Zinc Clarity

So far we have linked zinc deficiency to anorexia, ADHD, and depression. Meaning that patients with these conditions have a tendency to have lower serum zinc levels than people without them, and in anorexia and depression, human studies (only preliminary in the case of depression) have shown that supplementation can be helpful. The data for anorexia is robust (1), and the recommended daily supplementation for treatment of anorexia nervosa is 14mg a day, which is just a touch above the normal RDA. The "upper tolerable limit" is officially defined at 40mg a day, but low level toxicity (related to problems with copper absorption and metabolism) has been demonstrated at consistent supplementation with 60mg daily. However, one is more likely to run into problems above 150mg a day. (Eaton et al via Nora Gedgaudas says a Paleolithic daily intake of zinc was around 43mg daily)

There are many different formulations of zinc, and there is no consistent evidence at a population level that one formulation is better than another. Some will be more readily absorbed, but fortunately the labeling is supposed to account for that - indicating the amount of elemental zinc you will actually get if you take the supplement. Since nasal formulations can cause permanent loss of smell, they should be avoided. Though my (general mineral) supplement contains 7.5mg and it says "50% RDA,". The actual RDA varies by age and circumstance (11mg for adult men, 12-14 mg for breastfeeding moms). Vegetarians may need 50% more supplementation than meat-eaters, and people on thiazide diuretics (HCTZ for example) for high blood pressure may need 60% more.

The actual mechanisms of the zinc-related links to psychopathology remain obscure, though looking more closely at the variety of functions zinc modulates in the body, many could be at play. (And to clarify the finding that zinc is necessary for the formation of IL-6, yet zinc deficiency is associated with high levels of IL-6, those levels are from depression literature. That is, people who are depressed will tend to have low serum zinc and high IL-6.)

I'm not going to leave zinc behind, though, without touching upon one more rather obscure paper published online in "Neurochemical Research" in June, 2010. The title is "Zinc and Fatty Acids in Depression." (You didn't really think I could go another post without mentioning omega 3s and 6s, did you?)

This paper was poorly written, and the experimental methods had some issues, but there is something very likable about it despite the flaws.

These researchers took blood samples of zinc levels and fatty acids (obtained by gas chromatography of fats within the serum rather than through red blood cell membrane fraction which is what I am more used to seeing - usually I see a centrifuge mentioned in the RBC fraction measurements and I don't see one used here) and some other measurements, like BMI, standard clinical psychiatric interviews, and a couple standard rating rating scales for depression (Hamilton and Beck) of 88 psychiatric inpatients. Most of these inpatients were on antidepressants, not surprisingly. Oddly enough, the blood was drawn "at 8:00 am, after an overnight fasting with a quasi-empty bowel (1 cup herb tea without sugar and a slice of white bread)."

For the controls, "a convenient group" of 88 volunteers were recruited from the population and matched by age group and gender. "After an overnight fasting period, their blood sample was taken and prepared for chemical analysis under similar conditions as with the patients' samples." I'm not sure if that means they got the herb tea and slice of bread or not. Oh well.

What did they find?

First of all, there wasn't a big difference between the levels of zinc in the patients or in the controls. BUT, among the depressed people, the more depressed they were (by the Beck Depression Inventory) the lower their zinc level. The medication in this study seemed to have no relation to the zinc or fatty acid concentration (in a prior study, antidepressant medication normalized zinc levels (2)). Also, while the actual DHA and EPA (fish oil) levels were about the same between depressed individuals and controls, the ratios between the omega 6-born arachidonic acid and serum DHA and EPA were significantly correlated with the amount of depression symptoms. Meaning depressed patients had a more out-of-whack ratio between omega 6 and omega 3. Sounding very familiar.

Other nifty findings that make yo go "hmmm" - control subjects with higher zinc levels had higher levels of myristic acid (a type of saturated fat), and people who were depressed had higher amounts of stearic acid (another saturated fat). It's an observational study, so you get what you get and then you ponder on it.

And here in the discussion of the results, the researchers throw in something entirely unexpected, which is, really, why I like the paper. They suddenly start rambling on about skeletons. Right out of the blue. "Zn was demonstrated to contribute to stabilize the skeleton."

I'm not even sure what that means. But then - "in depressive disorders, the density of bone minerals was found to be low. Antidepressants... were reported to have a beneficial effect on [bone cells]." Then they go on to talk about how arachidonic acid (the HUFA created from the omega-6 PUFAs) and DHA enriched diets, given in a specific ratio, reduced the zinc content of piglets' femurs. As we've found out already, zinc metabolism is very complicated, but it appears to me we've found a sink where the body can store zinc and sequester it from the circulation - the bones. And a possible signal to get the body to store or release zinc in the bones is the omega 6 to omega 3 ratio.

Osteoporosis, demineralization of the bones, highly linked with depression, is another disease of civilization.

Now let's look at the zinc sink we already saw in a previous post - where inflammatory cytokine IL-6 seemed to help tuck zinc away in the liver. Turns out that in the livers of zinc deficient rats, there is a high amount of myristic acid and changes in the mRNA and protein messaging systems and transporters responsible for fatty acid metabolism. In this study, there was a linear relationship between the amount of zinc in the blood and the amount of myristic acid in the blood. Not sure what it means but definitely something to remember for future reference.

And finally - turns out the enzymes that change omega 6 acids into arachidonic acid, which is then used for complex signaling throughout the body, are zinc-dependent. Absolute zinc deficiency or a high amount of sequestered zinc (due to out of control inflammation?) could cause a lot of changes all along the omega 6 fatty acid metabolism pathway.

Let's examine the areas where zinc plays a major roll - inflammation and immunity, the brain (particularly the hippocampus, ground zero for depression), the liver (ground zero for the metabolism), the pancreatic beta cells, and the bones. We can't get too terribly excited about that - after all, zinc plays a role in so many chemical reactions in the body that of course we will find it in all the important areas related to the diseases of civilization. I mean, zinc even helps hair formation. (I had a few gray hairs prior to starting paleo eating, but they don't seem to be coming back. I read in Evolutionary Medicine Forum about some anecdotal evidence of gray hair reversal.)

There is a lot more to learn, some of which is not even known. Excess insulin has always had a starring role in the whole metabolic picture of the diseases of civilization, but the full screen view involves PUFA ratios and zinc. I've no doubt of it.