-
1.
Efficacy of oral compared with intramuscular vitamin B-12 supplementation after Roux-en-Y gastric bypass: a randomized controlled trial.
Schijns, W, Homan, J, van der Meer, L, Janssen, IM, van Laarhoven, CJ, Berends, FJ, Aarts, EO
The American journal of clinical nutrition. 2018;(1):6-12
-
-
Free full text
-
Abstract
BACKGROUND After Roux-en-Y gastric bypass (RYGB), patients often develop a vitamin B-12 deficiency. OBJECTIVE Our objective was to investigate whether oral supplementation increases and normalizes low vitamin B-12 concentrations (vitamin B-12 > 200 pmol/L) in RYGB patients as compared to intramuscular injections. DESIGN A randomized controlled trial in RYGB patients with subnormal serum B-12 concentrations was performed. One group (IM B-12) received bimonthly intramuscular hydroxocobalamin injections (2000 µg as loading dose and 1000 µg at follow-up) for 6 mo. The second group (oral B-12) received daily doses of oral methylcobalamin (1000 µg). Serum vitamin B-12 was determined at baseline (T0) and at 2 (T1), 4 (T2), and 6 mo (T3) after start of treatment. Concentrations of the secondary markers methylmalonic acid (MMA) and homocysteine (Hcy) were measured at T0 and T3. RESULTS Fifty patients were included and randomized, 27 in IM B-12 and 23 in oral B-12. The median vitamin B-12 concentration at T0 was 175 pmol/L (range: 114-196 pmol/L) for IM B-12 and 167 pmol/L (range: 129-199 pmol/L) for oral B-12. Vitamin B-12 normalized in all individuals, and there was no significant difference in vitamin B-12 between the two groups. MMA and Hcy concentrations decreased significantly after 6 mo within each group (P < 0.001 and P < 0.001 for MMA and P = 0.03 and P = 0.045 for Hcy, respectively). There was no significant difference between the groups at 6 mo for both MMA and Hcy (P = 0.53 and P = 0.79). CONCLUSION The efficacy of oral vitamin B-12 supplementation was similar to that of hydroxocobalamin injections in the present study. Oral supplementation can be used as an alternative to hydroxocobalamin injections to treat RYGB patients with low values of serum vitamin B-12. This trial was registered at clinicaltrials.gov as NCT02270749.
-
2.
Randomized phase 2 study of gemcitabine and cisplatin with or without vitamin supplementation in patients with advanced esophagogastric cancer.
van Zweeden, AA, van Groeningen, CJ, Honeywell, RJ, Giovannetti, E, Ruijter, R, Smorenburg, CH, Giaccone, G, Verheul, HMW, Peters, GJ, van der Vliet, HJ
Cancer chemotherapy and pharmacology. 2018;(1):39-48
-
-
Free full text
-
Abstract
PURPOSE Preclinical research and prior clinical observations demonstrated reduced toxicity and suggested enhanced efficacy of cisplatin due to folic acid and vitamin B12 suppletion. In this randomized phase 2 trial, we evaluated the addition of folic acid and vitamin B12 to first-line palliative cisplatin and gemcitabine in patients with advanced esophagogastric cancer (AEGC). METHODS Patients with AEGC were randomized to gemcitabine 1250 mg/m2 (i.v. days 1, 8) and cisplatin 80 mg/m2 (i.v. day 1) q 3 weeks with or without folic acid (450 µg/day p.o.) and vitamin B12 (1000 µg i.m. q 9 weeks). The primary endpoint was response rate (RR). Secondary endpoints included overall survival (OS), time to progression (TTP), toxicity, and exploratory biomarker analyses. Cisplatin sensitivity and intracellular platinum levels were determined in adenocarcinoma cell lines cultured under high and low folate conditions in vitro. RESULTS Adenocarcinoma cells cultured in medium with high folate levels were more sensitive to cisplatin and this was associated with increased intracellular platinum levels. In the randomized phase 2 clinical trial, which ran from October 2004 to September 2013, treatment was initiated in 78 of 82 randomized pts, 39 in each study arm. The RR was similar; 42.1% for supplemented patients vs. 32.4% for unsupplemented patients; p = 0.4. Median OS and TTP were 10.0 and 5.9 months for supplemented vs. 7.7 and 5.4 months for unsupplemented patients (OS, p = 0.9; TTP, p = 0.9). Plasma homocysteine was lower in the supplemented group [n = 20, 6.9 ± 1.6 (mean ± standard error of mean, SEM) µM; vs. 12.5 ± 4.0 µM; p < 0.001]. There was no significant difference in the Cmax of gemcitabine and cisplatin in the two treatment groups. CONCLUSION Folic acid and vitamin B12 supplementation do not improve the RR, PFS, or OS of cisplatin and gemcitabine in patients with AEGC.
