l-methylfolate / Generic mfg. - LARVOL DELTA

Personalised Nutraceutical Treatment Guided by MTHFR Genotype in Mental Health: A Retrospective Cohort Study. (PubMed, Nutrients) - "In this real-world primary care cohort, personalised nutraceutical treatment, grounded in one-carbon metabolism support and applied alongside usual care, was associated with clinically meaningful reductions in psychological distress. Outcomes were comparable across MTHFR genotypes when treatments were appropriately tailored, suggesting that genotype and biomarker-informed nutraceutical strategies may mitigate potential metabolic disadvantages. These findings support further controlled research into precision nutraceutical psychiatry for anxiety and depression. Secondary analyses of genotype subgroup, specific supplements, and biomarker-outcome associations are reported alongside Benjamini-Hochberg FDR-adjusted p-values and should be interpreted as hypothesis-generating."

Journal • Retrospective data • CNS Disorders • Depression • Metabolic Disorders • Mood Disorders • Psychiatry • MTHFR

Case Report: Persistent isolated hyperhomocysteinemia in an adolescent with celiac disease and homozygous MTHFR c.665C>T polymorphism: a multifactorial disturbance of one-carbon metabolism. (PubMed, Front Genet) - "Sequential trials of pyridoxine, hydroxocobalamin, and high-dose betaine produced modest or transient improvement...Combined oral methylfolate (1,000 µg daily) and vitamin B12 (cyanocobalamin 1,000 µg daily) reduced homocysteine from 66 to 24.6 μmol/L in 8 weeks. This case illustrates multifactorial hyperhomocysteinemia arising from interactions between celiac disease-related micronutrient vulnerability and reduced MTHFR activity. Recognition of gene-nutrient interactions is important when classical metabolic disorders are excluded and may guide targeted therapy."

Journal • Cardiovascular • Celiac Disease • Diabetes • Immunology • Metabolic Disorders • Otorhinolaryngology • Type 1 Diabetes Mellitus • MTHFR

Isolated Parosmia Caused by Vitamin B12 Deficiency. (PubMed, Intern Med) - "A laboratory evaluation demonstrated marked vitamin B12 deficiency without hematologic abnormalities, and oral methylcobalamin led to the complete resolution of parosmia within 3 months. Clinicians should consider vitamin B12 deficiency as a reversible cause of olfactory dysfunction."

Journal • Hematological Disorders • Otorhinolaryngology

Sensory ataxia associated with vitamin B12 deficiency and hypocalcaemia in a patient with 'hikikomori' syndrome. (PubMed, BMJ Case Rep) - "Sunlight exposure combined with methylcobalamin treatment improved both neurological symptoms and serum calcium levels. Repeated measurements during 4 years of follow-up demonstrated a strong positive association between serum vitamin B12 and corrected calcium levels. This case suggests that prolonged social withdrawal and reduced sunlight exposure may contribute to concurrent vitamin D and vitamin B12 deficiencies and that resultant hypocalcaemia may contribute to vitamin B12 deficiency."

Journal • Ataxia • Depression • Endocrine Disorders • Movement Disorders • Pain • Secondary Hyperparathyroidism

Revisiting the hematological manifestations of vitamin B12 deficiency. (PubMed, Front Nutr) - "Severe presentations, seen in approximately 10% of cases, include pancytopenia, hemolytic anemia, and pseudothrombotic microangiopathy, which may mimic hematological malignancies or thrombotic microangiopathies. Early recognition is crucial, as vitamin B12 replacement leads to rapid and often complete hematological recovery."

Journal • Review • Aplastic Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Myelodysplastic Syndrome • Oncology • Pediatrics • Psychiatry • Thrombocytopenia • HP

High-dose methylcobalamin in amyotrophic lateral sclerosis: mechanistic rationale, translational evidence, and clinical implications. (PubMed, Neurodegener Dis Manag) - "Clinical trials evaluating ultra-high-dose methylcobalamin demonstrate a potential attenuation of functional decline in patients treated during early disease stages, although effects on survival and respiratory outcomes remain inconsistent. This narrative review integrates molecular mechanisms, experimental evidence, biomarker research, and clinical trial data to examine the translational relevance, stage dependency, and therapeutic implications of high-dose methylcobalamin in ALS."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Metabolic Disorders

Protective role of L-methylfolate, vitamin B₂, and vitamin D₃ in modulating neurobehavioural and epigenetic outcomes of chronic stress. (PubMed, Nutr Neurosci) - "Multivitamin supplementation restored behaviour, normalized cortisol and organ function, preserved cortical integrity and hepatic methylation, and upregulated METTL3. These findings highlight multivitamins as functional food-based strategies for the prevention of depression-like behaviour."

