Intramuscular B12 Research Articles

Vitamin B12 deficiency in newborns: impact on individual's health status and healthcare costs.

The identification of vitamin B12 (B12) deficiency in the newborn may prevent neurological damage and a delay in the normal growth. In this study we characterized the incidence of B12 deficiency in newborns, the costs associated to the clinical diagnosis and management, and the relevance to optimize the use of cobalamin biomarkers during treatment follow-up. Starting from a continuous case series of 146,470 screened newborns (November, 1st 2021- December, 3rd 2023), the Regional Reference Laboratory for Neonatal Screening identified 87 newborns having altered levels of biomarkers of cobalamin metabolism measured by Newborn Screening. These subjects were confirmed with a nutritional B12 deficiency of maternal origin by performing the serum B12 measurements and plasma homocysteine (Hcy) both on the newborns and respective mothers. A cost analysis was performed to characterize the costs/year of identifying and managing B12 deficiency cases. At baseline, median (interquartile range) serum B12 levels of 185.0 (142.3-246.0) ng/L and threefold increased plasma Hcy concentrations above the normal level confirmed a severe condition of deficiency in the newborns. After intramuscular B12 supplementation, serum B12 measured at the first follow up visit showed a fivefold increase, and the levels of Hcy returned to normal. From the healthcare perspective, the costs for diagnosing and managing all newborns with B12 deficiency is 188,480 €/year. Preventing B12 depletion in newborns lowers healthcare costs and likely improves their health outcomes. Further studies are however required to address the clinical pathway to identify, treat and monitor pregnant women with marginal and low B12 status, in order to achieve these goals.

When Euphoria Turns to Neuropathy: Vitamin B12 Deficiency Related to Nitrous Oxide

Background: Nitrous oxide is a widely abused inhalant known for its rapid onset of euphoric sensations. Chronic use, however, can result in functional vitamin B12 deficiency, causing megaloblastic anemia, peripheral neuropathy, and subacute combined degeneration (SCD) of the spinal cord. Case Presentation: This case report examines a 43-year-old male with a history of attention-deficit/hyperactivity disorder (ADHD) and chronic back pain, who presented with neurological symptoms secondary to chronic nitrous oxide use, subsequent B12 deficiency. The patient reported a one week history of lower extremity swelling, paresthesias, and vertigo. He admitted to daily nitrous oxide use for the past month. Neurological examination revealed ataxia, impaired proprioception, and a positive Romberg test. Laboratory studies showed macrocytic anemia and a severely decreased B12 level. MRI of the cervical spine revealed T2 hyperintensity in the dorsal columns, consistent with SCD. He was treated with intramuscular B12 and advised to discontinue nitrous oxide use. At a three-month follow-up, significant neurological improvement was noted, allowing him to return to work. Conclusion: Chronic nitrous oxide use can lead to functional B12 deficiency and subacute combined degeneration, a potentially reversible condition if treated early. Differential diagnoses include pernicious anemia, malabsorption syndromes, and other neurological disorders. Prompt diagnosis through serum B12, methylmalonic acid, homocysteine levels, and spinal imaging is essential to prevent permanent neurological damage. Nitrous oxide abuse is an emerging cause of B12 deficiency. Early recognition and intervention are essential for recovery. Healthcare providers should consider B12 deficiency in patients presenting with neurological symptoms and a history of nitrous oxide use.

Primary Neurologic Symptoms: Have You Considered Pernicious Anemia?

