Just Eat Fish

I've covered the importance of omega 3 fatty acids in the brain a number of times. However, when anyone asks me for specific recommendations, I've had to be distressingly vague.  Typically I hem and haw and suggest that someone try to eat plenty of clean cold water marine fish, but if one wants to supplement, it's likely that a mix of EPA/DHA is better than DHA alone despite the fact that DHA is by far the major omega 3 in the brain.  But how much do we supplement?  Who knows?  See, the literature on fish oil supplementation is such a mish-mash of different doses and results than one would have to dedicate a zillion hours scanning through the literature, and frankly, there are better things to do.

Warning, fishing at a young age may lead to future moralizing on the internet

But this month we are in luck!  This paper was published in The Journal of Clinical Psychiatry, and it sheds a lot of light on the mysteries of fish oil supplementation and what is known about the efficacy when it comes to mental health.  I love it when academics comb the literature so I don't have to.

The paper is a meta-analysis of fish oil supplementation trials in depression.  There were straight up placebo controlled trials, trials of depression in Parkinson's, in pregnancy… the trials were many, and the results all over the place.  This meta-analysis paper like any decent one is fairly excruciating to read.   See, you have to take all the results and torture them with statistics until they reveal their secrets.  There are statistics for the different types of data, for the particular hypothesis you are attempting to disprove in relation to the data, for the fact that a single author of multiple papers on the same subject will likely have an "author bias" … it's a mess.  And with all that data and that torturing who knows what you have on the other side of the computation? 

Well, a few findings keep popping up, and you can likely hang your hat on them:

1) High dose EPA alone is no good.

2) Any dose of DHA alone is lousy, and may even be harmful.

3) A fish oil supplement worth its salt for depression symptoms, anyway has at least 60% EPA, and EPA may be the most helpful of the two components.  Fortunately, fish and mollusks and whatnot come supplied with fish oil in ratios of EPA higher than DHA, so it does not surprise me that our brains are optimized to run on a mix and not weird, farmed vegan algae DHA (sustainable though it may be).  

I KNOW.  There is hardly any EPA in the brain.  HOW CAN THIS BE?

Well, the authors conclude that EPA is the active component, stating that low dose EPA has been shown to be effective, and that it may be that EPA and DHA fight 1:1 for receptors, so in the mixed supplements, the EPA in excess of the DHA is the actual active ingredient.   Like most supplements (or anything, really), too high or too low is bad, so high dose EPA on its own passes some sort of goodness threshold on a U-curve and ceases to be healthful.  

Interesting item number 1:  The effect of dietary DHA supplementation on human brain levels has not been studied.  That's right.  It's entirely possible that dietary DHA might not lead to increases in cerebral DHA.  If one injects radiolabeled DHA into healthy humans, however, it is incorporated into the brain at an extremely slow rate (about 3.8 mg/day), with total brain turnover occurring after 2.5 years.  Guess how many randomized controlled fish oil trials lasted 2.5 years? (The fifteen trials included in this meta-analysis lasted from 4-16 weeks).

Interesting item number 2:  EPA is a precursor for DHA.  Given that fish sources tend to have more EPA than DHA, it could be that we are optimized to use the dietary EPA to make the DHA in such a way that it is incorporated into our brains.  (A bit of cloudy weather for this interesting item:  There have been studies of dietary EPA in humans and rats and it has not been shown to increase plasma or RBC DHA in humans or brain DHA in rats.)

Interesting item number 3:  EPA does enter the brain.  A tiny bit.  The ratio of EPA:DHA in the brain is actually 1:274.  And brain EPA in rat studies has been shown to help with neurogeneration and neuroprotection.  EPA for 9 months in a human case study study in brain atrophy seemed to increase the ratio of neurogenerative factors in the brain.

Interesting item number 4: EPA's effects could be in the body and these effects secondarily influence the brain.  EPA/arachidonic acid ratios seem to effect membrane fluidity, and EPA seems to increase the burning of polyunsaturated fatty acids which will produce ketone bodies.  And we all know that our brains love ketones.  

Interesting item number 5:  In trials of DHA alone, the DHA takers tended to do worse than placebo and it might actually lead to a pro-inflammatory environment.

So what is the dose?  All positive trials in the literature had a dose of EPA between 200-2200mg daily (with one lonely successful trial at 4000 mg/d).  In the trials with a mixed supplement of DHA and EPA, when you subtract the DHA from the EPA, the dose was also between 200-2200 mg.  

What do I make of it?

Here's a diagram of our metabolism.

Yes, it's complicated.  

Sometimes the best generalized advice is to keep things simple.