Vitamin B12 Supplementation Research Articles

Influence of folic acid and vitamin B12 supplementation on arsenic methylation: A double-blinded, placebo-controlled trial in Bangladeshi children

BackgroundInorganic arsenic is metabolized to monomethyl- (MMAs) and dimethyl- (DMAs) species via one-carbon metabolism (OCM); this facilitates urinary arsenic elimination. OCM is influenced by folate and vitamin B12 and previous randomized control trials (RCTs) showed that folic acid (FA) supplementation increases arsenic methylation in adults. This RCT investigated the effects of FA + B12 supplementation on arsenic methylation in children, a key developmental stage where OCM supports growth. MethodsA total of 240 participants (8–11 years, 53 % female) drinking from wells with arsenic concentrations > 50 μg/L, were encouraged to switch to low arsenic wells and were randomized to receive 400 μg FA + 5 μg B12 or placebo daily for 12-weeks. Urine and blood samples were collected at baseline, week 1 (only urine) and week 12. Generalized estimated equation (GEE) models were used to assess treatment effects on arsenic species in blood and urine. ResultsAt baseline, the mean ± SD total blood and urinary arsenic were 5.3 ± 2.9 μg/L and 91.2 ± 89.5 μg/L. Overall, total blood and urine arsenic decreased by 11.7% and 17.6%, respectively, at the end of follow up. Compared to placebo, the supplementation group experienced a significant increase in the concentration of blood DMAs by 14.0% (95% CI 5.0, 25.0) and blood secondary methylation index (DMAs/MMAs) by 0.19 (95% CI: 0.09, 0.35) at 12 weeks. Similarly, there was a 1.62% (95% CI: 0.43, 20.83) significantly higher urinary %DMAs and −1.10% (95% CI: −1.73, −0.48) significantly lower urinary %MMAs in the supplementatio group compared to the placebo group after 1 week. The direction of the changes in the urinary %iAs, %MMAs, and %DMAs at week 12 were consistent with those at week 1, though estimates were not significant. Treatment effects were stronger among participants with higher baseline blood arsenic concentrations. Results were consistent across males and females, and participants with higher and lower folate and B12 status at baseline. ConclusionThis RCT confirms that FA + B12 supplementation increases arsenic methylation in children as reflected by decreased MMAs and increased DMAs in blood and urine. Nutritional interventions may improve arsenic methylation and elimination in children, potentially reducing arsenic toxicity while also improving nutritional status.

Vitamin B1 supplementation ameliorates high-fat diet induced exercise fatigue and improves grip strength in male mice

Dietary deficiencies in vitamins such as thiamine (Vitamin B1) are common even in developed countries and can have a range of deleterious health effects. This trend in Vitamin B1 deficiency coincides with increased fat consumption in the American diet, particularly of soybean oil, the most widely consumed cooking oil in the U.S. which is also present in many processed foods. Here, we hypothesize that the concurrent malnutrition caused by a soybean oil-based high fat diet (SO-HFD) and a physiological deficiency in thiamine can impact regional gene expression in the brain and behavior. To test this, C57BL/6N male mice (N=10-12 per group) were fed either a low-fat chow (OSD) or an SO-HFD, with or without supplementation with 640 mg/kg of the thiamine analog thiamine tetrahydrofurfuryl disulfide (TTFD), for 18 weeks. Mice were subjected to a series of behavioral tests designed to evaluate cognition (passive avoidance test, PAT), strength (modified grip strength test, MGS), exercise endurance (treadmill test, EE), and locomotor/habituation activity (open field test, OFT). Our results showed no difference across groups on the PAT. On the MGS test, the force generated when normalized to body weight was lesser on all test days for SO-HFD as compared to OSD (p<0.05-0.0001). The TTFD supplementation improved MGS only in the SO group (p<0.05). On EE, OSD ran significantly longer before exhaustion as compared to SO (p<0.05-0.001). For one subset of animals TTFD supplementation improved the EE score in SO but not OSD (p<0.05-0.001). During the one-hour OFT, distance traveled decreased over time for both TTFD-supplemented groups only (p<0.05-0.01), indicating improvement in habituation/learning. Transcriptomic analysis of the hypothalamus and hippocampus from these mice revealed differentially expressed genes (p<0.05) that may contribute to alterations observed in the behavioral tests. Our results indicate that TTFD supplementation ameliorates HFD-induced deficits in strength and exercise endurance. TTFD supplementation improved habituation/learning on OFT regardless of diet. The Thiamine Advocacy Foundation, NIH R01DK127082 (FMS), DOD GW180072 (MCC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dietary Supplementation of Vitamin B12 to Rats Fed High-Amylose Cornstarch Normalizes Propionate Fermentation in the Colon.

