Comparison of the efficacy of parenteral and oral treatment for nutritional vitamin B12 deficiency in children

ABSTRACT

Objective: Although, oral replacement for vitamin B12 deficiency has been proved to be effective in adults, it is mainly treated with parenteral therapy. There are only few studies on oral replacement therapy of vitamin B12 with children. Therefore, we aimed to compare the efficacy of oral treatment with intramuscular vitamin B12 injections in pediatric population.

Methods: Children with serum cobalamin concentrations less than 300?pg/mL, were treated either with the parenteral therapy or with oral vitamin B12. The primary and secondary outcomes of the study were the normalization of serum vitamin B12 and hemoglobin at first month, respectively.

Results: Post-treatment vitamin B12 values were significantly higher than pre-treatment values (p-value <.001). Vitamin B12 increased from 183.5?±?47?pg/mL to 482?±?318.9?pg/mL in the oral and from 175.5?±?42.5?pg/mL to 838?±?547?pg/mL in the parenteral treatment arm (p-value <.001). Before treatment, 82 children had anemia according to age and gender. After treatment, 14/41 and 8/41 patients still had anemia at the first month of treatment in the parenteral and oral arms, respectively. The number of patients who still have anemia at the end of the 1st month of treatment did not significantly changed in the parenteral and oral treatment groups (p-value?=?.44).

Conclusions: In this study, both oral and parenteral formulations were shown to be effective in normalizing vitamin B12 levels. We suggest that oral formulations may be considered to be safe as a first line treatment for vitamin B12 deficiency in children.     

Haematological and Haemopoietic Studies in an Air-Breathing Fish on Cyanocobalamin and Folacin Deficient Diet

Experimental deficiencies of cyanocobalamin and folacin separately and in combination were induced in an air-breathing teleost fish Channa punctatus with the help of a complete vitamin test diet. Cyanocobalamin deficiency produced normocytic hypochromic anaemia while the folacin deficiency as well as the combined deficiency of both vitamins produced macrocytic hypochromic anaemia. Leucocytosis was observed in the individual and combined deficiencies of these vitamins with significant increase in thrombocytes and decrease in neutrophil population. The relative population of different developing stages in erythropoiesis showed significant change. Thus small lymphoid haemoblast decreased in number while young and mature reticulocyte populations increased. Recovery to normal condition could be obtained by restoring deficient groups of fishes to complete vitamin test diet fortified with an initial i.m. administration of 0.01 mg/g and 0.02 mg/g body wt. of cyanocobalamin and folacin respectively. A comparison of deficiency effects on C. punctatus with Labeo rohita shows that the former, a carnivorous species with higher Hb content in peripheral blood is more susceptible to deficiency than the latter, a herbivorous species of fish with lower Hb values.     

Vitamin B12 and Homocysteine Levels Predict Different Outcomes in Early Parkinson's Disease

Background : In moderately advanced Parkinson's disease (PD), low serum vitamin B12 levels are common and are associated with neuropathy and cognitive impairment. However, little is known about B12 in early PD. Objective : To determine the prevalence of low vitamin B12 status in early PD and whether it is associated with clinical progression. Methods : We measured vitamin B12 and other B12 status determinants (methylmalonic acid, homocysteine, and holotranscobalamin) in 680 baseline and 456 follow‐up serum samples collected from DATATOP participants with early, untreated PD. Borderline low B12 status was defined as serum B12 <184 pmol/L (250 pg/mL), and elevated homocysteine was defined as >15 µmol/L. Outcomes included the UPDRS, ambulatory capacity score (sum of UPDRS items 13‐15, 29&30), and MMSE, calculated as annualized rates of change. Results : At baseline, 13% had borderline low B12 levels, 7% had elevated homocysteine, whereas 2% had both. Elevated homocysteine at baseline was associated with worse scores on the baseline MMSE. Analysis of study outcomes showed that compared with the other tertiles, participants in the low B12 tertile (<234 pmol/L; 317 pg/mL) developed greater morbidity as assessed by greater annualized worsening of the ambulatory capacity score. Elevated homocysteine was associated with greater annualized decline in MMSE (?1.96 vs. 0.06; P = 0001). Blood count indices were not associated with B12 or homocysteine status. Conclusions : In this study of early PD, low B12 status was common. Low B12 at baseline predicted greater worsening of mobility whereas elevated homocysteine predicted greater cognitive decline. Given that low B12 and elevated homocysteine can improve with vitamin supplementation, future studies should test whether prevention or early correction of these nutritionally modifiable conditions slows development of disability. © 2018 International Parkinson and Movement Disorder Society     

