Vitamin B12 Supplementation Research Articles

The effect of parenteral vitamin B12 on the growth rate of dairy calves over the summer and autumn on seven farms from the Central Plateau, New Zealand

ABSTRACTAimsTo investigate the effect of parenteral vitamin B12 supplementation on the growth rate of dairy heifer calves over the summer and autumn on seven farms from the Central Plateau of New Zealand, an area historically associated with low cobalt levels in grazing pasture.MethodsThis was a controlled clinical trial conducted on a convenience sample of seven farms with young female calves randomly assigned to three vitamin B12 treatment groups and followed through a grazing season. Two treatment groups received either monthly SC injections of a short-acting (SA) B12 formulation or 3-monthly injections of a long-acting (LA) B12 formulation and the third group received no treatment (NT). No additional parenteral vitamin B12 was given; however, all calves received additional cobalt (0.04–0.4 mg Co/kg liveweight) in the mineralised anthelmintic drenches given orally every month. Liveweight was recorded in December/January and at the end of the trial in May/June/July depending on farm. Pasture cobalt concentrations (mg/kg DM) were measured every month using 500-g herbage samples from 100-m transects in the area about to be grazed by the trial groups.ResultsThere was evidence for a difference in growth rate between groups with mean final weight of 228 (95% CI = 212–243) kg for the LA groups, 224 (95% CI = 209–239) kg for the SA groups and 226 (95% CI = 211–241) kg for the NT groups respectively, (global p-value = 0.014). Calves given SA vitamin B12 were 3.77 (95% CI = 0.71–6.82) kg lighter than calves given LA vitamin B12 (p = 0.011). There was no evidence for a change in pasture cobalt concentrations (p = 0.32).Conclusions and clinical relevanceThe results of this trial raise the question as to whether the routine use of vitamin B12 supplementation in young cattle from areas traditionally thought to be cobalt deficient is necessary, and further raise the possibility that vitamin B12 supplementation by repeated injection of SA products may negatively impact growth rates.

Vegan/vegetarian diet and human milk donation: An EMBA survey across European milk banks.

The nutritional adequacy of human milk (HM) from vegan/vegetarian mothers has been a matter of debate, and a variety of recommendations regarding the eligibility of these mothers as human milk donors exists. According to the latest evidence, HM from vegans/vegetarians is similar in its composition to that from omnivores, however, some differences may be observed regarding vitamin B12 and omega-3 fatty acids concentrations. Maternal supplementation of these compounds has been proven effective in increasing their HM concentration. With this survey, we aimed to explore the practices currently in use in European human milk banks (HMBs) regarding potential donors following vegan/vegetarian diets. The online survey was distributed to European HMBs between January and July 2022. A total of 188 HMBs were contacted, and 118 replied (response rate 63%). Vegan and vegetarian mothers were recommended supplements of vitamin B12 to be accepted as donors in 27% and 26% of HMBs, respectively. Additional omega-3 fatty acid supplementation was required in 8% HMBs. In the remaining HMBs, these mothers were either systematically excluded or included regardless of supplementation. The dosage of the recommended supplements was extremely variable. Fifty-one percent of HMBs were following recommendations to guide their practice, national or local recommendations mainly. Great variability in European HMBs practices towards potential donors following vegan/vegetarian diets exists. Some of these practices can result in loss of donors and/or in potential nutritional deficiencies. Standardised evidence-based recommendations on this issue and their implementation in daily HMB practice are needed.

High-Dose Vitamin B6 (Pyridoxine) Displays Strong Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated Monocytes.

