Clinical trial challenges omega-3 claims for cognitive function and Alzheimer’s risk

A study has found that omega-3 fish oil supplementation does not provide any meaningful benefits for memory, cognition, or brain changes related to Alzheimer’s disease. Even though supplementing with fish oil provides the brain with omega-3, the researchers suggest the findings challenge the idea that such supplementation has preventative effects for Alzheimer’s. 

“We all wish there was a silver bullet for preventing Alzheimer’s, but our findings showed that fish oil supplements do not appear to protect brain health,” says the study’s lead investigator, Hussein Naji Yassine, director of the University of Southern California, US, Center for Personalized Brain Health.

“While omega-3s play an important role in forming brain cell connections needed for cognition, our results do not support fish oil supplements as a preventive measure against Alzheimer’s.”

Zooming in on DHA supplementation

The research in eBioMedicine was conducted by researchers from Keck Medicine of USC. The two-year, placebo-controlled, double-blinded clinical trial was conducted on 365 adults aged 55 to 80, who rarely consumed fish as a part of their diet.

Notably, 47% of the participants carried the strongest known genetic factor for developing late-onset Alzheimer’s — the APOE4 gene. They were randomly divided into getting a daily fish oil supplement of 2,000 mg docosahexaenoic acid (DHA) or a placebo.

Omega-3 reaching the brain did not equate to cognitive benefits for the consumer.Researchers investigated whether omega-3 from the supplements could enter the brain by measuring DHA levels in cerebrospinal fluid surrounding the brain and the spinal cord. They found that DHA levels had increased by 17% on average after six months of supplementation, which confirmed that the nutrient reached the brain.

However, the nutrients reaching the brain did not equate to cognitive benefits for the consumer. When assessing the participants’ memory and thinking ability at the start of the study and two years later, the researchers saw no increase in cognitive performance in the group eating DHA supplements.

They also conducted brain imaging scans, which demonstrated that the supplements did not slow the shrinkage of the hippocampus, a commonly used marker of Alzheimer’s risk and brain aging.

The authors of the paper say that these findings have led them to investigate this relationship further.

“We’re focused on better understanding how the brain processes omega-3s and whether factors, such as poor health, dietary pattern, genetic risk, and age, may change the brain’s ability to effectively absorb and use omega-3s,” says Yassine.

“We are working to develop medications that may help the brain better utilize these nutrients to preserve cognitive function.”

Healthy lifestyle as top priority

Omega-3’s association with brain health is a well-researched topic, backed by scientific results contradicting the new findings. An observational analysis on more than 217,000 adults, published earlier this year, showed a potential link between higher omega-3 fatty acids in the blood and a 35–40% lower risk of developing early-onset dementia, regardless of genetic predispositions for the disease.

The authors assert that maintaining good overall health is the most efficient way to reduce Alzheimer’s risk.Another study flagged potential negative effects of supplementing with omega-3. It linked the fatty acid eicosapentaenoic acid (EPA) to impaired healing after repeated traumatic brain injuries. Nutrition Insight spoke with the study author about the role of fatty acids in brain health and how formulators can better take into account ratios of these compounds when designing cognitive health products.

Another mechanistic study suggested that the benefits of supplementing with omega-3 fatty acid EPA vary significantly across individuals, highlighting that data on EPA’s effects on healthy people are scarce, while it has been shown to be beneficial for individuals with cardiovascular disease.

The new paper includes some lifestyle factors such as hypertension, obesity, physical inactivity, hyperlipidemia, and low dietary intake of omega-3, but it was not the main focus of the investigation.

The authors assert that maintaining good overall health is the most efficient way to reduce Alzheimer’s risk and support brain health and function.

“Staying healthy throughout life remains the most powerful tool we have for reducing Alzheimer’s risk, including regular exercise, quality sleep, and a balanced diet,” stresses Yassine.

“Living a healthy lifestyle is the brain’s equivalent of getting regular car maintenance and high-quality oil changes. The brain is more likely to lose greater function if health issues in other parts of the body go unaddressed, in the same way that car engines stop working if regular maintenance is skipped.”