Revisiting the Fish Oil is Good For Heart & Brain Mantra: SU.FOL.OM3 Trial Says High Omega-3 Good For the Heart, High Arachidonic Acid (LC N6-PUFA) Good for the Brain!

I never believed that it was a good idea to pay for and consume for the capped extract of what has long been the useless waste of the fishery industry and is now called "fish oil". Fishing, and eating real, whole fish, on the other hand, is something I wholeheartedly recommend.

I am, as most of you should know, no real fan of correlation analyses such as the one SuppVersity reader Roy Nelson, recently pointed me to, but in view of the fact that they are the best we have, when it comes to the assessment of the long-term effects of high vs. low omega-3 intakes (actually rather serum levels), I still decided to give the SU.FOL.OM3 trial a go.

The study is after all "more controlled" than your usual epidemiological guesswork and with 2,263 patients who were enrolled in the SUpplementation with FOLate, vitamins B-6 and B-12 and/or OMega-3 fatty acid trial (SU.FOL.OM3) sufficieently powered (meaning it has enough subjects to provide relevant results and determine even smaller inter-group differences relatively reliably).

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The intention of the researchers fro the Cnam, Université in France was to check, whether the number of major cardiovascular, cardiac and cerebrovascular events between those patients who had been randomized to receive the said combination of "health supplements" and their counter-parts in the placebo arm would differ during the 4.7 years of follow up.

By now you should be throwing your hands up in despair! 

It's of course total bullocks to use the data from a stud using a multi-ingredient supplement (Folate, vitamin B6 + b12 and omega-3) to draw any conclusions with respect to the cardioprotective effects of one of the ingredients. Luckily, the scientists appear to have realized that as well. Accordingly, their criterion was not "active" vs. "placebo" treatment, but rather "high" vs. "low" serum omega-3 levels, they adjusted for the fish oil and B-vitamin supplements (no idea how they did that) and to spice things up a bit, they included a bunch of other serum fatty acid levels in their analysis, too.

Another study suggests: Maybe it's not even about the fats you eat! Usually we assume that the fatty acid composition of our blood would be determined by the fats we eat. According to a recent study from the University of Eastern Finland, the type and amount of fat we eat is yet only one of at least two factors which determine the amount and ratio of fatty acids in our body.

Table 1: The associations of food consumption w/ fatty acids in plasma cholesteryl esters (Venalainen. 2014)

In particular, the Finnish researchers were able to prove that there is a highly signicant association between the amount of "garbage" carbohydrate foods (highly processed, low dietary fiber content) and the amount of oleic acid (MUFA) in the blood of 512 children 6-8 years of age from the city of Kuopio.The researchers explain this effect based on carbohydrate induced increases in hepatic delta-9-desaturase activity and a consequent increase in the conversion of saturated to mono-unstaturated fatty acids (Venäläinen. 2014).

What they found were significant risk increases for both types of major events (heat and brain) with high total fatty acid levels (+54%), which did yet lose their significance, when Fezeu et al. adjusted for tobacco smoking, alcohol consumption, systolic blood pressure, diabetes status, plasma cholesterol (HDL and LDL), triglycerides, n-3 supplementation and homocysteinemia.
That's in contrast to the positive effects 2nd and 4th quartile palmitic acid levels, as well as the borderline significant risk decrease (-21%) in those subects with the highest long-chain omega-3 levels (EPA + DPA + DHA) in their blood.

In spite of the fact that the overall brain + heart protective effects of omega-3 are obviously pretty pathetic (without DPA, high total N-3 and high DHA + EPA levels did not even correlate with reduced risk), the scientists heart-specific analysis would seem to support the hype around the holy omega-3s and their ability to save our fat asses.

Both, high stearidonic acid (C 18:4 n – 3) and DHA levels appear to have be associated with 37% and 16% reduced risks of incident cardiac events. In view of the absence of a clear trend (= more omega-3 = lower risk) for DHA and considering the fact that a high omega-3 to omega-6 ratio did not have the significant protective effect everybody believes it would have, the the public (in many countries even "official") hype does eventually appear to be over the tops.

Figure 3: Partially (age, BMI, initial e- vent, gender) and fully adjusted multi- variate hazard ratios for associations between baseline plasma lipid profile and incident cerebro-vascular events in the SU.FOL.OM3 study - high value = high risk with the given profile; e.g. -36% with high AA levels

If omega-3s are not so protective, maybe omega-6s are not so bad? In the end, the study at hand does confirm just that. There are no significant risk increases for either cardiac or cerebrovascular events associated with any of the various forms of omega-6 fatty acids, the scientists tested. On the contrary, very high amounts of the "big bad" long-chain omega-6 fatty acid arachidonic acid are actually associated with a -56% reduced risk of cerebrovascular events the amount of long-chain omega-3 fatty acids (DHA, EPA, DPA), on the other hand, is not.

Now this does not imply that omega-3 fats are junk and I have to admit that I am a bit skeptic how the scientists were able to "adjust for" the supplemental omega-3s. For me, the study at hand does nevertheless confirm that the "proven benefits" of omega-3 fatty acids should rather be considered "proven benefits" of high omega-3 foods.

Practically speaking this means: Keep eating your salmon, grass-fed beef, nuts, etc., but don't fool yourself to believe that popping a pill with waste-products of the fishery industry (that's what fish oil was for decades, before someone instigated the hype and people started to pay for the waste) will have you live healthily ever after.

References: 

• Fezeu LK, et al. "Baseline Plasma Fatty Acids Profile and Incident Cardiovascular Events in the SU.FOL.OM3 Trial: The Evidence Revisited." PLoS ONE (2014): e92548.
• Venäläinen, Taisa, et al. "Cross-Sectional Associations of Food Consumption with Plasma Fatty Acid Composition and Estimated Desaturase Activities in Finnish Children." Lipids (2014): 1-13.