Vitamin B6 is shown to have anti-inflammatory properties, which makes it an interesting nutraceutical agent. Vitamin B6 deficiency is well established as a contributor to inflammatory-related conditions, whilst B6 supplementation can reverse these inflammatory effects. There is less information available regarding the effects of high-dose vitamin B6 supplementation as a therapeutic agent. This study set out to examine the effects of high-dose vitamin B6 on an LPS-stimulated monocyte/macrophage cell population via an analysis of protein and gene expression using an RT2 profiler PCR array for Human Innate and Adaptive Immune responses. It was identified that high-dose vitamin B6 has a global anti-inflammatory effect on lipopolysaccharide-induced inflammation in monocyte/macrophage cells by downregulating the key broad-spectrum inflammatory mediators CCL2, CCL5, CXCL2, CXCL8, CXCL10, CCR4, CCR5, CXCR3, IL-1β, IL-5, IL-6, IL-10, IL-18, IL-23-a, TNF-α, CSF2, DDX58, NLRP3, NOD1, NOD2, TLR-1 -2 -4 -5 -7 -8 -9, MYD88, C3, FOXP3, STAT1, STAT3, STAT6, LYZ, CASP-1, CD4, HLA-E, MAPK1, MAPK8 MPO, MX-1, NF-κβ, NF-κβ1A, CD14, CD40, CD40LG, CD86, Ly96, ICAM1, IRF3, ITGAM, and IFCAM2. The outcomes of this study show promise regarding vitamin B6 within the context of a potent broad-spectrum anti-inflammatory mediator and could prove useful as an adjunct treatment for inflammatory-related diseases.

Can vitamin B6 alleviate the adverse reactions of quadruple anti-Helicobacter pylori regimen? : randomized controlled trial

BackgroundVitamin B6 is an essential water-soluble vitamin for humans. It is often used to prevent a variety of neuropathies, relieve vomiting, and relieve symptoms such as hand and foot neuritis.AimTo evaluate whether vitamin B6 can alleviate the adverse reactions caused by the quadruple anti-Helicobacter pylori treatment regimen containing minocycline and metronidazole.MethodsIn this randomized controlled trial, 280 patients with H. pylori infection were randomly placed into one of two treatment groups—the conventional treatment group and the vitamin B6 supplement treatment group—for 2 weeks. The primary endpoint was the total incidence of adverse reactions up to 2 weeks after treatment initiation. The study was designed according to CONSORT Medicinal Interventions. And it was registered with Chinese Clinical Trial Registry under the number ChiCTR2100053833.ResultsIn terms of efficacy, vitamin B6 does not affect the efficacy of conventional regimen. In the vitamin B6 supplement treatment group, the incidence of adverse reactions was 56.92%, which was significantly lower than the 74.62% observed in the conventional treatment group. In addition, the severity of adverse reactions was also significantly reduced. The proportion of moderate to severe central nervous system symptoms decreased from 58.7 to 14.63%. And, the proportion of moderate to severe gastrointestinal reactions decreased from 33.33 to 0%. We speculate that the mechanism of vitamin B6 of reducing adverse reaction may be related to the production of GABA in the brain.ConclusionsVitamin B6 can alleviate adverse reactions of the quadruple anti-H. pylori regimen containing minocycline and metronidazole.

OS09.6.A A MULTICENTER, PHASE I/II, OPEN-LABEL STUDY OF INTRATHECAL PEMETREXED FOR LEPTOMENINGEAL METASTASES FROM SOLID TUMOR (PMLM, NCT 05289908)

