Effect Of Vitamin B12 Supplementation Research Articles

Individuals Diagnosed With Type 2 Diabetes Mellitus and the Status of Vitamin B12 Deficiency: A Review.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with a multifactorial etiology and a significant global burden. In recent years, emerging evidence has suggested a potential link between T2DM and vitamin B12 deficiency, raising concerns about its impact on disease progression, management, and associated complications. This comprehensive review critically examines the current understanding of the prevalence, risk factors, clinical implications, and management strategies related to vitamin B12 deficiency in individuals diagnosed with T2DM. The review begins by providing an overview of the epidemiology of T2DM and its associated complications, underscoring the need for comprehensive management approaches. Subsequently, it delves into the physiology of vitamin B12, including its sources, absorption mechanisms, and biological functions, laying the groundwork for understanding the potential implications of deficiency in T2DM. A thorough analysis of the literature is conducted to elucidate the prevalence and risk factors of vitamin B12 deficiency in individuals with T2DM, considering factors such as age, duration of diabetes, medication use (e.g., metformin), dietary patterns, and comorbidities. Special attention is given to the role of metformin, the first-line therapy for T2DM, in precipitating or exacerbating vitamin B12 deficiency through mechanisms involving alterations in the gut microbiota and intestinal absorption. The review further explores the clinical manifestations and diagnostic challenges associated with vitamin B12 deficiency in the context of T2DM, emphasizing the importance of recognizing subtle symptoms and implementing appropriate screening protocols. It discusses the potential implications of vitamin B12 deficiency on glycemic control, diabetic neuropathy, cognitive function, cardiovascular health, and overall quality of life in individuals with T2DM. In addressing the management of vitamin B12 deficiency in T2DM, the review examines various therapeutic strategies, including oral and parenteral supplementation, dietary modifications, and lifestyle interventions. It critically evaluates the evidence supporting routine screening for vitamin B12 deficiency in individuals with T2DM and discusses controversies surrounding optimal supplementation protocols, dosing regimens, and monitoring strategies. Furthermore, the review highlights gaps in current knowledge and identifies areas for future research, such as the long-term effects of vitamin B12 supplementation on clinical outcomes in T2DM, the impact of genetic factors on vitamin B12 metabolism, and the potential role of personalized interventions. Overall, this review consolidates existing evidence and provides insights into the complex relationship between T2DM and vitamin B12 deficiency, aiming to inform clinical practice, enhance patient care, and guide future research endeavors in this important area of metabolic medicine.

Vitamin B12 supplementation during pregnancy for maternal and child health outcomes.

