Low Cholesterol and Suicide

Low serum cholesterol has been linked in numerous scientific papers to suicide, accidents, and violence (1)(2)(3)(4)(5)(6)(7)... there are a bunch more, but I'm a bit weary of linking! This is why I write a blog, and not a peer-reviewed journal. Anyway, no one knows to this day whether depression, violence, and suicidal risk have a metabolic byproduct of low cholesterol, or whether having low cholesterol will predispose you to suicide out of hand (here's a rather snarky editorial pointing out that fact (8)). Some trials of statins (with the resultant crackerjack drop in cholesterol) will show no effect on suicide (9). A statin skeptic's favorite study, the J-LIT trial, showed deaths by accidents/suicides increased threefold in the group with total cholesterol less than 160 (yes, the p was .09, but that means there is only a 91% chance that finding didn't happen by random happenstance (10)).

Now, why could serum cholesterol have anything to do with the brain and depression? Good question - and the first question to ask in any theory of the brain is do the peripheral levels of something have anything at all to do with the central nervous system amounts of the same thing - so do serum cholesterol levels match up to relative amounts of cholesterol in the brain? They do (11). And cholesterol is important in the brain. Synapses, where brain function goes live, have to have cholesterol to form. Brain signaling is all about membranes, and cell membranes are constructed from fat. Cholesterol and the omega 3 and 6 fatty acids are the most important molecules in the synapse. If your brain fat is significantly different from so-called "normal" fat (which I'll go back to the hunter gatherer paradigm and say an HG's brain is going to have the approximate fat constituents for which we are evolved), the signaling in your brain could be very different too (12). Scientific papers will call this "alterations of membrane fluidity." (13)

So we know that low serum cholesterol is associated with suicide, violence, and accidents. (Another wrench in the works - low serum cholesterol is also associated with low CSF serotonin - which is of course associated with increased violence and suicide! These association studies are enough to make anyone give up and go boar hunting.) But does dietary fat intake have anything to do with depression and suicide? (Remember, serum cholesterol is often a chancy thing to connect to diet, after all.) Well, of 3400 some-odd people in Finland, the omega-3 rich fish consumers (14) had significantly less depression than abstainers, but the finding was more robust among women (no one knows why). In this round-up of 408 suicide attempters and an equal number of controls, there was no difference in saturated fat intake between attempters and controls, but the attempters did report lower fiber and polyunsaturated fat intake.

And, finally, do statins cause depression? I've seen statins cause or exacerbate depression several times in my clinical practice, especially in women. (I've also seen them cause paranoid psychosis a couple of times - twice in women and once a long time ago in a man. The psychosis remitted with withdrawal of the statin). Very striking! But anecdotes aren't clinical trials. This brand new study shows no link, and statins actually seemed to decrease depression in elderly women. This study also shows no link. This study shows that chronic cholesterol depletion via statin use decreases the functioning of the serotonin 1A receptors in humans, by decreasing the ability of the receptor to bind to its friendly neighborhood G proteins and other binding proteins. (The serotonin 1A receptor is more highly associated with anxiety-type symptoms than depression).

Clear as mud! But stepping back to whole health, I never like the idea of "the lower the better, no matter what," which seems to be the prevailing winds of cholesterol treatment right now. Usually, chemicals in the body are important for something, or else they wouldn't be there, and typically, a U-shaped curve emerges, where too little or too much (cholesterol, vitamin D, omega 3s, immunoglobulins, you name it!) is bad for human health. Here's an example of the U-shaped curve from the J-Lit trial (via Hyperlipid), showing increased cardiac death at low and high serum cholesterol levels.

Statins may have their role, but please don't put them in the water. In my opinion, adopt a whole foods, paleo-style diet. Keep yourself in the middle of that U-shaped curve for what our human systems were evolved for. It may help your mood, too, especially if you are a woman who eats fish!

(Follow-up posts:  Low Cholesterol and Suicide 2 and Your Brain Needs Cholesterol, Don't Go Too Low)