Abstract BACKGROUND There has never been a dose-escalation study on intrathecal pemetrexed (IP) with vitamin supplementation. This phase I/II study was to evaluate the maximum-tolerated dosage (MTD) of IP with vitamin supplementation and the antitumor activity for leptomeningeal metastases (LM) from solid tumors. MATERIAL AND METHODS Phase I study followed the classic 3 + 3 design, with the dose of IP escalated from 15 mg. Phase II followed the Simon 2-stage design with the recommended dose determined in phase I. IP was administered twice per week for 2 weeks (induction therapy), followed by once per week for 4 weeks (consolidation therapy). Clinically stable or improved patients continued IP once a month (maintenance therapy). Vitamin B12 (1000 μg) and folic acid (400 μg, q.d.) were given at the beginning of treatment. Primary end points were MTD in phase I and clinical response rate (CRR) in phase I/II. All patients were assessed to investigate safety, CRR and overall survival (OS). RESULTS Between Feb 2022 and Jan 2023, 34 patients (male: 16; female: 18; age: 45-68 years; median: 56 years) were enrolled, including non-small lung cancer (20), small-cell lung cancer (3), breast cancer (8), others (3). Thirty-three patients had a confirmed LM diagnosis (positive CSF cytology). Remaining one had probable diagnosis (positive neuroimaging with typical clinical signs). Ten patients were enrolled in phase I. Three of 4 patients receiving IP at 15 mg completed induction and consolidation treatment without dose limiting toxicity (DLT). The dose was escalated to 20 mg. Two DLT (1 grade 4 hematologic toxicity and 1 grade 5 arachnoiditis) occurred in 6 patients at 20 mg. The MTD was determined to be 15 mg. Then 24 patients were enrolled in phase II and given 15 mg of IP. 82.4% (28/34) and 58.8% (20/34) patients completed induction and consolidation therapy, respectively. 41.2% (14/34) patients received maintenance therapy. Adverse events (AEs) rate was 73.5% (25/34). 50% (17/34) patients showed grade ≥ 3 AEs, including myelosuppression (11), elevation of hepatic aminotransferases (EHA) (5), elevation of blood bilirubin (EBB) (1), arachnoiditis (1), radiculitis (1), fatigue (1) and nausea (1). The overall CRR was 41.2% (14/34) by neuro-oncology proposal criteria, including 10 (29.4%) with improved neurological dysfunction, 11 (32.4%) with CSF cytological response and 4 (11.8%) with neuroimaging improvement. In a total of 28 patients receiving IP at 15 mg, 50% (14/28) patients showed grade ≥ 3 AEs, including myelosuppression (9), EHA (10), fatigue (1) and nausea (1). The CRR was 46.4% (13/28) in patients at 15 mg IP. Median survival was 7.6 (range 0.3-13.7) months in phase I, while has not yet been achieved in phase II until March 15, 2023. CONCLUSION MTD of IP was 15 mg with folic acid and vitamin B12 supplementation. IP is an optimal therapeutic option for LM from solid tumors.

Combined effects of vitamin B12 and fumarate on rumen propionate production and methanogenesis in dairy cow in vitro

AbstractThis study explored the combined effects of vitamin B12 and fumarate supplementation on methane (CH4) emission and propionate synthesis in dairy cows through simulated rumen fermentation in vitro. The experimental animals were 3 cows with an average milk yield of 23 ± 2.8 kg/d, a body weight of 618 ± 100 kg, and a parity of 3 ± 1 that were selected as rumen fluid donors. The TMR diet fed to cows is a fermentation substrate. Experiments adopted 2 × 2 factorial design, including control group, vitamin group (1 mg/g DM vitamin B12), fumarate group (100 mg/g DM), and combined addition group (1 mg/g DM vitamin B12 and 100 mg/g DM). All treatments had no effect on the dry matter degradation (DMD). Both vitamin B12 and fumarate reduced CH4 emission, increased the propionate concentration, and reduced the acetate/propionate ratio without any observed interaction. Vitamin B12 made Prevotella and Prevotellaceae_ UCG‐003 increase in quantity, and fumarate increased the abundance of Succinivibrionaceae_UCG‐002 and Selenomonas, both of which are propionate‐producing bacteria. At the species level, the supplementation of vitamin B12 and fumarate slightly changed the abundance of some strains, but it was not statistically significant. Shifts in the abundance of propionate‐producing bacteria and methanogenic archaea species suggest an increase in propionate production and a decrease in CH4 emission. In conclusion, the addition of vitamin B12 and fumarate changed the fermentation mode of the rumen and reduced the emission of CH4 by affecting the structure of the rumen microbial community, but no obvious interaction was found between the two.

The Role of One-Carbon Metabolism in Healthy Brain Aging.

Aging results in more health challenges, including neurodegeneration. Healthy aging is possible through nutrition as well as other lifestyle changes. One-carbon (1C) metabolism is a key metabolic network that integrates nutritional signals with several processes in the human body. Dietary supplementation of 1C components, such as folic acid, vitamin B12, and choline are reported to have beneficial effects on normal and diseased brain function. The aim of this review is to summarize the current clinical studies investigating dietary supplementation of 1C, specifically folic acid, choline, and vitamin B12, and its effects on healthy aging. Preclinical studies using model systems have been included to discuss supplementation mechanisms of action. This article will also discuss future steps to consider for supplementation. Dietary supplementation of folic acid, vitamin B12, or choline has positive effects on normal and diseased brain function. Considerations for dietary supplementation to promote healthy aging include using precision medicine for individualized plans, avoiding over-supplementation, and combining therapies.

Vitamin B12 effectiveness in the management of hospitalized COVID-19 and its clinical outcomes and complications: A randomized clinical trial.

