Tuesday, February 15, 2011

Mental Health and Omega 3/6 Ratio, A New Review

Twitter is a black hole for time spitting out information like Hawking radiation. (I may have achieved the geekiest simile ever!)  I've been a bit busy, as the applications for preschool are pretty detailed, asking for medical records, descriptions of my culture, and different ways we help the little one settle down or take her nap (bribery and threats, mostly.  Oh, wait, the correct answer is "routine.") And sure, she's allergic to sunscreen.  Well, with all that going on the blogging and reading has gone by the wayside a little.  Also, most papers come out as a preview in the last week of the month, so there tends to be a rush of exciting new information all at once.  Then a dry spell.  If I'm fired up, I'll actually look into a topic in depth and do a nearly proper literature review.  But not having had the time to do that... there's always twitter (and Jamie Scott, who is sending me a slew of papers about mitochondria, histamine, and sleep because he is awesome that way.  I'm hoping to settle down and look at them sometime over the next couple of weeks).

Twitter!  The be-ripped Martin Berkhan tweeted up a paper earlier today that is a new review of Omega 3s and 6s.  The article, Evolutionary Aspects of Diet: The Omega-6/Omega-3 Ratio and the Brain, is a tidy look at omega-3 and omega -6 biochemistry detailing all the conversions and enzymes along the way for the biochem geeks.  In the end, it describes the more interesting stuff about the evidence that omega 3s, in fact, do have an important role in the brain, and that one would be a sad and foolish monkey indeed to consume the modern 25:1 6:3 ratio (just say no to corn and safflower and soybean oil...)  Another interesting fact - the review is written by Artemis P Simopoulos, who pretty much first popularized the Mediterranean diet with her book The Omega Diet: The Lifesaving Nutritional Program Based on the Diet of the Island of Crete.  Guess she knows what she's talking about with respect to the omegas.  

Let's dig in.  Hmmm... "psychologic stress in humans induces the production of pro-inflammatory cytokines such as IFN gamma, TNF alpha, IL-6, and IL-1."  Yup.  Too much omega-6 compared to omega 3 can lead to the overproduction of inflammatory cytokines, which for various reasons is Not Good.  Theoretically, changes in PUFA ratios can alter the function and structure of the serotonin receptors (for example, essential fatty acids in the plasma predict the CSF metabolites of serotonin and dopamine)(1).  Treatment with DHA and EPA can be useful in major depressive disorder and bipolar disorder.  Other researchers note that as the dietary ratio of omega-6/omega-3 increases, depression symptoms, TNF-alpha, IL-6, and the IL-6 soluble receptor increases.  Another group studied brains of people suffering from depression when they died vs. controls.  A decrease in AA/DHA ratios were negatively correlated with age in depressed people, but not in controls.  All these lines of evidence, including the randomized controlled trials of omega-3 supplementation, seem to support the idea that our brain needs omega-3s to work well and keep the mood stable.    

Now onto the studies of cognition and omega-3 PUFAs.  Turns out that when the neurons are stimulated with neurotransmitters, the PUFAs in the cell membrane can be released to become all sorts of different inflammatory and anti-inflammatory or signaling molecules.  The PUFAs also seem to influence cell migration and cell self-destruction (called apoptosis) - they even influence the length of telomeres, which are known to decrease with age, cancer, and cardiovascular disease.   A lot of neurochemistry has been elucidated in this area - the details are nicely summarized by Simopolous.  Suffice it to say that brain inflammation is part of the pathology of schizophrenia, dementia, and likely autism, and that omega 6/3 ratios could be important, and omega 3 supplementation (if done early on), can possibly be helpful.  There is some controversy as to the best ratio with which to supplement (2:1 EPA to DHA is recommended by Simopolous), and in these unknowns I prefer to fall back to the primary sources - fatty fish themselves.   

A study of prisoners showed many violent incarcerated young folks have deficiency ("0% intake") in omega 3 fatty acids from fish and selenium in the Table 5 of the paper, called "Diet of disaffection: nutrient intakes from a sample of disadvantaged young people."  Only 17% of them get adequate intake of magnesium too.  Interesting.

When one looks at studies of substance abusers, one also finds deficiencies of omega 3s.  Alcoholics, for example, are a known population rife with nutrient deficiencies (a med school professor used to call it the BBB diet - "beer, bread, and bologna.")  A group of researchers carried out a small double-blind randomized controlled trial of 3g EPA and DHA vs soybean oil control in substance abusers. After three months, the treatment arm had significantly reduced feelings of anger, anxiety, and cravings.  The increase in plasma EPA strongly correlated with the reduced anxiety, and the effects persisted for 3 months after the end of the treatment.

Putting it all together - the overall evidence suggests that if you want to be anxious, moody, depressed, violent, and craving addictive substances, by all means slurp down those omega 6 PUFAs. If you want more control over your brain and urges, maybe look into avoiding any extra 6 (the animal fats will have all that is necessary) and be sure to get the omega 3s you need via fish a few times a week or properly sourced beef or other grassfed ruminant meat.  This brain chemistry thing ain't so hard after all.


