Metilfolato di calcio meglio conosciuto come L-metilfolato di calcio, noto anche come levomefolato di calcio, è la forma biologicamente attiva dell'acido folico (vitamina B₉) che non richiede conversione addizionale nel corpo per essere utilizzato. È essenziale per numerosi processi biologici, inclusi la sintesi del DNA, la riparazione cellulare e il metabolismo degli amminoacidi. 

Principali utilizzi e benefici 

Salute mentale. Il L-metilfolato di calcio è stato studiato per il suo ruolo nel supportare la salute mentale (1) e nel trattamento di condizioni come la depressione, contribuendo a regolare i livelli di neurotrasmettitori.

Sviluppo fetale. È essenziale per la prevenzione dei difetti del tubo neurale nei neonati, rendendolo un supplemento importante durante la gravidanza per sostenere il corretto sviluppo del feto.

Salute cardiovascolare. Contribuisce alla riduzione dei livelli di omocisteina nel sangue (2), un fattore di rischio per malattie cardiovascolari come l'aterosclerosi.

Funzione cognitiva. Il L-metilfolato di calcio può sostenere la funzione cognitiva e la salute del cervello (3), aiutando a prevenire il declino cognitivo legato all'età.

Assorbimento. Essendo la forma biologicamente attiva dell'acido folico, viene assorbito più efficacemente dal corpo, rendendolo particolarmente utile per individui con varianti genetiche (come la mutazione MTHFR) (4) che influenzano la conversione dell'acido folico.

Integratori Alimentari. Spesso usato in integratori alimentari per garantire un'adeguata assunzione di folato, specialmente per donne in gravidanza, persone con carenze di folato o individui con specifiche esigenze metaboliche.

Il L-metilfolato di calcio offre benefici significativi per la salute, fornendo supporto diretto a molteplici processi corporei senza la necessità di conversione enzimatica, rendendolo un'opzione efficace per l'integrazione di folato.

Processo industriale di sintesi chimica

• Sintesi di L-Metilfolato. La produzione inizia con la sintesi chimica o biotecnologica di L-Metilfolato, partendo da precursori come il folato o l'acido folico. Questo processo può includere diverse fasi di reazione per introdurre il gruppo metile nella molecola di folato.
• Conversione. Il L-Metilfolato ottenuto viene poi convertito nella sua forma di sale di calcio per migliorarne la stabilità e la solubilità. Questo viene realizzato aggiungendo una fonte di calcio alla soluzione di L-Metilfolato e regolando il pH per favorire la formazione del sale.
• Purificazione. Il sale di L-Metilfolato di Calcio grezzo viene purificato per rimuovere impurità e sottoprodotti della sintesi. La purificazione può includere tecniche come la cristallizzazione, la cromatografia e la filtrazione.
• Controllo Qualità. Il prodotto purificato è sottoposto a controlli di qualità per verificare la sua purezza, la composizione chimica e l'assenza di impurità. Questi test possono includere analisi spettroscopiche, cromatografiche e test di identità.
• Formulazione. Il L-Metilfolato di Calcio può essere formulato in varie forme per l'uso in integratori alimentari, come compresse, capsule o polveri, a seconda delle esigenze del prodotto finale.

Si presenta in forma di polvere bianca

Molecular Formula  C₂₀H₂₃CaN₇O₆

Molecular Weight  497.5 g/mol

CAS   151533-22-1

UNII    A9R10K3F2F

EC Number   691-636-3

Synonyms

• Levomefolate calcium
• Metafolin®
• Calcium levomefolate
• Levomefolinate calcium
• Bodyfolin

Bibliografia_____________________________________________________________________

(1) Rainka M, Aladeen T, Westphal E, Meaney J, Gengo F, Greger J, Capote H. L-Methylfolate Calcium Supplementation in Adolescents and Children: A Retrospective Analysis. J Psychiatr Pract. 2019 Jul;25(4):258-267. doi: 10.1097/PRA.0000000000000400. PMID: 31291206.

Abstract. Previous studies have shown l-methylfolate to be a safe and beneficial therapy for neuropsychiatric conditions, including major depressive disorder and schizophrenia in adults. The purpose of this study was to assess safety and describe patient experience using l-methylfolate calcium in a real-world pediatric and adolescent population. A retrospective chart review of patients (7 to 20 y of age, mean age 16 y) prescribed l-methylfolate calcium at a psychiatry clinic in Amherst, NY, between January 1, 2010 and November 10, 2015 was conducted. Patients to whom l-methylfolate calcium 15 mg/d (n=139) or 7.5 mg/d (n=7) was administered were identified; 44 patients who were prescribed but to whom l-methylfolate calcium was not administered were included as a comparator population. Common neuropsychiatric diagnoses included anxiety disorders (68% in the treatment population vs. 50% in the comparator population) and mood disorders (57% in the treatment population vs. 52% in the comparator population). Antidepressants (69% vs. 55%) and mood stabilizers or antiepileptic drugs (63% vs. 57%) were frequently prescribed in combination with l-methylfolate calcium. Adverse events occurred less frequently in the treated population, possibly due to the addition of l-methylfolate calcium (10% vs. 25%, P=0.02). The most common adverse events in the treated population were impaired sleep (5 patients) and increased anxiety (3 patients). Rates of laboratory abnormalities did not differ significantly between the treated and comparator populations (P=0.13). Positive subjective treatment experiences were reported by 22.5% of treated patients and negative subjective treatment experiences were reported by 5.4% of treated patients. L-methylfolate calcium was well-tolerated in a pediatric/adolescent population and may provide benefits for patients with a range of neuropsychiatric conditions.

