Background
Vitamin B12, also known as cobalamin, is a B vitamin composed of cobalt-containing porphyrin compounds. It is a coenzyme in the metabolism of methylmalonyl-CoA, homocysteine and folic acid. Vitamin B12 is synthesised in nature by microorganisms, and higher animals and plants cannot produce it. Vitamin B12 is the only vitamin that requires the help of an intestinal secretion (intrinsic factor) to be absorbed. Due to gastrointestinal abnormalities, some people lack this intrinsic factor and suffer from pernicious anaemia, even if they have sufficient sources in their diet. Vitamin B12 is essentially absent from plant foods. This vitamin remains in the intestine for a long time, taking about three hours to be absorbed (most water-soluble vitamins take only a few seconds). The main physiological function of vitamin B12 is to participate in the production of red blood cells in the bone marrow, to prevent pernicious anaemia and to prevent nerve damage in the brain. Vitamin B12 is a polycyclic compound containing trivalent cobalt. Four reduced pyrrole rings are linked together to form a corrin macrocycle (similar to porphyrin), which is the core of the vitamin B12 molecule. Compounds containing this ring are therefore called corrinoids. Vitamin B12 is a bright red, needle-shaped crystal, readily soluble in water and ethanol, most stable under weak acid conditions of pH 4.5-5.0, decomposes in strong acid (pH <2) or alkaline solution, and can be destroyed to some extent by exposure to heat, but the loss is small in short-term high-temperature sterilisation, and it is easily destroyed by strong light or external radiation. The loss in normal cooking is about 30%. Its physiological effects are 1. It promotes the development and maturation of red blood cells, keeps the body's blood formation function in a normal state, prevents pernicious anaemia and maintains the health of the nervous system; 2. It exists in the form of coenzymes and can increase the utilisation rate of folic acid and promote the metabolism of carbohydrates, fats and proteins; 3. It has the function of activating amino acids and promoting the biosynthesis of nucleic acids, which can promote the synthesis of proteins. It plays an important role in the growth and development of infants and young children; 4. metabolises fatty acids so that fats, carbohydrates and proteins are properly utilised by the body; 5. eliminates irritability, concentrates attention, improves memory and sense of balance; 6. is an essential vitamin for the healthy functioning of the nervous system and participates in the formation of a lipoprotein in nerve tissue.
Figure 1. Absorption, enterohepatic circulation and intracellular metabolism of vitamin B12. (Sources: Green R, et al. 2022)
Vit B12 is involved in the synthesis of deoxyribonucleic acid (DNA), the metabolism of fats, carbohydrates and proteins, and increases the synthesis of nucleic acids and proteins. If the body is deficient in Vit B12, the activity of transferring methyl groups from methyltetrahydrofolate is reduced and folic acid becomes an unusable form, leading to folate deficiency. When the body lacks B12, it also causes methionine metabolism disorders and damages vascular endothelial function. In short, it plays an important role in the synthesis of DNA, the production of red blood cells and the process of neural development. Therefore, monitoring serum vitamin B12 levels is of great clinical importance. The detection of vitamin B12 can be used to diagnose megaloblastic anaemia (MBA). Megaloblastic anaemia is characterised by a decrease in the number of red blood cells and the presence of abnormal and dysplastic red blood cells, which prevent them from entering the bloodstream properly. Vitamin B12 deficiency inhibits DNA synthesis, induces apoptosis of preerythroblasts and hinders the transformation of cells into reticulocytes, leading to pancytopenia and causing MBA. Related studies have found that the severity of MBA is also correlated with changes in folic acid or vitamin B12 levels. As the severity of megaloblastic anaemia increases, serum vitamin B12 levels gradually decrease, suggesting that the more severe the anaemia, the greater the decrease in vitamin B12 levels. Drugs can also affect serum vitamin B12 levels. Several clinical studies have shown that long-term use of metformin can lead to a decrease in the level of vitamin B12 in the circulation and even to vitamin B12 deficiency. The pathophysiological mechanism by which metformin causes a decrease in serum vitamin B12 levels is not fully understood. It is currently thought that it may cause Vit B12 absorption disorders by altering the intestinal environment, inhibiting the activity of calcium-dependent intrinsic factor-Vit B12 receptors, and interfering with the enterohepatic circulation of Vit B12. In addition, sodium aminosalicylate, neomycin, cholestyramine, colchicine, etc. can also interfere with vitamin B12 absorption and lead to a decrease in serum levels. In addition to abnormalities that cause a decrease, there are some conditions that can cause an increase in vitamin B12. These include diseases of the blood system, liver diseases (cirrhosis, alcoholic hepatitis and viral liver diseases), solid tumors and diseases of the nervous system. Therefore, testing serum vitamin B12 levels is one of the diagnostic methods for early detection of such diseases.
