A prospective, open-label, randomized, comparative clinical trial to assess the efficacy of NASO B12 or oral B12 supplementation along with standard of care in the treatment of anemia in women of reproductive age
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20250365Keywords:
Hemoglobin, Vitamin B12, Anemia, Iron deficiency, Naso B12, Iron folic acidAbstract
Background: Anemia is a prevalent health issue among women of reproductive age (WRA), often attributed to iron deficiency but also influenced by vitamin B12 deficiency. Despite widespread iron and folic acid (IFA) supplementation programs, anemia persists, necessitating comprehensive treatments. This study evaluated the efficacy of intranasal vitamin B12 supplementation (NASO B12 of Troikaa Pharmaceuticals Ltd.) with IFA compared to oral vitamin B12 with IFA and IFA alone, in WRA.
Methods: This open-label, randomized clinical trial enrolled 75 anemic WRA across three centers in Lucknow, India. Participants were randomized into three groups: NASO B12 + IFA, Oral B12 + IFA, and IFA alone. In the NASO B12 and oral B12 groups, B12 supplementation was administered on alternate days for two weeks, then weekly until day 42, while IFA was given daily in all groups for 84 days. Hemoglobin (Hb) and other hematological parameters were assessed at multiple intervals. Safety evaluations included vital signs and adverse events monitoring. ANOVA was used for statistical analysis, with p<0.05 indicating significance.
Results: Among 75 anemic women, NASO B12 demonstrated the fastest and most significant improvements in Hb and vitamin B12 levels, as well as a notably greater increase in RBC counts compared to both the Oral B12 and IFA groups. Hb levels increased significantly from baseline by 2.8 gm/dl at day 84. Vitamin B12 levels rose rapidly, exceeding 400 pg/mL by day 7 and sustaining through day 84. NASO B12 consistently improved RBC counts from day 7, reaching 4.53 mill/cmm by day 84. Changes in reticulocytes, ferritin, and folic acid supported hematopoietic normalization. The treatment was well-tolerated in all three groups, with no serious adverse events.
Conclusions: In conclusion, NASO B12, when combined with IFA, demonstrated superior and faster efficacy in improving hematological parameters compared to oral B12 + IFA and IFA alone, making it a promising treatment option for vitamin B12 deficiency and anemia in WRA.
Metrics
References
Let S, Tiwari S, Singh A, Chakrabarty M. Prevalence and determinants of anaemia among women of reproductive age in Aspirational Districts of India: an analysis of NFHS 4 and NFHS 5 data. BMC Public Health. 2024;24(1):437. DOI: https://doi.org/10.1186/s12889-024-17789-3
World Health Organization. Anaemia. 2023. Available at: https://www.who.int/news-room/fact-sheets/detail/anaemia. Accessed on 24 December 2024.
Ministry of Health and Family Welfare. National Family Health Survey (NFHS 5). 2019-2020. Compendium of Fact Sheets: Key indicators India and 14 states/UTs (phase II). Available at: https://mohfw.gov.in/sites/default/files/FinalCompendiumoffactsheetsIndiaand14StatesUTsPhaseII.pdf. Accessed on 24 December 2024.
Sarna A, Porwal A, Ramesh S, Agrawal PK, Acharya R, Johnston R, et al. Characterisation of the types of anaemia prevalent among children and adolescents aged 1-19 years in India: a population-based study. Lancet Child Adolescent Heal. 2020;4(7):515-25. DOI: https://doi.org/10.1016/S2352-4642(20)30094-8
Bansal PG, Toteja GS, Bhatia N, Vikram NK, Siddhu A. Impact of weekly iron folic acid supplementation with and without vitamin B12 on anaemic adolescent girls: a randomised clinical trial. Eur J Clin Nutrit. 2016;70(6):730-7. DOI: https://doi.org/10.1038/ejcn.2015.215
Chakrabarty M, Singh A, Singh S, Chowdhury S. Is the burden of anaemia among Indian adolescent women increasing? Evidence from Indian Demographic and Health Surveys (2015-21). PLOS Global Publ Health. 2023;3(9):e0002117. DOI: https://doi.org/10.1371/journal.pgph.0002117
Bhati BS, Bajpai S, Patel M, Gori M, Panasara P. Maternal anemia: a comprehensive study on fetomaternal consequences from menarche to menopause. Int J Reprod Contracept Obstet Gynecol. 2024;13:3056-60. DOI: https://doi.org/10.18203/2320-1770.ijrcog20242997
World Health Organization. The global prevalence of anaemia in 2011. 2015. Available at: https://apps.who.int/iris/bitstream/handle/10665/177094/9789241564960_eng.pdf?sequence=1. Accessed on 23 December 2024.
Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood J Am Society Hematol. 2017;129(19):2603-11. DOI: https://doi.org/10.1182/blood-2016-10-569186
Lee YP, Loh CH, Hwang MJ, Lin CP. Vitamin B12 deficiency and anemia in 140 Taiwanese female lacto-vegetarians. J Formos Med Assoc. 2021;120(11):2003-9. DOI: https://doi.org/10.1016/j.jfma.2021.04.007
Priyadarsini R, Dash SA, Singh AK, Mishra A. Assessment of Serum Iron, Folic Acid and Vitamin B12 Status in Young Adult Women with Anemia in Southern Odisha. Int J Acad Med Pharm. 2024;6(1):1182-6.
Saxena V, Kamath SS, Ratageri VH, Krishna Mohan R, Mohan V, Deb S, Bisht SS, Kariya P. IAP Standard Treatment Guidelines Committee. Available at: https://iapindia.org/pdf/Ch-044-Megaloblastic-Anemia.pdf Accessed on 24 December 2024.
