Friday, October 12, 2012

Omega 3, the Elderly, and Getting It Right

New study seen on twitter (as I see most cool stuff, partly because I can't really bear facebook and am pretty bad about checking out the usual blogs these days).

The Strokes. Last Night.

The Study (free full text): Older Women, Depression, Omega 3 Ratios, Inflammation, and Supplementation

Bam. I'm getting all Emeril about it because finally we are getting some thoughtful and complete studies. We're talking measuring the plasma membrane ratios of omega 3 to omega 6, supplementing, measuring again, and measuring inflammatory markers as well as response to supplementation. These studies are not phoned in by the statisticians after they whip up another algorithm on the supercomputer over at HSPH.*

Here we have a small randomized placebo-controlled trial of 22 elderly (66-95 y/o) depressed females given omega 3 supplementation (2.5 grams daily of an EPA/DHA 2:1 mix for 8 weeks) and 24 given a placebo (parrafin oil, lemon flavored, just like the other--known for being insoluble in water, poorly absorbed, and flammable). Not only were pre and post depression scales measured, but so were plasma membrane omega 6/3 ratios (measured as AA/EPA in HUMAN SUBJECTS, Chris Barrera), and lots of inflammatory markers (notably CD2, CD3, CD4, CD8, CD16, CD19 and the cytokines IL-5 and IL-15. What, no IL-6 and TNFa?  Little evolutionary psychiatry joke**).  (But it is important to remember that depression is associated with T cell dysfunction, particularly the regulatory T cells that but the kibosh on inflammation).

The paper proper begins with a rather awkward but correct statement: "An unbalance in polyunsaturated fatty acid (PUFA) status is observed in various pathological conditions, especially in chronic and/or degenerative diseases associated with antioxidant system deficiency."

Low DHA in the central nervous system has been associated with all sorts of badness, such as depression, anxiety, ADHD, and dementia. The elderly seem to be particularly at risk, because their ability to change other forms of omega 3 to the long chain forms needed in the CNS is decreased compared to younger folks. (Less delta6 desaturase activity.)


Rachmaninov (Vocalise for Violin).

After 8 weeks, only the intervention group with the omega 3 had a significant decrease in the Geriatric Depression Scale scores. AA/EPA ratio were significantly higher in depressed patients than in healthy ones (from another group of healthy, non-depressed elderly women who were not taking omega3 supplementation). Not surprisingly, the AA/EPA ratio decreased significantly in those taking the omega 3 supplement in the depression group, which correlated with the decreased depression scores. Ratios did not change in the placebo group or in the "healthy" group.

Inflammatory markers were significantly correlated with being depressed at the beginning of the study (not exactly a newsflash) but were not correlated at the end of the study, though there were some shifts in markers. Hey, it was only 8 weeks.

I like this study a lot, for several reasons. They used an omega 3 supplement with EPA greater than DHA, which are the only sorts of supplements shown to be effective in depression. They used an inert placebo (coconut oil is another acceptable substitute) in lieu of olive oil or (gasp) omega6 oil. They measured plasma ratios, depression scores, and inflammation.

I also learned something very interesting that I didn't know before, which is that mood stabilizers, particularly lithium, have been associated with greater AA turnover and increased DHA in the plasma membranes in the frontal cortex. One more mechanism whereby lithium is an essential micro nutrient? Maybe. One more reason to consider that we don't fully understand nutrition or the brain but we should probably take in a reasonable amount of these? Yes.

Stabby thinks we should add vitamin E as well.

*There is something to be said for supercomputers and 100,000 person data sets. But I'm not going to eat corn oil and kashi.

** from the study "numerous studies have indicated major depression as an inflammatory state with elevated levels of proinflammatory cytokines, e.g. Interleukin IL-6, IL-12, interferon (IFN)-γ [15], IL-1 and tumor necrosis factor (TNF)-α [16]. For this reason we decided to evaluate cytokines that have not yet been sufficiently studied to date, such as IL-5 and IL-15, in this study."


  1. Yay. Stabby also thinks that getting enough B6 is important for DHA utilization

  2. This paper relates to restoration of O-3 by krill oil, and reduction of anandamide thereby:

  3. Linked page says that the Crown Prince sardines are gluten free.

    I damn well hope so.

    It's sad that so many deem this worth comment.
    Oh well.

    Anyhow, me, I'll just eat fish, which has the further property of high deliciosity, and is thus a far better thymoleptic (^_^)

  4. Oy! Is that a poke in my side on the front page??? :) I must admit, I really came across as a rat-hater earlier... :)

    Beyond the downregulation of AA turnover by Lithium, are some interesting affects of AA on neurotransmitters (good review in [1]). It appears there is a great deal of interaction between AA and dopamine signaling pathways, and neither norepinephrine nor glutamate is spared as well. (all of the studies I believe done in various lower forms of life, probably for lack of adequate human tissues :) So, one wonders if AA is a mere intermediary by which Lithium exerts its MOA on dopamine? Of course there are other MOA's potentially at play: Lithium is apparently a real good GSK3B inhibitor which plays into ensuring melatonin degrades *on schedule* in the morning.

    So morning fish oil and vitamin D may use a lithium-orotate tablet as well. And their cofactors of course.

    I am an odd N=1 - If I use a fish oil with a higher EPA to DHA ratio, I get palpable depression within days. I tried too many fish oils such that thats the only difference that stands out between them (that and the Carlson's I use has many forms of vitamin-E added along with the higher DHA). A higher DHA:EPA ratio seems to occur in natural sources, so one wonders if the studies showing higher EPA:DHA really reflects EPA's impact on excessive AA levels. Alas I can't find studies that show higher DHA:EPA do good...
    [1] Arachidonic Acid Stimulates a Novel Cocaine-Sensitive Cation Conductance Associated with the Human Dopamine Transporter

  5. Awesome stuff, Dr Deans. As soon as I saw the study I thought of you and your (continually) important + unique blog.

    Much like yourself I'm pressed for time this days, so unfortunately learning seems to come in soundbites, which can be a hazard unto itself.

  6. In Canada we can get Harp Seal Oil softgel capsules. Don't know what it means but they contain EPA > or = 6%, DHA > or = 6% and DPA > or = 3%. Recommended: 6 x 500mg capsules per day. Depending on retail store: $5.99 to $8.99 for 300 capsules. In grocery stores there is no tax added. At healthfood stores the price of a bottle of capsules can run up to $28 and then there is 13% tax added. I guess at one place it's a 'food' and the other it's a 'supplement'.

    I know this is not available in the USA. You people ban seal product imports. The major export markets for seal oil are Korea and China. Even here, seal oil is sold in Korean supermarkets only. The seal oil is processed in Newfoundland, probably in one or two locations and several companies just get their own labels on the product.

    The Harp Seal Oil in large doses does not cause stomach irritation unlike the fish oils.

    People complain that all of these marine oils cause smelly burps. Possibly these people just have burping issues to begin with.

  7. The burping issue is easy to deal with: take it on an empty stomach (f.x. first thing in the morning) and wait a few seconds before eating/drinking else.

    That way it doesn't float on top of what's already in your stomach.


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