BackgroundVitamin B12, or cobalamin, is a nutrient that is vital for metabolic function. Absorption of ingested B12 is dependent on intrinsic factor, which is secreted by parietal cells within the stomach. Pernicious anemia is caused by an intrinsic factor deficiency or autoantibodies against intrinsic factor. The presence of parietal cell antibodies can destroy parietal cells, which can also lead to a deficiency in intrinsic factor. Both lead to megaloblastic anemia caused by vitamin B12 deficiency. The typical presentation of pernicious anemia includes fatigue, pale appearance, tingling sensation, depression, alterations to vision and smell, urinary incontinence, psychotic episodes, and weakness. The most effective treatment for pernicious anemia is intramuscular B12. Case ReportA 27-year-old woman with a history of vitiligo presented to the emergency department (ED) with bilateral lower extremity weakness, clumsiness, numbness, and tingling. Physical examination revealed ataxia, no sensation below her umbilicus, decreased strength, and hyperreflexia in both lower extremities. Complete blood count in the ED revealed low hemoglobin and hematocrit and elevated mean corpuscular volume, concerning for pernicious anemia. Further laboratory testing upon inpatient admission revealed a low vitamin B12 level and parietal cell antibodies in the blood. The patient's pernicious anemia was treated with intramuscular vitamin B12 injections, which led to near complete resolution of her symptoms. Why Should an Emergency Physician Be Aware of This?Early suspicion and detection of pernicious anemia in the ED can prevent serious and permanent hematologic and neurologic damage and the development of other autoimmune disorders.

Effect of B12 supplementation on renal anemia among hemodialysis patients at El-Najar hospital, Gaza strip

Introduction: Patients with end-stage renal disease (ESRD) are predisposed to nutritional deficiencies, resulting in vitamin B12 deficiency with negative hematologic consequences. Objective: This study aimed to investigate the impact of intramuscular B12 on renal anemia among ESRD patients receiving hemodialysis (HD) at El-Najar hospital, Gaza Strip. Patients and Methods: A case-control study conducted, which included 110 healthy controls and 110 HD patients who received B12 on a daily, weekly, and monthly basis over two months. Sociodemographics and current diseases were reported. Serum levels of serum B12, white blood cell (WBC), red blood cell (RBC), hemoglobin (Hb), mean corpuscular volume (MCV), and platelet (PLT) were recorded before and after treatment. Data analysis was conducted using SPSS. Results: Baseline serum B12 level was significantly lower in HD patients compared to controls (362.62 ± 166.40 versus 483.36 ± 115.07 ρg/mL, P<0.001), which significantly improved after vitamin B12 treatment (639.08 ± 362.99 ρg/mL, P<0.001). Additionally, mean WBCs, RBCs, Hb, and PLT levels were significantly increased after treatment (P<0.001). Serum B12 level was positively and significantly (P<0.001) correlated with levels of WBC (r = 0.45), RBC (r = 0.43), Hb (r = 0.39) and PLT (r = 0.51), and negatively correlated with MCV (r = -0.46, P<0.001). Conclusion: Administration of vitamin B12 improves serum B12 levels in HD patients, which was associated with increased WBCs, RBCs, Hb, and PLT levels and decreased MCV levels. Treatment by vitamin B12 can improve HD patients’ renal anemia. Future studies with larger sample sizes and prolonged follow-up are advocated.

Clinical Presentation of Subacute Combined Degeneration in a Patient With Chronic B12 Deficiency.

Subacute combined degeneration (SCD) is a rare complication of chronic vitamin B12 deficiency that presents with a variety of neurologic findings, including decreased sensation in the extremities, increased falls, and visual changes. Treatment of SCD involves prompt replacement of vitamin B12 and addressing the underlying conditions that cause the deficiency. Given the prevalence of B12 deficiency in the older adult population, clinicians should remain alert to its possibility in patients who present with progressive neuropathy. This report presents a case of a patient with progressive SCD secondary to chronic B12 deficiency despite monthly intramuscular B12 injections. Appropriate B12 replacement is aggressive and involves intramuscular B12 1000 mcg every other day for 2 to 3 weeks, followed by additional IM administration every 2 months before transitioning to oral therapy. Failure to adequately replenish B12 can lead to progression or lack of resolution of SCD symptoms.

