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. It also explores current controversies and considers potential future research directions. It is intended to give a general overview of homocysteine in relation to health and disease

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. While known deficiencies of B12 and iron are often replaced in AIG, acid is not. Moreover, patients with AIG are often prescribed acid suppression for a stomach that is decidedly no longer acidic, worsening the sequelae of gastric atrophy. Betaine hydrochloride (BHCL) is a short-acting acidifying agent, available over the counter in capsule form. Mealtime acid supplementation has an historic basis and could ameliorate many AIG-related gastrointestinal symptoms. Theoretically, acidification could also reduce the potential for hypergastrinemia and the production of N-nitroso compounds, consequently reducing the risk of gastric cancers. Supplemental vitamin C may also help in preventing gastric N-nitroso formation, regardless of the gastric pH. This narrative review describes the functions of gastric acid in gastrointestinal and immune health, documents the effects of hypochlorhydria in AIG, and proposes potential options for safely re-establishing the acid milieu of the stomach for patients with AIG

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. METHODS: We conducted a multicenter double-blind placebo-controlled randomized trial of oral FA (5 mg/d for 12 wk) in middle-aged patients treated with antidepressant medication participating in the FoLATED (Folate Augmentation of Treatment—Evaluation for Depression) trial. Participants defined as having “low” serum vitamin B-12 (vitamin B-12 ≥150 and <220 ng/L) or “marginal” serum vitamin B-12 (vitamin B-12 ≥ 220 and <280 ng/L) were included. The primary outcome of this substudy was MMA at week 12. A mixed-effects linear regression was fitted and reported using the adjusted mean difference (aMD). RESULTS: A total of 177 participants were included (85 randomly assigned to placebo and 92 to FA); the mean ± SD age was 46.2 ± 11.8 y, and 112 (63.3%) were female. The MMA analysis included 135 participants and the aMD was −0.01 (95% CI: −0.06, 0.04; P = 0.71). Serum folate was measured on 166 participants and increased in the supplementation group; the aMD was 21.6 μg/L (95% CI: 8.13, 25.02 μg/L; P < 0.001). A total of 117 participants were assessed for RBC folate, which also increased in the supplementation group; the aMD was 461 μg/L (95% CI: 387, 535 μg/L; P < 0.001). CONCLUSIONS: Supplementation of FA leads to an increase of serum and RBC folate, but does not change plasma MMA concentration in individuals with serum vitamin B-12 between 150 and 280 ng/L. We cannot exclude effects in older people or those with serum vitamin B-12 <150 ng/L. Previously reported associations may arise from effects of impaired vitamin B-12 status on folate metabolism. This trial was registered at www.isrctn.com as ISRCTN37558856

An update on vitamin B12-related gene polymorphisms and B12 status.

Vitamin B12 is an essential micronutrient in humans needed for health maintenance. Deficiency of vitamin B12 has been linked to dietary, environmental and genetic factors. Evidence for the genetic basis of vitamin B12 status is poorly understood. However, advancements in genomic techniques have increased the knowledge-base of the genetics of vitamin B12 status. Based on the candidate gene and genome-wide association (GWA) studies, associations between genetic loci in several genes involved in vitamin B12 metabolism have been identified. The objective of this literature review was to identify and discuss reports of associations between single-nucleotide polymorphisms (SNPs) in vitamin B12 pathway genes and their influence on the circulating levels of vitamin B12. Relevant articles were obtained through a literature search on PubMed through to May 2017. An article was included if it examined an association of a SNP with serum or plasma vitamin B12 concentration. Beta coefficients and odds ratios were used to describe the strength of an association, and a  < 0.05 was considered as statistically significant. Two reviewers independently evaluated the eligibility for the inclusion criteria and extracted the data. From 23 studies which fulfilled the selection criteria, 16 studies identified SNPs that showed statistically significant associations with vitamin B12 concentrations. Fifty-nine vitamin B12-related gene polymorphisms associated with vitamin B12 status were identified in total, from the following populations: African American, Brazilian, Canadian, Chinese, Danish, English, European ancestry, Icelandic, Indian, Italian, Latino, Northern Irish, Portuguese and residents of the USA. Overall, the data analyzed suggests that ethnic-specific associations are involved in the genetic determination of vitamin B12 concentrations. However, despite recent success in genetic studies, the majority of identified genes that could explain variation in vitamin B12 concentrations were from Caucasian populations. Further research utilizing larger sample sizes of non-Caucasian populations is necessary in order to better understand these ethnic-specific associations

Homocysteine and cognitive impairment; a case series in a General Practice setting

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: An elevated blood level of homocysteine is a risk factor for cognitive impairment and dementia. Homocysteine can be lowered by folate and/or vitamin B12 supplementation; antioxidants might also be required for optimal reduction in neurovascular tissue. This report presents clinical and radiological findings from administering the antioxidant N-acetylcysteine together with B vitamins to cognitively impaired patients with hyperhomocysteinaemia. Methods: A case series (n = 7) performed in a semi-rural General Practice setting. Formal cognitive assessments were performed in five patients, and radiological assessments in one patient, before and after supplementation. Results and discussion: The addition of N-acetylcysteine resulted in subjective clinical improvement in all patients, and an objective improvement in cognitive scores in five patients. One patient had radiological evidence of halted disease progression over a twelve month period. Conclusion: N-acetylcysteine, together with B vitamin supplements, improves cognitive status in hyperhomocysteinaemic patients. Randomized controlled clinical trials are required to formall

sj-docx-1-jpx-10.1177_23743735231151767 - Supplemental material for Examining the Diagnosis and Treatment Experiences of People Living With Autoimmune Gastritis and Pernicious Anemia

Supplemental material, sj-docx-1-jpx-10.1177_23743735231151767 for Examining the Diagnosis and Treatment Experiences of People Living With Autoimmune Gastritis and Pernicious Anemia by Martine Cotton and Andrew McCaddon in Journal of Patient Experience</p

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). Phase two involved analysis of individual accounts via posts in online patient forums. We identified 6 main themes: the diagnosis journey, seeking treatment, patient-provider relationships, HRQOL, patient disempowerment, and the “expert patient.” Our findings confirm significant knowledge gaps concerning AIG/PA across the healthcare community. These have a cascading effect starting with delays in diagnosis and poor treatment protocols and often lead to complete withdrawal from care seeking. The establishment of standard consensus guidelines and improved clinical awareness should be urgently addressed. Interventions that better help patients understand their illness are also needed to improve psychological health. Without these changes disengagement from health systems, and poor health outcomes, will continue for this population group