Homocysteine is an intermediate amino acid formed during the metabolism of methionine. Normally the body neutralizes it quickly, and to do so it needs three vitamins: B9 (folate), B12 and B6.
If these vitamins are lacking (or the MTHFR enzyme is impaired), homocysteine builds up. Its excess is toxic to the endothelium — the inner lining of the vessels — and is linked to atherosclerosis, thrombosis and cognitive decline.
Reference ranges
Reference for adults:
| Optimal | below 10 µmol/L |
| Normal (lab reference) | 5 – 15 µmol/L |
| Moderate hyperhomocysteinemia | 15 – 30 µmol/L |
| Intermediate | 30 – 100 µmol/L |
| Severe | above 100 µmol/L |
What an elevated level means
A high homocysteine damages the vascular endothelium and promotes clot formation. It is linked to the risk of heart attack, stroke and venous thrombosis, as well as to accelerated brain atrophy and dementia.
Main causes: deficiency of vitamins B12, B9 (folate) and B6; genetic variants of the MTHFR enzyme; reduced kidney function; hypothyroidism; smoking; excess coffee and alcohol; some medications (metformin and PPIs lower B12).
One point deserves emphasis: in vegans and vegetarians, B12 deficiency is a very common and easily missed cause.
What a low level means
A low homocysteine is usually not considered a problem and typically reflects a good supply of B-group vitamins.
Very low values are occasionally seen in pregnancy and with high-dose B-vitamin supplements — this usually has no clinical significance.
How the test is done
Venous blood, strictly fasting (8–12 hours): homocysteine rises after a protein meal.
Important: the sample must be delivered to the lab quickly and the plasma separated — with prolonged storage of whole blood, homocysteine is falsely elevated as it leaks out of the red cells. If the result is high, it makes sense to also check B12, folate and TSH.
What affects the value
- Vitamins B12, B9 (folate), B6 — their deficiency is the main cause of a rise.
- Genetics (MTHFR) — enzyme variants reduce folate processing.
- Kidney function — homocysteine rises as eGFR falls.
- Hypothyroidism — raises the level; check TSH when homocysteine is high.
- Smoking, alcohol, excess coffee — raise it.
- Medications — metformin and proton-pump inhibitors reduce B12 absorption.
Calculate using this marker
Calculators where Homocysteine is used directly:
Frequently asked questions
Is a homocysteine of 12 normal?
Formally yes (reference up to 15), but it is already above the optimum. Many specialists consider a level below 10 µmol/L the target, since the risk of vascular events starts rising from exactly this mark. It makes sense to check B12 and folate.
How do I lower homocysteine?
In the vast majority of cases — by replenishing B-group vitamins: folate, B12 and B6. With MTHFR gene variants, active forms are used (methylfolate, methylcobalamin). Doses should be chosen by a doctor based on your labs.
Is it true that lowering homocysteine does not prevent heart attacks?
This is an honest and important nuance. Homocysteine is reliably linked to vascular risk, but large trials that lowered it with B vitamins did not show a convincing reduction in the number of heart attacks. So it is regarded as a risk marker and a sign of vitamin deficiency, not as a treatment target in itself.