A Portable Integrated Electrochemical Sensing System for On-Site Nitrite Detection in Food.

Ensuring an appropriate nitrite level in food is essential to keep the body healthy. However, it still remains a huge challenge to offer a portable and low-cost on-site food nitrite analysis without any expensive equipment. Herein, a portable integrated electrochemical sensing system (IESS) is developed to achieve rapid on-site nitrite detection in food, which is composed of a low-cost disposable microfluidic electrochemical patch for few-shot nitrite detection, and a reusable smartphone-assisted electronic device based on self-designed circuit board for signal processing and wireless transmission. The electrochemical patch based on MXene-Ti3C2Tx/multiwalled carbon nanotubes-cyanocobalamin (MXene/MWCNTs-VB12)-modified working electrode achieves high sensitivity of 10.533 µA mm-1 and low nitrite detection limit of 4.22 µm owing to strong electron transfer ability of hybrid MXene/MWCNTs conductive matrix and high nitrite selectivity of VB12 bionic enzyme-based ion-selective layer. Moreover, the portable IESS can rapidly collect pending testing samples through a microfluidic electrochemical patch within 1.0 s to conduct immediate nitrite analysis, and then wirelessly transmit data from a signal-processing electronic device to a smartphone via Bluetooth module. Consequently, this proposed portable IESS demonstrates rapid on-site nitrite analysis and wireless data transmission within one palm-sized electronic device, which would pave a new avenue in food safety and personal bespoke therapy.

meso-Bromination of cyano- and aquacobalamins facilitates their processing into Co(II)-species by glutathione.

Cyanocobalamin (CNCbl), a medicinal form of vitamin B12, is resistant to glutathione (GSH), and undergoes intracellular processing via reductive decyanation producing the Co(II)-form of Cbl (Cbl(II)) mediated by the CblC-protein. Alteration of the CblC-protein structure might inhibit CNCbl processing. Here, we showed that introducing a bromine atom to the C10-position of the CNCbl corrin ring facilitates its reaction with GSH leading to the formation of Cbl(II) and cyanide dissociation. In a neutral medium, the reaction between C10-Br-CNCbl and GSH proceeds via the complexation of the reactants further leading to dimethylbenzimidazole (DMBI) substitution and electron transfer from GSH to the Co(III)-ion. The reaction is accelerated upon the GSH thiol group deprotonation. The key factors explaining the higher reactivity of C10-Br-CNCbl compared with unmodified CNCbl towards GSH are increasing the electrode potential of CNCbl two-electron reduction upon meso-bromination and the substantial labilization of DMBI, which was shown by comparing their reactions with cyanide and the pKa values of DMBI protonation (pKa base-off). Aquacobalamin (H2OCbl) brominated at the C10-position of the corrin reacts with GSH to give Cbl(II) via GSH complexation and subsequent reaction of this complex with a second GSH molecule, whereas unmodified H2OCbl generates glutathionyl-Cbl, which is resistant to further reduction by GSH.

Developing a single-stage continuous process strategy for vitamin B12 production with Propionibacterium freudenreichii.

BACKGROUND: Vitamin B12 is a widely used compound in the feed and food, healthcare and medical industries that can only be produced by fermentation because of the complexity of its chemical synthesis. Besides, the use of Generally Recognized as Safe (GRAS) and Qualified Presumption of Safety (QPS) microorganisms, like Propionibacterium freudenreichii, especially non-GMO wild-type producers, are becoming an interesting alternative in markets where many final consumers have high health and ecological awareness. In this study, the production of vitamin B12 using the Propionibacterium freudenreichii NBRC 12391 wild-type strain was characterized and optimized in shake flasks before assessing several scale-up strategies. RESULTS: Initial results established that: (i) agitation during the early stages of the culture had an inhibitory effect on the volumetric production, (ii) 5,6-dimethylbenzimidazole (DMBI) addition was necessary for vitamin B12 production, and (iii) kinetics of vitamin B12 accumulation were dependent on the induction time when DMBI was added. When scaling up in a bioreactor, both batch and fed-batch bioprocesses proved unsuitable for obtaining high volumetric productivities mainly due to carbon source limitation and propionic acid inhibition, respectively. To overcome these drawbacks, an anaerobic single-phase continuous bioprocess strategy was developed. This culture strategy was maintained stable during more than 5 residence times in two independent cultures, resulting in 5.7-fold increase in terms of volumetric productivity compared to other scale-up strategies. CONCLUSION: Overall, compared to previously reported strategies aimed to reduce propionic acid inhibition, a less complex anaerobic single-phase continuous and more scalable bioprocess was achieved.

