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Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B12 in combination on progression to severe outcomes in older patients with coronavirus (COVID-19).
Tan, CW, Ho, LP, Kalimuddin, S, Cherng, BPZ, Teh, YE, Thien, SY, Wong, HM, Tern, PJW, Chandran, M, Chay, JWM, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2020;:111017
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Abstract
OBJECTIVES The aim of this study was to determine clinical outcomes of older patients with coronavirus (COVID-19) who received a combination of vitamin D, magnesium, and vitamin B12 (DMB) compared with those who did not. We hypothesized that fewer patients administered this combination would require oxygen therapy, intensive care support, or a combination of both than those who did not. METHODS This was a cohort observational study of all consecutive hospitalized patients ≥50 y of age with COVID-19 in a tertiary academic hospital. Before April 6, 2020, no patients received the (DMB) combination. After this date, patients were administered 1000 IU/d oral vitamin D3, 150 mg/d oral magnesium, and 500 mcg/d oral vitamin B12 upon admission if they did not require oxygen therapy. Primary outcome was deterioration leading to any form of oxygen therapy, intensive care support, or both. RESULTS Between January 15 and April 15, 2020, we identified 43 consecutive patients ≥50 y of age with COVID-19. Seventeen patients received DMB before onset of primary outcome and 26 patients did not. Baseline demographic characteristics between the two groups were significantly different by age. In univariate analysis, age and hypertension had a significant influence on outcome. After adjusting for age or hypertension separately in a multivariate analysis, the intervention group retained protective significance. Fewer treated patients than controls required initiation of oxygen therapy during hospitalization (17.6 vs 61.5%, P = 0.006). DMB exposure was associated with odds ratios of 0.13 (95% confidence interval [CI], 0.03-0.59) and 0.20 (95% CI, 0.04-0.93) for oxygen therapy, intensive care support, or both on univariate and multivariate analyses, respectively. CONCLUSIONS A vitamin D / magnesium / vitamin B12 combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both. This study supports further larger randomized controlled trials to ascertain the full benefit of this combination in ameliorating the severity of COVID-19.
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Infantile Tremor Syndrome or a Neurocutaneous Infantile B12 Deficiency (NIB) Syndrome?
Chaudhary, H, Verma, S, Bhatia, P, Vaidya, PC, Singhi, P, Sankhyan, N
Indian journal of pediatrics. 2020;(3):179-184
Abstract
OBJECTIVES To prospectively study the clinical and developmental profile; hematological profile and the B-12 status using multiple parameters in children with Infantile tremor syndrome (ITS). METHODS In this observational study (NCT02762682) (July 2015 through December 2016) children (and their mothers) with a clinical diagnosis of ITS were evaluated clinically; and development was assessed by CAPUTE scales. A complete blood count (CBC); peripheral blood smear examination; markers of vitamin B12 status (serum B12, homocysteine, folate); acylcarnitines [using Tandem mass spectrometry (TMS)] and urine methylmalonic acid (MMA) [Gas chromatography mass spectrometry (GCMS)] were estimated. A control group of children and their mothers were sampled for comparison. RESULTS A total of 286 individuals were enrolled for this study. One-hundred-ten children with ITS were screened and 92 (20 with tremors; age 12.7 ± 5 mo, 61 boys) children and their mothers were enrolled. Fifty-one children and their mothers were enrolled as controls. The median clinical linguistic & auditory milestone-developmental quotient (CLAM-DQ) was 32 (IQR 20.6-45.5) and median cognitive adaptive test-developmental quotient (CAT-DQ) was 36.2 (IQR 18.7-49.0). All babies except 9 (ovo-veg) had vegetarian mothers. Head circumference below 2 SD (WHO standards) was seen in 84% and below 3 SD in 58%. The CBC findings were; Hb- 8.3 ± 1.6 g/dl, Thrombocytopenia-29 (32%), mean corpuscular volume (MCV)- 92.2 ± 13.4, MCV- more than 95 fL-38(42%), Red cell distribution width (RDW)- 21.6 ± 6.5, and macrocytes on peripheral smear in 68%. In 89 (97%) out of 92 children had laboratory features of deficient B12 status. Two-thirds of the mothers also had evidence of B12 deficiency. CONCLUSIONS ITS is, in all likelihood is a consequence of vitamin B12 defeciency. It has a significant impact on head growth and development of affected infants.
