Confused on seeing one negative report on omega-3 outcome?

Recently you were able to read headlines in the press saying something like:

"Study shows: fish oil has no benefit for your heart" or "Were we mislead by the fish oil/omega-3 industry? 

To make it clear from the very beginning: this is not correct, and do not get confused by such news. Let's look at what happened:

A group of scientists from Cleveland University published early this year the outcome of their "STRENGTH Trial," which was designed to prove once more that a 4 g daily dose of a fish oil concentrate (in this case EPA+DHA in free fatty acid form) taken over a given period would reduce the cardiovascular risk of the subjects in the treatment group compared to the placebo group. The placebo group received instead of the fish oil capsules the same amount of corn oil capsules. After 12 months into the study, the researchers saw no difference in the cardiovascular risk between them. They concluded that: "These findings do not support the use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in patients with high cardiovascular risk."

The press read this statement and saw an opportunity to release an easy sellable negative news and spread the word that omega-3/fish oil does not work and is not worth their money. I am not sure if you remember, but we had a similar situation a couple of years ago. Back then, a clinical study published showed an increase in prostate cancer after giving omega-3 to the subjects. Subsequently, a massive scandal was created; many people -especially men- stopped taking their Omega-3 supplements and medications because they were worried about prostate cancer risk. Before the publication of that negative trial result, many other studies showed that a regular omega-3 supplementation helped to reduce the risk of prostate and other cancer forms – but all these studies seemed to have lost their importance just because of that one study showing a positive correlation between omega-3 intake and prostate cancer development. So colossal damage was done, not only to the omega-3 industry but especially to all the people who stopped taking their daily dose of omega-3's. After about one year, the scientists who published the "Omega-3 Prostate Cancer Paper" had to recall their publication because they made a mistake in their study and statistical analysis of the results. Was there any comment published by the international news that this study was mistaken and withdrawn? No! Absolutely nothing! It just left a negative image on omega-3's and probably still today makes many men feel uncomfortable taking omega-3 because of a potential risk of developing prostate cancer. Again – this is not the case. If anything, omega-3 fatty acids are known to help to prevent or slow down cancer cell growth.

So, going back to the negative news published on the outcome of the STREGTH Trial and the statement that omega-3/fish oil does not reduce cardiovascular risk.

First of all, the scientists correctly say that their findings (so the outcome of their study using a specific omega-3 free fatty acid formulation) and not, in general, the omega-3 fatty acids or the fish oil did not show any reduction in the cardiovascular risk of the treatment group; this is important and needs to be understood.

About the same time when the outcome of the STRENGTH Trial was published, another very interesting meta-analysis [2] of 40 large clinical trials investigating the effect of EPA alone or EPA+DHA on the outcome of cardiovascular prevention, with a combined 135,267 patients, concluded that EPA+DHA is just as effective in preventing CV events than EPA alone. We know from several studies that DHA independently can be just as efficient, if not even more effective, in lowering blood triglyceride levels, heart rate, and blood pressure than EPA. Strange that nothing was found in our daily press about this positive news regarding reducing the cardiovascular risk when comparing the most recent 40 extensive clinical studies in this field. However, they did focus on the one study showing no effect.

Also very recently an EPA-rich drug was approved by the health authorities to reduce cardiovascular risk. To get such approval from the US FDA or European EMA, you need more proof than just one study outcome. Again, did you read anything of this in the daily press? No – it seems like nobody cares about the positive news.

Let me return once more to the STREGTH Trial outcome. The question is: why were the Cleveland scientists unable to show a positive effect of their omega-3 formulation on their subjects' heart health? Looking in more detail at their study data, I have two assumptions:

Was the initial EPA+DHA level in the Treatment Group so high to start with that the additional protection effect coming from the omega-3 drug possibly was not statistically detectable? Study data seem to indicate this direction. The average concentration of EPA+DHA found in the subjects' blood at the beginning of the study was 6.9 %. This is a high value. For an average US citizen, you would expect 3,5-4 %. Many studies have shown that such a high EPA+DHA concentration of 6.9% already has a cardioprotective effect. So, it may well be that the subjects in the omega-3 treatment group of that study were already protected from the beginning and that further omega-3 supplementation did not reflect any additional protection.

I firmly believe that if the average EPA+DHA concentration in the treatment group at the beginning of the study would have been around 3,5 5 and 9,4 5 at the end, then the STREGTH research would have shown a reduction in the cardiovascular risk.

Also, considering the high daily dose of omega-3 FFA and the duration of the trial, the recorded increase in EPA+DHA levels in the plasma of the subjects (from 6.9 to 9.4 %) seems low. Is it possible that there might have been an absorption problem due to a too late release of the omega-3 fatty acids from the special enteric-coated soft gels?

So, summarizing: Don't get confused by the outcome of one (1!) study. There are many reasons why a negative or positive result was obtained. To get a better idea if a particular compound (for example, fish oil omega-3's) has a beneficial health effect, you should always look at the meta-analysis of many clinical trials and compare their results. If you see that the vast majority of these trials show positive results, you can be pretty sure that you are on the correct way. In the case of fish oil omega-3 fatty acids, more than 4000 studies are published showing very different and numerous beneficial health effects. As mentioned above, a recent analysis comparing the last 40 large clinical trials on omega-3 and heart health has proven their cardioprotective properties. Finally, even the US FDA and European EMA have approved omega-3 based drugs to lower cardiovascular risk – especially in patients with a high-risk profile.

 

 

[1] SJ Nicholls et al., Effect of High Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk. Journal American Medical Association (JAMA). doi:10.1001/jama.2020.22258, Published online November 15, 2020.

[2]Aldo A., et.al. Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Up-Dated Meta-Analysis and Meta-Regression of Interventional Trials. Mayo Clin. Proc. (2021) Feb;96(2):