Omega-3 Supplements, Memory, and Alzheimer’s Prevention

Researchers at Keck Medicine enrolled 365 adults without dementia, ages 55 to 80, with an average age of 66.

The participants got very little DHA from food and had at least one dementia risk factor. Of the 365 people who joined the study, 225 finished the trial, and nearly half, or 47%, carried APOE4.

Each participant took either 2,000 milligrams of DHA or a placebo every day, and neither the volunteers nor the researchers knew who received the supplement.

According to the study, the trial supplement contained more than 90% DHA and about 1% EPA.

Researchers looked at the following outcomes:

• the size of brain regions associated with memory
• DHA levels in cerebrospinal fluid, the liquid surrounding the brain and spinal cord, after six months
• memory and thinking abilities throughout the study period

The team found that high-dose omega-3 supplements increased DHA in the fluid around the brain and spinal cord by 17%.

However, both groups performed about the same on memory and cognitive tests, and brain structure appeared similar in both groups.

The supplement also increased omega-3 levels in the blood. Over two years, participants’ omega-3 index, which measures EPA and DHA in red blood cells, rose from 4.9% to 11%.

“That’s a massive increase, but that doesn’t translate into clinical outcomes,” Yassine said.

According to the study, DHA reached the brain equally well in people with and without APOE4, the gene variant tied to a higher Alzheimer’s disease risk.

Earlier studies could not determine whether DHA failed to reach the brain or simply reached it without producing benefits. The authors say this trial resolves that question because DHA did get there.

“This tells us that just because a supplement reaches the brain doesn’t necessarily mean it will improve brain function or prevent cognitive decline,” Trinh said.

Long-term effects of omega-3 supplements remain unclear

The absence of measurable changes in memory and thinking may reflect how the body handles omega-3s, Yassine said.

He said it is “really important to distinguish between omega-3 metabolism and omega-3 supplements.”

Supplements can raise omega-3 levels, but the body may still break them down before they reach the right places. Obesity, smoking, and a lack of exercise can all reduce how much omega-3 gets into the brain, he said.

Fish and fish oil supplements may provide more than omega-3s. These sources can also contain other nutrients such as lutein, vitamin E, and selenium, Yassine said.

“A supplement can raise the level, but if you don’t change the holistic program, just going and increasing the level by itself may not be sufficient,” he said.

Researchers tend to interpret the findings in two different ways, according to Yassine.

Some see the results as evidence that supplements do not work on their own. Others say the study would need a longer follow-up period or sicker participants to answer the question.

Trinh pointed to the study’s duration. “It’s also important to recognize that Alzheimer’s disease develops over decades, so a two-year study may not be long enough to determine whether DHA supplementation has any long-term preventive benefits,” he said.

What omega-3s and fish oil may do for brain health

According to the National Center for Complementary and Integrative Health, fish oil supplements contain two omega-3 fatty acids: eicosapentaenoic acid, or EPA, and DHA.

The National Institutes of Health’s Office of Dietary Supplements says foods such as fish and flaxseed also contain omega-3s.

Research suggests omega-3s may help reduce inflammation, support heart health, and promote childhood growth and development.

DHA’s role in the brain

Some observational studies link diets high in omega-3s with a lower risk of cognitive decline and dementia.

Researchers say omega-3s may help preserve cognition by helping brain cells keep functioning and maintain their membranes, according to the Office of Dietary Supplements.

“Omega-3s are important for the brain, and we and many others have shown that having higher levels of omega-3s is associated with less Alzheimer’s pathology, better cognition, and many other protective outcomes,” Yassine said, contrasting those findings with the trial results.

Trinh agreed. “DHA plays an essential role in maintaining healthy brain cells, and there is evidence that eating fish as part of a healthy dietary pattern may support long-term brain health,” he said.

Research on omega-3s and brain health is still ongoing, and there is insufficient evidence to draw firm conclusions about how effective they are.

Who may benefit from omega-3 supplements?

Some people may still benefit from a supplement, Yassine said, including:

• people who do not eat fish, such as vegans, especially those with a genetic risk for dementia
• people whose omega-3 levels are very low

Some neurologists test omega-3 levels, although the test is not standard, Yassine said.

People with nutritional deficiencies or certain genetic or metabolic traits may respond differently to omega-3 supplements, and researchers still need to determine who is most likely to benefit, Trinh said.

He added that people already taking fish oil or other omega-3 supplements for other reasons, such as high triglycerides, should make those decisions with their healthcare professionals.

Ways to support brain health with age

Trinh said he tells his patients that “what is good for the heart is generally good for the brain.” He recommended these healthy habits:

• Regular physical activity: At least 150 minutes of moderate-intensity activity each week, as tolerated, including aerobic exercise such as brisk walking, swimming, or cycling, plus strength training
• Quality sleep: Aim for 7 to 9 hours each night.
• A brain-healthy diet: Follow a healthy eating pattern such as the Mediterranean or MIND diet, which emphasizes vegetables, fruits, whole grains, nuts, olive oil, and fish.
• Managing heart health: Keep blood pressure and cholesterol at healthy levels, manage diabetes, avoid smoking, and limit alcohol.
• Staying mentally active: Read, learn new skills, and take part in meaningful activities.
• Staying socially connected: Spend time with family, friends, and the wider community.
• Addressing hearing and vision loss: An important strategy that is often overlooked.

“Overall, this study reminds us that there is no magic pill for preventing Alzheimer’s disease and that maintaining brain health requires a much broader approach,” Trinh said.