Friday, April 1, 2011

That O6/O3 Ratio, Still Important

Oof.  I'm tired.  Oldest child has a spiky fever of unknown origin (FUO in the medical speak) and youngest child is nearly two and tiring by default.  I get these rather silly emails from babysomethingorother telling me about her 23 month old expected developmental stages.  This week's was about her learning to throw things.  Well, she's been throwing things with gusto for quite a while, babysomethingorother.  She also fingerpaints in yogurt on the refrigerator if I allow it.  I guess she's advanced.  Must be the pasture butter and salmon.  They are both sleeping now and thus, a post.

Well.  The lovely Victoria sent me this new paper last week.  If you can't be bothered to click, basically it is a PUFA and dementia and depression paper.  Dementia is bad, depression is bad.  Those with an early form of dementia called mild cognitive impairment who are also depressed are more likely to progress to severe dementia.  Is there a common biologic mechanism?  (Me: YES OF COURSE.  It's called inflammation.  Also, crappy brain energetics.  Researchers:  Let's take a calm and compelling look at the evidence, particularly as regards to the omega 3 and omega 6 fatty acids and the resultant suspected increase in vulnerability to inflammation.  Me: Sigh.  Yes, let's.)

Okay - so if you look at PUFA O3:O6 in the red blood cell plasma membranes, which is felt to be a marker of the bodily PUFA ratio in general, in general (but not always), studies have shown that a lower Omega 3 DHA is associated with depression (in young and old populations) and worsening dementia.  In this study, red blood cell PUFA status was compared between healthy controls and older people with mild cognitive impairment and also with depressive symptoms.

The methods section is tedious but important but we'll skip in my article to the results.  79 volunteers, 50 with mild cognitive impairment and 29 healthy controls.  Anyone on an omega 3 supplement was excluded (3 people total - in Australia something like 50% of the pregnant moms were excluded from the omega 3 study because they were already on supplements.  I guess the older crowd is not so proactive. )

It's complicated, but basically higher levels of n-6 PUFAs were associated with poorer cognitive performance, as well as lower levels of n-3 DHA and EPA.  Similar results were found for "self-reported mental health."  Also "Bodily Pain."  Many of these were linear relationships - basically the more inflammatory omega 6 you have glopping around in your bod, the more you are likely to be depressed, cognitively impaired, and in Bodily Pain.  The researchers go so far as to recommend that older adults have their RBC O3:O6 ratio measured to establish a risk profile for mild cognitive impairment or depression.

I would say - this is an actionable ratio, folks!  Can the corn chips and industrial salad dressings!  There is some evidence that the omega 6 metabolism pathway is overactive in depressed folks with early dementia.  All the more reason not to feed the O6 machine.  In the brain, we are supposed to have a crapload of DHA.  If we don't have enough DHA, it is replaced with a different looking and different functioning omega -derived AA.

Last year my beloved Texas Longhorns football team played for the national championship.  Our tried and true senior quarterback was taken out early in the game in a freak accident, to be replaced by an untried greenhorn.  We lost.  Our freshman replacement quarterback was well-intentioned but in the wrong place at the wrong time.  He just wasn't the same.

"Previous research has shown associations between better mental and physical health and a more varied diet in older age."  I'm not exactly sure what that means.  I think it means eat some fish already.


  1. I love the quarterback analogy!

    Do you ever get the feeling that 'we' (the paleo bunch) have developed some extra perception and cognitive powers? I find the more I read and study the more blindingly obvious that everything comes back to diet, just everything. I wonder, perhaps it's the balance of 03:06 in our brains :-)

  2. Dr. Deans,

    do you have a link to the full article? I get only the abstract and it doesn't include any information as to how "cognitive impairment" was measured.

    H. Anthony Semone, PhD
    Clinical Neuropsychologist

  3. @tony -- go to a university nearby to obtain the full version. Usually it can't be found for free.

    Dr Deans:
    You wisely point out that many mental conditions are caused by poor nutrition. It makes me wonder, how much is due to nutrition and stress, and how much (if any) due to simple genetics? Can stress relief, proper sleep and a paleo diet be the ultimate fix? Or am I just too idealistic?
    A definitive answer is probably impossible, but I'd like to hear your thoughts.

  4. Tony - If I have a moment tomorrow I'll be more detailed, but they did extensive cognitive testing. I have the full text printed out but it is downstairs somewhere. Usually these dementia studies are fairly rigorous. It's the medical literature and not the typical useless study you see in the nutrition literature. (hmmm that was cranky. Oh well).

    Ted - Who is to say? There's genetics, then epigenetics, then stress, sleep, temperament, experience, then diet... However, I would say we are likely born less broken than not?

  5. Tony - researchers used a variety of standard tests - stroop coulor word test, boston naming test, RAVLT, how many F or S words or words not containing E,A can you name in 60 seconds, digit span forward and backwards, trail-making, letter-number sequencing tests, some administered immediately, some testing delayed recall, then also standard depression, physical health, and mental health scales. It wasn't as exhaustive as some I've seen (some RCT omega3 trials used more intensive testing), but it wasn't bad and should be able to catch mild cognitive impairment and gradations thereof.

  6. Dr. Deans,

    thanks for the info; it is about what I expected. Of course, in the absence of effort testing - a condition which affects virtually all of cognitive testing, both clinical, and especially research based - there is no way to know if the obtained data were affected, and if so, how much, by "lack of effort."

    Moreover, since the tests that were used are not specific for cognitive impairment (save for Trail-Making), or have limited such specificity, but instead are subject to very high sensitivity to multiple independent variables, I would for one not trust at all the conclusions drawn by the experimenters.

    Just the view of a traditionally trained neuropsychologist who was taught that if you are going to evaluate the condition of the brain by way of psychological tests, then those tests should be highly specific for brain function while minimally sensitive to such things as depression, anxiety. As a currently trained neuropsychologist, it is increasingly regarded as a failure to meet the standard of care to omit tests of effort whether in clinical, forensic or research contexts.

    Keep up the good work on your site. It is of substantial value to me and to my other colleagues and patients as well.


  7. Tony, it is interesting the way they were able to find some linear differences. It's just an observational study, however, so take it for what it is worth.

    I agree as to the testing - was reading a recent article about ADHD studies and the issues with cognitive testing versus real-life situations and the problems that imposed on research. However, for basic executive functioning the tests they used in this study weren't too bad. It is actually similar to what I do in my office as a screen for dementia (I typically do digit span forward and backwards, clock drawing, copy a complicated figure, other tests of memory, F words and animal words, continue/complete a pattern, those sorts of things. But when I send someone out for neuropsych testing, I expect a long and detailed report!

  8. "...if you look at PUFA O3:O6 in the red blood cell plasma membranes, which is felt to be a marker of the bodily PUFA ratio in general..."

    Is it better to test red blood cell membranes or plasma for fatty acids?


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