Health effects of fish oil: Where do we stand?

These nutrients play important roles in brain function, normal growth and development, metabolism and curbing inflammation, according to the National Center for Complementary and Integrative Health. Our bodies cannot manufacture these fatty acids, so we must consume them.

Fatty fish, such as salmon, mackerel and sardines, are rich in both DHA and EPA. (There's a third omega-3 fatty acid, alpha-linolenic acid (ALA), found in walnuts, canola oil, flaxseeds, chia seeds and pumpkin seeds. Our bodies can convert ALA, in limited quantities, to DHA and EPA.)

Despite the plentiful options for adding DHA and EPA to our diet, many people prefer to hack the process by taking fish oil supplements, the same way you'd drink vegetable juice instead of eating actual veggies.

"A lot of people don't know why they take fish oil," said R. Preston Mason, a faculty member at Harvard Medical School and president of Elucida Research, a biotechnology research company. "You take fish oil for the omega-3 content. ... People have heard it's good for you, so they take it. It's a booming industry."

In fact, fish oil is the third most widely used supplement in the United States. A National Institutes of Health study published in 2015 estimated that 7.8% of Americans used fish oils in 2012, though other studies put the number of Americans using fish oil as high as 23%, according to Adam Ismail, executive director of the Global Organization for EPA and DHA Omega-3s.

Though a simple swap appears to make sense to huge numbers of people, the underlying science suggests that fish oil supplements may not do justice to our physical need for omega-3s.

And, over the years, opinion on its benefits has gone back and forth.

Fish oils had been used as a cure for generations in Northern European fishing communities, according to the National Museum of American History. In particular, citizens of Germany and Britain used cod liver oil to treat rickets, rheumatism, gout and tuberculosis during the 18th century.

Yet it is widely believed that fishermen of earlier centuries commonly used oils for a range of conditions including wounds, body aches, the common cold and skin diseases. Cod liver oil, as a mass-produced product, dates to the 1700s and 1800s, according to Ismail.

"In fact, it can be traced to the Viking era," Ismail wrote in an email. The age of the Vikings is commonly believed to range from the late eighth century to the mid-11th century.

Though the Vikings may have begun the disruptive technology of fish oil production, the commercial industry took flight at the beginning of the 19th century in northern Europe and North America, according to the Food and Agriculture Organization of the United Nations. Based mainly on surplus catches of herring, oil production activities found industrial uses in leather tanning, soap production and other non-food products.

Originally, the residue was used as fertilizer, but since the turn of the 20th century, the oil leftovers have been dried and ground into fish meal for animal feeding.

Some of the olders traditions continue unchanged into the 20th century, though the UN report notes that a number of options in the fields of energy saving, automation and environmental protection have increased in recent years. Unpalatable species of fish -- or so-called industrial fish, including menhaden, sand eel, anchoveta and pout -- are reduced into oil by standard methods -- essentially, heating, pressing and grinding.

While Europe may have dominated production in previous centuries, in the latter half of the 20th century, Peru and Chile came to the forefront of the industry, each exporting about 18,000 metric tons of fish oil worldwide. Iceland, Denmark, Norway and the United States also produce fish oil, with all production companies selling mainly to Asia and Europe.

Fish oil supplements taken during pregnancy have no effect on postpartum depression and do not help babies' brains develop more quickly, according to a 2010 study published in the Journal of the American Medical Association.

A team of Australian researchers had expected to find that fish oil had positive effects for the more than 2,000 pregnant women studied. However, the women who took the supplements during their pregnancy were just as likely to experience postpartum depression as those who didn't and the brains of their babies didn't appear to grow and develop more quickly than other babies. Yet, the supplements were associated with a reduced risk of preterm birth.

The authors attributed their study's silver lining to DHA, which benefits the cardiovascular and neurological systems, and the other disappointing results to overinflated claims from two past studies.

One study looked at a mother's seafood consumption and a child's verbal IQ score, while the second study looked at a mother's seafood consumption and depressive symptoms during pregnancy. But both of these studies involved the benefits of seafood rather than fish oil itself.

Fish oil supplements, particularly those with higher doses of EPA, were found to be "modestly effective" in the treatment of attention-deficit/hyperactivity disorder, according to a review published in the Journal of the American Academy of Child & Adolescent Psychiatry.

After reviewing and analyzing 10 clinical trials involving 699 participants, Yale Child Study Center researchers found "a small but significant effect" demonstrated by omega-3 fatty acid supplementation. Separately, the authors found that supplementation treated symptoms of inattention and hyperactivity. However, they cautioned against using omega-3s in lieu of pharmaceutical treatments.