Journal • CNS Disorders • Depression • Psychiatry • METTL3

B12-HD-RCT: Oral Versus Intravenous Vitamin B12 Replacement in Hemodialysis Patients (clinicaltrials.gov) - P=N/A | N=60 | Completed | Sponsor: Jinnah Hospital

New trial • Chronic Kidney Disease • Renal Disease

Bioequivalence Study of WP205 in Healthy Participants (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Wanbangde Pharmaceutical Group Co., LTD | Active, not recruiting ➔ Completed | Trial completion date: Nov 2028 ➔ Nov 2025

Trial completion • Trial completion date

Vitamin B12 Biomanufacturing. (PubMed, Adv Biochem Eng Biotechnol) - "It mainly exists in four forms: adenosylcobalamin, methylcobalamin, cyanocobalamin, and hydroxocobalamin (hydroxycobalamin). Finally, it provides an overview of the global market pattern of vitamin B12 and the development trends of cost control. This comprehensive and in-depth review is expected to help readers gain a thorough and in-depth understanding of the vitamin B12 biomanufacturing."

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Comprehensive safety assessment of novel dicholine folate vitamin. (PubMed, Toxicol Rep) - "In addition, subchronic oral toxicity studies in rats with calcium and sodium L-5-MTHF salts identified no adverse effects at the highest doses tested, and human clinical studies with L-5-MTHF salts support tolerability, including at intakes above the adult UL established for folic acid. Collectively, these data support the safety of dicholine L-5-MTHF at the proposed use level."

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Vitamin B Supplementation for Diabetic Peripheral Neuropathy: A Review and Meta-Analysis. (PubMed, J Clin Med) - "Sural nerve conduction velocity (MD 2.10 m/s, 95% CI 0.35 to 3.86) and amplitude (MD 0.88 µV, 95% CI 0.08 to 1.67) improved significantly...However, substantial heterogeneity and risk of bias preclude firm recommendations for routine use. Well-designed RCTs stratified by baseline vitamin status are needed."

Journal • Retrospective data • Review • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Pain • Peripheral Neuropathic Pain

Sensory Ataxia Mimicking Diabetic Neuropathy in a Long-Term Metformin User: A Case Report From Korea. (PubMed, Cureus) - "In a resource-limited primary care setting where confirmatory testing was not immediately available, empirical methylcobalamin was initiated. The patient subsequently reported resolution of paresthesia and substantial improvement in gait stability. This case highlights the importance of reassessing presumed diabetic neuropathy when bedside findings suggest an alternative and potentially reversible diagnosis."

Journal • Ataxia • CNS Disorders • Diabetes • Diabetic Neuropathy • Hematological Disorders • Metabolic Disorders • Movement Disorders • Pain

Serum Folate Forms Show Dose-Dependent Increases in Nonpregnant Ethiopian Women of Reproductive Age Participating in a Randomized Controlled Trial with Double-Fortified Salt Containing Iodine and Folic Acid. (PubMed, Curr Dev Nutr) - P=N/A | "This report focuses on changes in FOL-forms {5-methyltetrahydrofolate (5-methylTHF), unmetabolized FA (UMFA), nonmethyl folate (NMFOL; sum of 3 minor FOL-forms), and the oxidation product of 5-methylTHF [pyrazino-s-triazine derivative of 4α-hydroxy-5-methyltetrahydrofolate (MeFox)]} after consumption of iodized salt (IS), lower FA IS (LFS; ∼200 μg additional FA/d), or higher FA IS (HFS; ∼600 μg additional FA/d) from baseline to endline ∼6 mo later...The response of serum FOL-forms to the intervention was consistent with limited information from previous supplementation trials. This trial was registered at clinicaltrials.gov as NCT06223854; https://clinicaltrials.gov/study/NCT06223854?term=NCT06223854&viewType=Card&rank=1."

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A Retrospective Comparative Study of Sodium Ferulate Combined With Methylcobalamin for Oxaliplatin-Induced Peripheral Neuropathy in Patients With Colorectal Cancer. (PubMed, Br J Hosp Med (Lond)) - "The combination of sodium ferulate and methylcobalamin is superior to methylcobalamin monotherapy in alleviating the severity of neurotoxicity, improving nerve conduction function, enhancing clinical efficacy, and promoting quality of life in CRC patients with OIPN, with a comparable safety profile. It represents a promising clinical treatment option for OIPN."

