Thursday, January 12, 2012

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?

Yes, it's complicated.  

Sometimes the best generalized advice is to keep things simple.


  1. Eating fish is good advice, but everything is related, nothing exists in a vacuum...

    Fish have high levels of mercury, there have been cases of individuals who have gotten mercury tox from eating large predatory fish (these are the fish with relevant levels of omega 3s).

    If you stick to smaller fish with lower fat contents like sardines, you will never take in enough omega 3 to counter the omega 6 load from grains, nuts, oils, chicken/eggs and ruminant animals factory farmed on aforementioned grains.

    Unless of course you like eating lots and lots of sardines, which no one does, because that's gross. Then you also have to worry about the contaminants of cans...

    Our whole food system is unhealthy and screwed up, I tend to think supplements are a prerequisite.

    There are many studies which show omega 3 pills actually do improve mental disorders like depression and heart disease.

    Eh, I am extremely suspicious of any and all psychiatric research as the whole profession has become sort of an insurance bilking scam, diagnosing normal people with incurable brain diseases so they can then bill/prescribe/profit. There is a vested interest in discouraging unprofitable treatments like omega 3s. What a coincidence that it always turns out the only effective treatment for psychiatric illnesses are drugs that psychiatrists must prescribe, and drug companies must patent/sell. It's really interesting, isn't it, that lithium turns out to be riddled with complications (meanwhile the horror show of seroquel and zyprexa is consistently minimized), and it turns out that omega 3s and st johns wort don't help depression all that much, but the latest SSRI/SNRI does.

    In fact I can't think of any treatments endorsed by psychiatry, as a whole, which are not designer novel drug molecules that must be prescribed and monitored. Everything which is not a designer psychotropic drug is viewed as quackery, or "not intended for real depression". You never hear endorsements of glucose control for depression, or micronutrients, or omega 3s, other than this wishy-washy "maybe it's important...BUT NOT AS IMPORTANT AS YOUR PROZAC (R)"
    Kind of interesting it turns out this way, seeing as psychiatrists specialize in the prescribing and monitoring psychotropic drug therapy.

    *not knocking psychiatry in concept, i.e. therapy/treatment/medicine to help mentally ill people... just the state of affairs of the industry.

  2. Emily this was a timely post considering what I am writing now but I have a question for you. Since we both work on the brain, but in a different fashion I think we both agree with the needs for omega 3 (DHA/EPA). You are saying just eat fish is best for the brain and I cant argue with it. For people with neurological damage micro or macroscopically I actually recommend to them adding Krill oil for the better brain function than straight fish oil supplementation because the phospholipids in it are more bioavailable for the brain than the DHA or EPA in fish oils. I also like the astaxathin one gets too from this but most krill has too little for my liking for clinical uses for higher HS CRP. I am particularly fond of it in AD and PD patients. There is some data that this antioxident is pretty good at blocking IL-2 and this has been tied to the genesis of depression in the literature. I'd love to here your thoughts on this issue. Thanks

  3. "I love it when academics comb the literature so I don't have to."

    Hey, that's why I read your blog. Love the pictures :o)

  4. Are canned sardines supposed to be good?

  5. Since we know that there is a relationshiop between EPA and Arachidonic Acid in inflamation signalling, it would be nice if the dietary ratio of the two were brought into the analysis of EPA/depression. So anywhere from 200 to 2200 mg of EPA is good? Maybe that range will narrow a little once AA intake is factored in?

  6. I eat (local, wild) spanish mackerel weekly which has 75mg EPA and 281mg DHA per 100g. Should I consider looking for a fish with a ratio better favouring EPA?

    I'm throwing this out to anyone. Cheers!

  7. 1. Eating lots of sardines is not gross, it’s delicious!

    2. That said, I also love fish of all kinds, particularly sushi, of late. So, then, what about mercury levels?

  8. I learned from Seth Roberts that taking flax oil improves the health of your gums and improves your balance. So I switched from fish oil to flax oil and it worked.

    His thinking is that the flax oil works like a time release capsule because of the conversion process. Where as the fish oil hits your system quickly and then dissipates just as quickly.

    It could also be related to Interesting Item No 4.

  9. Thanks for the post. I've followed the whole fish oils thing with regards to autism spectrum conditions for quite a few years now and what seems to be emerging from the very mixed evidence base is that (a) the jury is still out on whether there is any significant effect on 'core' symptoms to be had - as per the recent Cochrane Library review: - allowing for the fact that controlled trials using the same formulation are fairly scant (b) most of the positive evidence seems to indicate that peripheral symptoms (attention, hyperactivity) are the main reported effects from such products.
    The problem as you highlight is the very complicated relationship between DHA and EPA which is even more complicated when you realise that many preparations add things like vitamin E into their products.
    (By the way, I hate what Blogger have done to the formatting of comments thanks to their 'reply to thread' setting! grumble, grumble)

  10. Is it possible to find another simple solution besides eating fish for those who are allergic to any fish product like my son? Do you consider a grass-fed ruminant meat and butter to be good sources for O3?