Since 2019, severe acute respiratory syndrome coronavirus 2, has spread and challenged the health care system for treatment which is mainly limited to supportive care. It is well-established that malnutrition impedes the immunity in human bodies, and makes it vulnerable to microorganisms. Vitamin B12 is one of the agents that has critical roles in body systems. Thus, the following clinical trial was conducted to assess its possible therapeutic value in COVID-19 patients. The present randomized clinical trial was carried out in Baharlou Hospital, and patients with confirmed COVID-19 infection within 24 h of admission were included. We used quadruple blocks randomization to divide patients into groups of case and control. The case group received 1000 mg of vitamin B12, daily for 7 day while the patients in control group were administered distilled water as placebo. The studied outcomes were duration of hospitalization, need for intensive care unit (ICU), mechanical ventilation, mortality rate and laboratory findings. The statistical analysis was done via SPSS version 22. After implementing inclusion and exclusion criteria, 34 participants were included in the study, 20 of which were male. Serum levels of creatinine, LDH (Lactate dehydrogenase), Ferritin, and CRP (C-reactive protein) had decreased in both groups. The improving changes of CRP, LDH, ferritin and creatinine was higher in case group. The increase of Alanine Transaminase and D-dimer was higher in control group. however there was no statistically significant difference. More patients were admitted to ICU in the control group but the difference was not statistically significant. Duration of hospitalization did not differ statistically between the groups. No in hospital mortality has been recorded. Our study suggests that vitamin B12 supplementation seem to have curative effect in COVID-19. Nutritious diet is necessary for proper functioning of the immune system. Since malnutrition is associated with poor prognosis in COVID-19 patients, and limited number of participants in this study, we suggest performing meta-analysis on similar studies to reach reliable result.

Maternal-Periconceptional Vitamin B12 Deficiency in Wistar Rats Leads to Sex-Specific Programming for Cardiometabolic Disease Risk in the Next Generation

BackgroundMaternal vitamin B12 deficiency plays a vital role in fetal programming, as corroborated by previous studies on murine models and longitudinal human cohorts. ObjectivesThis study assessed the effects of diet-induced maternal vitamin B12 deficiency on F1 offspring in terms of cardiometabolic health and normalization of these effects by maternal-periconceptional vitamin B12 supplementation. MethodsA diet-induced maternal vitamin B12 deficient Wistar rat model was generated in which female rats were either fed a control AIN-76A diet (with 0.01 g/kg vitamin B12) or the same diet with vitamin B12 removed. Females from the vitamin B12-deficient group were mated with males on the control diet. A subset of vitamin B12-deficient females was repleted with vitamin B12 on day 1 of conception. The offspring in the F1 generation were assessed for changes in body composition, plasma biochemistry, and molecular changes in the liver. A multiomics approach was used to obtain a mechanistic insight into the changes in the offspring liver. ResultsWe showed that a 36% reduction in plasma vitamin B12 levels during pregnancy in F0 females can lead to continued vitamin B12 deficiency (60%–70% compared with control) in the F1 offspring and program them for cardiometabolic adversities. These adversities, such as high triglycerides and low high-density lipoprotein cholesterol, were seen only among F1 males but not females. DNA methylome analysis of the liver of F1 3-mo-old offspring highlights sexual dimorphism in the alteration of methylation status of genes critical to signaling processes. Proteomics and targeted metabolomics analysis confirm that sex-specific alterations occur through modulations in PPAR signaling and steroid hormone biosynthesis pathway. Repletion of deficient mothers with vitamin B12 at conception normalizes most of the molecular and biochemical changes. ConclusionsMaternal vitamin B12 deficiency has a programming effect on the next generation and increases the risk for cardiometabolic syndrome in a sex-specific manner. Normalization of the molecular risk markers on vitamin B12 supplementation indicates a causal role.

