No Effect of Omega-3 Fatty Acid Supplementation on Cognition and Mood in Individuals with Cognitive Impairment and Probable Alzheimer’s Disease: A Randomised Controlled Trial

Phillips, Michelle; Childs, Caroline E.; Calder, Philip C.; Rogers, Peter J.

doi:10.3390/ijms161024600

Cited by 114 publications

(91 citation statements)

References 46 publications

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“…Improved memory performance in subjects with mild Alzheimer's disease was reported with 1.5 g EPA+DHA/day for 6 months (251) . However, a number of other studies using various doses and ratios of EPA and DHA reported no effect on cognitive performance in people with Alzheimer's disease (252)(253)(254)(255)(256)(257) . Meta-analyses provide a mixed view of the findings for n-3 fatty acid treatment in the area of cognitive impairment, reflecting the mixed findings from individual trials.…”

Section: Neurocognitive Healthmentioning

confidence: 99%

Very long-chainn-3 fatty acids and human health: fact, fiction and the future

2017

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Eicosapentaenoic acid (EPA) and docosahexaenoioc acid (DHA) appear to be the most important omega-3 (n-3) fatty acids, but roles for n-3 docosapentaenoic acid (DPA) are now also emerging. Intakes of EPA and DHA are usually low, typically below those recommended.Increased intakes result in higher concentrations of EPA and DHA in blood lipids, cells and tissues. Increased content of EPA and DHA modifies the structure of cell membranes and the function of membrane proteins. EPA and DHA modulate the production of lipid mediators and through effects on cell signaling can alter the patterns of gene expression. Through these mechanisms, EPA and DHA alter cell and tissue responsiveness in a way that often results in more optimal conditions for growth, development and maintenance of health. DHA has vital roles in brain and eye development and function. EPA and DHA have a wide range of physiological roles which are linked to certain health or clinical benefits, particularly related to cardiovascular disease, cancer, inflammation, and neurocognitive function. The benefits of EPA and DHA are evident throughout the life course. Future research will include better identification of the determinants of variation of responses to increased intake of EPA and DHA; more in-depth dose response studies of the effects of EPA and DHA; clearer identification of the specific roles of EPA, DPA and DHA; testing strategies to enhance delivery of n-3 fatty acids to the bloodstream; and exploration of sustainable alternatives to fish-derived very long chain n-3 fatty acids. Omega-3 (n-3) fatty acids -structure, metabolic interrelationships, dietary sources and intakes Omega-3 (n-3) fatty acids are a family of polyunsaturated fatty acids (PUFAs) (1) . They are defined by the position of the double bond closest to the methyl terminus of the hydrocarbon (acyl) chain. This is on carbon number three when counting the methyl carbon as number one.Eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) appear to be the most important n-3 fatty acids (2,3) , although roles for docosapentaenoic acid (DPA; 22:5n-3) are now also emerging (4,5) . Because of their long hydrocarbon chain, EPA, DPA and DHA are sometimes termed very long chain n-3 fatty acids, in order to differentiate them from the 18-carbon plant-derived n-3 fatty acids like -linolenic acid (ALA; 18:3n-3) and stearidonic acid (SDA; 18:4n-3). In this article, the term "very long chain n-3 fatty acids" will be used to individually and collectively describe EPA, DPA and DHA.EPA, DPA and DHA are metabolically related to one another, and there is a pathway by which EPA can be synthesized from the simpler plant-derived n-3 fatty acids (Figure 1).The conversion of ALA to EPA involves three steps catalyzed, in turn, by delta-6 desaturase, elongase 5 and delta-5 desaturase (Figure 1). Further conversion of EPA to DHA, via DPA, occurs by a complex pathway (Figure 1) involving chain elongation catalyzed by elongase 5, a second chain elongation catalyzed by elongase 2 or 5...

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Section: Neurocognitive Healthmentioning

confidence: 99%

Very long-chainn-3 fatty acids and human health: fact, fiction and the future

2017

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“…The role of fatty acids such as DHA and EPA in AD pathogenesis is also clarified to a certain extent by the foregoing data. The association of composite indices comprising of various ratios of PlsEtn and PtdEtn species bearing polyunsaturated fatty acids at sn‐2 position (DHA, adrenic acid, and EPA) with cognitive scores and AD diagnosis appear to confirm early studies on the association of these fatty acids with AD and might explain why interventional studies using these fatty acid preparations (vs. phospholipids bearing these fatty acids) failed [66,67]. It seems more likely that rather than the specific fatty acid such as DHA or EPA, the specific molecular configuration of the phospholipids these fatty acids are associated with is more important than fatty acids itself.…”

Section: Discussionmentioning

confidence: 70%

Plasmalogen deficiency and neuropathology in Alzheimer's disease: Causation or coincidence?

Senanayake¹,

Goodenowe²

2019

A&D Transl Res & Clin Interv

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Causation of Alzheimer's disease (AD) is not well understood. It is necessary to look beyond neuropathology to identify the underlying causes of AD and many other common neurological diseases. Lipid abnormalities are well documented in the preclinical phases of many neurological diseases including AD. Here, we use AD as an example to examine the role of lipid abnormalities as an underlying cause of neurodegeneration. Role of lipids, particularly phospholipids, in the optimal function of the nervous system, impact of the aberrations of phospholipid metabolism on β‐amyloid deposition and cholinergic neuronal function, epidemiological evidence on the association of phospholipids with AD, and preliminary data on the possible modulation of risk factors of AD by phospholipids are examined. Implications of these findings on diagnosis and prevention are also discussed.

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“…EPA and DHA supplementation increases RBC n-3 PUFA content, working memory performance, and blood oxygen level-dependent signal in the posterior cingulate cortex during greater working memory load in older adults with subjective memory impairment [22]. However, another RCT confirmed an overall negligible benefit of n-3 PUFA supplementation for individuals with CIND or AD [23]. Eriksdotter et al demonstrated the dose-response relationships between plasma levels of n-3 PUFA and preservation of cognition [24].…”

Section: The Intervention Studies Which Investigated the Association mentioning

confidence: 99%

Effects of N-3 Polyunsaturated Fatty Acids on Dementia

Yanai

2017

J Clin Med Res

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N-3 polyunsaturated fatty acids (PUFAs) including α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory effects and neuronal protective functions and may benefit prevention of dementia; however, the epidemiological evidence is very limited. Therefore, the literature about the association between n-3 PUFA and dementia was searched, by using Pubmed. In the analyses of observational studies, n-3 PUFA has been reported to be beneficially associated with dementia in 17 studies; however, the beneficial association between n-3 PUFA and dementia was denied by three studies. In the analyses of intervention studies, n-3 PUFA supplementation was beneficially associated with dementia in eight studies; however, five studies reported the negligible effect of n-3 PUFA for dementia. N-3 PUFA may improve Alzheimer’s disease by increasing clearance of amyloid-β peptide, neurotrophic and neuroprotective factors, and by anti-inflammatory effects. In conclusion, patients with mild memory and/or cognitive impairment can be treated by a long-term and higher intake of n-3 PUFA.

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No Effect of Omega-3 Fatty Acid Supplementation on Cognition and Mood in Individuals with Cognitive Impairment and Probable Alzheimer’s Disease: A Randomised Controlled Trial

Cited by 114 publications

References 46 publications

Very long-chainn-3 fatty acids and human health: fact, fiction and the future

Very long-chainn-3 fatty acids and human health: fact, fiction and the future

Plasmalogen deficiency and neuropathology in Alzheimer's disease: Causation or coincidence?

Effects of N-3 Polyunsaturated Fatty Acids on Dementia

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