Vitamin B12 deficiency is a major public health problem worldwide, with the highest burden in elderly people, pregnant women, and young children. Due to its role in DNA synthesis and methylation, folate metabolism, and erythropoiesis, vitamin B12 supplementation during pregnancy may confer longer-term benefits to maternal and child health outcomes. To evaluate the benefits and harms of oral vitamin B12 supplementation during pregnancy on maternal and child health outcomes. We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) on 2 June 2023, and reference lists of retrieved studies. Randomised controlled trials (RCTs), quasi-RCTs, or cluster-RCTs evaluating the effects of oral vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation during pregnancy. We used standard Cochrane methods. Four review authors independently assessed trial eligibility. Two review authors independently extracted data from included studies and conducted checks for accuracy. Three review authors independently assessed the risk of bias of the included studies using the Cochrane RoB 1 tool. We used GRADE to evaluate the certainty of evidence for primary outcomes. The review included five trials with 984 pregnant women. All trials were conducted in low- and middle-income countries, including India, Bangladesh, South Africa, and Croatia. At enrolment, 26% to 51% of pregnant women had vitamin B12 deficiency (less than 150 pmol/L), and the prevalence of anaemia (haemoglobin less than 11.0 g/dL) ranged from 30% to 46%. The dosage of vitamin B12 supplementation varied from 5 μg/day to 250 μg/day, with administration beginning at 8 to 28 weeks' gestation through to delivery or three months' postpartum, and the duration of supplementation ranged from 8 to 16 weeks to 32 to 38 weeks. Three trials, involving 609 pregnant women, contributed data for meta-analyses of the effects of vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation. Maternal anaemia: there may be little to no difference for maternal anaemia by intervention group, but the evidence is very uncertain (70.9% versus 65.0%; risk ratio (RR) 1.08, 95% confidence interval (CI) 0.93 to 1.26; 2 trials, 284 women; very low-certainty evidence). Maternal vitamin B12 status: vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain (25.9% versus 67.9%; RR 0.38, 95% CI 0.28 to 0.51; 2 trials, 272 women; very low-certainty evidence). Women who received vitamin B12 supplements during pregnancy may have higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (mean difference (MD) 60.89 pmol/L, 95% CI 40.86 to 80.92; 3 trials, 412 women). However, there was substantial heterogeneity (I2 = 85%). Adverse pregnancy outcomes: the evidence is uncertain about the effect on adverse pregnancy outcomes, including preterm birth (RR 0.97, 95% CI 0.55 to 1.74; 2 trials, 340 women; low-certainty evidence), and low birthweight (RR 1.50, 95% CI 0.93 to 2.43; 2 trials, 344 women; low-certainty evidence). Two trials reported data on spontaneous abortion (or miscarriage); however, the trials did not report quantitative data for meta-analysis and there was no clear definition of spontaneous abortion in the study reports. No trials evaluated the effects of vitamin B12 supplementation during pregnancy on neural tube defects. Infant vitamin B12 status: children born to women who received vitamin B12 supplementation had higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (MD 71.89 pmol/L, 95% CI 20.23 to 123.54; 2 trials, 144 children). Child cognitive outcomes: three ancillary analyses of one trial reported child cognitive outcomes; however, data were not reported in a format that could be included in quantitative meta-analyses. In one study, maternal vitamin B12 supplementation did not improve neurodevelopment status (e.g. cognitive, language (receptive and expressive), motor (fine and gross), social-emotional, or adaptive (conceptual, social, practical) domains) in children compared to placebo (9 months, Bayley Scales of Infant and Toddler Development Third Edition (BSID-III); 1 trial; low-certainty evidence) or neurophysiological outcomes (72 months, event-related potential measures; 1 trial; low-certainty evidence), though children born to women who received vitamin B12 supplementation had improved expressive language domain compared to placebo (30 months, BSID-III; 1 trial; low-certainty evidence). Oral vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency and may improve maternal vitamin B12 concentrations during pregnancy or postpartum compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain. The effects of vitamin B12 supplementation on other primary outcomes assessed in this review were not reported, or were not reported in a format for inclusion in quantitative analyses. Vitamin B12 supplementation during pregnancy may improve maternal and infant vitamin B12 status, but the potential impact on longer-term clinical and functional maternal and child health outcomes has not yet been established.

Effects of vitamin B12 supplementation on oxidative stress markers and pro-inflammatory cytokines during pregnancy and postpartum among Bangladeshi mother–child pairs

BackgroundThere is limited research to determine whether vitamin B12 (B12) supplementation during pregnancy and lactation is protective against oxidative stress and pro-inflammatory cytokines and whether this effect is transferred to breastfed infants via milk. In addition, associations among maternal plasma/ milk and infant B12 status and immune function markers are poorly characterized.ObjectivesTo evaluate effects of oral B12 supplementation during pregnancy and postpartum on maternal and infant 8-hydroxy-2′-deoxyguanosine (8-OH-dG, an oxidative stress marker) and proinflammatory cytokine levels, and examine associations between maternal plasma, breastmilk and infant B12 status as well as immune function markers.MethodIn a blinded, placebo-controlled trial, Bangladeshi women (n = 68, 18–35 years, hemoglobin < 11 g/dL, gestational weeks 11–14) received either 250 μg/day B12 or placebo throughout pregnancy up to 3-months postpartum. Samples were collected from mothers at baseline and 3-months postpartum and from infants at 3-months to measure B12 status indicators, 8-OH-dG and proinflammatory cytokines.ResultsMaternal postpartum B12 was positively associated with infant plasma B12. Higher milk B12 concentrations were associated with increased infant B12 (beta (β) = 277, 95% confidence interval (CI) = (132, 423), p<0.001) and lower total homocysteine (β = -7.63, 95% CI = (-12.40, -2.86), p = 0.002) levels. Maternal B12 supplementation reduced plasma 8-OH-dG concentrations among postpartum mothers and infants compared to the placebo group. Supplementation increased plasma TNF-α and IL-6 levels among mothers and IL-10 and IFN-γ levels among infants.ConclusionMilk and maternal plasma B12 at 3 months were associated with infant B12. Maternal B12 supplementation modulates 8-OH-dG and several cytokines which may protect against immune response-induced oxidative stress.Trial registration(clinicaltrials.gov: NCT01795131- 1st posted on 20/02/2013).