Use of chitosan in the treatment of obesity: evaluation of interaction with vitamin B12

Is well known that obesity has increased significantly in recent times and therefore many dietary supplements, synthetic or natural, have been proposed in order to prevent and/or to treat obesity or overweight. Chitosan, a polysaccharide with ability to act as a carrier and to absorb fat, has been used for this purpose. However, interactions with other molecules present in the body may also occur and, therefore, the purpose of this study was to evaluate interactions of chitosan with vitamin B12. Spectroscopic properties of vitamin B12 (acid aqueous solution) were monitored in the absence and the presence of chitosan in order to evaluate possible interactions between the two. Results showed that the rigid micro-environment generated by chitosan solution modifies the photophysical properties of vitamin B12. Thus, chitosan is able to eliminate vitamin B12 and, based on this information, some care must be taken during prolonged treatment with chitosan.     

Effects of low cobalamin diet and chronic cyanide toxicity in baboons.

The effects of a low cobalamin (Cbl) diet, together with chronic cyanide or thiocyanate administration in some animals have been investigated in baboons over a period of 42 months. All animals remained healthy throughout the study and gained weight at a similar rate. None became anaemic or showed major haematological changes and there were no major neurological changes. Plasma total Cbl in the animals on the low Cbl diet fell within 9 months to values below the lower limit in man and were lowest at 24 months in baboons not receiving cyanide or thiocyanate. A striking feature in all animals, however, was an apparently seasonal increase in the plasma total Cbl each autumn with a corresponding decrease the following spring. This fluctuation was detected by radioisotopic assay but not by Euglena. Methylmalonic (MMA) excretion after oral valine ranged from 0.1--8.4 mg/24 h and was greatest in animals on the low Cbl diet and not receiving cyanide or thiocyanate. The results suggested an inverse relationship between MMA excretion and plasma total Cbl. Plasma thiocyanate was consistently higher in animals receiving cyanide or thiocyanate and at the end of the study plasma cyanide was highest in animals on the low Cbl diet receiving cyanide. The results support the suggestions that cyanide affects bodily handling of Cbl and that hydroxo-cobalamin plays a part in detoxication of cyanide.     

Human serum vitamin B12 assay methods--a review

The clinical importance of a reliable human serum vitamin B12 assay to aid the diagnosis of pernicious anemia (PA) cannot be overemphasized. Our review of the literature indicates that a reference method for the quantitation of serum vitamin B12 (serum B12) with the required accuracy, precision and rapidity has not been reported to-date. Controversies, debates and criticisms over human serum B12 assays (especially commercial kits) have been common-place. Various methods of quantitation of B12 reviewed in this communication include: microbiological, radioisotopic, high-performance liquid chromatography (HPLC) and the most recent radioimmunoassay (RIA) techniques. This review attempts to provide awareness of the limitations of these methods and establishes the base for eventual development of a B12 reference method in our laboratory.     

Insoluble Powder Formulation as an Effective Nasal Drug Delivery System

Purpose. To evaluate the utility of insoluble powder formulation for nasal systemic drug delivery. Methods. To compare the efficacy of liquid and powder formulations, the nasal absorption of drugs was examined in rats using hydrophilic compounds with various molecular weights (MW) such as phenol red, cyanocobalamin, and fluorescein isothiocyanate (FITC)-Dextrans, and several kinds of powder. Intranasal residence time was also compared among the different formulations. Results. All the drugs examined were absorbed through the nasal mucosa to varying extent; their systemic bioavailability decreased with increasing MW. Insoluble calcium carbonate (CaCO₃) powder formulation provided increased absorption of drugs over the wide range of MW from 354 to 77,000 Da. In the case of phenol red, intranasal administration as a CaCO₃ powder formulation resulted in a plasma concentration profile similar to that of an intravenous bolus dose due to its very rapid and complete absorption from the nasal cavity. Furthermore, improved bioavailability of FITC-Dextran (MW 4,400; FD-4) was also achieved with other insoluble powders as well as CaCO₃, but not with soluble powders such as lactose, d-sorbitol, and d-mannitol. Insoluble powder formulation prolonged the residence time of FD-4 within the nasal cavity. Conclusions. Insoluble powder formulations improve nasal bioavailability predominantly by retarding drug elimination from the absorption site and appear to be effective for nasal systemic drug delivery.     