Riboflavin application regulates sugar and energy metabolism in strawberries during cold storage

The commercial and nutritional value of strawberry fruit is drastically reduced due to its susceptibility to decay fungal diseases. In this study, we employed 40 μM riboflavin to delay senescence and decay of strawberry fruit during storage at 4 °C for 12 d. The findings showed that the treatment decreased strawberries mass loss, respiration rate, ROS level, and MDA content and maintained soluble sugars level. Riboflavin treatment maintained high levels of ATP content and energy charge, and activated the activities of succinate dehydrogenase (SDH), cytochrome C oxidase (CCO), H+-ATPase, Ca+-ATPase, glucokinase (GK), fructokinase (FRK), glucose-6-phosphate dehydrogenase (G6PDH), and 6-phosphogluconate dehydrogenase (6-P-GDH) and up-regulated the expression of their encoding genes. In addition, riboflavin-mediated NAD kinase (NADK) activation accelerated the conversion of NAD+ to DADP+ and the accumulation of DADPH. The respiratory pathway switched from the glycolytic (EMP)-tricarboxylic acid cycle (TCA) to the pentose phosphate pathway (PPP), reducing respiratory consumption. As a result, our findings suggest that riboflavin supplementation after harvest maintains a higher level of energy and delays senescence in strawberries.

Advanced Messaging Intervention for Medication Adherence and Clinical Outcomes Among Patients With Cancer: Randomized Controlled Trial.

Medication adherence is crucial for improving clinical outcomes in the treatment of patients with cancer. The lack of adherence and adverse drug reactions can reduce the effectiveness of cancer therapy including the quality of life. The commonly used intervention methods for medication adherence continue to evolve, and the age of fifth-generation (5G) messaging has arrived. In this study, we conducted a prospective, pilot randomized controlled trial to evaluate the effect of 5G messaging on medication adherence and clinical outcomes among patients with cancer in China. The research population was patients with nonsmall cell lung cancer undergoing pemetrexed chemotherapy who require regular folic acid (FA) and vitamin B12 supplements. The intervention and control groups were assigned to 5G messaging and second-generation (2G) messaging, respectively. The patients' medication adherence and quality of life were assessed at baseline and 1-month and 3-month time points. Moreover, the chemotherapy-related hematologic or nonhematologic toxicities, as well as the serum levels of FA and vitamin B12, were measured. Of the 567 patients assessed for eligibility between January and May 2021, a total of 154 (27.2%) patients were included. Overall, 80 were randomized to the control group and 74 to the intervention group. The odds of adherence in the 5G messaging intervention group were significantly higher than the control group at the 1-month (62/69, 90% vs 56/74, 76%; adjusted odds ratio 2.67, 95% CI 1.02-7.71) and 3-month (50/60, 83% vs 48/64, 75%; adjusted odds ratio 2.36, 95% CI 1.00-5.23) time points. Correspondingly, the FA and vitamin B12 serum levels of patients in the 5G messaging group were higher than those of the control group. Regarding hematologic toxicities, only the incidence of leukopenia in the intervention group was lower than that in the control group (25/80, 31% in the control group vs 12/74, 16% in the intervention group; P=.04). There were no differences in nonhematologic toxicities and quality of life between the 2 groups. In summary, we conclude that compared with conventional 2G text-based messaging, a 5G messaging intervention can better improve medication adherence and clinical outcome among patients with cancer. Chinese Clinical Trial Registry ChiCTR2200058188; https://www.chictr.org.cn/showproj.html?proj=164489.

370 Biochemical Monitoring and Micronutrient Replacement Following Bariatric Surgery

Abstract Aim This project investigates whether patients received appropriate post-operative biochemical monitoring and micronutrient replacement after bariatric surgery, as per British Obesity & Metabolic Surgery Society (BOMSS) guidelines. Method A total of 27 Patients underwent either gastric bypass or sleeve gastrectomy between 1st August 2020 to 31st July 2021 at Northumbria Healthcare NHS Foundation Trust. Data was collected retrospectively. Results Most patients received appropriate micronutrient replacement, with 82% for A-Z multivitamin, 84% for calcium supplement, 72% for vitamin D supplement, 96% for vitamin B12 supplement, and 91% for ferrous sulphate for menstruating women. Similar results found with post-operative blood tests at 6 months, 81% for FBC/LFT/U&E, 74% for ferritin and folate, 74% for calcium and vitamin D, and 70% for vitamin B12. Similar findings at 12 months, 74% for FBC/LFT/U&E, 74% for ferritin and folate, 78% for calcium and vitamin D, 70% for vitamin B12, 67% for zinc, 70% for copper, and 67% for selenium. However, compliance with blood tests at 3 months was inferior, 48% for FBC/LFT/U&E, 37% for ferritin and folate, 37% for calcium and vitamin D, and 44% for vitamin B12. Conclusions Most patients received appropriate biochemical monitoring and micronutrient supplements. Unfortunately, less than half of the patients received monitoring blood tests at 3 months, which is a time where post-operative complications such as malnutrition can be identified and corrected. Several factors may have contributed to this, such as delay in communication between secondary and primary care or lack of facilitation to phlebotomy services.

