l-methylfolate / Generic mfg. - LARVOL DELTA

Vitamin B12: A Comprehensive Review of Natural vs Synthetic Forms of Consumption and Supplementation. (PubMed, Cureus) - "Vitamin B12, also known as cyanocobalamin, methylcobalamin, and adenosylcobalamin, is an essential vitamin that can be primarily obtained through the human diet. Although animal-based foods supply adequate B12 for most people, deficiency remains common in older adults, vegetarians and vegans, and in those with gastrointestinal disease or malabsorption...This comprehensive review summarizes B12 physiology, sources, absorption, and the clinical picture of deficiency, and compares natural and synthetic forms in common patient scenarios. We also note practical questions for future work, including long-term outcomes of supplementation and whether prophylaxis is useful in high-risk groups."

Journal • Review • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders

Associations of Dietary, Serum, and Red Blood Cell Folate With Frailty: A Cross-Sectional Study. (PubMed, Mol Nutr Food Res) - "U-shaped associations were also observed for serum total folate, 5-methylTHF, non-methyl folate, and RBC folate with frailty (p-nonlinear < 0.001), along with positive associations for serum UMFA and Mefox with frailty. Higher frailty prevalence was found in participants in the lowest quartile of serum total folate, 5-methylTHF, and non-methyl folate (ORs ranging from 1.16 to 1.29) and in the fourth quartile of non-methyl folate and RBC folate (ORs 1.18-1.31).U-shaped associations were observed for fortified foods folic acid and blood folate (serum total folate, 5-methylTHF, non-methyl folate, and RBC folate), an L-shaped association for natural food folate, and positive associations for serum UMFA and Mefox with frailty."

Journal • Observational data

Micronutrient bioavailability: concepts, influencing factors, and strategies for improvement. (PubMed, Front Nutr) - "Certain dietary factors increase the bioavailability of micronutrients: bioavailability can be enhanced by different vitamin forms (e.g., calcifediol is more bioavailable than cholecalciferol; methylfolate is more bioavailable than folic acid), and by the food matrix and nutrient interactions (e.g., fat increases absorption of fat-soluble vitamins; multiple vitamins support iron absorption and metabolism). These include permeation enhancers, lipid-based formulations, nutrient compounding/encapsulation, and phytase to increase bioavailability of minerals trapped by phytic acid. Solutions such as these will help supply highly absorbable and utilizable vitamins and minerals, help close widespread nutritional gaps, and support adequate nutritional status and optimal health across diverse populations worldwide."

Journal • Review • Cardiovascular • Hematological Disorders • Infectious Disease • Ophthalmology • Osteoporosis • Rheumatology

Multicenter randomized controlled trial of Yiqi Huoxue formula() for the treatment of ruptured lumbar disc herniation (PubMed, Zhongguo Gu Shang) - "After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy."

Clinical • Journal • Musculoskeletal Diseases • Orthopedics

One‑carbon pathway gene expression analyses in blood samples of subjects with trisomy 21. (PubMed, Clin Chim Acta) - "Additionally, plasmatic concentration of methylcobalamin (MeCbl) was evaluated in 10 subjects with T21 and 7 N subjects...This dysregulation affects genes located on both Hsa21 and other chromosomes resulting in metabolic alterations. Additionally, new gene interconnections were discovered that have not been previously reported in the literature."

Journal • Developmental Disorders • Genetic Disorders • ABCC3 • ABCC4 • NSD2 • PRMT2 • TRMT11

Electronic Structure of Coenzyme B12 Excited States as Probed by Time-Resolved X-ray Absorption and Emission Spectroscopies. (PubMed, J Phys Chem B) - "This excited-state feature is distinct from that of other alkylcobalamins including methylcobalamin suggesting that the structure of the excited state is distinct. The cascade of picosecond dark states also exhibits significant changes in the Kβ emission, particularly for the Kβ' region, illustrating higher spin density on the cobalt for the excited states than for the doublet photoproduct cob(II)alamin. These findings show the interplay between oxidation state, spin state, and covalency in the Kβ' region of the emission spectrum and illustrate the capability of transient X-ray spectroscopies to characterize excited state electronic structure."