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The impact of homocysteine, B12, and D vitamins levels on functional neurocognitive performance in HIV-positive subjects.
Falasca, K, Di Nicola, M, Di Martino, G, Ucciferri, C, Vignale, F, Occhionero, A, Vecchiet, J
BMC infectious diseases. 2019;(1):105
Abstract
BACKGROUND The correlation among high levels of total homocysteine, low levels of B12vitamin, and neurocognitive impairment in HIV negative patients has been the main research topic in some of the latest reviews. The aim of this study was to examine if the alteration of homocysteine, B12 vitamin, and D vitamins plasma levels was present in HIV-positive, and their relationship with cognitive function. METHODS 57 HIV infected were enrolled and underwent the serum measurement of homocysteine, B12, and D vitamins. The neurocognitive evaluation investigated 5 cognitive domains, through a neuropsychological battery test RESULTS Homocysteine was found to be elevated in 70.2% of cases, B12 vitamin mean levels were low in 8 participants (14.0%), and 8 patients had D hypovitaminosis (14.0%). Abnormal homocysteine levels were associated with worse performance of verbal fluency (p = 0.003) and worse executive function (Stroop E test p = 0.040). The 25-OH D hypovitaminosis was associated with worse performances in executive functions in three different tests: Stroop E (p = 0.049), Trail B (p = 0.035), and Wais Digit Span (p = 0.042). Pathological levels of B12 Vitamin were also associated to worse performances in executive functions (Trail B Test and Wais Digit Span respectively p = 0.002 and 0.029) and with a lower speed in psychomotor processing (Peg Board Test on dominant hand, p = 0.014). CONCLUSIONS In this study serum homocysteine, B12, and D vitamin levels are associated with neurocognitive performances; in fact low performance neurocognitive was correlated with hyperhomocysteine and low B12vitamin, and D vitamin levels. Evidence of the alteration of these parameters could facilitate the early identification of a neurocognitive impairment.
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Association Between Cognitive Impairment and Vitamin B12, Folate, and Homocysteine Status in Elderly Adults: A Retrospective Study.
Baroni, L, Bonetto, C, Rizzo, G, Bertola, C, Caberlotto, L, Bazzerla, G
Journal of Alzheimer's disease : JAD. 2019;(2):443-453
Abstract
BACKGROUND Cognitive disorders in old age have a serious impact on the health and social aspects of patients and their families. OBJECTIVE The scope of this paper is to explore the role of cobalamin and folate that has been linked to cognitive decline, not only as a deficiency state depending on malnutrition, but also a determinant in cognitive impairment. METHODS A 6-year observational, retrospective study was conducted by collecting the routine blood analyses and cognitive screening scores of patients aged 60 years or older, followed at our Centre for the Diagnosis and Treatment of Cognitive Disorders. RESULTS In a linear regression with a multi-vitamin model, higher folate concentrations were correlated with better cognitive performances through MMSE score, even after correction for sex, age, and years of education (beta = 0.144, p = 0.001). Estimated MMSE marginal means for folate versus homocysteine showed that folate deficiency was associated with worse cognitive performances, with a more severe cognitive impairment when hyperhomocysteinemia was present. CONCLUSION The assessment of B-vitamin status among elderly adults can contribute to an economic and practical approach to the prevention and management of cognitive decline. Future studies focused to define optimal vitamin status are warranted.
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Higher maternal plasma folate, vitamin B12 and homocysteine levels in women with preeclampsia.
Pisal, H, Dangat, K, Randhir, K, Khaire, A, Mehendale, S, Joshi, S
Journal of human hypertension. 2019;(5):393-399
Abstract
Micronutrients like vitamin B12 and folate play an important role in nucleic acid metabolism, cell growth, and are important determinants of fetal growth. The present study examined the levels of maternal and cord plasma folate, vitamin B12, homocysteine, and their association with birth outcome in women with preeclampsia (PE). This study includes 450 normotensive control (NC) and 350 women with PE. PE women were further classified into women delivering at term (n = 224) and preterm (n = 126). Maternal and cord blood was collected at delivery. The levels of maternal vitamin B12 (p < 0.05), folate (p < 0.01), and homocysteine (p < 0.01) were higher in the PE group as compared to the NC group. Maternal folate levels were higher in both term and preterm groups, while vitamin B12 levels were higher only in the preterm group as compared to NC group. In contrast, homocysteine was higher only in the term PE group. Similar changes were also observed in the cord plasma. There was a positive association of maternal plasma homocysteine with systolic (r = 0.151, p = 0.000, n = 578) and diastolic blood pressure (r = 0.213, p = 0.000, n = 578) in the whole cohort. A negative association of maternal folate with systolic blood pressure (r = -0.105, p = 0.048, n = 352) while a positive association with baby weight in the NC group (r = 0.116, p = 0.029, n = 352). The present study suggests that maternal and cord micronutrient levels are altered in women with PE.