The Effect of Vitamin B12 Supplementation on Leukocyte Telomere Length in Mildly Stunted Nepalese Children: A Secondary Outcome of a Randomized Controlled Trial

BackgroundVitamin B12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality. ObjectivesThe study aims to determine the effect of vitamin B12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B12 deficiency. MethodsThe study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 –11 mo, who were supplemented with 2 μg (2–3 recommended daily allowances) vitamin B12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B12 status, hemoglobin, sex, and growth indices. ResultsLTL at end-study did not differ between the vitamin B12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (–0.14, 0.21). There was no effect of vitamin B12 on LTL in any of the subgroups. ConclusionsProviding daily vitamin B12 for 1 y during infancy in a population at risk of vitamin B12 deficiency does not affect LTL.This trial was registered at clinicaltrials.gov as NCT02272842.

The effect of vitamin B12 supplementation during pregnancy on infant growth and development in Nepal: a community-based, double-blind, randomised, placebo-controlled trial

Vitamin B12 is required for healthy infant growth and development, but low and marginal vitamin B12 status is endemic in low-income and middle-income countries. We aimed to measure the effect of vitamin B12 supplementation from early pregnancy until 6 months post partum on infant growth and neurodevelopment. In this community-based, double-blind, placebo-controlled trial, we randomly assigned (1:1) 800 pregnant women (aged 20-40 years) who were up to 15 weeks pregnant-recruited from home visits and outpatient departments at three hospitals in Nepal-to daily supplementation with 50 μg oral vitamin B12 or placebo until 6 months postpartum. Independent scientists generated the list that linked allocation to participants' study identification number. Participants were masked to group assignment and all investigators were masked until data cleaning was completed. The primary outcomes were length-for-age Z score (LAZ) at age 12 months and the cognitive composite score of the Bayley Scales of Infant and Toddler Development (3rd edition) at age 6 months and 12 months. The primary and secondary outcomes, including adverse events, were assessed in the intention-to-treat population, for all participants with available outcome data. This trial is registered with ClinicalTrials.gov, NCT03071666. 800 eligible pregnant women were enrolled in the trial between March 28, 2017, and Oct 15, 2020, with 400 women randomly assigned to each group. Follow-up was completed on May 18, 2022. At baseline, 569 (71%) of 800 women had plasma vitamin B12 indicating low or marginal status (<221 pmol/L). We found no effect of vitamin B12 on the primary outcomes. The mean LAZ at age 12 months were -0·57 (SD 1·03) in the B12 group and -0·55 (1.03) in the placebo group (366 infants in the vitamin B12 group vs 363 infants in the placebo group) with a mean difference of -0·02 (95% CI -0·16 to 0·13). The mean cognitive composite scores were 97·7 (SD 10·5) in the B12 group and 97·1 (10·2) in the placebo group, with a mean difference of 0·5 (95% CI -0·6 to 1·7) measured in 364 and 361 infants. Stillbirths or infant deaths occurred in three (1%) of 374 women in the vitamin B12 group and nine (2%) of 379 women in the placebo group. Although vitamin B12 deficiency was prevalent in our study population and vitamin B12 supplementation from early pregnancy substantially improved vitamin B12 status, supplementation did not improve infant growth or neurodevelopment. Our findings support the current WHO recommendations of no routine vitamin B12 supplementation during pregnancy. Research Council of Norway.

Vitamin B12 status in infancy and the effect of a vitamin B12 injection in infants with subclinical vitamin B12 deficiency: study protocol for a register-based randomised controlled trial

IntroductionVitamin B12 (cobalamin) is crucial for optimal child development and growth, yet deficiency is common worldwide. The aim of this study is twofold; (1) to describe vitamin B12 status and...

