What are the uses of 5-Methyltetrahydrofolic Acid (5-MTHF) Glucosamine Salt Tablets?

Uses of 5-Methyltetrahydrofolate (5-MTHF) Glucosamine Salt Tablets

5-MTHF glucosamine salt tablets are primarily used for folate supplementation in individuals with MTHFR genetic polymorphisms (especially 677TT genotype), for prevention of neural tube defects in pregnancy, and for lowering elevated homocysteine levels in patients with moderate hyperhomocysteinemia. 1, 2

Primary Clinical Indications

MTHFR Genetic Polymorphisms

• Patients with MTHFR 677TT genotype should receive 5-MTHF rather than folic acid because this bypasses the deficient MTHFR enzyme and does not require conversion to the active form. 3, 2
• 5-MTHF reduces homocysteine levels by 25-30% in these patients, with an additional 7% reduction when combined with vitamin B12 (0.02-1 mg/day). 2
• The 677TT genotype occurs in 10-15% of the general population and is associated with 2-3 fold increased risk for atherosclerotic vascular disease and stroke when hyperhomocysteinemia is present. 2

Pregnancy and Neural Tube Defect Prevention

• 5-MTHF is the preferred form of folate supplementation during pregnancy, particularly for women with MTHFR polymorphisms, as it is immediately bioavailable and bypasses metabolic blocks in folic acid conversion. 4, 5, 6
• The standard dose is 400-800 μg daily for general population, with pregnant or lactating women requiring approximately 800 mcg daily. 1, 2
• 5-MTHF effectively prevents neural tube defects while avoiding the accumulation of unmetabolized folic acid (UMFA) that can occur with supraphysiological doses of synthetic folic acid. 4, 5

Homocysteine Lowering

• For patients with moderate homocysteinemia (fasting plasma homocysteine 15-30 mmol/L), 5-MTHF treatment should be considered, especially when elevated homocysteine is due to MTHFR 677TT genotype. 3, 1
• 5-MTHF provides direct vascular benefits beyond homocysteine lowering, including scavenging peroxynitrite radicals, protecting tetrahydrobiopterin from oxidation, improving endothelial nitric oxide synthase coupling, and reducing vascular superoxide production. 3, 2

Key Advantages Over Synthetic Folic Acid

Metabolic Superiority

• 5-MTHF is immediately bioavailable as the active form, while folic acid requires hepatic conversion through multiple enzymatic steps that can be impaired by genetic variants or drug interactions. 7, 8
• Absorption of 5-MTHF is not affected by gastrointestinal pH alterations, unlike folic acid which requires specific conditions for optimal absorption. 7
• 5-MTHF increases intracellular folate levels more effectively than folic acid, which primarily raises plasma levels without proportional intracellular increases. 3, 2

Safety Profile

• 5-MTHF does not mask vitamin B12 deficiency hematological symptoms, unlike folic acid which can conceal megaloblastic anemia while allowing neurological damage to progress. 7, 6, 8
• There is no tolerable upper intake level for 5-MTHF, and it does not lead to accumulation of unmetabolized folic acid in circulation. 5, 6
• 5-MTHF has reduced interactions with drugs that inhibit dihydrofolate reductase compared to folic acid. 7, 8

Specific Dosing Protocols

Standard Supplementation

• General population: 250-400 μg/day of dietary folate equivalents. 1
• Pregnancy/lactation: 800 μg daily. 1, 2

MTHFR 677TT Genotype with Hyperhomocysteinemia

• Combine 5-MTHF with vitamin B12 (1 mg weekly provides additional 7% homocysteine reduction), vitamin B6 (50 mg daily), and riboflavin for optimal homocysteine lowering. 2
• This combination addresses multiple enzymatic pathways in homocysteine metabolism. 2

Methotrexate Users

• Patients on methotrexate should receive folate supplementation to reduce gastrointestinal side effects and protect against elevated liver function tests. 2
• Standard dosing: 5 mg weekly (24-72 hours after methotrexate) or 1 mg daily for five days per week. 1

Common Pitfalls to Avoid

• Do not use standard folic acid instead of 5-MTHF in individuals with TT genotype, as it requires conversion by the deficient MTHFR enzyme and is less effective. 2
• Always check vitamin B12 status before initiating folate supplementation—both deficiencies cause elevated homocysteine, and isolated folate supplementation may mask B12 deficiency. 2
• Do not substitute folic acid for folinic acid when folinic acid is specifically indicated (such as with pyrimethamine therapy for toxoplasmosis or methotrexate rescue therapy). 1
• When using vitamin B12 supplementation alongside 5-MTHF, use methylcobalamin or hydroxycobalamin rather than cyanocobalamin, as these forms are more effective in reducing homocysteine levels. 2

Monitoring Parameters

• Measure plasma homocysteine as a functional marker of folate status, though recognize it is also affected by vitamins B2, B6, B12, and renal function. 1
• Serum/plasma folate reflects recent dietary intake and early changes in folate status. 1
• Red blood cell folate reflects long-term status over the preceding 3 months and tissue stores. 1