A New Shot at Using Fish Oil

December 6, 2022

A New Shot at Using Fish Oil

Injecting forms of omega-3 fatty acids directly into the bloodstream shows promise in treating stroke and other conditions

In a new push to figure out whether fish oil can help with conditions from heart disease to depression, scientists are digging deeper into its key nutrient: omega-3 fatty acids.

They are exploring higher doses and specific fish-oil components that may be more effective for targeted use, developing new delivery mechanisms, and studying ways to use omega-3s to treat acute events such as stroke, in addition to chronic diseases.

Eating fish with omega-3 fatty acids is beneficial for heart health, research suggests. But the findings of studies on the potential health benefits of fish-oil dietary supplements, which millions of people take daily, have been mixed.

Fish oil “is not a panacea,” said JoAnn Manson, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, who led a large randomized trial of omega-3s. But, she added, “The research to date would suggest there may be some benefits with targeted use.”

Studies suggest omega-3s may benefit patients with autoimmune diseases or reduce damage after strokes, she said. Other studies show that the fatty acids, which have anti-inflammatory properties, help certain critically ill patients recover after surgery.

Richard Deckelbaum, center, a professor at Columbia University, is leading research on an injectable therapeutic made with a high dose of omega-3s.Photo: Calla Kessler for The Wall Street Journal

One team at Columbia University has developed a therapeutic made with a high dose of omega-3s to protect and repair cells damaged when they are cut off from oxygen, such as in a stroke or in newborns during a complicated labor. The therapy, if proven to work, potentially could be used for other conditions as well, including heart attacks or sickle-cell disease, said Richard Deckelbaum, a professor of pediatrics, nutrition and epidemiology at Columbia who is leading the research.

The therapeutic, an emulsion of omega-3s—microdroplets of oil dispersed in a watery liquid—is injected directly into the bloodstream, unlike fish-oil pills which have to go through the digestive system. It hasn’t yet been tested in humans, but studies in mice and rats show that within an hour the omega-3s in the emulsion start preventing cells in the brain and other organs from dying when deprived of oxygen, such as in a stroke, reducing cell death by between 65% and 90%, he said.

“The whole omega-3 field has been based on oral intakes—supplements, eating fish,” Dr. Deckelbaum said. “We’re coming up with a new paradigm.”

Finding potent uses for omega-3s would mark a rare breakthrough in a field that has tried for decades to find major benefits from fish oil. In the 1970s, researchers discovered that Inuit people, whose diet consisted mostly of fish they caught, had low rates of cardiovascular disease. That led to reams of studies of omega-3s to try to unlock their suspected superpowers.

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Dr. Deckelbaum with a vial of the omega-3 emulsion, which is injected directly into the bloodstream, unlike fish-oil pills which go through the digestive system. Calla Kessler for The Wall Street Journal (2)

Omega-3s are essential fats the body needs to function, but can’t make on its own. Dietary sources of omega-3s include salmon, tuna and other cold-water fatty fish, as well as certain plant oils, nuts and seeds. An important part of human cell membranes, they help to give the body energy and are important to regulate functions in the blood vessels, the endocrine system and other parts of the body. They help reduce inflammation, a factor in many diseases.

The American Heart Association recommends eating fish at least twice a week for heart health. But researchers say the jury is still out on the health benefits of fish-oil supplements. Omega-3s taken at a dosage found in many over-the-counter supplements didn’t reduce the incidence of invasive cancer or a composite of major cardiovascular events in the Vitamin D and Omega-3 Trial, a study known as VITAL that Dr. Manson led and whose results were published in 2018.

In addition, high doses of omega-3 fatty acids have been linked to an increased risk of atrial fibrillation, an irregular heart rhythm, Dr. Manson said.

Some researchers had thought that omega-3s could help combat depression, because the brain requires those fatty acids to function properly and they help lower inflammation, a factor in depression. But recent studies of VITAL data and a review of several studies found no benefit for preventing depression, or improving mood.

