Methylfolate

BACKGROUND: Adjunctive l-methylfolate is commonly prescribed for children and adolescents with treatment-resistant mood disorders; however, the relationship between l-methylfolate augmentation across methylenetetrahydrofolate reductase (MTHFR) genotypes in youths with depressive symptoms is unclear. METHODS: We retrospectively examined the electronic health records of patients (N = 412) with depressive symptoms associated with unipolar depressive disorders and their MTHFR C677T genotypes from 2013 to 2019...

The epigenetic agents, L-acetylcarnitine (LAC) and L-methylfolate (MF) are putative candidates as add-on drugs in depression. We evaluated the effect of a combined treatment with LAC and MF in two different paradigms of chronic stress in mice and in human inducible pluripotent stem cells (hiPSCs) differentiated into dopaminergic neurons. Two groups of mice were exposed to chronic unpredictable stress (CUS) for 28 days or chronic restraint stress (CRS) for 21 day, and LAC (30 or 100 mg/kg) and/or MF (0.75 or 3 mg/kg) were administered i...

Purpose: To evaluate the effects of Ocufolin® on retinal microcirculation in patients with mild diabetic retinopathy carrying MTHFR polymorphisms. Methods: In a prospective, case-controlled study, eight patients with mild diabetic retinopathy and MTHFR polymorphisms and 15 normal controls (NC) were recruited. MTHFR polymorphisms were subtyped as normal, C677T, or A1298C. Best-corrected visual acuity (BCVA) was evaluated. Retinal blood flow velocity (BFV) was measured using Retinal Function Imager...

Purpose: IDH mutations in low-grade gliomas (LGGs) results in improved survival and DNA hypermethylation compared to IDH wild-type LGGs. IDH -mutant LGGs become hypomethylated during progression. It's uncertain if methylation changes occur during IDH wild-type GBM progression and if the methylome can be reprogrammed. This phase I study evaluated the safety, tolerability, efficacy and methylome changes after L-methylfolate (LMF) treatment, in combination with temozolomide and bevacizumab in patients with recurrent high-grade glioma...

This summary provides context for the role of L-methylfolate (LMF) in treating antidepressant non-responders. Bidirectional relationships have been observed between obesity and/or inflammation and depression. Studies have shown an increased prevalence of depression among patients with elevated body mass index and/or chronic inflammation and an increased risk of becoming obese and experiencing chronic inflammation in those with depression. These relationships can negatively affect the pathophysiology of depression...

OBJECTIVES: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021...

OBJECTIVES: To examine the strengths and limitations of existing data to provide guidance for the use of folate supplements as treatment, with or without other psychotropic medications, in various psychiatric disorders. To identify area for further research in terms of the biosynthesis of mechanism of folate and genetic variants in metabolic pathway in human. METHODS: A systematic review of published literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess whether folate supplements are beneficial in certain psychiatric disorders (depression, bipolar disorder, schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder)...

OBJECTIVES:   Partial response to pharmacotherapy is common in major depressive disorder (MDD) and many patients require alternative pharmacotherapy or augmentation, including adjunctive L-methylfolate. Given that L-methylfolate augmentation is rarely included in major clinical practice guidelines, we sought to systematically review evidence for L-methylfolate augmentation in adults with MDD and to examine its efficacy meta-analytically. METHODS:  We systematically searched PubMed for articles up to December 31, 2020, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations...

Depression is one of the most common mental health disorders and currently affects over 17 million Americans. Up to two-thirds of patients with depression in the United States will seek complementary and alternative or integrative medical treatments and thus medical providers who treat depression should understand that many integrative medical treatments have evidence of efficacy either as monotherapies or as add-on adjuncts to other treatments. This review references guidelines from the Canadian Network for Mood and Anxiety Treatments and Michigan Medicine, along with an updated literature review, to provide a framework for reviewing medications or herbal formulation, as well as other therapies, which have evidence in the treatment of depression...

Major depressive disorder (MDD) is a complex and common disorder, with many factors involved in its onset and development. The clinical management of this condition is frequently based on the use of some pharmacological antidepressant agents, together with psychotherapy and other alternatives in most severe cases. However, an important percentage of depressed patients fail to respond to the use of conventional therapies. This has created the urgency of finding novel approaches to help in the clinical management of those individuals...

OBJECTIVE: Evaluate depression scores, response, and remission rates in patients with major depression receiving adjunct therapy with folate (L-Methylfolate or folic acid) compared to selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor (SSRI or SNRI) monotherapy. METHODS: Academic Search Premier, CINAHL Complete, Cochrane Database of Systematic Reviews, Medline with Full Text, PsychInfo, PubMed, ClinicalTrials.org, and Google Scholar were searched utilizing specific key words...