Clinical • Journal • Retrospective data • Colorectal Cancer • Hematological Disorders • Oncology • Pain • Solid Tumor

Copper(II/III) Redox Couple Enables C─H Methylation via a Radical Mechanism Analogous to SAM Enzymes. (PubMed, Angew Chem Int Ed Engl) - "Many enzymatic C-H methylation reactions proceed through sequential one-electron steps mediated by distinct redox cofactors, such as Fe4S4 clusters and methylcobalamin...The CuIII-CH3 complex mediates C-H methylation through hydrogen atom transfer (HAT) and methyl radical transfer, affording methylated products from substrates similar to those targeted by radical SAM methyltransferases. By merging the characteristic HAT and radical rebound reactivity within a single organometallic center, this copper(II/III)-methyl species provides a synthetic platform that mirrors key mechanistic features of enzymatic C-H methylation."

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Synergistic pain relief in cervical radiculopathy: A randomized trial of topical methylcobalamin gel with phonophoresis and Mulligan mobilization. (PubMed, Acta Neurol Belg) - "The findings of this study suggests that efficacy of MeCbl gel application by phonophoresis in combination with Mulligan manual therapy is higher when compared with conventional MeCbl gel application and Mulligan manual therapy in the treatment of cervical radiculopathy. The improved results from the use of phonophoresis are most probably due to increased absorption of medication and its deep penetration into the tissues."

Clinical • Journal • Pain

Bacopa-Enriched Formulation Enhances Memory and Synaptic Plasticity in a Rat Model of Vascular Dementia. (PubMed, Behav Brain Res) - "This study evaluated the effect of a Bacopa-enriched formulation (BEF) containing Bacopa monnieri, coenzyme Q10, acetyl-L-carnitine, phosphatidylserine, benfotiamine, and methyl folate in a rat 2-vessel occlusion (2VO) model of VD. Motor and exploratory functions remained largely unaffected. Findings from this study suggest BEF's memory enhancement is primarily mediated via modulation of excitatory neurotransmission, enhancement of neuroplasticity, and modification of cognitive function biomarkers, with minimal cholinergic system involvement."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Pain • BDNF

Worsening Postural Orthostatic Tachycardia Syndrome Associated with Compounded Tirzepatide Use (ENDO 2026) - "A 47-year-old female with a history of dyslipidemia and obstructive sleep apnea presented with progressive episodes of palpitations, dizziness, diaphoresis, nausea, and near-syncope...Seven months prior to presentation, the patient began using compounded tirzepatide which contained methylcobalamin obtained from a medical spa, losing 20 pounds...Given the close temporal relationship between tirzepatide initiation and symptom progression, the absence of alternative etiologies, and improvement following discontinuation, drug-induced worsening of POTS was suspected. This case suggests a potential association between compounded tirzepatide and autonomic dysfunction, highlighting the need for clinical awareness as GLP-1RA use expands."

Cardiovascular • Dyslipidemia • Gynecology • Hypotension • Metabolic Disorders • Mood Disorders • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

The impact of vitamin B12 deficiency on urinary profile of de novo purine synthesis intermediates: consequences of the methylfolate trap. (PubMed, Nucleosides Nucleotides Nucleic Acids) - "In linear correlation analyses, urinary FIGLU correlated with serum MMA, and GAr, SAICAr, and AICAr correlated with FIGLU, a marker of THF deficiency (p < 0.05). These findings are consistent with methylfolate trapping, linking B12 deficiency to reduced availability of folate cofactors for histidine catabolism and DNPS."

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Intravenous Methylcobalamin-Induced Anaphylactic Shock: A Case Report. (PubMed, Curr Drug Saf) - "Anaphylactic shock, after slow intravenous methylcobalamin injection, is an uncommon but potentially serious adverse effect. The purpose of this case report is to highlight the importance of this rare but serious life-threatening adverse effect. To our knowledge, this is the first reported case of intravenous methylcobalamin-induced anaphylactic shock. Physicians and healthcare teams should be cautious while administering methylcobalamin to patients, especially via the intravenous route."

