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Effects of Folic Acid and Vitamin B12, Alone and in Combination on Cognitive Function and Inflammatory Factors in the Elderly with Mild Cognitive Impairment: A Single-blind Experimental Design.
Ma, F, Zhou, X, Li, Q, Zhao, J, Song, A, An, P, Du, Y, Xu, W, Huang, G
Current Alzheimer research. 2019;(7):622-632
Abstract
BACKGROUND Folate and vitamin B12 are well-known as essential nutrients that play key roles in the normal functions of the brain. Inflammatory processes play at least some role in the pathology of AD. Effective nutritional intervention approaches for improving cognitive deficits that reduce the peripheral inflammatory cytokine levels have garnered special attention. OBJECTIVE The present study aimed to determine whether supplementation with folic acid and vitamin B12, alone and in combination improves cognitive performance via reducing levels of peripheral inflammatory cytokines. METHODS 240 participants with MCI were randomly assigned in equal proportion to four treatment groups: folic acid alone, vitamin B12 alone, folic acid plus vitamin B12 or control without treatment daily for 6 months. Cognition was measured with WAIS-RC. The levels of inflammatory cytokines were measured using ELISA. Changes in cognitive function or blood biomarkers were analyzed by repeatedmeasure analysis of variance or mixed-effects models. This trial has been registered with trial number ChiCTR-ROC-16008305. RESULTS Compared with control group, the folic acid plus vitamin B12 group had significantly greater improvements in serum folate, homocysteine, vitamin B12 and IL-6, TNF-α, MCP-1. The folic acid plus vitamin B12 supplementation significantly changed the Full Scale IQ (effect size d = 0.169; P = 0.024), verbal IQ (effect size d = 0.146; P = 0.033), Information (d = 0.172; P = 0.019) and Digit Span (d = 0.187; P = 0.009) scores. Post hoc Turkey tests found that folic acid and vitamin B12 supplementation was significantly more effective than folic acid alone for all endpoints. CONCLUSIONS The combination of oral folic acid plus vitamin B12 in MCI elderly for six months can significantly improve cognitive performance and reduce the levels of inflammatory cytokines in human peripheral blood. The combination of folic acid and vitamin B12 was significantly superior to either folic acid or vitamin B12 alone.
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Inositol in preterm infants at risk for or having respiratory distress syndrome.
Howlett, A, Ohlsson, A, Plakkal, N
The Cochrane database of systematic reviews. 2019;(7):CD000366
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Abstract
BACKGROUND Inositol is an essential nutrient required by human cells in culture for growth and survival. Inositol promotes maturation of several components of surfactant and may play a critical role in fetal and early neonatal life. A drop in inositol levels in infants with respiratory distress syndrome (RDS) can be a sign that their illness will be severe. OBJECTIVES To assess the effectiveness and safety of supplementary inositol in preterm infants with or without respiratory distress syndrome (RDS) in reducing adverse neonatal outcomes including: death (neonatal and infant deaths), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC) and sepsis. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 11), MEDLINE via PubMed (1966 to 5 November 2018), Embase (1980 to 5 November 2018), and CINAHL (1982 to 5 November 2018). We searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCT) and quasi-randomised trials. SELECTION CRITERIA We included all randomised controlled trials of inositol supplementation of preterm infants compared with a control group that received a placebo or no intervention. Outcomes included neonatal death, infant death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC) and sepsis. DATA COLLECTION AND ANALYSIS The three review authors independently abstracted data on neonatal outcomes and resolved any disagreements through discussion and consensus. Outcomes were reported as typical risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH). We used the GRADE approach to assess the quality of evidence. MAIN RESULTS