Since propionate exerts several physiological effects, maintenance of its normal colonic fermentation is essential. To investigate whether vitamin B12 (VB12) is essential for normal propionate fermentation by colonic bacteria, via the succinate pathway, we examined if high-amylose cornstarch (HACS) feeding activated such a pathway, if high HACS feeding impaired propionate fermentation, and if oral VB12 supplementation normalized propionate fermentation. Male rats were given control, 20% HACS or 3% fucose diets (Expt. 1); a VB12-free control diet or one supplemented with 5-30% HACS (Expt. 2); and the 20% HACS diet supplemented with 0.025-25 mg/kg of VB12 (Expt. 3), for 14 d. HACS feeding significantly increased cecal succinate concentration, activating the succinate pathway (Expt. 1). Cecal cobalamin concentration in 20% and 30% HACS groups was about 75% of that in the control group (Expt. 2). Cecal succinate and propionate concentrations significantly increased and decreased in 30% HACS groups, respectively, compared with the control group. Although HACS group supplemented with 0.025 mg/kg of VB12 had a low concentration of cecal propionate, adding high amounts of VB12 to HACS diets provided sufficient amounts of VB12 to rat ceca and increased cecal propionate concentration (Expt. 3). Compared with the non-HACS group, the relative abundance of Akkermansia muciniphila, but not Bacteroides/Phocaeicola, was lower in the HACS counterpart and showed improvement with increased VB12 doses. To summarize, feeding high HACS decreased and increased cecal VB12 and succinate concentrations, respectively. Furthermore, colonic delivery of sufficient amounts of VB12 to rats likely reduced accumulation of succinate and normalized propionate fermentation.

Establishing the Law of Parsimony in a Case of Restless Legs Syndrome

Restless legs syndrome (RLS) is a common movement disorder characterized by uncomfortable sensations in the lower limbs relieved by limb movements. Clinical studies have established a possible association between RLS and vitamin B12 deficiency but not a causal one. RLS has rarely been reported as an isolated neurological manifestation of vitamin B12 deficiency. In this case report, we described a 24-year-old young man with RLS who responded poorly to symptomatic therapy. The etiological evaluation suggested vitamin B12 deficiency secondary to pernicious anemia. The patient responded rapidly to vitamin B12 supplementation and clinical manifestations of RLS resolved, suggesting a possible causal relationship.

Elevated homocysteine is negatively correlated with plasma cystathionine β-synthase activity in givosiran-treated patients.

Givosiran is a subcutaneously administered, liver-targeted RNA interference (RNAi) therapeutic that has been approved for treating acute hepatic porphyria (AHP). Elevation in plasma homocysteine (hyperhomocysteinemia) has been reported in AHP patients, and treatment with givosiran has been reported to further increase homocysteine levels in some patients. The mechanism of homocysteine elevation during givosiran treatment is unknown, but has been hypothesized to be mediated by a reduction in activity of cystathionine β-synthase (CBS), which uses homocysteine as a substrate. A liquid chromatography-tandem mass spectrometry-based assay was adapted to measure circulating CBS activity. Using plasma collected from the Phase III ENVISION study, CBS activity was measured to directly evaluate whether it is associated with elevated homocysteine levels in givosiran-treated patients. CBS activity was reduced following givosiran treatment and both homocysteine and methionine levels were inversely correlated with CBS activity. Following administration of a supplement containing vitamin B6, a cofactor for CBS, in four patients during the trial, plasma CBS activity was found to increase, mirroring a corresponding decrease in homocysteine levels. These results support the hypothesis that elevated homocysteine levels following givosiran treatment result from a reduction of CBS activity and that vitamin B6 supplementation lowers homocysteine levels by increasing CBS activity.

