Saturday, April 17, 2010

Fish Oil: Long-Term Decrease Of Heart Benefit, Possible Increased Risk For Stroke

The Italian GISSI-P trial is often cited to support fish oil supplementation for heart attack prevention. GISSI-P involved over 11,000 patients who were followed for 3.5 years. I was browsing this analysis of it:

Early Protection Against Sudden Death by n-3 Polyunsaturated Fatty Acids After Myocardial Infarction, Time-Course Analysis of the Results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione, Circulation, 2002

And saw that the benefit of taking fish oil eroded over time. The risk of death in the group taking fish oil rose over the 3.5 years of the study.

Then my eyes fell on that subgroup for nonfatal stroke, specifically 3 months in ... Does that record a relative risk (RR) of 10.51? Does that mean that people who took 1 gram of fish oil/day were ten times as likely as non-fish oil takers to have a stroke? Although the stroke risk declined over time, it remained above 1.00; the risk for stroke was always higher among fish oil takers than those in the control group who took no fish oil.

All of the participants of GISSI had recently had a heart attack - within 3 months. Taking fish oil did decrease their risk of death from a subsequent heart attack. But it also, if I'm reading this right, increased their risk for stroke - quite a lot at the beginning.


Matthew said...

The benefits probably declined due to people stopping taking the pills. Only 68% were still taking the pills at the end, still quite good as many people don't like taking fish oil. Also those at highest risk (and most likely to benefit) tend to die or not die at the start leaving lower risk people in both groups at the end of the.

The stroke effect may be real but total numbers were so low 19 non-fatal strokes out of 11,323 patients at 3 months its hard to know if it relevant. Would you rather have a non-fatal stroke or a fatal heart attack?

Still I am cautious about using isolated nutrients from food for health reasons. I'm not certain a fish oil pill has an equal effect as a sardine.

E. Stone said...

Did you see this study was supported by drug companies? Bristol-Myers Squibb and Upjohn? And the drug companies "supplied marketed capsules"? They knew going in this would boost sales. They're going to make sure anything bad is downplayed.

Bix said...

Matthew, you have a good point about compliance. Still, if lower risk people are left at the end of the study, I would think the effect would not be attenuated, even if compliance was lower. Some other authors said lack of compliance didn't fully explain the waning benefit. It is this long-term effect that's curious to me. Why was the fish oil group experiencing increasingly greater risk of death?

GISSI is unusual in that it had a long follow up. Burr et al was also unusual in that it had a long follow up. And it also found, not only a decrease in benefit, but an outright increased risk of death: "Those supplied with fish oil capsules had a higher risk of cardiac death."

Hooper et al speculated that the poor long-term showing of fish oil could be due to some contaminant in the supplement that builds over time. There was also the possibility that something in fish, but not fish oil supplements, was responsible for benefit, perhaps vitamin D or some amino acid. Yet another explanation is that omega-3/fish oil benefit is limited to just those at greatest risk, who already had a heart attack, because of an antiarrhythmic effect only, not because n-3 improved blood pressure or lipids.

Re: stroke: Relevance was assessed at P<0.05. There was a 95% probability that those episodes of stroke were not due to chance. And the increased risk for both fatal and nonfatal stroke remained throughout the 3.5 years of the study, RR>1.0.

I've begun to see fish oil as therapeutic, not preventative.

Bix said...

The last thing you said: "I'm not certain a fish oil pill has an equal effect as a sardine." So true. Add to that what E. Stone said about drug companies possibly benefitting from articles that extol the virtues of something they sell (fish oil) and the sceptic in me gets louder. Why not eat the fish?

Manu said...

Nutrition data says that farmed raised salmon is highly inflammatory and not good at all for your health.

As wild salmon is quite rich in omega3, it seems that farm raised (due to his feeding of processed vegetable fats etc) is quite high in arachdinoic(?) acid and other inflammatory acids...

I see the capsules being marketed as fish oil are mostly from salmon, and I'm 100% sure they all come from farmed raised fish...

is this something that clicks?

Bix said...

omg, That's a great question ... where does the fish oil come from?

I was thinking ... are fish really harvested just for their oil? Or is the oil a byproduct of some other process? (Pet food?) I don't know. But I wonder if the fish from which the oil is derived is the same quality as the fish they might be able to sell whole.

virginia said...

I've cut back on supplements after reading your thoughts on the subject, but I did find a "wild Alaskan sockeye salmon oil" capsule (expensive) that I take to combat inflammation for RA.

If "the benefit of taking fish oil eroded over time", is it possible that the patients returned to bad habits, thinking they were protected by the fish oil, when in reality it was their original focused attempt to change both life style and diet, combined with fish oil supplements, that yielded the newsworthy results?

After good lab numbers, I've found myself adding cheese, egg yolks etc back into my diet - who knows where I might be after 3.5 years. Just writing this, makes me more aware of that temptation.

Bix said...

Your numbers were good, that's great! What do you think it was? Was it something dietary?

The question you ask is what employing a control group attempts to answer. It's why a randomized control trial such as this is better than an observational study.

In this study there was a control group who received a placebo. Benefit from fish oil was measured relative to the control group. If patients returned to bad habits, thinking they were protected by the particular pill they were taking, then patients in all treatment groups (fish oil or placebo) may return to bad habits (randomization to assignment groups assists this, so, for instance, one treatment group doesn't have a lot of a type of person who has really fanatical healthy behavior), and you can factor this out or account for it.

An aside ... this study had a treatment arm that received vitamin E (300mg/d or about 450 IU). It failed to show benefit compared to placebo.

virginia said...

I've been battling this for so many years, that I now know the only solution for me is Lipitor, unfortunately. It has also helped my allergies this spring (anti-inflammatory?), and my RA (same reason, I'm guessing), so I'll just deal with it.

However, I had given myself permission to occasionally eat cheese and egg yolks again (eliminating them no longer worked to reduce my numbers), and that's why I wondered about the results of this study.

I understood the concept of the control group, but your explanation (as usual) made it crystal clear.

Manu said...

I'd assume the cheaper the capsules the more 'industrial' the source... The ones in europe at least are mostly from salmon, I'm 100% sure they all come from the norwegian salmon 'factories' has it is quite a big industry in norway.

Needless to say I'm not gonna buy them ever again, a can of sardines seems more benefitial than industrial capsules...

btw just wasting time at work but just saw that the doctor from heartscanblog, after advocating a plant based low carb diet, got immediately attacked in the comments

Bix said...

Virginia, I'm sorry. I got carried away. Teaching's in my blood.

Bix said...

Manu, you're turning me off supplements for good. Factory-farmed fish oil. Ugh.

Just read Dr. Davis. That's interesting. I have a post I wrote over the weekend with some new thoughts I had about diet. Changing my mind is in my blood too.

virginia said...

Keep getting "carried away" and keep changing your mind. That's why I head here every day!

I didn't read the study, or I might not have asked (smile).