Casey GJ, Tinh TT, Tien NT, Hanieh S, Cavalli-Sforza LT, Montresor A, Biggs BA. Sustained effectiveness of weekly iron-folic acid supplementation and regular deworming over 6 years in women in rural Vietnam. PLoS Negl Trop Dis. 2017;11(4):e0005446. DOI: https://doi.org/10.1371/journal.pntd.0005446
Vir SC, Singh N, Nigam AK, Jain R. Weekly iron and folic acid supplementation with counseling reduces anemia in adolescent girls: a large-scale effectiveness study in Uttar Pradesh, India. Food Nutr Bull. 2008;29(3):186-94. DOI: https://doi.org/10.1177/156482650802900304
Gosdin L, Sharma AJ, Tripp K, Amoaful EF, Mahama AB, Selenje L, et al. A School-Based Weekly Iron and Folic Acid Supplementation Program Effectively Reduces Anemia in a Prospective Cohort of Ghanaian Adolescent Girls. J Nutr. 2021;151(6):1646-55. DOI: https://doi.org/10.1093/jn/nxab024
Singh J, Dinkar A, Gupta P, Atam V. Vitamin B12 deficiency in northern India tertiary care: Prevalence, risk factors and clinical characteristics. J Fam Med Pri Care. 2022;11(6):2381-8. DOI: https://doi.org/10.4103/jfmpc.jfmpc_650_21
Labban H, Begum F, Paracha A, John V, Islam M. Hemolytic Anemia and Pancytopenia Secondary to Vitamin B12 Deficiency: Evaluation and Clinical Significance. Cureus. 2024;16(3):e57286. DOI: https://doi.org/10.7759/cureus.57286
Gupta A, Kant S, Ramakrishnan L, Pandey RM, Khandelwal R, Kapil U, et al. Impact of daily-supervised administration of a package of iron and folic acid and vitamin B12 on hemoglobin levels among adolescent girls (12-19 years): a cluster randomized control trial. Eur J Clin Nutr. 2021;75(11):1588-97. DOI: https://doi.org/10.1038/s41430-021-00878-6
Sood SK, Ramachandran K, Mathur M, Gupta K, Ramalingaswamy V, Swarnabai C, et al. WHO sponsored collaborative studies on nutritional anaemia in India: 1. The effects of supplemental oral iron administration to pregnant women. QJM. 1975;44(2):241-58.
Chandelia S, Chandra J, Narayan S, Aneja S, Chawla HM, Sharma S, et al. Addition of cobalamin to iron and folic acid improves hemoglobin rise in nutritional anemia. Indian J Pediatr. 2012;79:1592-6. DOI: https://doi.org/10.1007/s12098-012-0725-9
Wang H, Li L, Qin LL, Song Y, Vidal-Alaball J, Liu TH. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2018;3(3):CD004655. DOI: https://doi.org/10.1002/14651858.CD004655.pub3
Dave H, Agarwal V, Maseeh A, Patel K. Novel methylcobalamin nasal spray versus intramuscular injection: A randomized, crossover comparative bioavailability study. Int J Endocrinol Metabol Dis. 2021;7(1):1-6. DOI: https://doi.org/10.16966/2380-548X.171
Seth T, Suri V, Balat D, Murthy S, Agarwal A, Pandurangan P, et al. Rapid and Safe Correction of Vitamin B12 Deficiency using Novel Methylcobalamin Nasal Spray. Int J Endocrinol Metab Disord. 2021;7(1):1-10. DOI: https://doi.org/10.16966/2380-548X.172
Farookh SS, Jayanti CR, Geetha A. Comparison of the Efficacy of Oral Methylcobalamin Tablets vs. Nasal Spray (NASO B12) in Diabetic Patients on Metformin Therapy. J Diabetol. 2022;13(4):347-52. DOI: https://doi.org/10.4103/jod.jod_92_22
Langan RC, Goodbred AJ. Vitamin B12 deficiency: recognition and management. Am Fam Phys. 2017;96(6):384-9.
Krzywański J, Mikulski T, Pokrywka A, Młyńczak M, Krysztofiak H, Frączek B, et al. Vitamin B12 status and optimal range for hemoglobin formation in elite athletes. Nutrients. 2020;12(4):1038. DOI: https://doi.org/10.3390/nu12041038
Leishear K, Boudreau R, Studenski S, Ferrucci L, Rosano C, de Rekeneire N, et al. Vitamin B12 and neurological function: is there a threshold level? J Am Geriatr Soc. 2012;60(6):1057-63. DOI: https://doi.org/10.1111/j.1532-5415.2012.03998.x
Bulut EA, Soysal P, Aydin AE, Dokuzlar O, Kocyigit SE, Isik AT. Vitamin B12 deficiency might be related to sarcopenia in older adults. Experimental Gerontol. 2017;95:136-40. DOI: https://doi.org/10.1016/j.exger.2017.05.017
Clark KS, Hippel TG, Whitfield DB. Manual, semiautomated, and point-of-care testing in hematology. Rodak's Hematology-E-Book: Rodak's Hematology-E-Book. 2019;154. DOI: https://doi.org/10.1016/B978-0-323-53045-3.00020-9
Ginzburg YZ, Feola M, Zimran E, Varkonyi J, Ganz T, Hoffman R. Dysregulated iron metabolism in polycythemia vera: etiology and consequences. Leukemia. 2018;32(10):2105-16. DOI: https://doi.org/10.1038/s41375-018-0207-9
Kim A, Nemeth E. New insights into iron regulation and erythropoiesis. Current opinion in hematology. 2015;22(3):199-205. DOI: https://doi.org/10.1097/MOH.0000000000000132
Downloads
Published
How to Cite
Issue
Section