Journal

Nutraceuticals and neuroprotection for glaucoma-introducing the NP-10 System. (PubMed, Ther Adv Ophthalmol) - "Specific nutraceutical interventions, including saffron, French maritime pine, bilberry, palmitoylethanolamide, nicotinamide, methylfolate, methylcobalamin, macular carotenoids, Ginkgo biloba, pyruvate, and citicoline, may target multiple mechanisms to reduce IOP, modulate stress, improve ocular perfusion, enhance cellular bioenergetics, provide antioxidant and anti-inflammatory benefits, augment macular pigment, and improve visual function in glaucoma. With promising emerging evidence for neuroprotection, the NP-10 System provides a scaffold for future large, randomized trials to establish clinical efficacy, optimize formulations, and clarify safety profiles of these nutraceuticals, paving the way for integrating targeted nutritional support into proactive glaucoma care."

Journal • Review • CNS Disorders • Glaucoma • Inflammation • Metabolic Disorders • Ophthalmology

Benign proximal tubular albuminuria due to AMN mutation: A challenging presentation of Imerslund-Gräsbeck syndrome. (PubMed, Pediatr Nephrol) - "His history was negative for infections, but he was taking oral methylcobalamin treatment for a persistent deficiency...While typically presenting with megaloblastic anemia, AMN mutations show variable phenotypes. Proteinuria is resistant to ACE inhibitors, and currently, there is no specific treatment."

Journal • Hematological Disorders • Infectious Disease • Renal Disease • AMN

Long-term outcomes of JETALS (Japan early-stage trial of ultra-high dose methylcobalamin for ALS) study: effects of serum homocysteine levels on survivals in ALS patients (ALS-MND 2025) - "The intramuscular ultra-high dose (50 mg, 2 days a week) methylcobalamin was confirmed to prolong the survival or ventilator-free period when started early (<15 months after onset) at the end of 5 year periods of the study. It is likely that extremely lower levels of homocysteine may not prolong survivals, and the titrating its blood levels during the treatment may be useful, if the homocysteine plays a role in the mechanism of ultra-high dose methylcobalamin in ALS."

Clinical • Amyotrophic Lateral Sclerosis

ALSUntangled program (ALS-MND 2025) - "Over the past 16 years, ALSUntangled has published 83 peer-reviewed and open-access articles; some individual reviews have more than 50,000 downloads. We identified eight most promising AOTs—Acetyl-L-carnitine, Clenbuterol, L-Serine, Methylcobalamin, Nicotinamide riboside/ Pterostilbene, dextromethorphan/Quinidine, Tamoxifen and antiretrovirals—which target multiple overlapping mechanisms relevant to ALS pathogenesis, such as neuroinflammation, oxidative stress, mitochondrial dysfunction, microbiome alteration and antiretroviral activity [3]. We also highlighted "ten red flags" to be aware of when considering AOTs [4]."

Inflammation • Metabolic Disorders

Long-term efficacy of ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: phase II/III trial and open-label extension (ALS-MND 2025) - "In this study, the maintenance of treatment difference with methylcobalamin 50 mg group versus delayed start group suggested the disease-modifying effect of methylcobalamin for ALS. Delayed start results support the importance of early initiation and continued long-term treatment of methlycobalamin. Further studies are needed to elucidate the disease-modifying effects of methlycobalamin for ALS."

Clinical • P2/3 data • Amyotrophic Lateral Sclerosis • CNS Disorders

Clinical safety of ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis: open-label extension of a phase II/ III randomized controlled trial (ALS-MND 2025) - "There were no particular safety issues observed and no clear deterioration in survival rate or ALSFRS-R scores when ultra-high-dose methylcobalamin was administered intramuscularly in advanced ALS."