Establishing Clinical Decision Limits for Serum B12 Deficiency: Using Modified Delphi Methodology

Introduction: Essential nutrients such as iron and B12 have been established as vital components required for hematopoiesis. Patients are at risk of significant comorbidity when these are deficient, including hematologic manifestations and neurological deficits. B12 supplementation is relatively easy to use with no direct adverse effects. Current guidelines use a singular serum cobalamin level < 150 pmol that is static in nature and not adjusted based on patients' underlying age, comorbidities or medications. Many studies have shown symptoms related to deficiency can appear prior to reaching current biochemical definition of deficiency . Methylmalonic acid can be used to detect B12 deficiency earlier, with a sensitivity of approximately 95% however it's utility is limited due to lack of confidence in interpreting it's results and lack of availability . Also, little guidance is provided to clinicians in choosing a method and duration of supplementation in guidelines. Objective : The primary objective of this study was to establish an expert based consensus recommendations for the diagnosis of B12 deficiency using different biochemical tests while accounting for various comorbidities in diverse patient populations. The secondary objective was to provide recommendations around appropriate and cost-effective B12 supplementation when indicated. Methods : A detailed literature review was used to generate evidence based statements around diagnostic thresholds for B12 deficiency in various populations as well as guidelines to determine current target doses. A modified Delphi approach was used to evaluate the statements amongst 28 experts in various specialities, including biochemistry, general internal medicine, hematology, nephrology, gastroenterology, geriatrics, obstetrics/gynaecology and paediatrics. Two online survey cycles were performed. Only statements reaching consensus (score >7 by more than 70 % of the experts and a Cronbach's alpha statistic > 0.80) were included in the final iteration . Statements with a score of 5 or greater by <50% of the total respondents were discarded. Statements that were in between these ranges were adjusted based on comments and these new statements were disseminated for round two. Results: After the first cycle consensus was reached for 20 out of 21 of the statements (Table 1). Based on feedback 1 statement was split and one new statement was added. Only one statement, which was around the use of methylmalonic acid as an adjunct to diagnose B12 deficiency, did not meet consensus after the second cycle. A total of 22 statements achieved the pre-determined cut-off for consensus at the end of round two. An opt out rate of 28- 72 % was observed in statements made regarding the obstetric and paediatrics' population compared to less than 25 percent in all other statements. Discussion: This guideline provides a summary of B12 diagnostic and treatment threshold for various population that is both supported by existing literature and expert opinion. The high rate of consensus in our first round appears to be due to comfort around prescribing and overall safety of B12 supplementation. Statements made around methods of supplementation and duration were widely accepted. Most clinicians agreed that oral replacement was sufficient for patients unless there was evidence of neurological symptoms or previous gastric surgery . This is important given recent literature indicating the high cost Ontario faces due to inappropriate intramuscular B12 prescribing . A high opt out rate was noted in statements predominately geared towards the paediatric and obstetrical patient population which may be due to discomfort around prescribing in specific populations by general clinicians. Using a modified Delphi methodology, we were able to obtain consensus around adjusted diagnostics thresholds for identifying B12 deficiency in patients with varying comorbidities and metabolic demands. We devised guidance around treatment modalities and timelines to decrease the risk of supplementations faced by patients and potentially the health care system. We hope that these statements can be used as a framework for clinicians in all specialities to provide individualized, evidence based care. Disclosures Sholzberg: Amgen: Honoraria, Other: Scientific Advisory Board, Research Funding; Octapharma: Honoraria, Other: Scientific Advisory Board, Research Funding; Novartis: Honoraria, Other: Scientific Advisory Board; Takeda: Honoraria, Other: Scientific Advisory Board, Research Funding; NovoNordisk: Honoraria, Other: Scientific Advisory Board.

Vitamin B12 Replasman Tedavisi; Oral? İntramüsküler?

