A Brief Overview of the Diagnosis and Treatment of Cobalamin (B12) Deficiency.

Background: An increasing number of adult individuals are at risk of vitamin B12 deficiency, either from reduced nutritional intake or impaired gastrointestinal B12 absorption.

Objective: This study aims to review the current best practices for the diagnosis and treatment of individuals with vitamin B12 deficiency.

Methods: A narrative literature review of the diagnosis and treatment of vitamin B12 deficiency.

Creating a Framework for Treating Autoimmune Gastritis-The Case for Replacing Lost Acid.

Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, resulting in hypochlorhydria and eventual achlorhydria, as oxyntic glands in the corpus are destroyed and become atrophic. The permanent loss of gastric acid has many impacts-both theoretical and documented. The most concerning of these are hypergastrinemia and increased N-nitroso compounds, both of which increase the risk of gastric cancers.

Homocysteine-a retrospective and prospective appraisal.

The biologically important amino acid homocysteine links sulfur, methionine, and one-carbon metabolism. This review describes its initial discovery, the identification of the clinical condition of "homocystinuria" and the recognition of its close relationship to folate and vitamin B12 metabolism. It discusses the history behind its current association with diverse diseases including neural tube defects, cardio- and cerebrovascular disease and, more recently, dementia and Alzheimer's Disease.

Transcobalamin receptor gene polymorphisms and mutation in an elderly population.

Background & Aims: Cellular uptake of the essential nutrient vitamin B12 (cobalamin) occurs via the transcobalamin receptor (TCblR/CD320), a ubiquitous membrane receptor. Polymorphisms in the receptor exist, though the effect of such variants across patient populations is unknown.

Methods: We determined CD320 genotype in 377 randomly selected elderly individuals.

Examining the Diagnosis and Treatment Experiences of People Living With Autoimmune Gastritis and Pernicious Anemia.

There is limited research evaluating the diagnosis and treatment of patients with autoimmune gastritis (AIG) and pernicious anemia (PA). We used a 2-phase data collection process to examine the literature and individual patient accounts. Phase one comprised a systematically conducted literature review focusing on diagnosis and treatment, relationships with healthcare practitioners and health-related quality of life (HRQOL).

Plasma Methylmalonic Acid Concentration in Folic Acid-Supplemented Depressed Patients with Low or Marginal Vitamin B-12: A Randomized Trial.

Background: Individuals with low serum vitamin B-12 and high serum folate have higher plasma concentrations of methylmalonic acid (MMA). Whether folic acid (FA) causes an increase in MMA is not known.

Objectives: We aimed to determine the impact of FA supplementation on plasma MMA concentration in people with low or marginal serum vitamin B-12.

Vitamin B status in health and disease: a critical review. Diagnosis of deficiency and insufficiency - clinical and laboratory pitfalls.

Vitamin B (cobalamin) is an essential cofactor for two metabolic pathways. It is obtained principally from food of animal origin. Cobalamin becomes bioavailable through a series of steps pertaining to its release from dietary protein, intrinsic factor-mediated absorption, haptocorrin or transcobalamin-mediated transport, cellular uptake, and two enzymatic conversions ( methionine synthase and methylmalonyl-CoA-mutase) into cofactor forms: methylcobalamin and adenosylcobalamin.

COVID-19: A methyl-group assault?

The socio-economic implications of COVID-19 are devastating. Considerable morbidity is attributed to 'long-COVID' - an increasingly recognized complication of infection. Its diverse symptoms are reminiscent of vitamin B deficiency, a condition in which methylation status is compromised.

Alzheimer's Amyloidopathy: An Alternative Aspect.

The 'amyloid hypothesis' dominates Alzheimer's disease (AD) research but has failed to deliver effective therapies. Amyloid precursor protein (APP) and presenilin-1 (PSEN1) genetic mutations are undoubtedly pathogenic, albeit by unclear mechanisms. Conversely, high dose B-vitamins convincingly slow brain atrophy in a pre-stage state of sporadic AD.

Homocysteine and Dementia: An International Consensus Statement.

Identification of modifiable risk factors provides a crucial approach to the prevention of dementia. Nutritional or nutrient-dependent risk factors are especially important because dietary modifications or use of dietary supplements may lower the risk factor level. One such risk factor is a raised concentration of the biomarker plasma total homocysteine, which reflects the functional status of three B vitamins (folate, vitamins B12, B6).

Assessing the association between homocysteine and cognition: reflections on Bradford Hill, meta-analyses, and causality.

Hyperhomocysteinemia is a recognized risk factor for cognitive decline and incident dementia in older adults. Two recent reports addressed the cumulative epidemiological evidence for this association but expressed conflicting opinions. Here, the evidence is reviewed in relation to Sir Austin Bradford Hill's criteria for assessing "causality," and the latest meta-analysis of the effects of homocysteine-lowering on cognitive function is critically examined.

Folate Augmentation of Treatment--Evaluation for Depression (FolATED): randomised trial and economic evaluation.