  1. It always comes back to pastured meat (& fats derived therefrom), fatty fish, and avoiding the neolithic agents of the apocalypse. Simple. I can live with that.

  2. Do you have a link for the "substance abuse and omega-3" study? I speculated about a connection, but couldn't find more than the CB1-receptor (well, I didn't know pubmed back then).

    (And well, *WHICH* process that can go wrong in the human body, and involves possibly AA/EPA-based autocrines/paracrines/neurotransmitters, is *NOT* negatively influenced by a suboptimal n-3/n-6 ratio?)

  3. hi Tony - the reference is here: http://www.sciencemag.org/content/325/5948/1614.summary

    I was too lazy to link it last night. It seems to be an ongoing experiment in prison. I'd heard of it before via selenium research, but hadn't bothered to download the article from science yet - now I will.

  4. Oh, sorry - you meant the substance abuse study. I linked the prisoner study. Here's the reference (actually, full text on pubmed central. yippie!)


  5. "AA/DHA ratios decreased with age in depressed people, but not in controls."

    What is your interpretation of this?

  6. Hi John - I have a couple of thoughts on that one. Could be part of the reason people are vulnerable to depression is that they have inefficient enzymatic machinery to crank out the DHA. The ability to make ALA and EPA into DHA varies - DHA is the only omega 3 highly active in the brain. We also tend to have higher DHA requirements in youth (we are making a growing brain, after all) and in old age (where we have a higher inflammatory load), so some people as they get older don't have the machinery to keep up, others run out of the basic building blocks (the fish oils themselves), which can explain why we are more and more vulnerable to depression, anyway, as we get older.

  7. I have read that with all this process food we consume, we get get up to 20 times More Omega-6 than Omega-3, leading to a big imbalance.

  8. Hi Emily,

    What you said is what I'd guess [before seeing the quote], but it says the ratio decreased, meaning DHA is actually increasing relative to AA, which makes it look like low DHA isn't the problem. Do you have the ref?

    Masterjohn wrote on AA metabolism involving endocannabinoids regulating dopamine & cortisol and therefore anxiety & depression.

    Hi Arlene,

    Yea, it would be an even larger imbalance if the rancid omega 3 in soybean oil-filled foods wasn't counted.

  9. Hi John - you are right - the paper said "significant negative correlation" to decreased ratio - in simplifying that for the blog post, I dropped the double negative and wrote it backwards. Thanks for the catch! I'll fix it now.

    Here's the paper:

    Conklin SM, Runyan CA, Leonard S, Reddy RD, Muldoon MF,Yao JK (2010) Age-related changes of n-3 and n-6 polyunsaturated fatty acids in the anterior cingulate cortex of individuals with major depressive disorder. Prostaglandins Leukot Essent Fatty Acids 82(2–3):111–119

  10. Hi Emily,

    Though I am not an MD nor a researcher but thought you might be interested in some anecdotal evidence from my own experience.

    I am a 68 year old recovered alcoholic with 28 years of sobriety. I was diagnosed at age 50 with ADD/ADHD after passing the psychiatrist's test with scores better than 90%. She prescribed Ritalin Ln and Effexor Xr for the related systemic depression. The Effexor dose rose to 300 mg after a few months and continued until at age 58. I began taking 1200 mg of fish oil (Kirkland brand) twice a day in July of that year. In December I was able to reduce the Effexor by one half to 150 mg and has used that since with an improved mood. Even the winter months (December-February) have become easily tolerable.

    Though the Ritalin worked well for emotions and focus I quit taking it regularly because of the cumulative physical side effects - tics like tapping my hand and/or foot constantly at ever increasing intensities, etc.

  11. It is interesting how the apparently disparate Neolithic “agents of destruction” converge in their effects. And it all seems to point at inflammation, as you’ve been stressing on your posts.

    Beowulf’s tweet and linked paper highlight O6. As it turns out, consumption of foods rich in refined carbs in large amounts increases inflammatory markers in the hours immediately after it happens (http://bit.ly/g2Mofm), and also dramatically increases the cortisol response to stress (http://bit.ly/eLQbCp).

  12. Frank - glad you are feeling better with the O3!
    Stimulants can definitly cause tic-like side effects. Fortunately they tend to go away when the medicine is stopped.

    It is beautiful how it all works together, right Ned? The things I've dug up that have a *little* (I wouldn't call it conclusive) data showing they blunt the stress repsonse are the phospholipids and magnesium - both definitely low in average modern diets, and high in ancestral (or traditional) ones.

  13. Magnesium is a good point. Anecdotally regarding electrolytes: when I changed over to primal eating in the last months, I stopped using salt. I used less and less cured meat and less processed meat. At some point I read the report from Vilhjalmur Stefanson and thought why bother with salt, we don't need it. Guess I was eating far less fish (and more steak) than Stefanson and now I think it was a stupid mistake reducing salt like that, because the symptoms that I can only describe as hypothyroidism came back over the months (which might have been mediated by some sort of adrenal gland fatigue). Now I started to use salt again (in moderation) and the symptoms slowly yield.

