A comprehensive evaluation of the transition from traditional cobalamin supplementation to advanced nano-formulated delivery systems
DOI:
https://doi.org/10.18203/2394-6040.ijcmph20262313Keywords:
Vitamin B12, Cobalamin, DNA synthesis, Haematopoiesis, Neurological healthAbstract
Vitamin B12 (cobalamin) is essential for DNA synthesis, haematopoiesis, and neurological health. However, traditional oral delivery is hindered by a complex, saturable absorption pathway involving gastric intrinsic factor (GIF) and cubilin receptors, which limits passive absorption to approximately 1% to 2% at pharmacological doses. This review evaluates the transition from conventional supplements to liposomal delivery systems, focusing on how these nano-formulations bypass physiological bottlenecks and enhance systemic bioavailability. The review synthesizes clinical and physicochemical data regarding liposomal matrices, specifically those utilizing biomimetic phospholipid bilayers (e.g., non-GMO sunflower-derived phosphatidylcholine) with particle sizes <200 nm and negative zeta potentials. Liposomal B12 achieves significantly higher area under the curve (AUC) and peak plasma concentrations (Cmax) by utilizing alternative absorption routes such as membrane fusion and lymphatic transport. Clinical evidence indicates rapid serum repletion in geriatric populations (up to 270% increase) and improved nerve conduction velocity in patients with diabetic neuropathy. Liposomal encapsulation provides a highly bioavailable, non-invasive, and well-tolerated alternative to traditional oral doses and intramuscular injections, particularly for populations with compromised gastrointestinal absorption.
References
Antony AC. Megaloblastic anemias. In: Hoffman R, Benz EJ, Silberstein LE, editors. Hematology: Basic Principles and Practice. 8th edition. Amsterdam: Elsevier; 2023.
Gherasim C, Lofgren M, Banerjee R. Navigating the B12 pathway: transport, delivery, and cellular deficiency. J Biol Chem. 2013;288:13186-93.
Nielsen MJ, Rasmussen MR, Andersen CB, Nexo E, Moestrup SK. Vitamin B12 transport from food to the body's cells—a sophisticated, multistep pathway. Nat Rev Gastroenterol Hepatol. 2012;9:345-54.
Obeid R, Fedosov SN, Nexo E. Cobalamin absorption revisited. Nutrients. 2015;7:5408-21.
Bulake VS, Sahu A. The oral bioavailability of vitamin B12 at different doses in healthy Indian adults. Nutrients. 2024;16:3824.
He H, Lu Y, Qi J, Zhu Q, Chen Z, Wu W. Adapting liposomes for oral drug delivery. Acta Pharm Sin B. 2019;9:36-48.
West Bengal Chemical Industries Limited. Liposome: a gateway to advanced nutrient delivery. Kolkata: WBCIL Research & Development Division; 2021. Available at: https://www.wbcil. com/product-type/liposomal-technology/. Accessed on 10 March 2026.
Ko J, Kim CK. Factors affecting the pharmacokinetics and pharmacodynamics of liposomal drugs. J Pharm Investig. 2022;52:1-12.
Shade CW. Liposomes as advanced delivery systems for nutraceuticals. Integr Med (Encinitas). 2016;15:33-6.
Didangelos T, Karlafti E, Kotzakioulafi E, Margariti E, Giannoulaki P, Batanis G, et al. Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2021;13(2):395.
Privitera G. Route and type of formulation administered influences the absorption and disposition of vitamin B12 levels in serum. J Nutr Med Diet Care. 2018;4:027.
Smith AD, Warren MJ, Refsum H. Vitamin B12. Adv Food Nutr Res. 2018;83:215-79.
Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics. 2018;10(2):57.
Zhu Y, Wang M. Application of light scattering techniques to nanoparticle characterization and development. Molecules. 2024;29:812.
Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354(15):1567-77.
Dominguez JC, Orquiza MG, Soriano JR. A prospective open-label 24-week trial of methylcobalamin in the treatment of diabetic polyneuropathy. J Diabetes Mellitus. 2012;2:408-12.
Malyshok Y, Vasylenko Y. Liposomal technologies: effective delivery of vitamins and minerals. Grail Sci. 2026;64:616-20.
Julian TH, Syeed R, Glascow N, Angelini N, Zis P. Effects of vitamin B12 supplementation on pain relief in certain diseases: a literature review. Acta Biochim Pol. 2020;67:563-71.
Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354(15):1567-77.
Alawi M, Hashim NM, Ahmad N, Mahmood S, Ge Y. A Systematic Review of Advances in Plant-Based Phospholipid Liposomes in Breast Cancer Therapy: Characterization, Innovations, Clinical Applications, and Future Directions. Pharmaceuticals (Basel). 2025;18(9):1288.
Alvarez R. Advanced delivery systems for micronutrients: a contemporary review of liposomal stability and clinical outcomes. J Nanomed Nanotechnol. 2025;16:112-28.
Bhosale A. Impact of maternal vitamin B12 deficiency on fetal neurodevelopment in vegetarian populations. Int J Gynaecol Obstet. 2021;154:210-7.
Didangelos T, Karlafti E, Kotzakioulafi E, Margariti E, Giannoulaki P, Batanis G, et al. Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2021;13(2):395.
National Institute for Health and Care Excellence (NICE). Vitamin B12 deficiency in over 16s: diagnosis and management. London: NICE; 2024. Available at: https://www.nice.org.uk/guidance/ ng239. Accessed on 10 March 2026.
PlantaCorp GmbH. Human clinical study on the comparative bioavailability of various supple-mentation forms of vitamin B12 (Clinical Report No. 2026-B12-04). Hamburg: PlantaCorp GmbH; 2026. Available at: https://purazell.de/blog/wpcontent/ uploads/2026/03/Vitamin-B12-Bioavailability-Study.pdf. Accessed on 10 March 2026.
Privitera G. Route and type of formulation administered influences the absorption and disposition of vitamin B12 levels in serum. J Nutr Med Diet Care. 2018;4:027.
Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2017;8:CD006612.
PlantaCorp GmbH. Human clinical study on the comparative bioavailability of various supplementation forms of vitamin B12 (Clinical Report No. 2026-B12-04). Hamburg: PlantaCorp GmbH; 2026. Available at: https://purazell.de/blog /wpcontent/uploads/2026/03/Vitamin-B12-Bioavai lability-Study.pdf. Accessed on 10 March 2026.
Sawangjit R, Thongphui S, Chaichompu W, Phumart P. The impact of vitamin B12 supplementation on clinical outcomes in patients with diabetic neuropathy: a meta-analysis of randomized controlled trials. J Pers Med. 2022;12:2026.
Hofman R, van der Meer S. Safety and tolerability of lipid-based nano-carriers for high-dose micronutrient supplementation. J Clin Pharmacol Ther. 2025;14:88-95.
Zhang L, Wang Y, Chen H. Dose-response relationship and systemic toxicity assessment of liposomal methylcobalamin in adult populations. Int J Nanomed. 2024;19:1142-58.