Cyanocobalamin-Modified Colistin-Hyaluronan Conjugates: Synthesis and Bioactivity.

Polymeric drug delivery systems enhance the biopharmaceutical properties of antibiotics by increasing their bioavailability, providing programmable and controlled-release properties, and reducing toxicity. In addition, drug delivery systems are a promising strategy to improve the intestinal permeability of various antimicrobial agents, including colistin (CT). This study describes the modification of conjugates based on CT and hyaluronic acid (HA) with cyanocobalamin (vitamin B12). Vitamin B12 was chosen as a targeting ligand because it has its own absorption pathway in the small intestine. The resulting polysaccharide conjugates contained 95 µg/mg vitamin B12 and the CT content was 335 µg/mg; they consisted of particles of two sizes, 98 and 702 nm, with a ζ-potential of approximately -25 mV. An in vitro release test at pH 7.4 and pH 5.2 showed an ultra-slow release of colistin of approximately 1% after 10 h. The modified B12 conjugates retained their antimicrobial activity at the level of pure CT (minimum inhibitory concentration was 2 µg/mL). The resulting delivery systems also reduced the nephrotoxicity of CT by 30-40% (HEK 293 cell line). In addition, the modification of B12 improved the intestinal permeability of CT, and the apparent permeability coefficient of HA-CT-B12 conjugates was 3.5 × 10-6 cm/s, corresponding to an in vivo intestinal absorption of 50-100%. Thus, vitamin-B12-modified conjugates based on CT and HA may be promising oral delivery systems with improved biopharmaceutical properties.

Production and characterization of cyanocobalamin-enriched tomato (Solanum lycopersicum) fruits grown using hydroponics.

BACKGROUND: Vitamin B12 is an essential vitamin that is absent in plant-derived foods such as fruits and vegetables. This can result in an increased risk of developing vitamin B12 deficiency in strict vegetarians (vegans). There are several studies that have aimed to enhance nutrients in food crops. The purpose of the present study was to fortify tomato fruits with vitamin B12 (or cyanocobalamin). RESULTS: Tomato plants were grown for 70 days in hydroponic culture pots and treated with 5 µm of cyanocobalamin on days 1-24 after the fruiting, and then harvested for tomato fruits. The ripened tomato fruits contained 4.0 × 10-7  g of cyanocobalamin per 100 g of dry weight and showed a significant increase in glucose and lycopene levels. CONCLUSION: The present study highlights the use of a cyanocobalamin-supplementation system for the production of B12 fortified tomato fruits that can help prevent B12 deficiency in vegetarians. © 2022 Society of Chemical Industry.

[The Redox-Catalytic Properties of Cobalamins].

Vitamin B12, or cobalamin, is essential for normal body function and is used in the therapies of different diseases. Vitamin B12 has anti-inflammatory and antioxidant properties that can play an important role in the prevention of some diseases. On the other hand, it has been reported that vitamin B12 in combination with such reducing agents as ascorbate (vitamin C) and thiols showed prooxidant activity. This review provides information on the roles of vitamin B12 in diseases accompanied by inflammation and oxidative stress and the effects of vitamin B12 administrated alone and in combinations with different reducing agents such as ascorbate and thiols on oxidative stress. In addition, the mechanisms of prooxidant actions of combinations of vitamin B12 with these reducing agents depending on the form of vitamin B12 (hydroxocobalamin and cyanocobalamin) are discussed. Understanding the mechanisms of prooxidant action of vitamin B12 is necessary for developing strategies for therapeutic administration of vitamin B12.