Olivia Okereke, director of geriatric psychiatry at Massachusetts General Hospital and lead author of the VITAL depression study, said she and her colleagues are looking more closely at the findings and also plan to study the effects of higher doses of omega-3s. More research should be done to identify the mechanisms by which omega-3s might work against depression, said Katherine Appleton, a professor of psychology at Bournemouth University in Poole, England, who led the review of depression studies.

There are some other signals that omega-3s have potential benefits and should be studied further, Dr. Manson said. For example, she would like to see a randomized controlled trial in which young adults with a family history of autoimmune diseases are given a high dose of omega-3s to see if that reduces the risk of developing them.

A study of VITAL data that was published last year, which Dr. Manson was an author on, found signs that omega-3s may help reduce the risk of functional limitations or physical disabilities after strokes, she said. Dr. Deckelbaum’s research into an omega-3 emulsion to treat stroke damage “seems plausible but needs much more study,” she said.

Omega-3s given intravenously can help some critically ill patients recover more quickly after surgery by decreasing the inflammatory response, said Martin Rosenthal, a trauma and critical care surgeon at University of Florida Health in Gainesville, Fla., who has studied the fatty acids and their effects on patients.

A 2020 analysis of the results of previous studies published in the medical journal Critical Care, in which he participated as an author, found that patients in intensive-care units who were given intravenous omega-3 emulsions had shorter ICU and hospital stays and fewer infections after their procedures, he said.

“There are different nutrients we can use and exploit to help augment our immune system and portend to having better surgical outcomes,” he said.

Questions have emerged about the effectiveness of a fish oil-derived prescription drug called Vascepa. The drug is made of a high dose of a purified form of the omega-3 fatty acid eicosapentaenoic acid, or EPA. In 2019, the U.S. Food and Drug Administration approved it to reduce the risk of heart attacks, strokes and other serious cardiovascular-disease events in patients with elevated triglyceride levels who are at high risk and on cholesterol-lowering drugs.

Some researchers say that the placebo used in a large clinical trial of Vascepa may have raised the heart-disease risk for people who took it, making the benefit from Vascepa look larger than it would otherwise have been. Data from a recent analysis appeared to suggest that.

Amarin Corp., maker of the drug, said it stands by the results of the trial and doesn’t plan to replicate it. The placebo’s effects were small, in absolute terms, and didn’t exaggerate Vascepa’s benefits, the company said.

Dr. Deckelbaum and other scientists hope that the benefits of omega-3s will become clearer when it is delivered in new forms and for more diseases and conditions. The omega-3 emulsion that Dr. Deckelbaum and his colleagues developed is made up of omega-3 fatty acids in a diglyceride form–two fatty acids–that is substantially smaller than the triglyceride form normally contained in fish-oil supplements, he said.

“These particles have a better chance of getting across the blood-brain barrier much faster,” Dr. Deckelbaum said. “We also have other evidence that they’re incorporated into cell membranes more efficiently than triglycerides.” In addition to his academic posts, Dr. Deckelbaum is a founder of DeckTherapeutics Inc. and chair of its scientific-advisory board. The company was formed in 2019 to further develop the therapeutic for unmet medical needs, initially in children and later in adults.

It will take about three years to complete studies of the therapy in animals and then humans, said Soren Weis Dahl, chief executive officer of DeckTherapeutics.

If those studies are successful, the company plans to apply for regulatory approval initially to use the therapy to treat hypoxic-ischemic encephalopathy, or HIE, Dr. Dahl said. The condition occurs when an infant’s brain is deprived of oxygen before, during or after delivery due to complications such as separation of the placenta from the uterine wall. HIE is a leading cause of cerebral palsy, cognitive impairment and other disabilities. DeckTherapeutics received a small grant recently from the Bill & Melinda Gates Foundation, which is looking for therapeutics to treat HIE in the developing world.

Write to Betsy McKay at [email protected]