Summary
Evidence Report/Technology Assessment: Number 114
Under its Evidence-based Practice Program, the Agency for Healthcare Research and Quality (AHRQ) is developing scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools. Contractor institutions review all relevant scientific literature on assigned clinical care topics and produce evidence reports and technology assessments, conduct research on methodologies and the effectiveness of their implementation, and participate in technical assistance activities.
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Introduction / Methods / Results / Discussion / Availability of Full Report / References
Authors: MacLean CH, Issa AM, Newberry SJ, Mojica WA, Morton SC, Garland RH,
Hilton LG, Traina SB, Shekelle PG.
Introduction
This report was requested by the Agency for
Healthcare Research and Quality (AHRQ), the
National Institutes of Health (NIH) Office of
Dietary Supplements, and several NIH Institutes.
It is one of several reports focusing on the role of
omega-3 fatty acids (FA) in the prevention or
treatment of various diseases. Three Evidence-based
Practice Centers (EPCs) produced this
series of reports:
- The Southern California EPC ([SCEPC], based at RAND)
- The Tufts-New England Medical Center EPC.
- The University of Ottawa EPC.
This particular report focuses on
the effects of omega-3 FA on cognitive function
with aging, dementia, and neurological diseases.
Over the past 40 years, an increasing number
of physiological functions have been attributed to
omega-3 FA, including:
- Movement of calcium and other substances into and out of cells.
- Relaxation and contraction of muscles.
- Regulation of clotting and of secretion of substances that include digestive enzymes and hormones.
- Control of fertility, cell division, and growth.
In addition,
omega-3 FA may play an important role in brain
development and function.1 Docosahexaneoic
acid (DHA; 22:6n-3) is the precursor to a newly-described
metabolite called 10,17S-docosatriene,
which is part of a family of compounds called
resolvins.2,3 They are released in the brain in
response to an ischemic insult and counteract the
pro-inflammatory actions of infiltrating
leukocytes by blocking interleukin 1-beta-induced
NF-kappaB activation and cyclooxygenase-2
expression. DHA also plays a role in retinal rod
outer segments by influencing membrane fluidity
so as to optimize G protein coupled signaling.4,5
The major dietary sources of omega-3 FA in
the U.S. population are fish, fish oil, vegetable
oils (principally canola and soybean), walnuts,
wheat germ, and some dietary supplements.
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Methods
Study Questions
We convened a technical expert panel (TEP)
composed of distinguished basic scientists and
clinicians with established expertise in omega-3
FA, human nutrition, dietary assessment
methods, and neurology. The TEP advised us on
refining the preliminary questions posed to us by
AHRQ, determining the proper
inclusion/exclusion criteria for the study and the
populations of interest, establishing the proper
outcomes measures, and conducting the
appropriate analyses.
Based on the original questions that we
received from AHRQ and input from our TEP,
we addressed the following questions in this
study:
- What is the evidence that omega-3 FA play a role in maintaining cognitive function in normal aging?
- What is the evidence that omega-3 FA affect the incidence of dementia including Alzheimer's disease?
- What is the evidence that omega-3 FA are effective in the treatment of dementia including Alzheimer's disease?
- What is the evidence that omega-3 FA affect the incidence of neurological diseases?
- What is the evidence that omega-3 FA prevent the progression of multiple sclerosis?
Search Strategy
The following databases were searched: MEDLINE® (1966-2003), PreMEDLINE® (December, 2003), EMBASE (1980-2003), Cochrane Central Register of Controlled Trials (4th
Quarter, 2003), CAB HEALTH® (1973-2003), Dissertation
Abstracts (1861-2003). All of these databases were searched
using the OVID interface, except CAB HEALTH, which was
searched through SilverPlatter. Any duplicate records were
identified and removed within each search question using
Reference Manager® software. The citations obtained from
these literature searches were sent to the SCEPC via E-mail. We
also reviewed the reference lists of all applicable articles and
contacted our technical expert panel as well as industry experts
recommended by the Office of Dietary Supplements to identify
and obtain unpublished data.
Selection Criteria
Two reviewers independently reviewed each article
considered for inclusion in the study. Human controlled
clinical trials (randomized and non-randomized), prospective
cohort studies, case-control studies, and case series were
included; case reports were excluded.
For inclusion, studies also
had to describe a difference between omega-3 FA content in
study arms for all study designs except case series and describe
the effect of omega-3 FA on any of the following outcomes:
- Cognitive function with normal aging.
- Incidence of dementia.
- Treatment of dementia.
- Incidence of neurological disease.
- Progression of multiple sclerosis.
The reviewers resolved any
disagreements by consensus. Language was not a barrier to
inclusion.
Data Extraction and Analysis
For each article included in the study, two reviewers
independently extracted data about:
- Trial design.
- Outcomes of interest.
- The quality of the trial.
- Number and characteristics of the patients.
- Details on the intervention, such as the dose, frequency, and duration.
- Types of outcome measures.
- Adverse events.
- The elapsed time between the intervention and outcome measurements.
Any disagreements
between the reviewers were resolved through consensus. For
each article, we then evaluated the quality of the design and
execution of trials using a system developed by Jadad;
determined a combined applicability grade based on
applicability to the U.S. population and health state; performed
a meta-analysis of those studies that sufficiently assessed
interventions, populations, and outcomes to justify pooling;
and performed a qualitative analysis of the remaining studies.
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Results
We screened 5,865 article titles. From these article titles, we
chose to review 502 full-text articles, of which 497 were
retrievable. Of these full-text articles, 62 met our selection
criteria and were chosen for data extraction. After data
extraction, 12 articles met our inclusion criteria for our study
questions.
