More on Cyanocobalamin Safety/Toxicity

 

Cobalamin (vitamin B-12) is synthesized only by certain microbes (bacteria and archaeon), and five forms of vitamin B-12 have been found in foods, according to the British Journal of Nutrition: adenosylcobalamin and hydroxocobalamin are the predominant forms, and other forms found include methylcobalamin, cyanocobalamin, and sulphitocobalamin. Most of these forms are considered synthetic substances, with additional compounds subsequently bonded to the already-synthesized cobalamin.

Methylcobalamin is produced commercially from cyanocobalamin, which is initially produced by fermentation and conversion processes. Adenosylcobalamin is directly produced by bacteria, while methylcobalamin requires an additional process of stripping off the cyanide group (CN, a carbon and a nitrogen atom with a triple bond) and adding a methyl group (CH3). Fermentations producing cyanocobalamin, methylcobalamin, and adenosylcobalamin do not utilize genetically engineered bacteria. The cyanocobalamin form is safe, stable, and bioavailable, and has been used for the vast majority of public health studies over the past century.

The amount of cyanide in cyanocobalamin is trivial, less than in an almond or apple; cyanide tends to be ubiquitous in the food supply in extremely tiny amounts. Cyanide is also produced by our own cellular processes (no great surprise since it's simply a single carbon and nitrogen molecule bonded together), but is quickly absorbed into the bloodstream, converted into thiocyanate (a less toxic form), and excreted in the urine or converted to carbon dioxide and exhaled. 

In fact, the Institute of Medicine has not set an Upper Limit for vitamin B-12 because “no adverse effects have been associated with excess vitamin B-12 intake from food and supplements in healthy individuals” (and both supplementation and food fortification primarily use cyanocobalamin). That same IOM report features this quote: “the amount of cyanide in cyanocobalamin is considered to be physiologically insignificant.” It would take about 2,500 doses of 1,000 microgram cyanocobalamin tabs to approach a dangerous amount of cyanide.

The adenosylcobalamin form is predominant in foods as well as in the human body, whereas methylcobalamin is typically in the body at only half the amount of the adenosyl form. Both are coenzyme forms with separate enzyme systems, and both are needed by the body. Cyanocobalamin feeds both pathways and is an inexpensive, stable, safe, and effective form of vitamin B-12 that does not require genetically engineered bacteria to produce.

Does the Cyanocobalamin form of vitamin B-12 have toxic levels of cyanide?

All plants produce cyanide as a by-product of ethylene synthesis. Some plants naturally contain small amounts of cyanide compounds, including stone fruits (almonds, apples, cherries, peaches, and apricots) as well as lima beans, flax seeds, barley, sorghum, white clover, cassava (tapioca), and bamboo shoots.

The amount of cyanide (2% of the weight, or 20 micrograms cyanide in a 1 mg cyanocobalamin tab) is far less than ingested in many natural foods. Following absorption, vitamin B-12 from whatever source is transformed to either methylcobalamin or 5’-deoxyadenosylcobalamin (dibencoszide). Dibencozide is the predominant form of vitamin B-12 in human tissues (up to 70%).

The human body can detoxify a small amount of cyanide in the liver through the thiosulfate (sulfation) pathway. Poisoning occurs when there is not enough thiosulfate to neutralize all the cyanide present. When you’re talking about a dangerous dose of cyanide, it generally means between 50 and 200 milligrams of hydrogen cyanide… but a 1000 microgram (1 mg) pill of the vitamin B-12 supplement cyanocobalamin contains only 20 micrograms of cyanide, and according to dietitian Jack Norris, “the amount of cyanide in cyanocobalamin is considered to be physiologically insignificant.” That’s 20 micrograms, versus milligrams. There are 1000 micrograms in a milligram, which puts the amount of cyanide in a typical B12 supplement far below toxic levels. http://eatdrinkbetter.com/2012/02/22/cyanide/

Neither the U.S. National Institutes of Health’s Institute of Medicine (IOM) nor the European Food Safety Agency (EFSA) have set a Tolerable Upper Intake (UL) level of Vitamin B-12 since each agency has concluded that it is not possible to derive an Upper Level because no clearly defined adverse effect could be identified from medical reports.

• The IOM reported, “The IOM did not establish a UL for vitamin B-12 because of its low potential for toxicity. In Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, the IOM states that "no adverse effects have been associated with excess vitamin B-12 intake from food and supplements in healthy individuals". Findings from intervention trials support these conclusions.”
• The EFSA reported, “There are also no adverse effects known for vitamin B12 from foods, or from supplements in amounts far in excess of needs.”

Therefore, cyanocobalamin, the predominate form of supplemental vitamin B-12, has been deemed non-toxic even at high levels of intake and the presence of small amounts of cyanide is not unusual in foods.

Sources:
• Centers for Disease Control and Prevention
• Canadian Food Inspection Agency
• Phys.org
• NIH IOM http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
• EFSA http://www.slv.se/upload/dokument/efsa/upper_level_opinions_full-part33,0.pdf