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What you need to knowVitamin B12 deficiency may present with non-specific symptoms, but it warrants urgent evaluation and treatment when haematological or neurological features are presentCauses for B12 deficiency include nutritional, drug induced, and gastrointestinal; autoimmune pernicious anaemia is relatively rareConsider specialist referral if there is no obvious cause for B12 deficiency, if it is refractory to treatment, or if neurological features or persistent macrocytic anaemia is presentParenteral B12 replacement is indicated if urgent treatment is required, if gastrointestinal malabsorption is suspected, and in elderly peopleOral B12 replacement may be a suitable alternative in asymptomatic individuals with dietary B12 deficiency

Obesity is a worldwide epidemic responsible for 5% of global mortality. The risks of developing other key metabolic disorders like diabetes, hypertension and cardiovascular diseases (CVDs) are increased by obesity, causing a great public health concern. A series of epidemiological studies and animal models have demonstrated a relationship between the importance of vitamin B12 (B12) and various components of metabolic syndrome. High prevalence of low B12 levels has been shown in European (27%) and South Indian (32%) patients with type 2 diabetes (T2D). A longitudinal prospective study in pregnant women has shown that low B12 status could independently predict the development of T2D five years after delivery. Likewise, children born to mothers with low B12 levels may have excess fat accumulation which in turn can result in higher insulin resistance and risk of T2D and/or CVD in adulthood. However, the independent role of B12 on lipid metabolism, a key risk factor for cardiometabolic disorders, has not been explored to a larger extent. In this review, we provide evidence from pre-clinical and clinical studies on the role of low B12 status on lipid metabolism and insights on the possible epigenetic mechanisms including DNA methylation, micro-RNA and histone modifications. Although, there are only a few association studies of B12 on epigenetic mechanisms, novel approaches to understand the functional changes caused by these epigenetic markers are warranted.

A major gap is the absence of recommendations to address the high incidence and prevalence of health and social care needs that can persist for months or even years after birth, even among apparently healthy women.2 Instead, recommendations reflect evidence derived to fit a traditional model of postnatal care that has been described as “not fit for purpose”.6 Maternal recommendations do not tackle longer-term health impacts of prepregnancy and pregnancy complications, despite consequences for future maternal and child health.6 All women would benefit from post-partum assessment of risk for future metabolic and cardiovascular diseases to ensure those who have missed antenatal screening are identified. Given the global burden of chronic maternal morbidity and impacts on infant health,7 with more than 90% of this burden expected in low-income and middle-income countries (LMICs), these are important omissions. Since maternal morbidity can persist beyond the first 6 weeks after birth8 (the standard definition of the postnatal period), contacts with health workers at child health clinics within the first year of birth could be used for treatment of anaemia, screening and treatment of reproductive tract infections and cervical cancer, and provision of family planning counselling and contraception. Structured pelvic floor muscle exercises in early pregnancy for continent women could prevent onset of urinary incontinence in late pregnancy and up to 6 months postnatally, an intervention of potential benefit for millions of women.12 A recommendation that women should be screened for post-partum depression and anxiety with appropriate diagnostic and management services for those who screen positive requires considerable system change and clinical training to implement, with ongoing evaluation of benefit.

CONTEXT:Low vitamin B12 during pregnancy is associated with higher maternal obesity, insulin resistance (IR), and gestational diabetes mellitus. B12 is a key cofactor in one-carbon metabolism. OBJECTIVE:We hypothesize that B12 plays a role in epigenetic regulation by altering circulating microRNAs (miRs) during adipocyte differentiation and results in an adverse metabolic phenotype. DESIGN, SETTINGS, AND MAIN OUTCOME MEASURE:Human preadipocyte cell line (Chub-S7) was differentiated in various B12 concentrationscontrol (500 nM), low B12 (0.15 nM), and no B12 (0 nM). Maternal blood samples (n = 91) and subcutaneous adipose tissue (SAT) (n = 42) were collected at delivery. Serum B12, folate, lipids, plasma one-carbon metabolites, miR profiling, miR expression, and gene expression were measured. RESULTS:Our in vitro model demonstrated that adipocytes in B12-deficient conditions accumulated more lipids, had higher triglyceride levels, and increased gene expression of adipogenesis and lipogenesis. MiR array screening revealed differential expression of 133 miRs involving several metabolic pathways (adjusted P < 0.05). Altered miR expressions were observed in 12 miRs related to adipocyte differentiation and function in adipocytes. Validation of these data in pregnant women with low B12 confirmed increased expression of adipogenic and lipogenic genes and altered miRs in SAT and altered levels of 11 of the 12 miRs in circulation. After adjustment for other possible confounders, multiple regression analysis revealed an independent association of B12 with body mass index (β−0.264; 95% confidence interval, −0.469 to −0.058; P = 0.013) and was mediated by four circulating miRs targeting peroxisome proliferator-activated receptor γ and IR. CONCLUSIONS:Low B12 levels in pregnancy alter adipose-derived circulating miRs, which may mediate an adipogenic and IR phenotype, leading to obesity.

Background: Prolonged metformin treatment decreases vitamin B12 (B12) levels, whereas low B12 is associated with dyslipidaemia. Some studies have reported that metformin has no effect on intrahepatic triglyceride (TG) levels. Although AMP-activated protein kinase (AMPK) activation via adiponectin lowers hepatic TG content, its role in B12 deficiency and metformin has not been explored. We investigated whether low B12 impairs the beneficial effect of metformin on hepatic lipid metabolism via the AMPK-adiponectin axis. Methods: HepG2 was cultured using custom-made B12-deficient Eagle’s Minimal Essential Medium (EMEM) in different B12-medium concentrations, followed by a 24-h metformin/adiponectin treatment. Gene and protein expressions and total intracellular TG were measured, and radiochemical analysis of TG synthesis and seahorse mitochondria stress assay were undertaken. Results: With low B12, total intracellular TG and synthesized radiolabelled TG were increased. Regulators of lipogenesis, cholesterol and genes regulating fatty acids (FAs; TG; and cholesterol biosynthesis were increased. FA oxidation (FAO) and mitochondrial function were decreased, with decreased pAMPKα and pACC levels. Following metformin treatment in hepatocytes with low B12, the gene and protein expression of the above targets were not alleviated. However, in the presence of adiponectin, intrahepatic lipid levels with low B12 decreased via upregulated pAMPKα and pACC levels. Again, combined adiponectin and metformin treatment ameliorated the low B12 effect and resulted in increased pAMPKα and pACC, with a subsequent reduction in lipogenesis, increased FAO and mitochondrion function. Conclusions: Adiponectin co-administration with metformin induced a higher intrahepatic lipid-lowering effect. Overall, we emphasize the potential therapeutic implications for hepatic AMPK activation via adiponectin for a clinical condition associated with B12 deficiency and metformin treatment.

The Women's Health Strategy, launched in England in 2022, aims to improve maternal and child health outcomes, ensuring that women's health services are tailored to their individual needs throughout their lives - a welcome and promising step in the right direction.' Women now often enter pregnancy with advanced maternal age, with higher rates of obesity, cardiometabolic issues and mental health conditions. Anita Banerjee Women's Health Services, Guy's and St Thomas\" NHS Foundation Trust, London, UK Department of Women and Children's Health, School of Life Course and Population Sciences, King's College, London, UK Ponnusamy Saravanan· Diabetes, Endocrinology and Metabolism, George Eliot Hospital NHS Trust, Nuneaton, UK Warwick Applied Health, Warwick Medical School and Centre for Global Health, University of Warwick, Coventry, UK *Corresponding author.