Are Fish-Oil Pills Right for You? The latest findings on fish-oil supplements may be tough to swallow.

A flurry of new research on fish-oil supplements is raising eyebrows as well as questions about just how miraculous those omega-3 fatty acids really are. Live long, stay strong, say the ads for fish-oil pills, touting not only omega-3s familiar heart-health benefits but also mental and cellular protection. But recent clinical trials have reminded nutrition scientists that, after all, the strongest data linking omega-3s and reduced cardiovascular risk come from observational studies: Overall, people who eat more fish have lower rates of heart disease. Alice H. Lichtenstein, DSc, director of Tufts HNRCA Cardiovascular Nutrition Laboratory, points out, however, that people who eat more fish also tend to be more physically active, less likely to smoke and to eat a healthier diet in general, including more fruits and vegetables and probably less meat and cheese. Should the fish oils alone get the credit for healthier hearts-or are omega-3s only part of the story?Late last year (see the December 2010 Health letter), two new clinical trials produced decidedly mixed results about the popularly accepted cardio- vascular benefits of omega-3 supple- ments. In one, patients with early heart failure showed significant improvement on several markers of cardiovascular health when taking omega-3 fish oil supplements, compared to placebo. In the other trial, however, margarine enriched with omega-3s failed to provide any protection against a second heart attack, compared to placebo, for a group of heart-attack survivors.The American Heart Association continues to recommend eating fish twice a week, especially the fatty kinds such as salmon, mackerel and tuna that are highest in the most important omega-3s, known as DHA and EPA for short. And even the lead investigator for the study that produced disappointing results on heart-attack recurrence, Daan Kromhout, MPH, PhD, of Wageningen University in the Netherlands, says, Its still a good thing to eat fish once or twice a week. The results of this trial do not change that.Regardless of the benefts of omega-3s, healthily prepared fish provides an excellent source of protein with lower calories. As an entre, fish typically replaces main-dish options such as fatty meats, pizza or fried foods that are high in saturated fat. In general, too, research continues to show that a diet higher in polyunsaturated fats such as omega-3s and lower in saturated fats benefits your health. So dont let the latest debate about omega-3s keep you away from the fish counter!But is the evidence for the health benefits of omega-3s rock-solid enough that you should also be taking fish-oil supplements? Thats a more open question.Failing vs. AFIn another new study, for example, researchers failed to show that even high doses of omega-3s improved treatment of atrial fbrillation (AF)-the most common type of abnormal heart rhythm-better than placebo.Peter R. Kowey, MD, of the Lankenau Institute for Medical Research in Pennsylvania, and colleagues explained in the Journal of the American Medical Association (JAMA) that atrial fibrillation is responsible for reduced quality of life, costly hospitalizations, heart failure, stroke and death. No current therapy, drug, device or ablation [removal of tissue or cells] is uniformly effective, and several available therapies have the potential to cause harm. Consequently, useful alternatives are being sought. Limited data from small trials suggest omega-3 polyunsaturated fatty acids may provide a safe, effective treatment option for AF participants.So Dr. Kowey and colleagues put that treatment to the test with 663 AF patients over six months, splitting them into two groups: Half got a prescription-level dose of omega-3s (eight grams daily for the frst week, then four grams daily), while the rest got a placebo. No significant difference was seen between the omega-3 and placebo patients in incidence of AF events or heart flutter. Placebo patients actually did slightly better, a nonsignificant result the researchers said did not indicate evidence of harm from the fish-oil supplements.