Clinical • P2 data • Amyotrophic Lateral Sclerosis • Cardiovascular • CNS Disorders • Hypertension

Two Cases of Severe Food-Borne Botulism: Could High-Dose Methylcobalamin Accelerate Recovery? (PubMed, Cureus) - "Persistent bladder atony, fatigue, weakness, and poor concentration improved with structured physiotherapy accompanied by intramuscular methylcobalamin, which was initiated on day 1 of admission and subsequently transitioned to an eight-week course of oral methylcobalamin (500 µg daily) during the post-extubation rehabilitation phase. We discuss mechanistic plausibility and hypothesize that higher-dose methylcobalamin might accelerate neuromuscular recovery by stabilizing mitochondria, attenuating caspase-mediated apoptosis, and promoting axonal regeneration and sprouting."

Journal • Cardiovascular • CNS Disorders • Constipation • Critical care • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hypotension

Red urine in a 68-year-old man with amyotrophic lateral sclerosis. (PubMed, J Gen Fam Med) - No abstract available

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

A randomized controlled trial of electronic balance assistant combined with pharmacotherapy for vestibular rehabilitation in patients with acute peripheral vestibular injury (PubMed, Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi) - "Control group (conventional drug treatment): Patients received medication treatment for 2 weeks, including betahistine mesilate tablets, vitamin B1 tablets, methylcobalamin tablets, ginkgo biloba tablets, diphenhydramine hydrochloride injection (within 3 days of onset), metoclopramide hydrochloride injection, and glucocorticoids. After treatment, the visual, vestibular, and visual dependence scores of both groups significantly increased compared with those before treatment (all P<0.05); moreover, the post-treatment visual, vestibular, and visual dependence scores of the experimental group were significantly higher than those of the control group (all P<0.05). Compared with medication-only treatment, the combination of an electronic balance aid and medication for the treatment and rehabilitation training of patients with acute peripheral vestibular injury can significantly improve the therapeutic effect in the short term."

Clinical • Journal • Otorhinolaryngology • Vertigo

Preclinical safety evaluation of sodium L-methylfolate. (PubMed, Food Chem Toxicol) - "The lack of adverse findings observed with L-5-MTHF-Na are consistent with negative findings observed in published preclinical and clinical studies on calcium L-methylfolate (L-5-MTHF-Ca). In conclusion, L-5-MTHF-Na is shown to have an overall safe profile for its use as a dietary source of folate for nutritional purposes."

Journal • Preclinical • Hematological Disorders • Ophthalmology

Effects of Methylcobalamin on Mitochondrial Alterations in Schwann Cells Under Oxidative Stress. (PubMed, Biomedicines) - " MeCbl improved the mitochondrial structure and remodeled the stress-response pathways in Schwann cells under oxidative stress. By linking high-resolution organelle phenotypes to molecular networks, these findings support MeCbl as a rational adjunct to mitigate oxidative stress-driven peripheral neuropathy and identify an intervenable regulatory axis for future targeted therapies."

Journal • Metabolic Disorders • Pain

VDLIN: A Deep Learning-Based Platform for Methylcobalamin-Inspired Immunomodulatory Compound Screening. (PubMed, Adv Sci (Weinh)) - "Co7 thus emerges as a promising therapeutic candidate, offering advantages over MCB by balancing anti-inflammatory and immune-stimulatory functions. Taken together, this study sheds light on the intricate interplay between chromatin dynamics and immune regulation, presenting new opportunities for therapeutic interventions in inflammatory diseases and SARS-CoV-2 infection."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • EGR1

Bergeyella cardium variant induces a unique cytoplasmic vacuolization cell death floatptosis in macrophage. (PubMed, Cell Discov) - "Bacterial pathogens have evolved multiple mechanisms to modulate host cell death, evade host immunity, and establish persistent infection. SLC9A9 deficiency or amiloride administration increases host defense against BCV infection. These findings contribute to developing novel approaches to modulate cytoplasmic vacuolization cell death and treat infectious diseases."