Given "evidence of modest efficacy" and the "relatively benign" side-effects, omega-3 fatty acid supplementation, particularly with higher doses of EPA, "is a reasonable treatment strategy" to use either alone or along with the usual prescribed pharmaceutical drugs, the researchers concluded.

Also in 2011, a study published in the journal Pediatrics found that the babies of pregnant women who took fish oil supplements containing DHA had more fortified immune systems.

Specifically, those babies had fewer days with cold symptoms in their first six months of life than those whose mothers received a placebo, the researchers found. Newborns in the DHA group were also slightly less likely to come down with a cold in the first place.

Accelerated brain aging is more likely to occur in people who eat diets short on omega-3 fatty acids -- the kind found in fish oil, according to a study published in the journal Neurology.

Lead author Dr. Zaldy S. Tan and his colleagues at the University of California, Los Angeles looked at circulating levels of DHA and EPA in the blood of 1,575 people.

Next, they compared these levels with participants' MRI brain scans and cognitive test results: problem-solving, multitasking and abstract thinking.

They discovered that those participants who scored in the bottom 25% on various mental tests had lower levels of omega-3 fatty acids in their blood and lower brain volumes -- what equates to about two years of brain aging.

Tan and his co-authors said those with lower levels of omega-3 fatty acids were also more likely to have minute but significant structural changes in the brain, apparent on the MRI images. The brain scans of the low omega-3 fatty acids group even showed tiny lesions in the brain, which would raise their risk for death, stroke and dementia.

With blood vessels supplying a full third of the brain's volume, the results are consistent with signs of damage to that intricate network, according to the study authors.

Also in 2012, high-dose fish oil supplementation helped 17-year-old Bobby Ghassemi, who was in a coma after a car crash.

Two weeks after beginning a fish oil regimen, Ghassemi began to emerge from his coma, showing movement on his left side. Shortly after, he began to show signs of recognizing his family and his dog and of discerning things like colors and numbers. His family ardently believed high-dose fish oil helped his brain heal.

Eating a lot of oily fish or taking potent fish oil supplements was associated with a 43% increased risk of prostate cancer, according to a Fred Hutchinson Cancer Research Center study published online in the Journal of the National Cancer Institute. The researchers also discovered a 71% increased risk of aggressive prostate cancer among those consuming fish oil or large amounts of oily fish.

They researchers had looked at blood samples of men taking part in the Selenium and Vitamin E Cancer Prevention Trial, which ultimately found that selenium supplements did not prevent prostate cancer, while vitamin E supplements slightly increased risk of the disease.

However, blood samples from men who went on to develop prostate cancer over the course of the trial showed more omega-3 fats than those of healthy men.

Perhaps because of this well-publicize news, sales of fish oil supplements, which grew from about $100 million in the late 1980s and peaked at $1.3 billion during 2012, began to flatten and decline beginning in 2013, according to Ismail, of the Global Organization for EPA and DHA Omega-3s.

Fish oil may transform fat-storage cells into fat-burning cells, which may reduce weight gain in middle age, according to research conducted in mice and published in Scientific Reports. According to Kyoto University researchers, fish oil not only activates receptors in the digestive tract, it induces storage cells to metabolize fat.

The scientists fed fatty foods to one group of mice, and a second group ate non-fatty fish oil additive foods. The mice that ate fish oil gained 5% to 10% less weight and 15% to 25% less fat than the others, the researchers discovered. An animal study, more research is needed to see if the same effects occur in humans.

Women who took fish oil during the last three months of pregnancy lowered the risk of their children developing asthma, according to a Danish study published in the New England Journal of Medicine.

About 17% of children whose moms took fish-oil capsules had asthma by age 3, compared with nearly 24% of the children whose mothers were given placebos.

The doses were 15 to 20 times what most Americans consume from foods a day -- 2.4 grams per day -- yet no adverse effects occurred in either the mothers or babies. Still, the researchers hesitated to recommend that pregnant women routinely take fish oil until more studies are done.

While this is certainly good news, a very different study of fish oil authored by Harvard's Mason appeared around the same time.

"I just wanted to ask the question: What's actually inside these capsules?" Mason said of his study, which looked at a limited number of popular US fish oil supplements. "We were quite surprised to see that in some of these widely used supplements, only a third of the product was the favorable omega-3s, and the balance of them were these other lipids, including saturated fats, which we don't associate with health benefits."