Amaç: Bu çalışmanın amacı intramüsküler B12 replasman tedavisi ile oral B12 replasman tedavisinin kan B12 vitamini düzeyleri üzerine olan etkisinin karşılaştırılmasıdır.Materyal ve Metod: Çalışma Ankara Numune Eğitim Araştırma Hastanesi (EAH) Bilimsel Araştırmalar Değerlendirme Komisyonunun 24/07/2013 tarih ve 2013-646 sayılı kararı ile yapılmıştır. Ankara Numune EAH 3 Dahiliye polikliniğine Mayıs–Ekim 2012 tarihleri arasında başvuran ve yeni tanı B12 vitamini eksikliği saptanan, oral veya intramüsküler tedavi başlanan, bir ay sonra kontrole gelen hastalar retrospektif taranarak çalışmaya alınmıştır. İstatistiksel analizler “SPSS for Windows 20,0” paket programı ile yapılmıştır.Bulgular: Oral vitamin B12 replasman tedavisi alan 56, intramüsküler vitamin B12 replasman tedavisi alan 46 hasta bulundu. Başlangıç değerlerine göre tüm hastalarda anlamlı B12 vitamini düzey artışı olduğu görüldü. (220,73±243,47 pikogram/mililitre (pg/ml), p<0,001). Oral tedavi alanlarda B12 vitamini artışı 252,91±297,23 pg/ml, intramüsküler tedavi alanlarda B12 vitamini artışı 182,96±152,90 pg/ml olarak saptandı. Oral ve intramüsküler tedavi alan hastaların B12 vitamini düzey artışları arasında fark tespit edilmedi (p>0,05).Sonuç: Oral ve intramüsküler B12 replasman tedavi kollarına ayrılarak yapılan bir çalışmada 90 günlük tedavi sonrasında oral ve intramüsküler tedavi ile B12 vitamini düzeyinde artış olduğu bulunmuş ancak gruplar etkinlik açısından karşılaştırılmamıştır. Bizim çalışmamızda B12 vitamini eksikliği saptanan hastalarda oral ve intramüsküler B12 replasman tedavileri arasında fark saptanmamış olması, oral replasman tedavisinin intramüsküler tedaviye alternatif olabileceğini akla getirmektedir. Konu ile ilgili yeni, daha geniş kapsamlı randomize kontrollü çalışmalara ihtiyaç olduğu ortadadır.

Nitrous oxide-induced demyelination: Clinical presentation, diagnosis and treatment recommendations

BackgroundRecreational use of nitrous oxide (NO) in the general public has led to increasing reports of NO-induced demyelination (NOID). We describe the varying clinical presentations and pathophysiology, and offer a treatment paradigm. MethodsA literature search of MEDLINE and EMBASE resulted in 42 publications with 37 studies meeting the inclusion criteria, for a total of 51 patients. Our case series included 5 patients seen from 2014 to 2018 followed over 3–60 months. ResultsThose with sensory symptoms and subjective weakness were categorized as having “mild” symptoms (25%). Symptoms indicating involvement outside the dorsal columns such as observer-graded weakness were categorized as “moderate” (61%). Patients with the aforementioned plus cognitive effects were categorized as “severe” (12%). There was no dose-dependent relationship between the amount of NO used and clinical impairment. There was a trend between the severity of neurologic impairment and serum levels of B12. Two patients were noncompliant. One initiated only oral therapy and did not improve. One received injections a month apart and worsened. ConclusionsPatients with NOID tend to have worse symptoms when presenting with lower serum vitamin B12 levels and have good recovery rates when treated with intramuscular B12 and oral supplementation.

