Cyanocobalamin is a synthetic form of vitamin B12, which is essential for various biological processes in the human body, including the formation of red blood cells and the functioning of the nervous system. Let's break down the name and discuss the synthesis process of cyanocobalamin in phases.
The name describes the structure of the molecule:
- "Cyan-" refers to the cyanide group (CN-), which is attached to cobalamin during the synthesis process.
- "Cobalamin" refers to the family of compounds that contain cobalt at the center of their molecular structure. Vitamin B12 is one such compound and is commonly referred to as cobalamin.
The synthesis process takes place in different steps.
The synthesis of cyanocobalamin involves several phases, including fermentation, purification, and chemical modification. Here's a simplified overview of the synthesis process:
Phase 1: Fermentation The initial step involves the cultivation of certain strains of bacteria, such as Propionibacterium freudenreichii or Pseudomonas denitrificans, which naturally produce cobalamin. These bacteria are grown in large fermentation tanks under controlled conditions, providing them with a suitable environment for growth and cobalamin production. The bacteria consume various nutrients and precursors supplied in the growth medium, and through their metabolic pathways, they synthesize cobalamin.
Phase 2: Purification After the fermentation process, the bacterial culture is harvested, and the desired cobalamin is extracted. The extracted mixture contains impurities, such as other compounds produced by the bacteria, cellular debris, and media components. Purification techniques like filtration, centrifugation, chromatography, and precipitation are employed to separate and isolate the cobalamin from the impurities.
Phase 3: Chemical Modification Once the cobalamin is purified, it undergoes chemical modification to convert it into cyanocobalamin. In this step, a cyanide group (CN-) is added to the cobalamin molecule, resulting in the formation of cyanocobalamin. The addition of the cyanide group stabilizes the molecule and enhances its shelf life, making cyanocobalamin a commonly used form of vitamin B12 in supplements and pharmaceutical preparations.
It appears as a brown or yellow powder.
What it is for and where
Cyanocobalamin is a man-made form of vitamin B12. Vitamin B12 is important for growth, cell reproduction, blood formation, and protein and tissue synthesis. Here are some of its applications:
Food
Cyanocobalamin is used as a dietary supplement to help treat or prevent vitamin B12 deficiency, a condition that can lead to anemia, nerve damage, and tiredness.
Safety
Please note that while vitamin B12 is essential for health, too much can lead to side effects.
Medical
It's used in the medical field to treat certain conditions such as pernicious anemia and vitamin B12 deficiency related to poor nutrition or certain illnesses. A vitamin B12 deficiency can lead to different eye health problems, including optic neuropathy.
Cyanocobalamin is essential for the functioning of the nervous system and can help reduce the level of homocysteine in the blood, an amino acid that, if present in excessive amounts, can increase the risk of heart disease.
Cosmetics
Skin conditioning agent. It is the mainstay of topical skin treatment as it has the function of restoring, increasing or improving skin tolerance to external factors, including melanocyte tolerance. The most important function of the conditioning agent is to prevent skin dehydration, but the subject is rather complex and involves emollients and humectants that can be added in the formulation.
Animal Nutrition.
It's used in animal feed to ensure animals get adequate vitamin B12 in their diet.
- Molecular Formula C63H88CoN14O14P
- Molecular Weight 1355.4 g/mol
- CAS 68-19-9 13408-78-1
- UNII P6YC3EG204
- EC Number 200-680-0
Compendium of the most significant studies with reference to properties, intake, effects.
Buesing S, Costa M, Schilling JM, Moeller-Bertram T. Vitamin B12 as a Treatment for Pain. Pain Physician. 2019 Jan;22(1):E45-E52.