Unveiling the Chemical Diversity of the Deep-Sea Sponge Characella pachastrelloides.

Sponges are at the forefront of marine natural product research. In the deep sea, extreme conditions have driven secondary metabolite pathway evolution such that we might expect deep-sea sponges to yield a broad range of unique natural products. Here, we investigate the chemodiversity of a deep-sea tetractinellid sponge, Characella pachastrelloides, collected from ~800 m depth in Irish waters. First, we analyzed the MS/MS data obtained from fractions of this sponge on the GNPS public online platform to guide our exploration of its chemodiversity. Novel glycolipopeptides named characellides were previously isolated from the sponge and herein cyanocobalamin, a manufactured form of vitamin B12, not previously found in nature, was isolated in a large amount. We also identified several poecillastrins from the molecular network, a class of polyketide known to exhibit cytotoxicity. Light sensitivity prevented the isolation and characterization of these polyketides, but their presence was confirmed by characteristic NMR and MS signals. Finally, we isolated the new betaine 6-methylhercynine, which contains a unique methylation at C-2 of the imidazole ring. This compound showed potent cytotoxicity towards against HeLa (cervical cancer) cells.

Combined biotin, folic acid, and vitamin B12 supplementation given during the transition period to dairy cows: Part I. Effects on lactation performance, energy and protein metabolism, and hormones.

Biotin (B8), folates (B9), and vitamin B12 (B12) are involved and interrelated in several metabolic reactions related to energy and protein metabolism. We hypothesized that a low supply of one of the latter vitamins during the transition period would impair metabolic status. The purpose of this study was to evaluate the effect of B8 supplementation on the response of lactation performance and selected energy and protein metabolites and hormones to a combined supplementation of B9 and B12 given to periparturient dairy cows, from d -21 to 21 relative to calving. A total of 32 multiparous Holstein cows housed in tie stalls were randomly assigned, according to their previous 305-d milk yield, to 8 incomplete blocks of 4 treatments: (1) a 2-mL weekly i.m. injection of saline (0.9% NaCl; B8-/B9B12-); (2) 20 mg/d of dietary B8 (unprotected from ruminal degradation) and 2-mL weekly i.m. injection of 0.9% NaCl (B8+/B9B12-); (3) 2.6 g/d of dietary B9 (unprotected) and 2-mL weekly i.m. injection of 10 mg of B12 (B8-/B9B12+); and (4) 20 mg/d of dietary B8, 2.6 g/d of dietary B9, and weekly i.m. injection of 10 mg of B12 (B8+/B9B12+) in a 2 × 2 factorial arrangement. Milk yield and dry matter intake were obtained daily and milk components weekly. Blood samples were taken weekly from d -21 to calving and 3 times per week from calving to 21 d following parturition. Prepartum plasma concentrations of glucose, insulin, nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHB), and adiponectin were unaffected by treatments. Biotin, B9, and B12 supplements increased their respective concentrations in plasma and milk. Cows fed the B8 supplement tended to have lower dry matter intake, but only cows in B8+/B9B12- had greater plasma concentrations of NEFA compared with B8-/B9B12-. Milk and total solid yields were greater by 13.5 and 13.9%, respectively, for B8-/B9B12+ [45.5 (standard error, SE: 1.8) and 5.81 (0.22) kg/d, respectively] compared with B8-/B9B12- [40.1 (1.9) and 5.10 (0.23) kg/d, respectively], but these effects were suppressed when combined with the B8 supplement. Cows in the B8-/B9B12+ group had decreased plasma insulin and tended to have increased NEFA concentrations, but postpartum plasma concentrations of glucose, BHB, leptin, and adiponectin were not affected. These cows also mobilized more body fat reserves, as suggested by a tendency to increased plasma NEFA and more milk total solids compared with B8-/B9B12- cows. However, plasma concentrations of BHB and adiponectin were similar among treatments. This suggests that the B9 and B12 supplements enhanced efficiency of energy metabolism in early lactation cows. Folic acid and B12 supplementation increased postpartum plasma Cys and homocysteine concentrations but did not affect plasma Met concentration, suggesting an upregulation of the transsulfuration pathway. In summary, our results showed that, under the current experimental conditions, increasing B8 supply did not improve responses to the B9 and B12 supplementation.