Preparation and application of silver nanoparticle capped carbon dots composite as fluorescent probe for cobalt determination in vitamin B12 supplement samples

A simple and economical material of fluorescence nanocomposite was developed to quantify vitamin B12 through cobalt(II) ion measurement. The material was derived from carbon dots capped with silver nanoparticles, forming spherical AgNPs@CDs composite with the average diameter of 8.7 nm, expressing unique optical properties, and was used as an optical probe for Co(II) ion determination. The synthesized AgNPs@CDs showed a maximum absorption peak at the wavelength of 406 nm, while their fluorescence peak appeared at the wavelength of 526 nm under the excitation wavelength of 406 nm. The nanocomposites exhibited stable fluorescence with IC50 value against human cholangiocyte cell line of 137.7 ppm after 24 h of the treatment. The interaction between Co(II) ions and AgNPs@CDs effervesced molecular oxygen and caused fluorescence quenching of the composite material. The optimum conditions for Co(II) ion detection were pH 10, volume ratio between AgNPs@CDs and Co(II) ion of 0.10:0.90, and reaction time of 30 min. The linearity range based on the Stern–Volmer plot was 0.05–10.00 ppm, and the limit of detection and limit of quantification were 0.032 ppm and 0.095 ppm, respectively. The developed approach was used to determine the extracted Co(II) ions in commercial vitamin B12 supplement samples and their spiked extracts. The results showed good agreement with those from a conventional method of atomic emission spectrometry, and acceptable range of recovery from 90.0 to 105.0 % was obtained. The fluorescence quenching mechanism of the AgNPs@CDs was elucidated based on the characterization information from several analytical techniques, and electrocatalytic reaction between the nanocomposite and Co(II) species was proposed.

Influence of vitamins and food on the fluorescence spectrum of human urine.

Fluorescence spectroscopy of human urine is a method with the potential to gain importance as a diagnostic tool in the medical field, e.g.,for measuring Coproporphyrin III (CPIII) as an indicator of cancer and acute types of porphyria. Food can change human urine's color, which could influence the urine fluorescence spectrum and the detection of CPIII in urine. To determine if there is a noticeable influence on the urine fluorescence spectrum or on the detection of CPIII in urine, 16vitamin supplements, and three food items were tested. Such investigation may also prevent false interpretation of measured data. Urine samples were collected before and after (overnight, ca. 8 h) intake of each test substance. Samples were investigated by fluorescence spectrum analysis. At excitation wavelengths from 300to 500 nm and emission wavelengths from 400to 700 nm excitation-emission-matrices were measured. Data obtained from urine before intake were compared to the data from overnight urine. Furthermore, the investigation of any interference with the CPIII concentration was performed at an excitation wavelength of 407 ± 3 nm and emission wavelengths of 490-800 nm. Only vitamin B2, but none of the other tested substances, showed noticeable influence on the urine fluorescence spectrum. None of the tested substances showed noticeable interference with the recovery rate of CPIII. The correct interpretation of measured data by fluorescence spectroscopy is possible with the exception if vitamin B2 supplementation was performed; thus, the consumption of vitamin B2 supplements before fluorescence testing of the patient's urine should be avoided and/or must be requested. CPIII concentrations could reliably be measured in all cases.

Common Nutritional Shortcomings in Vegetarians and Vegans

The popularity of vegetarian and vegan diets is growing due to increased awareness of the environmental and health benefits of such diets. However, despite the consumption of meatless diets being associated with decreased risk of chronic diseases and mortality, followers of these diets are prone to certain nutritional inadequacies, which could limit health benefits. The main nutrients of concern are vitamin B12, vitamin D, iodine, selenium, calcium, and iron. It is essential for all those following vegetarian and vegan diets to implement vitamin B12 supplementation. To prevent vitamin B12 deficiency, adults should take one oral dose of 50–100 μg cyanocobalamin daily or 2000 μg weekly divided into two oral cyanocobalamin doses. Iodine supplementation is essential for pregnant and breastfeeding women and is recommended for vegetarians and vegans who are unable to access sea vegetables or iodine-fortified foods. The recommended dose of iodine supplement for adults is 150 μg daily. Selenium supplementation should be reserved for individuals with clinical evidence of deficiency due to concerns of adverse effects on lipid profiles and type 2 diabetes risk. It is recommended that vegetarian and vegan adults should supplement 4000 International Units (IU)/d of oral vitamin D to prevent deficiency as sunlight exposure is unreliable due to a range of lifestyle and environmental factors. This recommendation also applies to omnivores. As a precaution, those wishing to transition to a more plant-based diet should consider how they will substitute the nutrition they currently obtain from animal-based foods with plant-based sources or appropriate supplementation.

