by Dan Rusyniak
I will admit when I thought about my next Tox and Hound post, I had no idea what I was going to write on. Normally, I get my ideas from a recent case, a resident talk, the bathroom stall, or a suggestion from one of our readers. But this time, I drew a blank. It is always fascinating to see what pops in your head when you prod it for inspiration. What popped into my head was cobalt. Why cobalt? I have no idea. This is sadly what is deeply seated in my head – random tox facts. Read at your own nerdy peril.
Now that you have been warned, let’s talk about cobalt toxicity. Cobalt is one of those interesting elements that fall into the phenomenon of hormesis. Hormesis is when a beneficial effect occurs from a low exposure to something, but a high exposure to the same thing has a toxic effect. Cobalt is essential for life. It serves as the catalytic center of vitamin B12. The other name of vitamin B12 is cobalamin (short for cobalt-vitamin). As we all learned in medical school (but rarely see1,2), B12 deficiency can cause all sorts of problems: anemia, a sensorimotor (sensation and strength) neuropathy, myelopathy, cognitive deficits, and psychosis.3,4 We need cobalt to live. But, high levels are toxic. How do we know this? Because we poisoned a bunch of little kids with it. In the late 1920’s researchers found that administration of cobalt salts to rats caused an increase in the number of circulating red blood cells (polycythemia).5,6 And, since on the evolutionary tree, a rat and a kid are essentially the same thing (sorry, Diane . . .), it made perfect sense to give a concoction of cobalt and iron to kids with anemia (the trade name was Roncovite™). That was until we found out it didn’t. As it turns out, higher concentrations of cobalt over time can do some bad things. Some of the kids treated with Roncovite™ developed hypothyroidism and massive goiters.7 Turns out cobalt interferes with iodide binding in the thyroid.8 Fortunately, when the cobalt was stopped thyroid function returned to normal. Unfortunately, cobalt can also cause a fatal cardiomyopathy.9 After several deaths from cardiomyopathy and hypothyroidism were reported in kids taking cobalt, the practice of giving Roncovite™ was stopped. We poisoned a bunch of little kids with cobalt, but at least we learned a lesson.
Until, of course, we forgot and, moving up the evolutionary ladder, poisoned a bunch of middle aged adults. How did we do that, you ask? We hit them where it hurts – in the beer. Dow Brewery in Canada added cobalt sulfate to its beer. Why did they do that? Because it stabilized the foam. So, now when you poured the beer it kept its foamy head. I know there are bunch of beer snobs out there who will hate on me for this, but I am fine with a beer without foam; nothing worse than getting a cup of foam at a keg party. Sadly, the outcome was predictable. A large number of a heavy beer drinkers developed cardiomyopathy, heart failure10,11, and thyroid dysfunction.12 The mortality rate of those who developed symptoms was 40%! . . . Yikes! One unique aspect of this poisoning is the dose of cobalt in the beer was thought to be relatively low. Cobalt can inhibit lots of enzymes, but one thought contribute to cardiac toxicity is alpha-ketoglutarate dehydrogenase.13 This enzyme is involved in the Krebs cycle, so inhibiting it means less ATP production, something the heart kind of needs. The interesting thing is this. Normally, cobalt is not a potent inhibitor of this enzyme. But, add a bunch of NADH and *poof* Kreb cycle inhibition.13 And where would someone get an abundance of NADH from – oh yeah, alcohol. At least this is one thought behind why only heavy drinkers developed cardiomyopathy. We poisoned a bunch of middle-aged adults with cobalt, but at least we learned a lesson.
Until, of course, we forgot, climbing to the top rung of our evolutionary ladder, and poisoned a bunch of old people. How did we do that, you ask? By making their hip replacements out of chromium and cobalt. The problem arose mostly in persons who got their old ceramic hip prosthesis revised with metal-on-metal replacements.14 Over time the metal could erode and leach out cobalt. Fortunately, this is rare, but when it happens it has predictable complications. Patients can develop cardiomyopathy and hypothyroidism.15 As with little kids and middle-aged adults, this can have fatal results.16
Although, I have focused on the hypothyroidism and cardiomyopathy, other things have been reported from chronic cobalt poisoning including pericardial effusions, deafness, optic nerve atrophy, and peripheral neuropathy.17 Although the mechanisms behind the neurotoxicity are not fully worked out, cobalt does competes with calcium at the nerve terminal in the neuromuscular junction.18 And since you need calcium for normal neurotransmitter release, cobalt messes that up, or at least the story goes. Keep in mind this is rare, so unless they have symptoms don’t go asking your folks what type of hip they have and recommend they get it out. For those interested, there are some guidelines on how to manage these patients.19 So, we poisoned a bunch of old people with cobalt, but at least we learned our lesson.20
Until, of course, we forget.
Neonates and teens beware.
- Tox and Hound – Fellow Friday – Whence the Protons of Lactic Acidosis, Part II - August 14, 2020
- Tox and Hound – Fellow Friday – Whence the Protons of Lactic Acidosis? - July 24, 2020
- The Dantastic Mr. Tox & Howard – S03E03 – Inside Out - July 6, 2020