Combined biotin, folic acid, and vitamin B12 supplementation given during the transition period to dairy cows: Part II. Effects on energy balance and fatty acid composition of colostrum and milk.

Biotin (B8), folate (B9), and vitamin B12 (B12) are involved in several metabolic reactions related to energy metabolism. We hypothesized that a low supply of one of these vitamins during the transition period would impair metabolic status. This study was undertaken to assess the interaction between B8 supplement and a supplementation of B9 and B12 regarding body weight (BW) change, dry matter intake, energy balance, and fatty acid (FA) compositions of colostrum and milk fat from d -21 to 21 relative to calving. Thirty-two multiparous Holstein cows housed in tie stalls were randomly assigned, according to their previous 305-d milk yield, to 8 incomplete blocks in 4 treatments: (1) a 2-mL weekly i.m. injection of saline (0.9% NaCl; B8-/B9B12-); (2) 20 mg/d of dietary B8 (unprotected from ruminal degradation) and 2-mL weekly i.m. injection of 0.9% NaCl (B8+/B9B12-); (3) 2.6 g/d of dietary B9 (unprotected) and 2-mL weekly i.m. injection of 10 mg of B12 (B8-/B9B12+); (4) 20 mg/d of dietary B8, 2.6 g/d of dietary B9, and 2-mL weekly i.m. injection of 10 mg of B12 (B8+/B9B12+) in a 2 × 2 factorial arrangement. Colostrum was sampled at first milking. and milk samples were collected weekly on 2 consecutive milkings and analyzed for FA composition. Body condition score and BW were recorded every week throughout the trial. Within the first 21 d of lactation, B8-/B9B12+ cows had an increased milk yield by 13.5% [45.5 (standard error, SE: 1.8) kg/d] compared with B8-/B9B12- cows [40.1 (SE: 1.9)], whereas B8 supplement had no effect. Even though body condition score was not affected by treatment, B8-/B9B12+ cows had greater BW loss by 24 kg, suggesting higher mobilization of body reserves. Accordingly, milk de novo FA decreased and preformed FA concentration increased in B8-/B9B12+ cows compared with B8-/B9B12- cows. In addition, cows in the B8+/B9B12- group had decreased milk de novo FA and increased preformed FA concentration compared with B8-/B9B12- cows. Treatment had no effect on colostrum preformed FA concentration. Supplemental B8 decreased concentrations of ruminal biohydrogenation intermediates and odd- and branched-chain FA in colostrum and milk fat. Moreover, postpartum dry matter intake for B8+ cows tended to be lower by 1.6 kg/d. These results could indicate ruminal perturbation caused by the B8 supplement, which was not protected from rumen degradation. Under the conditions of the current study, in contrast to B8+/B9B12- cows, B8-/B9B12+ cows produced more milk without increasing dry matter intake, although these cows had greater body fat mobilization in early lactation as suggested by the FA profile and BW loss.

Differences in the Formation of Reactive Oxygen Species and Their Cytotoxicity between Thiols Combined with Aqua- and Cyanocobalamins.

Cobalamin is an essential nutrient required for the normal functioning of cells. Its deficiency can lead to various pathological states. Hydroxocobalamin (HOCbl) and cyanocobalamin (CNCbl) are the forms of vitamin B12 that are most commonly used for supplementation. There is substantial evidence indicating that cobalamins can both suppress and promote oxidative stress; however, the mechanisms underlying these effects are poorly understood. Here, it was shown that the oxidation of thiols catalyzed by HOCbl and CNCbl is accompanied by reactive oxygen species (ROS) production and induces, under certain conditions, oxidative stress and cell death. The form of vitamin B12 and the structure of thiol play a decisive role in these processes. It was found that the mechanisms and kinetics of thiol oxidation catalyzed by HOCbl and CNCbl differ substantially. HOCbl increased the rate of oxidation of thiols to a greater extent than CNCbl, but quenched ROS in combination with certain thiols. Oxidation catalyzed by CNCbl was generally slower. Yet, the absence of ROS quenching resulted in their higher accumulation. The aforementioned results might explain a more pronounced cytotoxicity induced by combinations of thiols with CNCbl. On the whole, the data obtained provide a new insight into the redox processes in which cobalamins are involved. Our results might also be helpful in developing new approaches to the treatment of some cobalamin-responsive disorders in which oxidative stress is an important component.