Responses of Fermentation Characteristics and Microbial Communities to Vitamin B12 Supplementation in In Vitro Ruminal Cultures

Vitamin B12, an important cofactor involved in propionate formation, is synthesized exclusively by bacteria and archaebacteria. Humans need to intake vitamin B12 through food, and dairy products are generally the best source of vitamin B12. In the present study, the effects of vitamin B12 supplementation in diets on in vitro ruminal fermentation characteristics and microbial communities were investigated to provide a reference for increasing the vitamin B12 content in milk by dietary supplementation. A completely randomized design was carried out using the in vitro rumen culture technique, and 5 vitamin B12 dose levels (0, 0.5, 1.0, 2.0, and 4 mg/g of dry matter) were used. The results showed that vitamin B12 supplementation in diets decreased acetate: propionate ratio and butyrate concentration. The change in the acetate: propionate ratio can be attributed to the increased relative abundances of the Proteobacteria phylum and the Negativicutes class, both of which are involved in propionate metabolism. The decrease in butyrate concentration can likely be attributed to a reduction in relative abundance of species belonging to the Clostridia class, which are known as the predominant butyrate producers in the mammalian intestine. In addition, vitamin B12 supplementation in diets reduced the CH4 production by altering the species composition of the archaeal community. In conclusion, dietary supplementation of vitamin B12 resulted in rumen perturbation. In vivo studies should be conducted cautiously when evaluating the effects of vitamin B12 supplementation on the synthesis and absorption of it, as well as its content in milk.

The effects of vitamin B12 supplementation on metabolic profile of patients with non-alcoholic fatty liver disease: a randomized controlled trial

The present study is the first effort to evaluate the effects of vitamin B12 supplementation on the serum level of liver enzymes, homocysteine, grade of hepatic steatosis, and metabolic profiles in patients with non-alcoholic fatty liver disease (NAFLD). Forty patients with NAFLD were enrolled in a double-blind placebo-controlled trial to receive either one oral tablet of vitamin B12 (1000 µg cyanocobalamin) or a placebo per day for 12 weeks. We investigated serum levels of homocysteine, aminotransferases, fasting blood glucose (FBG), lipids, malondialdehyde (MDA), and homeostasis model assessment of insulin resistance (HOMA-IR). The grade of liver steatosis and fibrosis was measured by real-time 2-dimensional shear wave elastography. Vitamin B12 supplementation significantly decreased serum levels of homocysteine compared to placebo (medians: − 2.1 vs. − 0.003 µmol/l; P = 0.038). Although serum alanine transaminase (ALT) in the vitamin B12 group decreased significantly, this change did not reach a significant level compared to the placebo group (medians: − 7.0 vs. 0.0 IU/l; P > 0.05). Despite the significant within-group decrease in FBG, MDA, and liver steatosis in the vitamin B12 group, between-group comparisons did not reveal any significant difference. Vitamin B12 supplementation might decrease serum levels of homocysteine in patients with NAFLD. The fasting blood glucose and serum levels of MDA were significantly improved in the trial group who received vitamin B12. However, these changes did not reach a significant level compared to the placebo group. In this respect, further studies with larger sample sizes, different doses, and types of vitamin B12 will reveal additional evidence.Trial Registration: At http://irct.ir/ as IRCT20120718010333N5 on December 25, 2019.

Vitamin B12 and/or folic acid supplementation on linear growth; a 6 years follow-up study of a randomised controlled trial in early childhood in North India.

Folate and vitamin B12 are essential for growth. Our objective was to estimate their long-term effects on linear growth in North Indian children. This is a follow-up study of a factorial designed, double-blind, randomized placebo-controlled trial in 1,000 young children. Starting at 6-30 months of age, we gave folic acid (∼2 RDAs), vitamin B12 (∼2 RDAs), both vitamins, or a placebo daily for six months. Six years after the end of supplementation, we measured height in 791 children. We used the plasma concentrations of cobalamin, folate, and total homocysteine to estimate vitamin status. The effect of the interventions, the association between height-for-age z-scores (HAZ) and baseline vitamin status, and the interactions between supplementation and baseline status were estimated in multiple regression models. Mean (SD) age at follow-up was 7.4 (0.7) years (range 6 to 9 years). There was a small, non-significant effect of vitamin B12 on linear growth and no effect of folic acid. We observed a subgroup-effect of vitamin B12 supplementation in those with plasma cobalamin concentration < 200 pmol/L (P interaction = 0.01). The effect of vitamin B12 supplementation in this group was 0.34 HAZ (95% CI: 0.11-0.58). We found an association between cobalamin status and HAZ in children not given vitamin B12 (P interaction = 0.001). In this group, each doubling of the cobalamin concentration was associated with 0.26 (95% CI: 0.15 to 0.38) higher HAZ. Suboptimal B12 status in early childhood seemingly limits linear growth in North Indian Children.

