There are multiple levels of iron deficiency: low ferritin is the first, as ferritin is a storage form of iron. This can progress to low iron saturation in the bloodstream. Finally, it can become iron deficiency (or microcytic) anemia.

The first two levels of iron deficiency can be caused by chronic infections or hypothyroidism—or of course via low dietary intake of iron. I don’t generally see these as underlying causes for overt iron deficiency anemia, though. That usually has a deeper cause. 

Iron deficiency anemia can occur as a result of blood loss of course, after an injury or with very heavy menses. If this is the cause, once it is corrected (and iron levels restored), anemia should not recur. Chronic anemia with no obvious bleed warrants a workup to make sure there isn’t a hidden bleed somewhere in the body (most commonly in the gut).

But another possible cause of chronic iron deficiency anemia is low levels of copper.

Copper and Hemoglobin

About 90% of copper in the blood is bound to ceruloplasmin, with the rest bound to albumin and amino acids. Ceruloplasmin oxidizes (removes an electron from) iron absorbed from the gut and stored in the tissues so that it can be transported by transferrin (the iron transport protein) and eventually used to form new red blood cells. Less copper means less ceruloplasmin, which means iron can’t get shuttled where it needs to go to make hemoglobin.

This is why low copper can lead to iron deficiency anemia.

Why Might You Be Low in Copper?

Copper isn’t stored well, so it has to be consumed from foods. It can be found in high doses in organ meats, seafoods, beans, nuts, and whole grains. If you’re eating a lot of processed foods and not taking a multivitamin, low copper is a solid possibility.

Any malabsorption syndrome, of course, will lead to low absorption of copper as well as low levels of all other nutrients.

Copper is also in a delicate balance with iron, as well as with zinc. High zinc suppresses copper absorption, and vice versa. So if you’ve supplemented with zinc for a long time in excess of what you’d find in a typical multivitamin and without counterbalancing with copper, this is a possibility. The ratio of copper to zinc should be about 1:7 (in favor of zinc).

If you’re taking long-term NSAIDs (such as ibuprofen or Aleve), there are two possible causes of anemia: first, NSAIDs predispose you to gastrointestinal bleeding, so it’s worth checking to see if you’re losing blood that way. Second, NSAIDs require copper to activate, so long-term use can deplete copper. 

If you are hypothyroid, your digestion is sluggish and poor at absorbing all nutrients, including micronutrients such as copper and iron both. (In fact, hypothyroidism can directly lead to low iron for this and other reasons). Copper is also necessary for thyroid functioning, as are zinc and selenium especially—so when your digestion is poor, you absorb less of these nutrients, which perpetuates hypothyroidism. It’s a negative feedback loop.

If you’ve been treated with chelating agents to remove heavy metals, you probably lost copper in the process as well.

Prolonged stress can also deplete copper. There are two reasons for this: first, copper (and Vitamin C) are required to produce norepinephrine (adrenaline) from dopamine. Adrenaline is the first neurotransmitter to get triggered in stress, later followed by cortisol. Prolonged stress will therefore deplete both copper and Vitamin C (and may also therefore lead to an excess of dopamine, causing a particular kind of anxiety).

Second, the adrenals use an enzyme called superoxide dismutase (SOD) to neutralize the reactive oxygen species created as a byproduct of the production of steroid hormones (like cortisol). SOD requires both copper and zinc as cofactors, so production of cortisol long-term can also deplete copper.

Testing for Copper Levels

While copper is primarily bound to ceruloplasmin in the bloodstream, the tissue concentration of copper is far higher than the concentration in the bloodstream. For this reason, RBC copper, or a hair mineral analysis, are better choices.

If your labs show that you are low in copper, this is the one I most often recommend.

I’d also suggest checking your RBC zinc while you’re at it, since the two act like a see-saw, or else just supplement presumptively. Here is the zinc I most often recommend. And make sure you always take minerals with food, as they can otherwise make you nauseous.