"Whippets"-Induced Cobalamin Deficiency Manifesting as Cervical Myelopathy

BACKGROUND: Nitrous oxide (N2O) is inhaled in anesthesia and as a recreational drug from whipped cream dispensers. Its abuse reaches approximately 10% in some age groups. By inactivating cobalamin (Cbl) (vitamin B12), N2O can cause neurologic and hematologic manifestations. We present a case of N2O-induced Cbl deficiency presenting as cervical myelopathy. CASE HISTORY: After regularly inhaling N2O for many months, a 31-year-old man developed limb paresthesiae and ataxia over 3 months. Examination revealed finger pseudoathetosis, hyporeflexia, decreased sensation, and gait ataxia. Brain magnetic resonance imaging (MRI) was normal, but the posterior columns of the cervical and upper thoracic cord revealed patchy nonenhancing hyperintense lesions. Serum Cbl was 98 pg/mL (normal = 170-900 pg/mL). Cbl replacement led to recovery within 3 months. DISCUSSION: This patient presented with the symptoms and signs of Cbl deficiency. The MRI lesions in the posterior columns aided the diagnosis. Physicians need to have a high level of suspicion in cases of unexplained Cbl deficiency and myelopathy.     

Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials

BACKGROUND: Vitamin B(12) deficiency is common, increasing with age. Most people are treated in primary care with intramuscular vitamin B(12). Several studies have reported equal efficacy of oral administration of vitamin B(12). OBJECTIVES: We set out to identify randomized controlled trial (RCT) evidence for the effectiveness of oral versus intramuscular vitamin B(12) to treat vitamin B(12) deficiency. METHODS: We conducted a systematic review searching databases for relevant RCTs. Outcomes included levels of serum vitamin B(12), total serum homocysteine and methylmalonic acid, haemoglobin and signs and symptoms of vitamin B(12) deficiency. RESULTS: Two RCTs comparing oral with intramuscular administration of vitamin B(12) met our inclusion criteria. The trials recruited a total of 108 participants and followed up 93 of these from 90 days to 4 months. In one of the studies, mean serum vitamin B(12) levels were significantly higher in the oral (643 +/- 328 pg/ml; n = 18) compared with the intramuscular group (306 +/- 118 pg/ml; n = 15) at 2 months (P < 0.001) and 4 months (1005 +/- 595 versus 325 +/- 165 pg/ml; P < 0.0005) and both groups had neurological responses. In the other study, serum vitamin B(12) levels increased significantly in those receiving oral vitamin B(12) and intramuscular vitamin B(12) (P < 0.001). CONCLUSIONS: The evidence derived from these limited studies suggests that 2000 microg doses of oral vitamin B(12) daily and 1000 microg doses initially daily and thereafter weekly and then monthly may be as effective as intramuscular administration in obtaining short-term haematological and neurological responses in vitamin B(12)-deficient patients.     

Melatonin prevents hypochlorous acid‐mediated cyanocobalamin destruction and cyanogen chloride generation

Hypochlorous acid (HOC l) is a potent cytotoxic oxidant generated by the enzyme myeloperoxidase (MPO ) in the presence of hydrogen peroxide (H₂O₂) and chloride (Cl^?). Elevated levels of HOC l play an important role in various pathological conditions through oxidative modification of several biomolecules. Recently, we have highlighted the ability of HOC l to mediate the destruction of the metal‐ion derivatives of tetrapyrrole macrocyclic rings such as hemoproteins and vitamin B₁₂ (VB ₁₂) derivatives. Destruction of cyanocobalamin, a common pharmacological form of VB ₁₂ mediated by HOC l, results in the generation of toxic molecular products such as chlorinated derivatives, corrin ring cleavage products, the toxic blood agents cyanide (CN ^?) and cyanogen chloride (CNC l), and redox‐active free cobalt. Here, we show that melatonin prevents HOC l‐mediated cyanocobalamin destruction, using a combination of UV ‐Vis spectrophotometry, high‐performance liquid chromatography analysis, and colorimetric CNC l assay. Identification of several melatonin oxidation products suggests that the protective role of melatonin against HOC l‐mediated cyanocobalamin destruction and subsequent CNC l generation is at the expense of melatonin oxidation. Collectively, this work highlights that, in addition to acting as an antioxidant and as a MPO inhibitor, melatonin can also prevent VB ₁₂ deficiency in inflammatory conditions such as cardiovascular and neurodegenerative diseases, among many others.