Effect of Vitamin B12 supplementation on the Diabetic Peripheral Neuropathy- a Review

Neuropathic pain is the unpleasant sensation due to lesion of nerves. It is common in patients with diabetes as fluctuations in blood glucose take a toll on the nervous system. Furthermore, high doses of metformin for the long duration in patients, with type 2 diabetes are found to interfere with the normal metabolism of the vitamin B12 in body that leads to its deficiency. Vitamin B12 is a water soluble vitamin found in our body responsible for the methylation, thus has a role in the myelin sheath and DNA synthesis. Deficiency of vitamin B12 has debilitating effect on the nerves which results in neuropathy. Various studies have been carried out to study whether Vitamin B12 has an effect on the nervous regeneration or can its use improve the diabetic or metformin induced neuropathy? In this paper, up-to-date evidence for effect of vitamin b12 supplementation on diabetic peripheral neuropathy has been studied and evaluated.

Effects of vitamin B12 supplementation on pain relief in certain diseases - a literature review.

Based on current scientific reports, vitamin B12 (cobalamin), used in the treatment of pernicious anemia, may be used as a pain reliever. It has been shown to be effective in the treatment of different sorts of pain, including diabetic neuropathic, musculoskeletal, abdominal, back and spine ones, but also pain in Alzheimer's disease and pain ailments resulting from the development of neoplasms. In addition, it helps regeneration of the sensory nerves and relieves pain in eye diseases, for example in dry eye syndrome. This review summarizes recent research reports on pain-relieving properties of vitamin B12.

Nutritional and hematological profile of children with severe acute malnutrition rehabilitated with or without vitamin B12

Background: Aim of the study was to study the effect of vitamin B12 supplementation in children with severe acute malnutrition (SAM).Methods: A total of 100 children were enrolled in the study in two different time frames. Group A consisted of 50 children with SAM enrolled from November 2016 to May 2017 and managed as per existing national protocol for facility-based SAM management while group B consisted of 50 children enrolled from June 2017 to Dec 2017 who were tested for vitamin B12 deficiency on admission and supplemented with vitamin B12 in presence of vitamin B12 deficiency hematological and anthropometric parameters of both groups were compared at 12 weeks of rehabilitation. Results: At 12±1 weeks, 38% children from group A and 24% from group B were still anemic (p=0.13). No one from either group had folic acid deficiency while deficiency of vitamin B12 was present in 14% and 6% cases in group A and group B respectively (p&gt;0.05). Mean weight gain at 12±1 weeks, in group A and non-supplemented sub-group of group B was comparable (p&gt;0.59). However, mean weight gain in supplemented sub-group of group B was significantly higher compared to group A (p&gt;0.05) and non-supplemented sub-group of group B (p&lt;0.05).Conclusions: Significant number of SAM children remain anemic when treated with current guidelines. Additional vitamin B12 supplementation in vitamin B12 deficient group showed improvement in weight gain among SAM children.

Lack of association between serum vitamin B12 and nocturnal sleep parameters following cyanocobalamin supplementation in healthy adults

BackgroundThis study examined the effect of vitamin B12 supplementation on sleep parameters of latency, total sleep time, wake-after-sleep onset, total time in bed and sleep efficiency in healthy adults. MethodsThis quasi-experimental pre-test, post-test design recruited adults 25–50 years old, with normal vitamin B12 levels. Sleep parameters were assessed using Phillips Respironics Actiwatch-2® on non-dominant wrist from Monday to Thursday for four weeks. Pre-supplementation data was collected for the first two weeks; then participants started 3mg pre-packaged cyanocobalamin supplements daily for 14 days. Post-supplementation data was collected for weeks three and four. Serum was collected by venipuncture at the beginning and end of the study for vitamin B12 assay. Descriptive statistics involved median and interquartile range [IQR]. A comparison of the sleep parameters before and after cyanocobalamin supplementation was done using non-parametric inferential analysis. ResultsFourteen healthy adult participants completed the study; nine females and five males with median age of 37[17] years and a normal range of serum vitamin B12 level (169–695 pmol/L). Median serum vitamin B12 level was significantly elevated following supplementation (355[217] to 961[679]) pmol/L; p = 0.020); but there was no change in any of the sleep parameters measured. Spearman's rho correlation analysis showed no correlation between serum vitamin B12 levels and the sleep parameters for pre-supplementation and post-supplementation weeks. ConclusionTwo weeks of cyanocobalamin supplementation (3mg/day) resulted in the expected increase in serum vitamin B12 levels in healthy adults but did not influence their sleep wake activity.