-
3.
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.
-
4.
Maternal and infant vitamin B12 status during infancy predict linear growth at 5 years.
Strand, TA, Ulak, M, Kvestad, I, Henjum, S, Ulvik, A, Shrestha, M, Thorne-Lyman, AL, Ueland, PM, Shrestha, PS, Chandyo, RK
Pediatric research. 2018;(5):611-618
Abstract
BACKGROUND Many children worldwide have poor vitamin B12 status. The objective of this study was to estimate association between maternal and infant vitamin B12 status and long-term growth. METHODS We randomly selected 500 Nepali mother-infant pairs and measured maternal intake and infant and maternal vitamin B12 status using plasma cobalamin, total plasma homocysteine, and methylmalonic acid concentrations. We revisited available children when they were 5 years old and measured growth. The associations between intake and maternal and infant markers of vitamin B12 and growth were estimated in multiple linear regression models adjusting for relevant confounders (n = 331). RESULTS Maternal vitamin B12 intake and status and vitamin B12 status in infancy predicted linear growth at 5 years of age, but not during infancy. Each microgram increase in the vitamin B12 intake of the mother during infancy was associated with an increase in height of 0.4 (0.2, 0.6) height-for-age z-scores and 1.7 (0.7, 2.7) cm around the child's fifth birthday. CONCLUSION Vitamin B12 status and intake in early life is an important determinant for linear growth at school age. Our findings should be verified in randomized, placebo controlled trials before translated into public health recommendations.
-
5.
Efficacy of Folic Acid and Vitamin B12 Replacement Therapies in the Reduction of Adverse Effects of Isotretinoin: A Randomized Controlled Trial.
Ghiasi, M, Mortazavi, H, Jafari, M
Skinmed. 2018;(4):239-245
Abstract
Previous studies have reported elevated homocysteine levels and folic acid and/or vitamin B12 deficiencies after isotretinoin therapy, which increase the risk of cardiovascular and neuropsychiatric disorders. Homocysteine is metabolized in the liver, a process requiring folate and vitamin B12. We conducted a randomized controlled trial to investigate whether folate and vitamin B12 replacement therapy with isotretinoin would be useful for preventing hyperhomocysteinemia. A total of 66 patients with acne were randomized into two groups: group A took isotretinoin, folic acid, and vitamin B12, whereas group B took isotretinoin alone. Treatment was continued for 2 months. Blood homocysteine, folic acid, and vitamin B12 levels were measured before and after treatment. In group A, a significant decrease in homocysteine level was observed after treatment (P=.0004), although it was still within the normal range. Folic acid and vitamin B12 levels significantly increased (P=.0026 and P=.0002, respectively). In group B, no significant changes were observed in the levels of homocysteine and vitamin B12, but folic acid levels decreased significantly (P=.02). We concluded that folic acid and vitamin B12 supplementation during isotretinoin therapy could be useful for preventing folate deficiency and improving blood homocysteine levels; this might as a result reduce the risks for cardiovascular and neuropsychiatric disorders in patients taking isotretinoin.
-
6.
