This study doesn't surprise me. I have been taking high-dose omega-3 for decades to keep my AA/EPA ratio between 1 and 3 as recommended by my good friend Barry Sears of Zone Diet fame. Having the proper balance of omega-3 and omega-6 is crucial for maintaining the right amount of inflammation in your body — neither too much nor too little, but just enough to fight infections and facilitate healing.
Questioning methodology to ensure rigorous study analysis prior to implementation is always necessary—but finding funding for a fish oil study will be a challenge. In the end—risk:benefit ratio is the top strength of this recommendation in a population who should have the most focus of quality of life, given how much time, money and effort is already invested in that treatment. So even an unpleasant fish taste may make the fish oil “not worth it”. Other than that, so little downside.
I’d be curious if the editors asked to have an independent verification of the statistics. Errors happen and when a result is this good, as an editor, I would ask to have an independent validation of the statistical analysis. The gold standard is to have 2 independent statistical analyses- but that’s labor intensive and oftentimes researchers don’t have the budget for 2 separate analytic teams.
The idea that EFAs could have an impact across multiple domains is very much in line with its impact on basic cellular signaling. Improve the stability of the cellular membrane and signaling improves, most notably insulin. Improvements one resistance and a cascade of events improve. This isn't about a fixing an endpoint, it's about improving overall physiology.
I should have addressed the corn oil placebo issue. In the REDUCE IT trial of icosapent ethyl (EPA), there was a large benefit but it was against a mineral oil placebo. This was problematic because mineral oil raised LDL-C and CRP and the worry was that benefit may have simply been harm in the placebo arm.
That was the reason for corn oil. They noted that the fish oil group had elevated levels of fatty acids but corn oil did not. They also write:
"Corn oil contains approximately 50% linoleic acid (which has antiinflammatory effects) and is a source of the antioxidant vitamin E. Use of corn oil as a placebo has been associated with lower levels of serum lipids and markers of inflammation. It is possible, but unlikely, that corn oil increased the risk of cardiovascular events in the placebo group in our trial."
I would also add that in the nonsignficant STRENGTH trial, corn oil was the placebo and there were no signs of harm.
So, it's possible that corn oil could have lessened the benefit of the active arm. The problem with fish oil trials is blinding. You need something that simulates fish oil or there is no blinding.
That doesn't negate using a faux placebo. Corn oil is a hydrogenated, toxic substance. Hydrogenated oils promote inflammation, they are not anti-inflmmatory.
A point estimate of overall mortality of 0.89 is large, even if many of these are cardiac-related. I’d frame it as “a large, clinically important, difference in overall mortality was not statistically significant. This may have been due to chance or beta error.”
The results are what they are. I concur. Fish oil is cheap, safe (except perhaps A fib), and I can see zero reason to reject these observed results.
Two things: You mention statins work. If you consider a 1-3% absolute risk reduction in cardiovascular events with no longevity or mortallity benefit, then yes, they work for 1-3%. But, they fail to work for 97-99%.
Number two, corn oil is hydrogenated and toxic to the body. Perhaps the corn oil was the culprit. They shouild have used a true inert placebo.
Zero adverse events. 'nuff said. As a pharmacist I have seen many studies on the possible good effects of fish oil. The worst any one has told me they have is "fish burps." Unpleasant, but not life changing.
Increasing the balance of Omega 3 fatty acids from natural sources with Omega 6 fa's which are mostly from manufactured foods can only have beneficial effects.
Lowering cardiac events, even if no change occurs in all cause mortality, reduces disease burden, theoretically leading to more health-ful years of life.
The RX product is generic and inexpensive in the USA, and should be covered for anyone with heart disease or CKD.
Did anyone look at the corn oil and health? It maybe the corn oil is not good for cardiovascular health rather than fish oil being that helpful. Possibly do a similar trial with olive oil and the other 2 oils.
Are there other statistics to compare event rates to? Does the treatment or placebo arm most closely match other statistics? In other words, what if corn oil isn't a placebo but is a hazard itself?
Corn oil is a hydrogenated toxic product, not a true placebo. The only thing you can draw from this study is that fish oil subjects did better than corn oil subjects. The end.
I'm not a doctor but as a layperson I think yes! It's always great to hear about a supplement working and the potential upside outweighs the downside. I've heard about fish oils/omega 3s --all good things. The Pisces trial (love the name) sounds promising!
This study doesn't surprise me. I have been taking high-dose omega-3 for decades to keep my AA/EPA ratio between 1 and 3 as recommended by my good friend Barry Sears of Zone Diet fame. Having the proper balance of omega-3 and omega-6 is crucial for maintaining the right amount of inflammation in your body — neither too much nor too little, but just enough to fight infections and facilitate healing.
