Monitoring Vitamin B12 in Women Treated with Metformin for Primary Prevention of Breast Cancer and Age-Related Chronic Diseases.
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SUBMITTER: Mastroianni A
PROVIDER: S-EPMC6567263 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
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Project description:ObjectiveRandomized controlled trials and observational studies have yielded inconsistent results on the effects of metformin on vitamin B12 reduction. We therefore performed a systematic review to analyze the effects of metformin on vitamin B12 concentration.MethodsPubMed, Medline, Embase, and the Cochrane central registry of controlled trials were searched to identify randomized controlled trials and observational studies exploring the association between metformin and vitamin B12 concentration in patients with type 2 diabetes mellitus or polycystic ovary syndrome. The main outcome measure was changes in serum vitamin B12 concentration after 6-208 weeks of treatment with metformin, as compared with placebo or other anti-hyperglycemic therapy.ResultsSix randomized controlled trials met the inclusion criteria. Serum vitamin B12 concentrations were significantly lower in patients treated with metformin than in those who received placebo or rosiglitazone (mean difference [MD], -53.93 pmol/L; 95% confidence interval [CI], -81.44 to -26.42 pmol/L, P?=?0.0001). Subgroup analysis identified four trials in which patients received a lower dose of metformin (<2000 mg/d) and two in which they received a higher dose (?2000 mg/d), with MDs in vitamin B12 concentration after metformin treatment of -37.99 pmol/L (95% CI, -57.44 to -18.54 pmol/L, P?=?0.0001) and -78.62 pmol/L (95% CI, -106.37 to -50.86 pmol/L, P<0.00001), respectively.ConclusionsThe reduction of vitamin B12 may be induced by metformin in a dose dependent manner.
| S-EPMC4069007 | biostudies-literature
Project description:BackgroundThe association between prolong metformin usage and B12 deficiency has been documented. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed substantial disparity among studies due to varied study definitions of vitamin B12 deficiency. Metformin blocks the calcium dependent absorption of the vitamin B12-Intrinsic Factor complex at the terminal ileum. Lack of intrinsic factor due to the presence of auto-antibodies to parietal cells (IFA) could lead to vitamin B12 deficiency and subsequently cause peripheral neuropathy. We investigated the prevalence of vitamin B12 deficiency using more sensitive, combined markers of vitamin B12 status (4cB12) and the immuno-biochemical mediators of vitamin B12 deficiency.MethodsIn this observational study, 200 consecutive consenting metformin-treated T2DM patients, aged 35 and above, attending the diabetic clinic at KATH were recruited. Vitamin B12 deficiency was classified based on the Fedosov age-normalized wellness quotient. Anthropometric measurement was taken as well as blood samples for immunological and biochemical mediators. Peripheral neuropathy was assessed using the Michigan Neuropathy Screening Instrument (MNSI). Statistical analysis was performed using the R Language for Statistical Computing.ResultsUsing the combined indicator (4cB12), the prevalence of metformin induced vitamin B12 deficiency was 40.5% whilst the prevalence of MNSI-Q and MNSI-PE diabetic neuropathy was 32.5% and 6.5% respectively. Participants with vitamin B12 deficiency had significantly higher levels of IFA, GPA, TNF-α, TC, LDL and albumin compared to those with normal vitamin B12 levels (p < 0.05). Correlation analysis revealed a statistically significant negative association between 4cB12 and the immunological markers [IFA (rs = -0.301, p<0.0001), GPA (rs = -0.244, p = 0.001), TNF-α (rs = -0.242, p = 0.001) and IL-6 (rs = -0.145, p = 0.041)]. Likewise, 4cB12 was negatively associated with TC (rs = -0.203, p = 0.004) and LDL (rs = -0.222, p = 0.002) but positively correlated with HDL (rs = 0.196, p = 0.005).ConclusionVitamin B12 deficiency and diabetic neuropathy are very high among metformin-treated T2DM patients and it is associated with increased GPA, IFA, TNF-α and cardiometabolic risk factors (higher LDL and TC and lower HDL). Upon verification of these findings in a prospective case-control study, it may be beneficial to include periodic measurement of Vitamin B12 using the more sensitive combined indicators (4cB 12) in the management of patients with T2DM treated with metformin in Ghana.