Background: Folate deficiency is associated with depression. Despite the biological plausibility of a causal link, the evidence that adding folate enhances antidepressant treatment is weak.

Objectives: (1) Estimate the clinical effectiveness and cost-effectiveness of folic acid as adjunct to antidepressant medication (ADM).

Patient journeys: diagnosis and treatment of pernicious anaemia.

Background: Instigating a patient support group for patients with pernicious anaemia (PA) revealed dissatisfaction with its current diagnosis and treatment. The authors investigated the clinical features, patient experience of diagnosis and treatment of PA in the UK.

Methods: A total of 889 patients registered with the PA Society support group completed an online survey or postal questionnaire.

Vitamin B12 in neurology and ageing; clinical and genetic aspects.

The classic neurological and psychiatric features associated with vitamin B12 deficiency have been well described and are the subject of many excellent review articles. The advent of sensitive diagnostic tests, including homocysteine and methylmalonic acid assays, has revealed a surprisingly high prevalence of a more subtle 'subclinical' form of B12 deficiency, particularly within the elderly. This is often associated with cognitive impairment and dementia, including Alzheimer's disease.

L-methylfolate, methylcobalamin, and N-acetylcysteine in the treatment of Alzheimer's disease-related cognitive decline.

Neuroinflammatory oxidative stress occurs early in AD pathology. Elevated blood Hcy is a useful marker for such neuroinflammation. Hcy contributes to pathological cascades involving AP and NFTs.

Vitamin B(12) and redox homeostasis: cob(II)alamin reacts with superoxide at rates approaching superoxide dismutase (SOD).

We report a kinetic study of the reaction between superoxide and an important intracellular form of vitamin B(12), cob(II)alamin. Superoxide is implicated in the pathophysiology of many inflammatory diseases, whereas vitamin B(12) derivatives are often beneficial in their treatment. We found that cob(II)alamin reacts with superoxide at rates approaching those of superoxide dismutase itself, suggesting a probable mechanism by which vitamin B(12) protects against chronic inflammation and modulates redox homeostasis.

Synthesis, synchrotron X-ray diffraction, and kinetic studies on the formation of a novel thiolatocobalamin of captopril: evidence for cis-trans isomerization in the beta-axial ligand.

The orally administered therapeutic captopril is widely used for treating hypertension, congestive heart failure, and cardiovascular disease. However, a number of undesirable side effects are associated with high doses of captopril. By coordinating a therapeutic to the upper (= beta) axial site of the naturally occurring macrocycle cobalamin (vitamin B(12)), the absorption and cellular uptake of the therapeutic can be significantly enhanced.

A novel role for vitamin B(12): Cobalamins are intracellular antioxidants in vitro.

Oxidative stress is a feature of many chronic inflammatory diseases. Such diseases are associated with up-regulation of a vitamin B(12) (cobalamin) blood transport protein and its membrane receptor, suggesting a link between cobalamin and the cellular response to inflammation. The ability of cobalamin to regulate inflammatory cytokines suggests that it may have antioxidative properties.

The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases.

Hyperhomocysteinemia (HHcy) is related to central nervous system diseases. Epidemiological studies show a positive, dose-dependent relationship between plasma total homocysteine (tHcy) concentration and neurodegenerative disease risk. tHcy is a marker of B-vitamin (folate, B(12), B(6)) status.

Methylmalonic acid and cognitive function in the Medical Research Council Cognitive Function and Ageing Study.

Background: An elevated blood concentration of homocysteine is an established risk factor for cognitive impairment and dementia, but associations between cognition and methylmalonic acid (MMA), a related metabolic marker of vitamin B-12 deficiency, are less clear.

Objective: The aim was to determine the utility of serum MMA and holotranscobalamin as markers of vitamin B-12 status in relation to cognitive function and to investigate their association with discrete cognitive domains.

Design: This was a cross-sectional survey of 84 nondemented elderly participants (aged >69 y) from the Welsh cohort of the Medical Research Council's Cognitive Function and Ageing Study.

Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology.

The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review the evidence on the drug treatment for dementia. The level of evidence (types) was rated using a standard system: Types 1a and 1b (evidence from meta-analysis of randomised controlled trials or at least one controlled trial respectively); types 2a and 2b (one well-designed study or one other type of quasi experimental study respectively); type 3 (non-experimental descriptive studies); and type 4 (expert opinion). There is type 1a evidence for cholinesterase inhibitors (donepezil, rivastigmine and galantamine) for mild to moderate Alzheimer's disease; memantine for moderate to severe Alzheimer's disease; and for the use of bright light therapy and aromatherapy.

Homocysteine and cognition--a historical perspective.

The discovery of a relationship between homocysteine and cognition stems from clinical observations of an association between vitamin B12 and folate deficiency and cognitive dysfunction. This retrospective details the history of vitamin B12 and folic acid and the conceptual evolution of their association with dementia. The hematological and neuropsychiatric manifestations of these deficiencies are discussed, together with the nature of their relationship with dementia, generalized cognitive decline and discrete neuropsychological function.

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).