Macro-B12 masking B12 deficiency

In clinical practice, the finding of an elevated serum B(12) concentration is often the consequence of supplementation with B(12) in either oral form or injections. Also, elevated serum B(12) may be associated with underlying disorders, like liver diseases or a (haematologic) malignancy. Only a few studies have shown that it may also be the consequence of complex formation of B(12)-vitamin binding proteins with immunoglobulins, the so-called macro-B(12). We describe a young woman who previously was diagnosed with B(12) deficiency, and in whom, after cessation of B(12) injection treatment, neurologic symptoms re-appeared, and despite this, repeatedly elevated serum B(12) concentrations above the upper limit of the assay were found. We demonstrated that this was caused by the presence of macro-B(12), which not only resulted in erroneous and longstanding elevated serum B(12), but also masked her underlying B(12) deficiency

The Origins of Salivary Vitamin A, Vitamin B12 and Vitamin D-Binding Proteins

Vitamin A- (retinol), vitamin B12- (haptocorrin) and vitamin D-binding proteins are the major circulatory transporters of their respective ligands; they are also constituents of the salivary proteome, the origins of which, remain unclear. The aim of this study was to explore how these proteins enter saliva and their relationship (if any) with vitamin status. Firstly, the three vitamin-binding proteins were quantified in resting whole mouth saliva and chewing-stimulated saliva from healthy donors (n = 10) to determine if they enter the mouth by salivary secretion or from the circulation. Secondly paired whole mouth saliva and serum samples were analysed from healthy donors (n = 14) to determine the relationships between the vitamin-binding proteins and vitamin status. Salivary output of all three vitamin-binding proteins studied increased when secretion was stimulated, suggesting they are secreted by the salivary glands. Whilst retinol-binding protein and haptocorrin were secreted by all major salivary glands, vitamin D-binding protein was restricted to the mucus glands. Salivary vitamin-binding protein concentrations were not found to be indicative of systemic vitamin status

Vitamin B12 and Folate Markers are Associated with Insulin Resistance During the Third Trimester of Pregnancy In South Asian Women, Living in the UK, With Gestational Diabetes and Normal Glucose Tolerance.

BACKGROUND: Gestational diabetes mellitus (GDM) can adversely affect the health of the developing foetus. Women of South Asian origin are particularly at risk of developing GDM. Insulin resistance (IR) contributes to the aetiology of GDM, and whilst studies have shown associations of vitamin B12 (B12) and folate status with GDM and IR, only a limited number of B12 and folate markers have been used. OBJECTIVE: To use a comprehensive panel of B12 and folate markers to examine their association with IR in pregnant women with diet-controlled GDM and normal glucose tolerance (NGT). METHODS: In this cross-sectional study, 59 British-Bangladeshi women (24 GDM and 35 NGT) with a mean age 29 years, BMI 26.7 kg/m2 and gestational age 33 weeks were recruited. Serum total B12, holotranscobalamin, folate, methylmalonic acid, plasma homocysteine and 5-methyltetrahydrofolate, and red cell folate (RCF) were measured along with other parameters. Independent sample t-test and chi-squared test were used to assess differences in markers between GDM and NGT women. Spearman's test was used to look for correlations. A simple multiple regression analysis was used to investigate if markers of B12 and folate status predicted IR, using the homeostatic model assessment of insulin resistance (HOMA-IR), adjusting for age, GDM status and BMI. RESULTS: There were no differences in concentrations of B12 and folate markers between GDM and NGT women. In Spearman's analysis HOMA-IR correlated negatively with total serum B12 (P < 0.001) and holotranscobalamin (P < 0.05), and positively with BMI (P < 0.001), blood pressure (P < 0.05) and triglycerides (P < 0.05) in all women. MMA did not correlate with any of the B12 markers. In regression analysis, total B12 (β = -0.622, P = 0.004), RCF (β = 0.387, P = 0.018) and BMI (β = 0.024, P < 0.001), were the significant predictors of HOMA-IR variance. CONCLUSIONS: Significant associations between markers of B12 and folate status with HOMA-IR were found during the third trimester in British-Bangladeshi women. B12 markers correlated poorly with each other

Vitamin B12 status in health and disease: a critical review. Diagnosis of deficiency and insufficiency – clinical and laboratory pitfalls

From Crossref journal articles via Jisc Publications RouterHistory: epub 2021-04-21, issued 2021-04-2

A genetic epidemiological study in British adults and older adults shows a high heritability of the combined indicator of vitamin B12 status (cB12) and connects B12 status with utilization of mitochondrial substrates and energy metabolism

Vitamin B12 deficiency is common among older adults. However, the most commonly used marker of deficiency, total serum vitamin B12 (B12), is not sensitive enough to diagnose true deficiency in a significant proportion of the population. The combined indicator of B12 status (cB12), formulated as a composite score of various biomarkers of vitamin B12 status (which also accounts for low folate status and age) has been shown to offer a more robust and powerful test to diagnose B12 deficiency. There are no epidemiological studies of cB12 variability in older adults. We carried out a twin study to characterize the relative contribution of heritable (h2) and environmental factors to the observed variability in cB12 score in an adult and older adult population (n=378). Furthermore, we tested for association between variability in cB12 and candidate polymorphisms and genes previously associated with B12 biomarker levels characterized in silico the mechanism linking the genetic variants and cB12 variability. We found the variability in cB12 and its constituents to be highly heritable (h2=55%–64%). The single nucleotide polymorphism rs291466 in HIBCH, previously associated with variation in MMA, was significantly associated with cB12 (R2=5%, P=5E-04). Furthermore, variants in MTRR, MMAB and MUT, underlying inborn errors of B12 metabolism, were nominally associated with variation in cB12. Pathway accompanied by expression quantitative trait loci analysis revealed that HIBCH rs291466 influences the concentration of MMA via the valine degradation pathway. Our study provides etiological insight into how B12 deficiency can manifest into impaired mitochondrial function through perturbations in mitochondrial “fuel” usage

Hyperhomocysteinemia and B-vitamin status after discontinuation of oral anticoagulation therapy in patients with a history of venous thromboembolism

Although hyperhomocysteinemia is an established risk factor for venous thromboembolism there is no consensus for routine determination of circulating homocysteine in the UK, either at the beginning or end of oral anticoagulation therapy. The purpose of this study was to evaluate the prevalence of hyperhomocysteinemia and its relationship to folate and vitamin B12 status in subjects with venous thromboembolism 4 weeks after discontinuation of warfarin therapy. In 78 consecutively recruited patients, plasma homocysteine was significantly higher (p &lt; 0.001) and red cell folate significantly lower (p = 0.03) than in controls. Plasma vitamin B12 was similar in both groups. Strikingly, 38.5% of patients had hyperhomocysteinemia (&gt; 15 micromol/l). Retrospective analysis revealed a significant positive association between plasma total homocysteine and duration of warfarin therapy (p &lt; 0.001) but a negative, though non-significant (p = 0.06), trend with warfarin dose. The results do not suggest any direct interaction between warfarin and plasma homocysteine but raise the possibility of reduced intake of a common food source of folate and vitamin K. One possibility is the shortage of green-leafy vegetables since patients are often advised to limit their intake of this major source of vitamin K. On the basis of this study we suggest that homocysteine screening should be carried out at the time that patients begin warfarin therapy.</p