L-methylfolate, a dietary supplement supplying ready-to-use vitamin B9, is used to secure folate status. It raises blood folate at least as well as folic acid and is well tolerated. As an add-on for depression not fully helped by antidepressants, it shows a modest high-dose effect on low-quality evidence. Main risks: hiding vitamin B12 deficiency and, based on folic acid data, possibly promoting existing bowel polyps; larger longevity claims remain unproven. (Full Review)
| Marker | Target | Why |
|---|---|---|
| Serum vitamin B12 with MMA | B12 at or above 148 pmol/L; MMA at or below 210 nmol/L | Safety check: low B12 stops or delays use |
| Red blood cell folate | Above 906 nmol/L (400 ng/mL) | Expected to rise; tracks tissue folate |
| Plasma total homocysteine | About 5–15 µmol/L | Expected to fall |
| MCV in a complete blood count | 80–100 fL | Safety check: rising MCV with normal folate suggests hidden B12 deficiency |
| PHQ-9 depression score (depression add-on use only) | No established target; change from own baseline | Expected to fall if the add-on works |
Cadence: Baseline B12, folate, homocysteine and complete blood count; homocysteine and plasma folate at 8–12 weeks; red blood cell folate at 12–24 weeks; then B12, folate and homocysteine every 6–12 months. Depression scores every 4 weeks for the first 3 months, then every 3 months. Phenytoin levels rechecked within 2–4 weeks of starting.