Evidence that Omega-3 FA Play a Role in Maintaining
Cognitive Function in Normal Aging
Only one study that
met inclusion criteria assessed the role of omega-3 FA in
maintaining cognitive function. Fish consumption was only
weakly associated with a reduced risk of cognitive impairment
and had no association with cognitive decline; omega-3 FA
consumption was not associated with either outcome.
Evidence that Omega-3 FA Affect the Incidence of
Dementia including Alzheimer's Disease
Three studies
evaluated the effect of omega-3 FA on the incidence of
dementia. All three of the studies assessed the incidence of
dementia relative to fish consumption; one also assessed risk
relative to total omega-3 fatty consumption, and relative to
each alpha-linolenic acid (ALA; 18:3n-3); eicosapentaenoic acid
(EPA; 20:5n-3), and DHA consumption. Fish was associated
with a significant reduction in the incidence of non-Alzheimer's
dementia in only one of the studies. Fish consumption was
associated with a reduced risk of Alzheimer's dementia in all
three of the studies but this association was significant in only
one study. Total omega-3 FA consumption and consumption of
DHA (but not ALA or EPA) were associated with a significant
reduction in the incidence of Alzheimer's.
Evidence that Omega-3 FA are Effective in the Treatment
of Dementia including Alzheimer's Disease
Only one study
assessed the effects of omega-3 FA for the treatment of
dementia. DHA resulted in a small improvement in scores on a
dementia rating scale.
Evidence that Omega-3 FA Affect the Incidence of
Neurological Diseases
Four studies addressed the association
of omega-3 FA consumption with risk or incidence of
particular neurological diseases other than dementia. Two
studies that assessed the association between omega-3 FA intake
and the incidence of multiple sclerosis found no significant
effects, although one study found a reduced risk with fish
consumption among women. The one study that assessed the
association between omega-3 FA consumption and the risk for Parkinson's disease found no significant association for fish,
ALA, EPA, or DHA. The one study that assessed the
association between maternal omega-3 FA consumption and
the risk of giving birth to a child with cerebral palsy found that
consumption of fish once a week throughout pregnancy was
associated with a lower risk.
Evidence that Omega-3 FA Prevent the Progression of
Multiple Sclerosis
Three studies reported on the effects of
omega-3 FA intake on the progression of multiple sclerosis. In
one study, treatment with an omega-3 FA supplement,
MaxEPA, had no effect on disability or relapse rates. However,
two other studies reported a significant reduction in disability
and one reported improvement on an index of disease
progression.
Thus, the quantity and strength of evidence for effects of
omega-3 FA on outcomes in the conditions assessed varied
greatly.
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Discussion
We offer the following observations and recommendations
regarding future research on the effects of omega-3 FA on the
neurological conditions reviewed:
- Additional research on the effects of omega-3 FA needs to be performed on all of the conditions reviewed in this report before recommendations regarding the use of omega-3 FA can be made for these conditions.
- Of particular importance, properly designed randomized clinical trials that are sufficiently powered and of an adequate length (e.g., 3 to 5 years of followup) need to be conducted for dementia, especially Alzheimer's disease, and for multiple sclerosis.
- Studies that assess the effects of omega-3 FA should be designed to evaluate the effect of source, dose, treatment duration, and the sustainment of effect after discontinuation of omega-3 FA consumption.
- Trials of omega-3 FA should include a baseline assessment of dietary omega-3 and omega-6 FA intake.
- In controlled trials that assess the effects of omega-3 FA, analysis should include and report explicit testing of the effects of the omega-3 FA relative to the control substance.
- All studies that assess the effects of omega-3 FA should use standard validated instruments to assess clinical outcomes.
- Observational studies should report data about type of fish consumed and method of preparation.
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Availability of Full Report
The full evidence report from which this summary was taken was prepared for the Agency for Healthcare Research and Quality (AHRQ) by the Southern California Evidence-based
Practice Center under Contract No. 290-02-0003. Printed copies may be obtained free of charge from the AHRQ Publications Clearinghouse by calling 800-358-9295. Requesters should ask for Evidence Report/Technology Assessment No. 114, Effects of Omega-3 Fatty Acids on Cognitive
Function with Aging, Dementia, and Neurological Diseases.
The Evidence Report is also online on the National Library of Medicine Bookshelf, or can be downloaded as a PDF File (860 KB). PDF Help.
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References
1. American Dietetic Association, Dietitans of Canada. Position of the
American Dietetic Association and Dietitians of Canada: vegetarian
diets. Can J Diet Pract Res 2003 Summer;64(2):62-81.
2. Marcheselli VL, Hong S, Lukiw WJ, et al. Novel docosanoids inhibit
brain ischemia-reperfusion-mediated leukocyte infiltration and proinflammatory
gene expression. J Biol Chem 2003;278(44):43807-17.
3. Serhan CN, Hong S, Gronert K, et al. Resolvins: a family of bioactive
products of omega-3 fatty acid transformation circuits initiated by
aspirin treatment that counter proinflammation signals. J Exp Med 2002;196(8):1025-37.
4. Hong S, Gronert K, Devchand PR, et al. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain,
human blood, and glial cells. Autacoids in anti-inflammation. J Biol
Chem 2003; 278(17):14677-87.
5. Niu SL, Mitchell DC, Lim SY, et al. Reduced G protein-coupled
signaling efficiency in retinal rod outer segments in response to n-3
fatty acid deficiency. J Biol Chem 2004;279(30):31098-104.
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AHRQ Publication Number 05-E011-1
Current as of February 2005
Internet Citation:
MacLean CH, Issa AM, Newberry SJ, et al. Effects of Omega-3 Fatty Acids on Cognitive Function with Aging, Dementia, and Neurological Diseases. Summary, Evidence Report/Technology Assessment: Number 114. AHRQ Publication Number 05-E011-1, February 2005. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/epcsums/o3cognsum.htm