Appropriateness of B12 Administration in a Real-World Population

IntroductionB12 deficiency can lead to multiple complications, including severe pancytopenia, spinal cord demyelination, and cognitive dysfunction. Randomized controlled trials have demonstrated oral B12 supplementation is as effective as parenteral B12 administration in improving hematologic abnormalities and raising B12 levels. Despite this evidence base, a high proportion of patients continue to receive intramuscular (IM) B12. We assessed the prevalence of inappropriate B12 supplementation in a large population-based cohort.MethodsWe undertook a population-based, retrospective cohort study with the Institute for Clinical and Evaluative Sciences (ICES) in Ontario, Canada. ICES houses health service records for 13 million Ontarians, including laboratory values from the Ontario Laboratories Information System (OLIS), which contains 92% of annual provincial test volumes; the Ontario Drug Benefit (ODB) database, which houses prescriptions, including IM B12, for all Ontarians aged 65 and above; and the Ontario Health Insurance Program (OHIP), which contains all billing claims for physician services (including intramuscular B12 injections).We included all patients (≥ 65 years or above) that received an IM B12 injection between September 1, 2009 and September 30, 2015, identified from both ODB and OHIP databases. Inappropriate B12 supplementation was defined as (1) IM B12 administration following a documented normal B12 level (≥250 pmol/L); or (2) no documented B12 testing in the 12 months prior to supplementation. Appropriate IM B12 supplementation occurred in those with documented B12 deficiency (<250 pmol/L) or a diagnosis of inflammatory bowel disease (IBD) or malabsorptive disorders. Other outcomes we evaluated included patterns of B12 prescribing, frequency of B12 level retesting in patients receiving supplementation, and the overall prevalence of B12 deficiency. Logistic regression analysis was used to determine physician and patient variables that predicted inappropriate B12 supplementation.ResultsA total of 173,138 Ontarians received at least one IM B12 prescription during the study interval. Of these, 37,801 (21.8%) had a normal serum B12 level (≥ 250 pmol/L) in the preceding twelve months, and an additional 73,886 (42.7%) had no documented B12 test in the preceding 12 months, suggesting that these prescriptions were inappropriate. Only 61,451 (35.5%) of patients that received IM B12 had documented B12 deficiency (<250 pmol/L) in the preceding 12 months. Only 1.1% (n=1925) of all IM prescriptions were to patients with B12 deficiency and either IBD or a malabsorptive disorder. Each patient received an average of 4.01 prescriptions during the study period (SD: 5.77; median: 2; range:1-198) from an average of 1.29 physicians (SD: 0.72; median: 1; range:1-32). The average length of time between the initial and first repeat prescription was 309.6 days (SD: 28.21, median: 263; range: 0-2206). On average, those patients that were tested were re-tested an average of 3.2 times during the 6-year study period (SD: 2.81, median: 3; range: 1-295). The overall prevalence of B12 deficiency in all patients tested in Ontario during the study interval was 7.7% (<150 pmol/L; n=500,453) or 46.9% (<250 pmol/L; n=3,056,986).ConclusionThe prevalence of inappropriate B12 supplementation is extensive. Nearly two-thirds (65.6%) of patients received an IM B12 injection with either a documented normal B12 level or without B12 documentation in the year prior to supplementation. In this era of Choosing Wisely, our findings suggest that initiatives are required to educate physicians and patients on appropriate indications for IM B12 prescriptions. DisclosuresNo relevant conflicts of interest to declare.

Use of Metformin for Cardiometabolic Risks in Psychiatric Practice: Need-to-Know Safety Issues

Metformin, a biguanide drug, is emerging as an important treatment option for the prevention or treatment of weight gain, type 2 diabetes mellitus, and the metabolic syndrome in psychiatric patients, especially those who require or receive antipsychotic drugs. Metformin treatment is commonly associated with gastrointestinal adverse effects; the risk of these is reduced by gradual dose uptitration, administration of the drug with meals, and use of a time-release formulation. Lactic acidosis, a potentially fatal complication of biguanide therapy, is very rare with metformin; the risk can be reduced by avoidance of its prescription in patients with impaired renal function, impaired liver function, cardiac failure, and certain other conditions. Long-term metformin use is associated with decreased vitamin B₁₂ levels, and even with biochemical B₁₂ deficiency; this complication can detected early by annual assessments of serum B₁₂ levels and prevented by annual intramuscular B₁₂ administration.

Should vitamin B12 tablets be included in more Canadian drug formularies? An economic model of the cost-saving potential from increased utilisation of oral versus intramuscular vitamin B12 maintenance therapy for Alberta seniors

ObjectiveThe aim of this study was to estimate the cost-savings attainable if all patients aged ≥65 years in Alberta, Canada, currently on intramuscular therapy were switched to oral therapy, from...

Subacute Combined Degeneration of the Spinal Cord due to Different Etiologies and Improvement of MRI Findings

Subacute combined degeneration (SCD) is a rare neurological complication of vitamin B12 deficiency, characterized by demyelination of the dorsal and lateral spinal cord. Herein, we describe three cases, who presented with SCD, one related to reduced intake of vitamin B12 because of a vegetarian diet and two related to nitrous oxide exposure during surgery. MR images of our patients revealed symmetrical hyperintense signals in dorsal and lateral columns in T2 weighted series. After treatment with intramuscular B12 injections (1 mg daily for 2 weeks, once weekly thereafter for three months) all patients showed improvement of their symptoms. Abnormalities of the spinal cord on MRI resolved in three months. In conclusion, SCD either due to nitrous oxide exposure or due to reduced intake of vitamin B12 is a reversible condition, when detected and treated early.