Effects of riboflavin on hyperalgesia and serum glutamine-to-glutamate ratio in rats with painful diabetic neuropathy

Previous studies have explored the antinociceptive effects of riboflavin (vitamin B2) across various experimental models. However, there remains a gap in the literature regarding its potential to alleviate neuropathic pain in diabetes. This study aims to investigate the effects of riboflavin on hyperalgesia and serum glutamine-to-glutamate ratio in rats with painful diabetic neuropathy. In fasted rats, a model of painful diabetic neuropathy was induced through intraperitoneal injection of streptozotocin. In the fifth week post-injection, diabetic rats experiencing neuropathic pain were administered daily doses of riboflavin (25 or 50 mg), dissolved in their drinking water, for a duration of two weeks. Results demonstrate that riboflavin significantly reduced mechanical and cold-induced hyperalgesia in diabetic rats compared to controls. Formalin-induced hyperalgesia was alleviated by riboflavin in the second phase. Additionally, riboflavin supplementation increased the serum glutamine-to-glutamate ratio in these animals. These findings highlight the therapeutic potential of riboflavin in managing neuropathic pain associated with diabetes.

Identifying Typical Presentations of Vitamin B-12 Deficiency among Individuals Attending Tertiary Care Hospital in Central Gujarat: A Case Control Study.

Introduction: Vitamin B12 is mainly obtained through non vegetarian diet, milk and milk products. Malabsorption and inadequate intake leads to haematological and neurological disorders. Objective:To determine the symptoms and signs associated with Vitamin B12 deficiency. Method: A case control study was conducted at the medicine department of tertiary care hospital. Patients visiting hospital with serum Vitamin B12 level below 200pg/ml were labelled as cases and more than 200 pg/ml were labelled as controls, irrespective of signs and symptoms of Vitamin B 12 deficiency.Controls were matched for age to minimize confounding. 160 cases and 160 controls were selected. Pretested semi structured questionnaire was used to identify signs and symptoms of Vitamin B12 deficiency among cases and controls. Chi square test was applied for each symptom between cases and control, of which 10 were significant (p<0.05). ROC curve was plotted for the 10 symptoms to check their usefulness for diagnosing vitamin B12 deficiency. Results: Area-Under Curve (AUC) was maximum under knuckle pigmentation (0.794), (Positive Likelihood Ratio (PLR)=3.24) followed by poor memory (0.684), (PLR=3.25) tingling and numbness (0.624), (PLR=1.84) and dizziness (0.605), (PLR=1.38) in respective order. Whereas fatigue, sore and swollen tongue, pale skin, breathlessness, palpitation, insomnia, memory loss were not associated with Vitamin B12 deficiency(p>0.05).Conclusion: Presence of knuckle pigmentation, poor memory, tingling and numbness, and dizziness can be defined as hallmarks of Vitamin B12 deficiency and can be used to predict and start Vitamin B12 supplementation.

Reticulocytes and Related Parameters in Clinical Practice

The development of hematologic analyzers allowed us to assess several additional parameters derived in addition to the number of reticulocytes. There is, among others, the calculation of immature reticulocyte fractions, reticulocyte maturity index, reticulocyte production index, and equivalent reticulocyte hemoglobin. The advantage of the equivalent hemoglobin and the content of hemoglobin is the insensitivity to interference by inflammation. These newly introduced parameters expand the possibilities to access bone marrow erythropoietic activity, iron stores, and the effectiveness of iron supplementation, vitamin B12, and folic acid supplementation. These parameters are also used to make decisions about blood transfusions or to detect occult internal bleeding.

Methionine Supplementation Alleviates the Germ Cell Apoptosis Increased by Maternal Caffeine Intake in a C. elegans Model.

