With all the conflicting research out there, fish oil is one of those things that’s hard to get a straight answer on — until now. That is, if you take the Oregon State University College of Pharmacy’s word for it.

A new report from the college contains definitive language on the effectiveness of omega-3 fatty acids in reducing cardiovascular events, such as heart attacks or strokes, controlling abnormal heartbeats, preventing cancer or dementia or benefiting cognitive function.

In short, they don’t, says OSU.

The report summarized the top research findings from the past decade — 81 studies in all — to arrive at its conclusion.

The idea was to go beyond the countless fish oil headlines and truly study the evidence behind such products, said Roger Citron, pharmacy program manager for OSU’s Drug Use Research and Management division.

“That’s the rub between a well-designed, good trial versus people trying to promote something for sales: whether or not there’s a lot of evidence to support the outcomes,” he said.

While findings like this tend to float in and out of the public consciousness, this particular report will have a lasting impact. In about a month, it will make it more difficult for low-income Oregonians to get fish oil.

The Oregon Health Authority tasked OSU with performing such analyses to help decide which drugs to cover under its Medicaid program, known as the Oregon Health Plan. After reading the report’s conclusions and resulting recommendations from a committee of experts, the agency’s acting director approved changes to fish oil’s coverage status under OHP.

Now, doctors who want to prescribe a Food and Drug Administration-approved fish oil medication for OHP beneficiaries will have to go through an additional authorization process.

The changes also officially prevent OHP beneficiaries from getting over-the-counter fish oil supplements covered under their insurance. Before the changes, there were not clear rules around coverage for such products.

Combing through research

For the cardiovascular portion of the report, its author, BingBing Liang, a clinical pharmacist at OSU, reviewed four meta-analyses to determine whether fish oil consumption protected against heart failure, irregular heartbeats, stroke and hypertension. A meta-analysis compares results from a number of different studies on the same subject.

Some of the analyses reported modest improvements, such as a reduction in strokes among women, while others reported no statistically significant outcomes.

Liang, who did not respond to a request seeking comment, concluded there is moderate evidence that omega-3 fatty acids do not prevent cardiovascular events, and they don’t affect irregular heartbeats.

She also reported finding low evidence that the products lower blood pressure and improve cardiac function in patients with chronic heart failure.

Liang used three large reviews to determine fish oil’s impact on cancer. One review found no benefit with respect to cancer prevention, another concluded fish oil reduced mortality among prostate cancer patients by 63 percent, and a final one found no clear benefit among patients with advanced cancers.

The OSU report concludes there is moderate evidence that omega-3 fatty acids do not prevent cancer.

For her review of fish oil’s impact on cognitive function and dementia, Liang relied on two different analyses. One found no benefit among healthy elderly subjects, and the other found small benefits to immediate recall, processing speed and attention among patients with cognitive impairment but no dementia.

The report concludes there is low evidence that omega-3 fatty acids do not prevent dementia in elderly patients, moderate evidence that they don’t benefit cognitive function in healthy, older patients with Alzheimer’s disease and a small benefit for those with cognitive impairment.

The three meta-analyses used to measure fish oil’s effect on depression reported slight overall benefits among research participants. Two meta-analyses into bipolar disorder also reported benefits, but one noted that half of the participants dropped out of two of the seven studies analyzed.

Liang concluded there is low evidence that omega-3 fatty acids have mixed results for the treatment of bipolar disorder and depression.

She also notes that problems with the latter bipolar disorder analysis weakened the evidence.

“Due to major concern of internal validity of the review studies, specifically small sample size and high level of attrition rate, the conclusion should be interpreted with caution,” Liang wrote.

Megan Herink, a clinical coordinator with OSU’s Drug Use Research and Management, said they use high standards to assess the quality of the studies they include in drug reviews.

“Anything that is poor-quality evidence or not a randomized control trial or isn’t looking at outcomes that we’re interested in, we will exclude those trials or studies,” she said. “But otherwise, it’s pretty comprehensive.”

