DFA: EPA/DHA and Cognitive Health (2011)


Harris WS, Mozaffarian D, Lefevre M, Toner CD, Colombo J, Cunnane SC, Holden JM, Klurfeld DM, Morris MC, Whelan J. Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids. J Nutr. 2009 Apr; 139 (4): 804S-19S.

PubMed ID: 19244379
Study Design:
Consensus Report
R - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

A workshop to consider whether the body of evidence specific to the major chronic diseases in the United States-coronary heart disease (CHD), cancer and cognitive decline-had evolved sufficiently to justify reconsideration of DRI for EPA+DHA.

Inclusion Criteria:

Not applicable

Exclusion Criteria:

Not applicable

Description of Study Protocol:


Not applicable 


Not applicable

Blinding used 

Not applicable


Not applicable 

Statistical Analysis

Data Collection Summary:

Timing of Measurements

  • Workshop held June 4-5, 2008
  • Implied, published studies after the 2002 IOM report. 

Dependent Variables

  • Cardiovascular disease
  • Cognitive development
  • Cognitive decline
  • Cancer
  • Total mortality.

Independent Variables

  • Conversion of ALA to EPA+DHA
  • n-3 PUFA intake
  • n-3 PUFA status.

Control Variables

Not applicable

Description of Actual Data Sample:
  • Initial N: Not applicable
  • Attrition (final N): Not applicable
  • Age: Not applicable
  • Ethnicity: Not applicable
  • Other relevant demographics: Not applicable
  • Anthropometrics: Not applicable
  • Location: Not applicable.


Summary of Results:

 Key Findings

Cognitive Development

  • Research using measures of attention in infancy (expressed in terms of duration of looking) is fairly consistent, shower shorter looking times (consistent with more mature cognitive development) during the first year with (n-3) LCPUFA-supplemented infants or infants from mothers with higher erythrocyte (n-3) LCPUFA levels
  • Although a few studies have reported better visual recognition memory in infants supplemented with (n-3) LCPUFA, most studies have not
  • The (n-3) LCPUFA status in breast-fed infants was found to be greatly correlated with retention of the ability to discriminate a non-native speech contrast (valid speech sounds not used in the individual's native language) at nine months and with receptive and expressive vocabulary (words actually spoken) at 14 months 
  • Blood levels of DHA have been shown to be highly positively correlated with performance on the Peabody Picture Vocabulary Test
  • The current maximum for DHA (0.35%) in infant formula may actually represent a minimum.

  Cognitive Decline

  • DHA is concentrated in the most metabolically active areas of the brain, such as the cerebral cortex, synaptosomes and mitochondria
  • Studies with aging animals have found that DHA composition of the brain decreases with age, and that loss of DHA is associated with decreases in antioxidant enzymes, scavengers of amyloid protein, hippocampal nerve growth, fluidity of synaptic membranes, and with increased oxidation of lipid membranes, ischemic damage, synaptic loss and amyloid burden
  • Among four prospective studies that examined fish consumption and the risk of developing dementia, three observed statistically significant decreased risks of 30-70% with consumption of one fish meal per week after adjustment for age, sex, educational level and various factors
  • A 60% reduction in the risk of developing incident AD over 3.9 years among persons who consumed one fish meal per week compared with persons who never or rarely consumed fish after adjustment for age, sex, race, apoplipoprotein E-4, education, and total energy intake was observed in the Chicago Health and Aging Project. Intake of EPA was not associated with AD risk. However, persons in quintiles three through five (median DHA intakes, 0.06 and 0.10 grams per day, respectively) had a 60-80% lower risk compared with persons in quintile one.
  • Four cohort studies have reported a protective effect against cognitive decline with higher (n-3) LCPUFA intakes. One standard deviation increase in erythrocyte total (n-3) LCPUFA and DHA were associated with a statistically significant 40% reductions in cognitive decline [as measured by a two-point drop of on the Mini-Mental Status Examination]. The annual rate of cognitive decline over six years was greatly reduced by 10% and 13%, respectively for persons who consumed one and two fish meals per week when compared with the rate among persons who consumed fish less often. Non-consumers had four times the risk of a two-point decline in MMSE score over five years. 
  • In one large randomized clinical trial of (n-3) LCPUFA and cognitive decline, positive effects were observed in a small group of patients with very mild AD.

 Other Findings

  • Uncertainty surrounds the extent of conversion in humans of the parent (n-3) PUFA, ALA, to its long-chain products, the potential health effects of ALA per se, and how ALA compares to stearidonic acid as a source of EPA, docosapentaenoic acid or DHA. The rate of conversion of ALA to EPA is low (about 5%), and to DHA even lower (about 0.5%).
  • This article also discusses issues surrounding (n-3) PUFA intake, exposure and biomarkers to assess status. 
Author Conclusion:

Workshop conclusions related to brain health.

  • Because of the demonstrably low conversion of dietary ALA to EPA and especially to DHA, protective tissue levels of EPA+DHA can currently be achieved only through direct intake of these fatty acids
  • Beneficial effects of EPA+DHA on cognitive decline are emerging, but the data are not yet sufficiently compelling to support an intake level different from that needed to achieve CHD risk reduction
  • There is no evidence that intakes of EPA+DHA in the range recommended are harmful.
Funding Source:
Technical Committee on Dietary Lipids of the International Life Sciences Institute North America
Other non-profit:
Reviewer Comments:
Quality Criteria Checklist: Review Articles
Relevance Questions
  1. Will the answer if true, have a direct bearing on the health of patients? Yes
  2. Is the outcome or topic something that patients/clients/population groups would care about? Yes
  3. Is the problem addressed in the review one that is relevant to dietetics practice? Yes
  4. Will the information, if true, require a change in practice? ???
Validity Questions
  1. Was the question for the review clearly focused and appropriate? Yes
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? ???
  3. Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? ???
  4. Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? No
  5. Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? Yes
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? Yes
  7. Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? No
  8. Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? Yes
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? Yes
  10. Was bias due to the review's funding or sponsorship unlikely? Yes