Vitamin B12 and chronic kidney disease.

Chronic Kidney Disease (CKD) is an emerging public health issue with a fast-growing global prevalence. Impairment in vitamin B12 metabolism is considered a nontraditional risk factor of poor outcomes associated with CKD, and there is greater interest from the scientific community than ever before to explore the role and influence of vitamin B12 in CKD. Homocysteine metabolism forms an important component of the vitamin B12 metabolic pathway. Hyperhomocysteinemia is frequently observed in CKD and End-Stage Kidney Disease (ESKD), but its representation as a prognostic marker for CKD outcomes is still not fully clear. This chapter reviews the vitamin B12 and homocysteine metabolic pathways and their dysfunction in CKD states. Biochemical factors and the MTHFR genetic polymorphisms which disrupt vitamin B12 and homocysteine metabolism are explored. The mechanisms of homocysteine-mediated and vitamin B12-mediated tissue damage in CKD are discussed. This chapter reviews current perspective on definition and measurement of plasma vitamin B12 levels in the CKD population. Updated evidence investigating the prognostic role of vitamin B12 for CKD outcomes is presented. Findings from major clinical trials conducted relating to outcomes from multivitamin (including folic acid and vitamin B12) supplementation in nondialysis and dialysis-dependent CKD are highlighted. The prognostic value of vitamin B12 and effects of vitamin B12 supplementation in the context of kidney transplantation and acute kidney injury is also reviewed. Future research considerations are summarized based on evidence gaps in our knowledge base of this topic. Greater abundance of high-level evidence to guide an approach toward vitamin B12 measurement, monitoring and supplementation in CKD may contribute to improved clinical outcomes.

The effect of vitamin B12-supplementation on actigraphy measured sleep pattern; a randomized control trial

Vitamin B12 deficiency is common worldwide and has been associated with poor sleep. The effect of vitamin B12 supplementation on sleep in infants is not known. To measure the effect of daily supplementation of vitamin B12 for one year on sleep in infants at risk of deficiency. This was an individually randomized double-blind placebo-controlled trial in 600 infants in low-to middle-income neighborhoods in Bhaktapur, Nepal of daily supplementation of vitamin B12 for one year. Infants were included if they were 6-11 month year-old and with a length-for-age less than one z-score. Sleep was a predefined, secondary outcome, and was measured by actigraphy including sleep duration at night and total sleep duration (day and night), sleep onset latency (SOL), and wake after sleep onset (WASO). The effect of vitamin B12 on sleep was additionally assessed in predefined subgroups defined by stunting, underweight, vitamin B12 status, low birthweight, anemia and exclusive breastfeeding for 3 months. There was no effect of vitamin B12 supplementation on sleep duration at night, total sleep duration, or WASO. There was a small significant negative effect for SOL. None of the included subgroup analyses revealed effect modification on any of the sleep outcomes. Overall, vitamin B12 supplementation did not have an effect on sleep in infants or for high-risk subgroups, with the exception of a small negative effect for SOL. The present study does not support vitamin B12 supplementation to improve sleep in infants. clinicaltrials.gov: NCT02272842. U1111-1161-5187.

Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression.

