No benefit for DHA in Alzheimer’s disease, time to move over for EPA?


Alzheimer’s disease is a progressive neurodegenerative disorder that represents the major cause of dementia in the world today.  In the UK alone, Alzheimer’s disease, and other forms of dementia, affects over 750,000 people, and these numbers are continuing to grow.  Oily fish, including encapsulated fish oils, are particularly high in two omega-3 fatty acids – docosahexaenoic (DHA) and eicosapentaenoic acid (EPA) – and these fats are known to have a profound role in brain function, with low levels influencing dementia risk.  Consequently, they have become the focus of many studies looking at methods to protect the brain from premature ageing.

 

However, following another announcement that “DHA supplements were ‘not useful’ in reducing cognitive decline associated with mild-to-moderate Alzheimer’s disease”, could it be that scientists are simply concentrating on the wrong fatty acid?  DHA is the major omega-3 fatty acid found in neurons, and as such, this fat has taken on (what would appear to be) a logical central role as a target for therapeutic intervention in Alzheimer’s disease.  Despite, however, a plethora of in vitro, animal model, and data gathered from human trials, this important structural fatty acid appears to have little, if any, benefit in treating the symptoms associated with Alzheimer’s.   Published in this month’s Journal of the American Medical Association (JAMA), researchers reported that DHA at a dose of 2 g/day did not affect cognitive and functional abilities after 18 months of supplementation.  These findings seem particularity striking, given that individuals within the DHA-supplemented group started the trial with low baseline DHA, with levels increasing to within a normal range during the trial, but without evidence of any benefit.1

So what is going on?  Whilst DHA provides an important structural role in brain nerve tissue, it is implied that EPA has a very direct protective role.  Indeed, recent studies have linked EPA to several modulating factors that are involved in the onset and progression of Alzheimer’s disease.   For example, it has been previously demonstrated in vitro and in animal studies that EPA (preferentially over DHA) stimulates the expression of several myelin proteins known to play a vital role in maintaining cell membrane integrity.2,3 More recently, EPA has been shown to reduce the loss of acetylcholine-producing neurons known to account for some of the degradation of cognitive function associated with Alzheimer’s disease.4 With regard to a direct neuroprotective influence, EPA has been shown to reduce grey matter atrophy associated with Huntington’s disease and it is also suggested that EPA protects DHA loss from cell membranes.5

A spokesperson from the Council for Responsible Nutrition (CRN), commenting on the study findings, suggested that the stage of disease progression was simply too advanced, and that a high dose supplementation of omega-3 would serve better as a preventative measure rather than as a treatment option.  Going along the lines of ‘closing the barn door after the horse has bolted’, supplementing DHA to individuals with advanced Alzheimer’s simply isn’t good enough.

However, the increasing evidence of the protective role of EPA (and certainly over DHA), in dementia initiation and progression, could point to the use of highly concentrated EPA-dominant oils as a preventative, and possibly therapeutic option for Alzheimer’s disease.  Indeed, given that the UK is not an oily-fish loving nation, the use of highly purified EPA as a preventative tool, would offer a safe alternative to fish consumption, whilst providing the higher dose that may be needed to protect from cognitive decline in later life.

1.  Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR, Weiner M, Shinto L, Aisen PS. Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Trial. JAMA: The Journal of the American Medical Association, 2010; 304 (17): 1903 DOI:

2.  Salvati S, Natali F, Attorri L, Raggi C, Di Biase A, Sanchez M. (2004) Stimulation of myelin proteolipid protein gene expression by eicosapentaenoic acid in C6 glioma cells.NeurochemistryInternational 44: 331-8.

3.  Salvati S, Natali F, Attorri L, Di Benedetto R, Leonardi F, Di Biase A, Ferri F, Fortuna S, Lorenzini P, Sanchez M, Ricceri L, Vitelli L. (2008) Eicosapentaenoic acid stimulates the expression of myelin proteins in rat brain.Journal of Neuroscience Research86: 776-84.

4. Taepavarapruk P, Song C. 2009 Reductions of acetylcholine release and nerve growth factor expression are correlated with memory impairment induced by interleukin-1beta administrations: effects of omega-3 fatty acid EPA treatment. Journal of  Neurochemistry. Dec 3. [Epub ahead of print]

5.  Puri BK, Bydder GM, Manku MS, Clarke A, Waldman AD, Beckmann CF. (2008) Reduction in cerebral atrophy associated with ethyl-eicosapentaenoic acid treatment in patients with Huntington’s disease.Journal of  International Medical Research. 36:896-905.

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