  11. Some info on canned fish and BPA

  12. Woo - as far as I know mercury is not an issue with coldwater salmon, particularly Alaskan. However, PCBs can be. The advantage of fish oil supplements is that they can be molecularly distilled. And frankly, all the ones I've seen have a mix of EPA/DHA and are heavier on the EPA side. The disadvantage - are they rancid?

    Jack - I know Dr. BG has concerns about heavy metals in krill oil. I've recommended it clinically on some occasions as something to try, and I've found (anecdotally) it works pretty well in older folks. They noticed it helped with executive function and with anxiety. I took it for a couple of months as a bit of an experiment, and I have to say it made me a little agitated, and I had a couple of younger patients complain of the same thing. Astaxathin is an interesting compound but I would say the jury is still out.

    Dim Tim - I think the literature has narrowed the range, but I still think there are too many variables to make much of it. Part of the paper I didn't blog on made a very reasonable suggestion to actually do a rigorous study (rather like the anxiety one done in medical students I blogged about recently), where inflammatory markers and RBC O3/O6 ratios were actually tested before and after supplementation. (seems like a no-brainer, right?)

    Unknown - I know there are websites noting mercury levels - Mark's Daily apple has linked them before. I think that sort of thing is quite important in children and women of childbearing age in particular.

    Chuck - I'm not the biggest fan of flax oil as ALA doesn't convert very well to the EPA and DHA we do use, leaving a lot of excess ALA about which can become rancid. However, as we know, that is the story on face, whereas what is actually going on in the body is far more complex.

    Paul - I have a few autism spectrum posts coming up, and one on the latest (excellent) review in Pediatrics on dietary therapies for ADHD. And yes, the formatting of comments is annoying. I really ought to switch over the wordpress like all the real bloggers.

    Galina - honestly, your answer may go back to Jack's point about the
    phospholipids. Maybe keeping the O6 low and eating organ meats (beef heart, marrow, eggs, chicken hearts - good sources of phospholipids) is all that is needed. Those sources aren't robust for O3 but you don't need a whole lot of it by any means.

  13. @Galina

    I for one think if unnatural amounts of n-6 are avoided and all your butter and meat and dairy is from ruminants, that you can have an evolutionarily concordant 6:3 ratio.

    Grass fed butter has a nearly 1:1 ratio, for instance.

    Hominins have not consistently enough occupied fish containing biomes for fish consumption to be necessary for development or health, IMO.

  14. I would love to "just eat fish" but unfortunately am allergic to them... any comments on what else I should be eating? I've seen a lot of other people's comments on substitutes; I'm curious as to your opinion.

  15. Kurt and Emily, thank you for answers. My son is now in college, I gave him a lot of pastured butter and beef tallow for cooking in the cooler to go together with 20 lb of grown beef. He is trying to buy mostly grass-fed meats like lamb and grass-fed tong, sometimes beef, but eating other organs is too much for him. He is avoiding O6-s, but eats regular eggs. Sometimes we do what can be done within a normal amount of effort. It is amazing, but he spent 800 dollars less per semester eating self-cooked high quality food than eating in a cafeteria during his first year in university. I am glad to learn that pastured butter contains that much of O3, I didn't know that.

  16. Matt, Kurt, and Galina -

    I'm of two minds about the whole evolved for fish story. On one hand, the human brain fat is literally 30% DHA, and there are countless observational studies showing improved brain health (less dementia, less depression) in fish-eating populations (particularly in women). Thus a narrative has developed about a supposed human population bottleneck that occurred about 75,000 years ago along with a "great leap forward" in technology.

    The narrative is that the bottleneck occurred next to the ocean in a marine-manging people, so that all modern humans are descended from these super-smart fish eaters. Once our brains began running on more fish oil, we somehow adapted to non-marine climes and hoarded what we could - the narrative is bolstered by stories of mountain dwelling people going to great lengths to get seafood (though they may have been trying to prevent iodine deficiency - Stephan has a long-ago article about this, and Chris Masterjohn's more recent one about Weston Price looking for vegans but finding only cannibals (the mountain people ate the fishermen! High in O3!) is also a good read.

    On the other hand, central Europe and mid-America are full of healthy people (like Kurt) who live far from the ocean. And I also wonder if our modern O6 crazy heavy diets created this fish oil "deficiency" we have today. And I know John Hawks has disputed the bottleneck theory, saying there was no population crash 75,000 years ago.

    Overall, one has to think of the long haul. Stephan wrote once he estimated 2 years for the excess linoleic acid to leave the fatty tissues -- in this paper we find that injected DHA is incorporated into the brain a few mg a day. At that rate, the few mg of O3s in a standard serving of grassfed beef or butter (with their favorable 1:1 O3/O6) would seem to be plenty. Especially if one adds phospholipids by not shirking the organ meats. (I make sure the chicken hearts cook in the bone broth).

