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Thursday, January 27, 2011

Dietary Fat Intake and Depression Risk

More sleep coming soon, but a paper came out yesterday that ought to be blogged about (open access, too from PLoS One):

Dietary Fat Intake and the Risk of Depression: The SUN Project

The paper begins mild-mannered:  "Emerging evidence relates some nutritional factors to depression risk.  However, there is a scarcity of longitudinal assessments on this relationship."

The researchers followed a group of Spanish university graduates, initially depression-free, for an open enrollment period of 1999-2010.  12,059 ultimately signed up.  At baseline they filled out a food frequency questionnaire to estimate the amount of saturated fat, polyunsaturated fats, trans fats, monounsaturated fats eaten, and the use of "culinary fats" (olive oil, seed oils, butter, and margarine).  During the follow up period (of median 6 years), 657 new cases of depression were identified (via a new diagnosis of depression by a physician or initiating the use of antidepressant drugs).  As is typical, confounders were accounted for, including adherence to a Mediterranean Diet (legumes, fruits, vegetables, fish, cereals, and low in meat and dairy products), which has already been shown to correlate with decreased depression (1).  Turns out there was a reasonably strong (and dose-dependent) correlation between trans fat usage and depression - the less trans fat the Spaniards ate, the less likely they were to become depressed, and those in the highest quintile of trans fat intake had a 48% increased risk of developing depression compared to those who ate no trans fats.  There was also a weaker inverse correlation with the amount of MUFA and PUFA eaten (meaning these types of fats may be protective against depression.) 

In Europe, suicide rates and mental disorders are higher in Northern Europe, and the lowest in the Southern Mediterranean countries.  I can think of a number of possible reasons for this trend (sunlight, relaxed lifestyle, vitamin D *cough*), but the overall food choices differ mainly with respect to olive oil and pulses.  Very little is known about the specific types of fat and risk for depression, except with respect to the omega 3s.  And even those studies are tricky - often, the omega3 capsule is compared to a placebo capsule of olive oil, and in some trials, both the fish oil group and the olive oil (control) group improve.  It could be that both fish oil and olive oil improve mood, or that the increased fat content in general improved mood, as there is some evidence that low fat diets adversely affect mood (2)(3). 

Now the discussion and speculation - always the most interesting part.  The commonly accepted mechanism now for depression is one of inflammation leading to a decrease in BDNF, which is a nerve fertilizer necessary for axonal growth, nerve survival, and synaptic plasticity and function.  Some of this awesome nerve fertilizer is made in the endothelium (possibly through a nitric oxide mechanism).  Now cardiovascular disease, which correlates with depression, is also likely mediated through inflammation and endothelial dysfunction.  Trans fats are thought to cause inflammation and endothelial dysfunction, so it would make a lot of sense if they trash your brain along with your coronary arteries. 

Here's a rather scary analysis (though also makes me question the conclusions of the whole study) - the people studied overall actually ate a lot of whole foods and a very low amount of trans fats, and most of it came from whole fat dairy (I'm assuming, then, they are talking about CLA, which as far as I know is a very good fat associated with reductions in diabetes and obesity (both of which individually correlate with depression also, of course) though it is in truth a natural trans fat).  In this study sample, in the highest quintile, trans fat made up only 0.4% of calories.  In America, trans fat intake is up to 2.5% of calories, and the main sources are artificial foods (such as processed snack foods and margarine.)

Olive oil, on the other hand, is thought to have antioxidant and anti-inflammatory effects, and various metabolites of olive oil can improve sleep and improve the binding of serotonin to its receptors.  The folks in the study overall (being a Mediterranean population) ate a ton of olive oil and very little butter, margarine, or seed oil.  (These researchers are big olive oil fans.)

So what can we glean from this study?  Not that much - the strength of the design was a large population, but a huge weakness is that the diet was measured only once, at the beginning of the study, through a food questionnaire.  It was felt that the use of college graduates would help the validation, as they might be more likely to give accurate information about diet.  However, it seems that most of this highly educated cohort ate very similar diets, which means the whole effort may have been something of a wash.  I'm always skeptical of the ability of epidemiologists to adjust for confounding variables.

But it does make sense biologically that olive oil and PUFA intake (since they weren't using seed oils, I'm guessing a lot of the PUFA was in fish) would correlate with a happier brain, while the inflammatory trans fats would trash the endothelium and BDNF.  So maybe we hang our hats on that a little.

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