Vitamin B12 is often used to improve cognitive function, depressive symptoms, and fatigue. In most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 supplementation in such cases is uncertain. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to assess the effects of vitamin B12 alone (B12 alone), in addition to vitamin B12 and folic acid with or without vitamin B6 (B complex) on cognitive function, depressive symptoms, and idiopathic fatigue in patients without advanced neurological disorders or overt vitamin B12 deficiency. Medline, Embase, PsycInfo, Cochrane Library, and Scopus were searched. A total of 16 RCTs with 6276 participants were included. Regarding cognitive function outcomes, we found no evidence for an effect of B12 alone or B complex supplementation on any subdomain of cognitive function outcomes. Further, meta-regression showed no significant associations of treatment effects with any of the potential predictors. We also found no overall effect of vitamin supplementation on measures of depression. Further, only one study reported effects on idiopathic fatigue, and therefore, no analysis was possible. Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.

The association between dietary vitamin B12 and lung cancer risk: findings from a prospective cohort study.

Since previous epidemiological studies reported inconsistent associations between dietary vitamin B12 intake and lung cancer risk, more studies are warranted to clarify this association in different populations. The association between dietary B12 intake and lung cancer risk was examined in the Singapore Chinese Health Study, an ongoing prospective cohort study of 63 257 Singaporean Chinese men and women, 45-74 years of age at enrollment during 1993-1998 and were followed up for incidence of lung cancer for up to 25 years. Dietary vitamin B12 intake was derived from a validated food frequency questionnaire. Cox proportional hazard regression method was used to estimate hazard ratio and 95% confidence interval (CI) of lung cancer associated with dietary vitamin B12 intake with adjustment for multiple potential confounders. After a mean follow-up of 17.64 years, 2001 study participants developed lung cancer. High levels of vitamin B12 intake were associated with significantly increased risk of lung cancer (Ptrend = 0.03). Compared with the lowest quintile, hazard ratios (95% CIs) of lung cancer for quintile 2, 3, 4, and 5 of vitamin B12 intake were 1.09 (0.95-1.25), 1.11 (0.96-1.28), 1.11 (0.97-1.29) and 1.18 (1.03-1.35), respectively. This positive association was more apparent in men than in women, in adenocarcinoma patients, or in participants with equal or less than 2 years follow-up than those with longer duration of follow-up. Higher intake of dietary vitamin B12 was associated with increased risk of lung cancer. This highlights the potential harmful effect of vitamin B12 supplementation for lung cancer.

Effects of vitamin B12 supplementation on neurodevelopment and growth in Nepalese Infants: A randomized controlled trial.

Vitamin B12 deficiency is common and affects cell division and differentiation, erythropoiesis, and the central nervous system. Several observational studies have demonstrated associations between biomarkers of vitamin B12 status with growth, neurodevelopment, and anemia. The objective of this study was to measure the effects of daily supplementation of vitamin B12 for 1 year on neurodevelopment, growth, and hemoglobin concentration in infants at risk of deficiency. This is a community-based, individually randomized, double-blind placebo-controlled trial conducted in low- to middle-income neighborhoods in Bhaktapur, Nepal. We enrolled 600 marginally stunted, 6- to 11-month-old infants between April 2015 and February 2017. Children were randomized in a 1:1 ratio to 2 μg of vitamin B12, corresponding to approximately 2 to 3 recommended daily allowances (RDAs) or a placebo daily for 12 months. Both groups were also given 15 other vitamins and minerals at around 1 RDA. The primary outcomes were neurodevelopment measured by the Bayley Scales of Infant and Toddler Development 3rd ed. (Bayley-III), attained growth, and hemoglobin concentration. Secondary outcomes included the metabolic response measured by plasma total homocysteine (tHcy) and methylmalonic acid (MMA). A total of 16 children (2.7%) in the vitamin B12 group and 10 children (1.7%) in the placebo group were lost to follow-up. Of note, 94% of the scheduled daily doses of vitamin B12 or placebo were reported to have been consumed (in part or completely). In this study, we observed that there were no effects of the intervention on the Bayley-III scores, growth, or hemoglobin concentration. Children in both groups grew on an average 12.5 cm (SD: 1.8), and the mean difference was 0.20 cm (95% confidence interval (CI): -0.23 to 0.63, P = 0.354). Furthermore, at the end of the study, the mean difference in hemoglobin concentration was 0.02 g/dL (95% CI: -1.33 to 1.37, P = 0.978), and the difference in the cognitive scaled scores was 0.16 (95% CI: -0.54 to 0.87, P = 0.648). The tHcy and MMA concentrations were 23% (95% CI: 17 to 30, P < 0.001) and 30% (95% CI: 15 to 46, P < 0.001) higher in the placebo group than in the vitamin B12 group, respectively. We observed 43 adverse events in 36 children, and these events were not associated with the intervention. In addition, 20 in the vitamin B12 group and 16 in the placebo group were hospitalized during the supplementation period. Important limitations of the study are that the strict inclusion criteria could limit the external validity and that the period of vitamin B12 supplementation might not have covered a critical window for infant growth or brain development. In this study, we observed that vitamin B12 supplementation in young children at risk of vitamin B12 deficiency resulted in an improved metabolic response but did not affect neurodevelopment, growth, or hemoglobin concentration. Our results do not support widespread vitamin B12 supplementation in marginalized infants from low-income countries. ClinicalTrials.gov NCT02272842 Universal Trial Number: U1111-1161-5187 (September 8, 2014) Trial Protocol: Original trial protocol: PMID: 28431557 (reference [18]; study protocols and plan of analysis included as Supporting information).