Six published randomised controlled trials were identified, with a total of 1177 infants. Study quality varied for the comparison 'Inositol supplementation to preterm infants (repeat doses in any amount and any duration of treatment) versus control' and interim analyses had occurred in several trials for the outcomes of interest. In this comparison, neonatal death was found to be significantly reduced (typical RR 0.53, 95% CI 0.31 to 0.91; typical RD -0.09, 95% CI -0.16 to -0.01; NNTB 11, 95% CI 6 to 100; 3 trials, 355 neonates). Infant deaths were not reduced (typical RR 0.89, 95% CI 0.71 to 1.13; typical RD -0.02, 95% CI -0.07 to 0.02; 5 trials, 1115 infants) (low-quality evidence). ROP stage 2 or higher or stage 3 or higher was not significantly reduced (typical RR 0.89, 95% CI 0.75 to 1.06; typical RD -0.04, 95% CI -0.10 to 0.02; 3 trials, 810 infants) (moderate-quality evidence). There were no significant findings for ROP (any stage), NEC (suspected or proven), sepsis, IVH grade greater than II (moderate-quality evidence). For the comparison 'Inositol supplementation IV initially followed by enteral administration (repeat doses of 80 mg/kg/day) in preterm infants born at less than 30 weeks' postmenstrual age (PMA) compared to placebo for preterm infants at risk for or having respiratory distress syndrome' the results from two studies of high quality were included (N = 760 neonates). Recruitment to the larger study (N = 638) was terminated because of a higher rate of deaths in the inositol group. We did not downgrade the quality of the study. The meta-analyses of the outcomes of 'Type 1 ROP or death before determination of ROP outcome using the adjudicated ROP outcome', 'Type 1 ROP including adjudicated ROP outcome', 'All-cause mortality (outcome collected through first event: death, hospital discharge, hospital transfer, or 120 days after birth)' and 'Severe IVH (grade 3 or 4)' did not show significant findings (moderate-quality evidence). There were no significant findings for the outcomes 'BPD or death by it prior to 37 weeks' postmenstrual age (outcomes collected through first event: death, hospital discharge, hospital transfer, or 120 days after birth)', 'Late onset sepsis (> 72 hours of age)', and 'Suspected or proven NEC' (high-quality evidence). AUTHORS' CONCLUSIONS Based on the evidence from randomised controlled trials to date, inositol supplementation does not result in important reductions in the rates of infant deaths, ROP stage 3 or higher, type 1 ROP, IVH grades 3 or 4, BPD, NEC, or sepsis. These conclusions are based mainly on two recent randomised controlled trials in neonates less than 30 weeks' postmenstrual age (N = 760), the most vulnerable population. Currently inositol supplementation should not be routinely instituted as part of the nutritional management of preterm infants with or without RDS. It is important that infants who have been enrolled in the trials included in this review are followed to assess any effects of inositol supplementation on long-term outcomes in childhood. We do not recommend any additional trials in neonates.
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High-Dose Vitamin B12 in Vasodilatory Shock: A Narrative Review.
Patel, JJ, Venegas-Borsellino, C, Willoughby, R, Freed, JK
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2019;(4):514-520
Abstract
Vasodilatory shock, as observed in postoperative states and sepsis, is hallmarked by low systemic vascular resistance and low blood pressure compensated by increased cardiac output. Gasotransmitters, such as nitric oxide and hydrogen sulfide, are implicated in the development and perpetuation of vasodilatory shock. Established therapies do not target these physiologic drivers of vasodilation. Due to their nontoxic and pleotropic effects, micronutrients are being used as rescue therapy in postoperative vasoplegia and septic shock. Here, we outline the pathophysiology of vasodilatory shock, describe the rationale for vitamin B12 (hydroxocobalamin) in vasodilatory shock, and identify literature evaluating its use in vasoplegic states.
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Interventions for infantile seborrhoeic dermatitis (including cradle cap).
