5-methyltetrahydrofolate and Diabetic-Neuropathies

One of the most frequently occurring complications of diabetes mellitus is peripheral neuropathy. Despite the painful symptoms associated with diabetic peripheral neuropathy (DPN), the current treatment landscape focuses on managing symptoms without addressing the underlying causes of DPN. This narrative review describes the mechanistic effects and clinical trial data supporting the use of L-methylfolate calcium (LMF), the bioactive form of folate, which is available in the United States as a prescription medical food that also contains other B vitamins for the dietary management of DPN.. Preclinical and clinical trial data evaluating the impact of LMF on DPN were identified using PubMed searches for articles published between 2010 and 2023. Search terms included: folate, LMF, diabetes, neuropathy, and neuropathic pain. Additionally, a literature search was conducted to identify studies related to LMF, genetic polymorphisms, and DPN pathophysiology.. Several studies show that the C677T variant of the methylenetetrahydrofolate reductase gene is linked to greater risk of DPN than other methylenetetrahydrofolate reductase variants due to its inhibitory effects on several folic acid metabolic pathways. One double-blind, randomized controlled trial, 5 open-label studies, and 1 retrospective study found that LMF has a significant beneficial effect on DPN that extends beyond symptomatic relief to include modulating the underlying pathophysiology that leads to the progression and symptoms of DPN. LMF also significantly improves patient quality of life, with minimal adverse effects.. Preclinical and clinical studies have found that LMF can be used to treat the underlying causes of DPN and provide long-lasting symptomatic relief.

Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Folic Acid; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Quality of Life; Randomized Controlled Trials as Topic; Retrospective Studies

Current therapies for diabetic peripheral neuropathy with pain mask the painful symptoms while the underlying pathology continues to progress. This study assessed changes in symptoms and quality of life in patients taking a novel prescription medical food, L-methylfolate-methylcobalamin-pyridoxal-5-phosphate (LMF-MC-PP, Metanx ), intended to address the underlying metabolic needs of patients with diabetic peripheral neuropathy.. Between November 2010 and April 2012, patients rated their experiences before and after using LMF-MC-PP through an automated telephone system that included symptomatic items from the Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire and questions related to quality of life and medication satisfaction.. A total of 544 patients participated in the study. Patients reported a mean reduction of 35% in NTSS-6 scores from after 12 weeks on LMF-MC-PP. Mean (standard deviation) score was reduced by 1.5 (1.8) at 12 weeks from a baseline of 4.3 (1.5) (p < 0.05). Patients achieved significant reductions in self-reported disruptions in work/school activities, social life, and family life, respectively. Overall pain rating decreased by 32% (p < 0.05). Patients previously treated with medications reported a 52% improvement in medication satisfaction (p < 0.05).. In a real-world clinical setting, patients with diabetic peripheral neuropathy treated with LMF-MC-PP achieved significant improvements in total symptom score (NTSS-6) and in quality of life and functioning, together with greater medication satisfaction. A limitation of this study was the use of a survey instrument to collect data on patient outcomes.

Topics: Adult; Aged; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Pain; Pyridoxal Phosphate; Quality of Life; Surveys and Questionnaires; Tetrahydrofolates; Vitamin B 12

Studies of monotherapy with L-methylfolate, methylcobalamin, or pyridoxal 5'-phosphate suggest that these B vitamins may reverse both the symptoms and the pathophysiology of diabetic peripheral neuropathy (DPN). The efficacy of oral-combination L-methylfolate, 3 mg; methylcobalamin, 2 mg; and pyridoxal 5'-phosphate, 35 mg (LMF-MC-PP) in restoring cutaneous sensitivity in patients with type 2 diabetes with DPN was evaluated in 20 type 2 diabetic patients who were given LMF-MC-PP twice daily for 4 weeks and then once daily for an additional 48 weeks. Statistically significant improvement in 1-point (tactile) and 2-point (discriminatory) static testing at the right and left great toe and heel in the patients was observed in all 3 follow-up periods: 1) baseline to 6 months, 2) baseline to 1 year, and 3) 6 months to 1 year. The greatest improvement occurred between baseline and 1 year of treatment. Treatment with oral LMF-MC-PP appears to promote restoration of lost cutaneous sensation in DPN.

Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Therapy, Combination; Follow-Up Studies; Humans; Pilot Projects; Pyridoxal Phosphate; Sensory Thresholds; Tetrahydrofolates; Touch; Treatment Outcome; Vitamin B 12