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A clinical trial found that taking high dose omega-3 supplements for 2 years did not help memory or thinking skills in older adults at increased risk of Alzheimer’s.
Researchers at Keck Medicine of USC led the study, which was published in eBioMedicine. Participants took either a daily high dose supplement of omega-3 fatty acid docosahexaenoic acid (DHA) or a placebo.
Fish oil is one of the most familiar ways people get omega-3s. However, the supplement in this clinical trial wasn’t made from fish, Hussein Yassine, MD, director of the USC Center for Personalized Brain Health with Keck Medicine of USC and the study’s lead researcher, told Healthline. This article uses the broader term omega-3 supplements.
The researchers found that taking supplements raised omega-3 levels in participants’ brains, yet it didn’t change their memory, thinking skills, or brain structure.
Dung Trinh, MD, an internist at MemorialCare Medical Group and chief medical officer of Healthy Brain Clinic in Irvine, California, who wasn’t involved in the study, told Healthline that the findings challenge the common belief that omega-3 supplements, such as fish oil, can help prevent Alzheimer’s disease or improve memory.
Millions of older adults take omega-3 supplements. In a 2017–2018 federal survey, 21.8% of U.S. adults age 60 and older reported taking an omega-3 fatty acid supplement in the past 30 days, according to the Centers for Disease Control and Prevention (CDC).
Getting omega-3s from food or supplements is important since the body cannot make them.
Omega-3 supplements, memory, and Alzheimer’s riskKeck Medicine researchers enrolled 365 adults who did not have dementia, and whose ages ranged from 55 to 80, with an average age of 66.
Subjects obtained little DHA from their diets and had at least one risk factor for dementia. Of the 365 people who enrolled, 225 completed the trial, according to the study. Nearly half (47%) carried APOE4.
Participants took either 2,000 milligrams (mg) of DHA or a placebo every day. Neither participants nor researchers knew who received the supplement.
The supplement in the trial contained more than 90% DHA and about 1% EPA, Yassine said.
Researchers measured:
Researchers found that high dose omega-3 supplements raised DHA levels in the fluid around the brain and spinal cord by 17%.
Both groups in the trial scored about the same on memory and thinking tests. Brain structure appeared the same in both groups.
The supplement also raised omega-3 levels in the blood. Over two years, participants’ omega-3 index, a measure of 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.
DHA reached the brain equally well in people with and without the gene variant APOE4, which is linked to a higher risk of Alzheimer’s disease, according to the study.
Earlier trials couldn’t tell whether DHA failed to reach the brain or reached it without helping, the study’s authors say. This trial answers that open question, since the DHA got 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.
The lack of measurable change in memory and thinking may come down to how the body uses omega-3s, according to Yassine.
He said it’s “really important to distinguish between omega-3 metabolism and omega-3 supplements.”
A supplement can raise omega-3 levels, yet 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.
Some fish and fish oil supplements may offer more than omega-3s. These sources may also include 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 fall into two camps on how to read the results, according to Yassine.
Some see the findings as evidence that supplements don’t work in isolation. Others argue the trial would need a longer follow-up or sicker participants to answer the question.
Trinh pointed to the study’s length. “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.
Fish oil supplements contain two omega-3 fatty acids, eicosapentaenoic acid (EPA) and DHA, according to the National Center for Complementary and Integrative Health (NCCIH).
Foods such as fish and flaxseed also contain omega-3s, according to the National Institutes of Health’s Office of Dietary Supplements (ODS).
Research suggests omega-3s may help reduce inflammation, support heart health, and promote childhood growth and development.
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 supporting brain cells in continuing to function and maintain their membranes, according to the ODS.
“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, in contrast to the trial findings.
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 ongoing, and there is insufficient evidence to draw firm conclusions about their effectiveness.
Some people may still benefit from a supplement, according to Yassine, including:
Some neurologists test omega-3 levels, though the test isn’t 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 learn who might benefit, Trinh said.
People who already take fish oil or other omega-3 supplements for other reasons, such as high triglycerides, should make those decisions with their healthcare professionals, he said.
Tips to support brain health as you ageTrinh said he tells his patients that “what is good for the heart is generally good for the brain.” He recommended the following healthy habits:
“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.