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.
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
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 , which may explain why DHA (or DHA with EPA) have not slowed cognitive decline or improved cognition in other trials . Modest improvements in memory may occur in adults with mild memory complaints  but this effect has not been reported by all trials .
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  suggests that treatment with DHA could slow neurodegeneration, but clinical trials have not yet tested whether it could prevent dementia.
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 . 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.
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 .
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 .
A meta-analysis of randomized trials reported that the most likely side effect of omega-3 fatty acids is gastrointestinal disturbances . Omega-3 fatty acids were suspected to raise the risk of major bleeding, particularly in older adults, but this finding is controversial .
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.
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 . 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 . DHA supplements made from fish oil or algae are widely available although their quality and content varies . 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.
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.
Check for drug-drug and drug-supplement interactions on Drugs.com.