| S-EPMC8009370 | biostudies-literature
Project description:Vitamin B12 insufficiency is a global health issue among women of childbearing age, yet few studies have investigated its prevalence and risk factors among healthy Middle Eastern populations. This cross-sectional study included 346 Saudi women aged 19-30 years and enrolled at King Saud University, Riyadh, Saudi Arabia. A series of questionnaires were administered to record the study participants' sociodemographic status, medical history, dietary intake, and physical activity. Participants' anthropometric data were also recorded and their fasting blood samples were analyzed. The rate of vitamin B12 insufficiency (≤220 pmol/L) was approximately 6% among the study participants. After adjusting for confounding factors, it was observed that the risk factors for vitamin B12 insufficiency included daily sitting time ≥ 7 h, low income (<10,000 Saudi riyal) and increasing age. The recommended dietary allowance of vitamin B12 (>2.4 mcg/day) has been shown to confer reasonable protection against vitamin B12 insufficiency. These study findings highlight that a combination of increased physical activity and dietary vitamin B12 intake above the current recommended dietary allowance may help improve the serum vitamin B12 levels of young women of childbearing age, especially those with a low socioeconomic status. Timely detection and protection against vitamin B12 insufficiency in this subpopulation are important to prevent maternal and fetal health risks.
| S-EPMC7792587 | biostudies-literature
Project description:PurposeTo examine the incidence of cataract and cataract extraction in a trial of folic acid and vitamins B6 and B12.MethodsIn a randomized, double-masked, placebo-controlled trial, 5442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or three or more CVD risk factors were randomly assigned to receive a combination of folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day), or placebo. A total of 3925 of these women did not have a diagnosis of cataract at baseline and were included in this analysis. The primary endpoint was age-related cataract, defined as an incident age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review. Extraction of incident age-related cataract was a secondary endpoint of the trial.ResultsDuring an average of 7.3 years of treatment and follow-up, 408 cataracts and 275 cataract extractions were documented. There were 215 cataracts in the combination treatment group and 193 in the placebo group (hazard ratio, HR, 1.10, 95% confidence interval, CI, 0.90-1.33; p = 0.36). For the secondary endpoint of cataract extraction, there were 155 in the combination treatment group and 120 in the placebo group (HR 1.28, 95% CI 1.01-1.63; p = 0.04).ConclusionsIn this large-scale randomized trial of women at high risk of CVD, daily supplementation with a combination of folic acid, vitamin B6, and vitamin B12 had no significant effect on cataract, but may have increased the risk of cataract extraction.
| S-EPMC4948058 | biostudies-literature
Project description:BackgroundMetformin can cause serum vitamin B12 deficiency, but studies on the influence of its duration and dose are lacking. We investigated vitamin B12 deficiency in patients with type 2 diabetes using metformin, in conjunction with other related factors.MethodThis cross-sectional study included 1111 patients with type 2 diabetes who took metformin for at least 6 months. Serum vitamin B12 levels were quantified using a competitive-binding immunoenzymatic assay, and vitamin B12 deficiency was defined as serum B12 <300 pg/mL. Information on metformin use and confounding variables were collected from records or questionnaires and interviews.ResultSerum vitamin B12 deficiency occurred in 22.2% of patients (n = 247). After adjusting for confounders, a 1 mg increase in daily metformin dose was associated with a 0.142 pg/mL decrease in vitamin B12 (P < .001). Compared with a daily dose of <1000 mg, the adjusted odds ratios for 1000 to 1500, 1500 to 2000, and ≥2000 mg metformin were 1.72 (P = .080), 3.34 (P < .001), and 8.67 (P < .001), respectively. Vitamin B12 deficiency occurred less often in patients taking multivitamins (odds ratio 0.23; P < .001). After adjusting for confounding factors, there was no correlation between B12 deficiency and duration of metformin use. Serum homocysteine levels showed significant negative correlation with vitamin B12.ConclusionMetformin at ≥1500 mg/d could be a major factor related to vitamin B12 deficiency, whereas concurrent supplementation of multivitamins may potentially protect against the deficiency. Serum homocysteine levels were negatively correlated with vitamin B12 levels, suggesting that B12 deficiency due to metformin use may occur at the tissue level. However, this hypothesis will require further study.