Journal • Cardiovascular • Infectious Disease

Functional characterization of vitamin B12 from an extremophile-Pseudomonas alcaliphila and assessment of its microbial chassis potential. (PubMed, Front Microbiol) - "Common forms of B12 include adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl) and cyanocobalamin (CNCbl)...Furthermore, recombinant Ectopseudomonas alcaliphila MSJ19 (EaMr) harboring the 3-HP pathway produced up to 3.3 mM 3-HP without external B12 supplementation, highlighting innate capability of the host to produce and utilize bioactive B12 in vivo. Collectively-in vitro, in silico and in vivo approaches establish a functional framework for certifying B12 bioactivity and demonstrating EaM as a potent chassis for production of value-added chemicals."

Journal

Ameliorative potentials of Methylcobalamin Vit B12 against teratogenic effects induced by lead in chick embryo. (PubMed, Sci Rep) - "The findings demonstrate that lead exposure induces notable teratogenic effects in chick embryos and that methylcobalamin effectively ameliorates these developmental abnormalities. This study supports the potential application of methylcobalamin as a protective agent against heavy metal-induced embryo toxicity in avian models."

Journal • Ophthalmology

Pharmacokinetics of (6S)-5-Methyltetrahydrofolate dicholine salt compared to folic acid: a randomized double-blind single dose cross-over study. (PubMed, Food Nutr Res) - "The present study describes the physicochemical properties of the (6S)-5-MethylTHF-2Chol salt as a source of methylfolate with respect to solubility, conductivity, and melting point...The crystalline structure of (6S)-5-MethylTHF-2Chol and its water solubility are advantageous in terms of stability in nutraceutical products and absorption in the gut. (6S)-5-MethylTHF-2Chol is the source of folate that may enable the development of new applications."

Journal • PK/PD data

Microenvironment-Modulating Hyaluronic Acid-Tannic Acid Hydrogel for Peripheral Nerve Injury Repair. (PubMed, Acta Biomater) - "Furthermore, incorporating methylcobalamin (MeCbl) into the hydrogel (HPTA@MeCbl) enables localized and sustained drug release, significantly enhancing axonal regrowth and functional recovery in both crush and transection nerve injury models. This work introduces a clinically translatable, microenvironment-modulating hydrogel platform with dual therapeutic functionalities, offering a promising strategy for advanced peripheral nerve repair."

Journal • Inflammation • Muscular Atrophy

Blood Based Vascular Marker Responses to Ocufolin® in Diabetic Retinopathy Patients Carrying MTHFR Polymorphisms. (PubMed, Biomark Insights) - "Normalizing folate metabolism through Ocufolin® significantly improved key blood-based biomarkers in patients with diabetic retinopathy. These metabolic improvements may underlie enhanced retinal perfusion and reduced oxidative stress, suggesting potential adjunctive therapeutic benefits for managing vascular retinopathies in this population."

Biomarker • Journal • Cardiovascular • Diabetes • Diabetic Retinopathy • Dyslipidemia • Hypertension • Metabolic Disorders • Retinal Disorders • Type 2 Diabetes Mellitus • CRP • MPO • MTHFR

Vitamins, Vascular Health and Disease. (PubMed, Nutrients) - "Therapeutic strategies to address vascular health and prevent hyperhomocysteinemia in order to preclude follow-on disorders include targeted vitamin supplementation, dietary improvements to ensure a sufficient intake of bioavailable nutrient forms, and, in certain clinical contexts, the use of active L-methylfolate or levoleucovorin (a drug product) to bypass metabolic conversion issues. These evidence-based interventions aim to restore endothelial homeostasis, slow disease progression, and improve patient outcomes across a variety of disorders linked to poor vascular health."

Journal • Review • Age-related Macular Degeneration • Alzheimer's Disease • Autism Spectrum Disorder • Cardiovascular • CNS Disorders • Dementia • Genetic Disorders • Macular Degeneration • Metabolic Disorders • Ophthalmology • Peripheral Arterial Disease • Retinal Disorders • Vascular Neurology