Expanding the spectrum of neonatal-onset AIFM1-associated disorders.

Pathogenic variants in AIFM1 have been associated with a wide spectrum of disorders, spanning from CMT4X to mitochondrial encephalopathy. Here we present a novel phenotype and review the existing literature on AIFM1-related disorders. We performed EEG recordings, brain MRI and MR Spectroscopy, metabolic screening, echocardiogram, clinical exome sequencing (CES) and family study. Effects of the variant were established on cultured fibroblasts from skin punch biopsy. The patient presented with drug-resistant, electro-clinical, multifocal seizures 6 h after birth. Brain MRI revealed prominent brain swelling of both hemispheres and widespread signal alteration in large part of the cortex and of the thalami, with sparing of the basal nuclei. CES analysis revealed the likely pathogenic variant c.5T>C; p.(Phe2Ser) in the AIFM1 gene. The affected amino acid residue is located in the mitochondrial targeting sequence. Functional studies on cultured fibroblast showed a clear reduction in AIFM1 protein amount and defective activities of respiratory chain complexes I, III and IV. No evidence of protein mislocalization or accumulation of precursor protein was observed. Riboflavin, Coenzyme Q10 and thiamine supplementation was therefore given. At 6 months of age, the patient exhibited microcephaly but did not experience any further deterioration. He is still fed orally and there is no evidence of muscle weakness or atrophy. This is the first AIFM1 case associated with neonatal seizures and diffuse white matter involvement with relative sparing of basal ganglia, in the absence of clinical signs suggestive of myopathy or motor neuron disease.

Vitamin and Mineral Deficiency 12 Years After Roux-en-Y Gastric Bypass a Cross-Sectional Multicenter Study

PurposeMicronutrient deficiencies are common after Roux-en-Y gastric bypass (RYGB). This study explores whether vitamin and mineral deficiency was associated with adherence to recommended supplementation 12 years after RYGB.Materials and MethodsThe cross-sectional Bariatric Surgery Observation Study (BAROBS) was conducted in 2018–2020 at three hospitals in Central Norway. We report data on 490 patients’ self-reported adherence to recommended supplements and vitamin and mineral levels in the blood. The patients, who had RYGB between 2003 and 2009, were recommended an over-the-counter multivitamin-mineral supplement, calcium/vitamin D (1000 mg/20 µg) and vitamin B12 injections (reimbursed), since bariatric supplements were not available then.ResultsMean (SD) age was 40.1 ± 9 years at RYGB, and time to follow-up 11.7 ± 1.6 years. Of 490 patients, 393 (80%) were women. Among 361 (74%) patients’ adherent to multivitamin-mineral supplements; folate, vitamin B2, and vitamin B6 deficiency were present in 39 (11%), 103 (29%), and 63 (17%) patients, respectively. The same deficiencies occurred in 44 (34%), 67 (52%), and 67 (52%) patients’ non-adherent to recommendations. Although 466 (95%) patients reported adherence to vitamin B12 supplements, sub-optimal levels were found in 73 (16%) patients.Though 336 (69%) patients adhered to calcium/vitamin D supplements (1000 mg/20 µg), sub-optimal vitamin D levels (< 75 nmol/l) were found in 174/336 (52%) adherent patients and 120/154 (78%) non-adherent patients.ConclusionTwelve years after RYGB, adherence to supplements, though in sub-optimal doses of new recommendations, decreases the probability of vitamin and mineral deficiency, especially for thiamine, vitamin B2, vitamin B6, folate, vitamin B12, and vitamin D, but does not eliminate it.Graphical

Benefit of high-dose oral riboflavin therapy in riboflavin transporter deficiency.

Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised by pontobulbar palsy, sensorineural deafness, sensory ataxia, muscle weakness, optic atrophy and respiratory failure. Riboflavin supplementation is beneficial in short-term reports, but the quantum of benefit in various clinical domains is not well understood. A PubMed search was conducted, which identified 94 genetically confirmed cases of RTD who received riboflavin supplementation and had follow-up assessments. Information on the clinical and functional status before and after riboflavin supplementation was collected and analysed. Seventy-six of the 94 patients (80.9%) showed an overall improvement after riboflavin supplementation, and the remaining (19.1%) were stable, though some patients had deteriorations in individual domains with no reported deaths. The domains that had the highest rates of response to riboflavin supplementation were gross motor function (93.3% improved), bulbar palsy (91.3%) and ataxia (90.0%). Improvements were also seen in limb muscle weakness, audiology, facial nerve palsy and respiratory function. Despite treatment, many patients required assistance to ambulate and had severe or profound hearing loss and some remained gastrostomy or tracheostomy dependent. Riboflavin supplementation is a lifesaving intervention for patients with RTD and results in a profound improvement in several functional domains, with early diagnosis and treatment further improving outcomes. Despite treatment, patients are left with residual disability. There is a need to accurately measure functional outcomes in children with RTD and develop additional disease-modifying therapies.

Association of MTHFR polymorphism, folic acid and vitamin B12 with serum homocysteine levels in pregnant women.

Homocysteine is known to be associated with adverse vascular and metabolic effects, as well as pregnancy complications. Its serum levels are influenced by the function of the enzyme methylenetetrahydrofolate reductase (MTHFR) and the dietary intake of folic acid, vitamin B12, and methionine. In this cross-sectional study, we investigated the association of genetic polymorphisms of the MTHFR gene with vitamin status in pregnant women during mandatory folic acid supplementation. The study included 102 pregnant women between 24 and 28 weeks of gestation who were attending regular outpatient examinations at the maternity clinic. Homocysteine, folic acid, vitamin B12 levels, and MTHFR gene polymorphisms (C677T and A1298C) were analyzed. Significant associations were found between vitamin B12 and folic acid levels with homocysteine (P < 0.001), with lower serum levels of these vitamins being associated with higher homocysteine levels. Surprisingly, there was no significant association between MTHFR genetic polymorphisms and serum homocysteine levels, likely attributed to the supplementation of folic acid and vitamin B12 in vitamin supplements for pregnant women, which counteracts the effect of the mutation. Remarkably, a high prevalence of MTHFR gene mutations was found, with the C677T polymorphism present in 56.9% and the A1298C polymorphism in 87.2% of pregnant women. These findings emphasize the importance of adequate folic acid and vitamin B12 intake during pregnancy to regulate homocysteine levels. Although the MTHFR gene mutations were highly prevalent, their influence on homocysteine levels in this population appears to be mitigated by vitamin supplementation. Further research is warranted to explore the impact of these mutations on other aspects of pregnancy outcomes. The trial is registrated at Clinicaltrail.gov (NCT04952324).

Oral Combination of Vitamin B1, B6, and B12 Supplementation on CD4+ T Cell and IFN-γ in Pulmonary Tuberculosis Patients with First-Line Opioid agonist therapy

Introduction: Tuberculosis (TB) is a wasting or consumption disease which causes metabolic changes in tuberculosis patients. The metabolic changes that can occur are decreased appetite, micronutrient malabsorption, and malnutrition. The purpose of this research was to determine the differences in the result of an oral combination of vitamins B1, B6, and B12 supplementations on Interferon Gamma (IFN-γ) levels and CD4+ T-cell counts in pulmonary tuberculosis patients receiving first-line Opioid Agonist Therapy (OAT) compared to only OAT therapy.

A Missense Variant in AIFM1 Caused Mitochondrial Dysfunction and Intolerance to Riboflavin Deficiency.

