DHA, Omega-3 Fatty Acid in salmon

DHA

  • Vitamins & Supplements
  • Updated June 17, 2016

Docosahexaenoic acid (DHA) is a long-chain omega-3 polyunsaturated fatty acid found in some fish and over-the-counter supplements. It is a building block of the brain involved with numerous cellular pathways. Clinical trials suggest that DHA supplements do not improve cognition in most elderly people, but could benefit people with minor cognitive impairment. The evidence from observational studies has some discrepancies but, overall, suggest that people with higher level of DHA are less likely to develop dementia.

Evidence

Numerous randomized trials and observational studies have examined the relationship between DHA and cognitive decline or dementia. Despite the number of high-quality studies, the evidence is rated low because of inconsistent results. Our search identified:

• 4 meta-analyses of randomized clinical trials in the elderly or people with mild cognitive impairment
• 2 meta-analyses or systematic reviews of observational studies
• 2 randomized controlled trials in elderly patients
• Numerous preclinical studies that established a compelling biological rationale for potential benefit

Potential Benefit

Clinical trials that have studied DHA and cognitive decline have had mixed results. In preliminary reports from the MAPT trial in 1680 older adults, 800 mg of DHA per day combined with physical activity, nutrition, and cognitive interventions led to improvements in cognition over 3 years. DHA alone resulted in less cognitive decline but only in people who had low levels of DHA at the start of the trial [6][7], which may explain why DHA (or DHA with EPA) have not slowed cognitive decline or improved cognition in other trials [8][9]. Modest improvements in memory may occur in adults with mild memory complaints [10][11] but this effect has not been reported by all trials [12].

Some observational research studies found that people who eat fish every week (i.e., a major source of dietary DHA) or have higher DHA levels also had a lower risk of dementia or a slower rate of brain aging [1-3], but other studies have not found this benefit. A strong rationale from preclinical research [4][5] suggests that treatment with DHA could slow neurodegeneration, but clinical trials have not yet tested whether it could prevent dementia.

APOE4 Carriers:

The presence of an APOE4 allele may affect the response to DHA but the results are very inconsistent, ranging from more benefit to no effects in APOE4 carriers [1][4][7][13]. Preliminary research shows that the APOE4 allele can change how the body and brain processes long-chain omega-3 fatty acids such as DHA [14-16]. For more information on what the APOE4 gene allele means for your health, read our APOE4 information page.

For Dementia Patients

According to meta-analyses of randomized trials, Alzheimer's patients are not likely to benefit from DHA supplements, although some modest benefits might be seen in people at early stages of cognitive decline [11][17].

Safety

Long-chain omega-3 fatty acids such as DHA are well-tolerated and generally recognized as safe at doses below 3 grams per day. They are one of the most widely consumed nutraceuticals in the Western world and have been studied extensively. Research has shown that DHA and other omega-3 compounds may reduce the risks of cardiovascular disease, cancer, age-related macular degeneration, Crohn’s disease, depression, and ADHD. However, doses higher than 3 grams per day may cause harm [18].

A meta-analysis of randomized trials reported that the most likely side effect of omega-3 fatty acids is gastrointestinal disturbances [19]. Omega-3 fatty acids were suspected to raise the risk of major bleeding, particularly in older adults, but this finding is controversial [19][20].

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

The most common food source of DHA is dark-meat fin-fish such as tuna, salmon, mackerel, herring, and sardines, with much lower levels in shellfish, tilapia, and fried fish [21]. Some studies have reported reduced dementia risk in people who eat fish regardless of whether that fish is rich in omega-3 fatty acids, suggesting that 1-2 servings of fish per week may have benefits beyond DHA content [1][22]. DHA supplements made from fish oil or algae are widely available although their quality and content varies [23]. Doctors can also prescribe pharmaceutical sources of DHA-containing fish oil (e.g., Lovaza® and Epanova®). These drugs have been rigorously tested and purified but are also expensive compared to other sources.

The dose of DHA that is most likely to benefit the brain is not known but likely falls within 180 to 2000 mg per day. Within this range, we don't yet know whether higher doses provide additional benefit to the brain. A blood test for DHA levels can help to identify people with extremely low levels but the costs may not be covered by health insurance. 

Learn More

Labdoor, United States Pharmacopeial Convention (USP), and ConsumerLab all provide information on the quality of DHA supplements.

Seafoodhealthfacts.org provides information on the omega-3 content of common seafood.