Victoire, A, Magin, P, Coughlan, J, van Driel, ML
The Cochrane database of systematic reviews. 2019;(3):CD011380
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Abstract
BACKGROUND Infantile seborrhoeic dermatitis (ISD) is a chronic, inflammatory, scaling skin condition, which causes redness and a greasy scaling rash in infants and young children. It can last from weeks to months, but rarely years. When it occurs on the scalp, it is referred to as 'cradle cap'. While benign and self-limiting, irrelevant of its location on the body, it can distress parents. The effectiveness of commonly promoted treatments is unclear. OBJECTIVES To assess the effects of interventions for infantile seborrhoeic dermatitis in children from birth to 24 months of age. SEARCH METHODS We searched the following databases up to 22 May 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched trials registers and checked reference lists of included studies for further references to randomised controlled trials (RCTs). We searched for unpublished RCTs and grey literature via web search engines, and wrote to authors and pharmaceutical companies. SELECTION CRITERIA We included RCTs of interventions for ISD in children from birth up to 24 months who were clinically diagnosed by a healthcare practitioner with ISD or cradle cap. We allowed comparison of any treatment to no treatment or placebo, and the comparison of two or more treatments or a combination of treatments. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. The primary outcome measures were 'Change in severity score from baseline to end of study' and 'Percentage of infants treated who develop adverse effects or intolerance to treatment'. The secondary outcome was 'Improvement in quality of life (QoL) as reported by parents'. MAIN RESULTS We included six RCTs (one with a cross-over design) randomising 310 children and reporting outcomes for 297 children. Most participants were aged under seven months with only two participants aged over one year (seven and 12 years old); where specified, 60% were boys. In two studies, condition severity was mild to moderate; one study included two participants with severe ISD; the other studies did not describe baseline severity or described it as body surface area affected.The study setting was not always clear but likely a paediatric outpatient clinic in the following countries: Thailand, Israel, USA, France, and Australia.Two studies compared oral biotin (a B group vitamin) against placebo, two studies compared proprietary products against placebo cream or a control shampoo, and two studies compared topical corticosteroids against other products. The studies were generally short-term, between 10 and 42 days' duration; only one study followed the participants until resolution of the rash or eight months of age.We assessed the risk of bias as unclear for most aspects due to lack of reporting, but two of the studies were at high risk of performance and detection bias due to the appearance of the intervention, the trial design (open-label), or use of overlabelled tubes. Two trials had a high risk of attrition bias.All the results given below were based on very low-quality evidence. Treatment duration ranged from one week to three weeks.For the two trials comparing biotin versus placebo (n = 35), one did not report a measure of change in severity (only change in duration of rash) while the other did not report raw data (only 'no statistically significant difference'), measured at three weeks. Neither trial reported on adverse events.Two trials compared proprietary products against placebo (n = 160). One trial assessed change in severity via percentage success (96% of participants in non-steroidal cream Promiseb versus 92% in placebo), and reported no adverse events (both assessed at day 14). The other trial assessed change in severity via reduction in lesional score (surface area covered), finding better results for lactamide MEA gel (a moisturising agent) plus shampoo (81.4%) compared with shampoo only (70.2%; P = 0.0092). No adverse events were described, but signs of discomfort were similar in both groups (both assessed at day 21).In the comparison of topical steroids versus another product, change in severity was measured through evaluation of cure and body surface (n = 102).In one trial comparing hydrocortisone 1% lotion with licochalcone 0.025% lotion, there was no significant difference in participants cured (95.8% with hydrocortisone compared to 97.1% with licochalcone). One person in the licochalcone group developed more erythema, but there were no other adverse events (both outcomes assessed at day 14). In the trial comparing flumethasone pivalate 0.02% ointment versus eosin 2% aqueous solution, a reduction in body surface area affected was seen in both groups at day 10 (9% with corticosteroid versus 7% with aqueous solution), with all infants showing less than 10% involvement. There were no adverse events (both outcomes assessed at day 10).No studies measured QoL.We found no trials testing commonly used treatments such as mineral oils, salicylic acid, or antifungals. AUTHORS' CONCLUSIONS Our review identified only a limited number of studies investigating the effects of interventions for ISD in infants and young children. Unlike the reviews investigating the effects of treatments in adults, our results showed that there is uncertainty regarding the effectiveness and safety of studied treatments due to the very low-certainty evidence for all comparisons and outcomes.We assessed most bias domains as at unclear risk, but there was a high risk of bias for (mainly) performance, attrition, and detection bias. Evidence was limited further by imprecision (small studies, low number of events), indirectness (mainly with the outcomes assessed), and poor trial reporting. In most studies, the prognosis for the condition was favourable regardless of intervention but interpretation is limited by the very low-certainty evidence.Further research is needed with large, well-conducted, and well-reported intervention trials, particularly of interventions commonly recommended or used, such as emollients or shampoos and brushing, antifungals, or steroids. All studies should report standardised and validated relevant outcome measures, including adverse events, severity, and QoL, and they should be conducted in primary care settings where the majority of ISD is managed. Future trials should compare against placebo, no treatment, or standard care.
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Effects of maternal B12 supplementation on neurophysiological outcomes in children: a study protocol for an extended follow-up from a placebo randomised control trial in Bangalore, India.