About half of the patients with Obsessive-compulsive disorder (OCD) do not respond to serotonin reuptake inhibitors (SRIs) or have a partial improvement in their symptoms. This study aimed to compare the efficiency and safety of aripiprazole, olanzapine, and L-methyl folate in patients with resistant OCD. The study consisted of an open-label prospective phase of 12-weeks to ascertain resistance to SRIs and a second 6-week open-label addition phase for non or, partial responders of the first phase. One-hundred-fifteen patients entered the 16-week open-label phase...

This narrative review was conducted using searches of the PubMed/Medline and Google Scholar databases from inception to November 2019. Clinical trials and relevant articles were identified by cross-referencing major depressive disorder (and/or variants) with the following terms: folate, homocysteine, S-adenosylmethionine (SAMe), L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, L-tryptophan, zinc, magnesium, vitamin D, omega-3 fatty acids, coenzyme Q10, and inositol. Manual reviews of references were also performed using article reference lists...

Antiseizure medications (ASM) may contribute to adverse fetal outcomes in pregnant women with epilepsy (WWE). Folate processing (Methylenetetrahydrofolate reductase, MTHFR) gene abnormalities are common in women with epilepsy and depression. L-methylfolate supplements may bypass MTHFR deficiencies, yet their use in WWE during gestation or on fetal development is not well studied. We examine pregnancy histories of three WWE who supplemented with either folate or L-methylfolate and methylcobalamin (methylated B12) during pregnancies...

We report a case of a 61-years-old woman in remission of psoriasis for 20 years. She presented recurrence of psoriasis in the form of plaques few days after taking L-methylfolate 15mg/day. The L-methylfolate was prescribed as an adjuvant for the treatment of depression in a patient with the methylenetetrahydrofolate reductase gene polymorphism (MTHFR).

Methotrexate (MTX; 4-amino-10-methylfolic acid) is a folic acid reductase inhibitor used to treat autoimmune diseases and certain types of cancer. Testicular toxicity resulting from MTX is a significant side effect that may cause subsequent infertility. The present study was conducted to examine the ameliorating effects of vitamin B17 (VitB17) against testicular toxicity induced by MTX in male rats. A total of 50 male albino rats were equally divided into five groups [control group; vitamin B17 group (VitB17) administered VitB17 only; methotrexate group administered MTX only; cotreated group, (VitB17+MTX) and posttreated group (MTX+VitB17)]...

This case study examines a 49-year-old Asian American female patient with long-standing fatigue and depression (20 years or more), for which pharmaceutical antidepressant therapies have been ineffective. History, physical examination, laboratory tests, and Genomind Genecept Assay genetic testing were used to determine symptom severity, investigate the presence of organic causes of fatigue, and provide a potential novel monotherapy for depression. Therapeutic intervention included a slow titration of L-methylfolate to an eventual therapeutic daily dose of 15 mg...

PURPOSE: To investigate conjunctival microvascular responses in patients with mild diabetic retinopathy (MDR) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms (D+PM) after administration of Ocufolin™, a medical food containing 900 μg L-methylfolate (levomefolate calcium or [6S]-5-methyltetrahydrofolic acid, calcium salt), methylcobalamin, and other ingredients. METHODS: Eight D+PM patients received Ocufolin™ for six months (6M). Bulbar conjunctival microvasculature and microcirculation metrics, including vessel diameter (D), axial blood flow velocity (Va), cross-sectional blood flow velocity (Vs), flow rate (Q), and vessel density (VD, Dbox), were measured at baseline, 4M, and 6M...

Major depressive disorder is most commonly treated with a combination of medication and psychotherapy. For those people that do not benefit from the standard therapy or prefer non-pharmacologic therapy, folate supplementation may be an option. Folate is normally acquired through the diet and folate deficiency is associated with depression. In the brain, folate is one nutrient among others involved in the production of the neurotransmitters that affect mood. Studies involving folate supplementation for the treatment of depression have had mixed results but have omitted to take into account the genetic polymorphisms, such as the ones in methyltetrahydrofolate reductase (MTHFR), that affect folate metabolism...

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the extension of use of calcium l-methylfolate to be used as a source of folate added for nutritional purposes to infant and follow-on formula, baby food and processed cereal-based food pursuant to Regulation (EU) 609/2013. In 2004, EFSA assessed the use of calcium l-methylfolate as a source of folate in foods for particular nutritional uses, food supplements and foods intended for the general population...