{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T11:57:29Z","timestamp":1785585449636,"version":"3.56.0"},"reference-count":16,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Vitamin B12 deficiency causes megaloblastic anemia and ineffective hematopoiesis. While intramuscular administration remains standard, intravenous and intranasal alternatives are increasingly used. Rigorous comparative data on hematological efficacy across routes remain limited. We thus aimed to compare intranasal, intramuscular, and intravenous vitamin B12 therapy for hematological recovery in vitamin B12 deficiency anemia, and to identify independent predictors of treatment response. In this prospective randomized controlled trial (IEC\/2024\/450; CTRI\/2024\/10\/075521), 153 adults with vitamin B12 deficiency were randomized to intranasal (\n n<\/jats:italic>\n \u2009=\u200955), intravenous (\n n<\/jats:italic>\n \u2009=\u200956), or intramuscular (\n n<\/jats:italic>\n \u2009=\u200942) administration. Hemoglobin (Hb), mean corpuscular volume (MCV), reticulocyte count, and lactate dehydrogenase (LDH) were assessed at baseline and on Days 7, 14, and 28. Inter\u2010group comparisons used the Kruskal\u2013Wallis test; covariate\u2010adjusted analyzes employed ANCOVA and multiple linear regression. All three routes produced significant hematological recovery (all within\u2010group\n p<\/jats:italic>\n \u2009<\u20090.001). Mean \u0394Hb was +2.48, +1.80, and +2.18\u2009g\/dL for intranasal, intravenous, and intramuscular groups. Although the unadjusted analysis detected an intergroup difference (H\u2009=\u20097.23,\n p<\/jats:italic>\n \u2009=\u20090.027), ANCOVA abolished the significance (all\n p<\/jats:italic>\n \u2009>\u20090.06). MCV reduction was equivalent (Kruskal\u2013Wallis\n p<\/jats:italic>\n \u2009=\u20090.948). LDH normalization was greater with parenteral routes (H\u2009=\u20098.17,\n p<\/jats:italic>\n \u2009=\u20090.017); intramuscular therapy produced the most pronounced reticulocytosis (H\u2009=\u200913.93,\n p<\/jats:italic>\n \u2009=\u20090.001). In multivariate regression (adj.\n R<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u20090.575), baseline Hb (\n \u03b2<\/jats:italic>\n \u2009=\u2009\u22120.298,\n p<\/jats:italic>\n \u2009<\u20090.001), vegan diet (\n \u03b2<\/jats:italic>\n \u2009=\u2009+1.30,\n p<\/jats:italic>\n \u2009=\u20090.001), and age (\n \u03b2<\/jats:italic>\n \u2009=\u2009\u22120.013\/year,\n p<\/jats:italic>\n \u2009=\u20090.039) were independent predictors; route was not. All three routes produce hemoglobin recovery at 28\u2009days with no statistically significant adjusted differences. Intranasal vitamin B12 is a safe, effective, noninvasive alternative suitable for long\u2010term maintenance and resource\u2010limited settings. All conclusions are restricted to short\u2010term hematological outcomes.\n <\/jats:p>\n \n Trial Registration:<\/jats:bold>\n CTRI\/2024\/10\/075521.\n <\/jats:p>","DOI":"10.1002\/ajh.70433","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T02:59:36Z","timestamp":1783047576000},"page":"2343-2352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Efficacy of Intranasal, Intramuscular, and Intravenous Vitamin\n B12<\/scp>\n Therapy for Hematological Recovery in Vitamin\n B12<\/scp>\n Deficiency Anemia: A Randomized Controlled Trial"],"prefix":"10.1002","volume":"101","author":[{"given":"Santosh Kumar","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Armed Forces Medical College (AFMC) Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0972-7695","authenticated-orcid":false,"given":"Rahil","family":"Arora","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Armed Forces Medical College (AFMC) Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman Kumar","family":"Pramanik","sequence":"additional","affiliation":[{"name":"Department of Medical Research Armed Forces Medical College (AFMC) Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Armed Forces Medical College (AFMC) Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alok","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Medicine Military Hospital Kirkee Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shantanu","family":"Khanna","sequence":"additional","affiliation":[{"name":"Department of Radiology Command Hospital, Air Force Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitya","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Medicine, Government Medical College and Hospital Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranay","family":"Juneja","sequence":"additional","affiliation":[{"name":"Department of Medicine, Government Medical College and Hospital Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Netri","family":"Upadhyay","sequence":"additional","affiliation":[{"name":"Department of Medicine, JNMC, DMIHER Wardha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0546-6585","authenticated-orcid":false,"given":"Uday","family":"Yanamandra","sequence":"additional","affiliation":[{"name":"Department of Medical Research Armed Forces Medical College (AFMC) Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu2030299"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.40"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1113996"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198806303182604"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/nure.12001"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/74.2.233"},{"issue":"5","key":"e_1_2_11_8_1","first-page":"979","article-title":"Vitamin B12 Deficiency","volume":"67","author":"Oh R.","year":"2003","journal-title":"American Family Physician"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2257.2006.00755.x"},{"issue":"7089","key":"e_1_2_11_10_1","first-page":"1088","article-title":"Normalisation of Serum Vitamin B12 Concentration by Intranasal Hydroxocobalamin in Vitamin B12\u2010Deficient Patients","volume":"314","author":"Slot W. B.","year":"1997","journal-title":"BMJ"},{"issue":"1","key":"e_1_2_11_11_1","first-page":"83","article-title":"Intranasal Hydroxocobalamin Administration in Elderly Patients With Vitamin B12 Deficiency","volume":"45","author":"Asselt D. Z.","year":"1998","journal-title":"British Journal of Clinical Pharmacology"},{"key":"e_1_2_11_12_1","article-title":"Oral Versus Intramuscular Vitamin B12 for Vitamin B12 Deficiency","volume":"3","author":"Vidal\u2010Alaball J.","year":"2005","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"e_1_2_11_13_1","article-title":"Efficacy of Different Routes of Vitamin B12 Supplementation for Treating Vitamin B12 Deficiency: A Systematic Review and Network Meta\u2010Analysis","volume":"16","author":"Abdelwahab O. A.","year":"2025","journal-title":"Frontiers in Pharmacology"},{"key":"e_1_2_11_14_1","first-page":"519","volume-title":"Hematology: Basic Principles and Practice","author":"Antony A. C.","year":"2013"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-05-1812"},{"issue":"4","key":"e_1_2_11_16_1","first-page":"253","article-title":"Erythrocyte and Plasma B12 Predict Functional Decline in Older Adults","volume":"12","author":"Matteini A. M.","year":"2008","journal-title":"Journal of Nutrition, Health & Aging"},{"issue":"4","key":"e_1_2_11_17_1","first-page":"347","article-title":"Early Biochemical and Hematological Response to Intramuscular Vitamin B12 Therapy in Vitamin B12\u2010Deficient Patients","volume":"62","author":"Tillemans A. P. H.","year":"2015","journal-title":"Annals of Nutrition & Metabolism"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.70433","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajh.70433","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.70433","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T11:19:16Z","timestamp":1785583156000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.70433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":16,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/ajh.70433"],"URL":"https:\/\/doi.org\/10.1002\/ajh.70433","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"assertion":[{"value":"2026-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}