Alternative Names
Cobalamin
Cyanocobalamin
Methylcobalamin
Adenosylcobalamin
Hydroxocobalamin
B12
References
- 1. Green R, Miller JW. Vitamin B12 deficiency. Vitam Horm. 2022, 119:405-439.
- 2. Ryan-Harshman M, Aldoori W. Vitamin B12 and health. Can Fam Physician. 2008, 54(4):536-41.
References
Synergistic Effect of Sonophoresis and Iontophoresis in Transdermal Drug Delivery
JOURNAL OF CHEMICAL ENGINEERING OF JAPAN
Authors: Shirouzu, Kenta; Nishiyama, Tetsuya; Hikima, Tomohiro; Tojo, Kakuji
Abstract
Synergistic effects of sonophoresis and iontophoresis oil skin penetration were investigated using vitamin B-12 (VB12, molecular weight 1355.4 and non-ionized compound at pH 7.4) as a model drug in the stratum corneum (SC) of hairless mice. Under passive penetration, SC acts as an effective diffusion barrier for VB12 and physical treatment is necessary to enhance skin penetration flux. Ultrasound (US) treatment (frequency of 300 kHz. intensity of 5.21 W/cm(2), and pulse mode of 5.4% duty cycle) under sonophoresis increased both VB12, solubility and diffusivity. in the skin according to its energy flux [J/cm(2)] (intensity x treatment time x duty cycle). The penetration flux of VIS, treated with US of 510 J/cm(2) was 12 times larger than that through intact skin. Iontophoresis (IP) application increased the convective water flow due 10 electro-osmosis, and resulted in in increase in the flux of non-electrolyte VB12 with IP (0.3 mA/cm(2)) by 20 times compared to the flux of passive experiments. Using US and IP combination, a synergistic effect oil the penetration flux of VB12, was achieved. This synergistic effect mail be caused by a different mechanism than the one responsible for enhancing skin penetration with only US or IP. Thus, the combination of US and IP treatment is an effective met hod for skin penetration of large molecules which enter in to systematic circulation with great difficulty.
Stability of cyanocobalamin in sugar-coated tablets
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Authors: Ohmori, Shinji; Kataoka, Masumi; Koyama, Hiroyoshi
Abstract
The purpose of this study was to clarify the stability of cyanocobalamin (VB12-CN) in sugar-coated tablets containing fursultiamine hydrochloride (TTFD-HCl), riboflavin (VB2), and pyridoxine hydrochloride (VB6), and to identify the factors affecting the stability of VB12-CN in these sugarcoated tablets. The stability of VB12-CN was investigated using high-performance liquid chromatography while decomposition was evaluated kinetically. The decomposition of VB12-CN in sugar-coated tablets with high equilibrium relative humidity (more than 60%) under closed conditions showed complex kinetics and followed an Avrami-Erofe'ev equation, which expresses a random nucleation (two-dimensional growth of nuclei) model. We showed that equilibrium relative humidity, the incorporation of VB2 and VB6, and sugar coating, are the main factors influencing decomposition and that these factors cause the complex decomposition kinetics. (c) 2007 Elsevier B.V. All rights reserved.