Folic and folinic acid load tests for dynamic assessments of compliance and metabolism in folate deficiency and hyperhomocysteinaemia patients unresponsive to high-dose folate replacement

We describe the utility of ‘folic and folinic acid load tests’ in the investigation of a 26-year-old woman with persistently low serum folate and moderate hyperhomocysteinaemia unresponsive to folic acid supplements. Serum folate, plasma 5-methyltetrahydrofolate (5-MTHF), red cell 5-MTHF and plasma total homocysteine at baseline, 2-h, 4-h and 2- or 4-days (if applicable) post administration of a large dose of oral folic acid, or oral or parenteral folinic acid were measured. The tests confirmed non-compliance but also suggested an unsuspected possible defect in the folate pathway based on differential response to folic versus folinic acid supplements. The folic and folinic acid load tests identify non-compliance and can help identify possible defects related to the absorption, transportation, or metabolism of folate.