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An observational study of vitamin b12 levels and peripheral neuropathy profile in patients of diabetes mellitus on metformin therapy.
Gupta, K, Jain, A, Rohatgi, A
Diabetes & metabolic syndrome. 2018;(1):51-58
Abstract
METHODS A descriptive, observational study was completed in a tertiary care hospital between November 2014 and March 2016. Fifty consecutive patients of Type 2-Diabetes Mellitus who had been on metformin therapy for at least three months were included in our study. Several Parameters were compared with vitamin B12 levels and severity of peripheral neuropathy (using Toronto Clinical Scoring System (TCSS) and Nerve Conduction Velocity). These included the duration of diabetes, duration of metformin usage, dietary history, and HbA1c levels. Definite B12 deficiency was defined as B12<150pg/ml and possible B12 deficiency as <220pg/ml. RESULTS In our study, we found a negative correlation between duration of metformin use and Vitamin B12 levels(r=-0.40). The mean Vitamin B12 levels seen in our study was 212.3pg/mL. There is a positive correlation between the duration of metformin therapy and peripheral neuropathy (r=0.40). The mean TCSS score was 6.8. The percentage of patients with mild neuropathy was 28%, with moderate neuropathy was 20% and severe neuropathy in 12% of the patients. The average duration of metformin use in patients without peripheral neuropathy was 5.5yrs whereas the average length of metformin use in patients with peripheral neuropathy was 10.4 yrs. CONCLUSION Patients on long-term metformin therapy are at a high risk for Vitamin B12 deficiency and peripheral neuropathy. Interval Screening for peripheral neuropathy is recommended for patients on metformin even if Vitamin B12 levels appear to be normal.
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Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis.
Yang, GT, Zhao, HY, Kong, Y, Sun, NN, Dong, AQ
World journal of gastroenterology. 2018;(12):1343-1352
Abstract
AIM: To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori (H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve (R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12 deficiency may be considered in patients with CAG. Furthermore, the timely supplementation of vitamin B12 during the clinical treatment of CAG can reduce or prevent peripheral nervous system lesions.
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Early pregnancy folate-cobalamin interactions and their effects on cobalamin status and hematologic variables throughout pregnancy.
Solé-Navais, P, Salat-Batlle, J, Cavallé-Busquets, P, Fernandez-Ballart, J, Ueland, PM, Ballesteros, M, Ornosa-Martín, G, Inglès-Puig, M, Colomina, JM, Murphy, MM
The American journal of clinical nutrition. 2018;(2):173-182
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Abstract
BACKGROUND Periconception folic acid supplementation is widespread, but how it interacts with cobalamin status is rarely considered. OBJECTIVE The aim of this study was to investigate whether first-trimester folate-cobalamin interactions affect pregnancy cobalamin status, hematologic variables, and pregnancy outcomes. DESIGN In the longitudinal Reus-Tarragona Birth Cohort study from <12 gestational weeks throughout pregnancy, fasting plasma and red blood cell (RBC) folate, plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), hemoglobin, mean cell volume (MCV), postglucose-load serum glucose, gestational hypertension, gestational age at birth, and birth weight were recorded in 563 participants. RESULTS The highest plasma folate concentrations occurred in the first trimester when folic acid supplement use was extensive. Supplementation beyond the first trimester interacted with time of pregnancy on plasma folate, RBC folate, and tHcy throughout pregnancy (P-interaction <0.001). Plasma folate and RBC folate were higher and tHcy was lower in continued supplement users than in nonusers. Elevated plasma folate (≥30 nmol/L) occurred in 78.9% of women who exceeded the recommended 400 µg folic acid/d. First-trimester folate-cobalamin status interactions were associated with MMA (P-interaction <0.001) throughout pregnancy. When plasma cobalamin was suboptimal (≤221 pmol/L; n = 36), participants with elevated plasma folate (n = 11) had higher MMA concentrations than did those with nonelevated plasma folate (n = 23). First-trimester folate-MMA status interactions were associated with MCV throughout pregnancy (P-interaction <0.01) and with cord plasma holoTC (P-interaction <0.05). The mean difference (95% CI) in MCV (fL) between women with elevated and nonelevated plasma folate status was -2.12 (-3.71, -0.52) for top-quartile plasma MMA (≥0.139 µmol/L) and 0.60 (-0.39, 1.60) for plasma MMA <0.139 µmol/L. Cord plasma holoTC was higher in women with elevated compared with nonelevated plasma folate status only for MMA <0.139 µmol/L. Folate-cobalamin interactions were not associated with the other investigated outcomes. CONCLUSION First-trimester folate-cobalamin status interactions were associated with plasma MMA and MCV throughout pregnancy. This trial was registered at www.clinicaltrials.gov as NCT01778205.