  17. It is somehow ironic that allergy to a sea-food is very common, unlike an allergy to beef, pork, lamb. My son also has a very mild intolerance to a chicken meat, which is manifested in a lips itching, unlike quite prominent reaction on a fish . I have an impression that ruminant meat and pork are the safest choices for a person with allergies, while fish and shell-fish, milk, eggs, nuts and, of course, wheat could be questionable, not necessary all at once. I do not question the data about our evolutionary history , it just the data looks strange for me when I look at it in the light of common allergies.

  18. About mercury in fish. Chris Kresser wrote that eating fish that have high selenium levels would be safe as selenium binds with mercury.

  19. Chris is right. There are research studies you can find online about the effects of selenium on mercury so it's not just some blogger's claim.

    Just be careful with kids because I'm not sure how efficient the process is in them.

    I'm coming around to krill oil because it seems to come with its own natural preservative for the omega-3s, and until we get rid of all these dams on the Western rivers that support grain agriculture (grr) and keep salmon from reproducing, the salmon will continue to be overfished. So I don't want to go crazy eating it, even though I love the stuff. I do get grass-fed dairy, so between that and small doses of krill oil and avoiding most vegetable oil (realistically, unless you NEVER eat outside your home, it's difficult to avoid all of it), I think I'll be OK.

  20. "On one hand, the human brain fat is literally 30% DHA"

    And the fact that this is true even for humans who have never eaten a single morsel of fresh fish during their whole ontogeny tells us quite a lot.

    Like John Hawks, I don't buy any of the variants of the aquatic ape or littoral hypothesis, including Cunnane's version. I think they are kind of modern paleo myths, like Dairy causing "mucus" or cancer...

    In pre-european north and south america, there was substantial trade in many goods, including dried fish. It's a bit hard to imagine unstable long chain n-3s being well preserved on a months-long trade route in fish without refrigeration, but easy to imagine them as quite valuable sources or protein and iodine.

  21. Even now Russians regularly eat salted dried fish.It stores very well. For centuries it was a common trade to deliver frozen fish by frozen rivers from places on a White see down south. My guess - the rest of Europe did the same.

  22. This from Wikipedia about trade in Canada along the traditional trading routes called The Grease Trail. I thought the fermented oils might also be a good source of Vitamin K2. Is it possible that fermentation preserved the omega 3 oils?

    Carrier people engaged in extensive trade with the coast along trails known as "Grease Trails". ... Imports consisted of various marine products, the most important of which was "grease", the oil extracted from eulachons (also known as "candlefish") by allowing them to rot, adding boiling water, and skimming off the oil. This oil is extremely nutritious and, unlike many other fats, contains desirable fatty acids. Other important imports were smoked eulachons and dried Red Laver seaweed. "Grease" and smoked eulachons are still considered by many to be delicacies and are prized gifts from visitors from the west.

  23. Related to this, I had an exchange with Peter at Hyperlipid earlier this week on EFAs -

    From Peter -

    "I stopped omega 3 supplementing about 3 or 4 years ago, mostly influenced by Chris Masterjohn. I think the dairy and eggs probably provide quite adequate amounts of DHA provided the dairy is in part grass fed. We do eat fish fairly regularly, say once a fortnight. The situation may not be so straightforward in places like the USA where dairy production appears to be designed to eliminate the omega 3 content.

    I think there is no doubt at all that bulk calories from any PUFA are probably the main driver of cirrhosis, but that's not saying that 1-5g/d of fish oil will do this..."

    Eating fish "regularly" once every 14 days is pretty close to no fish at all.

  24. There is a finnish Doctor Tolonen who has written for years about "fatty acid paradox" and therefore recommended EPA instead of DHA for psychiatric patients. Also, he promotes ethyl version of EPA for allegedly more efficient bioavailability through the blood-brain barrier. Mechanisms may be by inhibiting PLA2-enzyme, increasing prostaglandines (PGE3) and raising DHA levels somewhat independently(?).

    I still prefer food. ^^ I guess sardines have quite optimal EPA/DHA ratio, other neurologically beneficial components, less mercury and pollutants since they are small and are quite ecologically sound food source altogether. And they were given free to patients in Oslo Diet Heart study, one of the best cardiovascular prevention studies in history.

    Evolutionarily speaking, what is the EPA/DHA ratio within shellfishes? Humans probably ate fish only 40 k years at most, so the Omega 3 perhaps got their room from shorelife in general in our ancestors' diet.

    Speaking of which, nice review Emily.

    - NeoN

  25. I tried to find out about dried fish and O3

    Fish, cod, Atlantic, dried and salted
    Total Omega-3 fatty acids 378 mg /80 g

  26. >Kurt G. Harris MD
    "On one hand, the human brain fat is literally 30% DHA"

    >And the fact that this is true even for humans who have never eaten a single morsel of fresh fish during their whole ontogeny tells us quite a lot.

    What do you make out of this Kurt? Conversion from vegetale source is not so inefficient in the long term? Other sources than fish?

  27. Thanks for deciphering the complex paper! You mentioned that DHA alone is no good and you gave the example of farmed vegan algae DHA. But I've seen vegan algae supplements that contain both DHA and EPA such as this one: Would algae source of DHA and EPA as good as fish oil? Would love to hear your views. Thanks!


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