Caffeine (1,3,7-trimethylxanthine) is a widely consumed bioactive substance worldwide. Our recent study showed that a reduction in both reproduction and yolk protein production (vitellogenesis) caused by caffeine intake were improved by vitamin B12 supplementation, which is an essential co-factor in methionine metabolism. In the current study, we investigated the role of methionine in the reproduction of caffeine-ingested animals (CIAs). We assessed the effect of methionine metabolism on CIAs and found that caffeine intake decreased both methionine levels and essential enzymes related to the methionine cycle. Furthermore, we found that the caffeine-induced impairment of methionine metabolism decreased vitellogenesis and increased germ cell apoptosis in an LIN-35/RB-dependent manner. Interestingly, the increased germ cell apoptosis was restored to normal levels by methionine supplementation in CIAs. These results indicate that methionine supplementation plays a beneficial role in germ cell health and offspring development by regulating vitellogenesis.

Effect of Antiepileptic Drugs on Serum Vitamin B12 and Folic Acid Among Children with Epilepsy in Bangalore

In India, there are more than 12 million people diagnosed with epilepsy, and contributes nearly to the one sixth of global burden. Over 60% of diagnosis for epilepsy is done in childhood; hence, it is of major importance to pediatricians. we aimed to assess the levels of Vitamin B12 and Folic acid among children with epilepsy receiving antiepileptic drugs like Carbamazepine, Sodium Valproate and Levetiracetam monotherapy for >1 year. A total of 77 children with epilepsy (<18 years), on monotherapy with SV, CBZ, LEV, for minimum one year, were enrolled after obtaining consent from the parent/guardian. Children with co morbid condition like chronic kidney disease, chronic liver disease, those children who were on multiple AED’s, and children receiving treatment for <1year were excluded from the study. Out of the 77 patients, who were selected for the study, 46 were males and 31 were females. There has been a significant association between duration of treatment and Vitamin B12 and levels of Folic acid. There is also enough evidence to show that age of the patient and Folic acid levels are dependent variables. The proportion of children developing deficiency of Vitamin B12 or Folic acid after treatment with LEV is greater than the proportion treated with CBZ. The proportion of patients developing deficiency of Folic acid after treatment with LEV is greater than the same proportion after treatment with CBZ. Though there were a few significant findings as reported, we, the authors, feel that the study should be continued to ascertain if the AED’s have a significant role in Vitamin B12 and Folic acid metabolism and supplementation should be advised along with the AED’s.

Riboflavin Attenuates Fluoride-Induced Testicular Injury via Interleukin 17A-Mediated Classical Pyroptosis.

Male reproductive toxicity of fluoride is of great concern worldwide, yet the underlying mechanism is unclear. Pyroptosis is a novel mode of inflammatory cell death, and riboflavin with anti-inflammatory properties has the potential to protect against fluoride damage. However, it is unknown whether pyroptosis is involved in fluoride-induced testicular injury and riboflavin intervention. Here, we first found that riboflavin could alleviate fluoride-caused lower sperm quality and damaged testicular morphology by reducing pyroptosis based on a model of ICR mice treated with NaF (100 mg/L) and/or riboflavin supplementation (40 mg/L) via drinking water for 13 weeks. And then, together with the results of in vitro Leydig cell modelsm it was confirmed that the pyroptosis occurs predominantly through classical NLRP3/Caspase-1/GSDMD pathway. Furthermore, our results reveal that interleukin-17A mediates the process of pyroptosis in testes induced by fluoride and riboflavin attenuation according to the results of our established models of riboflavin- and/or fluoride-treated IL-17A knockout mice. The results not only declare a new mechanism by which fluoride induces testicular injury via interleukin 17A-mediated classical pyroptosis but also provide evidence for the potential clinical application of riboflavin as an effective therapy for fluoride toxicity.

Adult Vitamin B12 Deficiency-Associated Pseudo-Thrombotic Microangiopathy: A Systematic Review of Case Reports.

Cobalamin-deficient thrombotic microangiopathy or vitamin B12 deficiency presenting as pseudo-thrombotic microangiopathy is a rare disorder that can be misdiagnosed as thrombotic thrombocytopenic purpura. Patients with this condition are at risk of receiving unnecessary plasmapheresis with a potential delay in appropriate therapy with vitamin B12 supplementation. There are no established diagnostic criteria for this condition in clinical practice. We performed a systematic review of case reports published between January 2018 and January 2023 to analyze the clinical characteristics, risk factors, and patterns of laboratory markers to improve the diagnostic criteria for this condition.

Severe megaloblastic anemia in a patient with advanced lung adenocarcinoma during treatment with erlotinib: a case report and literature review

BackgroundErlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed.Case descriptionHerein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia.ConclusionsThis is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy.