Abstract. Background: First isolated as cyanocobalamin in 1948, vitamin B12 has been explored for pain treatment almost since its discovery. With the advent of the opioid epidemic, safer treatments for pain are needed.....Objectives: Our objective was to compile the latest information on potential mechanisms from animal studies and clinical trial data on vitamin B12 for the treatment of pain conditions.....Results: Animal studies support multiple beneficial effects of vitamin B12 including the regeneration of nerves and the inhibition of cyclooxygenase enzymes and other pain-signaling pathways. In addition, animal studies have demonstrated synergistic benefits of vitamin B12 combined with other pain medications, including nonsteroidal anti-inflammatory drugs and opiates. Clinical trials provide evidence for the effectiveness of vitamin B12 for the treatment of low back pain and neuralgia, although data is still fairly limited and optimal treatment regimens have not been identified. Limitations: More large, double-blind placebo-controlled trials are needed to fully establish efficacy and best dosing parameters. Conclusion: Vitamin B12 may prove to be an adjunctive or integrative treatment for pain conditions. While more research is needed, considering the low incidence of side effects and overall safety, B12 may be an additional tool to consider for pain treatment.
Andrès E, Vogel T, Federici L, Zimmer J, Kaltenbach G. Update on oral cyanocobalamin (vitamin B12) treatment in elderly patients. Drugs Aging. 2008;25(11):927-32. doi: 10.2165/0002512-200825110-00003.
Abstract. The objective of this review is to evaluate the usefulness of oral cobalamin (vitamin B12) treatment in elderly patients. PubMed was systematically searched for English and French articles published from January 1990 to January 2007. Prospective randomized studies (n=3), a systematic review by the Cochrane group (n=1) and prospective studies in a well defined population (n=5) provide evidence that oral cobalamin therapy may adequately treat cobalamin deficiency in elderly patients. However, the current literature does not suggest a strategy in terms of the form (hydroxy- or cyanocobalamin), frequency and duration of the treatment. This review confirms the previously reported efficacy of oral cobalamin treatment in elderly patients. Oral cobalamin treatment avoids the discomfort, inconvenience and cost of monthly injections.
Gulcan E, Toker S, Hatipoğlu H, Gulcan A, Toker A. Cyanocobalamin may be beneficial in the treatment of recurrent aphthous ulcers even when vitamin B12 levels are normal. Am J Med Sci. 2008 Nov;336(5):379-82. doi: 10.1097/MAJ.0b013e31816a05f2.
Abstract. Objective: To evaluate the efficacy of cyanocobalamin treatment in patients having recurrent aphthous ulcers (RAUs) with normal or decreased serum vitamin B12 (cobalamin) levels. Methods: Seventy-two patients with RAU were included in the study. In addition to serum cobalamin levels, hemanitic and biochemistrical parameters were measured. Patients with serum cobalamin levels < 140 pg/mL were defined as the cobalamin deficient group (CDG) whereas patients with cobalamin levels > or = 140 pg/mL were defined as the cobalamin normal group (CNG). The degree of aphthous ulcer healing was determined according to serum cobalamin levels at the first and sixth month after cyanocobalamin treatment protocol. Results: Of the 72 participants, 37 were in the CDG whereas 35 were considered to have normal cobalamin levels. In the first admission the cobalamin levels were 215.8 +/- 116.90 pg/mL in CNG and 107.43 +/- 29.35 pg/mL in the CDG. The frequency of aphthous ulcers was defined numerically according to monthly occurrence of the lesions. The mean aphthous ulcer frequency in CNG group was 1.9 +/- 0.7, whereas it was 2.4 +/- 0.9 in the CDG. A significant increase in cobalamin levels was observed after cyanocobalamin treatment in both groups. A significant decrease in aphthous ulcer frequency was also concurrently observed. 96% of the patients showed good response to replacement treatment, 4% of the study population did not respond to the treatment. Conclusion: Cyanocobalamin treatment maybe beneficial for patients with RAU even when serum cobalamin levels are normal. We suggest that higher serum cobalamin levels should be attained in patients with RAU for mucosal protection.