The OSU report also notes that fish oil supplements, which are not regulated by the FDA, contain varying concentrations of EPA and DHA, the long-chain fatty acids in fish oil, of between 20 and 80 percent. By contrast, Lovaza, an FDA-approved prescription fish oil medication, contains such fatty acids at a very high purity.

Not all agree

Donald Jump, a professor in OSU’s College of Public Health and Human Sciences, said the only conclusion he agrees with in the new report is that fish oil is safe.

Aside from that, he’s not buying it. For one, he said, the report’s focus was too broad, and he’s skeptical anyone could come up with definitive answers on fish oil’s effect on each condition.

“Each one of these things is a heroic effort,” he said, “and they did it for a lot of different conditions — cancer, cognitive function, heart disease — It’s like, holy cats, are you for real?”

Jump participated in a similar broad review of fish oil research over a number of years, and the results draw sharp contrast to the new report. Jump’s study, published in 2012 in the Journal of Lipid Research, found that consumption of omega-3 fatty acids may prevent cardiovascular disease.

When studies on the effectiveness of omega-3 fatty acids find no benefit, it’s sometimes because the researchers neglected to measure the amount of fatty acids in the blood or found no change in blood levels of the omega-3 fatty acid or blood levels of triglycerides, Jump said.

The best way to tell if omega-3 fatty acids are working is if a fasting patient’s blood triglycerides are lowered, he said.

Blood levels with less than 4 percent of omega-3 fatty acids do not offer much protection — it’s basically what people pick up normally through their diets — while an index around 8 percent would provide more significant benefits, he said.

Jump noted that this only applies to primary prevention, which refers to preventing a disease from presenting before symptoms occur. Secondary prevention, by contrast, refers to taking action against further adverse events once symptoms have materialized.

Overall, Jump still recommends everyone, even healthy people, take between 250 and 500 milligrams of combined EPA and DHA per day to prevent cardiovascular disease. However, he said, people should talk to their doctors first.

Tougher road to fish oil

After OSU completed its report, it went to the state’s Pharmacy and Therapeutics Committee, a group of pharmacists and doctors that makes coverage recommendations to the Oregon Health Authority.

On March 4, Tina Edlund, the OHA’s acting director, approved the committee’s recommendations, which take effect 60 days from that date.

Under the changes, Lovaza will be added to the OHA’s preferred drug list, which includes drugs deemed effective and covered under the Oregon Health Plan. It’s being added, however, under a so-called “non-preferred” status, meaning doctors must go through a few more hoops to prescribe the drug.

What those hoops are will be determined in a meeting today, but they will likely include questions such as whether the doctor has tried a different pill or has recommended exercise to the patient as an alternative, said Tom Burns, the OHA’s director of pharmacy programs.

Ironically, putting a drug on the preferred drug list actually can make it more difficult to prescribe for OHP beneficiaries.

In the case of Lovaza, which isn’t yet on the list, doctors currently can prescribe the drug with no restrictions.

“By putting it on the preferred drug list, it allows us to say, ‘OK, doc, we see that there are some medical benefit of this. We see there is some reason to have this drug covered. Here are the prior authorization steps that you must go through to prescribe this drug,’” Burns said.

As for over-the-counter fish oil supplements, they’re going to be even more difficult to get covered under OHP. If a doctor wants to prescribe them, both the doctor and the patient will have to go through a formal hearing process involving reviewing medical records. Ultimately, a judge would make the call.

Most OHP beneficiaries will opt to simply buy the supplements, which typically cost around $10 a container, rather than go through such a time-consuming process.

Burns said it’s unclear whether over-the-counter supplements currently are covered under OHP, but the new rule will prevent such coverage in most cases.

Some OHP beneficiaries likely will be upset by the changes, but Burns said in the end, the change makes the OHP a better steward of taxpayer money by not continuing to pay for ineffective treatments.

“The decision was made because there is no medical evidence to say that fish oils that are sold over the counter actually do what they claim they do,” he said. “There is medical evidence that says Lovaza, which is sold as a brand product, does what it says it does.”

— Reporter: 541-383-0304,

tbannow@bendbulletin.com