Oral Vitamin B12 Supplementation After Roux-en-Y Gastric Bypass: a Systematic Review.
Mahawar, KK, Reid, A, Graham, Y, Callejas-Diaz, L, Parmar, C, Carr, WR, Jennings, N, Singhal, R, Small, PK
Obesity surgery. 2018;(7):1916-1923
Abstract
BACKGROUND Many respectable guidelines recommend lifelong vitamin B12 injections for Roux-en-Y gastric bypass (RYGB) patients in the absence of lack of consensus on the efficacy of oral route of prophylaxis and the appropriate doses needed for this purpose. The purpose of this review was to examine the published English language scientific literature in accordance with PRISMA principles to find out if orally given vitamin B12 is adequate for prophylactic purposes in RYGB patients and the appropriate dosages needed for this purpose if it is. METHODS We examined the PubMed database for all English language articles examining various doses of oral vitamin B12 supplementation after proximal RYGB in adult patients. The search revealed 19 such articles. RESULTS The data suggest that oral vitamin B12 supplementation doses of ≤ 15 μg daily are insufficient to prevent deficiency in RYGB patients. Higher supplementation doses show better results and it appears that a dose of 600.0 μg vitamin B12 daily is superior to 350.0 μg daily suggesting an incremental dose-response curve. It further appears that supplementation doses of 1000.0 μg vitamin B12 daily lead to an increase in B12 levels and are sufficient for the prevention of its deficiency in most RYGB patients. CONCLUSION The review finds that oral supplementation doses of ≤ 15 μg vitamin B12 daily are inadequate for prophylaxis of vitamin B12 deficiency in adult RYGB patients but doses of 1000 μg vitamin B12 daily might be adequate. Future studies need to examine this and even higher oral doses for vitamin B12 supplementation for patients undergoing RYGB.
-
7.
Vitamin B12 and Homocysteine Levels Predict Different Outcomes in Early Parkinson's Disease.
Christine, CW, Auinger, P, Joslin, A, Yelpaala, Y, Green, R, ,
Movement disorders : official journal of the Movement Disorder Society. 2018;(5):762-770
Abstract
BACKGROUND In moderately advanced Parkinson's disease (PD), low serum vitamin B12 levels are common and are associated with neuropathy and cognitive impairment. However, little is known about B12 in early PD. OBJECTIVE To determine the prevalence of low vitamin B12 status in early PD and whether it is associated with clinical progression. METHODS We measured vitamin B12 and other B12 status determinants (methylmalonic acid, homocysteine, and holotranscobalamin) in 680 baseline and 456 follow-up serum samples collected from DATATOP participants with early, untreated PD. Borderline low B12 status was defined as serum B12 <184 pmol/L (250 pg/mL), and elevated homocysteine was defined as >15 µmol/L. Outcomes included the UPDRS, ambulatory capacity score (sum of UPDRS items 13-15, 29&30), and MMSE, calculated as annualized rates of change. RESULTS At baseline, 13% had borderline low B12 levels, 7% had elevated homocysteine, whereas 2% had both. Elevated homocysteine at baseline was associated with worse scores on the baseline MMSE. Analysis of study outcomes showed that compared with the other tertiles, participants in the low B12 tertile (<234 pmol/L; 317 pg/mL) developed greater morbidity as assessed by greater annualized worsening of the ambulatory capacity score. Elevated homocysteine was associated with greater annualized decline in MMSE (-1.96 vs. 0.06; P = 0001). Blood count indices were not associated with B12 or homocysteine status. CONCLUSIONS In this study of early PD, low B12 status was common. Low B12 at baseline predicted greater worsening of mobility whereas elevated homocysteine predicted greater cognitive decline. Given that low B12 and elevated homocysteine can improve with vitamin supplementation, future studies should test whether prevention or early correction of these nutritionally modifiable conditions slows development of disability. © 2018 International Parkinson and Movement Disorder Society.
-
8.