Vitamin B12 in Foods, Food Supplements, and Medicines-A Review of Its Role and Properties with a Focus on Its Stability.

Vitamin B12, also known as the anti-pernicious anemia factor, is an essential micronutrient totally dependent on dietary sources that is commonly integrated with food supplements. Four vitamin B12 forms-cyanocobalamin, hydroxocobalamin, 5'-deoxyadenosylcobalamin, and methylcobalamin-are currently used for supplementation and, here, we provide an overview of their biochemical role, bioavailability, and efficacy in different dosage forms. Since the effective quantity of vitamin B12 depends on the stability of the different forms, we further provide a review of their main reactivity and stability under exposure to various environmental factors (e.g., temperature, pH, light) and the presence of some typical interacting compounds (oxidants, reductants, and other water-soluble vitamins). Further, we explore how the manufacturing process and storage affect B12 stability in foods, food supplements, and medicines and provide a summary of the data published to date on the content-related quality of vitamin B12 products on the market. We also provide an overview of the approaches toward their stabilization, including minimization of the destabilizing factors, addition of proper stabilizers, or application of some (innovative) technological processes that could be implemented and contribute to the production of high-quality vitamin B12 products.

Use of organic phosphorous butafosfan and vitamin B12 combination in transition dairy cows.

Phosphorus is critical for life and an indispensable element for biologically occurring organic molecules such as DNA, ATP, and phosphoproteomes. Butafosfan is a synthetically produced organic phosphorous (phosphonic acid) compound that contains 17.3% phosphorus. It does not belong to the group of biologically occurring organic phosphorous compounds. Butafosfan has been used in many animal species as a metabolic stimulant interfering with energy metabolism. Vitamin B12 (VB12) is a unique cobalt-containing vitamin. It functions as a cofactor for the enzymes methionine synthase and methyl-malonyl-CoA mutase. It is necessary for the conversion of propionate into succinyl-CoA in ruminants. A combination of butafosfan and VB12 (iBC) has been available for veterinary use since 1958 and the first publication appeared in the 1970s in cows. However, the first molecular biological studies about its mode of action appeared in early 2000s. Recent studies revealed that iBC has significant effects on carbohydrate and lipid metabolism. Investigations between 1970 and 1994 focused mainly on cows at risk of metabolic and reproductive disease in the dry period. Studies as of 2000 investigated its efficacy for the prevention and treatment of subclinical and secondary ketosis, adjunctive/supportive therapy for displaced abomasum operation, milk fever, improvement of postoperative rumen activity, uterus involution, and mastitis in transition dairy cows.

Response to a glucose tolerance test in early-lactation Holstein cows receiving a supplementation of biotin, folic acid, and vitamin B12.

