Omega-3s show promise for very mild Alzheimer's
people with very mild Alzheimer's disease, but have no impact on
people with more advanced forms, says a new clinical trial.
"To our knowledge, this randomized, double-blind, placebo-controlled study is the first to be published on the effects of omega-3 fatty acid supplementation, mainly DHA… for Alzheimer's disease," wrote lead author Yvonne Freund-Levi in the Archives of Neurology (Vol. 63, pp. 1402-1408).
Alzheimer's disease is the most common form of dementia and currently affects over 13 million people worldwide. The direct and indirect cost of Alzheimer care is over $100 bn (€ 81 bn) in the US alone. The direct cost of Alzheimer care in the UK was estimated at £15 bn (€ 22 bn).
The researchers recruited 204 patients with varying degrees of Alzheimer's disease, and 174 patients completed the year-long study. Participants were initially assigned to either the omega-3 supplemented group (EPAX 1050TG, daily intake of 1720 mg DHA, 600 mg EPA) or an isocalorific placebo (corn oil with 0.6 g linoleic acid). Both the EPAX and placebos were provided by Pronova Biocare, which also partially funded the study.
After six months the omega-3 supplemented group showed 2.4 and 3.6-fold increases in the serum ratios of DHA and EPA, respectively. Both groups were then assigned to receive the omega-3 supplements for a further six months. Cognitive function was assessed used the Mini-Mental State Examination (MMSE) and the modified portion of the Alzheimer Disease Assessment Scale (ADAS-COG).
After 12 months both groups (omega-3/omega-3 and placebo/omega-3) had similar blood levels of DHA and EPA levels.
Freund-Levi and her co-workers report that, in general, no significant effect was observed for the MMSE and ADAS-COG scores after omega-3 supplementation. However, when the researchers looked at a subset of patients with very mild Alzheimer's (32 patients), a statistically significant effect was observed.
"Notwithstanding the negative results in the entire group of patients, our study indicated that the omega-3 fatty acid preparation conferred a slower decline of cognition in those with the mildest impairment compared with placebo control subjects with a similar degree of cognitive dysfunction at the start of the study," said Freund-Levi from the Karolinska University Hospital Huddinge in Sweden.
The improvements observed in this small subset were reportedly from the memory component, a result that reflects "a key symptom in Alzheimer's Disease, the episodic memory," said the researchers.
Although the mechanism of Alzheimer's is not clear, more support is gathering for the build-up of plaque from beta-amyloid deposits. The deposits are associated with an increase in brain cell damage and death from oxidative stress.
But how omega-3 fatty acids may interfere with the development of Alzheimer's disease is not clear, said the authors, but suggested that the benefits may be linked to the fish oil's anti-inflammatory effects, although no such effects were observed in this study.
"It is possible that when the disease is clinically apparent, the neuropathological involvement is too advanced to be substantially attenuated by anti-inflammatory [effects]," they said.
A critical period of two years or more before the onset of dementia may therefore be critical for the anti-inflammatory effects of the omega-3s, a suggestion that boosts dietary guidelines to increase omega-3 fatty acid intake from dietary or supplemental sources.
The study has several limitations, which are noted by the researchers. These include the second six-month period not being placebo-controlled, and improvements in the assessment scores could be due to practice effects and not the omega-3s.
"Studies in larger cohorts with mild cognitive impairment, including those at risk of Alzheimer's Disease, are needed to further explore the possibility that omega-3 fatty acids might be beneficial in halting initial progression of the disease," concluded Freund-Levi.