Does early vitamin B12 supplementation improve neurodevelopment and cognitive function in childhood and into school age: a study protocol for extended follow-ups from randomised controlled trials in India and Tanzania.
Winje, BA, Kvestad, I, Krishnamachari, S, Manji, K, Taneja, S, Bellinger, DC, Bhandari, N, Bisht, S, Darling, AM, Duggan, CP, et al
BMJ open. 2018;(2):e018962
Abstract
INTRODUCTION As many as 250 million children under the age of 5 may not be reaching their full developmental potential partly due to poor nutrition during pregnancy and the first 2 years of life. Micronutrients, including vitamin B12, are important for the development of brain structure and function; however, the timing, duration and severity of deficiencies may alter the impact on functional development outcomes. Consequently, to fully explore the effect of vitamin B12 on cognitive function, it is crucial to measure neurodevelopment at different ages, in different populations and with vitamin B12 supplementation at different times during the critical periods of neurodevelopment. METHODS AND ANALYSIS In this project, we follow up children from four recently completed randomised placebo-controlled trials of oral vitamin B12 supplementation, two in India and two in Tanzania, to explore the long-term effects on neurodevelopmental outcomes and growth. All the included trials provided at least two recommended dietary allowances of oral vitamin B12 daily for at least 6 months. Vitamin B12 was supplemented either during pregnancy, early infancy or early childhood. Primary outcomes are neurodevelopmental status, cognitive function and growth later in childhood. We apply validated and culturally appropriate instruments to identify relevant developmental outcomes. All statistical analyses will be done according to intention-to-treat principles. The project provides an excellent opportunity to examine the effect of vitamin B12 supplementation in different periods during early life and measure the outcomes later in childhood. ETHICS AND DISSEMINATION The study has received ethical approvals from all relevant authorities in Norway, USA, Tanzania and India and complies fully with ethical principles for medical research. Results will be presented at national and international research and policy meetings and published in peer-reviewed scientific journals, preferably open access. TRIAL REGISTRATION NUMBER NCT00641862 (Bangalore); NCT00717730, updated CTRI/2016/11/007494 (Delhi); NCT00197548 and NCT00421668 (Dar es Salaam).
-
9.
A systematic review of the vitamin B12, folate and homocysteine triad across body mass index.
Wiebe, N, Field, CJ, Tonelli, M
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2018;(11):1608-1618
Abstract
OBJECTIVE Multiple studies have explored the association between serum or plasma vitamin B12 status and obesity, in part because of the relationship between elevated homocysteine concentrations and atherosclerosis. This review will address the inconsistent finding of these studies with the objective of determining whether vitamin B12 concentrations are lower in people with higher body mass indices. DESIGN MEDLINE and EMBASE were searched to February 2017. Observational studies in general and clinical populations comparing serum/plasma B12 concentrations across groups of different body mass indices were selected. We did network and pairwise meta-analyses of serum/plasma B12, folate and homocysteine using frequentist techniques. Evidence-based items potentially indicating risk of bias were assessed. RESULTS Of 844 citations, we identified 19 eligible observational studies with 7,055 participants. The overall network, while showing no significant inconsistency between indirect and direct comparisons (P = 0.34), was qualitatively inconsistent. Based on the results of the meta-regression, in an exploratory sub-network meta-analysis where obesity groups were combined, we excluded disease-specific populations and studies with inadequate description of populations. The direction of the indirect and direct evidence was consistent. The pairwise results from this sub-network showed lower levels of B12 in people with higher body mass indices: obesity versus control difference in means (MD) -56 pmol L-1 (95% CI -90, -23), obesity versus overweight MD -21 pmol L-1 (95% CI -37, -5) and overweight versus control MD -51 pmol L-1 (95% CI -51, -24). Heterogeneity remained very large for most comparisons, and all the studies carried a high risk for bias. CONCLUSIONS This review did not establish an inverse association (or J-curve) between serum or plasma B12 concentrations and body mass index, but the direct pairwise evidence is consistent with an inverse association and supports further investigation.
-
10.
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.