Time to Cut Bait on Omega-3's Neuroprotective Claims

Hans-Christoph Diener, MD, PhD


February 02, 2022

This transcript has been edited for clarity.

Dear colleagues, I'm Christoph Diener from the University of Duisburg-Essen in Germany. This month I'm deviating from what I usually do, which is reporting a handful of recent studies that may impact your clinical practice. However, December 2021 was a very frustrating month for the neurology literature, and I couldn't find a single new study I'd consider truly important.

I did come across an interesting paper in JAMA, which related the results of a randomized, placebo-controlled study with almost 20,000 patients investigating whether omega-3 unsaturated fatty acids have an impact on the risk for depression. Although the results of the trial were negative, it nonetheless raised my interest in the topic of omega-3, which is something you see mentioned often in the mainstream press and advertised heavily on TV.

So, I performed a literature search on Medline that listed 33,000 papers on omega-3 unsaturated acid supplementation and different diseases. To give you an idea of the scope, here's a brief list of the conditions for which I found epidemiologic studies suggesting that omega-3 acids may have a benefit: cardiovascular disease, lipid disorders, type 2 diabetes, cancer, the tolerability of chemotherapy, Alzheimer's disease, depression, heart failure, lumbar disk prolapse, menopausal difficulties and premenstrual syndrome, rheumatoid arthritis, periodontitis, retinopathy, and nonalcoholic fatty liver disease.

Research interest in omega-3s began following the Second World War, when the first epidemiologic studies were performed. These studies noted that the Inuit communities in Greenland and in Alaska had a surprisingly low rate of cardiovascular diseases despite eating meat and considerable amounts of fish. The explanation was that omega-3 fatty acids contained in fish can lower lipids and provide cardioprotective effect.

My own reading through the omega-3 supplement literature concentrated on diseases relevant for neurologists. Regarding cardiovascular diseases, there is a meta-analysis of 86 studies with approximately 162,000 patients comparing omega-3 with placebo. It shows no benefit for overall mortality for myocardial infarction, stroke, or transient ischemic attack. The only trend was for decreased mortality in people with coronary heart disease, but the numbers needed to treat would be 334.

Then I looked at studies into whether omega-3 can prevent dementia or Alzheimer's disease. I found three studies for dementia and six studies for Alzheimer's disease with between 600 and 800 patients, which were also negative.

Finally, I checked the literature for the prevention and treatment of depression and anxiety disorders. I found 31 studies with more than 50,000 people, again with no benefit for omega-3.

At least in our field of neurology, I cannot see an indication for which omega-3 should be recommended or prescribed to our patient population with stroke, cognitive impairment, dementia, Alzheimer's disease, or depression and anxiety.

I think the scientific lesson to be learned is, even if you see associations in large-scale epidemiologic studies, this does not mean that there is a causal relationship. Obviously, these epidemiologic studies are heavily biased. For example, if we look at cardiovascular disease, people who take omega-3 fatty acids are probably more likely to be from a higher-income population, have a healthier lifestyle, and exercise more regularly. This could explain the benefits seen in epidemiologic studies, which have not been shown in randomized placebo-controlled trials.

Hopefully next month I can show you more new studies within neurology. However, for now, I'm Christoph Diener, from the medical faculty of the University of Duisburg-Essen, thanking you very much for listening and watching.

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