Homocysteine is an amino acid intermediate in the methionine-methylation cycle. Recycled to methionine via B12 and folate, or transsulfurated to cysteine via B6.
Mechanism — Elevated when B12, folate, or B6 are inadequate, or when MTHFR variants slow methylation. Damages vascular endothelium directly and promotes thrombosis. Marker of broader methylation dysfunction.
Lab range — Optimal under 8 umol/L. 'Normal' lab ranges often go to 15 — too lax. Elevated levels respond to methylated B-vitamins (methylfolate, methylcobalamin, P5P).
Caveats — Lowering homocysteine is straightforward; whether it reduces hard cardiovascular endpoints in trials is mixed. Treat the marker, but understand the marker is partly causal and partly downstream.