Garlind A, Vedin I, Vessby B, Wahlund L-O, Palmblad J. Omega-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial. Arch Neurol. 2006;63:1402-1408. Abstract