Depression as a risk factor for developing dementia: why supplementing with ethyl-EPA may be the answer to both

Approximately 600,000 people in the UK are now believed to have dementia. This figure represents 5% of the total population aged 65 and over, with Alzheimer’s disease accounting for 60% of all cases.  Interestingly, suffering from depression at a younger age may be a significant risk factor for dementia.1 In fact, it is thought that sufferers from major depression are at double the risk of developing dementia later in life compared to individuals who have not suffered with depression.  Difficulties often arise at the time of diagnosis, as similarities in symptoms between dementia and depression have often meant the two may be confused.

The increasing scientific focus on the mechanisms that occur within the body and brain of both depressed patients and those with dementia has linked the two conditions to an increase in inflammation within areas of the brain.   If chronic inflammatory changes are a common feature of depression, this could predispose depressed patients to neurodegenerative changes in later life.  For example, neuronal loss is a common feature of both major depression and dementia.

It is believed that the progress from depression to dementia could result from the activation of specific immune cells (macrophages) in the blood and specialist cells (microglia) in the brain that release destructive products called pro-inflammatory cytokines. These cytokines stimulate a cascade of inflammatory changes, including the production of more pro-inflammatory cytokines as well as the over production of the stress hormone cortisol.   Excess cortisol inhibits the production of various proteins required to repair damaged neuronal networks. In addition, toxic end products accumulate in neurones and other cells, called astrocytes, that normally function to provide nourishment to neurones, as well as being involved in the removal of neuronal ‘debris’ through a process known as phagocytosis.

Thus, increased neurodegeneration, reduced neuroprotection and neuronal repair are common pathological features of major depression.   Structural brain changes caused by inflammation have been detected in depressed patients by a process called MRI scanning and have been reported in several brain regions.  Similar findings have been reported in Alzheimer’s and Huntington’s disease, a particularly severe and aggressive form of dementia.

There is a further common feature shared by both major depression and dementia, in that both are associated with low levels of omega-3 fatty acids and both respond well to treatment using omega-3 fatty acids derived from fish oil.  However, what is also key to the success of the treatment of these conditions is the type of omega-3 used.  Fish oil contains both EPA and DHA; whilst DHA is the major structural fatty acid contributing significantly to the composition of neuronal networks, EPA appears to be primarily involved as a neuroprotectant. Indeed, DHA at a dose of 2 g/day has been shown to have no beneficial effect on cognitive and functional abilities after 18 months of supplementation.2 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.

EPA, on the other hand, 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.3 With regard to a direct neuroprotective influence, EPA has been shown to reduce gray matter atrophy associated with Huntington’s disease and it is also suggested that EPA protects DHA loss from cell membranes.4 Furthermore, EPA and not DHA also appears to be the primary antidepressant within fish oil,  with a 1g daily dose of ethyl-EPA having a significant impact on the symptoms of depression.5

Experts have long known that depression and dementia often co-exist, but it is not clear if one actually leads to the other.  Whilst there is an element of genetic predisposition related to some specific types of dementia progression, dementia is not considered to be a part of the normal aging process. Knowing that depression is a risk factor for developing dementia, and that depression can be treated successfully with ethyl-EPA, depressed individuals who supplement with ethyl-EPA may indirectly be protected against developing dementia later in life.

Chronic inflammation is now considered to be central to the pathogenesis not only of such conditions such as major depression and dementia, but also medical disorders as cardiovascular disease, diabetes and cancer. If the chronic inflammatory changes observed in these conditions can be at least partially reversed simply by raising omega-3 EPA levels, this supports the use of supplementation as a preventive tool against disease development.


1.  Milte CM, Sinn N, Street SJ, Buckley JD, Coates AM, Howe PR. 2011 Erythrocyte polyunsaturated fatty acid status, memory, cognition and mood in older adults with mild cognitive impairment and healthy controls. Prostaglandins Leukotrienes and Essential Fatty Acids. 84:153-61

2.  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. 2010 Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Trial. JAMA: The Journal of the American Medical Association.  304:1903 DOI:

3.  Taepavarapruk PSong C. 2010 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. 112:1054-64

4.  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.

5.  Martins JG. 2009 EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. Journal of the American College of Nutrition. 28:525-42.

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