    I guess stuff like phytates hindering mineral absorption in mamals, plants grown on depleted soil lead to a suboptimal intake of minerals (and who eats fish every day like Stefanson?). The paleo community should keep that point in mind, its not as important once you have the other ones right (like avoid antinutrients and optimize n-3/n-6) but it is important from my point of view.

    And thanks for the link!

  14. Hi Tony - when I switched to paleo I had leg cramps at night. supplemental magnesium fixed it. I've never seen convincing evidence that salt would be an issue except for those with hypertension that is responsive to salt restriction. However, though I have never restricted seasoning in my cooking, I find that when I get a mouthful of processed food, the salt can be overpowering. I buy Celtic Salt for a bit of mineral fun in my cooking. I add a bit of seaweed for iodine to stews and the like. I take a multi mineral (sometimes) on a week that I don't eat beef liver.

    I was struck by the typical mineral deficiencies (particularly selenium and magnesium) in large dietary studies - especially in women.

  15. Oh, and my farmers add some sort of organic ground oysters or some sort of sea mulch to their fertilizer - I'm hopeful that means my CSA box is chock full of minerals (but the CSA only runs about 22 weeks up here due to the short growing season.)

  16. Yeah, the processed food really is salty, automatically limits your consumption when one doesn't eat bread anymore. At the beginning of my dietary change, I first followed Lutz (limit carbs), but after some post-meal panic-attacks I followed more the Atkins Phase 1 thing (carbs are evil!). So I thought processed meat, sausages and cheese were OK to eat – and I was surprised how salty especially most cheeses tasted. It is really hard to eat the stuff without bread, no wonder people don't want to give up bread.

    I got some fleur de sel, which is nice. I never liked seaweed, but I think I should give it another try. I currently use a mineral supplement mainly for the iodine and selenium, but I guess real food (without starch or some other goo from god-knows-what-plant as binder) is better. I put Magnesium next on my list today.

    Hmm, I need to make liver myself! Never done it, but used to eat it as kid - a bit. My parents come from Czechoslovakia and both liver and kidneys were considered delicateses there, but in West-Germany were I grew up, intestines was not a "modern" food, more a poor man's thing. I must admit, I didn't like intestines as a kid, couldn't stand blood sausage and didn't eat fish and anything with bones still attached. I was a smug kid and payed the price for it. Now I miss liver and can't wait to buy some liver tomorrow and make it.

    Haven't ventured into CSA yet, the people here are crazy for "biologic"-food (whatever that means) or "organic", both with lots of grain, they would buy strichnin if it was grown "organic". What one can get here is organic-grain-fed meats and eggs (belch) for a premium, haven't see any pure-pasture meat yet, but haven't looked yet. And what you can get is meat and eggs that has access to pasture but gets fed grains - better then nothing. (My budget is a bit tight at the moment anyway)

    And oh, I can recommend plantains! Bananas unwanted cousin, they taste fried a lot like fried potatoes, have no sugar, no fructose, are mainly starch – and I hope they're low in antinutrients (as far as I understand it, it's a cultivated seedless fruit and most antinutrients would be in the peel or in the seeds). At least I got no reactions from them and I really like them. :-) A plantain a day, keeps the doctor away!

    And maybe, in ten years I will be able to buy some A2-milk and enjoy it. Let's see.

  17. And one more, I never had problems with hypertension, but with the "I don't eat salt" thing I started to get problems with hypotension - go figure. :-)

  18. Emily,

    Have you ever applied the evolutionary model to the diet of lactating mothers? I have been breastfeeding for the past nine months and prior to pregnancy and childbirth had been on a HFLC (Paleo) diet.

    I've definitely noticed diminished volume when my carbs dip below a certain point, usually around 60-70 grams per day. I read in the Handbook of Physiology (Section 5: Adipose Tissue) that the fatty acids secreted by mammary glands are derived from a glucose pathway.

    In terms of evolution, it seems hunter gatherers would have (a) breastfed as long as possible, and (b) spent some significant amount of time lactating while in in ketosis. Carb-loading definitely increases quanitity, but quality may be another matter.

  19. Allison - I started Paleo right after weaning my second child. Prior to that I ate what I would call "Michael Pollan" style - all whole, real foods, but plenty of whole grains, stuff I made myself. Oatmeal every morning, etc. No vegetable oil, thank heavens. Never had any problem with supply (in fact, quite the opposite. Both kids are very tall and we had hundreds of ounces of frozen milk to mix with their stupid baby cereal.) Since I am overall lower carb now, if I have another kid, I suppose I'll do an n=1 comparison.

  20. Just an anecdotal report from me...I definitely feel worse and more depressed from omega 6. I used some hemp seeds yesterday which are high in 06, after avoiding PUFAS for quite a while, and have felt more sluggish and depressed ever since. It's amazing to me that I can notice such a pronounced reaction.