Greibe E, Mahalle N, Bhide V, Heegaard CW, Naik S, Nexo E. Increase in circulating holotranscobalamin after oral administration of cyanocobalamin or hydroxocobalamin in healthy adults with low and normal cobalamin status. Eur J Nutr. 2018 Dec;57(8):2847-2855. doi: 10.1007/s00394-017-1553-5.
Abstract. Purpose: To investigate the absorption of synthetic cyanocobalamin and natural occurring hydroxocobalamin in populations with low and normal cobalamin (vitamin B12) status. Methods: We included adults with low (n = 59) and normal (n = 42) cobalamin status and measured the change in serum holotranscobalamin (ΔholoTC) before and after 2 day administration of different doses of cyanocobalamin and hydroxocobalamin (CobaSorb test). In the low status group, the test was performed using a cross-over design with identical doses of both cobalamin forms (1.5, 3, and 6 µg, respectively). In the normal status group, the test was performed with either 3, 6, and 9 µg cyanocobalamin (n = 28), or with 9 µg cyanocobalamin and 9 µg hydroxocobalamin (n = 14). Results: In both groups, median ΔholoTC (pmol/L) was higher after intake of cyanocobalamin compared to (hydroxocobalamin) [low status: 1.5 µg: 19 (6); 3 µg: 23 (7); 6 µg: 30 (14); normal status: 9 µg: 30 (13) pmol/L]. Independent of B12 form, no difference was observed in ΔholoTC between those receiving 1.5 and 3 µg in the low status group or 6 and 9 µg cyanocobalamin in the normal status group. However, in both groups, administration of 6 µg cobalamin resulted in a significant higher ΔholoTC than did 3 µg [low status: p = 0.02 (0.009) for cyanocobalamin (hydroxocobalamin); normal status: p = 0.03 for cyanocobalamin]. Conclusions: Administration of cyanocobalamin resulted in a more than twofold increase in holoTC in comparison with hydroxocobalamin. The absorptive capacity was reached only by doses above 3 µg cobalamin. Our results underscore the importance of using the same form of cobalamin when comparing uptake under different conditions.
Nava-Ocampo AA, Pastrak A, Cruz T, Koren G. Pharmacokinetics of high doses of cyanocobalamin administered by intravenous injection for 26 weeks in rats. Clin Exp Pharmacol Physiol. 2005 Jan-Feb;32(1-2):13-8. doi: 10.1111/j.1440-1681.2005.04145.x.
Abstract. 1. High doses of vitamin B12 (cyanocobalamin) may be therapeutically effective to treat neurological alterations secondary to a wide range of disease states. The aim of the present study was to evaluate the effect of dose and repeated administration on the pharmacokinetics of cyanocobalamin in rats. 2. Forty-eight rats were randomly assigned to receive 1, 5, 25 or 100 mg/kg cyanocobalamin for 182 days (26 weeks). Cyanocobalamin plasma levels were quantified by HPLC on days 1, 85 and 182 of treatment and were analysed by means of non-compartment pharmacokinetic (PK) analysis. In addition, population PK analysis was used to fit cyanocobalamin plasma concentrations to time by means of a two-compartment model for intravascular administration. 3. The half-life of cyanocobalamin ranged from approximately 20 to 50 min, clearance ranged from 4.5 to 9 mL/min and the volume of distribution at steady state ranged from 140 to 470 mL. A statistically significant negative relationship existed between the dose of cyanocobalamin and the normalized area under the plasma concentration-time curve (AUC). This non-linearity was not exhibited in population PK analysis. No evidence of toxicity was observed. 4. At very high and prolonged doses (up to 100 mg/kg for 26 weeks), intravascular administration of cyanocobalamin in rats follows a two-compartment kinetic model and cyanocobalamin undergoes extensive extravascular distribution. The negative relationship between dose and normalized AUC is compatible with possible saturation of tubular reabsorption, thus increasing renal clearance at higher doses.
Cyanocobalamin 
Propionibacterium freudenreichii