(2) Huang Y, Tan Y, Wang L, Lan L, Luo J, Wang J, Zeng H, Shu W. Consumption of very low-mineral water may threaten cardiovascular health by increasing homocysteine in children. Front Nutr. 2023 Mar 9;10:1133488. doi: 10.3389/fnut.2023.1133488. PMID: 36969809; 

Abstract. Introduction: Homocysteine (Hcy) is a critical factor for cardiovascular injury, and the elevation of Hcy in children will inevitably increase the risk of cardiovascular disease in adulthood. This study explored the effect of very low-mineral water on children's Hcy and cardiovascular health.....Conclusion: This study suggested that drinking very low-mineral water may increase Hcy level and oxidative stress, worsen lipid profile, and threaten the cardiovascular system in children. Reducing 1,25,(OH)2D3, and disordering of calcium metabolism might play important roles. This study first established an association between demineralized drinking water and cardiovascular health in children, suggesting a new environmental concern risk to cardiovascular health.

(3) Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA. Cerebral folate receptor autoantibodies in autism spectrum disorder. Mol Psychiatry. 2013 Mar;18(3):369-81. doi: 10.1038/mp.2011.175. 

Abstract. Cerebral folate deficiency (CFD) syndrome is a neurodevelopmental disorder typically caused by folate receptor autoantibodies (FRAs) that interfere with folate transport across the blood-brain barrier. Autism spectrum disorders (ASDs) and improvements in ASD symptoms with leucovorin (folinic acid) treatment have been reported in some children with CFD. In children with ASD, the prevalence of FRAs and the response to leucovorin in FRA-positive children has not been systematically investigated. In this study, serum FRA concentrations were measured in 93 children with ASD and a high prevalence (75.3%) of FRAs was found. In 16 children, the concentration of blocking FRA significantly correlated with cerebrospinal fluid 5-methyltetrahydrofolate concentrations, which were below the normative mean in every case. Children with FRAs were treated with oral leucovorin calcium (2 mg kg(-1) per day; maximum 50 mg per day). Treatment response was measured and compared with a wait-list control group. Compared with controls, significantly higher improvement ratings were observed in treated children over a mean period of 4 months in verbal communication, receptive and expressive language, attention and stereotypical behavior. Approximately one-third of treated children demonstrated moderate to much improvement. The incidence of adverse effects was low. This study suggests that FRAs may be important in ASD and that FRA-positive children with ASD may benefit from leucovorin calcium treatment. Given these results, empirical treatment with leucovorin calcium may be a reasonable and non-invasive approach in FRA-positive children with ASD. Additional studies of folate receptor autoimmunity and leucovorin calcium treatment in children with ASD are warranted.

(4) Knowles L, Morris AA, Walter JH. Treatment with Mefolinate (5-Methyltetrahydrofolate), but Not Folic Acid or Folinic Acid, Leads to Measurable 5-Methyltetrahydrofolate in Cerebrospinal Fluid in Methylenetetrahydrofolate Reductase Deficiency. JIMD Rep. 2016;29:103-107. doi: 10.1007/8904_2016_529. 

Abstract. S-adenosyl methionine, which is formed from methionine, is an essential methyl donor within the central nervous system. Methionine is formed by the enzyme methionine synthase for which 5-methyltetrahydrofolate (5-MTHF) and homocysteine are substrates. Patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency cannot make 5-MTHF and have extremely low levels in the CSF. As a consequence, methylation reactions in the CNS are compromised, and this is likely to play an important role in the neurological abnormalities that occur in MTHFR deficiency. Although treatment with oral betaine can remethylate homocysteine to methionine in the liver, betaine crosses the blood-brain barrier poorly, and CSF levels of methionine remain low. We report three patients with severe MTHFR deficiency (enzyme activity ≤1% of controls) who had undetectable levels of CSF 5-MTHF at diagnosis and while on treatment with either folic acid or calcium folinate. Only treatment with oral 5-MTHF given as calcium mefolinate at doses of 15-60 mg/kg/day resulted in an increase in CSF 5-MTHF.