| S-EPMC6867725 | biostudies-literature
Project description:Background: Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism affecting the synthesis or breakdown of glycogen in the liver. This study, for the first time, systematically assessed vitamin B12 status in a large cohort of hepatic GSD patients. Methods: Plasma vitamin B12, total plasma homocysteine (tHcy) and methylmalonic acid concentrations were measured in 44 patients with hepatic GSDs and compared to 42 healthy age- and gender-matched controls. Correlations of vitamin B12 status with different disease markers of GSDs (including liver transaminase activities and triglycerides) as well as the vitamin B12 intake were studied. Results: GSD patients had significantly higher plasma vitamin B12 concentrations than healthy controls (p = 0.0002). Plasma vitamin B12 concentration remained elevated in GSD patients irrespective of vitamin B12 intake. Plasma vitamin B12 concentrations correlated negatively with triglyceride levels, whereas no correlations were detected with liver transaminase activities (GOT and GPT) in GSD patients. Merging biomarker data of healthy controls and GSD patients showed a positive correlation between vitamin B12 status and liver function, which suggests complex biomarker associations. A combined analysis of biomarkers permitted a reliable clustering of healthy controls versus GSD patients. Conclusions: Elevated plasma concentration of vitamin B12 (irrespective of B12 intake) is a common finding in patients with hepatic GSD. The negative correlation of plasma vitamin B12 with triglyceride levels suggests an influence of metabolic control on the vitamin B12 status of GSD patients. Elevated vitamin B12 was not correlated with GOT and GPT in our cohort of GSD patients. Merging of data from healthy controls and GSD patients yielded positive correlations between these biomarkers. This apparent dichotomy highlights the intrinsic complexity of biomarker associations and argues against generalizations of liver disease and elevated vitamin B12 in blood. Further studies are needed to determine whether the identified associations are causal or coincidental, and the possible impact of chronically elevated vitamin B12 on GSD.
| S-EPMC7463656 | biostudies-literature
Project description:BackgroundB12 (cobalamin) deficiency has been reported in hypothyroid patients with variable prevalence rates thus routine screening of hypothyroid patients was recommended by some and discouraged by others. We aimed to assess the prevalence of B12 deficiency among hypothyroid patients and to evaluate for pernicious anemia and celiac disease as etiologies.MethodsA total 133 patients were included. Thyroid hormones and thyroid peroxidase (TPO) autoantibodies were measured. Serum B12 was measured and if deficient, intrinsic factor antibodies (IFAB) and tissue transglutaminase (tTG) antibodies were evaluated.ResultsOur study included 45 patients with overt hypothyroidism (OH), 48 patients with subclinical hypothyroidism (SCH), and 40 patients as controls. Mean age was 34.3 years and 82% were females. TPO antibodies were positive in 73.5% of OH and 51.1% of SCH patients. B12 deficiency was detected in 33.3%, 47.9%, and 37.5% of OH, SCH, and controls, respectively with no significant difference (P = .334). Borderline-to-low B12 level was more prevalent in the OH and the SCH groups compared to controls (68.9%, 85.4%, and 57.5%, respectively; P = .014). Among B12-deficient hypothyroid patients, 7.5% had positive IFAB and 13.3% had positive tTG antibodies. We did not find a significant association of TPO positivity and B12 deficiency (OR, 0.69; 95% CI 0.3-1.57; P = .147).ConclusionWe did not find a higher prevalence of B12 deficiency among hypothyroid patients nor an association with TPO positivity. Borderline B12 levels were more prevalent among hypothyroid patients.
