Cyanocobalamin - a very poor choice, part 1

We humans have cyanide in our bodies. It's a fairly simple, small molecule, so that's not surprising. Not only are we exposed to it from some foods (especially cassava), smoking, combustion of some materials, and some poisons and medications, but it turns out that our bodies make it! Who knew? The research on endogenous (i.e., made in the body) hydrogen cyanide (a poisonous cyanide compound) focuses on mammalian brain tissue:

Cyanide is generated in neurons and this report examines the two different receptors which mediate cyanide formation in neuronal tissue. An opiate receptor blocked by naloxone increases cyanide production both in rat brain and in rat pheochromocytoma (PC12) cells. A muscarinic receptor in PC12 cells releases cyanide and the effect is blocked by atropine. In rat brain, in vivo, a muscarinic agonist inhibits cyanide generation, possibly by acting on receptor subtypes different from those in PC12 cells. Cyanide generation by a muscarinic agonist in PC12 cells is blocked by pertussis toxin but that caused by an opiate is not. Thus, two different receptors and two different second messenger systems can mediate cyanide generation in PC12 cells. In parallel with the in vivo data, cultured primary rat cortical cells also show decreased cyanide release following muscarinic stimulation. Both blockade of cyanide generation by muscarinic receptor activation and cyanide release by opiate agonists from cortical cells are pertussis toxin insensitive. Similarly, little cyanide generation was seen following cholera toxin treatment. These data indicate that opiate receptors increase and muscarinic receptors decrease cyanide production in rat brain tissue by G-protein independent mechanisms. This work supports the suggestion that the powerful actions of cyanide may be important for neuromodulation in the CNS.

Abstract from https://www.ncbi.nlm.nih.gov/pubmed/15099699.

In very small amounts, it looks like our body finds cyanide useful. Too much cyanide is to be avoided, though, for it can cause seizures, coma, and death. Among other detoxification pathways, our body has an enzyme called rhodanese that helps us convert cyanide to thiocyanate (which apparently causes hypothyroidism, which is a problem, but not as big a problem as cyanide). Too high a cyanide load overwhelms the body's ability to detoxify cyanide before it can cause harm. However, even low-level exposure to cyanide over a long period of time apparently can harm us, so it's important to minimize our intake of cyanide-containing substances.

Chronic exposure to cyanide has been associated with development of pancreatic diabetes, hypothyroidism, and several neurological diseases in both humans and animals. However, there is a limited number of experimental models for these pathologies. Thus, in the present study 0, 0.15, 0.3, or 0.6 mg KCN/kg body weight/day was administered for 3 months to 26 rats. On the last day, plasma samples were obtained for glucose, cholesterol, and thyroidal hormone measurement, and the pancreas, thyroids, and whole central nervous system were collected for histopathologic study. There were no significant difference in plasma concentrations of the substances measured between groups, and no lesions were found in the pancrease or thyroid. The CNS of experimental animals revealed the presence of spheroids on the ventral horn of the spinal cord, neuron loss in the hippocampus, damaged Purkinje cells, and loss of cerebellar white matter. In conclusion, cyanide administration could promote neuropathological lesions in rats without affecting pancreas or thyroid gland metabolism.

Abstract from "Effects of low-dose long-term cyanide administration to rats," https://www.ncbi.nlm.nih.gov/pubmed/12481854.

Because it's stable (and so cheaper), the form of vitamin B12 that is typically put into fortified foods and vitamins is cyanocobalamin. "Cyano" stands for "cyanide." It seems to be generally assumed that 1) the cyanocobalamin will dissociate into cyanide and cobalamin (useable B12) during digestion, and 2) the cyanide dose from cyanocobalamin is too low to harm us. However, a recent study of brain tissue found that cyanocobalamin is present in the brain. If it dissociates in the brain--which is kind of the point of supplementing with cyanocobalamin in the first place as we want the benefit of the cobalamin--the cyanide will be added to that from endogenous hydrogen cyanide in the central nervous system. And if it doesn't dissociate in the brain, then it isn't helping us meet our brain's cobalamin needs.

I believe cyanocobalamin is a very poor choice of B12 supplement. The evidence clearly indicates that cyanide and its less toxic metabolite, thiocyanate, could exacerbate or even cause hypothyroidism and cyanide-related neurological problems. Cyanocobalamin is far from the only form of B12 available. There is even one form of B12, hydroxocobalamin, that is used to treat cyanide poisoning because the cobalamin binds more tightly to the "cyano" than to the "hydroxo" (hydroxyl), and our bodies can excrete the resulting cyanocobalamin.