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Fishing for answers.

"Study: Fish oil's work against heart attacks limited," ran the headline in USA Today in May. It was the latest disappointment from recent trials testing fish oil pills on people at high risk for heart attacks.

Yet many studies that follow fish eaters for years find a lower risk of heart disease, stroke, memory loss, depression, and a dozen other health problems. What gives?

Heart Attack & Stroke

"People who eat a diet that's high in fish have a lower risk of heart attacks and strokes in many observational studies," says JoAnn Manson, chief of preventive medicine at Brigham and Women's Hospital in Boston.

But those studies, which observe a lower risk in fish eaters, can't prove cause and effect. "Fish may replace foods--like red meat--that increase risk," notes Manson. "Or fish eaters may have other behaviors that lower their risk."

To prove cause and effect, researchers need a trial that randomly assigns people to take either a placebo or fish oil pills (since it's tough to find a placebo for salmon or tuna, and there's evidence that it's the omega-3 fats in fish oil that protect the heart).

Early trials on fish oil--from Italy in 1999 and Japan in 2007--were encouraging. (1,2) "But the recent randomized trials are casting doubt on the heart benefits of omega-3 fats," says Manson.

The latest: researchers gave more than 6,200 Italians at high risk for a heart attack either fish oil (1,000 milligrams a day) or a placebo. After five years, there was no difference in deaths or hospital admissions for cardiovascular causes. (3)

What could explain fish oil's flops?

"These trials are in people with a history of heart attack or those with a high risk of heart disease," says Manson. "Many of them are taking statins, aspirin, ACE inhibitors, and other medications that lower their heart disease risk." And since some drugs work through similar pathways as fish oil, they may lower risk so much that fish oil adds nothing. (4)

"The key question now is whether fish oil helps people at average risk who are not taking multiple medications," says Manson.

To find out, her Vitamin D and Omega-3 Trial (VITAL) is giving a total of 1,000 mg a day of the two major omega-3 fats in fish oil, EPA and DHA, to 25,000 men and women with no history of heart disease or stroke. Results are due in 2017.

Fish oil does have one clear benefit. If you have high triglycerides, talk to your doctor about taking 2,000 to 4,000 mg a day of EPA plus DHA.

Beyond Blood Vessels

What about benefits beyond the heart? Here's what we know so far:

* Memory loss. DHA doesn't seem to slow Alzheimer's disease or the usual cognitive decline that occurs as healthy people age, but few studies have been done. (5-7)

* Depression. The largest trial done so far was an industry-funded one of 432 people with major depression. EPA (1,050 mga day) plus DHA (150 mg a day) had a modest benefit among those who didn't also have anxiety disorder, but most studies have been disappointing. (8,9)

* Vision loss. DHA (350 mg a day) plus EPA (650 mg a day) didn't slow the progression of macular degeneration or prevent cataracts. (10,11)

* Type 2 diabetes. Oddly, some U.S. studies have found a higher risk in people who eat the most fish, while Australian studies have found a lower risk. (12) Stay tuned.

The Bottom Line

Manson is hoping that the VITAL trial sheds light on those and other questions.

"Our main goal is to look at cancer and cardiovascular disease," she says. "But we're also looking at diabetes, memory loss, depression, atrial fibrillation, cardiac function, bone health, fractures, falls, knee pain, asthma, thyroid disease, and autoimmune conditions like rheumatoid arthritis and lupus."

In the meantime, she says, "aim for two servings of fish a week. Unless you have high triglycerides, there isn't enough evidence to take fish oil supplements."

(1) Lancet 354: 447, 1999.

(2) Lancet 369:1090, 2007.

(3) N. Engl. J. Med. 368:1800, 2013.

(4) Arch. Intern. Med. 172: 686, 694, 2012.

(5) Neurol. 71: 430, 2008.

(6) Am. J. Clin. Nutr. 91:1725, 2010.

(7) JAMA 304: 1903, 2010.

(8) J. Clin. Psychiatr. 72: 1054, 2011.

(9) Mol. Psychiatr. 17: 1272, 2012.

(10) JAMA 2013. doi:10.1001/jama.2013.4997.

(11) JAMA Ophthalmol. 2013. doi:10.1001/jamaophthalmol.2013.4412.

(12) Diabetes Care 35: 918, 2012.
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Author:Liebman, Bonnie
Publication:Nutrition Action Healthletter
Article Type:Cover story
Geographic Code:1USA
Date:Jul 1, 2013
Words:749
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