The aim of the study was to evaluate glucose and insulin metabolism of cows receiving a supplementation of biotin (B8), folic acid (B9), and vitamin B12 (B12) during the transition period. According to a 2 × 2 factorial arrangement, 32 cows were randomly assigned to 9 incomplete blocks according to their previous 305-d milk yield. Within each block, cows were randomly assigned to 1 of the following levels of biotin from -27 to 28 d relative to the parturition: (1) no biotin supplement (B8-) or (2) 20 mg/d of dietary biotin (B8+). Within each level of biotin, the cows received either (1) 2-mL weekly intramuscular injections of saline 0.9% NaCl (B9B12-) or (2) 2.6 g/d of dietary folic acid and 2-mL weekly intramuscular injections of 10 mg of vitamin B12 (B9B12+). An intravenous glucose tolerance test was performed at 25 d in milk. Baseline plasma glucagon, glucose, and nonesterified fatty acid concentrations did not differ among treatments. For B9B12+ cows, baseline plasma insulin concentration and maximal glucose concentration after glucose administration were greater when also combined with biotin compared with no biotin combination, whereas there was no effect in B9B12- cows. There was no treatment effect on time to reach half-maximal glucose and insulin concentrations, glucose positive incremental area under the curve, and glucose and insulin clearance rates. Regarding insulin results, maximal plasma concentration and positive incremental area under the curve were respectively 51 and 74% greater for cows receiving the B8 supplement than for cows who did not. Moreover, plasma nonesterified fatty acid concentration nadir tended to be reached later for B8 cows. Insulin peak was reached earlier for cows in the group B9B12+ than cows in B9B12-, regardless of B8 supplementation. Under the current conditions, our results suggested that cows receiving a B8 supplement had a reduced insulin sensitivity in early lactation. Insulin response was faster for B9B12+ cows, but this was not translated into further improvements following the glucose administration challenge.

Effect of cyanocobalamin on oocyte maturation, in vitro fertilization, and embryo development in mice.

The aim of this study was to investigate the effect of cyanocobalamin supplementation on in vitro maturation (IVM), in vitro fertilization (IVF), and subsequent embryonic development competence to the blastocyst stage, and in vitro development of mouse 2-cell embryos. Cumulus cells were prepared from mouse cumulus-oocyte complexes (COCs) and incubated for 24 h in an in vitro culture (IVC) medium that contained different concentrations of cyanocobalamin (100, 200, 300 or 500 pM). We collected 2-cell embryos from superovulated NMRI mice and cultured them in the same concentrations of cyanocobalamin (100, 200, 300 or 500 pM). After 42 h of IVM, we observed significantly increased oocyte maturation in the 200 pM cyanocobalamin-treated group compared with the control group (P < 0.0001). Mature oocytes cultured in 200 pM cyanocobalamin were fertilized and cultured in IVC medium with cyanocobalamin (100, 200, 300 or 500 pM) during early embryogenesis. The matured oocytes that were cultured in 200 pM cyanocobalamin had significantly higher 2-cell development rates compared with the control oocytes (P < 0.01). Embryos obtained from in vitro mature oocytes and in vivo fertilized oocytes that were cultured in 200 pM cyanocobalamin had significantly greater frequencies of development to the blastocyst stage and a significant reduction in 2-cell blocked and degenerated embryos compared with the control embryos (P < 0.0001). Embryos derived from oocytes fertilized in vivo with 200 pM cyanocobalamin had a higher percentage of blastocyst embryos compared with those derived from matured oocytes cultured in vitro (P < 0.0001). These finding demonstrated that the effects of cyanocobalamin on oocyte maturation, fertilization, and embryo development in mice depend on the concentration used in IVC medium.

A pilot study comparing the pharmacokinetics of injectable cyanocobalamin and hydroxocobalamin associated with a trace mineral injection in cattle.

Injectable vitamin B12 (cobalamin) is traditionally used to prevent or treat vitamin B12 deficiencies in ruminants. Sheep and human studies have demonstrated the superiority of a single dose of hydroxocobalamin (OHB12) over cyanocobalamin (CNB12) in maintaining high levels of cobalamin in plasma and liver. However, limited data are available for cattle. The purpose of this study was to compare the pharmacokinetics of two forms of cobalamin-OHB12 and CNB12-as a single subcutaneous injection of 28 µg/kg BW at the same time of a trace mineral injection in six non-cobalt/B12 -deficient Holstein-Friesian steers. Plasma and liver samples were obtained to determine cobalamin concentration after treatment. Cyanocobalamin had lower retention in plasma and liver than OHB12 (p < .05). Cobalamin levels peaked in plasma by 8 h after treatment in both groups. However, OHB12 reached a higher peak compared to CNB12. Levels of cobalamin in plasma dropped closer to baseline levels 24 h after CNB12 treatment while OHB12 maintained higher concentrations. Hydroxocobalamin increased significantly hepatic concentration of cobalamin 28 days after treatment, while CNB12 did not increase liver levels relative to pre-treatment (p < .05). These results confirm that a single subcutaneous OHB12 injection increases the level of cobalamin in the blood in the first 24 hours, and this increase is maintained in the liver for at least 28 days.