Patients' Perspectives on Type 2 Diabetes, Vitamin B12 Deficiency, and Supplementation in Buraidah, Saudi Arabia.

Objectives Long-term metformin is associated with vitamin B12 deficiency. There is a significant misunderstanding among both physicians and patients regarding vitamin B12 indications. This study aims to identify knowledge gaps and attitudes towardvitamin B12 among diabetic patients. Materials and methods A cross-sectional study was conducted among type 2 diabetic patients visiting four primary healthcare centers in Buraidah, Saudi Arabia. The data were collected using a structured self-administeredquestionnaire. Data were collected on diabetes and vitamin B12 knowledge and attitude towardvitaminB12 supplementation.Logistic regression analyses were used to assess the predictors of knowledge and attitude. Results Of the 388 participants, 192 (49.5%) were male. About 84.5% of the total diabetics were on metformin. Nearly three-fourths (72.7%) were taking vitamin B12. A large proportion, 160 (41.2%), believed that it is necessary to take vitamin B12 for every diabetic patient. Nearly half, 193 (49.7%), did not know the factors affecting vitamin B12 deficiency. Young (less than 39 years) diabetics were more likely to perceive that vitamin B12 is recommended for all diabetics, OR (95% CI) [6.26 (1.86-21.06)], as compared to participants aged more than 59. Similarly, younger patients were more likely to assume vitamin B12 necessary, OR (95% CI) [3.71 (1.26-10.89)]. Conclusion We found the knowledge and attitude of diabetic patients regarding vitamin B12 to be poor. It is, therefore, recommended that primary health care providers educate their patients about vitamin B12 supplementation to reduce the number of medications and financial burden. Further large-scale studies are also needed to generate stronger evidence of the problem.

Riboflavin Increases Serum Glutamine Levels in Rats with Streptozotocin-induced Diabetes

Diabetes mellitus is one of the most common chronic diseases in the world. Metabolomic studies have demonstrated altered blood levels of glutamate and glutamine during type 1 diabetes and type 2 diabetes. Riboflavin is a precursor of flavin adenine dinucleotide and flavin mononucleotide, which are coenzymes necessary for the function of enzymes involved in various biochemical reactions, including those affecting amino acid metabolism. In this study, we investigated the effects of riboflavin on serum glutamate and glutamine levels in rats with streptozotocin-induced type 1 diabetes. Diabetic rats received riboflavin (25 mg, 50 mg, or 100 mg) dissolved in the drinking water daily for 2 weeks. Our results showed that riboflavin supplementation did not affect serum glutamate levels but increased serum glutamine levels in diabetic rats. We speculate that increased serum glutamine levels resulting from riboflavin supplementation may have beneficial effects during diabetes.

A review on vitamin B12 deficiency induced by metformin

Multiple studies have established a higher prevalence of vitamin B12 deficiency in patients who have type 2 diabetes mellitus (T2DM). Metformin is prescribed as the 1st line oral glucose-lowering medication for individuals with T2DM. However, metformin therapy has been linked to vitamin B12 malabsorption, which can result in both biochemical and clinical manifestations of vitamin B12 deficiency. The long-term use of metformin is associated with a significant decrease in vitamin B12 levels, particularly in doses greater than 2000 mg per day over a period of 4 years. Vitamin B12 is a water-soluble vitamin. It acts as a cofactor for enzymes involved in DNA synthesis and neuroprotection at the cellular level. Hence, vitamin B12 deficiency can lead to various clinical consequences, including hematologic abnormalities such as megaloblastic anemia and hypersegmented neutrophil formation, peripheral neuropathy, and progressive axonal demyelination, hyperhomocysteinemia (HHcy). The latest "standards of medical care in diabetes-2017" issued by the American diabetes association recommends periodic assessment of B12 status and, if necessary, the use of B12 replacement therapy in diabetic patients taking metformin. In order to address the vitamin B12 deficiency associated with metformin several therapies are available including prophylactic supplements of calcium and vitamin B12, discontinuation of metformin, and replenishment of vitamin B12 stores through intramuscular or oral therapy. It is important to regularly monitor vitamin B12 levels for at least annually to prevent complications of vitamin B12 deficiency and continue with supplementation if metformin is still being used.

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.