Journal • Allergy • Critical care • Gynecology • Immunology • Obstetrics

MACROCYTOSIS AND HYPERHOMOCYSTEINEMIA AS CLUES TO CHRONIC NITROUS OXIDE USE: A SINGLE-CENTER CASE SERIES (EHA 2026) - "Through oxidation of the cobalt atom, N ₂ O inactivates methylcobalamin and inhibits methionine synthase...All patients were treated with intramuscular cyanocobalamin, usually daily or on alternate days, although hydroxocobalamin is the formulation of choice in the current protocol due to its faster intracellular uptake...Variable Result Male sex 8 (80%) Age at presentation (years) 26.9 ± 4.2 Other drug use (excluding alcohol/tobacco) 8 (80%) History of thrombosis 0 (0%) Frequency of use – Daily 6 (60%) Frequency of use – Weekends 4 (40%) Months of use prior to presentation (n=8) 18.9 ± 14.3 Oral ulcers 1 (10%) Fatigue 1 (10%) Glossitis 1 (10%) Hemoglobin (g/dL) 13.69 ± 1.54 MCV (fL) 99.36 ± 4.52 Platelets (×10 ⁹ /L) 292.6 ± 58.1 Neutrophils (×10 ⁹ /L) 4.05 ± 0.97 Vitamin B12 (pg/mL) ( 187 – 883) 265.3 ± 83.8 Folate (ng/mL) (2.9 - 20.0) 9.51 ± 11.77 Homocysteine (mg/L) (0.68 - 2.16) 11.86 ± 7.68 Continuous variables..."

Clinical • Addiction (Opioid and Alcohol) • Ataxia • Cardiovascular • Mental Retardation • Metabolic Disorders • Movement Disorders • Preventive care • Thrombosis

Targeted Micronutrient Supplementation in Diabetic Retinopathy With MTHFR Polymorphisms: Biomarker Shifts and Clinical Uncertainty. (PubMed, Cell Biochem Funct) - "Disturbances in one-carbon metabolism, endothelial signaling, oxidative stress, and coagulation balance are central features of diabetes-associated microvascular disease, and targeted micronutrient supplementation-including L-methylfolate, methylcobalamin, pyridoxal-5'-phosphate, antioxidants, and thiol donors-may modulate homocysteine remethylation, endothelial function, and angiogenic signaling...While homocysteine-lowering effects were biochemically evident, they should be contextualized within prior large-scale trials demonstrating discordance between total homocysteine reduction and cardiovascular outcomes, and consideration of downstream metabolites, such as homocysteine-thiolactone, N-homocysteinylated proteins, and S-adenosylhomocysteine, may provide additional mechanistic insight. Collectively, these findings are hypothesis-generating, reflecting biochemical engagement of relevant vascular pathways rather than confirmed clinical benefit, and underscore the..."

Biomarker • Journal • Cardiovascular • Diabetes • Diabetic Retinopathy • Metabolic Disorders • Retinal Disorders • Type 2 Diabetes Mellitus • MTHFR

Clinical evaluation of adjunctive magnesium therapy in patients receiving antidepressants for depression-open label, nonrandomized clinical trial. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - P=N/A | "All patients received evidence-based antidepressants (either escitalopram, sertraline, duloxetine, amitriptyline, or fluoxetine). Adjunct antidepressant therapy with magnesium is a preliminary effective strategy for patients with depression, potentially augmenting treatment response and decreasing time lag of antidepressants. ClinicalTrials.gov ID: NCT05931965 ( https://clinicaltrials.gov/study/NCT05931965?cond=Depression&intr=magnesium,%20methylfolate,%20B12&rank=1 ), 14-06-2023 (retrospectively registered)."

Clinical • Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Multivitamin Supplementation Mitigates Chronic Stress Induced Testicular Dysfunction by Restoring One-Carbon Metabolism, Redox Balance, and Spermatogenesis in Rats. (PubMed, Physiol Behav) - "For 21 days, researchers assigned male Sprague Dawley rats to three groups: a control group, a stressed group, and a stressed group that received multivitamin treatment with L-methyl folate, vitamin D3, and vitamin B2...The biochemical, histological, epigenetic and molecular changes that occurred during the study were all reversed by multivitamin supplementation. These data show that multivitamin supplementation helps prevent testicular damage caused by stress because it restores hormonal balance, together with redox status and one-carbon metabolism and spermatogenesis, while supporting the use of multivitamin-based treatments as a potential additional method to maintain male reproductive health during chronic stress periods."

Journal • Preclinical • CNS Disorders • Depression • Infertility • Psychiatry • Sexual Disorders