Ligand-Tuning of the Stability of Pd(II) Conjugates with Cyanocobalamin.

Besides the well-known functions performed by vitamin B12 (CblCN) in biochemical processes of the human body, an increasing interest has been raised by the possibility of its use as a transmembrane drug carrier, capable, among others, of enhancing the accumulation of inorganic cytostatics in cancer cells. The present study was aimed at determining the possibility of the formation of CblCN conjugates with Pd(II) complexes. A key aspect was their stability, which we attempted to tune by appropriate choice of ligands. Syntheses, spectroscopic analysis of postreaction systems and kinetic investigations of conjugate formation reactions, have been complemented by DFT modelling. The obtained results showed that ligand charge, geometry and electron affinity may have a significant impact on carrier binding and release leading to the activation of the Pd(II) complex. This provides a rationale to expect that with appropriate composition of the coordination sphere, it will be possible to extend the spectrum of less toxic inorganic chemotherapeutics.

Lower Vitamin B12 Level at Multiple System Atrophy Diagnosis Is Associated With Shorter Survival.

BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative disorder from α-synuclein aggregation. in vitro studies suggest vitamin B12 may interrupt α-synuclein-mediated neurodegeneration. The objective of this study was to determine whether serum vitamin B12 level at MSA diagnosis is associated with survival. METHODS: One hundred eighty-two MSA patients evaluated at Mayo Clinic with vitamin B12 testing were studied. We determined the risk of death in relationship to serum vitamin B12 levels at MSA diagnosis, adjusting for predictors of poor survival. RESULTS: Predictors of shorter survival included vitamin B12 < 367 ng/L (HR, 1.8; 95% CI, 1.3-2.7), falls within 3 years of MSA diagnosis (HR, 1.6; 95% CI, 1.1-2.3), bladder symptoms (HR, 1.6; 95% CI, 1.0-2.6), urinary catheter requirement (HR, 1.7; 95% CI, 1.0-2.8), male sex (HR, 1.4; 95% CI, 1.0-2.0), and MSA-P subtype (HR, 1.5; 95% CI, 1.0-2.0). CONCLUSIONS: Low vitamin B12 levels are associated with shorter survival in MSA. Additional studies to explore this observation and assess the potential role of vitamin B12 as a modifiable survival factor are needed. © 2020 International Parkinson and Movement Disorder Society.

Relationship of Cerebrospinal Fluid Vitamin B12 Status Markers With Parkinson's Disease Progression.

BACKGROUND: Using blood specimens from untreated early Parkinson's disease (PD) patients from the DATATOP trial, we found that subjects in the low serum vitamin B12 tertile experienced greater annualized change in ambulatory capacity score, whereas those with moderately elevated (>15 µmol/L) total homocysteine had greater annualized declines in the Mini-Mental State Exam. METHODS: In this this study we sought to determine whether levels of cerebrospinal fluid (CSF) B12 markers were also associated with progression of PD. RESULTS: The annualized change in the UPDRS "walking" item, a component of the ambulatory capacity score, was worse in the low B12 tertile. No association with change in the Mini-Mental State Exam was seen for those 7% with the highest baseline CSF total homocysteine. CONCLUSIONS: In these untreated early-PD subjects, low CSF B12 predicted greater worsening of the UPDRS "walking" item, whereas CSF total homocysteine was not associated with progression of cognitive impairment. These findings extend and partially support our findings in serum. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Cross-sectional study of the effect of diet composition on plasma folate and vitamin B12 concentrations in Holstein cows in the United States and Canada.