Anand, S, Thomas, S, Jayachandra, M, Thomas, T, Strand, TA, Kurpad, AV, Duggan, CP, Srinivasan, K
BMJ open. 2019;(2):e024426
Abstract
INTRODUCTION Vitamin B12 deficiency is highly prevalent in pregnant Indian women. Neuropsychological tests have shown an association between low maternal vitamin B12 status and poorer cognitive performances in the offspring, although findings from these studies have been inconsistent. Vitamin B12 has an important role in the formation of myelin which is important for the transmission speed of neural impulses and myelination in the central nervous system has been linked to cognition. Assessing neurophysiological measures using event-related potentials (ERPs) in children may provide additional information on the effect of maternal vitamin B12 supplementation on offspring brain function. The study examines the effects of oral vitamin B12 daily supplements (50 µg) to pregnant Indian women on child neurophysiological function at 72 months. METHODS AND ANALYSIS We previously conducted a double-blind, placebo-controlled study to examine the effects of maternal vitamin B12 supplementation on cognitive outcomes in their offspring using the Bayley scales of infant development, third edition. In this extended follow-up of the same cohort of mother-child dyad, we propose to use ERP to study the long-term impact of maternal B12 supplementation on brain function in children at 72 months of age. We intend to use P300 and mismatch negativity (MMN) as measures of neurophysiological outcomes. The primary outcome of this study will be child neurophysiological measures (as measured by amplitude and latency of P300 and MMN) assessed at 72 months of age in children whose mothers received vitamin B12 compared with neurophysiological status of children whose mothers received placebo. ETHICS AND DISSEMINATION The study was approved by the Institutional Ethical Board of St. John's Medical College and the Harvard School of Public Health Human Subjects Committee. Results obtained will be presented at national and international research meetings and published in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER NCT00641862.
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Folate as an Adjuvant Therapy in Methanol Poisoning.
Theobald, J, Lim, C
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2019;(4):521-527
Abstract
Folate and its derivatives have long been used as an adjunctive treatment in methanol poisoning. Methanol is ultimately metabolized to formate, the toxic compound. The accumulation of formate can lead to acidemia, retinal damage, visual impairment, and death. Formate is converted to carbon dioxide and water in a folate-dependent manner, and folate is often given in cases of methanol poisoning. In this paper, the evidence for folate as an adjunctive therapy in methanol poisoning is reviewed.
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Vitamins in diet of patients with metabolic syndrome.
Kodentsova, VM, Risnik, DV, Sharafetdinov, KK, Nikityuk, DB
Terapevticheskii arkhiv. 2019;(2):118-125
Abstract
Aim - analysis of data on the role of vitamin and carotenoid deficiency in the development of metabolic syndrome (MS), the consumption of individual vitamins and vitamin supplements, as well as estimation of the effectiveness of the use of vitamins in patients with MS. A review of the existing literature has been carried out in the databases of RINC, CyberLeninka, Google Scholar, Pubmed. The lack of vitamins is a risk factor for MS and its components. The diet of people with MS is characterized by excessive caloric content and at the same time contains an inadequate amount of most vitamins. The most frequent in patients with MS is the deficiency (blood level) of vitamin D, E, B vitamins, carotenoids. Among patients with MS, individuals with a reduced concentration of vitamins in the blood plasma are often found. In turn, among those with a deficiency of vitamins, MS is more often found. Low concentrations of 25(OH)D in the serum are associated with an increased risk of MS. An inverse association between the concentration of the hormonal form of vitamin 1.25(OH)2D3 in the serum and the development of MC has been found. In patients with MS, the α-tocopherol concentration associated with lipids is lower than in healthy individuals, and γ-tocopherol, on the contrary, is higher. Taking high doses of one of the vitamin E homologues shifts the balance between tocopherols in the blood plasma. Sufficient supply of the body with all vitamins involved in the formation of metabolically active forms of vitamins (D, B6, PP) is a necessary condition for the exercise of these biological functions by these vitamins. The lack of vitamins is a risk factor for MS and its components. Enrichment of the diet of patients with MS should be considered as a necessary favorable background for its treatment. Since the body has functional connections between vitamins, it is advisable to use not individual vitamins, but their complexes.
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Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta-analysis.