As a disciple of this site, does the KM curve separate suspiciously early ?
Questioning methodology to ensure rigorous study analysis prior to implementation is always necessary—but finding funding for a fish oil study will be a challenge. In the end—risk:benefit ratio is the top strength of this recommendation in a population who should have the most focus of quality of life, given how much time, money and effort is already invested in that treatment. So even an unpleasant fish taste may make the fish oil “not worth it”. Other than that, so little downside.
I’d be curious if the editors asked to have an independent verification of the statistics. Errors happen and when a result is this good, as an editor, I would ask to have an independent validation of the statistical analysis. The gold standard is to have 2 independent statistical analyses- but that’s labor intensive and oftentimes researchers don’t have the budget for 2 separate analytic teams.
The idea that EFAs could have an impact across multiple domains is very much in line with its impact on basic cellular signaling. Improve the stability of the cellular membrane and signaling improves, most notably insulin. Improvements one resistance and a cascade of events improve. This isn't about a fixing an endpoint, it's about improving overall physiology.
the only thing this study proves is that fish oil is better than corn oil. No need for a study about that.
I should have addressed the corn oil placebo issue. In the REDUCE IT trial of icosapent ethyl (EPA), there was a large benefit but it was against a mineral oil placebo. This was problematic because mineral oil raised LDL-C and CRP and the worry was that benefit may have simply been harm in the placebo arm.
That was the reason for corn oil. They noted that the fish oil group had elevated levels of fatty acids but corn oil did not. They also write:
"Corn oil contains approximately 50% linoleic acid (which has antiinflammatory effects) and is a source of the antioxidant vitamin E. Use of corn oil as a placebo has been associated with lower levels of serum lipids and markers of inflammation. It is possible, but unlikely, that corn oil increased the risk of cardiovascular events in the placebo group in our trial."
I would also add that in the nonsignficant STRENGTH trial, corn oil was the placebo and there were no signs of harm.
So, it's possible that corn oil could have lessened the benefit of the active arm. The problem with fish oil trials is blinding. You need something that simulates fish oil or there is no blinding.
That doesn't negate using a faux placebo. Corn oil is a hydrogenated, toxic substance. Hydrogenated oils promote inflammation, they are not anti-inflmmatory.
I concur with your first point in your rebuttal.
A point estimate of overall mortality of 0.89 is large, even if many of these are cardiac-related. I’d frame it as “a large, clinically important, difference in overall mortality was not statistically significant. This may have been due to chance or beta error.”
The results are what they are. I concur. Fish oil is cheap, safe (except perhaps A fib), and I can see zero reason to reject these observed results.
Yes my first thought too, corn oils’ negative effects!
Two things: You mention statins work. If you consider a 1-3% absolute risk reduction in cardiovascular events with no longevity or mortallity benefit, then yes, they work for 1-3%. But, they fail to work for 97-99%.
Number two, corn oil is hydrogenated and toxic to the body. Perhaps the corn oil was the culprit. They shouild have used a true inert placebo.
Zero adverse events. 'nuff said. As a pharmacist I have seen many studies on the possible good effects of fish oil. The worst any one has told me they have is "fish burps." Unpleasant, but not life changing.
Increasing the balance of Omega 3 fatty acids from natural sources with Omega 6 fa's which are mostly from manufactured foods can only have beneficial effects.
Lowering cardiac events, even if no change occurs in all cause mortality, reduces disease burden, theoretically leading to more health-ful years of life.
The RX product is generic and inexpensive in the USA, and should be covered for anyone with heart disease or CKD.
Did anyone look at the corn oil and health? It maybe the corn oil is not good for cardiovascular health rather than fish oil being that helpful. Possibly do a similar trial with olive oil and the other 2 oils.
This, obviously. Corn kills people if not prepared properly, and that was before it was soaked in glyphosate.
Are there other statistics to compare event rates to? Does the treatment or placebo arm most closely match other statistics? In other words, what if corn oil isn't a placebo but is a hazard itself?
Corn oil is a hazard. This was not a true placebo. Rather a faux placebo.
I had that thought, too. But, then again, corn oil is in most manufactured food products already, so its not like it's a novel item to western diets.
Corn oil is a hydrogenated toxic product, not a true placebo. The only thing you can draw from this study is that fish oil subjects did better than corn oil subjects. The end.
you are right. corn oil is in most processed food products. Most processed food products in the US are toxic. That is why we are so sick.
I'm not a doctor but as a layperson I think yes! It's always great to hear about a supplement working and the potential upside outweighs the downside. I've heard about fish oils/omega 3s --all good things. The Pisces trial (love the name) sounds promising!