Homocysteine

What it is

Homocysteine is generated during methionine metabolism. It is normally re-methylated back to methionine (B12, folate dependent) or transsulfurated to cysteine (B6 dependent). Deficiencies in any of these B vitamins, kidney impairment, or genetic variation in MTHFR raise circulating homocysteine.

Reference ranges

• Optimal: <8 μmol/L.
• Normal: 5–15 μmol/L.
• Mild hyperhomocysteinaemia: 15–30.
• Moderate: 30–100.
• Severe: >100 (rare; usually genetic).

Why it matters

Elevated homocysteine associates with:

• Cardiovascular events (likely a marker more than a cause; lowering with B vitamins does not reduce cardiovascular events in RCTs).
• Cognitive decline and dementia (B-vitamin supplementation in elevated- homocysteine adults slows brain atrophy in some trials).
• Bone-fracture risk.
• Pregnancy complications.

What modifies it

• Adequate B12, folate, B6 intake.
• Renal function.
• Hypothyroidism raises it; treating lowers it.
• Coffee and alcohol modestly raise it.
• MTHFR C677T variant: more common, modestly raises it; clinical significance debated.

Practical use

Test if vegetarian/vegan (B12 risk), elderly, family history of premature ASCVD, unexplained cognitive symptoms, or recurrent pregnancy loss.

Related entries

Cardiovascular disease, Cognitive decline, Mediterranean diet.