References

  1. Huang TL (2010) Omega-3 fatty acids, cognitive decline, and Alzheimer's disease: a critical review and evaluation of the literature. JAlzheimersDis 21, 673-690.
  2. Cunnane SC, Chouinard-Watkins R, Castellano CA et al. (2012) Docosahexaenoic acid homeostasis, brain aging and Alzheimer's disease: Can we reconcile the evidence? Prostaglandins LeukotEssentFatty Acids.
  3. Zhang Y, Chen J, Qiu J et al. (2016) Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies. The American journal of clinical nutrition 103, 330-340.
  4. Cunnane SC, Plourde M, Pifferi F et al. (2009) Fish, docosahexaenoic acid and Alzheimer's disease. Progress in lipid research 48, 239-256.
  5. Cole GM, Ma QL, Frautschy SA (2009) Omega-3 fatty acids and dementia. Prostaglandins LeukotEssentFatty Acids 81, 213-221.
  6. Vellas B, Carrie I, Guyonnett S et al. (2015) MAPT (multi-domain Alzheimer’s prevention trial): Results at 36 months. Alzheimer's Association International Conference 11, P331.
  7. Rogers MB (2015) Health Interventions Boost Cognition—But Do They Delay Dementia? (accessed June 1, 2016 2016)
  8. Chew EY, Clemons TE, Agron E et al. (2015) Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. JAMA : the journal of the American Medical Association 314, 791-801.
  9. Sydenham E, Dangour AD, Lim WS (2012) Omega 3 fatty acid for the prevention of cognitive decline and dementia. Cochrane Database Syst Rev 6:CD005379., CD005379.
  10. Yurko-Mauro K, Alexander DD, Van Elswyk ME (2015) Docosahexaenoic acid and adult memory: a systematic review and meta-analysis. PloS one 10, e0120391.
  11. Mazereeuw G, Lanctot KL, Chau SA et al. (2012) Effects of omega-3 fatty acids on cognitive performance: a meta-analysis. NeurobiolAging 33, 1482-1429.
  12. Jackson PA, Forster JS, Bell JG et al. (2016) DHA Supplementation Alone or in Combination with Other Nutrients Does not Modulate Cerebral Hemodynamics or Cognitive Function in Healthy Older Adults. Nutrients 8, 86.
  13. Quinn JF, Raman R, Thomas RG et al. (2010) Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA 304, 1903-1911.
  14. Hennebelle M, Plourde M, Chouinard-Watkins R et al. (2014) Ageing and apoE change DHA homeostasis: relevance to age-related cognitive decline. The Proceedings of the Nutrition Society 73, 80-86.
  15. Vandal M, Alata W, Tremblay C et al. (2014) Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2. Journal of neurochemistry 129, 516-526.
  16. Thifault E, Cormier H, Bouchard-Mercier A et al. (2013) Effects of age, sex, body mass index and APOE genotype on cardiovascular biomarker response to an n-3 polyunsaturated fatty acid supplementation. Journal of nutrigenetics and nutrigenomics 6, 73-82.
  17. de Souza Fernandes DP, Canaan Rezende FA, Pereira Rocha G et al. (2015) Effect of Eicosapentaenoic Acid and Docosahexaenoic Acid Supplementations to Control Cognitive Decline in Dementia and Alzheimer's Disease: A Systematic Review. Nutr Hosp 32, 528-533.
  18. Tur JA, Bibiloni MM, Sureda A et al. (2012) Dietary sources of omega 3 fatty acids: public health risks and benefits. BrJNutr 107 Suppl 2:S23-52., S23-S52.
  19. Villani AM, Crotty M, Cleland LG et al. (2013) Fish oil administration in older adults: is there potential for adverse events? A systematic review of the literature. BMC geriatrics 13, 41.
  20. Wachira JK, Larson MK, Harris WS (2014) n-3 Fatty acids affect haemostasis but do not increase the risk of bleeding: clinical observations and mechanistic insights. The British journal of nutrition 111, 1652-1662.
  21. Chung H, Nettleton JA, Lemaitre RN et al. (2008) Frequency and type of seafood consumed influence plasma (n-3) fatty acid concentrations. JNutr 138, 2422-2427.
  22. Kim DH, Grodstein F, Rosner B et al. (2013) Seafood Types and Age-Related Cognitive Decline in the Women's Health Study. The journals of gerontology Series A, Biological sciences and medical sciences 68, 1255-1262.
  23. Zargar A, Ito MK (2011) Long chain omega-3 dietary supplements: a review of the National Library of Medicine Herbal Supplement Database. Metab SyndrRelat Disord 9, 255-271.
  24. Dacks PA, Shineman DW, Fillit HM (2013) Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease. J Nutr Health Aging 17, 240-251.