AIFM1 is a mitochondrial flavoprotein involved in caspase-independent cell death and regulation of respiratory chain complex biogenesis. Mutations in the AIFM1 gene have been associated with multiple clinical phenotypes, but the effectiveness of riboflavin treatment remains controversial. Furthermore, few studies explored the reasons underlying this controversy. We reported a 7-year-old boy with ataxia, sensorimotor neuropathy and muscle weakness. Genetic and histopathological analyses were conducted, along with assessments of mitochondrial function and apoptosis level induced by staurosporine. Riboflavin deficiency and supplementation experiments were performed using fibroblasts. A missense c.1019T > C (p. Met340Thr) variant of AIFM1 was detected in the proband, which caused reduced expression of AIFM1 protein and mitochondrial dysfunction as evidenced by downregulation of mitochondrial complex subunits, respiratory deficiency and collapse of ΔΨm. The proportion of apoptotic cells in mutant fibroblasts was lower than controls after induction of apoptosis. Riboflavin deficiency resulted in decreased AIFM1 protein levels, while supplementation with high concentrations of riboflavin partially increased AIFM1 protein levels in variant fibroblasts. In addition, mitochondrial respiratory function of mutant fibroblasts was partly improved after riboflavin supplementation. Our study elucidated the pathogenicity of the AIFM1 c.1019T > C variant and revealed mutant fibroblasts was intolerant to riboflavin deficiency. Riboflavin supplementation is helpful in maintaining the level of AIFM1 protein and mitochondrial respiratory function. Early riboflavin treatment may serve as a valuable attempt for patients with AIFM1 variant.

Over the Counter Supplements for Memory: A Review of Available Evidence.

In 2021, the Global Brain Health Supplement Industry Market size was valued at US$7.6 billion. It is predicted to increase to US$15.59 billionby 2030. Memory and its enhancement are a segment of the market that comprised the highest global revenue share in 2021. In the USA alone, dietary supplement sales reached US$18 billion in 2018. The US Food and Drug Administration (FDA) does not have the authority to approve dietary supplements' safety, effectiveness, or labeling before products go on the market. The FDA often does not even review supplements before they go to market. Supplement manufacturers are thus responsible for ensuring their products are safe and that their claims are truthful. An extensive review of current supplements on the market was performed by surveying memory products for sale at local and national pharmacies and grocery stores. A list of 103 supplements was compiled and the ingredients in these memory supplements were reviewed. The 18 most common ingredients in these supplements were identified. Each of the supplements included at least one of the 18 most common ingredients. Scientific data relative to these ingredients and their effect on memory was searched using PubMed and Cochrane library databases. Currently, there is no compelling evidence for use of apoaequorin, coenzyme Q10, coffee extracts, L-theanine, omega-3 fatty acids, vitamin B6, vitamin B9, or vitamin B12 supplementation for memory. On the other hand, there is some current evidence for memory benefit from supplementation with ashwagandha, choline, curcumin, ginger, Lion's Mane, polyphenols, phosphatidylserine, and turmeric. There are current studies with mixed results regarding the benefit of carnitine, gingko biloba, Huperzine A, vitamin D, and vitamin E supplementation for memory. Dietary supplements geared toward improving cognition are a billion-dollar industry that continues to grow despite lacking a solid scientific foundation for their marketing claims. More rigorous studies are needed relative to the long-term use of these supplements in homogenous populations with standardized measurements of cognition. Health care providers need to be aware of any and all supplements their older adult patients may be consuming and be educated about their side effects and interactions with prescription medications. Lastly, the FDA needs to take an active position relative to monitoring marketed supplements regarding safety, purity and claims of efficacy.

Nitrous oxide-induced polyneuropathy, pancytopenia and pulmonary embolism: a case report

BackgroundNitrous oxide is a medical and household gas that has seen its use drift to recreational purpose among the young population in recent years. Significant neurological, hematological and psychiatric side effects, generally related to an induced functional vitamin B12 deficiency, have been described separately in the literature.Case reportA 22-year-old woman of North African origin experienced an exceptional combination of polyneuropathy, bilateral pulmonary embolism and severe pancytopenia related to vitamin B12 deficiency and hyperhomocysteinemia induced by recreational nitrous oxide use. After treatment with vitamin B12 supplementation and intensive rehabilitative management, the patient progressively regained the ability to walk and her biological parameters gradually returned to normal. The pathophysiological mechanisms related to a decrease in vitamin B12 activity are the reduction of products needed for synthesis of deoxyribonucleic acid, carbohydrate or fatty acids, and the increase of hyperhomocysteinemia. Other mechanisms involving a direct action of N2O are also suspected.ConclusionThis case report brings elements to support our knowledge about pathological pathway, recovery and prognosis of recreational N2O abuse complications. The general and medical population should be aware to the serious consequences of this type of consumption.