The scientists offered several possible explanations for why their findings were at odds with prior results, including differences in study populations and treatment regimens. They also noted that nearly half the AF and heart flutter events took place during the first two weeks of the trial, suggesting that fish oil may not have rapid effects, even with high-loading doses.Its possible, they added, that omega-3s might perform better in primary prevention of AF-protecting people not yet suffering from the condition. But Dr. Kowey said, I know of no treatment that having failed in secondary prevention was then able to be successful in primary prevention.In an interview about the findings with a medical news service, Raymond Gibbons, MD, of the Mayo Clinic, who was not involved in the study, commented that this trial represents the latest evidence that the idea that supplements can favorably impact outcomes in arrhythmia patients is unproven.Disappointing Against AlzheimersAlmost simultaneously, results of another major new clinical trial disappointed those hoping omega-3 supplements might slow the decline of patients already diagnosed with mild to moderate Alzheimers disease. Animal studies of DHA have previously shown reductions in Alzheimer-like brain pathology. Moreover, the omega-3 fatty acid occurs naturally in the human brain, and Alzheimers patients have reduced levels.Several studies have found that consumption of fish, the primary dietary source of omega-3 fatty acids, is associated with a reduced risk of cognitive decline or dementia, noted Joseph F. Quinn, MD, of Oregon Health and Science University and the Portland VA Medical Center, and colleagues, also publishing in JAMA. Some studies have found that consumption of DHA, but not other omega-3 fatty acids, is associated with a reduced risk of Alzheimer disease. But those studies were observational, the researchers pointed out, and did not control who received DHA.To get more defnitive answers, Dr. Quinn and colleagues followed 402 Alzheimers patients for 18 months, with one group taking two grams daily of DHA and the rest a placebo. In the 295 patients who completed the trial, there was no signifcant difference in cognitive decline or other measures, including daily function, between the DHA and placebo patients. A subset of 105 patients scanned by MRI showed no effect of DHA treatment on total brain volume change during 18 months.In summary, these results indicate that DHA supplementation is not useful for the population of individuals with mild to moderate Alzheimer disease, the researchers concluded.Dr. Quinn and colleagues still held out hope that DHA might protect the brain if taken before the development of Alzheimers: It remains possible that an intervention with DHA might be more effective if initiated earlier in the course of the disease in patients who do not have dementia.Focusing on Fish for EyesNot all the latest news on omega-3s is negative, however-although the positive findings relate to fish rather than pills. In a study of 2,391 Maryland residntes, ages 65 to 84, researchers reported that those diagnosed with advanced age-related macular degeneration (AMD) were signifcantly less likely to consume at least one serving of fish or other seafood high in omega-3s than those without the condition.Bonnielin Swenor, MPH, of the Wilmer Eye Institute at Johns Hopkins University, and colleagues, writing in Ophthalmology, concluded, These data support a protective effect of fish/shellfish intake against advanced AMD.The findings are consistent with several prior observational studies linking omega-3 fatty acid intake and AMD risk reduction, including the Age-Related Eye Disease Study (AREDS) and the Blue Mountain Eye Study. Such a connection makes sense, experts say, since studies have shown high concentrations of omega-3s in the retina. AMD is the leading cause of blindness among older Americans, so the fndings represent more motivation to put fish on your plate.A Fork in the Road?But whether fish-oil supplements are also a good idea remains an open question. If youre popping pills instead of eating fish, thats probably not the best idea. For all the reasons enumerated earlier, fish is an important part of a healthy, varied diet.As for taking fish-oil supplements in addition to eating fish, the jurys still out. Tufts Lichtenstein notes that the data indicate people who report eating more fish (except breaded and fried) are at lower risk for heart disease. But she cautions that theres little data indicating fish-oil supplements lower cardiovascular risk, especially for primary prevention. Scientists havent identifed any downsides to fish-oil pills, taken in moderation (high intakes may stress your antioxidant system), but youll have to weigh their cost against the limited evidence for any benefit.The bottom line for omega-3s, for now, remains much the same as for most nutrients: Eating a variety of healthy foods is better than trying to get nutrition from pills. JAMA, Dec. 1, 2010 (AF); abstract at <jama.ama-assn.org/content/304/21/2363.abstract> JAMA, Nov. 3, 2010 (Alzheimers); abstract at<jama. ama-assn.org/cgi/content/abstract/304/17/1903> Ophthalmology, December 2010; abstract at <dx.doi. org/10.1016/j.ophtha.2010.03.058>