The effect of vitamin B12 supplement on post‐thaw motility, viability and DNA damage of human sperm

Sperm cryopreservation may lead to adverse effects on sperm structure and function. Cyanocobalamin (vitamin B12) has antioxidant potential and can protect DNA from free radical-induced damages. Recent studies have shown that vitamin B12 preserves glutathione that leads to modulate oxidative stress responses. Also, vitamin B12 might act directly as a scavenger of ROS. The aim of this study was to investigate the effects of vitamin B12 supplementation on human sperm parameters during the cryopreservation process. Thirty semen samples were obtained from normozoospermic men. Using cryopreservation medium supplemented with different concentrations of vitamin B12 (0, 0.5, 1, 2, 2.5mg/ml), the semen samples were cryopreserved. After thawing, all samples were evaluated for motility and viability. Based on results, 2mg/ml was considered as the optimal concentration of vitamin B12 for evaluating sperm DNA fragmentation. The results showed that 1 and 2mg/ml vitamin B12 significantly increased post-thawing motility and viability compared with the 0mg/ml vitamin B12 (p<.05). Also, by supplementing with 2mg/ml vitamin B12, DNA fragmentation decreased when compared to the control. The present study showed that cryopreservation medium supplemented with vitamin B12 at 2mg/ml couldimprove sperm quality after freeze-thaw process.

Vitamin B12 Deficiency Alters the Gut Microbiota in a Murine Model of Colitis.

Purpose: Inflammatory bowel disease (IBD) refers to a spectrum of autoimmune diseases, which result in chronic intestinal inflammation. Previous findings suggest a role for diet, nutrition and dysbiosis of the gut microbiota in both the development and progression of the condition. Vitamin B12 is a key cofactor of methionine synthase and is produced solely by microbes. Previous work links increased levels of homocysteine, a substrate of methionine synthase, MetH, to IBD indicating a potential role for vitamin B12 deficiency in intestinal injury and inflammation. This study assessed the role of vitamin B12 in shaping the gut microbiota and determining responses to intestinal injury using a reproducible murine model of colitis.Methods: The effects of vitamin B12 supplementation and deficiency were assessed in vivo; 3-week-old post-weanling C57Bl/6 mice were divided into three dietary treatment groups: (1) sufficient vitamin B12 (50 mg/Kg), (2) deficient vitamin B12 (0 mg/Kg) and (3) supplemented vitamin B12 (200 mg/Kg) for a period of 4 weeks. Intestinal injury was induced with 2% dextran sodium sulphate (DSS) via drinking water for 5 days. The impact of varying levels of dietary vitamin B12 on gut microbiota composition was assessed using 16S rRNA gene sequencing from fecal samples collected at day 0 and day 28 of the dietary intervention, and 7 days following induction of colitis on day 38, when blood and colonic tissues were also collected.Results: No significant alterations were found in the gut microbiota composition of disease-free animals in response to dietary interventions. By contrast, after DSS-induced colitis, >30 genera were significantly altered in vitamin B12 deficient mice. Altered B12 levels produced no significant effect on composite disease-activity scores; however, administration of a B12 deficient diet resulted in reduced DSS-induced epithelial tissue damage.Conclusions: Vitamin B12 supplementation does not alter the gut microbiota composition under healthy conditions, but does contribute to differential microbial responses and intestinal dysbiosis following the induction of experimental colitis.