| S-EPMC8943463 | biostudies-literature
Project description:ObjectivesTo compare the effectiveness of oral versus intramuscular (IM) vitamin B12 (VB12) in patients aged ≥65 years with VB12 deficiency.DesignPragmatic, randomised, non-inferiority, multicentre trial in 22 primary healthcare centres in Madrid (Spain).Participants283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm.InterventionsThe IM arm received 1 mg VB12 on alternate days in weeks 1-2, 1 mg/week in weeks 3-8 and 1 mg/month in weeks 9-52. The oral arm received 1 mg/day in weeks 1-8 and 1 mg/week in weeks 9-52.Main outcomesSerum VB12 concentration normalisation (≥211 pg/mL) at 8, 26 and 52 weeks. Non-inferiority would be declared if the difference between arms is 10% or less. Secondary outcomes included symptoms, adverse events, adherence to treatment, quality of life, patient preferences and satisfaction.ResultsThe follow-up period (52 weeks) was completed by 229 patients (80.9%). At week 8, the percentage of patients in each arm who achieved normal B12 levels was well above 90%; the differences in this percentage between the oral and IM arm were -0.7% (133 out of 135 vs 129 out of 130; 95% CI: -3.2 to 1.8; p>0.999) by per-protocol (PPT) analysis and 4.8% (133 out of 140 vs 129 out of 143; 95% CI: -1.3 to 10.9; p=0.124) by intention-to-treat (ITT) analysis. At week 52, the percentage of patients who achieved normal B12 levels was 73.6% in the oral arm and 80.4% in the IM arm; these differences were -6.3% (103 out of 112 vs 115 out of 117; 95% CI: -11.9 to -0.1; p=0.025) and -6.8% (103 out of 140 vs 115 out of 143; 95% CI: -16.6 to 2.9; p=0.171), respectively. Factors affecting the success rate at week 52 were age, OR=0.95 (95% CI: 0.91 to 0.99) and having reached VB12 levels ≥281 pg/mL at week 8, OR=8.1 (95% CI: 2.4 to 27.3). Under a Bayesian framework, non-inferiority probabilities (Δ>-10%) at week 52 were 0.036 (PPT) and 0.060 (ITT). Quality of life and adverse effects were comparable across groups. 83.4% of patients preferred the oral route.ConclusionsOral administration was no less effective than IM administration at 8 weeks. Although differences were found between administration routes at week 52, the probability that the differences were below the non-inferiority threshold was very low.Trial registration numbersNCT01476007; EUDRACT (2010-024129-20).
| S-EPMC7440823 | biostudies-literature
Project description:ObjectiveTo describe the prevalence of vitamin B12 deficiency among Jordanian patients with type 2 diabetes mellitus treated with metformin and to compare the findings with those who did not receive metformin.Design and methodTotal 155 patients with type 2 diabetes mellitus, aged between 48 and 82 years were enrolled in the current study. They were divided into two groups; the first (n = 120) was treated with metformin while the second (n = 35) was not. Patients' demographics (age, gender, duration of type 2 diabetes mellitus, smoking status), medication parameters (daily dosage and duration of metformin therapy), and biochemical parameters (hemoglobin level, mean corpuscular volume (MCV), serum vitamin B12, and folate level) were recorded. Definite deficiency was defined as serum vitamin B12 levels of < 150 pg/ml, whereas < 200 pg/ml indicated possible deficiency.ResultsThe mean serum ± standard deviation (SD) vitamin B12 level was significantly lower in patients who were treated with metformin (268.5 ± 35.8 vs. 389.5 ± 29.8 pg/ml, p = 0.029). The metformin group had significantly higher prevalence of definite deficiency (32% vs. 9%, p < 0.02) and possible deficiency (48% vs. 30%, p < 0.02). Within the metformin group, the mean serum ± SD vitamin B12 level was significantly lower in those on high dosage (175.2 ± 30.5 vs. 315.6 ± 37.8 pg/ml, p < 0.001). MCV (μm3) levels ± SD were higher in the metformin group (87.5 ± 2.9 vs. 83.7 ± 2.4) with no statistical significance.ConclusionThere is a significant association between metformin intake and vitamin B12 deficiency. Serum vitamin B12 levels should be checked by physicians and serial monitoring is necessary in patients who are treated with metformin.
| S-EPMC9803116 | biostudies-literature
Project description:Vitamin B12 (VB12) deficiency, which may lead to hematologic and neurologic symptoms, has been associated with metformin use, but the underlying mechanism is unclear. Here we report the B. ovatus as an effective VB12 catcher which was enriched in the type 2 diabetes patients suffered from VB12 deficiency after 3 to 6 months of metformin treatment. Colonization of B. ovatus increased the plasma levels of methylmalonic acid and homocysteine in high-fat diet (HFD)-fed mice treated with metformin, and compromised the efficacy of metformin against the HFD-induced metabolic disorders. Mechanistically, metformin increased the intracellular accumulation of VB12 in B. ovatus via btuB upregulation and promoted ATP production for energy-dependent translocation of VB12 transporters at the inner membrane, leading to an enhanced colonization of B. ovatus to compete for VB12 with hosts and subsequently an aggravated VB12 deficiency in the host. Our findings illustrate a previously unappreciated mechanism of metformin leads to host VB12 deficiency by acting directly on gut bacteria to increase their VB12 uptake and consumption, and suggest that inter-host-microbe competition for nutrients may broadly impact human health and drug safety.
| S-EPMC10366088 | biostudies-literature