L-Methylfolate is the ready-to-use form of vitamin B9. Head-to-head trials show it raises folate stores faster than synthetic folic acid and lowers the amino acid marker tied to blood vessel and brain ageing. Clinical evidence is thinner, resting mainly on company-funded depression trials. The main hazard: taken without checking vitamin B12, it can hide a nerve-damaging deficiency. (Full Review)
| Marker | Target | Why |
|---|---|---|
| Total homocysteine | 5–8 µmol/L | The functional readout of methyl-cycle capacity |
| Red cell folate | 400–800 ng/mL | Long-term folate stores, unaffected by yesterday's meal |
| Serum folate | 10–25 ng/mL | Short-term folate exposure and adherence |
| Serum vitamin B12 | 500–900 pg/mL | The partner nutrient without which folate cannot act |
| Methylmalonic acid (MMA) | < 250 nmol/L | Detects functional B12 deficiency that serum B12 misses |
| Complete blood count with MCV | MCV 85–92 fL | Detects the enlarged red cells of folate or B12 deficiency |
| High-sensitivity C-reactive protein | < 1.0 mg/L | The inflammatory phenotype that responded best in the depression trials |
| Estimated glomerular filtration rate | > 60 mL/min/1.73 m² | Kidney function raises homocysteine independently of folate |
| Serum 25-hydroxyvitamin D | No established target; track change from baseline | Deficiency co-travels with poor diet and confounds mood outcomes |
Cadence: Baseline panel before starting; homocysteine and red cell folate at 8–12 weeks, then every 6–12 months on maintenance dosing; vitamin B12 annually, or every six months on metformin or acid suppression. On 15 mg, a structured symptom review at 8 and 12 weeks.