What this test measures
Homocysteine is an amino acid produced during methionine metabolism. It is normally recycled back to methionine via methylation (requiring folate, B12, and methionine synthase) or transsulfurated to cysteine (requiring B6 and cystathionine beta-synthase). Deficiency in any of these vitamins or genetic enzyme defects (most commonly MTHFR C677T variant) raises plasma homocysteine.
Why it matters
Hyperhomocysteinaemia is very common in Indians — 30–60% prevalence in some studies — driven by widespread B12 deficiency (vegetarian / vegan diets), folate insufficiency, and a high prevalence of the MTHFR C677T polymorphism. Raised homocysteine is an independent risk factor for cardiovascular disease, venous thromboembolism, stroke, neural tube defects in pregnancy, and possibly dementia. While supplementation (B12 + folate + B6) reliably lowers homocysteine, RCTs of supplementation for primary CV prevention have shown modest or no benefit — most use is to detect underlying B12/folate deficiency.
How to prepare
Fast 8–12 hours; eating raises homocysteine acutely. Sample should be processed within 30 minutes of collection (homocysteine rises in vitro in unprocessed samples). Stop B-vitamin supplements 48 hours before unless monitoring therapy.
Markers & reference ranges
Reference ranges below are typical adult values. Your lab's reported range may differ slightly based on the assay platform and patient demographics — always read your report against the range printed on it.
| Marker | Normal range | If low | If high |
|---|---|---|---|
| Plasma Homocysteine (µmol/L)[1][2] | Adults 5 – 15 | Low values (< 5) are unusual and not clinically meaningful. | 15 – 30 µmol/L: moderately raised — usually B12 / folate deficiency. Order serum B12 and folate; supplement if deficient; re-test in 3 months. 30 – 100: significantly raised — strongly suggests B12 deficiency; investigate aetiology (vegetarian diet, pernicious anaemia, metformin, PPI use, malabsorption); consider MTHFR polymorphism. > 100: severe — possible inherited homocystinuria (rare CBS deficiency) or extreme B12 deficiency; refer to metabolic clinic. |
Homocysteine bands
| Homocysteine (µmol/L) | Status | Action |
|---|---|---|
| 5 – 15 | Normal | No action |
| 15 – 30 | Moderately raised | Check B12, folate; supplement if low; re-test 3 months |
| 30 – 100 | Significantly raised | Investigate B12 deficiency causes; MTHFR; consider treatment with B12 / folate / B6 |
| > 100 | Severe | Refer metabolic clinic; rule out inherited homocystinuria |
Frequently asked questions
Why is homocysteine high in Indian vegetarians?
B12 (cobalamin) comes almost exclusively from animal sources. Vegetarian and especially vegan diets without supplementation produce B12 deficiency, which raises homocysteine.
Should everyone be tested?
No — order in patients with unexplained venous thromboembolism, premature CAD, family history of homocystinuria, recurrent miscarriages, or as a B12 / folate marker in suggestive clinical settings.
Will B12 supplementation lower it?
Yes, reliably — B12 + folate ± B6 supplementation lowers homocysteine within 4–8 weeks. The harder question is whether lowering it reduces cardiovascular events — large RCTs (HOPE-2, VISP, NORVIT) showed limited or no event reduction.
What is MTHFR C677T?
A common genetic variant that reduces methylenetetrahydrofolate reductase activity and modestly raises homocysteine. Homozygous (TT) individuals have ~20% higher homocysteine and may benefit from folate / B12 supplementation.
Does coffee raise it?
Yes — chronic high coffee consumption modestly raises homocysteine. Smoking also raises it.
Is it linked to dementia?
Epidemiologically yes — raised homocysteine is associated with cognitive decline and dementia. Supplementation trials in cognitive prevention show mixed results.
Related Cardiac Markers tests
Tests commonly ordered alongside HOMOCYSTEINE, or that help interpret an unexpected result.
Sources & references
- AHA Scientific Statement — Hyperhomocysteinemia · accessed 2026-05-30T00:00:00.000Z
- NIH MedlinePlus — Homocysteine Test · accessed 2026-05-30T00:00:00.000Z
- Mayo Clinic Labs — Homocysteine · accessed 2026-05-30T00:00:00.000Z
- ICMR — B12 and folate deficiency in India · accessed 2026-05-30T00:00:00.000Z
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