Yang, W, Cai, X, Wu, H, Ji, L
Journal of diabetes. 2019;(9):729-743
Abstract
BACKGROUND Metformin is first-line therapy for patients with diabetes. However, it may lower vitamin B12 concentrations, which could have hematological or neurological implications. This meta-analyses reviewed all available studies on associations between metformin use and vitamin B12 levels, anemia, and neuropathy in diabetic patients. METHODS PubMed, Web of Knowledge, Cochrane Library, and Embase were searched to identify all relevant studies published in English prior to March 2018. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes and pooled mean differences (MDs) and 95% CIs were calculated for continuous outcomes. RESULTS Thirty-one studies were included in the meta-analyses. Compared with diabetic patients not taking metformin, patients taking metformin had a significantly higher risk of vitamin B12 deficiency (RR 2.09; 95% CI 1.49, 2.93; P < 0.0001; I2 = 64%) and significantly lower serum vitamin B12 concentrations (MD -63.70; 95% CI -74.35, -53.05] pM; P < 0.00001; I2 = 87%), which depended on dose and duration of treatment. Metformin use was also associated with significantly greater percentage decrease in serum vitamin B12 concentrations from baseline in diabetic patients (MD -14.68%; 95% CI -17.98%, -11.39%; P < 0.00001; I2 = 33%). Analyses revealed no significant association between metformin use and the prevalence of anemia or neuropathy. CONCLUSIONS Metformin use led to significantly lowered vitamin B12 concentrations and significantly higher risk of vitamin B12 deficiency in diabetic patients. More quality studies are needed to explore the associations between metformin use and anemia and neuropathy in these patients. Annual vitamin B12 assessment in diabetic patients taking metformin is recommended.
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Uneven distribution of cobamide biosynthesis and dependence in bacteria predicted by comparative genomics.
Shelton, AN, Seth, EC, Mok, KC, Han, AW, Jackson, SN, Haft, DR, Taga, ME
The ISME journal. 2019;(3):789-804
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The vitamin B12 family of cofactors known as cobamides are essential for a variety of microbial metabolisms. We used comparative genomics of 11,000 bacterial species to analyze the extent and distribution of cobamide production and use across bacteria. We find that 86% of bacteria in this data set have at least one of 15 cobamide-dependent enzyme families, but only 37% are predicted to synthesize cobamides de novo. The distribution of cobamide biosynthesis and use vary at the phylum level. While 57% of Actinobacteria are predicted to biosynthesize cobamides, only 0.6% of Bacteroidetes have the complete pathway, yet 96% of species in this phylum have cobamide-dependent enzymes. The form of cobamide produced by the bacteria could be predicted for 58% of cobamide-producing species, based on the presence of signature lower ligand biosynthesis and attachment genes. Our predictions also revealed that 17% of bacteria have partial biosynthetic pathways, yet have the potential to salvage cobamide precursors. Bacteria with a partial cobamide biosynthesis pathway include those in a newly defined, experimentally verified category of bacteria lacking the first step in the biosynthesis pathway. These predictions highlight the importance of cobamide and cobamide precursor salvaging as examples of nutritional dependencies in bacteria.
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Differential insulin response to oral glucose tolerance test (OGTT) in overweight/obese polycystic ovary syndrome patients undergoing to myo-inositol (MYO), alpha lipoic acid (ALA), or combination of both.
Genazzani, AD, Prati, A, Marchini, F, Petrillo, T, Napolitano, A, Simoncini, T
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2019;(12):1088-1093
Abstract
Polycystic ovary syndrome is characterized by several endocrine impairments, insulin resistance and hyperinsulinemia. We aimed to evaluate the effects of myo-inositol (MYO), alpha-lipoic acid (ALA) and a combination of both. Setting: retrospective study. Ninety overweight/obese patients were considered. Presence or absence of first grade diabetic relatives was checked. Patients were administered MYO (1 g/die per os), ALA (400 mg/die per os), MYO (1 gr/die) + ALA (400 mg/die) per os. Only 76 out of 90 patients completed the 12 weeks of treatment. Patients were evaluated before and after the treatment interval for LH, FSH, E2 (estradiol), A (androstenedione), T (testosterone) plasma levels, oral glucose tolerance test (OGTT). All treatments demonstrated specific positive effects: MYO modulated more hormonal profiles and OGTT in polycystic ovary syndrome (PCOS) with no familial diabetes, ALA improved insulin response to OGTT and metabolic parameters in all patients with no effects on reproductive hormones, MYO + ALA improved hormonal and metabolic aspects and insulin response to OGTT in all patients. Presence of familial diabetes is a relevant clinical aspect. MYO is less effective when familial diabetes is present, ALA improved only metabolic aspects while MYO + ALA was effective on all PCOS patients independently from familial diabetes.