When do the elderly patients with Alzheimer's disease need the vitamin B12 supplementation?

Serum vitamin B12 levels are usually subnormal in elderly subjects. It is still debated whether there is an association between cognitive impairment and vitamin B12 supplementation. The aim of this study was to examine the effects of vitamin B12 supplementation on cognitive functions and activities of daily living in elderly with Alzheimer disease having low vitamin B12 levels by using neuropsychological assessment scales. Eighty-seven elderly patients with Alzheimer disease having low vitamin B12 levels (<400 pg/ml) were evaluated in this study. Subjects were recommended to receive 1000 micrograms intramuscularly cyanocobalamin weekly for 1 month, then monthly for 5 months. All patients underwent comprehensive geriatric assessment at baseline and after 6 months. After 6 months, at the second evaluation, 36 subjects had not received intramuscular B12 supplementation. While their complete blood count parameters were stable, all of the following parameters were found to decrease significantly; vitamin B12 levels, activities of daily living, instrumental activities of daily living, mini-mental state examination, clock drawing and Yesavage geriatric depression scales scores, when compared to baseline. However, 51 subjects who had received B12 supplementation, showed statistically significant increase in their vitamin B12 levels, mini-mental state examination, clock-drawing test and Yesavage geriatric depression scales scores and preservation in their activities of daily living and instrumental activities of daily living scales' scores, when compared to baseline. Supplementation for elderly patients with Alzheimer disease having vitamin B12 levels lower than 400pg/ml seems to be favorable to maintain the cognitive status and the activities of daily living. Therefore, annual screening for vitamin B12 levels and intramuscular vitamin B12 supplementation is recommended to prevent probable neuropsychiatric problems, to maintain the functionality, and to decrease the morbidity in all geriatric subjects.

Normalization of vitamin B12 (B12) levels achieved following 1000 mcg oral Eligen® B12 therapy: A clinical study comparing the efficacy and safety of oral B12 therapy versus intramuscular (IM) therapy

B12 deficiency occurs from dietary insufficiency or impaired absorption. The traditional treatment method is B12 IM injections. Oral B12 therapy is not considered dependable. Eligen® technology uses a functional excipient that increases and accelerates B12 uptake and more closely resembles B12 IM serum profile than other oral B12 formulations. This was an open‐label, randomized 90‐day study to assess the relative efficacy and safety of oral Eligen® B12 versus intramuscular B12 in promptly and reliably normalizing low B12 levels. The primary measurement was serum cobalamin (B12), the secondary measurements included methylmalonic acid and homocysteine. Holotranscobalamin was an exploratory endpoint. Blood samples were collected at Baseline, Day 15, Day 31, Day 61, and Day 91. A total of 49 patients were enrolled (26 IM and 23 oral). At the first time point (Day 15) all study parameters had returned to the normal range with both treatments. Normalization was maintained at all intervals up to and including Day 91. Eligen® B12 was well tolerated with no adverse drug related events. This study shows that oral Eligen B12 1000 mcg offers an alternative treatment option for patients requiring IM dosing.

Cognitive and psychiatric effects of vitamin B12 replacement in dementia with low serum B12 levels: a nursing home study

The aim of this study is to determine whether B12 replacement would ameliorate cognitive and psychiatric symptoms in elderly subjects with dementia and low serum B12 levels. A test group (n = 28) of nursing home residents with low serum B12 levels (<250 pg/mL) and a matched comparison group (n = 28) with normal serum B12 levels (>300 pg/mL) were evaluated by blinded raters while the test group received intramuscular (IM) B12 replacement therapy. All subjects were assessed at baseline, 8 weeks, and 16 weeks with the Dementia Rating Scale, Brief Psychiatric Rating Scale, and Geriatric Depression Scale. Although B12 replacement produced significant improvement in hematologic and metabolic parameters, it yielded no significant effect on cognitive or psychiatric variables. A few subjects evidenced notable individual treatment responses; however, these were not statistically more frequent than in the normal B12 group. These results suggest that B12 replacement is unlikely to benefit cognitive or psychiatric symptoms in the vast majority of elderly dementia patients with low serum B12 levels.