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Comparative case-control study of homocysteine, vitamin B12, and folic acid levels in patients with epilepsy.
Pulido Fontes, L, Pulido Fontes, M, Quesada Jiménez, P, Muruzabal Pérez, J, Mendioroz Iriarte, M
Neurologia (Barcelona, Spain). 2017;(7):440-445
Abstract
INTRODUCTION Increased blood homocysteine levels are a known cardiovascular risk factor. Epileptic patients on long-term treatment with antiepileptic drugs may present higher homocysteine levels and, consequently, a potential increase in cardiovascular risk. MATERIAL AND METHODS We conducted an observational case-control study to compare plasma levels of homocysteine, folic acid, and vitamin B12. RESULTS Our study included a total of 88 subjects: 52 patients with epilepsy and 36 controls. Epileptic patients showed higher homocysteine levels (P=.084) and lower levels of folic acid (P<.05). CONCLUSION Homocysteine levels should be monitored in epileptic patients on long-term treatment with antiepileptic drugs. We suggest starting specific treatment in patients with high homocysteine levels.
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Vitamin B12 deficiency in inflammatory bowel disease: a prospective observational pilot study.
Battat, R, Kopylov, U, Byer, J, Sewitch, MJ, Rahme, E, Nedjar, H, Zelikovic, E, Dionne, S, Bessissow, T, Afif, W, et al
European journal of gastroenterology & hepatology. 2017;(12):1361-1367
Abstract
BACKGROUND AND AIM Diagnostic and management guidelines for vitamin B12 (cobalamin, Cbl) deficiency in inflammatory bowel disease (IBD) are lacking. True deficiency is defined as Cbl concentrations below reference range combined with elevated methylmalonic acid (MMA) concentrations. Studies analyzing Cbl status in IBD use only Cbl concentrations without confirmatory MMA. This study aims to determine the proportion of IBD patients with Cbl concentrations below reference range and their predisposing clinical and genetic characteristics. We then compared this to the proportion with true deficiency. PATIENTS AND METHODS In a prospective observational pilot study of adult IBD outpatients, Cbl concentrations, MMA levels, and fucosyltransferase 2 mutations were measured at clinic visits. RESULTS A total of 66 Crohn's disease (CD) and 30 ulcerative colitis (UC) patients were recruited. Mean Cbl concentrations (pmol/l) in CD (253.7) were not significantly lower than UC (320.5, P=0.24). Serum Cbl below reference range (<148) was observed in 7.6 and 10% of CD and UC patients, respectively (P=0.70). True deficiency in CD and UC was 3 and 3.3%, respectively (P=1.0). Patients with ileal resections more than 30 cm had lower mean Cbl concentrations (177, P=0.02) and a trend toward higher proportions with Cbl levels below reference range (40%, P=0.06), but not increased deficiency rates (0%, P=1.0). Disease location, severity, and fucosyltransferase 2 mutations were not associated with altered Cbl status. CONCLUSION True Cbl deficiency was rare in IBD patients in this study. A disparity in Cbl status exists when confirmatory MMA levels are used compared with Cbl concentrations alone. Asymptomatic IBD patients with low serum Cbl require confirmatory tests to guide management and avoid unnecessary treatment.