The objective of this cross-sectional study was to assess the variability of plasma folate and vitamin B12 concentrations in lactating Holstein cows across the United States and Canada. We also evaluated the effect of diet composition and cow characteristics on folate and vitamin B12 plasma vitamin concentrations. A total of 22 and 24 US and Canadian dairy herds were enrolled, totaling 427 and 476 cows at 10 to 197 days in milk across all US and Canadian herds, respectively. Blood samples were taken to analyze plasma folate and vitamin B12 concentrations, and ingredients of the diet were collected to determine nutrient composition. To reduce the number of interdependent variables in the analysis of the association of diet composition with plasma vitamin concentrations, we conducted a principal component analysis. Plasma folate concentrations were lower for US cows [13.4 ng/mL, 95% confidence interval (CI): 12.7-14.2] than for Canadian cows (14.5 ng/mL, 95% CI: 13.7-15.2), and the opposite was observed for plasma vitamin B12 concentrations (US 206 pg/mL, 95% CI: 192-221; Canada 170 pg/mL, 95% CI: 159-181). The highest plasma concentrations of both vitamins were observed in the Northwest region of the United States (Oregon and Washington). Cows in California had the lowest plasma folate concentrations, and cows in Québec and New York State had the lowest plasma vitamin B12 concentrations. Plasma folate concentrations were higher for multiparous than for primiparous cows and plasma vitamin B12 concentrations progressively increased from parity 1 to 3 and higher. For both studied vitamins, plasma concentrations were lower at 0 to 55 than at 56 to 200 days in milk. Of 3 principal components, the one associated with dietary carbohydrates was significantly correlated with plasma folate and vitamin B12 concentrations. Indeed, plasma folate concentrations decreased with dietary fiber concentrations (i.e., neutral and acid detergent fibers and lignin) and increased with dietary nonfiber carbohydrate concentrations. We obtained the opposite results for plasma vitamin B12 concentrations. Both multivariable models explained 41% (pseudo-R2) of the variation in plasma folate and vitamin B12 concentrations. Information gathered in this study is the first step toward determining sources of variation in plasma folate and vitamin B12 concentrations, as well as the vitamin status of cows.

Short communication: Potential prediction of vitamin B12 concentration based on mid-infrared spectral data using Holstein Dairy Herd Improvement milk samples.

The purpose of this study was (1) to predict the quantitative concentration of vitamin B12 in milk using mid-infrared (MIR) spectrometry, and (2) to evaluate the potential of MIR spectra to discriminate different clusters of records based on their B12 concentration. Milk samples were collected from 4,340 Holstein cows between 3 and 592 d in milk and located in 100 herds. Samples were taken using in-line milk meters and divided into 2 aliquots: one for MIR spectrometry and the other for B12 concentration reference analyses by radioassay. Analyses were performed on 311 selected spectral wavelengths. A partial least squares regression model was built to quantify B12 concentration. Discriminant analysis was used to isolate B12 concentration clusters. A B12 concentration threshold was set at 442 ng/dL, because this represents the cutoff value for a 250-mL glass of milk to fulfill 46% of the daily vitamin B12 recommended dietary allowance for individuals 14 yr or older. For each analysis, records coming from two-thirds of herds were used to calibrate prediction equations, and the remaining records (one-third of herds for validation) were used to assess the prediction performance. In the case of discriminant analysis, validation sets were divided into evaluation sets (one-third of herds) to obtain alternate probability cutoffs and in test sets (two-thirds of herds) to validate equations. Spectral and B12 concentration outliers were identified by calculating standardized Mahalanobis distance and with a residual analysis, respectively (n = 3,154). Regarding quantitative B12 concentration, cross-validation and validation coefficients of determination averaged 0.51 and 0.46, respectively, which are relatively low, which would limit the potential use of the developed quantitative equations. In addition, root mean square errors of prediction of cross validation and validation sets averaged 88.9 and 94.7 ng/dL, respectively. Area under the receiver operating characteristic curve of test sets averaged 0.81 based on the 442 ng/dL threshold, which could be considered to represent good accuracy of classification. However, the false discovery rate averaged 36%. In summary, models predicting quantitative B12 concentration had low cross-validation and validation coefficients of determination, limiting their use, but the proposed discriminant models could be used to identify milk samples with naturally high B12.