Saturated fats raise our bad cholesterol, or LDL.

Mason said he was also surprised to learn the fish oil supplements contain cholesterol.

"Omega-3s are highly vulnerable to breakdown during manufacturing. They become oxidized or rancid," Mason said. Along with the challenge of manufacturing these products without damage, most of them come in large shipments sailing the seas.

"During that process, they are often exposed to elevated temperatures, which will rapidly break them down," he said, adding that "in the lab, if we expose omega-3s to just normal environmental conditions, within hours, they're breaking down into these oxidized products.

"Once they are broken down, certainly they don't have their favorable benefits that we hope for," Mason said.

Though the same thing can happen with fish, you can smell fish and look it over before you purchase it.

"Imagine going to a store where the fish is rotted and smells terrible," Mason said, explaining that supplements contain deodorants and other chemicals to cover their bad smell.

He said he believes that supplementation is necessary for many people, but the bottom line is that there's no consistent quality.

Registered dietitian Nancy Copperman, who works for Northwell Health, reviewed the latest research and recommends a simple -- if more expensive -- option for consumers who want to add fish oil to their diets: "pharmaceutical-grade fish oil supplements that tend to be purer."

But don't believe all you read, says Copperman. In many studies of fish oil, "the data waned and waxed." Though some people did well, others did not, and even worse, the scientists were unable to replicate the good findings from one study to the next.

One exception is people who have very high triglycerides and are at risk of cardiovascular disease, Copperman said. "Adding a marine oil supplement -- again, it needs to be ... pharmaceutical-grade -- it does lower triglyceride levels in that population," she said, based on all the research she's seen over time.

There may also be some benefit in using fish oil to reduce ischemic stroke risk among people who have atherosclerosis, or hardening of the arteries, according to Copperman.

Since omega-3s are necessary nutrients, Copperman suggests that people stick with eating oily fish rather than taking supplements: When you're eating more fish, you are most likely eating less beef, including fatty hamburgers.

Fast food burgers, as well as other fatty foods such as cakes and cookies, contain lots of omega-6s, which in abundance may lead to an increased risk of cardiovascular disease, cancer and inflammatory and autoimmune diseases, according to the American Heart Association.

"You can't tell the omega-3 story without telling the omega-6 story," said Floyd "Ski" Chilton, a professor of physiology and pharmacology at the Wake Forest School of Medicine. Omega-3s and omega-6s come into our diet simultaneously and are metabolized by the same enzymes.

Over the past 50 years, the ratio shifted from two omega-6s for each omega-3 to what is now about a 10- or 15-to-one ratio of omega-6s to omega-3s, said Chilton. Working hard to metabolize omega-6s, our bodies cannot metabolize and effectively use omega-3s. Meanwhile, many people find it difficult to get enough omega-3s from the get-go.

There's dramatic ancestry-based variation in our ability to transform ALA into EPA or DHA, according to Chilton. African-Americans transform ALA into EPA or DHA very well, Europeans not so much, and Native Americans not at all, with variability among individuals within each group.

When it comes to supplementation, then, "the one-size-fits-all model is likely not appropriate," Chilton said, adding that we have entered the "bold new world of precision nutrition."

"Precision nutrition simply says that different individuals and in particular different ancestry-based populations, racial and ethnic populations may very well require -- when it comes to omega-3 and omega-6 fatty acids -- different recommendations," he said.

In a systematic review and meta-analysis of approximately 500 studies, researchers at Imperial College London found that adding omega-3 fish oil supplements to the diet during pregnancy and lactation reduced a child's risk of egg allergy by 30% at one year of life. The analysis didn't find a correlation between omega-3 supplements and a reduced risk of any other allergies, but using probiotics during late pregnancy and early breastfeeding reduced eczema risk by 22%.

"The studies only included participants with a high risk of developing allergies so it is unclear what effect probiotics or fish oil supplements would have in families with no history of allergies," Dr. Louisa James of Queen Mary University of London, who was not involved in the study, said in a statement. "While the results of this study are likely to inform the development of guidelines on maternal and infant diet, it seems that there is much more work to be done."

The UK's National Health Service recommends against taking fish oil supplements during pregnancy, as some can contain vitamin A, which in high doses can be harmful. In the US, neither the American Academy of Pediatrics nor the American College of Obstetricians and Gynecologists has a stated policy. Instead, they suggest that pregnant women eat fish that is low in mercury two or three times a week, avoiding fish high in mercury.